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Sample records for negative myeloproliferative neoplasms

  1. Myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Roaldsnes, Christina; Holst, René; Frederiksen, Henrik

    2017-01-01

    BACKGROUND: Polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF) are clonal disorders collectively named as myeloproliferative neoplasms (MPN). Published data on epidemiology of MPN after the discovery of the JAK2 mutation and the 2008 WHO classifications are scarce. We...

  2. Increased gene expression of histone deacetylases in patients with Philadelphia-negative chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Skov, Vibe; Larsen, Thomas Stauffer; Thomassen, Mads

    2012-01-01

    Abstract Myeloproliferation, myeloaccumulation (decreased apoptosis), inflammation, bone marrow fibrosis and angiogenesis are cardinal features of the Philadelphia-negative chronic myeloproliferative neoplasms: essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF...

  3. Interferon-alpha in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms. Status and perspectives

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Larsen, Thomas Stauffer; Riley, Caroline Hasselbalch

    2011-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms encompass essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). A major break-through in the understanding of the pathogenesis of these neoplasms occurred in 2005 by the discovery of the JAK2 V617F...

  4. Second malignancies in hydroxyurea and interferon-treated Philadelphia-negative myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Hansen, Iben Onsberg; Sørensen, Anders Lindholm; Hasselbalch, Hans Carl

    2017-01-01

    OBJECTIVE: In an era of controversy in regard to 'hydroxyurea-leukaemogenicity' and when interferon-alfa2 (IFN) is being revived in the treatment of Philadelphia-negative myeloproliferative neoplasms (MPNs), we aim in this single-centre observational study to describe the frequencies of second...... malignancies in a cohort of MPN patients treated with hydroxyurea (HU) or IFN monotherapy or the combination of these agents. PATIENTS AND METHODS: Records of a MPN cohort of 196 patients were reviewed, and a retrospective analysis was performed on 90 patients treated with HU, 38 patients treated with IFN...

  5. Thromboembolism prophylaxis in patients with Philadelphia-negative myeloproliferative neoplasms-Clinical practice among Nordic specialists.

    Science.gov (United States)

    Bjerrum, Ole Weis; Samuelsson, Jan; Ghanima, Waleed; Kauppila, Marjut; Andersen, Christen Lykkegaard

    2018-05-01

    Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs. The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems. The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients. The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Bone morbidity in chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Farmer, Sarah; Ocias, Lukas Frans; Vestergaard, Hanne

    2015-01-01

    Patients with the classical Philadelphia chromosome-negative chronic myeloproliferative neoplasms including essential thrombocythemia, polycythemia vera and primary myelofibrosis often suffer from comorbidities, in particular, cardiovascular diseases and thrombotic events. Apparently, there is also...

  7. Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics.

    Science.gov (United States)

    Langabeer, Stephen E

    2016-01-01

    The majority of patients with classical myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia, and primary myelofibrosis harbor distinct disease-driving mutations within the JAK2 , CALR , or MPL genes. The term triple-negative has been recently applied to those MPN without evidence of these consistent mutations, prompting whole or targeted exome sequencing approaches to determine the driver mutational status of this subgroup. These strategies have identified numerous novel mutations that occur in alternative exons of both JAK2 and MPL , the majority of which result in functional activation. Current molecular diagnostic approaches may possess insufficient coverage to detect these alternative mutations, prompting further consideration of targeted exon sequencing into routine diagnostic practice. How to incorporate these illuminating findings into the expanding molecular diagnostic algorithm for MPN requires continual attention.

  8. Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    OpenAIRE

    Singdong, Roongrudee; Siriboonpiputtana, Teerapong; Chareonsirisuthigul, Takol; Kongruang, Adcharee; Limsuwanachot, Nittaya; Sirirat, Tanasan; Chuncharunee, Suporn; Rerkamnuaychoke, Budsaba

    2016-01-01

    Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical ...

  9. Myeloproliferative neoplasm stem cells.

    Science.gov (United States)

    Mead, Adam J; Mullally, Ann

    2017-03-23

    Myeloproliferative neoplasms (MPNs) arise in the hematopoietic stem cell (HSC) compartment as a result of the acquisition of somatic mutations in a single HSC that provides a selective advantage to mutant HSC over normal HSC and promotes myeloid differentiation to engender a myeloproliferative phenotype. This population of somatically mutated HSC, which initiates and sustains MPNs, is termed MPN stem cells. In >95% of cases, mutations that drive the development of an MPN phenotype occur in a mutually exclusive manner in 1 of 3 genes: JAK2 , CALR , or MPL The thrombopoietin receptor, MPL, is the key cytokine receptor in MPN development, and these mutations all activate MPL-JAK-STAT signaling in MPN stem cells. Despite common biological features, MPNs display diverse disease phenotypes as a result of both constitutional and acquired factors that influence MPN stem cells, and likely also as a result of heterogeneity in the HSC in which MPN-initiating mutations arise. As the MPN clone expands, it exerts cell-extrinsic effects on components of the bone marrow niche that can favor the survival and expansion of MPN stem cells over normal HSC, further sustaining and driving malignant hematopoiesis. Although developed as targeted therapies for MPNs, current JAK2 inhibitors do not preferentially target MPN stem cells, and as a result, rarely induce molecular remissions in MPN patients. As the understanding of the molecular mechanisms underlying the clonal dominance of MPN stem cells advances, this will help facilitate the development of therapies that preferentially target MPN stem cells over normal HSC. © 2017 by The American Society of Hematology.

  10. Involvement of mast cells by the malignant process in patients with Philadelphia chromosome negative myeloproliferative neoplasms.

    Science.gov (United States)

    Wang, J; Ishii, T; Zhang, W; Sozer, S; Dai, Y; Mascarenhas, J; Najfeld, V; Zhao, Z J; Hoffman, R; Wisch, N; Xu, M

    2009-09-01

    The Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) are clonal hematologic malignancies frequently characterized by a mutation in JAK2 (JAK2V617F). Peripheral blood (PB) CD34(+) cells from patients with polycythemia vera (PV) and primary myelofibrosis (PMF) generated in vitro significantly fewer mast cells (MCs) than normal PB CD34(+) cells. The numbers of MC progenitors assayed from MPN CD34(+) cells were, however, similar to that assayed from normal CD34(+) cells. A higher percentage of the cultured MPN MCs expressed FcvarepsilonRIalpha, CD63 and CD69 than normal MCs, suggesting that cultured MPN MCs are associated with an increased state of MC activation. Further analysis showed that a higher proportion of cultured PV and PMF MCs underwent apoptosis in vitro. By using JAK2V617F, MplW515L and chromosomal abnormalities as clonality markers, we showed that the malignant process involved MPN MCs. JAK2V617F-positive MC colonies were assayable from the PB CD34(+) cells of each of the 17 JAK2V617F positive MPN patients studied. Furthermore, erlotinib, a JAK2 inhibitor, was able to inhibit JAK2V617F-positive PV MC progenitor cells, indicating that malignant MC progenitor cells are a potential cellular target for such JAK2 inhibitor-directed therapy.

  11. Frequency of janus associated kinase 2 (jak2) mutation in patients of bcr-abl negative myeloproliferative neoplasms

    International Nuclear Information System (INIS)

    Sadiq, M.A.; Ahmed, S.; Ali, N.

    2013-01-01

    To determine the frequency of Janus associated kinase 2 mutation in the patients of BCR-ABL negative classical myeloproliferative neoplasms. Study Design: Cross-sectional descriptive study Place and Duration of Study: Molecular Department of Haematology, Armed Forces Institute of Pathology (AFIP), Rawalpindi from Jul 2011 to Jul 2012. Patients and Methods: Ninety three consecutive patients of Polycythaemia vera (PV), Essential thrombocythaemia (ET) and Idiopathic myelofibrosis (IMF) diagnosed by the conventional haematological criteria were included in the study. All patients were screened for G-T point mutation (V617F) in the JAK2 gene on chromosome 9 by an allele specific PCR. Results: Out of the 93 myeloproliferative neoplasm (MPN) patients, 33(35%) had polycythaemia vera, 36(39%) had essential thrombocythaemia and 24(26%) had idiopathic myelofibrosis. JAK2 mutation was seen in 64/93 (69%) patients including 33/33(100%) in PV, 19/36(52.6%) in ET and 12/24(50%) in IMF. Conclusion: Classical myeloproliferative neoplasms are an important group of heamatological disorder in our country. JAK2 gene mutation is seen in significant proportion of these disorders (69%). JAK2 mutation analysis can be used to differentiate between polycythemia vera and secondary polycythemia in most cases with near certainty, where it was found in 100% of the cases. (author)

  12. Philadelphia chromosome-negative classical myeloproliferative neoplasms: revised management recommendations from European LeukemiaNet.

    Science.gov (United States)

    Barbui, Tiziano; Tefferi, Ayalew; Vannucchi, Alessandro M; Passamonti, Francesco; Silver, Richard T; Hoffman, Ronald; Verstovsek, Srdan; Mesa, Ruben; Kiladjian, Jean-Jacques; Hehlmann, Rȕdiger; Reiter, Andreas; Cervantes, Francisco; Harrison, Claire; Mc Mullin, Mary Frances; Hasselbalch, Hans Carl; Koschmieder, Steffen; Marchetti, Monia; Bacigalupo, Andrea; Finazzi, Guido; Kroeger, Nicolaus; Griesshammer, Martin; Birgegard, Gunnar; Barosi, Giovanni

    2018-05-01

    This document updates the recommendations on the management of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph-neg MPNs) published in 2011 by the European LeukemiaNet (ELN) consortium. Recommendations were produced by multiple-step formalized procedures of group discussion. A critical appraisal of evidence by using Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology was performed in the areas where at least one randomized clinical trial was published. Seven randomized controlled trials provided the evidence base; earlier phase trials also informed recommendation development. Key differences from the 2011 diagnostic recommendations included: lower threshold values for hemoglobin and hematocrit and bone marrow examination for diagnosis of polycythemia vera (PV), according to the revised WHO criteria; the search for complementary clonal markers, such as ASXL1, EZH2, IDH1/IDH2, and SRSF2 for the diagnosis of myelofibrosis (MF) in patients who test negative for JAK2V617, CALR or MPL driver mutations. Regarding key differences of therapy recommendations, both recombinant interferon alpha and the JAK1/JAK2 inhibitor ruxolitinib are recommended as second-line therapies for PV patients who are intolerant or have inadequate response to hydroxyurea. Ruxolitinib is recommended as first-line approach for MF-associated splenomegaly in patients with intermediate-2 or high-risk disease; in case of intermediate-1 disease, ruxolitinib is recommended in highly symptomatic splenomegaly. Allogeneic stem cell transplantation is recommended for transplant-eligible MF patients with high or intermediate-2 risk score. Allogeneic stem cell transplantation is also recommended for transplant-eligible MF patients with intermediate-1 risk score who present with either refractory, transfusion-dependent anemia, blasts in peripheral blood > 2%, adverse cytogenetics, or high-risk mutations. In these situations, the transplant procedure should be

  13. Philadelphia-negative classical myeloproliferative neoplasms: critical concepts and management recommendations from European LeukemiaNet.

    Science.gov (United States)

    Barbui, Tiziano; Barosi, Giovanni; Birgegard, Gunnar; Cervantes, Francisco; Finazzi, Guido; Griesshammer, Martin; Harrison, Claire; Hasselbalch, Hans Carl; Hehlmann, Rudiger; Hoffman, Ronald; Kiladjian, Jean-Jacques; Kröger, Nicolaus; Mesa, Ruben; McMullin, Mary F; Pardanani, Animesh; Passamonti, Francesco; Vannucchi, Alessandro M; Reiter, Andreas; Silver, Richard T; Verstovsek, Srdan; Tefferi, Ayalew

    2011-02-20

    We present a review of critical concepts and produce recommendations on the management of Philadelphia-negative classical myeloproliferative neoplasms, including monitoring, response definition, first- and second-line therapy, and therapy for special issues. Key questions were selected according the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk if age is greater than 60 years or there is a history of previous thrombosis. Risk stratification in primary myelofibrosis (PMF) should start with the International Prognostic Scoring System (IPSS) for newly diagnosed patients and dynamic IPSS for patients being seen during their disease course, with the addition of cytogenetics evaluation and transfusion status. High-risk patients with PV should be managed with phlebotomy, low-dose aspirin, and cytoreduction, with either hydroxyurea or interferon at any age. High-risk patients with ET should be managed with cytoreduction, using hydroxyurea at any age. Monitoring response in PV and ET should use the ELN clinicohematologic criteria. Corticosteroids, androgens, erythropoiesis-stimulating agents, and immunomodulators are recommended to treat anemia of PMF, whereas hydroxyurea is the first-line treatment of PMF-associated splenomegaly. Indications for splenectomy include symptomatic portal hypertension, drug-refractory painful splenomegaly, and frequent RBC transfusions. The risk of allogeneic stem-cell transplantation-related complications is justified in transplantation-eligible patients whose median survival time is expected to be less than 5 years.

  14. Drugs Approved for Myeloproliferative Neoplasms

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for myeloproliferative neoplasms. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters. The drug names link to NCI's Cancer Drug Information summaries.

  15. Molecular diagnostics of myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Langabeer, S. E.; Andrikovics, H.; Asp, J.

    2015-01-01

    Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been...

  16. Associations of Physical and Psychologic Symptom Burden in Patients With Philadelphia Chromosome-Negative Myeloproliferative Neoplasms.

    Science.gov (United States)

    McFarland, Daniel C; Shaffer, Kelly M; Polizzi, Heather; Mascarenhas, John; Kremyanskaya, Marina; Holland, Jimmie; Hoffman, Ronald

    2018-01-31

    The physical symptom burden of patients with myeloproliferative neoplasms (MPNs) may last for extended periods during their disease trajectories and lead to psychologic distress, anxiety, or depression or all of these. This study evaluated the relationship between physical symptom burden captured by the Physical Problem List (PPL) on the Distress Thermometer and Problem List and psychologic outcomes (distress, anxiety, and depression) in the MPN setting. Patients (N = 117) with MPNs completed questionnaires containing the Distress Thermometer and Problem List and the Hospital Anxiety and Depression Scale in a dedicated MPN clinic within an academic medical center. They reported symptoms from any of 22 physical problems on the PPL. Items endorsed by more than 10% of participants were assessed for their associations with distress (Distress Thermometer and Problem List), anxiety (Hospital Anxiety and Depression Scale-Anxiety), and depression (Hospital Anxiety and Depression Scale-Depression). The total number of endorsed PPL items per participant was also evaluated. Nine of 22 PPL items (fatigue, sleep, pain, dry skin/pruritus, memory/concentration, feeling swollen, breathing, and sexual) were reported by >10% of participants. In univariate analyses, all PPL items but one were associated with distress and depression, and all but 2 were associated with anxiety. In multivariate analyses, the total number of PPL items was associated with depression only (p symptom burden in MPN patients was clearly associated with psychologic symptoms. Depression was uniquely associated with overall physical symptom burden. As such, the endorsement of multiple PPL items on the Distress Thermometer and Problem List should prompt an evaluation for psychologic symptoms to improve MPN patients' overall morbidity and quality of life. Copyright © 2018 The Academy of Psychosomatic Medicine. Published by Elsevier Inc. All rights reserved.

  17. Calreticulin Mutations in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Noa Lavi

    2014-10-01

    Full Text Available With the discovery of the JAK2V617F mutation in patients with Philadelphia chromosome-negative (Ph− myeloproliferative neoplasms (MPNs in 2005, major advances have been made in the diagnosis of MPNs, in understanding of their pathogenesis involving the JAK/STAT pathway, and finally in the development of novel therapies targeting this pathway. Nevertheless, it remains unknown which mutations exist in approximately one-third of patients with non-mutated JAK2 or MPL essential thrombocythemia (ET and primary myelofibrosis (PMF. At the end of 2013, two studies identified recurrent mutations in the gene encoding calreticulin (CALR using whole-exome sequencing. These mutations were revealed in the majority of ET and PMF patients with non-mutated JAK2 or MPL but not in polycythemia vera patients. Somatic 52-bp deletions (type 1 mutations and recurrent 5-bp insertions (type 2 mutations in exon 9 of the CALR gene (the last exon encoding the C-terminal amino acids of the protein calreticulin were detected and found always to generate frameshift mutations. All detected mutant calreticulin proteins shared a novel amino acid sequence at the C-terminal. Mutations in CALR are acquired early in the clonal history of the disease, and they cause activation of JAK/STAT signaling. The CALR mutations are the second most frequent mutations in Ph− MPN patients after the JAK2V617F mutation, and their detection has significantly improved the diagnostic approach for ET and PMF. The characteristics of the CALR mutations as well as their diagnostic, clinical, and pathogenesis implications are discussed in this review.

  18. CALR, JAK2 and MPL mutation status in Argentinean patients with BCR-ABL1- negative myeloproliferative neoplasms.

    Science.gov (United States)

    Ojeda, Mara Jorgelina; Bragós, Irma Margarita; Calvo, Karina Lucrecia; Williams, Gladis Marcela; Carbonell, María Magdalena; Pratti, Arianna Flavia

    2018-05-01

    To establish the frequency of JAK2, MPL and CALR mutations in Argentinean patients with BCR-ABL1-negative  myeloproliferative neoplasms (MPN) and to compare their clinical and haematological features. Mutations of JAK2V617F, JAK2 exon 12, MPL W515L/K and CALR were analysed in 439 Argentinean patients with BCR-ABL1-negative MPN, including 176 polycythemia vera (PV), 214 essential thrombocythemia (ET) and 49 primary myelofibrosis (PMF). In 94.9% of PV, 85.5% ET and 85.2% PMF, we found mutations in JAK2, MPL or CALR. 74.9% carried JAK2V617F, 12.3% CALR mutations, 2.1% MPL mutations and 10.7% were triple negative. In ET, nine types of CALR mutations were identified, four of which were novel. PMF patients were limited to types 1 and 2, type 2 being more frequent. In ET, patients with CALR mutation were younger and had higher platelet counts than those with JAK2V617F and triple negative. In addition, JAK2V617F patients had high leucocyte and haemoglobin values compared with CALR-mutated and triple-negative patients. In PMF, patients with mutant CALR were associated with higher platelet counts. Our study underscores the importance of JAK2, MPL and CALR genotyping for accurate diagnosis of patients with BCR-ABL1-negative MPN.

  19. Characterization and Prognosis Significance of JAK2 (V617F), MPL, and CALR Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    Science.gov (United States)

    Singdong, Roongrudee; Siriboonpiputtana, Teerapong; Chareonsirisuthigul, Takol; Kongruang, Adcharee; Limsuwanachot, Nittaya; Sirirat, Tanasan; Chuncharunee, Suporn; Rerkamnuaychoke, Budsaba

    2016-10-01

    Background: The discovery of somatic acquired mutations of JAK2 (V617F) in Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) has not only improved rational disease classification and prognostication but also brings new understanding insight into the pathogenesis of diseases. Dosage effects of the JAK2 (V617F) allelic burden in Ph-negative MPNs may partially influence clinical presentation, disease progression, and treatment outcome. Material and Methods: Pyrosequencing was performed to detect JAK2 (V617F) and MPL (W515K/L) and capillary electrophoresis to identify CALR exon 9.0 mutations in 100.0 samples of Ph-negative MPNs (38.0 PV, 55 ET, 4 PMF, and 3 MPN-U). Results: The results showed somatic mutations of JAK2 (V617F) in 94.7% of PV, 74.5% of ET, 25.0% of PMF, and all MPN-U. A high proportion of JAK2 (V617F) mutant allele burden (mutational load > 50.0%) was predominantly observed in PV when compared with ET. Although a high level of JAK2 (V617F) allele burden was strongly associated with high WBC counts in both PV and ET, several hematological parameters (hemoglobin, hematocrit, and platelet count) were independent of JAK2 (V617F) mutational load. MPL (W515K/L) mutations could not be detected whereas CALR exon 9.0 mutations were identified in 35.7% of patients with JAK2 negative ET and 33.3% with JAK2 negative PMF. Conclusions: The JAK2 (V617F) allele burden may be involved in progression of MPNs. Furthermore, a high level of JAK2 (V617F) mutant allele appears strongly associated with leukocytosis in both PV and ET. Creative Commons Attribution License

  20. Bleeding complications in BCR-ABL negative myeloproliferative neoplasms: prevalence, type, and risk factors in a single-center cohort.

    Science.gov (United States)

    Kander, Elizabeth M; Raza, Sania; Zhou, Zheng; Gao, Juehua; Zakarija, Anaadriana; McMahon, Brandon J; Stein, Brady L

    2015-11-01

    The BCR-ABL1-negative myeloproliferative neoplasms (MPN) share an increased risk of thrombotic and hemorrhagic complications. Risk factors for hemorrhage are less well defined than those for thrombosis. Because patients with CALR mutations have higher platelet counts compared to JAK2 V617F-mutated patients, bleeding rates may be increased in this group. Our aim was to retrospectively evaluate whether acquired von Willebrand disease (AvWD), thrombocytosis, mutational status, or treatment history are associated with bleeding in a cohort of MPN patients. Using an electronic database, MPN patients seen between 2005 and 2013 were retrospectively identified using ICD-9 codes and billing records. A bleeding event was defined as one that was identified in the medical record and graded based on the Common Terminology Criteria for Adverse Event (CTCAE) version 4.0. Among 351 MPN patients, 15.6 % experienced 64 bleeding event types. There was no association of bleeding with mutational status, gender, MPN subtype, aspirin use, prior thrombosis, or platelet count at presentation. There was an association between bleeding and older age at diagnosis. aVWD was identified in six patients. In this single-center retrospective study, bleeding events were identified in 15 % of patients, and associated with older age at diagnosis. aVWD was rarely tested for in this cohort.

  1. Neurological Findings in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Semra Paydas

    2013-04-01

    Full Text Available Myeloproliferative neoplasms (MPN arise from genetic deficiencies at the level of pluripotent stem cells. Each of these neoplasms is a clonal stem cell disorder with specific phenotypic, genetic and clinical properties. Age is one of the most important factors in the development of symptoms and complications associated with MPNs.High white blood cell counts in chronic myelocytic leukemia also known as leukocytosis may lead to central nervous system findings. Tumors developing outside the bone marrow named as extramedullary myeloid tumors (EMMT could be detected at the initial diagnosis or during the prognosis of the disease, which may cause neurological symptoms due to pressure of leukemic cell mass on various tissues along with spinal cord. Central nervous system involvement and thrombocytopenic hemorrhage may lead to diverse neurological symptoms and findings.Transient ischemic attack and thrombotic stroke are the most common symptoms in polycythemia vera. Besides thrombosis and hemorrage, transformation to acute leukemia can cause neurological symptoms and findings. Transient ischemic attack, thrombotic stroke and specifically hemorrage can give rise to neurological symptoms similar to MPN in essential thrombocytosis.Extramedullary hematopoiesis refers to hematopoietic centers arise in organ/tissues other than bone marrow in myelofibrosis. Extramedullar hematopoietic centers may cause intracranial involvement, spinal cord compression, seizures and hydrocephalia. Though rare, extramedullary hematopoiesis can be detected in cranial/spinal meninges, paraspinal tissue and intracerebral regions. Extramedullary hematopoiesis has been reported in peripheral neurons, choroid plexus, pituitary, orbits, orbital and lacrimal fossa and in sphenoidal sinuses. [Cukurova Med J 2013; 38(2.000: 157-169

  2. Molecular diagnostics of myeloproliferative neoplasms.

    Science.gov (United States)

    Langabeer, Stephen E; Andrikovics, Hajnalka; Asp, Julia; Bellosillo, Beatriz; Carillo, Serge; Haslam, Karl; Kjaer, Lasse; Lippert, Eric; Mansier, Olivier; Oppliger Leibundgut, Elisabeth; Percy, Melanie J; Porret, Naomi; Palmqvist, Lars; Schwarz, Jiri; McMullin, Mary F; Schnittger, Susanne; Pallisgaard, Niels; Hermouet, Sylvie

    2015-10-01

    Since the discovery of the JAK2 V617F mutation in the majority of the myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia and primary myelofibrosis ten years ago, further MPN-specific mutational events, notably in JAK2 exon 12, MPL exon 10 and CALR exon 9 have been identified. These discoveries have been rapidly incorporated into evolving molecular diagnostic algorithms. Whilst many of these mutations appear to have prognostic implications, establishing MPN diagnosis is of immediate clinical importance with selection, implementation and the continual evaluation of the appropriate laboratory methodology to achieve this diagnosis similarly vital. The advantages and limitations of these approaches in identifying and quantitating the common MPN-associated mutations are considered herein with particular regard to their clinical utility. The evolution of molecular diagnostic applications and platforms has occurred in parallel with the discovery of MPN-associated mutations, and it therefore appears likely that emerging technologies such as next-generation sequencing and digital PCR will in the future play an increasing role in the molecular diagnosis of MPN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Detection of MPL exon10 mutations in 103 Chinese patients with JAK2V617F-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Chen, Xiuhua; Qi, Xiling; Tan, Yanhong; Xu, Zhifang; Xu, Aining; Zhang, Linlin; Wang, Hongwei

    2011-06-15

    JAK2V617F mutation has been reported in 90% of patients with polycythemia vera (PV) and about 50% of patients with essential thromobocythemia (ET) and primary myelofibrosis (PMF). Recently, acquired mutations in the transmembrane-juxtamembrane region of MPL (MPLW515 mutations) have been reported in approximately 5% of JAK2V617F-negative PMF and about 1% of all cases of ET. MPL is the receptor for thrombopoietin that regulates the production of platelets by bone marrow. It is likely that some mutations more closely related to ET in MPL exon10 may have been missed by current assays. We inferred that there might be other mutations in MPL exon10 for MPN patients in addition to MPLW515 mutations. To investigate its mutation types and prevalence in Chinese patients with myeloproliferative neoplasms (MPN), we performed mutation detection on MPL exon10 in 103 JAK2V617F-negative MPN patients by single strand conformation polymorphism (SSCP) and allele-specific PCR (AS-PCR) combined with sequencing. As a result, one previously unrecognized MPL mutation (12-bp in-frame insertion) was identified in one patient with ET in addition to an MPLW515K mutation identified in one PMF patient. This confirms our hypothesis that BCR/ABL negative and JAK2V617F-negative MPN patients have other mutations besides W515 mutation in MPL exon10 and mutations other than single nucleotide exchange also exist. In addition, MPL mutation was associated with Chinese MPN patients. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. The Prevalence of JAK2, MPL, and CALR Mutations in Chinese Patients With BCR-ABL1-Negative Myeloproliferative Neoplasms.

    Science.gov (United States)

    Lin, Yani; Liu, Enbin; Sun, Qi; Ma, Jiao; Li, QingHua; Cao, Zeng; Wang, Jun; Jia, Yujiao; Zhang, Hongju; Song, Zhen; Ai, Xiaofei; Shi, Lihui; Feng, Xiaofang; Li, Chenwei; Wang, Jianxiang; Ru, Kun

    2015-07-01

    To evaluate the mutation frequency of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 and the value of the combined tests in the diagnosis of BCR-ABL1-negative myeloproliferative neoplasms (MPNs). In the current study, mutations of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 were analyzed in 929 Chinese patients with BCR-ABL1-negative MPN, including 234 cases of polycythemia vera (PV), 428 ETs, 187 PMFs, and 80 unclassifiable MPNs (MPN-Us). Our result showed that the positive rate of any of four mutations in patients with PV, ET, PMF, and MPN-U was 89.3%, 83.4%, 87.2%, and 77.5%, respectively, which significantly improved the diagnostic rate, especially in ET and PMF. Meanwhile, we also found that the patients without any of four mutations were younger than those with one or more mutations. Unexpectedly, the coexistence of JAK2 V617F and CALR exon 9 was identified in six (0.6%) patients, and JAK2 V617F and MPL exon 10 were present simultaneously in two (0.2%) patients. In addition, we also identified several novel mutation types in CALR exon 9. The combined genetic tests of JAK2 V617F, JAK2 exon 12, MPL exon 10, and CALR exon 9 help improve the diagnostic rate for BCR-ABL1-negative MPN. Copyright© by the American Society for Clinical Pathology.

  5. Methylation profiling of SOCS1, SOCS2, SOCS3, CISH and SHP1 in Philadelphia-negative myeloproliferative neoplasm.

    Science.gov (United States)

    Zhang, Min Yue; Fung, Tsz Kin; Chen, Fang Yuan; Chim, Chor Sang

    2013-10-01

    Janus kinase-signal transducer and activator of transcription (JAK/STAT) signalling, pivotal in Philadelphia-negative (Ph-ve) myeloproliferative neoplasm (MPN), is negatively regulated by molecules including SOCSs, CISH and SHP1. SOCS1, SOCS2 and SOCS3 methylation have been studied in MPN with discordant results. Herein, we studied the methylation status of SOCS1, SOCS2 and SOCS3, CISH and SHP1 by methylation-specific polymerase chain reaction (MSP) in cell lines and 45 diagnostic marrow samples of Ph-ve MPN. Moreover, we attempted to explain the discordance of methylation frequency by mapping the studied MSP primers to the respective genes. Methylation was detected in normal controls using SOCS2 MSP primers in the 3'translated exonic sequence, but not primers around the transcription start site in the 5' untranslated regions (5'UTR). SOCS1, SOCS2, SOCS3 and CISH were completely unmethylated in primary MPN samples and cell lines. In contrast, methylation of SHP1 was detected in 8.9% primary marrow samples. Moreover, SHP1 was completely methylated in K562 cell line, leading to reversible SHP1 silencing. A review of methylation studies of SOCS1 and SOCS3 showed that spuriously high rates of SOCS methylation had been reported using MSP primers targeting CpG sites in the 3'translated exonic sequence, which is also methylated in normal controls. However, using MSP primers localized to the 5'UTR, methylation of SOCS1, SOCS2 and SOCS3 is infrequent across all studies. In summary, methylation of SOCS1, SOCS2, SOCS3 and CISH is infrequent in Ph-ve MPN. Appropriate MSP primers are important for accurate estimation of the methylation frequency. The role of SHP1 methylation in the pathogenesis of MPN warrants further investigation. © 2013 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  6. Patient characteristics and outcomes in adolescents and young adults with classical Philadelphia chromosome-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Boddu, Prajwal; Masarova, Lucia; Verstovsek, Srdan; Strati, Paolo; Kantarjian, Hagop; Cortes, Jorge; Estrov, Zeev; Pierce, Sherry; Pemmaraju, Naveen

    2018-01-01

    Little is known about the outcomes of Philadelphia-negative myeloproliferative neoplasms (MPNs) in adolescents and young adults (AYA). We reviewed all patients with essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) treated at our institution from 1988 to 2016 who were aged 16 to 39 years (AYA) and described their outcomes in comparison to older MPN population. Of 2206 patients, 185 (8.3%) were identified as AYA: 105 (57%) ET, 43 (23%) PV, and 37 (20%) MF. The median age was 33 years [range, 16-39], and median follow-up time 3 years [range, 0.04-25]. JAK2 allele burdens were significantly lower among AYA JAK2V617F-mutated patients in both PV (p = 0.001) and MF (p = 0.005). Seven percent of MPN AYA patients were diagnosed with a thrombotic event at, or prior to, diagnosis. Over the short median follow-up, 4 thrombotic (PV = 1, MF = 3) and 3 leukemia (ET = 2, MF = 1) events occurred. In multivariate analysis, AYA did not predict for thrombotic or transformational events across three cohorts. In the MF cohort, there was a reduced frequency of negative prognostic variables of anemia (p = 0.011) and leukocytosis (p = 0.048) in AYA when compared with non-AYA. Overall survival was significantly superior in the AYA cohorts in all three MPN groups, namely MF (p < 0.001), PV (p < 0.001), and ET (p = 0.002). Our findings suggest that MPN AYA patients exhibit an indolent clinical phenotype characterized by favorable survival outcomes.

  7. JAK2 and MPL gene mutations in V617F-negative myeloproliferative neoplasms.

    NARCIS (Netherlands)

    Siemiatkowska, A.M.; Bieniaszewska, M.; Hellmann, A.; Limon, J.

    2010-01-01

    We report three novel mutations in JAK2 exons 12, 19 and 25 in V617F-negative patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. Scanning of JAK2 exons 12-25 and MPL exon 10 revealed the presence of JAK2 alterations in six and MPL W515L/K mutations in five of 34

  8. Suspected myelodysplastic/myeloproliferative neoplasm in a feline leukemia virus-negative cat.

    Science.gov (United States)

    Weeden, Amy L; Taylor, Kyle R; Terrell, Scott P; Gallagher, Alexander E; Wamsley, Heather L

    2016-12-01

    A 10-year-old castrated Domestic Short-Haired cat was presented to a primary care veterinarian for a wellness examination and laboratory examination for monitoring of diabetes mellitus. The CBC revealed marked thrombocytosis, leukopenia and macrocytic, normochromic anemia. The cat tested negative for FeLV and feline immunodeficiency virus, but was positive for Mycoplasma haemominutum by PCR. Hematologic abnormalities were not responsive to therapy, so a repeat CBC and a bone marrow aspiration for cytology were performed. Additional blood smear findings included anisocytosis with megaloblastic erythroid precursors, large platelets, eosinophilic myelocytes and metamyelocytes, and rare unidentified blasts. The bone marrow smear was highly cellular, and the cytologic pattern was consistent with myelodysplastic syndrome with an erythroid predominance. At that time, 15% blasts were present. The cat was treated with a vitamin K 2 analog, doxycycline, and prednisolone, but without a clinical response. Within 3 months, euthanasia was elected due to declining quality of life, and a necropsy was performed. Postmortem bone marrow smears were highly cellular and dominated by monomorphic blasts of unknown line of origin (52%), persistent marked erythroid and megakaryocytic dysplasia, and ineffective erythropoiesis and granulopoiesis. Immunohistochemical, immunocytochemical, and cytochemical stains resulted in a diagnosis of acute myeloid leukemia of unclassified type. Additional histologic findings included mixed hepatitis with trematode infestation and lymphoplasmacytic interstitial nephritis with fibrosis. The marked thrombocytosis with myelodysplastic syndrome and the FeLV-negative status of this cat were unusual. The difficulty in classifying the myelodysplasia and subsequent leukemia highlights a need for further reporting and characterization of these types of disease. © 2016 American Society for Veterinary Clinical Pathology.

  9. Myeloproliferative neoplasms in five multiple sclerosis patients

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Bjerrum, Ole Weis

    2013-01-01

    The concurrence of myeloproliferative neoplasms (MPNs) and multiple sclerosis (MS) is unusual. We report five patients from a localized geographic area in Denmark with both MS and MPN; all the patients were diagnosed with MPNs in the years 2007-2012. We describe the patients' history and treatment...

  10. Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2

    NARCIS (Netherlands)

    Nangalia, J.; Massie, C.E.; Baxter, E.J.; Nice, F.L.; Gundem, G.; Wedge, D.C.; Avezov, E.; Li, J.; Kollmann, K.; Kent, D.G.; Aziz, A.; Godfrey, A.L.; Hinton, J.; Martincorena, I.; Loo, P. Van; Jones, A.V.; Guglielmelli, P.; Tarpey, P.; Harding, H.P.; Fitzpatrick, J.D.; Goudie, C.T.; Ortmann, C.A.; Loughran, S.J.; Raine, K.; Jones, D.R.; Butler, A.P.; Teague, J.W.; O'Meara, S.; McLaren, S.; Bianchi, M.; Silber, Y.; Dimitropoulou, D.; Bloxham, D.; Mudie, L.; Maddison, M.; Robinson, B.; Keohane, C.; Maclean, C.; Hill, K.; Orchard, K.; Tauro, S.; Du, M.Q.; Greaves, M.; Bowen, D.; Huntly, B.J.; Harrison, C.N.; Cross, N.C.; Ron, D.; Vannucchi, A.M.; Papaemmanuil, E.; Campbell, P.J.; Green, A.R.

    2013-01-01

    BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing

  11. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Joseph Tripodi

    2010-09-01

    Full Text Available Joseph Tripodi1, Ronald Hoffman1, Vesna Najfeld2, Rona Weinberg31The Myeloproliferative Disorders Program, Tisch Cancer Institute, Department of Medicine and 2Department of Medicine and Pathology, Mount Sinai School of Medicine, 3The Myeloproliferative Disorders Program, Cellular Therapy Laboratory, The New York Blood Center, New York, NY, USAAbstract: The Philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2 on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4% who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%.Keywords: TET2, myeloproliferative neoplasms, fluorescence in situ hybridization, cytogenetics

  12. [JAK2 V617F and exon 12 genetic variations in Korean patients with BCR/ABL1-negative myeloproliferative neoplasms].

    Science.gov (United States)

    Kim, Jeong Tae; Cho, Yong Gon; Choi, Sam Im; Lee, Young Jin; Kim, Hye Ran; Jang, Sook Jin; Moon, Dae Soo; Park, Young Jin; Park, Geon

    2010-12-01

    JAK2 genetic variations have been described in a high proportion of patients with BCR/ABL1-negative myeloproliferative neoplasms (MPN). This study was designed to analyze the frequencies of JAK2 V617F and exon 12 variations, and their correlations with clinical characteristics of Korean patients with BCR/ABL1-negative MPN. We examined a total of 154 patients with BCR/ABL1-negative MPN that included 24, 26, 89, and 15 patients with polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), and unclassified myeloproliferative neoplasms (MPNU), respectively. We performed allele-specific PCR to detect V617F in all BCR/ABL1-negative patients, and performed direct sequencing to detect exon 12 variations in 47 V617F-negative MPN patients. JAK2 c.1641+179_183del5 variation was detected by restriction fragment length polymorphism assay in 176 healthy subjects. JAK2 V617F was detected in 91 patients (59.1%): PV (91.6%), PMF (46.2%), ET (52.8%), and MPNU (66.7%). In V617F-negative MPN patients, no mutations were found in exon 12. The c.1641+179_183del5 was detected in 68.1% of V617F-negative MPN patients and 45.4% of healthy subjects (P=0.008). JAK2 V617F was closely correlated with age and leukocytosis in BCR/ABL1-negative MPN patients (P<0.05). However, c.1641+179_183del5 was not related to age, sex, or complete blood cell count parameters in V617F-negative MPN patients and healthy subjects. The c.1641+179_183del5 was associated with an increased odds ratio for MPN (odds ratio, 2.6; 95% confidences interval, 1.3-5.1; P=0.007). Frequencies of V617F are similar to reported results. JAK2 exon 12 mutations may be rare and c.1641+179_183del5 may influence the occurrence of MPN in Korean patients with V6 17F-negative MPN.

  13. Prognostic significance of ASXL1, JAK2V617F mutations and JAK2V617F allele burden in Philadelphia-negative myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Yonal-Hindilerden I

    2015-06-01

    Full Text Available Ipek Yonal-Hindilerden, Aynur Daglar-Aday, Basak Akadam-Teker, Ceylan Yilmaz, Meliha Nalcaci, Akif Selim Yavuz, Deniz SarginDivision of Hematology, Department of Internal Medicine, Istanbul Medical Faculty, Istanbul University, Fatih-Istanbul, Turkey Background: Despite insights into the genetic basis of Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPNs, a significant proportion of essential thrombocythemia (ET and primary myelofibrosis (PMF patients present with no known MPN disease alleles. There were no previous studies investigating the impact of ASXL1 mutations in Ph-negative MPNs in Turkey. In the current study, we investigated the prognostic significance of ASXL1 mutations in Turkish MPN patients. We also aimed to determine the prognostic significance of JAK2V617F allele burden and the relationship of JAK2V617F mutation with ASXL1 mutations in Ph-negative MPNs. Methods: About 184 patients from a single center diagnosed with Ph-negative MPNs were screened for ASXL1, JAK2V617F mutations, and JAK2V617F allele burden: 107 ET and 77 PMF. Results: A total of 29 ASXL1 mutations were detected in 24.7% of PMF and 8.4% of ET patients. ASXL1-mutated ET patients showed a trend toward an increase in the incidence of cerebrovascular events and higher total leukocyte counts. ASXL1-mutation in PMF was associated with older age and a higher prevalence of bleeding complications. In univariate analysis, overall survival (OS was significantly reduced in ASXL1-mutated PMF patients. In multivariate analysis, Dynamic International Prognostic Scoring System-plus high-risk category and ASXL1 mutation status were independently associated with shorter survival in PMF. In PMF, mutational status and allele burden of JAK2V617F showed no difference in terms of OS and leukemia-free survival. Conclusion: We conclude that ASXL1 mutations are molecular predictors of short OS in PMF. Keywords: Philadelphia-negative myeloproliferative neoplasms (Ph-negative

  14. Comparative study of different methodologies to detect the JAK2 V617F mutation in chronic BCR-ABL1 negative myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Alline Didone

    2016-04-01

    Full Text Available Objectives: A mutation in the JAK2 gene, V617F, has been identified in several BCR-ABL1 negative myeloproliferative neoplasms (MPN: polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF. Defining the presence or absence of this mutation is an essential part of clinical diagnostic algorithms and patient management. Here, we aimed to evaluate the performance of three PCR-based assays: Amplification Refractory Mutation System (ARMS, High-Resolution Melting analysis (HRM, and Sanger direct sequencing, and compare their results with those obtained by a PCR restriction fragment polymorphism assay (PCR-RFLP. Design and methods: We used blood samples from 136 patients (PV=20; PMF=20; ET=28, and other MPN suspected cases=68. Results: Comparable results were observed among the four assays in patients with PV, PMF, and MPN suspected cases. In patients with a diagnosis of ET, the JAK2 V617F mutation was detected in 67.8% of them by the PCR-ARMS and PCR-HRM assay and in 64% of them by the conventional Sanger sequence approach. The PCR-ARMS and PCR-HRM assays were 100% concordant. With these tests, only one of the 20 patients with ET and one of the three patients with clinically suspected MPN gave different results compared with those obtained by the PCR-RFLP. Conclusions: Our results have demonstrated that the PCR-ARMS and PCR-HRM assays could detect the JAK2 V617F mutation effectively in MPN patients, but PCR-HRM assays are rapid and the most cost-effective procedures. Keywords: Myeloproliferative, JAK2 V617F, Mutation, Wild type, Screening

  15. Safety and efficacy of combination therapy of interferon-alpha2 + JAK1-2 Inhibitor in the philadelphia-negative chronic myeloproliferative neoplasms. Preliminary results from the danish combi-trial-an open label, single arm, non-randomized multicenter phase II study

    DEFF Research Database (Denmark)

    Mikkelsen, S. U.; Kjaer, L.; Skov, V.

    2015-01-01

    Background: The Philadelphia-negative, chronic myeloproliferative neoplasms (MPN) include essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (MF) (PMF). Chronic inflammation and a deregulated immune system are considered important for clonal evolution and disease...

  16. Inheritance of the chronic myeloproliferative neoplasms. A systematic review

    DEFF Research Database (Denmark)

    Ranjan, Ajenthen; Penninga, E; Jelsig, Am

    2012-01-01

    This systematic review investigated the inheritance of the classical chronic myeloproliferative neoplasms (MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and chronic myelogenous leukemia (CML). Sixty-one articles were included and provided 135...

  17. The myeloproliferative neoplasms, unclassifiable: clinical and pathological considerations.

    Science.gov (United States)

    Gianelli, Umberto; Cattaneo, Daniele; Bossi, Anna; Cortinovis, Ivan; Boiocchi, Leonardo; Liu, Yen-Chun; Augello, Claudia; Bonometti, Arturo; Fiori, Stefano; Orofino, Nicola; Guidotti, Francesca; Orazi, Attilio; Iurlo, Alessandra

    2017-02-01

    In this study, we investigate in detail the morphological, clinical and molecular features of 71 consecutive patients with a diagnosis of myeloproliferative neoplasms, unclassifiable. We performed a meticulous morphological analysis and found that most of the cases displayed a hypercellular bone marrow (70%) with normal erythropoiesis without left-shifting (59%), increased granulopoiesis with left-shifting (73%) and increased megakaryocytes with loose clustering (96%). Megakaryocytes displayed frequent giant forms with hyperlobulated or bulbous nuclei and/or other maturation defects. Interestingly, more than half of the cases displayed severe bone marrow fibrosis (59%). Median values of hemoglobin level and white blood cells count were all within the normal range; in contrast, median platelets count and lactate dehydrogenase were increased. Little less than half of the patients (44%) showed splenomegaly. JAK2V617F mutation was detected in 72% of all patients. Among the JAK2-negative cases, MPLW515L mutation was found in 17% and CALR mutations in 67% of the investigated cases, respectively. Finally, by multiple correspondence analysis of the morphological profiles, we found that all but four of the cases could be grouped in three morphological clusters with some features similar to those of the classic BCR-ABL1-negative myeloproliferative neoplasms. Analysis of the clinical parameters in these three clusters revealed discrepancies with the morphological profile in about 55% of the patients. In conclusion, we found that the category of myeloproliferative neoplasm, unclassifiable is heterogeneous but identification of different subgroups is possible and should be recommended for a better management of these patients.

  18. Busulfan is effective second-line therapy for older patients with Philadelphia-negative myeloproliferative neoplasms intolerant of or unresponsive to hydroxyurea.

    Science.gov (United States)

    Douglas, Genevieve; Harrison, Claire; Forsyth, Cecily; Bennett, Michael; Stevenson, William; Hounsell, John; Ratnasingam, Sumita; Ritchie, David; Ross, David M; Grigg, Andrew

    2017-01-01

    Hydroxyurea (Hu) is widely used as first-line cytoreductive therapy for patients with high-risk Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPN), but a small proportion of patients have refractory disease or experience adverse effects. Studies have demonstrated busulfan (Bu) to be an active first-line agent, but data on its role as second-line or later therapy are minimal. To evaluate its efficacy and safety in this context, we undertook a multicenter audit of Ph-neg MPN patients who had received Bu as therapy for Hu intolerance or failure. Of 51 patients identified, 38 (75%) achieved either complete or partial hematological response following at least one Bu cycle. Bu was generally well tolerated, with only 21/135 (15%) cycles complicated by adverse effects, predominantly cytopenia; only 6% of cycles were ceased due to treatment complications. Bu is an effective and well-tolerated agent in patients with Ph-neg MPN in the setting of Hu intolerance or unresponsiveness.

  19. Cyclical thrombocytosis, acquired von Willebrand syndrome and aggressive non-melanoma skin cancers are common in patients with Philadelphia-negative myeloproliferative neoplasms treated with hydroxyurea.

    Science.gov (United States)

    Verner, Emma; Forsyth, Cecily; Grigg, Andrew

    2014-05-01

    Abstract Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea complications have been reported in Philadelphia-negative myeloproliferative neoplasms (MPNs), but their incidence and clinical consequences have not been defined in a large cohort of patients. We conducted a retrospective analysis of 188 consecutive patients with MPNs specifically addressing the incidence of these complications. Cyclical thrombocytosis was documented in 29 patients (15%), the majority of whom were receiving hydroxyurea. Acquired von Willebrand syndrome was identified in 17 of the 84 screened patients (20%), but was not associated with any major bleeding complications. Non-melanoma skin cancers were reported in 51 patients (27%). Hydroxyurea-related fever occurred in nine of 149 patients (6%) who received hydroxyurea. Seventy-three patients (39%) experienced a total of 98 major thrombotic events, with the majority of these occurring prior to or within 3 months of the diagnosis. Cyclical thrombocytosis, acquired von Willebrand syndrome, aggressive non-melanoma skin cancers and other hydroxyurea-related complications are not infrequent in MPNs and have important clinical consequences for management.

  20. The mutation profile of JAK2, MPL and CALR in Mexican patients with Philadelphia chromosome-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Labastida-Mercado, Nancy; Galindo-Becerra, Samantha; Garcés-Eisele, Javier; Colunga-Pedraza, Perla; Guzman-Olvera, Valeria; Reyes-Nuñez, Virginia; Ruiz-Delgado, Guillermo J; Ruiz-Argüelles, Guillermo J

    2015-03-01

    By using molecular markers, it is possible to gain information on both the classification and etiopathogenesis of chronic myeloproliferative neoplasias (MPN). In a group of 27 Mexican mestizo patients with MPNs, we studied seven molecular markers: the BCR/ABL1 fusion gene, the JAK2 V617F mutation, the JAK2 exon 12 mutations, the MPL W515L mutation, the MPL W515K mutation, and the calreticulin (CALR) exon 9 deletion or insertion. Patients with the BCR/ABL1 fusion gene were excluded. We studied 14 patients with essential thrombocythemia (ET), eight with polycythemia vera (PV), four with primary myelofibrosis (MF), and one with undifferentiated MPN. We found twelve individuals with the JAK2 V617F mutation; five of them had been clinically classified as PV, five as ET, and one as MF. One patient with the MPL W515L was identified with a clinical picture of ET. Five patients with the CALR mutation were identified, four ET and one MF. No individuals with either the MPL W515K mutation or the JAK2 exon 12 mutations were identified. The most consistent relationship was that between PV and the JAK2 V617F mutation (p=.01). Despite its small size, the study shows much less prevalence of JAK2 mutation in PV, ET and MF, which does not match international data. Copyright © 2015 King Faisal Specialist Hospital & Research Centre. Published by Elsevier B.V. All rights reserved.

  1. Mechanisms of mutations in myeloproliferative neoplasms.

    Science.gov (United States)

    Levine, Ross L

    2009-12-01

    In recent years, a series of studies have provided genetic insight into the pathogenesis of myeloproliferative neoplasms (MPNs). It is now known that JAK2V617F mutations are present in 90% of patients with polycythaemia vera (PV), 60% of patients with essential thrombocytosis (ET) and 50% of patients with myelofibrosis (MF). Despite the high prevalence of JAK2V617F mutations in these three myeloid malignancies, several questions remain. For example, how does one mutation contribute to the pathogenesis of three clinically distinct diseases, and how do some patients develop these diseases in the absence of a JAK2V617F mutation? Single nucleotide polymorphisms at various loci and somatic mutations, such as those in MPLW515L/K, TET2 and in exon 12 of JAK2, may also contribute to the pathogenesis of these MPNs. There are likely additional germline and somatic genetic factors important to the MPN phenotype. Additional studies of large MPN and control cohorts with new techniques will help identify these factors.

  2. Diagnosis, prevention, and management of bleeding episodes in Philadelphia-negative myeloproliferative neoplasms: recommendations by the Hemostasis Working Party of the German Society of Hematology and Medical Oncology (DGHO) and the Society of Thrombosis and Hemostasis Research (GTH).

    Science.gov (United States)

    Appelmann, Iris; Kreher, Stephan; Parmentier, Stefani; Wolf, Hans-Heinrich; Bisping, Guido; Kirschner, Martin; Bergmann, Frauke; Schilling, Kristina; Brümmendorf, Tim H; Petrides, Petro E; Tiede, Andreas; Matzdorff, Axel; Griesshammer, Martin; Riess, Hanno; Koschmieder, Steffen

    2016-04-01

    Philadelphia-negative myeloproliferative neoplasms (Ph-negative MPN) comprise a heterogeneous group of chronic hematologic malignancies. The quality of life, morbidity, and mortality of patients with MPN are primarily affected by disease-related symptoms, thromboembolic and hemorrhagic complications, and progression to myelofibrosis and acute leukemia. Major bleeding represents a common and important complication in MPN, and the incidence of such bleeding events will become even more relevant in the future due to the increasing disease prevalence and survival of MPN patients. This review discusses the causes, differential diagnoses, prevention, and management of bleeding episodes in patients with MPN, aiming at defining updated standards of care in these often challenging situations.

  3. No development of neutralizing antibodies against recombinant interferon-alpha in Ph-negative myeloproliferative neoplasms-a prospective study

    DEFF Research Database (Denmark)

    Ocias, Lukas Frans; Lund Hansen, Dennis; Kielsgaard Kristensen, Thomas

    2015-01-01

    not responding adequately to rIFN-alpha treatment, but the phenomenon has not been thoroughly investigated in MPNs. Patients and Methods Newly diagnosed patients with MPNs enrolled in the Danish multicenter trial - DALIAH (Low-dose rIFN-alpha versus Hydroxyurea in The Treatment of Ph-Negative MPNs) were included...

  4. Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

    Science.gov (United States)

    Milosevic Feenstra, Jelena D; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N; Cazzola, Mario; Kralovics, Robert

    2016-01-21

    Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed "triple negative." We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. © 2016 by The American Society of Hematology.

  5. [Clinical significance of JAK2、CALR and MPL gene mutations in 1 648 Philadelphia chromosome negative myeloproliferative neoplasms patients from a single center].

    Science.gov (United States)

    Li, M Y; Chao, H Y; Sun, A N; Qiu, H Y; Jin, Z M; Tang, X W; Han, Y; Fu, C C; Chen, S N; Wu, D P

    2017-04-14

    Objective: To explore the prevalences of JAK2, CALR and MPL gene mutations and the mutation types in patients with Philadelphia chromosome negative myeloproliferative neoplasms (MPNs) , and to compare their clinical characteristics of different mutation types with each other and mutation negative group. Methods: The mutations of JAK2 V617F, JAK2 gene at exon 12, CALR gene at exon 9 and MPL gene at exon 10 in 1 648 Ph negative MPNs patients were detected by direct sequencing. Results: ① The JAK2V617F mutation was found in 471 (92.7%) of 508 PV patients, 819 (78.1%) of 1 049 ET patients and 74 (81.3%) of 91 PMF patients respectively, with the total mutation rate as 82.8% (1 364/1 648) . The JAK2 exon12 mutation was found in 9 (1.7%) of 508 PV patients, none was found in ET or PMF patients, with the total mutation rate as 0.5% (9/1 648) . The CALR mutation was found in 132 (12.6%) of 1 049 ET patients and 11 (12.1%) of 91 PMF patients respectively, with the total mutation rate as 8.7% (143/1 648) ; the MPL mutation was found in 9 (0.9%) of 1 049 ET patients and 1 (1.1%) of 91 PMF patients respectively, with the total mutation rate as 0.6% (10/1 648) . The co-occurrence of any two types of driver gene mutations was not detected by direct sequencing. ②The median onset age of patients with JAK2V617F[61 (15-95) y] was significant higher than of with JAK2 exon12 mutation[49 (33-62) y] or without mutations[42 (3-78) y] ( P MPL mutation[59 (22-71) y] ( P >0.05) . Patients with JAK2V617F had higher white blood cell count and hemoglobin level ( P MPL mutation ( P =0.013) . The platelet count of patients with CALR mutation was significantly higher than of with JAK2V617F[966 (400-2 069) ×10(9)/L vs 800 (198-3 730) ×10(9)/L, P MPL gene mutation revealed normal karyotype. Conclusions: Driver gene mutations detection could ensure the diagnosis and prognosis judgment of MPN more reliable, different subtypes of MPNs had different profiles of driver gene mutations, the latter

  6. Epigenetic therapy in myeloproliferative neoplasms: evidence and perspectives

    Science.gov (United States)

    Vannucchi, Alessandro M; Guglielmelli, Paola; Rambaldi, Alessandro; Bogani, Costanza; Barbui, Tiziano

    2009-01-01

    The classic Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), which include polycythaemia vera, essential thrombocythaemia and primary myelofibrosis, originate from a stem cell-derived clonal myeloproliferation that manifests itself with variable haematopoietic cell lineage involvement; they are characterized by a high degree of similarities and the chance to transform each to the other and to evolve into acute leukaemia. Their molecular pathogenesis has been associated with recurrent acquired mutations in janus kinase 2 (JAK2) and myeloproliferative leukemia virus oncogene (MPL). These discoveries have simplified the diagnostic approach and provided a number of clues to understanding the phenotypic expression of MPNs; furthermore, they represented a framework for developing and/or testing in clinical trials small molecules acting as tyrosine kinase inhibitors. On the other hand, evidence of abnormal epigenetic gene regulation as a mechanism potentially contributing to the pathogenesis and the phenotypic diversity of MPNs is still scanty; however, study of epigenetics in MPNs represents an active field of research. The first clinical trials with epigenetic drugs have been completed recently, whereas others are still ongoing; results have been variable and at present do not allow any firm conclusion. Novel basic and translational information concerning epigenetic gene regulation in MPNs and the perspectives for therapy will be critically addressed in this review. PMID:19522842

  7. [Approach to diagnosis and management of myeloproliferative neoplasm variants].

    Science.gov (United States)

    Mitsumori, Toru; Kirito, Keita

    2015-08-01

    Myeloproliferative neoplasm (MPN) variants are defined as relatively uncommon myeloid neoplasms which do not meet the criteria for either classical MPN or myelodysplastic syndrome. Due to the lack of specific markers, it has been challenging to accurately diagnose these malignant diseases. Recent studies have revealed new genetic abnormalities in MPN variants. These research advances are anticipated to open new approaches to not only achieving accurate diagnosis but also novel therapeutic options for these diseases.

  8. Myelodysplastic/ Myeloproliferative Neoplasms Treatment (PDQ®)—Health Professional Version

    Science.gov (United States)

    Myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are treated with chemotherapy or other drugs, stem cell transplant, supportive care, and targeted therapy. They include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), and atypical chronic myeloid leukemia (aCML). Learn about the clinical features and treatment options for these leukemias.

  9. Allo-SCT for  Philadelphia-negative myeloproliferative neoplasms in blast phase: a study from the Societe Française de Greffe de Moelle et de Therapie Cellulaire (SFGM-TC).

    Science.gov (United States)

    Cahu, X; Chevallier, P; Clavert, A; Suarez, F; Michallet, M; Vincent, L; Vigouroux, S; Blaise, D; Mariette, C; Bilger, K; Robin, M; Yakoub-Agha, I; Peffault de Latour, R; Mohty, M

    2014-06-01

    Progression of Philadelphia-negative myeloproliferative (MPN) or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) to acute myeloid leukemia (AML) is an adverse event in the course of the disease. Although allogeneic hematopoietic SCT (allo-SCT) is considered as the only curative therapy, few data exist on the outcome of patients with Philadelphia-negative MPN or MDS/MPN in blast phase who received an allo-SCT. Sixty patients were included in this retrospective study. AML was secondary to an MPN in 43 cases, whereas AML evolved from an MDS/MPN in 17 cases. Patients received allo-SCT in CR or advanced disease in 26 cases and 34 cases, respectively. With a median follow-up of 31 months (range, 25-44), OS and leukemia-free survival (LFS) were, respectively, 18% and 9% at 3 years. CR at transplant was associated with an improved LFS in univariate and multivariate analysis. The 3-year LFS was 18% for patients undergoing allo-SCT in CR versus 3% in advanced disease (P=0.008). Absence of thrombosis and an intermediate or favorable AML karyotype were associated with an improved outcome for patients who received allo-SCT in CR. New strategies are needed to improve the outcome of patients with MPN-MDS/MPN in blast phase.

  10. Current approaches to challenging scenarios in myeloproliferative neoplasms.

    Science.gov (United States)

    Zimran, Eran; Hoffman, Ronald; Kremyanskaya, Marina

    2018-06-01

    The Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia and primary myelofibrosis are clonal hematological malignancies that originate at the level of the hematopoietic stem cell, and are characterized by excessive proliferation of cells belonging to one or more of the myeloid lineages. Central to the pathogenesis of the MPNs is constitutive activation of the JAK/STAT signaling pathway due to a family of driver mutations affecting JAK2, CALR or MPL. These disorders share common clinical and laboratory features, a significant burden of systemic symptoms, increased risk of developing arterial and venous thrombotic events, and the potential to progress to myelofibrosis and acute leukemia. Areas covered: We identified four clinical situations which represent challenging management dilemmas for patients with MPNs. Our conclusions and recommendations are based on a literature search using MEDLINE and recent meeting abstracts using the keywords, focusing on publications directly addressing these scenarios and on recent contributions to the field. Expert commentary: Multi-center efforts to study large cohorts of MPN patients have led to more uniform and evidence-based approaches to key aspects in MPN management. However, treatment strategies to deal with specific clinical scenarios are lacking.

  11. AKT is a therapeutic target in myeloproliferative neoplasms.

    Science.gov (United States)

    Khan, I; Huang, Z; Wen, Q; Stankiewicz, M J; Gilles, L; Goldenson, B; Schultz, R; Diebold, L; Gurbuxani, S; Finke, C M; Lasho, T L; Koppikar, P; Pardanani, A; Stein, B; Altman, J K; Levine, R L; Tefferi, A; Crispino, J D

    2013-09-01

    The majority of patients with BCR-ABL1-negative myeloproliferative neoplasms (MPN) harbor mutations in JAK2 or MPL, which lead to constitutive activation of the JAK/STAT, PI3K and ERK signaling pathways. JAK inhibitors by themselves are inadequate in producing selective clonal suppression in MPN and are associated with hematopoietic toxicities. MK-2206 is a potent allosteric AKT inhibitor that was well tolerated, including no evidence of myelosuppression, in a phase I study of solid tumors. Herein, we show that inhibition of PI3K/AKT signaling by MK-2206 affected the growth of both JAK2V617F- or MPLW515L-expressing cells via reduced phosphorylation of AKT and inhibition of its downstream signaling molecules. Moreover, we demonstrate that MK-2206 synergizes with ruxolitinib in suppressing the growth of JAK2V617F-mutant SET2 cells. Importantly, MK-2206 suppressed colony formation from hematopoietic progenitor cells in patients with primary myelofibrosis and alleviated hepatosplenomegaly and reduced megakaryocyte burden in the bone marrows, livers and spleens of mice with MPLW515L-induced MPN. Together, these findings establish AKT as a rational therapeutic target in the MPNs.

  12. Targeted cancer exome sequencing reveals recurrent mutations in myeloproliferative neoplasms

    Science.gov (United States)

    Tenedini, E; Bernardis, I; Artusi, V; Artuso, L; Roncaglia, E; Guglielmelli, P; Pieri, L; Bogani, C; Biamonte, F; Rotunno, G; Mannarelli, C; Bianchi, E; Pancrazzi, A; Fanelli, T; Malagoli Tagliazucchi, G; Ferrari, S; Manfredini, R; Vannucchi, A M; Tagliafico, E

    2014-01-01

    With the intent of dissecting the molecular complexity of Philadelphia-negative myeloproliferative neoplasms (MPN), we designed a target enrichment panel to explore, using next-generation sequencing (NGS), the mutational status of an extensive list of 2000 cancer-associated genes and microRNAs. The genomic DNA of granulocytes and in vitro-expanded CD3+T-lymphocytes, as a germline control, was target-enriched and sequenced in a learning cohort of 20 MPN patients using Roche 454 technology. We identified 141 genuine somatic mutations, most of which were not previously described. To test the frequency of the identified variants, a larger validation cohort of 189 MPN patients was additionally screened for these mutations using Ion Torrent AmpliSeq NGS. Excluding the genes already described in MPN, for 8 genes (SCRIB, MIR662, BARD1, TCF12, FAT4, DAP3, POLG and NRAS), we demonstrated a mutation frequency between 3 and 8%. We also found that mutations at codon 12 of NRAS (NRASG12V and NRASG12D) were significantly associated, for primary myelofibrosis (PMF), with highest dynamic international prognostic scoring system (DIPSS)-plus score categories. This association was then confirmed in 66 additional PMF patients composing a final dataset of 168 PMF showing a NRAS mutation frequency of 4.7%, which was associated with a worse outcome, as defined by the DIPSS plus score. PMID:24150215

  13. Defining the Thrombotic Risk in Patients with Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Fabrizio Vianello

    2011-01-01

    Full Text Available Polycythemia vera (PV and essential thrombocythemia (ET are two Philadelphia-negative myeloproliferative neoplasms (MPN associated with an acquired mutation in the JAK2 tyrosine kinase gene. There is a rare incidence of progression to myelofibrosis and myeloid metaplasia in both disorders, which may or may not precede transformation to acute myeloid leukemia, but thrombosis is the main cause of morbidity and mortality. The pathophysiology of thrombosis in patients with MPN is complex. Traditionally, abnormalities of platelet number and function have been claimed as the main players, but increased dynamic interactions between platelets, leukocytes, and the endothelium do probably represent a fundamental interplay in generating a thrombophilic state. In addition, endothelial dysfunction, a well-known risk factor for vascular disease, may play a role in the thrombotic risk of patients with PV and ET. The identification of plasma markers translating the hemostatic imbalance in patients with PV and ET would be extremely helpful in order to define the subgroup of patients with a significant clinical risk of thrombosis.

  14. Hypothetical atopic dermatitis-myeloproliferative neoplasm (AD-MPN syndrome

    Directory of Open Access Journals (Sweden)

    Toshiaki eKawakami

    2015-08-01

    Full Text Available Atopic dermatitis (AD is a chronic inflammatory skin disease. Myeloproliferative neoplasms (MPNs are hematopoietic malignancies caused by uncontrolled proliferation of hematopoietic stem/progenitor cells. Recent studies have described several mutant mice exhibiting both AD-like skin inflammation and MPN. Common pathways for skin inflammation encompass overexpression of thymic stromal lymphopoietin and reduced signaling of epidermal growth factor receptor in the epidermis, while overproduction of granulocyte-colony stimulating factor by keratinocytes and constitutive activation of Stat5 in hematopoietic stem cells are important for the development of MPN. The murine studies suggest the existence of a similar human disease tentatively termed the AD-MPN syndrome.

  15. Platelet indices in Philadelphia-negative chronic myeloproliferative neoplasms / Indicii plachetari de volum în neoplasmele mieloproliferative cronice Philadelphia-negative

    Directory of Open Access Journals (Sweden)

    Olteanu Ariela-Ligia

    2015-06-01

    Full Text Available Introducere: Neoplasmele mieloproliferative cronice cromozom Philadelphia negative (Ph-MPN -policitemia vera (PV, trombocitemia esenţială (TE şi mielofibroza primară (MP - sunt caracterizate de o rată mare de complicaţii trombotice, parţial date de activarea trombocitară. Trombocitele mari sunt mai active, cu o funcţie procoagulantă crescută şi au rol patogenic demonstrat în tromboza arterială şi venoasă. În studiul nostru am încercat să stabilim dacă indicii trombocitari (MPV, PDW, P-LCR, furnizaţi de analizoarele de hematologie în hemoleucograma completă, sunt modificaţi la pacienţii diagnosticaţi cu Ph-MPN comparativ cu subiecţii sănătoşi. Material şi metodă: Hemoleucograma, ce a inclus şi indicii trombocitari, a fost determinată la 102 pacienţi Ph- MPN şi la 102 subiecţi sănătoşi cu ajutorul analizorului de hematologie Sysmex XS 1000i (metoda impedanţei, iar testele biochimice (glucoza şi parametrii metabolismului lipidic, pe analizorul Architect c8000. Prezenţa mutaţiei JAK2 V617F, la pacienţii cu Ph-MPN, a fost evidenţiată prin tehnica ARMS-PCR. Rezultate: Indicii de volum plachetari (IVP măsuraţi prin metoda impedanţei, nu au fost semnificativ modificaţi la pacienţii cu Ph-MPN comparativ cu cei ai subiecţilor sănătoşi. Totuşi, am observat o moderată corelaţie între valoarea acestor indici şi prezenţa mutaţiei JAK2V617F, fără însă a se atinge o diferenţă semnificativă din punct de vedere statistic. IVP au fost crescuţi la micul subgrup de pacienţi trataţi cu anagrelide şi scăzuţi la cei trataţi cu simvastatin, comparativ cu pacienţii care nu au primit aceste terapii. Concluzii: Folosind metoda impedanţei în determinarea indicilor trombocitari, în studiul nostru nu am demonstrat o diferenţă semnificativă între valorile indicilor trombocitari la pacienţii cu Ph- MPN comparativ cu subiecţii sănătoşi. Sunt necesare studii ulterioare pentru a demonstra o

  16. Relationship of JAK2V617F gene mutation with cell proliferation and coagulation function in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Xiao-Nan Zhang

    2017-05-01

    Full Text Available Objective: To study the relationship of JAK2V617F gene mutation with cell proliferation and coagulation function in myeloproliferative neoplasms. Methods: Patients who were diagnosed with BCR-ABL-negative myeloproliferative neoplasms in Anyang District Hospital between June 2014 and August 2016 were selected, JAK2V617F gene mutation was detected, and according to the test results, the patients were divided into mutation-positive group and mutation-negative group. The expression of JAK2/STATs signaling pathway molecules and cell proliferation genes in bone marrow fluid as well as the coagulation function indexes in peripheral blood were detected. Results: p-JAK2, p-STAT3, p-STAT5, Survivin, C-myc, CyclinD1 and ASXL1 protein expression in myeloproliferative neoplasms of mutation-positive group were significantly higher than those of mutation-negative group, and peripheral blood PT and APTT levels were significantly lower than those of mutation-negative group while TT and FIB levels were not significantly different from those of mutation-negative group. Conclusion: JAK2V617F gene mutation in myeloproliferative neoplasms can promote the cell proliferation and cause the hypercoagulable state.

  17. Molecular genetic tests for JAK2V617F, Exon12_JAK2 and MPLW515K/L are highly informative in the evaluation of patients suspected to have BCR-ABL1-negative myeloproliferative neoplasms.

    Science.gov (United States)

    dos Santos, Marcos Tadeu; Mitne-Neto, Miguel; Miyashiro, Kozue; Chauffaille, Maria de Lourdes L Ferrari; Rizzatti, Edgar Gil

    2014-02-01

    Polycythaemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (MF), are the most common myeloproliferative neoplasms (MPN) in patients without the BCR-ABL1 gene rearrangement. They are caused by clonal expansion of haematopoietic stem cells and share, as a diagnostic criterion, the identification of JAK2V617F mutation. Classically, when other clinical criteria are present, a JAK2V617F negative case requires the analysis of Exon12_JAK2 for the diagnosis of PV, and of MPL515K/L mutations for the diagnosis of ET and MF. Here, we evaluated 78 samples from Brazilian patients suspected to have MPN, without stratification for PV, ET or MF. We found that 28 (35.9%) are JAK2V617F carriers; from the 50 remaining samples, one (2%) showed an Exon12_JAK2 mutation, and another (2%) was positive for MPLW515L mutation. In summary, the investigation of JAK2V617F, Exon12_JAK2 and MPLW515K/L was relevant for the diagnosis of 38.4% of patients suspected to have BCR-ABL1-negative MPN, suggesting that molecular genetic tests are useful for a quick and unequivocal diagnosis of MPN.

  18. A Multiplex Snapback Primer System for the Enrichment and Detection of JAK2 V617F and MPL W515L/K Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Zhiyuan Wu

    2014-01-01

    Full Text Available A multiplex snapback primer system was developed for the simultaneous detection of JAK2 V617F and MPL W515L/K mutations in Philadelphia chromosome- (Ph- negative myeloproliferative neoplasms (MPNs. The multiplex system comprises two snapback versus limiting primer sets for JAK2 and MPL mutation enrichment and detection, respectively. Linear-After exponential (LATE PCR strategy was employed for the primer design to maximize the amplification efficiency of the system. Low ionic strength buffer and rapid PCR protocol allowed for selective amplification of the mutant alleles. Amplification products were analyzed by melting curve analysis for mutation identification. The multiplex system archived 0.1% mutation load sensitivity and <5% coefficient of variation inter-/intra-assay reproducibility. 120 clinical samples were tested by the multiplex snapback primer assay, and verified with amplification refractory system (ARMS, quantitative PCR (qPCR and Sanger sequencing method. The multiplex system, with a favored versatility, provided the molecular diagnosis of Ph-negative MPNs with a suitable implement and simplified the genetic test process.

  19. A Multiplex Snapback Primer System for the Enrichment and Detection of JAK2 V617F and MPL W515L/K Mutations in Philadelphia-Negative Myeloproliferative Neoplasms

    Science.gov (United States)

    Zhang, Yunqing; Zhang, Xinju; Xu, Xiao; Kang, Zhihua; Li, Shibao; Zhang, Chen; Su, Bing

    2014-01-01

    A multiplex snapback primer system was developed for the simultaneous detection of JAK2 V617F and MPL W515L/K mutations in Philadelphia chromosome- (Ph-) negative myeloproliferative neoplasms (MPNs). The multiplex system comprises two snapback versus limiting primer sets for JAK2 and MPL mutation enrichment and detection, respectively. Linear-After exponential (LATE) PCR strategy was employed for the primer design to maximize the amplification efficiency of the system. Low ionic strength buffer and rapid PCR protocol allowed for selective amplification of the mutant alleles. Amplification products were analyzed by melting curve analysis for mutation identification. The multiplex system archived 0.1% mutation load sensitivity and <5% coefficient of variation inter-/intra-assay reproducibility. 120 clinical samples were tested by the multiplex snapback primer assay, and verified with amplification refractory system (ARMS), quantitative PCR (qPCR) and Sanger sequencing method. The multiplex system, with a favored versatility, provided the molecular diagnosis of Ph-negative MPNs with a suitable implement and simplified the genetic test process. PMID:24729973

  20. Association Of Tnf Polymorphisms With Jak2 (v617f) Myeloproliferative Neoplasms In Brazilian Patients.

    OpenAIRE

    Macedo, Luciana Conci; de Cesare Quintero, Fernanda; Pagliari-E-Silva, Sara; Pagnano, Katia Borgia Barbosa; Rodrigues, Camila; de Alencar, Josiane Bazzo; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

    2016-01-01

    The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V...

  1. Molecular mechanisms associated with leukemic transformation of MPL-mutant myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Beer, Philip A; Ortmann, Christina A; Stegelmann, Frank

    2010-01-01

    Somatic activating mutations in MPL, the thrombopoietin receptor, occur in the myeloproliferative neoplasms, although virtually nothing is known about their role in evolution to acute myeloid leukemia. In this study, the MPL T487A mutation, identified in de novo acute myeloid leukemia......, was not detected in 172 patients with a myeloproliferative neoplasm. In patients with a prior MPL W515L-mutant myeloproliferative neoplasm, leukemic transformation was accompanied by MPL-mutant leukemic blasts, was seen in the absence of prior cytoreductive therapy and often involved loss of wild-type MPL...

  2. [Evidence on chronic myeloproliferative neoplasms from landmark clinical trials].

    Science.gov (United States)

    Yamaguchi, Hiroki

    2015-08-01

    Mutations in the JAK2 gene are thought to underlie the development of chronic myeloproliferative neoplasms (cMPN). Indeed, ≥95% of polycythemia vera patients, and half or more of essential thrombocythemia and primary myelofibrosis (PMF) patients, harbor the JAK2V617F mutation. Besides the JAK2V617F mutation, the JAK2 exon 12 deletion, the MPLW515L/K, and CALR mutation have been discovered and shown to be involved in the pathogenesis of these diseases. Based on these advancements in the study of cMPN, the JAK2 inhibitor was developed as a new therapy for PMF. Moreover, recent advancements in our ability to diagnose cMPN have paralleled the development of large clinical trials for patients with cMPN. This article provides explanatory information from these large clinical trials that is useful for the actual clinical practice of caring for patients with cMPN in Japan.

  3. Non-driver mutations in myeloproliferative neoplasm-associated myelofibrosis

    Directory of Open Access Journals (Sweden)

    Bing Li

    2017-05-01

    Full Text Available Abstract We studied non-driver mutations in 62 subjects with myeloproliferative neoplasm (MPN-associated myelofibrosis upon diagnosis, including 45 subjects with primary myelofibrosis (PMF and 17 with post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF. Fifty-eight subjects had ≥1 non-driver mutation upon diagnosis. Mutations in mRNA splicing genes, especially in U2AF1, were significantly more frequent in PMF than in post-PV/ET MF (33 vs. 6%; P = 0.015. There were also striking differences in clonal architecture. These data indicate different genomic spectrums between PMF and post-PV/ET MF.

  4. Current opinion and consensus statement regarding the diagnosis, prognosis, and treatment of patients with essential thrombocythemia: a survey of the Spanish Group of Ph-negative Myeloproliferative Neoplasms (GEMFIN) using the Delphi method.

    Science.gov (United States)

    Besses, C; Hernández-Boluda, J C; Pérez Encinas, M; Raya, J M; Hernández-Rivas, J M; Jiménez Velasco, A; Martínez Lopez, J; Vicente, V; Burgaleta, C

    2016-04-01

    The current consensus on the diagnosis, prognosis, and treatment of essential thrombocythemia (ET) is based on experts' recommendations. However, several aspects of the diagnosis of, prognosis of, and therapy for ET are still controversial. The Delphi method was employed with an expert panel of members of the Spanish Group of Ph-negative Myeloproliferative Neoplasms in order to identify the degree of agreement on the diagnosis, prognosis, and treatment of ET. Nine leading experts selected a total of 41 clinical hematologists with well-known expertise in ET. An electronic questionnaire was used to collect the questions rated in a four-step scale. The questions were grouped into four blocks: diagnosis, risk stratification, goals of therapy, and treatment strategy. After the first round consisting of 80 questions, a second round including 14 additional questions focused on the recommendations advocated by experts of the European LeukemiaNet in 2011 was analyzed. The median and mean values for the first and second rounds were calculated. A summary of the conclusions considered as the most representative of each block of questions is presented. The Delphi method is a powerful instrument to address the current approaches and controversies surrounding ET.

  5. Chronic myeloproliferative neoplasms and subsequent cancer risk: a Danish population-based cohort study

    DEFF Research Database (Denmark)

    Frederiksen, Henrik; Farkas, Dóra Körmendiné; Christiansen, Christian Fynbo

    2011-01-01

    Patients with chronic myeloproliferative neoplasms, including essential thrombocythemia (ET), polycythemia vera (PV), and chronic myeloid leukemia (CML), are at increased risk of new hematologic malignancies, but their risk of nonhematologic malignancies remains unknown. In the present study, we...

  6. JAK2 mutations and clinical practice in myeloproliferative neoplasms.

    Science.gov (United States)

    Tefferi, Ayalew

    2007-01-01

    With the discovery in the last 3 years of novel Janus kinase 2 (JAK2) and thrombopoietin receptor (MPL) mutations, the pathogenetic understanding of and clinical practice for myeloproliferative neoplasms (MPNs) have entered a new era. Each one of these newly discovered mutations, including JAK2V617F, MPLW515L, and a JAK2 exon 12 mutation, has been shown to result in constitutive activation of JAK-STAT signaling and also induce a MPN phenotype in mice. Thus, JAK2 is now considered to be a legitimate target for drug development in MPNs, and small molecule JAK2 inhibitors have already gone through successful preclinical testing, and early-phase human trials in primary myelofibrosis have already begun. Furthermore, JAK2 mutation screening has now become a front-line diagnostic test in the evaluation of both "erythrocytosis" and thrombocytosis and the 2001 World Health Organization diagnostic criteria for polycythemia vera, essential thrombocythemia, and primary myelofibrosis have now been revised to incorporate JAK2V617F mutation screening.

  7. Impact of Inflammation on Myeloproliferative Neoplasm Symptom Development

    Directory of Open Access Journals (Sweden)

    Holly L. Geyer

    2015-01-01

    Full Text Available Myeloproliferative neoplasms (essential thrombocythemia, ET; polycythemia vera, PV; myelofibrosis, MF are monoclonal malignancies associated with genomic instability, dysregulated signaling pathways, and subsequent overproduction of inflammatory markers. Acknowledged for their debilitating symptom profiles, recent investigations have aimed to determine the identity of these markers, the upstream sources stimulating their development, their prevalence within the MPN population, and the role they play in symptom development. Creation of dedicated Patient Reported Outcome (PRO tools, in combination with expanded access to cytokine analysis technology, has resulted in a surge of investigations evaluating the potential associations between symptoms and inflammation. Emerging data demonstrates clear relationships between individual MPN symptoms (fatigue, abdominal complaints, microvascular symptoms, and constitutional symptoms and cytokines, particularly IL-1, IL-6, IL-8, and TNF-α. Information is also compiling on the role symptoms paradoxically play in the development of cytokines, as in the case of fatigue-driven sedentary lifestyles. In this paper, we explore the symptoms inherent to the MPN disorders and the potential role inflammation plays in their development.

  8. Cytokine Regulation of Microenvironmental Cells in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Gregor Hoermann

    2015-01-01

    Full Text Available The term myeloproliferative neoplasms (MPN refers to a heterogeneous group of diseases including not only polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF, but also chronic myeloid leukemia (CML, and systemic mastocytosis (SM. Despite the clinical and biological differences between these diseases, common pathophysiological mechanisms have been identified in MPN. First, aberrant tyrosine kinase signaling due to somatic mutations in certain driver genes is common to these MPN. Second, alterations of the bone marrow microenvironment are found in all MPN types and have been implicated in the pathogenesis of the diseases. Finally, elevated levels of proinflammatory and microenvironment-regulating cytokines are commonly found in all MPN-variants. In this paper, we review the effects of MPN-related oncogenes on cytokine expression and release and describe common as well as distinct pathogenetic mechanisms underlying microenvironmental changes in various MPN. Furthermore, targeting of the microenvironment in MPN is discussed. Such novel therapies may enhance the efficacy and may overcome resistance to established tyrosine kinase inhibitor treatment in these patients. Nevertheless, additional basic studies on the complex interplay of neoplastic and stromal cells are required in order to optimize targeting strategies and to translate these concepts into clinical application.

  9. Myeloproliferative neoplasms: JAK2 signaling pathway as a central target for therapy.

    Science.gov (United States)

    Pasquier, Florence; Cabagnols, Xenia; Secardin, Lise; Plo, Isabelle; Vainchenker, William

    2014-09-01

    The discovery of the JAK2V617F mutation followed by the discovery of other genetic abnormalities allowed important progress in the understanding of the pathogenesis and management of myeloproliferative neoplasms (MPN)s. Classical Breakpoint cluster region-Abelson (BCR-ABL)-negative neoplasms include 3 main disorders: essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF). Genomic studies have shown that these disorders are more heterogeneous than previously thought with 3 main entities corresponding to different gene mutations: the JAK2 disorder, essentially due to JAK2V617F mutation, which includes nearly all PVs and a majority of ETs and PMFs with a continuum between these diseases and the myeloproliferative leukemia (MPL) and calreticulin (CALR) disorders, which include a fraction of ET and PMF. All of these mutations lead to a JAK2 constitutive activation. Murine models either with JAK2V617F or MPLW515L, but also with JAK2 or MPL germ line mutations found in hereditary thrombocytosis, have demonstrated that they are drivers of myeloproliferation. However, the myeloproliferative driver mutation is still unknown in approximately 15% of ET and PMF, but appears to also target the JAK/Signal Transducer and Activator of Transcription (STAT) pathway. However, other mutations in genes involved in epigenetics or splicing also can be present and can predate or follow mutations in signaling. They are involved either in clonal dominance or in phenotypic changes, more particularly in PMF. They can be associated with leukemic progression and might have an important prognostic value such as additional sex comb-like 1 mutations. Despite this heterogeneity, it is tempting to target JAK2 and its signaling for therapy. However in PMF, Adenosine Tri-Phosphate (ATP)-competitive JAK2 inhibitors have shown their interest, but also their important limitations. Thus, other approaches are required, which are discussed in this review. Copyright © 2014

  10. Philadelphia-negative classical myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Barbui, T.; Barosi, G.; Birgegard, G.

    2011-01-01

    the criterion of clinical relevance. Statements were produced using a Delphi process, and two consensus conferences involving a panel of 21 experts appointed by the European LeukemiaNet (ELN) were convened. Patients with polycythemia vera (PV) and essential thrombocythemia (ET) should be defined as high risk...

  11. The JAK2 GGCC (46/1 Haplotype in Myeloproliferative Neoplasms: Causal or Random?

    Directory of Open Access Journals (Sweden)

    Luisa Anelli

    2018-04-01

    Full Text Available The germline JAK2 haplotype known as “GGCC or 46/1 haplotype” (haplotypeGGCC_46/1 consists of a combination of single nucleotide polymorphisms (SNPs mapping in a region of about 250 kb, extending from the JAK2 intron 10 to the Insulin-like 4 (INLS4 gene. Four main SNPs (rs3780367, rs10974944, rs12343867, and rs1159782 generating a “GGCC” combination are more frequently indicated to represent the JAK2 haplotype. These SNPs are inherited together and are frequently associated with the onset of myeloproliferative neoplasms (MPN positive for both JAK2 V617 and exon 12 mutations. The association between the JAK2 haplotypeGGCC_46/1 and mutations in other genes, such as thrombopoietin receptor (MPL and calreticulin (CALR, or the association with triple negative MPN, is still controversial. This review provides an overview of the frequency and the role of the JAK2 haplotypeGGCC_46/1 in the pathogenesis of different myeloid neoplasms and describes the hypothetical mechanisms at the basis of the association with JAK2 gene mutations. Moreover, possible clinical implications are discussed, as different papers reported contrasting data about the correlation between the JAK2 haplotypeGGCC_46/1 and blood cell count, survival, or disease progression.

  12. Deep sequencing reveals double mutations in cis of MPL exon 10 in myeloproliferative neoplasms.

    Science.gov (United States)

    Pietra, Daniela; Brisci, Angela; Rumi, Elisa; Boggi, Sabrina; Elena, Chiara; Pietrelli, Alessandro; Bordoni, Roberta; Ferrari, Maurizio; Passamonti, Francesco; De Bellis, Gianluca; Cremonesi, Laura; Cazzola, Mario

    2011-04-01

    Somatic mutations of MPL exon 10, mainly involving a W515 substitution, have been described in JAK2 (V617F)-negative patients with essential thrombocythemia and primary myelofibrosis. We used direct sequencing and high-resolution melt analysis to identify mutations of MPL exon 10 in 570 patients with myeloproliferative neoplasms, and allele specific PCR and deep sequencing to further characterize a subset of mutated patients. Somatic mutations were detected in 33 of 221 patients (15%) with JAK2 (V617F)-negative essential thrombocythemia or primary myelofibrosis. Only one patient with essential thrombocythemia carried both JAK2 (V617F) and MPL (W515L). High-resolution melt analysis identified abnormal patterns in all the MPL mutated cases, while direct sequencing did not detect the mutant MPL in one fifth of them. In 3 cases carrying double MPL mutations, deep sequencing analysis showed identical load and location in cis of the paired lesions, indicating their simultaneous occurrence on the same chromosome.

  13. Association of TNF polymorphisms with JAK2 (V617F) myeloproliferative neoplasms in Brazilian patients.

    Science.gov (United States)

    Macedo, Luciana Conci; de Cesare Quintero, Fernanda; Pagliari-E-Silva, Sara; Pagnano, Katia Borgia Barbosa; Rodrigues, Camila; de Alencar, Josiane Bazzo; Sell, Ana Maria; Visentainer, Jeane Eliete Laguila

    2016-03-01

    The classical chromosome Philadelphia-negative myeloproliferative neoplasms (MPNs) are a group of disorders that share clinical, hematological, and histological features. Proinflammatory cytokines such as tumor necrosis factor-α (TNF-α) are elevated in patients with MPN. The aim of this study was to verify the association between the polymorphisms of TNF gene (-308G/A and -238 G/A) in BCR-ABL-negative MPN in our population. Blood samples obtained from MPN patients were genotyped for the JAK2V617F mutation and both TNF polymorphisms using PCR-RFLP. Thirty three (26.8%) patients with polycythemia vera (PV), 35 (28.7%) essential thrombocythemia (ET), 22 (17.7%) primary myelofibrosis (PMF), and 33 (26.8%) with unclassifiable MPN (MPNu) were included in the study. The JAK2 V617F mutation was detected in 94 (76.42%) patients. Were observed a significant increase on the frequency of the TNF-238 GA genotype in MPN patients compared to controls (OR=2.21, 95% CI=1.02-4.80, P<0.04). The distribution of the genotypes and allelic frequencies of TNF-308 was significantly different among the MPNs, JAK2V617F positive, PV and PMF, and controls. Our data has demonstrated that the polymorphisms on TNF-238 GA, TNF-308 GA were associated to MPN development in this population, triggered by JAK2 V617F mutation. Copyright © 2015. Published by Elsevier Inc.

  14. Proinflammatory Cytokine IL-6 and JAK-STAT Signaling Pathway in Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Vladan P. Čokić

    2015-01-01

    Full Text Available The recent JAK1/2 inhibitor trial in myeloproliferative neoplasms (MPNs showed that reducing inflammation can be more beneficial than targeting gene mutants. We evaluated the proinflammatory IL-6 cytokine and JAK-STAT signaling pathway related genes in circulating CD34+ cells of MPNs. Regarding laboratory data, leukocytosis has been observed in polycythemia vera (PV and JAK2V617F mutation positive versus negative primary myelofibrosis (PMF patients. Moreover, thrombocytosis was reduced by JAK2V617F allele burden in essential thrombocythemia (ET and PMF. 261 significantly changed genes have been detected in PV, 82 in ET, and 94 genes in PMF. The following JAK-STAT signaling pathway related genes had augmented expression in CD34+ cells of MPNs: CCND3 and IL23A regardless of JAK2V617F allele burden; CSF3R, IL6ST, and STAT1/2 in ET and PV with JAK2V617F mutation; and AKT2, IFNGR2, PIM1, PTPN11, and STAT3 only in PV. STAT5A gene expression was generally reduced in MPNs. IL-6 cytokine levels were increased in plasma, as well as IL-6 protein levels in bone marrow stroma of MPNs, dependent on JAK2V617F mutation presence in ET and PMF patients. Therefore, the JAK2V617F mutant allele burden participated in inflammation biomarkers induction and related signaling pathways activation in MPNs.

  15. Laboratory practice guidelines for detecting and reporting JAK2 and MPL mutations in myeloproliferative neoplasms: a report of the Association for Molecular Pathology.

    Science.gov (United States)

    Gong, Jerald Z; Cook, James R; Greiner, Timothy C; Hedvat, Cyrus; Hill, Charles E; Lim, Megan S; Longtine, Janina A; Sabath, Daniel; Wang, Y Lynn

    2013-11-01

    Recurrent mutations in JAK2 and MPL genes are genetic hallmarks of BCR-ABL1-negative myeloproliferative neoplasms. Detection of JAK2 and MPL mutations has been incorporated into routine diagnostic algorithms for these diseases. This Special Article summarizes results from a nationwide laboratory survey of JAK2 and MPL mutation analysis. Based on the current practice pattern and the literature, this Special Article provides recommendations and guidelines for laboratory practice for detection of mutations in the JAK2 and MPL genes, including clinical manifestations for prompting the mutation analysis, current and recommended methodologies for testing the mutations, and standardization for reporting the test results. This Special Article also points to future directions for genomic testing in BCR-ABL1-negative myeloproliferative neoplasms. Copyright © 2013 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  16. Myeloproliferative neoplasms and inflammation: whether to target the malignant clone or the inflammatory process or both.

    Science.gov (United States)

    Koschmieder, S; Mughal, T I; Hasselbalch, H C; Barosi, G; Valent, P; Kiladjian, J-J; Jeryczynski, G; Gisslinger, H; Jutzi, J S; Pahl, H L; Hehlmann, R; Maria Vannucchi, A; Cervantes, F; Silver, R T; Barbui, T

    2016-05-01

    The Philadelphia-negative myeloproliferative neoplasms (MPNs) are clonal disorders involving hematopoietic stem and progenitor cells and are associated with myeloproliferation, splenomegaly and constitutional symptoms. Similar signs and symptoms can also be found in patients with chronic inflammatory diseases, and inflammatory processes have been found to play an important role in the pathogenesis and progression of MPNs. Signal transduction pathways involving JAK1, JAK2, STAT3 and STAT5 are causally involved in driving both the malignant cells and the inflammatory process. Moreover, anti-inflammatory and immune-modulating drugs have been used successfully in the treatment of MPNs. However, to date, many unresoved issues remain. These include the role of somatic mutations that are present in addition to JAK2V617F, CALR and MPL W515 mutations, the interdependency of malignant and nonmalignant cells and the means to eradicate MPN-initiating and -maintaining cells. It is imperative for successful therapeutic approaches to define whether the malignant clone or the inflammatory cells or both should be targeted. The present review will cover three aspects of the role of inflammation in MPNs: inflammatory states as important differential diagnoses in cases of suspected MPN (that is, in the absence of a clonal marker), the role of inflammation in MPN pathogenesis and progression and the use of anti-inflammatory drugs for MPNs. The findings emphasize the need to separate the inflammatory processes from the malignancy in order to improve our understanding of the pathogenesis, diagnosis and treatment of patients with Philadelphia-negative MPNs.

  17. Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

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    Haixiu Guo

    Full Text Available Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs. In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL. CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET and 5.3% of cases with primary myelofibrosis (PMF. Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR. Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

  18. Non-invasive imaging of retinal blood flow in myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Willerslev, Anne; Hansen, Mathias M; Klefter, Oliver Niels

    2017-01-01

    PURPOSE: To study the circulation in the retinal vessels in patients with blood dyscrasia due to myeloproliferative neoplasms using non-invasive retinal imaging. METHODS: Prospective consecutive case series of seven treatment-naïve patients with chronic myeloid leukaemia (n = 2), polycythemia vera...... present at baseline in patients with chronic myeloid leukaemia and were replaced by normal patterns at follow-up. Retinopathy, in the form of cotton-wool spots and retinal haemorrhages, was found at presentation in the two patients with chronic myeloid leukaemia and in one patient with polycythemia vera...

  19. The 2016 WHO classification and diagnostic criteria for myeloproliferative neoplasms: document summary and in-depth discussion

    OpenAIRE

    Barbui, Tiziano; Thiele, Jürgen; Gisslinger, Heinz; Kvasnicka, Hans Michael; Vannucchi, Alessandro M.; Guglielmelli, Paola; Orazi, Attilio; Tefferi, Ayalew

    2018-01-01

    The new edition of the 2016 World Health Organization (WHO) classification system for tumors of the hematopoietic and lymphoid tissues was published in September 2017. Under the category of myeloproliferative neoplasms (MPNs), the revised document includes seven subcategories: chronic myeloid leukemia, chronic neutrophilic leukemia, polycythemia vera (PV), primary myelofibrosis (PMF), essential thrombocythemia (ET), chronic eosinophilic leukemia-not otherwise specified and MPN, unclassifiable...

  20. Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN: analysis from the German SAL-MPN-registry

    Directory of Open Access Journals (Sweden)

    A. Kaifie

    2016-03-01

    Full Text Available Abstract Background Patients with Ph-negative myeloproliferative neoplasms (MPN, such as polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF, are at increased risk for thrombosis/thromboembolism and major bleeding. Due to the morbidity and mortality of these events, antiplatelet and/or anticoagulant agents are commonly employed as primary and/or secondary prophylaxis. On the other hand, disease-related bleeding complications (i.e., from esophageal varices are common in patients with MPN. This analysis was performed to define the frequency of such events, identify risk factors, and assess antiplatelet/anticoagulant therapy in a cohort of patients with MPN. Methods The MPN registry of the Study Alliance Leukemia is a non-interventional prospective study including adult patients with an MPN according to WHO criteria (2008. For statistical analysis, descriptive methods and tests for significant differences as well as contingency tables were used to identify the odds of potential risk factors for vascular events. Results MPN subgroups significantly differed in sex distribution, age at diagnosis, blood counts, LDH levels, JAK2V617F positivity, and spleen size (length. While most thromboembolic events occurred around the time of MPN diagnosis, one third of these events occurred after that date. Splanchnic vein thrombosis was most frequent in post-PV-MF and MPN-U patients. The chance of developing a thromboembolic event was significantly elevated if patients suffered from post-PV-MF (OR 3.43; 95 % CI = 1.39–8.48 and splenomegaly (OR 1.76; 95 % CI = 1.15–2.71. Significant odds for major bleeding were previous thromboembolic events (OR = 2.71; 95 % CI = 1.36–5.40, splenomegaly (OR = 2.22; 95 % CI 1.01–4.89, and the administration of heparin (OR = 5.64; 95 % CI = 1.84–17.34. Major bleeding episodes were significantly less frequent in ET patients compared to other MPN subgroups

  1. JAK2 mutation in a patient with CLL with coexistent myeloproliferative neoplasm (MPN).

    Science.gov (United States)

    Kodali, Srinivas; Chen, Chi; Rathnasabapathy, Chenthilmurugan; Wang, Jen Chin

    2009-12-01

    JAK2 mutation has not been described in patients with chronic lymphocytic leukemia (CLL). We found JAK2 mutation in a patient with CLL and coexisting myeloproliferative neoplasm (MPN). In this patient, we demonstrated the presence of the JAK2 mutation in CD34(+) progenitor cells, myeloid lineage cells, megakaryocytes, B lymphocytes but not in T lymphocytes. This case represents the first case report of JAK2 mutation in CLL and may also suggest that, JAK2 mutation most likely represents a secondary event from primary gene mutations involving the primitive stem cells which give rise to MPN and CLL. Furthermore, in this case, we believe that we are the first to demonstrate that JAK2 mutation in myeloid and B lymphoid cells but not T lymphocytes in a case of coexisting CLL and MPN.

  2. Transformation of an Unclassified Myeloproliferative Neoplasm with a Rare BCR-JAK2 Fusion Transcript Resulting from the Translocation (9;22)(p24;q11)

    OpenAIRE

    A. N. Chamseddine; P. Etancelin; D. Penther; F. Parmentier; C. Kuadjovi; V. Camus; N. Contentin; P. Lenain; C. Bastard; H. Tilly; F. Jardin

    2015-01-01

    BCR-ABL1 negative myeloproliferative neoplasms (MPNs) are known to contain alterations of the tyrosine kinase JAK2 (located on 9p24) that result in constitutive activation of the encoded protein. JAK2 fusions are reported in acute and chronic leukemias of myeloid and lymphoid phenotypes. Here, we report an unclassified case of MPN (MPN-U) showing a t(9;22)(p24;q11), which generates a BCR-JAK2 fusion gene by fusing the BCR at intron 13 to JAK2 at intron 17 on the derivative chromosome 22. Most...

  3. Jak2 46/1 Haplotype Is Associated With Jak2 V617f--positive Myeloproliferative Neoplasms In Brazilian Patients.

    OpenAIRE

    Macedo, L C; Santos, B C; Pagliarini-e-Silva, S; Pagnano, K B B; Rodrigues, C; Quintero, F C; Ferreira, M E; Baraldi, E C; Ambrosio-Albuquerque, E P; Sell, A M; Visentainer, J E L

    2016-01-01

    This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially t...

  4. Associations between gender, disease features and symptom burden in patients with myeloproliferative neoplasms: an analysis by the MPN QOL International Working Group.

    Science.gov (United States)

    Geyer, Holly L; Kosiorek, Heidi; Dueck, Amylou C; Scherber, Robyn; Slot, Stefanie; Zweegman, Sonja; Te Boekhorst, Peter Aw; Senyak, Zhenya; Schouten, Harry C; Sackmann, Federico; Fuentes, Ana Kerguelen; Hernández-Maraver, Dolores; Pahl, Heike L; Griesshammer, Martin; Stegelmann, Frank; Döhner, Konstanze; Lehmann, Thomas; Bonatz, Karin; Reiter, Andreas; Boyer, Francoise; Etienne, Gabriel; Ianotto, Jean-Christophe; Ranta, Dana; Roy, Lydia; Cahn, Jean-Yves; Harrison, Claire N; Radia, Deepti; Muxi, Pablo; Maldonado, Norman; Besses, Carlos; Cervantes, Francisco; Johansson, Peter L; Barbui, Tiziano; Barosi, Giovanni; Vannucchi, Alessandro M; Paoli, Chiara; Passamonti, Francesco; Andreasson, Bjorn; Ferrari, Maria L; Rambaldi, Alessandro; Samuelsson, Jan; Cannon, Keith; Birgegard, Gunnar; Xiao, Zhijian; Xu, Zefeng; Zhang, Yue; Sun, Xiujuan; Xu, Junqing; Kiladjian, Jean-Jacques; Zhang, Peihong; Gale, Robert Peter; Mesa, Ruben A

    2017-01-01

    The myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia and myelofibrosis, are distinguished by their debilitating symptom profiles, life-threatening complications and profound impact on quality of life. The role gender plays in the symptomatology of myeloproliferative neoplasms remains under-investigated. In this study we evaluated how gender relates to patients' characteristics, disease complications and overall symptom expression. A total of 2,006 patients (polycythemia vera=711, essential thrombocythemia=830, myelofibrosis=460, unknown=5) were prospectively evaluated, with patients completing the Myeloproliferative Neoplasm-Symptom Assessment Form and Brief Fatigue Inventory Patient Reported Outcome tools. Information on the individual patients' characteristics, disease complications and laboratory data was collected. Consistent with known literature, most female patients were more likely to have essential thrombocythemia (48.6% versus 33.0%; Pgender contributes to the heterogeneity of myeloproliferative neoplasms by influencing phenotypic profiles and symptom expression. Copyright© Ferrata Storti Foundation.

  5. [Hungarian Philadelphia negative chronic myeloproliferative neoplasia registry. Evaluation of the Polycythemia vera patients].

    Science.gov (United States)

    Dombi, Péter; Illés, Árpád; Demeter, Judit; Homor, Lajos; Simon, Zsófia; Kellner, Ádám; Karádi, Éva; Valasinyószki, Erika; Udvardy, Miklós; Egyed, Miklós

    2017-06-01

    Intruduction and aim: The Hungarian National Registry for Philadelphia chromosome negative myeloproliferative neoplasms has been developed. The aim of the recent study is to assess the clinical characteristics of Hungarian patients with polycythemia vera. Data of 351 JAK2 V617F and exon 12 mutation positive polycythemia vera patients were collected online from 15 haematology centres reporting epidemiologic, clinical characteristics, diagnostic tools, therapeutic interventions, thromboembolic complications, disease transformations. Vascular events prior to and after diagnosis were evaluated upon the Landolfi risk assessment scale. 116 thromboembolic events were reported in 106 PV patients prior to diagnosis and 152 occasions in 102 patients during follow-up. The frequency of major arterial events were significantly reduced (ppolycythemia vera. The Landolfi risk stratification was proven to be useful. Based on evaluated data, accuracy of diagnostic criteria and compliance to risk-adapted therapeutic guidelines are needed. Orv Hetil. 2017; 158(23): 901-909.

  6. An international consortium proposal of uniform response criteria for myelodysplastic/myeloproliferative neoplasms (MDS/MPN) in adults.

    Science.gov (United States)

    Savona, Michael R; Malcovati, Luca; Komrokji, Rami; Tiu, Ramon V; Mughal, Tariq I; Orazi, Attilio; Kiladjian, Jean-Jacques; Padron, Eric; Solary, Eric; Tibes, Raoul; Itzykson, Raphael; Cazzola, Mario; Mesa, Ruben; Maciejewski, Jaroslaw; Fenaux, Pierre; Garcia-Manero, Guillermo; Gerds, Aaron; Sanz, Guillermo; Niemeyer, Charlotte M; Cervantes, Francisco; Germing, Ulrich; Cross, Nicholas C P; List, Alan F

    2015-03-19

    Myelodysplastic syndromes (MDS) and myeloproliferative neoplasms (MPN) are hematologically diverse stem cell malignancies sharing phenotypic features of both myelodysplastic syndromes and myeloproliferative neoplasms. There are currently no standard treatment recommendations for most adult patients with MDS/MPN. To optimize efforts to improve the management and disease outcomes, it is essential to identify meaningful clinical and biologic end points and standardized response criteria for clinical trials. The dual dysplastic and proliferative features in these stem cell malignancies define their uniqueness and challenges. We propose response assessment guidelines to harmonize future clinical trials with the principal objective of establishing suitable treatment algorithms. An international panel comprising laboratory and clinical experts in MDS/MPN was established involving 3 independent academic MDS/MPN workshops (March 2013, December 2013, and June 2014). These recommendations are the result of this collaborative project sponsored by the MDS Foundation. © 2015 by The American Society of Hematology.

  7. Critical appraisal of the role of ruxolitinib in myeloproliferative neoplasm-associated myelofibrosis

    Directory of Open Access Journals (Sweden)

    Barosi G

    2015-05-01

    Full Text Available Giovanni Barosi,1 Vittorio Rosti,1 Robert Peter Gale2 1Center for the Study of Myelofibrosis, IRCCS Policlinico S Matteo Foundation, Pavia, Italy; 2Haematology Research Centre, Division of Experimental Medicine, Department of Medicine, Imperial College London, London, UK Abstract: The recent approval of molecular-targeted therapies for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF has dramatically changed its therapeutic landscape. Ruxolitinib, a JAK1/JAK2 tyrosine kinase inhibitor, is now widely used for first- and second-line therapy in persons with MPN-MF, especially those with disease-related splenomegaly, intermediate- or high-risk disease, and constitutional symptoms. The goal of this work is to critically analyze data supporting use of ruxolitinib in the clinical settings approved by the US Food and Drug Administration (FDA and European Medicines Agency (EMA. We systematically reviewed the literature and analyzed the risk of biases in the two randomized studies (COMFORT I and COMFORT II on which FDA and EMA approval was based. Our strategy was to apply the Grading of Recommendation, Assessment, Development and Evaluation (GRADE approach by evaluating five dimensions of evidence: (1 overall risk of bias, (2 imprecision, (3 inconsistency, (4 indirectness, and (5 publication bias. Based on these criteria, we downgraded the evidence from the COMFORT I and COMFORT II trials for performance, attrition, and publication bias. In the disease-associated splenomegaly sphere, we upgraded the quality of evidence because of large effect size but downgraded it because of comparator choice and outcome indirectness (quality of evidence, low. In the sphere of treating persons with intermediate- or high-risk disease, we downgraded the evidence because of imprecision in effect size measurement and population indirectness. In the sphere of disease-associated symptoms, we upgraded the evidence because of the large effect size, but downgraded it

  8. Vascular events in Korean patients with myeloproliferative neoplasms and their relationship to JAK2 mutation.

    Science.gov (United States)

    Bang, Soo-Mee; Lee, Jong-Seok; Ahn, Jeong Yeal; Lee, Jae Hoon; Hyun, Myung Soo; Kim, Bong Seog; Park, Moo Rim; Chi, Hyun-Sook; Kim, Ho Young; Kim, Hyo Jung; Lee, Moon Hee; Kim, Hwak; Won, Jong Ho; Yoon, Hwi Joong; Oh, Do-Yeun; Nam, Eun-Mi; Bae, Sung Hwa; Kim, Byoung-Kook

    2009-03-01

    Evaluation of the Janus kinase 2 (JAK2) V617F mutation has been widely used for the diagnosis of myeloproliferative neoplasms (MPN). However, its prognostic relevance to clinical outcome is not completely understood. We investigated the association of JAK2 V617F with vascular events in Korean patients with myeloproliferative neoplasms (MPN). We studied 283 patients from 15 centers, who were diagnosed with MPN. The JAK2 V617F status was evaluated by allele-specific polymerase chain reaction (PCR) and sequencing. The patients' diagnoses were essential thrombocythemia (ET n = 146), polycythemia vera (PV n = 120), primary myelofibrosis (n = 12), and unclassifiable MPN (MPNu n = 5). JAK2 V617F was detected in 89 (61%) patients with ET, 103 (86%) with PV, four (33%) with myelofibrosis, and four (80%) with MPNu. A higher number of leukocytes, haemoglobin levels and BM cellularity as well as an older age, lower platelet counts, and diagnosis of PV were significantly correlated with JAK2 V617F. Eighty-three and 43 episodes of thrombosis and bleeding occurred in 100 patients each before and after the diagnosis. Vascular events more frequently occurred in 37% of patients with JAK2 V617F than in 29% of those without the mutation (p = 0.045). Among 175 patients whose samples were available for sequencing, 28 patients with homozygous JAK2 V617F had vascular events more frequently (57%) than those who were heterozygotes (39%) or had the wild type (27%) (p = 0.03). The multivariate analysis showed that a JAK2 homozygous mutation, hypercholesterolemia and older age were independent risk factors for a vascular event. The results of this study showed that Korean patients with MPN had a similar JAK2 mutation rate and frequency of vascular events when compared to Western patients. The presence of V617F was significantly related to vascular events. Therefore, initial evaluation for the JAK2 mutation and careful monitoring for vascular events should be performed in MPN patients.

  9. The thrombopoietin receptor, MPL, is critical for development of a JAK2V617F-induced myeloproliferative neoplasm.

    Science.gov (United States)

    Sangkhae, Veena; Etheridge, S Leah; Kaushansky, Kenneth; Hitchcock, Ian S

    2014-12-18

    The most frequent contributing factor in Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is the acquisition of a V617F mutation in Janus kinase 2 (JAK2) in hematopoietic stem cells (HSCs). Recent evidence has demonstrated that to drive MPN transformation, JAK2V617F needs to directly associate with a functional homodimeric type I cytokine receptor, suggesting that, although acquiring JAK2V617F may promote disease, there are additional cellular components necessary for MPN development. Here we show that loss of the thrombopoietin (TPO) receptor (MPL) significantly ameliorates MPN development in JAK2V617F(+) transgenic mice, whereas loss of TPO only mildly affects the disease phenotype. Specifically, compared with JAK2V617F(+) mice, JAK2V617F(+)Mpl(-/-) mice exhibited reduced thrombocythemia, neutrophilia, splenomegaly, and neoplastic stem cell pool. The importance of MPL is highlighted as JAK2V617FMpl(+/-) mice displayed a significantly reduced MPN phenotype, indicating that Mpl level may have a substantial effect on MPN development and severity. Splenomegaly and the increased neoplastic stem cell pool were retained in JAK2V617F(+)Tpo(-/-) mice, although thrombocytosis was reduced compared with JAK2V617F(+) mice. These results demonstrate that Mpl expression, but not Tpo, is fundamental in the development of JAK2V617F(+) MPNs, highlighting an entirely novel target for therapeutic intervention. © 2014 by The American Society of Hematology.

  10. The role of JAK1/2 inhibitors in the treatment of chronic myeloproliferative neoplasms.

    Science.gov (United States)

    Keohane, Clodagh; Mesa, Ruben; Harrison, Claire

    2013-01-01

    In 2005, the description of the JAK2V617F mutation for the first time provided a molecular key to enable more rapid diagnosis and target for novel therapeutics in the myeloproliferative neoplasms. In 2007, the first-in-class agent INC18424, ruxolitinib, JAKafi, or JAKAVI was first tested in patients with intermediate-risk 2 or high-risk myelofibrosis regardless of whether they possessed the JAK2V617F mutation. Patients treated with this agent had major reduction in splenomegaly as well as impressive reduction, and in some cases resolution, of symptoms. This study was followed by the two Controlled Myelofibrosis Study with Oral JAK Inhibitor Therapy (COMFORT) trials (the first-ever phase III trials in myelofibrosis), which confirmed results in these aspects were superior to either placebo or standard care, and updated results show a survival advantage with this therapy. This paper discusses these results and data from other JAK inhibitors while speculating on the future of these therapies. It also reflects on the fact that the true targets and agents' mode of action are uncertain. Unlike targeted therapy for chronic myeloid leukemia (CML), these agents do not deliver molecular remission, and it is not clear whether their predominant benefit is mediated via JAK2, JAK1, or both. Nonetheless, the advent of the JAK inhibitor is a welcome advance and has made a dramatic improvement to the therapeutic landscape of these conditions.

  11. Multiparameter flow cytometry reveals myelodysplasia-related aberrant antigen expression in myelodysplastic/myeloproliferative neoplasms.

    Science.gov (United States)

    Kern, Wolfgang; Bacher, Ulrike; Schnittger, Susanne; Alpermann, Tamara; Haferlach, Claudia; Haferlach, Torsten

    2013-05-01

    Within the myelodysplastic/myeloproliferative neoplasm (MDS/MPN) category of the WHO (2008), only chronic myelomonocytic leukemia was so far evaluated by multiparameter flow cytometry (MFC). To investigate the potential of MFC for MDS/MPNs, unclassifiable (MDS/MPNu), and refractory anemia associated with ring sideroblasts and marked thrombocytosis (RARS-T), we studied 91 patients with these entities (60 males/31 females; 35.3-87.4 years) for MDS-related aberrant immunophenotypes (≥ 2 different cell lineages with ≥ 3 aberrantly expressed antigens). Data were correlated with cytomorphology and cytogenetics. MFC identified MDS-related immunophenotypes in 54/91 (59.3%) of patients. Patients with or without MDS-related immunophenotype did not differ significantly by demographic characteristics, blood values, or median overall survival. MDS-related immunophenotype cases showed a higher number of aberrantly expressed antigens (mean ± SD, 4.9 ± 2.4 vs. 2.0 ± 1.4; P MPNu and RARS-T. MFC therefore may be helpful to separate cases into more "MDS-like" or "MPN-like" subgroups. Copyright © 2012 International Clinical Cytometry Society.

  12. Splenectomy in patients with Myeloproliferative Neoplasms: efficacy, complications and impact on survival and transformation

    Science.gov (United States)

    Santos, Fabio P S; Tam, Constantine S; Kantarjian, Hagop; Cortes, Jorge; Thomas, Deborah; Pollock, Raphael; Verstovsek, Srdan

    2013-01-01

    Background Splenectomy may be an effective therapeutic option for treating massive splenomegaly in patients with myeloproliferative neoplasms (MPNs). There is still limited data on its short- and long-term benefits and risks. Methods Efficacy and short-term complications were analyzed in 94 patients with different MPNs who underwent splenectomy at MD Anderson. The long-term impact of splenectomy on overall survival (OS) and transformation free survival (TFS) was evaluated in 461 patients with myelofibrosis (MF) seen at MD Anderson including 50 who underwent splenectomy during disease evolution. Results Splenectomy improved anemia and thrombocytopenia in 47% and 66% of patients, respectively. Most common complications were leukocytosis (76%), thrombocytosis (43%), and venous thromboembolism (16%). Post-operative mortality was 5%. Among patients with MF, splenectomy during disease evolution was associated with decreased OS (Hazard Ratio [HR] =2.17, pSplenectomy is a possible therapeutic option for patients with MF and other MPNs, and its greatest benefits are related to improvement in spleen pain and discomfort, anemia and thrombocytopenia. However, in patients with MF it appears to be associated with increased mortality. PMID:23573823

  13. Philadelphia chromosome-negative myeloproliferative disorders: biology and treatment.

    Science.gov (United States)

    Hoffman, Ronald; Prchal, Josef T; Samuelson, Scott; Ciurea, Stefan O; Rondelli, Damiano

    2007-01-01

    The Philadelphia chromosome (Ph)-negative myeloproliferative disorders (MPDs) include essential thrombocythemia (ET), idiopathic myelofibrosis (IMF), and polycythemia vera (PV). All of these disorders are clonal hematologic malignancies originating at the level of the pluripotent hematopoietic stem cell. Recently, activating mutations of the intracellular cytokine-signaling molecule JAK2 have been identified in > 90% of patients with PV and in 50% of those with IMF and ET. In addition, a mutation of the thrombopoietin receptor, MPLW515L, has been documented in some patients with IMF. Both mutations activate JAK-STAT signaling pathways and likely play a role in disease progression. Both ET and PV are associated with prolonged clinical courses associated with frequent thrombotic and hemorrhagic events, and progression to myelofibrosis and acute leukemia. IMF has a much poorer prognosis and is associated with cytopenias, splenomegaly, extramedullary hematopoiesis, and bone marrow fibrosis. Stratification of risk for the development of complications from Ph-negative MPDs has guided the identification of appropriate therapies for this population. Intermediate/high-risk IMF or myelofibrosis after ET or PV is associated with a sufficiently poor prognosis to justify the use of allogeneic stem cell transplantation, which is capable of curing such patients. Reduced-intensity conditioning in preparation for allogeneic stem cell transplantation has permitted older patients with IMF to undergo transplantation with increasing success.

  14. Circulating endothelial cells in patients with venous thromboembolism and myeloproliferative neoplasms.

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    Cláudia Torres

    Full Text Available BACKGROUND: Circulating endothelial cells (CEC may be a biomarker of vascular injury and pro-thrombotic tendency, while circulating endothelial progenitor cells (CEP may be an indicator for angiogenesis and vascular remodelling. However, there is not a universally accepted standardized protocol to identify and quantify these cells and its clinical relevancy remains to be established. OBJECTIVES: To quantify CEC and CEP in patients with venous thromboembolism (VTE and with myeloproliferative neoplasms (MPN, to characterize the CEC for the expression of activation (CD54, CD62E and procoagulant (CD142 markers and to investigate whether they correlate with other clinical and laboratory data. PATIENTS AND METHODS: Sixteen patients with VTE, 17 patients with MPN and 20 healthy individuals were studied. The CEC and CEP were quantified and characterized in the blood using flow cytometry, and the demographic, clinical and laboratory data were obtained from hospital records. RESULTS: We found the CEC counts were higher in both patient groups as compared to controls, whereas increased numbers of CEP were found only in patients with MPN. In addition, all disease groups had higher numbers of CD62E+ CEC as compared to controls, whereas only patients with VTE had increased numbers of CD142+ and CD54+ CEC. Moreover, the numbers of total and CD62+ CEC correlated positively with the white blood cells (WBC counts in both groups of patients, while the numbers of CEP correlated positively with the WBC counts only in patients with MPN. In addition, in patients with VTE a positive correlation was found between the numbers of CD54+ CEC and the antithrombin levels, as well as between the CD142+ CEC counts and the number of thrombotic events. CONCLUSIONS: Our study suggests that CEC counts may reveal endothelial injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes depending on the disease status.

  15. Safety and efficacy of ruxolitinib in splanchnic vein thrombosis associated with myeloproliferative neoplasms.

    Science.gov (United States)

    Pieri, Lisa; Paoli, Chiara; Arena, Umberto; Marra, Fabio; Mori, Fabio; Zucchini, Mery; Colagrande, Stefano; Castellani, Alessandro; Masciulli, Arianna; Rosti, Vittorio; De Stefano, Valerio; Betti, Silvia; Finazzi, Guido; Ferrari, Maria Luisa; Rumi, Elisa; Ruggeri, Marco; Nichele, Ilaria; Guglielmelli, Paola; Fjerza, Rajmonda; Mannarelli, Carmela; Fanelli, Tiziana; Merli, Lucia; Corbizi Fattori, Giuditta; Massa, Margherita; Cimino, Giuseppe; Rambaldi, Alessandro; Barosi, Giovanni; Cazzola, Mario; Barbui, Tiziano; Vannucchi, Alessandro M

    2017-02-01

    Splanchnic vein thrombosis (SVT) is one of the vascular complications of myeloproliferative neoplasms (MPN). We designed a phase 2 clinical trial to evaluate safety and efficacy of ruxolitinib in reducing splenomegaly and improving disease-related symptoms in patients with MPN-associated SVT. Patients diagnosed with myelofibrosis (12 cases), polycythemia vera (5 cases) and essential thrombocythemia (4 cases) received ruxolitinib for 24 weeks in the core study period. Spleen volume was assessed by magnetic resonance imaging (MRI) and splanchnic vein circulation by echo-Doppler analysis. Nineteen patients carried JAK2V617F, one had MPLW515L, and one CALRL367fs*46 mutation. Eighteen patients had spleno-portal-mesenteric thrombosis, two had Budd-Chiari syndrome, and one had both sites involved; 16 patients had esophageal varices. Ruxolitinib was well tolerated with hematological toxicities consistent with those of patients without SVT and no hemorrhagic adverse events were recorded. After 24 weeks of treatment, spleen volume reduction ≥35% by MRI was achieved by 6/21 (29%) patients, and a ≥50% spleen length reduction by palpation at any time up to week 24 was obtained by 13/21 (62%) patients. At week 72, 8 of the 13 (62%) patients maintained the spleen response by palpation. No significant effect of treatment on esophageal varices or in splanchnic circulation was observed. MPN-related symptoms, evaluated by MPN-symptom assessment form (SAF) TSS questionnaire, improved significantly during the first 4 weeks and remained stable up to week 24. In conclusion, this trial shows that ruxolitinib is safe in patients with MPN-associated SVT, and effective in reducing spleen size and disease-related symptoms. © 2016 Wiley Periodicals, Inc.

  16. Analysis of genomic aberrations and gene expression profiling identifies novel lesions and pathways in myeloproliferative neoplasms

    International Nuclear Information System (INIS)

    Rice, K L; Lin, X; Wolniak, K; Ebert, B L; Berkofsky-Fessler, W; Buzzai, M; Sun, Y; Xi, C; Elkin, P; Levine, R; Golub, T; Gilliland, D G; Crispino, J D; Licht, J D; Zhang, W

    2011-01-01

    Polycythemia vera (PV), essential thrombocythemia and primary myelofibrosis, are myeloproliferative neoplasms (MPNs) with distinct clinical features and are associated with the JAK2V617F mutation. To identify genomic anomalies involved in the pathogenesis of these disorders, we profiled 87 MPN patients using Affymetrix 250K single-nucleotide polymorphism (SNP) arrays. Aberrations affecting chr9 were the most frequently observed and included 9pLOH (n=16), trisomy 9 (n=6) and amplifications of 9p13.3–23.3 (n=1), 9q33.1–34.13 (n=1) and 9q34.13 (n=6). Patients with trisomy 9 were associated with elevated JAK2V617F mutant allele burden, suggesting that gain of chr9 represents an alternative mechanism for increasing JAK2V617F dosage. Gene expression profiling of patients with and without chr9 abnormalities (+9, 9pLOH), identified genes potentially involved in disease pathogenesis including JAK2, STAT5B and MAPK14. We also observed recurrent gains of 1p36.31–36.33 (n=6), 17q21.2–q21.31 (n=5) and 17q25.1–25.3 (n=5) and deletions affecting 18p11.31–11.32 (n=8). Combined SNP and gene expression analysis identified aberrations affecting components of a non-canonical PRC2 complex (EZH1, SUZ12 and JARID2) and genes comprising a ‘HSC signature' (MLLT3, SMARCA2 and PBX1). We show that NFIB, which is amplified in 7/87 MPN patients and upregulated in PV CD34+ cells, protects cells from apoptosis induced by cytokine withdrawal

  17. Myeloproliferative neoplasms (MPNs) have a significant impact on patients’ overall health and productivity: the MPN Landmark survey

    International Nuclear Information System (INIS)

    Mesa, Ruben; Miller, Carole B.; Thyne, Maureen; Mangan, James; Goldberger, Sara; Fazal, Salman; Ma, Xiaomei; Wilson, Wendy; Paranagama, Dilan C.; Dubinski, David G.; Boyle, John; Mascarenhas, John O.

    2016-01-01

    The Philadelphia chromosome−negative myeloproliferative neoplasms (MPN) myelofibrosis (MF), polycythemia vera (PV), and essential thrombocythemia (ET) negatively affect patient quality of life (QoL) and are associated with increased risk of mortality. The MPN Landmark survey was conducted from May to July 2014 in patients with MF, PV, or ET under active management in the United States. The survey assessed respondent perceptions of disease burden and treatment management and included questions on overall disease burden, QoL, activities of daily living, and work productivity. Outcomes were further analyzed by calculated (ie, not respondent-reported) prognostic risk score and symptom severity quartile. The survey was completed by 813 respondents (MF, n = 207; PV, n = 380; ET, n = 226). The median respondent age in each of the 3 MPN subtypes ranged from 62 to 66 years; median disease duration was 4 to 7 years. Many respondents reported that they had experienced MPN-related symptoms ≥1 year before diagnosis (MF, 49 %; PV, 61 %; ET, 58 %). Respondents also reported that MPN-related symptoms reduced their QoL, including respondents with low prognostic risk scores (MF, 67 %; PV, 62 %; ET, 57 %) and low symptom severity (MF, 51 %; PV, 33 %; ET, 15 %). Many respondents, including those with a low prognostic risk score, reported that their MPN had caused them to cancel planned activities or call in sick to work at least once in the preceding 30 days (cancel planned activities: MF, 56 %; PV, 35 %; ET, 35 %; call in sick: MF, 40 %; PV, 21 %; ET, 23 %). These findings of the MPN Landmark survey support previous research about the symptom burden experienced by patients with MPNs and are the first to detail the challenges that patients with MPNs experience related to reductions in activities of daily living and work productivity. The online version of this article (doi:10.1186/s12885-016-2208-2) contains supplementary material, which is available to authorized users

  18. Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms

    OpenAIRE

    Yu, Chunjie; Yang, Qiong; Chen, Yuhong; Wang, Demin; Levine, Ross; Crispino, John; Wen, Qiang; Huang, Zan

    2016-01-01

    Background Myeloproliferative neoplasms (MPN) are a group of blood cancers that boost normal blood cell production in the bone marrow. Abnormal mutations in stem cells were found accompanying with the occurrence of MPN. It has been shown that MPL mutations (MPL W515L or MPL W515K) were involved in patients with MPN. Since tyrosine residues 625 and 630 mediate normal MPL signaling, whether them affect MPL W515L-induced myeloproliferative neoplasms (MPNs) is unknown. Results In this study, we f...

  19. JAK inhibitors for the treatment of myeloproliferative neoplasms and other disorders [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    William Vainchenker

    2018-01-01

    Full Text Available JAK inhibitors have been developed following the discovery of the JAK2V617F in 2005 as the driver mutation of the majority of non-BCR-ABL1 myeloproliferative neoplasms (MPNs. Subsequently, the search for JAK2 inhibitors continued with the discovery that the other driver mutations (CALR and MPL also exhibited persistent JAK2 activation. Several type I ATP-competitive JAK inhibitors with different specificities were assessed in clinical trials and exhibited minimal hematologic toxicity. Interestingly, these JAK inhibitors display potent anti-inflammatory activity. Thus, JAK inhibitors targeting preferentially JAK1 and JAK3 have been developed to treat inflammation, autoimmune diseases, and graft-versus-host disease. Ten years after the beginning of clinical trials, only two drugs have been approved by the US Food and Drug Administration: one JAK2/JAK1 inhibitor (ruxolitinib in intermediate-2 and high-risk myelofibrosis and hydroxyurea-resistant or -intolerant polycythemia vera and one JAK1/JAK3 inhibitor (tofacitinib in methotrexate-resistant rheumatoid arthritis. The non-approved compounds exhibited many off-target effects leading to neurological and gastrointestinal toxicities, as seen in clinical trials for MPNs. Ruxolitinib is a well-tolerated drug with mostly anti-inflammatory properties. Despite a weak effect on the cause of the disease itself in MPNs, it improves the clinical state of patients and increases survival in myelofibrosis. This limited effect is related to the fact that ruxolitinib, like the other type I JAK2 inhibitors, inhibits equally mutated and wild-type JAK2 (JAK2WT and also the JAK2 oncogenic activation. Thus, other approaches need to be developed and could be based on either (1 the development of new inhibitors specifically targeting JAK2V617F or (2 the combination of the actual JAK2 inhibitors with other therapies, in particular with molecules targeting pathways downstream of JAK2 activation or the stability of JAK2

  20. Determining the role of inflammation in the selection of JAK2 mutant cells in myeloproliferative neoplasms.

    Science.gov (United States)

    Zhang, Jie; Fleischman, Angela G; Wodarz, Dominik; Komarova, Natalia L

    2017-07-21

    Myeloproliferative neoplasm (MPN) is a hematologic malignancy characterized by the clonal outgrowth of hematopoietic cells with a somatically acquired mutation most commonly in JAK2 (JAK2 V617F ). This mutation endows upon myeloid progenitors cytokine independent growth and consequently leads to excessive production of myeloid lineage cells. It has been previously suggested that inflammation may play a role in the clonal evolution of JAK2 V617F mutants. In particular, it is possible that one or more cellular kinetic parameters of hematopoietic stem cells (HSCs) are affected by inflammation, such as division or death rates of cells, and the probability of HSC differentiation. This suggests a mechanism that can steer the outcome of the cellular competition in favor of the mutants, initiating the disease. In this paper we create a number of mathematical evolutionary models, from very abstract to more concrete, that describe cellular competition in the context of inflammation. It is possible to build a model axiomatically, where only very general assumptions are imposed on the modeling components and no arbitrary (and generally unknown) functional forms are used, and still generate a set of testable predictions. In particular, we show that, if HSC death is negligible, the evolutionary advantage of mutant cells can only be conferred by an increase in differentiation probability of HSCs in the presence of inflammation, and if death plays a significant role in the dynamics, an additional mechanism may be an increase of HSC's division-to-death ratio in the presence of inflammation. Further, we show that in the presence of inflammation, the wild type cell population is predicted to shrink under inflammation (even in the absence of mutants). Finally, it turns out that if only the differentiation probability is affected by the inflammation, then the resulting steady state population of wild type cells will contain a relatively smaller percentage of HSCs under inflammation. If

  1. Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders

    OpenAIRE

    Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H. Phillip

    2007-01-01

    Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk i...

  2. Social Media and Myeloproliferative Neoplasms (MPN): Analysis of Advanced Metrics From the First Year of a New Twitter Community: #MPNSM.

    Science.gov (United States)

    Pemmaraju, Naveen; Utengen, Audun; Gupta, Vikas; Kiladjian, Jean-Jacques; Mesa, Ruben; Thompson, Michael A

    2016-12-01

    The social media platform Twitter has provided the hematology/oncology community with unprecedented, novel methods of interpersonal communication and increased ability for the dissemination of important updates in a rapidly moving field. The advent, and subsequent success, of disease-specific Twitter communities have further enabled interested healthcare stakeholders to become quickly organized around a unique set of rare medical conditions, such as hematologic malignancies, that, historically, generally lack large amounts of reliable online information. One example is the Twitter community #MPNSM (myeloproliferative neoplasms on social media), which was started approximately one and half years ago and has served as a recognized venue for discussion among many members of the MPN community, including patients, researchers, providers, and advocacy organizations. This article will focus on understanding the impact of the founding of this community via the analysis of advanced Twitter metrics of user experience, from the first year of use for this novel healthcare hashtag.

  3. Mutation Analysis of JAK2V617F, FLT3-ITD, NPM1, and DNMT3A in Chinese Patients with Myeloproliferative Neoplasms

    Directory of Open Access Journals (Sweden)

    Min Wang

    2014-01-01

    Full Text Available Since the discovery of JAK2V617F tyrosine kinase-activating mutation, several genes have been found mutated in myeloproliferative neoplasms (MPNs. FLT3-ITD, NPM1, and DNMT3A mutations frequently occurred in AML patients and have been found conferred with myeloproliferative neoplasms in mouse model. Therefore, we sought to search for mutations in JAK2V617F, FLT3-ITD, NPM1, and DNMT3A in 129 cases including 120 classic MPN cases and 9 MDS/MPN cases. JAK2V617F mutation was found in 60% of the 120 classic MPNs. However, none of the patients displayed FLT3-ITD and NPM1 mutations; only 2 patients harbored DNMT3A R882 mutation. Further studies including whole-genome sequence will be conducted to investigate the possible involvement of these genes in MPN.

  4. Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium

    International Nuclear Information System (INIS)

    Tefferi, A; Abdel-Wahab, O; Cervantes, F; Crispino, J D; Finazzi, G; Girodon, F; Gisslinger, H; Gotlib, J; Kiladjian, J-J; Levine, R L; Licht, J D; Mullally, A; Odenike, O; Pardanani, A; Silver, R T; Solary, E; Mughal, T

    2011-01-01

    Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7–8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new ‘Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed

  5. Mutations with epigenetic effects in myeloproliferative neoplasms and recent progress in treatment: Proceedings from the 5th International Post-ASH Symposium

    Energy Technology Data Exchange (ETDEWEB)

    Tefferi, A [Division of Hematology, Department of Medicine, Rochester, MN (United States); Abdel-Wahab, O [Department of Medicine, Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Cervantes, F [Hematology Department, Hospital Clínic, Institut d' Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona (Spain); Crispino, J D [Department of Hematology, Northwestern University, Chicago, IL (United States); Finazzi, G [Hematology Department of Ospedali Riuniti di Bergamo, Bergamo (Italy); Girodon, F [Laboratoire d' Hématologie, Hôpital du Bocage, Dijon (France); Gisslinger, H [Division of Hematology and Blood Coagulation, Department of Internal Medicine I, Medical University of Vienna, Vienna (Austria); Gotlib, J [Division of Hematology, Stanford University School of Medicine, Stanford, CA (United States); Kiladjian, J-J [Centre d' Investigations Cliniques 9504, Assistance Publique-Hôpitaux de Paris, Hôpital Saint-Louis, Université Paris 7, Paris (France); Levine, R L [Department of Medicine, Human Oncology and Pathogenesis Program and Leukemia Service, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Licht, J D [Department of Hematology, Northwestern University, Chicago, IL (United States); Mullally, A [Division of Hematology, Department of Medicine, Brigham and Women' s Hospital, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA (United States); Odenike, O [Section of Hematology and Oncology, University of Chicago, Chicago, IL (United States); Pardanani, A [Division of Hematology, Department of Medicine, Rochester, MN (United States); Silver, R T [Division of Hematology and Medical Oncology, Department of Medicine, Weill Medical College of Cornell University, New York, NY (United States); Solary, E [Inserm U1009, Institut Gustave Roussy, Université Paris XI, Villejuif (France); Mughal, T [Department of Haematology, Guys Hospital Medical School, London (United Kingdom); Division of Hematology, Department of Medicine, Rochester, MN (United States)

    2011-03-01

    Immediately following the 2010 annual American Society of Hematology (ASH) meeting, the 5th International Post-ASH Symposium on Chronic Myelogenous Leukemia and BCR-ABL1-Negative Myeloproliferative Neoplasms (MPNs) took place on 7–8 December 2010 in Orlando, Florida, USA. During this meeting, the most recent advances in laboratory research and clinical practice, including those that were presented at the 2010 ASH meeting, were discussed among recognized authorities in the field. The current paper summarizes the proceedings of this meeting in BCR-ABL1-negative MPN. We provide a detailed overview of new mutations with putative epigenetic effects (TET oncogene family member 2 (TET2), additional sex comb-like 1 (ASXL1), isocitrate dehydrogenase (IDH) and enhancer of zeste homolog 2 (EZH2)) and an update on treatment with Janus kinase (JAK) inhibitors, pomalidomide, everolimus, interferon-α, midostaurin and cladribine. In addition, the new ‘Dynamic International Prognostic Scoring System (DIPSS)-plus' prognostic model for primary myelofibrosis (PMF) and the clinical relevance of distinguishing essential thrombocythemia from prefibrotic PMF are discussed.

  6. High frequency of endothelial colony forming cells marks a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis.

    Directory of Open Access Journals (Sweden)

    Vittorio Rosti

    Full Text Available Increased mobilization of circulating endothelial progenitor cells may represent a new biological hallmark of myeloproliferative neoplasms. We measured circulating endothelial colony forming cells (ECFCs in 106 patients with primary myelofibrosis, fibrotic stage, 49 with prefibrotic myelofibrosis, 59 with essential thrombocythemia or polycythemia vera, and 43 normal controls. Levels of ECFC frequency for patient's characteristics were estimated by using logistic regression in univariate and multivariate setting. The sensitivity, specificity, likelihood ratios, and positive predictive value of increased ECFC frequency were calculated for the significantly associated characteristics. Increased frequency of ECFCs resulted independently associated with history of splanchnic vein thrombosis (adjusted odds ratio = 6.61, 95% CI = 2.54-17.16, and a summary measure of non-active disease, i.e. hemoglobin of 13.8 g/dL or lower, white blood cells count of 7.8×10(9/L or lower, and platelet count of 400×10(9/L or lower (adjusted odds ratio = 4.43, 95% CI = 1.45-13.49 Thirteen patients with splanchnic vein thrombosis non associated with myeloproliferative neoplasms were recruited as controls. We excluded a causal role of splanchnic vein thrombosis in ECFCs increase, since no control had elevated ECFCs. We concluded that increased frequency of ECFCs represents the biological hallmark of a non-active myeloproliferative neoplasm with high risk of splanchnic vein thrombosis. The recognition of this disease category copes with the phenotypic mimicry of myeloproliferative neoplasms. Due to inherent performance limitations of ECFCs assay, there is an urgent need to arrive to an acceptable standardization of ECFC assessment.

  7. Development of a Targeted Next-Generation Sequencing Assay to Detect Diagnostically Relevant Mutations of JAK2, CALR, and MPL in Myeloproliferative Neoplasms.

    Science.gov (United States)

    Frawley, Thomas; O'Brien, Cathal P; Conneally, Eibhlin; Vandenberghe, Elisabeth; Percy, Melanie; Langabeer, Stephen E; Haslam, Karl

    2018-02-01

    The classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), consisting of polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a heterogeneous group of neoplasms that harbor driver mutations in the JAK2, CALR, and MPL genes. The detection of mutations in these genes has been incorporated into the recent World Health Organization (WHO) diagnostic criteria for MPN. Given a pressing clinical need to screen for mutations in these genes in a routine diagnostic setting, a targeted next-generation sequencing (NGS) assay for the detection of MPN-associated mutations located in JAK2 exon 14, JAK2 exon 12, CALR exon 9, and MPL exon 10 was developed to provide a single platform alternative to reflexive, stepwise diagnostic algorithms. Polymerase chain reaction (PCR) primers were designed to target mutation hotspots in JAK2 exon 14, JAK2 exon 12, MPL exon 10, and CALR exon 9. Multiplexed PCR conditions were optimized by using qualitative PCR followed by NGS. Diagnostic genomic DNA from 35 MPN patients, known to harbor driver mutations in one of the target genes, was used to validate the assay. One hundred percent concordance was observed between the previously-identified mutations and those detected by NGS, with no false positives, nor any known mutations missed (specificity = 100%, CI = 0.96, sensitivity = 100%, CI = 0.89). Improved resolution of mutation sequences was also revealed by NGS analysis. Detection of diagnostically relevant driver mutations of MPN is enhanced by employing a targeted multiplex NGS approach. This assay presents a robust solution to classical MPN mutation screening, providing an alternative to time-consuming sequential analyses.

  8. The Hepatocyte Growth Factor (HGF/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

    Directory of Open Access Journals (Sweden)

    Marjorie Boissinot

    2014-08-01

    Full Text Available Met is the receptor of hepatocyte growth factor (HGF, a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML, and myeloproliferative neoplasms (MPNs. The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs.

  9. Social Media and Myeloproliferative Neoplasms (MPN)--Focus on Twitter and the Development of a Disease-specific Community: #MPNSM.

    Science.gov (United States)

    Pemmaraju, Naveen; Gupta, Vikas; Mesa, Ruben; Thompson, Michael A

    2015-12-01

    The advent of social media has led to the ability for individuals all over the world to communicate with each other, in real time, about mutual topics of interest in an unprecedented manner. Recently, the use of social media has increased among people interested in healthcare and medical research, particularly in the field of hematology and oncology, a field which frequently experiences rapid shifts of information and novel, practice-changing discoveries. Among the many social media platforms available to cancer patients and providers, one platform in particular, Twitter, has become the focus for the creation of disease-specific communities, especially for those interested in, affected by, or those who perform research in the fields of rare cancers, which historically have had a dearth of reliable information available. This article will focus on the initiation and progress of one such Twitter hematology/oncology community, #mpnsm, which was originally created for the purpose of serving as a venue for improving the interaction among patients, providers, researchers, and organizations with interest in the myeloproliferative neoplasms (MPNs) and to further the availability of reliable up-to-date analysis; relevant expert commentary; and readily usable information for patients, providers, and other groups interested in this field.

  10. [Identification of a novel aberrant spliceosome of MPL gene (MPLL391-V392ins12)in patients with myeloproliferative neoplasms].

    Science.gov (United States)

    Tian, Ruiyuan; Chen, Xiuhua; Chang, Jianmei; Zhang, Na; Tan, Yanhong; Xu, Zhifang; Ren, Fanggang; Zhao, Junxia; Pan, Jie; Guo, Haixiu; Wang, Xiaojuan; Wang, Hongwei

    2015-07-01

    To identify the MPL L391-V392ins12 spliceosome and analyze its frequencies in patients with myeloproliferative neoplasms (MPN). MPL aberrant spliceosome was identified through reverse transcription polymerase chain reaction (RT-PCR)combined with cloning sequencing. The mutation of this spliceosome in 248 MPN patients and 200 normal people was determined by allele-specific polymerase chain reaction (AS-PCR). A novel aberrant spliceosome of MPL gene (MPL L391-V392ins12)was identified, i.e. 36 bp intron was retained between exon7 and exon8, and there were 12 amino acids (EGLKLLPADIPV)inserted. MPL L391-V392ins12 mutation was detected in 19 (7.66%)of the 248 patients with MPN, including 1 (1.92%) of 52 patients with PV, 14 (9.66%) of 145 with ET, and 4 (7.84%) of 51 with PMF. And the mutation was not detected in the group of 200 normal people. MPL L391-V392ins12 spliceosome is an aberrant spliceosome present in the MPN. It can be detected in PV, ET and PMF, and more frequently in ET and PMF. This mutation may play an important role in the process of MPN.

  11. The Role of Genotypes That Modify the Toxicity of Chemical Mutagens in the Risk for Myeloproliferative Neoplasms

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    Carol Ann Gross-Davis

    2015-02-01

    Full Text Available Background: The etiology of myeloproliferative neoplasms (MPN (polycythemia vera; essential thrombocythemia; primary myelofibrosis is unknown, however they are associated with a somatic mutation—JAK2 V617F—suggesting a potential role for environmental mutagens. Methods: We conducted a population-based case-control study in three rural Pennsylvania counties of persons born 1921–1968 and residing in the area between 2000–2008. Twenty seven MPN cases and 292 controls were recruited through random digit dialing. Subjects were genotyped and odds ratios estimated for a select set of polymorphisms in environmentally sensitive genes that might implicate specific environmental mutagens if found to be associated with a disease. Results: The presence of NAT2 slow acetylator genotype, and CYP1A2, GSTA1, and GSTM3 variants were associated with an average 3–5 fold increased risk. Conclusions: Exposures, such as to aromatic compounds, whose toxicity is modified by genotypes associated with outcome in our analysis may play a role in the environmental etiology of MPNs.

  12. TET2, ASXL1, IDH1, and IDH2 Single Nucleotide Polymorphisms in Turkish Patients with Chronic Myeloproliferative Neoplasms

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    Nur Soyer

    2017-06-01

    Full Text Available We aimed to determine the genotype distribution, allele frequency, and prognostic impact of IDH1/2, TET2, and ASXL1 single nucleotide polymorphisms (SNPs in myeloproliferative neoplasms (MPNs. TET2 (rs763480, ASXL1 (rs2208131, and IDH1 (rs11554137 variant homozygous genotype frequencies were found at rates of 1.5%, 9.2%, and 2.3%, respectively. No IDH2 SNP was identified. IDH1 and TET2 frequencies were 5% in essential thrombocythemia (ET and 1.7% in ET and 5% in primary myelofibrosis (PMF, respectively. ASXL1 frequencies were 8.3%-10% in MPN subgroups. The TET2 mutant allele T and ASXL1 mutant allele G had the highest frequencies with 0.272 in the PMF and 0.322 in the polycythemia vera (PV group, respectively. There was no impact of the SNPs on prognosis. IDH1 frequency in MPNs was found similar to the literature. ASXL1 frequencies were similar between ET, PV, and PMF patients. The ASXL1 and TET2 allele frequencies of the Turkish population are similar to those of the European population. The role of SNPs in MPNs might be further evaluated in larger multicenter studies.

  13. Heterozygous and homozygous JAK2(V617F states modeled by induced pluripotent stem cells from myeloproliferative neoplasm patients.

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    Joseph Saliba

    Full Text Available JAK2(V617F is the predominant mutation in myeloproliferative neoplasms (MPN. Modeling MPN in a human context might be helpful for the screening of molecules targeting JAK2 and its intracellular signaling. We describe here the derivation of induced pluripotent stem (iPS cell lines from 2 polycythemia vera patients carrying a heterozygous and a homozygous mutated JAK2(V617F, respectively. In the patient with homozygous JAK2(V617F, additional ASXL1 mutation and chromosome 20 allowed partial delineation of the clonal architecture and assignation of the cellular origin of the derived iPS cell lines. The marked difference in the response to erythropoietin (EPO between homozygous and heterozygous cell lines correlated with the constitutive activation level of signaling pathways. Strikingly, heterozygous iPS cells showed thrombopoietin (TPO-independent formation of megakaryocytic colonies, but not EPO-independent erythroid colony formation. JAK2, PI3K and HSP90 inhibitors were able to block spontaneous and EPO-induced growth of erythroid colonies from GPA(+CD41(+ cells derived from iPS cells. Altogether, this study brings the proof of concept that iPS can be used for studying MPN pathogenesis, clonal architecture, and drug efficacy.

  14. Allogeneic hematopoietic stem cell transplant in adult patients with myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) overlap syndromes.

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    Sharma, Prashant; Shinde, Shivani S; Damlaj, Moussab; Hefazi Rorghabeh, Mehrdad; Hashmi, Shahrukh K; Litzow, Mark R; Hogan, William J; Gangat, Naseema; Elliott, Michelle A; Al-Kali, Aref; Tefferi, Ayalew; Patnaik, Mrinal M

    2017-04-01

    MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasm) overlap syndromes are myeloid malignancies for which allogeneic hematopoietic stem cell transplant (allo-HSCT) is potentially curative. We describe transplant outcomes of 43 patients - 35 with chronic myelomonocytic leukemia, CMML (of which 17 had blast transformation, BT) and eight with MDS/MPN-unclassifiable (MDS/MPN,U). At median follow-up of 21 months, overall survival (OS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 55%, 29%, and 25% respectively in CMML without BT and 47%, 40%, and 34% respectively in CMML with BT. Higher HSCT-comorbidity index (HSCT-CI >3 versus ≤3; p = 0.015) and splenomegaly (p = 0.006) predicted worse OS in CMML without BT. In CMML with BT, engraftment failure (p = 0.006) and higher HSCT-CI (p = 0.03) were associated with inferior OS, while HSCT within 1-year of diagnosis was associated with improved OS (p = 0.045). In MDS/MPN,U, at median follow-up of 15 months, OS, CIR, and NRM were 62%, 30%, and 14%, respectively.

  15. The role of thrombocytapheresis in the contemporary management of hyperthrombocytosis in myeloproliferative neoplasms: A case-based review.

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    Boddu, Prajwal; Falchi, Lorenzo; Hosing, Chitra; Newberry, Kate; Bose, Prithviraj; Verstovsek, Srdan

    2017-07-01

    Extreme thrombocytosis induces an acquired thrombotic-hemorrhagic diathesis, and left uncontrolled is a harbinger of potentially fatal vascular complications. Currently, cytoreduction with medical therapy remains the mainstay of hyperthrombocytosis management. However, it offers a less-than-ideal option in situations where a rapid reduction in platelets is urgently needed, as in the presence of vital end-organ ischemia or to ameliorate of life-threatening hemorrhage. The role of thrombocytapheresis, or plateletpheresis, in hyperthrombocytosis has become increasingly obsolete given the proactive titration of cytoreductive therapies and early identification and correction of reversible causes of reactive thrombocytosis. Despite its narrowed indications, plateletpheresis continues to offer a valuable temporizing measure in platelet count reduction before cytoreductive agents exert their maximal effect. In this context, it is important for the treating physician to be aware of the symptoms and risks associated with hyperthrombocytosis to inform best clinical practices. In this review, we discuss the role of plateletpheresis in the modern-day management of hyperthrombocytosis in patients with myeloproliferative neoplasms through a case based review of the literature. It becomes apparent throughout the discussion that the decision to perform plateletpheresis should be individualized based upon the clinical scenario, degree of thrombocytosis, available infrastructure and every patient's risk profile. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. The Hepatocyte Growth Factor (HGF)/Met Axis: A Neglected Target in the Treatment of Chronic Myeloproliferative Neoplasms?

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    Boissinot, Marjorie [Translational Neuro-Oncology Group, Leeds Institute of Cancer and Pathology, University of Leeds, Level 5 Wellcome Trust Brenner Building, St James’s Hospital, Leeds LS9 7TF (United Kingdom); Vilaine, Mathias [Institute of Research on Cancer and Aging (IRCAN), CNRS-Inserm-UNS UMR 7284, U 1081, Centre A. Lacassagne, 33 Avenue Valombrose, Nice 06189 (France); Hermouet, Sylvie, E-mail: sylvie.hermouet@univ-nantes.fr [Centre Hospitalier Universitaire (CHU), Place Alexis Ricordeau, Nantes 44093 (France); Inserm UMR892, Centre de Recherche en Cancérologie Nantes-Angers, Institut de Recherche en Santé, Université de Nantes, 8 quai Moncousu, Nantes cedex 44007 (France)

    2014-08-12

    Met is the receptor of hepatocyte growth factor (HGF), a cytoprotective cytokine. Disturbing the equilibrium between Met and its ligand may lead to inappropriate cell survival, accumulation of genetic abnormalities and eventually, malignancy. Abnormal activation of the HGF/Met axis is established in solid tumours and in chronic haematological malignancies, including myeloma, acute myeloid leukaemia, chronic myelogenous leukaemia (CML), and myeloproliferative neoplasms (MPNs). The molecular mechanisms potentially responsible for the abnormal activation of HGF/Met pathways are described and discussed. Importantly, inCML and in MPNs, the production of HGF is independent of Bcr-Abl and JAK2V617F, the main molecular markers of these diseases. In vitro studies showed that blocking HGF/Met function with neutralizing antibodies or Met inhibitors significantly impairs the growth of JAK2V617F-mutated cells. With personalised medicine and curative treatment in view, blocking activation of HGF/Met could be a useful addition in the treatment of CML and MPNs for those patients with high HGF/MET expression not controlled by current treatments (Bcr-Abl inhibitors in CML; phlebotomy, hydroxurea, JAK inhibitors in MPNs)

  17. JAK2 V617F-dependent upregulation of PU.1 expression in the peripheral blood of myeloproliferative neoplasm patients.

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    Tamotsu Irino

    Full Text Available Myeloproliferative neoplasms (MPN are multiple disease entities characterized by clonal expansion of one or more of the myeloid lineages (i.e. granulocytic, erythroid, megakaryocytic and mast cell. JAK2 mutations, such as the common V617F substitution and the less common exon 12 mutations, are frequently detected in such tumor cells and have been incorporated into the diagnostic criteria published by the World Health Organization since 2008. However, the mechanism by which these mutations contribute to MPN development is poorly understood. We examined gene expression profiles of MPN patients focusing on genes in the JAK-STAT signaling pathway using low-density real-time PCR arrays. We identified the following 2 upregulated genes in MPN patients: a known target of the JAK-STAT axis, SOCS3, and a potentially novel target, SPI1, encoding PU.1. Induction of PU.1 expression by JAK2 V617F in JAK2-wildtype K562 cells and its downregulation by JAK2 siRNA transfection in JAK2 V617F-positive HEL cells supported this possibility. We also found that the ABL1 kinase inhibitor imatinib was very effective in suppressing PU.1 expression in BCR-ABL1-positive K562 cells but not in HEL cells. This suggests that PU.1 expression is regulated by both JAK2 and ABL1. The contribution of the two kinases in driving PU.1 expression was dominant for JAK2 and ABL1 in HEL and K562 cells, respectively. Therefore, PU.1 may be a common transcription factor upregulated in MPN. PU.1 is a transcription factor required for myeloid differentiation and is implicated in erythroid leukemia. Therefore, expression of PU.1 downstream of activated JAK2 may explain why JAK2 mutations are frequently observed in MPN patients.

  18. The effects of hematopoietic stem cell transplant on splenic extramedullary hematopoiesis in patients with myeloproliferative neoplasm-associated myelofibrosis.

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    Pizzi, Marco; Gergis, Usama; Chaviano, Felicia; Orazi, Attilio

    2016-09-01

    Hematopoietic stem cell transplant (HSCT) is the only curative treatment for myeloproliferative neoplasm-associated myelofibrosis (MPN-MF). The main clinical manifestation of MPN-MF is splenomegaly secondary to extramedullary hematopoiesis (EMH). The effects of HSCT on splenic EMH and associated vascular and stromal changes are unknown. This study compares the findings seen in spleens following HSCT with those of nontransplanted patients, normal controls, and matched bone marrow (BM) samples. This study included three transplanted MPN-MF spleens, three nontransplanted MPN-MF spleens, and three normal controls. Spleens were assessed for: (a) presence/extent of EMH; (b) presence of Gamna-Gandy bodies; (c) splenic fibrosis; (d) CD34-positive microvessel density; (e) CD8-positive sinusoids; (f) frequency of smooth muscle actin-positive myoid cells; and (g) nerve growth factor receptor-positive adventitial reticulum cells. In two cases, matched BM samples were assessed for cellularity, presence of atypical megakaryocytes, and fibrosis. Compared with normal controls, all MPN-MF spleens were larger in size, had EMH, red pulp fibrosis, higher CD34-positive microvessel density, and decreased CD8-positive sinusoids. Compared with nontransplanted cases, post-HSCT spleens showed disappearance or reduction of EMH. Gamna-Gandy bodies were increased; no differences in the remaining parameters were found. A reduction of splenic EMH was associated with normalization of BM cellularity and megakaryopoiesis. HSCT reduces/abrogates splenic EMH and is associated with an increased number of Gamna-Gandy bodies, which may suggest vascular damage. The lack of stromal changes in spleens removed shortly after transplant is in line with similar observations in the BM, where a longer interval is often necessary for resolution of fibrosis. Copyright © 2016 King Faisal Specialist Hospital & Research Centre. Published by Elsevier Ltd. All rights reserved.

  19. Tyrosine 625 plays a key role and cooperates with tyrosine 630 in MPL W515L-induced signaling and myeloproliferative neoplasms.

    Science.gov (United States)

    Yu, Chunjie; Yang, Qiong; Chen, Yuhong; Wang, Demin; Levine, Ross; Crispino, John; Wen, Qiang; Huang, Zan

    2016-01-01

    Myeloproliferative neoplasms (MPN) are a group of blood cancers that boost normal blood cell production in the bone marrow. Abnormal mutations in stem cells were found accompanying with the occurrence of MPN. It has been shown that MPL mutations (MPL W515L or MPL W515K) were involved in patients with MPN. Since tyrosine residues 625 and 630 mediate normal MPL signaling, whether them affect MPL W515L-induced myeloproliferative neoplasms (MPNs) is unknown. In this study, we further tested their functions in MPL W515L-induced myeloproliferative neoplasms (MPNs) by substituting either or both of them with phenylalanine in MPL W515L (termed as MPL515/625, MPL515/630 and MPL515/625/630, respectively). In vitro, MPL515/630 but not MPL515/625 or MPL515/625/630 retained the ability to induce TPO-independent proliferation and increase colony-forming unit megakaryocytes (CFU-Mk). Accordingly, differential activation of the downstream signaling by four mutants was observed and constitutively active STAT5 or AKT instead of STAT3 partially compensated MPL515/625/630 function. Further support this, STAT5-deficiency impaired MPL W515L-induced CFU-Mk expansion. In vivo, MPL515/630 but not MPL515/625 or MPL515/625/630 induced typical features of MPNs with high WBC and platelet counts, splenomegaly, hepatomegaly and hypercellularity in the bone marrow. Surprisingly, MPL515/625 also caused hypercellularity of bone marrow and splenomegaly without any other significant features. We also observed differential effects of the four mutants on progenitors, myeloid cells and megakaryocytes. Our studies have revealed distinct features of tyrosine sites 625 and 630 in mediating MPL W515L-induced megakaryocyte hyperproliferation and MPNs. Our study also suggests that MPL cytosolic phosphorylated Y625 and flanking amino acids could become targets for pharmacologic inhibition in MPNs.

  20. Improved diagnosis of the transition to JAK2 (V⁶¹⁷F homozygosity: the key feature for predicting the evolution of myeloproliferative neoplasms.

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    Mariana Selena Gonzalez

    Full Text Available Most cases of BCR-ABL1-negative myeloproliferative neoplasms (MPNs, essential thrombocythemia, polycythemia vera and primary myelofibrosis are associated with JAK2 (V617F mutations. The outcomes of these cases are critically influenced by the transition from JAK2 (V617F heterozygosity to homozygosity. Therefore, a technique providing an unbiased assessment of the critical allele burden, 50% JAK2 (V617F, is highly desirable. In this study, we present an approach to assess the JAK2 (V617F burden from genomic DNA (gDNA and complementary DNA (cDNA using one-plus-one template references for allele-specific quantitative-real-time-PCR (qPCR. Plasmidic gDNA and cDNA constructs encompassing one PCR template for JAK2 (V617F spaced from one template for JAK2(Wild Type were constructed by multiple fusion PCR amplifications. Repeated assessments of the 50% JAK2(V617F burden within the dynamic range of serial dilutions of gDNA and cDNA constructs resulted in 52.53 ± 4.2% and 51.46 ± 4.21%, respectively. The mutation-positive cutoff was estimated to be 3.65% (mean +2 standard deviation using 20 samples from a healthy population. This qPCR approach was compared with the qualitative ARMS-PCR technique and with two standard methods based on qPCR, and highly significant correlations were obtained in all cases. qPCR assays were performed on paired gDNA/cDNA samples from 20 MPN patients, and the JAK2 (V617F expression showed a significant correlation with the allele burden. Our data demonstrate that the qPCR method using one-plus-one template references provides an improved assessment of the clinically relevant transition of JAK2 (V617F from heterozygosity to homozygosity.

  1. JAK2 46/1 haplotype is associated with JAK2 V617F--positive myeloproliferative neoplasms in Brazilian patients.

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    Macedo, L C; Santos, B C; Pagliarini-e-Silva, S; Pagnano, K B B; Rodrigues, C; Quintero, F C; Ferreira, M E; Baraldi, E C; Ambrosio-Albuquerque, E P; Sell, A M; Visentainer, J E L

    2015-10-01

    This study aimed to verify the association between the JAK2 46/1 haplotype (V617F positive) and some hematological parameters in BCR-ABL-negative chronic myeloproliferative neoplasms (cMPNs) in our population. The blood samples obtained from the patients with cMPN were genotyped for the JAK2 V617F mutation and JAK2 rs10974944 SNP screening using a PCR-RFLP assay. The JAK2 V617F mutation was detected in 80.15% of patients. The G variant of rs10974944 was more frequent in all MPNs, especially those that were JAK2 V617F positive, than in the control population. We also compared the 46/1 haplotype status in each MPN disease entity, polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF), and MPNu with controls. The G allele frequency relative to controls was significantly enriched in patients with PV and ET, but not in those with PMF and MPNu. PV and ET patients especially, all of whom had the JAK2 V617F mutation, showed significant excess of the G allele. The frequency of JAK2 V617F mutation was associated with elevated hematological parameters, but when we analyze the occurrence of the mutation and the presence of the G allele, just the high hemoglobin was significantly. In agreement with previous reports, JAK2 46/1 haplotype for JAK2 V617F was associated with cMPN positive in Brazilian patients. © 2015 John Wiley & Sons Ltd.

  2. Risk for Arterial and Venous Thrombosis in Patients With Myeloproliferative Neoplasms: A Population-Based Cohort Study.

    Science.gov (United States)

    Hultcrantz, Malin; Björkholm, Magnus; Dickman, Paul W; Landgren, Ola; Derolf, Åsa R; Kristinsson, Sigurdur Y; Andersson, Therese M L

    2018-03-06

    Patients with myeloproliferative neoplasms (MPNs) are reported to be at increased risk for thrombotic events. However, no population-based study has estimated this excess risk compared with matched control participants. To assess risk for arterial and venous thrombosis in patients with MPNs compared with matched control participants. Matched cohort study. Population-based setting in Sweden from 1987 to 2009, with follow-up to 2010. 9429 patients with MPNs and 35 820 matched control participants. The primary outcomes were rates of arterial and venous thrombosis. Flexible parametric models were used to calculate hazard ratios (HRs) and cumulative incidence with 95% CIs. The HRs for arterial thrombosis among patients with MPNs compared with control participants at 3 months, 1 year, and 5 years were 3.0 (95% CI, 2.7 to 3.4), 2.0 (CI, 1.8 to 2.2), and 1.5 (CI, 1.4 to 1.6), respectively. The corresponding HRs for venous thrombosis were 9.7 (CI, 7.8 to 12.0), 4.7 (CI, 4.0 to 5.4), and 3.2 (CI, 2.9 to 3.6). The rate was significantly elevated across all age groups and was similar among MPN subtypes. The 5-year cumulative incidence of thrombosis in patients with MPNs showed an initial rapid increase followed by gentler increases during follow-up. The HR for venous thrombosis decreased during more recent calendar periods. No information on individual laboratory results or treatment. Patients with MPNs across all age groups have a significantly increased rate of arterial and venous thrombosis compared with matched control participants, with the highest rates at and shortly after diagnosis. Decreases in the rate of venous thrombosis over time likely reflect advances in clinical management. The Cancer Research Foundations of Radiumhemmet, Blodcancerfonden, the Swedish Research Council, the regional agreement on medical training and clinical research between Stockholm County Council and Karolinska Institutet, the Adolf H. Lundin Charitable Foundation, and Memorial Sloan

  3. mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms.

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    Costanza Bogani

    Full Text Available BACKGROUND: Dysregulated signaling of the JAK/STAT pathway is a common feature of chronic myeloproliferative neoplasms (MPN, usually associated with JAK2V617F mutation. Recent clinical trials with JAK2 inhibitors showed significant improvements in splenomegaly and constitutional symptoms in patients with myelofibrosis but meaningful molecular responses were not documented. Accordingly, there remains a need for exploring new treatment strategies of MPN. A potential additional target for treatment is represented by the PI3K/AKT/mammalian target of rapamycin (mTOR pathway that has been found constitutively activated in MPN cells; proof-of-evidence of efficacy of the mTOR inhibitor RAD001 has been obtained recently in a Phase I/II trial in patients with myelofibrosis. The aim of the study was to characterize the effects in vitro of mTOR inhibitors, used alone and in combination with JAK2 inhibitors, against MPN cells. FINDINGS: Mouse and human JAK2V617F mutated cell lines and primary hematopoietic progenitors from MPN patients were challenged with an allosteric (RAD001 and an ATP-competitive (PP242 mTOR inhibitor and two JAK2 inhibitors (AZD1480 and ruxolitinib. mTOR inhibitors effectively reduced proliferation and colony formation of cell lines through a slowed cell division mediated by changes in cell cycle transition to the S-phase. mTOR inhibitors also impaired the proliferation and prevented colony formation from MPN hematopoietic progenitors at doses significantly lower than healthy controls. JAK2 inhibitors produced similar antiproliferative effects in MPN cell lines and primary cells but were more potent inducers of apoptosis, as also supported by differential effects on cyclinD1, PIM1 and BcLxL expression levels. Co-treatment of mTOR inhibitor with JAK2 inhibitor resulted in synergistic activity against the proliferation of JAK2V617F mutated cell lines and significantly reduced erythropoietin-independent colony growth in patients with

  4. Genetic polymorphisms of hemostatic factors and thrombotic risk in non BCR-ABL myeloproliferative neoplasms: A pilot study

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    Dambrauskienė R

    2017-06-01

    Full Text Available The most important complications of Philadelphianegagive (non BCR-ABL myeloproliferative neoplasms (MPNs are vascular events. Our aim was to evaluate the effects of single nucleotide polymorphisms (SNPs, platelet glycoproteins (GPs (Ia/IIa, Ibα, IIb/IIIa and VI, von Willebrand factor (vWF, coagulation factor VII (FVII, β-fibrinogen, and the risk of thrombosis in patients with non BCR-ABL MPNs at the Lithuanian University of Health Sciences. Kaunas, Lithuania. Genotyping was done for 108 patients. The TT genotype of the GP Ia/IIa c.807C>T polymorphism was more frequently found in the group of MPN patients with arterial thrombosis compared to MPN patients who were thrombosis-free [26.5 vs. 11.5%, p = 0.049; odds ratio (OR 2.68; 95% confidence interval (95% CI 1.01-7.38]. The CT genotype of the β-fibrinogen c.-148C>T polymorphism occurred more frequently in MPN patients with arterial, and total thrombosis compared to the wild or homozygous genotype (57.7 vs. 40.0 vs. 12.5%; p = 0.027, (64.7 vs. 44.4 vs. 25%; p = 0.032, respectively. The carrier state for the c.-323P10 variant of FVII SNP (summation of P10/10 and P0/10 was more frequent in MPN patients with thrombosis compared to the wild-type genotype carriers (71.4 vs. 43.4%; p = 0.049; OR 3.26; 95% CI 1.01-11.31. The coexistence of heterozygous β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP, increased the risk of arterial thrombosis (21.1 vs. 3.7%, p = 0.008; OR 6.93; 95% CI 1.38-34.80. The TT genotype of GP Ia/IIa c.807C>T, the CT genotype of β-fibrinogen c.-148C>T and FVII c.-323P0/10 SNP could be associated with risk of thrombosis in MPN patients.

  5. A new internet-based tool for reporting and analysing patient-reported outcomes and the feasibility of repeated data collection from patients with myeloproliferative neoplasms.

    Science.gov (United States)

    Brochmann, Nana; Zwisler, Ann-Dorthe; Kjerholt, Mette; Flachs, Esben Meulengracht; Hasselbalch, Hans Carl; Andersen, Christen Lykkegaard

    2016-04-01

    An Internet-based tool for reporting and analysing patient-reported outcomes (PROs) has been developed. The tool enables merging PROs with blood test results and allows for computation of treatment responses. Data may be visualized by graphical analysis and may be exported for downstream statistical processing. The aim of this study was to investigate, whether patients with myeloproliferative neoplasms (MPNs) were willing and able to use the tool and fill out questionnaires regularly. Participants were recruited from the outpatient clinic at the Department of Haematology, Roskilde University Hospital, Denmark. Validated questionnaires that were used were European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, Myeloproliferative Neoplasm Symptom Assessment Form, Brief Fatigue Inventory and Short Form 36 Health Survey. Questionnaires were filled out ≥ 6 months online or on paper according to participant preference. Regularity of questionnaire submission was investigated, and participant acceptance was evaluated by focus-group interviews. Of 135 invited patients, 118 (87 %) accepted participation. One hundred and seven participants (91 %) preferred to use the Internet-based tool. Of the 118 enrolled participants, 104 (88 %) submitted PROs regularly ≥ 6 months. The focus-group interviews revealed that the Internet-based tool was well accepted. The Internet-based approach and regular collection of PROs are well accepted with a high participation rate, persistency and adherence in a population of MPN patients. The plasticity of the platform allows for adaptation to patients with other medical conditions.

  6. MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms

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    Timur Selçuk Akpınar

    2013-03-01

    Full Text Available OBJECTIVE: The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K were described in patients with essential thrombocythemia (ET and primary (idiopathic myelofibrosis (PMF. The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. METHODS: A total of 77 patients (66 were diagnosed with ET and 11 with PMF and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. RESULTS: In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66 and 6 had PMF (54.5%, 6/11. In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively, had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. CONCLUSION: MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation.

  7. MPL W515L/K Mutations in Chronic Myeloproliferative Neoplasms.

    Science.gov (United States)

    Akpınar, Timur Selçuk; Hançer, Veysel Sabri; Nalçacı, Meliha; Diz-Küçükkaya, Reyhan

    2013-03-01

    The MPL gene encodes the thrombopoietin receptor. Recently MPL mutations (MPL W515L or MPL W515K) were described in patients with essential thrombocythemia (ET) and primary (idiopathic) myelofibrosis (PMF). The prevalence and the clinical importance of these mutations are not clear. In the present study, we aimed to investigate the frequency and clinical significance of MPL W515L/K mutations in our patients with ET and PMF. A total of 77 patients (66 were diagnosed with ET and 11 with PMF) and 42 healthy controls were included in the study. Using peripheral blood samples, the presence of MPL W515L/K mutations and JAK-2 V617F mutation were analyzed by real-time polymerase chain reaction. In our study, MPL W515L/K or JAK-2 V617F mutations were not observed in healthy controls. JAK-2 V617F mutation was present in 35 patients, of whom 29 had ET (43.9%, 29/66) and 6 had PMF (54.5%, 6/11). In the patient group, MPL W515L/K mutations were found in only 2 PMF cases, and these cases were negative for JAK-2 V617F mutation. The prevalence of MPL W515L/K mutations in the patient group was 2.6%, and the prevalence of MPL W515L/K mutations among the cases negative for the JAK-2 V617F mutation was found to be 4.8%. The 2 cases with MPL W515L/K mutations had long follow-up times (124 months and 71 months, respectively), had no thrombotic or hemorrhagic complications, and had no additional cytogenetic anomalies. MPL W515L/K mutations may be helpful for identifying clonal disease in MPN patients with no established Ph chromosome or JAK-2 V617F mutation. None declared.

  8. The C allele of JAK2 rs4495487 is an additional candidate locus that contributes to myeloproliferative neoplasm predisposition in the Japanese population

    Directory of Open Access Journals (Sweden)

    Ohyashiki Junko H

    2012-01-01

    Full Text Available Abstract Background Polycythemia vera (PV, essential thrombocythemia (ET, and primary myelofibrosis (PMF are myeloproliferative neoplasms (MPNs characterized in most cases by a unique somatic mutation, JAK2 V617F. Recent studies revealed that JAK2 V617F occurs more frequently in a specific JAK2 haplotype, named JAK2 46/1 or GGCC haplotype, which is tagged by rs10974944 (C/G and/or rs12343867 (T/C. This study examined the impact of single nucleotide polymorphisms (SNPs of the JAK2 locus on MPNs in a Japanese population. Methods We sequenced 24 JAK2 SNPs in Japanese patients with PV. We then genotyped 138 MPN patients (33 PV, 96 ET, and 9 PMF with known JAK2 mutational status and 107 controls for a novel SNP, in addition to two SNPs known to be part of the 46/1 haplotype (rs10974944 and rs12343867. Associations with risk of MPN were estimated by odds ratios and their 95% confidence intervals using logistic regression. Results A novel locus, rs4495487 (T/C, with a mutated T allele was significantly associated with PV. Similar to rs10974944 and rs12343867, rs4495487 in the JAK2 locus is significantly associated with JAK2-positive MPN. Based on the results of SNP analysis of the three JAK2 locus, we defined the "GCC genotype" as having at least one minor allele in each SNP (G allele in rs10974944, C allele in rs4495487, and C allele in rs12343867. The GCC genotype was associated with increased risk of both JAK2 V617F-positive and JAK2 V617F-negative MPN. In ET patients, leukocyte count and hemoglobin were significantly associated with JAK2 V617F, rather than the GCC genotype. In contrast, none of the JAK2 V617F-negative ET patients without the GCC genotype had thrombosis, and splenomegaly was frequently seen in this subset of ET patients. PV patients without the GCC genotype were significantly associated with high platelet count. Conclusions Our results indicate that the C allele of JAK2 rs4495487, in addition to the 46/1 haplotype, contributes

  9. MPL mutation profile in JAK2 mutation-negative patients with myeloproliferative disorders.

    Science.gov (United States)

    Ma, Wanlong; Zhang, Xi; Wang, Xiuqiang; Zhang, Zhong; Yeh, Chen-Hsiung; Uyeji, Jennifer; Albitar, Maher

    2011-03-01

    Mutations in the thrombopoietin receptor gene (myeloproliferative leukemia, MPL) have been reported in patients with JAK2 V617F-negative chronic myeloproliferative disorders (MPDs). We evaluated the prevalence of MPL mutations relative to JAK2 mutations in patients with suspected MPDs. A total of 2790 patient samples submitted for JAK2 mutation analysis were tested using real-time polymerase chain reaction and bidirectional sequencing of plasma RNA. JAK2 V617F-negative samples were tested for JAK2 exons 12 to 14 mutations, and those with negative results were then tested for mutations in MPL exons 10 and 11. Of the 2790 patients, 529 (18.96%) had V617F, 12 (0.43%) had small insertions or deletions in exon 12, and 7 (0.25%) had other JAK2 mutations in exons 12 to 14. Of the 2242 JAK2 mutation-negative patients, 68 (3.03%) had MPL mutations. W515L was the predominant MPL mutation (n=46; 68%), and 10 (15%) patients had other W515 variants. The remaining MPL mutations (n=12, 17%) were detected at other locations in exons 10 and 11 and included 3 insertion/deletion mutations. The S505N mutation, associated with familial MPD, was detected in 3 patients. Overall, for every 100 V617F mutations in patients with suspected MPDs, there were 12.9 MPL mutations, 2.3 JAK2 exon 12 mutations, and 1.3 JAK2 exons 13 to 14 mutations. These findings suggest that MPL mutation screening should be performed before JAK2 exons 12 to 14 testing in JAK2 V617F-negative patients with suspected MPDs.

  10. Adaptor protein Lnk negatively regulates the mutant MPL, MPLW515L associated with myeloproliferative disorders.

    Science.gov (United States)

    Gery, Sigal; Gueller, Saskia; Chumakova, Katya; Kawamata, Norihiko; Liu, Liqin; Koeffler, H Phillip

    2007-11-01

    Recently, activating myeloproliferative leukemia virus oncogene (MPL) mutations, MPLW515L/K, were described in myeloproliferative disorder (MPD) patients. MPLW515L leads to activation of downstream signaling pathways and cytokine-independent proliferation in hematopoietic cells. The adaptor protein Lnk is a negative regulator of several cytokine receptors, including MPL. We show that overexpression of Lnk in Ba/F3-MPLW515L cells inhibits cytokine-independent growth, while suppression of Lnk in UT7-MPLW515L cells enhances proliferation. Lnk blocks the activation of Jak2, Stat3, Erk, and Akt in these cells. Furthermore, MPLW515L-expressing cells are more susceptible to Lnk inhibitory functions than their MPL wild-type (MPLWT)-expressing counterparts. Lnk associates with activated MPLWT and MPLW515L and colocalizes with the receptors at the plasma membrane. The SH2 domain of Lnk is essential for its binding and for its down-regulation of MPLWT and MPLW515L. Lnk itself is tyrosine-phosphorylated following thrombopoietin stimulation. Further elucidating the cellular pathways that attenuate MPLW515L will provide insight into the pathogenesis of MPD and could help develop specific therapeutic approaches.

  11. Chronic Myeloproliferative Neoplasms Treatment

    Science.gov (United States)

    ... Treatment for information on diagnosis , staging , and treatment. Polycythemia Vera Key Points Polycythemia vera is a disease ... blood tests are used to diagnose polycythemia vera. Polycythemia vera is a disease in which too many ...

  12. Gene expression profiling of loss of TET2 and/or JAK2V617F mutant hematopoietic stem cells from mouse models of myeloproliferative neoplasms

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    Takuro Kameda

    2015-06-01

    Full Text Available Myeloproliferative neoplasms (MPNs are clinically characterized by the chronic overproduction of differentiated peripheral blood cells and the gradual expansion of malignant intramedullary/extramedullary hematopoiesis. In MPNs mutations in JAK2 MPL or CALR are detected mutually exclusive in more than 90% of cases [1,2]. Mutations in them lead to the abnormal activation of JAK/STAT signaling and the autonomous growth of differentiated cells therefore they are considered as “driver” gene mutations. In addition to the above driver gene mutations mutations in epigenetic regulators such as TET2 DNMT3A ASXL1 EZH2 or IDH1/2 are detected in about 5%–30% of cases respectively [3]. Mutations in TET2 DNMT3A EZH2 or IDH1/2 commonly confer the increased self-renewal capacity on normal hematopoietic stem cells (HSCs but they do not lead to the autonomous growth of differentiated cells and only exhibit subtle clinical phenotypes [4,6–8,5]. It was unclear how mutations in such epigenetic regulators influenced abnormal HSCs with driver gene mutations how they influenced the disease phenotype or whether a single driver gene mutation was sufficient for the initiation of human MPNs. Therefore we focused on JAK2V617F and loss of TET2—the former as a representative of driver gene mutations and the latter as a representative of mutations in epigenetic regulators—and examined the influence of single or double mutations on HSCs (Lineage−Sca-1+c-Kit+ cells (LSKs by functional analyses and microarray whole-genome expression analyses [9]. Gene expression profiling showed that the HSC fingerprint genes [10] was statistically equally enriched in TET2-knockdown-LSKs but negatively enriched in JAK2V617F–LSKs compared to that in wild-type-LSKs. Double-mutant-LSKs showed the same tendency as JAK2V617F–LSKs in terms of their HSC fingerprint genes but the expression of individual genes differed between the two groups. Among 245 HSC fingerprint genes 100 were more

  13. The impact of interferon-alpha2 on HLA genes in patients with polycythemia vera and related neoplasms

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

    2017-01-01

    Gene expression profiling in Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) have unraveled significant deregulation of several immune and inflammation genes of potential importance for clonal evolution. Other mechanisms might be downregulation of major histocompatibility class ...

  14. Concurrence of B-lymphoblastic leukemia and myeloproliferative neoplasm with copy neutral loss of heterozygosity at chromosome 1p harboring a MPL W515S mutation.

    Science.gov (United States)

    Tao, Jiangchuan; Zhang, Xiaohui; Lancet, Jeffrey; Bennett, John M; Cai, Li; Papenhausen, Peter; Moscinski, Lynn; Zhang, Ling

    2014-01-01

    B-lymphoblastic leukemia (B-ALL) is a neoplasm of precursors committed to B-cell lineage, whereas myeloproliferative neoplasm (MPN) is a clonal proliferation derived from myeloid stem cells. Concurrent B-ALL with MPN is uncommon except in the presence of abnormalities of the PDGFRA, PDGFRB, or FGFR1 genes or the BCR-ABL1 fusion gene. Herein, we describe a rare concurrence, B-ALL with MPN without the aforementioned genetic aberrations, in a 64-year-old male patient. The patient was initially diagnosed with B-ALL with normal karyotype and responded well to aggressive chemotherapy but had sustained leukocytosis and splenomegaly. The posttreatment restaging bone marrow was free of B-ALL but remained hypercellular with myeloid predominance. Using a single nucleotide polymorphism microarray study, we identified a copy neutral loss of heterozygosity at the terminus of 1p in the bone marrow samples taken at diagnosis and again at remission, 49% and 100%, respectively. Several additional genetic abnormalities were present in the initial marrow sample but not in the remission marrow samples. Retrospective molecular studies detected a MPL W515S homozygous mutation in both the initial and remission marrows for B-ALL, at 30-40% and 80% dosage effect, respectively. In summary, we present a case of concurrent B-ALL and MPN and demonstrate a stepwise cytogenetic and molecular approach to the final diagnosis. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms.

    Science.gov (United States)

    Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

    2011-07-01

    Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC(50)) of MPLW515L mutations or the TEL-JAK2 fusion gene; IC(50)=11-120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs.

  16. Acquired copy-neutral loss of heterozygosity of chromosome 1p as a molecular event associated with marrow fibrosis in MPL-mutated myeloproliferative neoplasms.

    Science.gov (United States)

    Rumi, Elisa; Pietra, Daniela; Guglielmelli, Paola; Bordoni, Roberta; Casetti, Ilaria; Milanesi, Chiara; Sant'Antonio, Emanuela; Ferretti, Virginia; Pancrazzi, Alessandro; Rotunno, Giada; Severgnini, Marco; Pietrelli, Alessandro; Astori, Cesare; Fugazza, Elena; Pascutto, Cristiana; Boveri, Emanuela; Passamonti, Francesco; De Bellis, Gianluca; Vannucchi, Alessandro; Cazzola, Mario

    2013-05-23

    We studied mutations of MPL exon 10 in patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF), first investigating a cohort of 892 consecutive patients. MPL mutation scanning was performed on granulocyte genomic DNA by using a high-resolution melt assay, and the mutant allele burden was evaluated by using deep sequencing. Somatic mutations of MPL, all but one involving codon W515, were detected in 26/661 (4%) patients with ET, 10/187 (5%) with PMF, and 7/44 (16%) patients with post-ET myelofibrosis. Comparison of JAK2 (V617F)-mutated and MPL-mutated patients showed only minor phenotypic differences. In an extended group of 62 MPL-mutated patients, the granulocyte mutant allele burden ranged from 1% to 95% and was significantly higher in patients with PMF or post-ET myelofibrosis compared with those with ET. Patients with higher mutation burdens had evidence of acquired copy-neutral loss of heterozygosity (CN-LOH) of chromosome 1p in granulocytes, consistent with a transition from heterozygosity to homozygosity for the MPL mutation in clonal cells. A significant association was found between MPL-mutant allele burden greater than 50% and marrow fibrosis. These observations suggest that acquired CN-LOH of chromosome 1p involving the MPL location may represent a molecular mechanism of fibrotic transformation in MPL-mutated myeloproliferative neoplasms.

  17. Protracted Clonal Trajectory of a JAK2 V617F-Positive Myeloproliferative Neoplasm Developing during Long-Term Remission from Acute Myeloid Leukemia

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    Stephen E. Langabeer

    2018-01-01

    Full Text Available Although transformation of the myeloproliferative neoplasms (MPNs to acute myeloid leukemia (AML is well documented, development of an MPN in patients previously treated for, and in remission from, AML is exceedingly rare. A case is described in which a patient was successfully treated for AML and in whom a JAK2 V617F-positive MPN was diagnosed after seven years in remission. Retrospective evaluation of the JAK2 V617F detected a low allele burden at AML diagnosis and following one course of induction chemotherapy. This putative chemoresistant clone subsequently expanded over the intervening seven years, resulting in a hematologically overt MPN. As AML relapse has not occurred, the MPN may have arose in a separate initiating cell from that of the AML. Alternatively, both malignancies possibly evolved from a common precursor defined by a predisposition mutation with divergent evolution into MPN through acquisition of the JAK2 V617F and AML through acquisition of different mutations. This case emphasizes the protracted time frame from acquisition of a disease-driving mutation to overt MPN and further underscores the clonal complexity in MPN evolution.

  18. Efficacy of NS-018, a potent and selective JAK2/Src inhibitor, in primary cells and mouse models of myeloproliferative neoplasms

    International Nuclear Information System (INIS)

    Nakaya, Y; Shide, K; Niwa, T; Homan, J; Sugahara, S; Horio, T; Kuramoto, K; Kotera, T; Shibayama, H; Hori, K; Naito, H; Shimoda, K

    2011-01-01

    Aberrant activation of Janus kinase 2 (JAK2) caused by somatic mutation of JAK2 (JAK2V617F) or the thrombopoietin receptor (MPLW515L) plays an essential role in the pathogenesis of myeloproliferative neoplasms (MPNs), suggesting that inhibition of aberrant JAK2 activation would have a therapeutic benefit. Our novel JAK2 inhibitor, NS-018, was highly active against JAK2 with a 50% inhibition (IC 50 ) of <1 n, and had 30–50-fold greater selectivity for JAK2 over other JAK-family kinases, such as JAK1, JAK3 and tyrosine kinase 2. In addition to JAK2, NS-018 inhibited Src-family kinases. NS-018 showed potent antiproliferative activity against cell lines expressing a constitutively activated JAK2 (the JAK2V617F or MPLW515L mutations or the TEL–JAK2 fusion gene; IC 50 =11–120 n), but showed only minimal cytotoxicity against most other hematopoietic cell lines without a constitutively activated JAK2. Furthermore, NS-018 preferentially suppressed in vitro erythropoietin-independent endogenous colony formation from polycythemia vera patients. NS-018 also markedly reduced splenomegaly and prolonged the survival of mice inoculated with Ba/F3 cells harboring JAK2V617F. In addition, NS-018 significantly reduced leukocytosis, hepatosplenomegaly and extramedullary hematopoiesis, improved nutritional status, and prolonged survival in JAK2V617F transgenic mice. These results suggest that NS-018 will be a promising candidate for the treatment of MPNs

  19. Antecedent cardiovascular disease and autoimmunity in Philadelphia-negative chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Sørensen, Anders Lindholm; Hasselbalch, Hans K

    2016-01-01

    leukemia (CLL) patients. Odds ratios (ORs) and p-values using Fischer's exact tests were calculated. The data was adjusted for confounding effects by logistic regression. Results: A significantly increased risk of MPNs compared to CLL was observed in subjects with a prior history of any autoimmune disease...... (OR = 1.86, 95%CI 1.16-2.98). A positive association between JAK2-V617F positive MPN and any autoimmune disease was observed at follow-up (OR = 2.62, 95% CI 1.21-5.67). A significantly increased risk of MPN compared to CLL was also observed in subjects with prior thromboembolic events (TE-events) (OR...... in the hematopoietic stem cell resulting in MPNs, or whether this association actually reflects a long-lasting pre-MPN-diagnosis phase, in which the MPN-disease per se contributes to a chronic inflammatory state and immune deregulation....

  20. Whole blood transcriptional profiling reveals deregulation of oxidative and antioxidative defence genes in myelofibrosis and related neoplasms. Potential implications of downregulation of Nrf2 for genomic instability and disease progression

    DEFF Research Database (Denmark)

    Hasselbalch, Hans Carl; Thomassen, Mads; Riley, Caroline Hasselbalch

    2014-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms - essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) (MPNs) - have recently been shown to be associated with chronic inflammation, oxidative stress and accumulation of reactive oxygen species (ROS). Using...

  1. Low frequency of c-MPL gene mutations in Iranian patients with Philadelphia-negative myeloproliferative disorders.

    Science.gov (United States)

    Ghotaslou, A; Nadali, F; Chahardouli, B; Alizad Ghandforosh, N; Rostami, S H; Alimoghaddam, K; Ghavamzadeh, A

    2015-01-01

    Myeloproliferative disorders are a group of diseases characterized by increased proliferation of myeloid lineage. In addition to JAK2V617F mutation, several mutations in the c-MPL gene have been reported in patients with philadelphia-negative chronic myeloproliferative disorders that could be important in the pathogenesis of diseases. The aim of the present study was to investigate the frequency of c-MPL and JAK2V617F mutations in Iranian patients with Philadelphia-negativemyeloproliferative disorders. Peripheral blood samples were collected from 60 patients with Philadelphia-negative MPD) Subgroups ET and PMF) and 25 healthy subjects as control group. The mutation status of c-MPL and Jak2V617F were investigated by using Amplification-refractory mutation system (ARMS) and Allele-Specific PCR (AS-PCR), respectively. The results were confirmed by sequencing. Among 60 patients, 34 (56.6%) and 1(1.7%) had Jak2V617F and c-MPL mutation, respectively. Patients with Jak2V617F mutation had higher WBC counts and hemoglobin concentration than those without the mutation (p= 0.005, p=0.003). In addition, for all healthy subjects in control group, mutations were negative. The present study revealed that the c-MPL mutations unlike the Jak2V617F mutations are rare in Iranian patients with Ph-negative MPNs and the low mutation rate should be considered in the design of screening strategies of MPD patients.

  2. Rare Cancers and Social Media: Analysis of Twitter Metrics in the First 2 Years of a Rare-Disease Community for Myeloproliferative Neoplasms on Social Media-#MPNSM.

    Science.gov (United States)

    Pemmaraju, Naveen; Utengen, Audun; Gupta, Vikas; Kiladjian, Jean-Jacques; Mesa, Ruben; Thompson, Michael A

    2017-12-01

    The use of social media has now become a standard means of communication for many individuals worldwide. The use of one specific form of social media, Twitter, has increased among healthcare providers, both as a means of information gathering and as a conduit for original content creation. Recently, major efforts by users have been put forward to help streamline the unprecedented amount of information that can be found on Twitter. These efforts have led to the creation of diseasespecific hashtag (#) medical communities and have greatly enhanced the ability to understand and better categorize the available data on Twitter. Specifically, for those involved in rare cancer fields, adhering to organically designed and consistently used hashtags has led to the rapid, reliable dissemination of information and the ability to efficiently discuss and debate topics of interest in the field. For the field of myeloproliferative neoplasms (MPNs), the creation of #MPNSM (myeloproliferative neoplasms on social media) in 2015 has facilitated interactions among healthcare stakeholders from all over the world in the MPN field. In order to better understand the trends and topics of interest to Twitter users of this novel medical community, we conducted the present analysis which focuses on Twitter analytics from the first two years of #MPNSM. In this analysis, we observed a sustained increase in the number of Twitter users, number of tweets, number of impressions, and number of retweets over time, demonstrating the feasibility of creating and maintaining a disease-specific hashtag for a rare cancer over time.

  3. The JAK2 V617F mutation involves B- and T-lymphocyte lineages in a subgroup of patients with Philadelphia-chromosome negative chronic myeloproliferative disorders

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Christensen, Jacob Haaber; Hasselbalch, Hans Carl

    2007-01-01

    The JAK2 V617F mutation is a frequent genetic event in the three classical Philadelphia-chromosome negative chronic myeloproliferative disorders (Ph(neg.)-CMPD), polycythemia vera (PV), essential thrombocythemia (ET) and idiopathic myelofibrosis (IMF). Its occurrence varies in frequency in regards...

  4. An International MDS/MPN Working Group’s perspective and recommendations on molecular pathogenesis, diagnosis and clinical characterization of myelodysplastic/myeloproliferative neoplasms

    Science.gov (United States)

    Mughal, Tariq I.; Cross, Nicholas C.P.; Padron, Eric; Tiu, Ramon V.; Savona, Michael; Malcovati, Luca; Tibes, Raoul; Komrokji, Rami S.; Kiladjian, Jean-Jacques; Garcia-Manero, Guillermo; Orazi, Attilio; Mesa, Ruben; Maciejewski, Jaroslaw P.; Fenaux, Pierre; Itzykson, Raphael; Mufti, Ghulam; Solary, Eric; List, Alan F.

    2015-01-01

    In the 2008 WHO classification, chronic myeloid malignancies that share both myelodysplastic and myeloproliferative features define the myelodysplastic/myeloproliferative group, which includes chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, atypical chronic myeloid leukemia, refractory anemia with ring sideroblasts and thrombocytosis, and myelodysplastic/myeloproliferative unclassified. With the notable exception of refractory anemia with ring sideroblasts and thrombocytosis, there is much overlap among the various subtypes at the molecular and clinical levels, and a better definition of these entities, an understanding of their biology and an identification of subtype-specific molecular or cellular markers are needed. To address some of these challenges, a panel comprised of laboratory and clinical experts in myelodysplastic/myeloproliferative was established, and four independent academic MDS/MPN workshops were held on: 9th March 2013, in Miami, Florida, USA; 6th December 2013, in New Orleans, Louisiana, USA; 13th June 2014 in Milan, Italy; and 5th December 2014 in San Francisco, USA. During these meetings, the current understanding of these malignancies and matters of biology, diagnosis and management were discussed. This perspective and the recommendations on molecular pathogenesis, diagnosis and clinical characterization for adult onset myelodysplastic/myeloproliferative is the result of a collaborative project endorsed and supported by the MDS Foundation. PMID:26341525

  5. Recent advances in the bcr-abl negative chronic myeloproliferative diseases

    Directory of Open Access Journals (Sweden)

    Stroncek David F

    2006-10-01

    Full Text Available Abstract The chronic myeloproliferative disorders are clonal hematopoietic stem cell disorders of unknown etiology. In one of these (chronic myeloid leukemia, there is an associated pathognomonic chromosomal abnormality known as the Philadelphia chromosome. This leads to constitutive tyrosine kinase activity which is responsible for the disease and is used as a target for effective therapy. This review concentrates on the search in the other conditions (polycythemia vera, essential thrombocythemia and idiopathic mylofibrosis for a similar biological marker with therapeutic potential. There is no obvious chromosomal marker in these conditions and yet evidence of clonality can be obtained in females by the use of X-inactivation patterns. PRV-1mRNA over expression, raised vitamin B12 levels and raised neutrophil alkaline phosphatase scores are evidence that cells in these conditions have received excessive signals for proliferation, maturation and reduced apoptosis. The ability of erythroid colonies to grow spontaneously without added external erythropoietin in some cases, provided a useful marker and a clue to this abnormal signaling. In the past year several important discoveries have been made which go a long way in elucidating the involved pathways. The recently discovered JAK2 V617F mutation which occurs in the majority of cases of polycythemia vera and in about half of the cases with the two other conditions, enables constitutive tyrosine kinase activity without the need for ligand binding to hematopoietic receptors. This mutation has become the biological marker for these conditions and has spurred the development of a specific therapy to neutralize its effects. The realization that inherited mutations in the thrombopoietin receptor (c-Mpl can cause a phenotype of thrombocytosis such as in Mpl Baltimore (K39N and in a Japanese family with S505A, has prompted the search for acquired mutations in this receptor in chronic myeloproliferative

  6. Clinical Characteristics of Cerebrovascular Pathology with Patients Suffering from Ph-Negative Myeloproliferative Disease

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    Marine M. Tanashyan

    2016-09-01

    Full Text Available Background: Disturbances of microcirculation play a significant role in the development and progression of both acute and chronic cerebrovascular diseases (CVD and may be associated with different hemogram abnormalities. One of the reasons of the prothrombogenic state of the endothelium is the increase in the number of blood corpuscles leading to (non-Ph myeloproliferative disorders (MPD including essential thrombocythemia (ET, polycythemia vera (PV, and primary myelofibrosis (PM. Materials and Methods: The study included 167 patients: 102 patients with Ph-MPD and the control group comprising 65 patients with CVD. According to MPD subtype, the patients were divided into three groups: patients with ET (37%, n = 38, male/female 7/31, age 52 ± 7 years, those with PV (40%, n = 41, male/female 20/21, age 50 ± 6 years and those with PM (23%, n = 23, male/female 5/18, age 54 ± 4 years. Results: In 79% (n = 81 of cases in the study group (with Ph-MPD, patients had chronic CVD, with the most frequently identified symptoms being asthenia (92% and headache (72%. Headache in Ph-MPD patients was more frequently (86% associated with PM, while in patients with PV and ET it was equally distributed (70%. Neurological symptoms in 53% of cases were associated with focal changes of the brain on MRI localized in the subcortical area of the frontal and parietal lobes. Twenty-one (21% patients suffered an acute cerebrovascular accident, 8 of them had thrombotic occlusion of one of the internal carotid arteries leading to hemispheric infarcts. Endothelial function (as measured by flow-dependent dilation of the brachial artery was severely impaired in all study groups (median 5% with normal cut-off at 10%, the lowest degree of vasodilator activity being specific for patients with a history of stroke (p = 0.011. Conclusion: Patients suffering from MPD had asymptomatic focal changes in the brain in the absence of concomitant vascular disease (hypertension

  7. A nationwide population-based cross-sectional survey of health-related quality of life in patients with myeloproliferative neoplasms in Denmark (MPNhealthSurvey: survey design and characteristics of respondents and nonrespondents

    Directory of Open Access Journals (Sweden)

    Brochmann N

    2017-03-01

    Full Text Available Nana Brochmann,1 Esben Meulengracht Flachs,2 Anne Illemann Christensen,3 Christen Lykkegaard Andersen,1 Knud Juel,3 Hans Carl Hasselbalch,1 Ann-Dorthe Zwisler4 1Department of Hematology, Zealand University Hospital, University of Copenhagen, Roskilde, 2Department of Occupational and Environmental Medicine, Bispebjerg University Hospital, Copenhagen, 3National Institute of Public Health, University of Southern Denmark, Copenhagen, 4Danish Knowledge Centre for Rehabilitation and Palliative Care, University of Southern Denmark and Odense University Hospital, Odense, Denmark Objective: The Department of Hematology, Zealand University Hospital, Denmark, and the National Institute of Public Health, University of Southern Denmark, created the first nationwide, population-based, and the most comprehensive cross-sectional health-related quality of life (HRQoL survey of patients with myeloproliferative neoplasms (MPNs. In Denmark, all MPN patients are treated in public hospitals and treatments received are free of charge for these patients. Therefore, MPN patients receive the best available treatment to the extent of its suitability for them and if they wish to receive the treatment. The aims of this article are to describe the survey design and the characteristics of respondents and nonrespondents. Material and methods: Individuals with MPN diagnoses registered in the Danish National Patient Register (NPR were invited to participate. The registers of the Danish Civil Registration System and Statistics Denmark provided information regarding demographics. The survey contained 120 questions: validated patient-reported outcome (PRO questionnaires and additional questions addressing lifestyle. Results: A total of 4,704 individuals were registered with MPN diagnoses in the NPR of whom 4,236 were eligible for participation and 2,613 (62% responded. Overall, the respondents covered the broad spectrum of MPN patients, but patients 70–79 years old, living with

  8. A new era for IFN-α in the treatment of Philadelphia-negative chronic myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Hasselbalch, H.C.

    2011-01-01

    In recent years, several studies have shown that IFN-α2 is able to induce molecular remissions with undetectable JAK2V617F in a subset of patients with essential thrombocythemia (ET) and polycythemia vera (PV), even with normalization of the bone marrow and sustained molecular remissions after...

  9. Neoplasias mieloproliferativas: revisão dos critérios diagnósticos e dos aspectos clínicos Myeloproliferative neoplasms: a review of diagnostic criteria and clinical aspects

    Directory of Open Access Journals (Sweden)

    Maria de Lourdes L. F. Chauffaille

    2010-01-01

    Full Text Available As síndromes mieloproliferativas crônicas, atualmente denominadas neoplasias mieloproliferativas (NMP, de acordo com a 4ª. edição da classificação da Organização Mundial da Saúde (OMS, são doenças clonais de célula-tronco hematopoética, nas quais há a proliferação aumentada de uma ou mais das séries mieloides (granulocítica, eritrocítica, megacariocítica ou mastocítica com maturação eficaz. A progressão de todas é caracterizada por fibrose medular ou transformação leucêmica. Pela classificação da OMS, as NMP incluem: leucemia mieloide crônica (LMC, policitemia vera (PV, mielofibrose idiopática crônica (MF, trombocitemia essencial (TE, leucemia neutrofílica crônica (LNC, leucemia eosinofílica crônica não especificada(LEC, mastocitose (M e neoplasia mieloproliferativa inclassificável (NMI. É interessante notar que tanto a LMC (BCR/ABL1 como PV, MF e TE (JAK2 V617F e éxon 12, MPLW515L/K e M (KITD816V tiveram suas bases moleculares desvendadas e apresentam em comum a ativação constitutiva de tirosino-quinase graças às mutações adquiridas pela célula-tronco hematopoética. A mutação JAK2 V617F é observada em mais de 90% dos casos de PV, mas também em cerca de 50%-60% das MF e TE, levando ao questionamento de como uma única lesão molecular desencadeia três manifestações clínicas diversas. Já há evidências de que eventos genéticos e epigenéticos adicionais contribuem para a patogênese, tais como MPLW515L e MPLW515K. No presente manuscrito são apresentados os aspectos clínicos, a fisiopatologia e os critérios diagnósticos das diferentes NMP.Chronic myeloproliferative disorders, currently called myeloproliferative neoplasms (MPN, according to the 4th edition of the World Health Organization (WHO classification are clonal diseases of hematopoietic stem cells, in which there is increased proliferation of the myeloid series (granulocytic, erythrocytic, megakaryocytic series or mast cells

  10. EXEL-8232, a small-molecule JAK2 inhibitor, effectively treats thrombocytosis and extramedullary hematopoiesis in a murine model of myeloproliferative neoplasm induced by MPLW515L.

    Science.gov (United States)

    Wernig, G; Kharas, M G; Mullally, A; Leeman, D S; Okabe, R; George, T; Clary, D O; Gilliland, D G

    2012-04-01

    About 10% of patients with essential thrombocythemia (ET) or myelofibrosis (MF) that lack mutations in JAK2 harbor an activating mutation in the thrombopoietin receptor, MPLW515L. Distinct from the JAK2V617F retroviral transplant model, the MPLW515L model recapitulates many features of ET and MF, including severe fibrosis and thrombocytosis. We have tested EXEL-8232, an experimental potent JAK2 inhibitor, for efficacy in suppression of thrombocytosis in vivo and for its ability to attenuate MPLW515L myeloproliferative disease. EXEL-8232 was administered for 28 days q12 h by oral gavage at doses of 30 or 100 mg/kg, prospectively. Animals treated with EXEL-8232 at 100 mg/kg had normalized high platelet counts, eliminated extramedullary hematopoiesis in the spleen and eliminated bone marrow fibrosis, whereas the wild-type controls did not develop thrombocytopenia. Consistent with a clinical response in this model, we validated surrogate end points for response to treatment, including a reduction of endogenous colony growth and signaling inhibition in immature erythroid and myeloid primary cells both in vitro and upon treatment in vivo. We conclude that EXEL-8232 has efficacy in treatment of thrombocytosis in vivo in a murine model of ET and MF, and may be of therapeutic benefit for patients with MPL-mutant MPN.

  11. Histomorphologic spectrum of BAP1 negative melanocytic neoplasms in a family with BAP1-associated cancer susceptibility syndrome.

    Science.gov (United States)

    Marušić, Zlatko; Buljan, Marija; Busam, Klaus J

    2015-06-01

    Multiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms. We report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1-associated cancer susceptibility syndrome. The neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up. We report two new cases of melanoma arising in a BAP1-deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1-deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. Oncogenes in myeloproliferative disorders.

    Science.gov (United States)

    Tefferi, Ayalew; Gilliland, D Gary

    2007-03-01

    Myeloproliferative disorders (MPDs) constitute a group of hematopoietic malignancies that feature enhanced proliferation and survival of one or more myeloid lineage cells. William Dameshek is credited for introducing the term "MPDs" in 1951 when he used it to group chronic myeloid leukemia (CML), polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) under one clinicopathologic category. Since then, other myeloid neoplasms have been added to the MPD member list: chronic neutrophilic (CNL), eosinophilic (CEL) and myelomonocytic (CMML) leukemias; juvenile myelomonocytic leukemia (JMML); hypereosinophilic syndrome (HES); systemic mastocytosis (SM); and others. Collectively, MPDs are stem cell-derived clonal proliferative diseases whose shared and diverse phenotypic characteristics can be attributed to dysregulated signal transduction--a consequence of acquired somatic mutations. The most recognized among the latter is BCR-ABL, the disease-causing mutation in CML. Other mutations of putative pathogenetic relevance in MPDs include: JAK2V617F in PV, ET, and PMF; JAK2 exon 12 mutations in PV; MPLW515L/K in PMF and ET; KITD816V in SM; FIP1L1-PDGFRA in CEL-SM; rearrangements of PDGFRB in CEL-CMML and FGFR1 in stem cell leukemia-lymphoma syndrome; and RAS/PTPN11/NF1 mutations in JMML. This increasing repertoire of mutant molecules has streamlined translational research and molecularly targeted drug development in MPDs.

  13. Lympho- and Myeloproliferative Malignancies Occurring in the Same Host: Description of a Nationwide Discovery Cohort

    DEFF Research Database (Denmark)

    Holst, Johanne Marie; Plesner, Trine Lindhardt; Pedersen, Martin Bjerregård

    2017-01-01

    Background: So far, myeloid and lymphoid malignancies have been considered as diseases with distinct pathogenetic mechanisms. However, recent studies (Frederiksen H et al, Blood 2011) have reported an increased risk of lymphoid malignancies in patients with chronic myeloproliferative neoplasms (M...

  14. Treatment Options for Chronic Myeloproliferative Neoplasms

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options for primary myelofibrosis. Prognosis (chance of recovery ) depends ... factors affect prognosis (chance of recovery) and treatment options for essential thrombocythemia. Prognosis (chance of recovery ) and ...

  15. Treatment Option Overview (Myelodysplastic/Myeloproliferative Neoplasms)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ... factors affect prognosis (chance of recovery) and treatment options. The prognosis (chance of recovery ) and treatment options ...

  16. Treatment Option Overview (Chronic Myeloproliferative Neoplasms)

    Science.gov (United States)

    ... factors affect prognosis (chance of recovery) and treatment options for primary myelofibrosis. Prognosis (chance of recovery ) depends ... factors affect prognosis (chance of recovery) and treatment options for essential thrombocythemia. Prognosis (chance of recovery ) and ...

  17. General Information about Chronic Myeloproliferative Neoplasms

    Science.gov (United States)

    ... Treatment for information on diagnosis , staging , and treatment. Polycythemia Vera Key Points Polycythemia vera is a disease ... blood tests are used to diagnose polycythemia vera. Polycythemia vera is a disease in which too many ...

  18. Myeloid Neoplasms in the Guise of Nutritional Deficiency

    Science.gov (United States)

    Parthasarathy, Veda

    2012-01-01

    The classic BCR-ABL-negative myeloproliferative neoplasms (MPNs) which include polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are among the most frequent hematologic neoplasms. Because of their relatively smooth clinical course, it is likely that many of these MPNs actually go undetected. Considering the high prevalence of iron, folic-acid, and vitamin B12 deficiencies in developing countries, their coexistence with MPN can be expected frequently. In such situations where both disorders coexist, MPN is often overlooked. This causes considerable diagnostic delay. In this paper, two cases of PMF and one case of PV where the diagnosis of MPN was delayed for about 3 years are discussed. Presence of concomitant vitamin B12, folate, and iron deficiencies perhaps camouflaged the underlying MPN. Bearing in mind the possibility of MPN, even in the setting of apparent nutritional deficiency and performing a bone marrow evaluation, is the crucial step in unveiling the hidden MPN. PMID:23227377

  19. Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

    DEFF Research Database (Denmark)

    Riley, C.H.; Morten Krogh, Jensen; Brimnes, M.K.

    2011-01-01

    Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these ......Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone...

  20. Chronic myeloproliferative disorders: A rarest case with oral manifestations and dental management

    Directory of Open Access Journals (Sweden)

    Pritesh B Ruparelia

    2012-01-01

    Full Text Available Chronic myeloproliferative disorders (CMPD are rarest hematological disorders (malignant myeloid neoplasms. The three most common chronic myeloproliferative disorders are polycythemia vera, essential thrombocythemia and chronic idiopathic myelofibrosis. Clinical manifestations (including oral manifestations of these disorders are overlapping with each other and with other hematologic disorders, which makes the diagnosis of CMPD a challenging task. In this article we report a rare to rarest case of CMPD at dental outpatient department, its oral manifestations and its management in dental clinics.

  1. Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms: a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study.

    Science.gov (United States)

    Jovanovic, J V; Ivey, A; Vannucchi, A M; Lippert, E; Oppliger Leibundgut, E; Cassinat, B; Pallisgaard, N; Maroc, N; Hermouet, S; Nickless, G; Guglielmelli, P; van der Reijden, B A; Jansen, J H; Alpermann, T; Schnittger, S; Bench, A; Tobal, K; Wilkins, B; Cuthill, K; McLornan, D; Yeoman, K; Akiki, S; Bryon, J; Jeffries, S; Jones, A; Percy, M J; Schwemmers, S; Gruender, A; Kelley, T W; Reading, S; Pancrazzi, A; McMullin, M F; Pahl, H L; Cross, N C P; Harrison, C N; Prchal, J T; Chomienne, C; Kiladjian, J J; Barbui, T; Grimwade, D

    2013-10-01

    Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

  2. Myeloid Neoplasms with t(5;12 and ETV6-ACSL6 Gene Fusion, Potential Mimickers of Myeloid Neoplasm with PDGFRB Rearrangement: Case Report with Imatinib Therapy and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Javier De Luca-Johnson

    2016-01-01

    Full Text Available We report the second case of ETV6-ACSL6 associated myeloproliferative neoplasm that has received a full course of imatinib therapy. The patient was a 51-year-old previously healthy man who presented with three months of worsening dyspnea and was found to have a white count of 216,000/cmm, of which 84% were eosinophil lineage. Cytogenetic analysis revealed a t(5;12(q31~33;p13. FISH was negative for PDGFRB rearrangement but additional FISH testing demonstrated an ACSL6 rearrangement. ETV6-ACSL6 gene fusion is a rare abnormality that most often presents as a myeloproliferative-type disorder with prominent eosinophilia or basophilia. Review of the literature yielded a total of 11 previous cases. This gene fusion results in a t(5;12(q31~33;p13 that mimics the t(5;12 found in ETV6-PDGFRB neoplasms. Identification of the fusion genes involved in t(5;12 in eosinophilia-associated myeloproliferative disorders is crucial to direct an effective treatment plan. In particular, while tyrosine kinase inhibitor therapy is effective in patients with PDGFRB rearrangement, there is little information on imatinib efficacy in patients with ETV6-ACSL6 gene fusion. Our patient was found to be nonresponsive to imatinib therapy.

  3. Colon neoplasm

    International Nuclear Information System (INIS)

    Kimura F, K.

    1991-01-01

    The main aspects of colon neoplasms are described, including several factors that predispose the disease, the occurrence, the main biomedical radiography and the evaluation after the surgery. (C.G.C.)

  4. Group G streptococcal myositis in a patient with myeloproliferative neoplasm

    Directory of Open Access Journals (Sweden)

    Monica Midha, MD MBS

    2016-01-01

    Full Text Available While many cases of streptococcal infection are due to Lancefield groups A and B, there has been a rise in reported cases of infections due to group G streptococcus. We present a case of an individual with a hematologic malignancy who developed myositis secondary to group G streptococcus, with no clearly identifiable source of infection. The patient was managed with antibiotic therapy rather than surgical intervention due to high surgical risk related to severe thrombocytopenia. Targeted antibiotics initiated early in the course of disease may prevent the need for surgical intervention. Early diagnosis and treatment are critical to avoid the high morbidity and mortality of life-threatening infections caused by group G streptococcus.

  5. World Health Organization-defined classification of myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Madelung, Ann Brinch; Bondo, Henrik; Stamp, Inger

    2013-01-01

    marrow biopsies including 43 controls. Diagnoses were determined according to the 2008 criteria of the World Health Organization (WHO). The participants were blinded to all clinical data except patient age. After initial evaluation all hematopathologists participated in a 3-day meeting with a leading...... clinician chaired by an expert hematopathologists. In cases with lack of consensus on fiber grading (n = 57), a new evaluation was performed. In cases with discordance on morphological diagnosis (n = 129), an additional nonblinded evaluation taking clinical data into consideration was carried out...

  6. Inflammation as a Driver of Clonal Evolution in Myeloproliferative Neoplasm

    Science.gov (United States)

    2017-10-01

    cell line RAW264.7. We will measure TNF and IL-10 at 0, 3, 6, 9, 18, and 24 hours after LPS stimulation by intracellular flow cytometry, ELISA , and...and MIG empty vector transplanted mice and stimulate with LPS for 24 hours. The amount of TNF in the supernatant will be quantified by ELISA ...were harvested and TNFα was measured by ELISA . Trametinib, but not ruxolitinib, reduced TNFα production at all time points. 8 We next examined

  7. Adrenal neoplasms

    International Nuclear Information System (INIS)

    Low, G.; Dhliwayo, H.; Lomas, D.J.

    2012-01-01

    Adenoma, myelolipoma, phaeochromocytoma, metastases, adrenocortical carcinoma, neuroblastoma, and lymphoma account for the majority of adrenal neoplasms that are encountered in clinical practice. A variety of imaging methods are available for evaluating adrenal lesions including ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and nuclear medicine techniques such as meta-iodobenzylguanidine (MIBG) scintigraphy and positron-emission tomography (PET). Lipid-sensitive imaging techniques such as unenhanced CT and chemical shift MRI enable detection and characterization of lipid-rich adenomas based on an unenhanced CT attenuation of ≤10 HU and signal loss on opposed-phase compared to in-phase T1-weighted images, respectively. In indeterminate cases, an adrenal CT washout study may differentiate adenomas (both lipid-rich and lipid-poor) from other adrenal neoplasms based on an absolute percentage washout of >60% and/or a relative percentage washout of >40%. This is based on the principle that adenomas show rapid contrast washout while most other adrenal neoplasms including malignant tumours show slow contrast washout instead. 18 F-2-fluoro-2-deoxy-D-glucose–PET ( 18 FDG-PET) imaging may differentiate benign from malignant adrenal neoplasms by demonstrating high tracer uptake in malignant neoplasms based on the increased glucose utilization and metabolic activity found in most of these malignancies. In this review, the multi-modality imaging appearances of adrenal neoplasms are discussed and illustrated. Key imaging findings that facilitate lesion characterization and differentiation are emphasized. Awareness of these imaging findings is essential for improving diagnostic confidence and for reducing misinterpretation errors.

  8. Review of current classification, molecular alterations, and tyrosine kinase inhibitor therapies in myeloproliferative disorders with hypereosinophilia

    Directory of Open Access Journals (Sweden)

    Havelange V

    2013-08-01

    Full Text Available Violaine Havelange,1,2 Jean-Baptiste Demoulin1 1de Duve Institute, Université catholique de Louvain, Brussels, Belgium; 2Department of Hematology, Cliniques universitaires Saint-Luc, Université catholique de Louvain, Brussels, Belgium Abstract: Recent advances in our understanding of the molecular mechanisms underlying hypereosinophilia have led to the development of a 'molecular' classification of myeloproliferative disorders with eosinophilia. The revised 2008 World Health Organization classification of myeloid neoplasms included a new category called “myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB or FGFR1.” Despite the molecular heterogeneity of PDGFR (platelet-derived growth factor receptor rearrangements, tyrosine kinase inhibitors at low dose induce rapid and complete hematological remission in the majority of these patients. Other kinase inhibitors are promising. Further discoveries of new molecular alterations will direct the development of new specific inhibitors. In this review, an update of the classifications of myeloproliferative disorders associated with hypereosinophilia is discussed together with open and controversial questions. Molecular mechanisms and promising results of tyrosine kinase inhibitor treatments are reviewed. Keywords: hypereosinophilia, classification, myeloproliferative disorders, molecular alterations, tyrosine kinase inhibitor

  9. Increase in circulating CD4⁺CD25⁺Foxp3⁺ T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

    DEFF Research Database (Denmark)

    Riley, Caroline Hasselbalch; Jensen, Morten Krogh; Brimnes, Marie Klinge

    2011-01-01

    Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-a2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these ......Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-a2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone...

  10. [Diagnostic molecular pathology of lymphatic and myeloid neoplasms].

    Science.gov (United States)

    Klapper, W; Kreipe, H

    2015-03-01

    Molecular pathology has been an integral part of the diagnostics of tumors of the hematopoietic system substantially longer than for solid neoplasms. In contrast to solid tumors, the primary objective of molecular pathology in hematopoietic neoplasms is not the prediction of drug efficacy but the diagnosis itself by excluding reactive proliferation and by using molecular features for tumor classification. In the case of malignant lymphomas, the most commonly applied molecular tests are those for gene rearrangements for immunoglobulin heavy chains and T-cell receptors. However, this article puts the focus on new and diagnostically relevant assays in hematopathology. Among these are mutations of MYD88 codon 265 in lymphoplasmacytic lymphomas, B-raf V600E in hairy cell leukemia and Stat3 exon 21 in indolent T-cell lymphomas. In myeloproliferative neoplasms, MPL W515, calreticulin exon 9 and the BCR-ABL and JAK2 V617F junctions are the most frequently analyzed differentiation series. In myelodysplastic and myeloproliferative neoplasms, SRSF2, SETBP1 and CSF3R mutations provide important differential diagnostic information. Genes mutated in myelodysplastic syndromes (MDS) are particularly diverse but their analysis significantly improves the differential diagnostics between reactive conditions and MDS. The most frequent changes in MDS include mutations of TET2 and various genes encoding splicing factors.

  11. Nye molekylaere markører ved de kroniske myeloproliferative sygdomme

    DEFF Research Database (Denmark)

    Larsen, Thomas Stauffer; Pallisgaard, Niels; Christensen, Jacob Haaber

    2006-01-01

    The Philadelphia-negative chronic myeloproliferative disorders feature autonomous myeloid hyperproliferation and hypersensitivity to a number of growth factors, which most recently have been shown to be explained by a guanine-to-thymidine mutation in the Janus tyrosine kinase (JAK2) gene, implica...

  12. Outcomes following splenectomy in patients with myeloid neoplasms.

    Science.gov (United States)

    Rialon, Kristy L; Speicher, Paul J; Ceppa, Eugene P; Rendell, Victoria R; Vaslef, Steven N; Beaven, Anne; Tyler, Douglas S; Blazer, Dan G

    2015-03-15

    Myeloid neoplasms are classified into five major categories. These patients may develop splenomegaly and require splenectomy to alleviate mechanical symptoms, to ameliorate transfusion-dependent cytopenias, or to enhance stem cell transplantation. The objective of this study was to determine which clinical variables significantly impacted morbidity, mortality, and survival in patients with myeloid neoplasms undergoing splenectomy, and to determine if operative outcomes have improved over time. The records of all patients with myeloid neoplasms undergoing splenectomy from 1993 to 2010 were retrospectively reviewed. Eighty-nine patients (n = 89) underwent splenectomy for myeloid neoplasms. Over half of patients who had symptoms preoperatively had resolution of their symptoms post-splenectomy. The morbidity rate was 38%, with the most common complications being bleeding (14%) or infection (20%). Thirty-day mortality rate was 18% and median survival after splenectomy was 278 days. Decreased survival was associated with a diagnosis of myelodysplastic syndrome/myeloproliferative neoplasm, anemia, abnormal white blood cell count, and hypoalbuminemia. Patients who underwent stem cell transplantation did not show an increased risk for morbidity or mortality. Patients with myeloid neoplasms have a poor prognosis after splenectomy and the decision to operate is a difficult one, associated with high morbidity and mortality. © 2014 Wiley Periodicals, Inc.

  13. Gestational trophoblastic neoplasms

    International Nuclear Information System (INIS)

    Demas, B.E.; Hricak, H.; Braga, C.

    1988-01-01

    Twenty-four women with suspected gestational trophoblastic neoplasms were evaluated prospectively to identify imaging algorithms optimal for treatment planning. All underwent chest radiography, chest CT, hepatic and cranial CT or MR imaging, and pelvic MR imaging. Ten also underwent pelvic CT, 13 pelvic US. The most sensitive imaging combination was chest CT, hepatic and cranial CT or MR imaging, and pelvic MR imaging. However, correct assignment to ACOG therapeutic categories was achieved by means of history, physical examination, beta subunit of human chorionic gonadotropin measurements, and chest radiography in 81% of patients. Hepatic and cranial imaging defined the need for radiation therapy. Chest CT was needed only when chest radiographs were negative. Pelvic imaging aided diagnosis but did not assist in treatment planning

  14. The Bone Marrow-Mediated Protection of Myeloproliferative Neoplastic Cells to Vorinostat and Ruxolitinib Relies on the Activation of JNK and PI3K Signalling Pathways.

    Directory of Open Access Journals (Sweden)

    Bruno A Cardoso

    Full Text Available The classical BCR-ABL-negative Myeloproliferative Neoplasms (MPN are a group of heterogeneous haematological diseases characterized by constitutive JAK-STAT pathway activation. Targeted therapy with Ruxolitinib, a JAK1/2-specific inhibitor, achieves symptomatic improvement but does not eliminate the neoplastic clone. Similar effects are seen with histone deacetylase inhibitors (HDACi, albeit with poorer tolerance. Here, we show that bone marrow (BM stromal cells (HS-5 protected MPN-derived cell lines (SET-2; HEL and UKE-1 and MPN patient-derived BM cells from the cytotoxic effects of Ruxolitinib and the HDACi Vorinostat. This protective effect was mediated, at least in part, by the secretion of soluble factors from the BM stroma. In addition, it correlated with the activation of signalling pathways important for cellular homeostasis, such as JAK-STAT, PI3K, JNK, MEK-ERK and NF-κB. Importantly, the pharmacological inhibition of JNK and PI3K pathways completely abrogated the BM protective effect on MPN cell lines and MPN patient samples. Our findings shed light on mechanisms of tumour survival and may indicate novel therapeutic approaches for the treatment of MPN.

  15. The Bone Marrow-Mediated Protection of Myeloproliferative Neoplastic Cells to Vorinostat and Ruxolitinib Relies on the Activation of JNK and PI3K Signalling Pathways

    Science.gov (United States)

    Cardoso, Bruno A.; Belo, Hélio; Barata, João T.; Almeida, António M.

    2015-01-01

    The classical BCR-ABL-negative Myeloproliferative Neoplasms (MPN) are a group of heterogeneous haematological diseases characterized by constitutive JAK-STAT pathway activation. Targeted therapy with Ruxolitinib, a JAK1/2-specific inhibitor, achieves symptomatic improvement but does not eliminate the neoplastic clone. Similar effects are seen with histone deacetylase inhibitors (HDACi), albeit with poorer tolerance. Here, we show that bone marrow (BM) stromal cells (HS-5) protected MPN-derived cell lines (SET-2; HEL and UKE-1) and MPN patient-derived BM cells from the cytotoxic effects of Ruxolitinib and the HDACi Vorinostat. This protective effect was mediated, at least in part, by the secretion of soluble factors from the BM stroma. In addition, it correlated with the activation of signalling pathways important for cellular homeostasis, such as JAK-STAT, PI3K, JNK, MEK-ERK and NF-κB. Importantly, the pharmacological inhibition of JNK and PI3K pathways completely abrogated the BM protective effect on MPN cell lines and MPN patient samples. Our findings shed light on mechanisms of tumour survival and may indicate novel therapeutic approaches for the treatment of MPN. PMID:26623653

  16. Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Uzma Zaidi

    2017-07-01

    Full Text Available Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including TET2, BCOR, BCR, and ABL1 were identified in a triple negative essential thrombocythemia (ET patient. The individual role of some of these variants in disease pathogenesis has yet to be studied. Somatic mutations in the same genes have been reported with variable frequencies in myeloid malignancies. However, no pathogenic impact of these variants could be found; therefore, long-term follow up of patients with genetic analysis of a large cohort and the use of whole genome sequencing is required to assess the effects of these variants.

  17. The pseudokinase domain of JAK2 is a dual-specificity protein kinase that negatively regulates cytokine signaling

    DEFF Research Database (Denmark)

    Ungureanu, Daniela; Wu, Jinhua; Pekkala, Tuija

    2011-01-01

    Human JAK2 tyrosine kinase mediates signaling through numerous cytokine receptors. The JAK2 JH2 domain functions as a negative regulator and is presumed to be a catalytically inactive pseudokinase, but the mechanism(s) for its inhibition of JAK2 remains unknown. Mutations in JH2 lead to increased...... JAK2 activity, contributing to myeloproliferative neoplasms (MPNs). Here we show that JH2 is a dual-specificity protein kinase that phosphorylates two negative regulatory sites in JAK2: Ser523 and Tyr570. Inactivation of JH2 catalytic activity increased JAK2 basal activity and downstream signaling....... Notably, different MPN mutations abrogated JH2 activity in cells, and in MPN (V617F) patient cells phosphorylation of Tyr570 was reduced, suggesting that loss of JH2 activity contributes to the pathogenesis of MPNs. These results identify the catalytic activity of JH2 as a previously unrecognized...

  18. The neoplasms imagery

    International Nuclear Information System (INIS)

    Giger, M.; Pilizzari, CH.

    1996-01-01

    New devices of NMR imaging and computed tomography give three-dimensional images of the human body and automatically interpret the anatomical pictures. These new techniques are useful for the detection and the treatment of neoplasms. They are explained into details. (O.M.)

  19. Are chronic myeloproliferative neoplasms associated with age-related macular degeneration?

    DEFF Research Database (Denmark)

    Bak, M.; Sorensen, T. L.; Flachs, E. M.

    2015-01-01

    population-based matched cohort study using Danish registries. We included all patients age 18+ or older with a first listed diagnosis of MPN in the Danish National Patient Registry between 1994 and 2013. Patients with Essential Thrombocythemia (ET), Polycythemia Vera (PV), Myelofibrosis (MF), Unclassifiable...

  20. Age-Related Macular Degeneration in Patients With Chronic Myeloproliferative Neoplasms

    DEFF Research Database (Denmark)

    Bak, Marie; Sørensen, Torben Lykke; Flachs, Esben Meulengracht

    2017-01-01

    , and December 31, 2013, of essential thrombocythemia, polycythemia vera, myelofibrosis, or unclassifiable MPNs. For each patient, 10 age- and sex-matched controls were included. All patients without prior AMD were followed up from the date of diagnosis (or corresponding entry date for the controls) until......, 3063 with polycythemia vera, 547 with myelofibrosis, and 1720 with unclassifiable MPNs) and 4.3 (95% CI, 4.1-4.4) for the 77445 controls, while the 10-year risk of AMD was 2.4% (95% CI, 2.1%-2.8%) for patients with MPNs and 2.3% (95% CI, 2.2%-2.4%) for the controls. The risk of AMD was increased...... overall for patients with MPNs (adjusted HR, 1.3; 95% CI, 1.1-1.5), with adjusted HRs for the subtypes of 1.2 (95% CI, 1.0-1.6) for essential thrombocythemia, 1.4 (95% CI, 1.2-1.7) for polycythemia vera, 1.7 (95% CI, 0.8-4.0) for myelofibrosis, and 1.5 (95% CI, 1.1-2.1) for unclassifiable MPNs...

  1. Risk factors for neoplasms

    International Nuclear Information System (INIS)

    Brachner, A.; Grosche, B.

    1991-06-01

    A broad survey is given of risk factors for neoplasms. The main carcinogenic substances (including also ionizing radiation and air pollution) are listed, and are correlated with the risk factors for various cancers most frequently explained and discussed in the literature. The study is intended to serve as a basis for a general assessment of the incidence of neoplasms in children, and of cancer mortality in the entire population of Bavaria in the years 1983-1989, or 1979-1988, respectively, with the principal idea of drawing up an environment-related health survey. The study therefore takes into account not only ionizing radiation as a main risk factor, but also other risk factors detectable within the ecologic context, as e.g. industrial installations and their effects, refuse incineration plants or waste dumps, or the social status. (orig./MG) [de

  2. The Jak2 Inhibitor, G6, Alleviates Jak2-V617F–Mediated Myeloproliferative Neoplasia by Providing Significant Therapeutic Efficacy to the Bone Marrow

    Directory of Open Access Journals (Sweden)

    Annet Kirabo

    2011-11-01

    Full Text Available We recently developed a Janus kinase 2 (Jak2 small-molecule inhibitor called G6 and found that it inhibits Jak2-V617F– mediated pathologic cell growth in vitro, ex vivo, and in vivo. However, its ability to inhibit Jak2-V617F–mediated myeloproliferative neoplasia, with particular emphasis in the bone marrow, has not previously been examined. Here, we investigated the efficacy of G6 in a transgenic mouse model of Jak2-V617F–mediated myeloproliferative neoplasia. We found that G6 provided therapeutic benefit to the peripheral blood as determined by elimination of leukocytosis, thrombocytosis, and erythrocytosis. G6 normalized the pathologically high plasma concentrations of interleukin 6 (IL-6. In the liver, G6 eliminated Jak2-V617F–driven extramedullary hematopoiesis. With respect to the spleen, G6 significantly reduced both the spleno-megaly and megakaryocytic hyperplasia. In the critically important bone marrow, G6 normalized the pathologically high levels of phospho-Jak2 and phospho–signal transducer and activator of transcription 5 (STAT5. It significantly reduced the megakaryocytic hyperplasia in the marrow and completely normalized the M/E ratio. Most importantly, G6 selectively reduced the mutant Jak2 burden by 67% on average, with virtual elimination of mutant Jak2 cells in one third of all treated mice. Lastly, clonogenic assays using marrow stem cells from the myeloproliferative neoplasm mice revealed a time-dependent elimination of the clonogenic growth potential of these cells by G6. Collectively, these data indicate that G6 exhibits exceptional efficacy in the peripheral blood, liver, spleen, and, most importantly, in the bone marrow, thereby raising the possibility that this compound may alter the natural history of Jak2-V617F–mediated myeloproliferative neoplasia.

  3. MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients.

    Science.gov (United States)

    Pardanani, Animesh D; Levine, Ross L; Lasho, Terra; Pikman, Yana; Mesa, Ruben A; Wadleigh, Martha; Steensma, David P; Elliott, Michelle A; Wolanskyj, Alexandra P; Hogan, William J; McClure, Rebecca F; Litzow, Mark R; Gilliland, D Gary; Tefferi, Ayalew

    2006-11-15

    Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia vera, 318 with essential thrombocythemia (ET), 88 with myelodysplastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients. The diagnosis of patients with mutant MPL alleles at the time of molecular testing was de novo MMM in 12 patients, ET in 4, post-ET MMM in 1, and MMM in blast crisis in 3. Six patients carried the MPLW515L and JAK2V617F alleles concurrently. We conclude that MPLW515L or MPLW515K mutations are present in patients with MMM or ET at a frequency of approximately 5% and 1%, respectively, but are not observed in patients with polycythemia vera (PV) or other myeloid disorders. Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease.

  4. Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients.

    Science.gov (United States)

    Cabagnols, Xénia; Favale, Fabrizia; Pasquier, Florence; Messaoudi, Kahia; Defour, Jean Philippe; Ianotto, Jean Christophe; Marzac, Christophe; Le Couédic, Jean Pierre; Droin, Nathalie; Chachoua, Ilyas; Favier, Remi; Diop, M'boyba Khadija; Ugo, Valérie; Casadevall, Nicole; Debili, Najet; Raslova, Hana; Bellanné-Chantelot, Christine; Constantinescu, Stefan N; Bluteau, Olivier; Plo, Isabelle; Vainchenker, William

    2016-01-21

    Mutations in signaling molecules of the cytokine receptor axis play a central role in myeloproliferative neoplasm (MPN) pathogenesis. Polycythemia vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum is detected in essential thrombocythemia (ET) with mutations in JAK2, the thrombopoietin (TPO) receptor (MPL), and the calreticulin (CALR) genes. Here, we studied the mutational profile of 17 ET patients negative for JAK2V617F, MPLW515K/L, and CALR mutations, using whole-exome sequencing and next-generation sequencing (NGS) targeted on JAK2 and MPL. We found several signaling mutations including JAK2V617F at very low allele frequency, 1 homozygous SH2B3 mutation, 1 MPLS505N, 1 MPLW515R, and 2 MPLS204P mutations. In the remaining patients, 4 presented a clonal and 7 a polyclonal hematopoiesis, suggesting that certain triple-negative ETs are not MPNs. NGS on 26 additional triple-negative ETs detected only 1 MPLY591N mutation. Functional studies on MPLS204P and MPLY591N revealed that they are weak gain-of-function mutants increasing MPL signaling and conferring either TPO hypersensitivity or independence to expressing cells, but with a low efficiency. Further studies should be performed to precisely determine the frequency of MPLS204 and MPLY591 mutants in a bigger cohort of MPN. © 2016 by The American Society of Hematology.

  5. Dendritic cell neoplasms: an overview.

    Science.gov (United States)

    Kairouz, Sebastien; Hashash, Jana; Kabbara, Wadih; McHayleh, Wassim; Tabbara, Imad A

    2007-10-01

    Dendritic cell neoplasms are rare tumors that are being recognized with increasing frequency. They were previously classified as lymphomas, sarcomas, or histiocytic neoplasms. The World Health Organization (WHO) classifies dendritic cell neoplasms into five groups: Langerhans' cell histiocytosis, Langerhans' cell sarcoma, Interdigitating dendritic cell sarcoma/tumor, Follicular dendritic cell sarcoma/tumor, and Dendritic cell sarcoma, not specified otherwise (Jaffe, World Health Organization classification of tumors 2001; 273-289). Recently, Pileri et al. provided a comprehensive immunohistochemical classification of histiocytic and dendritic cell tumors (Pileri et al., Histopathology 2002;59:161-167). In this article, a concise overview regarding the pathological, clinical, and therapeutic aspects of follicular dendritic, interdigitating dendritic, and Langerhans' cell tumors is presented.

  6. [Spontaneous neoplasms in guinea pigs].

    Science.gov (United States)

    Khar'kovskaia, N A; Khrustalev, S A; Vasil'eva, N N

    1977-01-01

    The authors present an analysis of the data of foreign literature and the results of their personal studies of spontaneous neoplasms in 40 guinea pigs of national breeding observed during observed during a 5-year period. In 4 of them malignant tumors were diagnosed-lympholeucosis (2 cases), dermoid ovarian cysts and also cancer and adenoma of the adrenal cortex (in one animal). The neoplasms described developed in guinea pigs, aged over 4 years, and they are referred to as mostly common tumors in this species of animals.

  7. Clinicopathological features of transient myeloproliferative syndrome and congenital leukaemia

    International Nuclear Information System (INIS)

    Sajid, N.; Ahmed, N.; Mahmood, S.

    2010-01-01

    The objectives of the study were to determine the spectrum of the clinical and pathological findings, the management and prognosis of patients of transient myeloproliferative syndrome (TMS) and congenital leukaemia. Study Design: Case series. Place and Duration of Study: The study was conducted over a period of 8 years, from January 2000 to December 2007, at the Children's Hospital and the Institute of Child Health, Lahore. Methodology: Suspected patients presenting with fever, pallor, bruises and hepatosplenomegaly and diagnosed as either transient myeloproliferative disorder or congenital leukaemia were studied. The complete blood count, reticulocyte count, leukocyte alkaline phosphatase score, liver function tests, karyotyping studies and bone marrow aspiration biopsy were performed in all of those patients. Management and out come was noted. Results were described as frequency percentages. Results: Out of 10,000 patients presenting during this period, 24 patients were diagnosed as either of transient myeloproliferative syndrome or congenital leukaemia. Fifteen of these were diagnosed as patients of TMS and 9 as patients of congenital leukaemia. Down syndrome (DS) was diagnosed in 75% of these patients. TMS patients were put on supportive treatment and recovered spontaneously. One DS patient with congenital leukaemia went into spontaneous remission and 2 of DS patients with congenital leukaemia responded to chemotherapy while rest of them either died or lost to follow-up. Conclusion: TMS and congenital leukaemia were not very uncommon in the studied population. Majority had Down syndrome. It is important to differentiate their clinical and pathological presentations for proper management. TMS may resolve with supportive treatment while congenital leukaemia is a fatal condition requiring chemotherapy. (author)

  8. Pulmonary hypertension in patients with chronic myeloproliferative disorders

    Directory of Open Access Journals (Sweden)

    Yochai Adir

    2015-09-01

    Full Text Available Pulmonary hypertension (PH is a major complication of several haematological disorders. Chronic myeloproliferative diseases (CMPDs associated with pulmonary hypertension have been included in group five of the clinical classification for pulmonary hypertension, corresponding to pulmonary hypertension for which the aetiology is unclear and/or multifactorial. The aim of this review is to discuss the epidemiology, pathogenic mechanism and treatment approaches of the more common forms of pulmonary hypertension in the context of CMPD's: chronic thromboembolic pulmonary hypertension, precapillary pulmonary hypertension and drug-induced PH.

  9. Radiation-Induced Neoplasms in Beagles after Administrations of {sup 90}Sr and {sup 226}Ra

    Energy Technology Data Exchange (ETDEWEB)

    Goldman, M.; Dungworth, D. L.; Bulgin, M. S.; Rosenblatt, L. S.; Richards, W. P.C.; Bustad, L. K. [Radiobiology Laboratory and Department of Veterinary Pathology, University of California, Davis, CA (United States)

    1969-11-15

    The comparative carcinogenic efficiency of two bone-seeking radionuclides is under study in a colony of several hundred beagles. The toxicity of internally deposited alpha emitters ({sup 226}Ra and its daughters) and of beta irradiation ({sup 90}Sr) at comparable dosage rates indicates marked differences in site of appearance and mode of action in litters studied up to 7 years of age. Radiation carcinogenesis in beagles exposed to {sup 90}Sr daily from midgestation to adulthood (1.5 yr) is at present confined to dogs fed 4 {mu}Ci {sup 90}Sr/d or higher. The 20 cases constitute a spectrum of myeloproliferative disorders characterized by terminal anaemias, and ranging from myeloid metaplasia to granulocytic leukaemia. Continuous high-level {sup 90}Sr irradiation to bone and marrow from early life onward causes a thickened hypocellular bone ('pachyostosis'), some instances of myelofibrosis, and persistent mild leukopenia on which the final spectrum of terminal disoideis is superimposed. In contrast, up to 100 {mu}Cl {sup 226}Ra given intravenously (8 equally spaced injections at 14 to 18 months of age) to young adults is not a potent marrow cell carcinogen. The higher LET, shorter-range alpha particles are efficient in inducing bone cancers (14 cases) and skeletal lesions similar to those documented in watch-dial luminizers exposed to {sup 226}Ra in the early 1900's. The incidence of haematopoietic and skeletal neoplasms observed is dose-rate related, and the morphologic characteristics have several analogues in human cancer. The use of identically treated litters rather than individuals affords additional opportunity to study possible familial factors in the distribution of the neoplasms. Pathogenic evaluation at this juncture strongly indicates that continued bone and marrow irradiation in early life is more likely to induce haematopoietic neoplasms than is skeletal irradiation starting in young adulthood, which induces osseous neoplasms. (author)

  10. Cardiac effects of noncardiac neoplasms

    International Nuclear Information System (INIS)

    Schoen, F.J.; Berger, B.M.; Guerina, N.G.

    1984-01-01

    Clinically significant cardiovascular abnormalities may occur as secondary manifestations of noncardiac neoplasms. The principal cardiac effects of noncardiac tumors include the direct results of metastases to the heart or lungs, the indirect effects of circulating tumor products (causing nonbacterial thrombotic endocarditis, myeloma-associated amyloidosis, pheochromocytoma-associated cardiac hypertrophy and myofibrillar degeneration, and carcinoid heart disease), and the undesired cardiotoxicities of chemotherapy and radiotherapy. 89 references

  11. The SKI proto-oncogene enhances the in vivo repopulation of hematopoietic stem cells and causes myeloproliferative disease.

    Science.gov (United States)

    Singbrant, Sofie; Wall, Meaghan; Moody, Jennifer; Karlsson, Göran; Chalk, Alistair M; Liddicoat, Brian; Russell, Megan R; Walkley, Carl R; Karlsson, Stefan

    2014-04-01

    The proto-oncogene SKI is highly expressed in human myeloid leukemia and also in murine hematopoietic stem cells. However, its operative relevance in these cells remains elusive. We have over-expressed SKI to define its intrinsic role in hematopoiesis and myeloid neoplasms, which resulted in a robust competitive advantage upon transplantation, a complete dominance of the stem and progenitor compartments, and a marked enhancement of myeloid differentiation at the expense of other lineages. Accordingly, enforced expression of SKI induced a gene signature associated with hematopoietic stem cells and myeloid differentiation, as well as hepatocyte growth factor signaling. Here we demonstrate that, in contrast to what has generally been assumed, the significant impact of SKI on hematopoiesis is independent of its ability to inhibit TGF-beta signaling. Instead, myeloid progenitors expressing SKI are partially dependent on functional hepatocyte growth factor signaling. Collectively our results demonstrate that SKI is an important regulator of hematopoietic stem cell activity and its overexpression leads to myeloproliferative disease.

  12. Methemoglobinemia in Young Patients With Hematologic Cancer or Aplastic Anemia Treated With Dapsone

    Science.gov (United States)

    2017-04-13

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Methemoglobinemia; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

  13. Tissue, Blood, and Body Fluid Sample Collection From Patients With Hematologic Cancer

    Science.gov (United States)

    2017-09-20

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nonmalignant Neoplasm

  14. Gastrointestinal Surgery of Neuroendocrine Neoplasms

    DEFF Research Database (Denmark)

    Hansen, Carsten Palnæs; Olsen, Ingrid Marie Holst; Knigge, Ulrich

    2015-01-01

    Surgery is the only treatment that may cure the patient with gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs) and should always be considered as the first-line treatment if radical resection can be achieved. Even in cases where radical surgery is not possible, palliative resection may...... be performed to reduce local or hormone-induced symptoms and to improve quality of life. The surgical procedures for GEP-NENs are accordingly described below. In most patients life-long follow-up is required, even following radical surgery, as recurrence may occur several years later....

  15. Prenatal ultrasound findings of fetal neoplasms

    International Nuclear Information System (INIS)

    Lee, Soo Hyun; Cho, Jeong Yeon; Song, Mi Jin; Min, Jee Yeon; Han, Byoung Hee; Lee, Young Ho; Cho, Byung Jae; Kim, Seung Hyup

    2002-01-01

    A variety of neoplasms can develop in each tetal organ. Most fetal neoplasms can be detected by careful prenatal ultrasonographic examination. Some neoplosms show specific ultrasonographic findings suggesting the differential diagnosis, but others do not. Knowledge of the presence of a neoplasm in the fetus may alter the prenatal management of a pregnancy and the mode of delivery, and facilitates immediate postnatal treatment. During the last five years, we experienced 32 cases of fetal neoplasms in a variety of organs. We describe their typical and ultrasonographic findings with correlating postnatal CT, MRI, and pathologic findings

  16. RUNX1/AML1 point mutations take part in the pathogenesis of radiation-and therapy-related myeloid neoplasms

    International Nuclear Information System (INIS)

    Harada, Yuka; Kimura, Akiro; Harada, Hironori

    2012-01-01

    High frequency of myelodysplastic syndrome (MDS) has been reported in Hiroshima A-bomb exposed survivors, in resident around Semipalatinsk Nuclear Laboratory and in exposed people by Chernobyl Nuclear Power Station Accident. MDS/acute myeloid leukemia (AML) is thought to be caused by mutation of runt-related transcription factor 1 (RUNX1) gene after a long time post exposure to relatively low dose radiation. In this study, participation of RUNX1/AML1 point mutations was examined in pathogenesis of the title neoplasms experienced in authors' facility. Subjects were 18/417 cases in whom myeloproliferative neoplasms (MPN) had switched to MDS or AML in the follow-up period of 1-25 years, and 11/124 cases in whom t-MN (therapy-related myeloid neoplasms) had developed during the remission of acute promyelocytic leukemia (APL) in the 1-9.7 years follow up. Point mutations were analyzed by PCR-single strand conformation polymorphism (PCR-SSCP) followed by base sequencing. In the former cases above, RUNX1 point mutation was found in 5/18 cases and in the latter, 4/11. When patients with persistent decrease of blood cells post therapy of APL were followed up for mutation, their RUNX1 point mutation was detected before they were diagnosed to be morbid of MDS/AML. The point mutation was thus a biomarker of myelo-hematogenic cancer, and was thought useful for early diagnosis of MDS and AML. (T.T.)

  17. The Spindle Cell Neoplasms of the Oral Cavity.

    Science.gov (United States)

    Shamim, Thorakkal

    2015-01-01

    Spindle cell neoplasms are defined as neoplasms that consist of spindle-shaped cells in the histopathology. Spindle cell neoplasms can affect the oral cavity. In the oral cavity, the origin of the spindle cell neoplasms may be traced to epithelial, mesenchymal and odontogenic components. This article aims to review the spindle cell neoplasms of the oral cavity with emphasis on histopathology.

  18. Clinical outcomes of myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement.

    Science.gov (United States)

    Umino, Kento; Fujiwara, Shin-Ichiro; Ikeda, Takashi; Toda, Yumiko; Ito, Shoko; Mashima, Kiyomi; Minakata, Daisuke; Nakano, Hirofumi; Yamasaki, Ryoko; Kawasaki, Yasufumi; Sugimoto, Miyuki; Yamamoto, Chihiro; Ashizawa, Masahiro; Hatano, Kaoru; Sato, Kazuya; Oh, Iekuni; Ohmine, Ken; Muroi, Kazuo; Kanda, Yoshinobu

    2018-02-28

    Myeloid/lymphoid neoplasms with fibroblast growth factor receptor-1 (FGFR1) rearrangement are hematopoietic stem cell disorders with a poor prognosis, but no established standard therapy. We experienced a patient with T-lymphoblastic lymphoma (LBL) associated with FGFR1 rearrangement who underwent cord blood transplantation, but died of pulmonary complication. We collected the clinical data of patients with FGFR1 rearrangement from the medical literature and analyzed 45 patients, including our patient. The primary diagnoses were myeloproliferative neoplasm (MPN) or myelodysplastic syndromes (MDS) in 14 and acute leukemia or LBL in 31. In MPN and MDS patients, the cumulative incidence of transformation to blast phase (BP) at 12 months was 46.2%. The 1-year overall survival (OS) from diagnosis in all cases was 43.1%. With regard to the impact of treatment response on survival, the achievement of complete response with a landmark at 2 months after diagnosis of BP was associated with a superior OS (40.0% vs. 26.0% P = 0.011 for 1-year OS from BP). Allogeneic hematopoietic stem cell transplantation (HSCT) was performed in 13 patients, and the 1-year OS from allogeneic HSCT was 61.5%. The hazard ratio for mortality was 0.34 (95% CI, 0.08-1.51, P = 0.15) for allogeneic HSCT treated as a time-dependent covariate, which suggests that allogeneic HSCT may confer a clinical benefit. The further accumulation of clinical data is needed to determine the optimal therapeutic approach for these neoplasms.

  19. JAK2 inhibitor therapy in myeloproliferative disorders: rationale, preclinical studies and ongoing clinical trials.

    Science.gov (United States)

    Pardanani, A

    2008-01-01

    The recent identification of somatic mutations such as JAK2V617F that deregulate Janus kinase (JAK)-signal transducer and activator of transcription signaling has spurred development of orally bioavailable small-molecule inhibitors that selectively target JAK2 kinase as an approach to pathogenesis-directed therapy of myeloproliferative disorders (MPD). In pre-clinical studies, these compounds inhibit JAK2V617F-mediated cell growth at nanomolar concentrations, and in vivo therapeutic efficacy has been demonstrated in mouse models of JAK2V617F-induced disease. In addition, ex vivo growth of progenitor cells from MPD patients harboring JAK2V617F or MPLW515L/K mutations is also potently inhibited. JAK2 inhibitors currently in clinical trials can be grouped into those designed to primarily target JAK2 kinase (JAK2-selective) and those originally developed for non-MPD indications, but that nevertheless have significant JAK2-inhibitory activity (non-JAK2 selective). This article discusses the rationale for using JAK2 inhibitors for the treatment of MPD, as well as relevant aspects of clinical trial development for these patients. For instance, which group of MPD patients is appropriate for initial Phase I studies? Should JAK2V617F-negative MPD patients be included in the initial studies? What are the likely consequences of 'off-target' JAK3 and wild-type JAK2 inhibition? How should treatment responses be monitored?

  20. Navigating the evolving paradigms in the diagnosis and treatment of myeloproliferative disorders.

    Science.gov (United States)

    Mesa, Ruben A

    2007-01-01

    The diagnosis and management of the BCR-ABL-negative myeloproliferative disorders (MPDs) of polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are at an explosive crossroads of scientific investigation and evolving paradigms since the discovery of the tyrosine kinase-activating JAK2V617F mutation in 2005. Additional discovery of relevant molecular lesions (JAK2 exon 12 mutations and c-MplW515L/K) have only further enriched our understanding of MPD pathogenesis. The improved diagnostic certainty these molecular markers provide have resulted in the modification, and simplification, of the World Health Organization (WHO) diagnostic algorithms for MPDs. Despite these scientific advances, however, the initial management of MPDs continues to rely upon a risk-based strategy to minimize the risk of vascular events with control of erythrocytosis, targeted antiplatelet therapy, and risk-based myelosuppressive therapy. No current medical therapy has altered the natural trend of the MPDs to lead to overt severe myelofibrosis or acute leukemia. Investigations into targeted therapies for MPDs are proceeding at a brisk pace with agents aimed at immunomodulation, decreasing marrow stromal reaction to the aberrant clone, DNA hypomethylation, or the inhibition of tyrosine kinases. Specific inhibition of JAK2 itself appears promising by in vitro investigations, and clinical trials with multiple agents are planned to commence enrollment in 2007. The potential impact of JAK2 inhibitors on the manifestations of the MPDs is unclear, but is awaited with great interest.

  1. Anal channel neoplasm: a neoplasm radio chemo curable

    International Nuclear Information System (INIS)

    Torres Lopez, M.; Avondet, I.; Vazquez, J.; Santini Blasco, A.

    1997-01-01

    Presently work is made an exhaustive revision of the anatomy of the region, the history of the treatments and of the current treatments of channel cancer anal. It makes emphasis in the importance of the conservative treatment with radiochemotherapy (RQT). The present is a prospective study,longitudinal and descriptive. Material and method: between January of 1989 and December of 1994 20 patients attended with cancer of anal channel with an illness metastasis. An average age it was of 62.4 years.The sex, 16 men and 4 women. The performance status 0,1 or 2 of the scale of the ECOQ. In the pathological anatomy: 15 patient epidermic neoplasm, 5 patient basal neoplasm. State I: 2 patients, II: 12 patients, III: 6 patients, IV: 0 patients.Treatment: the radiotherapy one carries out with cobalt 60 and it irradiates the primary tumour and the ganglion structures region, pelvic and inguinal. It surrendered to Gy/dia from Monday to Friday up to 50 Gy. The chemotherapy one carries out with mitomicine C 10 mg/ previous day to the radiotherapy and 5-UGH 1 intravenous g/my in infusion the days from 1 to 4 and from 29 to 32 after the radiotherapy.Results: to) control locorregional patient RC-16 (80%) ,RP 2 patients (10%) , without answer or with progression lesional a patient (5%) .b) State vital: living 15 patients, died 5 patients(continuation 12 to 60 months) .e)Tolerance: there were not deaths for the gastrointestinal treatment and haematological with toxicity moderate.To conclude:1) The radiochemotherapy is the treatment of elect.2)A feasible treatment of being carried out in our environment.3)Required of a good relationship predictable interdisciplinary.4)Toxicity and tolerable.5)Results of conservation of the sphincter in 80%(AU) [es

  2. Blastic plasmacytoid dendritic cell neoplasm: report of two pediatric cases.

    Science.gov (United States)

    Dharmani, Preeti Ashok; Mittal, Neha Manish; Subramanian, P G; Galani, Komal; Badrinath, Yajamanam; Amare, Pratibha; Gujral, Sumeet

    2015-01-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare subtype of acute leukemia that typically follows a highly aggressive clinical course in adults, whereas experience in children with this disease is very limited. We report cases of two children in whom bone marrow showed infiltration by large atypical monocytoid 'blast-like' cells which on immunophenotyping expressed CD4, CD56, HLA-DR and CD33 while were negative for CD34 other T-cell, B-cell and myeloid markers. The differential diagnoses considered were AML, T/NK-cell leukemia and acute undifferentiated leukemia. Additional markers CD303/BDCA-2 and CD123 which are recently validated plasmacytoid dendritic cell markers were done which helped us clinch the diagnosis of this rare neoplasm. An accurate diagnosis of BPDCN is essential in order to provide prompt treatment. Due to its rarity and only recent recognition as a distinct clinicopathological entity, no standardized therapeutic approach has been established for BPDCN.

  3. Blastic plasmacytoid dendritic cell neoplasm with absolute monocytosis at presentation

    Directory of Open Access Journals (Sweden)

    Jaworski JM

    2015-02-01

    Full Text Available Joseph M Jaworski,1,2 Vanlila K Swami,1 Rebecca C Heintzelman,1 Carrie A Cusack,3 Christina L Chung,3 Jeremy Peck,3 Matthew Fanelli,3 Micheal Styler,4 Sanaa Rizk,4 J Steve Hou1 1Department of Pathology and Laboratory Medicine, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 2Department of Pathology, Mercy Fitzgerald Hospital, Darby, PA, USA; 3Department of Dermatology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA; 4Department of Hematology/Oncology, Hahnemann University Hospital/Drexel University College of Medicine, Philadelphia, PA, USA Abstract: Blastic plasmacytoid dendritic cell neoplasm is an uncommon malignancy derived from precursors of plasmacytoid dendritic cells. Nearly all patients present initially with cutaneous manifestations, with many having extracutaneous disease additionally. While response to chemotherapy initially is effective, relapse occurs in most, with a leukemic phase ultimately developing. The prognosis is dismal. While most of the clinical and pathologic features are well described, the association and possible prognostic significance between peripheral blood absolute monocytosis (>1.0 K/µL and blastic plasmacytoid dendritic cell neoplasm have not been reported. We report a case of a 68-year-old man who presented with a rash for 4–5 months. On physical examination, there were multiple, dull-pink, indurated plaques on the trunk and extremities. Complete blood count revealed thrombocytopenia, absolute monocytosis of 1.7 K/µL, and a negative flow cytometry study. Biopsy of an abdominal lesion revealed typical features of blastic plasmacytoid dendritic cell neoplasm. Patients having both hematologic and nonhematologic malignancies have an increased incidence of absolute monocytosis. Recent studies examining Hodgkin and non-Hodgkin lymphoma patients have suggested that this is a negative prognostic factor. The association between

  4. Hemorrhagic and thrombotic complications in patients with myeloproliferative diseases

    Directory of Open Access Journals (Sweden)

    Carla Valladares Vignal

    Full Text Available OBJECTIVE: To correlate the incidence of hemorrhage and thrombosis to bleeding time (BT and platelet aggregation in 27 consecutive patients with myeloproliferative diseases (MPD. DESIGN: Retrospective study. SETTING: Public tertiary referral center. PATIENTS: Eighteen patients with chronic myelogenous leukemia (CML, 5 with polycytemia vera (PV, 2 with essential thrombocytemia (ET and 2 with idiopathic myelofibrosis (MF. Duke's BT and epinephrine-induced platelet aggregation were performed on the patients and on 10 healthy individuals. RESULTS: Eleven patients presented symptoms (41 %: 9 with hemorrhage (33% and 5 with thrombosis (19%.There were less symptomatic patients in the CML group (28% than in the other MPD (67%, without statistical significance (Fisher, p=0.06. Duke's BT was longer in symptomatic patients (Mann-Whitney, p<0.05. Platelet aggregation was abnormal in 7 patients (26% and 71% of them were symptomatic (Fisher, p = 0.07. CONCLUSIONS: The high incidence of bleeding and thrombosis in patients with MPD was related to prolonged BT, but not to platelet aggregation abnormalities.

  5. [MPLW515L point mutation in patients with myeloproliferative disease].

    Science.gov (United States)

    Xia, Jun; Xu, Wei; Zhang, Su-Jiang; Fan, Lei; Qiao, Chun; Li, Jian-Yong

    2008-12-01

    In order to investigate the frequency of MPLW515L and JAK2V617F point mutations of the patients with myeloproliferative disease (MPD) in Nanjing area, MPLW515L and JAK2V617F point mutations were simultaneously detected by alleles specific polymerase chain reaction (AS-PCR) and sequencing in 190 MPD patients. The results showed that MPLW515L point mutation was detected in 1 out of 102 essential thrombocythemia (ET) patients (1.0%) and was not detected in 32 polycythemia vera (PV) patients, 13 idiopathic myelofibrosis (IMF) patients, 43 chronic myelogenous leukemia (CML) patients. JAK2V617F point mutation was detected in 20 out of 32 PV patients (62.5%), 43 out of 102 ET patients (42.2%), 5 out of 13 IMF patients (38.5%), and was not detected in 43 CML patients. It is concluded that MPLW515L point mutation exists in ET patient, but is not found in PV, IMF and CML. JAK2V617F point mutation exists in PV, ET and IMF, but not in CML.

  6. Brain and spinal cord neoplasms

    International Nuclear Information System (INIS)

    Anderson, R.E.; Bragg, D.G.; Youker, J.E.

    1985-01-01

    Traditional means of detecting CNS neoplasms include plain film studies, isotope brain scans, angiography, pneumoencephalography, and myelography. Computed tomography (CT) scanning has replaced nearly all of these studies in both the initial detection and follow-up of brain tumors. Air studies (pneumoencephalography and ventriculography) have been virtually eliminated, except in certain unusual circumstances when two positions need to be checked, or hydrocephalus followed. The nuclear brain scan has a very limited role at present, being useful primarily for detecting skull or meningeal metastases. Myelography, however, remains a valuable imaging tool for the assessment of tumors of the spinal canal. CT scanning has not only improved our ability to detect smaller brain tumors, but also CT guided stereotactic biopsy techniques provide a safer means of obtaining tissue from these smaller lesions, regardless of location. Surgical techniques, guided by CT sterotactic techniques, show promise as well, but the impact of these therapeutic techniques on survival statistics remains to be defined. CT has revolutionized the approach to the detection and diagnosis of space-occupying lesions in the brain. Tumors can be detected at a smaller site

  7. RENAL DAMAGE WITH MALIGNANT NEOPLASMS

    Directory of Open Access Journals (Sweden)

    I. B. Kolina

    2015-01-01

    Full Text Available The relationship between renal damage and malignant neoplasms is one of the most actual problems of the medicine of internal diseases. Very often, exactly availability of renal damage determines the forecast of cancer patients. The range of renal pathologies associated with tumors is unusually wide: from the mechanical effect of the tumor or metastases on the kidneys and/or the urinary tract and paraneoplastic manifestations in the form of nephritis or amyloidosis to nephropathies induced with drugs or tumor lysis, etc. Thrombotic complications that develop as a result of exposure to tumor effects, side effects of certain drugs or irradiation also play an important role in the development of the kidney damage. The most frequent variants of renal damage observed in the practice of medical internists (therapists, urologists, surgeons, etc., as well as methods of diagnosis and treatment approaches are described in the article. Timely and successful prevention and treatment of tumor-associated nephropathies give hope for retaining renal functions, therefore, a higher life standard after completion of anti-tumor therapy. Even a shortterm episode of acute renal damage suffered by a cancer patient must be accompanied with relevant examination and treatment. In the caseof transformation of acute renal damage into the chronic kidney disease, such patients need systematic and weighted renoprotective therapy and correct dosing of nephrotoxic drugs.

  8. Metastatic neoplasms of the central nervous system

    International Nuclear Information System (INIS)

    Fenner, W.R.

    1990-01-01

    Metastatic neoplasms to the central nervous system are often encountered in the practice of surgical neuropathology. It is not uncommon for patients with systemic malignancies to present to medical attention because of symptoms from a brain metastasis and for the tissue samples procured from these lesions to represent the first tissue available to study a malignancy from an unknown primary. In general surgical pathology, the evaluation of a metastatic neoplasm of unknown primary is a very complicated process, requiring knowledge of numerous different tumor types, reagents, and staining patterns. The past few years, however, have seen a remarkable refinement in the immunohistochemical tools at our disposal that now empower neuropathologists to take an active role in defining the relatively limited subset of neoplasms that commonly metastasize to the central nervous system. This information can direct imaging studies to find the primary tumor in a patient with an unknown primary, clarify the likely primary site of origin in patients who have small tumors in multiple sites without an obvious primary lesion, or establish lesions as late metastases of remote malignancies. Furthermore, specific treatments can begin and additional invasive procedures may be prevented if the neuropathologic evaluation of metastatic neoplasms provides information beyond the traditional diagnosis of ''metastatic neoplasm.'' In this review, differential cytokeratins, adjuvant markers, and organ-specific antibodies are described and the immunohistochemical signatures of metastatic neoplasms that are commonly seen by neuropathologists are discussed

  9. Clinico-roentgenological characteristic of early stomach neoplasm

    International Nuclear Information System (INIS)

    Golub, G.D.

    1988-01-01

    Peculiarities of clinic and roentgenosemiotics of early stomach neoplasms in patients were analyzed. Roentgenological picture of early stomach neoplasms depends on anatomic growth shape and size of neoplasms, its localization and on manifestation of inflammatory and functional chages accompanying the neoplasm. Application of complex of gastrological examination including roentgenological diagnostic method, gastrofibroscopy and morphological examination of the tissue permits to diagnose early stomach neoplasm in 95,4 % of patients. 8 refs

  10. Role of JAK-STAT signaling in the pathogenesis of myeloproliferative disorders.

    Science.gov (United States)

    Levine, Ross L; Wernig, Gerlinde

    2006-01-01

    The identification of JAK2V617F mutations in polycythemia vera (PV), essential thrombocytosis (ET), and myelofibrosis (MF) represents an important advance in our understanding of these myeloproliferative disorders (MPD). Most, if not all, patients with PV and a significant number of patients with ET and MF are JAK2V617F positive, and the mutation likely arises in the hematopoietic stem cell compartment. JAK2V617F is a constitutively active tyrosine kinase that is able to activate JAK-STAT signaling most efficiently when co-expressed with the erythropoietin receptor (EPOR), the thrombopoietin receptor (MPL), or the granulocyte colony-stimulating factor receptor (GCSFR). Data from murine models supports the central role of JAK2V617F in the pathogenesis of MPD, as expression of JAK2V617F in a bone marrow transplantation assay results in polycythemia and myelofibrosis in recipient mice. Activation of JAK-STAT signaling by JAK2V617F in some, but not all MPD patients with ET and MF led to the identification of the constitutively active MPLW515L allele in ET and MF. Small molecule inhibitors of JAK-STAT signaling are currently being developed, which offer potential for molecularly targeted therapy for patients with PV, ET, and MF. Despite these advances, many questions remain regarding the role of a single disease allele in three phenotypically distinct MPD, the potential clinical efficacy of JAK2 inhibitors, and the identity of oncogenic alleles in JAK2V617F/MPLW515-negative MPD.

  11. Histopathological audit of salivary gland neoplasms

    International Nuclear Information System (INIS)

    Memon, J.M.; Sheikh, B.

    2014-01-01

    Salivary gland neoplasms are uncommon but important presentation to general surgeons. Objective: To analyze the relative frequency and distribution of Salivary gland neoplasms in our division. Setting: Department of surgery and pathology, Peoples Medical University hospital and GMMMC hospital Sukkur. Study design: Descriptive (case series) Subjects and methods: A total of 40 patients registered for salivary gland tumors from oct 2008 to 0ct 2013 were included in the study. A thorough history, clinical examination, routine haematological and biochemical studies were done in all patients. FNAC was done in all cases. All patients were subjected to surgical intervention on standard rules. Each resected specimen was sent for histopathology. Information about age, gender and tumor location was obtained from clinical record and frequency of different neoplasms was studied from histopathological report. All data was collected on especially designed proforma. Data analysis was done using spss version 17. Results: A total of 40 patients were registered for salivary gland neoplasms. 28 patients (70%) had parotid lesions, 10 patients (25%) had submandibular gland involvement and 2 patients ( 5%) had minor salivary gland tumors. Patients were between 15 - 80 years of age( mean age =34.7 years) 24 patients(60%) were male and 16 (40%) were female,with male to female ratio of 1.5:1.32 . 22 (80%) had benign lesions and 8 patients (20%) had malignant lesions. Pleomorphic adenoma was the most common benign tumor affecting the parotid gland. Adenocarcinoma represented as the most prevelant parotid malignancy. Benign neoplasms occurred in third and fourth decades of life and malignant neoplasms were diagnosed in sixth and seventh decades of life. Conclusion:Salivary gland neoplasms are uncommon but they have occasioned much interest and debate because of broad histological spectrum. The data presented in this study is corroborated with most of the studied literature worldwide. (author)

  12. [The lymph nodes imprint for the diagnosis of lymphoid neoplasms].

    Science.gov (United States)

    Peniche-Alvarado, Carolina; Ramos-Peñafiel, Christian Omar; Martínez-Murillo, Carlos; Romero-Guadarrama, Mónica; Olarte-Carrillo, Irma; Rozen-Fuller, Etta; Martínez-Tovar, Adolfo; Collazo-Jaloma, Juan; Mendoza-García, Carlos Alberto

    2013-01-01

    lymphoma is the most frequent lymphoid neoplasm in our country. Its diagnosis is based on histopathological findings. The lymph node imprint has been used for more than 40 years. The aim was to establish the sensitivity, specificity, positive predictive value and negative predictive value of lymph node imprint and estimate the inter-observer rate. we did an observational, retrospective, prolective study, based on the lymph node imprint obtained by excisional biopsies over a period of 6 years. the inclusion criteria was met on 199 samples, 27.1 % were considered as reactive (n = 54), 16.1 % Hodgkin lymphoma (n = 32), 40.2 % (n = 80) non-Hodgkin lymphoma and 16.6 % (n = 33) as metastatic carcinoma. Comparing with the final histopathology report, the sensitivity and specificity of lymph node imprint were 88 % (0.81-0.95) and 64 % (0.55-0.73) respectively, the positive predictive value was 67 % (0.59-0.76) and the negative predictive value was 86 % (0.79-0.94). The interobserver kappa index was 0.467. the lymph node imprint remains as a useful tool for the diagnosis of lymphoid neoplasm. The agreement between observers was acceptable.

  13. The second international congress on myeloproliferative and myelodysplastic syndromes.

    Science.gov (United States)

    Silver, R T; Bennett, J M; Deininger, M; Feldman, E; Rafii, S; Silverstein, R L; Solberg, L A; Spivak, J L

    2004-09-01

    This meeting was convened by Richard T. Silver, M.D. and co-chaired by Jerry L. Spivak, M.D. It was held from 16 to 18 October 2003 in New York City, New York, USA. Thirty-nine invited speakers from nine different countries participated in the conference. There were more than 350 attendees. There were formal presentations and discussions on biology, clinical aspects, and management of patients with these diverse bone marrow stem cell disorders linked by a variable progression to acute myeloid leukemia. Of considerable interest, a clinical symposium exclusively for patients was held the day preceding the meeting at which John Bennett, Tiziano Barbui, Richard Silver, Jerry Spivak, and Ayalew Tefferi spoke on various topics pertaining to these diseases. This proved to be highly informative to the patients who reported that they enjoyed the program immensely. This was sponsored by the Cancer Research & Treatment Fund, Inc. Representatives of the Myelodysplasia Foundation were also present. This meeting report provides a summary of five different sections prepared by one or more of the session chairs. The keynote address was given by Shahin Rafii (Cornell Medical Center). Most appropriately, this talk focused on the expression and activation of angiogenic factors which play a crucial role in the progression of both myeloproliferative disorders and myelodysplastic syndromes (MDS). Among the known factors, vascular endothelial growth tyrosine kinase receptors (VEGF-R1, R2, and R3) support proliferation, survival, and mobility. Rafii's team has demonstrated that these receptors are expressed on subsets of primary hematopoietic cells as well as leukemic cells. Some leukemic cells express both VEGF-A and VEGF-R2, resulting in the generation of an autocrine loop that supports survival and within the osteoblastic zone translocating these cells to the vascular enriched niche for receipt of molecular instructions required for proliferation and differentiation. A pathologic

  14. Nutritional survey of neoplasm patients receiving radiotherapy

    International Nuclear Information System (INIS)

    Li Xinli; Zhu Shengtao

    2001-01-01

    Objective: In order to know the nutriture of neoplasm patients receiving radiotherapy and give nutritional guidance properly, the authors make the following survey. Methods: A dietary survey of twenty-four-hour retrospective method was used; The patients' activity was recorded and their twenty-four hours caloric consumption was calculated. Results: Of all the patients, the intake of protein is more than recommended, percentage of calorific proportion is about 15%-19% of gross caloric. A larger portion of patients' caloric intake, especially female patients, is lower than caloric consumption. Among all the patients, the intake of vegetables is not enough; The consumption of milk and milky products is lower; it is common and serious that neoplasm patients receiving radiotherapy have vitamine and mineral's scarcity. Conclusions: Nutriture of neoplasm patients is not optimistic, it is imperative to improve their nutriture

  15. Orbital roof encephalocele mimicking a destructive neoplasm.

    Science.gov (United States)

    Alsuhaibani, Adel H; Hitchon, Patrick W; Smoker, Wendy R K; Lee, Andrew G; Nerad, Jeffrey A

    2011-01-01

    The purpose of this case report is to report an orbital roof encephalocele mimicking a destructive orbital neoplasm. Orbital roof encephalocele is uncommon but can mimic neoplasm. One potential mechanism for the orbital roof destruction is a post-traumatic "growing orbital roof fracture." The growing fracture has been reported mostly in children but can occur in adults. Alternative potential etiologies for the encephalocele are discussed, including Gorham syndrome. Orbital roof encephalocele is uncommon in adults, and the findings can superficially resemble an orbital neoplasm. Radiographic and clinical features that might suggest the correct diagnosis include a prior history of trauma, overlying frontal lobe encephalomalacia without significant mass effect or edema, and an orbital roof defect. The "growing fracture" mechanism may be a potential explanation for the orbital roof destruction in some cases.

  16. Intrathoracic neoplasms in the dog and cat

    International Nuclear Information System (INIS)

    Weller, R.E.

    1991-06-01

    Neoplasms of the thoracic cavity are as diverse as the structures and tissues that comprise the thorax. This paper summarizes the clinical signs, diagnosis and treatment of thoracic neoplasms in the dog and cat. Specific diagnostic techniques are evaluated, as is the utility of imaging techniques for clinical staging. Surgery is recommended as the treatment of choice for intrathoracic neoplasms, with exception for multiple tumor masses, metastasis, or poor patient health. Radiation therapy, chemotherapy, and hyperthermia are discussed individually or in combination with surgery or each other. Prognosis for specific tumors is discussed, as is lymph node involvement as a prognostic indicator. As the use of newer diagnostic procedures become more available in veterinary medicine, it should be possible to offer patients a variety of positive choices that will enhance their survival and quality of life

  17. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  18. Presence of Donor-Derived DNA in Semen Samples From Cancer Survivors Who Underwent Donor Stem Cell Transplant

    Science.gov (United States)

    2014-12-08

    Cancer Survivor; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Testicular Germ Cell Tumor

  19. Baclofen-Amitriptyline Hydrochloride-Ketamine Gel in Treating Peripheral Neuropathy Caused by Chemotherapy in Patients With Cancer

    Science.gov (United States)

    2017-07-25

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neurotoxicity; Pain; Unspecified Adult Solid Tumor, Protocol Specific

  20. American Ginseng in Treating Patients With Fatigue Caused by Cancer

    Science.gov (United States)

    2016-12-19

    Chronic Myeloproliferative Disorders; Fatigue; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  1. Lactobacillus in Preventing Infection in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer or Myelodysplastic Syndrome

    Science.gov (United States)

    2017-02-02

    Breast Cancer; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  2. Radiology of pancreatic neoplasms: An update.

    Science.gov (United States)

    de la Santa, Luis Gijón; Retortillo, José Antonio Pérez; Miguel, Ainhoa Camarero; Klein, Lea Marie

    2014-09-15

    Diagnostic imaging is an important tool to evaluate pancreatic neoplasms. We describe the imaging features of pancreatic malignancies and their benign mimics. Accurate detection and staging are essential for ensuring appropriate selection of patients who will benefit from surgery and for preventing unnecessary surgeries in patients with unresectable disease. Ultrasound, multidetector computed tomography with multiplanar reconstruction and magnetic resonance imaging can help to do a correct diagnosis. Radiologists should be aware of the wide variety of anatomic variants and pathologic conditions that may mimic pancreatic neoplasms. The knowledge of the most important characteristic key findings may facilitate the right diagnosis.

  3. Splanchnic venous thrombosis driven by a constitutively activated ...

    African Journals Online (AJOL)

    Introduction: Splanchnic venous thrombosis (SVT) has varied etiology with Philadelphia-negative myeloproliferative neoplasms (MPNs) being the most frequent underlying prothrombotic factor. Hematological indices often remain within normal range because of portal hypertension and its sequelae, causing diagnostic ...

  4. Whole blood transcriptional profiling reveals significant down-regulation of human leukocyte antigen class I and II genes in essential thrombocythemia, polycythemia vera and myelofibrosis

    DEFF Research Database (Denmark)

    Skov, Vibe; Riley, Caroline Hasselbalch; Thomassen, Mads

    2013-01-01

    Gene expression profiling studies in the Philadelphia-negative chronic myeloproliferative neoplasms have revealed significant deregulation of several immune and inflammation genes that might be of importance for clonal evolution due to defective tumor immune surveillance. Other mechanisms might b...

  5. Perspectives on chronic inflammation in essential thrombocythemia, polycythemia vera, and myelofibrosis

    DEFF Research Database (Denmark)

    Hasselbalch, Hans K

    2012-01-01

    The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because...

  6. Radiation treatment of spinal cord neoplasms

    International Nuclear Information System (INIS)

    Smirnov, R.V.

    1982-01-01

    Results of radiation treatment of spinal cord neoplasms are presented. The results of combined (surgical and radiation) treatment of tumors are studied. On the whole it is noted that radiation treatment of initial spinal cord tumours is not practised on a large scale because of low radiostability of spinal cord

  7. Benign neoplasms of the trachea : case reports

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hak Hee; Mun, Kyung Mi; Kim, Bum Soo; Choi, Kyu Ho; Shinn, Kyung Sub [Kangnam St. Mary' s Hospital Catholic Univ. Medical College, Seoul (Korea, Republic of)

    1997-03-01

    Benign tumors of the trachea are rare, accounting for approximately 10% of all primary tracheal neoplasms. They are frequently misdiagnosed and managed as bronchial asthma or chronic bronchitis. We report a lipoma and a leiomyoma of the trachea with emphasis on the clinical, radiographic and CT findings, and review the literature.

  8. CT features of abdominal plasma cell neoplasms

    International Nuclear Information System (INIS)

    Monill, J.; Pernas, J.; Montserrat, E.; Perez, C.; Clavero, J.; Martinez-Noguera, A.; Guerrero, R.; Torrubia, S.

    2005-01-01

    The aim of this study was to describe the CT features of abdominal plasma cell neoplasms. We reviewed CT imaging findings in 11 patients (seven men, four women; mean age 62 years) with plasma cell neoplasms and abdominal involvement. Helical CT of the entire abdomen and pelvis was performed following intravenous administration of contrast material. Images were analyzed in consensus by two radiologists. Diagnoses were made from biopsy, surgery and/or clinical follow-up findings. Multiple myeloma was found in seven patients and extramedullary plasmacytoma in four patients. All patients with multiple myeloma had multifocal disease with involvement of perirenal space (4/7), retroperitoneal and pelvic lymph nodes (3/7), peritoneum (3/7), liver (2/7), subcutaneous tissues (2/7) and kidney (1/7). In three of the four patients with extramedullary plasmacytoma, a single site was involved, namely stomach, vagina and retroperitoneum. In the fourth patient, a double site of abdominal involvement was observed with rectal and jejunal masses. Plasma cell neoplasm should be considered in the differential diagnosis of single or multiple enhancing masses in the abdomen or pelvis. Abdominal plasma cell neoplasms were most frequently seen as well-defined enhancing masses (10/11). (orig.)

  9. The new WHO nomenclature: lymphoid neoplasms.

    Science.gov (United States)

    Leclair, Susan J; Rodak, Bernadette F

    2002-01-01

    The development of the WHO classification of lymphoid neoplasms is a remarkable example of cooperation and communication between pathologists and oncologists from around the world. Joint classification committees of the major hematopathology societies will periodically review and update this classification, facilitating further progress in the understanding and treatment of hematologic malignancies.

  10. Solid Pseudopapillary Neoplasm of the Pancreas

    African Journals Online (AJOL)

    Solid pseudopapillary neoplasm is a rare pancreatic tumour predominantly affecting young women. We present two cases in young female patients. Both tumours were surgically removed as abdominal masses, one from the pancreatic tail and the other posterior to the stomach with an unclear organ of origin. On gross ...

  11. Radiologic features of cystic, endocrine and other pancreatic neoplasms

    International Nuclear Information System (INIS)

    Balci, N. Cem; Semelka, Richard C.

    2001-01-01

    This article presents imaging features of cystic, endocrine and other pancreatic neoplasms. Microcystic adenoma which is composed of small cysts ( 2 cm) are accounted for mucinous cystic neoplasms, its variant along pancreatic duct is ductectatic mucinous cystic neoplasm. Endocrine tumors of pancreas are hypervascular and can be depicted on early dynamic enhanced crosssectional imaging modalities or on angiography when they are <1 cm. Pancreatic metastases and lymphomas are rare neoplasms which should also be included in differential diagnosis for pancreatic masses

  12. A comparative study of 99Tcm (V)-DMSA imaging with histopathological examination in ovarian neoplasms

    International Nuclear Information System (INIS)

    Zhao Xinming; Wang Jianfang; Xu Fang; Yin Jie; Wei Lanxiu; Sun Li

    1999-01-01

    Objective: To assess the clinical value of 99 Tc m (V)-Dmsa imaging in detecting the ovarian and the pelvic cavity neoplasms. Methods: 99 Tc m (V)-DMSA imaging was performed on 24 patients with diagnosed ovarian neoplasms which were pathologically confirmed after operation. Results: 14 of the 15 patients with malignant ovarian tumors had positive 99 Tc m (V)-DMSA scintigraphy. However, 7 of 9 cases with benign ovarian tumors had negative 99 Tc m (V)-DMSA scintigraphy. The sensitivity, specificity, positive predictive value, negative predictive value, false positive rate, false negative rate, and accuracy of 99 Tc m (V)-DMSA imaging for detecting malignant ovarian tumors were 93.33%, 77.78%, 87.50%, 87.50%, 14.29%, 6.67% and 87.50%, respectively. Conclusions: 99 Tc m (V)-DMSA imaging is of important value in detecting malignant and benign ovarian and pelvic tumors

  13. Aortic thrombus in a patient with myeloproliferative thrombocytosis, successfully treated by pharmaceutical therapy: a case report

    Directory of Open Access Journals (Sweden)

    Imai Norikazu

    2010-07-01

    Full Text Available Abstract Introduction Thrombosis in myeloproliferative thrombocytosis occurs usually in the microvessels and medium-sized arteries and veins and only rarely in the aorta. Aortic thrombosis is usually treated with thrombectomy. Reported here is a rare case that was treated pharmacologically. Case presentation A 60-year-old Japanese woman presented with numbness of both lower extremities. Her platelet count was 1787 × 103/μl. Through bone marrow examination, we diagnosed her condition as myelodysplastic and/or myeloproliferative disorder-unclassifiable. Abdominal ultrasonography and computed tomographic scan revealed aortic thrombosis. Her platelet count was controlled with hydroxyurea and ranimustine. Aspirin and ticlopidine improved the numbness in both lower limbs on the second day. Aortic thrombosis was not observed in a computed tomographic scan on the seventh day. Conclusion For aortic thrombosis, surgical management is usually adopted, but pharmacological management is also an option because of its immediate curative effects.

  14. Intrathoracic neoplasms in the dog and cat

    Energy Technology Data Exchange (ETDEWEB)

    Weller, R.E.

    1994-03-01

    Very little is known regarding the epidemiology, etiology, and mechanisms of spontaneous intrathoracic neoplasia in companion animals. Much of what we know or suspect about thoracic neoplasia in animals has been extrapolated from experimentally-induced neoplasms. Most studies of thoracic neoplasia have focused on the pathology of primary and metastatic neoplasms of the lung with little attention given to diagnostic and therapeutic considerations. Although the cited incidence rate for primary respiratory tract neoplasia is low, 8.5 cases per 100,000 dogs and 5.5 cases per 100,000 cats, intrathoracic masses often attract attention out of proportion to their actual importance since they are often readily visualized on routine thoracic radiographs.

  15. Primary bone neoplasms in dogs: 90 cases

    Directory of Open Access Journals (Sweden)

    Maria E. Trost

    2012-12-01

    Full Text Available A retrospective study of necropsy and biopsy cases of 90 primary bone tumors (89 malignant and one benign in dogs received over a period of 22 years at the Laboratório de Patologia Veterinária, Universidade Federal de Santa Maria, was performed. Osteosarcoma was the most prevalent bone tumor, accounting for 86.7% of all malignant primary bone neoplasms diagnosed. Most cases occurred in dogs of large and giant breeds with ages between 6 and 10-years-old. The neoplasms involved mainly the appendicular skeleton, and were 3.5 times more prevalent in the forelimbs than in the hindlimbs. Osteoblastic osteosarcoma was the predominant histological subtype. Epidemiological and pathological findings of osteosarcomas are reported and discussed.

  16. Solid and papillary neoplasm of the pancreas

    DEFF Research Database (Denmark)

    Jørgensen, L J; Hansen, A B; Burcharth, F

    1992-01-01

    In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymoge......In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well...... as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide...

  17. Prevalence of colorectal neoplasm among patients with newly diagnosed coronary artery disease.

    Science.gov (United States)

    Chan, Annie On On; Jim, Man Hong; Lam, Kwok Fai; Morris, Jeffrey S; Siu, David Chun Wah; Tong, Teresa; Ng, Fook Hong; Wong, Siu Yin; Hui, Wai Mo; Chan, Chi Kuen; Lai, Kam Chuen; Cheung, Ting Kin; Chan, Pierre; Wong, Grace; Yuen, Man Fung; Lau, Yuk Kong; Lee, Stephen; Szeto, Ming Leung; Wong, Benjamin C Y; Lam, Shiu Kum

    2007-09-26

    Colorectal neoplasm and coronary artery disease (CAD) share similar risk factors, and their co-occurrence may be associated. To investigate the prevalence of colorectal neoplasm in patients with CAD in a cross-sectional study and to identify the predisposing factors for the association of the 2 diseases. Patients in Hong Kong, China, were recruited for screening colonoscopy after undergoing coronary angiography for suspected CAD during November 2004 to June 2006. Presence of CAD (n = 206) was defined as at least 50% diameter stenosis in any 1 of the major coronary arteries; otherwise, patients were considered CAD-negative (n = 208). An age- and sex-matched control group was recruited from the general population (n = 207). Patients were excluded for use of aspirin or statins, personal history of colonic disease, or colonoscopy in the past 10 years. The prevalence of colorectal neoplasm in CAD-positive, CAD-negative, and general population participants was determined. Bivariate logistic regression was performed to study the association between colorectal neoplasm and CAD and to identify risk factors for the association of the 2 diseases after adjusting for age and sex. The prevalence of colorectal neoplasm in the CAD-positive, CAD-negative, and general population groups was 34.0%, 18.8%, and 20.8% (P < .001 by chi2 test), prevalence of advanced lesions was 18.4%, 8.7%, and 5.8% (P < .001), and prevalence of cancer was 4.4%, 0.5%, and 1.4% (P = .02), respectively. Fifty percent of the cancers in CAD-positive participants were early stage. After adjusting for age and sex, an association still existed between colorectal neoplasm and presence of CAD (odds ratio [OR], 1.88; 95% confidence interval [CI], 1.25-2.70; P = .002) and between advanced lesions and presence of CAD (OR, 2.51; 95% CI, 1.43-4.35; P = .001). The metabolic syndrome (OR, 5.99; 95% CI, 1.43-27.94; P = .02) and history of smoking (OR, 4.74; 95% CI, 1.38-18.92; P = .02) were independent factors for the

  18. The neoplasms of the operated stomach

    International Nuclear Information System (INIS)

    Ositrova, L.I.; Golubovich, I.A.; Mashevskaya, L.S.

    1988-01-01

    It is shown that operation and rexction in case of primary and recurrent neoplasm of operated stomach remains low. However radical operation is the only method permitting to hope for healing of shuch patients. A thorough medical examination is necessary at first 3 years following operation. Surgical treatment is accompanied by preoperational irradiation in such patients. Au 198 in 1.48 GBq is intravenously injected to some patients. 10 refs

  19. Granular cell tumor: An uncommon benign neoplasm

    Directory of Open Access Journals (Sweden)

    Tirthankar Gayen

    2015-01-01

    Full Text Available Granular cell tumor is a distinctly rare neoplasm of neural sheath origin. It mainly presents as a solitary asymptomatic swelling in the oral cavity, skin, and rarely internal organs in the middle age. Histopathology is characteristic, showing polyhedral cells containing numerous fine eosinophilic granules with indistinct cell margins. We present a case of granular cell tumor on the back of a 48-year-old woman which was painful, mimicking an adnexal tumor.

  20. Neoplasms HIV associated Kaposi sarcoma not

    International Nuclear Information System (INIS)

    Lombardo, K.; Sosa, A.; Krygier, G.; Muse, I.

    2004-01-01

    Abstract - The incidence of malignancies in virus carriers acquired immunodeficiency (HIV) has increased in conjunction with the disease during the past decade. 40% of all AIDS patients develop cancer during the course of HIV infection. Kaposi's sarcoma (KS), Non-Hodgkin lymphoma (NHL) and cervical cancer have an impact extremely high in HIV infected patients, and they are considered as disease AIDS-defining stage. Many reports suggest that other neoplasms they can have a high impact on the population of HIV carrier, including head and neck carcinoma, rectal cancer - anal, plasma cytomas, and melanoma lung cancer. Methods - We examined the spectrum of cancer in HIV-infected patients, specifically neoplasms except Kaposi sarcoma diagnosed between 1/1998 - 6/2004. Information on age, sex, factors was gathered risk for AIDS, neoplasms and mortality rate. Results: The total number of patients in our study was 21 patients, what 15 were male (71%) and 6 females (29%); the median age was 36 (29-70). Tumors were reported: 11 Non-Hodgkin lymphomas (52%), 2 Hodgkin's lymphoma (6.6%), 1 medullary thyroid cancer (6.6%), 1 melanoma (6.6%), 1 rectal cancer (5%) and three head and neck cancers (14%), 1 cancer 1 lung and breast cancer. Five of the patients were intravenous drug abusers (24%); 4 patients were homosexual, bisexual March 8 straight, on 6 patients know the data. Conclusions - The spectrum of malignancies associated with infection HIV in our study was similar to that described in other populations. ratio between the immune system and the epidemiology of the virus-induced tumors is to importance to identify new therapeutic approaches in the treatment and / or prevention of these neoplasms

  1. Neoplasm carcinoid: Description of a case

    International Nuclear Information System (INIS)

    Carrillo, Luis; Abarca, Jaysoom; Penaherrera, Vicente; Legarda, Eduardo

    2004-01-01

    We describe a case of small bowel obstruction associated with a carcinoid neoplasm of the ileum in a 78 year old man who was presented with abdominal pain, vomiting, and a mass in right lower quadrant. Carcinoids are neuroendocrine neoplasm originating in multiple locations throughout the body human. About 75% of such neoplasm are located within the gastrointestinal tract and are capable of rpoducing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. The incidence of these tumours is approximately 2.5 in 100.000 people per year. The former classification system of fore gut, midgut and hind gut tumors is still used in clinical routine. Determination of the histopathology of carcinoid tumors is of utmost importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonin and gastrin. New localization procedures include somatostatin receptor scintigraphy and positron emission tomography. Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemo embolization. New therapies, such as ling acting somatostatin analogs, together with further development of tumor targeted treatments, will come into clinical use in the near future. (The author)

  2. MR appearance of skeletal neoplasms following cryotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Richardson, M.L. [Dept. of Radiology SB-05, Washington Univ., Seattle, WA (United States); Lough, L.R. [Pitts Radiological Associates, Columbia, SC (United States); Shuman, W.P. [Dept. of Radiology, Medical Center Hospital of Vermont, Burlington, VT (United States); Lazerte, G.D. [Dept. of Pathology RC-72, Washington Univ., Medical Center Hospital of Vermont, Burlington, VT (United States); Conrad, E.U. [Dept. of Orthopedic Surgery RK-10, Washington Univ., Medical Center of Vermont, Burlington, VT (United States)

    1994-02-01

    Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

  3. MR appearance of skeletal neoplasms following cryotherapy

    International Nuclear Information System (INIS)

    Richardson, M.L.; Lough, L.R.; Shuman, W.P.; Lazerte, G.D.; Conrad, E.U.

    1994-01-01

    Cryotherapy is an increasingly popular mode of therapy adjunctive to surgical curettage in the treatment of certain skeletal neoplasms, such as giant cell tumors or chondrosarcomas. The magnetic resonance (MR) findings following cryotherapy have not been previously reported. We reviewed the MR findings in seven patients with skeletal neoplasms following curettage and cryotherapy. In six cases we found a zone of varying thickness extending beyond the surgical margins, corresponding to an area of cryoinjury to medullary bone. This zone displayed low signal intensity on T1-weighted images and high signal intensity on T2-weighted images, consistent with the presence of marrow edema. This zone of edema almost certainly reflects underlying thermal osteonecrosis. This zone may vary in size and intensity over time as the area of cryoinjury evolves or resolves. MR is currently the imaging procedure of choice for follow-up of most musculoskeletal neoplasms. Knowledge of the MR findings following cryotherapy should help prevent confusion during the interpretation of follow-up MR examinations. (orig.)

  4. Endocrine neoplasms in familial syndromes of hyperparathyroidism.

    Science.gov (United States)

    Li, Yulong; Simonds, William F

    2016-06-01

    Familial syndromes of hyperparathyroidism, including multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), and the hyperparathyroidism-jaw tumor (HPT-JT), comprise 2-5% of primary hyperparathyroidism cases. Familial syndromes of hyperparathyroidism are also associated with a range of endocrine and nonendocrine tumors, including potential malignancies. Complications of the associated neoplasms are the major causes of morbidities and mortalities in these familial syndromes, e.g., parathyroid carcinoma in HPT-JT syndrome; thymic, bronchial, and enteropancreatic neuroendocrine tumors in MEN1; and medullary thyroid cancer and pheochromocytoma in MEN2A. Because of the different underlying mechanisms of neoplasia, these familial tumors may have different characteristics compared with their sporadic counterparts. Large-scale clinical trials are frequently lacking due to the rarity of these diseases. With technological advances and the development of new medications, the natural history, diagnosis, and management of these syndromes are also evolving. In this article, we summarize the recent knowledge on endocrine neoplasms in three familial hyperparathyroidism syndromes, with an emphasis on disease characteristics, molecular pathogenesis, recent developments in biochemical and radiological evaluation, and expert opinions on surgical and medical therapies. Because these familial hyperparathyroidism syndromes are associated with a wide variety of tumors in different organs, this review is focused on those endocrine neoplasms with malignant potential. © 2016 Society for Endocrinology.

  5. Agreement Between Cytology and Histopathology for Regional Lymph Node Metastasis in Dogs With Melanocytic Neoplasms.

    Science.gov (United States)

    Grimes, Janet A; Matz, Brad M; Christopherson, Pete W; Koehler, Jey W; Cappelle, Kelsey K; Hlusko, Katelyn C; Smith, Annette

    2017-07-01

    Melanocytic neoplasms are common in dogs and frequently occur within the oral cavity or in haired skin. The behavior of melanocytic neoplasms is variable and depends on tumor location, size, and histopathologic features. This study compared cytopathology and histopathology of 32 lymph nodes from 27 dogs diagnosed with melanocytic neoplasms. Agreement between the original cytology report, cytology slide review, original histopathology report, and histopathology slide review was determined for each lymph node. A subset of lymph nodes was subjected to immunohistochemistry (Melan-A) and additional histochemical stains/techniques (Prussian blue, bleach) to assist in differentiation of melanocytes and melanophages. Agreement ranged from slight to fair for each of the variables evaluated with weighted kappa (κ w ) or kappa (κ) analysis (original cytology vs cytology review κ w = 0.24; original cytology vs original histopathology κ w = 0.007; original cytology vs histopathology review κ w = 0.23; cytology review vs original histopathology κ w = 0.008; cytology review vs histopathology review κ w = 0.006; and original histopathology vs histopathology review κ = 0.18). The diagnoses (metastatic, equivocal, or negative for metastasis) of the original report and slide review for both cytology and histopathology were not significantly correlated with survival in this population of patients. Overall, agreement between cytology and histopathology was poor even with a single clinical or anatomic pathologist performing slide review. Consensus between routine cytology and histopathology for staging of lymph nodes in patients with melanocytic neoplasms is poor and does not correlate with survival.

  6. Nye sygdomsmarkører ved de kroniske myeloproliferative neoplasier

    DEFF Research Database (Denmark)

    Holmström, Morten Orebo; Ocias, Lukas Frans; Kallenbach, Klaus

    2015-01-01

    The chaperone and calcium storing protein calreticulin is coded by CALR, and newly identified mutations in CALR are found in respectively 49-70% and 56-88% of JAK2- and MPL-negative patients with essential thrombocytaemia (ET) and primary myelofibrosis (PMF). A total of 41 mutations have been...

  7. Molecular pathology of chondroid neoplasms: part 1, benign lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bell, W.C. [University of Alabama at Birmingham, Department of Pathology, Birmingham, AL (United States); University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States); University of Alabama at Birmingham, Department of Diagnostic Radiology, Birmingham, AL (United States); Klein, M.J. [University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States); University of Alabama at Birmingham, Department of Pathology, Birmingham, AL (United States); University of Alabama at Birmingham, Department of Diagnostic Radiology, Birmingham, AL (United States); Pitt, M.J. [University of Alabama at Birmingham, Department of Diagnostic Radiology, Birmingham, AL (United States); University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States); Siegal, G.P. [University of Alabama at Birmingham, Departments of Pathology, Cell Biology, and Surgery, and the Center for Metabolic Bone Disease, Birmingham, AL (United States)

    2006-11-15

    This two-part review presents an overview of the molecular findings associated with both benign and malignant chondroid neoplasms. This first part presents a brief review of methods in molecular pathology along with a review of the cytogenetic and molecular genetic findings in benign chondroid neoplasms. Clinical aspects of the various lesions are briefly discussed, and each tumor is illustrated with representative radiographic and pathologic images. Malignant chondroid neoplasms will be considered in the second part of this review. (orig.)

  8. Molecular pathology of chondroid neoplasms: part 1, benign lesions

    International Nuclear Information System (INIS)

    Bell, W.C.; Klein, M.J.; Pitt, M.J.; Siegal, G.P.

    2006-01-01

    This two-part review presents an overview of the molecular findings associated with both benign and malignant chondroid neoplasms. This first part presents a brief review of methods in molecular pathology along with a review of the cytogenetic and molecular genetic findings in benign chondroid neoplasms. Clinical aspects of the various lesions are briefly discussed, and each tumor is illustrated with representative radiographic and pathologic images. Malignant chondroid neoplasms will be considered in the second part of this review. (orig.)

  9. Metastases in cranean of differential neoplasm tyroids

    International Nuclear Information System (INIS)

    Lopez Chapuis, D.; Garrido Vazquez, P.; Vallverdu Carbajal, M.

    1994-01-01

    Two cases of matastases are presented in cranial calota of differentiated neoplasm of tyroids, one of them without other distance lesions ,in which the cranial tumours was the element that it take was to the diagnose. For the local control the surgical resection of the metastasis is recommended in calota, associated to external radiotherapy , while that the total thyroidectomy allows the detection and treatment of other metastasis with Iodine. In this situation the prediction it is unfavourable, with a half survive of 4,5 year(AU) [es

  10. Treatment of hepatic neoplasm through extrahepatic collaterals

    Energy Technology Data Exchange (ETDEWEB)

    Soo, C.S.; Chuang, V.P.; Wallace, S.; Charnsangavej, C.; Carrasco, H.

    1983-04-01

    Twenty-nine patients with hepatic artery occlusion were treated with additional hepatic infusion or embolization through extrahepatic collaterals. Seventeen courses of hepatic infusion were performed in 13 patients through the inferior pancreaticoduodenal artery, left gastric artery, or right gastric artery. Twenty-five hepatic embolization procedures were performed in 16 patients through the right and left phrenic arteries, left and right gastric arteries, pancreaticoduodenal artery, gastroduodenal artery, or omentoepiploic artery. In one patient gastric ulcers developed following left gastric artery infusion. No complication related to the embolization procedure was observed in the embolization group. The extrahepatic collaterals are important alternative routes for continuous transcatheter management of hepatic neoplasms following hepatic artery occlusion.

  11. Treatment of hepatic neoplasm through extrahepatic collaterals

    International Nuclear Information System (INIS)

    Soo, C.S.; Chuang, V.P.; Wallace, S.; Charnsangavej, C.; Carrasco, H.

    1983-01-01

    Twenty-nine patients with hepatic artery occlusion were treated with additional hepatic infusion or embolization through extrahepatic collaterals. Seventeen courses of hepatic infusion were performed in 13 patients through the inferior pancreaticoduodenal artery, left gastric artery, or right gastric artery. Twenty-five hepatic embolization procedures were performed in 16 patients through the right and left phrenic arteries, left and right gastric arteries, pancreaticoduodenal artery, gastroduodenal artery, or omentoepiploic artery. In one patient gastric ulcers developed following left gastric artery infusion. No complication related to the embolization procedure was observed in the embolization group. The extrahepatic collaterals are important alternative routes for continuous transcatheter management of hepatic neoplasms following hepatic artery occlusion

  12. Four types of neoplasms in Asian sea bass (Lates calcarifer

    Directory of Open Access Journals (Sweden)

    Ramalingam Vijayakumar

    2015-06-01

    Full Text Available Objective: To describe and observe four types of neoplasms on different parts (external and internal organs of an Asian sea bass (Lates calcarifer. Methods: The sample was collected from local fish landing center (south east coast of India. Histopathology of normal and tumour tissues were analyzed. Results: A total of 83 tumour masses (neoplasm were recorded on the fish skin, also the neoplasms were recorded in internal organs of fish such as liver, stomach and ovary. Conclusions: Aetiology of such neoplasm’s are unknown, further more researches need to confirm the causative agent for this type of neoplasm.

  13. Unusual cystic pancreatic neoplasms -image-pathological correlations

    International Nuclear Information System (INIS)

    Hilendarov, A.; Simova, E.; Petrova, A.; Traikova, N.; Deenichin, G.

    2013-01-01

    The aim is to present the variety of signs and symptoms from the diagnostic imaging methods of atypical neoplasms of the pancreas, presented as a type of cystic lesions. This often leads to unnecessary surgery or inappropriate tracking. In 115 patients (85 men and 30 women) with cystic lesions of the pancreas ultrasonic (US),computer tomography (CT) and magnetic resonance imaging (MRI) were performed and verified through histological and macroscopic pathology preparations. The ultrasound machines equipped with linear and convex transducers, MDCT and MRI imaging systems were used. In 14 of 115 patients atypical neoplasms of the pancreas were diagnosed: two cases with macroscopic serous cystic neoplasms, two nonmucinous cystic neoplasms, two hemorrhagic mucinous neoplasms, two ductal adenocarcinomas with cystic changes, one islet cell cystic tumor, two lymphoepithetial cysts, one lymphangioma, one solid papillary epithelial neoplasm and one mucinous adenocarcinoma. The authors take into consideration and overlapping of clinical symptoms and laboratory tests. Although much of the imaging features and morphological characteristics of cystic neoplasms of the pancreas are well known, should be known about the atypical unusual images in so-called 'typical' cystic neoplasms, cystic images in solid neoplasms and various atypical tumors with cystic lesions. (authors)

  14. Expansion of circulating CD56bright natural killer cells in patients with JAK2-positive chronic myeloproliferative neoplasms during treatment with interferon-α

    DEFF Research Database (Denmark)

    Riley, Caroline H; Hansen, Morten; Brimnes, Marie K

    2015-01-01

    with IFN-α compared to patients that are untreated, treated with hydroxyurea and healthy controls, P ... cell response to target-cell recognition during treatment with IFN-α in four patients. We also report low levels of circulating NK cells in untreated patients compared to healthy donors, patients treated with hydroxyurea and IFN-α, P = 0.02. Based on our findings, one might speculate whether treatment...

  15. A new internet-based tool for reporting and analysing patient-reported outcomes and the feasibility of repeated data collection from patients with myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Brochmann, Nana; Zwisler, Ann-Dorthe; Kjerholt, Mette

    2016-01-01

    PURPOSE: An Internet-based tool for reporting and analysing patient-reported outcomes (PROs) has been developed. The tool enables merging PROs with blood test results and allows for computation of treatment responses. Data may be visualized by graphical analysis and may be exported for downstream...

  16. Novel BET protein proteolysis-targeting chimera exerts superior lethal activity than bromodomain inhibitor (BETi) against post-myeloproliferative neoplasm secondary (s) AML cells.

    Science.gov (United States)

    Saenz, D T; Fiskus, W; Qian, Y; Manshouri, T; Rajapakshe, K; Raina, K; Coleman, K G; Crew, A P; Shen, A; Mill, C P; Sun, B; Qiu, P; Kadia, T M; Pemmaraju, N; DiNardo, C; Kim, M-S; Nowak, A J; Coarfa, C; Crews, C M; Verstovsek, S; Bhalla, K N

    2017-09-01

    The PROTAC (proteolysis-targeting chimera) ARV-825 recruits bromodomain and extraterminal (BET) proteins to the E3 ubiquitin ligase cereblon, leading to degradation of BET proteins, including BRD4. Although the BET-protein inhibitor (BETi) OTX015 caused accumulation of BRD4, treatment with equimolar concentrations of ARV-825 caused sustained and profound depletion (>90%) of BRD4 and induced significantly more apoptosis in cultured and patient-derived (PD) CD34+ post-MPN sAML cells, while relatively sparing the CD34+ normal hematopoietic progenitor cells. RNA-Seq, Reverse Phase Protein Array and mass cytometry 'CyTOF' analyses demonstrated that ARV-825 caused greater perturbations in messenger RNA (mRNA) and protein expressions than OTX015 in sAML cells. Specifically, compared with OTX015, ARV-825 treatment caused more robust and sustained depletion of c-Myc, CDK4/6, JAK2, p-STAT3/5, PIM1 and Bcl-xL, while increasing the levels of p21 and p27. Compared with OTX015, PROTAC ARV-771 treatment caused greater reduction in leukemia burden and further improved survival of NSG mice engrafted with luciferase-expressing HEL92.1.7 cells. Co-treatment with ARV-825 and JAK inhibitor ruxolitinib was synergistically lethal against established and PD CD34+ sAML cells. Notably, ARV-825 induced high levels of apoptosis in the in vitro generated ruxolitinib-persister or ruxolitinib-resistant sAML cells. These findings strongly support the in vivo testing of the BRD4-PROTAC based combinations against post-MPN sAML.

  17. Management of solid-pseudopapillary neoplasms of the pancreas: a comparison with standard pancreatic neoplasms

    NARCIS (Netherlands)

    de Castro, S. M. M.; Singhal, D.; Aronson, D. C.; Busch, O. R. C.; van Gulik, T. M.; Obertop, H.; Gouma, D. J.

    2007-01-01

    BACKGROUND: Solid-pseudopapillary neoplasms (SPNs) of the pancreas are increasingly diagnosed, but the exact surgical management in terms of extent of the resection is not well defined. MATERIALS AND METHODS: Patients operated on in our hospital between January 1993 and March 2005 formed the study

  18. Peptichemio in pretreated patients with plasmacell neoplasms.

    Science.gov (United States)

    Paccagnella, A; Salvagno, L; Chiarion-Sileni, V; Bolzonella, S; De Besi, P; Frizzarin, M; Pappagallo, G L; Fosser, V P; Fornasiero, A; Segati, R

    1986-09-01

    Twenty-one patients with alkylator-resistant plasmacell neoplasms were treated with Peptichemio (PTC) at a dose of 40 mg/m2 for 3 days every 3 weeks or, in the case of persistent leukopenia and/or thrombocytopenia, at the single dose of 70 mg/m2 every 2-3 weeks according to haematological recovery. Seventeen patients, 10 with multiple myeloma and seven with extramedullary plasmacytoma (EMP), were fully evaluable. Six of 17 patients (35%) responded: three of seven EMP patients had a complete remission and 3 of 10 multiple myeloma patients had an objective response greater than 50%. The median duration of response was 8.5 months. An EMP patient obtained a complete response lasting for 16 months. The most frequent toxic effect were phlebosclerosis, occurring in all the patients, and myelosuppression, which was severe in only one case. PTC appears to be an active drug in patients with plasmacell neoplasms even if resistant to alkylating agents.

  19. Pancreatic neuroendocrine neoplasms; Neuroendokrine Neoplasien des Pankreas

    Energy Technology Data Exchange (ETDEWEB)

    Beiderwellen, K.; Lauenstein, T.C. [Universitaetsklinikum Essen, Institut fuer Diagnostische und Interventionelle Radiologie und Neuroradiologie, Essen (Germany); Sabet, A.; Poeppel, T.D. [Universitaetsklinikum Essen, Klinik fuer Nuklearmedizin, Essen (Germany); Lahner, H. [Universitaetsklinikum Essen, Klinik fuer Endokrinologie und Stoffwechselerkrankungen, Essen (Germany)

    2016-04-15

    Pancreatic neuroendocrine neoplasms (NEN) account for 1-2 % of all pancreatic neoplasms and represent a rare differential diagnosis. While some pancreatic NEN are hormonally active and exhibit endocrine activity associated with characteristic symptoms, the majority are hormonally inactive. Imaging techniques such as ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) or as combined PET/CT play a crucial role in the initial diagnosis, therapy planning and control. Endoscopic ultrasound (EUS) and multiphase CT represent the reference methods for localization of the primary pancreatic tumor. Particularly in the evaluation of small liver lesions MRI is the method of choice. Somatostatin receptor scintigraphy and somatostatin receptor PET/CT are of particular value for whole body staging and special aspects of further therapy planning. (orig.) [German] Neuroendokrine Neoplasien (NEN) des Pankreas stellen mit einem Anteil von 1-2 % aller pankreatischen Tumoren eine seltene Differenzialdiagnose dar. Ein Teil der Tumoren ist hormonell aktiv und faellt klinisch durch charakteristische Symptome auf, wohingegen der ueberwiegende Anteil hormonell inaktiv ist. Bildgebende Verfahren wie Sonographie, Computertomographie (CT), Magnetresonanztomographie (MRT) und nicht zuletzt Positronenemissionstomographie (PET oder kombiniert als PET/CT) spielen eine zentrale Rolle fuer Erstdiagnose, Therapieplanung und -kontrolle. Die Endosonographie und die multiphasische CT stellen die Referenzmethoden zur Lokalisation des Primaertumors dar. Fuer die Differenzierung insbesondere kleiner Leberlaesionen bietet die MRT die hoechste Aussagekraft. Fuer das Ganzkoerperstaging und bestimmte Aspekte der Therapieplanung lassen sich die Somatostatinrezeptorszintigraphie und v. a. die Somatostatinrezeptor-PET/CT heranziehen. (orig.)

  20. Plasma Cell Neoplasms (Including Multiple Myeloma)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells form cancerous tumors. When there is only one tumor, the disease is called a plasmacytoma. When there are multiple tumors, it is called multiple myeloma. Start here to find information on plasma cell neoplasms treatment, research, and statistics.

  1. [Closed needle-biopsy in the diagnosis of neoplasms].

    Science.gov (United States)

    Sforza, M; Perelli Ercolini, M; Beani, G

    1979-04-01

    The AA. demonstrate with this communication the validity of the needle biopsie for the diagnosis of neoplasms. They had used it for the breast, thyroid, flg and some other superficial tumefactions. In the mass-screening for the feminine neoplasms the clinical examination and the needle biopsy are very good method for a careful diagnosis.

  2. Characteristic radionuclide appearance of certain pediatric central nervous system neoplasms

    International Nuclear Information System (INIS)

    Conway, J.J.

    1974-01-01

    The results of 5 years experience in the localization of brain neoplasms in children are summarized. The radiopharmaceutical of choice was /sup 99m/Tc-labeled pertechnetate administered in a dosage of 100μ Ci/lb. The appearance of the most common neoplasms of the central nervous system in childhood is characterized. (U.S.)

  3. Multiple neoplasms, single primaries, and patient survival

    Directory of Open Access Journals (Sweden)

    Amer MH

    2014-03-01

    Full Text Available Magid H Amer Department of Medicine, St Rita's Medical Center, Lima, OH, USA Background: Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. Methods: This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Results: Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284, and three or more primaries (n=38. Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%, with a tendency to develop thrombosis (20.2%, had a strong family history of similar cancer (22.3%, and usually presented with earlier stage 0 through stage II disease (78.9%. When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001. Five-year survival rates were higher for metachronous cancers (95% than for synchronous primaries (59% and single primaries (59%. The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991. Conclusion: Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent

  4. Cytogenetic Evolution in Myeloid Neoplasms at Relapse after Allogeneic Hematopoietic Cell Transplantation: Association with Previous Chemotherapy and Effect on Survival.

    Science.gov (United States)

    Ertz-Archambault, Natalie; Kosiorek, Heidi; Slack, James L; Lonzo, Melissa L; Greipp, Patricia T; Khera, Nandita; Kelemen, Katalin

    2017-05-01

    Cytogenetic evolution (CGE) in patients with myeloid neoplasms who relapsed after an allogeneic (allo) hematopoietic cell transplantation (HCT) has been evaluated by only few studies. The effect of the CGE on survival of relapsed allo-HCT recipients is not clear. The effect of previously received chemotherapy to induce CGE in this patient population has not been studied. The aims of our study are to (1) characterize the patterns of cytogenetic change in patients with myeloid neoplasms who relapsed after an allo-HCT, (2) evaluate the effect of CGE on survival, and (3) explore the association of CGE with previous chemotherapy (including the lines of salvage therapy, type of induction, and conditioning therapy). Of 49 patients with a myeloid malignancy (27 acute myeloid leukemia [AML], 19 myelodysplastic syndrome [MDS]/myeloproliferative neoplasm [MPN], and 3 chronic myelogenous leukemia) who relapsed after an allo-HCT, CGE was observed in 25 (51%), whereas 24 patients had unchanged cytogenetic findings at relapse. The CGE group carried more cytogenetic abnormalities at original diagnosis. The most frequent cytogenetic change was the acquisition of 3 or more new chromosomal abnormalities followed by acquisition of unbalanced abnormalities, aneuploidy, and emergence of apparently new clones unrelated to the original clone. The CGE cohort had higher proportion of MDS and MPN and fewer patients with de novo AML. Disease risk assessment category showed a trend to higher frequency of high-risk patients in the CGE group, though the difference was not statistically significant. Time from diagnosis to transplantation and time from transplantation to relapse were not different between the CGE and non-CGE groups. CGE and non-CGE cohorts had similar exposures to salvage therapy and to induction chemotherapy, as well as similar conditioning regimens; thus, no particular type of chemotherapy emerged as a predisposing factor to CGE. CGE was associated with significantly shortened

  5. Zosteriform cutaneous leiomyoma: a rare cutaneous neoplasm

    International Nuclear Information System (INIS)

    Bari, A.U.

    2013-01-01

    Cutaneous leiomyomas are firm, round to oval, skin-coloured to brownish papules and nodules that may present as a solitary, few discrete or multiple clustered lesions. Different uncommon patterns of multiple leiomyoma distribution have been noted as bilateral, symmetrical, linear, zosteriform, or dermatomal-like arrangement. One such rare presentation was seen in a 23-year-old patient who presented with zosteriform skin coloured, occasionally painful cutaneous lesions over left shoulder region. Histopathology confirmed the diagnosis of cutaneous leiomyoma. He was symptomatically managed with non-steroidal anti-inflammatory agents and topical capcicum cream. Case is reported here due to rare occurrence of this benign cutaneous neoplasm in an atypical pattern and on uncommon site. (author)

  6. Radioisotope diagnostics of neoplasms in children

    International Nuclear Information System (INIS)

    Mechev, D.S.; Sinyuta, B.T.; Borisyuk, T.B.

    1982-01-01

    On the basis of radioisotope studies of 111 children with neoplasms of locomotor system, retroperitoneal space, maxillofacial region and neck, the limits and possibilities of the method of positive radiodiagnostics with short-life radionuclides sup(99M)Tc pertechnetate and 99 Tc pyrophosphate have been analyzed. It is pointed out that sensitivity of the investigation method with sup(99M)Tc pyrophosphate is higher (91.6%) than that of the method with 99 Tc pertechnetate (84.5%). Specificity of the investigation method with 99 Tc p.ertechnetate is higher (71.5%) than that of the method with sup(99M)Tc pyrophosphate (30%). The method of positive radiodiagnostics is characterized by safety, atraumatism, low radiation burdens and possibility of its realization in ambulatory conditions

  7. Rectal neoplasms. Postoperative follow-up

    International Nuclear Information System (INIS)

    Galano Urgelles, Rolando; Rodriguez Fernandez, Zenen; Casaus Prieto, Arbelio

    1997-01-01

    A study of 31 patients operated on for rectal neoplasms between September, 1989 and September, 1995 in SantiAug de Cuba was performed. Patients Webre followed-up during this period for the purpose of the study. There was a frank predominance of males and ages between 45 and 64, of the stage II and the groups BI and BII according to Dukes' classification. Most patients received 5-fluoracil, without tumor relapses. The current survival rate of the series was 76 % at the end of the investigation. It is recommended that all patients operated on for this segment be followed-up after the operation; to continue with cytostatic treatment using 5-fluoracil, and to emphasize the importance of the use of tumor markers during the follow-up, in addition to transrectal ultrasound, as well as to make an early diagnosis through mass screening methods

  8. Surgical and molecular pathology of pancreatic neoplasms.

    Science.gov (United States)

    Hackeng, Wenzel M; Hruban, Ralph H; Offerhaus, G Johan A; Brosens, Lodewijk A A

    2016-06-07

    Histologic characteristics have proven to be very useful for classifying different types of tumors of the pancreas. As a result, the major tumor types in the pancreas have long been classified based on their microscopic appearance. Recent advances in whole exome sequencing, gene expression profiling, and knowledge of tumorigenic pathways have deepened our understanding of the underlying biology of pancreatic neoplasia. These advances have not only confirmed the traditional histologic classification system, but also opened new doors to early diagnosis and targeted treatment. This review discusses the histopathology, genetic and epigenetic alterations and potential treatment targets of the five major malignant pancreatic tumors - pancreatic ductal adenocarcinoma, pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, acinar cell carcinoma and pancreatoblastoma.

  9. Prognostic factors in childhood intracranial neoplasms

    International Nuclear Information System (INIS)

    Ampil, F.L.

    1987-01-01

    Thirty-six cases of primary intracranial neoplasm in children (over 1 year but under 13 years of age) seen at the university medical center between 1951 and 1982 were reviewed because of concern as to the results and after-effects of applied therapy. The overall 5-year actuarial survival rate was 17 %. Several factors of possible prognostic relevance, such as patient's age, intracranial location of the tumor, application or nonapplication of therapy, single or multiple modes of therapy, and extent of surgery, were analyzed. Completeness of surgical removal of the tumor proved to be the only statistically significant factor that correlated with survival. There was only one recorded case of severe learning disability and abnormal neuropsychologic development among the 12 living patients. The influence of patient's age (and technical factors) at the time of irradiation in correlation with the child's subsequent posttreatment functional performance, as reported in the literature, is reviewed. (author)

  10. Multiple neoplasms, single primaries, and patient survival

    International Nuclear Information System (INIS)

    Amer, Magid H

    2014-01-01

    Multiple primary neoplasms in surviving cancer patients are relatively common, with an increasing incidence. Their impact on survival has not been clearly defined. This was a retrospective review of clinical data for all consecutive patients with histologically confirmed cancer, with emphasis on single versus multiple primary neoplasms. Second primaries discovered at the workup of the index (first) primary were termed simultaneous, if discovered within 6 months of the index primary were called synchronous, and if discovered after 6 months were termed metachronous. Between 2005 and 2012, of 1,873 cancer patients, 322 developed second malignancies; these included two primaries (n=284), and three or more primaries (n=38). Forty-seven patients had synchronous primaries and 275 had metachronous primaries. Patients with multiple primaries were predominantly of Caucasian ancestry (91.0%), with a tendency to develop thrombosis (20.2%), had a strong family history of similar cancer (22.3%), and usually presented with earlier stage 0 through stage II disease (78.9%). When compared with 1,551 patients with a single primary, these figures were 8.9%, 15.6%, 18.3%, and 50.9%, respectively (P≤0.001). Five-year survival rates were higher for metachronous cancers (95%) than for synchronous primaries (59%) and single primaries (59%). The worst survival rate was for simultaneous concomitant multiple primaries, being a median of 1.9 years. The best survival was for patients with three or more primaries (median 10.9 years) and was similar to the expected survival for the age-matched and sex-matched general population (P=0.06991). Patients with multiple primaries are usually of Caucasian ancestry, have less aggressive malignancies, present at earlier stages, frequently have a strong family history of similar cancer, and their cancers tend to have indolent clinical behavior with longer survival rates, possibly related to genetic predisposition

  11. Percutaneous thermal ablation of renal neoplasms

    International Nuclear Information System (INIS)

    Tacke, J.; Mahnken, A.H.; Guenther, R.W.

    2005-01-01

    Due to modern examination techniques such as multidetector computed tomography and high-field magnetic resonance imaging, the detection rate of renal neoplasms is continually increasing. Even though tumors exceeding 4 cm in diameter rarely metastasize, all renal lesions that are possible neoplasms should be treated. Traditional treatment techniques include radical nephrectomy or nephron-sparing resection, which are increasingly performed laparoscopically. Modern thermal ablation techniques such as hyperthermal techniques like radiofrequency ablation RFA, laser induced thermal ablation LITT, focused ultrasound FUS and microwave therapy MW, as well as hypothermal techniques (cryotherapy) may be a useful treatment option for patients who are unfit for or refuse surgical resection. Cryotherapy is the oldest and best known thermal ablation technique and can be performed laparoscopically or percutaneously. Since subzero temperatures have no antistyptic effect, additional maneuvers must be performed to control bleeding. Percutaneous cryotherapy of renal tumors is a new and interesting method, but experience with it is still limited. Radiofrequency ablation is the most frequently used method. Modern probe design allows volumes between 2 and 5 cm in diameter to be ablated. Due to hyperthermal tract ablation, the procedure is deemed to be safe and has a low complication rate. Although there are no randomized comparative studies to open resection, the preliminary results for renal RFA are promising and show RFA to be superior to other thermal ablation techniques. Clinical success rates are over 90% for both, cryo- and radiofrequency ablation. Whereas laser induced thermal therapy is established in hepatic ablation, experience is minimal with respect to renal application. For lesions of more than 2 cm in diameter, additional cooling catheters are required. MR thermometry offers temperature control during ablation. Microwave ablation is characterized by small ablation volumes

  12. Molecular pathology of chondroid neoplasms: part 2, malignant lesions

    International Nuclear Information System (INIS)

    Bell, W.C.; Klein, M.J.; Pitt, M.J.; Siegal, G.P.

    2006-01-01

    This is the second part of a two-part review presenting an overview of the molecular findings associated with both benign and malignant chondroid neoplasms. The first part presented a brief review of modern methods in molecular pathology, along with a review of the cytogenetic and molecular genetic findings in benign chondroid neoplasms. This second part reviews the cytogenetic and molecular genetic findings in malignant chondroid neoplasms. Clinical aspects of the various lesions are briefly discussed, and each tumor is illustrated with representative radiographic and pathologic images. (orig.)

  13. Molecular pathology of chondroid neoplasms: part 2, malignant lesions

    Energy Technology Data Exchange (ETDEWEB)

    Bell, W.C. [University of Alabama at Birmingham, Department of Pathology, Birmingham, AL (United States); University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States); Klein, M.J. [University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States); University of Alabama at Birmingham, Department of Pathology, Birmingham, AL (United States); Pitt, M.J. [University of Alabama at Birmingham, Department of Diagnostic Radiology, Birmingham, AL (United States); University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States); Siegal, G.P. [University of Alabama at Birmingham, Departments of Pathology, Cell Biology, and Surgery, Birmingham, AL (United States); University of Alabama at Birmingham, Center for Metabolic Bone Disease, Birmingham, AL (United States)

    2006-12-15

    This is the second part of a two-part review presenting an overview of the molecular findings associated with both benign and malignant chondroid neoplasms. The first part presented a brief review of modern methods in molecular pathology, along with a review of the cytogenetic and molecular genetic findings in benign chondroid neoplasms. This second part reviews the cytogenetic and molecular genetic findings in malignant chondroid neoplasms. Clinical aspects of the various lesions are briefly discussed, and each tumor is illustrated with representative radiographic and pathologic images. (orig.)

  14. Chronic inflammation as a promotor of mutagenesis in essential thrombocythemia, polycythemia vera and myelofibrosis. A human inflammation model for cancer development?

    DEFF Research Database (Denmark)

    Hasselbalch, Hans K

    2013-01-01

    The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are acquired stem cell neoplasms, in which a stem cell lesion induces an autonomous proliferative advantage. In addition to the JAK2V617 mutation several other mutations have been described. Recently chronic inflammation has be...

  15. Myeloproliferative Disease: An Unusual Cause of Raynaud’s Phenomenon and Digital Ischaemia

    Directory of Open Access Journals (Sweden)

    Celia Beynon

    2016-01-01

    Full Text Available We describe a 59-year-old female who presented with ischaemic digits, preceded by a 6-month history of Raynaud’s phenomenon affecting her fingers and toes. There were no clinical or laboratory features of primary vasculitis or connective tissue disease, Doppler imaging was normal, and bloods were unremarkable aside from a platelet count of 786 × 109/L (150–400 and white cells of 16 × 109/L (4–11. In view of the thrombocytosis a JAK2 mutation assay was requested which confirmed a JAK2 V617F mutation, suggesting essential thrombocytosis (ET as the cause. She received treatment with hydroxycarbamide which normalised her platelet count and led to a complete resolution of her Raynaud’s symptoms. Raynaud’s phenomenon is a rare manifestation of ET. Myeloproliferative disorders such as ET should be considered in the differential diagnosis of Raynaud’s phenomenon and vasculitis.

  16. Mesenteric venous thrombosis secondary to an unsuspected JAK2 V617F-positive myeloproliferative disorder.

    LENUS (Irish Health Repository)

    2012-01-31

    BACKGROUND: Mesenteric venous thrombosis (MVT) is a rare but potentially fatal cause of mesenteric ischaemia. It presents insidiously and often diagnosis is made at emergency surgery. In half of the cases MVT develops without a causative factor, while in cases in which a pro-thrombotic state is found to exist MVT may be the first clinically detected consequence of that state. The myeloproliferative disorders (MPD) are known to contribute to the development of pro-thrombotic states. Recently, the JAK2 V617F mutation has been associated with the MPDs. CONCLUSION: We describe a case of MVT occurring secondary to an unsuspected MPD, in which the patient was subsequently found to carry this mutation. We highlight the necessity to screen for this mutation in cases of intra-abdominal thromboses so that appropriate systemic anticoagulation may be instituted, and the patient may be followed so as to detect the development of an overt MPD.

  17. Pathogenetic Role of JAK2 V617F Mutation in Chronic Myeloproliferative Disorders

    Directory of Open Access Journals (Sweden)

    Hui-Chi Hsu

    2007-03-01

    Full Text Available The molecular pathogenesis of chronic myeloproliferative disorders (MPDs is poorly understood. The hematopoietic progenitor cells of patients with polycythemia vera (PV or essential thrombocythemia (ET are characterized by hypersensitiv-ity to hematopoietic growth factors and formation of endogenous erythroid colonies. Recently, 4 groups reported almost simultaneously Janus kinase 2 (JAK2 V617F mutation in more than 80% of PV patients, 30% of patients with ET and in about 50% of patients with idiopathic myelofibrosis. The identification of the JAK2 mutation represents a major advance in the understanding of the molecular pathogenesis of MPDs that will likely permit a new classification and the development of novel therapeutic strategies for these diseases.

  18. Eponyms in cardiothoracic radiology: Part I. Neoplasms.

    Science.gov (United States)

    Mohammed, Tan-Lucien H; Saettele, Megan R; Saettele, Timothy; Patel, Vikas; Kanne, Jeffrey P

    2014-01-01

    Eponyms serve the purpose of honoring individuals who have made important observations and discoveries. As with other fields of medicine, eponyms are frequently encountered in radiology, particularly in chest radiology. However, inappropriate use of an eponym may lead to potentially dangerous miscommunication. Moreover, an eponym may honor the incorrect person or a person who falls into disrepute. Despite their limitations, eponyms are still widespread in medical literature. Furthermore, in some circumstances, more than one individual may have contributed to the description or discovery of a particular anatomical structure or disease, whereas in others, an eponym may have been incorrectly applied initially and propagated for years in medical literature. Nevertheless, radiologic eponyms are a means of honoring those who have made lasting contributions to the field of radiology, and familiarity with these eponyms is critical for proper reporting and accurate communication. In addition, the acquisition of some historical knowledge about those whose names are associated with various structures or pathologic conditions conveys a sense of humanity in the field of medicine. In this article, the first of a multipart series, the authors discuss a number of chest radiology eponyms as they relate to neoplasms, including relevant clinical and imaging features, as well biographic information of the respective eponym׳s namesake. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Minimally-aggressive gestational trophoblastic neoplasms.

    Science.gov (United States)

    Cole, Laurence A

    2012-04-01

    We have previously defined a new syndrome "Minimally-aggressive gestational trophoblastic neoplasms" in which choriocarcinoma or persistent hydatidiform mole has a minimal growth rate and becomes chemorefractory. Previously we described a new treatment protocol, waiting for hCG rise to >3000 mIU/ml and disease becomes more advanced, then using combination chemotherapy. Initially we found this treatment successful in 8 of 8 cases, here we find this protocol appropriate in a further 16 cases. Initially we used hyperglycosylated hCG, a limited availability test, to identify this syndrome. Here we propose also using hCG doubling rate to detect this syndrome. Minimally aggressive gestational trophoblastic disease can be detected by chemotherapy resistance or low hyperglycosylated hCG, disease by hyperglycosylated hCG and by hCG doubling test. All were recommended to hold off further chemotherapy until hCG >3000mIU/ml. One case died prior to the start of the study, one case withdrew because of a lung nodule and one withdrew refusing the suggested combination chemotherapy. The remaining 16 women were all successfully treated. A total of 8 plus 16 or 24 of 24 women were successfully treated using the proposed protocol, holding back on chemotherapy until hCG >3000mIU/ml. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. INTRACRANIAL NEOPLASMS IN IBADAN, NIGERIA B.J. OLASODE ...

    African Journals Online (AJOL)

    hi-tech

    2000-01-01

    Jan 1, 2000 ... Results: Two hundred and ten intracronial neoplasms comprising 172 ... accounted for the largest group of tumours followed by metastases to the brain. ..... Percentage .... astrocytomas may be attributed to the increasing use.

  1. Adrenocortical oncocytic neoplasm presenting with Cushing's syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Kabayegit Ozlem

    2008-07-01

    Full Text Available Abstract Introduction Oncocytic neoplasms occur in several organs and are most commonly found in the thyroid, kidneys and salivary glands. Oncocytic neoplasms of the adrenal cortex are extremely rare and are usually non-functioning. Case presentation We report the case of an adrenocortical oncocytic neoplasm with uncertain malignant potential in a 31-year-old man with Cushing's syndrome. The patient had been operated on following diagnosis of a 7 cm adrenal mass. Following surgery, the Cushing's syndrome resolved. The patient is still alive with no metastases one year after the surgery. Conclusion Adrenocortical oncocytic neoplasms must be considered in the differential diagnosis of both functioning and non-functioning adrenal masses.

  2. Preoperation diagnosis of stomach neoplasm metases in the liver

    International Nuclear Information System (INIS)

    Fisher, M.E.; Zholnerovich, E.M.; Zelenkevich, A.S.

    1988-01-01

    It is shown that application of ultrasonography and computerized tomography in examining the upper part of abdomen in patients with stomach neoplasm permits to judge on metastases into the liver. Application of invasive methods of examination is indicated only in case of indefinite data of ultrasonography and computerized tomography. It is shown that application of invasive methods isn't advisable in patients with stomach neoplasm to which palliative operations are indicated. 4 refs

  3. Respiratory muscle strength of patients with esophagus and stomach neoplasms

    Directory of Open Access Journals (Sweden)

    Evelyn Aline Boscolo Ruivo

    Full Text Available Abstract Introduction: In cancer patients, the reduced food intake causes weight loss and promotes protein-calorie malnutrition. This results in loss of lean body mass, which affects both skeletal muscles and respiratory muscles. Objective: Evaluate and compare the respiratory muscle strength of patients with esophageal and stomach neoplasia during the preoperative period. Methods: This is a cross-sectional study carried out with 24 patients of both genders hospitalized in a teaching hospital. They underwent a physical therapy evaluation composed of anthropometric data and measurement of respiratory muscle strength through manovacuometry. Paired and unpaired t-tests were used to compare the values obtained with the predicted equations. Results: Regarding the disease prevalence, 66.66%(16 of the individuals had stomach neoplasm and 33.33%(8 esophageal neoplasm. Of the patients with esophageal neoplasm, 100% were men with a mean age of 63 ± 9.16 years. Of those with stomach neoplasm, 68.75% were men with a mean age of 69.36 ± 10.92 years. Female patients with stomach neoplasm had significantly higher BMI (p = 0.01 than male patients, and they were classified as overweight. Both neoplasms had significantly lower real values (p ≤ 0.05 than predicted values at the maximal expiratory pressure. Conclusion: Patients with esophageal and stomach neoplasms in the preoperative period present reduction in the expiratory muscle strength. There were no statistically significant differences, when we compared the maximum respiratory pressures between the two types of neoplasms investigated.

  4. Squamous neoplasms arising within tattoos: clinical presentation, histopathology and management.

    Science.gov (United States)

    Junqueira, A L; Wanat, K A; Farah, R S

    2017-08-01

    Tattooing, which involves the placement of ink into the skin, is an ancient decorative technique that has remained popular in modern society. Tattoos have long been known to cause cutaneous reactions, which include the emergence of neoplasms such as keratoacanthoma (KA) and squamous cell carcinoma (SCC) in tattooed areas of the skin. We review the clinical presentations, histology and treatment options for squamous neoplasms, primarily KA and SCC, arising in tattoos. © 2017 British Association of Dermatologists.

  5. Inferior phrenic artery embolization in the treatment of hepatic neoplasms

    International Nuclear Information System (INIS)

    Duprat, G.; Charnsangavej, C.; Wallace, S.; Carrasco, C.H.

    1988-01-01

    Twenty-nine inferior phrenic artery embolizations were performed in 20 patients with primary or metastatic hepatic neoplasms. All patients had interruption of their hepatic arteries by previous infusion of chemotherapy, hepatic arterial embolization or surgical ligation. In one patient, bilateral pleural effusions developed following embolization of the inferior phrenic artery. No other severe complications occurred. Inferior phrenic artery embolization is a safe procedure and permits the continuation of transcatheter treatment of hepatic neoplasms. (orig.)

  6. Inferior phrenic artery embolization in the treatment of hepatic neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Duprat, G.; Charnsangavej, C.; Wallace, S.; Carrasco, C.H.

    Twenty-nine inferior phrenic artery embolizations were performed in 20 patients with primary or metastatic hepatic neoplasms. All patients had interruption of their hepatic arteries by previous infusion of chemotherapy, hepatic arterial embolization or surgical ligation. In one patient, bilateral pleural effusions developed following embolization of the inferior phrenic artery. No other severe complications occurred. Inferior phrenic artery embolization is a safe procedure and permits the continuation of transcatheter treatment of hepatic neoplasms.

  7. Plurihormonal Cosecretion by a Case of Adrenocortical Oncocytic Neoplasm

    Directory of Open Access Journals (Sweden)

    J. J. Corrales

    2016-01-01

    Full Text Available Adrenocortical oncocytic neoplasms (oncocytomas are extremely rare; only approximately 159 cases have been described so far. The majority are nonfunctional and benign. We describe an unusual case of a functional oncocytoma secreting an excess of glucocorticoids (cortisol and androgens (androstenedione and DHEAS, a pattern of plurihormonal cosecretion previously not reported in men, presenting with endocrine manifestations of Cushing’s syndrome. The neoplasm was considered to be of uncertain malignant potential (borderline according to the Lin-Weiss-Bisceglia criteria.

  8. Origin of B-Cell Neoplasms in Autoimmune Disease.

    Directory of Open Access Journals (Sweden)

    Kari Hemminki

    Full Text Available Autoimmune diseases (ADs are associated with a number of B-cell neoplasms but the associations are selective in regard to the type of neoplasm and the conferred risks are variable. So far no mechanistic bases for these differential associations have been demonstrated. We speculate that developmental origin of B-cells might propose a mechanistic rationale for their carcinogenic response to autoimmune stimuli and tested the hypothesis on our previous studies on the risks of B-cell neoplasms after any of 33 ADs. We found that predominantly germinal center (GC-derived B-cells showed multiple associations with ADs: diffuse large B cell lymphoma associated with 15 ADs, follicular lymphoma with 7 ADs and Hodgkin lymphoma with 11 ADs. Notably, these neoplasms shared significant associations with 5 ADs (immune thrombocytopenic purpura, polymyositis/dermatomyositis, rheumatoid arthritis, Sjogren syndrome and systemic lupus erythematosis. By contrast, primarily non-GC neoplasms, acute lymphocytic leukemia, chronic lymphocytic leukemia and myeloma associated with 2 ADs only and mantle cell lymphoma with 1 AD. None of the neoplasms shared associated ADs. These data may suggest that autoimmune stimulation critically interferes with the rapid cell division, somatic hypermutation, class switch recombination and immunological selection of maturing B-cell in the GC and delivers damage contributing to transformation.

  9. CT characteristics of primary retroperitoneal neoplasms in children

    International Nuclear Information System (INIS)

    Xu Yufeng; Wang Jichen; Peng Yun; Zeng Jinjin

    2010-01-01

    Primary retroperitoneal neoplasms are uncommon in children. Retroperitoneal neoplasms are either mesodermal, neurogenic, germ cell ectodermal or lymphatic in origin. In general, primary retroperitoneal neoplasms in children have different spectrum and prevalence compared to those in adults. Neuroblastoma, rhabdomyosarcoma, benign teratoma and lymphoma are the common retroperitoneal neoplasms. In this review, the clinical and CT futures of common retroperitoneal neoplasms in children are described. Coarse, amorphous, and mottled calcification are very common in neuroblastoma. Paraganglioma tends to show marked and early enhancement and may present with clinical symptoms associated with the excess catecholamine. Sarcomas are often very large and have heterogeneous appearance. Imaging cannot be reliably used to identify the type of retroperitoneal sarcomas due to overlapped radiographic features. In children, lipoblastoma is the most common lipomatous tumor in the retroperitoneum. The percentage of visible fat in tumor varies depending on the cellular composition of the lesion. The CT characteristics of teratoma are quite variable, which may be cystic, solid, on a combination of both. Typically teratoma appears as a large complex mass containing fluid, fat, fat-fluid level, and calcifications. Lymphoma is often homogeneous on both enhanced and unenhanced CT scans. Necrosis and calcification are rare on CT. In conclusion, making a final histological diagnosis of retroperitoneal tumor base on CT features is not often possible; however, CT can help to develop a differential diagnosis and determine the size and extent of the retroperitoneal neoplasms.

  10. Primitive neuroectodermal tumor or small cell carcinoma of the kidney, arare neoplasm: Case Report

    International Nuclear Information System (INIS)

    Radhi, A.; Ratnakar, K.S.; Al-Durazi, M.; Khalifa, F.

    2002-01-01

    Small cell carcinoma is a malignancy primarily recognized in thebronchopulmonary region. Extrapulmonary locations are extremely uncommon. Wereport here a case of renal tumor encountered in a 34-year-old female, withextensive metastases in liver, lung and bone. Histological examination wasmost compatible with primitive neuroectodermal tumor (PNET) small cellcarcinoma. There were negative immunohistochemical markers for cytokeratin,any hormonal peptides and epithelial membrane antigens, which is consistentwith the designation of neoplasm as PNET. Previously reported cases have allbeen in the elderly and, to the best of our knowledge, this is the first caseof proven PNET of the kidney described in a young female. (author)

  11. A Web-Based Stem Cell Transplant Support System or Standard Care in Young Patients Undergoing Stem Cell Transplant and Their Families

    Science.gov (United States)

    2011-07-11

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Neuroblastoma; Ovarian Cancer; Psychosocial Effects of Cancer and Its Treatment; Sarcoma

  12. Donor Umbilical Cord Blood Transplant in Treating Patients With Hematologic Cancer

    Science.gov (United States)

    2017-11-27

    Chronic Myeloproliferative Disorders; Diamond-blackfan Anemia; Fanconi Anemia; Graft Versus Host Disease; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases

  13. Non-Ablative Allo HSCT For Hematologic Malignancies or SAA

    Science.gov (United States)

    2011-12-07

    Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases; Precancerous/Nonmalignant Condition; Small Intestine Cancer

  14. Ovarian neoplasms in atomic bomb survivors

    International Nuclear Information System (INIS)

    Tokuoka, Shoji

    1986-01-01

    A recent pathological and epidemiological study on females with ovarian neoplasms among the Radiation Effects Research Foundation (RERF) Life Span Study (LSS) Extended Sample ascertained 194 malignant and 106 benign ovarian tumor cases which had occurred during the period 1950 - 80. Of the 194 cases of ovarian cancer, 128 (66 %) were reviewed microscopically and the age-adjusted incidence of ovarian cancer revealed a statistically significant linear increase with increasing exposure dose, both in microscopically reviewed and in all cases. The radiation-related excess of ovarian cancer appeared to be highest in women less than 20 years of age when exposed, with these women having the longest latent period for tumor development, compared to the older age groups. The histological distribution of cancer types among exposed individuals appeared not very different from that seen in the general population. The analysis of 106 autopsy subjects with benign ovarian tumors, of which 89 were reviewed microscopically, depicted a trend of increasing radiation-related tumor excess with increasing exposure dose among exposed cases, though the trend is not statistically significant when observation was limited to microscopically reviewed subjects. The histological distribution of benign tumor types among exposed cases appeared not very different from that seen in the general population. The findings are consistent with a hypothesis that radiation-injured ovaries in association with secondary excess of gonadotrophic hormones are important causative factors in the development of ovarian tumors, which has been suggested by experimental findings concerning the induction of ovarian tumors by ionizing radiation and by a recent analysis of breast carcinogenesis in exposed females of Hiroshima and Nagasaki. (author)

  15. Secondary malignant neoplasms in testicular cancer survivors.

    Science.gov (United States)

    Curreri, Stephanie A; Fung, Chunkit; Beard, Clair J

    2015-09-01

    Testicular cancer is the most common cancer among men aged 15 to 40 years, and the incidence of testicular cancer is steadily increasing. Despite successful treatment outcomes and the rate of survival at 5 to 10 years being 95%, survivors can experience late effects of both their cancer and the treatment they received, including secondary malignant neoplasms (SMNs). We discuss the development of non-germ cell SMNs that develop after diagnosis and treatment of testicular cancer and their effect on mortality. Patients diagnosed with testicular cancer frequently choose postoperative surveillance if they are diagnosed with clinical stage I disease. These patients may experience an increased risk for developing SMNs following radiation exposure from diagnostic imaging. Similarly, radiotherapy for testicular cancer is associated with increased risks of developing both solid tumors and leukemia. Studies have reported that patients exposed to higher doses of radiation have an increased risk of developing SMNs when compared with patients who received lower doses of radiation. Patients treated with chemotherapy also experience an increased risk of developing SMNs following testicular cancer, though the risk following chemotherapy and radiation therapy combined is not well described. A large population-based study concluded that the rate ratios for both cancer-specific and all-cause mortality for SMNs among testicular cancer survivors were not significantly different from those of matched first cancers. Although it is known that patients who receive adjuvant chemotherapy or radiotherapy or who undergo routine diagnostic or follow-up imaging for a primary testicular cancer are at an increased risk for developing SMNs, the extent of this risk is largely unknown. It is critically important that research be conducted to determine this risk and its contributing factors as accurately as possible. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Imaging findings of abdominal extraosseous plasma cell neoplasm

    International Nuclear Information System (INIS)

    Park, Yang Sin; Byun, Jae Ho; Won, Hyung Jin; Kim, Ah Young; Shin, Yong Moon; Kim, Pyo Nyun; Ha, Hyun Kwon; Lee, Moon Gyu; Bae, Kyung Soo

    2006-01-01

    To evaluate the imaging findings of abdominal extraosseous plasma cell neoplasm. From April 2000 to January 2005, eight patients (four men, four women; mean age, 50.6 years) with pathologically proved, extraosseous plasma cell neoplasm involving the abdominal organs were included in this study. The diagnoses were based on consensus agreement between two radiologists who retrospectively reviewed CT, ultrasonography, and enteroclysis findings. We evaluated the findings by focusing on the location, size, margin, and enhancement pattern of the lesion, and lymphadenopathy on each image. There were multiple myeloma in four patients and extramedullary plasmacytoma in the remaining four. Involved abdominal organs were the liver (n = 4), spleen (n 4), lymph node (n = 3), stomach (n = 1), small bowel (n = 1), and colon (n 1). The hepatic involvement of plasma cell neoplasm presented as a homogeneous, well-defined, solitary mass (n = 1), multiple nodules (n = 1), and hepatomegaly (n = 2). Its involvement of the spleen and lymph node appeared as splenomegaly and lymphadenopathy, respectively. Its involvement of the gastrointestinal tract including the stomach, small bowel, and colon, presented as a homogeneous, diffuse wall thickening or mass in the gastrointestinal tract. Abdominal extraosseous plasma cell neoplasm involves occasionally the liver, spleen, and lymph node, and rarely the gastrointestinal tract. When we encounter a well-defined, homogeneous lesion of the abdominal organs in patients diagnosed or suspected as having plasma cell neoplasm, we should consider its involvement of the abdominal organs

  17. Differential expression and prognostic value of the chemokine receptor CXCR4 in bronchopulmonary neuroendocrine neoplasms

    Science.gov (United States)

    Specht, Elisa; Wirtz, Ralph M.; Sayeg, Manal; Baum, Richard P.; Schulz, Stefan; Lupp, Amelie

    2015-01-01

    Introduction For many tumors, the overexpression of the chemokine receptor CXCR4 is associated with increased malignancy and poor patient outcomes. However, comprehensive data for neuroendocrine neoplasms of the lung are still lacking. Methods CXCR4 expression was evaluated in a panel of bronchopulmonary neuroendocrine neoplasms (BP-NEN) comprising typical carcinoids (n = 26), atypical carcinoids (n = 30), and small cell lung cancers (SCLC, n = 34). Samples were analyzed by immunohistochemistry using the novel monoclonal rabbit anti-human CXCR4 antibody UMB-2 and by qRT-PCR. The expression was correlated with clinical data and overall patient survival. Results CXCR4 was predominantly localized at the plasma membrane of the tumor cells. CXCR4 was expressed with a high intensity in almost all of the 30 SCLC samples. In contrast, it was detected infrequently and with low intensity in the typical carcinoid and atypical carcinoid samples. There was a significant correlation between the immunohistochemistry and qRT-PCR data. Additionally, there was a significant negative relationship between CXCR4 expression and overall survival. Conclusions With increasing malignancy, BP-NEN clearly differ in the extent of CXCR4 expression. As in other tumor entities, CXCR4 overexpression significantly correlates with negative patient outcome. Due to its particular high expression rate in SCLC, CXCR4 may serve as a promising new target for diagnostic and pharmacological intervention as well as for peptide receptor-based radionuclide therapy. PMID:25671300

  18. The radiological and histopathological differential diagnosis of chordoid neoplasms in skull base

    Directory of Open Access Journals (Sweden)

    PAN Bin-cai

    2013-07-01

    -called physaliferous cells within myxoid matrix. Areas of cartilage presented in individual cases. The tumor cells of chordoma were diffusely immuno-positive for PCK and EMA. Chordoid meningioma is characterized by a homogeneous contrast-enhancing mass with dural tail sign. The epithelioid cells were arranged in cords and clusters within a myxoid matrix, which was highly reminiscent of chordoma. The ratio of myxoid component and conventional meningioma was different in tumors. EMA was detectable in all chordoid meningiomas, and 4/5 cases were positive for D2-40. That was a finding which was helpful in distinguishing chordoid meningioma from chordoma. Chordoid gliomas were localized in the third ventricle with homogeneous enhancement on MRI examination. The tumors were composed of clusters and cords of epithelioid tumor cells within a variably mucinous stroma containing lymphoplasmacytic infiltratation. The most distinctive immunohistochemical feature of chordoid gliomas is their strong diffuse reactivity for GFAP. EMA and PCK positive expression can also be seen focally in individual cases. Although extraskeletal myxoid chondrosarcomas share the similar radiological and histological appearance with chordoma, all chondrosarcomas in the present study are completely negative for epithelial markers except for immuno-positivity of S-100 focally. In addition, Galectin-3 can be detected in most of chordoid neoplasms in skull base. Conclusion The specific localization and MRI features of tumors are useful diagnostic clues for the differential diagnosis of chordoid neoplasms in skull base. However, combining with histological features, a panel of selected immunostains, including PCK, EMA, GFAP, S-100 and D2-40, is helpful in making an accurate diagnosis for those diagnostically challenging cases which usually appear to have atypical radiological features or in an unusual site. Ki-67 index and Galectin-3 are not recommended to use as diagnostic markers for chordoid neoplasms of skull base

  19. Incidence and significance of Multiple Primary Malignant Neoplasms

    International Nuclear Information System (INIS)

    Choi, Eun Kyung; Cho, Moon June; Ha, Sung Whan; Park, Charn Il; Bang, Young Ju; Kim, Noe Kyung

    1986-01-01

    To know the three questions about multiple primary cancers: 1) what are the characteristics of persons having multiple primary cancer? 2) Dose presence of a single primary concern after the susceptibility to multiple primary cancers? 3) Dose the location of one multiple primary cancer influence the site of others?, we analysed 121 cases of multiple primary malignant neoplasms registered in Seoul National University Hospital during 8years from July 1978 to August 1986. Of 121 cases, double primary malignant neoplasms were 119 cases and triple were 2 cases. The incidence of multiple primary malignant neoplasms was 0.7%. The metachronous tumor(> 6 months) was found in 70 cases and the median time between the first and the second was 32 months. The most commonly associated tumors were stomach and primary liver carcinoma. Cervix and Lung cancer, Stomach and Rectal cancer, Stomach and Esophagus cancer were also commonly associated

  20. Small-bowel neoplasms in patients undergoing video capsule endoscopy

    DEFF Research Database (Denmark)

    Rondonotti, E; Pennazio, M; Toth, E

    2008-01-01

    BACKGROUND AND STUDY AIM: Small-bowel tumors account for 1% - 3% of all gastrointestinal neoplasms. Recent studies with video capsule endoscopy (VCE) suggest that the frequency of these tumors may be substantially higher than previously reported. The aim of the study was to evaluate the frequency......, clinical presentation, diagnostic/therapeutic work-up, and endoscopic appearance of small-bowel tumors in a large population of patients undergoing VCE. PATIENTS AND METHODS: Identification by a questionnaire of patients with VCE findings suggesting small-bowel tumors and histological confirmation...... of the neoplasm seen in 29 centers of 10 European Countries. RESULTS: Of 5129 patients undergoing VCE, 124 (2.4%) had small-bowel tumors (112 primary, 12 metastatic). Among these patients, indications for VCE were: obscure gastrointestinal bleeding (108 patients), abdominal pain (9), search for primary neoplasm...

  1. Interdisciplinary Management of Cystic Neoplasms of the Pancreas

    Directory of Open Access Journals (Sweden)

    Linda S. Lee

    2012-01-01

    Full Text Available Cystic neoplasms of the pancreas are increasingly recognized due to the frequent use of abdominal imaging. It is reported that up to 20% of abdominal cross-sectional scans identify incidental asymptomatic pancreatic cysts. Proper characterization of pancreatic cystic neoplasms is important not only to recognize premalignant lesions that will require surgical resection, but also to allow nonoperative management of many cystic lesions that will not require resection with its inherent morbidity. Though reliable biomarkers are lacking, a wide spectrum of diagnostic modalities are available to evaluate pancreatic cystic neoplasms, including radiologic, endoscopic, laboratory, and pathologic analysis. An interdisciplinary approach to management of these lesions which incorporates recent, specialty-specific advances in the medical literature is herein suggested.

  2. Neoplasms among atomic bomb survivors in Hiroshima City. First report

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Tomin; Ishida, Morihiro

    1960-04-01

    The 1957-1958 incidence of neoplasms among the survivors of the Hiroshima A-bomb, varies directly with radiation dose insofar as it may be inferred from distance from the hypocenter at exposure. The incidence of all malignant neoplasms among the survivors who were within 1000 meters is more than 4 times that of the non-exposed population. The incidence of benign neoplasms among the survivors exposed within 1500 meters is also significantly higher than that among the non-exposed. For survivors under 1500 meters significant differences are seen between the numbers of observed cancers of the lung, stomach, uterus and ovary and the expected cases calculated from the age-specific rates of the non-exposed portion of the Hiroshima population. The increased incidence among survivors within 1500 meters is not related to sex or age. 18 references, 2 figures, 14 tables.

  3. Solute carrier transporters: potential targets for digestive system neoplasms.

    Science.gov (United States)

    Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

    2018-01-01

    Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues of digestive systems and mediate specific uptake of small molecule substrates in facilitative manner. Given the important role of SLC proteins in maintaining normal functions of digestive system, dysregulation of these protein in digestive system neoplasms may deliver biological and clinical significance that deserves systemic studies. In this review, we critically summarized the recent advances in understanding the role of SLC proteins in digestive system neoplasms. We highlighted that several SLC subfamilies, including metal ion transporters, transporters of glucose and other sugars, transporters of urea, neurotransmitters and biogenic amines, ammonium and choline, inorganic cation/anion transporters, transporters of nucleotide, amino acid and oligopeptide organic anion transporters, transporters of vitamins and cofactors and mitochondrial carrier, may play important roles in mediating the initiation, progression, metastasis, and chemoresistance of digestive system neoplasms. Proteins in these SLC subfamilies may also have diagnostic and prognostic values to particular cancer types. Differential expression of SLC proteins in tumors of digestive system was analyzed by extracting data from human cancer database, which revealed that the roles of SLC proteins may either be dependent on the substrates they transport or be tissue specific. In addition, small molecule modulators that pharmacologically regulate the functions of SLC proteins were discussed for their possible application in the treatment of digestive system neoplasms. This review highlighted the potential of SLC family proteins as drug target for the treatment of digestive system neoplasms.

  4. When negation is not negation

    OpenAIRE

    Milicevic, Nataša

    2008-01-01

    In this paper I will discuss the formation of different types of yes/no questions in Serbian (examples in (1)), focusing on the syntactically and semantically puzzling example (1d), which involves the negative auxiliary inversion. Although there is a negative marker on the fronted auxiliary, the construction does not involve sentential negation. This coincides with the fact that the negative quantifying NPIs cannot be licensed. The question formation and sentential negation have similar synta...

  5. Assessing the occupational nature of malignant lung neoplasms

    International Nuclear Information System (INIS)

    Sevc, J.; Klener, V.; Plank, V.

    1989-01-01

    The development of lung carcinoma in uranium miners is discussed. In spite of the decreasing radiation risks in mines, the absolute number of neoplasms has increased since the 1960's; this is due to the increasing number of miners, improved diagnostic methods and the aging of miners who thus enter higher age groups where a higher incidence of neoplasms can be expected. The probabilistic method was shown to be of help in deciding whether individual cases of lung carcinoma should be considered an occupational disease; new possible improvements of the method are suggested. (J.J.). 12 refs

  6. Postoperative meningeal enhancement on MRI in children with brain neoplasms

    International Nuclear Information System (INIS)

    Lee, Min Hee; Han, Bokyung Kim; Yoon, Hye Kyung; Shin, Hyung Jin

    2000-01-01

    The meninges composed of the dura, the arachnoid and the pia are significant sites of blood-brain barrier. Physical disruption of the integrity of the meninges from a variety of causes including surgery results in various patterns of meningeal enhancement on contrast enhanced MR images. It is important to distinguish normal reactive or benign postoperative enhancement from more serious leptomeningeal metastasis or infection, particularly in children with intracranial neoplasms. We present various patterns of meningeal enhancement on MRI in children following surgery for brain neoplasms. (author)

  7. Unicentric Castleman’s Disease Masquerading Pancreatic Neoplasm

    Directory of Open Access Journals (Sweden)

    Saurabh Jain

    2012-01-01

    Full Text Available Castleman’s disease is a rare nonclonal proliferative disorder of the lymph nodes with an unknown etiology. Common locations of Castleman’s disease are mediastinum, neck, axilla, and abdomen. Castleman’s disease of a peripancreatic location masquerading as pancreatic neoplasm is an even rarer entity. On search of published data, we came across about 17 cases published on peripancreatic Castleman’s disease until now. Here we are reporting a case of retropancreatic Castleman's disease masquerading as retroperitoneal neoplasm in a 46-year-old male patient.

  8. Myeloproliferative disorders in patients with rheumatoid arthritis treated with total body irradiation

    International Nuclear Information System (INIS)

    Urowitz, M.B.; Rider, W.D.

    1985-01-01

    Four patients with refractory rheumatoid arthritis were treated with total body irradiation administered in two sittings, 300 to 400 rads to each half of the body. All four patients had taken antimetabolites prior to receiving total body irradiation, and two continued to use them after total body irradiation. Two patients had taken alkylating agents before, and one had used them after total body irradiation. All patients showed clinical improvement. However, in two patients myeloproliferative disorders developed: a myelodysplastic preleukemia at 40 months after total body irradiation in one and acute myelogenous leukemia at 25 months in the other. Total body irradiation differs from total nodal irradiation in the total dose of irradiation (300 to 400 rads versus 2,000 to 3,000), and in the duration of the therapy (two sittings versus treatment over several weeks to months). Furthermore, the patients in the total body irradiation study frequently used cytotoxic drugs before and/or after irradiation, whereas in one total nodal irradiation study, azathioprine (2 mg/kg per day or less) was permitted, but no other cytotoxic agents were allowed. Rheumatologists may therefore face a binding decision when deciding to treat a patient with rheumatoid arthritis with either a cytotoxic drug or irradiation

  9. Inflammatory nodule mimicking a phrenic neoplasm.

    Science.gov (United States)

    Vannucci, Jacopo; Scarnecchia, Elisa; Del Sordo, Rachele; Cagini, Lucio; Puma, Francesco

    2016-05-01

    Isolated phrenic nerve nodule is usually a primitive tumour. Surgery is diagnostic and therapeutic at the same time. We report the case of a completely serum-negative Caucasian male with a right diaphragmatic relaxation associated to an isolated small nodule of the phrenic nerve. The patient was referred to our unit complaining shortness of breath and progressive fatigue. A standard chest X-ray showed right diaphragmatic palsy; chest scanning revealed a nodular lesion belonging to the right phrenic nerve. Positron emission tomography was negative for glucose uptake. The preoperative diagnosis of primitive neurogenic tumour was thus supposed, and the patient treated by the lesion's surgical resection along with diaphragmatic plication. Histopathological examination revealed an idiopathic inflammatory nodule of the phrenic nerve. Such condition has not previously been reported in the literature among the possible aetiology of a diaphragmatic relaxation. © 2014 John Wiley & Sons Ltd.

  10. Plasma Cell Neoplasms (Including Multiple Myeloma)—Health Professional Version

    Science.gov (United States)

    There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma. Find evidence-based information on plasma cell neoplasms treatment, research, and statistics.

  11. Reconstruction techniques in the treatment of vertebral neoplasms.

    Science.gov (United States)

    Biagini, R; Boriani, S; Casadei, R; Bandiera, S; De Iure, F; Campanacci, L; Demitri, S; Orsini, U; Di Fiore, M

    1997-01-01

    The authors present a new system for the topographical description of vertebral neoplasms. The general criteria of reconstruction after curettage or vertebral resection are evaluated. The literature is reviewed in terms of the use of prostheses, bone grafts, cement and stabilization systems in the treatment of tumors of the spine. Indications for the different methods are discussed.

  12. Neoplasms radiosensitivity: how to increase the efficiency of radiotherapy

    International Nuclear Information System (INIS)

    Calais, G.

    1991-01-01

    The hypoxia in the neoplasms is a radioresistance factor. This article is about the methods able to reduce the hypoxia in tumors: use of hyperbaric oxygen, radiosensitizers (as metronidazole), hyperthermia and modification of oxygen release in the tissues in modifying the blood flow and in reducing the hemoglobin affinity for oxygen [fr

  13. The radiotherapy value in recurrence control mammary neoplasm

    International Nuclear Information System (INIS)

    Torres Lopez, M.; Santini Blasco, A.

    1996-01-01

    In base on the retrospective analysis of 250 patient carrying of mammals neoplasms recurrence, their general characteristics are determined and the results are emphasized obtained by the radiotherapy, as well as the list that the indicative predict. It culminates in the necessity of indicating the adyuvance postoperative radiotherapy when factors unfavorable presage of recurrence(AU ) [es

  14. Childhood neoplasms presenting at autopsy: A 20-year experience.

    Science.gov (United States)

    Bryant, Victoria A; Booth, John; Palm, Liina; Ashworth, Michael; Jacques, Thomas S; Sebire, Neil J

    2017-09-01

    The aims of the review are to establish the number of undiagnosed neoplasms presenting at autopsy in a single centre and to determine the incidence and most common causes of sudden unexpected death due to neoplasia in infancy and childhood (SUDNIC). Retrospective observational study of paediatric autopsies performed on behalf of Her Majesty's Coroner over a 20-year period (1996-2015; n = 2,432). Neoplasms first diagnosed at autopsy were identified from an established database and cases meeting the criteria for sudden unexpected death were further categorised. Thirteen previously undiagnosed neoplasms were identified, including five haematological malignancies, two medulloblastomas, two neuroblastomas, two cardiac tumours and two malignancies of renal origin. Eight cases met the criteria for SUDNIC (0.33% of autopsies), the commonest group of which were haematological malignancies (n = 3). Neoplasms presenting as unexpected death in infancy and childhood and diagnosed at autopsy are rare. The findings suggest that haematological malignancies are the commonest cause of SUDNIC and highlight the importance of specialist autopsy in cases of sudden unexpected death. © 2017 Wiley Periodicals, Inc.

  15. Cystic lesion of pancreas - Intraductal papillary mucinous neoplasm

    Directory of Open Access Journals (Sweden)

    Rajiv Baijal

    2013-01-01

    Full Text Available Intraductal papillary mucinous neoplasm (IPMN of the pancreas is an intraductal mucin-producing epithelial neoplasm that arises from the main and/or branched pancreatic duct. It usually presents as cystic lesion of pancreas. There are well known differential diagnosis of cystic pancreatic lesion. Pancreatic cystic neoplasms are detected at an increasing frequency due to an increased use of abdominal imaging. The diagnosis and treatment of intraductal papillary mucinous tumors (IPMN of the pancreas has evolved over the past decade. IPMN represents a spectrum of disease, ranging from benign to malignant lesions, making the early detection and characterization of these lesions important. Definitive management is surgical resection for appropriate candidates, as benign lesions harbor malignant potential. IPMN has a prognosis, which is different from adenocarcinoma of the pancreas. We report a case of a 58-year-old male with intraductal papillary neoplasm involving main duct and side branches presenting to us with clinical symptoms of chronic pancreatitis with obstructive jaundice and cholangitis treated surgically.

  16. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 19...

  17. Childhood Renal Neoplasms in Lagos Nigera- A 28 Year Review ...

    African Journals Online (AJOL)

    Childhood Renal Neoplasms in Lagos Nigera- A 28 Year Review. ... Most of the patients presented with abdominal mass with a unilaterally enlarged kidney, abdominal pain, haematuria and weight loss. All of them had nephrectomy as initial treatment followed by radiotherapy and chemotherapy. Nigerian Quarterly Journal ...

  18. A Survey Of Cutaneous Neoplasms Among Horses Used For ...

    African Journals Online (AJOL)

    A Survey Of Cutaneous Neoplasms Among Horses Used For Cultural Festivals In Borno State, Nigeria. ... Histologically, the papillomas were deeply subdivided into epithelial lobules with the outer and inner aspects of the epithelium running approximately parallel to each other. Irregular sub-dermal masses or cords of ...

  19. Age-specific incidence of all neoplasms after colorectal cancer.

    Science.gov (United States)

    Levi, Fabio; Randimbison, Lalao; Blanc-Moya, Rafael; La Vecchia, Carlo

    2014-10-01

    Patients diagnosed with a specific neoplasm tend to have a subsequent excess risk of the same neoplasm. The age incidence of a second neoplasm at the same site is approximately constant with age, and consequently the relative risk is greater at younger age. It is unclear whether such a line of reasoning can be extended from a specific neoplasm to the incidence of all neoplasms in subjects diagnosed with a defined neoplasm. We considered the age-specific incidence of all non-hormone-related epithelial neoplasms after a first primary colorectal cancer (n = 9542) in the Vaud Cancer Registry data set. In subjects with a previous colorectal cancer, the incidence rate of all other epithelial non-hormone-related cancers was stable around 800 per 100,000 between age 30 and 60 years, and rose only about twofold to reach 1685 at age 70 to 79 years and 1826 per 100,000 at age 80 years or older. After excluding synchronous cancers, the rise was only about 1.5-fold, that is, from about 700 to 1000. In the general population, the incidence rate of all epithelial non-hormone-related cancers was 29 per 100,000 at age 30 to 39 years, and rose 30-fold to 883 per 100,000 at age 70 to 79 years. Excluding colorectal cancers, the rise of all non-hormone-related cancers was from 360 per 100,000 at age 40 to 49 years to 940 at age 70 to 79 years after colorectal cancer, and from 90 to 636 per 100,000 in the general population (i.e., 2.6- vs. 7.1-fold). The rise of incidence with age of all epithelial non-hormone-related second cancers after colorectal cancer is much smaller than in the general population. This can possibly be related to the occurrence of a single mutational event in a population of susceptible individuals, although alternative models are plausible within the complexity of the process of carcinogenesis. Copyright © 2014 Elsevier Inc. All rights reserved.

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  19. File list: Unc.Neu.20.AllAg.Nerve_Sheath_Neoplasms [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. File list: His.Neu.10.AllAg.Nerve_Sheath_Neoplasms [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Pol.Neu.05.AllAg.Nerve_Sheath_Neoplasms [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  2. File list: ALL.Neu.05.AllAg.Nerve_Sheath_Neoplasms [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  3. Negative mass

    International Nuclear Information System (INIS)

    Hammond, Richard T

    2015-01-01

    Some physical aspects of negative mass are examined. Several unusual properties, such as the ability of negative mass to penetrate any armor, are analysed. Other surprising effects include the bizarre system of negative mass chasing positive mass, naked singularities and the violation of cosmic censorship, wormholes, and quantum mechanical results as well. In addition, a brief look into the implications for strings is given. (paper)

  4. Changing patterns of radiosensitivity of hematopoietic progenitors from chronically irradiated dogs prone either to aplastic anemia or to myeloproliferative disease

    International Nuclear Information System (INIS)

    Seed, T.M.; Kaspar, L.V.

    1990-01-01

    Hematopoietic patterns have been assessed in chronic 60 Co gamma irradiated dogs during preclinical phases of evolving aplastic anemia (AA) or myeloproliferative disease (MPD), principally myeloid leukemia. The results support the concept that acquired radioresistance of vital granulocyte/monocyte lineage-committed hematopoietic progenitors is temporally, perhaps causally, linked to the processes mediating hematopoietic recovery and accommodation under chronic irradiation, and in turn to preclinical events of evolving MPD. In addition, the marked differential responses of progenitors to gamma and neutron irradiation in vitro might suggest differences in the nature of cellular lesions elicited by chronic gamma irradiation, in vivo. (author)

  5. Changing patterns of radiosensitivity of hematopoietic progenitors from chronically irradiated dogs prone either to aplastic anemia or to myeloproliferative disease

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Kaspar, L.V. (Oak Ridge National Lab., TN (USA))

    1990-01-01

    Hematopoietic patterns have been assessed in chronic {sup 60}Co gamma irradiated dogs during preclinical phases of evolving aplastic anemia (AA) or myeloproliferative disease (MPD), principally myeloid leukemia. The results support the concept that acquired radioresistance of vital granulocyte/monocyte lineage-committed hematopoietic progenitors is temporally, perhaps causally, linked to the processes mediating hematopoietic recovery and accommodation under chronic irradiation, and in turn to preclinical events of evolving MPD. In addition, the marked differential responses of progenitors to gamma and neutron irradiation in vitro might suggest differences in the nature of cellular lesions elicited by chronic gamma irradiation, in vivo. (author).

  6. Synchronous myeloproliferative and inflammatory disease of the nasal cavity and paranasal sinuses: an interesting differential diagnostic problem.

    Science.gov (United States)

    László, Iván; Gábor, Vass; Zsolt, Bella; László, Tiszlavicz; József, Jóri

    2009-09-01

    The authors present a case of synchronous manifestation of a myeloproliferative--extramedullary plasmocytoma--and a chronic inflammatory disease of the nose and the paranasal sinuses. They emphasise the importance of imaging techniques and immunohistochemistry in the differential diagnosis. They discuss on the basis of published articles the new classification, clinical manifestations, diagnostic and therapeutical approaches of this tumour belonging to the group of monoclonal gammopathies, which originates from an abnormal proliferation of mature B-lymphocytes, and is a rarity in the literature even nowadays.

  7. Studies on 99Tcm-sulfur colloid bone marrow scintigraphy in myeloproliferative disorders

    International Nuclear Information System (INIS)

    Liu Yong; Zhang Yifan; Jia Fangxian; Kang Fu; Jian Shiquan

    2002-01-01

    Objective: To discuss the imaging features and changing patterns of bone marrow scintigraphy in myeloproliferative disorders (MPD) as well as its clinical significance. Methods: Bone marrow scintigraphy using 99 Tc m -sulfur colloid 370-550 MBq was performed on 85 MPD patients, including 40 cases of idiopathic myelofibrosis (IMF), 15 of polycythemia vera (PV), 5 of essential thrombocythaemia (ET), 30 of chronic granulocytic leukemia. Also, 40 cases of myelodysplastic syndromes (MDS) were observed in this study. Results: Abnormal bone marrow imaging was found in 88.2% of the 85 patients. The suppression rate of central bone marrow (CBM) and expansion rate of peripheral bone marrow (PBM) in these MPD patients were 61.2% and 56.5%, respectively. The imaging patterns was classified into three types according to the distribution and activity of bone marrow. 1) reduced imaging (31.8%); 2) increased and expanded imaging (27.1%); 3) depressed and expanded imaging (29.4%). Splenomegaly with minimal residual marrow activity was typical for late stages of MPD. Expansion of PBM was the further feature, but of no major importance for improving hematopoiesis of MPD, and it tended to retract during clinical recovery in chronic granulocytic leukemia (CGL). With expanding PBM, unmatched peripheral blood decreasing was found in MDS. The expansion pattern of PBM in different MPD was of relatively definite features. Conclusions: The imaging pattern of bone marrow was correlated with blood work-up data and clinical course or stages of MPD. Bone marrow scintigraphy may be proven useful in differential diagnosis and evaluation of clinical staging and prognosis of MPD

  8. Negative Leadership

    Science.gov (United States)

    2013-03-01

    Negative Leadership by Colonel David M. Oberlander United States Army United States Army War...SUBTITLE Negative Leadership 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Colonel David M...Dr. Richard C. Bullis Department of Command Leadership , and Management 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING

  9. Negative liability

    NARCIS (Netherlands)

    Dari-Mattiacci, G.

    2009-01-01

    Negative and positive externalities pose symmetrical problems to social welfare. The law internalizes negative externalities by providing general tort liability rules. According to such rules, those who cause harm to others should pay compensation. In theory, in the presence of positive

  10. Negative ... concord?

    NARCIS (Netherlands)

    Giannakidou, A

    The main claim of this paper is that a general theory of negative concord (NC) should allow for the possibility of NC involving scoping of a universal quantifier above negation. I propose that Greek NC instantiates this option. Greek n-words will be analyzed as polarity sensitive universal

  11. Sensitivity of 2-[18F]fluoro-2-deoxyglucose positron emission tomography for advanced colorectal neoplasms: a large-scale analysis of 7505 asymptomatic screening individuals.

    Science.gov (United States)

    Sekiguchi, Masau; Kakugawa, Yasuo; Terauchi, Takashi; Matsumoto, Minori; Saito, Hiroshi; Muramatsu, Yukio; Saito, Yutaka; Matsuda, Takahisa

    2016-12-01

    The sensitivity of 2-[ 18 F]fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for advanced colorectal neoplasms among healthy subjects is not yet fully understood. The present study aimed to clarify the sensitivity by analyzing large-scale data from an asymptomatic screening population. A total of 7505 asymptomatic screenees who underwent both FDG-PET and colonoscopy at our Cancer Screening Division between February 2004 and March 2013 were analyzed. FDG-PET and colonoscopy were performed on consecutive days, and each examination was interpreted in a blinded fashion. The results of the two examinations were compared for each of the divided six colonic segments, with those from colonoscopy being set as the reference. The relationships between the sensitivity of FDG-PET and clinicopathological features of advanced neoplasms were also evaluated. Two hundred ninety-one advanced neoplasms, including 24 invasive cancers, were detected in 262 individuals. Thirteen advanced neoplasms (advanced adenomas) were excluded from the analysis because of the coexistence of lesions in the same colonic segment. The sensitivity, specificity, and positive and negative predictive values of FDG-PET for advanced neoplasms were 16.9 % [95 % confidence interval (CI) 12.7-21.8 %], 99.3 % (95 % CI 99.2-99.4 %), 13.5 % (95 % CI 10.1-17.6 %), and 99.4 % (95 % CI 99.3-99.5 %), respectively. The sensitivity was lower for lesions with less advanced histological grade, of smaller size, and flat-type morphology, and for those located in the proximal part of the colon. FDG-PET is believed to be difficult to use as a primary screening tool in population-based colorectal cancer screening because of its low sensitivity for advanced neoplasms. Even when it is used in opportunistic cancer screening, the limit of its sensitivity should be considered.

  12. Laparoscopic Low Anterior Resection and Eversion Technique Combined With a Nondog Ear Anastomosis for Mid- and Distal Rectal Neoplasms

    Science.gov (United States)

    Zhuo, Changhua; Liang, Lei; Ying, Mingang; Li, Qingguo; Li, Dawei; Li, Yiwei; Peng, Junjie; Huang, Liyong; Cai, Sanjun; Li, Xinxiang

    2015-01-01

    Abstract The transanal eversion and prolapsing technique is a well-established procedure, and can ensure an adequate distal margin for patients with low rectal neoplasms. Potential leakage risks, however, are associated with bilateral dog ear formation, which results from traditional double-stapling anastomosis. The authors determined the feasibility of combining these techniques with a commercial stapling set to achieve a nondog ear (end-to-end) anastomosis for patients with mid- and distal rectal neoplasms. Patients with early-stage (c/ycT1–2N0), mid- to distal rectal neoplasms and good anal sphincter function were included in this study. Laparoscopic low anterior resection was performed with a standard total mesorectal excision technique downward to the pelvic floor as low as possible. The bowel was resected proximal to the lesion with an endoscopic linear stapler. An anvil was inserted extracorporeally into the proximal colon via an extended working pore. The distal rectum coupled with the lesion was prolapsed and everted out of the anus. The neoplasm was resected with a sufficient margin above the dentate line under direct sight. A transrectal anastomosis without dog ears was performed intracorporeally to reconstitute the continuity of the bowel. Eleven cases, 6 male and 5 female patients, were included in this study. The mean operative time was 191 (129–292) minutes. The mean blood loss was 110 (30–300) mL. The median distal margin distance from the lower edge of the lesion to the dentate line was 1.5 (0.5–2.5) cm. All the resection margins were negative. Most patients experienced uneventful postoperative recoveries. No patient had anastomotic leak. Most patients had an acceptable stool frequency after loop ileostomy closure. Our preliminary data demonstrated the safety and feasibility of achieving a sound anastomosis without risking potential anastomotic leakage because of dog ear formation. PMID:26683958

  13. 3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer

    Science.gov (United States)

    2017-12-05

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Unspecified Adult Solid Tumor, Protocol Specific

  14. Aprepitant, Granisetron, & Dexamethasone in Preventing Nausea & Vomiting in Pts. Receiving Cyclophosphamide Before a Stem Cell Transplant

    Science.gov (United States)

    2016-02-12

    Breast Cancer; Chronic Myeloproliferative Disorders; Gestational Trophoblastic Tumor; Leukemia; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Nausea and Vomiting; Neuroblastoma; Ovarian Cancer; Testicular Germ Cell Tumor

  15. Opioid Titration Order Sheet or Standard Care in Treating Patients With Cancer Pain

    Science.gov (United States)

    2012-08-04

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  16. Methadone, Morphine, or Oxycodone in Treating Pain in Patients With Cancer

    Science.gov (United States)

    2012-11-09

    Brain and Central Nervous System Tumors; Chronic Myeloproliferative Disorders; Leukemia; Lymphoma; Lymphoproliferative Disorder; Multiple Myeloma and Plasma Cell Neoplasm; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Pain; Precancerous Condition; Unspecified Adult Solid Tumor, Protocol Specific

  17. Central Cemento-Ossifying Fibroma: Primary Odontogenic or Osseous Neoplasm?

    Science.gov (United States)

    Woo, Sook-Bin

    2015-12-01

    Currently, central cemento-ossifying fibroma is classified by the World Health Organization as a primary bone-forming tumor of the jaws. However, histopathologically, it is often indistinguishable from cemento-osseous dysplasias in that it forms osteoid and cementicles (cementum droplets) in varying proportions. It is believed that pluripotent cells within the periodontal membrane can be stimulated to produce either osteoid or woven bone and cementicles when stimulated. If this is true, cemento-ossifying fibroma would be better classified as a primary odontogenic neoplasm arising from the periodontal ligament. Cemento-ossifying fibromas also do not occur in the long bones. The present report compares several entities that fall within the diagnostic realm of benign fibro-osseous lesions and reviews the evidence for reclassifying central cemento-ossifying fibroma as a primary odontogenic neoplasm. Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.

  18. Lesions and Neoplasms of the Penis: A Review.

    Science.gov (United States)

    Heller, Debra S

    2016-01-01

    In addition to practitioners who care for male patients, with the increased use of high-resolution anoscopy, practitioners who care for women are seeing more men in their practices as well. Some diseases affecting the penis can impact on their sexual partners. Many of the lesions and neoplasms of the penis occur on the vulva as well. In addition, there are common and rare lesions unique to the penis. A review of the scope of penile lesions and neoplasms that may present in a primary care setting is presented to assist in developing a differential diagnosis if such a patient is encountered, as well as for practitioners who care for their sexual partners. A familiarity will assist with recognition, as well as when consultation is needed.

  19. Intraductal papillary neoplasm of the bile duct: a case report.

    Science.gov (United States)

    Peeters, Karen; Delvaux, Peter; Huysentruyt, Frederik

    2017-08-01

    Intraductal papillary neoplasm of the bile duct (IPNB) is a rare variant of bile duct tumors, characterized by papillary growth within the bile duct lumen and is regarded as a biliary counterpart of intraductal papillary mucinous neoplasm (IPMN) of the pancreas. IPNBs are mainly found in patients from Far Eastern areas, where hepatolithiasis and clonorchiasis are endemic. The Western experience, however, remains limited. In this article, we report a 56-year-old man, referred to our hospital because of deranged liver function tests. Further imaging modalities showed a cystic lesion of 9 cm diameter, arising from the left hepatic duct. Inlying was a heterogeneous, lobulated mass. The patient underwent a left hemihepatectomy and adjuvant chemotherapy. Despite recent advanced technologies, diagnosis of IPNB is still challenging, especially in western countries due to its rarity. Early identification and resection of lesions, even in asymptomatic or minimally symptomatic patients, are however important prognostic factors.

  20. Food habits in atomic bomb survivors suffering from malignant neoplasms

    International Nuclear Information System (INIS)

    Morimoto, Kazue; Inoue, Hisako; Uchino, Chito

    1984-01-01

    Food habits were surveyed in patients admitted to 13 hospitals in Nagasaki prefecture and other prefectures to compare the incidence of malignant neoplasms according to the food intake between atomic bomb exposed group and non-exposed group. The incidence of malignant neoplasms was significantly higher in male patients having the low intake of milk and salted fish than in those having the high intake of them in atomic bomb exposed group, while it was significantly higher in male patients having the low intake of potatoes and milk and in female patients having the low intake of boiled fish paste than in those having the high intake of them in non-exposed group. (Namekawa, K.)

  1. A broad survey of cathepsin K immunoreactivity in human neoplasms.

    Science.gov (United States)

    Zheng, Gang; Martignoni, Guido; Antonescu, Cristina; Montgomery, Elizabeth; Eberhart, Charles; Netto, George; Taube, Janis; Westra, William; Epstein, Jonathan I; Lotan, Tamara; Maitra, Anirban; Gabrielson, Edward; Torbenson, Michael; Iacobuzio-Donahue, Christine; Demarzo, Angelo; Shih, Ie Ming; Illei, Peter; Wu, T C; Argani, Pedram

    2013-02-01

    Cathepsin K is consistently and diffusely expressed in alveolar soft part sarcoma (ASPS) and a subset of translocation renal cell carcinomas (RCCs). However, cathepsin K expression in human neoplasms has not been systematically analyzed. We constructed tissue microarrays (TMA) from a wide variety of human neoplasms, and performed cathepsin K immunohistochemistry (IHC). Only 2.7% of 1,140 carcinomas from various sites exhibited cathepsin K labeling, thus suggesting that among carcinomas, cathepsin K labeling is highly specific for translocation RCC. In contrast to carcinomas, cathepsin K labeling was relatively common (54.6%) in the 414 mesenchymal lesions studied, including granular cell tumor, melanoma, and histiocytic lesions, but not paraganglioma, all of which are in the morphologic differential diagnosis of ASPS. Cathepsin K IHC can be helpful in distinguishing ASPS and translocation RCC from some but not all of the lesions in their differential diagnosis.

  2. Rectum neoplasms treatment advanced with radio and chemotherapy before - surgery

    International Nuclear Information System (INIS)

    Luongo Cespedes, A.; Aguiar Vitacca, S.

    1993-01-01

    In Uruguay the colorectal neoplasms has a can rate of mobility. The surgery has 13-26% local recurrence. The irradiation before surgery has demonstrated to improve the resect and the local control.The objective of this protocol it is to decrease the percentage of local relapse , using radiotherapy(RT) before surgery and concomitant chemotherapy that potencies the effect of the RT, improvement this way the therapeutic quotient (AU) [es

  3. Advances in the diagnosis and treatment of gastric neuroendocrine neoplasms

    OpenAIRE

    Tan, Huangying

    2016-01-01

    Gastric neuroendocrine neoplasms (g-NENs) are a group of heterogeneous tumors arising from the endocrine cells of stomach. Most g-NENs progresses slowly and have a long disease course; however, some other g-NENs grow rapidly, similar to the progression of gastric adenocarcinoma. g-NENs have complex and diverse clinical manifestations and their prognosis and treatment strategies depend highly on clinical subtype, pathological grade, tumour stage, and other factors. Due to their low prevalence,...

  4. Analyses of critical target cell responses during preclinical phases of evolving chronic radiation-induced myeloproliferative disease-exploitation of a unique canine model

    International Nuclear Information System (INIS)

    Seed, T.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.; Frazier, M.E.

    1988-01-01

    This document briefly summarizes and highlights ongoing studies on the cellular and molecular processes involved in the induction and progression of myeloid leukemia in dogs chronically exposed to low daily doses of wholebody gamma irradiation. Under such conditions, select groups of dogs exhibit extremely high frequencies of myeloproliferative disease (MPD) (i.e., /congruent/50%) of which myeloid leukemia is most prominent. 2 figs

  5. Analyses of critical target cell responses during preclinical phases of evolving chronic radiation-induced myeloproliferative disease-exploitation of a unique canine model

    Energy Technology Data Exchange (ETDEWEB)

    Seed, T.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.; Frazier, M.E.

    1988-01-01

    This document briefly summarizes and highlights ongoing studies on the cellular and molecular processes involved in the induction and progression of myeloid leukemia in dogs chronically exposed to low daily doses of wholebody gamma irradiation. Under such conditions, select groups of dogs exhibit extremely high frequencies of myeloproliferative disease (MPD) (i.e., /congruent/50%) of which myeloid leukemia is most prominent. 2 figs.

  6. Technology insight: endoscopic submucosal dissection of gastrointestinal neoplasms.

    Science.gov (United States)

    Yamamoto, Hironori

    2007-09-01

    Gastrointestinal neoplasms can be cured by local resection as long as the lesions are in the early stage and have not metastasized. Endoscopic resection is a minimally invasive treatment for early-stage gastrointestinal neoplasms, and endoscopic submucosal dissection (ESD) is one type of endoscopic resection that has been developed in the past 10 years. For ESD to be a reliable, curative treatment for gastrointestinal neoplasms, it is necessary for the endoscopist to detect the lesion early, make a precise pretreatment diagnosis, ensure that the patient has the correct indication for endoscopic resection, and have the skill to perform ESD. For early lesion detection, endoscopists should pay attention to subtle changes in the surface structure, the color of the mucosa and the visibility of underlying submucosal vessels. Chromoendoscopy and magnifying endoscopy are useful for determining the margin of the lesions for pretreatment diagnosis, and endoscopic ultrasonography and magnifying endoscopy are useful for determining the depth of invasion. For ESD to be successful, local injection of sodium hyaluronate helps maintain mucosal elevation during dissection. Selecting the appropriate knife, using transparent hoods wisely, employing a good strategy that uses gravity, and having good control of bleeding are all needed to make ESD reliable.

  7. Appendiceal pathology at the time of oophorectomy for ovarian neoplasms.

    Science.gov (United States)

    Timofeev, Julia; Galgano, Mary T; Stoler, Mark H; Lachance, Jason A; Modesitt, Susan C; Jazaeri, Amir A

    2010-12-01

    To investigate the prevalence of appendiceal pathology in women undergoing surgery for a suspected ovarian neoplasm and the predictive value of intraoperative findings to determine the need for appendectomy at the time of surgery. Retrospective analysis of patients who underwent oophorectomy and appendectomy during the same surgical procedures at the University of Virginia Health System from 1992 to 2007. Observations were stratified based on the nature (benign, borderline, or malignant) and histology (serous compared with mucinous) of the ovarian neoplasm, frozen compared with final pathological diagnosis, and the gross appearance of the appendix. Among the 191 patients identified, frozen section was consistent with seven mucinous and 35 serous carcinomas, 16 serous and 33 mucinous borderline tumors, 71 mucinous and serous cystadenomas, and 29 cases of suspected metastatic tumor from a gastrointestinal primary. The highest rates of coexisting appendiceal pathology were associated with serous ovarian cancers (94.4% of grossly abnormal and 35.3% of normal appendices) and ovarian tumors suspected to be of primary gastrointestinal origin (83.3% grossly abnormal and 60.0% normal appendices harbored coexisting mucinous neoplasms). Linear regression analysis revealed that appearance of the appendix and frozen section diagnosis of the ovarian pathology were statistically significant predictors of coexisting appendiceal pathology, but the latter was more important. The prevalence of coexisting, clinically significant appendiceal pathology is low with a frozen section diagnosis of serous or mucinous cystadenoma. Appendectomy is recommended when frozen section diagnosis is mucinous or serous ovarian carcinoma, borderline tumor or metastatic carcinoma of suspected gastrointestinal origin.

  8. Low-grade appendiceal mucinous neoplasm mimicking an adnexal mass.

    Science.gov (United States)

    Cristian, Daniel Alin; Grama, Florin Andrei; Becheanu, Gabriel; Pop, Anamaria; Popa, Ileana; Şurlin, Valeriu; Stănilescu, Sorin; Bratu, Ana Magdalena; Burcoş, Traean

    2015-01-01

    We present a rare case of malignant epithelial neoplasm of the appendix, an uncommon disorder encountered in clinical practice, which poses a variety of diagnostic and therapeutic challenges. We report a particular case in which the appendix was abnormally located in the pelvis, mimicking an adnexal mass. Therefore, it was difficult to make the preoperative diagnosis on clinical examination, imaging studies and laboratory tests and we discovered the lesion during the diagnostic laparoscopy. No lymphadenopathy or mucinous ascites were found. The case was completely handled via the laparoscopic approach keeping the appendix intact during the operation. The frozen section, the detailed histopathology overview as well as multiple immunostaining with a complex panel of markers report diagnosed a low-grade appendiceal mucinous neoplasm (LAMN) with no invasion of the wall. No adjuvant therapy was considered needed. At a one-year follow-up oncological assessment, the patient was free of disease. In women with cystic mass in the right iliac fossa an appendiceal mucocele should be considered in the differential diagnosis. Laparoscopic appendectomy can represent an adequate operation for the appendiceal mucinous neoplasm if the histological report is clear and surgical precautionary measures are taken.

  9. Tryptophan autofluorescence imaging of neoplasms of the human colon

    Science.gov (United States)

    Banerjee, Bhaskar; Renkoski, Timothy; Graves, Logan R.; Rial, Nathaniel S.; Tsikitis, Vassiliki Liana; Nfonsom, Valentine; Pugh, Judith; Tiwari, Piyush; Gavini, Hemanth; Utzinger, Urs

    2012-01-01

    Detection of flat neoplasia is a major challenge in colorectal cancer screening, as missed lesions can lead to the development of an unexpected `incident' cancer prior to the subsequent endoscopy. The use of a tryptophan-related autofluorescence has been reported to be increased in murine intestinal dysplasia. The emission spectra of cells isolated from human adenocarcinoma and normal mucosa of the colon were studied and showed markedly greater emission intensity from cancerous cells compared to cells obtained from the surrounding normal mucosa. A proto-type multispectral imaging system optimized for ultraviolet macroscopic imaging of tissue was used to obtain autofluorescence images of surgical specimens of colonic neoplasms and normal mucosa after resection. Fluorescence images did not display the expected greater emission from the tumor as compared to the normal mucosa, most probably due to increased optical absorption and scattering in the tumors. Increased fluorescence intensity in neoplasms was observed however, once fluorescence images were corrected using reflectance images. Tryptophan fluorescence alone may be useful in differentiating normal and cancerous cells, while in tissues its autofluorescence image divided by green reflectance may be useful in displaying neoplasms.

  10. Clinical parameters predictive of malignancy of thyroid follicular neoplasms

    International Nuclear Information System (INIS)

    Davis, N.L.; Gordon, M.; Germann, E.; Robins, R.E.; McGregor, G.I.

    1991-01-01

    Needle aspiration biopsy is commonly employed in the evaluation of thyroid nodules. Unfortunately, the cytologic finding of a 'follicular neoplasm' does not distinguish between a thyroid adenoma and a follicular cancer. The purpose of this study was to identify clinical parameters that characterize patients with an increased risk of having a thyroid follicular cancer who preoperatively have a 'follicular neoplasm' identified by needle aspiration biopsy. A total of 395 patients initially treated at Vancouver General Hospital and the British Columbia Cancer Agency between the years of 1965 and 1985 were identified and their data were entered into a computer database. Patients with thyroid adenomas were compared to patients with follicular cancer using the chi-square test and Student's t-test. Statistically significant parameters that distinguished patients at risk of having a thyroid cancer (p less than 0.05) included age greater than 50 years, nodule size greater than 3 cm, and a history of neck irradiation. Sex, family history of goiter or neoplasm, alcohol and tobacco use, and use of exogenous estrogen were not significant parameters. Patients can be identified preoperatively to be at an increased risk of having a follicular cancer and accordingly appropriate surgical resection can be planned

  11. Environmental exposure to cooking oil fumes and cervical intraepithelial neoplasm

    International Nuclear Information System (INIS)

    Wu, M.-T.; Lee, L.-H.; Ho, C.-K.; Wu, S.-C.; Lin, L.-Y.; Cheng, B.-H.; Liu, C.-L.; Yang, C.-Y.; Tsai, H.-T.; Wu, T.-N.

    2004-01-01

    The fumes from cooking oil, similar to cigarette smoke, contain numerous carcinogens such as polycyclic aromatic hydrocarbons, aromatic amines, nitro-polycyclic aromatic hydrocarbons, etc. In this study, we examined the association between exposure to cooking oil fumes and the risk of cervical intraepithelial neoplasm. The study population in this nested case-control study consisted of women above the age of 19 years living in Chia-Yi County, located in the southwestern Taiwan, who had received pap smear screening between October, 1999, and December, 2000 (n=32,466). The potential cases were women having lesions greater than cervical intraepithelium neoplasm II (≥CIN2) reconfirmed by cervical biopsy (n=116). The potential controls (case: control=1:2) were age-matched (±2 years) and residence-matched women who had normal pap smears within 6 months of the cases. In total, 100 cases and 197 controls were completely interviewed by public health nurses about cooking methods, ventilation, and other potential risk factors. Women who cooked at home in a kitchen (n=269) without the presence of a fume extractor at least once a week between the ages of 20 and 40 had a 2.29 times higher risk [95% confidence interval (CI)=1.08-4.87] of developing cervical intraepithelial neoplasm than those who did not cook once a week in such a kitchen during the same age span, after adjusting for other potential confounders. This finding was further strengthened by the finding that women who did not use the fume extractors had a 2.47 times higher risk (95% CI=1.15-5.32) of developing cervical intraepithelial neoplasm than women who cooked in kitchens with fume extractors that were always switched on while cooking. We also found a joint protective effect of fume extractor use among women older than 40 years (n=202) if they used the extractors during both age spans of their lives, ages 20-40 and >40 years. Comparing our findings on women more than 40 years old who used fume extractors during

  12. Tumor taxonomy for the developmental lineage classification of neoplasms

    International Nuclear Information System (INIS)

    Berman, Jules J

    2004-01-01

    The new 'Developmental lineage classification of neoplasms' was described in a prior publication. The classification is simple (the entire hierarchy is described with just 39 classifiers), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. A taxonomy is a list of the instances that populate a classification. The taxonomy of neoplasia attempts to list every known term for every known tumor of man. The taxonomy provides each concept with a unique code and groups synonymous terms under the same concept. A Perl script validated successive drafts of the taxonomy ensuring that: 1) each term occurs only once in the taxonomy; 2) each term occurs in only one tumor class; 3) each concept code occurs in one and only one hierarchical position in the classification; and 4) the file containing the classification and taxonomy is a well-formed XML (eXtensible Markup Language) document. The taxonomy currently contains 122,632 different terms encompassing 5,376 neoplasm concepts. Each concept has, on average, 23 synonyms. The taxonomy populates 'The developmental lineage classification of neoplasms,' and is available as an XML file, currently 9+ Megabytes in length. A representation of the classification/taxonomy listing each term followed by its code, followed by its full ancestry, is available as a flat-file, 19+ Megabytes in length. The taxonomy is the largest nomenclature of neoplasms, with more than twice the number of neoplasm names found in other medical nomenclatures, including the 2004 version of the Unified Medical Language System, the Systematized Nomenclature of Medicine Clinical Terminology, the National Cancer Institute's Thesaurus, and the International Classification of Diseases Oncolology version. This manuscript describes a comprehensive taxonomy of neoplasia that collects synonymous terms under a unique code number and assigns each

  13. Negative CO

    NARCIS (Netherlands)

    Meysman, F.J.R.; Montserrat, F.

    2017-01-01

    Negative emission technologies (NETs) target the removal of carbon dioxide (CO2) from the atmosphere, and are being actively investigated as a strategy to limit global warming to within the 1.5–2°C targets of the 2015 UN climate agreement. Enhanced silicate weathering (ESW) proposes to

  14. Negative Certainty

    Science.gov (United States)

    Ariso, José María

    2017-01-01

    The definitions of "negative knowledge" and the studies in this regard published to date have not considered the categorial distinction Wittgenstein established between knowledge and certainty. Hence, the important role that certainty, despite its omission, should have in these definitions and studies has not yet been shown. In this…

  15. Multiple neoplasms among cervical cancer patients in the material of the lower Silesian cancer registry.

    Science.gov (United States)

    Izmajłowicz, Barbara; Kornafel, Jan; Błaszczyk, Jerzy

    2014-01-01

    According to the definition by the International Agency for Research on Cancer (IARC), primary multiple neoplasms are two or more neoplasms of different histopathological build in one organ, or two or more tumors occurring in one patient, regardless of the time of their occurrence (synchronic - up to 6 months, metachronous - after 6 months), coming from an organ or a tissue and not being an infiltration from another neoplasm, a relapse or a metastasis. It was the aim of the study to analyze the frequency of the occurrence of multiple neoplasms among patients suffering from uterine cervix cancer, with a special interest in coexistent neoplasms, the time of their occurrence and total 5-year survivals. The data from the Lower Silesian Cancer Registry concerning the years 1984-2009 formed the material of the present study. 5.3% of all cervix neoplasms occurred as multiple cancers. Cervix neoplasms were 13.4% of multiple neoplasms. On average, cervical cancer occurred as a subsequent cancer in 6 patients yearly (60.7% of the occurrences of cervical cancer were in the period of 5 years following treatment for the first neoplasm). 5-year survival in patients suffering from primarily multiple cervix neoplasms constituted 57% and was convergent with the results for all patients suffering from cervical cancer. Cervical cancer as the first neoplasm occurred in 287 patients, on average in 11 patients annually. In the period of the first 5 years after the treatment of cervical cancer, there were 42.8% occurrences of other cancers. Cervical neoplasms most frequently coexisted with cancers of the breast, lung and large intestine. The frequency of the occurrence of multiple neoplasm among cervical cancer patients is increasing. Most frequently they coexist with other tobacco-related neoplasms, those related to HPV infections and with secondary post-radiation neoplasms. These facts should be taken into consideration during post-treatment observation and when directing diagnostic

  16. Neoplasms in young dogs after irradiation during development

    International Nuclear Information System (INIS)

    Benjamin, S.A.; Williams, J.S.; Angleton, G.M.; Saunders, W.J.; Miller, G.K.; Lee, A.C.

    1985-01-01

    To study the lifetime effects of irradiation during development, 1680 beagle dogs were given single, whole body exposures to 60Co gamma radiation at one of 6 pre- or postnatal ages. Four groups of 120 dogs each (480 or 29%) received 0.16 or 0.83 Gy at early prenatal times, 8 or 28 days postcoitus (dpc). Four groups of 120 dogs each (29%) received 0.16 or 0.83 Gy in the perinatal period at 55 dpc or 2 days postpartum (dpp). Groups of 120 and 240 dogs (21%) received 0.83 Gy at later postnatal times, 70 or 365 dpp, respectively. A group of 360 dogs (21%) were sham-irradiated. The youngest dogs are now 12 years old. Through 4 years of age, 20 dogs had neoplasms diagnosed. Five malignancies and one benign tumor were seen in the first two years, including the only fatal malignancies which occurred in 4 perinatally irradiated dogs. Up to two years of age, the other non-fatal malignancy and benign tumor were found in dogs irradiated at 365 dpp and 55 dpc. The remaining 14 neoplasms, 12 benign and 2 non-fatal malignant, were diagnosed between two and four years of age. Respective numbers of these benign and non-fatal malignant tumors found in control, perinatally irradiated, and all other irradiated dogs were 2 and 0; 5 and 1; and 5 and 1. Eight of the benign lesions were minute papillomas of the eyelids which were more frequent in the perinatally irradiated dogs. Overall, 71% (5 of 7) of the malignancies seen in the first four years of life occurred in the 29% of the dogs irradiated in the perinatal period. Sixty-seven percent (8 of 12) of all neoplasms, excluding eyelid papillomas, also occurred in perinatally irradiated dogs. These data suggest an increased risk for neoplasia after perinatal irradiation

  17. Immunohistochemical study of p16 INK4A and survivin expressions in cervical squamous neoplasm

    Directory of Open Access Journals (Sweden)

    Tan Geok

    2010-01-01

    Full Text Available Introduction:Cervical cancer is the second most common cancer affecting Malaysian women. Despite the implementation of pap smear screening, many women are still diagnosed only in the advanced stage of cervical cancer. This could partly be due to failure of detection of its precursor lesions; hence the need to search for novel biomarkers to assist in the screening and diagnosis of cervical neoplasia. This study aims to determine the expression of p16INK4A and survivin as possible predictive biomarkers in cervical squamous neoplasm. Material and Methods: This is a retrospective study on 201 cases of cervical neoplasm comprising of 129 cervical intraepithelial neoplasia (CIN and 72 squamous cell carcinoma (SCC. All samples were evaluated by two independent observers using p16INK4A and survivin monoclonal antibodies. The p16 INK4A expression was graded as negative, focal and diffuse positivity. The intensity for survivin expression was graded as weak, moderate and intense. Results: It is seen that p16 INK4A expression in CIN 1, CIN 2 and CIN 3 were 25.4%, 42.9% and 95.9% respectively. Majority of SCC (98.6% showed p16 INK4A expression. Survivin expressions in CIN 1, CIN 2, CIN 3 and SCC were 56.7%, 33.4%, 87.5% and 98.6%. There was a linear relationship between increasing grade of CIN and p16 INK4A expressions. Conclusion: Our study showed that p16 INK4A expressions correlate well with the increasing grade of CIN. Although survivin does not correlate well to the increasing grade of CIN, it could be useful in differentiating CIN 3 from SCC.

  18. Distinct molecular features of different macroscopic subtypes of colorectal neoplasms.

    Directory of Open Access Journals (Sweden)

    Kenichi Konda

    Full Text Available Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs.We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI] and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers alterations in 158 CRNs including 56 polypoid neoplasms (PNs, 25 granular type laterally spreading tumors (LST-Gs, 48 non-granular type LSTs (LST-NGs, 19 depressed neoplasms (DNs and 10 small flat-elevated neoplasms (S-FNs on the basis of macroscopic appearance.S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs (P<0.001. By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively (P<0.007. We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively (P<0.005. Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05. PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41.We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

  19. Metanephric stromal tumor: A novel pediatric renal neoplasm

    Directory of Open Access Journals (Sweden)

    Rajalakshmi V

    2009-07-01

    Full Text Available Metanephric stromal tumor of kidney is a novel pediatric benign stromal specific renal neoplasm. A few cases have been reported in adults also. This tumor is usually centered in the renal medulla with a characteristic microscopic appearance which differentiates this lesion from congenital mesoblastic nephroma and clear cell sarcoma of the kidney. In most cases complete excision alone is curative. The differentiation of metanephric stromal tumor from clear cell sarcoma of the kidney will spare the child from the ill effects of adjuvant chemotherapy. In this communication we describe the gross and microscopic features of metanephric stromal tumor in a one-month-old child with good prognosis.

  20. Inflammatory demyelinating pseudotumor with hemorrhage masquerading high grade cerebral neoplasm

    Directory of Open Access Journals (Sweden)

    Amit Agrawal

    2015-03-01

    Full Text Available Demyelinating pseudotumors are rare, benign, solitary intracranial space occupying lesions which masquerade cerebral neoplasms. Contrast MRI shows open ring enhancement which is fairly specific for this entity. Advanced MRI techniques like MR spectroscopy and magnetizing transfer techniques can help differentiating these lesions. NAA/Cr ratio is significantly elevated in central regions of demyelinating pseudotumors than in gliomas and other lesions. Presence of abundant foamy macrophages, lymphoid inflammatory infiltrates around blood vessels, sheets of gemistocytic astrocytes with well-developed processes, well defined border of the lesion absence of neovascularity and necrosis should help us diagnose demyelinating pseudotumor fairly confidently on histopathology.

  1. Rupture of a Solid Pseudopapillary Neoplasm of the pancreas

    Directory of Open Access Journals (Sweden)

    Barbara Rampersad

    2018-03-01

    Full Text Available An acute presentation of a spontaneously ruptured Solid-Pseudopapillary Neoplasm (SPN in an 8 year old female is discussed with a review of the world literature. Our literature search revealed 15 other cases of ruptured SPN and with this case the total is now 16. Notably, 12 patients were 16 years of age or less at presentation as in our case. Although rupture of a SPN is rarely reported it appears to be more probable in the pediatric patient. Additionally, larger tumor size and trauma may be contributing factors.

  2. Cervical intraepitheial neoplasm with ichthyosis uteri- A case report

    Directory of Open Access Journals (Sweden)

    Karishma Malla Vaidya

    2018-04-01

    Full Text Available A rare condition in which the entire surface of the endometrium is replaced by stratified squamous epithelium is called Ichthyosis uteri. Originally described as an endometrial response to iatrogenically-introduced caustic substances, similar changes have since been described in association with a variety of inflammatory conditions of the endometrium.Here we report a case of intraepithelial neoplasm III, with ichthyosis uteri. A 75-years-old female with hypetension, underwent total abdominal hysterectomy with bilateral salphingo-ophorectomy for watery discharge per vaginal since four months.

  3. Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

    Science.gov (United States)

    Bruner, David I.; Pritchard, Amy M.; Clarke, Jonathan

    2013-01-01

    While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. PMID:24106538

  4. Solute carrier transporters: potential targets for digestive system neoplasms

    OpenAIRE

    Xie, Jing; Zhu, Xiao Yan; Liu, Lu Ming; Meng, Zhi Qiang

    2018-01-01

    Jing Xie,1,2 Xiao Yan Zhu,1,2 Lu Ming Liu,1,2 Zhi Qiang Meng1,2 1Department of Integrative Oncology, Fudan University Shanghai Cancer Center, 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China Abstract: Digestive system neoplasms are the leading causes of cancer-related death all over the world. Solute carrier (SLC) superfamily is composed of a series of transporters that are ubiquitously expressed in organs and tissues o...

  5. Pediatric liver neoplasms: a radiologic-pathologic correlation

    International Nuclear Information System (INIS)

    Helmberger, T.K.; Reiser, M.F.; Ros, P.R.; Mergo, P.J.; Tomczak, R.

    1999-01-01

    Only 1-2 % of all pediatric tumors occur in the liver. Two thirds of these tumors are malignant and almost all of the tumors cause clinical symptoms due to their mass effects. Besides the poor prognosis in most of the malignant tumors, for further treatment the origin and nature of the neoplasm has to be known. Due to the mostly unimpeded growth into the peritoneal cavity, the origin of the tumors is primarily often unclear and can non-invasively only be determined by advanced imaging techniques. The display of the macro- and microhistological key features of primary pediatric liver neoplasms, including hepatoblastoma (HB), infantile hemangioendothelioma (IHE), mesenchymal hamartoma (MH), undifferentiated (embryonal) sarcoma (UES), and hepatocellular carcinoma (HCC), together with their imaging representation by ultrasound, computed tomography, and magnetic resonance imaging, may deepen the understanding of the underlying pathology and its imaging appearance. Furthermore, in many cases sufficient information may be provided not only to differentiate benign from malignant tumors, but also to guide for adequate treatment. (orig.)

  6. Immunoglobulin therapy in hematologic neoplasms and after hematopoietic cell transplantation.

    Science.gov (United States)

    Ueda, Masumi; Berger, Melvin; Gale, Robert Peter; Lazarus, Hillard M

    2018-03-01

    Immunoglobulins are used to prevent or reduce infection risk in primary immune deficiencies and in settings which exploit its anti-inflammatory and immune-modulatory effects. Rigorous proof of immunoglobulin efficacy in persons with lympho-proliferative neoplasms, plasma cell myeloma, and persons receiving hematopoietic cell transplants is lacking despite many clinical trials. Further, there are few consensus guidelines or algorithms for use in these conditions. Rapid development of new therapies targeting B-cell signaling and survival pathways and increased use of chimeric antigen receptor T-cell (CAR-T) therapy will likely result in more acquired deficiencies of humoral immunity and infections in persons with cancer. We review immunoglobulin formulations and discuss efficacy and potential adverse effects in the context of preventing infections and in graft-versus-host disease. We suggest an algorithm for evaluating acquired deficiencies of humoral immunity in persons with hematologic neoplasms and recommend appropriate use of immunoglobulin therapy. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Endoscopic approach for a laryngeal neoplasm in a dog

    Directory of Open Access Journals (Sweden)

    Pedro Paulo Maia Teixeira

    2015-01-01

    Full Text Available Laryngeal and tracheal tumors are rare in pets; some piece of information on their disease behavior, therapy and evolution are limited. Neoplasms in this area are a diagnostic challenge. In many cases, they can be biopsied and excised using endoscopic instruments, but there is no report of this in canines. The goal of this study is to report a successful case of a laryngeal neoplasm removal through endoscopy. A head and neck radiogram revealed a mass in the laryngeal lumen protruding into the trachea. The patient then underwent an endoscopy to confirm the radiographic diagnosis and to surgically remove the tumor. The histopathological diagnosis was poorly differentiated carcinoma. The most appropriate treatment for laryngeal tumors is the resection of the submucosa or a partial laryngectomy however, partial and total laryngectomies are associated with many postoperative complications. In contrast, the endoscopic approach allows for highly magnified visualization of the lesion in situ, which facilitates the surgical removal of the mass through videosurgery. With little manipulation of the affected area, the chances of postoperative complications are reduced, leading to a more rapid recovery.

  8. Classifying the evolutionary and ecological features of neoplasms

    Science.gov (United States)

    Maley, Carlo C.; Aktipis, Athena; Graham, Trevor A.; Sottoriva, Andrea; Boddy, Amy M.; Janiszewska, Michalina; Silva, Ariosto S.; Gerlinger, Marco; Yuan, Yinyin; Pienta, Kenneth J.; Anderson, Karen S.; Gatenby, Robert; Swanton, Charles; Posada, David; Wu, Chung-I; Schiffman, Joshua D.; Hwang, E. Shelley; Polyak, Kornelia; Anderson, Alexander R. A.; Brown, Joel S.; Greaves, Mel; Shibata, Darryl

    2018-01-01

    Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive benefits. There is widespread recognition of the importance of these evolutionary and ecological processes in cancer, but to date, no system has been proposed for drawing clinically relevant distinctions between how different tumours are evolving. On the basis of a consensus conference of experts in the fields of cancer evolution and cancer ecology, we propose a framework for classifying tumours that is based on four relevant components. These are the diversity of neoplastic cells (intratumoural heterogeneity) and changes over time in that diversity, which make up an evolutionary index (Evo-index), as well as the hazards to neoplastic cell survival and the resources available to neoplastic cells, which make up an ecological index (Eco-index). We review evidence demonstrating the importance of each of these factors and describe multiple methods that can be used to measure them. Development of this classification system holds promise for enabling clinicians to personalize optimal interventions based on the evolvability of the patient’s tumour. The Evo- and Eco-indices provide a common lexicon for communicating about how neoplasms change in response to interventions, with potential implications for clinical trials, personalized medicine and basic cancer research. PMID:28912577

  9. Dermal Squamomelanocytic Tumor: Neoplasm of Uncertain Biological Potential

    Directory of Open Access Journals (Sweden)

    Mirsad Dorić

    2008-05-01

    Full Text Available We report a case of exceedingly rare cutaneous neoplasm with histological features of malignancy and uncertain biological potential. The nodular, darkly pigmented facial tumor with central exulceration, size 12x10x7 mm, of the skin 61-year-old man preauricular left was completely exised.Histologically tumor consists of atypical squamous cells, which express signs of moderate to significant pleomorphism, mitotically active, with foci forming of parakeratotic horn cysts (“pearls”. Characteristically tumor also consists of large number of atypical melanocytes with multifocal pattern, inserted between atypical squamous cells, and which contain large amount of dark brown pigment melanin. Immunohistochemically, squamous cells stain positively with keratin (CK116, melanocytes were stained with S -100 protein, HMB 45, and vimentin, but failed to stain with CK 116.To our knowledge this is the sixth reported case in world literature. The follow-up time of four years no evidence of recurrence or metastasis, similar all reported cases, but it is too short period in estimation to guarantee a benign course. However, it appears that this group of neoplasm may have different prognosis from pure squamous carcinoma or malignant melanoma.

  10. Molecular pathology of intraductal papillary mucinous neoplasms of the pancreas.

    Science.gov (United States)

    Paini, Marina; Crippa, Stefano; Partelli, Stefano; Scopelliti, Filippo; Tamburrino, Domenico; Baldoni, Andrea; Falconi, Massimo

    2014-08-07

    Since the first description of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in the eighties, their identification has dramatically increased in the last decades, hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases. However, the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions. The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed. We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms, identifying some genes, molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy. The knowledge of molecular biology of IPMNs has impressively developed over the last few years. A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified, in pancreatic juice or in blood or in the samples from the pancreatic resections, but further researches are required to use these informations for clinical intent, in order to better define the natural history of these diseases and to improve their management.

  11. Malignant neurogenic neoplasms of the head and neck

    International Nuclear Information System (INIS)

    Kuczkowski, J.; Starzynska, A.

    1996-01-01

    The authors present 17 cases of malignant neurogenic neoplasms of the head and neck observed in the Department of Otolaryngology in the years 1948-1993. The latest opinions on etiopathology, diagnosis and treatment of these tumors were described. Age and sex of patients, localization of tumor, symptoms histopathology and treatment were analyzed. Progressions of the disease were estimated retrospectively. It has been proved that these tumors develop quickly, give pain and paresthesia. Their diagnosis is very difficult because of their submucosal growth and difficult histopathological interpretation. A characteristic feature of these neurogenic tumors is the ability to give distant metastases. This feature differentiates them from squamous neoplasms, which give mainly nodal metastases. All the patients were subjected to surgery combined with conventional or high voltage radiotherapy. The positive effect of combined chemotherapy in cases of esthesioneuroblastoma is worthy of note. The prognosis in these tumors is often unfavorable. In the group under discussion 13 patients died because of recurrences, two patients are considered to be cured and the remaining 2 patients have had no recurrence for 2 and 3 years. (author)

  12. Photodynamic therapy of early stage oral cavity and oropharynx neoplasms: an outcome analysis of 170 patients

    NARCIS (Netherlands)

    Karakullukcu, Baris; van Oudenaarde, Kim; Copper, Marcel P.; Klop, W. M. C.; van Veen, Robert; Wildeman, Maarten; Bing Tan, I.

    2011-01-01

    The indications of photodynamic therapy (PDT) of oral cavity and oropharynx neoplasms are not well defined. The main reason is that the success rates are not well established. The current paper analyzes our institutional experience of early stage oral cavity and oropharynx neoplasms (Tis-T2) to

  13. [Incidence of haematological neoplasms in Castilla y León, Spain].

    Science.gov (United States)

    Rodríguez-García, José Antonio; Vázquez, Lourdes; Ramos, Fernando; Cuevas, Beatriz; Martín, Alejandro; Smucler, Alicia; Guerola, Dulce Nombre; Cantalapiedra, Alberto; Alonso, José María; Fernández, Silvia; Díez, Eva; Rodríguez, María Jesús; Calmuntia, María José; Aguilar, Carlos; Sierra, Magdalena; Gracia, José Antonio; Cebeira, María José; Cantalejo, Rosa

    2015-06-08

    We aimed to assess the incidence of haematological neoplasms (HNs) in Castilla y León (2,5 million inhabitants) and its distribution by age, gender and histological type. The epidemiological profile based on the described variables of the 10,943 HNs diagnosed during a 10-years period was analyzed, compared with other studies. The overall age-adjusted incidence was 29.4 cases/10(5) inhabitants-year, with some geographical differences. The mean age was 67.3 years, with a turning point between the 6th-7th decades of life from which there was a very significant increase of incidence. Two relevant facts where simultaneous with advancing age: decreased lymphoid neoplasms incidence and increased low degree neoplasms incidence. Lymphoid low degree neoplasms accounted for half of the registered processes, showed the greatest preference for male and reached the mode before the rest of neoplasms. Myeloid neoplasms incidence (9.5) was higher than that reported in other European registries, specially compared to southern European countries, opposite to lymphoid neoplasms incidence (20.0). A higher myeloid neoplasms incidence and lower lymphoid one than expected was observed. The turning point of incidence is between the 6th-7th decades of life, with a preference for male that decreases with age. There is an increased incidence of HNs in the area where a higher density of potentially polluting facilities is concentrated. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

  14. Helicobacter pylori-related chronic gastritis as a risk factor for colonic neoplasms.

    Science.gov (United States)

    Inoue, Izumi; Kato, Jun; Tamai, Hideyuki; Iguchi, Mikitaka; Maekita, Takao; Yoshimura, Noriko; Ichinose, Masao

    2014-02-14

    To summarize the current views and insights on associations between Helicobacter pylori (H. pylori)-related chronic gastritis and colorectal neoplasm, we reviewed recent studies to clarify whether H. pylori infection/H. pylori-related chronic gastritis is associated with an elevated risk of colorectal neoplasm. Recent studies based on large databases with careful control for confounding variables have clearly demonstrated an increased risk of colorectal neoplasm associated with H. pylori infection. The correlation between H. pylori-related chronic atrophic gastritis (CAG) and colorectal neoplasm has only been examined in a limited number of studies. A recent large study using a national histopathological database, and our study based on the stage of H. pylori-related chronic gastritis as determined by serum levels of H. pylori antibody titer and pepsinogen, indicated that H. pylori-related CAG confers an increased risk of colorectal neoplasm, and more extensive atrophic gastritis will probably be associated with even higher risk of neoplasm. In addition, our study suggested that the activity of H. pylori-related chronic gastritis is correlated with colorectal neoplasm risk. H. pylori-related chronic gastritis could be involved in an increased risk of colorectal neoplasm that appears to be enhanced by the progression of gastric atrophy and the presence of active inflammation.

  15. Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®)—Patient Version

    Science.gov (United States)

    Plasma cell neoplasms occur when abnormal plasma cells or myeloma cells form tumors in the bones or soft tissues of the body. Multiple myeloma, plasmacytoma, lymphoplasmacytic lymphoma, and monoclonal gammopathy of undetermined significance (MGUS) are different types of plasma cell neoplasms. Find out about risk factors, symptoms, diagnostic tests, prognosis, and treatment for these diseases.

  16. Minimal residual disease or cure in MPNs?

    DEFF Research Database (Denmark)

    Bjørn, Mads Emil; Hasselbalch, Hans Carl

    2017-01-01

    INTRODUCTION: The therapeutic landscape of the Philadelphia-negative myeloproliferative neoplasms (MPNs) is markedly changing consequent to the development of JAK-inhibitors and the use of ruxolitinib (RUX) in patients with myelofibrosis (MF) and patients with polycythemia vera (PV) who develop r...

  17. No Evidence for JAK2(V617F) Mutation in Monoclonal B Cells in 2 Patients with Polycythaemia Vera and Concurrent Monoclonal B Cell Disorder

    NARCIS (Netherlands)

    Stijnis, C.; Kroes, W. G. M.; Balkassmi, S.; Marijt, E. W. A.; van Rossum, A. P.; Bakker, E.; Vlasveld, L. T.

    2012-01-01

    Occurrence of Philadelphia chromosome-negative myeloproliferative neoplasms (Ph- MPN) and lymphoproliferative disorders, like B cell chronic lymphocytic leukaemia (B-CLL), in the same patient is rare. JAK2(V617F) mutation was recently introduced as a powerful diagnostic tool for Ph- MPN. JAK2(V617F)

  18. Minimal residual disease after long-term interferon-alpha2 treatment

    DEFF Research Database (Denmark)

    Utke Rank, Cecilie; Weis Bjerrum, Ole; Larsen, Thomas Stauffer

    2016-01-01

    Essential thrombocythemia (ET) and polycythemia vera (PV) are Philadelphia chromosome-negative chronic myeloproliferative neoplasms (MPNs) characterized by the JAK2 V617F mutation, which can be found in more than 98% of PV patients and in ∼ 50% of ET patients. Assessment of the JAK2 V617F allele...

  19. Targeting angiogenesis-dependent calcified neoplasms using combined polymer therapeutics.

    Directory of Open Access Journals (Sweden)

    Ehud Segal

    Full Text Available There is an immense clinical need for novel therapeutics for the treatment of angiogenesis-dependent calcified neoplasms such as osteosarcomas and bone metastases. We developed a new therapeutic strategy to target bone metastases and calcified neoplasms using combined polymer-bound angiogenesis inhibitors. Using an advanced "living polymerization" technique, the reversible addition-fragmentation chain transfer (RAFT, we conjugated the aminobisphosphonate alendronate (ALN, and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropylmethacrylamide (HPMA copolymer through a Glycine-Glycine-Proline-Norleucine linker, cleaved by cathepsin K, a cysteine protease overexpressed at resorption sites in bone tissues. In this approach, dual targeting is achieved. Passive accumulation is possible due to the increase in molecular weight following polymer conjugation of the drugs, thus extravasating from the tumor leaky vessels and not from normal healthy vessels. Active targeting to the calcified tissues is achieved by ALN's affinity to bone mineral.The anti-angiogenic and antitumor potency of HPMA copolymer-ALN-TNP-470 conjugate was evaluated both in vitro and in vivo. We show that free and conjugated ALN-TNP-470 have synergistic anti-angiogenic and antitumor activity by inhibiting proliferation, migration and capillary-like tube formation of endothelial and human osteosarcoma cells in vitro. Evaluation of anti-angiogenic, antitumor activity and body distribution of HPMA copolymer-ALN-TNP-470 conjugate was performed on severe combined immunodeficiency (SCID male mice inoculated with mCherry-labeled MG-63-Ras human osteosarcoma and by modified Miles permeability assay. Our targeted bi-specific conjugate reduced VEGF-induced vascular hyperpermeability by 92% and remarkably inhibited osteosarcoma growth in mice by 96%.This is the first report to describe a new concept of a narrowly-dispersed combined polymer therapeutic designed to target both tumor and

  20. One Patient, Two Uncommon B-Cell Neoplasms: Solitary Plasmacytoma following Complete Remission from Intravascular Large B-Cell Lymphoma Involving Central Nervous System

    Directory of Open Access Journals (Sweden)

    Joycelyn Lee

    2014-01-01

    Full Text Available Second lymphoid neoplasms are an uncommon but recognized feature of non-Hodgkin’s lymphomas, putatively arising secondary to common genetic or environmental risk factors. Previous limited evaluations of clonal relatedness between successive mature B-cell malignancies have yielded mixed results. We describe the case of a man with intravascular large B-cell lymphoma involving the central nervous system who went into clinical remission following immunochemotherapy and brain radiation, only to relapse 2 years later with a plasmacytoma of bone causing cauda equina syndrome. The plasmacytoma stained strongly for the cell cycle regulator cyclin D1 on immunohistochemistry, while the original intravascular large cell lymphoma was negative, a disparity providing no support for clonal identity between the 2 neoplasms. Continued efforts atcataloging and evaluating unique associations of B-cell malignancies are critical to improving understanding of overarching disease biology in B-cell malignancies.

  1. CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts.

    Science.gov (United States)

    Kim, Hyoung Jung; Yu, Eun Sil; Byun, Jae Ho; Hong, Seung-Mo; Kim, Kyoung Won; Lee, Jong Seok; Kim, So Yeon

    2014-01-01

    The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.

  2. Clinical Significance of Colonoscopy in Patients with Upper Gastrointestinal Polyps and Neoplasms: A Meta-Analysis

    Science.gov (United States)

    Wu, Zhen-Jie; Lin, Yuan; Xiao, Jun; Wu, Liu-Cheng; Liu, Jun-Gang

    2014-01-01

    Background Some authors have studied the relationship between the presence of polyps, adenomas and cancers of upper gastrointestinal tract (stomach and duodenum) and risk of colorectal polyps and neoplasms; however, the results are controversial, which may be due to study sample size, populations, design, clinical features, and so on. No meta-analysis, which can be generalized to a larger population and could provide a quantitative pooled risk estimate of the relationship, of this issue existed so far. Methods We performed a meta-analysis to evaluate risk of colorectal polyps or neoplasms in patients with polyps, adenomas or cancers in upper gastrointestinal tract comparing with controls. A search was conducted through PubMed, EMBASE, reference lists of potentially relevant papers, and practice guidelines up to 27 November 2013 without languages restriction. Odd ratios (ORs) were pooled using random-effects models. Results The search yielded 3 prospective and 21 retrospective case-control studies (n = 37152 participants). The principal findings included: (1) OR for colorectal polyps was 1.15 (95% CI, 1.04–1.26) in the gastric polyps group comparing with control groups; (2) Patients with gastric polyps and neoplasms have higher risk (OR, 1.31 [95% CI, 1.06–1.62], and 1.72 [95% CI, 1.42–2.09], respectively) of colorectal neoplasms comparing with their controls; and (3) Positive association was found between the presence of colorectal neoplasms and sporadic duodenal neoplasms (OR, 2.59; 95% CI, 1.64–4.11). Conclusions Findings from present meta-analysis of 24 case-control studies suggest that the prevalence of colorectal polyps was higher in patients with gastric polyps than in those without gastric polyps, and the risk of colorectal neoplasms increases significantly in patients with gastric polyps, neoplasms, and duodenal neoplasms. Therefore, screening colonoscopy should be considered for patients with upper gastrointestinal polyps and neoplasms. PMID

  3. Thyroid neoplasms after radiation therapy for adolescent acne vulgaris

    International Nuclear Information System (INIS)

    Paloyan, E.; Lawrence, A.M.

    1978-01-01

    There is a potential hazard of thyroid cancer after exposure to external irradiation for the treatment of adolescent acne vulgaris. We noted a 60% incidence of thyroid carcinoma among 20 patients with such a history, who were operated on for thyroid nodules during a five-year period. Eighty-three percent of the patients with carcinoma had either a follicular or a mixed papillary-follicular carcinoma; 17% had a papillary carcinoma; 33% had regional node metastases; none had evidence of distant metastases. The interval between radiation exposure and thyroidectomy ranged from nine to 41 years. This association of thyroid neoplasms and a prior history of radiation for acne vulgaris may be coincidental and therefore remains to be proved by retrospective surveys of large numbers of treated patients with appropriate controls

  4. Gorlin-Goltz syndrome and neoplasms: a case study.

    Science.gov (United States)

    Lopes, Nilza N F; Caran, Eliana M; Lee, Maria Lucia; Silva, Nasjla Saba; Rocha, André Caroli; Macedo, Carla R D

    2010-01-01

    Gorlin syndrome is a rare autosomal dominant disorder exhibiting high penetrance and variable expressivity. It is characterized by facial dysmorphism, skeletal anomalies, multiple basal cell carcinomas, odontogenic keratocysts (OKC), palmar and plantar pits, bifid ribs, vertebral anomalies and a variety of other malformations. Various neoplasms, such as medulloblastomas, meningiomas, ovarian and cardiac fibromas are also found in this syndrome. To describe a twelve-year-old patient with Gorlin-Goltz syndrome, with basal cell carcinomas and promyelocytic leukemia developed after receiving craniospinal radiation for a medulloblastoma. Bifid ribs as well as mandibular and maxillar OKC were also diagnosed Conclusion: The patient with Gorlin-Goltz syndrome should receive close follow-up for early detection of malformations nd malignant neoplasias.

  5. Autopsy findings of malignant neoplasms treated with radiation

    International Nuclear Information System (INIS)

    Okazaki, Atsushi; Ito, Jun; Tatezawa, Takashi; Nishimura, Toshinobu; Niibe, Hideo.

    1984-01-01

    Autopsy findings in 26 cases of malignant neoplasms treated with radiation were analysed and following results were obtained. 1. Causes of death except for neoplastic extension were 58% (15/26) and infection was the single predominant cause of death (73% : 11/15) with 50% (4/8) in lung cancer. 2. Distant metastases were found in 73% (19/26). In 7 cases, no obvious metastasis was found before and after autopsy. On the other hand, the patients with metastases over 2 organs before autopsy revealed metastases in 82% (9/11) to the other organs at autopsy. 3. Radiation therapy was effective and the primary tumor disappeared completely in 71% (10/14) with curative irradiation. In metastatic lesions, tumor cells were almost disappeared with dosage over 40 Gy. (author)

  6. CT diagnosis of hyperdense intracranial neoplasms. Review of the literature

    International Nuclear Information System (INIS)

    Ishikura, Reiichi; Ando, Kumiko; Tominaga, Satoru; Nakao, Norio; Ikeda, Jouta; Takemura, Yuriko; Morikawa, Tsutomu

    1999-01-01

    In contrast to typical astrocytic tumors that show hypodense areas on computed tomographic images, some intracranial tumors show hyperdense areas on CT images. The major reasons for hyperdensity on CT images are hypercellular lesions, intratumoral calcification, and intratumoral hemorrhage. Malignant lymphomas, germinomas, and medulloblastomas show homogenous hyperdensity on CT images because of their hypercellularity. Tumorous lesions such as subependymal giant cell astrocytomas, oligodendrogliomas, ependymomas, central neurocytomas, craniopharyngiomas, and meningiomas often present with hyperdense calcified lesions on CT images. Intratumoral hemorrhage also causes hyperdensity on CT images, and is often associated with metastatic brain tumors, glioblastomas, pituitary adenomas, and rarely with any of the other intracranial tumors. Although magnetic resonance imaging is now the major diagnostic tool for diseases of the central nervous system, the first imaging studies for patients with neurologic symptoms are still CT scans. Hyperdense areas on CT images are a clue to making an accurate diagnosis of intracranial neoplasms. (author)

  7. Uterine Rupture Due to Invasive Metastatic Gestational Trophoblastic Neoplasm

    Directory of Open Access Journals (Sweden)

    David I Bruner

    2013-09-01

    Full Text Available While complete molar pregnancies are rare, they are wrought with a host of potential complications to include invasive gestational trophoblastic neoplasia. Persistent gestational trophoblastic disease following molar pregnancy is a potentially fatal complication that must be recognized early and treated aggressively for both immediate and long-term recovery. We present the case of a 21-year-old woman with abdominal pain and presyncope 1 month after a molar pregnancy with a subsequent uterine rupture due to invasive gestational trophoblastic neoplasm. We will discuss the complications of molar pregnancies including the risks and management of invasive, metastatic gestational trophoblastic neoplasia. [West J Emerg Med. 2013;14(5:444–447.

  8. THE THERAPEUTIC USE OF RADIOACTIVE GOLD SEEDS IN NEOPLASMS

    Energy Technology Data Exchange (ETDEWEB)

    Lachance, Paul; Vallee, A. F.

    1963-06-15

    A method and the apparatus for the treatment of neoplasms with Au/sup 198/ seeds are described. The introducer or gun is loaded with a magazine or cartridge containing 15 radioactive gold grains and then irradiated. The grains are cylinders made of gold encased in Pt with measurements of: length, 2.1 mm; diameter, 0.4 mm; weight, 25 mgm; platinum casing, 0.2 mm. The seeds are ready for use 7 to 10 days after irradiation or when gamma activity is around 3 to 4.5 mC per seed. A permanent implant gives to the tumor an approximate dose of 6000- 7000 r in 4 to 5 days. The effectiveness and advantages of the method are also discussed. (P.C.H.)

  9. Multiple primary malignant neoplasms in breast cancer patients in Israel

    International Nuclear Information System (INIS)

    Schenker, J.G.; Levinsky, R.; Ohel, G.

    1984-01-01

    The data of an epidemiologic study of multiple primary malignant neoplasms in breast cancer patients in Israel are presented. During the 18-year period of the study 12,302 cases of breast carcinoma were diagnosed, and, of these, 984 patients (8%) had multiple primary malignant tumors. Forty-seven of these patients developed two multiple primary cancers. A significantly higher than expected incidence of second primary cancers occurred at the following five sites: the opposite breast, salivary glands, uterine corpus, ovary, and thyroid. Cancers of the stomach and gallbladder were fewer than expected. Treatment of the breast cancer by irradiation was associated with an increased risk of subsequent cancers of lung and hematopoietic system. The prognosis was mainly influenced by the site and malignancy of the second primary cancer. The incidence of multiple primary malignancies justifies a high level of alertness to this possibility in the follow-up of breast cancer patients

  10. Localization of gonadotropin binding sites in human ovarian neoplasms

    International Nuclear Information System (INIS)

    Nakano, R.; Kitayama, S.; Yamoto, M.; Shima, K.; Ooshima, A.

    1989-01-01

    The binding of human luteinizing hormone and human follicle-stimulating hormone to ovarian tumor biopsy specimens from 29 patients was analyzed. The binding sites for human luteinizing hormone were demonstrated in one tumor of epithelial origin (mucinous cystadenoma) and in one of sex cord-stromal origin (theca cell tumor). The binding sites for human follicle-stimulating hormone were found in three tumors of epithelial origin (serous cystadenoma and mucinous cystadenoma) and in two of sex cord-stromal origin (theca cell tumor and theca-granulosa cell tumor). The surface-binding autoradiographic study revealed that the binding sites for gonadotropins were localized in the stromal tissue. The results suggest that gonadotropic hormones may play a role in the growth and differentiation of a certain type of human ovarian neoplasms

  11. Percutaneous thermal ablation of renal neoplasms; Perkutane Thermoablation von Nierentumoren

    Energy Technology Data Exchange (ETDEWEB)

    Tacke, J. [Inst. fuer Diagnostische und Interventionelle Radiologie/Neuroradiologie, Klinikum Passau (Germany); Mahnken, A.H.; Guenther, R.W. [Klinik fuer Radiologische Diagnostik, Universitaetsklinikum Aachen (Germany)

    2005-12-15

    Due to modern examination techniques such as multidetector computed tomography and high-field magnetic resonance imaging, the detection rate of renal neoplasms is continually increasing. Even though tumors exceeding 4 cm in diameter rarely metastasize, all renal lesions that are possible neoplasms should be treated. Traditional treatment techniques include radical nephrectomy or nephron-sparing resection, which are increasingly performed laparoscopically. Modern thermal ablation techniques such as hyperthermal techniques like radiofrequency ablation RFA, laser induced thermal ablation LITT, focused ultrasound FUS and microwave therapy MW, as well as hypothermal techniques (cryotherapy) may be a useful treatment option for patients who are unfit for or refuse surgical resection. Cryotherapy is the oldest and best known thermal ablation technique and can be performed laparoscopically or percutaneously. Since subzero temperatures have no antistyptic effect, additional maneuvers must be performed to control bleeding. Percutaneous cryotherapy of renal tumors is a new and interesting method, but experience with it is still limited. Radiofrequency ablation is the most frequently used method. Modern probe design allows volumes between 2 and 5 cm in diameter to be ablated. Due to hyperthermal tract ablation, the procedure is deemed to be safe and has a low complication rate. Although there are no randomized comparative studies to open resection, the preliminary results for renal RFA are promising and show RFA to be superior to other thermal ablation techniques. Clinical success rates are over 90% for both, cryo- and radiofrequency ablation. Whereas laser induced thermal therapy is established in hepatic ablation, experience is minimal with respect to renal application. For lesions of more than 2 cm in diameter, additional cooling catheters are required. MR thermometry offers temperature control during ablation. Microwave ablation is characterized by small ablation volumes

  12. Blastic plasmacytoid dendritic cell neoplasm (BPDCN): the cutaneous sanctuary.

    Science.gov (United States)

    Pileri, A; Delfino, C; Grandi, V; Agostinelli, C; Pileri, S A; Pimpinelli, N

    2012-12-01

    Blastic plasmacytoid dendritic cell neoplasm (BPDNC) is a rare tumour, which stems from plasmacytoid dendritic cells. Although the aetiology is still unclear, in the last few years various reports suggested a potential role of chromosomal aberrations in the oncogenesis. The disease is currently enclosed among "acute myeloid leukemia (AML) and related precursor neoplasms" in the last WHO classification. BPDCN has an aggressive course, however, it has been suggested that an exclusive cutaneous involvement at presentation is related to a better clinical outcome. We review the literature about BPDCN, and we present a series of 11 cases, all characterised by disease limited to the skin at presentation. Furthermore, we examined all cases of the last 10 years stored in the database of the multidisciplinary study group on cutaneous lymphomas of the University of Florence. Basing on the clinical features, patient were classified into two groups: with a single-lesion or multiple eruptive-lesions presentation. The former were treated with radiotherapy (limited field, electron beam therapy). The latter were treated with different therapeutic options, depending on age and co-morbidities. All patients with a single lesion achieved complete response. Five of 6 patients with eruptive lesions achieved a clinical response (2 complete and 3 partial response). Notably, the progression free survival was higher in the single-lesion than in the eruptive-lesion group (23 vs. 9 months). However all patients relapsed and 8 of 11 died. Although the small number of selected patients, we could speculate that the concept of "cutaneous sanctuary" is particularly true in patients with a single lesion-presentation. In these patients, especially if >70 year-old aged, radiotherapy should be encouraged as the treatment of choice.

  13. File list: NoD.Neu.05.AllAg.Nerve_Sheath_Neoplasms [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  20. Comparison between MRI with MR cholangiopancreatography and endoscopic ultrasonography for differentiating malignant from benign mucinous neoplasms of the pancreas

    International Nuclear Information System (INIS)

    Hwang, Jiyoung; Hong, Seong Sook; Kim, Hyun-joo; Kim, Young Kon; Jeong, Woo Kyung; Min, Ji Hye

    2018-01-01

    To compare diagnostic performance of magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) for differentiating malignant from benign intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) of the pancreas. This retrospective study included 55 patients with 47 surgically confirmed IPMNs (12 malignant, 35 benign) and eight MCNs (two malignant, six benign) who underwent contrast-enhanced pancreas MRI and EUS. Contrast enhancement was not routinely used at EUS examination. Two observers independently evaluated the MRIs, and another reviewed EUS images. They recorded their confidence for malignancy with each imaging modality. We calculated diagnostic performance using the area under the receiver operating characteristic curves (A z ), and to determine the accuracy, sensitivity, specificity, and positive (PPV) and negative predictive (NPV) values. The A z values of MRI were higher than those of EUS (0.712 and 0.688 for MRI vs. 0.543 for EUS; p = 0.007). The diagnostic accuracies (74.5%), specificity (78.0% and 80.5%) and PPV (50.0%) of MRI in two observers were higher than those (56.4%, 58.5% and 29.2%, respectively) of EUS (p = 0.013-0.049). MRI showed better diagnostic performance than EUS for differentiating malignant from benign pancreatic IPMN and MCN. (orig.)

  1. Comparison between MRI with MR cholangiopancreatography and endoscopic ultrasonography for differentiating malignant from benign mucinous neoplasms of the pancreas

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Jiyoung; Hong, Seong Sook; Kim, Hyun-joo [Seoul Hospital, Department of Radiology, Soonchunhyang University College of Medicine, Seoul (Korea, Republic of); Kim, Young Kon; Jeong, Woo Kyung [Sungkyunkwan University School of Medicine, Department of Radiology and Center for Imaging Science, Samsung Medical Center, Seoul (Korea, Republic of); Min, Ji Hye [Chungnam National University College of Medicine, Department of Radiology, Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2018-01-15

    To compare diagnostic performance of magnetic resonance imaging (MRI) and endoscopic ultrasonography (EUS) for differentiating malignant from benign intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) of the pancreas. This retrospective study included 55 patients with 47 surgically confirmed IPMNs (12 malignant, 35 benign) and eight MCNs (two malignant, six benign) who underwent contrast-enhanced pancreas MRI and EUS. Contrast enhancement was not routinely used at EUS examination. Two observers independently evaluated the MRIs, and another reviewed EUS images. They recorded their confidence for malignancy with each imaging modality. We calculated diagnostic performance using the area under the receiver operating characteristic curves (A{sub z}), and to determine the accuracy, sensitivity, specificity, and positive (PPV) and negative predictive (NPV) values. The A{sub z} values of MRI were higher than those of EUS (0.712 and 0.688 for MRI vs. 0.543 for EUS; p = 0.007). The diagnostic accuracies (74.5%), specificity (78.0% and 80.5%) and PPV (50.0%) of MRI in two observers were higher than those (56.4%, 58.5% and 29.2%, respectively) of EUS (p = 0.013-0.049). MRI showed better diagnostic performance than EUS for differentiating malignant from benign pancreatic IPMN and MCN. (orig.)

  2. A case series of clinically undiagnosed hematopoietic neoplasms discovered at autopsy.

    Science.gov (United States)

    Podduturi, Varsha; Guileyardo, Joseph M; Soto, Luis R; Krause, John R

    2015-06-01

    In the United States, autopsy rates have diminished to less than 5% during the last half of the 20th century and the beginning of the 21st century for a multitude of reasons. Many believe this results in unrecognized malignancies that could have explained a patient's death. We describe six deaths in which hematopoietic neoplasms were identified at autopsy but were not diagnosed clinically. The six undiagnosed hematopoietic malignancy cases discovered at autopsy include four men and two women ranging from 50 to 78 years of age. One patient was African American and five patients were white, all with multiple comorbidities. The tumors included diffuse large B-cell lymphoma, activated B-cell type, intravascular large B-cell lymphoma, ALK-negative anaplastic large cell lymphoma arising in a setting of human immunodeficiency virus, and a myeloid sarcoma. These cases illustrate the importance of the traditional postmortem examination in not only confirming clinical diagnoses but also identifying previously unknown diagnoses. Hematologic malignancies may present with nonspecific clinical manifestations, and this series of cases also emphasizes the necessity for widening the differential diagnosis in patients with unexplained lactic acidosis and hepatic failure to include hematopoietic malignancies since prompt treatment may be lifesaving. Copyright© by the American Society for Clinical Pathology.

  3. Coexisting Primary Ovarian and Omental Hydatid Disease Mimicking an Ovarian Neoplasm: A Case Report.

    Science.gov (United States)

    Tas, Emre E; Yegin Akcay, Gulin F; Yildirim, Fatma; Yavuz, Filiz

    2018-05-01

    Hydatid disease is a parasitic infection that most commonly affects the liver and lungs, although the disease can arise in any part of the body. Cysts may mimic many benign and malignant conditions. The diagnosis cannot be confirmed preoperatively in all cases. A 44-yr-old menopausal woman was admitted to the department of gynecology with complaints of abdominal distention. A fixed abdominopelvic mass was identified. Radiology revealed a 20-cm mass with branched septations and solid components. CA-125 level was 55 kU/L, and Risk of Malignancy Index-2 score was 880. These findings suggested the presence of an ovarian neoplasm, and laparotomy was performed. Cystic masses measuring 22 cm and 4 cm, originating from the omentum majus and left ovary, respectively, were found during surgery. Frozen-section analysis revealed hydatid disease. Infracolic omentectomy and total abdominal hysterectomy with bilateral salpingo-oopherectomy were performed. Results of a serum Echinococcus hemagglutination test performed immediately after surgery were negative. The patient was prescribed albendazole for 6 mo and discharged on the third postoperative day with no complaints. The incidence of hydatid disease in the female reproductive system is very rare; however, clinicians must be aware of this disease and take necessary precautions while operating because any spillage may lead to anaphylactic shock and increased risk of recurrence.

  4. Myeloproliferative disorder FOP-FGFR1 fusion kinase recruits phosphoinositide-3 kinase and phospholipase Cγ at the centrosome

    Directory of Open Access Journals (Sweden)

    Tassin Anne-Marie

    2008-04-01

    Full Text Available Abstract Background The t(6;8 translocation found in rare and agressive myeloproliferative disorders results in a chimeric gene encoding the FOP-FGFR1 fusion protein. This protein comprises the N-terminal region of the centrosomal protein FOP and the tyrosine kinase of the FGFR1 receptor. FOP-FGFR1 is localized at the centrosome where it exerts a constitutive kinase activity. Results We show that FOP-FGFR1 interacts with the large centrosomal protein CAP350 and that CAP350 is necessary for FOP-FGFR1 localisation at centrosome. FOP-FGFR1 activates the phosphoinositide-3 kinase (PI3K pathway. We show that p85 interacts with tyrosine 475 of FOP-FGFR1, which is located in a YXXM consensus binding sequence for an SH2 domain of p85. This interaction is in part responsible for PI3K activation. Ba/F3 cells that express FOP-FGFR1 mutated at tyrosine 475 have reduced proliferative ability. Treatment with PI3K pathway inhibitors induces death of FOP-FGFR1 expressing cells. FOP-FGFR1 also recruits phospholipase Cγ1 (PLCγ1 at the centrosome. We show that this enzyme is recruited by FOP-FGFR1 at the centrosome during interphase. Conclusion These results delineate a particular type of oncogenic mechanism by which an ectopic kinase recruits its substrates at the centrosome whence unappropriate signaling induces continuous cell growth and MPD.

  5. Differential labeling of platelet alpha 2 adrenoceptors by 3H dihydroergocryptine and 3H yohimbine in patients with myeloproliferative disorders

    International Nuclear Information System (INIS)

    Swart, S.S.; Wood, J.K.; Barnett, D.B.

    1985-01-01

    Platelet alpha adrenoceptor status was examined using the radioligands 3 H-yohimbine ( 3 H-YOH) and 3 H-dihydroergocryptine ( 3 H-DHE) in 14 patients with myeloproliferative disorder (MPD) and 10 normal controls. Platelets from normal controls and MPD patients sensitive to adrenaline induced aggregation exhibited approximately 50% more binding sites identified by 3 H-DHE than 3 H-YOH, whereas MPD platelets insensitive to adrenaline showed selective loss of these extra 3 H-DHE sites. In functional studies after 30 minutes preincubation with the unlabelled antagonists, DHE was more potent than YOH at inhibiting adrenaline induced aggregation in normal platelets. In addition, the affinity constant for DHE was virtually identical in binding and functional experiments, whereas for YOH the affinity constant for binding was approximately 10 fold more potent than that for aggregation. These results suggest that the alpha adrenoceptor binding site on human platelets labelled by 3 H-DHE may be of more functional relevance than that labelled by 3 H-YOH alone

  6. Molecular Diagnostics in the Neoplasms of Small Intestine and Appendix: 2018 Update.

    Science.gov (United States)

    Zhang, Yingtao; Zulfiqar, Muhammad; Bluth, Martin H; Bhalla, Amarpreet; Beydoun, Rafic

    2018-06-01

    Neoplasms of the small intestine are rare in comparison with colorectal tumors. The most common tumor types arising in the small intestine are adenocarcinomas, well-differentiated neuroendocrine tumors, gastrointestinal stromal tumors, and lymphoma. Primary appendiceal neoplasms are rare and found in less than 2% of appendectomy specimens with an incidence of approximately 1.2 cases per 100,000 people per year in the United States. This article explores molecular diagnostics in the neoplasms of small intestine and appendix. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Tumor registry data, Hiroshima and Nagasaki 1957-1959: malignant neoplasms

    Energy Technology Data Exchange (ETDEWEB)

    Harada, Tomin; Ide, Masao; Ishida, Morihiro; Troup, G M

    1963-10-03

    The report concerns three aspects of the Hiroshima and Nagasaki Tumor Registry data, 1957-1959: comparability, reliability and validity of incidence rates of malignant neoplasms obtained from the Tumor Registries and various statistical problems of registered data related to the Life Span Study sample and Adult Health Study sample; incidence rates of main site of malignant neoplasms obtained from the Tumor Registries are compared with those of the United States and Denmark; and incidence of malignant neoplasm among Hiroshima and Nagasaki A-bomb survivors. 15 references, 7 figures, 30 tables.

  8. Simultaneous liver mucinous cystic and intraductal papillary mucinous neoplasms of the bile duct: a case report.

    Science.gov (United States)

    Budzynska, Agnieszka; Hartleb, Marek; Nowakowska-Dulawa, Ewa; Krol, Robert; Remiszewski, Piotr; Mazurkiewicz, Michal

    2014-04-14

    Cystic hepatic neoplasms are rare tumors, and are classified into two separate entities: mucinous cystic neoplasms (MCNs) and intraductal papillary mucinous neoplasms of the bile duct (IPMN-B). We report the case of a 56-year-old woman who presented with abdominal pain and jaundice due to the presence of a large hepatic multilocular cystic tumor associated with an intraductal tumor. Partial hepatectomy with resection of extrahepatic bile ducts demonstrated an intrahepatic MCN and an intraductal IPMN-B. This is the first report of the simultaneous occurrence of these two histologically distinct entities in the liver.

  9. Giant solitary fibrous tumour of the pleura: a rare but usually benign intrathoracic neoplasm

    DEFF Research Database (Denmark)

    Bodtger, Uffe; Pedersen, Jesper Holst; Skov, Birgit Guldhammer

    2009-01-01

    BACKGROUND: Low forced expiratory volume (FEV(1)) and low performance status usually preclude surgical treatment of lung neoplasms. Earlier case reports have suggested that curative, safe surgery is possible in extrapulmonal intrathoracic neoplasms. METHODS: A case report of an 83-year-old women...... with progressing dyspnoea secondary to a huge left-side neoplasm. RESULTS: Work-up reveal an FEV(1) of 0.4 L, and a giant solitary fibrous tumor of the pleura. The tumor was surgically removed in toto without complications: weighting approximately 3 kg, and benign histology. The patient was without dyspnoea...

  10. Diagnostic and therapeutic implications of genetic heterogeneity in myeloid neoplasms uncovered by comprehensive mutational analysis

    Directory of Open Access Journals (Sweden)

    Sarah M. Choi

    2017-01-01

    Full Text Available While growing use of comprehensive mutational analysis has led to the discovery of innumerable genetic alterations associated with various myeloid neoplasms, the under-recognized phenomenon of genetic heterogeneity within such neoplasms creates a potential for diagnostic confusion. Here, we describe two cases where expanded mutational testing led to amendment of an initial diagnosis of chronic myelogenous leukemia with subsequent altered treatment of each patient. We demonstrate the power of comprehensive testing in ensuring appropriate classification of genetically heterogeneous neoplasms, and emphasize thoughtful analysis of molecular and genetic data as an essential component of diagnosis and management.

  11. Presence of calreticulin mutations in JAK2-negative polycythemia vera.

    Science.gov (United States)

    Broséus, Julien; Park, Ji-Hye; Carillo, Serge; Hermouet, Sylvie; Girodon, François

    2014-12-18

    Calreticulin (CALR) mutations have been reported in Janus kinase 2 (JAK2)- and myeloproliferative leukemia (MPL)-negative essential thrombocythemia and primary myelofibrosis. In contrast, no CALR mutations have ever been reported in the context of polycythemia vera (PV). Here, we describe 2 JAK2(V617F)-JAK2(exon12)-negative PV patients who presented with a CALR mutation in peripheral granulocytes at the time of diagnosis. In both cases, the CALR mutation was a 52-bp deletion. Single burst-forming units-erythroid (BFU-E) from 1 patient were grown in vitro and genotyped: the same CALR del 52-bp mutation was noted in 31 of the 37 colonies examined; 30 of 31 BFU-E were heterozygous for CALR del 52 bp, and 1 of 31 BFU-E was homozygous for CALR del 52 bp. In summary, although unknown mutations leading to PV cannot be ruled out, our results suggest that CALR mutations can be associated with JAK2-negative PV. © 2014 by The American Society of Hematology.

  12. Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

    International Nuclear Information System (INIS)

    Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J.; Davenport, Matthew S.; Caoili, Elaine M.; Else, Tobias

    2015-01-01

    There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

  13. Pediatric adrenocortical neoplasms: can imaging reliably discriminate adenomas from carcinomas?

    Energy Technology Data Exchange (ETDEWEB)

    Flynt, Kelsey A.; Dillman, Jonathan R.; Smith, Ethan A.; Strouse, Peter J. [University of Michigan Health System, Section of Pediatric Radiology, C. S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Davenport, Matthew S.; Caoili, Elaine M. [University of Michigan Health System, Division of Abdominal Imaging, Department of Radiology, Ann Arbor, MI (United States); Else, Tobias [University of Michigan Health System, Division of Metabolism, Endocrinology and Diabetes, Department of Internal Medicine, Ann Arbor, MI (United States)

    2015-08-15

    There is a paucity of literature describing and comparing the imaging features of adrenocortical adenomas and carcinomas in children and adolescents. To document the CT and MRI features of adrenocortical neoplasms in a pediatric population and to determine whether imaging findings (other than metastatic disease) can distinguish adenomas from carcinomas. We searched institutional medical records to identify pediatric patients with adrenocortical neoplasms. Pre-treatment CT and MRI examinations were reviewed by two radiologists in consensus, and pertinent imaging findings were documented. We also recorded relevant histopathological, demographic, clinical follow-up and survival data. We used the Student's t-test and Wilcoxon rank sum test to compare parametric and nonparametric continuous data, and the Fisher exact test to compare proportions. We used receiver operating characteristic (ROC) curve analyses to evaluate the diagnostic performances of tumor diameter and volume for discriminating carcinoma from adenoma. A P-value ≤0.05 was considered statistically significant. Among the adrenocortical lesions, 9 were adenomas, 15 were carcinomas, and 1 was of uncertain malignant potential. There were no differences in mean age, gender or sidedness between adenomas and carcinomas. Carcinomas were significantly larger than adenomas based on mean estimated volume (581 ml, range 16-2,101 vs. 54 ml, range 3-197 ml; P-value = 0.003; ROC area under the curve = 0.92) and mean maximum transverse plane diameter (9.9 cm, range 3.0-14.9 vs. 4.4 cm, range 1.9-8.2 cm; P-value = 0.0001; ROC area under the curve = 0.92). Carcinomas also were more heterogeneous than adenomas on post-contrast imaging (13/14 vs. 2/9; odds ratio [OR] = 45.5; P-value = 0.001). Six of 13 carcinomas and 1 of 8 adenomas contained calcification at CT (OR = 6.0; P-value = 0.17). Seven of 15 children with carcinomas exhibited metastatic disease at diagnosis, and three had inferior vena cava invasion. Median

  14. Laparoscopic Low Anterior Resection and Eversion Technique Combined With a Nondog Ear Anastomosis for Mid- and Distal Rectal Neoplasms: A Preliminary and Feasibility Study.

    Science.gov (United States)

    Zhuo, Changhua; Liang, Lei; Ying, Mingang; Li, Qingguo; Li, Dawei; Li, Yiwei; Peng, Junjie; Huang, Liyong; Cai, Sanjun; Li, Xinxiang

    2015-12-01

    The transanal eversion and prolapsing technique is a well-established procedure, and can ensure an adequate distal margin for patients with low rectal neoplasms. Potential leakage risks, however, are associated with bilateral dog ear formation, which results from traditional double-stapling anastomosis. The authors determined the feasibility of combining these techniques with a commercial stapling set to achieve a nondog ear (end-to-end) anastomosis for patients with mid- and distal rectal neoplasms. Patients with early-stage (c/ycT1-2N0), mid- to distal rectal neoplasms and good anal sphincter function were included in this study. Laparoscopic low anterior resection was performed with a standard total mesorectal excision technique downward to the pelvic floor as low as possible. The bowel was resected proximal to the lesion with an endoscopic linear stapler. An anvil was inserted extracorporeally into the proximal colon via an extended working pore. The distal rectum coupled with the lesion was prolapsed and everted out of the anus. The neoplasm was resected with a sufficient margin above the dentate line under direct sight. A transrectal anastomosis without dog ears was performed intracorporeally to reconstitute the continuity of the bowel. Eleven cases, 6 male and 5 female patients, were included in this study. The mean operative time was 191 (129-292) minutes. The mean blood loss was 110 (30-300) mL. The median distal margin distance from the lower edge of the lesion to the dentate line was 1.5 (0.5-2.5) cm. All the resection margins were negative. Most patients experienced uneventful postoperative recoveries. No patient had anastomotic leak. Most patients had an acceptable stool frequency after loop ileostomy closure. Our preliminary data demonstrated the safety and feasibility of achieving a sound anastomosis without risking potential anastomotic leakage because of dog ear formation.

  15. Second neoplasms following radiotherapy or chemotherapy for cancer

    International Nuclear Information System (INIS)

    Penn, I.

    1982-01-01

    While radiotherapy and antineoplastic chemotherapy often control malignancies they may, paradoxically, cause new cancers to develop as long-term complications. Although almost any type of neoplasm can occur, radiation-induced malignancies are most likely to affect the myelopoietic tissues and the thyroid gland. The former tissues are also most frequently involved by chemotherapy. The combination of intensive radiotherapy and intensive chemotherapy is particularly leukemogenic. Acute myeloid leukemia has occurred with increased frequency following treatment of Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, ovarian cancer, polycythemia vera, carcinoma of the thyroid gland, and carcinoma of the breast. Radiation-induced malignancies usually occur in the field of irradiation. Tumors developing in an irradiated field include a substantial number of soft tissue sarcomas or osteosarcomas. There is a 20-fold increase of second cancers following treatment of childhood malignancies, mostly sarcomas of bone and soft tissues, but including leukemia, and carcinomas of the thyroid gland, skin, and breast. The latent period between radiotherapy and the appearance of a second cancer ranges from 2 years to several decades, often being 10-15 years. With chemotherapy the mean latent period is shorter, approximately 4 years. The mechanism of oncogenesis by radiotherapy or chemotherapy is poorly understood and probably involves a complex interplay of somatic mutation, co-oncogenic effects, depression of host immunity, stimulation of cellular proliferation, and genetic susceptibility

  16. Neurotensin receptors in human neoplasms: high incidence in Ewing's sarcomas.

    Science.gov (United States)

    Reubi, J C; Waser, B; Schaer, J C; Laissue, J A

    1999-07-19

    Receptors for regulatory peptides, such as somatostatin or vasoactive intestinal peptide (VIP), expressed at high density by neoplastic cells, can be instrumental for tumor diagnosis and therapy. Little is known about the expression of neurotensin receptors in human tumors. In the present study, 464 human neoplasms of various types were investigated for their neurotensin receptor content by in vitro receptor autoradiography on tissue sections using 125I-[Tyr3]-neurotensin as radioligand. Neurotensin receptors were identified and localized in tumor cells of 11/17 Ewing's sarcomas, 21/40 meningiomas, 10/23 astrocytomas, 5/13 medulloblastomas, 7/24 medullary thyroid cancers and 2/8 small cell lung cancers. They were rarely found in non-small cell lung cancers and breast carcinomas; they were absent in prostate, ovarian, renal cell and hepatocellular carcinomas, neuroendocrine gut tumors, pituitary adenomas, schwannomas, neuroblastomas and lymphomas. When present, the receptors bound with nanomolar affinity neurotensin and acetyl-neurotensin-(8-13), with lower affinity neuromedin N, diethylenetriamine penta-acetic acidneurotensin-(8-13) and SR 48692, but not neurotensin-(1-11). They were all of the NT1 type, without high affinity for levocabastine. Further, in 2 receptor-positive Ewing's sarcomas, neurotensin mRNA was detected by in situ hybridization techniques. Since neurotensin is known to stimulate cell proliferation, the presence of neurotensin receptors in human neoplasia may be of biological relevance, possibly as an integrative part of an autocrine feedback mechanism of tumor growth stimulation.

  17. Mucinous cystic neoplasm of the pancreas in a male patient

    Directory of Open Access Journals (Sweden)

    Kazuhiro Yoshida

    2011-04-01

    Full Text Available Mucinous cystic neoplasms (MCNs make up a morphologic family of similar appearing tumors arising in the ovary and various extraovarian organs such as pancreas, hepatobiliary tract and mesentery. MCNs of the pancreas occur almost exclusively in women. Here, we report a rare case of MCN in a male patient. A 39-year-old man was admitted to our hospital with the chief complaint of back pain. Abdominal computed tomography revealed a multilocular cyctic mass 6.3 cm in diameter in the pancreatic tail. In addition, the outer wall and septae with calcification were demonstrated in the cystic lesion. On magnetic resonance imaging , the cystic fluid had low intensity on T1-weighted imaging and high intensity on T2-weighted imaging. Endoscopic retrograde cholangio-pancreatography (ERCP showed neither communication between the cystic lesion and the main pancreatic duct nor encasement of the main pancreatic duct. Endoscopic ultrasonography revealed neither solid component nor thickness of the septae in the cystic lesion. Consequently, we performed distal pancreatectomy with splenectomy under the diagnosis of cystic neoplasia of the pancreas. Histopathologically, the cystic lesion showed two distinct component: an inner epithelial layer and an outer densely cellular ovarian-type stromal layer. Based on these findings, the cystic lesion was diagnosed as MCN.

  18. Current trend of malignant neoplasms among atomic bomb survivors

    International Nuclear Information System (INIS)

    Hamada, Tadao

    1984-01-01

    A survey was made on 7,589 admitted patients and 1,965 autopsy cases. The overall incidence of malignant neoplasms tended to decrease in the group exposed to atomic bomb within 2 km in autopsy cases and to increase in admitted patients. The incidence of pulmonary cancer tended to increase in both autopsy cases and admitted patients. The incidence of gastric cancer tended to increase up to 1975, and thereafter tended to decrease. The incidence of liver cancer tended to increase in both autopsy cases and admitted patients, which was marked in males. The incidence of leukemia was high in the group exposed to atomic bomb within 2 km in autopsy cases, and in the group within 1 km and the group which entered the city after the explosion in admitted patients. The incidence of malignant lymphoma tended to decrease, and the incidence of carcinoma of the colon tended to gradually increase in both autopsy cases and admitted patients. The incidence of multiple carcinomas tended to increase in both atomic bomb exposed group and non-exposed group, being higher in atomic bomb group than in non-exposed group. The incidence of breast cancer became constant since 1970. The incidence of carcinoma of the thyroid gland tended to decrease, although it was high in the group exposed near the explosion. (Namekawa, K.)

  19. Meningioma as second malignant neoplasm after oncological treatment during childhood

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, H.L.; Gebhardt, U. [Klinikum Oldenburg (Germany). Dept. of Pediatric Hematology and Oncology; Warmuth-Metz, M. [University Hospital Wuerzburg (Germany). Dept. of Neuroradiology; Pietsch, T. [Bonn Univ. (Germany). Dept. of Neuropathology; Soerensen, N. [Evangelisches Krankenhaus, Oldenburg (Germany). Dept. of Neurosurgery; Kortmann, R.D. [University Hospital Leipzig (Germany). Dept. of Radiooncology

    2012-05-15

    A total of 38 patients (18 female/20 male) with childhood meningioma were recruited from the German registry HIT-Endo (1989-2009). In 5 cases meningioma occurred as second malignant neoplasm (SMN). Histologies were confirmed by reference assessment in all cases (SMN: 2 WHO I, 1 WHO II, 2 WHO III). The SMNs were diagnosed at a median age of 12.4 years with a median latency of 10.2 years after primary malignancy (PMN; 4 brain tumors, 1 lymphoblastic leukemia; median age at diagnosis 2.7 years). Meningioma occurred as SMN in the irradiated field of PMN (range 12-54 Gy). The outcome after treatment of SMN meningioma (surgery/irradiation) was favorable in terms of psychosocial status and functional capacity in 4 of 5 patients (1 death). We conclude that survivors of childhood cancer who were exposed to radiation therapy at young age harbor the risk of developing meningioma as a SMN at a particularly short latency period in case of high dose exposure. (orig.)

  20. Parathyroid carcinoma: an unusual presentation of a rare neoplasm

    Directory of Open Access Journals (Sweden)

    Shruti, Sharma

    2017-12-01

    Full Text Available Parathyroid carcinoma is an extremely rare malignant endocrine neoplasm that is very challenging in its diagnosis as well as its treatment. Clinically the disease is detected earlier in patients who present with hyperparathyroidism with signs of profound hypercalcemia. Differentiation between benign and malignant disease of the parathyroid is challenging both for the clinician and for the pathologist. Complete surgical resection at the time of first operation offers the best chance of cure. Even after radical excision which is the standard management, local recurrence and metastases are frequent. The disease usually has a slow indolent course and most patients suffer from complications of hypercalcemia rather than tumor invasion or metastasis.We report a case of a 31-year-old woman who presented with renal colic. Various hematological, biochemical and radiological investigations were performed and a slightly enlarged right parathyroid was found. A clinical diagnosis of parathyroid adenoma was made and a right parathyroidectomy was done. Intraoperatively the surgeon had no suspicion of malignancy but microscopically the lesion was malignant and a final diagnosis of parathyroid carcinoma was rendered based on the criteria of invasion. Since there is no gold standard, a multidisciplinary approach, including the entire clinical, biochemical, radiological and pathological profile of the disease aids in an accurate diagnosis. Here we are reporting a case of a functional parathyroid carcinoma presenting in a relatively young patient with all the biochemical and radiological investigations and findings pointing towards a benign parathyroid disease.

  1. Microvessel and mast cell densities in malignant laryngeal neoplasm

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    Balica Nicolae Constantin

    2014-01-01

    Full Text Available Laryngeal neoplasm contributes to 30-40% of carcinomas of the head and neck. Mast cells are normal connective tissue residents, well represented in the respiratory tract. Experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis, which may also permit metastasis. The aim of this study was to evaluate the correlation between mast cell density, microvascular density, histopathological type and histological grade. Our study included 38 laryngeal carcinomas as follows: adenoid cystic carcinoma (2 cases, malignant papilloma (2 cases and squamous cell carcinoma (34 cases. The combined technique of CD 34-alcian blue safranin (ABS was used to identify microvessel and mast cell density, which was quantified by the hot spot method. A significant correlation was found between both mast cell and microvascular density, and G1/G2 histological grade (p=0.002 and p=0.004, respectively. Squamous cell carcinoma was significantly correlated with mast cell density (p=0.003, but not with microvascular density (p=0.454.

  2. Trisomy 19 as the sole chromosomal anomaly in hematologic neoplasms.

    Science.gov (United States)

    Johansson, B; Billström, R; Mauritzson, N; Mitelman, F

    1994-05-01

    Trisomy 19 was found as the sole chromosomal aberration in three hematologic malignancies: one chronic myelomonocytic leukemia and two cases of of immunophenotypically immature acute myeloid leukemia (AML). A compilation of previously published hematologic neoplasms with +19 as the only change reveals that this anomaly is strongly associated with myeloid malignancies; 25 of 31 cases have been myelodysplastic syndromes (MDS) or AML. Eight of the 11 MDS cases have been either refractory anemia (RA) or RA with excess of blasts, and four of the 14 AML cases have had preleukemic myelodysplastic cases phase, with the +19 accruing during the time of leukemic transformation. The AML cases have, in general, been either or early maturation arrest, i.e. undifferentiated or AML-M1/M2, or of myelomonocytic-monoblastic origin, i.e., AML-M4/M5. None of the MDS or AML cases with +19 had had a previous history of radio- or chemotherapy. We conclude that trisomy 19, as the sole anomaly, is a characteristic abnormality in de novo myeloid malignancies. No clinical features seem to characterize patients with +19 AML and MDS and the prognostic impact of the aberration remains to be elucidated.

  3. Microsatellite Status of Primary Colorectal Cancer Predicts the Incidence of Postoperative Colorectal Neoplasms.

    Science.gov (United States)

    Takiyama, Aki; Tanaka, Toshiaki; Yamamoto, Yoko; Hata, Keisuke; Ishihara, Soichiro; Nozawa, Hiroaki; Kawai, Kazushige; Kiyomatsu, Tomomichi; Nishikawa, Takeshi; Otani, Kensuke; Sasaki, Kazuhito; Watanabe, Toshiaki

    2017-10-01

    Few studies have evaluated the risk of postoperative colorectal neoplasms stratified by the nature of primary colorectal cancer (CRC). In this study, we revealed it on the basis of the microsatellite (MS) status of primary CRC. We retrospectively reviewed 338 patients with CRC and calculated the risk of neoplasms during postoperative surveillance colonoscopy in association with the MS status of primary CRC. A propensity score method was applied. We identified a higher incidence of metachronous rectal neoplasms after the resection of MS stable CRC than MS instable CRC (adjusted HR 5.74, p=0.04). We also observed a higher incidence of colorectal tubular adenoma in patients with MSS CRC (adjusted hazard ratio 7.09, pcolorectal cancer influenced the risk of postoperative colorectal neoplasms. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  4. Analysis of errors during medical and computerized diagnostics of spherical lung neoplasms

    International Nuclear Information System (INIS)

    Pozmogov, A.I.; Petruk, D.A.

    1985-01-01

    Reasons for errors in medical and computerized diagnostics of spherical lung neoplasms are studied based on material of 212 case records and clinicoroentgenological data; it should promote improvement of their diagnostics

  5. An extremely rare neoplasm, histiocytic sarcoma: A report of two cases with an aggressive clinical course

    Directory of Open Access Journals (Sweden)

    Erkan Kayikcioglu

    2017-07-01

    Conclusions: HS is an extremely rare malignant neoplasm of the monocytic/macrophage lineage, with no standardized chemotherapy regimen for multisystemic disease. Metastatic patients have a more aggressive clinical course than those with unifocal disease.

  6. Gd-EOB-DTPA-enhanced magnetic resonance imaging for bile duct intraductal papillary mucinous neoplasms

    OpenAIRE

    Ying, Shi-Hong; Teng, Xiao-Dong; Wang, Zhao-Ming; Wang, Qi-Dong; Zhao, Yi-Lei; Chen, Feng; Xiao, Wen-Bo

    2015-01-01

    AIM: To investigate gadolinium-ethoxybenzyl-diethylenetriamine-pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) of intraductal papillary mucinous neoplasms of the bile duct (IPMN-B).

  7. Esophageal and stomach malignant neoplasms characterization at Conjunto Hospitalar de Sorocaba

    OpenAIRE

    Mauro Razuk Filho; Júlio César Martinez

    2014-01-01

    ABSTRACT Objectives: the aim of this study is to collect and organize data on the incidence and prevalence of patients with malignant neoplasms of the esophagus and stomach in Conjunto Hospitalar de Sorocaba of the past six years. Methods: we conducted a survey of data on incidence, prevalence, age and sex of patients with malignant neoplasms of the esophagus and stomach that were admitted, treated and/or surgery at Conjunto Hospitalar de Sorocaba, in the last six years. Results: we analyz...

  8. Renal Function Outcomes for Multifocal Renal Neoplasms Managed by Radiofrequency Ablation

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Pushpender, E-mail: pugupta@wakehealth.edu; Allen, Brian C., E-mail: bcallen2@wakehealth.edu; Chen, Michael Y., E-mail: mchen@wakehealth.edu; Childs, David D., E-mail: dchilds@wakehealth.edu; Kota, Gopi, E-mail: gkota@wakehealth.edu; Zagoria, Ronald J., E-mail: rzagoria@wakehealth.edu [Wake Forest University School of Medicine, Department of Radiology (United States)

    2013-10-15

    Purpose: To evaluate renal function changes related to radiofrequency ablation (RFA) for the treatment of multifocal renal neoplasms. Methods: This is an institutional review board-approved, Health Insurance Portability and Accountability Act compliant retrospective study of all patients treated with computed tomography guided RFA for multifocal renal neoplasms at one institution. Fifty-seven subjects, mean age 70 (range 37-88) years, underwent RFA of 169 renal neoplasms (average size 2.0 cm). Subjects had between 2 and 8 (mean 2.96) neoplasms ablated. Estimated glomerular filtration rate (eGFR) was measured before and after RFA. Complications related to RFA were recorded. Results: eGFR decreased on average of 4.4 % per tumor treated and 6.7 % per ablation session (average 1.76 tumors treated per session). For subjects with the largest neoplasm measuring >3 cm, eGFR decreased an average of 14.5 % during the course of their treatment. If the largest neoplasm measured 2-3 cm, eGFR decreased an average of 7.7 %, and if the largest neoplasm measured <2 cm, eGFR decreased an average of 3.8 %. Subjects with reduced baseline renal function were more likely to have a greater decline in eGFR after RFA. There was a minor complication rate of 6.3 % (6 of 96 sessions), none of which required treatment, and a major complication rate of 4.2 % (4 of 96 sessions). Conclusion: RFA for the treatment of multifocal renal neoplasms results in mild decline of renal function.

  9. A mutação JAK2 V617F e as síndromes mieloproliferativas JAK2 V617F mutation and the myeloproliferative disorders

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    Bárbara C. R. Monte-Mór

    2008-01-01

    Full Text Available Síndromes mieloproliferativas (SMPs são doenças hematopoéticas de origem clonal que apresentam amplificação de uma ou mais linhagens mielóides. Policitemia vera (PV, trombocitemia essencial (TE, mielofibrose idiopática (MF e leucemia mielóide crônica (LMC são consideradas SMPs clássicas e apresentam características clínicas e biológicas comuns. Ao contrário de LMC, cuja etiologia está relacionada à proteína constitutivamente ativa Bcr-Abl, o mecanismo molecular de PV, TE e MF permaneceu por muito tempo desconhecido. Esta revisão se foca na recente descoberta da mutação JAK2 V617F em pacientes com PV, TE e MF, sua relação com o fenótipo mieloproliferativo e implicações na abordagem clínica de pacientes.Myeloproliferative disorders are clonal hematopoietic diseases that are characterized by the amplification of one or more myeloid lineages. Polycythemia vera, essential thrombocythemia, idiopathic myelofibrosis and chronic myeloid leukemia are considered classic myeloproliferative disorders and share common clinical and biological features. While the genetic basis of chronic myeloid leukemia is shown to be the constitutive active protein BCR-ABL, the main molecular lesions in polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis remain unknown. This review focuses on the recent discovery of the JAK2 V617F mutation, its relationship to the myeloproliferative phenotype and implications in the clinical approach of patients.

  10. The Synchronous Prevalence of Colorectal Neoplasms in Patients with Stomach Cancer

    Science.gov (United States)

    Lee, Sang Su; Kim, Cha Young; Ha, Chang Yoon; Min, Hyun Ju; Kim, Hyun Jin; Kim, Tae Hyo

    2011-01-01

    Purpose The association between stomach cancer and colorectal cancer is controversial. The purpose of this study was to determine the synchronous prevalence of colorectal neoplasms in patients with stomach cancer. Methods A total of 123 patients with stomach cancer (86 male) and 246 consecutive, age- and sex-matched persons without stomach cancer were analyzed from July 2005 to June 2010. All of them underwent colonoscopy within 6 months after undergoing gastroscopy. Results The prevalence of colorectal neoplasms was significantly higher in the stomach cancer group (35.8%) than in the control group (17.9%) (P neoplasms were more prevalent in the patients with stomach cancer (odds ratio [OR], 3.10; 95% confidence interval [CI], 1.71 to 5.63). In particular, the difference in the prevalence of colorectal neoplasms was more prominent in the patients above 50 years old (OR, 3.54; 95% CI, 1.80 to 6.98). Conclusion The results showed that the synchronous prevalence of colorectal neoplasms was higher in patients with stomach cancer than in those without stomach cancer. Therefore, patients with stomach cancer should be regarded as a high-risk group for colorectal neoplasms, and colonoscopy should be recommended for screening. PMID:22102975

  11. Leucemia mieloide crônica e outras doenças mieloproliferativas crônicas Chronic myeloid leukemia and other chronic myeloproliferative disorders

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    Vaneuza M. Funke

    2010-05-01

    HSCT have been restricted as a result of mortality related to this procedure and imatinib mesylate has become the new treatment of choice for this disease. In Brazil and possibly in other developing countries, socio-economic conditions make HSCT still feasible as first-line treatment in some situations. The HSCT remains indicated for Ph negative myeloproliferative disorders such as high risk myelofibrosis or patients with polycythemia vera or essential thrombocytosis that have evolved to myelofibrosis with high-risk features.

  12. Atopic dermatitis-like disease and associated lethal myeloproliferative disorder arise from loss of Notch signaling in the murine skin.

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    Alexis Dumortier

    2010-02-01

    Full Text Available The Notch pathway is essential for proper epidermal differentiation during embryonic skin development. Moreover, skin specific loss of Notch signaling in the embryo results in skin barrier defects accompanied by a B-lymphoproliferative disease. However, much less is known about the consequences of loss of Notch signaling after birth.To study the function of Notch signaling in the skin of adult mice, we made use of a series of conditional gene targeted mice that allow inactivation of several components of the Notch signaling pathway specifically in the skin. We demonstrate that skin-specific inactivation of Notch1 and Notch2 simultaneously, or RBP-J, induces the development of a severe form of atopic dermatitis (AD, characterized by acanthosis, spongiosis and hyperkeratosis, as well as a massive dermal infiltration of eosinophils and mast cells. Likewise, patients suffering from AD, but not psoriasis or lichen planus, have a marked reduction of Notch receptor expression in the skin. Loss of Notch in keratinocytes induces the production of thymic stromal lymphopoietin (TSLP, a cytokine deeply implicated in the pathogenesis of AD. The AD-like associated inflammation is accompanied by a myeloproliferative disorder (MPD characterized by an increase in immature myeloid populations in the bone marrow and spleen. Transplantation studies revealed that the MPD is cell non-autonomous and caused by dramatic microenvironmental alterations. Genetic studies demontrated that G-CSF mediates the MPD as well as changes in the bone marrow microenvironment leading to osteopenia.Our data demonstrate a critical role for Notch in repressing TSLP production in keratinocytes, thereby maintaining integrity of the skin and the hematopoietic system.

  13. Impact of oral hygiene on the development of oropharyngeal neoplasms

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    D. G. Kiparisova

    2015-01-01

    Full Text Available Objective. To evaluate the impact of oral hygiene on the development of oropharyngeal malignancies.Subjects and methods. The data of a prospective study of dental health indicators were analyzed in 586 patients (there were 76.4 % men and 23.6 % women with oropharyngeal malignancies. In the examinees, the sites of oropharyngeal neoplasms were as follows: the tongue in 195 (33 % cases, mouth floor in 147 (25 %, oropharynx in 139 (24 %, maxilla in 36 (6 %, buccal mucosa in 21 (4 %, soft palate in 18 (3 %, retromolar area in 14 (2 %, mandibula in 12 (2 %, and nose in 4 (1 %. The patients, examination employed routine dental examinations, determination of oral hygiene index, CFE index (a sum of carious, filled, and extracted teeth, and assessment of a patient, s skill and desire to perform individual oral hygiene. The patient hygiene performance (PHP index (Podshadley, Haley, 1968 was used to estimate his/her baseline ability. The rates of initial visits made by patients with oropharyngeal tumors to physicians of different specialties were also analyzed.Results. In the patients with oropharyngeal malignancies, the CFE index was high and amounted to 15 ± 0.4 с with a preponderance of carious and extracted teeth in the pattern; the PHP index was 1.4 ± 0.1, which corresponded to a satisfactory index. Thus, among the comparison group patients, satisfactory oral cavity sanitation was noted in only 4.8 % of the patients having a sanitation certificate. Consequently, 95.2 % of the patients were unready for specialized treatment. Out of the examinees, 176 (30 % made an initial visit for complaints to a dentist, 155 (26.5 % to an oncologist, 107 (18.3 % to an ENT doctor, 103 (17.7 % to a local therapist, and 43 (7.5 % to a surgeon. The collected history data also revealed that 59.2 % of the patients had self-treatment before going to specialists (according to them. Self-treatment or treatment by a noncancer specialist was ascertained to take an average of

  14. Peritoneal dissemination complicating morcellation of uterine mesenchymal neoplasms.

    Directory of Open Access Journals (Sweden)

    Michael A Seidman

    Full Text Available BACKGROUND: Power morcellation has become a common technique for the minimally invasive resection of uterine leiomyomas. This technique is associated with dissemination of cellular material throughout the peritoneum. When morcellated uterine tumors are unexpectedly found to be leiomyosarcomas or tumors with atypical features (atypical leiomyoma, smooth muscle tumor of uncertain malignant potential, there may be significant clinical consequences. This study was undertaken to determine the frequency and clinical consequence of intraperitoneal dissemination of these neoplasms. METHODOLOGY/PRINCIPAL FINDINGS: From 2005-2010, 1091 instances of uterine morcellation were identified at BWH. Unexpected diagnoses of leiomyoma variants or atypical and malignant smooth muscle tumors occurred in 1.2% of cases using power morcellation for uterine masses clinically presumed to be "fibroids" over this period, including one endometrial stromal sarcoma (ESS, one cellular leiomyoma (CL, six atypical leiomyomas (AL, three smooth muscle tumor of uncertain malignant potential (STUMPs, and one leiomyosarcoma (LMS. The rate of unexpected sarcoma after the laparoscopic morcellation procedure was 0.09%, 9-fold higher than the rate currently quoted to patients during pre-procedure briefing, and this rate may increase over time as diagnostically challenging or under-sampled tumors manifest their biological potential. Furthermore, when examining follow-up laparoscopies, both from in-house and consultation cases, disseminated disease occurred in 64.3% of all tumors (zero of one ESS, one of one CL, zero of one AL, four of four STUMPs, and four of seven LMS. Only disseminated leiomyosarcoma, however, was associated with mortality. Procedures are proposed for pathologic evaluation of morcellation specimens and associated follow-up specimens. CONCLUSIONS/SIGNIFICANCE: While additional study is warranted, these data suggest uterine morcellation carries a risk of disseminating

  15. Role of imprint/exfoliative cytology in ulcerated skin neoplasms.

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    Ramakrishnaiah, Vishnu Prasad Nelamangala; Babu, Ravindra; Pai, Dinker; Verma, Surendra Kumar

    2013-12-01

    Imprint cytology is a method of studying cells by taking an imprint from the cut surface of a wedge biopsy specimen or from the resected margins of a surgical specimen. It is rapid, simple and fairly accurate. Exfoliative cytology is an offshoot from the imprint cytology where in cells obtained from the surface of ulcers, either by scrape or brush, are analyzed for the presence of malignant cells. We undertook this study to see the role of imprint/exfoliative cytology in the diagnosis of ulcerated skin neoplasm and to check the adequacy of resected margins intra-operatively. This was a prospective investigative study conducted from September 2003 to July 2005. All patients presenting to surgical clinic with ulcerated skin and soft tissue tumours were included in the study. A wedge biopsy obtained from the ulcer and imprint smears were taken from the cut surface. Exfoliative cytology was analyzed from the surface smears. Wedge biopsy specimen was sent for histopathological (HPE) examination. The cytology and HPE were analyzed by a separate pathologist. Imprint cytology was also used to check the adequacy of resected margins in case of wide excision. This was compared with final HPE. Total of 107 patients was included in the present study and 474 imprint smears were done, with an average of 4.43 slides per lesion. Out of 59 wide excision samples, 132 imprint smears were prepared for assessing resected margins accounting for an average of 2.24 slides per each excised lesion. On combining imprint cytology with exfoliative cytology the overall sensitivity, specificity and positive predictive value were 90.38 %, 100 % and 90.38 % respectively. Only one out of 59 cases had a positive resected margin which was not picked by imprint cytology. Imprint cytology can be used for rapid and accurate diagnosis of various skin malignancies. It can also be used to check the adequacy of the resected margin intraoperatively.

  16. Minichromosome Maintenance Expression Defines Slow-Growing Gastroenteropancreatic Neuroendocrine Neoplasms

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    Simon Schimmack

    2016-10-01

    Full Text Available BACKGROUND: Small intestinal neuroendocrine neoplasm (SI-NEN proliferation is quantified by Ki67 measurements which capture G1-G2M phases of the cell cycle. G0 and early G1 phases, typical of slow-growing cells, can be detected by minichromosome maintenance protein (MCM expression. We hypothesized that these replication licensing markers may provide clinically relevant information to augment Ki67 in low-grade neuroendocrine neoplasia. METHODS: Immunohistochemical staining (IHC, Western blot analysis, quantitative polymerase chain reaction, and copy number variations of MCM2, MCM3, and Ki67 were undertaken in SI-NENs (n = 22. MCM and Ki67 expression was compared by Kaplan-Meier survival analysis (tissue microarray, independent set [n = 55]. Forty-three pancreatic NENs and 14 normal tissues were included as controls. RESULTS: In SI-NENs, MCM2 (mean: 21.2%: range: 16%-25% and MCM3 (28.7%: 22%-34% were detected in significantly more cells than Ki67 (2.3%: 0%-7%, P < .01. MCM2 mRNA correlated with Ki67 IHC (P < .05. MCM3 protein expression was higher in metastases (38-fold than in normal small intestine (P = .06 and was largely absent in normal neuroendocrine cells. There was considerable variation at the MCM copy number level (0-4 copies. MCM3 expression in proliferating cells significantly predicted overall survival (P < .002. Combinations of Ki67 and MCM2/3 in algorithms differentiated low and higher proliferative lesions (overall survival: 12 vs 6.1 years, P = .06. MCM expression was not informative in pancreatic NENs. CONCLUSION: MCMs are expressed in a higher proportion of NEN cells than Ki67 in slow-growing small intestinal lesions and correlate with survival. Assessment can be used to augment Ki67 to improve prognostic classification in these low-grade tumors.

  17. Thermal and epithermal neutrons in the treatment of neoplasms

    International Nuclear Information System (INIS)

    Sweet, W.H.; Wellum, G.; Tolpin, E.; Messer, J.R.

    1975-01-01

    Progress is reported in the preparation and testing of boron compounds for use as targets in the neutron capture therapy of neoplasms. The synthesis and structural confirmation of the disulfide, B 1 H 11 SSB 12 H 11 -4 is reported as well as a new structural model for its mono-oxidized derivative, B 12 H 11 SOSB 12 H 11 -4 , which showed useful tumor:blood concentration ratios in rats after three I. V. injections. The material, B 12 H 11 (SH) 2 -2 , was isolated and identified from impure Cs 2 B 12 H 11 SH. The former anion was shown to be responsible, in its oxidized form, for the excellent tumor uptake results shown by impure B 12 H 11 SH -2 in the past. As a consequence of this work, a borane polymer was synthesized which has shown extremely encouraging tumor uptake properties. The synthesis of this polymer depended on our production and characterization of the first stable thiyl radical at room temperature, B 12 H 11 -S: -2 . The retesting of certain phosphate boranes is reported. And a reagent, namely acetyl sulfenyl chloride, lSCOCH 3 , has been found which will produce B 12 H 11 SH -2 in a laboratory synthesis. The ability of sulfur derivatives of B 12 H 11 SH -2 to bind to proteins was examined, as was the blood distribution of two of these interesting boranes. The amount of non-protein bound borane was related to the rate of blood clearance of the borane in rats. Progress is also reported on dog irradiation experiments. (U.S.)

  18. Secondary myeloid neoplasms: bone marrow cytogenetic and histological features may be relevant to prognosis

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    Roberta Sandra da Silva Tanizawa

    Full Text Available Abstract Background: Secondary myeloid neoplasms comprise a group of diseases arising after chemotherapy, radiation, immunosuppressive therapy or from aplastic anemia. Few studies have addressed prognostic factors in these neoplasms. Method: Forty-two patients diagnosed from 1987 to 2008 with secondary myeloid neoplasms were retrospectively evaluated concerning clinical, biochemical, peripheral blood, bone marrow aspirate, biopsy, and immunohistochemistry and cytogenetic features at diagnosis as prognostic factors. The International Prognostic Scoring System was applied. Statistical analysis employed the Kaplan–Meier method, log-rank and Fisher's exact test. Results: Twenty-three patients (54.8% were male and the median age was 53.5 years (range: 4–88 years at diagnosis of secondary myeloid neoplasms. Previous diseases included hematologic malignancies, solid tumors, aplastic anemia, autoimmune diseases and conditions requiring solid organ transplantations. One third of patients (33% were submitted to chemotherapy alone, 2% to radiotherapy, 26% to both modalities and 28% to immunosuppressive agents. Five patients (11.9% had undergone autologous hematopoietic stem cell transplantation. The median latency between the primary disease and secondary myeloid neoplasms was 85 months (range: 23–221 months. Eight patients were submitted to allogeneic hematopoietic stem cell transplantation to treat secondary myeloid neoplasms. Important changes in bone marrow were detected mainly by biopsy, immunohistochemistry and cytogenetics. The presence of clusters of CD117+ cells and p53+ cells were associated with low survival. p53 was associated to a higher risk according to the International Prognostic Scoring System. High prevalence of clonal abnormalities (84.3% and thrombocytopenia (78.6% were independent factors for poor survival. Conclusion: This study demonstrated that cytogenetics, bone marrow biopsy and immunohistochemistry are very important

  19. Bortezomib as a new therapeutic approach for blastic plasmacytoid dendritic cell neoplasm.

    Science.gov (United States)

    Philippe, Laure; Ceroi, Adam; Bôle-Richard, Elodie; Jenvrin, Alizée; Biichle, Sabeha; Perrin, Sophie; Limat, Samuel; Bonnefoy, Francis; Deconinck, Eric; Saas, Philippe; Garnache-Ottou, Francine; Angelot-Delettre, Fanny

    2017-11-01

    Blastic plasmacytoid dendritic cell neoplasm is an aggressive hematologic malignancy with a poor prognosis. No consensus regarding optimal treatment modalities is currently available. Targeting the nuclear factor-kappa B pathway is considered a promising approach since blastic plasmacytoid dendritic cell neoplasm has been reported to exhibit constitutive activation of this pathway. Moreover, nuclear factor-kappa B inhibition in blastic plasmacytoid dendritic cell neoplasm cell lines, achieved using either an experimental specific inhibitor JSH23 or the clinical drug bortezomib, interferes in vitro with leukemic cell proliferation and survival. Here we extended these data by showing that primary blastic plasmacytoid dendritic cell neoplasm cells from seven patients were sensitive to bortezomib-induced cell death. We confirmed that bortezomib efficiently inhibits the phosphorylation of the RelA nuclear factor-kappa B subunit in blastic plasmacytoid dendritic cell neoplasm cell lines and primary cells from patients in vitro and in vivo in a mouse model. We then demonstrated that bortezomib can be associated with other drugs used in different chemotherapy regimens to improve its impact on leukemic cell death. Indeed, when primary blastic plasmacytoid dendritic cell neoplasm cells from a patient were grafted into mice, bortezomib treatment significantly increased the animals' survival, and was associated with a significant decrease of circulating leukemic cells and RelA nuclear factor-kappa B subunit expression. Overall, our results provide a rationale for the use of bortezomib in combination with other chemotherapy for the treatment of patients with blastic plasmacytoid dendritic cell neoplasm. Based on our data, a prospective clinical trial combining proteasome inhibitor with classical drugs could be envisaged. Copyright© Ferrata Storti Foundation.

  20. Thread sign in biliary intraductal papillary mucinous neoplasm: a novel specific finding for MRI

    International Nuclear Information System (INIS)

    Hong, Gil-Sun; Byun, Jae Ho; Kim, Jin Hee; Kim, Hyoung Jung; Lee, Seung Soo; Lee, Moon-Gyu; Hong, Seung-Mo

    2016-01-01

    To evaluate thread sign of biliary intraductal papillary mucinous neoplasm (B-IPMN) on magnetic resonance imaging (MRI). Thread sign was defined as intraductal linear or curvilinear hypointense striations. Two radiologists independently evaluated the presence and location of thread sign on MR cholangiography (thin-slice, thick-slab and 3D MRC) and axial MR images (T2 TSE, T2 HASTE and DWI) in patients with B-IPMN (n = 38) and in matched control groups with benign (n = 36) or malignant (n = 35) biliary diseases. Sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of thread sign for diagnosing B-IPMN were evaluated. Thread sign was observed only in patients with B-IPMN on MRC (44.7-52.6 % [17/38-20/38], P < 0.001) and axial MR images (31.6 % [12/38], P < 0.001), except in one patient with recurrent pyogenic cholangitis on MRC (2.8 %, 1/36). The sensitivity, specificity, accuracy, PPV and NPV of thread sign for diagnosing B-IPMN on MRC were 0.53, 0.99, 0.83, 0.95 and 0.80, respectively (reader 1) and 0.45, 1.0, 0.81, 1.0 and 0.77, respectively (reader 2). Thread sign was detected mainly at the extrahepatic bile duct (52.6 %, 20/38). B-IPMN can manifest thread sign, a novel specific MR finding, mainly at the extrahepatic bile duct on MRI, especially on MRC. (orig.)

  1. Fine-needle aspiration findings of a rare hematopoietic neoplasm presenting as obstructive jaundice.

    Science.gov (United States)

    Tracht, Jessica; Ahmed, Ali M; Rosenblum Donath, Frida

    2017-12-01

    A 51-year-old female who presented with obstructive jaundice was found to have masses in the pancreatic head and tail as well as suspicious liver and periaortic masses on imaging. Aspiration cytology of the pancreatic tail mass showed abundant large single cells with vacuolated eosinophilic cytoplasm, marked nuclear pleomorphism, large bizarre irregular nuclei, binucleation, and prominent nucleoli. Numerous cells also showed intracytoplasmic black to brown pigmentation. A cell block was obtained and extensive immunohistochemical staining was performed. S-100, HMB-45, Sox10, pancytokeratin, CK7, RCC antigen, synaptophysin, HepPar 1, inhibin, CD45, CD21, and CD123 were negative, making melanoma, epithelial malignancies, lymphoma, follicular dendritic and plasmacytoid dendritic cell neoplasms less likely. CD4 and CD56 showed partial positivity, and CD68, CD163, and CD14 were positive, supporting the diagnosis of histiocytic sarcoma. Surgical specimens and immunohistochemistry confirmed the cytologic findings. Histiocytic sarcoma is a rare aggressive malignancy of histiocytic origin with most cases presenting in adults in extranodal sites, most commonly the intestinal tract. Few cases are reported in the literature, presenting diagnostic challenges for cytopathologists when seen on fine-needle aspiration. We present the first reported case of histiocytic sarcoma presenting as a pancreatic mass, diagnosed by endoscopic ultrasound guided fine-needle aspiration (EUS-FNA). This entity is rarely described on cytology and arose in a location in which EUS-FNA is the diagnostic modality of choice. This case study highlights that cytopathologists should be aware of histiocytic sarcoma occurring in extranodal locations accessible by EUS-FNA and be familiar with the cytomorphologic appearance. © 2017 Wiley Periodicals, Inc.

  2. Blood responses under chronic low daily dose gamma irradiation: Pt. 2; Differential preclinical responses of irradiated female dogs in progression to either aplastic anemia or myeloproliferative disease

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    Seed, T.; Carnes, B.; Tolle, D.; Fritz, T. (Argonne National Lab., IL (United States). Biological and Medical Research Div.)

    1993-05-01

    Female beagle dogs were chronically exposed to low daily doses of [sup 60]Co gamma rays and responded in one of three distinct hemopathological patterns. These patterns, reflective of distinct subgroups, were characterized by (a) low radioresistance resulting in progressive hematopoietic suppression, terminal aplastic anemia (AA), and relatively short (<400 days) survival ([sup -]S-AA subgroups); (b) high radioresistance, initially coupled with strong but aberrant regenerative hematopoiesis, and later with the development of myeloproliferative disease (MPD) ([sup +]-R-MPD subgroup); and (c) high radioresistance, coupled with an early phase of strong regenerative hematopoiesis, but later with no myeloproliferative disease ([sup +]R-nonMPD subgroup). In this study, the changes in circulating blood cells levels (granulocytes, monotcytes, erythrocytes, lymphocytes and platelets) were sequentially assessed in time and fitted to a flexible, quadratic-linear-type response model previously developed. The results are consistent with our earlier observations of blood responses of chronically irradiated male dogs, in the subgroups of female dogs prone to specific radiogenic hematopathologies (i.e. AA and MPD) can be readily identified and staged in specific preclinical periods by a series of marked differential blood responses. (Author).

  3. Imaging features of intraductal papillary neoplasm of the bile duct

    International Nuclear Information System (INIS)

    Liu Yubao; Li Meng; Zhong Xiaomei; Liu Zaiyi; Liang Changhong

    2014-01-01

    Objective: To investigate the CT and MRI features of intraductal papillary neoplasm of the bile duct (IPNB). Methods: Thirty eight patients with IPNB finally diagnosed by puncture biopsy or surgery were enrolled in this study. All the CT or MRI data were investigated retrospectively. Twenty one patients underwent CT examinations, 17 patients underwent MRI examinations. The features of IPNB including the distribution features of the nodules or masses, CT and MRI features of cholangiectasis, mucus were analyzed. The accuracy differences of CT and MRI for the preoperatively diagnosing mucus and tumor growing along mucous were compared by nonparametric test. Results: The lesions (including 5 patients with solitary lesions and 19 patients with multiple lesions) were located in intrahepatic bile duct in 24 patients, 3 patients occurred simultaneously in intrahepatic and portal bile duct, 2 lesions occurred in portal bile duct, 8 lesions occurred in common bile duct, the lesions of 1 patient occurred simultaneously in common bile duct, cystic duct and gallbladder. Seventeen and 11 patients appeared nodules locating in dilated bile duct on CT and MRI, respectively. Four and 5 patients appeared cystic lesions with multiple nodules of the liver on CT and MRI, respectively. Higher contrast enhancement on CT and MRI in arterial phase than that in portal vein and equilibrium phase were observed in 18 and 12 patients, respectively. Excluding the patients undergoing puncture, CT was better than MRI in evaluating whether the mucus was present, with the accuracies of 30.0% (6/20) and 6.3% (1/16) for CT and MRI, respectively (Z=2.58, P<0.05). CT was worse than MRI in preoperatively evaluating the features of tumor growing along mucous, with the accuracies of 77.8% (14/18) and 92.6% (13/14) for CT and MRI, respectively (Z=4.23, P<0.01). Conclusion: IPNB had the features of growing along mucous of the bile duct, nodule or mass in dilated bile duct and other features, CT and MRI are

  4. Transabdominal Ultrasound Colonography for Detection of Colorectal Neoplasms: Initial Clinical Experience.

    Science.gov (United States)

    Liu, Jin-Ya; Chen, Li-Da; Xu, Jian-Bo; Wu, Hui; Ye, Jin-Ning; Zhang, Xin-Hua; Xie, Xiao-Yan; Wang, Wei; Lu, Ming-De

    2017-10-01

    We investigated the feasibility of using ultrasound colonography (USC) to visualize the healthy colon and rectum and detect colorectal polyps. Eight healthy volunteers underwent USC after standard bowel preparation. The feasibility and image quality of USC in different segments were evaluated. Then, USC was conducted on eight patients with known colonic neoplasms using colonoscopy as the reference standard. For volunteers, USC examinations were successfully performed on four (50.0%) ascending, three (37.5%) transverse and eight (100%) descending colons, as well as all sigmoid colons and rectums. One of four (25.0%) ascending, two of eight (25.0%) descending and all sigmoid colons and rectums were well visualized and free of artifacts. For patients, colonoscopy revealed that eight patients had 17 neoplasms in the distal sigmoid colon and rectum, which included 3 lesions ≤5 mm, 3 lesions 6-9 mm and 11 lesions ≥10 mm. USC visualized 12 of 17 (70.6%) neoplasms. Lesion detection by USC was 0% (0/3), 33.3% (1/3) and 100% (11/11) for neoplasms ≤5, 6-9 mm and ≥10 mm in size. USC can visualize the sigmoid colon and rectum well and detect distal sigmoid and rectal neoplasms ≥10 mm in diameter. Copyright © 2017 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  5. Helicobacter pylori infection is an independent risk factor of early and advanced colorectal neoplasm.

    Science.gov (United States)

    Kim, Tae Jun; Kim, Eun Ran; Chang, Dong Kyung; Kim, Young-Ho; Baek, Sun-Young; Kim, Kyunga; Hong, Sung Noh

    2017-06-01

    The role of Helicobacter pylori (H. pylori) in the development of colorectal neoplasm remains controversial. We examined the association between H. pylori infection and colorectal neoplasm in a large sample of healthy participants who underwent screening colonoscopy. A cross-sectional study of 8916 men, who participated in a regular health-screening examination that included an H. pylori-specific immunoglobulin G antibody test and colonoscopy, was conducted to evaluate the association between H. pylori and colorectal neoplasm. Multivariable analyses adjusted for age, body mass index, smoking status, alcohol intake, regular exercise, regular aspirin use, and family history of colorectal cancer showed that the odds ratio (OR) (95% confidence interval [CI]) for any adenoma and advanced neoplasm was 1.32 (1.07-1.61) and 1.90 (1.05-3.56) in participants with H. pylori infection and without H. pylori infection, respectively. The association persisted after further adjustment for inflammatory markers or metabolic variables including fasting blood glucose, triglycerides, high-density lipoprotein-cholesterol, and low-density lipoprotein-cholesterol. Regarding the location, a positive association was confined to cases with proximal adenomas and was observed similarly in all the evaluated subgroups. In a large-scale study, carefully controlled for confounding factors, involving asymptomatic participants without a history of colonoscopy, H. pylori infection was significantly associated with the risk of any colorectal adenoma and advanced colorectal neoplasm. Prospective studies are necessary to determine whether H. pylori eradication can reduce this risk. © 2017 John Wiley & Sons Ltd.

  6. Classification tree analysis of second neoplasms in survivors of childhood cancer

    International Nuclear Information System (INIS)

    Jazbec, Janez; Todorovski, Ljupčo; Jereb, Berta

    2007-01-01

    Reports on childhood cancer survivors estimated cumulative probability of developing secondary neoplasms vary from 3,3% to 25% at 25 years from diagnosis, and the risk of developing another cancer to several times greater than in the general population. In our retrospective study, we have used the classification tree multivariate method on a group of 849 first cancer survivors, to identify childhood cancer patients with the greatest risk for development of secondary neoplasms. In observed group of patients, 34 develop secondary neoplasm after treatment of primary cancer. Analysis of parameters present at the treatment of first cancer, exposed two groups of patients at the special risk for secondary neoplasm. First are female patients treated for Hodgkin's disease at the age between 10 and 15 years, whose treatment included radiotherapy. Second group at special risk were male patients with acute lymphoblastic leukemia who were treated at the age between 4,6 and 6,6 years of age. The risk groups identified in our study are similar to the results of studies that used more conventional approaches. Usefulness of our approach in study of occurrence of second neoplasms should be confirmed in larger sample study, but user friendly presentation of results makes it attractive for further studies

  7. Influence of transcatheter hepatic artery embolization using iodized oil on radiofrequency ablation of hepatic neoplasms

    International Nuclear Information System (INIS)

    Du Xilin; Ma Qingjiu; Wang Yiqing; Wang Zhimin; Zhang Hongxin

    2004-01-01

    Objective: To observe the effect of iodized oil on radiofrequency thermal ablation (RFA) of hepatic neoplasms by using a cluster array of ten separate electrodes. Methods: The patients were divided into 2 groups, group A with transcatheter hepatic artery embolization, group B without transcatheter hepatic artery embolization. All patients were undergone radiofrequency ablation of hepatic neoplasms. Results: The time of RFA for group A was (9 ± 2.1) minutes, showing the diameter of necrosis of (5.3 ± 1.4) cm. The time of RFA for group B was (16 ± 4. 6) minutes demonstrating the diameter of necrosis of (3.5 ± 1.8) cm (P<0.01). Conclusions: These findings suggest that radiofrequency thermal ablation of hepatic neoplasms with transcatheter hepatic artery embolization using iodized oil might improve the safety and synergic effect

  8. Serous Cystadenoma of the Pancreas Presenting as a Third Primary Neoplasm

    Directory of Open Access Journals (Sweden)

    Aydın Şeref Köksal

    2003-01-01

    Full Text Available Serous cystadenomas are the most common cystic neoplasms of the pancreas. They may occur solely or coexist with other neoplasms. A 10 cm mass involving the body of the pancreas was observed in the computed tomography of a 61-year-old man with a previous history of bladder and prostate carcinoma. Ultrasonography and computed tomography of the mass demonstrated multiple small cysts associated with a central calcified scar. A distal pancreatectomy was performed. Pathological examination confirmed the diagnosis of serous microcystic adenoma. This is the first report of a serous cystadenoma of the pancreas with two metachronous neoplasms. This feature should be kept in mind during the diagnosis and evaluation of patients with serous cystadenoma.

  9. A STUDY OF P53 EXPRESSION IN UROTHELIAL NEOPLASMS OF URINARY BLADDER

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    G. Sathish Kumar

    2017-07-01

    Full Text Available BACKGROUND Urothelial Cell Carcinoma (UCC of urinary bladder is the seventh commonest cancer wordwide.1 At initial diagnosis, 30% of UCC display solid and invasive growth patterns and are locally advanced or metastatic at the time of diagnosis. 70% of tumours are noninvasive papillary UCC confined to the epithelium and subepithelial connective tissue,2 which can be managed by endoscopic resection. A significant number of post-resected cases, progress for recurrence of tumour and infiltration to muscle layers. Invasive bladder cancer has high morbidity and uniform mortality when it is metastatic. There are no effective tools to predict aggressiveness of tumour, so that these cases can be managed more successfully. Mutated Tp53/p53 is the genetic abnormality most frequently associated with UCC and related to cell transformation, malignancy and high recurrence rates.2 MATERIALS AND METHODS This is a descriptive study conducted in the departments of urology and pathology and during the period of March 2014 to February 2015. All consecutive cystoscopic biopsies, Trans urethral resection of bladder tumour (TURBT and radical cystectomy specimens histopathologically diagnosed as UCC were included in the study. p53 expression was assessed by immunohistochemistry. Positive and negative controls were used. Bivariate analysis was done using Chi-square test in all cases. RESULTS A total of 80 cases were analysed. Significant association of p53 expression was found in higher grades of tumour. Also, noted relation of p53 mutation with tumour size, multifocality, multiplicity, muscle invasion and tumour stage, which were statistically not significant. CONCLUSION Bladder tumour grade shows significant association to p53 expression. Papillary neoplasm of low malignant potential (PUNLMP tumours are negative for p53, and in the present study, there was significant difference in p53 over expression low-grade papillary UCC compared with PUNLMP. 90% of low

  10. Expression of activating natural killer-cell receptors is a hallmark of the innate-like T-cell neoplasm in peripheral T-cell lymphomas.

    Science.gov (United States)

    Uemura, Yu; Isobe, Yasushi; Uchida, Akiko; Asano, Junko; Nishio, Yuji; Sakai, Hirotaka; Hoshikawa, Masahiro; Takagi, Masayuki; Nakamura, Naoya; Miura, Ikuo

    2018-04-01

    Peripheral T- or natural killer (NK)-cell lymphomas are rare and difficult-to-recognize diseases. It remains arduous to distinguish between NK cell- and cytotoxic T-lymphocyte-derived lymphomas through routine histological evaluation. To clarify the cells of origin, we focused on NK-cell receptors and examined the expression using immunohistochemistry in 22 cases with T- and NK-cell neoplasms comprising angioimmunoblastic T-cell lymphoma, anaplastic lymphoma kinase (ALK)-positive and -negative anaplastic large-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type, monomorphic epitheliotropic intestinal T-cell lymphoma, aggressive NK-cell leukemia, and other peripheral T-cell lymphomas. Inhibitory receptor leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1) was detected in 14 (64%) cases, whereas activating receptors DNAM1, NKp46, and NKG2D were expressed in 7 (32%), 9 (41%), and 5 (23%) cases, respectively. Although LILRB1 was detected regardless of the disease entity, the activating NK-cell receptors were expressed predominantly in TIA-1-positive neoplasms (DNAM1, 49%; NKp46, 69%; and NKG2D, 38%). In addition, NKp46 and NKG2D were detected only in NK-cell neoplasms and cytotoxic T-lymphocyte-derived lymphomas including monomorphic epitheliotropic intestinal T-cell lymphoma. One Epstein-Barr virus-harboring cytotoxic T-lymphocyte-derived lymphoma mimicking extranodal NK/T-cell lymphoma, nasal type lacked these NK-cell receptors, indicating different cell origin from NK and innate-like T cells. Furthermore, NKG2D expression showed a negative impact on survival among the 22 examined cases, which mainly received the standard chemotherapy regimen (log-rank test, P = .024). We propose that the presence of activating NK-cell receptors may provide new insights into understanding peripheral T-cell lymphomas and characterizing them as innate-like T-cell neoplasm. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on

  11. Dietary patterns and risk of advanced colorectal neoplasms: A large population based screening study in Germany.

    Science.gov (United States)

    Erben, Vanessa; Carr, Prudence R; Holleczek, Bernd; Stegmaier, Christa; Hoffmeister, Michael; Brenner, Hermann

    2018-06-01

    Specific components of the diet such as red and processed meat have been associated with the risk of developing colorectal cancer. However, evidence on the association of dietary patterns with colorectal neoplasms is sparse. The aim of this study was to analyze the association of dietary patterns with prevalence of advanced colorectal neoplasms among older adults in Germany. A cross-sectional study was conducted among participants of screening colonoscopy in Saarland, Germany, who were enrolled in the KolosSal study (Effektivität der Früherkennungs-Koloskopie: eine Saarland-weite Studie) from 2005 to 2013. Information on diet and lifestyle factors was obtained through questionnaires and colonoscopy results were extracted from physicians' reports. Associations of a priori defined dietary patterns (vegetarian or adapted versions of the Healthy Eating Index [HEI] and the Dietary Approaches to Stop Hypertension [DASH] index) with the risk of advanced colorectal neoplasms were assessed by multiple logistic regression analyses with comprehensive adjustment for potential confounders. A total of 14,309 participants were included (1561 with advanced colorectal neoplasms). Healthier eating behavior was associated with lower prevalence of advanced colorectal neoplasms in a dose-response manner. Adjusted odds ratios (95% confidence intervals) comparing the highest with the lowest categories of adapted HEI and DASH were 0.61 (0.50, 0.76) and 0.70 (0.55, 0.89), respectively. No significant associations were observed for a vegetarian eating pattern (adjusted OR 0.80 (0.55, 1.17)). Healthy dietary patterns, as described by a high HEI or DASH score, but not a vegetarian diet alone, are associated with reduced risk of advanced colorectal neoplasms. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Immunomodifying effect of VCG vaccine in treatment of urinary bladder neoplasm

    International Nuclear Information System (INIS)

    Neprina, G.S.; Panteleeva, E.S.; Vatin, O.E.; Karyakin, O.B.; Kurasova, V.G.; Filatov, P.P.; Dunchik, V.N.

    1989-01-01

    It is shown that immunotherapy realization using VCG vaccine after completion of PCT (polychemotherapy) course in patients suffering from later stages of urinary bladder neoplasm, allowed one to maximally connect stages of chemo- and radiation therapy at the expense of sufficient increase of the quantity of main groups of immunocompetent cells. Introduction of incometacin to immunocorrection scheme allowed one to remove disbalance in immunoregulating lymphocyte system which testifies to advisability of combined applicaion of VCG vaccine and indometacin in complex treatment of cerinary bladder neoplasms. 5 refs

  13. Confocal laser scanning microscopy in vivo for diagnosing melanocytic skin neoplasms

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    A. A. Kubanova

    2014-01-01

    Full Text Available The authors discuss the use of confocal laser scanning microscopy in vivo (CLSM for diagnosing melanocytic skin neoplasms and its value for early diagnostics of melanoma. CLSM is an innovation noninvasive visual examination method for real-time multiple and painless examinations of the patient’s skin without injuring the skin integument. The method ensures early diagnostics of skin melanomas with high sensitivity and specificity, which makes it possible to use CLSM for screening melanocytic skin neoplasms for the sake of the early onset of treatment to save patient life and health.

  14. Malignant Nonfunctioning Neuroendocrine Neoplasm of the Pancreas in a 10-Year-Old Child

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    Ahmed Marwan

    2009-04-01

    Full Text Available Malignant neoplasms of the pancreas are extremely rare in children and only represent a small percentage of pediatric cancer-related deaths. The paucity of cases reported in the literature, in addition to the lack of understanding of biologic behavior, has led to a lack of consensus concerning optimal management strategy. Presentation differs compared to adult counterparts and generally prognosis is improved even when lymph node metastases occur. Here we review the literature and report the case of a 10-year-old autistic female with a malignant nonfunctioning pancreatic endocrine neoplasm of the head of the pancreas successfully extirpated via pancreaticoduodenectomy.

  15. Surgical management of neoplasms of the ampulla of Vater: Local resection or pancreatoduodenectomy and prognostic factors for survival

    NARCIS (Netherlands)

    de Castro, S. M. M.; van Heek, N. T.; Kuhlmann, K. F. D.; Busch, O. R. C.; Offerhaus, G. J. A.; van Gulik, T. M.; Obertop, H.; Gouma, D. J.

    2004-01-01

    yBackground. Neoplasms of the ampulla of Vater have a better 5-year survival than pancreatic and bile duct neoplasms after resection. This study was Performed to analyze the outcome after local resection and pancreatoduodenectomy (PD) and to identify predictive factors for survival. Methods. We used

  16. Endoscopic Ultrasound Fine-Needle Aspiration Characteristics of Primary Adenocarcinoma versus Other Malignant Neoplasms of The Pancreas

    Directory of Open Access Journals (Sweden)

    Veronika Gagovic

    2012-01-01

    Full Text Available BACKGROUND: Endoscopic ultrasound (EUS with fine-needle aspiration (FNA is often used to assist in the evaluation of pancreatic lesions and may help to diagnose benign versus malignant neoplasms. However, there is a paucity of literature regarding comparative EUS characteristics of various malignant pancreatic neoplasms (primary and metastatic.

  17. Multimodal MRI in the characterization of glial neoplasms: the combined role of single-voxel MR spectroscopy, diffusion imaging and echo-planar perfusion imaging

    International Nuclear Information System (INIS)

    Zonari, Paolo; Baraldi, Patrizia; Crisi, Girolamo

    2007-01-01

    Diffusion-weighted imaging (DWI), perfusion-weighted imaging (PWI) and MR spectroscopy (MRS) provide useful data for tumor evaluation. To assess the contribution of these multimodal techniques in grading glial neoplasms, we compared the value of DWI, PWI and MRS in the evaluation of histologically proven high- and low-grade gliomas in a population of 105 patients. Independently for each modality, the following variables were used to compare the tumors: minimum apparent diffusion coefficient (ADC) and maximum relative cerebral blood volume (rCBV) normalized values between tumor and healthy tissue, maximum Cho/Cr ratio and minimum NAA/Cr ratio in tumor, and scored lactate and lipid values in tumor. The Mann-Whitney and Wilcoxon tests were employed to compare DWI, PWI and MRS between tumor types. Logistic regression analysis was used to determine which parameters best increased the diagnostic accuracy in terms of sensitivity, specificity, and positive and negative predictive values. ROC curves were determined for parameters with high sensitivity and specificity to identify threshold values to separate high- from low-grade lesions. Statistically significant differences were found for rCBV tumor/normal tissue ratio, and NAA/Cr ratio in tumor and Cho/Cr ratio in tumor between low- and high-grade tumors. The best performing single parameter for group classification was the normalized rCBV value; including all parameters, statistical significance was reached by rCBV tumor/normal tissue ratio, NAA/Cr tumor ratio and lactate. From the ROC curves, a high probability for a neoplasm to be a high-grade lesion was associated with a rCBV tumor/normal tissue ratio of >1.16 and NAA/Cr tumor ratio of <0.44. Combining PWI and MRS with conventional MR imaging increases the accuracy of the attribution of malignancy to glial neoplasms. The best performing parameter was found to be the perfusion level. (orig.)

  18. Identification of Two Distinct Molecular Subtypes of Non-Invasive Follicular Neoplasm with Papillary-Like Nuclear Features by Digital RNA Counting.

    Science.gov (United States)

    Giannini, Riccardo; Ugolini, Clara; Poma, Anello Marcello; Urpì, Maria; Niccoli, Cristina; Elisei, Rossella; Chiarugi, Massimo; Vitti, Paolo; Miccoli, Paolo; Basolo, Fulvio

    2017-10-01

    The follicular variant (FV) of papillary thyroid cancer (PTC) is one of the most common variants of PTC. Clinically, non-infiltrative FVPTC is considered a low-risk variant of PTC, and the non-invasive encapsulated forms of FVPTC represent a group of thyroid tumors with a particularly good prognosis. Consequently, these neoplasms have been very recently reclassified as non-invasive follicular neoplasms with papillary-like nuclear features (NIFTP). From a molecular standpoint, NIFTP appears to be similar to follicular neoplasms. However, only limited data are currently available regarding their gene expression profile. The aim of this study was to identify specific molecular signatures of 26 NIFTPs compared to those of 19 follicular adenomas (FAs) and 18 infiltrative FVPTCs (IFVPTCs). A nanoString custom assay was used to perform mRNA expression analysis. All cases were also genotyped for BRAF, N-, H-, and K-RAS mutations. Samples were grouped on the basis of gene expression profiles by Pearson's correlation and non-negative matrix factorization clustering analysis. Finally, the uncorrelated shrunken centroid machine-learning algorithm was used to classify the samples. The results revealed distinct expression profiles of FAs and IFVPTCs. NIFTP samples can exhibit different expression profiles, more similar to FAs (FA-like) or to IFVPTCs (IFVPTC-like), and these different expression profiles largely depend on the presence of different mutations (RAS or BRAF). In conclusion, although further validation of the model is required by using a larger group of prospective cases, these data reinforce the hypothesis that IFVPTC-like NIFTPs might represent precursors of IFVPTC.

  19. Nodular fasciitis: A pseudomalignant clonal neoplasm characterized by USP gene rearrangements and spontaneous regression

    LENUS (Irish Health Repository)

    Hennebry, Jennifer

    2017-01-01

    Introduction: Nodular fasciitis (NF) is a rapidly growing, self-limited, myofibroblastic neoplasm that typically arises in subcutaneous tissues of young adults and regresses spontaneously. Nodular fasciitis mimics sarcoma on clinical, radiological, and histological grounds and is usually, diagnosed following excision.\\r\

  20. Successful Control of Liver Metastases From Pancreatic Solid-Pseudopapillary Neoplasm (SPN) Using Hepatic Arterial Embolization

    Energy Technology Data Exchange (ETDEWEB)

    Violari, Elena G., E-mail: eviolari@live.com; Brody, Lynn A.; Covey, Anne M.; Erinjeri, Joseph P.; Getrajdman, George I.; Sofocleous, Constantinos T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States); Reidy, Diane L. [Memorial Sloan-Kettering Cancer Center, Department of Medicine, Gastrointestinal Oncology Service (United States); Jarnagin, William R. [Memorial Sloan-Kettering Cancer Center, Department of Surgery, Hepatopancreatobiliary Service (United States); Brown, Karen T. [Memorial Sloan-Kettering Cancer Center, Department of Radiology, Interventional Radiology Service (United States)

    2015-04-15

    No systemic agents that are known to be effective for the treatment of solid-pseudopapillary neoplasm (SPN) are available. We report the prolonged and sustained control of metastatic pancreatic SPN to the liver using hepatic arterial embolization (HAE), where a total of 13 HAE sessions were performed over a 6-year period.

  1. Evaluation of a selective management strategy of patients with primary cystic neoplasms of the pancreas

    NARCIS (Netherlands)

    de Castro, S. M. M.; Houwert, J. T.; van der Gaag, N. A.; Busch, O. R. C.; van Gulik, T. M.; Gouma, D. J.

    2011-01-01

    Recent studies have shown that a selective group of patients with primary cystic neoplasms of the pancreas can be managed conservatively by radiological follow-up. The aim of this study was to analyze if such a strategy is efficient and safe. A retrospective analyses was performed of patients who

  2. Diagnostic yield of combined magnetic resonance spectroscopy and diffusion weighted imaging in intracranial neoplasms

    Directory of Open Access Journals (Sweden)

    Ayat E. El Sherbeny

    2014-09-01

    Conclusion: MRS has a robust diagnostic accuracy in cases of well defined high or low grade brain neoplasms. ADC value had the ability to confirm and differentiate low from high grade tumors in many situations where there were diagnostic confusions with MRS due to borderline values.

  3. The 2016 revision of the World Health Organization classification of lymphoid neoplasms | Center for Cancer Research

    Science.gov (United States)

    A revision of the nearly 8-year-old World Health Organization classification of the lymphoid neoplasms and the accompanying monograph is being published. It reflects a consensus among hematopathologists, geneticists, and clinicians regarding both updates to current entities as well as the addition of a limited number of new provisional entities.

  4. Smell and taste in patients with neoplasms tumors of palatine tonsils treated by radiation

    International Nuclear Information System (INIS)

    Korytowska, A.; Szmeja, Z.; Wojtowicz, J.G.

    1993-01-01

    The smell and taste investigations were made in group of 47 subjects with neoplasms of palatine tonsils surgical treated with radiation and in group of 7 subjects treated only by radiation. The investigation presents mostly quantitative disturbance of smell in both groups but with temporary character. (author)

  5. Preparation of {sup 125}I-labeled monoclonal antibody of bladder neoplasm using lactoperoxidase

    Energy Technology Data Exchange (ETDEWEB)

    Huaifen, Li; Huisheng, Niu; Mingyue, Yuan; Yongzhi, Huang [Chinese Acaolemy of Medical Sciences, Tianjin (China). Inst. of Radiation Medicine

    1994-11-01

    {sup 125}I-labelled monoclonal antibody of bladder neoplasm ({sup 125}I-L{sub 4}B{sub 4}) is prepared using lactoperoxidase. The in-vivo radioactive distribution of {sup 125}I-L{sub 4}B{sub 4} in bare mice shows that {sup 125}I-L{sub 4}B{sub 4} concentrates in the tumour.

  6. Preparation of 125I-labeled monoclonal antibody of bladder neoplasm using lactoperoxidase

    International Nuclear Information System (INIS)

    Li Huaifen; Niu Huisheng; Yuan Mingyue; Huang Yongzhi

    1994-01-01

    125 I-labelled monoclonal antibody of bladder neoplasm ( 125 I-L 4 B 4 ) is prepared using lactoperoxidase. The in-vivo radioactive distribution of 125 I-L 4 B 4 in bare mice shows that 125 I-L 4 B 4 concentrates in the tumour

  7. Synthetic display of three-dimensional CT and MPR for gastric neoplasm

    International Nuclear Information System (INIS)

    Ogura, Toshihiro; Maruyama, Masakazu

    1998-01-01

    We attempted to obtain synthesized three dimensional (3D) and MPR (Multi Planar Reconstruction) helical CT scans (3D-MPR-CT) of gastric neoplasm by using the air as a contrast medium, and we assessed the usefulness of 3D-MPR-CT gastroendoscopy in the diagnosis of gastric neoplasm. Five minutes before the scan, 20 mg Scopolamine Butylbromide (Buscopan) was injected intramuscularly to minimize gastric peristalsis. An effervescent agent (bubble-make granules) was fed to extend the stomach wall. Non-ionic contrast material (100 mL) was power injected immediately before the scan start. Axial images were obtained with an intersection gap of 5-mm, a 5-mm/sec table speed, and 1-mm reconstruction intervals. 3D-MPR-CT images were reconstructed from these images. In abdominal study, 3D-MPR-CT images enabled the visualization of neoplasm and its adjacent structures in versatile directions, including a view similar to endoscopic observation, proximal aspect of narrowing by tumor and also could get the information about invasive depth of gastric neoplasm. Reports on some clinical cases and the advantages and disadvantages of 3D-MPR-CT gastroendoscopy were discussed. (author)

  8. Histologically benign but clinically malignant neoplasms in the thorax: CT–pathological overview

    International Nuclear Information System (INIS)

    Kim, E.Y.; Kim, T.S.; Han, J.; Kim, H.; Choi, Y.S.

    2012-01-01

    The purpose of this article is to review the computed tomography (CT) and histopathological features of uncommon primary neoplasms of the thorax that can manifest clinically malignant features (multiplicity of pulmonary nodules, an invasive nature, and metastases or recurrence after surgery) with little evidence of histological malignancy.

  9. Molecular genetics of intraductal papillary-mucinous neoplasms of the pancreas.

    Science.gov (United States)

    Furukawa, Toru

    2007-01-01

    Intraductal papillary-mucinous neoplasms of the pancreas show characteristic clinicopathological and molecular pathobiological features which are distinct from those of conventional ductal adenocarcinomas. Alterations of KRAS, AKT/PKB, CDKN2A, TP53, SMAD4, STK11/LKB1, and DUSP6, and other molecular alterations, including global expression studies as well as their clinical implications, are discussed.

  10. Fine needle aspiration biopsy diagnosis of metastatic neoplasms of the breast. A three-case report

    Directory of Open Access Journals (Sweden)

    Raquel Garza-Guajardo

    2005-09-01

    Full Text Available Abstract Metastases to the breast are unusual lesions that make up approximately 2% of all malignant mammary neoplasms and may mimic both benign and malignant primary neoplasms from a clinical point of view, as well as in imaging studies. Arriving at a correct diagnosis is therefore essential in order to establish appropriate management. We present three cases of metastatic neoplasms diagnosed through fine needle aspiration biopsy and immunocytochemistry. The cytological diagnoses were: medulloblastoma in an 18-year-old woman, melanoma in a 26-year-old man, and an exceptional case of ovarian sarcoma originating from a granulosa cell tumor with metastases to both breasts. A metastatic disease should be considered in the differential diagnosis of a palpable mass in the breast, especially if there is a history of an extramammary malignant neoplasm. Fine needle aspiration biopsy is the method of choice for the management of these cases. Whenever possible the exam of the material obtained should be compared to the previous biopsy, which is usually enough to arrive at a correct diagnosis, thus preventing unnecessary surgical procedures.

  11. Multiphoton microscopy as a diagnostic imaging modality for pancreatic neoplasms without hematoxylin and eosin stains

    Science.gov (United States)

    Chen, Youting; Chen, Jing; Chen, Hong; Hong, Zhipeng; Zhu, Xiaoqin; Zhuo, Shuangmu; Chen, Yanling; Chen, Jianxin

    2014-09-01

    Hematoxylin and eosin (H&E) staining of tissue samples is the standard approach in histopathology for imaging and diagnosing cancer. Recent reports have shown that multiphoton microscopy (MPM) provides better sample interface with single-cell resolution, which enhances traditional H&E staining and offers a powerful diagnostic tool with potential applications in oncology. The purpose of this study was to further expand the versatility of MPM by establishing the optical parameters required for imaging unstained histological sections of pancreatic neoplasms, thereby providing an efficient and environmentally sustainable alternative to H&E staining while improving the accuracy of pancreatic cancer diagnoses. We found that the high-resolution MPM images clearly distinguish between the structure of normal pancreatic tissues compared with pancreatic neoplasms in unstained histological sections, and discernable differences in tissue architecture and cell morphology between normal versus tumorigenic cells led to enhanced optical diagnosis of cancerous tissue. Moreover, quantitative assessment of the cytomorphological features visualized from MPM images showed significant differences in the nuclear-cytoplasmic ratios of pancreatic neoplasms compared with normal pancreas, as well as further distinguished pancreatic malignant tumors from benign tumors. These results indicate that the MPM could potentially serve as an optical tool for the diagnosis of pancreatic neoplasms in unstained histological sections.

  12. Myeloid neoplasm with prominent eosinophilia and PDGFRA rearrangement treated with imatinib mesylate

    DEFF Research Database (Denmark)

    Rathe, Mathias; Kielsgaard Kristensen, Thomas; Møller, Michael Boe

    2010-01-01

    of FIP1L1-PDGFRA positive disease has been reported. We report a 2-year-old female with a myeloid neoplasm associated with eosinophilia and rearrangement of PDGFRA. Treatment with imatinib resulted in complete and durable clinical, hematological, and molecular remission within 3 months after starting...

  13. Surgical Management of Penile and Preputial Neoplasms in Equine with Special Reference to Partial Phallectomy

    Directory of Open Access Journals (Sweden)

    Awad Rizk

    2013-01-01

    Full Text Available Penile and preputial neoplasia in horses occurs infrequently and represents diagnostic and therapeutic challenges. The present study was carried out on a total number of 21 equids (14 stallions and 7 donkeys suffered from different penile and preputial neoplasia. Diagnosis of neoplasms was based up on history of the case, clinical examination as well as histopathological evaluation. Animals with penile and preputial neoplasms were underwent local excision and partial phallectomy with a slightly modified version of the techniques described by William’s. The diagnosed neoplasms were penile and preputial squamous cell carcinomas (SCCs; ; sarcoid (; a-fibrosarcoma; and a melanoma. Local excision was curative in all cases except 5 stallions with SCCs. These stallions had extensive damage of the glans penis, free part of the penis and the inner lamina of the internal fold of the prepuce, and they underwent a partial phallectomy with successful outcome. Follow-up information was obtained by visit and telephone inquiries. In conclusion, penile and preputial neoplasms are commonly encountered in elderly male horses and SCCs are the most common type affecting male external genitalia. Partial phallectomy is effective for management of equine neoplasia if they are confined to the glans and body of the penis and there is no proximal spread or involvement to regional lymph nodes.

  14. Single-incision laparoscopic cecectomy for low-grade appendiceal mucinous neoplasm after laparoscopic rectectomy

    Science.gov (United States)

    Fujino, Shiki; Miyoshi, Norikatsu; Noura, Shingo; Shingai, Tatsushi; Tomita, Yasuhiko; Ohue, Masayuki; Yano, Masahiko

    2014-01-01

    In this case report, we discuss single-incision laparoscopic cecectomy for low-grade appendiceal neoplasm after laparoscopic anterior resection for rectal cancer. The optimal surgical therapy for low-grade appendiceal neoplasm is controversial; currently, the options include appendectomy, cecectomy, right hemicolectomy, and open or laparoscopic surgery. Due to the risk of pseudomyxoma peritonei, complete resection without rupture is necessary. We have encountered 5 cases of low-grade appendiceal neoplasm and all 5 patients had no lymph node metastasis. We chose the appendectomy or cecectomy without lymph node dissection if preoperative imaging studies did not suspect malignancy. In the present case, we performed cecectomy without lymph node dissection by single-incision laparoscopic surgery (SILS), which is reported to be a reduced port surgery associated with decreased invasiveness and patient stress compared with conventional laparoscopic surgery. We are confident that SILS is a feasible alternative to traditional surgical procedures for borderline tumors, such as low-grade appendiceal neoplasms. PMID:24868331

  15. The Disruption of Geniculocalcarine Tract in Occipital Neoplasm: A Diffusion Tensor Imaging Study

    Directory of Open Access Journals (Sweden)

    Yan Zhang

    2016-01-01

    Full Text Available Aim. Investigate the disruption of geniculocalcarine tract (GCT in different occipital neoplasm by diffusion tensor imaging (DTI. Methods. Thirty-two subjects (44.1 ± 3.6 years who had single occipital neoplasm (9 gliomas, 6 meningiomas, and 17 metastatic tumors with ipsilateral GCT involved and thirty healthy subjects (39.2 ± 3.3 years underwent conventional sequences scanning and diffusion tensor imaging by a 1.5T MR scanner. The diffusion-sensitive gradient direction is 13. Compare the fractional anisotropy (FA and mean diffusivity (MD values of healthy GCT with the corresponding values of GCT in peritumoral edema area. Perform diffusion tensor tractography (DTT on GCT by the line propagation technique in all subjects. Results. The FA values of GCT in peritumoral edema area decreased (P=0.001 while the MD values increased (P=0.002 when compared with healthy subjects. There was no difference in the FA values across tumor types (P=0.114 while the MD values of GCT in the metastatic tumor group were higher than the other groups (P=0.001. GCTs were infiltrated in all the 9 gliomas cases, with displacement in 2 cases and disruption in 7 cases. GCTs were displaced in 6 meningiomas cases. GCTs were displaced in all the 7 metastatic cases, with disruption in 7 cases. Conclusions. DTI represents valid markers for evaluating GCT’s disruption in occipital neoplasm. The disruption of GCT varies according to the properties of neoplasm.

  16. Modern classification of neoplasms: reconciling differences between morphologic and molecular approaches

    International Nuclear Information System (INIS)

    Berman, Jules

    2005-01-01

    For over 150 years, pathologists have relied on histomorphology to classify and diagnose neoplasms. Their success has been stunning, permitting the accurate diagnosis of thousands of different types of neoplasms using only a microscope and a trained eye. In the past two decades, cancer genomics has challenged the supremacy of histomorphology by identifying genetic alterations shared by morphologically diverse tumors and by finding genetic features that distinguish subgroups of morphologically homogeneous tumors. The Developmental Lineage Classification and Taxonomy of Neoplasms groups neoplasms by their embryologic origin. The putative value of this classification is based on the expectation that tumors of a common developmental lineage will share common metabolic pathways and common responses to drugs that target these pathways. The purpose of this manuscript is to show that grouping tumors according to their developmental lineage can reconcile certain fundamental discrepancies resulting from morphologic and molecular approaches to neoplasm classification. In this study, six issues in tumor classification are described that exemplify the growing rift between morphologic and molecular approaches to tumor classification: 1) the morphologic separation between epithelial and non-epithelial tumors; 2) the grouping of tumors based on shared cellular functions; 3) the distinction between germ cell tumors and pluripotent tumors of non-germ cell origin; 4) the distinction between tumors that have lost their differentiation and tumors that arise from uncommitted stem cells; 5) the molecular properties shared by morphologically disparate tumors that have a common developmental lineage, and 6) the problem of re-classifying morphologically identical but clinically distinct subsets of tumors. The discussion of these issues in the context of describing different methods of tumor classification is intended to underscore the clinical value of a robust tumor classification. A

  17. Therapy-related myeloid neoplasm in an 18-year-old boy with B-lymphoblastic leukemia.

    Science.gov (United States)

    Qing, Xin; Panosyan, Eduard; Yue, Changjun; Ji, Ping; Gotesman, Moran; French, Samuel; Cai, Junchao

    2017-12-01

    Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy. Acute myeloid leukemia or myelodysplastic syndrome during the course of ALL is a rare entity. Some of these cases are therapy-related while the others occur due to lineage switch. The correct diagnosis relies on comparing the immunophenotypes and cytogenetic/molecular alterations of the myeloid neoplasm and the ALL. We present the clinical, pathologic and cytogenetic features of a case of an 18-year-old male with prior treatment for B-lymphoblastic leukemia (B-ALL) who developed therapy-related myeloid neoplasm (t-MN) 4-5years after his initial diagnosis of B-ALL. A 13-year-old boy with no significant past medical history presented to Harbor-UCLA Medical Center (HUMC) in November 2012 with night sweats, fevers and chills, nausea, vomiting, diarrhea, fatigue, weakness, and weight loss. Peripheral blood flow cytometric analysis disclosed B-ALL. The blasts expressed CD10, CD19, CD22 (dim), CD34, CD38, HLA-DR, and TdT, and were negative for CD20, CD13, CD33, CD117, and cytoplasmic MPO. Chromosomal analysis and a supplemental fluorescence in situ hybridization (FISH) study performed on the bone marrow aspirate showed an abnormal karyotype (47,XY,+X,del(9)(p21p21)[4]/46,XY[16]). He achieved remission after induction chemotherapy and remained in remission until March 2016 when bilateral testicular masses were noted. Biopsy of the left testicular mass showed relapsed B-ALL. Cerebrospinal fluid (CSF) contained rare TdT-positive blasts, suggestive of minimal/early involvement by B-ALL. However, there was no evidence of acute leukemia in his bone marrow at this time. He was then treated with COG protocol AALL1331 randomized to blinatumomab arm and achieved second remission. In June 2017, the patient's peripheral blood smear showed 11% circulating monoblasts. By flow cytometry, the blasts expressed CD4, CD11b, CD13, CD15, CD33, CD38, CD56, and CD64. In addition, a few TdT-positive blasts were seen in

  18. Assessment of a Revised Management Strategy for Patients With Intraductal Papillary Mucinous Neoplasms Involving the Main Pancreatic Duct.

    Science.gov (United States)

    Sugimoto, Motokazu; Elliott, Irmina A; Nguyen, Andrew H; Kim, Stephen; Muthusamy, V Raman; Watson, Rabindra; Hines, O Joe; Dawson, David W; Reber, Howard A; Donahue, Timothy R

    2017-01-18

    According to the 2012 International Consensus Guidelines, the diagnostic criterion of intraductal papillary mucinous neoplasms (IPMNs) involving the main duct (MD IPMNs) or the main and branch ducts (mixed IPMNs) of the pancreatic system is a main pancreatic duct (MPD) diameter of 5.0 mm or greater on computed tomography (CT) or magnetic resonance imaging (MRI). However, surgical resection is recommended for patients with an MPD diameter of 10.0 mm or greater, which is characterized as a high-risk stigma. An MPD diameter of 5.0 to 9.0 mm is not an indication for immediate resection. To determine an appropriate cutoff (ie, one with high sensitivity and negative predictive value) of the MPD diameter on CT or MRI as a prognostic factor for malignant disease and to propose a new management algorithm for patients with MD or mixed IPMNs. This retrospective cohort study included 103 patients who underwent surgical resection for a preoperative diagnosis of MD or mixed IPMN and in whom IPMN was confirmed by surgical pathologic findings at a single institution from July 1, 1996, to December 31, 2015. Malignant disease was defined as high-grade dysplasia or invasive adenocarcinoma on results of surgical pathologic evaluation. An appropriate MPD diameter on preoperative CT or MRI to predict malignant disease was determined using a receiver operating characteristic curve analysis. The prognostic value of the new management algorithm that incorporated the new MPD diameter cutoff was evaluated. Among the 103 patients undergoing resection for an MD or mixed IPMN (59 men [57.3%]; 44 women [42.7%]; median [range] age, 71 [48-86] years), 64 (62.1%) had malignant disease. Diagnostic accuracy for malignant neoplasms was highest at an MPD diameter cutoff of 7.2 mm (area under the receiver operating characteristic curve, 0.70; 95% CI, 0.59-0.81). An MPD diameter of 7.2 mm or greater was also an independent prognostic factor for malignant neoplasms (odds ratio, 12.76; 95% CI, 2

  19. Clinicopathologic features of hepatic neoplasms in explanted livers: a single institution experience

    International Nuclear Information System (INIS)

    Mourad, W.; Tulbah, A.; Al-Omari, M.; Al-Mana, H.; Khalaf, H.; Neiamatallah, M.

    2007-01-01

    Hepatic neoplasms can be the primary indication for hepatic transplantation. The tumors can also be incidentally identified in explanted livers. We explored the clinicopathologic features of hepatic neoplasms identified in explanted livers. All explanted livers resected between 2001 and 2006 were evaluated for the presence of neoplasms and their clinicopathologic features were examined. In 198 liver transplants, 15 neoplasms (15.3%) were identified. Patient ages ranged from 5 to 63 years (median, 56 years). The primary etiology of hepatic disease was hepatitis C virus in 12 cases, hepatitis B virus in 1 case, cryptogenic cirrhosis in 1 case and congenital hepatic fibrosis in 1 case. Serum alpha-fetoprotein was significantly elevated (>400 U/L) in only 2 cases. CA19-9 was not elevated in any of the cases. The tumors included hepatocellular carcinoma (HCC) in 13 cases, 1 case of cholangiocarcinoma and 1 case of combined HCC and hepatoblastoma. The tumors ranged in size from 0.5 to 5 cm (median 1.4 cm) and were multifocal in 5 of the cases (33%). Tissue alpha-fetoprotein expression was only seen in the cases associated with elevated serum levels. In our institution hepatic neoplasma are seen in more than 15% of explanted livers. They can be incidentally identified, are frequently not associated with elevated serum levels of alpha-fetoprotein and CA19-9, are commonly multifocal but small and are associated with good prognosis. Elevated serum alpha-fetoprotein, albeit specific, is not a very sensitive marker in the detection of hepatic neoplasms. (author)

  20. Solid and papillary epithelial neoplasm of the pancreas : radiologic pathologic correlation

    International Nuclear Information System (INIS)

    Kim, Ji Hyung; Kim, Ki Whang; Cho, Nam Hoon

    1996-01-01

    To report variable radiologic manifestastions and to accomplish detailed radiologic-pathologic correlation of solid and papillary epithelial neoplasm of the pancreas. In 23 patients with surgically confirmed solid and papillary epithelial neoplasm, retrospective examination of operative records, gross and micropathologic findings, and radiologic findings including US(n=17), CT(n=23), ERCP(n=9), MRI(n=3) were carried out. On the basis of pathologic findings, detailed analysis of radiologic findings of solid and papillary epithelial neoplasm was then performed. Most pancreatic solid and papillary epithelial neoplasms(n=17) were seen as a mass with heterogeneous internal density consisting of cystic change, hemorrhagic necrosis, and tumor tissue, although the mass con also be seen to be homogeneous(n=6). On gross specimens, a capsule which showed enhancement on the delayed phase of the enhanced CT scan was demonstrated in 22 cases. In was seen as an echogenic rim on the ultrasound images and a low signal rim on the MR images. Calcification of the mass was seen in ten cases, nine of which showed peripheral calcification along the tumor capsule ; five cases showed calcifications within the mass. On pathologic examination, ten cases had a single or multiple cystic appearance ; in seven of these cases, this appeared on CT scan. In addition to usual mixed internal density caused by hemorrhagic necrosis of the tumor, enhanced capsule and internal multicystic appearance on CT scan were other characteristics of pancreatic solid and papillary epithelial neoplasm. These could be useful findings in the radiologic approach and in the differential diagnosis of pancreatic masses