The non-specific symptoms of breast implant-associated anaplastic large cell lymphoma resulting in delayed diagnosis: A case-based review

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Reem Dina Jarjis

2015-12-01

Full Text Available Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL is a rare entity that has become known as a distinct clinical condition recently. In general, BIA-ALCL patients with a history of breast implants present with non-specific implant-related complications, resulting in delayed diagnosis and appropriate treatment because of the lack of awareness of BIA-ALCL. The cause and pathogenesis have still not been identified, and there are no evidence-based guidelines on how this condition should be detected, treated or followed up because of the rarity of available data. We present the first published Danish case of anaplastic lymphoma kinase negative BIA-ALCL, and review the current literature to raise awareness of and discuss management options for this rare clinical entity.

Fine needle aspiration cytology of ALK1(-), CD30+ anaplastic large cell lymphoma post renal transplantation: a case report and literature review.

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Balachandran, Indra; Walker, Joe W; Broman, Jerry

2010-03-01

Post transplant lymphoproliferative disorders (PTLD) complicates the course of 0.3 to 3% of renal transplant patients receiving immunosuppression. Epstein-Barr virus (EBV) related non-Hodgkin's lymphomas of B-cell type is more common than those of T-cell origin. CD30 positive Anaplastic Large Cell Lymphoma (ALCL) is a Non-Hodgkin's lymphoma (B or T cell type) that accounts for a small percentage of PTLD's. ALCL of T-cell type are a spectrum of disease ranging from primary cutaneous to systemic nodal ALCL. The systemic nodal ALCL is further subdivided into anaplastic lymphoma kinase-1 (ALK-1) positive or negative. ALK-1 protein is a gene fusion product of translocation (2;5) and carries prognostic implications. We present an unusual manifestation of ALK-1 negative CD30 positive ALCL in a post renal transplant patient in FNA cytology with all supportive adjuvant studies and differential diagnoses and review the cytology literature on this topic.

Anaplastic large cell lymphoma (ALCL) and breast implants: breaking down the evidence.

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Ye, Xuan; Shokrollahi, Kayvan; Rozen, Warren M; Conyers, Rachel; Wright, Penny; Kenner, Lukas; Turner, Suzanne D; Whitaker, Iain S

2014-01-01

Systemic anaplastic large cell lymphoma (ALCL) is a distinct disease classification provisionally sub-divided into ALCL, Anaplastic Lymphoma Kinase (ALK)(+) and ALCL, ALK(-) entities. More recently, another category of ALCL has been increasingly reported in the literature and is associated with the presence of breast implants. A comprehensive review of the 71 reported cases of breast implant associated ALCL (iALCL) is presented indicating the apparent risk factors and main characteristics of this rare cancer. The average patient is 50 years of age and most cases present in the capsule surrounding the implant as part of the periprosthetic fluid or the capsule itself on average at 10 years post-surgery suggesting that iALCL is a late complication. The absolute risk is low ranging from 1:500,000 to 1:3,000,000 patients with breast implants per year. The majority of cases are ALK-negative, yet are associated with silicone-coated implants suggestive of the mechanism of tumorigenesis which is discussed in relation to chronic inflammation, immunogenicity of the implants and sub-clinical infection. In particular, capsulotomy alone seems to be sufficient for the treatment of many cases suggesting the implants provide the biological stimulus whereas others require further treatment including chemo- and radiotherapy although reported cases remain too low to recommend a therapeutic approach. However, CD30-based therapeutics might be a future option. Copyright © 2014 Elsevier B.V. All rights reserved.

ALK-1-negative anaplastic large cell lymphoma associated with breast implants: a new clinical entity.

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Lazzeri, Davide; Agostini, Tommaso; Bocci, Guido; Giannotti, Giordano; Fanelli, Giovanni; Naccarato, Antonio Giuseppe; Danesi, Romano; Tuccori, Marco; Pantaloni, Marcello; D'Aniello, Carlo

2011-10-01

Concerns have been raised recently regarding the increasing number of reports of non-Hodgkin lymphoma (NHL) that developed in close proximity to silicone or saline breast implants. In particular, an increased risk of anaplastic large cell lymphoma (ALCL) in patients with breast prostheses has been proposed. We reviewed clinical and pathologic findings in 40 women who received a diagnosis of breast NHL arising in association with breast implants and of 27 patients who had a diagnosis of ALCL with breast involvement reported in the published literature. Among the 40 reported cases of prosthesis-associated breast lymphomas, 28 were anaplastic lymphoma kinase-1-negative (ALK-1(-)) ALCLs, whereas of 27 ALCLs in patients without implants found in the literature, only 10 were ALK-1(-). The finding of 28 cases of breast ALK-1(-) ALCL occurring in patients with implants compared with 10 cases in women without implants is in favor of an association between silicone breast prostheses and ALK-1(-) ALCL. Although the incidence of this type of lymphoma remains remarkably low given that breast prostheses have been widely used for decades, clinical and pathologic evidence for a causative role is becoming dramatically strong. The histologic, phenomenologic, and clinical similarities of the majority of implant-related ALK-1(-) ALCLs suggest a common mechanism, especially when compared with the counterpart of patients without implants in which very few and highly dishomogeneous cases of the same malignancy were detected. There is convincing evidence that primary implant-related ALK-1(-) ALCL represents a distinct clinicopathologic entity that has been inappropriately fitted into the category of systemic ALK-1(-) ALCL. Thus it should be recognized as a separate category and classified on its own. Copyright © 2011 Elsevier Inc. All rights reserved.

Tyrosine phosphorylation in human lymphomas

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Haralambieva, E; Jones, M.; Roncador, GM; Cerroni, L; Lamant, L; Ott, G; Rosenwald, A; Sherman, C; Thorner, P; Kusec, R; Wood, KM; Campo, E; Falini, B; Ramsay, A; Marafioti, T; Stein, H; Kluin, PM; Pulford, K; Mason, DY

2002-01-01

In a previous study, we showed that the high level of protein tyrosine phosphorylation present in lymphomas containing an anaplastic lymphoma kinase (ALK) can be demonstrated in routinely processed paraffin tissue sections using immunolabelling techniques. In the present study we investigated

Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

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Million, Lynn, E-mail: lmillion@stanford.edu [Stanford Cancer Institute, Stanford, California (United States); Yi, Esther J.; Wu, Frank; Von Eyben, Rie [Stanford Cancer Institute, Stanford, California (United States); Campbell, Belinda A. [Department of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne (Australia); Dabaja, Bouthaina [The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsang, Richard W. [Department of Radiation Oncology, Princess Margaret Cancer Centre, Toronto, Ontario (Canada); Ng, Andrea [Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Wilson, Lynn D. [Department of Therapeutic Radiology/Radiation Oncology, Yale School of Medicine, Yale Cancer Center, New Haven, Connecticut (United States); Ricardi, Umberto [Department of Oncology, University of Turin, Turin (Italy); Kirova, Youlia [Institut Curie, Paris (France); Hoppe, Richard T. [Stanford Cancer Institute, Stanford, California (United States)

2016-08-01

Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumors were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.

Spinal cord compression caused by anaplastic large cell lymphoma in an HIV infected individual

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Kumar Susheel

2010-01-01

Full Text Available Lymphomas occur with an increased frequency in patients with Human Immunodeficiency Virus (HIV infection. These are usually high-grade immunoblastic lymphomas and primary central nervous system lymphomas. Anaplastic large cell lymphoma (ALCL is a distinct type of non-Hodgkin′s lymphoma. It is uncommon in HIV infected individuals. We describe here an uncommon presentation of this relatively rare lymphoma in the form of spinal cord compression syndrome in a young HIV infected individual.

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report.

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Daneshbod, Yahya; Omidvari, Shapour; Daneshbod, Khosrow; Negahban, Shahrzad; Dehghani, Mehdi

2006-10-19

Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

Diffuse large B cell lymphoma of thyroid as a masquerader of anaplastic carcinoma of thyroid, diagnosed by FNA: a case report

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Dehghani Mehdi

2006-01-01

Full Text Available Abstract Background Both thyroid lymphoma and anaplastic carcinoma of thyroid present with rapidly growing mass in eldery patients. Anaplastic carcinoma has high mortality rate and combination of surgery, radiation therapy and multidrug chemotherapy are the best chance for cure. Prognosis of thyroid lymphoma is excellent and chemotherapy for widespred lymphoms and radiotherapy with or without adjuvant chemotherapy for tumors localized to the gland, are the treatment of choice. Case report This article reports a 70 year old man presenting with diffuse neck swelling and hoarseness of few weeks duration. Fine needle aspiration was done and reported as anaplastic carcinoma of thyroid which thyroidectomy was planned. The slides were sent for second opinion. After review, with initial diagnosis of anaplastic carcinoma versus lymphoma, immunocytochemical study was performed. Smears were positive for B cell markers and negative for cytokeratin, so with the impression of diffuse large B cell lymphoma, the patient received two courses of chemotherapy by which the tumor disappeared during two weaks. Conclusion Despite previous reports, stating easy diagnosis of high-grade thyroid lymphoma on the grounds of cytomorphological features we like to emphasize, overlapping cytologic features of the curable high grade thyroid lymphoma form noncurable anaplastic thyroid carcinoma and usefulness of immunocytochemistry to differentiate these two disease.

Anaplastic Lymphoma Kinase Is a Regulator of Alcohol Consumption and Excitatory Synaptic Plasticity in the Nucleus Accumbens Shell

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Regina A. Mangieri

2017-08-01

Full Text Available Anaplastic lymphoma kinase (ALK is a receptor tyrosine kinase recently implicated in biochemical, physiological, and behavioral responses to ethanol. Thus, manipulation of ALK signaling may represent a novel approach to treating alcohol use disorder (AUD. Ethanol induces adaptations in glutamatergic synapses onto nucleus accumbens shell (NAcSh medium spiny neurons (MSNs, and putative targets for treating AUD may be validated for further development by assessing how their manipulation modulates accumbal glutamatergic synaptic transmission and plasticity. Here, we report that Alk knockout (AlkKO mice consumed greater doses of ethanol, relative to wild-type (AlkWT mice, in an operant self-administration model. Using ex vivo electrophysiology to examine excitatory synaptic transmission and plasticity at NAcSh MSNs that express dopamine D1 receptors (D1MSNs, we found that the amplitude of spontaneous excitatory post-synaptic currents (EPSCs in NAcSh D1MSNs was elevated in AlkKO mice and in the presence of an ALK inhibitor, TAE684. Furthermore, when ALK was absent or inhibited, glutamatergic synaptic plasticity – long-term depression of evoked EPSCs – in D1MSNs was attenuated. Thus, loss of ALK activity in mice is associated with elevated ethanol consumption and enhanced excitatory transmission in NAcSh D1MSNs. These findings add to the mounting evidence of a relationship between excitatory synaptic transmission onto NAcSh D1MSNs and ethanol consumption, point toward ALK as one important molecular mediator of this interaction, and further validate ALK as a target for therapeutic intervention in the treatment of AUD.

Targeted therapy for Hodgkin lymphoma and systemic anaplastic large cell lymphoma: focus on brentuximab vedotin

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Chen X

2013-12-01

Full Text Available Xueyan Chen, Lorinda A Soma, Jonathan R FrommDepartment of Laboratory Medicine, University of Washington Medical Center, Seattle, WA, USAAbstract: Despite the relative success of chemotherapy for Hodgkin lymphoma (HL and systemic anaplastic large cell lymphoma (ALCL, novel therapeutic agents are needed for refractory or relapsed patients. Targeted immunotherapy has emerged as a novel treatment option for these patients. Although unconjugated anti-cluster of differentiation (CD30 antibodies showed minimal antitumor activity in early clinical trials, development of antibody–drug conjugates (ADCs appears promising. Brentuximab vedotin is an ADC composed of an anti-CD30 antibody linked to a potent microtubule-disrupting agent monomethyl auristatin E (MMAE. It has the ability to target CD30-positive tumor cells and, once bound to CD30, brentuximab vedotin is internalized and MMAE is released to induce cell cycle arrest and apoptosis. In two phase II trials, objective response was reported in 75% and 86% of patients with refractory or relapsed HL and systemic ALCL, respectively, with an acceptable toxicity profile. Based on these studies, the US Food and Drug Administration (FDA granted accelerated approval of brentuximab vedotin in August 2011 for the treatment of refractory and relapsed HL and ALCL. We review the key characteristics of brentuximab vedotin, clinical data supporting its therapeutic efficacy, and current ongoing trials to explore its utility in other CD30-positive malignancies.Keywords: classical Hodgkin lymphoma, systemic anaplastic large cell lymphoma, CD30, brentuximab vedotin, SGN-35

Primary cutaneous anaplastic large cell lymphoma masquerading as large pyogenic granuloma

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Anupama Bains

2016-01-01

Full Text Available Primary cutaneous anaplastic large cell lymphoma (pcALCL forms 9% of the cutaneous T-cell lymphomas. It usually presents as solitary reddish brown ulcerating nodule or indurated plaque. Sometimes, it mimics other dermatological diseases such as eczema, pyoderma gangrenosum, pyogenic granuloma, morphea, and squamous cell carcinoma. Our case presented with large pyogenic granuloma like lesion with regional lymphadenopathy. Since pcALCL is rare, one can misdiagnose such cases and therefore high index of suspicion is necessary.

Successful oral desensitization against skin rash induced by alectinib in a patient with anaplastic lymphoma kinase-positive lung adenocarcinoma: A case report.

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Shirasawa, Masayuki; Kubotaa, Masaru; Harada, Shinya; Niwa, Hideyuki; Kusuhara, Seiichiro; Kasajima, Masashi; Hiyoshi, Yasuhiro; Ishihara, Mikiko; Igawa, Satoshi; Masuda, Noriyuki

2016-09-01

Alectinib has been approved for the treatment of patients with anaplastic lymphoma kinase (ALK) gene rearrangement-positive advanced non-small cell lung cancer. In terms of adverse effects, the occurrence of a severe skin rash induced by alectinib is reportedly rare, compared with the occurrence of skin rash induced by epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). In the present case report, a 76-year-old woman with ALK-positive lung adenocarcinoma experienced disease progression after undergoing first-line chemotherapy. Subsequently, alectinib was administered as a second-line therapy. However, she discontinued alectinib therapy after 11days because of the occurrence of an alectinib-induced skin rash. Since the skin rash improved within one week, we attempted to perform oral desensitization to alectinib. The patient has not shown any recurrence of the rash or disease progression for 7 months since the successful oral desensitization to alectinib. Here, we describe the first case of successful oral desensitization against a skin rash induced by alectinib in a patient with ALK-positive lung adenocarcinoma. Desensitization to overcome adverse effects and to enable sustained treatment with alectinib should be considered in patients who develop alectinib sensitivities. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression.

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Georgakis, Georgios V; Li, Yang; Rassidakis, Georgios Z; Medeiros, L Jeffrey; Younes, Anas

2006-12-01

Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.

Treatment Options for Paediatric Anaplastic Large Cell Lymphoma (ALCL: Current Standard and beyond

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Nina Prokoph

2018-03-01

Full Text Available Anaplastic Lymphoma Kinase (ALK-positive Anaplastic Large Cell Lymphoma (ALCL, remains one of the most curable cancers in the paediatric setting; multi-agent chemotherapy cures approximately 65–90% of patients. Over the last two decades, major efforts have focused on improving the survival rate by intensification of combination chemotherapy regimens and employing stem cell transplantation for chemotherapy-resistant patients. More recently, several new and ‘renewed’ agents have offered the opportunity for a change in the paradigm for the management of both chemo-sensitive and chemo-resistant forms of ALCL. The development of ALK inhibitors following the identification of the EML4-ALK fusion gene in Non-Small Cell Lung Cancer (NSCLC has opened new possibilities for ALK-positive ALCL. The uniform expression of CD30 on the cell surface of ALCL has given the opportunity for anti-CD30 antibody therapy. The re-evaluation of vinblastine, which has shown remarkable activity as a single agent even in the face of relapsed disease, has led to the consideration of a revised approach to frontline therapy. The advent of immune therapies such as checkpoint inhibition has provided another option for the treatment of ALCL. In fact, the number of potential new agents now presents a real challenge to the clinical community that must prioritise those thought to offer the most promise for the future. In this review, we will focus on the current status of paediatric ALCL therapy, explore how new and ‘renewed’ agents are re-shaping the therapeutic landscape for ALCL, and identify the strategies being employed in the next generation of clinical trials.

Pathobiology of Anaplastic Large Cell Lymphoma

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Pier Paolo Piccaluga

2010-01-01

Full Text Available The authors revise the concept of anaplastic large cell lymphoma (ALCL in the light of the recently updated WHO classification of Tumors of Hematopoietic and Lymphoid Tissues both on biological and clinical grounds. The main histological findings are illustrated with special reference to the cytological spectrum that is indeed characteristic of the tumor. The phenotype is reported in detail: the expression of the ALK protein as well as the chromosomal abnormalities is discussed with their potential pathogenetic implications. The clinical features of ALCL are presented by underlining the difference in terms of response to therapy and survival between the ALK-positive and ALK-negative forms. Finally, the biological rationale for potential innovative targeted therapies is presented.

Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma.

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Coco, Simona; De Mariano, Marilena; Valdora, Francesca; Servidei, Tiziana; Ridola, Vita; Andolfo, Immacolata; Oberthuer, André; Tonini, Gian Paolo; Longo, Luca

2012-10-01

The anaplastic lymphoma kinase (ALK) gene has been found either rearranged or mutated in several neoplasms such as anaplastic large-cell lymphoma, non-small-cell lung cancer, neuroblastoma and anaplastic thyroid cancer. Medulloblastoma (MB) is an embryonic pediatric cancer arising from nervous system, a tissue in which ALK is expressed during embryonic development. We performed an ALK mutation screening in 52 MBs and we found a novel heterozygous germline deletion of a single base in exon 23 (3605delG) in a case with marked anaplasia. This G deletion results in a frameshift mutation producing a premature stop codon in exon 25 of ALK tyrosine kinase domain. We also screened three human MB cell lines without finding any mutation of ALK gene. Quantitative expression analysis of 16 out of 52 samples showed overexpression of ALK mRNA in three MBs. In the present study, we report the first mutation of ALK found in MB. Moreover, a deletion of ALK gene producing a stop codon has not been detected in human tumors up to now. Further investigations are now required to elucidate whether the truncated form of ALK may have a role in signal transduction.

Treatment of primary cutaneous anaplastic large cell lymphoma with superficial x-rays

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Jepsen, Malene E; Gniadecki, Robert

2015-01-01

The optimal radiation schedule for primary cutaneous anaplastic lymphoma (PCALCL) has not been investigated. We report here satisfactory outcomes of low-dose (16-20 Gy, 3-5 fractions), superficial X-ray radiation (40-50 kV) in a series of 10 patients with PCALCL. Only 1 patient developed a local...

Isolated cutaneous involvement in a child with nodal anaplastic large cell lymphoma

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Vibhu Mendiratta

2016-01-01

Full Text Available Non-Hodgkin lymphoma is a common childhood T-cell and B-cell neoplasm that originates primarily from lymphoid tissue. Cutaneous involvement can be in the form of a primary extranodal lymphoma, or secondary to metastasis from a non-cutaneous location. The latter is uncommon, and isolated cutaneous involvement is rarely reported. We report a case of isolated secondary cutaneous involvement from nodal anaplastic large cell lymphoma (CD30 + and ALK + in a 7-year-old boy who was on chemotherapy. This case is reported for its unusual clinical presentation as an acute febrile, generalized papulonodular eruption that mimicked deep fungal infection, with the absence of other foci of systemic metastasis.

Adverse renal effects of anaplastic lymphoma kinase inhibitors and the response to alectinib of an ALK+ lung cancer patient with renal dysfunction

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Shimada M

2017-06-01

Full Text Available Midori Shimada,1,2 Minoru Fukuda,2,3 Masaaki Fukuda,2 Takeshi Kitazaki,2 Kohji Hashiguchi,2 Takaya Ikeda,1 Hiroyuki Yamaguchi,1 Katsumi Nakatomi,1 Kazuto Ashizawa,3 Hiroshi Mukae1 1Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 2Department of Respiratory Medicine, Japanese Red Cross Nagasaki Genbaku Hospital, 3Clinical Oncology Center, Nagasaki University Hospital, Nagasaki, Japan Abstract: A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK gene translocation was identified, the therapy was changed to crizotinib. However, the patient’s blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months. Here, we describe the case in which alectinib treatment had beneficial clinical effects on ALK-positive lung adenocarcinoma, which controlled the adverse renal effects by dose reduction and drug breaks. Keywords: lung cancer, ALK, renal dysfunction, alectinib

Therapeutic options in peripheral T cell lymphoma

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Yaping Zhang

2016-04-01

Full Text Available Abstract Peripheral T cell lymphoma (PTCL is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK-positive anaplastic large cell lymphoma (ALCL, the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10–30 %. Novel targeted therapies and combination chemotherapies are required for the treatment of patients with PTCL. In recent years, some retrospective and prospective studies have been performed concerning PTCL. Consequently, a number of novel agents and their relevant combination therapies have been identified, including histone deacetylase inhibitors, immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, bendamustine, l-asparaginase, and other targeted agents. It is hoped that these innovative approaches will finally improve outcomes in patients with PTCL. This review summarizes the currently available approaches for the treatment of PTCL with an emphasis on potential new agents, including the role of stem cell transplantation.

Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

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DiBonaventura MD

2017-12-01

Full Text Available Marco D DiBonaventura,1 William Wong,2 Bijal Shah-Manek,3,4 Mathias Schulz2 1Ipsos Healthcare, Global Evidence, Value & Access, New York, NY, 2Genentech, US Medical Affairs, San Francisco, CA, 3Ipsos Healthcare, Global Evidence, Value & Access, San Francisco, CA, 4College of Pharmacy, Touro University California, CA, USA Background: Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods: Participating oncologists (N=95 in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor, collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results: A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male. The patients in our sample were older (median age of 60 vs 53 years, were more likely to be current smokers (12% vs 1%, had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0, and were less likely to have an adenocarcinoma histology (83% vs 96% relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively as was the disease control rate (89.9% vs 78.8%, respectively, though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0% and dose reductions (3.4% due to adverse events were uncommon in alectinib.Conclusion: Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

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Colomba, A [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Giuriato, S; Dejean, E [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Thornber, K [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Delsol, G [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Tronchère, H [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France); Meggetto, F [Centre de Recherches en Cancérologie de Toulouse, UMR1037-Université Toulouse III, IFR150-IFRBMT, Toulouse (France); Payrastre, B; Gaits-Iacovoni, F [INSERM, U1048, Université Toulouse III, Toulouse, Institut des Maladies Métaboliques et Cardiovasculaires, Toulouse (France)

2011-06-01

Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas.

Inhibition of Rac controls NPM–ALK-dependent lymphoma development and dissemination

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Colomba, A; Giuriato, S; Dejean, E; Thornber, K; Delsol, G; Tronchère, H; Meggetto, F; Payrastre, B; Gaits-Iacovoni, F

2011-01-01

Nucleophosmin-anaplastic lymphoma kinase (NPM–ALK) is a tyrosine kinase oncogene responsible for the pathogenesis of the majority of human ALK-positive lymphomas. We recently reported that it activated the Rac1 GTPase in anaplastic large-cell lymphoma (ALCL), leading to Rac-dependent formation of active invadopodia required for invasiveness. Herein, we went further into the study of this pathway and used the inhibitor of Rac, NSC23766, to validate its potential as a molecular target in ALCL in vitro and in vivo in a xenograft model and in a conditional model of NPM–ALK transgenic mice. Our data demonstrate that Rac regulates important effectors of NPM–ALK-induced transformation such as Erk1/2, p38 and Akt. Moreover, inhibition of Rac signaling abrogates NPM–ALK-elicited disease progression and metastasis in mice, highlighting the potential of small GTPases and their regulators as additional therapic targets in lymphomas

Novel covalent modification of human anaplastic lymphoma kinase (ALK and potentiation of crizotinib-mediated inhibition of ALK activity by BNP7787

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Parker AR

2015-02-01

Full Text Available Aulma R Parker,1 Pavankumar N Petluru,1 Vicki L Nienaber,2 Min Zhao,1 Philippe Y Ayala,1 John Badger,2 Barbara Chie-Leon,2 Vandana Sridhar,2 Cheyenne Logan,2 Harry Kochat,1 Frederick H Hausheer1 1BioNumerik Pharmaceuticals, Inc., San Antonio, TX, USA; 2Zenobia Therapeutics, Inc., La Jolla, CA, USA Abstract: BNP7787 (Tavocept, disodium 2,2’-dithio-bis-ethanesulfonate is a novel, investigational, water-soluble disulfide that is well-tolerated and nontoxic. In separate randomized multicenter Phase II and Phase III clinical trials in non-small-cell lung cancer (NSCLC patients, treatment with BNP7787 in combination with standard chemotherapy resulted in substantial increases in the overall survival of patients with advanced adenocarcinoma of the lung in the first-line treatment setting. We hypothesized that BNP7787 might interact with and modify human anaplastic lymphoma kinase (ALK. At least seven different variants of ALK fusions with the gene encoding the echinoderm microtubule-associated protein-like 4 (EML4 are known to occur in NSCLC. EML4–ALK fusions are thought to account for approximately 3% of NSCLC cases. Herein, we report the covalent modification of the kinase domain of human ALK by a BNP7787-derived mesna moiety and the functional consequences of this modification in ALK assays evaluating kinase activity. The kinase domain of the ALK protein crystallizes as a monomer, and BNP7787-derived mesna-cysteine adducts were observed at Cys 1235 and Cys 1156. The BNP7787-derived mesna adduct at Cys 1156 is located in close proximity to the active site and results in substantial disorder of the P-loop and activation loop (A-loop. Comparison with the P-loop of apo-ALK suggests that the BNP7787-derived mesna adduct at Cys 1156 interferes with the positioning of Phe 1127 into a small pocket now occupied by mesna, resulting in a destabilization of the loop's binding orientation. Additionally, in vitro kinase activity assays indicate that BNP7787

The heat shock protein-90 co-chaperone, Cyclophilin 40, promotes ALK-positive, anaplastic large cell lymphoma viability and its expression is regulated by the NPM-ALK oncoprotein

International Nuclear Information System (INIS)

Pearson, Joel D; Mohammed, Zubair; Bacani, Julinor T C; Lai, Raymond; Ingham, Robert J

2012-01-01

Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is a T cell lymphoma defined by the presence of chromosomal translocations involving the ALK tyrosine kinase gene. These translocations generate fusion proteins (e.g. NPM-ALK) with constitutive tyrosine kinase activity, which activate numerous signalling pathways important for ALK+ ALCL pathogenesis. The molecular chaperone heat shock protein-90 (Hsp90) plays a critical role in allowing NPM-ALK and other signalling proteins to function in this lymphoma. Co-chaperone proteins are important for helping Hsp90 fold proteins and for directing Hsp90 to specific clients; however the importance of co-chaperone proteins in ALK+ ALCL has not been investigated. Our preliminary findings suggested that expression of the immunophilin co-chaperone, Cyclophilin 40 (Cyp40), is up-regulated in ALK+ ALCL by JunB, a transcription factor activated by NPM-ALK signalling. In this study we examined the regulation of the immunophilin family of co-chaperones by NPM-ALK and JunB, and investigated whether the immunophilin co-chaperones promote the viability of ALK+ ALCL cell lines. NPM-ALK and JunB were knocked-down in ALK+ ALCL cell lines with siRNA, and the effect on the expression of the three immunophilin co-chaperones: Cyp40, FK506-binding protein (FKBP) 51, and FKBP52 examined. Furthermore, the effect of knock-down of the immunophilin co-chaperones, either individually or in combination, on the viability of ALK+ ALCL cell lines and NPM-ALK levels and activity was also examined. We found that NPM-ALK promoted the transcription of Cyp40 and FKBP52, but only Cyp40 transcription was promoted by JunB. We also observed reduced viability of ALK+ ALCL cell lines treated with Cyp40 siRNA, but not with siRNAs directed against FKBP52 or FKBP51. Finally, we demonstrate that the decrease in the viability of ALK+ ALCL cell lines treated with Cyp40 siRNA does not appear to be due to a decrease in NPM-ALK levels or the

Breast implants and anaplastic large-cell lymphoma: a danish population-based cohort study.

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Vase, Maja Ølholm; Friis, Søren; Bautz, Andrea; Bendix, Knud; Sørensen, Henrik Toft; d'Amore, Francesco

2013-11-01

A potential link between breast implants and anaplastic large-cell lymphoma (ALCL) has been suggested. We examined lymphoma occurrence in a nationwide cohort of 19,885 Danish women who underwent breast implant surgery during 1973-2010. Standardized incidence ratios (SIR), with 95% confidence intervals (CI), for ALCL and lymphoma overall associated with breast implantation were calculated. During 179,246 person-years of follow-up, we observed 31 cases of lymphoma among cohort members. No cases of ALCL were identified. SIRs for ALCL and lymphoma overall were zero (95% CI, 0-10.3) and 1.20 (95% CI, 0.82-1.70), respectively. In our nationwide cohort study, we did not find an increased risk of lymphoma in general, or ALCL in particular, among Danish women who underwent breast implantation. However, our evaluation of ALCL risk was limited by the rarity of the disease. Our results do not support an association between breast implants and ALCL and are consistent with other studies on cancer risk and breast implants. ©2013 AACR.

TARC, a CC chemokine, is frequently expressed in classic Hodgkin's lymphoma but not in NLP Hodgkin's lymphoma, T-cell-rich B-cell lymphoma, and most cases of anaplastic large cell lymphoma

NARCIS (Netherlands)

Peh, SC; Kim, LH; Poppema, S

Thymus and activation-regulated chemokine (TARC) has been identified as a lymphocyte-directed CC chemokine that attracts activated T-helper type 2 (Th2) cells in humans. Recent studies showed that the T cells surrounding Reed-Sternberg cells in Hodgkin's lymphomas (HL) are Th2 type. Anaplastic large

ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma.

NARCIS (Netherlands)

Paepe, P. de; Baens, M; Krieken, J.H.J.M. van; Verhasselt, B.; Stul, M.; Simons, A.; Poppe, B.; Laureys, G.; Brons, P.P.T.; Vandenberghe, P.; Speleman, F.; Praet, M.; Wolf-Peeters, C. de; Marynen, P.; Wlodarska, I.

2003-01-01

We present 3 cases of large B-cell lymphoma (LBCL) with a granular cytoplasmic staining for anaplastic lymphoma kinase (ALK). All of the cases showed striking similarities in morphology and immunohistochemical profile characterized by a massive monomorphic proliferation of CD20-/CD138+

PIM kinases as potential therapeutic targets in a subset of peripheral T cell lymphoma cases.

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Esperanza Martín-Sánchez

Full Text Available Currently, there is no efficient therapy for patients with peripheral T cell lymphoma (PTCL. The Proviral Integration site of Moloney murine leukemia virus (PIM kinases are important mediators of cell survival. We aimed to determine the therapeutic value of PIM kinases because they are overexpressed in PTCL patients, T cell lines and primary tumoral T cells. PIM kinases were inhibited genetically (using small interfering and short hairpin RNAs and pharmacologically (mainly with the pan-PIM inhibitor (PIMi ETP-39010 in a panel of 8 PTCL cell lines. Effects on cell viability, apoptosis, cell cycle, key proteins and gene expression were evaluated. Individual inhibition of each of the PIM genes did not affect PTCL cell survival, partially because of a compensatory mechanism among the three PIM genes. In contrast, pharmacological inhibition of all PIM kinases strongly induced apoptosis in all PTCL cell lines, without cell cycle arrest, in part through the induction of DNA damage. Therefore, pan-PIMi synergized with Cisplatin. Importantly, pharmacological inhibition of PIM reduced primary tumoral T cell viability without affecting normal T cells ex vivo. Since anaplastic large cell lymphoma (ALK+ ALCL cell lines were the most sensitive to the pan-PIMi, we tested the simultaneous inhibition of ALK and PIM kinases and found a strong synergistic effect in ALK+ ALCL cell lines. Our findings suggest that PIM kinase inhibition could be of therapeutic value in a subset of PTCL, especially when combined with ALK inhibitors, and might be clinically beneficial in ALK+ ALCL.

High intratumoral macrophage content is an adverse prognostic feature in anaplastic large cell lymphoma

DEFF Research Database (Denmark)

Pedersen, Martin Bjerregård; Hamilton-Dutoit, Stephen Jacques; Bendix, Knud

2014-01-01

AIMS: Macrophage infiltration has been associated with prognosis in several cancers, including lymphoma, but has not been assessed systematically in anaplastic large cell lymphoma (ALCL). The aim of the study was to correlate expression of the macrophage-associated antigens CD68 and CD163 with pre......-therapeutic parameters and outcome in a cohort of treatment-naive ALCL patients. METHODS AND RESULTS: Pre-therapeutic tumour specimens from 52 patients with ALCL were included in a tissue microarray. The intratumoral macrophage content was assessed by immunohistochemical staining for CD68 and CD163, and quantified using......-free survival in ALK-negative patients (P macrophages correlates with an adverse outcome in ALK-negative ALCL....

Anaplastic Large Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related human papillary thyroid carcinoma after the Chernobyl accident.

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Arndt, Annette; Steinestel, Konrad; Rump, Alexis; Sroya, Manveer; Bogdanova, Tetiana; Kovgan, Leonila; Port, Matthias; Abend, Michael; Eder, Stefan

2018-04-06

Childhood radiation exposure has been associated with increased papillary thyroid carcinoma (PTC) risk. The role of anaplastic lymphoma kinase (ALK) gene rearrangements in radiation-related PTC remains unclear, but STRN-ALK fusions have recently been detected in PTCs from radiation exposed persons after Chernobyl using targeted next-generation sequencing and RNA-seq. We investigated ALK and RET gene rearrangements as well as known driver point mutations in PTC tumours from 77 radiation-exposed patients (mean age at surgery 22.4 years) and PTC tumours from 19 non-exposed individuals after the Chernobyl accident. ALK rearrangements were detected by fluorescence in situ hybridisation (FISH) and confirmed with immunohistochemistry (IHC); point mutations in the BRAF and RAS genes were detected by DNA pyrosequencing. Among the 77 tumours from exposed persons, we identified 7 ALK rearrangements and none in the unexposed group. When combining ALK and RET rearrangements, we found 24 in the exposed (31.2%) compared to two (10.5%) in the unexposed group. Odds ratios increased significantly in a dose-dependent manner up to 6.2 (95%CI: 1.1, 34.7; p = 0.039) at Iodine-131 thyroid doses >500 mGy. In total, 27 cases carried point mutations of BRAF or RAS genes, yet logistic regression analysis failed to identify significant dose association. To our knowledge we are the first to describe ALK rearrangements in post-Chernobyl PTC samples using routine methods such as FISH and IHC. Our findings further support the hypothesis that gene rearrangements, but not oncogenic driver mutations, are associated with ionizing radiation-related tumour risk. IHC may represent an effective method for ALK-screening in PTCs with known radiation aetiology, which is of clinical value since oncogenic ALK activation might represent a valuable target for small molecule inhibitors. © 2018 The Authors The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and

EMMPRIN (CD147) is induced by C/EBPβ and is differentially expressed in ALK+ and ALK- anaplastic large-cell lymphoma.

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Schmidt, Janine; Bonzheim, Irina; Steinhilber, Julia; Montes-Mojarro, Ivonne A; Ortiz-Hidalgo, Carlos; Klapper, Wolfram; Fend, Falko; Quintanilla-Martínez, Leticia

2017-09-01

Anaplastic lymphoma kinase-positive (ALK+) anaplastic large-cell lymphoma (ALCL) is characterized by expression of oncogenic ALK fusion proteins due to the translocation t(2;5)(p23;q35) or variants. Although genotypically a T-cell lymphoma, ALK+ ALCL cells frequently show loss of T-cell-specific surface antigens and expression of monocytic markers. C/EBPβ, a transcription factor constitutively overexpressed in ALK+ ALCL cells, has been shown to play an important role in the activation and differentiation of macrophages and is furthermore capable of transdifferentiating B-cell and T-cell progenitors to macrophages in vitro. To analyze the role of C/EBPβ for the unusual phenotype of ALK+ ALCL cells, C/EBPβ was knocked down by RNA interference in two ALK+ ALCL cell lines, and surface antigen expression profiles of these cell lines were generated using a Human Cell Surface Marker Screening Panel (BD Biosciences). Interesting candidate antigens were further analyzed by immunohistochemistry in primary ALCL ALK+ and ALK- cases. Antigen expression profiling revealed marked changes in the expression of the activation markers CD25, CD30, CD98, CD147, and CD227 after C/EBPβ knockdown. Immunohistochemical analysis confirmed a strong, membranous CD147 (EMMPRIN) expression in ALK+ ALCL cases. In contrast, ALK- ALCL cases showed a weaker CD147 expression. CD274 or PD-L1, an immune inhibitory receptor ligand, was downregulated after C/EBPβ knockdown. PD-L1 also showed stronger expression in ALK+ ALCL compared with ALK- ALCL, suggesting an additional role of C/EBPβ in ALK+ ALCL in generating an immunosuppressive environment. Finally, no expression changes of T-cell or monocytic markers were detected. In conclusion, surface antigen expression profiling demonstrates that C/EBPβ plays a critical role in the activation state of ALK+ ALCL cells and reveals CD147 and PD-L1 as important downstream targets. The multiple roles of CD147 in migration, adhesion, and invasion, as well as

ALK signaling and target therapy in anaplastic large cell lymphoma

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Fabrizio eTabbo

2012-05-01

Full Text Available The discovery by Morris SW et al. in 1994 of the genes contributing to the t(2;5(p23;q35 translocation has put the foundation for a molecular based recognition of Anaplastic Large Cell Lymphoma (ALCL and pointed out the need for a further stratification of T-cell neoplasia. Likewise the detection of ALK genetic lesions among many human cancers has defined unique subsets of cancer patients, providing new opportunities for innovative therapeutic interventions. The objective of this review is to appraise the molecular mechanisms driving ALK-mediated transformation, and to maintain the neoplastic phenotype. The understanding of these events will allow the design and implementation of novel tailored strategies for a well-defined subset of cancer patients.

Anaplastic Large-Cell Lymphoma in a Child with Type I Diabetes and Unrecognised Coeliac Disease

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Jemima Sharp

2012-01-01

Full Text Available Screening for coeliac disease is recommended for children from certain risk groups, with implications for diagnostic procedures and dietetic management. The risk of a malignant complication in untreated coeliac disease is not considered high in children. We present the case of a girl with type I diabetes who developed weight loss, fatigue, and inguinal lymphadenopathy. Four years before, when she was asymptomatic, a screening coeliac tTG test was positive, but gluten was not eliminated from her diet. Based on clinical examination, a duodenal biopsy, and an inguinal lymph node biopsy were performed, which confirmed both coeliac disease and an anaplastic large-cell lymphoma. HLA-typing demonstrated that she was homozygous for HLA-DQ8, which is associated with higher risk for celiac disease, more severe gluten sensitivity, and diabetes susceptibility. She responded well to chemotherapy and has been in remission for over 4 years. She remains on a gluten-free diet. This is the first case reporting the association of coeliac disease, type I diabetes, and anaplastic large-cell lymphoma in childhood. The case highlights the malignancy risk in a genetically predisposed individual, and the possible role of a perpetuated immunologic response by prolonged gluten exposure.

Primary Cutaneous CD 30+ Anaplastic Large Cell Lymphoma. A Case Report and Literature Review

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Miguel Ángel Serra Valdés

2014-03-01

Full Text Available Primary cutaneous CD 30+ anaplastic large cell lymphoma is part of the spectrum of primary cutaneous CD30 + lymphoproliferative disorders, together with lymphomatoid papulosis. Its frequency is less than 0.5 x 100 000 inhabitants per year. It accounts for a very small proportion of non-Hodgkins lymphomas. The case of an 80-year-old female patient whose diagnosis was established in 2006 because of lesions on the face and neck is presented. The lesions continued to grow in an exaggerated fashion lately leading to deformity of her face. She was admitted due to neurological manifestations unrelated to the lesions. The presentation of this case is necessary because it requires performing differential diagnosis in clinical practice. Given its rarity, it is of interest to the medical community, especially trainees.

An oncogenic axis of STAT-mediated BATF3 upregulation causing MYC activity in classical Hodgkin lymphoma and anaplastic large cell lymphoma.

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Lollies, A; Hartmann, S; Schneider, M; Bracht, T; Weiß, A L; Arnolds, J; Klein-Hitpass, L; Sitek, B; Hansmann, M-L; Küppers, R; Weniger, M A

2018-01-01

Classical Hodgkin lymphoma (cHL) and anaplastic large cell lymphoma (ALCL) feature high expression of activator protein-1 (AP-1) transcription factors, which regulate various physiological processes but also promote lymphomagenesis. The AP-1 factor basic leucine zipper transcription factor, ATF-like 3 (BATF3), is highly transcribed in cHL and ALCL; however, its functional importance in lymphomagenesis is unknown. Here we show that proto-typical CD30 + lymphomas, namely cHL (21/30) and primary mediastinal B-cell lymphoma (8/9), but also CD30 + diffuse large B-cell lymphoma (15/20) frequently express BATF3 protein. Mass spectrometry and co-immunoprecipitation established interactions of BATF3 with JUN and JUNB in cHL and ALCL lines. BATF3 knockdown using short hairpin RNAs was toxic for cHL and ALCL lines, reducing their proliferation and survival. We identified MYC as a critical BATF3 target and confirmed binding of BATF3 to the MYC promoter. JAK/STAT signaling regulated BATF3 expression, as chemical JAK2 inhibition reduced and interleukin 13 stimulation induced BATF3 expression in cHL lines. Chromatin immunoprecipitation substantiated a direct regulation of BATF3 by STAT proteins in cHL and ALCL lines. In conclusion, we identified STAT-mediated BATF3 expression that is essential for lymphoma cell survival and promoted MYC activity in cHL and ALCL, hence we recognized a new oncogenic axis in these lymphomas.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature.

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Berlin, Eva; Singh, Kunwar; Mills, Christopher; Shapira, Ilan; Bakst, Richard L; Chadha, Manjeet

2018-01-01

We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging). The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature

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Eva Berlin

2018-01-01

Full Text Available We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging. The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

[A morphometric analysis of the nuclei and nucleoli in tumor cells in lymphogranulomatosis, diffuse large B-cell lymphoma and anaplastic large cell lymphoma].

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Gorgidze, L A; Vorob'ev, I A

2009-01-01

To make a comparative morphometric analysis of the nuclei and nucleoli of tumor cells in lymphogranulomatosis (LGM), diffuse large B-cell lymphoma (DLBCL) and anaplastic large cell lymphoma (ALCL) for differential diagnosis of these lymphomas. Biopsy material (lymph node biopsies) was frozen in hexane, fixed and stained, then microscopic pictures were made. Mean area of tumor cell nuclei in LGM was 97.25 +/- 68.77 mcm2, in DLBCL and ALCL--55.89 +/- 20.13 mcm2 and 70.31 +/- 34.64 mcm2, respectively. The area differences were significant (p nucleoli of the former are larger than those of the latter. Mean area of the nucleoli in DLBCL was 3.05 +/- 1.58, in ALCL--5.53 +/- 4.94 mcm2. The differences are significant (p Nucleoli in Hodgkin 's cells are significantly larger than those in the tumor cells in ALCL and DLBCL and the nucleoli with the area more than 12 mcm2 can be used in differential diagnosis between LGM and DLBCL but not between LGM and ALCL.

Patients harboring EGFR mutation after primary resistance to crizotinib and response to EGFR-tyrosine kinase inhibitor

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Wang WX

2016-01-01

Full Text Available Wenxian Wang,1 Xiaowen Jiang,1 Zhengbo Song,1,2 Yiping Zhang1,2 1Department of Chemotherapy, Zhejiang Cancer Hospital, 2Key Laboratory Diagnosis and Treatment Technology on Thoracic Oncology, Hangzhou, Zhejiang, People’s Republic of China Abstract: Anaplastic lymphoma kinase (ALK rearrangement lung cancer responds to ALK tyrosine kinase inhibitors. It is known that many cases ultimately acquired resistance to crizotinib. However, a case of primary resistance is rare. We present a case of harboring exon 19 deletion in epidermal growth factor receptor in ALK rearranged lung adenocarcinoma, who experienced a partial tumor response to icotinib after failure with crizotinib therapy and chemotherapy. Considering the partial response, we conclude that it is important to find the cause of resistance to crizotinib. We detected gene mutations with plasma by the next-generation sequencing; the next-generation sequencing demonstrates an attractive system to identify mutations improving the outcome of patients with a deadly disease. Keywords: non-small cell lung cancer, anaplastic lymphoma kinase, crizotinib, epidermal growth factor receptor

Rearranged anaplastic lymphoma kinase (ALK) gene found for the first time in adult-onset papillary thyroid cancer cases among atomic bomb survivors

International Nuclear Information System (INIS)

Hamatani, K.; Mukai, M.; Takahashi, K.; Nakachi, K.; Kusunoki, Y.; Hayashi, Y.

2012-01-01

Full text of the publication follows: Thyroid cancer is one of the malignancies most strongly associated with ionizing radiation in humans. Epidemiology studies of atomic bomb (A-bomb) survivors have indicated that excess relative risk of papillary thyroid cancer per Gy was remarkably high in the survivors. We therefore aim to clarify mechanisms linking A-bomb radiation exposure and development of papillary thyroid cancer. Toward this end, we intend to clarify characteristics of gene alterations occurring in radiation-associated adult-onset papillary thyroid cancer from the Life Span Study cohort of A-bomb survivors. We have thus far found that with increased radiation dose, papillary thyroid cancer cases with chromosomal rearrangements (mainly RET/PTC rearrangements) significantly increased and papillary thyroid cancer cases with point mutations (mainly BRAF-V600E) significantly decreased. Papillary thyroid cancer cases with non-detected gene alterations that carried no mutations in RET, NTRK1, BRAF or RAS genes tended to increase with increased radiation dose. In addition, we found that relative frequency of these papillary thyroid cancer cases significantly decreased with time elapsed since exposure. Through analysis of papillary thyroid cancer cases with non-detected gene alterations, we recently discovered a new type of rearrangement for the first time in papillary thyroid cancer, i.e., rearranged anaplastic lymphoma kinase (ALK) gene, although identification of any partner gene(s) is needed. Specifically, rearrangement of ALK was found in 10 of 19 exposed papillary thyroid cancer cases with non-detected gene alterations but not in any of the six non-exposed papillary thyroid cancer cases. Furthermore, papillary thyroid cancer with ALK rearrangement was frequently found in the cases with high radiation dose or with short time elapsed since A-bomb exposure. These results suggest that chromosomal rearrangement, typically of RET and ALK, may play an important

Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1)

DEFF Research Database (Denmark)

Marzec, Michal; Zhang, Qian; Goradia, Ami

2008-01-01

The mechanisms of malignant cell transformation caused by the oncogenic, chimeric nucleophosmin (NPM)/anaplastic lymphoma kinase (ALK) remain only partially understood, with most of the previous studies focusing mainly on the impact of NPM/ALK on cell survival and proliferation. Here we report th...

Brigatinib in Patients With Crizotinib-Refractory Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: A Randomized, Multicenter Phase II Trial.

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Kim, Dong-Wan; Tiseo, Marcello; Ahn, Myung-Ju; Reckamp, Karen L; Hansen, Karin Holmskov; Kim, Sang-We; Huber, Rudolf M; West, Howard L; Groen, Harry J M; Hochmair, Maximilian J; Leighl, Natasha B; Gettinger, Scott N; Langer, Corey J; Paz-Ares Rodríguez, Luis G; Smit, Egbert F; Kim, Edward S; Reichmann, William; Haluska, Frank G; Kerstein, David; Camidge, D Ross

2017-08-01

Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B). Investigator-assessed confirmed objective response rate (ORR) was the primary end point. Results Of 222 patients enrolled (arm A: n = 112, 109 treated; arm B: n = 110, 110 treated), 154 (69%) had baseline brain metastases and 164 of 222 (74%) had received prior chemotherapy. With 8.0-month median follow-up, investigator-assessed confirmed ORR was 45% (97.5% CI, 34% to 56%) in arm A and 54% (97.5% CI, 43% to 65%) in arm B. Investigator-assessed median progression-free survival was 9.2 months (95% CI, 7.4 to 15.6) and 12.9 months (95% CI, 11.1 to not reached) in arms A and B, respectively. Independent review committee-assessed intracranial ORR in patients with measurable brain metastases at baseline was 42% (11 of 26 patients) in arm A and 67% (12 of 18 patients) in arm B. Common treatment-emergent adverse events were nausea (arm A/B, 33%/40%), diarrhea (arm A/B, 19%/38%), headache (arm A/B, 28%/27%), and cough (arm A/B, 18%/34%), and were mainly grades 1 to 2. A subset of pulmonary adverse events with early onset (median onset: day 2) occurred in 14 of 219 treated patients (all grades, 6%; grade ≥ 3, 3%); none occurred after escalation to 180 mg in arm B. Seven of 14 patients were successfully retreated with brigatinib. Conclusion Brigatinib yielded substantial whole-body and intracranial responses as well as robust progression-free survival; 180 mg (with lead-in) showed

Cost-effectiveness of ceritinib in patients previously treated with crizotinib in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer in Canada.

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Hurry, Manjusha; Zhou, Zheng-Yi; Zhang, Jie; Zhang, Chenxue; Fan, Liangyi; Rebeira, Mayvis; Xie, Jipan

2016-10-01

To assess the cost-effectiveness of ceritinib vs alternatives in patients who discontinue treatment with crizotinib in anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC) from a Canadian public healthcare perspective. A partitioned survival model with three health states (stable, progressive, and death) was developed. Comparators were chosen based on reported utilization from a retrospective Canadian chart study; comparators were pemetrexed, best supportive care (BSC), and historical control (HC). HC comprised of all treatment alternatives reported. Progression-free survival and overall survival for ceritinib were estimated using data reported from single-arm clinical trials (ASCEND-1 [NCT01283516] and ASCEND-2 [NCT01685060]). Survival data for comparators were obtained from published clinical trials in a NSCLC population and from a Canadian retrospective chart study. Parametric models were used to extrapolate outcomes beyond the trial period. Drug acquisition, administration, resource use, and adverse event (AE) costs were obtained from databases. Utilities for health states and disutilities for AEs based on EQ-5D were derived from literature. Incremental costs per quality-adjusted life year (QALY) gained were estimated. Univariate and probabilistic sensitivity analyses were performed. Over 4 years, ceritinib was associated with 0.86 QALYs and total direct costs of $89,740 for the post-ALK population. The incremental cost-effectiveness ratio (ICER) was $149,117 comparing ceritinib vs BSC, $80,100 vs pemetrexed, and $104,436 vs HC. Additional scenarios included comparison to docetaxel with an ICER of $149,780 and using utility scores reported from PROFILE 1007, with a reported ICER ranging from $67,311 vs pemetrexed to $119,926 vs BSC. Due to limitations in clinical efficacy input, extensive sensitivity analyses were carried out whereby results remained consistent with the base-case findings. Based on the willingness-to-pay threshold for

Anaplastic large cell lymphoma associated with breast implants

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Vid Bajuk

2017-02-01

Full Text Available An increasing number of women worldwide decide for esthetic correction of breasts with silicone implants and post-cancer breast reconstruction with tissue expanders and silicone breast implants. It is estimated that more than 10 million women around the globe have them. Tere are approximately 200 known cases of patients with anaplastic large cell lymphoma (ALCL linked with silicone breast implants reported in medical literature. ALCL is a rare disease with an annual incidence of 0.1–0.3/100 000 women with breast silicone implants. In the presence of clinical signs, physician should also consider this rare form of ALCL in differential diagnosis. Patients are on average 50 years old. Long afer implantation surgery, the patient may experience breast swelling, pain and/or asymmetry. In diagnostics, ultrasound and cytological examination are required. During ultrasound examination fluid formation (seroma or solid tumor mass can be detected. Treatment is individualized. Due to tumor nature, implant resection and total capsulectomy are usually indicated; also, chemo- and radiotherapy might rarely be required. Five-year survival rate depends on tumor form and correlates well with clinical fndings of seroma or solid mass. In the more frequent form, seroma, fve-year survival rate is 100 %, while in the case of solid tumor mass fve-year survival rate is 75 %. The rarity of this disease makes it difficult to diagnose, but nevertheless, early detection and treatment are important for better recovery.

Multi-gene epigenetic silencing of tumor suppressor genes in T-cell lymphoma cells; delayed expression of the p16 protein upon reversal of the silencing

DEFF Research Database (Denmark)

Nagasawa, T; Zhang, Q; Raghunath, P N

2006-01-01

To understand better T-cell lymphomagenesis, we examined promoter CpG methylation and mRNA expression of closely related genes encoding p16, p15, and p14 tumor suppressor genes in cultured malignant T-cells that were derived from cutaneous, adult type, and anaplastic lymphoma kinase (ALK)-express...

Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth.

Science.gov (United States)

Gururajan, Murali; Dasu, Trivikram; Shahidain, Seif; Jennings, C Darrell; Robertson, Darrell A; Rangnekar, Vivek M; Bondada, Subbarao

2007-01-01

Curcumin (diferuloylmethane), a component of dietary spice turmeric (Curcuma longa), has been shown in recent studies to have therapeutic potential in the treatment of cancer, diabetes, arthritis, and osteoporosis. We investigated the ability of curcumin to modulate the growth of B lymphomas. Curcumin inhibited the growth of both murine and human B lymphoma in vitro and murine B lymphoma in vivo. We also demonstrate that curcumin-mediated growth inhibition of B lymphoma is through inhibition of the survival kinase Akt and its key target Bad. However, in vitro kinase assays show that Akt is not a direct target of curcumin. We identified a novel target for curcumin in B lymphoma viz spleen tyrosine kinase (Syk). Syk is constitutively activated in primary tumors and B lymphoma cell lines and curcumin down-modulates Syk activity accompanied by down-regulation of Akt activation. Moreover, we show that overexpression of Akt, a target of Syk, or Bcl-x(L), a target of Akt can overcome curcumin-induced apoptosis of B lymphoma cells. These observations suggest a novel growth promoting role for Syk in lymphoma cells.

Real-world usage and clinical outcomes of alectinib among post-crizotinib progression anaplastic lymphoma kinase positive non-small-cell lung cancer patients in the USA

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DiBonaventura, Marco D; Wong, William; Shah-Manek, Bijal; Schulz, Mathias

2018-01-01

Background Alectinib is an approved treatment for anaplastic lymphoma kinase (ALK)-positive patients with advanced non-small-cell lung cancer. Despite positive supporting clinical data, there is a lack of real-world information on the usage and patient outcomes of those treated with alectinib post-crizotinib progression. Methods Participating oncologists (N=95) in the USA were recruited from an online physician panel to participate in a retrospective patient chart review. Physicians randomly selected eligible patients (ie, patients who progressed on crizotinib as their first ALK inhibitor and were treated with alectinib as their second ALK inhibitor), collected demographics and clinical history from their medical charts, and entered the data into an online data collection form. Results A total of N=207 patient charts were included (age: 60.1±10.4 years; 53.6% male). The patients in our sample were older (median age of 60 vs 53 years), were more likely to be current smokers (12% vs 1%), had better performance status (45% vs 33% had an Eastern Cooperative Oncology Group [ECOG] of 0), and were less likely to have an adenocarcinoma histology (83% vs 96%) relative to published clinical trials. The objective response rate was higher than in clinical trials (67.1% vs 51.3%, respectively) as was the disease control rate (89.9% vs 78.8%, respectively), though it varied by race/ethnicity, ECOG, and prior treatment history. Discontinuation (0.0%) and dose reductions (3.4%) due to adverse events were uncommon in alectinib. Conclusion Patients using alectinib post-crizotinib in clinical practice are older, more racially/ethnically and histologically diverse than patients in published trials. Real-world response rates were high and similar to those reported in clinical studies, though there is some variation by patient characteristics. Alectinib was well tolerated in clinical practice as reflected by the rates of discontinuation, dose reductions, and dose interruptions. PMID

Successful Treatment in a Child with Anaplastic Large Cell Lymphoma and Coexistence of Pulmonary Tuberculosis

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Margarita Baka

2013-01-01

Full Text Available A 13-year-old girl was admitted to our department with a history of severe pain of her left axilla and fever. On physical examination, a block of lymph nodes in her left axilla, diffuse papular rash, and red-violet swelling of her supraclavicular and subclavian region were noted. Imaging investigations revealed left axillar and supraclavicular lymphadenopathy and a small nodular shade in the upper lobe of her left lung. A biopsy from an axillary lymph node established the diagnosis of anaplastic large cell lymphoma (ALCL, whereas DNA of Mycobacterium tuberculosis was detected by polymerase chain reaction (PCR in the same tissue biopsy. Patient was started on chemotherapy for ALCL and achieved remission of all initially involved fields. Nevertheless, two new nodular lesions were detected in the left lower lobe. Biopsy revealed granulomas, and PCR was positive for M. tuberculosis. Our patient received treatment with the combination of isoniazid and rifampin (12 months, pyrazinamide (the first 2 months, and maintenance chemotherapy for her ALCL for one year simultaneously. Four years later, she is disease free for both mycobacterial infection and lymphoma. We are reporting this successful management of mycobacterial infection in a patient with ALCL despite intensive chemotherapy that the patient received at the same time.

Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

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Clemens, Mark W; Medeiros, L Jeffrey; Butler, Charles E; Hunt, Kelly K; Fanale, Michelle A; Horwitz, Steven; Weisenburger, Dennis D; Liu, Jun; Morgan, Elizabeth A; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R; Ferry, Judith A; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; DiNapoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M; Hanson, Summer E; Nastoupil, Loretta J; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H; Miranda, Roberto N

2016-01-10

Breast implant-associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. © 2015 by American Society of Clinical Oncology.

Complete Surgical Excision Is Essential for the Management of Patients With Breast Implant–Associated Anaplastic Large-Cell Lymphoma

Science.gov (United States)

Clemens, Mark W.; Medeiros, L. Jeffrey; Butler, Charles E.; Hunt, Kelly K.; Fanale, Michelle A.; Horwitz, Steven; Weisenburger, Dennis D.; Liu, Jun; Morgan, Elizabeth A.; Kanagal-Shamanna, Rashmi; Parkash, Vinita; Ning, Jing; Sohani, Aliyah R.; Ferry, Judith A.; Mehta-Shah, Neha; Dogan, Ahmed; Liu, Hui; Thormann, Nora; Di Napoli, Arianna; Lade, Stephen; Piccolini, Jorge; Reyes, Ruben; Williams, Travis; McCarthy, Colleen M.; Hanson, Summer E.; Nastoupil, Loretta J.; Gaur, Rakesh; Oki, Yasuhiro; Young, Ken H.

2016-01-01

Purpose Breast implant–associated anaplastic large-cell lymphoma (BI-ALCL) is a rare type of T-cell lymphoma that arises around breast implants. The optimal management of this disease has not been established. The goal of this study is to evaluate the efficacy of different therapies used in patients with BI-ALCL to determine an optimal treatment approach. Patients and Methods In this study, we applied strict criteria to pathologic findings, assessed therapies used, and conducted a clinical follow-up of 87 patients with BI-ALCL, including 50 previously reported in the literature and 37 unreported. A Prentice, Williams, and Peterson model was used to assess the rate of events for each therapeutic intervention. Results The median and mean follow-up times were 45 and 30 months, respectively (range, 3 to 217 months). The median overall survival (OS) time after diagnosis of BI-ALCL was 13 years, and the OS rate was 93% and 89% at 3 and 5 years, respectively. Patients with lymphoma confined by the fibrous capsule surrounding the implant had better event-free survival (EFS) and OS than did patients with lymphoma that had spread beyond the capsule (P = .03). Patients who underwent a complete surgical excision that consisted of total capsulectomy with breast implant removal had better OS (P = .022) and EFS (P = .014) than did patients who received partial capsulectomy, systemic chemotherapy, or radiation therapy. Conclusion Surgical management with complete surgical excision is essential to achieve optimal EFS in patients with BI-ALCL. PMID:26628470

Epstein-Barr virus-associated peripheral T-Cell lymphoma involving spleen in a renal transplant patient.

Science.gov (United States)

Lee, Hye Kyung; Kim, Hee Jung; Lee, Eun Hee; Kim, Suk Young; Park, Tae In; Kang, Chang Suk; Yang, Woo Ick

2003-01-01

The incidence of posttransplantation lymphoproliferative disorders (PTLDs) has increased in recent years. Although rare, various types of T-cell lymphoma have been reported and their association with Epstein-Barr virus (EBV) has been compared with B-cell PTLDs. We report a case of splenic peripheral T-cell lymphoma occurring in a 47-yr-old male patient 7 yr after renal allograft transplantation. The spleen showed sinusoidal proliferation of focal CD30 positive, large, atypical lymphoid cells. Positivity for CD3 and cytolytic granule-associated proteins was also demonstrated in the tumor cells, while anaplastic large cell lymphoma kinase (ALK) and CD8 were not expressed. Strong nuclear signals for EBV mRNA were noted by EBER1 in situ hybridization. A molecular genetic study demonstrated a rearrangement of the gamma T-cell receptor gene. To our knowledge, this case is unique in terms of a posttransplant T-cell lymphoma that shows focal CD30, cytolytic granule-associated proteins, and EBV positivity. PMID:12692428

Lymphoma of the eyelid

DEFF Research Database (Denmark)

Svendsen, Frederik Holm; Heegaard, Steffen

2017-01-01

Lymphoma of the eyelid constitutes 5% of ocular adnexal lymphoma. In previously published cases, 56% of lymphomas of the eyelid are of B-cell origin and 44% are of T-cell origin. The most frequent B-cell lymphomas are extranodal marginal zone lymphoma (27 cases-14%) and diffuse large B......-cell lymphoma (18 cases-9%). T-cell lymphomas are most frequently mycosis fungoides (25 cases-13%), extranodal natural killer/T-cell, nasal-type lymphoma (12 cases-6%), and primary cutaneous anaplastic large-cell lymphoma (12 cases-6%). This distribution differs from the distribution of ocular adnexal lymphoma...... and that of cutaneous lymphoma. The majority of subtypes occur in elderly patients, except for lymphoblastic lymphoma of B-cell and T-cell origin and Burkitt lymphoma, which occur in children and adolescents. Several subtypes have a male predominance, including peripheral T-cell lymphoma and Burkitt lymphoma. Only...

MHC-I-induced apoptosis in human B-lymphoma cells is dependent on protein tyrosine and serine/threonine kinases

DEFF Research Database (Denmark)

Pedersen, Anders Elm; Bregenholt, S; Johansen, B

1999-01-01

B lymphoma cells, is dependent on protein tyrosine kinases and the phosphatidylinositol 3 (PI-3) kinase. Functional studies showed that MHC-I crosslinking induced almost complete inhibition of the spontaneous proliferation of the B lymphoma cells as early as 6 h post-crosslinking and apoptosis 24 h...... post-crosslinking. Preincubation with either protein tyrosine kinase or protein serine/threonine kinase inhibitors reduced the MHC-I-induced apoptosis to background levels, whereas inhibition of PI-3 kinase had no effect. These data demonstrate a pivotal role for protein tyrosine and serine...

Insights into the Pathogenesis of Anaplastic Large-Cell Lymphoma through Genome-wide DNA Methylation Profiling

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Melanie R. Hassler

2016-10-01

Full Text Available Aberrant DNA methylation patterns in malignant cells allow insight into tumor evolution and development and can be used for disease classification. Here, we describe the genome-wide DNA methylation signatures of NPM-ALK-positive (ALK+ and NPM-ALK-negative (ALK− anaplastic large-cell lymphoma (ALCL. We find that ALK+ and ALK− ALCL share common DNA methylation changes for genes involved in T cell differentiation and immune response, including TCR and CTLA-4, without an ALK-specific impact on tumor DNA methylation in gene promoters. Furthermore, we uncover a close relationship between global ALCL DNA methylation patterns and those in distinct thymic developmental stages and observe tumor-specific DNA hypomethylation in regulatory regions that are enriched for conserved transcription factor binding motifs such as AP1. Our results indicate similarity between ALCL tumor cells and thymic T cell subsets and a direct relationship between ALCL oncogenic signaling and DNA methylation through transcription factor induction and occupancy.

Targeting Bruton Tyrosine Kinase: A novel strategy in the treatment of B-cell lymphomas

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Sklavenitis-Pistofidis R.

2017-06-01

Full Text Available In normal B-cells, Bruton tyrosine kinase (Btk, a non-receptor tyrosine kinase involved in B-cell receptor (BCR signalling, is essential for cell survival and maturation. Not surprisingly, Btk is also implicated in the pathogenesis of B-cell lymphomas, like Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL, Mantle Cell Lymphoma (MCL and Waldenström’s Macroglobulinemia (WM, which are driven by aberrant BCR signalling. Thus, targeting Btk represents a promising therapeutic strategy in the treatment of B-cell lymphoma patients. Ibrutinib, a selective Btk inhibitor, has already been approved as second-line treatment of CLL/SLL, MCL and WM patients, while more clinical studies of ibrutinib and novel Btk inhibitors are currently under way. In light of results of the RESONATE-2 trial, the approval of ibrutinib as a first-line treatment of CLL/SLL may well be approaching. Herein, we review Btk’s role in normal and malignant BCR signalling, as well as ibrutinib’s performance in B-cell lymphoma treatment and prognosis.

Antineoplastic activity of the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine in anaplastic large cell lymphoma

Science.gov (United States)

Hassler, Melanie R.; Klisaroska, Aleksandra; Kollmann, Karoline; Steiner, Irene; Bilban, Martin; Schiefer, Ana-Iris; Sexl, Veronika; Egger, Gerda

2012-01-01

DNA methylation is an epigenetic mechanism establishing long-term gene silencing during development and cell commitment, which is maintained in subsequent cell generations. Aberrant DNA methylation is found at gene promoters in most cancers and can lead to silencing of tumor suppressor genes. The DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine (5-aza-CdR) is able to reactivate genes silenced by DNA methylation and has been shown to be a very potent epigenetic drug in several hematological malignancies. In this report, we demonstrate that 5-aza-CdR exhibits high antineoplastic activity against anaplastic large cell lymphoma (ALCL), a rare CD30 positive non-Hodgkin lymphoma of T-cell origin. Low dose treatment of ALCL cell lines and xenografted tumors causes apoptosis and cell cycle arrest in vitro and in vivo. This is also reflected in genome-wide expression analyses, where genes related to apoptosis and cell death are amongst the most affected targets of 5-aza-CdR. Furthermore, we observed demethylation and re-expression of p16INK4A after drug administration and senescence associated β-galactosidase activity. Thus, our data provide evidence that 5-aza-CdR is highly efficient against ALCL and warrants further clinical evaluation for future therapeutic use. PMID:22687603

Alisertib in Combination With Vorinostat in Treating Patients With Relapsed or Recurrent Hodgkin Lymphoma, B-Cell Non-Hodgkin Lymphoma, or Peripheral T-Cell Lymphoma

Science.gov (United States)

2018-04-10

Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-Cell Lymphoma; Chronic Lymphocytic Leukemia; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Hepatosplenic T-Cell Lymphoma; Intraocular Lymphoma; Lymphomatous Involvement of Non-Cutaneous Extranodal Site; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Nodal Marginal Zone Lymphoma; Primary Cutaneous B-Cell Non-Hodgkin Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-Cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides and Sezary Syndrome; Recurrent Non-Hodgkin Lymphoma; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Small Intestinal Lymphoma; Splenic Marginal Zone Lymphoma; T-Cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Pan-SRC kinase inhibition blocks B-cell receptor oncogenic signaling in non-Hodgkin lymphoma.

Science.gov (United States)

Battistello, Elena; Katanayeva, Natalya; Dheilly, Elie; Tavernari, Daniele; Donaldson, Maria C; Bonsignore, Luca; Thome, Margot; Christie, Amanda L; Murakami, Mark A; Michielin, Olivier; Ciriello, Giovanni; Zoete, Vincent; Oricchio, Elisa

2018-05-24

In diffuse large B-cell lymphoma (DLBCL), activation of the B-cell receptor (BCR) promotes multiple oncogenic signals, which are essential for tumor proliferation. Inhibition of the Bruton's tyrosine kinase (BTK), a BCR downstream target, is therapeutically effective only in a subgroup of patients with DLBCL. Here, we used lymphoma cells isolated from patients with DLBCL to measure the effects of targeted therapies on BCR signaling and to anticipate response. In lymphomas resistant to BTK inhibition, we show that blocking BTK activity enhanced tumor dependencies from alternative oncogenic signals downstream of the BCR, converging on MYC upregulation. To completely ablate the activity of the BCR, we genetically and pharmacologically repressed the activity of the SRC kinases LYN, FYN, and BLK, which are responsible for the propagation of the BCR signal. Inhibition of these kinases strongly reduced tumor growth in xenografts and cell lines derived from patients with DLBCL independent of their molecular subtype, advancing the possibility to be relevant therapeutic targets in broad and diverse groups of DLBCL patients. © 2018 by The American Society of Hematology.

Silicone-induced granuloma of breast implant capsule (SIGBIC: similarities and differences with anaplastic large cell lymphoma (ALCL and their differential diagnosis

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Fleury EF

2017-03-01

Full Text Available Eduardo de Faria Castro Fleury,1 Milena Morais Rêgo,1 Luciana Costa Ramalho,1 Veronica Jorge Ayres,1 Rodrigo Oliveira Seleti,2 Carlos Alberto Pecci Ferreira,2 Decio Roveda Jr 2 1Radiology Department, IBCC – Instituto Brasileiro de Controle do Câncer, 2Irmandade Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil Abstract: Primary breast lymphoma is a rare disease and accounts for 0.5% of cases of breast cancer. Most primary breast lymphomas develop from B cells, and the involvement of T cells is rare. Anaplastic large cell lymphoma (ALCL is a recently discovered T-cell lymphoma associated with breast implants. Only a few cases have been reported to date. It is believed that the incidence of ALCL is increasing because of the increasing number of breast implants. The clinical presentation is variable and can manifest as a palpable mass in the breast or armpit, breast pain, or capsular contracture. Because of the rarity of the disease and the lack of knowledge to date, clinical diagnosis is often delayed, with consequent delays in treatment. The cause and pathogenesis have not been fully elucidated, and there are no evidence-based guidelines for diagnosis, treatment, or follow-up of this disease. We present a review of cases of patients with silicone breast implants, including ALCL, a rare type of breast cancer that is still under study, and silicone-induced granuloma of breast implant capsule and its differential diagnosis, and discuss if a silicone-induced granuloma of breast implant capsule could be the precursor of the disease. Keywords: lymphoma, granuloma, breast cancer, implant

Insight into resistance mechanism of anaplastic lymphoma kinase to alectinib and JH-VIII-157-02 caused by G1202R solvent front mutation

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Wang H

2018-05-01

Full Text Available Han Wang,1–3 Yao Wang,1–3 Wentao Guo,4 Bin Du,1–3 Xiaobing Huang,1–3 Riping Wu,1–3 Baoyu Yang,1–3 Xiaoyan Lin,1–3,5 Yilan Wu6 1Department of Medical Oncology, Fujian Medical University Union Hospital, Fuzhou, People’s Republic of China; 2Stem Cell Research Institute, Fujian Medical University, Fuzhou, People’s Republic of China; 3Fujian Key Laboratory of Translational Cancer Medicine, Fuzhou, People’s Republic of China; 4School of Pharmacy, Wenzhou Medical University, Wenzhou, People’s Republic of China; 5Graduate School of Education, Fujian Medical University, Fuzhou, People’s Republic of China; 6School of Nursing, Fujian University of Traditional Chinese Medicine, Fuzhou, People’s Republic of China Background: Mutated anaplastic lymphoma kinase (ALK drives the development of advanced non-small cell lung cancer (NSCLC. Most reported small-molecule inhibitors targeting the ALK domain do not display good inhibition of the G1202R solvent front mutation. The solvent front mutation was assumed to hinder drug binding. However, a different fact could be uncovered by the simulations reported in this study through a structural analog of alectinib (JH-VIII-157-02, which demonstrated potent effects against the G1202R mutation. Methods: Molecular docking, conventional molecular dynamics (MD simulations, free energy calculations, and umbrella sampling (US simulations were carried out to make clear the principles of the binding preferences of alectinib and JH-VIII-157-02 toward ALKWT and the ALK G1202R (ALKG1202R mutation. Results: JH-VIII-157-02 has similar binding affinities to both ALKWT and ALKG1202R whereas it has has a much lower binding affinity for alectinib to ALKG1202R. Analysis of individual energy terms indicate the major variation involves the van der Waals and entropy terms. Structural analysis reveals that the conformational change of the ATP-binding glycine-rich loop was primarily responsible for the alectinib

CTOP/ITE/MTX Compared With CHOP as the First-line Therapy for Newly Diagnosed Young Patients With T Cell Lymphoma

Science.gov (United States)

2017-11-10

ALK-negative Anaplastic Large Cell Lymphoma; Peripherial T Cell Lymphoma,Not Otherwise Specified; Angioimmunoblastic T Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Hepatosplenic T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma

Fusion Protein Cytokine Therapy After Rituximab in Treating Patients With B-Cell Non-Hodgkin Lymphoma

Science.gov (United States)

2015-06-03

Anaplastic Large Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Marginal Zone Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Comparison of primary thyroid lymphoma with anaplastic thyroid carcinoma on computed tomographic imaging

International Nuclear Information System (INIS)

Ishikawa, Hitoshi; Mitsuhashi, Norio; Niibe, Hideo

2002-01-01

Primary non-Hodgkin's lymphoma (LY) and anaplastic carcinoma (AC) of the thyroid gland are rare malignant tumors, and the initial symptoms of these diseases are very similar. The aim of our study was to compare the characteristics of the two diseases using computed tomographic (CT) scans in order to make an accurate differential diagnosis. Ten patients with LY and 10 with AC were analyzed. Differences in the CT findings of the two diseases were evaluated before treatment and statistically tested with either Student's t-test or the chi-square test. In the analysis of characteristics of CT imaging, the existence of calcification and necrosis, and heterogeneous tumor were dominant findings in AC, and there was a statistically significant difference in frequency between the two diseases (p<0.01). Calcification detected in AC was usually multiple and/or gross (mean size: φ8.2 mm). All lymphadenopathies were delineated as having the same homogeneous attenuation as the tumors in the thyroid gland in LY, but were shown as irregular rim enhancement in AC. The CT features of the two diseases are characteristic in terms of calcification, necrosis, and tumor composition. Evaluation by means of CT imaging is useful in distinguishing between LY and AC. (author)

Truncated ALK derived from chromosomal translocation t(2;5)(p23;q35) binds to the SH3 domain of p85-PI3K.

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Polgar, Doris; Leisser, Christina; Maier, Susanne; Strasser, Stephan; Rüger, Beate; Dettke, Markus; Khorchide, Maya; Simonitsch, Ingrid; Cerni, Christa; Krupitza, Georg

2005-02-15

The chromosomal translocation t(2;5)(p23;q35) is associated with "Anaplastic large cell lymphomas" (ALCL), a Non Hodgkin Lymphoma occurring in childhood. The fusion of the tyrosine kinase gene-ALK (anaplastic lymphoma kinase) on chromosome 2p23 to the NPM (nucleophosmin/B23) gene on chromosome 5q35 results in a 80 kDa chimeric protein, which activates the "survival" kinase PI3K. However, the binding mechanism between truncated ALK and PI3K is poorly understood. Therefore, we attempted to elucidate the molecular interaction between ALK and the regulatory p85 subunit of PI3K. Here we provide evidence that the truncated ALK homodimer binds to the SH3 domain of p85. This finding may be useful for the development of a new target-specific intervention.

Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

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Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

2012-08-01

Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

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

Bacterial Biofilm Infection Detected in Breast Implant-Associated Anaplastic Large-Cell Lymphoma.

Science.gov (United States)

Hu, Honghua; Johani, Khalid; Almatroudi, Ahmad; Vickery, Karen; Van Natta, Bruce; Kadin, Marshall E; Brody, Garry; Clemens, Mark; Cheah, Chan Yoon; Lade, Stephen; Joshi, Preeti Avinash; Prince, H Miles; Deva, Anand K

2016-06-01

A recent association between breast implants and the development of anaplastic large-cell lymphoma (ALCL) has been observed. The purpose of this study was to identify whether bacterial biofilm is present in breast implant-associated ALCL and, if so, to compare the bacterial microbiome to nontumor capsule samples from breast implants with contracture. Twenty-six breast implant-associated ALCL samples were analyzed for the presence of biofilm by real-time quantitative polymerase chain reaction, next-generation sequencing, fluorescent in situ hybridization, and scanning electron microscopy, and compared to 62 nontumor capsule specimens. Both the breast implant-associated ALCL and nontumor capsule samples yielded high mean numbers of bacteria (breast implant-associated ALCL, 4.7 × 10 cells/mg of tissue; capsule, 4.9 × 10 cells/mg of tissue). Analysis of the microbiome in breast implant-associated ALCL specimens showed significant differences with species identified in nontumor capsule specimens. There was a significantly greater proportion of Ralstonia spp. present in ALCL specimens compared with nontumor capsule specimens (p capsule specimens compared with breast implant-associated ALCL specimens (p < 0.001). Bacterial biofilm was visualized both on scanning electron microscopy and fluorescent in situ hybridization. This novel finding of bacterial biofilm and a distinct microbiome in breast implant-associated ALCL samples points to a possible infectious contributing cause. Breast implants are widely used in both reconstructive and aesthetic surgery, and strategies to reduce their contamination should be more widely studied and practiced. Risk, V.

Stages of Childhood Non-Hodgkin Lymphoma

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Patients with anaplastic large cell lymphoma have a receptor , called CD30, on the surface of their T ...

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Patient Version

Science.gov (United States)

Childhood non-Hodgkin lymphoma has different types including Burkitt, diffuse large B-cell, primary mediastinal B-cell, lymphoblastic, and anaplastic large cell lymphoma. Get information about the risk factors, symptoms, tests to diagnose, staging, and treatment of all types of newly diagnosed and recurrent NHL and lymphoproliferative disease in this expert-reviewed summary.

[Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors].

Science.gov (United States)

Zhang, Guowei; Wang, Huijuan; Ma, Zhiyong

2017-04-20

At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

Recent Advances and Prospect of Advanced Non-small Cell Lung Cancer Targeted 
Therapy: Focus on Small Molecular Tyrosine Kinase Inhibitors

Directory of Open Access Journals (Sweden)

Guowei ZHANG

2017-04-01

Full Text Available At present the treatment of advanced non-small cell lung cancer enters a targeted era and develops rapidly. New drugs appear constantly. Small molecular tyrosine kinase inhibitors have occupied the biggest piece of the territory, which commonly have a clear biomarker as predictor, and show remarkable effect in specific molecular classification of patients. The epidermal growth factor tyrosine kinase inhibitors such as gefitinib, erlotinib, icotinib and anaplastic lymphoma kinase tyrosine kinase inhibitors crizotinib have brought a milestone advance. In recent years new generations of tyrosine kinase inhibitors have achieved a great success in patients with acquired resistance to the above two kinds of drugs. At the same time new therapeutic targets are constantly emerging. So in this paper, we reviewed and summarized the important drugs and clinical trails on this topic, and made a prospect of the future development.

Vorinostat, Rituximab, Ifosfamide, Carboplatin, and Etoposide in Treating Patients With Relapsed or Refractory Lymphoma or Previously Untreated T-Cell Non-Hodgkin Lymphoma or Mantle Cell Lymphoma

Science.gov (United States)

2017-04-17

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage I Cutaneous T-cell Non-Hodgkin Lymphoma; Stage I Mantle Cell Lymphoma; Stage I Mycosis Fungoides/Sezary Syndrome; Stage II Cutaneous T-cell Non-Hodgkin Lymphoma; Stage II Mycosis Fungoides/Sezary Syndrome; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Waldenström Macroglobulinemia

Everolimus and Lenalidomide in Treating Patients With Relapsed or Refractory Non-Hodgkin or Hodgkin Lymphoma

Science.gov (United States)

2018-02-07

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Treatment Options for Childhood Non-Hodgkin Lymphoma

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Patients with anaplastic large cell lymphoma have a receptor , called CD30, on the surface of their T ...

Treatment Option Overview (Childhood Non-Hodgkin Lymphoma)

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... Patients with anaplastic large cell lymphoma have a receptor , called CD30, on the surface of their T ...

Crizotinib for Untreated Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer: An Evidence Review Group Perspective of a NICE Single Technology Appraisal.

Science.gov (United States)

Morgan, Philip; Woolacott, Nerys; Biswas, Mousumi; Mebrahtu, Teumzghi; Harden, Melissa; Hodgson, Robert

2017-09-01

As part of the National Institute for Health and Care Excellence (NICE) single technology appraisal process, the manufacturer of crizotinib submitted evidence on the clinical and cost effectiveness of crizotinib in untreated anaplastic lymphoma kinase-positive (ALK-positive) non-small-cell lung cancer (NSCLC). Crizotinib has previously been assessed by NICE for patients with previously treated ALK-positive NSCLC (TA 296). It was not approved in this previous appraisal, but had been made available through the cancer drugs fund. As part of this new appraisal, the company included a price discount patient access scheme (PAS). The Centre for Reviews and Dissemination and Centre for Health Economics Technology Appraisal Group at the University of York was commissioned to act as the independent Evidence Review Group (ERG). This article provides a description of the company's submission and the ERG's review and summarises the resulting NICE guidance issued in August 2016. The main clinical-effectiveness data were derived from a multicentre randomised controlled trial-PROFILE 1014-that compared crizotinib with pemetrexed chemotherapy in combination with carboplatin or cisplatin in patients with untreated non-squamous ALK-positive NSCLC. In the trial, crizotinib demonstrated improvements in progression-free survival (PFS) and overall survival (OS). The company's economic model was a three-state 'area under the curve' Markov model. The base-case incremental cost-effectiveness ratio (ICER) was estimated to be greater than £50,000 per quality-adjusted life-year (QALY) gained (excluding the PAS discount). The ERG assessment of the evidence submitted by the company raised a number of concerns. In terms of the clinical evidence, the OS benefit was highly uncertain due to the cross-over permitted in the trial and the immaturity of the data; only 26% of events had occurred by the data cut-off point. In the economic modelling, the most significant concerns related to the analysis

Clinical roundtable monograph: CD30 in lymphoma: its role in biology, diagnostic testing, and targeted therapy.

Science.gov (United States)

Sotomayor, Eduardo M; Young, Ken H; Younes, Anas

2014-04-01

CD30, a member of the tumor necrosis factor receptor superfamily, is a transmembrane glycoprotein receptor consisting of an extracellular domain, a transmembrane domain, and an intracellular domain. CD30 has emerged as an important molecule in the field of targeted therapy because its expression is generally restricted to specific disease types and states. The major cancers with elevated CD30 expression include Hodgkin lymphoma and anaplastic large T-cell lymphoma, and CD30 expression is considered essential to the differential diagnosis of these malignancies. Most commonly, CD30 expression is detected and performed by immunohistochemical staining of biopsy samples. Alternatively, flow cytometry analysis has also been developed for fresh tissue and cell aspiration specimens, including peripheral blood and bone marrow aspirate. Over the past several years, several therapeutic agents were developed to target CD30, with varying success in clinical trials. A major advance in the targeting of CD30 was seen with the development of the antibody-drug conjugate brentuximab vedotin, which consists of the naked anti-CD30 antibody SGN-30 conjugated to the synthetic antitubulin agent monomethyl auristatin E. In 2011, brentuximab vedotin was approved by the US Food and Drug Administration for use in Hodgkin lymphoma and anaplastic large cell lymphoma based on clinical trial data showing high response rates in these indications. Ongoing trials are examining brentuximab vedotin after autologous stem cell transplantation, as part of chemotherapy combination regimens, and in other CD30-expressing malignancies, including primary mediastinal large B-cell lymphomas, diffuse large B-cell lymphoma, lymphoma positive for Epstein-Barr virus, peripheral T-cell lymphoma not otherwise specified, and cutaneous anaplastic large cell lymphoma.

Clinicopathological study of primary gastric lymphoma

International Nuclear Information System (INIS)

Al-Shehabi, Zubeir A.; Saleh, Rana S.; Zezafon, Hassan B.

2007-01-01

Objective was to present a histopathologic and immunohistochemical analysis of primary gastric lymphomas that was reclassified according to the new World Health Organization classification of lymphoid neoplasms. We reviewed the morphological and immunohistochemical features of 28 patients with gastric lymphomas, diagnosed in the Department of pathology at the University Hospital of Tishreen University, Lattakia, Syria, during the period 1994-2003. Specimens were obtained from endoscopic and surgical biopsies. The immunohistochemical study was performed to analyze the immunophenotype of these lymphomas. Patients were aged 17-71 years. There was a slight predominance of females (male to female ratio, 13:15). Seventeen of the patients had tumors mainly located in the gastric antrum. Histologically, the most common lymphoma was of mucosa-associated lymphoid tissue (MALT) type (20 patients), also with diffuse large B-cell lymphoma (7 patients) and anaplastic large cell lymphoma (one patient). Our study demonstrates the different patterns of gastric lymphomas in Lattakia, Syria during a 10-year period in 28 Syrian patients, and reveals that the most primary gastric lymphomas are B-cell MALT lymphomas. (author)

The European Medicines Agency Review of Brentuximab Vedotin (Adcetris) for the Treatment of Adult Patients With Relapsed or Refractory CD30+ Hodgkin Lymphoma or Systemic Anaplastic Large Cell Lymphoma: Summary of the Scientific Assessment of the Committee for Medicinal Products for Human Use.

Science.gov (United States)

Gravanis, Iordanis; Tzogani, Kyriaki; van Hennik, Paula; de Graeff, Pieter; Schmitt, Petra; Mueller-Berghaus, Jan; Salmonson, Tomas; Gisselbrecht, Christian; Laane, Edward; Bergmann, Lothar; Pignatti, Francesco

2016-01-01

On October 25, 2012, a conditional marketing authorization valid throughout the European Union (EU) was issued for brentuximab vedotin for the treatment of adult patients with relapsed or refractory CD30+ Hodgkin lymphoma (HL) and for the treatment of adult patients with relapsed or refractory systemic anaplastic large cell lymphoma (sALCL). For HL, the indication is restricted to treatment after autologous stem cell transplantation (ASCT) or after at least two previous therapies when ASCT or multiagent chemotherapy is not a treatment option. Brentuximab vedotin is an antibody-drug conjugate (ADC) composed of a CD30-directed monoclonal antibody (recombinant chimeric IgG1) that is covalently linked to the antimicrotubule agent monomethyl auristatin E (MMAE). Binding of the ADC to CD30 on the cell surface initiates internalization of the MMAE-CD30 complex, followed by proteolytic cleavage that releases MMAE. The recommended dose is 1.8 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks. Brentuximab vedotin as a single agent was evaluated in two single-arm studies. Study SG035-003 included 102 patients with relapsed or refractory HL. An objective response was observed in 76 patients (75%), with complete remission in 34 (33%). Study SG035-004 included 58 patients with relapsed or refractory sALCL. An objective response was observed in 50 patients (86%), with complete remission in 34 (59%). The most frequently observed toxicities were peripheral sensory neuropathy, fatigue, nausea, diarrhea, neutropenia, vomiting, pyrexia, and upper respiratory tract infection. The present report summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of the product characteristics, are available on the European Medicines Agency website (http://www.ema.europa.eu). Brentuximab vedotin was approved in the European Union for the treatment of adult

Clinical analysis and prognostic significance of haemophagocytic lymphohistiocytosis-associated anaplastic large cell lymphoma in children.

Science.gov (United States)

Pasqualini, Claudia; Minard-Colin, Veronique; Saada, Veronique; Lamant, Laurence; Delsol, Georges; Patte, Catherine; Le Deley, Marie-Cécile; Valteau-Couanet, Dominique; Brugières, Laurence

2014-04-01

Haemophagocytic lymphohistiocytosis (HLH) has been rarely described in children treated for an anaplastic large-cell lymphoma (ALCL). We evaluated the incidence, the clinical and histological characteristics and the prognosis of HLH associated-ALCL. The medical, biological, cytological and histological data of patients treated for ALK-positive ALCL in the paediatric department of a single institution between 1975 and 2008 were analysed and assessed for HLH according to diagnosis criteria of the Histiocyte Society. Data concerning a series of 50 consecutive children with ALCL were reviewed. HLH-associated ALCL was observed in 12% of the patients. Lung involvement was significantly more frequent in HLH-associated ALCL patients than in the group without HLH (P = 0·004), as well as central nervous system (CNS) and bone marrow involvement (P = 0·001 and P = 0·007 respectively). The histological subtype in children with HLH-associated ALCL did not differ from that of the group without HLH. There was no significant difference between the two groups in 5-year EFS and OS (P = 0·91 and P > 0·99 respectively). In conclusion, HLH is not rare in paediatric ALCL. Despite a high incidence of visceral, CNS and bone marrow involvement, HLH does not seem to exert a significant impact on outcome in children treated for ALCL. © 2014 John Wiley & Sons Ltd.

Childhood Non-Hodgkin Lymphoma Treatment (PDQ®)—Health Professional Version

Science.gov (United States)

Childhood non-Hodgkin lymphoma (NHL) has three main types (aggressive mature B-cell [Burkitt, diffuse large B-cell, primary mediastinal B-cell], lymphoblastic and anaplastic large cell lymphoma) and other less common types of NHL. Get detailed information about the presentation, diagnosis, staging, prognosis, and treatment of all types of newly diagnosed and recurrent childhood NHL and lymphoproliferative disease in this summary for clinicians.

Redundant and nonredundant roles for Cdc42 and Rac1 in lymphomas developed in NPM-ALK transgenic mice

DEFF Research Database (Denmark)

Choudhari, Ramesh; Minero, Valerio Giacomo; Menotti, Matteo

2016-01-01

Increasing evidence suggests that Rho family GTPases could have a critical role in the biology of T-cell lymphoma. In ALK-rearranged anaplastic large cell lymphoma (ALCL), a specific subtype of T-cell lymphoma, the Rho family GTPases Cdc42 and Rac1 are activated by the ALK oncogenic activity. In ...

Phosphatidylinositol-3-kinase-dependent phosphorylation of SLP-76 by the lymphoma-associated ITK-SYK fusion-protein

International Nuclear Information System (INIS)

Hussain, Alamdar; Faryal, Rani; Nore, Beston F.; Mohamed, Abdalla J.; Smith, C.I. Edvard

2009-01-01

Recurrent chromosomal translocations have long been implicated in various types of lymphomas and other malignancies. Novel recurrent t(5;9)(q33;q22) has been recently discovered in un-specified peripheral T-cell lymphoma. To elucidate the role of this translocation, the corresponding fusion construct encoding the N-terminal portion of the ITK kinase and the C-terminal catalytic region of the SYK kinase was generated. We herein show that the ITK-SYK fusion-protein is constitutively active. Moreover, we demonstrate that ITK-SYK is phosphorylated on key tyrosine residues and is capable of potently phosphorylating the related adapter proteins BLNK and SLP-76. In transiently transfected cells, SYK was phosphorylated at Y352 but not detectably at the activation-loop tyrosines Y525/Y526. In contrast, ITK-SYK was phosphorylated both at Y212 and the activation-loop tyrosines Y385/Y386, corresponding to Y352 and Y525/Y526 in SYK, respectively. In resting primary lymphocytes, ITK-SYK predominantly localizes to the cell surface. In addition, we demonstrate that following stimulation, the ITK-SYK fusion-protein in cell lines translocates to the cell membrane and, moreover, that this phenomenon as well as SLP-76 phosphorylation are blocked upon phosphatidylinositol-3-kinase (PI3-kinase) inhibition.

Hematopoietic Cell Transplantation for Systemic Mature T-Cell Non-Hodgkin Lymphoma

Science.gov (United States)

Smith, Sonali M.; Burns, Linda J.; van Besien, Koen; LeRademacher, Jennifer; He, Wensheng; Fenske, Timothy S.; Suzuki, Ritsuro; Hsu, Jack W.; Schouten, Harry C.; Hale, Gregory A.; Holmberg, Leona A.; Sureda, Anna; Freytes, Cesar O.; Maziarz, Richard Thomas; Inwards, David J.; Gale, Robert Peter; Gross, Thomas G.; Cairo, Mitchell S.; Costa, Luciano J.; Lazarus, Hillard M.; Wiernik, Peter H.; Maharaj, Dipnarine; Laport, Ginna G.; Montoto, Silvia; Hari, Parameswaran N.

2013-01-01

Purpose To analyze outcomes of hematopoietic cell transplantation (HCT) in T-cell non-Hodgkin lymphoma. Patients and Methods Outcomes of 241 patients (112 anaplastic large-cell lymphoma, 102 peripheral T-cell lymphoma not otherwise specified, 27 angioimmunoblastic T-cell lymphoma) undergoing autologous HCT (autoHCT; n = 115; median age, 43 years) or allogeneic HCT (alloHCT; n = 126; median age, 38 years) were analyzed. Primary outcomes were nonrelapse mortality (NRM), relapse/progression, progression-free survival (PFS), and overall survival (OS). Patient, disease, and HCT-related variables were analyzed in multivariate Cox proportional hazard models to determine association with outcomes. Results AutoHCT recipients were more likely in first complete remission (CR1; 35% v 14%; P = .001) and with chemotherapy-sensitive disease (86% v 60%; P < .001), anaplastic large-cell histology (53% v 40%; P = .04), and two or fewer lines of prior therapy (65% v 44%; P < .001) compared with alloHCT recipients. Three-year PFS and OS of autoHCT recipients beyond CR1 were 42% and 53%, respectively. Among alloHCT recipients who received transplantations beyond CR1, 31% remained progression-free at 3 years, despite being more heavily pretreated and with more refractory disease. NRM was 3.5-fold higher (95% CI, 1.80 to 6.99; P < .001) for alloHCT. In multivariate analysis, chemotherapy sensitivity (hazard ratio [HR], 1.8; 95% CI, 1.16 to 2.87) and two or fewer lines of pretransplantation therapy (HR, 5.02; 95% CI, 2.15 to 11.72) were prognostic of survival. Conclusion These data describe the roles of autoHCT and alloHCT in T-cell non-Hodgkin lymphoma and suggest greater effectiveness earlier in the disease course, and limited utility in multiply relapsed disease. Notably, autoHCT at relapse may be a potential option for select patients, particularly those with anaplastic large-cell lymphoma histology. PMID:23897963

Stages of Non-Small Cell Lung Cancer

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

Treatment Options by Stage (Non-Small Cell Lung Cancer)

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

Treatment Option Overview (Non-Small Cell Lung Cancer)

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

General Information about Non-Small Cell Lung Cancer

Science.gov (United States)

... Common Cancer Types Recurrent Cancer Common Cancer Types Bladder Cancer Breast Cancer Colorectal Cancer Kidney (Renal Cell) Cancer ... certain genes, such as the epidermal growth factor receptor (EGFR) gene or the anaplastic lymphoma kinase (ALK) ...

Breast Implant–Associated Anaplastic Large-Cell Lymphoma: Long-Term Follow-Up of 60 Patients

Science.gov (United States)

Miranda, Roberto N.; Aladily, Tariq N.; Prince, H. Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E.; Amin, Mitual B.; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S.; Shifrin, David A.; O'Malley, Dennis P.; Cheah, Chan Y.; Bacchi, Carlos E.; Gualco, Gabriela; Li, Shiyong; Keech, John A.; Hochberg, Ephram P.; Carty, Matthew J.; Hanson, Summer E.; Mustafa, Eid; Sanchez, Steven; Manning, John T.; Xu-Monette, Zijun Y.; Miranda, Alonso R.; Fox, Patricia; Bassett, Roland L.; Castillo, Jorge J.; Beltran, Brady E.; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H.; Medeiros, L. Jeffrey

2014-01-01

Purpose Breast implant–associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. Patients and Methods We reviewed the literature for all published cases of breast implant–associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. Results The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Conclusion Most patients with breast implant–associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants. PMID:24323027

Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients.

Science.gov (United States)

Miranda, Roberto N; Aladily, Tariq N; Prince, H Miles; Kanagal-Shamanna, Rashmi; de Jong, Daphne; Fayad, Luis E; Amin, Mitual B; Haideri, Nisreen; Bhagat, Govind; Brooks, Glen S; Shifrin, David A; O'Malley, Dennis P; Cheah, Chan Y; Bacchi, Carlos E; Gualco, Gabriela; Li, Shiyong; Keech, John A; Hochberg, Ephram P; Carty, Matthew J; Hanson, Summer E; Mustafa, Eid; Sanchez, Steven; Manning, John T; Xu-Monette, Zijun Y; Miranda, Alonso R; Fox, Patricia; Bassett, Roland L; Castillo, Jorge J; Beltran, Brady E; de Boer, Jan Paul; Chakhachiro, Zaher; Ye, Dongjiu; Clark, Douglas; Young, Ken H; Medeiros, L Jeffrey

2014-01-10

Breast implant-associated anaplastic large-cell lymphoma (ALCL) is a recently described clinicopathologic entity that usually presents as an effusion-associated fibrous capsule surrounding an implant. Less frequently, it presents as a mass. The natural history of this disease and long-term outcomes are unknown. We reviewed the literature for all published cases of breast implant-associated ALCL from 1997 to December 2012 and contacted corresponding authors to update clinical follow-up. The median overall survival (OS) for 60 patients was 12 years (median follow-up, 2 years; range, 0-14 years). Capsulectomy and implant removal was performed on 56 of 60 patients (93%). Therapeutic data were available for 55 patients: 39 patients (78%) received systemic chemotherapy, and of the 16 patients (28%) who did not receive chemotherapy, 12 patients opted for watchful waiting and four patients received radiation therapy alone. Thirty-nine (93%) of 42 patients with disease confined by the fibrous capsule achieved complete remission, compared with complete remission in 13 (72%) of 18 patients with a tumor mass. Patients with a breast mass had worse OS and progression-free survival (PFS; P = .052 and P = .03, respectively). The OS or PFS were similar between patients who received and did not receive chemotherapy (P = .44 and P = .28, respectively). Most patients with breast implant-associated ALCL who had disease confined within the fibrous capsule achieved complete remission. Proper management for these patients may be limited to capsulectomy and implant removal. Patients who present with a mass have a more aggressive clinical course that may be fatal, justifying cytotoxic chemotherapy in addition to removal of implants.

Primary "cutaneous" T-cell anaplastic large cell lymphoma, CD30+, neutrophil-rich variant with subcutaneous panniculitic lesions, in a post-renal transplant patient: report of unusual case and literature review.

Science.gov (United States)

Salama, S

2005-06-01

Posttransplantation lymphoproliferative disorders (PTLD) presenting clinically in the skin are rare and usually of B-cell phenotype. Only 7 cases of cutaneous T-cell PTLD have been previously reported, mostly mycosis fungoides type, with no known cases of "cutaneous" presentation by CD30 (Ki-1) anaplastic large cell lymphoma (ALCL). The case reported is a 59-year-old male who developed multiple skin nodules on the right leg, 6 years following renal transplantation. Initial biopsy showed ALCL involving the dermis with a background rich in neutrophils. The neoplastic cells were of T-cell phenotype, strongly CD30 with typical staining, and BCL-2 positive, but P53 negative. No EBV was detected by IHC, ISH, or DNA analysis. One year later, he developed painful subcutaneous nodules with surrounding erythema, resembling deep pustules or panniculitis, which on biopsy showed preferential involvement of the subcutaneous fat and prominent component of neutrophils. Twenty-two months following diagnosis, he died of cardiac failure with terminal myocardial infarct. There was however no clinical evidence of systemic spread of the lymphoma.This report adds to the clinical and morphologic spectrum of these rare "cutaneous" lymphomas of T-cell lineage arising in the posttransplantation setting, and suggests that EBV does not play a role in their pathogenesis.

Anaplastic thyroid cancer

Science.gov (United States)

... page: //medlineplus.gov/ency/article/000352.htm Anaplastic thyroid cancer To use the sharing features on this page, ... of cancer of the thyroid gland. Causes Anaplastic thyroid cancer is an invasive type of thyroid cancer that ...

CK1δ in lymphoma: gene expression and mutation analyses and validation of CK1δ kinase activity for therapeutic application

Directory of Open Access Journals (Sweden)

Brigitte Sophia Winkler

2015-02-01

Full Text Available The prognosis of lymphoid neoplasms has improved considerably during the last decades. However, treatment response for some lymphoid neoplasms is still poor, indicating the need for new therapeutic approaches. One promising new strategy is the inhibition of kinases regulating key signal transduction pathways, which are of central importance in tumorigenesis. Kinases of the CK1 family may represent an attractive drug target since CK1 expression and/or activity are associated with the pathogenesis of malignant diseases. Over the last years efforts were taken to develop highly potent and selective CK1-specific inhibitor compounds and their therapeutic potential has now to be proved in pre-clinical trials. Therefore, we analyzed expression and mutational status of CK1δ in several cell lines representing established lymphoma entities, and also measured the mRNA expression level in primary lymphoma tissue as well as non-neoplastic blood cells. For a selection of lymphoma cell lines we furthermore determined CK1δ kinase activity and demonstrated therapeutic potential of CK1-specific inhibitors as a putative therapeutic option in the treatment of lymphoid neoplasms.

FDG-PET in lymphomas

International Nuclear Information System (INIS)

Knapp, W. H.

2009-01-01

Lymphomas are a heterogeneous group of neoplasms in which two major subtypes are distinguished, Hodgkin's disease (HD) and non-Hodgkin's lymphomas (NHL). The incidence of lymphomas is about 20 per 100000 inhabitants (Jemal et al 2002) and 7-8 times higher than that of HD. Since NHL has a worse prognosis, the death rates of NHL are 14 times higher than those for HD. Lymphomas account for about 4 % of all cancer incidences. In USA, lymphomas are the fifth most frequent cancer type diagnosed and the third most frequent form of cancer death (Jemal et al 2002). Concerning HD, there is a preponderance for males with a gender ratio of 1.33 for incidence and 1.12 for mortality. For NHL incidences and mortality rates of genders are almost equal. HL comprises different subtypes among which nodular sclerosis is the most frequent one (60-70 %). Other histopathologic subtypes are those of mixed cellularity, lymphocyte reach and lymphocyte depleted characteristics. The most frequent subgroup of NHL are B-cell lymphomas (80-90 % of all NHL). Two thirds of this subgroup are diffuse large B-cell lymphomas, one third follicular lymphomas. Other (less frequent) subtypes are mantle cell, peripheral T-cell, anaplastic large-cell-lymphomas etc. For NHL increasing incidence has been observed in the last decades. Within 15 years the incidence increased by 50 % in the USA (Jemal et al 2002). Etiology of lymphomas is still unknown. In a certain proportion of NHL viral causes are assumed. Diagnosis is based on histology (needle biopsy) with consecutive sub typing. Prognosis depends on stage, expansion state, histology and proliferation rates. (author)

Dysregulated choline metabolism in T-cell lymphoma: role of choline kinase-α and therapeutic targeting

International Nuclear Information System (INIS)

Xiong, J; Bian, J; Wang, L; Zhou, J-Y; Wang, Y; Zhao, Y; Wu, L-L; Hu, J-J; Li, B; Chen, S-J; Yan, C; Zhao, W-L

2015-01-01

Cancer cells have distinct metabolomic profile. Metabolic enzymes regulate key oncogenic signaling pathways and have an essential role on tumor progression. Here, serum metabolomic analysis was performed in 45 patients with T-cell lymphoma (TCL) and 50 healthy volunteers. The results showed that dysregulation of choline metabolism occurred in TCL and was related to tumor cell overexpression of choline kinase-α (Chokα). In T-lymphoma cells, pharmacological and molecular silencing of Chokα significantly decreased Ras-GTP activity, AKT and ERK phosphorylation and MYC oncoprotein expression, leading to restoration of choline metabolites and induction of tumor cell apoptosis/necropotosis. In a T-lymphoma xenograft murine model, Chokα inhibitor CK37 remarkably retarded tumor growth, suppressed Ras-AKT/ERK signaling, increased lysophosphatidylcholine levels and induced in situ cell apoptosis/necropotosis. Collectively, as a regulatory gene of aberrant choline metabolism, Chokα possessed oncogenic activity and could be a potential therapeutic target in TCL, as well as other hematological malignancies with interrupted Ras signaling pathways

Pseudocarcinomatous hyperplasia in anaplastic large cell lymphoma, a mimicker of poorly differentiated squamous cell carcinoma: report of a case and review of the literature.

Science.gov (United States)

Price, Alexandra; Miller, Jason H; Junkins-Hopkins, Jacqueline M

2015-11-01

Pseudocarcinomatous hyperplasia can occasionally be observed in biopsies of CD30-positive lymphoproliferative disorders. It is important to be cognizant of this association, because epithelial hyperproliferation can overshadow large atypical lymphoid cells, leading to an erroneous diagnosis of squamous cell carcinoma (SCC) or keratoacanthoma. Herein, we present a case of anaplastic large cell lymphoma (ALCL) with pseudocarcinomatous hyperplasia simulating a poorly differentiated carcinoma and review the literature on this subject. Immunohistochemical staining with p63 helped delineate the infiltrating tongues of pseudocarcinomatous hyperplasia from the malignant infiltrate. We present this case to raise awareness of the potential for pseudocarcinomatous hyperplasia to occur in the setting of CD30+ lymphoproliferative disorders. Clinicians and dermatopathologists should consider the possibility of ALCL or lymphomatoid papulosis when examining lesions with features of inflamed SCC, especially if the tumor presents on a site or in a patient that is not typical of SCC. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor

NARCIS (Netherlands)

Debelenko, LV; Arthur, DC; Pack, SD; Helman, LJ; Schrump, DS; Tsokos, M

Inflammatory myofibroblastic tumor (IMT) is a rare childhood neoplasm. The natural history of this disease is poorly understood. Recently chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been implicated in this tumor. We have studied a case of ALK-positive soft

Meta-analysis of Neuroblastomas Reveals a Skewed ALK Mutation Spectrum in Tumors with MYCN Amplification

NARCIS (Netherlands)

de Brouwer, Sara; de Preter, Katleen; Kumps, Candy; Zabrocki, Piotr; Porcu, Michaël; Westerhout, Ellen M.; Lakeman, Arjan; Vandesompele, Jo; Hoebeeck, Jasmien; van Maerken, Tom; de Paepe, Anne; Laureys, Geneviève; Schulte, Johannes H.; Schramm, Alexander; van den Broecke, Caroline; Vermeulen, Joëlle; van Roy, Nadine; Beiske, Klaus; Renard, Marleen; Noguera, Rosa; Delattre, Olivier; Janoueix-Lerosey, Isabelle; Kogner, Per; Martinsson, Tommy; Nakagawara, Akira; Ohira, Miki; Caron, Huib N.; Eggert, Angelika; Cools, Jan; Versteeg, Rogier; Speleman, Frank

2010-01-01

Purpose: Activating mutations of the anaplastic lymphoma kinase (ALK) were recently described in neuroblastoma. We carried out a meta-analysis of 709 neuroblastoma tumors to determine their frequency and mutation spectrum in relation to genomic and clinical parameters, and studied the prognostic

Ipilimumab and Local Radiation Therapy in Treating Patients With Recurrent Melanoma, Non-Hodgkin Lymphoma, Colon, or Rectal Cancer

Science.gov (United States)

2017-01-12

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Colon Cancer; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Melanoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Rectal Cancer; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Clinical significance of cyclin-dependent kinase inhibitor p27Kip1 expression and proliferation in non-Hodgkin's lymphoma

DEFF Research Database (Denmark)

Møller, Michael Boe; Skjødt, Karsten; Mortensen, Leif Spange

1999-01-01

The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL...... between p27Kip1 and Ki-67 expression. Low expression of p27Kip1, defined as nuclear p27Kip1 expression in lymphomas behaved differently as those with low p27Kip1...... expression tended to do better. Likewise, a high proliferation rate (Ki-67 >40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27Kip1, and not Ki-67, maintained independent prognostic significance...

Intravesicular taxane-induced dermatotoxicity in a 78-year-old man with urothelial carcinoma and primary cutaneous anaplastic large cell lymphoma.

Science.gov (United States)

J Pelletier, Daniel; O'Donnell, Michael; Stone, Mary Seabury; Liu, Vincent

2018-06-01

Patients treated with intravesical bacillus Calmette-Guérin therapy for urothelial carcinoma often become refractory and experience recurrent disease, thus necessitating alternative intravesical treatment modalities if the patient is to be spared the morbidities associated with radical cystectomy. Intravesical treatment with taxane-based chemotherapy, such as docetaxel, has gained traction in urologic oncology, proving to be an effective salvage therapy in such patients. Systemic taxane-based chemotherapeutic regimens have long been used in several advanced malignancies, and their systemic side-effects and associated histologic correlates have been extensively documented. In contrast to adverse effects associated with systemic administration, intravesical taxane administration has thus far proven to be well-tolerated, with little to no systemic absorption. To our knowledge, features of taxane-induced systemic effects have not been reported in this setting. Herein, we report a case of a patient with recurrent urothelial carcinoma treated with intravesical docetaxel, along with primary cutaneous anaplastic large cell lymphoma, who developed characteristic dermatotoxic histologic findings associated with intravenous taxane administration. As such histopathologic findings often represent close mimickers of neoplastic and infectious etiologies, knowledge of the potential for systemic manifestations of taxane therapy in patients treated topically may prevent potentially costly diagnostic pitfalls. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anaplastic large cell lymphoma of the breast arising around mammary implant capsule: an Italian report.

Science.gov (United States)

Farace, Francesco; Bulla, Antonio; Marongiu, Francesco; Campus, Gian Vittorio; Tanda, Francesco; Lissia, Amelia; Cossu, Antonio; Fozza, Claudio; Rubino, Corrado

2013-06-01

Anaplastic large cell lymphoma (ALCL) of the breast is a very rare nonepithelial neoplasm. In the literature, this tumor has sometimes been described in proximity of breast implants (60 implant-related ALCL reported). In 2010, a patient who had undergone a right mastectomy and tissue expander/implant reconstruction for a "ductal" carcinoma 10 years before was referred to our unit for evaluation. On examination, an enlarged reconstructed right breast was found. The reconstructed breast did not show tenderness or signs of infection, ulceration, or breakdown. Mammograms and ultrasound scan did not suggest the presence of recurrent cancer, infection, deflation of the implant, or severe capsule contracture. The patient underwent mammary implant replacement. About 3 weeks after surgery, the patient came back to our unit for a new mild enlargement of the operated breast and the implant was removed. Three months later, the patient returned with a skin lesion in the right parasternal region. A radical excisional biopsy was performed under local anesthesia and the diagnosis of ALK-1-negative ALCL was finally made. The clinical and histological diagnosis of this disease is difficult as it can often be mistaken for a simple seroma (breast enlargement), an infection, or an unspecific reaction to silicone (redness and/or tension of the skin, itching, and fever). We strongly suggest considering ALCL in any patient with a spontaneous breast seroma lasting more than 6 months after mammary prosthesis implantation. The suspicion of ALCL must be suggested to the pathologist immediately. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The importance of Notch signaling in peripheral T-cell lymphomas

DEFF Research Database (Denmark)

Kamstrup, Maria Rørbæk; Biskup, Edyta; Gjerdrum, Lise Mette Rahbek

2014-01-01

Peripheral T-cell lymphomas (PTLs) represent an area of high medical need. Previously, we demonstrated high expression of Notch, a known oncogene, in primary cutaneous anaplastic large cell lymphoma (ALCL). In this study, we performed immunohistochemical staining for Notch1 in lymph nodes from PTL...... cases) (p > 0.05). In the ALK+ ALCL cell line, Karpas-299, pharmacological inhibition of Notch with γ-secretase inhibitor (GSI) I was far more potent than with GSI IX, XX and XXI with regard to cell viability and apoptosis. In conclusion, PTL tumor cells have prominent Notch1 expression and treatment...... with Notch inhibitors has cytotoxic effects....

Postoperative radiotherapy of supratentorial anaplastic gliomas

International Nuclear Information System (INIS)

Wendt, T.G.; Bacherler, B.; Baumer, K.; Rohloff, R.; Willich, N.

1986-01-01

Between 1970 and 1983, 149 patients with high grade anaplastic supratentorial gliomas received a postoperative irradiation during primary treatment. 118 out of these patients had an anaplastic astrocytoma, 18 an anaplastic oligodendroglioma, and 13 an anaplastic ependymoma. Most of these patients were treated by irradiation of a great volume with 50 Gy within five weeks, the others by irradiation of the total brain with 50 Gy within five weeks and saturation with 10 Gy within one week. The one-year survival of the total group was 35.5% and the two-year survival 10.6%. Patients at an age of less than 40 years show a significantly longer survival than older patients (one-year survival rates 40% and 30.7%, respectively). Patients suffering from anaplastic tumors with astrocytic and oligodendrocytic differentiation have a comparable prognosis. Patients suffering from anaplastic tumors with ependymal differentiation, however, have prolonged survival times. The therapy results of different treatment methods are discussed using the communications of literature. (orig.) [de

Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers

Science.gov (United States)

2018-05-21

Adenoid Cystic Carcinoma; Adnexal Carcinoma; Apocrine Carcinoma; Eccrine Porocarcinoma; Extraocular Cutaneous Sebaceous Carcinoma; Hidradenocarcinoma; Keratoacanthoma; Malignant Sweat Gland Neoplasm; Merkel Cell Carcinoma; Microcystic Adnexal Carcinoma; NK-Cell Lymphoma, Unclassifiable; Non-Melanomatous Lesion; Paget Disease; Papillary Adenocarcinoma; Primary Cutaneous Mucinous Carcinoma; Refractory Anaplastic Large Cell Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Refractory Mycosis Fungoides; Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Sezary Syndrome; Signet Ring Cell Carcinoma; Skin Basal Cell Carcinoma; Skin Basosquamous Cell Carcinoma; Skin Squamous Cell Carcinoma; Spiradenocarcinoma; Squamous Cell Carcinoma of Unknown Primary Origin; Stage III Skin Cancer; Stage IV Skin Cancer; Sweat Gland Carcinoma; Trichilemmocarcinoma; Vulvar Squamous Cell Carcinoma

High ALK mRNA expression has a negative prognostic significance in rhabdomyosarcoma

OpenAIRE

Bonvini, P; Zin, A; Alaggio, R; Pawel, B; Bisogno, G; Rosolen, A

2013-01-01

Background: Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase aberrantly expressed in cancer, but its clinical and functional importance remain controversial. Mutation or amplification of ALK, as well as its expression levels assessed by conventional immunohistochemistry methods, has been linked to prognosis in cancer, although with potential bias because of the semi-quantitative approaches. Herein, we measured ALK mRNA expression in rhabdomyosarcoma (RMS) and determined its clin...

Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4–ALK-rearranged non–small–cell lung cancer harbored coexisting EGFR mutation

International Nuclear Information System (INIS)

Miyanaga, Akihiko; Kawamoto, Masashi; Tsuchiya, Shinichi; Hagiwara, Koichi; Soda, Manabu; Takeuchi, Kengo; Yamamoto, Nobuyuki; Mano, Hiroyuki; Ishikawa, Yuichi; Gemma, Akihiko; Shimizu, Kumi; Noro, Rintaro; Seike, Masahiro; Kitamura, Kazuhiro; Kosaihira, Seiji; Minegishi, Yuji; Shukuya, Takehito; Yoshimura, Akinobu

2013-01-01

The EML4–ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non–small–cell lung cancers (NSCLCs). The EML4–ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS. We report that a case of EML4–ALK-positive NSCLC with EGFR mutation had a response of stable disease to both an EGFR tyrosine kinase inhibitor (EGFR-TKI) and ALK inhibitor. We described the first clinical report of a patient with EML4–ALK-positive NSCLC with EGFR mutation that had a response of stable disease to both single-agent EGFR-TKI and ALK inhibitor. EML4–ALK translocation may be associated with resistance to EGFR-TKI, and EGFR signaling may contribute to resistance to ALK inhibitor in EML4–ALK-positive NSCLC

Plasma cytokine profiles at diagnosis in pediatric patients with non-hodgkin lymphoma

DEFF Research Database (Denmark)

Mellgren, Karin; Hedegaard, Chris Juul; Schmiegelow, Kjeld

2012-01-01

Non-Hodgkin lymphoma (NHL) has been associated with elevated levels of inflammatory and immune-regulating cytokines, and polymorphisms in the genes encoding interleukin (IL)-10 and tumor necrosis factor (TNF)-α have been associated with increased incidence of certain subtypes of NHL. The aim......, between 1995 and 2008. Cytokines and growth factors were measured in serum using the Luminex platform by application of a 30-plex kit. Levels of IL-6, IL-2R, IL-10, TNF-RI, and macrophage inflammatory protein-1α were significantly higher in patients with anaplastic large-cell lymphoma compared...... with patients diagnosed with B-cell lymphomas and lymphoblastic lymphomas. High levels of IL-4, IL-13, TNF-RI, and epidermal growth factor were associated with a poorer general condition at diagnosis. The present study suggests that NHL subgrouping and the general condition of pediatric patients at diagnosis...

Primary anaplastic large cell lymphoma of the breast arising in reconstruction mammoplasty capsule of saline filled breast implant after radical mastectomy for breast cancer: an unusual case presentation

Directory of Open Access Journals (Sweden)

Sur Monalisa

2009-04-01

Full Text Available Abstract Background Primary non-Hodgkin lymphoma (NHL of the breast represents 0.04–0.5% of malignant lesions of the breast and accounts for 1.7–2.2% of extra-nodal NHL. Most primary cases are of B-cell phenotype and only rare cases are of T-cell phenotype. Anaplastic large cell lymphoma (ALCL is a rare T-cell lymphoma typically seen in children and young adults with the breast being one of the least common locations. There are a total of eleven cases of primary ALCL of the breast described in the literature. Eight of these cases occurred in proximity to breast implants, four in relation to silicone breast implant and three in relation to saline filled breast implant with three out of the eight implant related cases having previous history of breast cancer treated surgically. Adjuvant postoperative chemotherapy is given in only one case. Secondary hematological malignancies after breast cancer chemotherapy have been reported in literature. However in contrast to acute myeloid leukemia (AML, the association between lymphoma and administration of chemotherapy has never been clearly demonstrated. Case Presentation In this report we present a case of primary ALCL of the breast arising in reconstruction mamoplasty capsule of saline filled breast implant after radical mastectomy for infiltrating ductal carcinoma followed by postoperative chemotherapy twelve years ago. Conclusion Primary ALK negative ALCL arising at the site of saline filled breast implant is rare. It is still unclear whether chemotherapy and breast implantation increases risk of secondary hematological malignancies significantly. However, it is important to be aware of these complications and need for careful pathologic examination of tissue removed for implant related complications to make the correct diagnosis for further patient management and treatment. It is important to be aware of this entity at this site as it can be easily misdiagnosed on histologic grounds and to exclude

Classical and anaplastic seminoma: Difference in survival

International Nuclear Information System (INIS)

Bobba, V.S.; Mittal, B.B.; Hoover, S.V.; Kepka, A.

1987-01-01

The authors undertook a retrospective study of seminoma patients treated with radiation therapy between 1961 and 1985. The classical group consisted of 66 patients, of whom 47 were stage I and 19 were stage II. The anaplastic group consisted of 21 patients, of whom 11 were stage I, nine were stage II, and one was stage III. The median follow-up was 66 months. The five-year crude survival rate for the entire group was 92%, for classical 96%, and for anaplastic 78% (P<.005). Similarly, there was a significant difference (P<.005) in actuarial relapse-free survival at 5 years between classical and anaplastic seminoma. For classical stage I, the relapse-free actuarial 5-year survival rate was 96; for classical stage II, 84%. For anaplastic stage I the relapse-free actuarial 5-year survival rate was 82%, and for stage II 75%. Six patients in the classical group (9%) failed treatment. In the anaplastic group, five patients or 24 failed treatment. Therefore, the authors' data suggest a difference in survival and failure rate between classical and anaplastic seminoma. Extratesticular seminoma with anaplastic histology has an even worse prognosis

Dose-Effect Relationship of Alkylating Agents on Testicular Function in Male Survivors of Childhood Lymphoma.

Science.gov (United States)

Servitzoglou, Marina; De Vathaire, Florent; Oberlin, Odile; Patte, Catherine; Thomas-Teinturier, Cécile

2015-01-01

The purpose of our study was to assess the gonadal function in male survivors of childhood lymphoma. We studied 171 male survivors of childhood lymphoma (83 with B-cell non-Hodgkin lymphoma [B-NHL], 32 with T-cell non-Hodgkin lymphoma [T-NHL], 50 with Hodgkin lymphoma [HL], and 6 with anaplastic large-cell lymphoma [ALCL]), measuring follicle-stimulating hormone [FSH] and luteinizing hormone [LH] levels at a median age of 21.1 (17-30.4) years after a median delay of 9.3 (2-22.4) years from treatment. FSH levels were above normal range (≥10 IU/L) in 42.1% and LH levels ≥8 IU/L in only 8.9% of survivors. In multivariate analysis, only the following chemotherapeutic agents were associated with higher FSH or LH levels: cyclophosphamide (P alkylating agents on childhood lymphoma survivors is dose dependent and not correlated to diagnosis, age, or pubertal status at diagnosis.

Activity of the novel BCR kinase inhibitor IQS019 in preclinical models of B-cell non-Hodgkin lymphoma

Directory of Open Access Journals (Sweden)

P. Balsas

2017-03-01

Full Text Available Abstract Background Pharmacological inhibition of B cell receptor (BCR signaling has recently emerged as an effective approach in a wide range of B lymphoid neoplasms. However, despite promising clinical activity of the first Bruton’s kinase (Btk and spleen tyrosine kinase (Syk inhibitors, a small fraction of patients tend to develop progressive disease after initial response to these agents. Methods We evaluated the antitumor activity of IQS019, a new BCR kinase inhibitor with increased affinity for Btk, Syk, and Lck/Yes novel tyrosine kinase (Lyn, in a set of 34 B lymphoid cell lines and primary cultures, including samples with acquired resistance to the first-in-class Btk inhibitor ibrutinib. Safety and efficacy of the compound were then evaluated in two xenograft mouse models of B cell lymphoma. Results IQS019 simultaneously engaged a rapid and dose-dependent de-phosphorylation of both constitutive and IgM-activated Syk, Lyn, and Btk, leading to impaired cell proliferation, reduced CXCL12-dependent cell migration, and induction of caspase-dependent apoptosis. Accordingly, B cell lymphoma-bearing mice receiving IQS019 presented a reduced tumor outgrowth characterized by a decreased mitotic index and a lower infiltration of malignant cells in the spleen, in tight correlation with downregulation of phospho-Syk, phospho-Lyn, and phospho-Btk. More interestingly, IQS019 showed improved efficacy in vitro and in vivo when compared to the first-in-class Btk inhibitor ibrutinib, and was active in cells with acquired resistance to this latest. Conclusions These results define IQS019 as a potential drug candidate for a variety of B lymphoid neoplasms, including cases with acquired resistance to current BCR-targeting therapies.

Prevalence and natural history of ALK positive non-small-cell lung cancer and the clinical impact of targeted therapy with ALK inhibitors

Directory of Open Access Journals (Sweden)

Chia PL

2014-11-01

Full Text Available Puey Ling Chia,1 Paul Mitchell,1 Alexander Dobrovic,2–4 Thomas John1,2,4 1Department of Medical Oncology, Olivia-Newton John Cancer and Wellness Centre, Victoria, Australia; 2Ludwig Institute for Cancer Research, Austin Health, Victoria, Australia; 3Department of Pathology, University of Melbourne, Victoria, Australia; 4School of Cancer Medicine, La Trobe University, Victoria, Australia Abstract: Improved understanding of molecular drivers of carcinogenesis has led to significant progress in the management of lung cancer. Patients with non-small-cell lung cancer (NSCLC with anaplastic lymphoma kinase (ALK gene rearrangements constitute about 4%–5% of all NSCLC patients. ALK+ NSCLC cells respond well to small molecule ALK inhibitors such as crizotinib; however, resistance invariably develops after several months of treatment. There are now several newer ALK inhibitors, with the next generation of agents targeting resistance mutations. In this review, we will discuss the prevalence and clinical characteristics of ALK+ lung cancer, current treatment options, and future directions in the management of this subset of NSCLC patients. Keywords: anaplastic lymphoma kinase (ALK, gene rearrangements, lung cancer, kinase inhibitors, lung adenocarcinoma

[Prostatic granulomas revealing a peripheral T-cell lymphoma].

Science.gov (United States)

Foguem, C; Curlier, E; Rouamba, M-M; Regent, A; Philippe, P

2009-02-01

The presence of granulomas on tissue biopsie has been reported in a wide range of disorders. The clinical presentation and the diagnostic work-up of granulomatosis can be difficult as it is illustrated in the following report. A 59-year-old patient was referred in 2002 for a granulomatous prostatitis. Physical examination was normal. Except for the increase of prostate-specific antigen (which motivated a biopsy), the laboratory results were normal. Thoracic CT-scan disclosed mediastinal lymph nodes. A minor salivary gland biopsy was consistent with the diagnosis of sarcoidosis. In 2004, the patient presented an epidermal necrolysis, and in 2005 the deterioration of general status raised suspicion of a lymphoproliferative disorder. Liver and bone marrow biopsies revealed a granulomatous process. Despite steroid therapy, the patient died. Autopsy discloses a anaplasic T cell lymphoma. This report illustrates the relationship between sarcoidosis and lymphoma as a mode of presentation, a complication, or an accidental but misleading association? The association between anaplastic lymphoma and sarcoidosis is exceptional.

MUC1 (CD227) interacts with lck tyrosine kinase in Jurkat lymphoma cells and normal T cells.

Science.gov (United States)

Mukherjee, P; Tinder, T L; Basu, G D; Gendler, S J

2005-01-01

MUC1 (CD227) is a large transmembrane epithelial mucin glycoprotein, which is aberrantly overexpressed in most adenocarcinomas and is a target for immune therapy for epithelial tumors. Recently, MUC1 has been detected in a variety of hematopoietic cell malignancies including T and B cell lymphomas and myelomas; however, its function in these cells is not clearly defined. Using the Jurkat T cell lymphoma cell line and normal human T cells, we demonstrate that MUC1 is not only expressed in these cells but is also phosphorylated upon T cell receptor (TCR) ligation and associates with the Src-related T cell tyrosine kinase, p56lck. Upon TCR-mediated activation of Jurkat cells, MUC1 is found in the low-density membrane fractions, where linker of T cell activation is contained. Abrogation of MUC1 expression in Jurkat cells by MUC1-specific small interfering RNA resulted in defects in TCR-mediated downstream signaling events associated with T cell activation. These include reduction in Ca2+ influx and extracellular signal-regulated kinase 1/2 phosphorylation, leading to a decrease in CD69 expression, proliferation, and interleukin-2 production. These results suggest a regulatory role of MUC1 in modulating proximal signal transduction events through its interaction with proteins of the activation complex.

Immunohistochemical Profile of Hodgkin and Non-Hodgkin Lymphoma

International Nuclear Information System (INIS)

Shahid, R.; Gulzar, R.; Avesi, L.; Hassan, S.; Danish, F.; Mirza, T.

2016-01-01

Objective: To analyze the frequencies of histological types of lymphoma, diagnosed with complete immunohistochemical profile in younger and older age group. Study Design: Cross-sectional analytical study. Place and Duration of Study: Dow Diagnostic Research and Reference Laboratory, Dow University of Health Sciences, Karachi, from January 2009 to September 2013. Methodology: Consecutive cases of lymphomas, which were diagnosed using immunohistochemistry, were analyzed according to WHO classification. Frequency and percentages for different types of lymphomas were calculated. Hodgkin and non-Hodgkin lymphomas characteristics in two age groups of less than and more than 40 years were compared, applying chi-square test. Results: Out of the 318 cases, 79 (25 percentage) were Hodgkin Lymphomas (HL) and 239 (75 percentage) were Non-Hodgkin Lymphomas (NHL). Mixed Cellularity Hodgkin Lymphoma (MCHL) was the commonest (n=48). Amongst the NHL, 215 (89.95 percentage) were B cell lymphomas and 24 (10.05percentage) were T-cell lymphomas. Diffuse Large B-Cell Lymphoma (DLBCL) was the commonest lymphoma (n=165, 69.95 percentage of NHL). Anaplastic T-Cell Lymphoma (ALCL, n=10) was the commonest T-cell lymphoma. The frequency of HL was significantly higher in the younger age group and that of NHL was higher in the older age group (p < 0.001). Primary lymph node involvement was reported in 175 (55 percentage) and cervical lymph node was the most frequent site. Extra nodal involvement was seen in 93 (29 percentage) of all cases and was reported in 87 (36.4 percentage) of NHL and 6 (7.5 percentage) of HL. The most common extra nodal site was the gastrointestinal tract. Conclusion: Hodgkin lymphoma comprises 25 percentage and non-Hodgkin lymphoma comprises 75 percentage of all lymphomas. Both occur in younger age groups than reported in the West. B-cell NHL is three times more common than T-cell lymphoma. DLBCL is the most frequent lymphoma. ALCL is the most common T-cell, and mixed

A Study Of Oral PF-02341066, A C-Met/Hepatocyte Growth Factor Tyrosine Kinase Inhibitor, In Patients With Advanced Cancer

Science.gov (United States)

2018-01-29

Non-Small Cell Lung Cancer ALK-positive; Non-Small Cell Lung Cancer c-Met Dependent; Non-Small Cell Lung Cancer ROS Marker Positive; Systemic Anaplastic Large-Cell Lymphoma; Advanced Malignancies Except Leukemia

17-DMAG in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphomas

Science.gov (United States)

2013-01-24

Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage IV Adult Diffuse Small Cleaved Cell Lymphoma; Stage IV Adult Hodgkin Lymphoma; Stage IV Adult T-cell Leukemia/Lymphoma; Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma; Stage IV Grade 1 Follicular Lymphoma; Stage IV Grade 2 Follicular Lymphoma; Stage IV Grade 3 Follicular Lymphoma; Stage IV Mantle Cell Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Mycosis Fungoides/Sezary Syndrome; Stage IV Small Lymphocytic Lymphoma; Unspecified Adult Solid Tumor, Protocol Specific; Waldenstr

Genetically Modified Peripheral Blood Stem Cell Transplant in Treating Patients With HIV-Associated Non-Hodgkin or Hodgkin Lymphoma

Science.gov (United States)

2015-05-06

Adult Nasal Type Extranodal NK/T-cell Lymphoma; AIDS-related Diffuse Large Cell Lymphoma; AIDS-related Diffuse Mixed Cell Lymphoma; AIDS-related Diffuse Small Cleaved Cell Lymphoma; AIDS-related Immunoblastic Large Cell Lymphoma; AIDS-related Lymphoblastic Lymphoma; AIDS-related Peripheral/Systemic Lymphoma; AIDS-related Small Noncleaved Cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; HIV-associated Hodgkin Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage I AIDS-related Lymphoma; Stage II AIDS-related Lymphoma; Stage III AIDS-related Lymphoma; Stage IV AIDS-related Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Membrane-associated signaling in human B-lymphoma lines

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Tauzin, Sebastien; Ding, Heidrun; Burdevet, Dimitri [Department of Pathology and Immunology, Centre medical universitaire, 1, rue Michel-Servet, 1211 Geneva 11 (Switzerland); Borisch, Bettina [Department of Social and Preventive Medicine, Centre medical universitaire, 1, rue Michel-Servet, 1211 Geneva 11 (Switzerland); Hoessli, Daniel C., E-mail: danielhoessli@gmail.com [Department of Pathology and Immunology, Centre medical universitaire, 1, rue Michel-Servet, 1211 Geneva 11 (Switzerland)

2011-01-15

In B-non-Hodgkin lymphomas, Lyn and Cbp/PAG constitute the core of an oncogenic signalosome that captures the Phosphatidylinositol-3-kinase, the Spleen tyrosine kinase and the Signal transducer and activator of transcription-3 to generate pro-survival and proliferative signals. Lymphoma lines corresponding to follicular, mantle-cell and Burkitt-derived lymphomas display type-specific signalosome organizations that differentially activate PI3K, Syk and STAT3. In the follicular lymphoma line, PI3K, Syk and STAT3 were optimally activated upon association with the Lyn-Cbp/PAG signalosome, while in the Burkitt lymphoma-derived line, the association with Cbp/PAG and activation of PI3K were interfered with by the latent membrane proteins encoded by the Epstein-Barr virus. In the Jeko-1 mantle-cell line, a weak association of Syk with the Lyn-Cbp/PAG signalosome resulted in poor activation of Syk, but in those cells, as in the follicular and Burkitt-derived lines, efficient apoptosis induction by the Syk inhibitor R406 indicated that Syk is nonetheless an important prosurvival element and therefore a valuable therapeutic target. In all configurations described herein is the Lyn-Cbp/PAG signalosome independent of external signals and provides efficient means of activation for its associated lipid and protein kinases. In follicular and Burkitt-derived lines, Syk appears to be activated following binding to Cbp/PAG and no longer requires B-cell receptor-associated activation motifs for activation. Assessment of the different modalities of Lyn-Cbp/PAG signalosome organization could help in selecting the appropriate combination of kinase inhibitors to eliminate a particular type of lymphoma cells.

Plasma Cell-Free DNA in Paediatric Lymphomas

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Mussolin, Lara; Burnelli, Roberta; Pillon, Marta; Carraro, Elisa; Farruggia, Piero; Todesco, Alessandra; Mascarin, Maurizio; Rosolen, Angelo

2013-01-01

Background: Extracellular circulating DNA (cfDNA) can be found in small amounts in plasma of healthy individuals. Increased levels of cfDNA have been reported in patients with cancer of breast, cervix, colon, liver and it was shown that cfDNA can originate from both tumour and non-tumour cells. Objectives: Levels of cfDNA of a large series of children with lymphoma were evaluated and analyzed in relation with clinical characteristics. Methods: plasma cfDNA levels obtained at diagnosis in 201 paediatric lymphoma patients [43 Hodgkin lymphomas (HL), 45 anaplastic large cell lymphomas (ALCL), 88 Burkitt lymphomas (BL), 17 lymphoblastic (LBL), 8 diffuse large B cell lymphoma (DLBCL)] and 15 healthy individuals were determined using a quantitative PCR assay for POLR2 gene and, in addition, for NPM-ALK fusion gene in ALCL patients. Wilcoxon rank sum test was used to compare plasma levels among different patient subgroups and controls and to analyze relationship between levels of cfDNA and clinical characteristics. Results: Levels of cfDNA in lymphoma patients were significantly higher compared with controls (p<0.0001). CfDNA was associated with median age (p=0.01) in HL, and with stage in ALCL (p=0.01). In HL patients high cfDNA levels were correlated with poor prognosis (p=0.03). In ALCL we found that most of the cfDNA (77%) was non-tumor DNA. Conclusion: level of plasma cfDNA might constitute an important non-invasive tool at diagnosis in lymphoma patients' management; in particular in patients with HL, cfDNA seems to be a promising prognostic biomarker. PMID:23678368

Excellent outcome of immunomodulation or Bruton’s tyrosine kinase inhibition in highly refractory primary cutaneous diffuse large B-cell lymphoma, leg type

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Eva Gupta

2015-12-01

Full Text Available Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT is a rare diffuse large B-cell lymphoma confined to the skin of the legs. The typical presentation is characterized by solitary or multiple growing plaques, usually confined to one leg. We report a case of PCDLBCL-LT of activated B-cell subtype characterized by multiple local relapses in the legs, initially, and systemic relapses about seven years after the diagnosis. Local relapses were sensitive to radiation therapy. Cutaneous and systemic relapses responded well to immunomodulatory therapy with lenalidomide followed by Bruton’s tyrosine kinase inhibition with ibrutinib. Ibrutinib is the only treatment that resulted in long-lasting complete remission. Lenalidomide and especially ibrutinib appear to have a significant activity against this lymphoma and should be incorporated in the treatment of this resistant and aggressive lymphoma. To our knowledge, this is the first case of PCDLBCL-LT reported in the literature exhibiting a complete response to ibrutinib.

Epigenetic Silencing of the Proapoptotic Gene BIM in Anaplastic Large Cell Lymphoma through an MeCP2/SIN3a Deacetylating Complex

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Rocco Piazza

2013-05-01

Full Text Available BIM is a proapoptotic member of the Bcl-2 family. Here, we investigated the epigenetic status of the BIM locus in NPM/ALK+ anaplastic large cell lymphoma (ALCL cell lines and in lymph node biopsies from NPM/ALK+ ALCL patients. We show that BIM is epigenetically silenced in cell lines and lymph node specimens and that treatment with the deacetylase inhibitor trichostatin A restores the histone acetylation, strongly upregulates BIM expression, and induces cell death. BIM silencing occurs through recruitment of MeCP2 and the SIN3a/histone deacetylase 1/2 (HDAC1/2 corepressor complex. This event requires BIM CpG methylation/demethylation with 5-azacytidine that leads to detachment of the MeCP2 corepressor complex and reacetylation of the histone tails. Treatment with the ALK inhibitor PF2341066 or with an inducible shRNA targeting NPM/ALK does not restore BIM locus reacetylation; however, enforced expression of NPM/ALK in an NPM/ALK-negative cell line significantly increases the methylation at the BIM locus. This study demonstrates that BIM is epigenetically silenced in NPM/ALK-positive cells through recruitment of the SIN3a/HDAC1/2 corepressor complex and that NPM/ALK is dispensable to maintain BIM epigenetic silencing but is able to act as an inducer of BIM methylation.

Cerebral oligodendroglioma: MR features indicating anaplastic changes

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Choi, Choong Gon; Chang, Kee Hyun; Han, Moon Hee; Chi, Je Geun [Seoul National Univ., Seoul (Korea, Republic of); Yoon, Hyun Ki [Ulsan Univ., Seoul (Korea, Republic of)

1995-10-15

The purpose of this study is to find helpful MR findings for predicting anaplastic oligodendrogliomas. Retrospective analysis of 46 MR images and 37 CT scans was performed for 46 patients with pathologically-proven cerebral oligodendrogliomas. A neuropathologist graded the tumors as one of low-grade (n = 16), intermediate-grade (n = 12), or anaplastic oligodendroglioma (n 18). MR imaging features were retrospectively analysed with respect to histologic grading of the tumors. Contrast enhancement was observed always in anaplastic group (17/17), in a portion of intermediate-grade group (4/10) but not in low-grade group (0/4). Peritumoral edema was observed infrequently in anaplastic group (4/18) or intermediate-grade group (1/12). Cystic changes (25/46) or calcifications on CT Scans (14/37) were not related with histologic grading. Grossly identifiable hemorrhage was rare in this series (2/46). Among the various imaging features, only tumor enhancement and peritumoral edema were statistically significant for trend test ({rho} < 0.05). When considering the diagnosis of oligodendrogliomas, the presence of contrast enhancement or peritumoral edema is a helpful features suggesting anaplastic oligodendrogliomas.

Novel Bruton's tyrosine kinase inhibitors currently in development

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D'Cruz OJ

2013-03-01

Full Text Available Osmond J D'Cruz,1 Fatih M Uckun1,21Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles, Los Angeles, CA, USA; 2Department of Pediatrics, University of Southern California, Los Angeles, CA, USAAbstract: Bruton's tyrosine kinase (Btk is intimately involved in multiple signal-transduction pathways regulating survival, activation, proliferation, and differentiation of B-lineage lymphoid cells. Btk is overexpressed and constitutively active in several B-lineage lymphoid malignancies. Btk has emerged as a new antiapoptotic molecular target for treatment of B-lineage leukemias and lymphomas. Preclinical and early clinical results indicate that Btk inhibitors may be useful in the treatment of leukemias and lymphomas.Keywords: tyrosine kinase, personalized therapy, kinase inhibitors, Btk, leukemia, lymphoma

Molecular Pathology of Anaplastic Thyroid Carcinomas: A Retrospective Study of 144 Cases.

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Bonhomme, Benjamin; Godbert, Yann; Perot, Gaelle; Al Ghuzlan, Abir; Bardet, Stéphane; Belleannée, Geneviève; Crinière, Lise; Do Cao, Christine; Fouilloux, Geneviève; Guyetant, Serge; Kelly, Antony; Leboulleux, Sophie; Buffet, Camille; Leteurtre, Emmanuelle; Michels, Jean-Jacques; Tissier, Frédérique; Toubert, Marie-Elisabeth; Wassef, Michel; Pinard, Clémence; Hostein, Isabelle; Soubeyran, Isabelle

2017-05-01

Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors. Fluorescence in situ hybridization analysis for ALK rearrangement was performed on tissue microarrays. A panel of 50 genes using next-generation sequencing and TERT promoter mutations using Sanger sequencing were also screened. Fluorescence in situ hybridization was interpretable for 90 (62.5%) cases. One (1.1%) case was positive for an ALK rearrangement with a borderline threshold (15% positive cells). Next-generation sequencing results were interpretable for 94 (65.3%) cases, and Sanger sequencing (TERT) for 98 (68.1%) cases. A total of 210 mutations (intronic and exonic) were identified. TP53 alterations were the most frequent (54.4%). Forty-three percent harbored a mutation in the (H-K-N)RAS genes, 13.8% a mutation in the BRAF gene (essentially p.V600E), 17% a PI3K-AKT pathway mutation, 6.4% both RAS and PI3K pathway mutations, and 4.3% both TP53 and PTEN mutations. Nearly 10% of the cases showed no mutations of the RAS, PI3K-AKT pathways, or TP53, with mutations of ALK, ATM, APC, CDKN2A, ERBB2, RET, or SMAD4, including mutations not yet described in thyroid tumors. Genes encoding potentially druggable targets included: mutations in the ATM gene in four (4.3%) cases, in ERBB2 in one (1.1%) case, in MET in one (1.1%) case, and in ALK in one (1.1%) case. A TERT promoter alteration was found in 53 (54.0%) cases, including 43 C228T and 10 C250T mutations. Three out of our cases did not harbor mutations in the panel of genes with therapeutic

Gingival Anaplastic Large-Cell Lymphoma Mimicking Hyperplastic Benignancy as the First Clinical Manifestation of AIDS: A Case Report and Review of the Literature

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Rafaela Elvira Rozza-de-Menezes

2013-01-01

Full Text Available This paper presents an unusual case of gingival ALCL, which mimicked a benign hyperplastic lesion that occurred in a 57-year-old white man representing the first clinical manifestation of acquired immunodeficiency syndrome (AIDS. The patient was referred to the Dental Clinic of PUCPR complaining of a lobulated nodule on the gingiva of his upper central incisors. The presence of advanced chronic periodontitis and dental plaque raised suspicion for a benignancy. An excisional biopsy was performed, and large pleomorphic cells with an abundant cytoplasm, sometimes containing prominent nucleoli and “Hallmark” cells, were observed through hematoxylin and eosin staining. The tumor cells showed strong CD30 expression, EMA, Ki-67, and LCA, and negative stain for p80NPM/ALK, CKAE1/AE3, CD20, CD3, CD56, and CD15. The final diagnosis was ALCL (ALK-negative. Further laboratory tests revealed positivity for human immunodeficiency virus (HIV. The patient was submitted to chemotherapy, but four months after diagnosis, the patient died due to pneumonia and respiratory failure. Oral anaplastic large-cell lymphoma (ALCL is a rare disorder. Only 5 cases involving the gingiva have been reported, and to our knowledge, this is the first case reported of the ALCL, which mimicked a hyperplastic benignancy as the first clinical manifestation of AIDS.

Primary focal T-cell lymphoma of the liver: a case report and review of the literature.

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Cerban, Razvan; Gheorghe, Liana; Becheanu, Gabriel; Serban, Valentin; Gheorghe, Cristian

2012-06-01

We present the case of a previously healthy 62 year old man who developed primary non-Hodgkin lymphoma of the liver. Biopsy confirmed that it was a diffuse large anaplastic T-cell lymphoma of an extremely rare type. The diagnosis of this type of lesions is suggested by the presence of a hepatic mass without lymphadenopathy, splenomegaly or bone marrow involvement associated with normal tumor markers (carcinoembryonic antigen, alpha-fetoprotein and CA 19-9 levels). Histological examination of tissue is essential to confirm the diagnosis. Treatment options are surgical resection and/or chemotherapy but the rate of response to treatment varies widely. Some patients can achieve prolonged remission.

Crizotinib in patients with advanced, inoperable inflammatory myofibroblastic tumours with and without anaplastic lymphoma kinase gene alterations (European Organisation for Research and Treatment of Cancer 90101 CREATE): a multicentre, single-drug, prospective, non-randomised phase 2 trial.

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Schöffski, Patrick; Sufliarsky, Jozef; Gelderblom, Hans; Blay, Jean-Yves; Strauss, Sandra J; Stacchiotti, Silvia; Rutkowski, Piotr; Lindner, Lars H; Leahy, Michael G; Italiano, Antoine; Isambert, Nicolas; Debiec-Rychter, Maria; Sciot, Raf; Van Cann, Thomas; Marréaud, Sandrine; Nzokirantevye, Axelle; Collette, Sandra; Wozniak, Agnieszka

2018-06-01

An inflammatory myofibroblastic tumour (IMFT) is a rare mesenchymal neoplasm characterised by anaplastic lymphoma kinase (ALK) gene rearrangements. We assessed the activity and safety of crizotinib, a tyrosine kinase inhibitor, targeting ALK in patients with advanced IMFT either with or without ALK alterations. We did a multicentre, biomarker-driven, single-drug, non-randomised, open-label, two-stage phase 2 trial (European Organisation for Research and Treatment of Cancer 90101 CREATE) at 13 study sites (five university hospitals and eight specialty clinics) in eight European countries (Belgium, France, Germany, Italy, Netherlands, Poland, Slovakia, and the UK). Eligible participants were patients aged at least 15 years with a local diagnosis of advanced or metastatic IMFT deemed incurable with surgery, radiotherapy, or systemic therapy; measurable disease; an Eastern Cooperative Oncology Group performance status of 0-2; and adequate haematological, renal, and liver function. Central reference pathology was done for confirmation of the diagnosis, and ALK positivity or negativity was assessed centrally using immunohistochemistry and fluorescence in-situ hybridisation based on archival tumour tissue and defined as ALK immunopositivity or rearrangements in at least 15% of tumour cells. Eligible ALK-positive and ALK-negative patients received oral crizotinib 250 mg twice per day administered on a continuous daily dosing schedule (the duration of each treatment cycle was 21 days) until documented disease progression, unacceptable toxicity, or patient refusal. If at least two of the first 12 eligible and assessable ALK-positive patients achieved a confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, a maximum of 35 patients were to be enrolled. If at least six ALK-positive patients achieved a confirmed response, the trial would be deemed successful. The primary endpoint was the proportion of patients who achieved

Leptomeningeal metastases from anaplastic thyroid carcinoma

International Nuclear Information System (INIS)

Solomon, B.; Rischin, D.; Lyons, B.; Peters, L.J.

2000-01-01

Anaplastic thyroid carcinoma is an extremely aggressive neoplasm that accounts for 1-3% of all thyroid cancers. ' Most patients have metastatic disease at presentation and die in a short period of time, often with uncontrolled local disease. We report a case of anaplastic thyroid cancer characterised by good response to initial treatment both locally and in distant metastases, and the subsequent development of refractory metastatic disease in an unusual site, the leptomeninges

Vorinostat in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma and Liver Dysfunction

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2014-02-21

Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Stage III Adult Burkitt Lymphoma; Stage III Adult Diffuse Large Cell Lymphoma; Stage III Adult Diffuse Mixed Cell Lymphoma; Stage III Adult Diffuse Small Cleaved Cell Lymphoma; Stage III Adult Hodgkin Lymphoma; Stage III Adult Immunoblastic Large Cell Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-cell Leukemia/Lymphoma; Stage III Cutaneous T-cell Non-Hodgkin Lymphoma; Stage III Grade 1 Follicular Lymphoma; Stage III Grade 2 Follicular Lymphoma; Stage III Grade 3 Follicular Lymphoma; Stage III Mantle Cell Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Mycosis Fungoides/Sezary Syndrome; Stage III Small Lymphocytic Lymphoma; Stage IV Adult Burkitt Lymphoma; Stage IV Adult Diffuse Large Cell Lymphoma; Stage IV Adult Diffuse Mixed Cell Lymphoma; Stage

The Role of Activator Protein-1 (AP-1) Family Members in CD30-Positive Lymphomas

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Garces de los Fayos Alonso, Ines; Lagger, Sabine; Merkel, Olaf; Kenner, Lukas

2018-01-01

The Activator Protein-1 (AP-1) transcription factor (TF) family, composed of a variety of members including c-JUN, c-FOS and ATF, is involved in mediating many biological processes such as proliferation, differentiation and cell death. Since their discovery, the role of AP-1 TFs in cancer development has been extensively analysed. Multiple in vitro and in vivo studies have highlighted the complexity of these TFs, mainly due to their cell-type specific homo- or hetero-dimerization resulting in diverse transcriptional response profiles. However, as a result of the increasing knowledge of the role of AP-1 TFs in disease, these TFs are being recognized as promising therapeutic targets for various malignancies. In this review, we focus on the impact of deregulated expression of AP-1 TFs in CD30-positive lymphomas including Classical Hodgkin Lymphoma and Anaplastic Large Cell Lymphoma. PMID:29597249

Fisetin targets phosphatidylinositol-3-kinase and induces apoptosis of human B lymphoma Raji cells

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Ji Yeon Lim

2015-01-01

Full Text Available Aberrant regulation of phosphatidylinositol-3-kinases (PI3Ks is known to be involved in the progression of cancers. PI3K-binding flavonoids such as quercetin and myricetin have been shown to inhibit PI3K activity, but the direct targeting of fisetin to PI3K has not been established. Here, we carried out an in silico investigation of fisetin binding to PI3K and determined fisetin’s inhibitory activity in enzymatic and cell-based assays. In addition, fisetin induced apoptosis in human Burkitt’s lymphoma Raji cells by inhibiting both PI3Ks and mammalian target of rapamycin (mTOR. Our results indicate that fisetin may serve as a natural backbone for the development of novel dual inhibitors of PI3Ks and mTOR for the treatment of cancer.

The dichloromethane extract of the ethnomedicinal plant Neurolaena lobata inhibits NPM/ALK expression which is causal for anaplastic large cell lymphomagenesis.

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Unger, Christine; Popescu, Ruxandra; Giessrigl, Benedikt; Laimer, Daniela; Heider, Susanne; Seelinger, Mareike; Diaz, Rene; Wallnöfer, Bruno; Egger, Gerda; Hassler, Melanie; Knöfler, Martin; Saleh, Leila; Sahin, Emine; Grusch, Michael; Fritzer-Szekeres, Monika; Dolznig, Helmut; Frisch, Richard; Kenner, Lukas; Kopp, Brigitte; Krupitza, Georg

2013-01-01

The present study investigates extracts of Neuolaena lobata, an anti-protozoan ethnomedicinal plant of the Maya, regarding its anti-neoplastic properties. Firstly, extracts of increasing polarity were tested in HL-60 cells analyzing inhibition of cell proliferation and apoptosis induction. Secondly, the most active extract was further tested in anaplastic large cell lymphoma (ALCL) cell lines of human and mouse origin. The dichloromethane extract inhibited proliferation of HL-60, human and mouse ALCL cells with an IC50 of ~2.5, 3.7 and 2.4 µg/ml, respectively and arrested cells in the G2/M phase. The extract induced the checkpoint kinases Chk1 and Chk2 and perturbed the orchestrated expression of the Cdc25 family of cell cycle phosphatases which was paralleled by the activation of p53, p21 and downregulation of c-Myc. Importantly, the expression of NPM/ALK and its effector JunB were drastically decreased, which correlated with the activation of caspase 3. Subsequently also platelet derived growth factor receptor β was downregulated, which was recently shown to be transcriptionally controlled by JunB synergizing with ALK in ALCL development. We show that a traditional healing plant extract downregulates various oncogenes, induces tumor suppressors, inhibits cell proliferation and triggers apoptosis of malignant cells. The discovery of the 'Active Principle(s)' is warranted.

Management of mantle cell lymphoma in the elderly: current and potential strategies.

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Vignon, Marguerite; Venon, Marie-Dominique; Hermine, Olivier; Delarue, Richard

2013-12-01

Mantle cell lymphoma is a distinct subtype of B-cell non-Hodgkin lymphoma, accounting for 3-10 % of all non-Hodgkin lymphoma cases. The median age at diagnosis is nearly 70 years. The prognosis of patients is based on the Mantle Cell Lymphoma International Prognostic Index, which is calculated on the basis of four independent prognostic factors (age, performance status, serum lactate dehydrogenase and leukocyte count). Treatment of elderly patients with de novo untreated mantle cell lymphoma is based on rituximab combined with chemotherapy. The most commonly used regimen is the classical CHOP21 (cyclophosphamide, doxorubicin, vincristine and prednisone) regimen. Bendamustine is also an option, especially for patients with cardiac comorbidities. In elderly patients who are relatively young and fit, an approach based on treatment usually used for younger patients, with cytarabine-based induction followed by autologous stem cell transplantation, should be discussed. Treatment of relapsing patients is based on the use of newer effective drugs, including bortezomib, lenalidomide and thalidomide, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus. These drugs are often combined with rituximab and can be prescribed in combination with chemotherapy. Promising new drugs are Bruton tyrosine kinase inhibitors and other inhibitors of the phosphoinositide 3-kinase (PI3K)-mTOR-protein kinase B (AKT) pathway. Despite these new advances, mantle cell lymphoma remains an incurable disease, and further basic and clinical research is warranted.

Lymphomas or leukemia presenting as ovarian tumors. An analysis of 42 cases.

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Osborne, B M; Robboy, S J

1983-11-15

Forty cases of ovarian lymphoma and two of extramedullary leukemia were examined with emphasis on histologic types correlated with age, modes of presentation, operative findings, including frequency of bilaterality and omental spread, clinical course following therapy, and problems in differential diagnosis. Although most cases were referred with diagnoses other than lymphoma (granulosa cell tumor or dysgerminoma, occasionally anaplastic tumor, Krukenberg tumor, or metastatic breast carcinoma), utilization of sections cut at 4 mu and stained with hematoxylin and eosin, or sections stained by the methyl green pyronine (MGP), naphthol-ASD esterase (NASD) or periodic acid-Schiff (PAS) methods helped bring out the lymphoid or hematopoietic nature of the cells. Sixteen patients were under 20 years of age. They had small noncleaved cell lymphoma (undifferentiated Burkitt's and non-Burkitt's, 10 cases), diffuse immunoblastic large cell lymphoma (4 cases), or acute granulocytic leukemia (2 cases). Twenty-six patients were 29 to 74 years of age and had diffuse large cell lymphoma (10 cases), diffuse immunoblastic large cell lymphoma (9 cases), follicular (nodular) lymphoma (6 cases) or small noncleaved cell lymphoma (1 case). Pain with an abdominal or pelvic mass was the most common presentation. Nine tumors were discovered during investigation of other gynecologic complaints. At laparotomy, the tumors in 55% of cases involved both ovaries, and in 64% also involved extragonadal sites (usually omentum, fallopian tubes, or lymph nodes). Seventeen patients had tumor affecting one ovary, seven of these without any evidence of extragonadal spread. Forty-two percent (15) of 37 patients with follow-up were alive after 2 years. Only nine patients survived more than 5 years; two subsequently died of lymphoma. Favorable prognostic features included: (1) FIGO stage IA; (2) unilateral ovarian involvement; (3) focal involvement of one ovary; and (4) follicular (nodular) lymphoma.

Anaplastic carcinoma

International Nuclear Information System (INIS)

Parikh, D.M.; Agarwal, S.; Rao, R.S.

1999-01-01

Thyroid carcinoma (TC) is a slow growing tumor with an indolent course and has an excellent prognosis. However, a sharp contrast exists in the biological behavior of TC, which in its well-differentiated form is associated with long-term survival, but in its undifferentiated form is one of the most lethal neoplasms known. The anaplastic carcinoma (ANC) form has a fulminanat course with poor prognosis and almost invariably, a fatal outcome

Successful treatment of follicular lymphoma with second-generation tyrosine kinase inhibitors administered for coexisting chronic myeloid leukemia.

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

2018-06-01

Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic myeloid leukemia (CML). However, the effects of these agents on mature B cell lymphoma are not well known. We describe a 50-year-old man who was diagnosed with CML in the chronic phase and treated with imatinib. After 3 years of imatinib therapy that achieved a complete cytogenetic response of CML, he developed Philadelphia-negative follicular lymphoma (FL). Rituximab monotherapy induced a partial response of FL, and he subsequently achieved a major molecular response (MMR) of CML. Three years later, however, the MMR was lost, followed by the progression of FL. Imatinib was switched to nilotinib for the treatment of CML, while we chose watchful waiting for FL. He achieved MMR again under treatment with nilotinib for 8 months including one month of substitutional use of dasatinib due to adverse events, but thereafter nilotinib was switched to bosutinib due to hyperbilirubinemia. With the administration of second-generation TKIs (2G-TKIs) for a total of 18 months, he achieved a complete response to FL without antilymphoma treatment. This is the first report to suggest that 2G-TKIs may have direct or indirect effects on FL.

Characteristic mTOR activity in Hodgkin-lymphomas offers a potential therapeutic target in high risk disease – a combined tissue microarray, in vitro and in vivo study

International Nuclear Information System (INIS)

Márk, Ágnes; Kopper, László; Sebestyén, Anna; Hajdu, Melinda; Váradi, Zsófia; Sticz, Tamás Béla; Nagy, Noémi; Csomor, Judit; Berczi, Lajos; Varga, Viktória; Csóka, Monika

2013-01-01

Targeting signaling pathways is an attractive approach in many malignancies. The PI3K/Akt/mTOR pathway is activated in a number of human neoplasms, accompanied by lower overall and/or disease free survival. mTOR kinase inhibitors have been introduced in the therapy of renal cell carcinoma and mantle cell lymphoma, and several trials are currently underway. However, the pathological characterization of mTOR activity in lymphomas is still incomplete. mTOR activity and the elements of mTOR complexes were investigated by immunohistochemistry on tissue microarrays representing different human non-Hodgkin-lymphomas (81 cases) and Hodgkin-lymphomas (87 cases). The expression of phospho-mTOR, phospho-4EBP1, phospho-p70S6K, phospho-S6, Rictor, Raptor and Bcl-2, Bcl-xL, Survivin and NF-kappaB-p50 were evaluated, and mTOR activity was statistically analyzed along with 5-year survival data. The in vitro and in vivo effect of the mTOR inhibitor rapamycin was also examined in human Hodgkin-lymphoma cell lines. The majority (>50%) of mantle cell lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma, anaplastic large-cell lymphoma and Hodgkin-lymphoma cases showed higher mTOR activity compared to normal lymphoid tissues. Hodgkin-lymphoma was characterized by high mTOR activity in 93% of the cases, and Bcl-xL and NF-kappaB expression correlated with this mTOR activity. High mTOR activity was observed in the case of both favorable and unfavorable clinical response. Low mTOR activity was accompanied by complete remission and at least 5-year disease free survival in Hodgkin-lymphoma patients. However, statistical analysis did not identify correlation beetween mTOR activity and different clinical data of HL patients, such as survival. We also found that Rictor (mTORC2) was not overexpressed in Hodgkin-lymphoma biopsies and cell lines. Rapamycin inhibited proliferation and induced apoptosis in Hodgkin-lymphoma cells both in vitro and in vivo, moreover, it increased the apoptotic

Epithelioid inflammatory myofibroblastic sarcoma responsive to surgery and an ALK inhibitor in a patient with panhypopituitarism.

Science.gov (United States)

Kurihara-Hosokawa, Kotomi; Kawasaki, Isao; Tamai, Anna; Yoshida, Yoko; Yakushiji, Yosuke; Ueno, Hiroki; Fukumoto, Mariko; Fukushima, Hiroko; Inoue, Takeshi; Hosoi, Masayuki

2014-01-01

We encountered a case of epithelioid inflammatory myofibroblastic sarcoma (EIMS) originating from an abdominal organ that rapidly regrew twice. The patient underwent two surgeries. Large tumors grew within three months after the second surgery. The patient subsequently received chemotherapy with an anaplastic lymphoma kinase (ALK) inhibitor. Although EIMS has a poor prognosis, the patient continues to be alive with disease 14 months after surgical treatment and the administration of the ALK inhibitor.

Suprasellar Anaplastic Meningioma Masquerading As Craniopharyngioma: A Case Report

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Eman Abdelzaher

2014-06-01

Full Text Available Anaplastic meningiomas are uncommon. We report the clinical, radiological and pathological features of an anaplastic meningioma in a young male Egyptian patient presenting as a suprasellar solid/cystic enhancing mass resembling a craniopharyngioma. [J Interdiscipl Histopathol 2014; 2(3.000: 154-157

Primary bony non-Hodgkin lymphoma of the cervical spine: a case report

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Sedrak Mark F

2010-02-01

Full Text Available Abstract Introduction Non-Hodgkin lymphoma primarily originating from the bone is exceedingly rare. To our knowledge, this is the first report of primary bone lymphoma presenting with progressive cord compression from an origin in the cervical spine. Herein, we discuss the unusual location in this case, the presenting symptoms, and the management of this disease. Case presentation We report on a 23-year-old Caucasian-American man who presented with two months of night sweats, fatigue, parasthesias, and progressive weakness that had progressed to near quadriplegia. Magnetic resonance (MR imaging demonstrated significant cord compression seen primarily at C7. Surgical management, with corpectomy and dorsal segmental fusion, in combination with adjuvant chemotherapy and radiation therapy, halted the progression of the primary disease and preserved neurological function. Histological analysis demonstrated an aggressive anaplastic large cell lymphoma. Conclusion Isolated primary bony lymphoma of the spine is exceedingly rare. As in our case, the initial symptoms may be the result of progressive cervical cord compression. Anterior corpectomy with posterolateral decompression and fusion succeeded in preventing progressive neurologic decline and maintaining quality of life. The reader should be aware of the unique presentation of this disease and that surgical management is a successful treatment strategy.

Epigenetic regulation of CD44 in Hodgkin and non-Hodgkin lymphoma

International Nuclear Information System (INIS)

Eberth, Sonja; Schneider, Björn; Rosenwald, Andreas; Hartmann, Elena M; Romani, Julia; Zaborski, Margarete; Siebert, Reiner; Drexler, Hans G; Quentmeier, Hilmar

2010-01-01

Epigenetic inactivation of tumor suppressor genes (TSG) by promoter CpG island hypermethylation is a hallmark of cancer. To assay its extent in human lymphoma, methylation of 24 TSG was analyzed in lymphoma-derived cell lines as well as in patient samples. We screened for TSG methylation using methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) in 40 lymphoma-derived cell lines representing anaplastic large cell lymphoma, Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), Hodgkin lymphoma and mantle cell lymphoma (MCL) as well as in 50 primary lymphoma samples. The methylation status of differentially methylated CD44 was verified by methylation-specific PCR and bisulfite sequencing. Gene expression of CD44 and its reactivation by DNA demethylation was determined by quantitative real-time PCR and on the protein level by flow cytometry. Induction of apoptosis by anti-CD44 antibody was analyzed by annexin-V/PI staining and flow cytometry. On average 8 ± 2.8 of 24 TSG were methylated per lymphoma cell line and 2.4 ± 2 of 24 TSG in primary lymphomas, whereas 0/24 TSG were methylated in tonsils and blood mononuclear cells from healthy donors. Notably, we identified that CD44 was hypermethylated and transcriptionally silenced in all BL and most FL and DLBCL cell lines, but was usually unmethylated and expressed in MCL cell lines. Concordant results were obtained from primary lymphoma material: CD44 was not methylated in MCL patients (0/11) whereas CD44 was frequently hypermethylated in BL patients (18/29). In cell lines with CD44 hypermethylation, expression was re-inducible at mRNA and protein levels by treatment with the DNA demethylating agent 5-Aza-2'-deoxycytidine, confirming epigenetic regulation of CD44. CD44 ligation assays with a monoclonal anti-CD44 antibody showed that CD44 can mediate apoptosis in CD44 + lymphoma cells. CD44 hypermethylated, CD44 - lymphoma cell lines were consistently

Anaplastic meningioma: The dark side of meningiomas

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Andreea Cioca

2017-06-01

Full Text Available Anaplastic meningioma is a rare malignant tumor of the meninges, with a very aggressive behavior and a grim prognosis. Here we report a case of a 64-year old man which presented to the neurosurgery department with motor deficit in the right hemi–body, loss of speech and disorientation. Magnetic resonance imaging detected a mass located in the left frontal lobe that measured 7/8/7 cm, leading to the conclusion that surgery is necessary. Microscopic examination of the tumor showed great number of hypercellular areas with a high mitotic index, and focal necrosis with psammoma bodies. Using a panel of antibodies such as EMA, vimentin, CD34 GFAP, pancytokeratin and Ki67, we concluded that he final diagnosis was anaplastic meningioma, WHO grade III. Due to its morphological similarity with other tumors, the diagnosis of anaplastic meningioma may be challenging.

Remarkable Presentation: Anaplastic Thyroid Carcinoma Arising from Chronic Hyperthyroidism

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Habib G. Zalzal

2018-01-01

Full Text Available Background. Undifferentiated anaplastic carcinoma rarely develops from chronic hyperthyroidism. Although acute hyperthyroidism can develop prior to anaplastic transformation, chronic hyperthyroidism was thought to be a protective measure against thyroid malignancy. Methods. A 79-year-old female presented acutely to the hospital with dyspnea. She had been taking methimazole for chronic hyperthyroidism due to toxic thyroid nodules, previously biopsied as benign. Upon admission, imaging showed tracheal compression, requiring a total thyroidectomy with tracheostomy for airway management. Results. Pathology demonstrated undifferentiated anaplastic thyroid carcinoma. The patient passed away shortly after hospital discharge. Despite treatment with methimazole for many years, abrupt enlargement of her toxic multinodular goiter was consistent with malignant transformation. Chronic hyperthyroidism and toxic nodules are rarely associated with thyroid malignancy, with only one previous report documenting association with anaplastic thyroid carcinoma. Conclusion. Progressive thyroid enlargement and acute worsening of previously controlled hyperthyroidism should promote concern for disease regardless of baseline thyroid function.

MicroRNA181a Is Overexpressed in T-Cell Leukemia/Lymphoma and Related to Chemoresistance

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Zi-Xun Yan

2015-01-01

Full Text Available MicroRNAs (miRs play an important role in tumorogenesis and chemoresistance in lymphoid malignancies. Comparing with reactive hyperplasia, miR181a was overexpressed in 130 patients with T-cell leukemia/lymphoma, including acute T-cell lymphoblastic leukemia (n=32, T-cell lymphoblastic lymphoma (n=16, peripheral T-cell lymphoma, not otherwise specified (n=45, anaplastic large cell lymphoma (n=15, and angioimmunoblastic T-cell lymphoma (n=22. Irrespective to histological subtypes, miR181a overexpression was associated with increased AKT phosphorylation. In vitro, ectopic expression of miR181a in HEK-293T cells significantly enhanced cell proliferation, activated AKT, and conferred cell resistance to doxorubicin. Meanwhile, miR181a expression was upregulated in Jurkat cells, along with AKT activation, during exposure to chemotherapeutic agents regularly applied to T-cell leukemia/lymphoma treatment, such as doxorubicin, cyclophosphamide, cytarabine, and cisplatin. Isogenic doxorubicin-resistant Jurkat and H9 cells were subsequently developed, which also presented with miR181a overexpression and cross-resistance to cyclophosphamide and cisplatin. Meanwhile, specific inhibition of miR181a enhanced Jurkat and H9 cell sensitivity to chemotherapeutic agents, further indicating that miR181a was involved in acquired chemoresistance. Collectively, miR181a functioned as a biomarker of T-cell leukemia/lymphoma through modulation of AKT pathway. Related to tumor cell chemoresistance, miR181a could be a potential therapeutic target in treating T-cell malignancies.

Diversity of imaging and pathological features at different stages of primary central nervous system lymphoma

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Jing LIU

2018-01-01

Full Text Available Objective The clinical, imaging and pathological manifestations of one patient at different stages of primary central nervous system lymphoma (PCNSL have been analyzed to disclose its pathogenesis. Methods and Results A 29-year-old female patient showed recurrent onsets. On the first onset, the main clinical manifestation was blurred vision and visual field defect. Cranial MRI showed a patchy lesion in the right parietal and occipital lobes without obvious occupying sign. T1WI showed slight low-intensity sign, T2WI and FLAIR showed high-intensity signs. Enhanced scanning showed heterogeneous punctate enhancement. The lesion disappeared gradually after glucocorticoid impact therapy. Headache, vomiting and left limb paralysis were the main clinical manifestations on the second onset, and MRI showed a lesion in the right frontal and parietal lobes with obvious occupying sign and solid enhancement, low-intensity on T1WI, high-intensity on T2WI and FLAIR. The tumor was totally removed under microscope. Histological findings showed large tumor cells, rich cytoplasm, nuclei with various sizes and shapes, conspicuous mitosis, patchy necrosis, and interstitial small vessel hyperplasia. Immunohistochemical staining showed that membrane of tumor cells was positive for CD20, and nuclei were positive for paired box gene 5 (PAX5 and multiple myeloma oncogene 1 (MUM1. In a few tumor cells, membrane was positive for CD10 and CD30, and nuclei were positive for cyclin D1. Besides, tumor cells were negative for CD3, anaplastic lymphoma kinase (ALK and glial fibrillary acidic protein (GFAP. Ki?67 labeling index was about 80%. EBER in situ hybridization (ISH assay showed that mRNA coded by Epstein?Barr (EB virus was negative. The tumor showed angiotropic characteristics, and the walls of involved blood vessels were wrapped and destructed. The final diagnosis was confirmed as diffuse large B cell lymphoma. Conclusions PCNSL has various imaging features, revealing as

Abstracts from the 5th International Conference for Healthcare and Medical Students (ICHAMS)

OpenAIRE

Sweeney, Yvonne; O?Neill, Hugh; Duffy, Garry; Creegan, Daniel; Bustos, Viviana; Harvey, Brian J.; Dalphy, Alexander; O?Grady, Anthony; Kay, Elaine; Samelska, Katarzyna; Izdebska, Justyna; Kurowska, Anna; Al-Zubaidy, Rena; Mroz, Magdalena; Harvey, Brian

2016-01-01

Table of contents O1: Assessing the protective effect of dexrazoxane against doxorubicin-induced toxicity in HL-1 cardiomyocytes Yvonne Sweeney, Hugh O?Neill, Garry Duffy O2: Role of KCNQ1 in epithelial barrier repair Daniel Creegan, Viviana Bustos, Brian J. Harvey O3: The suitability of non-small cell lung cancer cytology preparations for the analysis of anaplastic lymphoma kinase gene rearrangements Alexander Dalphy, Anthony O?Grady, Elaine Kay O4: Penetrating keratoplasty and descemet?s st...

A 6-gene signature identifies four molecular subgroups of neuroblastoma

OpenAIRE

Abel, Frida; Dalevi, Daniel; Nethander, Maria; Jörnsten, Rebecka; De Preter, Katleen; Vermeulen, Joëlle; Stallings, Raymond; Kogner, Per; Maris, John; Nilsson, Staffan

2011-01-01

Abstract Background There are currently three postulated genomic subtypes of the childhood tumour neuroblastoma (NB); Type 1, Type 2A, and Type 2B. The most aggressive forms of NB are characterized by amplification of the oncogene MYCN (MNA) and low expression of the favourable marker NTRK1. Recently, mutations or high expression of the familial predisposition gene Anaplastic Lymphoma Kinase (ALK) was associated to unfavourable biology of sporadic NB. Also, various other genes have been linke...

Ibrutinib: a first in class covalent inhibitor of Bruton's tyrosine kinase.

Science.gov (United States)

Davids, Matthew S; Brown, Jennifer R

2014-05-01

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton's tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton's tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin's lymphoma, such as diffuse large B-cell lymphoma and Waldenström's macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies.

Massage Therapy Given by Caregiver in Treating Quality of Life of Young Patients Undergoing Treatment for Cancer

Science.gov (United States)

2018-05-24

Accelerated Phase Chronic Myelogenous Leukemia; Acute Undifferentiated Leukemia; Angioimmunoblastic T-cell Lymphoma; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Burkitt Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Mantle Cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Essential Thrombocythemia; Extramedullary Plasmacytoma; Intraocular Lymphoma; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Meningeal Chronic Myelogenous Leukemia; Noncontiguous Stage II Mantle Cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Primary Myelofibrosis; Primary Systemic Amyloidosis; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Refractory Multiple Myeloma; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Childhood Anaplastic Large Cell

CEOP/IVE/GDP Compared With CEOP as the First-line Therapy for Newly Diagnosed Adult Patients With PTCL

Science.gov (United States)

2016-04-18

Peripheral T-Cell Lymphoma; Angioimmunoblastic T Cell Lymphoma; ALK-negative Anaplastic Large Cell Lymphoma; Enteropathy Associated T Cell Lymphoma; Subcutaneous Panniculitis Like T Cell Lymphoma; Acute Adult T-Cell Leukemia/Lymphoma

World Health Organisation Classification of Lymphoid Tumours in Veterinary and Human Medicine: a Comparative Evaluation of Gastrointestinal Lymphomas in 61 Cats.

Science.gov (United States)

Wolfesberger, B; Fuchs-Baumgartinger, A; Greß, V; Hammer, S E; Gradner, G; Knödl, K; Tichy, A; Rütgen, B C; Beham-Schmid, C

2018-02-01

To diagnose and classify the various entities of lymphomas, the World Health Organisation (WHO) classification is applied in human as well as in veterinary medicine. We validated the concordance of these classification systems by having a veterinary and human pathologist evaluate gastrointestinal lymphoma tissue from 61 cats. In 59% of all cases, there was a match between their respective diagnoses of the lymphoma subtype. A complete consensus between the two evaluators was obtained for all samples with a diagnosis of diffuse large B-cell lymphoma, T-cell anaplastic large cell lymphoma and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue. A corresponding diagnosis was also made in the majority of samples with enteropathy associated T-cell lymphoma (EATL) type II, although this subtype in cats has similarities to the 'indolent T-cell lymphoproliferative disorder of the gastrointestinal tract', a provisional entity newly added to the revised human WHO classification in 2016. Very little consensus has been found with cases of EATL type I due to the fact that most did not meet all of the criteria of human EATL I. Hence, the human pathologist assigned them to the heterogeneous group of peripheral T-cell lymphomas (not otherwise specified). Consequently, concrete guidelines and advanced immunophenotyping based on the model of human medicine are essential to differentiate these challenging entities in veterinary medicine. Copyright © 2017 Elsevier Ltd. All rights reserved.

NPM-ALK mediates phosphorylation of MSH2 at tyrosine 238, creating a functional deficiency in MSH2 and the loss of mismatch repair

International Nuclear Information System (INIS)

Bone, K M; Wang, P; Wu, F; Wu, C; Li, L; Bacani, J T; Andrew, S E; Lai, R

2015-01-01

The vast majority of anaplastic lymphoma kinase-positive anaplastic large cell lymphoma (ALK+ALCL) tumors express the characteristic oncogenic fusion protein NPM-ALK, which mediates tumorigenesis by exerting its constitutive tyrosine kinase activity on various substrates. We recently identified MSH2, a protein central to DNA mismatch repair (MMR), as a novel binding partner and phosphorylation substrate of NPM-ALK. Here, using liquid chromatography–mass spectrometry, we report for the first time that MSH2 is phosphorylated by NPM-ALK at a specific residue, tyrosine 238. Using GP293 cells transfected with NPM-ALK, we confirmed that the MSH2 Y238F mutant is not tyrosine phosphorylated. Furthermore, transfection of MSH2 Y238F into these cells substantially decreased the tyrosine phosphorylation of endogenous MSH2. Importantly, gene transfection of MSH2 Y238F abrogated the binding of NPM-ALK with endogenous MSH2, re-established the dimerization of MSH2:MSH6 and restored the sensitivity to DNA mismatch-inducing drugs, indicative of MMR return. Parallel findings were observed in two ALK+ALCL cell lines, Karpas 299 and SUP-M2. In addition, we found that enforced expression of MSH2 Y238F into ALK+ALCL cells alone was sufficient to induce spontaneous apoptosis. In conclusion, our findings have identified NPM-ALK-induced phosphorylation of MSH2 at Y238 as a crucial event in suppressing MMR. Our studies have provided novel insights into the mechanism by which oncogenic tyrosine kinases disrupt MMR

Ibrutinib: a first in class covalent inhibitor of Bruton’s tyrosine kinase

Science.gov (United States)

Davids, Matthew S; Brown, Jennifer R

2015-01-01

Ibrutinib (formerly PCI-32765) is a potent, covalent inhibitor of Bruton’s tyrosine kinase, a kinase downstream of the B-cell receptor that is critical for B-cell survival and proliferation. In preclinical studies, ibrutinib bound to Bruton’s tyrosine kinase with high affinity, leading to inhibition of B-cell receptor signaling, decreased B-cell activation and induction of apoptosis. In clinical studies, ibrutinib has been well-tolerated and has demonstrated profound anti-tumor activity in a variety of hematologic malignancies, most notably chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), leading to US FDA approval for relapsed CLL and MCL. Ongoing studies are evaluating ibrutinib in other types of non-Hodgkin’s lymphoma, such as diffuse large B-cell lymphoma and Waldenström’s macrogobulinemia, in larger Phase III studies in CLL and MCL, and in combination studies with monoclonal antibodies and chemotherapy. Future studies will combine ibrutinib with other promising novel agents currently in development in hematologic malignancies. PMID:24941982

Anaplastic thyroid cancer, tumorigenesis and therapy.

LENUS (Irish Health Repository)

O'Neill, J P

2010-03-01

Anaplastic thyroid cancer (ATC) is a fatal endocrine malignancy. Current therapy fails to significantly improve survival. Recent insights into thyroid tumorigenesis, post-malignant dedifferentiation and mode of metastatic activity offer new therapeutic strategies.

Crizotinib-Resistant ROS1 Mutations Reveal a Predictive Kinase Inhibitor Sensitivity Model for ROS1- and ALK-Rearranged Lung Cancers.

Science.gov (United States)

Facchinetti, Francesco; Loriot, Yohann; Kuo, Mei-Shiue; Mahjoubi, Linda; Lacroix, Ludovic; Planchard, David; Besse, Benjamin; Farace, Françoise; Auger, Nathalie; Remon, Jordi; Scoazec, Jean-Yves; André, Fabrice; Soria, Jean-Charles; Friboulet, Luc

2016-12-15

The identification of molecular mechanisms conferring resistance to tyrosine kinase inhibitor (TKI) is a key step to improve therapeutic results for patients with oncogene addiction. Several alterations leading to EGFR and anaplastic lymphoma kinase (ALK) resistance to TKI therapy have been described in non-small cell lung cancer (NSCLC). Only two mutations in the ROS1 kinase domain responsible for crizotinib resistance have been described in patients thus far. A patient suffering from a metastatic NSCLC harboring an ezrin (EZR)-ROS1 fusion gene developed acquired resistance to the ALK/ROS1 inhibitor crizotinib. Molecular analysis (whole-exome sequencing, CGH) and functional studies were undertaken to elucidate the mechanism of resistance. Based on this case, we took advantage of the structural homology of ROS1 and ALK to build a predictive model for drug sensitivity regarding future ROS1 mutations. Sequencing revealed a dual mutation, S1986Y and S1986F, in the ROS1 kinase domain. Functional in vitro studies demonstrated that ROS1 harboring either the S1986Y or the S1986F mutation, while conferring resistance to crizotinib and ceritinib, was inhibited by lorlatinib (PF-06463922). The patient's clinical response confirmed the potency of lorlatinib against S1986Y/F mutations. The ROS1 S1986Y/F and ALK C1156Y mutations are homologous and displayed similar sensitivity patterns to ALK/ROS1 TKIs. We extended this analogy to build a model predicting TKI efficacy against potential ROS1 mutations. Clinical evidence, in vitro validation, and homology-based prediction provide guidance for treatment decision making for patients with ROS1-rearranged NSCLC who progressed on crizotinib. Clin Cancer Res; 22(24); 5983-91. ©2016 AACR. ©2016 American Association for Cancer Research.

Expression of the Eukaryotic Translation Initiation Factors 4E and 2α in Non-Hodgkin’s Lymphomas

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Wang, Songtao; Rosenwald, Igor B.; Hutzler, Michael J.; Pihan, German A.; Savas, Lou; Chen, Jane-Jane; Woda, Bruce A.

1999-01-01

Transition of cells from quiescence to proliferation requires an increase in the rate of protein synthesis, which is regulated in part by two key translation initiation factors, 4E and 2α. The expression and activity of both factors are increased transiently when normal resting cells are stimulated to proliferate. They are constitutively elevated in oncogene transformed cultured cells, and overexpression of either initiation factor in rodent cells makes them tumorigenic. In this study we investigate an association between the expression of translation initiation factors and lymphomagenesis. We have analyzed the expression of the protein synthesis initiation factors 4E and 2α by immunohistochemistry in reactive lymph nodes and several types of non-Hodgkin’s lymphoma representing a wide range of clinical behaviors based on the Revised European-American Lymphoma behavioral classification. The study included 7 benign lymph nodes with follicular hyperplasia, 26 indolent lymphomas (6 marginal zone lymphomas, 7 small lymphocytic lymphomas, and 13 follicular lymphomas, grades 1 and 2), 16 moderately aggressive lymphomas (8 mantle cell lymphomas and 8 follicular lymphomas, grade 3), 24 aggressive lymphomas (14 large-B-cell lymphomas and 10 anaplastic large-cell lymphomas), and 15 highly aggressive lymphomas (7 lymphoblastic lymphomas and 8 Burkitt’s lymphomas). Strong expression of initiation factors 4E and 2α was demonstrated in the germinal centers of reactive follicles. Minimal or no expression was seen in the mantle zones and surrounding paracortices, indicating that high expression of initiation factors 4E and 2α is associated with the active proliferation of lymphocytes. Most cases of aggressive and highly aggressive lymphomas showed strong expression of initiation factors 4E and 2α, in contrast to the cases of indolent and moderately aggressive lymphoma, in which their expression was intermediate between the germinal centers and the mantles of reactive

CT imaging features of anaplastic thyroid carcinoma

International Nuclear Information System (INIS)

Shi Zhenshan; You Ruixiong; Cao Dairong; Li Yueming; Zhuang Qian

2013-01-01

Objective: To investigate the CT characteristics of anaplastic thyroid carcinoma and evaluate the diagnostic value of CT in this disease. Methods: The CT findings of 10 patients with pathologically proved anaplastic thyroid carcinoma were retrospectively reviewed. The patients included 7 females and 3 males. Their age ranged from 25.0 to 78 years with median of 61 years. Multi-slices plain and post contrast CT scans were performed in all patients. Results: Unilateral thyroid was involved in 6 patients. Unilateral thyroid and thyroid isthmus were both involved in 2 patients due to big size. Bilateral thyroid were involved in 2 patients. The maximum diameter of anaplastic thyroid carcinoma ranged from 2.9-12.8 cm with mean of (4.5 ± 1.4) cm. All lesions demonstrated unclear margins and envelope invasion. The densities of all lesions were heterogeneous and obvious necrosis areas were noted on precontrast images. Seven lesions showed varied calcifications, and coarse granular calcifications were found in 5 lesions among them. All lesions showed remarkable heterogenous enhancement on post-contrast CT. The CT value of solid portion of the tumor increased 40 HU after contrast media administration. The ratios of CT value which comparing of the tumor with contralateral sternocleidomastoid muscle were 0.69-0.82 (0.76 ± 0.18) and 1.25-1.41 (1.33 ± 0.28) on pre and post CT, respectively. Enlarged cervical lymph nodes were found in 6 cases (60.0%). It showed obvious homogeneous enhancement or irregular ring-like enhancement on post-contrast images and dot calcifications were seen in 1 case. Conclusions: Relative larger single thyroid masses with coarse granular calcifications, necrosis,envelope invasion, remarkable heterogeneous enhancing and enlarged lymph nodes on CT are suggestive of anaplastic thyroid carcinoma. (authors)

Anaplastic ganglioglioma arising from a Lhermitte-Duclos-like lesion. Case report.

Science.gov (United States)

Takei, Hidehiro; Dauser, Robert; Su, Jack; Chintagumpala, Murali; Bhattacharjee, Meenakshi B; Jones, Jeremy; Adesina, Adekunle M

2007-08-01

The authors report the case of a 7-year-old boy with a history of developmental delay who presented with aggressive behavior. A magnetic resonance (MR) image showed a mass lesion originating from the cerebellar vermis with an atypical folial pattern and contrast enhancement. Histologically, the subtotally resected specimen consisted mostly of neuropil with nodular foci of ganglion cells. Lhermitte-Duclos disease (LDD) was diagnosed in the patient. A retrospective review of the tissue sections showed a nidus of associated astrocytic proliferation, suggesting a diagnosis of ganglioglioma. Five years later, the patient experienced an altered mental state and a facial droop. An MR image revealed a cerebellar mass with cystic areas and an enhancing nodule. The resected tissue specimen consisted primarily of a mixed proliferation of glial and ganglion cells consistent with a ganglioglioma. Two years later, a third craniectomy was performed in the patient for worsening headache and ataxia. Histologically, the tumor showed progressive anaplasia and was most accurately classified as an anaplastic ganglioglioma. Immunohistochemically, most of the tumor cells were immunoreactive for anti-phospho-mammalian target of rapamycin (mTOR) and phospho-S6 ribosomal protein antibodies. In contrast, the subpopulation of neoplastic ganglion cells in the tissue, particularly from the first surgery, did not express phosphatase and tensin homolog deleted from chromosome 10 (PTEN). This immunohistochemical pattern suggests that the large dysplastic ganglion cells (the gangliocytomatous component) forming the greater part of the lesion were associated with activation of the phosphatidylinositol 3-kinase-PTEN/Akt/mTOR signaling pathway, a feature previously reported in LDD. This case represents the first report of an anaplastic ganglioglioma arising in an LDD-like lesion.

Anaplastic pleomorphic xanthoastrocytoma

Directory of Open Access Journals (Sweden)

Li-wei SHAO

2017-09-01

Full Text Available Objective To investigate the clinicopathological features, immune phenotype and gene mutation characteristics, and diagnosis or differential diagnosis of anaplastic pleomorphic xanthoastrocytoma (PXA. Methods and Results A 11 - year- old male patient presented with more than half month of headache, and left upper limb weakness. Cranial CT and MRI revealed a large space-occupying lesion in the right parietal lobe and basal ganglia which was suggested as glioma. During operation the tumor was examined. It was a cystic-solid lesion. The solid part was soft and greyish yellow with rich blood supply and without membrane, and the boundary was clear. Intraoperative freezing pathologic examination showed the tumor was a low grade glioma. The right parietal glioma was completely removed piece by piece under the microscopy. Histologically, the tumor cells were polymorphism, including spindle or round astrocytes, monocytes and multinuclear tumor giant cells. Mitoses were rarely seen. Differentiation of mature neuronal cells or ganglion cells with lymphocyte infiltration were seen in focal region. In some regions, tumor cells were anaplastic, and cellularity were increased. Atypical round or spindle cells were seen, and atypical mitoses > 5/10 high power field (HPF were found. icrovascular proliferation, perivascular pseudorosettes and localized necrosis were also evident. Immunohistochemically, tumor cells were positive for glial fibrillary acidic protein (GFAP, BRAF V600E, S-100 protein (S-100, CD34, synaptophysin (Syn, non- phosphorylation neurofilament heauy chain SMI- 32 and P53, but negative for isocitrate dehydrogenase 1(IDH1, neurofilament protein (NF and epithelial membrane antigen (EMA. Ki - 67 labeling index was about 3% in low grade tumor cells, while Ki-67 labeling index was about 30% in high grade tumor cells. In reticular fibre tissue staining, a lot of reticular fibre tissue were seen. BRAF V600E heterozygous mutation c.1799A > T was

Radiographically Negative, Asymptomatic, Sentinel Lymph Node Positive Cutaneous T-Cell Lymphoma in a 3-Year-Old Male: A Case Report

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Jeffrey Carson

2012-01-01

Full Text Available We present a case of a 3-year-old male originally diagnosed with a CD30+ anaplastic cutaneous T-cell lymphoma with no evidence of systemic disease after CT scan, PET scan, and bone marrow aspiration. Sentinel lymph node biopsy (SLNB was performed as an additional step in the workup and showed microscopic disease. Current management/recommendations for cutaneous T-cell lymphoma do not include SLNB. Medical and surgical management of cutaneous malignancies is dramatically different for local versus advanced disease. Therefore adequate evaluation is necessary to properly stage patients for specific treatment. Such distinction in extent of disease suggests more extensive therapy including locoregional radiation and systemic chemotherapy versus local excision only. Two international case reports have described SLNB in cutaneous T-cell lymphoma with one demonstrating evidence of node positive microscopic disease despite a negative metastatic disease workup. This case is being presented as a novel case in a child with implications including lymphoscintigraphy and SLNB as a routine procedure for evaluation and staging of cutaneous T-cell lymphoma if the patient does not demonstrate evidence of metastatic disease on routine workup.

Risk of lymphoma in women with breast implants: analysis of clinical studies.

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Largent, Joan; Oefelein, Michael; Kaplan, Hilton M; Okerson, Ted; Boyle, Peter

2012-05-01

Large studies suggest that the overall rate of lymphoma in women with breast implants is no greater than in the general population; clinical reports suggest an association between breast implants and the rare non-Hodgkin lymphoma, anaplastic large cell lymphoma (ALCL). Observed cases of lymphoma reported in Allergan-sponsored breast implant clinical studies were compared with expected cases on the basis of the incidence of lymphoma among women in the National Cancer Institute's Surveillance Epidemiology and End Results program, using standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). In clinical studies, there were 28 observed cases of lymphoma among 89 382 patients and 204 682 person-years of follow-up compared with 43 expected cases [SIR: 28/43=0.65 (95% CI: 0.43-0.94), P=0.02]. SIRs were calculated stratifying by baseline cancer history: women without prior cancer [SIR: 17/24=0.70 (95% CI: 0.41-1.13), P=0.17] and women with prior cancer [SIR: 11/14=0.79 (95% CI: 0.39-1.41), P=0.52]. SIRs were calculated by implant shell type: textured shell implants [SIR: 16/23=0.70 (95% CI: 0.40-1.13), P=0.16] and smooth shell implants [SIR: 12/19=0.63 (95% CI: 0.33-1.10), P=0.12]. Surveillance Epidemiology and End Results reported 12 cases of primary breast ALCL in women between 1996 and 2007 without a history of cancer, for an average annual incidence of 4.28 (95% CI: 3.51-5.05)/100 million women in the US - these women may or may not have breast implants. In clinical studies, three ALCL cases were reported in women with breast implants and a history of breast cancer, yielding a crude incidence rate of 1.46 (95% CI: 0.30-4.3)/100 000 person-years. Large clinical studies, based on over 200 000 person-years of follow-up, suggest no evidence of an increased risk of lymphoma among women who have received breast implants.

Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods.

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Leilei Liu

Full Text Available Anaplastic lymphoma kinase (ALK and echinoderm microtubule-associated protein-like 4 (EML4 gene rearrangements occur in approximately 5% of non-small-cell lung cancers (NSCLC, leading to the overexpression of anaplastic lymphoma kinase and predicting a response to the targeted inhibitor, crizotinib. Malignant pleural effusion occurs in most patients with advanced lung cancer, especially adenocarcinoma, and tissue samples are not always available from these patients. We attempted to clarify the feasibility of detecting the EML4-ALK fusion gene in pleural effusion cells using different methods. We obtained 66 samples of pleural effusion from NSCLC patients. The pleural effusion fluid was centrifuged, and the cellular components obtained were formalin fixed and paraffin embedded. The EML4-ALK fusion gene status was determined with fluorescent in situ hybridization (FISH, reverse transcription-polymerase chain reaction (RT-PCR, and immunohistochemistry (IHC. EML4-ALK was detected in three of 66 patient samples (4.5% with RT-PCR. When the RT-PCR data were used as the standard, one false positive and one false negative samples were identified with IHC; and one false negative sample was identified with FISH. These results suggest that a block of pleural effusion cells can be used to detect the EML4-ALK fusion gene. IHC had good sensitivity, but low specificity. FISH had low sensitivity, but high specificity. RT-PCR is a good candidate method for detecting EML4-ALK in blocks of pleural effusion cells from lung cancer patients.

Synthesis, molecular docking, DFT calculations and cytotoxicity activity of benzo[g]quinazoline derivatives in choline chloride-urea

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Lakshmanan, Sivalingam; Govindaraj, Dharman; Ramalakshmi, Narayanan; Antony, S. Arul

2017-12-01

Green and highly efficient one-pot three component approach for the synthesis of benzo[g]quinazoline derivatives (6a-g) using Choline chloride-urea (DES). Synthesized compounds 6b and 6g showed the most potent biological activity against A549 lung cancer cell line. Docking simulation was performed to position compounds 6b and 6g showed the greater affinity for anaplastic lymphoma kinase (ALK) receptor. Quantum chemical studies were carried out on these compounds to understand the structural features essential for activity using DFT/6-31G level of theory.

Second-generation inhibitors of Bruton tyrosine kinase

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Jingjing Wu

2016-09-01

Full Text Available Abstract Bruton tyrosine kinase (BTK is a critical effector molecule for B cell development and plays a major role in lymphoma genesis. Ibrutinib is the first-generation BTK inhibitor. Ibrutinib has off-target effects on EGFR, ITK, and Tec family kinases, which explains the untoward effects of ibrutinib. Resistance to ibrutinib was also reported. The C481S mutation in the BTK kinase domain was reported to be a major mechanism of resistance to ibrutinib. This review summarizes the clinical development of novel BTK inhibitors, ACP-196 (acalabrutinib, ONO/GS-4059, and BGB-3111.

Anaplastic thyroid carcinoma in Denmark 1996-2012

DEFF Research Database (Denmark)

Hvilsom, Gitte Bjørn; Londero, Stefano Christian; Hahn, Christoffer Holst

2018-01-01

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is the least common but most malignant thyroid cancer. We aimed to examine the characteristics as well as evaluate the incidence, prognostic factors, and if introduction of a fast track cancer program might influence survival in a cohort of ATC...

Influence of cations on activity and distribution of protein kinase C in S49 lymphoma cells

International Nuclear Information System (INIS)

Brunton, L.; Watson, M.; Schultz, M.; Trejo, J.; Speizer, L.

1987-01-01

In S49 lymphoma cells, the distribution of protein kinase C (PKC) between soluble and membrane fractions can be regulated by the concentration of Ca ++ in the homogenization buffer. When cells are fractionated with 10μM Ca ++ and low Mg ++ (0.3mM), PKC is largely (56%) membrane-bound. Mg ++ inhibits this effect of Ca ++ by 75%; the EC 50 for Mg ++ reducing the translocation induced by 10μM Ca ++ is 1mM, as detected by binding of [ 3 H] phorbol dibutyrate ([ 3 H]PDB). Other divalent cations have different effects. When Cu ++ (1mM) is included in the homogenization buffer, both the enzymic activity of PKC and its capacity to bind [ 3 H]PDB are lost in both the cytosolic and membrane fractions. Cd ++ and Zn ++ (at 1mM) also inhibit the binding of [ 3 H]PDB to PKC in cytosolic fractions. K + , Li + , Co ++ and Mn ++ at 1mM do not mimic these effects. With Ca ++ at 500μM, the EC 50 for inhibition by Cu ++ of [ 3 H]PDB binding and enzymic activity of PKC are 25μM and 75μM, respectively. These effects of Cu ++ are also noticeable when the cation is added to intact S49 cells. The effect of Cu ++ on PKC is only relatively specific: [Cu ++ ] ≥ 100μM inhibits the activity of cyclic AMP-dependent protein kinase in vitro. Knowledge of these effects of heavy metals on PKC may prove helpful in manipulation of the enzyme pharmacologically as well as in determining the role of PKC in the cellular responses to heavy metals

Brentuximab Vedotin + Rituximab as Frontline Therapy for Pts w/ CD30+ and/or EBV+ Lymphomas

Science.gov (United States)

2015-04-28

Adult Grade III Lymphomatoid Granulomatosis; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Epstein-Barr Virus Infection; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Progressive Hairy Cell Leukemia, Initial Treatment; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis

Response to crizotinib in a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant

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Zhao, Zheng; Song, Zhangjun; Wang, Xuwei; Sun, Haifeng; Yang, Xiaomin; Yuan, Yong; Yu, Pan

2017-01-01

ROS1 fusion is a common genetic alteration in non-small-cell lung cancer. Crizotinib, an anaplastic lymphoma kinase inhibitor, shows efficacy in the treatment of lung cancer cases with ROS1 translocation. We report the response to crizotinib of a lung adenocarcinoma patient harboring a novel SLC34A2-ROS1 fusion variant, which was different from the two common SLC34A2-ROS1 fusion types reported in the literature. After crizotinib administration, overall recovery was good in this patient; the primary lesion was successfully treated, the lymph node metastases had disappeared, and the metabolism was normal. PMID:28860822

The role of oestrogen receptor {alpha} in human thyroid cancer: contributions from coregulatory proteins and the tyrosine kinase receptor HER2.

LENUS (Irish Health Repository)

Kavanagh, Dara O

2012-02-01

Epidemiological, clinical, and molecular studies suggest a role for oestrogen in thyroid cancer. How oestrogen mediates its effects and the consequence of it on clinical outcome has not been fully elucidated. The participation of coregulatory proteins in modulating oestrogen receptor (ER) function and input of crosstalk with the tyrosine kinase receptor HER2 was investigated. Oestrogen induced cell proliferation in the follicular thyroid cancer (FTC)-133 cells, but not in the anaplastic 8305C cell line. Knockdown of the coactivator steroid receptor coactivator (SRC)-1 inhibited FTC-133 basal, but not oestrogen induced, cell proliferation. Oestrogen also increased protein expression of SRC-1 and the ER target gene cyclin D1 in the FTC-133 cell line. ERalpha, ERbeta, the coregulatory proteins SRC-1 and nuclear corepressor (NCoR), and the tyrosine kinase receptor HER2 were localised by immunohistochemistry and immnofluorescence in paraffin-embedded tissue from thyroid tumour patients (n=111). ERalpha was colocalised with both SRC-1 and NCoR to the nuclei of the tumour epithelial cells. Expression of ERalpha and NCoR was found predominantly in non-anaplastic tumours and was significantly associated with well-differentiated tumours and reduced incidence of disease recurrence. In non-anaplastic tumours, HER2 was significantly associated with SRC-1, and these proteins were associated with poorly differentiated tumours, capsular invasion and disease recurrence. Totally, 87% of anaplastic tumours were positive for SRC-1. Kaplan-Meier estimates of disease-free survival indicated that in thyroid cancer, SRC-1 strongly correlates with reduced disease-free survival (P<0.001), whereas NCoR predicted increased survival (P<0.001). These data suggest opposing roles for the coregulators SRC-1 and NCoR in thyroid tumour progression.

Clinicopathological profile of patients with non-hodgkin's lymphoma at a regional cancer center in Northeast India

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Adhikarimayum Ambika Devi

2017-01-01

Full Text Available Context: Incidence of non-Hodgkin's lymphoma (NHL is increasing in all parts of the world, especially over the past few decades. An insight into the clinical presentation may help in the prevention, control, and treatment of NHL. Aim: To observe the clinicopathological patterns of NHL among patients in Northeast India. Subjects and Methods: A retrospective case study on 100 proven cases of NHL registered at the Regional Institute of Medical Sciences, Manipur, during the period January 2013–May 2017 was conducted, and data were reviewed and analyzed. Statistical Analysis Used: Data were analyzed using SPSS-21 and results were presented in percentages and simple frequency. Results: Majority (43.0% of the patients were in the age group of 41 and 60 years. The mean age was 54.01 ± 18.1 years. Male:female ratio was 1.2:1. The most common presenting symptom was neck swelling (57.0%, and peripheral lymphadenopathy (76.0% was the most common sign. Primary site distribution was nodal (57.0% and extra-nodal NHL (43.0%. Most common nodal site involved was cervical lymph nodes (65.0%, and gastrointestinal tract (17.0% was the most common extranodal subsite. Majority of the patients were in stage II (36.0% at the time of diagnosis. B-cell NHL accounts for 66.0% compared to T-cell lymphoma (23.0%. Diffuse large B-cell lymphoma was the most frequent B-cell lymphoma (45.0%, and anaplastic large cell lymphoma was the most common T-cell variant (15.0%. Conclusions: A thorough insight into the clinical spectrum of NHL is necessary for optimum management and improved treatment outcome.

Combination of Ibrutinib and ABT-199 in Diffuse Large B-Cell Lymphoma and Follicular Lymphoma.

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Kuo, Hsu-Ping; Ezell, Scott A; Schweighofer, Karl J; Cheung, Leo W K; Hsieh, Sidney; Apatira, Mutiah; Sirisawad, Mint; Eckert, Karl; Hsu, Ssucheng J; Chen, Chun-Te; Beaupre, Darrin M; Versele, Matthias; Chang, Betty Y

2017-07-01

Diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma are the most prevalent B-lymphocyte neoplasms in which abnormal activation of the Bruton tyrosine kinase (BTK)-mediated B-cell receptor signaling pathway contributes to pathogenesis. Ibrutinib is an oral covalent BTK inhibitor that has shown some efficacy in both indications. To improve ibrutinib efficacy through combination therapy, we first investigated differential gene expression in parental and ibrutinib-resistant cell lines to better understand the mechanisms of resistance. Ibrutinib-resistant TMD8 cells had higher BCL2 gene expression and increased sensitivity to ABT-199, a BCL-2 inhibitor. Consistently, clinical samples from ABC-DLBCL patients who experienced poorer response to ibrutinib had higher BCL2 gene expression. We further demonstrated synergistic growth suppression by ibrutinib and ABT-199 in multiple ABC-DLBCL, GCB-DLBCL, and follicular lymphoma cell lines. The combination of both drugs also reduced colony formation, increased apoptosis, and inhibited tumor growth in a TMD8 xenograft model. A synergistic combination effect was also found in ibrutinib-resistant cells generated by either genetic mutation or drug treatment. Together, these findings suggest a potential clinical benefit from ibrutinib and ABT-199 combination therapy. Mol Cancer Ther; 16(7); 1246-56. ©2017 AACR . ©2017 American Association for Cancer Research.

Is Latin America Ready to Identify Anaplastic Large Cell Lymphoma in Breast Implants Patients? Regional Encounter During the National Plastic Surgery Meeting in Cancun, Mexico.

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Ramos-Gallardo, Guillermo; Cuenca-Pardo, Jesus; Cardenas-Camarena, Lazaro; Duran-Vega, Hector; Rodríguez-Olivares, Eugenio; Bayter-Marin, Jorge Enrique; Levelier De Doig Alvear, Gerardo; Vazquez, Guillermo; Fontbona-Torres, Montserrat; Galán-Suárez, Ricardo; Guzman-Stein, Gabriela; Guzmán-Padilla, Sergio; Echeverría-Roldán, Guillermo; Silva-Gavarrete, Jose Fernando; Vallarta-Rodríguez, Alfonso; Contreras-Bulnes, Livia; Oaxaca-Escobar, Carlos Guillemro; Caravantes-Cortes, Isabel; Flores, María Eugenia; Cowes-McGowen, Jorge; Maciel-Sosa, María Liz; Delgado-Binasco, Ricardo; Rincón-Rubio, Linda

2018-05-16

Anaplastic large cell lymphoma associated with breast implants is receiving increased attention. Most cases have been reported in Europe, North America (USA and Canada), Australia and New Zealand. Fewer cases have been reported in Latin America (including Mexico), Africa and Asia. This report was delivered during our national plastic surgery meeting in Cancun in May 2017. Before the meeting, two participants reviewed the literature. The review was performed using the following information sources: PubMed, Embase, Cochrane, Fisterra, Google Scholar and LILACS, with entries from 1980 to August 2015 in several languages (English, Spanish, French and Portuguese). The results were revealed during the meeting to the other participants. The consensus was divided into two parts. The first part included an open-ended question regarding the incidence and prevalence of the problem. The second part included clinical scenarios with different items that were rated by the participants. After this activity, accordance among the responses was evaluated. Seven cases were reported during the meeting (3 from Mexico, 3 from Chile and 1 from Argentina). Fifty percent of the participants reported consulting with guidelines and clinical centers to help with potential cases. Most agreed that further studies must be done in cases of chronic seroma where the capsule plays an important role. A current debate exists about the incidence of this problem in Latin America because we did not report the same number of cases as Europe, Australia or North America. More studies are required to determine the differences among reports in Latin America. Most representatives agreed that further studies must be done. Concern is increasing, and the problem is known. Other factors involved may be considered, and the problem must not be ignored. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the

Regulation of radiation-induced protein kinase Cδ activation in radiation-induced apoptosis differs between radiosensitive and radioresistant mouse thymic lymphoma cell lines

International Nuclear Information System (INIS)

Nakajima, Tetsuo; Yukawa, Osami; Tsuji, Hideo; Ohyama, Harumi; Wang, Bing; Tatsumi, Kouichi; Hayata, Isamu; Hama-Inaba, Hiroko

2006-01-01

Protein kinase Cδ (PKCδ) has an important role in radiation-induced apoptosis. The expression and function of PKCδ in radiation-induced apoptosis were assessed in a radiation-sensitive mouse thymic lymphoma cell line, 3SBH5, and its radioresistant variant, XR223. Rottlerin, a PKCδ-specific inhibitor, completely abolished radiation-induced apoptosis in 3SBH5. Radiation-induced PKCδ activation correlated with the degradation of PKCδ, indicating that PKCδ activation through degradation is involved in radiation-induced apoptosis in radiosensitive 3SBH5. In radioresistant XR223, radiation-induced PKCδ activation was lower than that in radiosensitive 3SBH5. Cytosol PKCδ levels in 3SBH5 decreased markedly after irradiation, while those in XR223 did not. There was no apparent change after irradiation in the membrane fractions of either cell type. In addition, basal cytosol PKCδ levels in XR223 were higher than those in 3SBH5. These results suggest that the radioresistance in XR223 to radiation-induced apoptosis is due to a difference in the regulation of radiation-induced PKCδ activation compared to that of 3SBH5. On the other hand, Atm -/- mouse thymic lymphoma cells were more radioresistant to radiation-induced apoptosis than wild-type mouse thymic lymphoma cells. Irradiated wild-type cells, but not Atm -/- cells, had decreased PKCδ levels, indicating that the Atm protein is involved in radiation-induced apoptosis through the induction of PKCδ degradation. The decreased Atm protein levels induced by treatment with Atm small interfering RNA had no effect on radiation-induced apoptosis in 3SBH5 cells. These results suggest that the regulation of radiation-induced PKCδ activation, which is distinct from the Atm-mediated cascade, determines radiation sensitivity in radiosensitive 3SBH5 cells

The Pim kinases: new targets for drug development.

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Swords, Ronan; Kelly, Kevin; Carew, Jennifer; Nawrocki, Stefan; Mahalingam, Devalingam; Sarantopoulos, John; Bearss, David; Giles, Francis

2011-12-01

The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that the Pim kinases function as effective inhibitors of apoptosis and when overexpressed, produce resistance to the mTOR (mammalian target of rapamycin) inhibitor, rapamycin . Overexpression of the PIM kinases has been reported in several hematological and solid tumors (PIM 1), myeloma, lymphoma, leukemia (PIM 2) and adenocarcinomas (PIM 3). As such, the Pim kinases are a very attractive target for pharmacological inhibition in cancer therapy. Novel small molecule inhibitors of the human Pim kinases have been designed and are currently undergoing preclinical evaluation.

KSHV/HHV-8 associated lymph node based lymphomas in HIV seronegative subjects. Case report and review of the literature

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Quyen Nguyen, MD

2016-12-01

Full Text Available Extracavitary primary effusion lymphoma (ExPEL is a rare, high-grade lymphoproliferative disorder that displays immunoblastic, plasmablastic, or anaplastic morphology. It usually lacks expression of B-cell and T-cell markers, but often expresses the plasma cell markers CD138 and MUM1, and the activation marker CD30, along with EMA. ExPEL, similar to classic PEL occurring as lymphomatous effusions in serous body cavities without an associated tumor mass, is consistently associated with human herpes virus-8 (HHV8 infection, while a majority of cases also exhibits Epstein–Barr virus (EBV co-infection. Clinically, it is characterized by an almost exclusive male predominance (98% male, HIV-positivity (96% of patients are HIV+, acute presentation with B symptoms, and unfavorable overall survival (40% of patients die within 2 months. We report an asymptomatic HIV-negative female patient with incidentally found splenomegaly and extensive PET FDG-avid retroperitoneal, pelvic, and mediastinal lymphadenopathy. A core biopsy of her right pelvic lymph node showed aggregates of atypical cells with anaplastic features. Immunohistochemistry revealed that the neoplastic cells were positive for CD45, CD20, CD30, MUM1, CD138, EMA, CD3, HHV-8 and EBER. The diagnosis of ExPEL was established. Against medical advice and given the absence of significant symptoms, the patient refused to start treatment. Four months after the diagnosis, the patient remains asymptomatic, and follow-up CT scan demonstrates stability of her lymphadenopathy. We present here a case of ExPEL in which the patient's presentation defies the clinical norms, illustrating that ExPEL should also be included in the differential diagnosis of lymphomas occurring in asymptomatic HIV-negative patients.

Demographics and outcome in paediatric non-hodgkin lymphoma: single centre experience at the children hospital, lahore, pakistan

International Nuclear Information System (INIS)

Faizan, M.; Khan, S.

2018-01-01

To describe the patient demographics and outcome analysis in paediatric non-Hodgkin lymphoma (NHL) patients. Study Design:An observational study. Place and Duration of Study:The Hematology/Oncology Unit of The Children's Hospital and Institute of Child Health, Lahore, from January 2012 till December 2014. Methodology:Demographics including age, gender, histopathology, stage and outcome data, in biopsy proven NHL patients were analyzed. Burkitts/B Cell and Diffuse Large B Cell lymphoma patients were treated with MCP 842 Protocol while T/B-cell lymphoblastic lymphoma (LL) patients were treated with EURO-LB 02 protocol. Results:Ninety-one patients were treated during the study period at CHL. Data was insufficient in 18 patients, so they were excluded from the study. Patients included were 73. Males were 53 (72.6%). Thirty-seven (50.7%) were 5-10 years of age, and 22 (30.1%) 10-16 years old. Abdominal mass was the commonest presentation seen in 32 (43.8%), lymphadenopathy in 27 (37%), intussusception in 5 (6.8%), while intestinal obstruction, obstructive uropathy, nasopharyngeal mass, gastric mass, primary bone lymphoma, pericardial effusion, jaw swelling, cheek swelling and paraspinal mass present in one (1%) each. Histopathological subtypes consist of Burkitt's lymphoma (BL) in 32 (43.8%), B cell NHL in 10 (13.7%), lymphoblastic lymphoma (LL) in 26 (35.6%), diffuse large B cell lymphoma (DLBCL) in 2 (2.8%), and anaplastic large cell lymphoma (ALCL) in 1 (1.4%). Sixty-seven (91%) presented in stage III, and six (8.4%) in stage IV. Forty-eight (65.8%) patients had completed treatment and are well to date, 16 (21.9%) died, 5 (6.8%) left against medical advice (LAMA), and 4 (5.5%) patients relapsed. Conclusion:Burkitt's lymphoma was the commonest type of NHL seen in this cohort that predominantly presented with an abdominal mass. Children usually presented in advanced stage with delayed diagnosis. Better supportive care can improve the prognosis

Radiotherapy in anaplastic thyroid carcinoma: An Australian experience

International Nuclear Information System (INIS)

So, Kevin; Smith, Robin E.; Davis, Sidney R.

2017-01-01

Anaplastic thyroid cancer is a rare and fatal malignancy, associated with significant local tumour and often treatment related morbidity. We report our experience in treating this cancer over a 20-year period. A retrospective review of prospectively collected data from a single Australian Institution (Alfred Health Radiation Oncology) was carried out on patients referred with anaplastic thyroid carcinoma between 1992 and 2013. Thirty patients (17 females and 13 males) were identified with a median age at presentation of 72 years. At presentation, six (20%), 14 (47%) and 10 (33%) patients had stage IVA, IVB and IVC disease respectively. Thirteen patients underwent radical surgical resection with five having microscopic residual (R1) and eight having macroscopic residual (R2) disease. Twenty-eight patients were offered radiotherapy with 27 proceeding with treatment. Of those who received radiotherapy, three, six and 18 were treated with adjuvant, definitive and palliative intent respectively. Six patients had concomitant chemotherapy of which three received trimodality therapy. Only one patient experienced a grade 3 toxicity (oesophagitis). Median survival was 5.3 months and at last follow-up or time of death, 19 of 27 (70.4%) maintained loco-regional control. All patients who had R1 surgical resections and radiotherapy had loco-regional control. Seven of nine (77.8%) and 12 of 18 (66.7%) achieved loco-regional control after receiving definitive or palliative radiotherapy, respectively. Our study suggests that radiotherapy with or without surgery or chemotherapy is well-tolerated and results in durable loco-regional control in a high proportion of patients with anaplastic thyroid carcinoma.

Targeted therapeutic approach for an anaplastic thyroid cancer in vitro and in vivo.

Science.gov (United States)

Stenner, Frank; Liewen, Heike; Zweifel, Martin; Weber, Achim; Tchinda, Joelle; Bode, Beata; Samaras, Panagiotis; Bauer, Stefan; Knuth, Alexander; Renner, Christoph

2008-09-01

Anaplastic thyroid carcinoma (ATC) is among the most aggressive human malignancies, being responsible for the majority of thyroid cancer-related deaths. Despite multimodal therapy including surgery, chemotherapy, and radiotherapy, the outcome of ATC is poor. The human ATC cell line MB1, derived from tumor tissue of a 57-year-old man with thyroid cancer and pronounced neutrophilia, was established from surgically excised tumor tissue. The karyotype of the cell line shows many chromosomal abnormalities. Preclinical investigations have shown antitumor activity and effectiveness of the BRAF kinase inhibitor Sorafenib and the proteasome inhibitor Bortezomib. After establishment of the MB1 cell line these agents were applied in vitro and, showing activity in a cell culture model, were also used for in vivo treatment. Sorafenib had some clinical effect, namely normalization of leucocytosis, but had no sustained impact on subsequent tumor growth and development of distant metastasis. Molecular diagnostics of the tumor demonstrated no BRAF mutations in exons 11 and 15 concordant with a rather modest effect of Sorafenib on MB1 cell growth. Clinical benefit was seen with subsequent bortezomib therapy inducing a temporary halt to lymph node growth and a progression-free interval of 7 weeks. Our observations together with previous data from preclinical models could serve as a rationale for selecting those patients suffering from ATC most likely to benefit from targeted therapy. A prospective controlled randomized trial integrating kinase and proteasome inhibitors into a therapeutic regime for ATC is warranted.

Overexpression of c-erbB2 is a negative prognostic factor in anaplastic astrocytomas

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Gulati Michel

2010-03-01

Full Text Available Abstract The epidermal growth factor receptor (EGFR family, consisting of four tyrosine kinase receptors, c-erbB1-4, seems to be influential in gliomagenesis. The aim of this study was to investigate EGFR gene amplification and expression of c-erbB1-4 receptor proteins in human anaplastic astrocytomas. Formalin-fixed and paraffin-embedded sections from 31 cases were investigated by standard immunohistochemical procedures for expression of c-erbB1-4 receptor proteins using commercial antibodies. EGFR gene amplification was studied by fluorescence in situ hybridization using paraffin-embedded tissues. Two monoclonal antibodies, NCL-EGFR-384 and NCL-EGFR, were used for EGFR detection and they displayed positive immunoreactivity in 97% and 71%, respectively. For c-erbB2 detection three monoclonal antibodies, CB11, 3B5, and 5A2, were applied and they displayed positive immunoreactivity in 45%, 100%, and 52%, respectively. Positive immunostaining for c-erbB3 and c-erbB4 was encountered in 97% and 74%, respectively. The EGFR gene was amplified in 9 out of 31 tumors (29%. After adjusting for age, Karnofsky performance status, and extent of surgical resection, Cox multiple regression analysis with overall survival as the dependent variable revealed that c-erbB2 overexpression detected by the monoclonal antibody clone CB11 was a statistically significant poor prognostic factor (P = 0.004. This study shows the convenience and feasibility of immunohistochemistry when determining the expression of receptor proteins in tissue sections of human astrocytomas. The synchronous overexpression of c-erbB1-4 proteins in anaplastic astrocytomas supports their role in the pathogenesis of these tumors. Further, c-erbB2 overexpression seems to predict aggressive behaviour.

The second-generation ALK inhibitor alectinib effectively induces apoptosis in human neuroblastoma cells and inhibits tumor growth in a TH-MYCN transgenic neuroblastoma mouse model.

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Lu, Jiaxiong; Guan, Shan; Zhao, Yanling; Yu, Yang; Woodfield, Sarah E; Zhang, Huiyuan; Yang, Kristine L; Bieerkehazhi, Shayahati; Qi, Lin; Li, Xiaonan; Gu, Jerry; Xu, Xin; Jin, Jingling; Muscal, Jodi A; Yang, Tianshu; Xu, Guo-Tong; Yang, Jianhua

2017-08-01

Activating germline mutations of anaplastic lymphoma kinase (ALK) occur in most cases of hereditary neuroblastoma (NB) and the constitutively active kinase activity of ALK promotes cell proliferation and survival in NB. Therefore, ALK kinase is a potential therapeutic target for NB. In this study, we show that the novel ALK inhibitor alectinib effectively suppressed cell proliferation and induces apoptosis in NB cell lines with either wild-type ALK or mutated ALK (F1174L and D1091N) by blocking ALK-mediated PI3K/Akt/mTOR signaling. In addition, alectinib enhanced doxorubicin-induced cytotoxicity and apoptosis in NB cells. Furthermore, alectinib induced apoptosis in an orthotopic xenograft NB mouse model. Also, in the TH-MYCN transgenic mouse model, alectinib resulted in decreased tumor growth and prolonged survival time. These results indicate that alectinib may be a promising therapeutic agent for the treatment of NB. Copyright © 2017 Elsevier B.V. All rights reserved.

Recent Advances in Targetable Therapeutics in Metastatic Non-Squamous NSCLC

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Pranshu eBansal

2016-05-01

Full Text Available Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC. With the discovery of epidermal growth factor receptor (EGFR mutations, anaplastic lymphoma kinase (ALK rearrangements and effective targeted therapies, therapeutic options are expanding for patients with lung adenocarcinoma. Here, we review novel therapies in non-squamous NSCLC, which are directed against oncogenic targets, including EGFR, ALK, ROS1, BRAF, MET, human epidermal growth factor receptor 2 (HER2, vascular endothelial growth factor receptor 2 (VEGFR2, RET and NTRK. With the rapidly evolving molecular testing and development of new targeted agents, our ability to further personalize therapy in non-squamous NSCLC is rapidly expanding.

Mechanisms of Acquired Resistance to ALK Inhibitors and the Rationale for Treating ALK-positive Lung Cancer

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Isozaki, Hideko [Department of Clinical Pharmaceutics, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Takigawa, Nagio, E-mail: ntakigaw@gmail.com [Department of General Internal Medicine 4, Kawasaki Medical School, Okayama 700-8505 (Japan); Kiura, Katsuyuki [Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama 700-8558 (Japan)

2015-04-30

The discovery of an echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene led to improved clinical outcomes in patients with lung cancer after the development of the first ALK-targeting agent, crizotinib. Some second-generation ALK tyrosine kinase inhibitors (TKIs), which might be more potent than crizotinib or effective on crizotinib-resistant patients, have been developed. Although these ALK-TKIs show an excellent response initially, most patients eventually acquire resistance. Therefore, careful consideration of the resistance mechanisms might lead to superior therapeutic strategies. Here, we summarize the history of ALK-TKIs and their underlying resistance mechanisms in both the preclinical and clinical settings. In addition, we discuss potential future treatment strategies in ALK-TKI-naïve and -resistant patients with lung cancer harboring the EML4-ALK fusion gene.

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

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Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

2005-01-01

p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

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Shah Keerti V

2005-02-01

Full Text Available Abstract Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT, and 8 supratentorial primitive neuroectodermal tumors (sPNET using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3 was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein.

Increased p53 immunopositivity in anaplastic medulloblastoma and supratentorial PNET is not caused by JC virus

Science.gov (United States)

Eberhart, Charles G; Chaudhry, Aneeka; Daniel, Richard W; Khaki, Leila; Shah, Keerti V; Gravitt, Patti E

2005-01-01

Background p53 mutations are relatively uncommon in medulloblastoma, but abnormalities in this cell cycle pathway have been associated with anaplasia and worse clinical outcomes. We correlated p53 protein expression with pathological subtype and clinical outcome in 75 embryonal brain tumors. The presence of JC virus, which results in p53 protein accumulation, was also examined. Methods p53 protein levels were evaluated semi-quantitatively in 64 medulloblastomas, 3 atypical teratoid rhabdoid tumors (ATRT), and 8 supratentorial primitive neuroectodermal tumors (sPNET) using immunohistochemistry. JC viral sequences were analyzed in DNA extracted from 33 frozen medulloblastoma and PNET samples using quantitative polymerase chain reaction. Results p53 expression was detected in 18% of non-anaplastic medulloblastomas, 45% of anaplastic medulloblastomas, 67% of ATRT, and 88% of sPNET. The increased p53 immunoreactivity in anaplastic medulloblastoma, ATRT, and sPNET was statistically significant. Log rank analysis of clinical outcome revealed significantly shorter survival in patients with p53 immunopositive embryonal tumors. No JC virus was identified in the embryonal brain tumor samples, while an endogenous human retrovirus (ERV-3) was readily detected. Conclusion Immunoreactivity for p53 protein is more common in anaplastic medulloblastomas, ATRT and sPNET than in non-anaplastic tumors, and is associated with worse clinical outcomes. However, JC virus infection is not responsible for increased levels of p53 protein. PMID:15717928

Lymphoma classification update: B-cell non-Hodgkin lymphomas.

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Jiang, Manli; Bennani, N Nora; Feldman, Andrew L

2017-05-01

Lymphomas are classified based on the normal counterpart, or cell of origin, from which they arise. Because lymphocytes have physiologic immune functions that vary both by lineage and by stage of differentiation, the classification of lymphomas arising from these normal lymphoid populations is complex. Recent genomic data have contributed additional complexity. Areas covered: Lymphoma classification follows the World Health Organization (WHO) system, which reflects international consensus and is based on pathological, genetic, and clinical factors. A 2016 revision to the WHO classification of lymphoid neoplasms recently was reported. The present review focuses on B-cell non-Hodgkin lymphomas, the most common group of lymphomas, and summarizes recent changes most relevant to hematologists and other clinicians who care for lymphoma patients. Expert commentary: Lymphoma classification is a continually evolving field that needs to be responsive to new clinical, pathological, and molecular understanding of lymphoid neoplasia. Among the entities covered in this review, the 2016 revision of the WHO classification particularly impact the subclassification and genetic stratification of diffuse large B-cell lymphoma and high-grade B-cell lymphomas, and reflect evolving criteria and nomenclature for indolent B-cell lymphomas and lymphoproliferative disorders.

Pembrolizumab and Vorinostat in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, or Hodgkin Lymphoma

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2018-04-23

Grade 3a Follicular Lymphoma; Grade 3b Follicular Lymphoma; Recurrent Classical Hodgkin Lymphoma; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mediastinal (Thymic) Large B-Cell Cell Lymphoma; Refractory Classical Hodgkin Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mediastinal (Thymic) Large B-Cell Cell Lymphoma

Incidentally Detected Kaposi Sarcoma of Adrenal Gland with Anaplastic Features in an HIV Negative Patient

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Zeliha Esin Celik

2016-01-01

Full Text Available Kaposi sarcoma (KS, a vascular tumor caused by infection with human herpesvirus 8 (HHV8, is a systemic disease that can present with cutaneous lesions with or without visceral involvement. Very few cases of KS, most of which were associated with AIDS, have been reported in the adrenal gland. Anaplastic transformation of KS is a rare clinical presentation known as an aggressive disease with local recurrence and metastatic potential. We report here a 47-year-old HIV negative male presented with extra-adrenal symptoms and had an incidentally detected anaplastic adrenal KS exhibited aggressive clinical course. To the best of our knowledge, this is the first case of anaplastic primary adrenal KS without mucocutaneous involvement but subsequently developed other side adrenal metastases in an HIV negative patient.

Activity of second-generation ALK inhibitors against crizotinib-resistant mutants in an NPM-ALK model compared to EML4-ALK

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Fontana, Diletta; Ceccon, Monica; Gambacorti-Passerini, Carlo; Mologni, Luca

2015-01-01

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor involved in both solid and hematological tumors. About 80% of ALK-positive anaplastic large-cell lymphoma (ALCL) cases are characterized by the t(2;5)(p23;q35) translocation, encoding for the aberrant fusion protein nucleophosmin (NPM)-ALK, whereas 5% of non-small-cell lung cancer (NSCLC) patients carry the inv(2)(p21;p23) rearrangement, encoding for the echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion. The ALK/c-MET/ROS inhibitor crizotinib successfully improved the treatment of ALK-driven diseases. However, several cases of resistance appeared in NSCLC patients, and ALK amino acid substitutions were identified as a leading cause of resistance to crizotinib. Second-generation ALK inhibitors have been developed in order to overcome crizotinib resistance. In this work, we profiled in vitro the activity of crizotinib, AP26113, ASP3026, alectinib, and ceritinib against six mutated forms of ALK associated with clinical resistance to crizotinib (C1156Y, L1196M, L1152R, G1202R, G1269A, and S1206Y) and provide a classification of mutants according to their level of sensitivity/resistance to the drugs. Since the biological activity of ALK mutations extends beyond the specific type of fusion, both NPM-ALK- and EML4-ALK-positive cellular models were used. Our data revealed that most mutants may be targeted by using different inhibitors. One relevant exception is represented by the G1202R substitution, which was highly resistant to all drugs (>10-fold increased IC 50 compared to wild type) and may represent the most challenging mutation to overcome. These results provide a prediction of cross-resistance of known crizotinib-resistant mutations against all second-generation tyrosine kinase inhibitors (TKIs) clinically available, and therefore could be a useful tool to help clinicians in the management of crizotinib-resistance cases

Preclinical Evaluation of the Novel BTK Inhibitor Acalabrutinib in Canine Models of B-Cell Non-Hodgkin Lymphoma.

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Bonnie K Harrington

Full Text Available Acalabrutinib (ACP-196 is a second-generation inhibitor of Bruton agammaglobulinemia tyrosine kinase (BTK with increased target selectivity and potency compared to ibrutinib. In this study, we evaluated acalabrutinib in spontaneously occurring canine lymphoma, a model of B-cell malignancy similar to human diffuse large B-cell lymphoma (DLBCL. First, we demonstrated that acalabrutinib potently inhibited BTK activity and downstream effectors in CLBL1, a canine B-cell lymphoma cell line, and primary canine lymphoma cells. Acalabrutinib also inhibited proliferation in CLBL1 cells. Twenty dogs were enrolled in the clinical trial and treated with acalabrutinib at dosages of 2.5 to 20mg/kg every 12 or 24 hours. Acalabrutinib was generally well tolerated, with adverse events consisting primarily of grade 1 or 2 anorexia, weight loss, vomiting, diarrhea and lethargy. Overall response rate (ORR was 25% (5/20 with a median progression free survival (PFS of 22.5 days. Clinical benefit was observed in 30% (6/20 of dogs. These findings suggest that acalabrutinib is safe and exhibits activity in canine B-cell lymphoma patients and support the use of canine lymphoma as a relevant model for human non-Hodgkin lymphoma (NHL.

Lennert's Lymphoma

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Narayanrao, Suresh T.; Pillai, R.; Nada, Aymen; Hasan, Suhel

2005-01-01

Lymphoepithelioid cell lymphoma (Lennert's lymphoma) is a rare morphological variant of peripheral T-cell lymphoma characterized by the presence of numerous clusters of epithelioid histiocytes without formation of discrete granulomas and the intervening atypical lymphocytes. Lennert's lymphoma is often misinterpreted as granulomatous lymphadenitis or Hodgkin's disease. This report describes fine needle aspiration cytology and histological findings in a case of Lennert's lymphoma. (author)

Identification of genuine primary pulmonary NK cell lymphoma via clinicopathologic observation and clonality assay.

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Gong, Li; Wei, Long-Xiao; Huang, Gao-Sheng; Zhang, Wen-Dong; Wang, Lu; Zhu, Shao-Jun; Han, Xiu-Juan; Yao, Li; Lan, Miao; Li, Yan-Hong; Zhang, Wei

2013-08-19

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is an uncommon lymphoma associated with the Epstein-Barr virus (EBV). It most commonly involves the nasal cavity and upper respiratory tract. Primary pulmonary NK/T cell lymphoma is extremely rare. If a patient with a NK or T-cell tumor has an unusual reaction to treatment or an unusual prognosis, it is wise to differentiate NK from T-cell tumors. The clinicopathologic characteristics, immunophenotype, EBV in situ hybridization, and T cell receptor (TCR) gene rearrangement of primary pulmonary NK cell lymphoma from a 73-year-old Chinese woman were investigated and the clonal status was determined using female X-chromosomal inactivation mosaicism and polymorphisms at the phosphoglycerate kinase (PGK) gene. The lesion showed the typical histopathologic characteristics and immunohistochemical features of NK/T cell lymphoma. However, the sample was negative for TCR gene rearrangement. A clonality assay demonstrated that the lesion was monoclonal. It is concluded that this is the first recorded case of genuine primary pulmonary NK cell lymphoma. The purpose of the present work is to recommend that pathologists carefully investigate the whole lesion to reduce the likelihood that primary pulmonary NK cell lymphoma will be misdiagnosed as an infectious lesion. In addition, TCR gene rearrangement and clonal analysis, which is based on female X-chromosomal inactivation mosaicism and polymorphisms at PGK and androgen receptor (AR) loci, were found to play important roles in differentiating NK cell lymphoma from T cell lymphoma. The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5205300349457729.

Renal Cell Carcinoma Metastatic to Thyroid Gland, Presenting Like Anaplastic Carcinoma of Thyroid

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Khalid Riaz

2013-01-01

Full Text Available Background. Renal cell carcinoma (RCC has unpredictable and diverse behavior. The classic triad of hematuria, loin pain, and abdominal mass is uncommon. At time of diagnosis, 25%–30% of patients are found to have metastases. Bones, lungs, liver, and brain are the frequent sites of metastases. RCC with metastasis to the head and neck region and thyroid gland is the rarest manifestation and anaplastic carcinoma behaving metastatic thyroid mass is an extremely rare presentation of RCC. Case Presentation. A 56-year-old Saudi man with past history of right radical nephrectomy 5 years back presented with 3 months history of rapid increasing neck mass with dysphagia, presenting like anaplastic thyroid carcinoma. Tru-cut biopsy turned out to be metastatic renal cell carcinoma. Patient was treated with radiation therapy 30 Gy in 10 fractions to mass. Patient died 4 months after the discovery of anaplastic thyroid looking metastasis. Conclusion. Rapidly progressing thyroid metastases secondary to RCC are rare and found often unresectable which are not amenable to surgery. Palliative radiotherapy can be considered for such patients.

Radioimmunotherapy for first-line and relapse treatment of aggressive B-cell non-Hodgkin lymphoma: an analysis of 215 patients registered in the international RIT-Network

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Hohloch, Karin; Lankeit, H.K.; Truemper, L. [Georg August University, Hematology and Oncology, Goettingen (Germany); Zinzani, P.L. [University of Bologna, Institute of Hematology and Medical Oncology ' ' L. e A. Seragnoli' ' , Bologna (Italy); Scholz, C.W. [Charite, University Berlin, Hematology, Oncology and Tumor Immunology, Berlin (Germany); Lorsbach, M.; Windemuth-Kieselbach, C. [Alcedis GmbH, Giessen (Germany)

2014-08-15

Very few reliable clinical data about the use of radioimmunotherapy in aggressive B-cell lymphoma exist. Patients with aggressive B-cell lymphoma registered in the international RIT-Network were analysed with regard to prior treatment, response and side effects. The RIT-Network is a web-based registry that collects observational data from radioimmunotherapy-treated patients with malignant lymphoma across 13 countries. This analysis included 215 with aggressive B-cell lymphoma out of 232 patients registered in the RIT-Network. Histological subtypes were as follows: 190 diffuse large B-cell, 15 primary mediastinal, 9 anaplastic large cell, and 1 intravascular lymphoma. The median age of the patients was 62 years (range 17 - 88), with 27 % above the age of 70 years. Radioimmunotherapy was mainly used as consolidation after first-line or second-line chemotherapy (56.1 %), as part of third-line to eighth-line therapy for relapse (16.4 %), and in refractory disease (12.2 %). Grade IV neutropenia and thrombopenia and grade III anaemia were observed. The median time to recovery of blood count was 81 days (range 0 - 600 days). The overall response rate was 63.3 %. The complete response rate was 76.4 % in patients treated as part of first-line therapy, and 44.3 % in patients with relapse. Mean overall survival in first-line therapy patients was 32.7 months and 14.0 months in patients with relapse or refractory disease, respectively. Most patients with aggressive B-cell lymphoma in the RIT-Network received radioimmunotherapy as consolidation after first-line therapy with excellent complete remission and overall survival rates compared to published data. In relapsed aggressive B-cell lymphoma, radioimmunotherapy is a safe and feasible treatment leading to satisfactory response rates with acceptable toxicity. (orig.)

B-cell receptor signaling as a driver of lymphoma development and evolution.

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Niemann, Carsten U; Wiestner, Adrian

2013-12-01

The B-cell receptor (BCR) is essential for normal B-cell development and maturation. In an increasing number of B-cell malignancies, BCR signaling is implicated as a pivotal pathway in tumorigenesis. Mechanisms of BCR activation are quite diverse and range from chronic antigenic drive by microbial or viral antigens to autostimulation of B-cells by self-antigens to activating mutations in intracellular components of the BCR pathway. Hepatitis C virus infection can lead to the development of splenic marginal zone lymphoma, while Helicobacter pylori infection is associated with the development of mucosa-associated lymphoid tissue lymphomas. In some of these cases, successful treatment of the infection removes the inciting antigen and results in resolution of the lymphoma. Chronic lymphocytic leukemia has been recognized for decades as a malignancy of auto-reactive B-cells and its clinical course is in part determined by the differential response of the malignant cells to BCR activation. In a number of B-cell malignancies, activating mutations in signal transduction components of the BCR pathway have been identified; prominent examples are activated B-cell-like (ABC) diffuse large B-cell lymphomas (DLBCL) that carry mutations in CD79B and CARD11 and display chronic active BCR signaling resulting in constitutive activation of the NF-κB pathway. Despite considerable heterogeneity in biology and clinical course, many mature B-cell malignancies are highly sensitive to kinase inhibitors that disrupt BCR signaling. Thus, targeted therapy through inhibition of BCR signaling is emerging as a new treatment paradigm for many B-cell malignancies. Here, we review the role of the BCR in the pathogenesis of B-cell malignancies and summarize clinical results of the emerging class of kinase inhibitors that target this pathway. Copyright © 2013. Published by Elsevier Ltd.

High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

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2010-08-05

Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

Mantle Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Marginal Zone Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Integrated DNA methylation and copy-number profiling identify three clinically and biologically relevant groups of anaplastic glioma.

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Wiestler, Benedikt; Capper, David; Sill, Martin; Jones, David T W; Hovestadt, Volker; Sturm, Dominik; Koelsche, Christian; Bertoni, Anna; Schweizer, Leonille; Korshunov, Andrey; Weiß, Elisa K; Schliesser, Maximilian G; Radbruch, Alexander; Herold-Mende, Christel; Roth, Patrick; Unterberg, Andreas; Hartmann, Christian; Pietsch, Torsten; Reifenberger, Guido; Lichter, Peter; Radlwimmer, Bernhard; Platten, Michael; Pfister, Stefan M; von Deimling, Andreas; Weller, Michael; Wick, Wolfgang

2014-10-01

The outcome of patients with anaplastic gliomas varies considerably. Whether a molecular classification of anaplastic gliomas based on large-scale genomic or epigenomic analyses is superior to histopathology for reflecting distinct biological groups, predicting outcomes and guiding therapy decisions has yet to be determined. Epigenome-wide DNA methylation analysis, using a platform which also allows the detection of copy-number aberrations, was performed in a cohort of 228 patients with anaplastic gliomas (astrocytomas, oligoastrocytomas, and oligodendrogliomas), including 115 patients of the NOA-04 trial. We further compared these tumors with a group of 55 glioblastomas. Unsupervised clustering of DNA methylation patterns revealed two main groups correlated with IDH status: CpG island methylator phenotype (CIMP) positive (77.5 %) or negative (22.5 %). CIMP(pos) (IDH mutant) tumors showed a further separation based on copy-number status of chromosome arms 1p and 19q. CIMP(neg) (IDH wild type) tumors showed hallmark copy-number alterations of glioblastomas, and clustered together with CIMP(neg) glioblastomas without forming separate groups based on WHO grade. Notably, there was no molecular evidence for a distinct biological entity representing anaplastic oligoastrocytoma. Tumor classification based on CIMP and 1p/19q status was significantly associated with survival, allowing a better prediction of outcome than the current histopathological classification: patients with CIMP(pos) tumors with 1p/19q codeletion (CIMP-codel) had the best prognosis, followed by patients with CIMP(pos) tumors but intact 1p/19q status (CIMP-non-codel). Patients with CIMP(neg) anaplastic gliomas (GBM-like) had the worst prognosis. Collectively, our data suggest that anaplastic gliomas can be grouped by IDH and 1p/19q status into three molecular groups that show clear links to underlying biology and a significant association with clinical outcome in a prospective trial cohort.

Isotype-specific inhibition of the phosphatidylinositol-3-kinase pathway in hematologic malignancies

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Castillo JJ

2014-02-01

Full Text Available Jorge J Castillo,1 Meera Iyengar,2 Benjamin Kuritzky,2 Kenneth D Bishop2 1Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA, 2Division of Hematology and Oncology, Rhode Island Hospital, Providence, RI, USA Abstract: In the last decade, the advent of biological targeted therapies has revolutionized the management of several types of cancer, especially in the realm of hematologic malignancies. One of these pathways, and the center of this review, is the phosphatidylinositol-3-kinase (PI3K pathway. The PI3K pathway seems to play an important role in the pathogenesis and survival advantage in hematologic malignancies, such as leukemia, lymphoma, and myeloma. The objectives of the present review, hence, are to describe the current knowledge on the PI3K pathway and its isoforms, and to summarize preclinical and clinical studies using PI3K inhibitors, focusing on the advances made in hematologic malignancies. Keywords: phosphatidylinositol-3-kinase pathway, inhibitors, leukemia, lymphoma, myeloma

Immunohistochemistry for predictive biomarkers in non-small cell lung cancer.

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Mino-Kenudson, Mari

2017-10-01

In the era of targeted therapy, predictive biomarker testing has become increasingly important for non-small cell lung cancer. Of multiple predictive biomarker testing methods, immunohistochemistry (IHC) is widely available and technically less challenging, can provide clinically meaningful results with a rapid turn-around-time and is more cost efficient than molecular platforms. In fact, several IHC assays for predictive biomarkers have already been implemented in routine pathology practice. In this review, we will discuss: (I) the details of anaplastic lymphoma kinase (ALK) and proto-oncogene tyrosine-protein kinase ROS (ROS1) IHC assays including the performance of multiple antibody clones, pros and cons of IHC platforms and various scoring systems to design an optimal algorithm for predictive biomarker testing; (II) issues associated with programmed death-ligand 1 (PD-L1) IHC assays; (III) appropriate pre-analytical tissue handling and selection of optimal tissue samples for predictive biomarker IHC.

Anaplastic myxopapillary ependymoma in an infant: Case report and literature review.

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Trivedi, Darshan; Xiong, Zhenggang

2017-05-01

A 7-month-old boy presented with gastrointestinal disturbance, mild neurologic deficit of the left lower extremity and levo-scoliosis of the thoracic spine. Magnetic resonance imaging demonstrated a large intramedullary lesion involving the thoracic spine, from level T1 to T11. Histologic analysis showed a glial tumor with fibrillary processes arranged in radial pattern around mucoid fibrovascular cores with a high proliferative index (focally up to 80%) and prominent vascular endothelial hyperplasia. These findings were consistent with an anaplastic myxopapillary ependymoma. Subtotal resection was performed via a T3-T10 laminoplasty. A ventricular shunt was placed, and the patient subsequently received chemoradiation therapy. To date, this is the second case of a myxopapillary ependymoma with high-grade anaplastic features and the first case in an infant reported in the literature.

CHOEP-21 chemotherapy for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs) in Maharaj Nakorn Chiang Mai Hospital.

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Rattarittamrong, Ekarat; Norasetthada, Lalita; Tantiworawit, Adisak; Chai-Adisaksopha, Chatree; Nawarawong, Weerasak

2013-11-01

To determine the effectiveness and tolerability of the combination of chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) with the addition of etoposide (CHOEP-21) for newly diagnosed nodal peripheral T-cell lymphomas (PTCLs). Between January 2009 and October 2011, patients aged 18 to 60 years with newly diagnosed nodal PTCLs at the Maharaj Nakorn Chiang Mai Hospital were enrolled to receive CHOEP-21 every three weeks for eight cycles. G-CSF prophylaxis was given to all patients. Twenty-four patients were enrolled. Twenty of them were male with a median age of 49 years. The majority of patients (66.7%) had PTCL, not otherwise specified (PTCL, NOS), and 95.8% of the patients were in stage III or IV. The overall response rate was 58% with 42% having complete response. The response rates were better among patients with ALK-negative anaplastic large cell lymphoma (ALCL; 100%) and angioimmunoblastic T-cell lymphoma (AITL; 85%) than those with PTCL, NOS (44%). With a median follow-up of 21 months, the patients had an estimated 2-year event-free survival, and an overall survival rate of 37.6% and 54.4%, respectively. The most common adverse effects were infection and hematologic toxicities that was manageable. Although CHOEP-21 induced favorable responses in patients with ALK-negative ALCL and AITL, the responses were not durable and further therapy is mandated in management of patients with nodal PTCL.

Canine osteosarcoma cells exhibit resistance to aurora kinase inhibitors.

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Cannon, C M; Pozniak, J; Scott, M C; Ito, D; Gorden, B H; Graef, A J; Modiano, J F

2015-03-01

We evaluated the effect of Aurora kinase inhibitors AZD1152 and VX680 on canine osteosarcoma cells. Cytotoxicity was seen in all four cell lines; however, half-maximal inhibitory concentrations were significantly higher than in human leukaemia and canine lymphoma cells. AZD1152 reduced Aurora kinase B phosphorylation, indicating resistance was not because of failure of target recognition. Efflux mediated by ABCB1 and ABCG2 transporters is one known mechanism of resistance against these drugs and verapamil enhanced AZD1152-induced apoptosis; however, these transporters were only expressed by a small percentage of cells in each line and the effects of verapamil were modest, suggesting other mechanisms contribute to resistance. Our results indicate that canine osteosarcoma cells are resistant to Aurora kinase inhibitors and suggest that these compounds are unlikely to be useful as single agents for this disease. Further investigation of these resistance mechanisms and the potential utility of Aurora kinase inhibitors in multi-agent protocols is warranted. © 2013 Blackwell Publishing Ltd.

Conjunctival Lymphoma

DEFF Research Database (Denmark)

Kirkegaard, Marina M; Rasmussen, Peter K; Coupland, Sarah E

2016-01-01

IMPORTANCE: To date, the clinical features of the various subtypes of conjunctival lymphoma (CL) have not been previously evaluated in a large cohort. OBJECTIVE: To characterize subtype-specific clinical features of CL and their effect on patient outcome. DESIGN, SETTING, AND PARTICIPANTS...... age was 61.3 years, and 55.1% (145 of 263) were female. All lymphomas were of B-cell type. The most frequent subtype was extranodal marginal zone lymphoma (EMZL) (68.4% [180 of 263]), followed by follicular lymphoma (FL) (16.3% [43 of 263]), mantle cell lymphoma (MCL) (6.8% [18 of 263]), and diffuse...... large B-cell lymphoma (DLBCL) (4.6% [12 of 263). Conjunctival lymphoma commonly manifested in elderly individuals (age range, 60-70 years old), with EMZL having a female predilection (57.8% [104 of 180]) and MCL having a marked male predominance (77.8% [14 of 18]). Unlike EMZL and FL, DLBCL and MCL were...

Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

International Nuclear Information System (INIS)

Sabet, Amir; Ahmadzadehfar, Hojjat; Herrlinger, Ulrich; Wilinek, Winfried; Biersack, Hans-Jürgen; Ezziddin, Samer

2011-01-01

A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition

Cryptococcal meningoencephalitis in patients with mantle cell lymphoma on ibrutinib.

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Sun, Kai; Kasparian, Saro; Iyer, Swaminathan; Pingali, Sai Ravi

2018-01-01

Ibrutinib, a Bruton's tyrosine kinase inhibitor, has been increasingly widely used in relapsed and refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukaemia [1, 2]. With its use becoming more common, there have been emerging case reports of opportunistic infections like cryptococcal infections [3-8]. These infections in patients receiving ibrutinib were mostly reported in patients with chronic lymphocytic leukaemia, who have poor immune reconstitution. Here, we report two cases of cryptococcal meningoencephalitis in patients with MCL on ibrutinib.

[Clinical utility of real-time fluorescent PCR for combined detection of anaplastic lymphoma kinase and c-ros oncogene 1 receptor tyrosine kinase in non-small cell lung cancer].

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Bai, D Y; Zhang, H P; Zhong, S; Suo, W H; Gao, D H; Ding, Y; Tu, J H

2016-12-23

Objective: To investigate the clinical application value of combined detection of ALK fusion gene and c-ros oncogene 1 receptor tyrosine kinase (ROS1) fusion gene in non-small cell lung cancer (NSCLC) using real-time fluorescent PCR. Methods: A kit for combined detection of ALK fusion gene and ROS1 fusion gene based on fluorescent PCR was used to simultaneously detect the two fusion genes in 302 cases of NSCLC specimens. The results were validated through Sanger sequencing. The consistency of the two detection methods was analyzed. Results: All 302 cases of NSCLC specimens were successfully analyzed through fluorescent PCR (302/302). 12 cases (4.0%) were found to contain ALK fusion gene, including 3 cases with ALK-M1, 3 with ALK-M2, 3 with ALK-M3, 1 with ALK-M4, and 2 with ALK-M6 fusion gene.12 cases (4.0%) were found to contain ROS1 fusion gene, including 1 case with ROS1-M7, 8 cases with ROS1-M8, 1 case with ROS1-M12, 1 case with ROS1-M14, and 1 case with double-positive ROS1-M3 and ROS1-M8 fusion genes. The total detection rate of ALK fusion gene and ROS1 fusion gene was 7.9% (24/302) and 278 cases showed to be negative for ALK fusion gene and ROS1 fusion gene. The successful detection rates for Sanger DNA sequencing were also 100%. The positive, negative and total coincidence rates obtained by real-time fluorescent PCR and by Sanger DNA sequencing were all 100%. Conclusions: The results of Sanger DNA sequencing demonstrate that the real-time fluorescent PCR assay is equally effective in detecting ALK and ROS1 fusion genes in NSCLC tissues. Furthermore, real-time fluorescent PCR assay can be used to detect trace ALK and ROS1 fusion gene simultaneously in tiny samples, and can save time and avoid repeated sampling. It is worthy of recommendation as a rapid and reliable detection technique.

Composite Lymphoma : EBV-positive Classic Hodgkin Lymphoma and Peripheral T-cell Lymphoma A Case Report

NARCIS (Netherlands)

Gualco, Gabriela; Chioato, Lucimara; Van Den Berg, Anke; Weiss, Lawrence M.; Bacchi, Carlos E.

Composite lymphomas are rare and defined as hematopoietic neoplasms with more than I malignant lymphomatous clone showing different phenotypic features. Of all possible combinations between non-Hodgkin lymphomas, B cell or T cell, and Hodgkin lymphoma, the least frequent are the ones combining

Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

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Biersack Hans-Jürgen

2011-08-01

Full Text Available Abstract A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

TrkAIII Promotes Microtubule Nucleation and Assembly at the Centrosome in SH-SY5Y Neuroblastoma Cells, Contributing to an Undifferentiated Anaplastic Phenotype

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Antonietta R. Farina

2013-01-01

Full Text Available The alternative TrkAIII splice variant is expressed by advanced stage human neuroblastomas (NBs and exhibits oncogenic activity in NB models. In the present study, employing stable transfected cell lines and assays of indirect immunofluorescence, immunoprecipitation, Western blotting, microtubule regrowth, tubulin kinase, and tubulin polymerisation, we report that TrkAIII binds α-tubulin and promotes MT nucleation and assembly at the centrosome. This effect depends upon spontaneous TrkAIII activity, TrkAIII localisation to the centrosome and pericentrosomal area, and the capacity of TrkAIII to bind, phosphorylate, and polymerise tubulin. We propose that this novel role for TrkAIII contributes to MT involvement in the promotion and maintenance of an undifferentiated anaplastic NB cell morphology by restricting and augmenting MT nucleation and assembly at the centrosomal MTOC.

Primary effusion lymphoma associated with Human Herpes Virus-8 and Epstein Barr virus in an HIV-infected woman from Kampala, Uganda: a case report

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Osuwat Lawrence O

2011-02-01

Full Text Available Abstract Introduction Primary effusion lymphoma is a recently recognized entity of AIDS related non-Hodgkin lymphomas. Despite Africa being greatly affected by the HIV/AIDS pandemic, an extensive MEDLINE/PubMed search failed to find any report of primary effusion lymphoma in sub-Saharan Africa. To our knowledge this is the first report of primary effusion lymphoma in sub-Saharan Africa. We report the clinical, cytomorphologic and immunohistochemical findings of a patient with primary effusion lymphoma. Case presentation A 70-year-old newly diagnosed HIV-positive Ugandan African woman presented with a three-month history of cough, fever, weight loss and drenching night sweats. Three weeks prior to admission she developed right sided chest pain and difficulty in breathing. On examination she had bilateral pleural effusions. Haematoxylin and eosin stained cytologic sections of the formalin-fixed paraffin-embedded cell block made from the pleural fluid were processed in the Department of Pathology, Makerere University, College of Health Sciences, Kampala, Uganda. Immunohistochemistry was done at the Institute of Haematology and Oncology "L and A Seragnoli", Bologna University School of Medicine, Bologna, Italy, using alkaline phosphatase anti-alkaline phosphatase method. In situ hybridization was used for detection of Epstein-Barr virus. The tumor cells were CD45+, CD30+, CD38+, HHV-8 LANA-1+; but were negative for CD3-, CD20-, CD19-, and CD79a- and EBV RNA+ on in situ hybridization. CD138 and Ki-67 were not evaluable. Our patient tested HIV positive and her CD4 cell count was 127/μL. Conclusions A definitive diagnosis of primary effusion lymphoma rests on finding a proliferation of large immunoblastic, plasmacytoid and anaplastic cells; HHV-8 in the tumor cells, an immunophenotype that is CD45+, pan B-cell marker negative and lymphocyte activated marker positive. It is essential for clinicians and pathologists to have a high index of suspicion of

Peripheral T-Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Angioimmunoblastic T-Cell Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Anaplastic Carcinoma and Toxic Multinodular Goiter: An Unusual Presentation

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Marcelino, Mafalda; Marques, Pedro; Lopes, Luis; Leite, Valeriano; de Castro, João Jácome

2014-01-01

A 70-year-old male was referred with hyperthyroidism and multinodular goiter (MNG). Thyroid ultrasonography showed 2 nodules, one in the isthmus and the other in the left lobe, 51 and 38 mm in diameter, respectively. Neck CT showed a large MNG, thyroid scintigraphy showed increased uptake in the nodule in the left lobe, and fine-needle aspiration biopsy showed a benign cytology of the nodule in the isthmus. The patient declined surgery and was treated with methimazole. After being lost to follow-up for 3 years, the patient returned with complaints of dyspnea, dysphagia, and hoarseness; he was still hyperthyroid. Cervical CT showed a large mass in the isthmus and left lobe with invasion of surrounding tissues, the trachea, the esophagus, and the recurrent laryngeal nerve. Bronchoscopy showed extensive infiltration and compression of the trachea to 20% of its caliber. A tracheal biopsy revealed an anaplastic thyroid carcinoma. The tumor was considered unresectable, and radiotherapy was given. One month later, the patient died. The association between a toxic thyroid nodule and anaplastic thyroid carcinoma has apparently not been reported so far. PMID:25759806

Malignant lymphoma of the conjunctiva

DEFF Research Database (Denmark)

Kirkegaard, Marina M.; Coupland, Sarah E.; Prause, Jan U.

2015-01-01

Conjunctival lymphomas constitute 25% of all ocular adnexal lymphomas. The majority are B-cell non-Hodgkin lymphomas (NHLs) (98%), whereas conjunctival T-cell NHLs are rare (2%). The most frequent subtype of conjunctival B-cell lymphoma is extranodal marginal zone lymphoma (EMZL; 81%), followed...... by follicular lymphoma (8%), diffuse large B-cell lymphoma (3%), and mantle cell lymphoma (3%). Extranodal marginal zone lymphoma occurs slightly more often in women and, along with follicular lymphoma, presents late in the seventh decade of life, whereas diffuse large B-cell lymphoma and especially mantle cell...... lymphoma have a predilection for the male gender and typically present in the eighth decade. Extranodal marginal zone lymphoma and follicular lymphoma present most frequently in the forniceal and bulbar conjunctiva. Conjunctival diffuse large B-cell lymphoma, mantle cell lymphoma and T-cell NHLs...

Tandem autologous-allo-SCT is feasible in patients with high-risk relapsed non-Hodgkin's lymphoma.

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Crocchiolo, R; Castagna, L; Fürst, S; El-Cheikh, J; Faucher, C; Oudin, C; Granata, A; Bouabdallah, R; Coso, D; Chabannon, C; Balzarotti, M; Santoro, A; Blaise, D

2013-02-01

Allo-SCT is used to exploit GVL effect in high-risk relapsed non-Hodgkin's lymphoma (NHL). Here, we retrospectively analyzed 34 high-risk NHL patients who underwent auto-SCT followed closely by reduced-intensity allo-SCT ('tandem auto-allo') from January 2002 to November 2010. The search for an allogeneic donor was started at the beginning of salvage regimen. Median patients' age was 47 (27-68) years; histotypes were: diffuse large B-cell n=5, follicular n=14, transformed follicular n=4, mantle-cell n=5, plasmocytoid lymphoma n=1, anaplastic large T-cell n=2, peripheral T-cell n=3. Donors were HLA-identical siblings (n=29) or 10/10-matched unrelated individuals (n=5). Median interval between auto-SCT and allo-SCT was 77 days (36-197). At a median follow-up of 46 (8-108) months since allo-SCT, 5-year OS is 77% (61-93) and PFS is 68% (51-85). Disease relapse or progression occurred in six patients, 100-day TRM was 0%, 2-year TRM incidence was 6%. In conclusion, tandem transplantation is feasible in high-risk NHL patients having a HLA-identical donor. This approach could represent a suitable therapeutic option for those patients with high-risk NHL potentially benefitting from further therapy after auto-SCT. Donor searches should be started promptly whenever such an approach is chosen.

Detailed Functional and Proteomic Characterization of Fludarabine Resistance in Mantle Cell Lymphoma Cells.

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Lucie Lorkova

Full Text Available Mantle cell lymphoma (MCL is a chronically relapsing aggressive type of B-cell non-Hodgkin lymphoma considered incurable by currently used treatment approaches. Fludarabine is a purine analog clinically still widely used in the therapy of relapsed MCL. Molecular mechanisms of fludarabine resistance have not, however, been studied in the setting of MCL so far. We therefore derived fludarabine-resistant MCL cells (Mino/FR and performed their detailed functional and proteomic characterization compared to the original fludarabine sensitive cells (Mino. We demonstrated that Mino/FR were highly cross-resistant to other antinucleosides (cytarabine, cladribine, gemcitabine and to an inhibitor of Bruton tyrosine kinase (BTK ibrutinib. Sensitivity to other types of anti-lymphoma agents was altered only mildly (methotrexate, doxorubicin, bortezomib or remained unaffacted (cisplatin, bendamustine. The detailed proteomic analysis of Mino/FR compared to Mino cells unveiled over 300 differentially expressed proteins. Mino/FR were characterized by the marked downregulation of deoxycytidine kinase (dCK and BTK (thus explaining the observed crossresistance to antinucleosides and ibrutinib, but also by the upregulation of several enzymes of de novo nucleotide synthesis, as well as the up-regulation of the numerous proteins of DNA repair and replication. The significant upregulation of the key antiapoptotic protein Bcl-2 in Mino/FR cells was associated with the markedly increased sensitivity of the fludarabine-resistant MCL cells to Bcl-2-specific inhibitor ABT199 compared to fludarabine-sensitive cells. Our data thus demonstrate that a detailed molecular analysis of drug-resistant tumor cells can indeed open a way to personalized therapy of resistant malignancies.

Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

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Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

2014-01-01

The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

The B-cell receptor controls fitness of MYC-driven lymphoma cells via GSK3β inhibition.

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Varano, Gabriele; Raffel, Simon; Sormani, Martina; Zanardi, Federica; Lonardi, Silvia; Zasada, Christin; Perucho, Laura; Petrocelli, Valentina; Haake, Andrea; Lee, Albert K; Bugatti, Mattia; Paul, Ulrike; Van Anken, Eelco; Pasqualucci, Laura; Rabadan, Raul; Siebert, Reiner; Kempa, Stefan; Ponzoni, Maurilio; Facchetti, Fabio; Rajewsky, Klaus; Casola, Stefano

2017-06-08

Similar to resting mature B cells, where the B-cell antigen receptor (BCR) controls cellular survival, surface BCR expression is conserved in most mature B-cell lymphomas. The identification of activating BCR mutations and the growth disadvantage upon BCR knockdown of cells of certain lymphoma entities has led to the view that BCR signalling is required for tumour cell survival. Consequently, the BCR signalling machinery has become an established target in the therapy of B-cell malignancies. Here we study the effects of BCR ablation on MYC-driven mouse B-cell lymphomas and compare them with observations in human Burkitt lymphoma. Whereas BCR ablation does not, per se, significantly affect lymphoma growth, BCR-negative (BCR - ) tumour cells rapidly disappear in the presence of their BCR-expressing (BCR + ) counterparts in vitro and in vivo. This requires neither cellular contact nor factors released by BCR + tumour cells. Instead, BCR loss induces the rewiring of central carbon metabolism, increasing the sensitivity of receptor-less lymphoma cells to nutrient restriction. The BCR attenuates glycogen synthase kinase 3 beta (GSK3β) activity to support MYC-controlled gene expression. BCR - tumour cells exhibit increased GSK3β activity and are rescued from their competitive growth disadvantage by GSK3β inhibition. BCR - lymphoma variants that restore competitive fitness normalize GSK3β activity after constitutive activation of the MAPK pathway, commonly through Ras mutations. Similarly, in Burkitt lymphoma, activating RAS mutations may propagate immunoglobulin-crippled tumour cells, which usually represent a minority of the tumour bulk. Thus, while BCR expression enhances lymphoma cell fitness, BCR-targeted therapies may profit from combinations with drugs targeting BCR - tumour cells.

The effect of low level laser on anaplastic thyroid cancer

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Rhee, Yun-Hee; Moon, Jeon-Hwan; Ahn, Jin-Chul; Chung, Phil-Sang

2015-02-01

Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Here we report that the effects of laser irradiation on anaplastic thyroid cancer cells leads to hyperplasia. 650nm of laser diode was performed with a different time interval (0, 15, 30, 60J/cm2 , 25mW) on anaplastic thyroid cancer cell line FRO in vivo. FRO was orthotopically injected into the thyroid gland of nude mice and the irradiation was performed with the same method described previously. After irradiation, the xenograft evaluation was followed for one month. The thyroid tissues from sacrificed mice were undergone to H&E staining and immunohistochemical staining with HIF-1α, Akt, TGF-β1. We found the aggressive proliferation of FRO on thyroid gland with dose dependent. In case of 60 J/ cm2 of energy density, the necrotic bodies were found in a center of the thyroid. The phosphorylation of HIF-1α and Akt was detected in the thyroid gland, which explained the survival signaling of anaplastic cancer cell was turned on the thyroid gland. Furthermore, TGF-β1 expression was decreased after irradiation. In this study, we demonstrated that insufficient energy density irradiation occurred the decreasing of TGF-β1 which corresponding to the phosphorylation of Akt/ HIF-1α. This aggressive proliferation resulted to the hypoxic condition of tissue for angiogenesis. We suggest that LLLT may influence to cancer aggressiveness associated with a decrease in TGF-β1 and increase in Akt/HIF-1α.

Thirty-nine cases of intracranial hemangiopericytoma and anaplastic hemangiopericytoma: A retrospective review of MRI features and pathological findings

International Nuclear Information System (INIS)

Zhou, Jun-lin; Liu, Jian-li; Zhang, Jing; Zhang, Ming

2012-01-01

Objective: To retrospectively review the imaging features of surgically and pathologically confirmed intracranial hemangiopericytoma and anaplastic hemangiopericytoma. Methods: Thirty-nine cases of surgically and pathologically confirmed hemangiopericytoma and anaplastic hemangiopericytoma were analyzed retrospectively. The MRI features were compared with pathological findings in all cases. Results: Of the 39 cases, 21 were anaplastic hemangiopericytoma (WHO grade III) and the remaining cases were hemangiopericytoma (WHO grade II); all lesions were solitary. MRI of anaplastic hemangiopericytoma showed that 20 cases were lobulated, and nine grew cross-leaf. The lesions showed mixed iso-high-low signal (n = 20) or iso-signal (n = 1) on plain T1WI, and mixed high-low signal (n = 20) or iso-signal (n = 1) on plain T2WI. After contrast injection, marked heterogeneous enhancement was seen in 19 cases. Significant necrosis and cystic changes were seen in 16 cases, and the “dural tail sign” was found in two cases. Ten cases had bony destruction, and 16 showed significant peritumoral edema. In 18 cases of hemangiopericytoma, nine were oval-shaped and three grew cross-leaf. The lesions showed mixed iso-low signal (n = 10) or iso-signal (n = 8) on plain T1WI, and mixed iso-high signal (n = 10) or iso-signal (n = 8) on plain T2WI. After contrast injection, significant uniform enhancement was seen in 10 cases. Significant necrosis and cystic changes were seen in seven cases, and “dural tail sign” was seen in six cases. Two cases had bony destruction. No case showed significant peritumoral edema. Pathological immunohistochemical Ki67 staining showed a concentration of ∼18.4% positive cells in anaplastic hemangiopericytoma, whereas in hemangiopericytoma it was 7.12%. Conclusion: Imaging findings of intracranial anaplastic hemangiopericytoma had more pronounced lobulation, cross-leaf growth tendency, more and easier bleeding, more necrosis, more cystic changes giving

Pleomorphic xanthoastrocytoma with anaplastic features

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Cheng ZHI

2015-08-01

Full Text Available Objective  To explore the clinical pathological characteristics, immunophenotyping, diagnosis and differential diagnosis and prognosis of pleomorphic xanthoastrocytoma (PXA with anaplastic features.  Methods  HE staining was used for histological observation. The expressions of glial fibrillary acidic protein (GFAP, vimentin (Vim, CD34, epithelial membrane antigen (EMA, progestrone receptor (PR, neurofilment protein (NF, neuronal nuclei (NeuN, synaptophysin (Syn, Nestin (Nes, S-100 protein (S-100, P53 and Ki-67 labeling index were detected by immunohistochemical method. BRAF mutation was detected by polymerase chain reaction (PCR amplification.  Results  A 43-year-old male patient presented with repeatedly paroxysmal tic of limbs and disturbance of consciousness. Cranial MRI revealed multiple abnormal signals in left temporo-occipito-parietal lobe and posterior horn of lateral ventricle, with unclear borderline and cystic degeneration. Surgical removal of the lesion was performed. Histologically, the tumor was biphasic. One part was composed of spindle cells arranged in fascicles or as running water, with weird multinuclear giant cells. Abundant vacuolated lipidized cytoplasm could be seen. Mitosis and "map"-like necrosis were noted. Another part revealed the tumor cells were consistent in size and uniform in distribution, with loose background tissue. Immunohistochemistry showed tumor cells were diffusely positive for GFAP, Vim, S-100, Nes, CD34 and P53, and negative for EMA, Syn, NeuN and NF. Ki-67 labeling index was about 15%. Reticular fiber staining showed abundant reticular fibers in the tumor tissue. BRAF mutation detected by PCR amplification was not found.  Conclusions  Classified as grade Ⅱ in the World Health Organization (WHO classification, the prognosis of PXA is good. A diagnosis of PXA with anaplastic features should be considered when the tumor demonstrates mitotic activity > 5/10 high power field (HPF and/or areas of

Privileged scaffolds or promiscuous binders: a glance of pyrrolo[2,1-f][1,2,4]triazines and related bridgehead nitrogen heterocycles in medicinal chemistry.

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Song, Yu'ning; Zhan, Peng; Zhang, Qingzhu; Liu, Xinyong

2013-01-01

Pyrrolo[2,1-f][1,2,4]triazine template, a unique bridgehead nitrogen heterocycle, certainly deserves the title of "privileged scaffold" in the drug discovery field because of the versatility and potential to yield derivatives with a wide range of biological activities, such as anti-anaplastic lymphoma kinase (ALK), Janus kinase 2 (JAK2), VEGFR-2, EGFR and/or HER2, Met kinase, p38α mitogen-activated protein (MAP) kinase and insulin-like growth factor receptor (IGF-1R) kinase activities, etc. These different biological properties of pyrrolo[2,1-f][1,2,4]triazine derivatives have motivated new studies in searching for novel derivatives with improved activity and also other applications in pharmaceutical field. However, no systematic review is available in the literature on the pyrrolo[2,1- f][1,2,4]triazine derivatives concerning the design of potent drug-like compounds. Owing to the importance of this heterocyclic system, the present paper is an attempt to the pharmacological activities, structural modifications and the structure-activity relationship (SAR) reported for bridgehead nitrogen heterocycles in the current literature, making an effort to highlight the importance and therapeutic potentials of the pyrrolo[2,1-f][1,2,4]triazine scaffold and its bridgehead nitrogen bioisosters as heterocyclic privileged medicinal scaffolds.

Salvage Lenvatinib Therapy in Metastatic Anaplastic Thyroid Cancer.

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Iñiguez-Ariza, Nicole M; Ryder, Mabel M; Hilger, Crystal R; Bible, Keith C

2017-07-01

Historical anaplastic thyroid cancer (ATC) outcomes have been terrible, with a median survival of only five months and <20% one-year survival. Improved outcomes are now achieved with aggressive initial therapy in stages IVA and IVB disease, but patients with distant metastatic disease (stage IVC) still do poorly; improved therapies are sorely needed. Kinase inhibitors have emerged as promising agents in the therapy of advanced medullary and differentiated thyroid cancer, but there are limited data regarding the use of lenvatinib in ATC. The aim of this study was to delineate clinical outcomes in a series of patients with advanced ATC in response to lenvatinib therapy. A retrospective analysis was conducted involving all lenvatinib-treated Mayo Clinic ATC patients in 2015. Of 28 distinct ATC patients seen in 2015, three (11%) with metastatic disease of ECOG performance status 2-3 were treated with lenvatinib. Two patients were male; age range at ATC diagnosis was 57-84 years. All three patients attained successful local control of their disease with surgery and/or combined chemoradiotherapy. Lenvatinib was offered as the second, third, or fourth line of therapy at the time of metastatic disease progression. Two patients incurred minor responses to therapy, with structural regression of distant metastatic tumor disease soon after starting lenvatinib treatment (at one to two months), while one patient achieved stable disease, but no Response Evaluation Criteria In Solid Tumors partial responses resulted. Overall survival after starting lenvatinib was two, six, and seven months. Fatigue and hypertension were prominent, and one patient developed pulmonary emboli while on lenvatinib. This initial single-institution experience suggests that lenvatinib may have some disease-modifying activity in metastatic ATC that is otherwise refractory to cytotoxic chemotherapy. Unfortunately, observed benefits were transient, and toxicities were prominent. Clinical trials are required

Composite lymphoma: Mycosis fungoides with hodgkin′s lymphoma

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Mehta Jalpa

2005-01-01

Full Text Available Mycosis fungoides (MF is a malignant lymphoma, primarily of the skin and is characterized by infiltration of the skin by atypical T-cells which have a tendency for epidermotropism. Hodgkins disease (HD is considered to be a malignant lymphoma affecting predominantly the lymph nodes and characterized by presence of Reed- Sternberg cells on histopathology, though, the exact origin of the Reed Sternberg cell and the nature of the malignant cell is not known yet. Few cases of association of mycosis fungoides with Hodgkin′s lymphoma have been reported in the literature. It was reported in the past that when mycosis fungoides spreads to the lymph nodes and other viscera it frequently gets transformed into a more common lymphoma like Hodgkin′s lymphoma. However it has now been proved that the two malignancies are distinct and that such patients probably have a tumour diathesis.

Crizotinib-induced Rectal Perforation with Abscess.

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Yanagisawa, Asako; Hayama, Noriko; Amano, Hiroyuki; Nakamura, Makoto; Hirano, Satoshi; Nakamura, Sukeyuki; Tabeta, Hiroshi

2017-12-01

An 86-year-old Japanese man was diagnosed with stage IV lung adenocarcinoma. The patient was treated with crizotinib after echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) rearrangement was detected from his pleural effusion. He subsequently developed abdominal pain and rebound tenderness in the right lower abdomen. Contrast-enhanced abdominal CT showed a low-density area in the abdominal cavity. The size of the abscess was decreased by drainage and the administration of antibiotics. Fistulography revealed a fistula from the rectum to the abscess, and a diagnosis of lower intestinal tract perforation with abscess formation was made. Crizotinib was discontinued and treatment with alectinib was initiated. The patient remains under treatment as an outpatient at our department without adverse effects.

Primary lymphoma of the liver treated by extended hepatectomy and chemotherapy: a case report Linfoma primário do fígado tratado por hepatectomia ampliada e quimioterapia: relato de caso

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Eleazar Chaib

2002-09-01

Full Text Available Primary lymphoma of the liver is an extremely rare entity. A case of anaplastic large B-cell (both CD-20 and lambda positive non-Hodgkin's lymphoma that was confined to the liver in a 33-year-old man is reported. The patient was treated with an extended right hepatectomy and combination chemotherapy: cyclophosphamide, adriamycin, vincristine, and prednisone. The patient was disease free 24 months after the procedure.O linfoma primário do fígado é uma entidade extremamente rara. Os autores relatam um caso de linfoma não-Hodgkin de células B grandes anaplásicas (positivo para CD-20 e Lambda em um paciente do sexo masculino de 33 anos. O tumor estava localizado no lobo hepático direito e foi tratado por hepatectomia direita ampliada e quimioterapia pós-operatória com ciclofosfamida, adriamicina, vincristina e prednisone. Vinte quatro meses de seguimento o paciente encontra-se sem recidiva tumoral.

A Case of Diffuse Large B-Cell Lymphoma Mimicking Primary Effusion Lymphoma-Like Lymphoma

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Daisuke Usuda

2017-11-01

Full Text Available A 93-year-old female was transferred to the emergency ward of our hospital due to disturbance of consciousness and hypotension. Computed tomography showed bilateral pleural and pericardial effusion without evidence of tumor masses or lymphadenopathy. Cytodiagnosis of pleural effusion revealed proliferation of atypical lymphoid-like cells with pan-B surface markers. We suspected primary effusion lymphoma-like lymphoma; however, the monoclonality of these cells was not confirmed. Cytodiagnosis of bone marrow revealed lymphoma cells with monoclonal B-cell markers. These findings prompted a diagnosis of diffuse large B-cell lymphoma with bone marrow invasion. In the case of pericardial or pleural effusion, clinicians should consider carefully both hematological malignancy and its classification.

PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.

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Anella Yahiaoui

Full Text Available Activated B-cell-like diffuse large B-cell lymphoma relies on B-cell receptor signaling to drive proliferation and survival. Downstream of the B-cell receptor, the key signaling kinases Bruton's tyrosine kinase and phosphoinositide 3-kinase δ offer opportunities for therapeutic intervention by agents such as ibrutinib, ONO/GS-4059, and idelalisib. Combination therapy with such targeted agents could provide enhanced efficacy due to complimentary mechanisms of action. In this study, we describe both the additive interaction of and resistance mechanisms to idelalisib and ONO/GS-4059 in a model of activated B-cell-like diffuse large B-cell lymphoma. Significant tumor regression was observed with a combination of PI3Kδ and Bruton's tyrosine kinase inhibitors in the mouse TMD8 xenograft. Acquired resistance to idelalisib in the TMD8 cell line occurred by loss of phosphatase and tensin homolog and phosphoinositide 3-kinase pathway upregulation, but not by mutation of PIK3CD. Sensitivity to idelalisib could be restored by combining idelalisib and ONO/GS-4059. Further evaluation of targeted inhibitors revealed that the combination of idelalisib and the phosphoinositide-dependent kinase-1 inhibitor GSK2334470 or the AKT inhibitor MK-2206 could partially overcome resistance. Characterization of acquired Bruton's tyrosine kinase inhibitor resistance revealed a novel tumor necrosis factor alpha induced protein 3 mutation (TNFAIP3 Q143*, which led to a loss of A20 protein, and increased p-IκBα. The combination of idelalisib and ONO/GS-4059 partially restored sensitivity in this resistant line. Additionally, a mutation in Bruton's tyrosine kinase at C481F was identified as a mechanism of resistance. The combination activity observed with idelalisib and ONO/GS-4059, taken together with the ability to overcome resistance, could lead to a new therapeutic option in activated B-cell-like diffuse large B-cell lymphoma. A clinical trial is currently underway to

Primary lymphoma of the brain

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Brain lymphoma; Cerebral lymphoma; Primary lymphoma of the central nervous system; Lymphoma - brain ... The cause of primary brain lymphoma is not known. People with a weakened immune system are at high risk for primary lymphoma of the brain. ...

Non-Hodgkin's lymphoma in a chronic myelocytic leukemia patient treated with imatinib

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Semra Paydaş

2011-09-01

Full Text Available Imatinib is an important example of tyrosine kinase inhibitors (TKIs used in clinical practice. Imatinib blocks the ATP binding site of the Bcr-Abl fusion protein and selectively inhibits Bcr-Abl tyrosine kinase (TK activity. Treatment of chronic myelocytic leukemia (CML with imatinib is encouraging and it has an acceptable toxicity profile, and as such has changed the management of CML during the last decade. As with all drugs used in clinical practice, side effects of imatinib have been reported in studies with extended follow-up periods. In addition, some neoplastic disorders have been reported to occur during imatinib therapy. Herein we present a CML case that developed non-Hodgkin’s lymphoma (NHL while receiving imatinib treatment.

Gastric low-grade MALT lymphoma, high-grade MALT lymphoma and diffuse large B cell lymphoma show different frequencies of trisomy

NARCIS (Netherlands)

Hoeve, M A; Gisbertz, I A; Schouten, H C; Schuuring, E; Bot, F J; Hermans, J; Hopman, A; Kluin, P M; Arends, J E; van Krieken, J H

1999-01-01

Gastric MALT lymphoma is a distinct entity related to Helicobacter pylori gastritis. Some studies suggest a role for trisomy 3 in the genesis of these lymphomas, but they mainly focused on low-grade MALT lymphoma. Gastric MALT lymphoma, however, comprises a spectrum from low- to high-grade cases.

Clinical, pathological, and radiological characteristics of solitary ground-glass opacity lung nodules on high-resolution computed tomography

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Qiu ZX

2016-09-01

Full Text Available Zhi-Xin Qiu,1 Yue Cheng,1 Dan Liu,1 Wei-Ya Wang,2 Xia Wu,2 Wei-Lu Wu,2 Wei-Min Li1,2 1Department of Respiratory Medicine, 2Department of Pathology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China Background: Lung nodules are being detected at an increasing rate year by year with high-resolution computed tomography (HRCT being widely used. Ground-glass opacity nodule is one of the special types of pulmonary nodules that is confirmed to be closely associated with early stage of lung cancer. Very little is known about solitary ground-glass opacity nodules (SGGNs. In this study, we analyzed the clinical, pathological, and radiological characteristics of SGGNs on HRCT.Methods: A total of 95 resected SGGNs were evaluated with HRCT scan. The clinical, pathological, and radiological characteristics of these cases were analyzed.Results: Eighty-one adenocarcinoma and 14 benign nodules were observed. The nodules included 12 (15% adenocarcinoma in situ (AIS, 14 (17% minimally invasive adenocarcinoma (MIA, and 55 (68% invasive adenocarcinoma (IA. No patients with recurrence till date have been identified. The positive expression rates of anaplastic lymphoma kinase and ROS-1 (proto-oncogene tyrosine-protein kinase ROS were only 2.5% and 8.6%, respectively. The specificity and accuracy of HRCT of invasive lung adenocarcinoma were 85.2% and 87.4%. The standard uptake values of only two patients determined by 18F-FDG positron emission tomography/computed tomography (PET/CT were above 2.5. The size, density, shape, and pleural tag of nodules were significant factors that differentiated IA from AIS and MIA. Moreover, the size, shape, margin, pleural tag, vascular cluster, bubble-like sign, and air bronchogram of nodules were significant determinants for mixed ground-glass opacity nodules (all P<0.05.Conclusion: We analyzed the clinical, pathological, and radiological characteristics of SGGNs on HRCT and found that the size, density

Hodgkin lymphoma - children

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... families share common experiences may help ease your stress. American Childhood Cancer Organization - www.acco.org Leukemia and ... Cancer - Hodgkin lymphoma - children; Childhood Hodgkin lymphoma ... Cancer Institute website. Childhood Hodgkin lymphoma treatment (PDQ) - health professional ...

BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.

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Chiappetta, Gennaro; Basile, Anna; Arra, Claudio; Califano, Daniela; Pasquinelli, Rosa; Barbieri, Antonio; De Simone, Veronica; Rea, Domenica; Giudice, Aldo; Pezzullo, Luciano; De Laurenzi, Vincenzo; Botti, Gerardo; Losito, Simona; Conforti, Daniela; Turco, Maria Caterina

2012-01-01

Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism. BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

Lymphoma of the Eyelid

DEFF Research Database (Denmark)

Svendsen, Frederik Holm; Rasmussen, Peter Kristian; Coupland, Sarah E.

2017-01-01

Purpose To document subtype-specific clinical features of lymphoma of the eyelid, and their effect on patient outcome. Design Retrospective observational case series. Methods Patient data were collected from 7 international eye cancer centers from January 1, 1980 through December 31, 2015....... The cases included primary and secondary lymphomas affecting the eyelid. Overall survival, disease-specific survival (DSS), and progression-free survival were the primary endpoints. Results Eighty-six patients were included. Mean age was 63 years and 47 (55%) were male. Non-Hodgkin B-cell lymphomas...... constituted 83% (n = 71) and T-cell lymphomas constituted 17% (n = 15). The most common subtypes were extranodal marginal-zone lymphoma (EMZL) (37% [n = 32]), follicular lymphoma (FL) (23% [n = 20]), diffuse large B-cell lymphoma (DLBCL) (10% [n = 9]), mantle cell lymphoma (MCL) (8% [n = 7]), and mycosis...

Mantle-cell lymphoma.

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Barista, I; Romaguera, J E; Cabanillas, F

2001-03-01

During the past decade, mantle-cell lymphoma has been established as a new disease entity. The normal counterparts of the cells forming this malignant lymphoma are found in the mantle zone of the lymph node, a thin layer surrounding the germinal follicles. These cells have small to medium-sized nuclei, are commonly indented or cleaved, and stain positively with CD5, CD20, cyclin D1, and FMC7 antibodies. Because of its morphological appearance and a resemblance to other low-grade lymphomas, many of which grow slowly, this lymphoma was initially thought to be an indolent tumour, but its natural course was not thoroughly investigated until the 1990s, when the BCL1 oncogene was identified as a marker for this disease. Mantle-cell lymphoma is a discrete entity, unrelated to small lymphocytic or small-cleaved-cell lymphomas.

Transformation of marginal zone lymphoma (and association with other lymphomas).

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Casulo, Carla; Friedberg, Jonathan

Marginal zone lymphomas (MZL) are a diverse group of indolent lymphoproliferative disorders that comprise three subtypes: nodal, splenic and mucosal associated marginal zone lymphomas (MALT). Histologic transformation (HT) to an aggressive lymphoma is a rare event that can occur in any subtype, and at lower frequency compared to other indolent non Hodgkin lymphomas (NHL) like follicular lymphoma. There are few data directly associated with risk and prognosis of transformation in MZL. However, recent advances in the understanding of molecular and genetic features of MALT have contributed to an evolving appreciation of HT in this disease. Optimal treatment of HT of MZL remains unknown. Much of the approach to managing transformed MZL is extrapolated from other indolent NHLs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adult T-Cell Leukemia/Lymphoma

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-term ...

Next-generation sequencing identifies deregulation of microRNAs involved in both innate and adaptive immune response in ALK+ ALCL.

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Julia Steinhilber

Full Text Available Anaplastic large cell lymphoma (ALCL is divided into two systemic diseases according to the expression of the anaplastic lymphoma kinase (ALK. We investigated the differential expression of miRNAs between ALK+ ALCL, ALK- ALCL cells and normal T-cells using next generation sequencing (NGS. In addition, a C/EBPβ-dependent miRNA profile was generated. The data were validated in primary ALCL cases. NGS identified 106 miRNAs significantly differentially expressed between ALK+ and ALK- ALCL and 228 between ALK+ ALCL and normal T-cells. We identified a signature of 56 miRNAs distinguishing ALK+ ALCL, ALK- ALCL and T-cells. The top candidates significant differentially expressed between ALK+ and ALK- ALCL included 5 upregulated miRNAs: miR-340, miR-203, miR-135b, miR-182, miR-183; and 7 downregulated: miR-196b, miR-155, miR-146a, miR-424, miR-503, miR-424*, miR-542-3p. The miR-17-92 cluster was also upregulated in ALK+ cells. Additionally, we identified a signature of 3 miRNAs significantly regulated by the transcription factor C/EBPβ, which is specifically overexpressed in ALK+ ALCL, including the miR-181 family. Of interest, miR-181a, which regulates T-cell differentiation and modulates TCR signalling strength, was significantly downregulated in ALK+ ALCL cases. In summary, our data reveal a miRNA signature linking ALK+ ALCL to a deregulated immune response and may reflect the abnormal TCR antigen expression known in ALK+ ALCL.

Recent advances in post autologous transplantation maintenance therapies in B-cell non-Hodgkin lymphomas

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Epperla, Narendranath; Fenske, Timothy S; Hari, Parameswaran N; Hamadani, Mehdi

2015-01-01

Lymphomas constitute the second most common indication for high dose therapy (HDT) followed by autologous hematopoietic cell transplantation (auto-HCT). The intent of administering HDT in these heterogeneous disorders varies from cure (e.g., in relapsed aggressive lymphomas) to disease control (e.g., most indolent lymphomas). Regardless of the underlying histology or remission status at transplantation, disease relapse remains the number one cause of post auto-HCT therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at prevention of post auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. In relapsed, chemosensitive diffuse large B-cell lymphoma (DLBCL), although post auto-HCT maintenance rituximab seems to be safe and feasible, it does not provide improved survival outcomes and is not recommended. The preliminary results with anti- programmed death -1 (PD-1) antibody therapy as post auto-HCT maintenance in DLBCL is promising but requires randomized validation. Similarly in follicular lymphoma, maintenance therapies including rituximab following auto-HCT should be considered investigational and offered only on a clinical trial. Rituximab maintenance results in improved progression-free survival but has not yet shown to improve overall survival in mantle cell lymphoma (MCL), but given the poor prognosis with post auto-HCT failure in MCL, maintenance rituximab can be considered on a case-by-case basis. Ongoing trials evaluating the efficacy of post auto-HCT maintenance with novel compounds (e.g., immunomodulators, PD-1 inhibitors, proteasome inhibitors and bruton’s tyrosine kinase inhibitors) will likely change the practice landscape in the near future for B cell non-Hodgkin lymphomas patients following HDT and auto-HCT. PMID:26421260

Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas.

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Fanale, Michelle A; Horwitz, Steven M; Forero-Torres, Andres; Bartlett, Nancy L; Advani, Ranjana H; Pro, Barbara; Chen, Robert W; Davies, Andrew; Illidge, Tim; Uttarwar, Mayur; Lee, Shih-Yuan; Ren, Hong; Kennedy, Dana A; Shustov, Andrei R

2018-05-10

This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30 + peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789. © 2018 by The American Society of Hematology.

Primary peritoneal anaplastic giant cell carcinoma: case report of an unusual and highly malignant müllerian neoplasm.

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Lu, Xian; Zhang, Cunxian; Liu, Fang; Sung, C James; Steinhoff, Margaret M; Lawrence, W Dwayne

2008-01-01

Virtually all primary peritoneal carcinomas (PPCs) are of serous papillary type. We report an unusual histologic type of PPC composed of anaplastic giant cells, which exhibited an aggressive clinical course. A 72-year-old woman presented with lower abdominal pain. Computed tomography showed a diffuse omental thickening. The patient underwent an exploratory laparotomy with omentectomy, total hysterectomy, bilateral salpingo-oophorectomy, and appendectomy. Pathologic examination revealed extensive omental replacement by tumor but only superficial surface cortical involvement of both ovaries, a disease distribution consistent with a typical müllerian-derived PPC. However, this neoplasm was composed of diffuse anaplastic tumor giant cells, rather than serous carcinoma, which is the usual histologic type encountered in PPC. The patient died within 1 month after surgery. We report this unusual histologic variant of PPC to raise awareness that anaplastic giant cell carcinoma may arise in the pelvic peritoneum as a primary tumor.

Gemcitabine Hydrochloride, Carboplatin, Dexamethasone, and Rituximab in Treating Patients With Previously Treated Lymphoid Malignancies

Science.gov (United States)

2017-05-28

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenstrom Macroglobulinemia

Gastric Lymphoma with Secondary Trigeminal Nerve Lymphoma: A Case Report

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Warissara Rongthong

2017-05-01

Full Text Available Data supporting the role of radiotherapy in secondary trigeminal nerve lymphoma is scarce. Here, I report the case of 64-year-old Thai male diagnosed as gastric diffuse large B cell lymphoma with secondary trigeminal nerve lymphoma. He had previously received one cycle of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, followed by five cycles of rituximab plus CHOP (R-CHOP with intrathecal methotrexate (MTX and cytarabine (Ara-C. One month after the last cycle of R-CHOP, he developed a headache and numbness on the left side of his face. MRI revealed thickening of the left trigeminal nerve. He received one intrathecal injection of MTX and Ara-C, followed by systemic chemotherapy. After receiving intrathecal chemotherapy, his symptoms disappeared. Clinical response and MRI studies suggested secondary trigeminal nerve lymphoma. Two months later, our patient’s secondary trigeminal nerve lymphoma had progressed. Salvage whole brain irradiation (36 Gy with boost dose (50 Gy along the left trigeminal nerve was given. Unfortunately, our patient developed heart failure and expired during the radiotherapy session. In conclusion and specific to secondary central nervous system lymphoma (SCNSL, radiotherapy may benefit patients who fail to respond to systemic chemotherapy and palliative treatment. The results this report fail to support the role of radiotherapy in secondary trigeminal nerve lymphoma.

[Secondary orbital lymphoma].

Science.gov (United States)

Basanta, I; Sevillano, C; Álvarez, M D

2015-09-01

A case is presented of an 85 year-old Caucasian female with lymphoma that recurred in the orbit (secondary ocular adnexal lymphoma). The orbital tumour was a diffuse large B-cell lymphoma according to the REAL classification (Revised European-American Lymphoma Classification). Orbital lymphomas are predominantly B-cell proliferations of a variety of histological types, and most are low-grade tumours. Patients are usually middle-aged or elderly, and it is slightly more common in women. A palpable mass, proptosis and blepharoptosis are the most common signs of presentation. Copyright © 2011 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Lymphoma Research Foundation

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... Follow LRF Watch LRF Contact Us National Headquarters Wall Street Plaza 88 Pine Street, Suite 2400 | New York, NY 10005 212-349-2910 | 212-349-2886 Fax LRF@lymphoma.org LRF Helpline 800-500-9976 Helpline@lymphoma.org © 2012 Lymphoma Research Foundation | Privacy Policy

Molecular diagnosis of Burkitt's lymphoma

NARCIS (Netherlands)

Dave, SS; Fu, K; Wright, GW; Lam, LT; Kluin, P; Boerma, EJ; Greiner, TC; Weisenburger, DD; Rosenwald, A; Ott, G; Muller-Hermelink, H; Gascoyne, RD; Delabie, J; Rimsza, LM; Braziel, RM; Grogan, TM; Campo, E; Jaffe, ES; Dave, BJ; Sanger, W; Bast, M; Vose, JM; Armitage, JO; Connors, JM; Smeland, EB; Kvaloy, S; Holte, H; Fisher, RI; Miller, TP; Montserrat, E; Wilson, WH; Bahl, M; Zhao, H; Yang, LM; Powell, J; Simon, R; Chan, WC; Staudt, LM

2006-01-01

Background: The distinction between Burkitt's lymphoma and diffuse large-B-cell lymphoma is crucial because these two types of lymphoma require different treatments. We examined whether gene-expression profiling could reliably distinguish Burkitt's lymphoma from diffuse large-B-cell lymphoma.

Ran GTPase-activating protein 1 is a therapeutic target in diffuse large B-cell lymphoma.

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Kung-Chao Chang

Full Text Available Lymphoma-specific biomarkers contribute to therapeutic strategies and the study of tumorigenesis. Diffuse large B-cell lymphoma (DLBCL is the most common type of malignant lymphoma. However, only 50% of patients experience long-term survival after current treatment; therefore, developing novel therapeutic strategies is warranted. Comparative proteomic analysis of two DLBCL lines with a B-lymphoblastoid cell line (LCL showed differential expression of Ran GTPase-activating protein 1 (RanGAP1 between them, which was confirmed using immunoblotting. Immunostaining showed that the majority of DLBCLs (92%, 46/50 were RanGAP1(+, while reactive lymphoid hyperplasia (n = 12 was RanGAP1(+ predominantly in germinal centers. RanGAP1 was also highly expressed in other B-cell lymphomas (BCL, n = 180 with brisk mitotic activity (B-lymphoblastic lymphoma/leukemia: 93%, and Burkitt lymphoma: 95% or cell-cycle dysregulation (mantle cell lymphoma: 83%, and Hodgkin's lymphoma 91%. Interestingly, serum RanGAP1 level was higher in patients with high-grade BCL (1.71 ± 2.28 ng/mL, n = 62 than in low-grade BCL (0.75 ± 2.12 ng/mL, n = 52 and healthy controls (0.55 ± 1.58 ng/mL, n = 75 (high-grade BCL vs. low-grade BCL, p = 0.002; high-grade BCL vs. control, p < 0.001, Mann-Whitney U test. In vitro, RNA interference of RanGAP1 showed no effect on LCL but enhanced DLBCL cell death (41% vs. 60%; p = 0.035 and cell-cycle arrest (G0/G1: 39% vs. 49%, G2/M: 19.0% vs. 7.5%; p = 0.030 along with decreased expression of TPX2 and Aurora kinases, the central regulators of mitotic cell division. Furthermore, ON 01910.Na (Estybon, a multikinase inhibitor induced cell death, mitotic cell arrest, and hyperphosphorylation of RanGAP1 in DLBCL cell lines but no effects in normal B and T cells. Therefore, RanGAP1 is a promising marker and therapeutic target for aggressive B-cell lymphoma, especially DLBCL.

Transformation of follicular lymphoma to plasmablastic lymphoma with c-myc gene rearrangement.

Science.gov (United States)

Ouansafi, Ihsane; He, Bing; Fraser, Cory; Nie, Kui; Mathew, Susan; Bhanji, Rumina; Hoda, Rana; Arabadjief, Melissa; Knowles, Daniel; Cerutti, Andrea; Orazi, Attilio; Tam, Wayne

2010-12-01

Follicular lymphoma (FL) is an indolent lymphoma that transforms to high-grade lymphoma, mostly diffuse large B-cell lymphoma, in about a third of patients. We present the first report of a case of FL that transformed to plasmablastic lymphoma (PBL). Clonal transformation of the FL to PBL was evidenced by identical IGH/BCL2 gene rearrangements and VDJ gene usage in rearranged IGH genes. IGH/ BCL2 translocation was retained in the PBL, which also acquired c-myc gene rearrangement. Genealogic analysis based on somatic hypermutation of the rearranged IGH genes of both FL and PBL suggests that transformation of the FL to PBL occurred most likely by divergent evolution from a common progenitor cell rather than direct evolution from the FL clone. Our study of this unusual case expands the histologic spectrum of FL transformation and increases our understanding of the pathogenetic mechanisms of transformation of indolent lymphomas to aggressive lymphomas.

Signaling through intercellular adhesion molecule 1 (ICAM-1) in a B cell lymphoma line

DEFF Research Database (Denmark)

Holland, J; Owens, T

1997-01-01

Intercellular adhesion molecule 1 (ICAM-1) (CD54) is an adhesion molecule of the immunoglobulin superfamily. The interaction between ICAM-1 on B lymphocytes and leukocyte function-associated antigen 1 on T cells plays a major role in several aspects of the immune response, including T-dependent B...... cell activation. While it was originally believed that ICAM-1 played a purely adhesive role, recent evidence suggests that it can itself transduce biochemical signals. We demonstrate that cross-linking of ICAM-1 results in the up-regulation of class II major histocompatibility complex, and we...... investigate the biochemical mechanism for the signaling role of ICAM-1. We show that cross-linking of ICAM-1 on the B lymphoma line A20 induces an increase in tyrosine phosphorylation of several cellular proteins, including the Src family kinase p53/p56(lyn). In vitro kinase assays showed that Lyn kinase...

Molecular perspectives in differentiated thyroid cancer.

Science.gov (United States)

Buffet, C; Groussin, L

2015-02-01

Progress in understanding the molecular genetics of thyroid cancer in the last 20 years has accelerated recently with the advent of high-throughput sequencing technologies known as Next-Generation Sequencing. Besides classical molecular abnormalities involving the MAPK (Mitogen Activated Protein Kinase) and PI3K (PhosphoInositide 3-Kinase) pathways that play a key role in follicular-derived thyroid tumorigenesis, new molecular abnormalities have been discovered. The major advances in recent years have been the discovery of new somatic driver gene point mutations (such as RASAL1 [RAS protein activator Like 1] mutations in follicular cancer) and/or mutations that have prognostic value (such as TERT [Telomerase reverse transcriptase] promoter mutations); new chromosomal rearrangements, usually having close connection with exposure to ionizing radiation (such as ALK [Anaplastic Lymphoma Kinase] rearrangements); and deregulation of some gene or microRNA expression representing a molecular signature. Progress made in understanding the molecular mechanisms of thyroid cancer offers new perspectives for the diagnosis of the benign or malignant status of a thyroid nodule, to refine prognosis and offer new perspectives of targeted therapy for radioiodine-refractory cancers. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Therapy of non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Coffey, J.; Hodgson, D.C.; Gospodarowicz, M.K.

2003-01-01

Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas

Pim kinases are upregulated during Epstein-Barr virus infection and enhance EBNA2 activity

International Nuclear Information System (INIS)

Rainio, Eeva-Marja; Ahlfors, Helena; Carter, Kara L.; Ruuska, Marja; Matikainen, Sampsa; Kieff, Elliott; Koskinen, Paeivi J.

2005-01-01

Latent Epstein-Barr virus (EBV) infection is strongly associated with B-cell proliferative diseases such as Burkitt's lymphoma. Here we show that the oncogenic serine/threonine kinases Pim-1 and Pim-2 enhance the activity of the viral transcriptional activator EBNA2. During EBV infection of primary B-lymphocytes, the mRNA expression levels of pim genes, especially of pim-2, are upregulated and remain elevated in latently infected B-cell lines. Thus, EBV-induced upregulation of Pim kinases and Pim-stimulated EBNA2 transcriptional activity may contribute to the ability of EBV to immortalize B-cells and predispose them to malignant growth

Potential role of enzastaurin in the treatment of patients with relapsed or refractory advanced cutaneous T-cell lymphomas: a review

Directory of Open Access Journals (Sweden)

Katz DA

2012-06-01

Full Text Available Deborah A Katz, Janet MD Plate, Sunita Nathan, Lydia UshaDivision of Hematology and Oncology, Rush University Medical Center, Chicago, IL, USAAbstract: Cutaneous T-cell lymphomas (CTCLs are rare extranodal non-Hodgkin lymphomas characterized by neoplastic T-lymphocyte accumulation in the skin. The two most common types of CTCLs are mycosis fungoides and the leukemic variant, Sézary syndrome. Prognosis of CTCLs depends on the stage, with a poor prognosis in advanced-stage disease. A number of agents have recently been developed for the treatment of CTCLs: chemotherapeutic agents such as pralatrexate, interferon-alpha, retinoids such as bexarotene, monoclonal antibodies such as alemtuzumab, and histone deacetylase inhibitors such as vorinostat and romidepsin. Nevertheless, there is no cure for CTCLs except for allogeneic stem cell transplant. A promising new drug is enzastaurin. Enzastaurin is a novel serine/threonine kinase inhibitor that binds to protein kinase C-β (PKC-β and inhibits the phosphoinositide-3 kinase (PI3K/AKT/phosphatase and tensin homolog (PTEN signaling pathway. Enzastaurin induces apoptosis and inhibits angiogenesis; it was also shown to suppress growth of CTCL cell lines in vitro. Given its low toxicity, enzastaurin has been tested against both solid tumors and hematologic malignancies. This article is focused on the potential role of enzastaurin in the treatment of CTCLs. A phase II multicenter trial evaluated enzastaurin monotherapy in patients with CTCLs. However, the results from this study were disappointing, demonstrating that enzastaurin had only modest clinical activity. Hence, enzastaurin is not currently developed for treating CTCLs. Potential strategies to improve enzastaurin efficacy against CTCLs are discussed: validation of enzastaurin targets such as PKC-β expression in CTCL lesions and or/blood; measurement of serum vascular endothelial growth factor levels; dose optimization; combining enzastaurin with

Initiative For Thyroid Cancer Diagnosis: Decision Support System For Anaplast Thyroid Cancer

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Jamil Ahmed Chandio

2017-12-01

Full Text Available Due to the high level exposure of biomedical image analysis, Medical image mining has become one of the well-established research area(s of machine learning. AI (Artificial Intelligence techniques have been vastly used to solve the complex classification problems of thyroid cancer. Since the persistence of copycat chromatin properties and unavailability of nuclei measurement techniques, it is really problem for doctors to determine the initial phases of nuclei enlargement and to assess the early changes of chromatin distribution. For example involvement of multiple transparent overlapping of nuclei may become the cause of confusion to infer the growth pattern of nuclei variations. Un-decidable nuclei eccentric properties may become one of the leading causes for misdiagnosis in Anaplast cancers. In-order to mitigate all above stated problems this paper proposes a novel methodology so called “Decision Support System for Anaplast Thyroid Cancer” and it proposes a medical data preparation algorithm AD (Analpast_Cancers which helps to select the appropriate features of Anaplast cancers such as (1 enlargement of nuclei, (2 persistence of irregularity in nuclei and existence of hyper chromatin. Proposed methodology comprises over four major layers, first layer deals with the noise reduction, detection of nuclei edges and object clusters. Second layer selects the features of object of interest such as nuclei enlargement, irregularity and hyper chromatin. Third layer constructs the decision model to extract the hidden patterns of disease associated variables and final layer evaluates the performance evaluation by using confusion matrix, precision and recall measures. The overall classification accuracy is measured about 97.2% with 10-k fold cross validation.

Inflammatory Myofibroblastic Tumor of the Nasal Septum

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Yuri Okumura

2013-01-01

Full Text Available We report an extremely rare case of inflammatory myofibroblastic tumor of the posterior edge of the nasal septum. An 11-year-old boy presented with frequent epistaxis and nasal obstruction persisting for one year. Based on the clinical presentation and imaging studies, juvenile angiofibroma was suspected, but angiography suggested the possibility of another type of tumor. Transnasal endoscopic surgery found that the tumor protruded into the nasopharynx from the posterior end of the nasal septum. Histological examination identified spindle cells with immunoreaction for vimentin, smooth muscle actin, and anaplastic lymphoma kinase (ALK, but not for desmin and cytokeratin. This is a report of inflammatory myofibroblastic tumor mimicking juvenile angiofibroma. This case suggests that angiography is helpful in the differential diagnosis of epipharyngeal tumor in adolescence.

Monoclonal Antibody Therapy Before Stem Cell Transplant in Treating Patients With Relapsed or Refractory Lymphoid Malignancies

Science.gov (United States)

2017-10-10

Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; T-cell Large Granular Lymphocyte Leukemia; Testicular Lymphoma; Waldenström Macroglobulinemia

Imaging of MALT lymphomas

International Nuclear Information System (INIS)

Rodallec, M.; Guermazi, A.; Attal, P.; Zagdanski, A.M.; Frija, J.; De Kerviler, E.; Brice, P.

2002-01-01

The broad category of non-Hodgkin's lymphoma includes a large variety of different diseases including indolent as well as aggressive lymphomas. Mucosa-associated lymphoid tissue (MALT) lymphoma arises in the extranodal mucosal lymphoid tissue and has only been recognised as a distinct entity in recent years. It affects one or several extranodal structures such as the stomach, the lung, the eye and salivary glands. The lymphoma is generally of low grade and has indolent course. The aim of this article is to exemplify the most common radiological patterns of MALT lymphoma. (orig.)

Ligation of major histocompatibility complex class I antigens (MHC-I) prevents apoptosis induced by Fas or SAPK/JNK activation in T-lymphoma cells

DEFF Research Database (Denmark)

Lamberth, K; Claesson, M H

2001-01-01

Early apoptosis in Jurkat T-lymphoma cells was induced by agonistic anti-Fas Ab or by anisomycin which activates the stress kinases SAPK/JNK. Apoptosis was inhibited by ligation of major histocompatibility complex class I antigens (MHC-I). MHC-I ligation induced upregulation of the anti-apoptotic......Early apoptosis in Jurkat T-lymphoma cells was induced by agonistic anti-Fas Ab or by anisomycin which activates the stress kinases SAPK/JNK. Apoptosis was inhibited by ligation of major histocompatibility complex class I antigens (MHC-I). MHC-I ligation induced upregulation of the anti......-apoptotic Bcl-2 protein and stabilized the mitochondrial membrane potential (Deltapsim). MHC-I ligation also prevented downregulation of Bcl-2 and destabilization of Deltapsim induced by anti-Fas Ab treatment or anisomycin exposure. Studies on three different Jurkat cell mutants deficient for src p56(lck), ZAP......-70 kinase, or TCR/CD3 gamma-chain showed that the cells undergo apoptosis after Fas ligation. Anisomycin exposure induced apoptosis in the src p56(lck)-deficient cell line but not in the two other mutant cell lines. Simultaneous cross-linking of MHC-I and Fas ligation inhibited apoptosis in the ZAP...

Breast Augmentation

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... Administration (FDA) has identified a possible association between breast implants and the development of anaplastic large cell lymphoma (ALCL), a rare cancer of the immune system. The FDA believes that ...

Immunohistochemical Characterization of Canine Lymphomas

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Roxana CORA

2017-11-01

Full Text Available Lymphomas occur by clonal expansion of lymphoid cells and have distinctive morphological and immunophenotypic features. Determination of canine lymphoma immunophenotype is useful for accurate prognosis and further therapy. In the suggested study, we performed an immunohistochemical evaluation of some cases with canine lymphoma diagnosed in the Department of Pathology (Faculty of Veterinary Medicine, Cluj-Napoca, Romania, in order to characterize them. The investigation included 39 dogs diagnosed with different anatomical forms of lymphoma, following necropsy analysis or assessment of biopsies. The diagnosis of lymphoma was confirmed by necropsy and histopathology (Hematoxylin-eosin stain examinations. The collected specimens were analyzed by immunohistochemistry technique (automatic method using the following antibodies: CD3, CD20, CD21 and CD79a. The analyzed neoplasms were characterized as follows: about 64.10% of cases were diagnosed as B-cell lymphomas, 33.34% of cases as T-cell lymphomas, whereas 2.56% of cases were null cell type lymphomas (neither B nor T. Most of multicentric (80%, mediastinal (60% and primary central nervous system lymphomas (100% had B immunophenotype, while the majority of cutaneous (80% and digestive (100% lymphomas had T immunophenotype. Immunohistochemical description of canine lymphomas can deliver some major details concerning their behavior and malignancy. Additionally, vital prognosis and efficacy of some therapeutic protocols are relying on the immunohistochemical features of canine lymphoma.

Cyclin-dependent kinase 9 is a novel specific molecular target in adult T-cell leukemia/lymphoma.

Science.gov (United States)

Narita, Tomoko; Ishida, Takashi; Ito, Asahi; Masaki, Ayako; Kinoshita, Shiori; Suzuki, Susumu; Takino, Hisashi; Yoshida, Takashi; Ri, Masaki; Kusumoto, Shigeru; Komatsu, Hirokazu; Imada, Kazunori; Tanaka, Yuetsu; Takaori-Kondo, Akifumi; Inagaki, Hiroshi; Scholz, Arne; Lienau, Philip; Kuroda, Taruho; Ueda, Ryuzo; Iida, Shinsuke

2017-08-31

Cyclin-dependent kinase 9 (CDK9), a subunit of the positive transcription elongation factor b (P-TEFb) complex, regulates gene transcription elongation by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (RNAPII). The deregulation of CDK9/P-TEFb has important implications for many cancer types. BAY 1143572 is a novel and highly selective CDK9/P-TEFb inhibitor currently being investigated in phase 1 studies. We evaluated the therapeutic potential of BAY 1143572 in adult T-cell leukemia/lymphoma (ATL). As a result of CDK9 inhibition and subsequent inhibition of phosphorylation at serine 2 of the RNAPII CTD, BAY 1143572 decreased c-Myc and Mcl-1 levels in ATL-derived or human T-cell lymphotropic virus type-1 (HTLV-1)-transformed lines and primary ATL cells tested, leading to their growth inhibition and apoptosis. Median inhibitory concentrations for BAY 1143572 in ATL-derived or HTLV-1-transformed lines (n = 8), primary ATL cells (n = 11), and CD4 + cells from healthy volunteers (n = 5) were 0.535, 0.30, and 0.36 μM, respectively. Next, NOG mice were used as recipients of tumor cells from an ATL patient. BAY 1143572-treated ATL-bearing mice (once daily 12.5 mg/kg oral application) demonstrated significantly decreased ATL cell infiltration of the liver and bone marrow, as well as decreased human soluble interleukin-2 receptor levels in serum (reflecting the ATL tumor burden), compared with untreated mice (n = 8 for both). BAY 1143572-treated ATL-bearing mice demonstrated significantly prolonged survival compared with untreated ATL-bearing mice (n = 7 for both). Collectively, this study indicates that BAY 1143572 showed strong potential as a novel treatment of ATL. © 2017 by The American Society of Hematology.

The Danish National Lymphoma Registry

DEFF Research Database (Denmark)

Arboe, Bente; El-Galaly, Tarec Christoffer; Clausen, Michael Roost

2016-01-01

BACKGROUND: The Danish National Lymphoma Register (LYFO) prospectively includes information on all lymphoma patients newly diagnosed at hematology departments in Denmark. The validity of the clinical information in the LYFO has never been systematically assessed. AIM: To test the coverage and data...... of 3% (N = 364) was made from all patients in the LYFO. In addition, four subtypes of lymphomas were validated: CNS lymphomas, diffuse large B-cell lymphomas, peripheral T-cell lymphomas, and Hodgkin lymphomas. A total of 1,706 patients from the period 2000-2012 were included. The positive predictive...... was good with high PPVs (87% to 100%), and high completeness (92% to 100%). CONCLUSION: The LYFO is a unique, nationwide clinical database characterized by high validity, good coverage and prospective data entry. It represents a valuable resource for future lymphoma research....

Hodgkin lymphoma

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Lymphoma - Hodgkin; Hodgkin disease; Cancer - Hodgkin lymphoma ... to 70 years old. Past infection with the Epstein-Barr virus ( EBV ) is thought to contribute to some cases. People with HIV infection are at increased risk compared to the general population.

Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

International Nuclear Information System (INIS)

Ishiura, Yoshihito; Kotani, Norihiro; Yamashita, Ryusuke; Yamamoto, Harumi; Kozutsumi, Yasunori; Honke, Koichi

2010-01-01

The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

Detection of protein kinase activity by renaturation in sodium dodecyl sulfate-polyacrylamide gels

International Nuclear Information System (INIS)

Anostario, M. Jr.; Harrison, M.L.; Geahlen, R.L.

1986-01-01

The authors have developed a procedure for identifying protein kinase activity in protein samples following electrophoresis on SDS-polyacrylamide gels. Proteins are allowed to renature directly in the gel by removal of detergent. The gel is then incubated with [γ- 32 P]ATP to allow renatured protein kinases to autophosphorylate or to phosphorylate various substrates which can be incorporated into the gel. The positions of the radiolabeled proteins can then be detected by autoradiography. With this technique, using purified catalytic subunit of cAMP-dependent protein kinase, enzyme concentrations as low as 0.01 μg can be detected on gels containing 1.0 mg/ml casein. The procedure is also applicable for the determination of active subunits of multisubunit protein kinases. For example, when the two subunits of casein kinase II are separated by SDS-polyacrylamide gel electrophoresis and allowed to renature, only the larger α subunit shows activity. This procedure can also be used to detect and distinguish kinases present in heterogeneous mixtures. Starting with a particulate fraction from LSTRA, a murine T cell lymphoma, several distinct enzymes were detected, including a 30,000 Dalton protein with protein-tyrosine kinase activity. This same enzyme has also been detected in T lymphocytes and other T lymphoid cell lines

Discordant lymphoma consisting of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood: a case report

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Caracciolo Francesco

2011-09-01

Full Text Available Abstract Introduction Discordant lymphomas are rare entities characterized by the simultaneous presence of two distinct types of lymphomas in different anatomic sites. We describe a very rare case of simultaneous occurrence of splenic mantle cell lymphoma and marginal zone lymphoma involving the bone marrow and peripheral blood. Case presentation We report the case of a 60-year-old asymptomatic Caucasian woman in whom discordant lymphomas were discovered when a slight lymphocytosis and a conspicuous splenomegaly were observed. The different morphological, immunophenotypical and immunohistochemical features found in the different pathologic samples obtained from peripheral blood, bone marrow and spleen sections made it possible to differentiate two types of non-Hodgkin B-cell lymphomas: a mantle cell lymphoma infiltrating the spleen and a marginal zone lymphoma involving both the bone marrow and peripheral blood. Since a similar IgH gene rearrangement was found both in the bone marrow and in the spleen, the hypothesis of a common origin, followed by a different clonal selection of the neoplastic lymphocytes may be taken into consideration. Conclusion Our case emphasizes the usefulness of investigating simultaneous specimens from different anatomic sites from the same patient and the relevant diagnostic role of splenectomy.

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classical Burkitt's lymphoma: A case report and review

OpenAIRE

Chettiankandy, Tabita Joy; Tupkari, Jagdish Vishnu; Kumar, Keshav; Ahire, Manisha Sandeep

2016-01-01

B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Burkitt's lymphoma (BL), is a diagnostic provisional category in the World Health Organization 2008 classification of lymphomas. This category was designed as a measure to accommodate borderline cases that cannot be reliably classified into a single distinct disease entity after all available morphological, immunophenotypical and molecular studies have been performed. Typica...

How I treat double-hit lymphoma.

Science.gov (United States)

Friedberg, Jonathan W

2017-08-03

The 2016 revision of the World Health Organization (WHO) classification for lymphoma has included a new category of lymphoma, separate from diffuse large B-cell lymphoma, termed high-grade B-cell lymphoma with translocations involving myc and bcl-2 or bcl-6 . These lymphomas, which occur in hit lymphomas (or triple-hit lymphomas if all 3 rearrangements are present). It is important to differentiate these lymphomas from the larger group of double-expressor lymphomas, which have increased expression of MYC and BCL-2 and/or BCL-6 by immunohistochemistry, by using variable cutoff percentages to define positivity. Patients with double-hit lymphomas have a poor prognosis when treated with standard chemoimmunotherapy and have increased risk of central nervous system involvement and progression. Double-hit lymphomas may arise as a consequence of the transformation of the underlying indolent lymphoma. There are no published prospective trials in double-hit lymphoma, however retrospective studies strongly suggest that aggressive induction regimens may confer a superior outcome. In this article, I review my approach to the evaluation and treatment of double-hit lymphoma, with an eye toward future clinical trials incorporating rational targeted agents into the therapeutic armamentarium. © 2017 by The American Society of Hematology.

Severe Erosive Pill Esophagitis Induced by Crizotinib Therapy: A Case Report and Literature Review

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Patrick Jung

2016-01-01

Full Text Available Previous case reports have described esophagitis thought to be secondary to crizotinib, an oral tyrosine-kinase inhibitor used in the treatment of anaplastic lymphoma kinase- (ALK- positive non-small cell lung cancer (NSCLC. In those reports, the interval development of esophagitis was between two days and three months after initiating or reinitiating crizotinib therapy. We present a woman who developed ulcerative esophagitis ten months after beginning crizotinib therapy, which is highly unusual. We believe the provoking factor was a change in her medication administration routine, done to accommodate religious practices during the period of Ramadan. This case illustrates the mechanism of pill esophagitis and reinforces the importance of patient education when it comes to medication administration. Clinicians may consider early imaging or investigations in patients with concerning symptomatology in the context of crizotinib therapy or other offending medications. Future research may help to uncover additional risk factors for this exceedingly rare diagnosis in this patient population. Most importantly, this case highlights nonpharmacologic ways to improve tolerability and decrease adverse effects of a highly effective chemotherapeutic agent.

The Evolution of Therapies in Non-Small Cell Lung Cancer

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Boolell, Vishal, E-mail: vishal.boolell@monashhealth.org.au; Alamgeer, Muhammad [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Watkins, David N. [Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia); Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); UNSW Faculty of Medicine, St Vincent’s Clinical School, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Department of Thoracic Medicine, St Vincent’s Hospital, 390 Victoria Street, Darlinghurst, Sydney NSW 2010 (Australia); Ganju, Vinod [Department of Medical Oncology, Monash Medical Centre, 823-865 Centre Road, East Bentleigh VIC 3165 (Australia); Hudson Institute of Medical Research, Monash University, 27-31 Wright Street, Clayton VIC 3168 (Australia)

2015-09-09

The landscape of advanced non-small lung cancer (NSCLC) therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs). Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4) and programmed death-1 receptor (PD-1), which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

A comparative study of cell cycle mediator protein expression patterns in anaplastic and papillary thyroid carcinoma.

Science.gov (United States)

Evans, Juanita J; Crist, Henry S; Durvesh, Saima; Bruggeman, Richard D; Goldenberg, David

2012-07-01

Anaplastic thyroid carcinoma (ATC) is an extremely aggressive and rapidly fatal neoplasm. The aim of this study was to identify a limited cell cycle associated protein expression pattern unique to ATC and to correlate that pattern with clinical outcome. This represents one of the largest tissue micro-array projects comparing the cell cycle protein expression data of ATC to other well-differentiated tumors in the literature. Tissue microarrays were created from 21 patients with ATC and an age and gender matched cohort of patients with papillary thyroid carcinoma (PTC). Expression of epidermal growth factor receptor, cyclin D1, cyclin E, p53, p21, p16, aurora kinase A, opioid growth factor (OGF), OGF-receptor, thyroglobulin and Ki-67 was evaluated in a semi-quantitative fashion. Differences in protein expression between the cohorts were evaluated using chi-square tests with Bonferroni adjustments. Survival time and presence of metastasis at presentation were collected. The ATC cohort showed a statistically significant decrease (p cycle with aberrant expression of multiple protein markers suggesting increased proliferative activity and loss of control of cell cycle progression to G₁ phase. These findings support the assertion that ATC may represent the furthest end of a continuum of thyroid carcinoma dedifferentiation.

ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers

International Nuclear Information System (INIS)

Wellstein, Anton

2012-01-01

The intracellular anaplastic lymphoma kinase (ALK) fragment shows striking homology with members of the insulin receptor family and was initially identified as an oncogenic fusion protein resulting from a translocation in lymphoma and more recently in a range of cancers. The full-length ALK transmembrane receptor of ~220 kDa was identified based on this initial work. This tyrosine kinase receptor and its ligands, the growth factors pleiotrophin (PTN) and midkine (MK) are highly expressed during development of the nervous system and other organs. Each of these genes has been implicated in malignant progression of different tumor types and shown to alter phenotypes as well as signal transduction in cultured normal and tumor cells. Beyond its role in cancer, the ALK receptor pathway is thought to contribute to nervous system development, function, and repair, as well as metabolic homeostasis and the maintenance of tissue regeneration. ALK receptor activity in cancer can be up-regulated by amplification, overexpression, ligand binding, mutations in the intracellular domain of the receptor and by activity of the receptor tyrosine phosphatase PTPRz. Here we discuss the evidence for ligand control of ALK activity as well as the potential prognostic and therapeutic implications from gene expression and functional studies. An analysis of 18 published gene expression data sets from different cancers shows that overexpression of ALK, its smaller homolog LTK (leukocyte tyrosine kinase) and the ligands PTN and MK in cancer tissues from patients correlate significantly with worse course and outcome of the disease. This observation together with preclinical functional studies suggests that this pathway could be a valid therapeutic target for which complementary targeting strategies with small molecule kinase inhibitors as well as antibodies to ligands or the receptors may be used.

Imaging of non-hodgkin lymphomas

DEFF Research Database (Denmark)

El-Galaly, Tarec Christoffer; Hutchings, Martin

2015-01-01

Optimal lymphoma management requires accurate pretreatment staging and reliable assessment of response, both during and after therapy. Positron emission tomography with computerized tomography (PET/CT) combines functional and anatomical imaging and provides the most sensitive and accurate methods...... for lymphoma imaging. New guidelines for lymphoma imaging and recently revised criteria for lymphoma staging and response assessment recommend PET/CT staging, treatment monitoring, and response evaluation in all FDG-avid lymphomas, while CT remains the method of choice for non-FDG-avid histologies. Since...... interim PET imaging has high prognostic value in lymphoma, a number of trials investigate PET-based, response-adapted therapy for non-Hodgkin lymphomas (NHL). PET response is the main determinant of response according to the new response criteria, but PET/CT has little or no role in routine surveillance...

Multimodality imaging of cardiothoracic lymphoma

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Carter, Brett W., E-mail: bcarter2@mdanderson.org [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Wu, Carol C. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Khorashadi, Leila [Department of Radiology, Mount Auburn Hospital, Cambridge, MA 02138 (United States); Godoy, Myrna C.B.; Groot, Patricia M. de [The University of Texas MD Anderson Cancer Center, Department of Diagnostic Radiology, Section of Thoracic Imaging, 1515 Holcombe Blvd., Unit 1478, Houston, TX 77030 (United States); Abbott, Gerald F. [Department of Radiology, Massachusetts General Hospital, 55 Fruit Street, FND-202, Boston, MA 02114 (United States); Lichtenberger III, John P. [Department of Radiology, David Grant Medical Center, Travis AFB, CA 94535 (United States)

2014-08-15

Lymphoma is the most common hematologic malignancy and represents approximately 5.3% of all cancers. The World Health Organization published a revised classification scheme in 2008 that groups lymphomas by cell type and molecular, cytogenetic, and phenotypic characteristics. Most lymphomas affect the thorax at some stage during the course of the disease. Affected structures within the chest may include the lungs, mediastinum, pleura, and chest wall, and lymphomas may originate from these sites as primary malignancies or secondarily involve these structures after arising from other intrathoracic or extrathoracic sources. Pulmonary lymphomas are classified into one of four types: primary pulmonary lymphoma, secondary pulmonary lymphoma, acquired immunodeficiency syndrome-related lymphoma, and post-transplantation lymphoproliferative disorders. Although pulmonary lymphomas may produce a myriad of diverse findings within the lungs, specific individual features or combinations of features can be used, in combination with secondary manifestations of the disease such as involvement of the mediastinum, pleura, and chest wall, to narrow the differential diagnosis. While findings of thoracic lymphoma may be evident on chest radiography, computed tomography has traditionally been the imaging modality used to evaluate the disease and effectively demonstrates the extent of intrathoracic involvement and the presence and extent of extrathoracic spread. However, additional modalities such as magnetic resonance imaging of the thorax and {sup 18}F-FDG PET/CT have emerged in recent years and are complementary to CT in the evaluation of patients with lymphoma. Thoracic MRI is useful in assessing vascular, cardiac, and chest wall involvement, and PET/CT is more accurate in the overall staging of lymphoma than CT and can be used to evaluate treatment response.

President's categorical course on lymphoma

International Nuclear Information System (INIS)

Hoppe, Richard T.

1997-01-01

Improvements in the classification, staging, and treatment of the lymphomas, complemented by an improved understanding of the biology of these diseases, has led to an improved outcome of therapy for both Hodgkin's disease and many of the non-Hodgkin's lymphomas. The rapid changes that have occurred in this field in the last decade make it timely to review this subject for radiation oncologists in a comprehensive fashion. This course is designed to meet broad educational needs required for understanding these diseases and providing effective care for patients with lymphoma. The faculty includes many leaders from both laboratory and clinical disciplines dealing with lymphomas, who will address a variety of scientific and clinical topics. The morning session will be devoted to Hodgkin's disease, including new concepts in its biology, a review of clinical trials for early stage disease, a discussion of the role of high dose therapy, and description of long term complications of treatment. The afternoon sessions will be devoted to the non-Hodgkin's lymphomas, including new concepts in pathology and biology, a description of specific entities including the low grade lymphomas, MALT lymphomas, extranodal lymphomas, intermediate grade lymphomas, mantle cell lymphomas, and summary discussions of the role of radioimmuno-therapy and high dose therapy. Although the role of radiation therapy in the management of patients with lymphoma has changed dramatically in the past two decades, radiation remains the most effective single agent for the treatment of these diseases and it is especially important for radiation onologists to keep abreast of these new concepts. This course has been designed to achieve that goal

Ibrutinib targets mutant-EGFR kinase with a distinct binding conformation.

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Wang, Aoli; Yan, Xiao-E; Wu, Hong; Wang, Wenchao; Hu, Chen; Chen, Cheng; Zhao, Zheng; Zhao, Peng; Li, Xixiang; Wang, Li; Wang, Beilei; Ye, Zi; Wang, Jinhua; Wang, Chu; Zhang, Wei; Gray, Nathanael S; Weisberg, Ellen L; Chen, Liang; Liu, Jing; Yun, Cai-Hong; Liu, Qingsong

2016-10-25

Ibrutinib, a clinically approved irreversible BTK kinase inhibitor for Mantle Cell Lymphoma (MCL) and Chronic Lymphocytic Leukemia (CLL) etc, has been reported to be potent against EGFR mutant kinase and currently being evaluated in clinic for Non Small Cell Lung Cancer (NSCLC). Through EGFR wt/mutant engineered isogenic BaF3 cell lines we confirmed the irreversible binding mode of Ibrutinib with EGFR wt/mutant kinase via Cys797. However, comparing to typical irreversible EGFR inhibitor, such as WZ4002, the washing-out experiments revealed a much less efficient covalent binding for Ibrutinib. The biochemical binding affinity examination in the EGFR L858R/T790M kinase revealed that, comparing to more efficient irreversible inhibitor WZ4002 (Kd: 0.074 μM), Ibrutinib exhibited less efficient binding (Kd: 0.18 μM). An X-ray crystal structure of EGFR (T790M) in complex with Ibrutinib exhibited a unique DFG-in/c-Helix-out inactive binding conformation, which partially explained the less efficiency of covalent binding and provided insight for further development of highly efficient irreversible binding inhibitor for the EGFR mutant kinase. These results also imply that, unlike the canonical irreversible inhibitor, sustained effective concentration might be required for Ibrutinib in order to achieve the maximal efficacy in the clinic application against EGFR driven NSCLC.

Kinase-dead ATM protein is highly oncogenic and can be preferentially targeted by Topo-isomerase I inhibitors.

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Yamamoto, Kenta; Wang, Jiguang; Sprinzen, Lisa; Xu, Jun; Haddock, Christopher J; Li, Chen; Lee, Brian J; Loredan, Denis G; Jiang, Wenxia; Vindigni, Alessandro; Wang, Dong; Rabadan, Raul; Zha, Shan

2016-06-15

Missense mutations in ATM kinase, a master regulator of DNA damage responses, are found in many cancers, but their impact on ATM function and implications for cancer therapy are largely unknown. Here we report that 72% of cancer-associated ATM mutations are missense mutations that are enriched around the kinase domain. Expression of kinase-dead ATM (Atm(KD/-)) is more oncogenic than loss of ATM (Atm(-/-)) in mouse models, leading to earlier and more frequent lymphomas with Pten deletions. Kinase-dead ATM protein (Atm-KD), but not loss of ATM (Atm-null), prevents replication-dependent removal of Topo-isomerase I-DNA adducts at the step of strand cleavage, leading to severe genomic instability and hypersensitivity to Topo-isomerase I inhibitors. Correspondingly, Topo-isomerase I inhibitors effectively and preferentially eliminate Atm(KD/-), but not Atm-proficientor Atm(-/-) leukemia in animal models. These findings identify ATM kinase-domain missense mutations as a potent oncogenic event and a biomarker for Topo-isomerase I inhibitor based therapy.

CARDIAC LYMPHOMA IN DOG

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G. D. Cruz

2016-11-01

Full Text Available Lymphoma is a lymphoid tumor that originates in hematopoietic organs such as lymph node, spleen or liver. In dogs, the overall prevalence of cardiac tumors was estimated to be only 0.19% based on the results of the survey of a large database, and lymphomas accounts for approximately 2% of all cardiac tumors. In general, the involvement of the myocardium is rarely described in canine lymphoma. Currently, there is no evidence of a viral association with primary cardiac lymphoma in dogs, but other types of immunosuppression may contribute to abnormal events, such as involvement primary cardiac. The aim of this study was to analyze a case of sudden death of a bitch, SRD, aged 10, who had the final diagnosis of cardiac lymphoma.

Translation initiation complex eIF4F is a therapeutic target for dual mTOR kinase inhibitors in non-Hodgkin lymphoma

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Stenson, Mary J.; Maurer, Matthew J.; Wellik, Linda E.; Link, Brian; Hege, Kristen; Dogan, Ahmet; Sotomayor, Eduardo; Witzig, Thomas; Gupta, Mamta

2015-01-01

Deregulated mRNA translation has been implicated in disease development and in part is controlled by a eukaryotic initiation complex eIF4F (composed of eIF4E, eIF4G and eIF4A). We demonstrate here that the cap bound fraction from lymphoma cells was enriched with eIF4G and eIF4E indicating that lymphoma cells exist in an activated translational state. Moreover, 77% (110/142) of diffuse large B cell lymphoma tumors expressed eIF4E and this was associated with an inferior event free survival. Over-expression of wild-type eIF4E (eIF4EWT) but not cap-mutant eIF4E (eIF4Ecap mutant) increased the activation of the eIF4F complex. Treatment with the active-site dual mTOR inhibitor CC214-1 reduced the level of the eIF4F complex by decreasing the cap bound fraction of eIF4G and increasing the levels of 4E-BP1. CC214-1 inhibited both the cap dependent and global protein translation. CC214-1 inhibited c-Myc, and cyclin D3 translation by decreasing polysomal fractions from lymphoma cells. Inhibition of eIF4E with shRNA further decreased the CC214-1 induced inhibition of the eIF4F complex, c-Myc, cyclin D3 translation, and colony formation. These studies demonstrate that the eIF4F complex is deregulated in aggressive lymphoma and that dual mTOR therapy has therapeutic potential in these patients. PMID:25839159

The mouse lymphoma thymidine kinase assay for the assessment and comparison of the mutagenic activity of cigarette mainstream smoke particulate phase.

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Schramke, H; Meisgen, T J; Tewes, F J; Gomm, W; Roemer, E

2006-10-29

The mouse lymphoma thymidine kinase assay (MLA) has been optimized to quantitatively determine the in vitro mutagenicity of cigarette mainstream smoke particulate phase. To test whether the MLA is able to discriminate between different cigarette types, specially constructed cigarettes each containing a single tobacco type - Bright, Burley, or Oriental - were investigated. The mutagenic activity of the Burley cigarette was statistically significantly lower, up to approximately 40%, than that of the Bright and Oriental cigarettes. To determine the impact of two different sets of smoking conditions, American-blend cigarettes were smoked under US Federal Trade Commission/International Organisation for Standardisation conditions and under Massachusetts Department of Public Health (MDPH) conditions. Conventional cigarettes - eight from the US commercial market plus the Reference Cigarettes 1R4F and 2R4F - and an electrically heated cigarette smoking system (EHCSS) prototype were tested. There were no statistically significant differences between the two sets of smoking conditions on a per mg total particulate matter basis, although there was a consistent trend towards slightly lower mutagenic activity under MDPH conditions. The mutagenic activity of the EHCSS prototype was distinctly lower than that of the conventional cigarettes under both sets of smoking conditions. These results show that the MLA can be used to assess and compare the mutagenic activity of cigarette mainstream smoke particulate phase in the comprehensive toxicological assessment of cigarette smoke.

A review of a novel, Bruton's tyrosine kinase inhibitor, ibrutinib.

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Lee, Chung-Shien; Rattu, Mohammad A; Kim, Sara S

2016-02-01

Ibrutinib, a Bruton's kinase inhibitor, was granted an accelerated approval by the US Food and Drug Administration in November, 2013, for the treatment of relapsed or refractory mantle cell lymphoma and subsequently for the treatment of relapsed refractory chronic lymphocytic leukemia in February, 2014. In the pivotal phase 2 study of 111 patients with relapsed or refractory mantle cell lymphoma, the overall response rate in patients who received ibrutinib 560 mg daily was 68%. The median progression-free survival was 13.9 months, and the overall survival was 58% at 18 months. In a recently published phase 3 trial (RESONATE) that compared ibrutinib and ofatumumab for the treatment of relapsed and refractory chronic lymphocytic leukemia or small lymphocytic lymphoma, ibrutinib at the daily dosage of 420 mg demonstrated a significantly higher overall response rate (43% in ibrutinib vs. 4% in ofatumumab) and a significantly improved overall survival at 12 months (90% ibrutinib vs. 81% ofatumumab). Similar clinical benefits were shown regardless of del (17 p). Ibrutinib was well tolerated, and dose-limiting toxicity was not observed. Ibrutinib has shown durable remission, improved progression-free survival and overall survival, and favorable safety profile in indolent B-cell lymphoid malignancies. Ibrutinib, as a monotherapy, is an effective treatment modality as a salvage therapy for treatment of mantle cell lymphoma and chronic lymphocytic leukemia / small lymphocytic lymphoma, particularly in older patients (age ≥70 years) who are not a candidate for intensive chemotherapy and/or those with del (17 p). In patients with chronic lymphocytic leukemia and del (17 p), the current practice guideline recommends ibrutinib as an upfront treatment option. Current on-going trials will further define its role as upfront therapy and/or as a combination therapy in indolent B-cell lymphoid malignancies. © The Author(s) 2014.

Malignant lymphoma in african lions (panthera leo).

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Harrison, T M; McKnight, C A; Sikarskie, J G; Kitchell, B E; Garner, M M; Raymond, J T; Fitzgerald, S D; Valli, V E; Agnew, D; Kiupel, M

2010-09-01

Malignant lymphoma has become an increasingly recognized problem in African lions (Panthera leo). Eleven African lions (9 male and 2 female) with clinical signs and gross and microscopic lesions of malignant lymphoma were evaluated in this study. All animals were older adults, ranging in age from 14 to 19 years. Immunohistochemically, 10 of the 11 lions had T-cell lymphomas (CD3(+), CD79a(-)), and 1 lion was diagnosed with a B-cell lymphoma (CD3(-), CD79a(+)). The spleen appeared to be the primary site of neoplastic growth in all T-cell lymphomas, with involvement of the liver (6/11) and regional lymph nodes (5/11) also commonly observed. The B-cell lymphoma affected the peripheral lymph nodes, liver, and spleen. According to the current veterinary and human World Health Organization classification of hematopoietic neoplasms, T-cell lymphoma subtypes included peripheral T-cell lymphoma (4/11), precursor (acute) T-cell lymphoblastic lymphoma/leukemia (2/11), chronic T-cell lymphocytic lymphoma/leukemia (3/11), and T-zone lymphoma (1/11). The single B-cell lymphoma subtype was consistent with diffuse large B-cell lymphoma. Feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) testing by immunohistochemistry on sections of malignant lymphoma was negative for all 11 lions. One lion was seropositive for FeLV. In contrast to domestic and exotic cats, in which B-cell lymphomas are more common than T-cell lymphomas, African lions in this study had malignant lymphomas that were primarily of T-cell origin. Neither FeLV nor FIV, important causes of malignant lymphoma in domestic cats, seems to be significant in the pathogenesis of malignant lymphoma in African lions.

Ibrutinib for the treatment of mantle cell lymphoma.

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Herrera, Alex F; Jacobsen, Eric D

2014-11-01

Ibrutinib (PCI-32765)--a potent, covalent inhibitor of Bruton tyrosine kinase (BTK), an important kinase in the B-cell receptor signaling pathway--was recently approved by the FDA for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The drug was granted accelerated approval based on the findings of an international, multicenter, single-arm phase II study that enrolled patients with relapsed or refractory MCL. In the study, ibrutinib (560 mg daily) was well tolerated as a single agent and resulted in an overall response rate of 68% and an estimated median response duration of 17.5 months. Ibrutinib's response rate and duration of response compare favorably with those for other novel agents approved for the treatment of relapsed or refractory MCL, while being less toxic than most chemotherapy or chemoimmunotherapy regimens. Ibrutinib is currently being studied in combination with chemoimmunotherapy, monoclonal antibody therapy, and novel agents in both the initial and the relapsed/refractory treatment settings. We review the mechanism of action, preclinical and clinical development, and the role of ibrutinib in the context of other available treatments. ©2014 American Association for Cancer Research.

Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma

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Xiao Yi Zhou

2018-06-01

Full Text Available Purpose: Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. Observations: A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Conclusions and importance: Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy. Keywords: Lymphoma, Triple-hit lymphoma, Orbital mass

Anomalous expression of Thy1 (CD90) in B-cell lymphoma cells and proliferation inhibition by anti-Thy1 antibody treatment

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Ishiura, Yoshihito [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kotani, Norihiro, E-mail: kotani@kochi-u.ac.jp [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); Yamashita, Ryusuke [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Yamamoto, Harumi [Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Kozutsumi, Yasunori [CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Laboratory of Membrane Biochemistry and Biophysics, Graduate School of Biostudies, Kyoto University, Yoshida Shimo-Adachi, Sakyo, Kyoto 606-8501 (Japan); Honke, Koichi [Department of Biochemistry, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan); CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012 (Japan); Kochi System Glycobiology Center, Kochi University Medical School, Kohasu, Okocho, Nankoku, Kochi 783-8505 (Japan)

2010-05-28

The anti-CD20 monoclonal antibody (Ab) rituximab is accepted to be an effective therapeutic Ab for malignant B-cell lymphoma; however, discovery of other cell surface antigens is required for the option of antibody medicine. Considering that many tumor-associated antigens are glycans, we have searched glycoconjugates for the candidate antigens that therapeutic Abs target. To this end, we first focused on the difference in the glycogenes expression in terms of Epstein-Barr virus (EBV) infection of a Burkitt's lymphoma cell line, Akata. Using DNA array, flow cytometry and Western blotting, we found that Thy1 was highly expressed in EBV-positive Akata cells. Subsequently, Thy1 was found to be expressed in other B-cell lymphoma cell lines: BJAB, MutuI, and MutuIII, irrespective of EBV infection. Treatment of these cells with an anti-Thy1 monoclonal antibody inhibited proliferation more strongly than the therapeutic Ab rituximab. The B-cell lymphoma cell lines were classified based on the extent of the proliferation inhibition, which was not correlated with the expression level of Thy1. It is suggested that stable residence of receptor tyrosine kinases in lipid rafts sustains cell growth in B-cell lymphoma cells.

Inflammatory myofibroblastic tumor of the lung in pregnancy mimicking carcinoid tumor

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Venkata Nagarjuna Maturu

2016-01-01

Full Text Available Inflammatory myofibroblastic tumors (IMT are uncommon neoplasms of the lung in adults. They constitute less than 1% of all lung neoplasms and usually present as parenchymal masses. Diagnosis requires a high index of suspicion. They are characterized by spindle-shaped tumor cells (fibroblasts/myofibroblasts in a background of lymphoplasmacytic infiltrate. About 50% of the tumors harbor an ALK gene rearrangement. They have to be differentiated from inflammatory pseudotumors (IPT, which show increased number of IgG4 plasma cells on immunostaining and are negative for anaplastic lymphoma kinase (ALK protein. Herein, we present a case of a 28-year old female who presented with hemoptysis and was diagnosed with an IMT of lung in the first trimester of pregnancy. We have not only reviewed the occurrence of IMT during pregnancy but also discuss the management options for IMT during pregnancy.

Extra-nodal lymphoma. A survey of Japan lymphoma radiation therapy group

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Oguchi, Masahiko; Ikeda, Hiroshi; Nakamura, Shigeo

2002-01-01

The purpose of this study was to examine, retrospectively, national-wide clinical data of patients with localized extranodal non-Hodgkin's lymphoma (NHL) who were treated by radiation therapy with or without chemotherapy. The survey was carried out at 25 radiation oncology institutions in Japan in 1998. In 1999, according to the Revised European American Lymphoma (REAL) classification, central pathological review conducted at Aichi cancer center was carried out for the data from 7 radiation oncology institutions. The 5-year progression free survival rates (PFS) were calculated to identify prognostic factors. Survey: Data from 1, 141 patients with stage I and II NHL were recruited from 1988 through 1992. Of them, 787 patients, who were treated using definitive radiotherapy with or without chemotherapy for intermediate and high-grade lymphomas in Working Formulation, constituted the core of this study. Primary tumors arose mainly from extra-nodal organs (71%) in the head and neck (Waldeyer's ring: 41%, thyroid gland: 7%, nasal cavities: 5%, oral cavities: 4%, sinus: 3%, orbital structures: 3%, skin: 2% and etc.). The median age of 60 years for patients with extra-nodal NHL was higher than that of 56 years for patients with nodal NHL (p<0.01). Female were dominant in incidence of extra-nodal NHL arising from the thyroid gland, skin and gastrointestinal tract. The percentage of stage I to the extra-nodal NHL from orbit, sino-nasal presentation was higher than that of other NHLs. The percentage of stage II to the extra-nodal NHL from Waldeyer's ring and thyroid gland was higher than that of other NHLs. Central pathological review was carried out for pathological data from 79 patients (Waldeyer's ring: 45, thyroid gland: 19, sinonasal cavities: 15). Of these, diffuse large B cell lymphoma (DLBCL) composed 63% of all patients, mucosa associated lyumphoid tissue lymphoma (MALT-L): 16%, Natural Killer/T cell lymphoma (NK/T-L): 11%, and mantle cell lymphoma: 5% in REAL

De novo anaplastic Kaposi sarcoma in a HIV-negative man: A case report and review of the literature

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Slim Charfi

2017-07-01

Full Text Available Anaplastic Kaposi sarcoma is a rare variant of Kaposi’s and is typically associated with an agressive clinical course. We report a case of a 67-year-old HIV negative man, presented with multiple, pink nodules on the left ankle and a keratotic lesion of the right heel. Initial histopathological exam concluded to an undifferentiated sarcoma. A second biopsy was performed and concluded to an anaplastic Kaposi sarcoma. Immunohistochemical study was positive for HHV8. Treatment consisted on a tumor excision of all lesions. Our case and the review of the literature highlight the benefit of the non conservative surgical treatment for this aggressive form of Kaposi sarcoma.

FilGAP, a Rac-specific Rho GTPase-activating protein, is a novel prognostic factor for follicular lymphoma

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Nishi, Tatsuya; Takahashi, Hiroyuki; Hashimura, Miki; Yoshida, Tsutomu; Ohta, Yasutaka; Saegusa, Makoto

2015-01-01

FilGAP, a Rho GTPase-activating protein (GAP), acts as a mediator of Rho/ROCK (Rho-associated protein kinase)-dependent amoeboid movement, and its knockdown results in Rac-driven mesenchymal morphology. Herein, we focus on the possible roles of FilGAP expression in normal and malignant lymphocytes. Eighty-three cases of follicular lymphoma (FL), 84 of diffuse large B-cell lymphoma (DLBCL), and 25 of peripheral T-cell lymphoma (PTCL), as well as 10 of normal lymph nodes, were immunohistochemically investigated. In normal lymph nodes, FilGAP immunoreactivity was significantly higher in lymphocytes in the mantle zone as compared to those in the germinal center and paracortical areas. In contrast, the expression levels of both cytoplasmic and perinuclear Rac1 were significantly lower in the germinal center as compared to paracortical regions, suggesting that changes in the FilGAP/Rac axis may occur in B-cell lineages. In malignant lymphomas, FilGAP expression was significantly higher in B-cell lymphomas than PTCL, and the immunohistochemical scores were positively correlated with cytoplasmic Rac1 scores in FL and DLBCL, but not in PTCL. Patients with FL and germinal center B-cell-like (GCB)-type DLBCL showing high FilGAP scores had poor overall survival rates as compared to the low-score patients. Moreover, multivariate Cox regression analysis showed that a high FilGAP score was a significant and independent unfavorable prognostic factor in FL, but not in DLBCL. In conclusion, FilGAP may contribute to change in cell motility of B-lymphocytes. In addition, its expression appears to be useful for predicting the behavior of B-cell lymphoma, in particular FL

Management of relapsed/refractory marginal zone lymphoma: focus on ibrutinib

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Denlinger NM

2018-03-01

Full Text Available Nathan M Denlinger, Narendranath Epperla, Basem M William Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center (OSUCCC-James, The Ohio State University, Columbus, OH, USA Abstract: Marginal zone lymphomas (MZLs consist of a diverse family of malignancies, which are derived from B-cells. The disease subtypes are recognized extranodal, nodal, and splenic MZLs. The disease characteristics, clinical course, and treatment vary considerably based on the site of involvement. In 2017, the US Food and Drug Administration approved ibrutinib, a first in class Bruton’s tyrosine kinase inhibitor that revolutionized the care of chronic lymphocytic leukemia patients; for, the treatment of relapsed/refractory MZL based on pivotal open-label Phase II trial demonstrated an overall response rate of 48%, with a complete response rate of 3%, median progression-free survival of 14.2 months, and median overall survival not yet reached at a median follow-up of 19.4 months. In this review, we aim to summarize the current conundrums in the management of MZL and the evolving role of ibrutinib in the treatment of MZL. Keywords: non-Hodgkin’s lymphoma, marginal zone, ibrutinib

Crizotinib-Resistant Mutants of EML4-ALK Identified Through an Accelerated Mutagenesis Screen

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Zhang, Sen; Wang, Frank; Keats, Jeffrey; Zhu, Xiaotian; Ning, Yaoyu; Wardwell, Scott D; Moran, Lauren; Mohemmad, Qurish K; Anjum, Rana; Wang, Yihan; Narasimhan, Narayana I; Dalgarno, David; Shakespeare, William C; Miret, Juan J; Clackson, Tim; Rivera, Victor M

2011-01-01

Activating gene rearrangements of anaplastic lymphoma kinase (ALK) have been identified as driver mutations in non-small-cell lung cancer, inflammatory myofibroblastic tumors, and other cancers. Crizotinib, a dual MET/ALK inhibitor, has demonstrated promising clinical activity in patients with non-small-cell lung cancer and inflammatory myofibroblastic tumors harboring ALK translocations. Inhibitors of driver kinases often elicit kinase domain mutations that confer resistance, and such mutations have been successfully predicted using in vitro mutagenesis screens. Here, this approach was used to discover an extensive set of ALK mutations that can confer resistance to crizotinib. Mutations at 16 residues were identified, structurally clustered into five regions around the kinase active site, which conferred varying degrees of resistance. The screen successfully predicted the L1196M, C1156Y, and F1174L mutations, recently identified in crizotinib-resistant patients. In separate studies, we demonstrated that crizotinib has relatively modest potency in ALK-positive non-small-cell lung cancer cell lines. A more potent ALK inhibitor, TAE684, maintained substantial activity against mutations that conferred resistance to crizotinib. Our study identifies multiple novel mutations in ALK that may confer clinical resistance to crizotinib, suggests that crizotinib's narrow selectivity window may underlie its susceptibility to such resistance and demonstrates that a more potent ALK inhibitor may be effective at overcoming resistance. PMID:22034911

Nodular breast lymphoma

International Nuclear Information System (INIS)

Rodriguez, M.; Sahagun, E.; Pena, J.; Mendez, J.

1996-01-01

We attempt to correlate the histological types [in three cases of B-cell non-Hodgkin's lymphoma (NHL), one case of T-cell NHL and one of Hodgkin's disease] with the radiological presentation and compare our findings with the literature reviewed. Among the mammographic studies, performed over and 18-month period, we have assessed five patients (four women and one man, aged as having lymphoma. the man presented bilateral involvement. Both mammography and a broader study with ultrasound and chest and abdominal CT scan were performed in every case. Four patients underwent breast ultrasound. The definitive diagnosis was based on biopsy in all cases. Three of the five cases involved primary lymphomas and the other two were secondary. Four patients presented NHL and the remaining patient had Hodgkin's disease. In mammography, the nodules showed different degrees of margin definition. In ultrasound, all the lesion were hypoechoic. The radiological diagnosis of breast lymphoma is difficult in the absence of a previous diagnosis of lymphoma. This lesion should be included in the differential diagnosis in the presence of a breast nodule associated with axillary lymph nodes, especially when the latter are bilateral. (Author)

Diagnosis and Treatment B non-Hodgkin Lymphoma with System Biology Approaches

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Ali Salari

2016-04-01

Full Text Available Lymphomas are solid tumors of immune system and Non-Hodgkin Lymphomas (NHL is the most prevalent lymphomas; with wide ranges of histological and clinical features, it is so difficult to identify them. Herein, various bioinformatics tools (such as gene differential expressions, epigenetics and protein analysis employed to find new treatment approach for NHL based on gene expression variation between classic Hodgkin and B NHL. Microarray libraries GSE20011 downloaded from NCBI database and analyzed with GEO2R software, then differential expression genes analyzed by four databases (DAVID, Wikipathways, BioCarta and KEGG databases. Kinase, transcription factor, microRNA analysis and protein-protein interaction network performed by X2K ,ChEA, microRNA TargetScan and Genes2Networks software respectively. Finally, drug target identified and carried out by Drug Pair Seeker and Connectivity MAP databases. The results showed GATA2 Transcription Factor (TF up-regulates genes while Sox2 down-regulates them.  Functional analysis of up-regulated genes showed highly activation in B cell receptor signaling pathway while programmed cell death and apoptosis program noted in down-regulated genes. Drug discovery facilities revealed that Verteporfin drug induces down-regulated genes while Prochlorperazine represses up-regulated genes. Three microRNA34a34c and miR-449 repressed up-regulated gene networks. The finding paves the roads toward B-NHL therapy with 34a/b and miR-449 microRNAs and Prochlorperazine / Verteporfin drugs.

Identification of a nucleoside analog active against adenosine kinase-expressing plasma cell malignancies.

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Nayar, Utthara; Sadek, Jouliana; Reichel, Jonathan; Hernandez-Hopkins, Denise; Akar, Gunkut; Barelli, Peter J; Sahai, Michelle A; Zhou, Hufeng; Totonchy, Jennifer; Jayabalan, David; Niesvizky, Ruben; Guasparri, Ilaria; Hassane, Duane; Liu, Yifang; Sei, Shizuko; Shoemaker, Robert H; Warren, J David; Elemento, Olivier; Kaye, Kenneth M; Cesarman, Ethel

2017-06-01

Primary effusion lymphoma (PEL) is a largely incurable malignancy of B cell origin with plasmacytic differentiation. Here, we report the identification of a highly effective inhibitor of PEL. This compound, 6-ethylthioinosine (6-ETI), is a nucleoside analog with toxicity to PEL in vitro and in vivo, but not to other lymphoma cell lines tested. We developed and performed resistome analysis, an unbiased approach based on RNA sequencing of resistant subclones, to discover the molecular mechanisms of sensitivity. We found different adenosine kinase-inactivating (ADK-inactivating) alterations in all resistant clones and determined that ADK is required to phosphorylate and activate 6-ETI. Further, we observed that 6-ETI induces ATP depletion and cell death accompanied by S phase arrest and DNA damage only in ADK-expressing cells. Immunohistochemistry for ADK served as a biomarker approach to identify 6-ETI-sensitive tumors, which we documented for other lymphoid malignancies with plasmacytic features. Notably, multiple myeloma (MM) expresses high levels of ADK, and 6-ETI was toxic to MM cell lines and primary specimens and had a robust antitumor effect in a disseminated MM mouse model. Several nucleoside analogs are effective in treating leukemias and T cell lymphomas, and 6-ETI may fill this niche for the treatment of PEL, plasmablastic lymphoma, MM, and other ADK-expressing cancers.

ESMO Consensus Conference on malignant lymphoma

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Buske, C; Hutchings, M; Ladetto, M

2018-01-01

The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop recommen......The European Society for Medical Oncology (ESMO) consensus conference on mature B cell lymphomas and chronic lymphocytic leukaemia (CLL) was held on 20 June 2015 in Lugano, Switzerland, and included a multidisciplinary panel of 25 leading experts. The aim of the conference was to develop...... of the three key areas identified. This manuscript presents the consensus recommendations regarding the clinical management of elderly patients diagnosed with malignant lymphoma. Four clinically-relevant topics identified by the panel were: 1) how to define patient fitness, 2) assessing quality of life, 3......) diagnostic work-up and 4) clinical management of elderly patients with lymphoma. Each of these key topics is addressed in the context of five different lymphoma entities, namely: CLL, follicular lymphoma, mantle cell lymphoma, peripheral T-cell lymphoma and diffuse large B-cell lymphoma. Results, including...

Characterization of primary cutaneous CD8+/CD30+ lymphoproliferative disorders.

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Martires, Kathryn J; Ra, Seong; Abdulla, Farah; Cassarino, David S

2015-11-01

CD30 primary cutaneous lymphoproliferative diseases include both lymphomatoid papulosis (LyP) and primary cutaneous anaplastic large cell lymphoma (PCALCL). The neoplastic cell of most primary CD30 lymphoproliferative disorders is CD4 positive. The terminology LyP "type D" has been used to describe a growing number of cases of LyP with a predominantly CD8 infiltrate. PCALCL with a CD8 phenotype has also been described, which presents a particularly difficult diagnostic and management challenge, given the difficulty in distinguishing it histologically from other cytotoxic lymphomas such as primary cutaneous aggressive epidermotropic CD8 cytotoxic T-cell lymphoma and CD8 gamma/delta and natural killer/T-cell lymphoma. We report 7 additional cases of these rare cutaneous CD8/CD30 lymphoproliferative disorders. We also present a unique case of CD8/CD30 LyP with histologic similarities to LyP type B. In all 7 of our cases of CD8 LyP and CD8 anaplastic large cell lymphoma, we found focal to diffuse MUM-1 positivity. We propose that MUM-1 may represent an adjunctive marker for CD8 lymphoproliferative disease. Finally, we review the current literature on cases of CD8 LyP and PCALCL. For the 106 cases examined, we found similar clinical and histologic features to those reported for traditional CD4CD30 LyP and PCALCL.

Treatment results of localized gastric lymphoma

International Nuclear Information System (INIS)

Abe, Tatsuyuki; Gomi, Hiromichi; Sakaino, Shinjiro; Nakajima, Yasuo

2008-01-01

Between 2000 and 2007, 17 patients with localized gastric lymphoma (10 mucosa-associated lymphoid tissue lymphomas and 7 diffuse large B-cell lymphomas) were treated with radiotherapy alone or doxorubicin-based chemotherapy followed by radiotherapy. Radiation dose of mucosa-associated lymphoid tissue (MALT) lymphoma was 30 Gy with a daily fraction size of 1.5 Gy. Sixteen patients achieved complete remission and the 5-year overall survival of MALT lymphoma and diffuse large B-cell lymphoma (DLBCL) were 100% and 87%, respectively. No gastric perforation and hemorrhage were noticed. Using AP/LR 2-port radiotherapy markedly decreased the liver dose. (author)

Intraocular lymphoma

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Li-Juan Tang

2017-08-01

Full Text Available Intraocular lymphoma (IOL is a rare lymphocytic malignancy which contains two main distinct forms. Primary intraocular lymphoma (PIOL is mainly a sub-type of primary central nervous system lymphoma (PCNSL. Alternatively, IOL can originate from outside the central nervous system (CNS by metastasizing to the eye. These tumors are known as secondary intraocular lymphoma (SIOL. The IOL can arise in the retina, uvea, vitreous, Bruch’s membrane and optic nerve. There are predominantly of B-cell origin; however there are also rare T-cell variants. Diagnosis remains challenging for ophthalmologists and pathologists, due to its ability to masquerade as noninfectious or infectious uveitis, white dot syndromes, or occasionally as other metastatic cancers. Laboratory tests include flow cytometry, immunocytochemistry, interleukin detection (IL-10: IL-6, ratio >1, and polymerase chain reaction (PCR amplification. Methotrexate-based systemic chemotherapy with external beam radiotherapy and intravitreal chemotherapy with methotrexate are useful for controlling the disease, but the prognosis remains poor. Therefore, it is important to make an early diagnose and treatment. This review is focused on the clinical manifestations, diagnosis, treatment and prognosis of the IOL.

SUMOylation Confers Posttranslational Stability on NPM-ALK Oncogenic Protein

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Deeksha Vishwamitra

2015-09-01

Full Text Available Nucleophosmin-anaplastic lymphoma kinase–expressing (NPM-ALK+ T-cell lymphoma is an aggressive form of cancer that commonly affects children and adolescents. The expression of NPM-ALK chimeric oncogene results from the chromosomal translocation t(2;5(p23;q35 that causes the fusion of the ALK and NPM genes. This translocation generates the NPM-ALK protein tyrosine kinase that forms the constitutively activated NPM-ALK/NPM-ALK homodimers. In addition, NPM-ALK is structurally associated with wild-type NPM to form NPM/NPM-ALK heterodimers, which can translocate to the nucleus. The mechanisms that sustain the stability of NPM-ALK are not fully understood. SUMOylation is a posttranslational modification that is characterized by the reversible conjugation of small ubiquitin-like modifiers (SUMOs with target proteins. SUMO competes with ubiquitin for substrate binding and therefore, SUMOylation is believed to protect target proteins from proteasomal degradation. Moreover, SUMOylation contributes to the subcellular distribution of target proteins. Herein, we found that the SUMOylation pathway is deregulated in NPM-ALK+ T-cell lymphoma cell lines and primary lymphoma tumors from patients. We also identified Lys24 and Lys32 within the NPM domain as the sites where NPM-ALK conjugates with SUMO-1 and SUMO-3. Importantly, antagonizing SUMOylation by the SENP1 protease decreased the accumulation of NPM-ALK and suppressed lymphoma cell viability, proliferation, and anchorage-independent colony formation. One possible mechanism for the SENP1-mediated decrease in NPM-ALK levels was the increase in NPM-ALK association with ubiquitin, which facilitates its degradation. Our findings propose a model in which aberrancies in SUMOylation contribute to the pathogenesis of NPM-ALK+ T-cell lymphoma. Unraveling such pathogenic mechanisms may lead to devising novel strategies to eliminate this aggressive neoplasm.

Isolated orbital mass as the primary presentation of a triple-hit lymphoma transformed from a systemic follicular lymphoma.

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Zhou, Xiao Yi; Lu, Xinyan; Raparia, Kirtee; Chen, Yi-Hua

2018-06-01

Triple-hit lymphoma is a highly aggressive B-cell lymphoma. We report a case of triple-hit lymphoma transformed from systemic follicular lymphoma (FL) after 9-year remission and presented primarily as an isolated orbital mass without systemic symptoms or lymphadenopathy. A 58-year-old female presented with intermittent vertical binocular diplopia, left upper eyelid swelling and pain and was found to have a 2.9 cm orbital mass. Histological section revealed a CD10-positive large B-cell lymphoma, consistent with transformation of FL. Fluorescent in situ hybridization (FISH) analysis demonstrated rearrangements involving C-MYC, BCL-2 and BCL-6 genes, indicating a high grade, triple-hit lymphoma. Triple-hit lymphoma transformed from a low-grade lymphoma may initially present as an isolated orbital mass without systemic evidence of transformation. Early recognition of double or triple-hit lymphomas is important since these patients require aggressive chemotherapy.

Linfoma não-Hodgkin em crianças com imunodeficiência: relato de cinco casos Non-Hodgkin's lymphoma in children with immunodeficiency: report of five cases

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Maria Christina L. A. Oliveira

2008-01-01

Full Text Available Neste estudo é relatado o quadro clínico de cinco crianças com linfoma não-Hodgkin secundário a imunodeficiência ou imunossupressão: três portadoras do vírus da imunodeficiência humana, uma com imunodeficiência primária e uma após transplante hepático. De acordo com a classificação atual, os tipos histológicos foram: linfoma linfoblástico de células B precursoras (2, linfoma cutâneo de grandes células anaplásico (1, linfoma de células B periféricas, sugestivo de Burkitt (1, e linfoma linfoblástico de células T precursoras (1. Todos os pacientes foram submetidos a quimioterapia, sendo que dois estão em remissão clínica, dois morreram e um continua em tratamento. Após a introdução da terapia anti-retroviral combinada e o aumento dos transplantes de órgãos sólidos ocorre maior risco de neoplasia nesses pacientes. Desse modo, é importante o seguimento desses pacientes para determinar os fatores de risco para o desenvolvimento de neoplasias e definir adequada estratégia de tratamento.The outcomes of five children with non-Hodgkin's lymphomas associated with immunodeficiency or immunosuppression is reported: three children with HIV, one with primary immunodeficiency and one after liver transplantation. According to the REAL classification, two patients had precursor B-lymphoblastic lymphomas, one had an anaplastic large cell lymphoma, one had a peripheral B-cell neoplasm suggestive of Burkitt's lymphoma, and one had precursor T-lymphoblastic lymphoma. All patients received chemotherapy. Two are in complete remission, two died and one remains under treatment. There has been an increasing awareness of the risk of non-Hodgkin's lymphoma and lymphoproliferative disorders after active antiretroviral therapy and with the expansion of solid organ transplant programs in the pediatric setting. Thus, for these patients it is important to establish risk factors for hematological disorders and determine the optimal and safest

Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

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Maher Kurdi

2014-01-01

Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

Non-Hodgkin's lymphomas

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Glatstein, E.; Wasserman, T.H.

1987-01-01

Non-Hodgkin's lymphomas are a varied and complex group of diseases that must be distinguished from Hodgkin's disease. The latter almost always begins in lymph nodes and spreads primarily in an axial fashion; non-Hodgkin's lymphomas may begin either in lymph nodes or in extranodal tissue and can spread both in an axial fashion and centrifugally. Because of changes in pathology terminology and the introduction of a classification using cell surface markers, many prognostic groups of patients with lymphomas have evolved. Therapeutic choices and prognosis are greatly influenced by variations in anatomic sites and extent of disease. Currently, the decisions on management require a balancing of radiation therapy with systemic chemotherapy. In some cases, radiation therapy alone may be sufficient; however, because most patients with non-Hodgkins's lymphomas tend to have advanced disease, a large percentage of patients will be managed with chemotherapy alone or in combination with radiation therapy

Psoriasis and risk of malignant lymphoma

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Kamstrup, M R; Skov, L; Zachariae, C

2018-01-01

In patients with psoriasis, the risk of lymphoma has been a subject of controversy and data from larger studies are limited1-4 . We therefore investigated the 5-year risk of new-onset Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) (excluding cutaneous T-cell lymphoma [CTCL]), and CTCL...

Lymphoma of the Urinary Bladder

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Anthony Kodzo-Grey Venyo

2014-01-01

Full Text Available Background. Lymphoma of the urinary bladder (LUB is rare. Aims. To review the literature on LUB. Methods. Various internet databases were used. Results. LUB can be either primary or secondary. The tumour has female predominance; most cases occur in middle-age women. Secondary LUB occurs in 10% to 25% of leukemias/lymphomas and in advanced-stage systemic lymphoma. Less than 100 cases have been reported. MALT typically affects adults older than 60 years; 75% are female. Diffuse large B-cell lymphoma is also common and may arise from transformation of MALT. LUB presents with haematuria, dysuria, urinary frequency, nocturia, and abdominal or back pain. Macroscopic examination of LUBs show large discrete tumours centred in the dome or lateral walls of the bladder. Positive staining of LUB varies by the subtype of lymphoma; B-cell lymphomas are CD20 positive. MALT lymphoma is positively stained for CD20, CD19, and FMC7 and negatively stained for CD5, CD10, and CD11c. LUB stains negatively with Pan-keratin, vimentin, CK20, and CK7. MALT lymphoma exhibits t(11; 18(q21: 21. Radiotherapy is an effective treatment for the MALT type of LUB with no recurrence. Conclusions. LUB is diagnosed by its characteristic morphology and immunohistochemical characteristics. Radiotherapy is a useful treatment.

Lymphoma Caused by Intestinal Microbiota

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Mitsuko L. Yamamoto

2014-09-01

Full Text Available The intestinal microbiota and gut immune system must constantly communicate to maintain a balance between tolerance and activation: on the one hand, our immune system should protect us from pathogenic microbes and on the other hand, most of the millions of microbes in and on our body are innocuous symbionts and some can even be beneficial. Since there is such a close interaction between the immune system and the intestinal microbiota, it is not surprising that some lymphomas such as mucosal-associated lymphoid tissue (MALT lymphoma have been shown to be caused by the presence of certain bacteria. Animal models played an important role in establishing causation and mechanism of bacteria-induced MALT lymphoma. In this review we discuss different ways that animal models have been applied to establish a link between the gut microbiota and lymphoma and how animal models have helped to elucidate mechanisms of microbiota-induced lymphoma. While there are not a plethora of studies demonstrating a connection between microbiota and lymphoma development, we believe that animal models are a system which can be exploited in the future to enhance our understanding of causation and improve prognosis and treatment of lymphoma.

Negative Regulation of Receptor Tyrosine Kinase (RTK Signaling: A Developing Field

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Fernanda Ledda

2007-01-01

Full Text Available ophic factors control cellular physiology by activating specific receptor tyrosine kinases (RTKs. While the over activation of RTK signaling pathways is associated with cell growth and cancer, recent findings support the concept that impaired down-regulation or deactivation of RTKs may also be a mechanism involved in tumor formation. Under this perspective, the molecular determinants of RTK signaling inhibition may act as tumor-suppressor genes and have a potential role as tumor markers to monitor and predict disease progression. Here, we review the current understanding of the physiological mechanisms that attenuate RTK signaling and discuss evidence that implicates deregulation of these events in cancer.Abbreviations: BDP1: Brain-derived phosphatase 1; Cbl: Casitas B-lineage lymphoma; CIN-85: Cbl-interacting protein of 85 kDa; DER: Drosophila EGFR; EGFR: Epidermal growth factor receptor; ERK 1/2: Extracellular signal-regulated kinase 1/2; Grb2: Growth factor receptor-bound protein 2; HER2: Human epidermal growth factor receptor 2; LRIG: Leucine-rich repeats and immunoglobulin-like domain 1; MAPK: Mitogen-activated protein kinase; Mig 6: Mitogen-inducible gene 6; PTEN: Phosphatase and tensin homologue; RET: Rearranged in transformation; RTK: Receptor tyrosine kinase. SH2 domain: Src-homology 2 domain; SH3 domain: Src-homology 3 domain; Spry: Sprouty.

17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

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Xiao, Y; Guan, J

2015-01-01

Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

Interferon-β-induced activation of c-Jun NH2-terminal kinase mediates apoptosis through up-regulation of CD95 in CH31 B lymphoma cells

International Nuclear Information System (INIS)

Takada, Eiko; Shimo, Kuniaki; Hata, Kikumi; Abiake, Maira; Mukai, Yasuo; Moriyama, Masami; Heasley, Lynn; Mizuguchi, Junichiro

2005-01-01

Type I interferon (IFN)-induced antitumor action is due in part to apoptosis, but the molecular mechanisms underlying IFN-induced apoptosis remain largely unresolved. In the present study, we demonstrate that IFN-β induced apoptosis and the loss of mitochondrial membrane potential (ΔΨm) in the murine CH31 B lymphoma cell line, and this was accompanied by the up-regulation of CD95, but not CD95-ligand (CD95-L), tumor necrosis factor (TNF), or TNF-related apoptosis-inducing ligand (TRAIL). Pretreatment with anti-CD95-L mAb partially prevented the IFN-β-induced loss of ΔΨm, suggesting that the interaction of IFN-β-up-regulated CD95 with CD95-L plays a crucial role in the induction of fratricide. IFN-β induced a sustained activation of c-Jun NH 2 -terminal kinase 1 (JNK1), but not extracellular signal-regulated kinases (ERKs). The IFN-β-induced apoptosis and loss of ΔΨm were substantially compromised in cells overexpressing a dominant-negative form of JNK1 (dnJNK1), and it was slightly enhanced in cells carrying a constitutively active JNK construct, MKK7-JNK1 fusion protein. The IFN-β-induced up-regulation of CD95 together with caspase-8 activation was also abrogated in the dnJNK1 cells while it was further enhanced in the MKK7-JNK1 cells. The levels of cellular FLIP (c-FLIP), competitively interacting with caspase-8, were down-regulated by stimulation with IFN-β but were reversed by the proteasome inhibitor lactacystin. Collectively, the IFN-β-induced sustained activation of JNK mediates apoptosis, at least in part, through up-regulation of CD95 protein in combination with down-regulation of c-FLIP protein

Emerging biomarkers in anaplastic oligodendroglioma: implications for clinical investigation and patient management.

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Sahebjam, Solmaz; McNamara, Mairéad G; Mason, Warren P

2013-07-01

Oligodendrogliomas are heterogeneous tumors with a variable response to treatment. This clinical variability underlines the urgent need for markers that can reliably aid diagnosis and guide clinical decision-making. Long-term follow-up data from the EORTC 26951 and RTOG 9402 clinical trials in newly diagnosed anaplastic oligodendroglioma have established chromosome 1p19q codeletion as a predictive marker of response to procarbazine, lomustine and vincristine chemotherapy in anaplastic oligodendrogliomas. In addition, MGMT promoter hypermethylation has been strongly associated with glioma CpG island hypermethylation phenotype (G-CIMP+) status, this has been suggested as an epiphenomenon of genome-wide methylation, conferring a more favorable prognosis. Molecular profiling of these tumors has identified several other markers with potential clinical significance: mutations of IDH, CIC, FUBP1 and CDKN2A require further validation before they can be implemented as clinical decision-making tools. Additionally, recent data on the clinical significance of intrinsic glioma subtyping appears promising. Indeed, existing evidence suggests that comprehensive analyses such as intrinsic glioma subtyping or G-CIMP status are superior to single molecular markers. Clearly, with evolving treatment strategies and in the era of individualized therapy, broader omics-based molecular evaluations are required to improve outcome prediction and to identify patients who will benefit from specific treatment strategies.

Malignant lymphomas of the stomach

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Drgona, L.

2011-01-01

Primary gastric lymphomas are the most common extra nodal lymphomas. They can be presented as aggressive or indolent, majority of indolent lymphomas are associated to H. pylori infection. The basic diagnostic procedures are endoscopy, endo sonography and biopsy of gastric tissue. Therapy is related to the histological subtype, stage, H. pylori positivity, clinical symptoms and condition of patient. The aim of the treatment is remission as well as good quality of life. The prognosis of patients with primary gastric lymphomas is relatively good. (author)

Non-Hodgkin's lymphoma - Part II: Management of primary extranodal lymphomas, generalized disease and salvage treatment

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Gospodarowicz, Mary K.; Sutcliffe, Simon B.

1996-01-01

Objective: To review the approach to the diagnosis, classification, assessment, treatment and continuing management of patients with primary extranodal non-Hodgkin's lymphoma, and the management of generalized disease with the emphasis on the current role of salvage treatment with high dose chemotherapy and stem cell/bone marrow support strategies. Non-Hodgkin's lymphoma may involve any part of the body. Many lymphomas, such as MALT, angiocentric T-cell, etc., commonly present in extranodal sites. Lymphomas presenting in the GI tract, and head and neck, are most common with the single most common site being the stomach. Gastric lymphoma is associated with Helicobacter pylorii and is most common in areas endemic for Helicobacter pylorii infection. Recent advances in the understanding of the etiology of gastric MALT, thyroid, and intestinal lymphomas present new opportunities for the application of novel therapeutic approaches e.g. antibiotic therapy for Helicobacter pylori and early stage IPSID. Lymphomas presenting in the orbit, thyroid, breast, bone, extradural and skin are of interest because of the importance of expert RT in securing local control. Primary brain lymphomas present a particular challenge to the radiation oncologist. Although localized, primary brain lymphomas are extremely difficult to control. Rare sites of extranodal lymphoma include testis, female genital tract, and lung. Extranodal lymphomas are often localized and cure with RT or CMT is possible. They represent a assorted group of diseases with diverse presentations, prognosis, sensitivity to RT and expected outcome. They are of particular importance to radiation oncologists as they require special attention to patterns of spread and treatment planning. The principles of management of primary extranodal lymphoma, however, follow those applicable to localized nodal presentations. Although primary extranodal lymphomas are highly curable, a proportion of patients will fail with disseminated

Arctigenin induces the apoptosis of primary effusion lymphoma cells under conditions of glucose deprivation.

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Baba, Yusuke; Shigemi, Zenpei; Hara, Naoko; Moriguchi, Misato; Ikeda, Marina; Watanabe, Tadashi; Fujimuro, Masahiro

2018-02-01

Kaposi's sarcoma-associated herpesvirus (KSHV) is the causative agent of primary effusion lymphoma (PEL) and Kaposi's sarcoma. PEL is a type of non-Hodgkin's B-cell lymphoma, affecting immunosuppressed individuals, such as post-transplant or AIDS patients. However, since PEL is resistant to chemotherapeutic regimens, new effective treatment strategies are required. Arctigenin, a natural lignan compound found in the plant Arctium lappa, has been widely investigated as a potential anticancer agent in the clinical setting. In the present study, we examined the cytotoxic effects of arctigenin by cell viability assay and found that arctigenin markedly inhibited the proliferation of PEL cells compared with KSHV-uninfected B-lymphoma cells under conditions of glucose deprivation. Arctigenin decreased cellular ATP levels, disrupted mitochondrial membrane potential and triggered caspase-9-mediated apoptosis in the glucose-deprived PEL cells. In addition, western blot analysis using phospho-specific antibodies were used to evaluate activity changes in the signaling pathways of interest. As a result, arctigenin suppressed the activation of the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38 MAPK) signaling pathways by inhibiting ERK and p38 MAPK phosphorylation in the glucose-deprived PEL cells. We confirmed that an inhibitor of ERK (U0126) or p38 MAPK (SB202190 and SB203580) suppressed the proliferation of the BC3 PEL cells compared with the KSHV-negative DG75 cells. Moreover, RT-PCR and luciferase reporter assay revealed that arctigenin and p38 MAPK inhibition by SB202190 or SB203580 downregulated the transcriptional expression of unfolded protein response (UPR)‑related molecules, including GRP78 and ATF6α under conditions of glucose deprivation. Finally, we confirmed that arctigenin did not affect KSHV replication in PEL cells, suggesting that arctigenin treatment for PEL does not contribute to the risk of de novo KSHV

Enzooty of non-Hodgkin's malignant lymphoma of Papio hamadryas in Sukhumi monkey colony. Clinical and morphological signs of pre-lymphoma.

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Yakovleva, Lelita A; Lapin, Boris A; Agumava, Aslan A

2018-04-01

Inoculation of hamadryas baboons with blood of leukemia ill people-induced malignant non-Hodgkin's lymphoma in experimental animals for a very considerable latency period. At close contact of inoculated baboons with healthy non-inoculated animals, the lymphoma spread between them. The epidemiological analysis, postmortem examination, histological analysis, tissue culturing, and PCR were used for the diagnostics of lymphoma and pre-lymphoma, purification, identification of STLV-1, and HVP viruses. Characteristic clinical and morphological signs designated by us as pre-lymphoma often precede the lymphoma development. In some cases, pre-lymphoma does not develop in lymphoma because animals die from various diseases and do not reach the point of the lymphoma development. The horizontal transmission of lymphoma arising with the participation of T-lymphotropic retrovirus STLV-1 is shown. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

International Lymphoma Epidemiology Consortium

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The InterLymph Consortium, or formally the International Consortium of Investigators Working on Non-Hodgkin's Lymphoma Epidemiologic Studies, is an open scientific forum for epidemiologic research in non-Hodgkin's lymphoma.

Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

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... Non-Hodgkin Lymphoma Peripheral T-Cell Lymphoma Primary Central Nervous System Lymphoma T-Cell Lymphoma Transformed Mycosis Fungoides Waldenstrom Macroglobulinemia Young Adult Lymphoma Overview Treatment Options Relapsed/Refractory Long-Term ...

Double-hit lymphomas constitute a highly aggressive subgroup in diffuse large B-cell lymphomas in the era of rituximab.

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Kobayashi, Tsutomu; Tsutsumi, Yasuhiko; Sakamoto, Natsumi; Nagoshi, Hisao; Yamamoto-Sugitani, Mio; Shimura, Yuji; Mizutani, Shinsuke; Matsumoto, Yosuke; Nishida, Kazuhiro; Horiike, Shigeo; Asano, Naoko; Nakamura, Shigeo; Kuroda, Junya; Taniwaki, Masafumi

2012-11-01

The incorporation of rituximab in immunochemotherapy has improved treatment outcomes for diffuse large B-cell lymphoma, but the prognosis for some diffuse large B-cell lymphomas remains dismal. Identification of adverse prognostic subgroups is essential for the choice of appropriate therapeutic strategy. We retrospectively investigated the impact of so-called 'double-hit' cytogenetic abnormalities, i.e. cytogenetic abnormalities involving c-MYC co-existing with other poor prognostic cytogenetic abnormalities involving BCL2, BCL6 or BACH2, on treatment outcomes for 93 consecutive diffuse large B-cell lymphoma patients. According to the revised international prognostic index, no patients were cytogenetically diagnosed with double-hit lymphomas in the 'very good' risk group or in the 'good' risk group, while 5 of 33 patients had double-hit lymphomas in the 'poor' risk group. All the double-hit lymphoma patients possessed both nodal and extranodal involvement. The overall complete response rate was 89.3%, overall survival 87.1% and progression-free survival 75.8% over 2 years (median observation period: 644 days). The complete response rates were 93.2% for the non-double-hit lymphoma patients and 40.0% for the double-hit lymphoma patients. Significantly longer progression-free survival and overall survival were observed for the 'very good' and the 'good' risk patients than for the 'poor' risk patients. Moreover, the progression-free survival of double-hit lymphoma was significantly shorter than that of the non-double-hit lymphoma 'poor' risk patients (P = 0.016). In addition, the overall survival of the double-hit lymphoma patients also tended to be shorter than that of the non-double-hit lymphoma 'poor' risk group. The diagnosis of double-hit lymphoma can help discriminate a subgroup of highly aggressive diffuse large B-cell lymphomas and indicate the need for the development of novel therapeutic strategies for double-hit lymphoma.

Cerebral lymphoma - CT and MRI diagnostic

International Nuclear Information System (INIS)

Popovska, T.; Yanakiev, A.; Zashev, I.

2012-01-01

Lymphoma (Hodgkin's and non-Hodgkin's) is a disease of the lymphatic system where the central neural system is affected in very rare cases. According to different authors the frequency of cases with lymphoma where the neural system is affected varies between 0, 2 % and 0, 5 %, and the primary cerebral lymphoma accounts for about 1-2% of ail brain neoplasms. The intracranial form of iymphoma is usually a late onset of the disease with serious and potentially fatal complications for the patient. These complications usually appear several years after diagnosing the disease, but the cerebral lymphoma may occur even in patients who are in remission which is the case with our patient. We present you a case with a 38 -year-old female, who was hospitalized in the Neuro ward with the following complaints -loss of speech for a few minutes, dizziness, weakness, tingling in her right leg as well as shuffling. This patient was diagnosed with histological B-cell non-Hodgkin's lymphoma 8 years ago. CT and MRI were carried out on that patient. Despite both clinical and radiographic suspicions for intracranial forms of lymphoma, the patient was still difficult to diagnose. A definitive diagnosis was given after a surgery and histological examination, i.e. non-Hodgkin's lymphoma - large B-cell lymphoma. This case is of interest because of its rare intracranial localization of the lymphoma. The knowledge of CT and MRI images of the intracranial form of lymphoma may help diagnosing, but images should be interpreted together with the clinical and paraclinical results Hodgkin's and non-Hodgkin's) is a disease of the lymphatic system where the central neural system is affected in very rare cases. According to different authors the frequency of cases with lymphoma where the neural system is affected varies between 0, 2 % and 0, 5 %, and the primary cerebral lymphoma accounts for about 1-2% of ail brain neoplasms. The intracranial form of iymphoma is usually a late onset of the disease

The efficacy and safety of alectinib in the treatment of ALK+ NSCLC: a systematic review and meta-analysis

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Fan JS

2018-03-01

Full Text Available Junsheng Fan,1,2,* Zengfei Xia,1,* Xiaoli Zhang,1,* Yuqing Chen,1 Ruolan Qian,1 Sihan Liu,1 Danming You,1 Jian Zhang,1 Peng Luo1 1Department of Oncology, Zhujiang Hospital of Southern Medical University, Guangzhou, China; 2Department of Respiratory Medicine, Shanghai Tenth People’s Hospital, Tongji University, Shanghai, China *These authors contributed equally to this work Background: Alectinib is a second-generation anaplastic lymphoma kinase (ALK inhibitor approved by the US Food and Drug Administration to treat crizotinib-refractory non-small cell lung cancer. We performed this meta-analysis to synthesize the results of different clinical trials to evaluate the efficacy and safety of alectinib. Methods: A search of 3 databases, including PubMed, Web of Science, and the Cochrane Library, was performed from the inception of each database through September 5, 2017. We have pooled the overall response rate (ORR, disease control rate, progression-free survival, and intracranial ORR to evaluate the efficacy of alectinib. Discontinuation rate, rate of dose reduction or interruption due to adverse events as well as the incidence of several adverse events were aggregated to evaluate its safety. Results: A total of 8 studies with 626 patients have been included in our study. The pooled efficacy parameters are as follows: ORR 70% (95% CI: 57% to 82%, disease control rate 88% (95% CI: 82% to 94%, progression-free survival 9.36 months (95% CI: 7.38% to 11.34%, and intracranial ORR 52% (95% CI: 45% to 59%. ALK inhibitor-naïve patients tend to have better responses than crizotinib-pretreated patients. The aggregate discontinuation rate is 7% (95% CI: 4% to 10%, and the pooled rate of dose reduction or interruption is 33% (95% CI: 24% to 42%. The incidences of most adverse events were relatively low, while the incidences of 2 frequently reported adverse events, myalgia (18% and anemia (25%, were even higher than with the first-generation ALK inhibitor

Risks of Breast Implants

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... have a risk of developing a type of cancer called breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) in the breast tissue surrounding the implant. BIA-ALCL is not breast cancer. Women diagnosed with BIA-ALCL may need to ...

EBV AND HIV-RELATED LYMPHOMA

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Michele Bibas

2009-12-01

Full Text Available HIV-associated lymphoproliferative disorders represent a heterogeneous group of diseases, arising in the presence of HIV-associated immunodeficiency. The overall prevalence of HIV-associated lymphoma is significantly higher compared to that of the general population and it continues to be relevant even after the wide availability of highly active antiretroviral therapy (HAART (1. Moreover, they still represent one of the most frequent cause of death in HIV-infected patients. Epstein–Barr virus (EBV, a γ-Herpesviruses, is involved in human lymphomagenesis, particularly in HIV immunocompromised patients. It has been largely implicated in the development of B-cell lymphoproliferative disorders as Burkitt lymphoma (BL, Hodgkin disease (HD, systemic non Hodgkin lymphoma (NHL, primary central nervous system lymphoma (PCNSL, nasopharyngeal carcinoma (NC. Virus-associated lymphomas are becoming of significant concern for the mortality of long-lived HIV immunocompromised patients, and therefore, research of advanced strategies for AIDS-related lymphomas is an important field in cancer chemotherapy. Detailed understanding of the EBV  lifecycle and related cancers at the molecular level is required for novel strategies of molecular-targeted cancer chemotherapy The linkage of HIV-related lymphoma with EBV infection of the tumor clone has several pathogenetic, prognostic and possibly therapeutic implications which are reviewed herein

Heart of Lymphoma: Primary Mediastinal Large B-Cell Lymphoma with Endomyocardial Involvement

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Elisa Rogowitz

2013-01-01

Full Text Available Primary mediastinal B-cell lymphoma (PMBCL is an uncommon aggressive subset of diffuse large B-cell lymphomas. Although PMBCL frequently spreads locally from the thymus into the pleura or pericardium, it rarely invades directly through the heart. Herein, we report a case of a young Mexican female diagnosed with PMBCL with clear infiltration of lymphoma through the cardiac wall and into the right atrium and tricuspid valve leading to tricuspid regurgitation. This was demonstrated by cardiac MRI and transthoracic echocardiogram. In addition, cardiac MRI and CT scan of the chest revealed the large mediastinal mass completely surrounding and eroding into the superior vena cava (SVC wall causing a collar of stokes. The cardiac and SVC infiltration created a significant therapeutic challenge as lymphomas are very responsive to chemotherapy, and treatment could potentially lead to vascular wall rupture and hemorrhage. Despite the lack of conclusive data on chemotherapy-induced hemodynamic compromise in such scenarios, her progressive severe SVC syndrome and respiratory distress necessitated urgent intervention. In addition to the unique presentation of this rare lymphoma, our case report highlights the safety of R-CHOP treatment.

The evolving field of kinase inhibitors in thyroid cancer.

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Marotta, V; Sciammarella, C; Vitale, M; Colao, A; Faggiano, A

2015-01-01

Most of the genetic events implicated in the pathogenesis of thyroid cancer (TC) involve genes with kinase activity. Thus, kinase inhibitors (KIs) are very relevant in this field. KIs are considered the most suitable treatment for patients with iodine-refractory differentiated TC; these patients comprise the subgroup with the poorer prognosis. To date, only sorafenib has been approved for this indication, but promising results have been reported with several other KIs. In particular, lenvatinib has demonstrated excellent efficacy, with both progression-free survival and objective tumour response being better than with sorafenib. Despite being considered to be well tolerated, both sorafenib and lenvatinib have shown a remarkable toxicity, which has led to dose reductions in the majority of patients and to treatment discontinuation in a significant proportion of cases. The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). Vandetanib and cabozantinib have been approved for the treatment of advanced, progressive medullary TC (MTC). Nevertheless, the toxicity of both compounds suggests their selective use in those patients with strong disease progression. Treatment with the mTOR-inhibitor everolimus, alone or in combination with somatostatin analogues, should be studied in metastatic MTC patients with slow progression of disease, these representing the vast majority of patients. KIs did not significantly impact on the clinical features of anaplastic TC (ATC). Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell lymphoma

Directory of Open Access Journals (Sweden)

Chioniso Patience Masamha

2016-03-01

Full Text Available Abstract The t(11;14 translocation resulting in constitutive cyclin D1 expression is an early event in mantle cell lymphoma (MCL transformation. Patients with a highly proliferative phenotype produce cyclin D1 transcripts with truncated 3′UTRs that evade miRNA regulation. Here, we report the recurrence of a novel gene fusion in MCL cell lines and MCL patient isolates that consists of the full protein coding region of cyclin D1 (CCND1 and a 3′UTR consisting of sequences from both the CCND1 3′UTR and myotonic dystrophy kinase-related Cdc42-binding kinase's (MRCK intron one. The resulting CCND1/MRCK mRNA is resistant to CCND1-targeted miRNA regulation, and targeting the MRCK region of the chimeric 3′UTR with siRNA results in decreased CCND1 levels.

TGFbeta1-mediated inactivation of G1 phase cyclin-dependent kinases in malignant B lymphoma cells

Czech Academy of Sciences Publication Activity Database

Tvrdík, Daniel; Djaborkhel, Rashed; Raška, Ivan; Müller, Julius

č. 8 (2001), s. 36 ISSN 1107-3756. [World Congress on Advances in Oncology /6./ and International Symposium on Molecular Medicine /4./. 18.10.2001-20.10.2001, Crete] R&D Projects: GA MŠk VS96130; GA ČR GA302/99/0587; GA ČR GA304/00/1481; GA ČR GA304/01/0564 Keywords : lymphoma lells * CDK * CDK-inhibitors Subject RIV: EB - Genetics ; Molecular Biology

MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

Science.gov (United States)

2014-05-22

Adult Grade III Lymphomatoid Granulomatosis; B-cell Chronic Lymphocytic Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Refractory Hairy Cell Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Testicular Lymphoma; Waldenström Macroglobulinemia

Use of conivaptan to allow aggressive hydration to prevent tumor lysis syndrome in a pediatric patient with large-cell lymphoma and SIADH.

Science.gov (United States)

Rianthavorn, Pornpimol; Cain, Joan P; Turman, Martin A

2008-08-01

The available treatment options for hyponatremia secondary to SIADH are limited and not completely effective. Conivaptan is a vasopressin 1a and 2 receptor antagonist recently approved by the US Food and Drug Administration (FDA) for treating euvolemic and hypervolemic hyponatremia in adult patients. However, data on efficacy and safety of conivaptan in pediatrics are limited. We report a case of a 13-year-old boy with extensively metastasized anaplastic large-cell lymphoma. He also developed hyponatremia due to syndrome of inappropriate antidiuretic hormone secretion (SIADH) prior to chemotherapy initiation. SIADH management in this case was complicated when fluid restriction was not safely attainable. Conivaptan played a significant role in this situation by allowing provision of a large amount of intravenous fluid prior to and during induction chemotherapy. It proved to be an important component in preventing uric acid nephropathy/tumor lysis syndrome. Conivaptan induced free-water clearance as indicated by increased urine output and decreased urine osmolality. The patient responded to conivaptan without any adverse effects.

Molecular Pathogenesis of MALT Lymphoma

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Katharina Troppan

2015-01-01

Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

A cyclin-dependent kinase inhibitor, dinaciclib in preclinical treatment models of thyroid cancer.

Directory of Open Access Journals (Sweden)

Shu-Fu Lin

Full Text Available We explored the therapeutic effects of dinaciclib, a cyclin-dependent kinase (CDK inhibitor, in the treatment of thyroid cancer.Seven cell lines originating from three pathologic types of thyroid cancer (papillary, follicular and anaplastic were studied. The cytotoxicity of dinaciclib was measured using a lactate dehydrogenase assay. The expression of proteins associated with cell cycle and apoptosis was assessed using Western blot analysis and immunofluorescence microscopy. Cell cycle distribution was measured by flow cytometry and immunofluorescence microscopy. Apoptosis and caspase-3 activity were measured by flow cytometry and fluorometric assay. Mice bearing flank anaplastic thyroid cancer (ATC were treated with intraperitoneal injections of dinaciclib.Dinaciclib inhibited thyroid cancer cell proliferation in a dose-dependent manner. Dinaciclib had a low median-effect dose (≤ 16.0 nM to inhibit cell proliferation in seven thyroid cancer cell lines. Dinaciclib decreased CDK1, cyclin B1, and Aurora A expression, induced cell cycle arrest in the G2/M phase, and induced accumulation of prophase mitotic cells. Dinaciclib decreased Mcl-1, Bcl-xL and survivin expression, activated caspase-3 and induced apoptosis. In vivo, the growth of ATC xenograft tumors was retarded in a dose-dependent fashion with daily dinaciclib treatment. Higher-dose dinaciclib (50 mg/kg caused slight, but significant weight loss, which was absent with lower-dose dinaciclib (40 mg/kg treatment.Dinaciclib inhibited thyroid cancer proliferation both in vitro and in vivo. These findings support dinaciclib as a potential drug for further studies in clinical trials for the treatment of patients with refractory thyroid cancer.

Systemic treatment in EGFR-ALK NSCLC patients: second line therapy and beyond

International Nuclear Information System (INIS)

Karachaliou, Niki; Rosell, Rafael

2014-01-01

Lung cancer is the most frequently diagnosed cancer and a leading cause of cancer mortality worldwide, with adenocarcinoma being the most common histological subtype. Deeper understanding of the pathobiology of non-small cell lung cancer (NSCLC) has led to the development of small molecules that target genetic mutations known to play critical roles in progression to metastatic disease and to influence response to targeted therapies. The principle goal of precision medicine is to define those patient populations most likely to respond to targeted therapies. However, the cancer genome landscape is composed of relatively few “mountains” [representing the most commonly mutated genes like KRAS, epidermal growth factor (EGFR), and anaplastic lymphoma kinase (ALK)] and a vast number of “hills” (representing low frequency but potentially actionable mutations). Low-frequency lesions that affect a druggable gene product allow a relatively small population of cancer patients for targeted therapy to be selected

Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells.

Science.gov (United States)

Tanimoto, Azusa; Yamada, Tadaaki; Nanjo, Shigeki; Takeuchi, Shinji; Ebi, Hiromichi; Kita, Kenji; Matsumoto, Kunio; Yano, Seiji

2014-07-15

Alectinib is a new generation ALK inhibitor with activity against the gatekeeper L1196M mutation that showed remarkable activity in a phase I/II study with echinoderm microtubule associated protein-like 4 (EML4)--anaplastic lymphoma kinase (ALK) non-small cell lung cancer (NSCLC) patients. However, alectinib resistance may eventually develop. Here, we found that EGFR ligands and HGF, a ligand of the MET receptor, activate EGFR and MET, respectively, as alternative pathways, and thereby induce resistance to alectinib. Additionally, the heat shock protein 90 (Hsp90) inhibitor suppressed protein expression of ALK, MET, EGFR, and AKT, and thereby induced apoptosis in EML4-ALK NSCLC cells, even in the presence of EGFR ligands or HGF. These results suggest that Hsp90 inhibitors may overcome ligand-triggered resistance to new generation ALK inhibitors and may result in more successful treatment of NSCLC patients with EML4-ALK.

Malignant T cells exhibit CD45 resistant Stat 3 activation and proliferation in cutaneous T cell lymphoma

DEFF Research Database (Denmark)

Krejsgaard, T; Helvad, Rikke; Ralfkiær, Elisabeth

2010-01-01

CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator of transcr......CD45 is a protein tyrosine phosphatase, which is well-known for regulating antigen receptor signalling in T and B cells via its effect on Src kinases. It has recently been shown that CD45 can also dephosphorylate Janus kinases (Jaks) and thereby regulate Signal transducer and activator...... of transcription (Stat) activation and cytokine-induced proliferation in lymphocytes. Consequently, CD45 dysregulation could be implicated in aberrant Jak/Stat activation and proliferation in lymphoproliferative diseases. Despite high expression of the CD45 ligand, Galectin-1, in skin lesions from cutaneous T......-cell lymphoma (CTCL), the malignant T cells exhibit constitutive activation of the Jak3/Stat3 signalling pathway and uncontrolled proliferation. We show that CD45 expression is down-regulated on malignant T cells when compared to non-malignant T cells established from CTCL skin lesions. Moreover, CD45 cross...

Clonal heterogeneity of small-cell anaplastic carcinoma of the lung demonstrated by flow-cytometric DNA analysis

DEFF Research Database (Denmark)

Vindeløv, L L; Hansen, H H; Christensen, I J

1980-01-01

Flow-cytometric DNA analysis yields information on ploidy and proliferative characteristics of a cell population. The analysis was implemented on small-cell anaplastic carcinoma of the lung using a rapid detergent technique for the preparation of fine-needle aspirates for DNA determination and a ...

A case of lung adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene

International Nuclear Information System (INIS)

Tanaka, Hisashi; Hayashi, Akihito; Morimoto, Takeshi; Taima, Kageaki; Tanaka, Yoshihito; Shimada, Michiko; Kurose, Akira; Takanashi, Shingo; Okumura, Ken

2012-01-01

Lung cancer is the leading cause of cancer-related death worldwide. Epidermal growth factor receptor (EGFR) - tyrosine kinase inhibitor (TKI) is used for the patients with EGFR-mutant lung cancer. Recently, phase III studies in the patients with EGFR-mutant demonstrated that EGFR-TKI monotherapy improved progression-free survival compared with platinum-doublet chemotherapy. The echinoderm microtubule-associated protein-like 4 (EML4) - anaplastic lymphoma kinase (ALK) fusion oncogene represents one of the newest molecular targets in non-small cell lung cancer (NSCLC). Patients who harbor EML4-ALK fusions have been associated with a lack of EGFR or KRAS mutations. We report a 39-year-old patient diagnosed as adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene. We treated this patient with erlotinib as the third line therapy, but no clinical benefit was obtained. We experienced a rare case with EGFR mutation and EML4-ALK. Any clinical benefit using EGFR-TKI was not obtained in our case. The therapeutic choice for the patients with more than one driver mutations is unclear. We needs further understanding of the lung cancer molecular biology and the biomarker infomation

Management of lung cancer brain metastasis: An overview

Directory of Open Access Journals (Sweden)

Himanshu Srivastava

2017-01-01

Full Text Available With the improvements in systemic treatment for lung cancer, distant metastasis to sanctuary sites such as brain has become an increasingly more important issue. The management of these patients consists of supportive care and disease-directed treatment. Combined modality treatment (surgical resection or radiosurgery, followed by whole brain radiotherapy of brain metastases has greatly improved the local control of disease in patients with single lesion, good functional performance status, and controlled extracranial disease as demonstrated in prospective randomized studies. For patients with multiple brain metastases, conventional fractionated whole brain radiotherapy continues to be a standard and efficacious treatment. At present, experience with the use of molecularly targeted tyrosine kinase inhibitors in nonsmall cell lung cancer patients with activating mutations in the epidermal growth factor receptor gene and anaplastic lymphoma kinase gene is growing. However, their effectiveness in patients with brain metastases is not well established. In the arena of targeted therapies, vascular endothelial growth factor pathway inhibitors such as bevacizumab have shown some activity in brain metastases. Further prospective studies are necessary to facilitate selection of patient subpopulation for targeted agents in future studies.

The Evolution of Therapies in Non-Small Cell Lung Cancer

Directory of Open Access Journals (Sweden)

Vishal Boolell

2015-09-01

Full Text Available The landscape of advanced non-small lung cancer (NSCLC therapies has rapidly been evolving beyond chemotherapy over the last few years. The discovery of oncogenic driver mutations has led to new ways in classifying NSCLC as well as offered novel therapeutic targets for anticancer therapy. Targets such as epidermal growth factor receptor (EGFR mutations and anaplastic lymphoma kinase (ALK gene rearrangements have successfully been targeted with appropriate tyrosine kinase inhibitors (TKIs. Other driver mutations such as ROS, MET, RET, BRAF have also been investigated with targeted agents with some success in the early phase clinical setting. Novel strategies in the field of immune-oncology have also led to the development of inhibitors of cytotoxic T lymphocyte antigen-4 (CTLA-4 and programmed death-1 receptor (PD-1, which are important pathways in allowing cancer cells to escape detection by the immune system. These inhibitors have been successfully tried in NSCLC and also now bring the exciting possibility of long term responses in advanced NSCLC. In this review recent data on novel targets and therapeutic strategies and their future prospects are discussed.

Novel targeted therapeutics: inhibitors of MDM2, ALK and PARP

Directory of Open Access Journals (Sweden)

Hsueh Chung-Tsen

2011-04-01

Full Text Available Abstract We reviewed preclinical data and clinical development of MDM2 (murine double minute 2, ALK (anaplastic lymphoma kinase and PARP (poly [ADP-ribose] polymerase inhibitors. MDM2 binds to p53, and promotes degradation of p53 through ubiquitin-proteasome degradation. JNJ-26854165 and RO5045337 are 2 small-molecule inhibitors of MDM2 in clinical development. ALK is a transmembrane protein and a member of the insulin receptor tyrosine kinases. EML4-ALK fusion gene is identified in approximately 3-13% of non-small cell lung cancer (NSCLC. Early-phase clinical studies with Crizotinib, an ALK inhibitor, in NSCLC harboring EML4-ALK have demonstrated promising activity with high response rate and prolonged progression-free survival. PARPs are a family of nuclear enzymes that regulates the repair of DNA single-strand breaks through the base excision repair pathway. Randomized phase II study has shown adding PARP-1 inhibitor BSI-201 to cytotoxic chemotherapy improves clinical outcome in patients with triple-negative breast cancer. Olaparib, another oral small-molecule PARP inhibitor, demonstrated encouraging single-agent activity in patients with advanced breast or ovarian cancer. There are 5 other PARP inhibitors currently under active clinical investigation.

Pomalidomide and Dexamethasone in Treating Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma or Newly Diagnosed or Relapsed or Refractory Intraocular Lymphoma

Science.gov (United States)

2017-08-28

B-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma; Central Nervous System Lymphoma; Intraocular Lymphoma; Primary Diffuse Large B-Cell Lymphoma of the Central Nervous System; Recurrent Adult Diffuse Large Cell Lymphoma; Retinal Lymphoma

Anti-ICOS Monoclonal Antibody MEDI-570 in Treating Patients With Relapsed or Refractory Peripheral T-cell Lymphoma Follicular Variant or Angioimmunoblastic T-cell Lymphoma

Science.gov (United States)

2018-05-09

Follicular T-Cell Lymphoma; Grade 1 Follicular Lymphoma; Grade 2 Follicular Lymphoma; Grade 3a Follicular Lymphoma; Recurrent Angioimmunoblastic T-Cell Lymphoma; Recurrent Follicular Lymphoma; Recurrent Mature T- and NK-Cell Non-Hodgkin Lymphoma; Recurrent Mycosis Fungoides; Recurrent Primary Cutaneous T-Cell Non-Hodgkin Lymphoma; Refractory Angioimmunoblastic T-Cell Lymphoma; Refractory Follicular Lymphoma; Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Stage IB Mycosis Fungoides AJCC v7; Stage II Mycosis Fungoides AJCC v7; Stage III Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage III Mycosis Fungoides AJCC v7; Stage IV Cutaneous T-Cell Non-Hodgkin Lymphoma; Stage IV Mycosis Fungoides AJCC v7

Radiotherapy of primary gastric malignant lymphoma

International Nuclear Information System (INIS)

Monzen, Yoshio; Mutsukura, Masahide; Moriuchi, Yukiyoshi

2017-01-01

Fifteen patients with primary gastric malignant lymphoma who underwent radiotherapy were examined. Median age was 68 years, and male to female ratio was 1:2. All the cases were stage I including 7 cases of diffuse large B-cell lymphoma (DLBCL), 7 cases of MALT lymphoma, and 1 case of follicular lymphoma. Therapy methods were as follows. For DLBCL, 30 Gy of radiotherapy was performed after chemotherapy. For six cases of MALT lymphomas, 30 Gy of radiotherapy was performed. For one patient diagnosed as high-grade gastric MALT lymphoma was treated in the same way as DLBCL. For one patient with follicular lymphoma, 30 Gy of radiotherapy was performed. The radiotherapy was applied with 3-dimensional fixed multi-portal irradiation, with the reduced irradiation of the liver and kidney. There was no recurrence of disease in all cases, and all patients have been alive, and no-recurrence living periods are 20 to 120 months. There was no harmful adverse event, and the tumor had disappeared with 30 Gy of radiation therapy in all cases. Considering the occurrence of secondary cancer, it was considered that a dosage of more than 30 Gy was not necessary for primary gastric malignant lymphoma. (J.P.N.)

Differential Expression of FAK and Pyk2 in Metastatic and Non-metastatic EL4 Lymphoma Cell Lines

OpenAIRE

Zhang, Zhihong; Knoepp, Stewart M.; Ku, Hsun; Sansbury, Heather M.; Xie, Yuhuan; Chahal, Manpreet S.; Tomlinson, Stephen; Meier, Kathryn E.

2011-01-01

The murine EL4 lymphoma cell line exists in variants that are either sensitive or resistant to phorbol 12-myristate 13-acetate (PMA). In sensitive cells, PMA causes Erk MAPK activation and Erk-mediated growth arrest. In resistant cells, PMA induces a low level of Erk activation, without growth arrest. A relatively unexplored aspect of the phenotypes is that resistant cells are more adherent to culture substrate than are sensitive cells. In this study, the roles of the protein tyrosine kinases...

Case Report

DEFF Research Database (Denmark)

Sylvester-Hvid, Amalie; Avnstorp, Magnus B; Wagenblast, Lene

2017-01-01

Introduction Breast seroma may be caused by a variety of factors including lymphatic disruption, continuous inflammation and foreign bodies such as breast implants. In cases of breast implants associated seroma the diagnosis of Anaplastic Large Cell Lymphoma (ALCL) should be investigated. Present...

Disease: H01601 [KEGG MEDICUS

Lifescience Database Archive (English)

Full Text Available ype ICD-10: C84.6 C84.7 MeSH: D017728 PMID:25869285 (gene, drug) ... AUTHORS ... Hapgood G, Savage KJ ... TITLE ... The biology and managem...ent of systemic anaplastic large cell lymphoma. ... JOURNAL ... Blood 126:17-25 (2015)

Ibrutinib Treatment of Mantle Cell Lymphoma Relapsing at Central Nervous System: A Case Report and Literature Review

Directory of Open Access Journals (Sweden)

Donato Mannina

2017-01-01

Full Text Available Mantle cell lymphoma (MCL accounts for about 5% of all lymphomas. Its clinical and histological features are heterogeneous. After a frequently good initial response, the disease generally and repeatedly relapses and finally the outcome is poor. Particularly severe is the prognosis of the rare occurrence of CNSi (Central Nervous System involvement. Ibrutinib, an oral inhibitor of Bruton tyrosine kinase (BTK, has shown strong activity in relapsing patients with Chronic Lymphocytic Leukemia (CLL and MCL. Few reports are available about treatment with ibrutinib of patients presenting CNSi by lymphoproliferative diseases (LPD. In all of them, ibrutinib, at the dosage between 420 and 560 mg/day, showed an impressive effectiveness. Here we describe a case of MCL with CNS relapse showing an excellent response to ibrutinib administered at the unusual dose of 280 mg/day because of concomitant treatment of cardiological disease.

Classification of malignant lymphomas

International Nuclear Information System (INIS)

Schneider, M.; Thyss, A.

1986-01-01

Malignant lymphomas, primary tumors of the lymphoid tissues, were first described in 1832 by Thomas Hodgkin. The histological characteristics were later defined by Sternberg and Reed, and Virchow introduced the concept of lymphosarcoma in 1863. Today, these pathologies are grouped together under the synonymous terms hematosarcoma or malignant lymphoma, which are in turn divided into Hodgkin's disease (HD) and non-Hodgkin's malignant lymphomas (NHL). The therapy of lymphomas is controversial. The validity of treatment for asymptomatic patients is questioned, owing to the indolent course of many lymphomas. Results for histologically unfavorable forms are highly disparate. Exclusive radiotherapy has occasionally produced up to 78% disease-free survival at 5 years for truly localized stages. Today, however, use of chemotherapy/radiotherapy combinations is almost universal, with chemotherapy occasionally being used alone and providing 90% disease-free survival at 5 years. Chemotherapy is the main treatment for disseminated forms; the major associations include doxorubicin hydrochloride (Adriamycin), cyclophosphamide, vincristine sulfate, methotrexate, and prednisone. Radiotherapy is used more for adjuvant purposes. Synthesis of recent studies allows us to reasonably expect 40% relapse-free survival at 10 years and the establishment of a cure plateau in the near future

Danish National Lymphoma Registry

DEFF Research Database (Denmark)

Arboe, Bente; Josefsson, Pär; Jørgensen, Judit

2016-01-01

AIM OF DATABASE: The Danish National Lymphoma Registry (LYFO) was established in order to monitor and improve the diagnostic evaluation and the quality of treatment of all lymphoma patients in Denmark. STUDY POPULATION: The LYFO database was established in 1982 as a seminational database including...... all lymphoma patients referred to the departments of hematology. The database became nationwide on January 1, 2000. MAIN VARIABLES: The main variables include both clinical and paraclinical variables as well as details of treatment and treatment evaluation. Up to four forms are completed for each......-100 years) and a male/female ratio of 1.23:1. Patients can be registered with any of 42 different subtypes according to the World Health Organization classifications. CONCLUSION: LYFO is a nationwide database for all lymphoma patients in Denmark and includes detailed information. This information is used...

[Plasmablastic lymphoma].

Science.gov (United States)

Fernández-Álvarez, Rubén; Sancho, Juan-Manuel; Ribera, Josep-María

2016-11-04

Plasmablastic lymphoma (PBL) is a rare and aggressive subtype of non-Hodgkin lymphoma that commonly occurs in human immunodeficiency virus (HIV)-positive individuals, and affects oral sites. Occasionally, it has been described in HIV-negative patients and involving non-oral sites. Pathologically, PBL is a high-grade B-cell lymphoma that displays the immunophenotype of a terminally differentiated B-lymphocyte with loss of B-cell markers (CD20) and expression of plasma-cell antigens. Epstein-Barr virus infection and MYC rearrangements are frequently observed. Treatment of PBL is challenging because of the lack of established treatment and poor outcomes, with median survival times shorter than one year. In this review, we discuss the clinical and epidemiologic spectrum of PBL as well as its distinct pathological features. Finally, we summarize the currently available approaches for the treatment of patients with PBL. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Investigation of the results of therapy of anaplastic thyroid gland carcinomas

International Nuclear Information System (INIS)

Ooijen, M. van.

1979-01-01

The results of the treatment of 28 patients with an anaplastic thyroid gland carcinoma are investigated, to see whether an optimal therapy is indicated. The execution of an operation before radiotherapy does not appear to improve the prognosis (statistically this conclusion is not wholly justified). The presence of metastases at the beginning of the therapy gave rise to a worse prognosis than the absence of metastases. The combination treatment of chemotherapy and either surgery or radiotherapy was only applied to two patients so no conclusions can be made about its benefit. (C.F.)

Avelumab, Utomilumab, Rituximab, Ibrutinib, and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma or Mantle Cell Lymphoma

Science.gov (United States)

2018-06-13

CCND1 Positive; CD20 Positive; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory Diffuse Large B-Cell Lymphoma; Refractory Mantle Cell Lymphoma; Transformed Follicular Lymphoma to Diffuse Large B-Cell Lymphoma

Radiotherapy of malignant lymphomas

Energy Technology Data Exchange (ETDEWEB)

Kujawska, J [Instytut Onkologii, Krakow (Poland)

1979-01-01

The paper discusses current views on the role of radiotherapy in the treatment of patients with malignant lymphomas. Principles of radiotherapy employed in the Institute of Oncology in Cracow in case of patients with malignant lymphomas are also presented.

Primary Breast Mucosa-Associated Lymphoid Tissue (MALT Lymphoma Transformation to Diffuse Large B-cell Lymphoma: A Case Report

Directory of Open Access Journals (Sweden)

Şerife Hülya Arslan

2012-09-01

Full Text Available Primary non-Hodgkin’s lymphoma (NHL of the breast constitutes 0.04%-0.53% of all malignancies and 2.2% of extra nodal lymphomas. In total, 7%-8% of all B-cell lymphomas are the mucosa-associated lymphoid tissue (MALT type, of which up to 50% of primary gastric MALT lymphoma. Herein we present a patient with breast MALT lymphoma that transformed to diffuse large B-cell lymphoma (DLBCL. A 69-year-old female presented with a mass on her left breast. Physical examination showed a 3 × 3-cm mass located 1 cm from the areola on the upper lateral quadrant of the breast at the 1 o’clock position, which was fixed and firm. Excisional biopsy was performed and pathologic examination of the specimen showed MALT lymphoma transformation to DLBCL. The patient was staged as II-EA. The rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP protocol was scheduled as treatment. Following 6 courses of R-CHOP, 2 additional courses of rituximab were administered. Positron emission tomography (PET-CT was done at the end of the treatment. PET showed that the patient was in complete remission. At the time this report was written, the patient was being followed-up at the outpatient clinic on a regular basis. Lymphoma of the breast is a rarity among malignant tumors of the breast. The most common type of lymphoma is DLBCL. Breast MALT lymphoma is extremely rare. Primary MALT lymphoma of the breast can transform from low grade to high grade and recurrence is possible; therefore, such patients should be monitored carefully for transformation.

Hodgkin Lymphoma (For Kids)

Science.gov (United States)

... First Aid & Safety Doctors & Hospitals Videos Recipes for Kids Kids site Sitio para niños How the Body Works ... Educators Search English Español Hodgkin Lymphoma KidsHealth / For Kids / Hodgkin Lymphoma What's in this article? What Is ...

THE MANAGEMENT OF AN ORAL ANAPLASTIC SARCOMA IN A PYGMY HIPPOPOTAMUS (CHOEROPSIS LIBERIENSIS) USING INTRALESIONAL CHEMOTHERAPY.

Science.gov (United States)

Franklinos, Lydia H V; Masters, Nicholas; Feltrer, Yedra; Pocknell, Ann; Bolt, David M; Dakin, Stephanie; Berry, Karla; Molenaar, Fieke M

2017-03-01

An adult female captive pygmy hippopotamus (Choeropsis liberiensis) was diagnosed with an oral anaplastic sarcoma. The tumor was surgically debulked and intralesional chemotherapy with mitomycin C (0.4 mg/cm 3 of tumor) and cisplatin (1 mg/cm 3 of tumor) was administered. Chemotherapeutic treatment proved difficult due to the risks of repeated anesthetics and unknown drug efficacies. Marked proliferation of the mass was observed during estrus, and chemotherapy was repeated as an experimental treatment to slow tumor progression in order for the animal to remain in the species breeding program. Tumor proliferation was detected during the first trimester of pregnancy; however, in the lactation period, the mass became quiescent. No adverse reactions to chemotherapeutic drugs were observed and the animal continues to be monitored for tumor progression. This is the first report of an anaplastic sarcoma and of chemotherapy use in a pygmy hippopotamus and it highlights logistical considerations for treating neoplasia in this species.

Molecular resemblance of an AIDS-associated lymphoma and endemic Burkitt lymphomas: Implications for their pathogenesis

International Nuclear Information System (INIS)

Haluska, F.G.; Russo, G.; Croce, C.M.; Kant, J.; Andreef, M.

1989-01-01

Non-Hodgkin lymphoma is a common feature of AIDS. Approximately 30-40% of these tumors exhibit clinical features suggestive of endemic Burkitt lymphoma: they are aggressive malignancies that occur in association with Epstein-Barr virus infection, they arise in the setting of immunosuppression, and they carry t(8;14) translocations without detectable rearrangement of the MYC oncogene. To understand the molecular basis of these parallels, the authors analyzed a case of Epstein-Barr-positive AIDS-associated undifferentiated lymphoma. Southern blots show that the tumor exhibits immunoglobulin joining segment rearrangement but no rearrangement of the MYC oncogene. Cloning of the rearranged joining segment allowed the isolation of recombinant clones encompassing the translocation breakpoint, and sequencing of the translocation junction disclosed that the breakpoint is situated 7 base pairs from the chromosome 14 site involved in a previously described endemic Burkitt lymphoma translocation. Furthermore, the breakpoint is situated far from MYC on chromosome 8, a constant finding in endemic Burkitt lymphomas. That the molecular architecture of the translocation in this case is strikingly similar to previously analyzed translocations from endemic Burkitt lymphomas strongly suggests that common molecular mechanisms must be operative in the pathogenesis of these tumors

Epstein-Barr Virus in Classical Hodgkin Lymphoma

International Nuclear Information System (INIS)

Azhar, M.; Din, H. U.; Muhammad, I.; Hashmi, S. N.; Akhtar, F.

2016-01-01

Background: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. Method: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. Results: Out of 55 patients, 38 (69 percent) were male and 17 (31 percent) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80 percent) were positive for latent membrane protein-1. Among positive cases 32 (72.72 percent) were male and 12 (27.28 percent) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3 percent as well as among both genders. Out of total 55 cases, 79.16 percent (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33 percent (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100 percent (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80 percent of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16 percent cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100 percent of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. Conclusion: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma

Transmission of naturally occurring lymphoma in macaque monkeys.

OpenAIRE

Hunt, R D; Blake, B J; Chalifoux, L V; Sehgal, P K; King, N W; Letvin, N L

1983-01-01

Spontaneously occurring rhesus monkey lymphomas were transmitted into healthy rhesus monkeys by using tumor cell suspensions. The naturally arising tumors included an immunoblastic sarcoma and an undifferentiated lymphoma. Recipient animals developed undifferentiated lymphomas, poorly differentiated lymphomas, or parenchymal lymphoproliferative abnormalities suggestive of early lesions of lymphoma. Some of these animals developed such opportunistic infections as cytomegalovirus hepatitis and ...

The Four types of Tregs in malignant lymphomas

Directory of Open Access Journals (Sweden)

Wang Jing

2011-12-01

Full Text Available Abstract Regulatory T cells (Tregs are a specialized subpopulation of CD4+ T cells, which act to suppress the activation of other immune cells. Tregs represent important modulators for the interaction between lymphomas and host microenvironment. Lymphomas are a group of serious and frequently fatal malignant diseases of lymphocytes. Recent studies revealed that some lymphoma T cells might adopt a Treg profile. Assessment of Treg phenotypes and genotypes in patients may offer prediction of outcome in many types of lymphomas including diffuse large B-cell lymphoma, follicular lymphoma, cutaneous T cell lymphoma, and Hodgkin's lymphoma. Based on characterized roles of Tregs in lymphomas, we can categorize the various roles into four groups: (a suppressor Tregs; (b malignant Tregs; (c direct tumor-killing Tregs; and (d incompetent Tregs. The classification into four groups is significant in predicting prognosis and designing Tregs-based immunotherapies for treating lymphomas. In patients with lymphomas where Tregs serve either as suppressor Tregs or malignant Tregs, anti-tumor cytotoxicity is suppressed thus decreased numbers of Tregs are associated with a good prognosis. In contrast, in patients with lymphomas where Tregs serve as tumor-killing Tregs and incompetent Tregs, anti-tumor cytotoxicity is enhanced or anti-autoimmune Tregs activities are weakened thus increased numbers of Tregs are associated with a good prognosis and reduced numbers of Tregs are associated with a poor prognosis. However, the mechanisms underlying the various roles of Tregs in patients with lymphomas remain unknown. Therefore, further research is needed in this regard as well as the utility of Tregs as prognostic factors and therapy strategies in different lymphomas.

Primary intracerebral lymphoma: Case report

Directory of Open Access Journals (Sweden)

Olcay Eser

2012-09-01

Full Text Available We describe a case of primary central nervous lymphoma (PCNSL that may be confused with magnetic resonance imaging (MRI findings of high grade glioma. Primary central nervous lymphoma is a rare tumour and it account for 0.3-3% of intracranial tumours. A 61 year’s old woman was admitted to our clinic with a severe headache, vomiting, left hemiparesia and transient loss of consciousness. Primary central nervous lymphoma may show various biological and radiological characteristics. We herein emphasized being confused with MRI findings of PCNSL and high grade glioma. J Clin Exp Invest 2012; 3 (3: 409-411Key words: Primary central nervous lymphoma, high grade glioma, B-cell, diagnosis

Lymphoma cytogenetics.

Science.gov (United States)

Dave, Bhavana J; Nelson, Marilu; Sanger, Warren G

2011-12-01

Lymphomas are a heterogeneous group of neoplasms with distinct morphologic, immunologic, and cytogenetic characteristics. Overlapping morphologic and immunophenotypic features often makes accurate diagnosis difficult. Cytogenetics helps simplify the diagnostic complexities presented in transforming and progressive lymphoid malignancies. Genetic studies using technical advances such as fluorescence in situ hybridization and the newer approaches of array comparative genomic hybridization and gene expression profiling play a critical and often defining role in the diagnosis, progression, prognosis, and therapeutic stratification. This article reviews characteristic cytogenetic abnormalities in specific subtypes of lymphomas at diagnosis, disease progression, and prognosis.

Radiotherapy of adult nodal non Hodgkin's lymphoma

International Nuclear Information System (INIS)

Gamen, G.; Thirion, P.

1999-01-01

The role of radiotherapy in the treatment of nodal non-Hodgkin's lymphoma has been modified by the introduction of efficient chemotherapy and the development of different pathological classifications. The recommended treatment of early-stage aggressive lymphomas is primarily a combination chemotherapy. The interest of adjuvant radiotherapy remains unclear and has to be established through large prospective trials. If radiation therapy has to be delivered, the historical results of exclusive radiation therapy showed that involved-fields and a dose of 35-40 Gy (daily fraction of 1.8 Gy, 5 days a week) are the optimal schedule. The interest of radiotherapy in the treatment of advanced-stage aggressive lymphoma is yet to be proven. Further studies had to stratify localized stages according to the factors of the International Prognostic Index. For easy-stage low-grade lymphoma, radiotherapy remains the standard treatment. However, the appropriate technique to use is controversial. Involved-field irradiation at a dose of 35 Gy seems to be the optimal schedule, providing a 10 year disease-free survival rate of 50 % and no major toxicity. There is no standard indication of radiotherapy in the treatment advanced-stage low-grade lymphoma. For 'new' nodal lymphoma's types, the indication of radiotherapy cannot be established (mantle-zone lymphoma, marginal zone B-cell lymphoma) or must take into account the natural history (Burkitt's lymphoma, peripheral T-cell lymphoma) and the sensibility to others therapeutic methods. (authors)

Ocular Adnexal Follicular Lymphoma

DEFF Research Database (Denmark)

Rasmussen, Peter K; Coupland, Sarah E; Finger, Paul T

2014-01-01

that involved 6 eye cancer centers from January 1, 1980, through December 31, 2010. A total of 105 patients with follicular OAL were identified, of which 7 patients were excluded because of missing clinical data. The median follow-up time was 52 months (range, 13-118 months). MAIN OUTCOMES AND MEASURES Overall...... in conjunction with a concurrent systemic lymphoma, and 10 (10%) presented with an ocular adnexal relapse. The lacrimal gland (28%), conjunctiva (28%), and orbit (28%) were the most frequently involved sites. Of the 69 patients with primary follicular lymphoma, 38 (55%) presented with Ann Arbor stage IE lymphoma...

EBV-positive B cell cerebral lymphoma 12 years after sex-mismatched kidney transplantation: post-transplant lymphoproliferative disorder or donor-derived lymphoma?

LENUS (Irish Health Repository)

Phelan, Paul J

2010-06-01

We present a follow-up case report of possible transmission of lymphoma 12 years after deceased-donor renal transplantation from a male donor who was found at autopsy to have had an occult lymphoma. The female recipient underwent prompt transplant nephrectomy. However, 12 years later, she presented with cerebral B cell lymphoma. A donor origin for the cerebral lymphoma was supported by in situ hybridization demonstration of a Y chromosome in the lymphoma. There was a dramatic resolution of the cerebral lesions with tapering of immunosuppression and introduction of rituximab treatment. The finding of a Y chromosome in the cerebral lymphoma does not exclude a host contribution to lymphoma development.

Modern radiation therapy for primary cutaneous lymphomas

DEFF Research Database (Denmark)

Specht, Lena; Dabaja, Bouthaina; Illidge, Tim

2015-01-01

Primary cutaneous lymphomas are a heterogeneous group of diseases. They often remain localized, and they generally have a more indolent course and a better prognosis than lymphomas in other locations. They are highly radiosensitive, and radiation therapy is an important part of the treatment......, either as the sole treatment or as part of a multimodality approach. Radiation therapy of primary cutaneous lymphomas requires the use of special techniques that form the focus of these guidelines. The International Lymphoma Radiation Oncology Group has developed these guidelines after multinational...... meetings and analysis of available evidence. The guidelines represent an agreed consensus view of the International Lymphoma Radiation Oncology Group steering committee on the use of radiation therapy in primary cutaneous lymphomas in the modern era....

Follicular non-Hodgkin's lymphoma

International Nuclear Information System (INIS)

Hayashi, D.; Lee, J.C.; Devenney-Cakir, B.; Zaim, S.; Ounadjela, S.; Solal-Celigny, P.; Juweid, M.; Guermazi, A.

2010-01-01

Follicular non-Hodgkin's lymphoma (NHL) is a unique subtype of NHL, which is indolent, incurable with a high prevalence of residual mass after treatment, and may transform to more aggressive NHL. The aim of this review is to (1) describe the histological and flow cytometry characteristics of follicular NHL; (2) introduce the Follicular Lymphoma International Prognostic Index 2 (FLIPI-2), which allows better treatment selection and patient stratification for clinical trials; (3) illustrate the classic and atypical ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET)/CT appearance of follicular NHL; and (4) characterize the appearance of nodal and extranodal follicular NHL with pathological correlation. Imaging is essential in every step of the management of patients with follicular lymphoma. Overall survival is improved with better predictive tools and new targeted biological therapies. Radiologists should be aware of possible active residual mass, indolent recurrence, transformation, and association with other primary cancers in patients treated for follicular lymphoma.

Treatment options for ocular adnexal lymphoma (OAL

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Victoria Mary Lendrum Cohen

2009-11-01

Full Text Available Victoria Mary Lendrum CohenSt. Bartholomew’s and Moorfields Eye Hospital, London UKAbstract: Most lymphomas that involve the ocular adnexal structure are low grade, B cell, non-Hodgkin’s lymphomas. The treatment depends upon the grade and stage of the disease. High grade lymhoma requires treatment with systemic chemotherapy whereas the localized low grade (extranodal marginal zone lymphoma can be successfully managed with local radiotherapy. Chlamydia psittaci infection is associated with low grade ocular lymphoma; however there is wide geographic variation in the strength of this association. Blanket antibiotic therapy is not advised unless there is proof of an infective agent. The monoclonal antibody, rituximab, may be successful for CD20 positive lymphoma, although it is likely that rituximab will have better long-term results when used in combination with systemic chemotherapy.Keywords: ocular adnexal lymphoma, mucosa associated lymphoid tissue, extranodal marginal zone lymphoma, Chlamydia psittaci, rituximab, radiotherapy, chemotherapy

Imaging of primary pediatric lymphoma of bone

International Nuclear Information System (INIS)

Milks, Kathryn S.; McLean, Thomas W.; Anthony, Evelyn Y.

2016-01-01

Primary pediatric bone lymphoma is a rare form of non-Hodgkin lymphoma. Unlike nodal forms of lymphoma, imaging abnormalities in lymphoma of bone do not resolve rapidly in conjunction with treatment and radiologic findings can remain abnormal for years, making it difficult to evaluate treatment response. To evaluate the utility of imaging in assessment of patients with primary pediatric bone lymphoma. At our institution between 2004 and 2013, six cases of pathology-proven primary pediatric bone lymphoma were diagnosed. Retrospective chart review was performed to assess imaging utilization. Our data were qualitatively compared with existing literature to construct an algorithm for imaging patients with primary lymphoma of bone. Imaging evaluation of patients with primary pediatric bone lymphoma was highly variable at our institution. Conventional imaging was routinely used to evaluate response to treatment, despite lack of appreciable osseous change. Imaging in the absence of symptoms did not alter clinical management. Only positron emission tomography CT (PET/CT) proved capable of demonstrating imaging changes from the pretreatment to the post-treatment scans that were consistent with the clinical response to treatment. Surveillance imaging is likely unnecessary in patients with a known diagnosis of pediatric lymphoma of bone. Pretreatment and post-treatment PET/CT is likely sufficient to assess response. There is little data to support the use of interim and surveillance PET/CT. (orig.)

PET CT and lymphomas

International Nuclear Information System (INIS)

Castro, R.

2012-01-01

This presentation is about Tc and lymphomas. Classification and clinical cases of various cancer such as gastro duodenal or ulcer, mama, medullary, lymph and neck, leukemia, nodular sclerosis. Metabolic information, anatomical nature of lymphoma and its clinical presentation determine the extent that PET should be used in the patient.

Radiological characteristics of AIDS- related lymphoma

International Nuclear Information System (INIS)

Ramos, Gloria Maria Martins G.; Marchiori, Edson

1996-01-01

The epidemic of acquired immunodeficiency syndrome (AIDS) increased the incidence of lymphoma, particularly the non-Hodgkin's lymphoma. The lymphoma in immune deficient patients is usually high-grade, very aggressive and with poor prognostic. We report the radiologic characteristics of AIDS-related lymphoma in 19 patients and correlate with the literature. The disease was predominant in homosexual male patients, with mean age of 38 years. The radiological characteristics are nonspecific to differential diagnosis, but we must suspect of lymphoma. We found ring-enhanced lesions in the radiologic studies of central nervous system. Hylar and mediastinal lymphadenopath, nodules and alveolar infiltration were detected on thoracic examinations. Abdominal examinations showed hepatosplenomegaly, lymphadenopathy, hepatic focal lesions and thickneded with distorted mucosa in the alimentary tract. Bone involvement presented as focal and disseminated destructive lesions. (author)

[Sonographically detectable splenic disorders in dogs with malignant lymphoma].

Science.gov (United States)

Eberhardt, F; Köhler, C; Krastel, D; Winter, K; Alef, M; Kiefer, I

2015-01-01

To evaluate the frequency of different sonographic splenic disorders in dogs with different anatomic forms of malignant lymphoma. Additionally, the occurrence of the moth-eaten pattern in the parenchyma of the spleen in patients with diseases other than lymphoma should be investigated. Retrospective analysis of patient data collected from dogs histologically or cytologically diagnosed with malignant lymphoma and for which ultrasonographic images were available before the initiation of therapy. Patient data from dogs with a moth-eaten pattern within the splenic parenchyma were evaluated separately. Exclusion criterion was the administration of cytostatic agents prior to diagnosis. In 84% of 164 dogs with malignant lymphoma, an altered pattern of the spleen was diagnosed ultrasonographically. Ninety-four of these 137 patients had a moth-eaten pattern of the splenic parenchyma and 43 dogs displayed abnormalities in the form of splenomegaly, coarse echotexture or other changes of the parenchyma. When a moth-eaten pattern was diagnosed, the affected dogs suffered significantly more often from a multicentric lymphoma (95%) than from any other anatomical lymphoma form. Only one dog displayed a moth-eaten pattern of the splenic parenchyma without diagnosis of a malignant lymphoma. The positive predictive value of the moth-eaten pattern for malignant lymphoma was 99% and, in particular, for the multicentric lymphoma this was 95%. In total, 84% of the 164 dogs displayed a multicentric lymphoma, 5% a mediastinal or a cutaneous lymphoma, respectively, 4% a gastrointestinal lymphoma, and one animal had an ocular or renal lymphoma, respectively. Sonographic changes of the spleen are often diagnosed in dogs with malignant lymphoma, independent of the anatomical lymphoma form. When the moth-eaten pattern is observed, it is very likely that the affected dog suffers from a malignant lymphoma, most probably a multicentric lymphoma.

Iodine I 131 Monoclonal Antibody BC8 Before Autologous Stem Cell Transplant in Treating Patients With Relapsed or Refractory Hodgkin Lymphoma or Non-Hodgkin Lymphoma

Science.gov (United States)

2017-11-15

Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma

The radiographic findings in diagnosis of pulmonary lymphoma

International Nuclear Information System (INIS)

Song Wei; Wang Li; Yan Hongzhen

2001-01-01

Objective: To study the radiographic findings in the diagnosis of pulmonary lymphoma and pseudo lymphoma. Methods: Eight patients with pulmonary lymphoma and 2 with pseudo lymphoma were examined by X-ray film, tomography, and CT. Results: Single or multiple nodules or masses were observed in 8 patients with pulmonary lymphoma, shaggy borders or halo of ground-glass attenuation in 7 patients, 2 patients had multiple patchy infiltrates bilaterally, 2 had diffuse interstitial infiltrates and 1 had miliary nodules. Multiple consolidations with air bronchogram and without hilar and mediastinal lymphadenopathy were observed in 2 patients with pulmonary pseudo lymphoma. Conclusion: Radiographic findings of pulmonary lymphoma were varied, the most common findings were the nodules or masses with shaggy borders or halo of ground-glass attenuation. The specific findings of pulmonary pseudo lymphoma were multiple consolidations with air bronchogram and without hilar and mediastinal lymphadenopathy. The final diagnosis relied on pathology

Cutaneous double-hit B-cell lymphoma: an aggressive form of B-cell lymphoma with a propensity for cutaneous dissemination.

Science.gov (United States)

Magro, Cynthia M; Wang, Xuan; Subramaniyam, Shivakumar; Darras, Natasha; Mathew, Susan

2014-04-01

Diffuse large cell B-cell lymphoma of the skin is most commonly represented by diffuse large cell variants of primary cutaneous follicle center cell lymphoma and the leg-type lymphoma. In a minority of cases, the infiltrates are an expression of stage 4 disease of established extracutaneous B-cell lymphoma. We describe 3 patients with an aggressive form of B-cell lymphoma secondarily involving the skin. Two of the patients were in the ninth decade of life, whereas 1 patient was 34 years of age. In the elderly patients, there was an antecedent and/or concurrent history of follicular lymphoma, whereas in the younger patient, the tumor was a de novo presentation of this aggressive form of lymphoma. The elderly patients succumbed to their disease within less than a year from the time of diagnosis, whereas 1 patient is alive but with persistent and progressive disease despite chemotherapeutic intervention. The infiltrates in all 3 cases were diffuse and composed of large malignant hematopoietic cells that exhibited a round nucleus with a finely dispersed chromatin. Phenotypically, the tumor cells were Bcl-2 and CD10 positive, whereas Bcl-6 and Mum-1 showed variable positivity. One case showed combined Mum-1 positivity along with an acute lymphoblastic lymphoma phenotype, including the absence of CD20 expression. In each case, there was a c-MYC and BCL2/IGH rearrangement diagnostic of double-hit lymphoma. In one case, there was an additional BCL6 rearrangement, defining what is in essence triple-hit lymphoma. In conclusion, double-hit lymphoma is an aggressive form of B-cell neoplasia resistant to standard chemotherapy regimens, which in many but not all cases represents tumor progression in the setting of a lower grade B-cell malignancy.

Precursor B lymphoblastic lymphoma of the orbit in a child: an unusual presentation of a non-Hodgkin lymphoma

NARCIS (Netherlands)

Faridpooya, K.; Mulder, M. M. S.; Merks, J. H. M.; de Smet, M. D.; Pals, S. T.; Saeed, P.

2006-01-01

OBJECTIVE: The majority of ocular adnexal lymphomas are marginal zone lymphomas, which occur rarely in children. This case report describes a 6 years old child with a precursor B lymphoblastic lymphoma presenting in the ocular adnexa. The combination of multi-agent chemotherapy with adjuvant

Unusual presentation of anaplastic thyroid carcinoma with diffuse neck and thoracic nodules and hyperthyroidism

Directory of Open Access Journals (Sweden)

Yun-Hsuan Lin

2017-06-01

Full Text Available Anaplastic thyroid carcinoma (ATC is a highly aggressive endocrine tumor that can be expected to have a poor clinical outcome. Cutaneous metastases from ATC are rare and in the context of disseminated metastases. Owing to the rarity of the disease, no standard treatment has been documented, and few treatment modalities are effective. This case reports neck and thoracic cutaneous metastasis from ATC, with concurrent hyperthyroidism.

Methylation patterns in marginal zone lymphoma.

Science.gov (United States)

Arribas, Alberto J; Bertoni, Francesco

Promoter DNA methylation is a major regulator of gene expression and transcription. The identification of methylation changes is important for understanding disease pathogenesis, for identifying prognostic markers and can drive novel therapeutic approaches. In this review we summarize the current knowledge regarding DNA methylation in MALT lymphoma, splenic marginal zone lymphoma, nodal marginal zone lymphoma. Despite important differences in the study design for different publications and the existence of a sole large and genome-wide methylation study for splenic marginal zone lymphoma, it is clear that DNA methylation plays an important role in marginal zone lymphomas, in which it contributes to the inactivation of tumor suppressors but also to the expression of genes sustaining tumor cell survival and proliferation. Existing preclinical data provide the rationale to target the methylation machinery in these disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Follicular lymphoma of the ocular adnexal region

DEFF Research Database (Denmark)

Rasmussen, Peter Kristian; Ralfkiaer, E.; Prause, J.U.

2015-01-01

Purpose To characterize the clinicopathological features of follicular lymphoma of the ocular adnexal region. Methods Retrospective nation-based study of Danish patients with ocular adnexal follicular lymphoma from January 1st 1980 through December 31st 2009. Results Twenty-four patients...... with ocular adnexal follicular lymphoma were identified. Fourteen (58%) of the patients were females. The median age was 63 years (range: 42–96 years). Eleven (46%) of the patients had primary ocular adnexal lymphoma, seven (29%) had an ocular adnexal lesion in conjunction with a concurrent systemic lymphoma...... and six patients (25%) presented with an ocular adnexal relapse. The most frequently affected sites were the lacrimal gland (38%) and the orbit (33%). Thirteen patients (54%) presented with Ann Arbor stage IE lymphoma, four (17%) had stage IIE, two patients (8%) stage IIIE, and five patients (21%) had...

P276-00, a cyclin-dependent kinase inhibitor, modulates cell cycle and induces apoptosis in vitro and in vivo in mantle cell lymphoma cell lines

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Shirsath Nitesh P

2012-10-01

Full Text Available Abstract Background Mantle cell lymphoma (MCL is a well-defined aggressive lymphoid neoplasm characterized by proliferation of mature B-lymphocytes that have a remarkable tendency to disseminate. This tumor is considered as one of the most aggressive lymphoid neoplasms with poor responses to conventional chemotherapy and relatively short survival. Since cyclin D1 and cell cycle control appears as a natural target, small-molecule inhibitors of cyclin-dependent kinases (Cdks and cyclins may play important role in the therapy of this disorder. We explored P276-00, a novel selective potent Cdk4-D1, Cdk1-B and Cdk9-T1 inhibitor discovered by us against MCL and elucidated its potential mechanism of action. Methods The cytotoxic effect of P276-00 in three human MCL cell lines was evaluated in vitro. The effect of P276-00 on the regulation of cell cycle, apoptosis and transcription was assessed, which are implied in the pathogenesis of MCL. Flow cytometry, western blot, immunoflourescence and siRNA studies were performed. The in vivo efficacy and effect on survival of P276-00 was evaluated in a Jeko-1 xenograft model developed in SCID mice. PK/PD analysis of tumors were performed using LC-MS and western blot analysis. Results P276-00 showed a potent cytotoxic effect against MCL cell lines. Mechanistic studies confirmed down regulation of cell cycle regulatory proteins with apoptosis. P276-00 causes time and dose dependent increase in the sub G1 population as early as from 24 h. Reverse transcription PCR studies provide evidence that P276-00 treatment down regulated transcription of antiapoptotic protein Mcl-1 which is a potential pathogenic protein for MCL. Most importantly, in vivo studies have revealed significant efficacy as a single agent with increased survival period compared to vehicle treated. Further, preliminary combination studies of P276-00 with doxorubicin and bortezomib showed in vitro synergism. Conclusion Our studies thus provide

Dosimetric comparison between helical tomotherapy and volumetric modulated arc-therapy for non-anaplastic thyroid cancer treatment.

Science.gov (United States)

Khalifa, Jonathan; Vieillevigne, Laure; Boyrie, Sabrina; Ouali, Monia; Filleron, Thomas; Rives, Michel; Laprie, Anne

2014-11-26

To evaluate and compare dosimetric parameters of volumetric modulated arctherapy (VMAT) and helical tomotherapy (HT) for non-anaplastic thyroid cancer adjuvant radiotherapy. Twelve patients with non-anaplastic thyroid cancer at high risk of local relapse received adjuvant external beam radiotherapy with curative intent in our institution, using a two-dose level prescription with a simultaneous integrated boost approach. Each patient was re-planned by the same physicist twice using both VMAT and HT. Several dosimetric quality indexes were used: target coverage index (proportion of the target volume covered by the reference isodose), healthy tissue conformity index (proportion of the reference isodose volume including the target volume), conformation number (combining both previous indexes), Dice Similarity Coefficient (DSC), and homogeneity index ((D2%-D98%)/prescribed dose). Dose-volume histogram statistics were also compared. HT provided statistically better target coverage index and homogeneity index for low risk PTV in comparison with VMAT (respectively 0.99 vs. 0.97 (p=0.008) and 0.22 vs. 0.25 (p=0.016)). However, HT provided poorer results for healthy tissue conformity index, conformation number and DSC with low risk and high risk PTV. As regards organs at risk sparing, by comparison with VMAT, HT statistically decreased the D2% to medullary canal (25.3 Gy vs. 32.6 Gy (p=0.003)). Besides, HT allowed a slight sparing dose for the controlateral parotid (Dmean: 4.3 Gy vs. 6.6 Gy (p=0.032)) and for the controlateral sub-maxillary gland (Dmean: 29.1 Gy vs. 33.1 Gy (p=0.041)). Both VMAT and HT techniques for adjuvant treatment of non-anaplastic thyroid cancer provide globally attractive treatment plans with slight dosimetric differences. However, helical tomotherapy clearly provides a benefit in term of medullary canal sparing.

Imaging Characteristics in ALK Fusion-Positive Lung Adenocarcinomas by Using HRCT

Science.gov (United States)

Okumura, Sakae; Kuroda, Hiroaki; Uehara, Hirofumi; Mun, Mingyon; Takeuchi, Kengo; Nakagawa, Ken

2014-01-01

Objectives: We aimed to identify high-resolution computed tomography (HRCT) features useful to distinguish the anaplastic lymphoma kinase gene (ALK) fusion-positive and negative lung adenocarcinomas. Methods: We included 236 surgically resected adenocarcinoma lesions, which included 27 consecutive ALK fusion-positive (AP) lesions, 115 epidermal growth factor receptor mutation-positive lesions, and 94 double-negative lesions. HRCT parameters including size, air bronchograms, pleural indentation, spiculation, and tumor disappearance rate (TDR) were compared. In addition, prevalence of small lesions (≤20 mm) and solid lesions (TDR ≤20%) were compared. Results: AP lesions were significantly smaller and had lower TDR (%) than ALK fusion-negative (AN) lesions (tumor diameter: 20.7 mm ± 14.1 mm vs. 27.4 mm ± 13.8 mm, respectively, p 20 mm (n = 7, 25.9%) showed a solid pattern. Among all small lesions, AP lesions had lower TDR and more frequent spiculation than AN lesions (p 20 mm lesions may be ALK fusion-negative. PMID:24899136

Effective treatment with icotinib in lung adenocarcinoma with EGFR and ALK co-alterations and brain metastasis

Directory of Open Access Journals (Sweden)

Ye CY

2016-10-01

Full Text Available Chenyang Ye,1,* Ji Wang,2,* Shu Zheng,1 Ying Chai3 1Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education, Provincial Key Laboratory of Molecular Biology in Medical Sciences, The Second Affiliated Hospital, Zhejiang University School of Medicine, 2Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, 3Department of Thoracic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China *These authors contributed equally to this work Abstract: We report a rare case of advanced lung cancer with epidermal growth factor receptor and anaplastic lymphoma kinase co-alterations and brain metastasis, in which icotinib treatment was effective for both the primary lung tumor and the brain metastasis. The patient achieved important clinical remission with a progression-free survival for two years. Our treatment strategy appears to be a promising therapeutic approach for this subgroup of patients. Keywords: lung cancer, brain metastasis, EGFR, ALK, icotinib

Molecular Profiling to Optimize Treatment in Non-Small Cell Lung Cancer: A Review of Potential Molecular Targets for Radiation Therapy by the Translational Research Program of the Radiation Therapy Oncology Group

International Nuclear Information System (INIS)

Ausborn, Natalie L.; Le, Quynh Thu; Bradley, Jeffrey D.; Choy, Hak; Dicker, Adam P.; Saha, Debabrata; Simko, Jeff; Story, Michael D.; Torossian, Artour; Lu, Bo

2012-01-01

Therapeutic decisions in non-small cell lung cancer (NSCLC) have been mainly based on disease stage, performance status, and co-morbidities, and rarely on histological or molecular classification. Rather than applying broad treatments to unselected patients that may result in survival increase of only weeks to months, research efforts should be, and are being, focused on identifying predictive markers for molecularly targeted therapy and determining genomic signatures that predict survival and response to specific therapies. The availability of such targeted biologics requires their use to be matched to tumors of corresponding molecular vulnerability for maximum efficacy. Molecular markers such as epidermal growth factor receptor (EGFR), K-ras, vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR), and anaplastic lymphoma kinase (ALK) represent potential parameters guide treatment decisions. Ultimately, identifying patients who will respond to specific therapies will allow optimal efficacy with minimal toxicity, which will result in more judicious and effective application of expensive targeted therapy as the new paradigm of personalized medicine develops.

Summary of presentations from the 46th Annual Meeting of the American Society of Clinical Oncology: focus on non-small cell lung cancer (2010).

Science.gov (United States)

Stinchcombe, Thomas E; Baggstrom, Maria Q; Somaiah, Neeta; Simon, George R; Govindan, Ramaswamy

2011-01-01

The promising results of crizotinib in molecularly selected patients with advanced non-small cell lung cancer (NSCLC) whose tumor cells had a novel fusion protein involving anaplastic lymphoma kinase presented at the 2010 American Society of Clinical Oncology reinforce once again the importance of understanding molecular heterogeneity of lung cancer and careful patient selection. Several other important issues were the subject of presentations related to lung cancer at the recently concluded American Society of Clinical Oncology annual meeting. The articles covered a wide variety of topics including optimal staging techniques to detect mediastinal nodal involvement, the role of platinum-based doublet chemotherapy in the management of elderly patients with advanced NSCLC, use of maintenance therapy with gemcitabine, and the impact of early introduction of organized palliative care in improving the quality of life of patients with advanced NSCLC. This report provides a brief overview of the presentations related to lung cancer that are relevant to clinical practice and future research.

Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

International Nuclear Information System (INIS)

Junor, E.J.; Paul, J.; Reed, N.S.

1992-01-01

Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author)

Anaplastic thyroid carcinoma: 91 patients treated by surgery and radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Junor, E.J.; Paul, J.; Reed, N.S. (Beatson Oncology Centre, Glasgow (United Kingdom))

1992-04-01

Ninety-one patients with histologically proven anaplastic carcinoma of the thyroid were referred to the Beatson Oncology Centre between 1961 and 1986. The female:male ratio was 2.4:1 and the median age at presentation was 70 (range 38-92) years. All patients had a thyroid mass at presentation and the most common symptoms were dyspnoea, dyspnagia and dysphonia. Five patients had a total thyroidectomy and 28 partial thyroidectomy. Ninety five per cent of patients received external beam radiotherapy. Results show dyspnoea to be the only symptom strongly influencing survival. Total or partial thyroidectomy is associated with increased survival. This association is most marked for patients presenting without dyspnoea. Eighty per cent of patients responded to radiotherapy. (Author).

Stages of Adult Hodgkin Lymphoma

Science.gov (United States)

... Lymphocyte-rich classical Hodgkin lymphoma. Age, gender, and Epstein-Barr infection can affect the risk of adult Hodgkin lymphoma. Anything that increases your risk of getting a disease is called a risk factor . Having a risk ...

Stages of Childhood Hodgkin Lymphoma

Science.gov (United States)

... Version Key Points Childhood Hodgkin lymphoma is a disease in which malignant (cancer) cells form in the lymph system. There are two types of childhood Hodgkin lymphoma. Epstein-Barr virus infection increases the risk of childhood Hodgkin ...

Primary periosteal lymphoma: an unusual presentation of non-Hodgkin's lymphoma with radiographic, MR imaging, and pathologic correlation

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Campbell, Scot E.; Beall, Douglas P.; Sanders, Timothy G. [Department of Radiology, Wilford Hall Medical Center, 759th MDTS/MTRD, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States); Filzen, Timothy W.; Parsons, Theodore W. [Department of Orthopedic Surgery, Wilford Hall Medical Center, 59th MDW/MCSO, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States); Bezzant, Shane M. [Department of Radiology, Brooke Army Medical Center, 3851 Roger Brooke Drive, Bldg 3600, Fort Sam Houston, TX 78234-6200 (United States); Burton, Mark P. [Department of Pathology, Wilford Hall Medical Center, 59th MDW/MTLP, 2200 Bergquist Drive, Suite 1, Lackland AFB, TX 78236-5300 (United States)

2003-04-01

This report describes a primary periosteal location of non-Hodgkin's lymphoma, without nodal disease, and without adjacent intramedullary disease at presentation. The clinical and imaging appearance of periosteal lymphoma simulates other neoplastic osseous surface tumors more than that of lymphoma in other locations. Consideration of this rare presentation of non-Hodgkin's lymphoma in the differential diagnosis of periosteal bone lesions can be helpful to ensure proper diagnosis and treatment. (orig.)

Mantle cell lymphoma of the larynx: Primary case report

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Naciri Sarah

2012-07-01

Full Text Available Abstract Introduction Primary laryngeal lymphomas are exceedingly rare. Only about a hundred cases have been reported. They consist mainly of non-Hodgkin lymphoma, especially of diffuse large B-cell lymphoma and mucosa-associated lymphoid tissue. We report the first case of a primary laryngeal mantle cell lymphoma. Case presentation We report a case of a primary mantle cell lymphoma of the larynx in a 70-year-old North African non-smoker male. We present a detailed report of his clinical and paraclinical data as well as treatment options. Conclusions Mantle cell lymphoma is a very aggressive lymphoma subset associated with poor prognosis. Laryngeal mantle cell lymphoma is exceedingly rare. To the best of our knowledge, this is the first case to ever be reported.

Primary Hepatosplenic Large B-Cell Lymphoma

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M.R. Morales-Polanco

2008-03-01

Full Text Available Diffuse large B-cell lymphoma is the most common form of lymphoma. It usually begins in the lymph nodes; up to 40% may have an extranodal presentation. According to a definition of primary extranodal lymphoma with presentation only in extranodal sites, there are reports of large B-cell lymphomas limited to liver or spleen as separate entities, and to date there have been only three documented cases of primary hepatosplenic presentation. This paper reports a fourth case. Due to a review of the literature and the clinical course of the case reported, we conclude that primary hepatosplenic large B-cell lymphoma has been found predominantly in females older than 60 years. The patients reported had <2 months of evolution prior to diagnosis, prominent B symptoms, splenomegaly in three and hepatomegaly in two, none with lymph node involvement. All had thrombocytopenia and abnormal liver function tests; three had anemia and elevated serum lactic dehydrogenase levels, two with hemophagocytosis in bone marrow. Because of the previously mentioned data, it can be stated that primary hepatosplenic lymphoma is an uncommon and aggressive form of disease that requires immediate recognition and treatment.

A comparative evaluation of supervised and unsupervised representation learning approaches for anaplastic medulloblastoma differentiation

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Cruz-Roa, Angel; Arevalo, John; Basavanhally, Ajay; Madabhushi, Anant; González, Fabio

2015-01-01

Learning data representations directly from the data itself is an approach that has shown great success in different pattern recognition problems, outperforming state-of-the-art feature extraction schemes for different tasks in computer vision, speech recognition and natural language processing. Representation learning applies unsupervised and supervised machine learning methods to large amounts of data to find building-blocks that better represent the information in it. Digitized histopathology images represents a very good testbed for representation learning since it involves large amounts of high complex, visual data. This paper presents a comparative evaluation of different supervised and unsupervised representation learning architectures to specifically address open questions on what type of learning architectures (deep or shallow), type of learning (unsupervised or supervised) is optimal. In this paper we limit ourselves to addressing these questions in the context of distinguishing between anaplastic and non-anaplastic medulloblastomas from routine haematoxylin and eosin stained images. The unsupervised approaches evaluated were sparse autoencoders and topographic reconstruct independent component analysis, and the supervised approach was convolutional neural networks. Experimental results show that shallow architectures with more neurons are better than deeper architectures without taking into account local space invariances and that topographic constraints provide useful invariant features in scale and rotations for efficient tumor differentiation.

Dynamic mathematical modeling of IL13-induced signaling in Hodgkin and primary mediastinal B-cell lymphoma allows prediction of therapeutic targets.

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Raia, Valentina; Schilling, Marcel; Böhm, Martin; Hahn, Bettina; Kowarsch, Andreas; Raue, Andreas; Sticht, Carsten; Bohl, Sebastian; Saile, Maria; Möller, Peter; Gretz, Norbert; Timmer, Jens; Theis, Fabian; Lehmann, Wolf-Dieter; Lichter, Peter; Klingmüller, Ursula

2011-02-01

Primary mediastinal B-cell lymphoma (PMBL) and classical Hodgkin lymphoma (cHL) share a frequent constitutive activation of JAK (Janus kinase)/STAT signaling pathway. Because of complex, nonlinear relations within the pathway, key dynamic properties remained to be identified to predict possible strategies for intervention. We report the development of dynamic pathway models based on quantitative data collected on signaling components of JAK/STAT pathway in two lymphoma-derived cell lines, MedB-1 and L1236, representative of PMBL and cHL, respectively. We show that the amounts of STAT5 and STAT6 are higher whereas those of SHP1 are lower in the two lymphoma cell lines than in normal B cells. Distinctively, L1236 cells harbor more JAK2 and less SHP1 molecules per cell than MedB-1 or control cells. In both lymphoma cell lines, we observe interleukin-13 (IL13)-induced activation of IL4 receptor α, JAK2, and STAT5, but not of STAT6. Genome-wide, 11 early and 16 sustained genes are upregulated by IL13 in both lymphoma cell lines. Specifically, the known STAT-inducible negative regulators CISH and SOCS3 are upregulated within 2 hours in MedB-1 but not in L1236 cells. On the basis of this detailed quantitative information, we established two mathematical models, MedB-1 and L1236 model, able to describe the respective experimental data. Most of the model parameters are identifiable and therefore the models are predictive. Sensitivity analysis of the model identifies six possible therapeutic targets able to reduce gene expression levels in L1236 cells and three in MedB-1. We experimentally confirm reduction in target gene expression in response to inhibition of STAT5 phosphorylation, thereby validating one of the predicted targets.

Primary malignant intramedullary lymphoma

International Nuclear Information System (INIS)

Orrego P, E.; Heinicke Y, H.; Arbaiza A, D.; Yepez R, V.

1999-01-01

A case of primary malignant intramedullary lymphoma, localized in the dorsal part of the spinal cord is presented. The clinical symptoms were associated with motor and sensitive deficit. Clinical investigations excluded the presence of lymphoma in other locations in the central nervous system and the extra neural organs. Postoperative radiotherapy and chemotherapy improved relict neurological symptoms. (authors)

Among B cell non-Hodgkin's lymphomas, MALT lymphomas express a unique antibody repertoire with frequent rheumatoid factor reactivity

NARCIS (Netherlands)

Bende, Richard J.; Aarts, Wilhelmina M.; Riedl, Robert G.; de Jong, Daphne; Pals, Steven T.; van Noesel, Carel J. M.

2005-01-01

We analyzed the structure of antigen receptors of a comprehensive panel of mature B nonHodgkin's lymphomas (B-NHLs) by comparing, at the amino acid level, their immunoglobulin (Ig)V-H-CDR3s with CDR3 sequences present in GenBank. Follicular lymphomas, diffuse large B cell lymphomas, Burkitt's

A critical appraisal of ibrutinib in the treatment of mantle cell lymphoma and chronic lymphocytic leukemia

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Tucker DL

2015-06-01

Full Text Available David L Tucker, Simon A Rule Department of Haematology, Plymouth Hospitals NHS Trust, Plymouth, UK Abstract: Although chemo-immunotherapy remains at the forefront of first-line treatment for mantle cell lymphoma (MCL and chronic lymphocytic leukemia (CLL, small molecules, such as ibrutinib, are beginning to play a significant role, particularly in patients with multiply relapsed or chemotherapy-refractory disease and where toxicity is an overriding concern. Ibrutinib is a first-in-class, oral inhibitor of Bruton’s tyrosine kinase, which functions by irreversible inhibition of the downstream signaling pathway of the B-cell receptor, which normally promotes cell survival and proliferation. Early clinical trials have demonstrated excellent tolerability and a modest side-effect profile even in elderly and multiply pretreated patient cohorts. Although the majority of disease responses tend to be partial, efficacy data have also been encouraging with more than two-thirds of patients with CLL and MCL demonstrating a durable response, even in the high-risk disease setting. Resistance mechanisms are only partially understood and appear to be multifactorial, including the binding site mutation C481S, and escape through other common cell-signaling pathways. This article appraises the currently available data on safety and efficacy from clinical trials of ibrutinib in the management of MCL and CLL, both as a single agent and in combination with other therapies, and considers how this drug is likely to be used in future clinical practice. Keywords: ibrutinib, mantle cell lymphoma, chronic lymphocytic leukemia, Bruton’s tyrosine kinase, lymphoproliferative disorders

Hodgkin's Lymphoma of the Breast

African Journals Online (AJOL)

TNHJOURNALPH

RESULT. A tissue diagnosis of Hodgkin's lymphoma with typical ... It was the first cancer to be cured ... ultrasonography showed enlarged liver. The .... McMillan A, Horning S. Non-Hodgkins lymphoma of the Breast. Cancer. 2007;110:25-30. 5.

Genotoxic effects of synthetic amorphous silica nanoparticles in the mouse lymphoma assay

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Eşref Demir

Full Text Available Synthetic amorphous silica nanoparticles (SAS NPs have been used in various industries, such as plastics, glass, paints, electronics, synthetic rubber, in pharmaceutical drug tablets, and a as food additive in many processed foods. There are few studies in the literature on NPs using gene mutation approaches in mammalian cells, which represents an important gap for genotoxic risk estimations. To fill this gap, the mouse lymphoma L5178Y/Tk+/− assay (MLA was used to evaluate the mutagenic effect for five different concentrations (from 0.01 to 150 μg/mL of two different sizes of SAS NPs (7.172 and 7.652 nm and a fine collodial form of silicon dioxide (SiO2. This assay detects a broad spectrum of mutational events, from point mutations to chromosome alterations. The results obtained indicate that the two selected SAS NPs are mutagenic in the MLA assay, showing a concentration-dependent effect. The relative mutagenic potencies according to the induced mutant frequency (IMF are as follows: SAS NPs (7.172 nm (IMF = 705.5 × 10−6, SAS NPs (7.652 nm (IMF = 575.5 × 10−6, and SiO2 (IMF = 57.5 × 10−6. These in vitro results, obtained from mouse lymphoma cells, support the genotoxic potential of NPs as well as focus the discussion of the benefits/risks associated with their use in different areas. Keywords: Synthetic amorphous silica nanoparticles, Mouse lymphoma assay, Mutagenic agents, Thymidine kinase (Tk gene, In vitro mutagenicity

Appendiceal and ovarian Burkitt's lymphoma presenting as acute appendicitis

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Donovan Hui

2018-05-01

Full Text Available Burkitt's lymphoma is an extremely aggressive B-cell non-Hodgkin lymphoma. Patients with the sporadic form of Burkitt's lymphoma typically present with a rapidly growing abdominal mass, pain and distension. Involvement of either the appendix and/or ovaries in females is a rare manifestation of the disease. We present an unusual case of a 13 year old girl with appendiceal and ovarian Burkitt's lymphoma presenting with signs of acute appendicitis. This case demonstrates the potential for secondary involvement of the appendix and/or ovaries from Burkitt's lymphoma as well as the importance of the histopathology. Keywords: Appendicitis, Appendix, Burkitt's lymphoma, Lymphoma, Ovarian tumor

Clinical, immunophenotypic, and genetic analysis of adult lymphomas with morphologic features of Burkitt lymphoma

NARCIS (Netherlands)

Haralambieva, E; Boerma, EJ; van Imhoff, GW; Rosati, S; Schuuring, E; Muller-Hermelink, HK; Kluin, PM; Ott, G

A prompt distinction of Burkitt lymphoma (BL) versus diffuse large B cell lymphomas (DLBCL) has important clinical implications; however, this distinction can be difficult. We analyzed 74 adult gray zone and 10 reference pediatric BL using immunohistochemistry (Ki-67, CD10, bcl2, bcl6) and

A Rare Case of Composite Dural Extranodal Marginal Zone Lymphoma and Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

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Mark Bustoros

2018-04-01

Full Text Available BackgroundPrimary extranodal marginal zone lymphoma (MZL of the dura is a rare neoplastic entity in the central nervous system (CNS.MethodsWe used literature searches to identify previously reported cases of primary dural MZL. We also reviewed clinical, pathologic, and radiographic data of an adult patient with concurrent dural MZL and chronic lymphocytic leukemia (CLL/small lymphocytic lymphoma (SLL.ResultsWe identified 104 cases of dural MZL in the literature. None of them presented concurrently with another type of non-Hodgkin lymphoma. This is the first report of composite lymphoma consisting of dural MZL and CLL/SLL in the bone marrow and lymph nodes.ConclusionPrimary dural MZL is a rare, indolent low-grade CNS lymphoma, with a relatively good prognosis. Its treatment is multidisciplinary and often requires surgical intervention due to brain compression, along with low to moderate doses of radiotherapy and/or systemic chemotherapy.

Dabrafenib and Trametinib Treatment in Patients With Locally Advanced or Metastatic BRAF V600-Mutant Anaplastic Thyroid Cancer

NARCIS (Netherlands)

Subbiah, Vivek; Kreitman, Robert J; Wainberg, Zev A; Cho, Jae Yong; Schellens, Jan H M; Soria, Jean Charles; Wen, Patrick Y; Zielinski, Christoph; Cabanillas, Maria E; Urbanowitz, Gladys; Mookerjee, Bijoyesh; Wang, Dazhe; Rangwala, Fatima; Keam, Bhumsuk

2018-01-01

Purpose We report the efficacy and safety of dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) combination therapy in BRAF V600E-mutated anaplastic thyroid cancer, a rare, aggressive, and highly lethal malignancy with poor patient outcomes and no systemic therapies with clinical benefit.

Prognostic Assessment in Patients with Indolent B-Cell Lymphomas

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Luca Arcaini

2012-01-01

Full Text Available Follicular lymphoma (FL is an indolent lymphoma with long median survival. Many studies have been performed to build up prognostic scores potentially useful to identify patients with poorer outcome. In 2004, an international consortium coordinated by the International Follicular Lymphoma Prognostic Factor project was established and a new prognostic study was launched (FLIPI2 using progression-free survival (PFS as main endpoint and integrating all the modern parameters prospectively collected. Low-grade non-Hodgkin lymphomas were once considered as a heterogenous group of lymphomas characterized by an indolent clinical course. Each entity is characterized by unique clinicobiologic features. Some studies have been focused on prognostic factors in single lymphoma subtypes, with the development of specific-entity scores based on retrospective series, for instance splenic marginal zone lymphoma (SMZL. A widely accepted prognostic tool for clinical usage for indolent non-follicular B-cell lymphomas is largely awaited. In this paper we summarized the current evidence regarding prognostic assessment of indolent follicular and non-follicular lymphomas.

Lymphoma risk in systemic lupus

DEFF Research Database (Denmark)

Bernatsky, Sasha; Ramsey-Goldman, Rosalind; Joseph, Lawrence

2014-01-01

OBJECTIVE: To examine disease activity versus treatment as lymphoma risk factors in systemic lupus erythematosus (SLE). METHODS: We performed case-cohort analyses within a multisite SLE cohort. Cancers were ascertained by regional registry linkages. Adjusted HRs for lymphoma were generated...

MYC/BCL2/BCL6 triple hit lymphoma: a study of 40 patients with a comparison to MYC/BCL2 and MYC/BCL6 double hit lymphomas.

Science.gov (United States)

Huang, Wenting; Medeiros, L Jeffrey; Lin, Pei; Wang, Wei; Tang, Guilin; Khoury, Joseph; Konoplev, Sergej; Yin, C Cameron; Xu, Jie; Oki, Yasuhiro; Li, Shaoying

2018-05-21

High-grade B-cell lymphomas with MYC, BCL2, and BCL6 rearrangements (triple hit lymphoma) are uncommon. We studied the clinicopathologic features of 40 patients with triple hit lymphoma and compared them to 157 patients with MYC/BCL2 double hit lymphoma and 13 patients with MYC/BCL6 double hit lymphoma. The triple hit lymphoma group included 25 men and 15 women with a median age of 61 years (range, 34-85). Nine patients had a history of B-cell lymphoma. Histologically, 23 (58%) cases were diffuse large B-cell lymphoma and 17 cases had features of B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Most cases of triple hit lymphoma were positive for CD10 (100%), BCL2 (95%), BCL6 (82%), MYC (74%), and 71% with MYC and BCL2 coexpression. P53 was overexpressed in 29% of triple hit lymphoma cases. The clinicopathological features of triple hit lymphoma patients were similar to patients with MYC/BCL2 and MYC/BCL6 double hit lymphoma, except that triple hit lymphoma cases were more often CD10 positive compared with MYC/BCL6 double hit lymphoma (p hit lymphoma and double hit lymphoma and overall survival in triple hit lymphoma patients was 17.6 months, similar to the overall survival of patients with double hit lymphoma (p = 0.67). Patients with triple hit lymphoma showing P53 overexpression had significantly worse overall survival compared with those without P53 overexpression (p = 0.04). On the other hand, double expressor status and prior history of B-cell lymphoma did not correlate with overall survival. In conclusion, most patients with triple hit lymphoma have an aggressive clinical course and poor prognosis and these tumors have a germinal center B-cell immunophenotype, similar to patients with double hit lymphomas. P53 expression is a poor prognostic factor in patients with triple hit lymphoma.

V-cbl, an oncogene from a dual-recombinant murine retrovirus that induces early B-lineage lymphomas

International Nuclear Information System (INIS)

Langdon, W.Y.; Klinken, S.P.; Hartley, J.W.; Morse, H.C. III; Ruscetti, S.K.

1989-01-01

Cas NS-1 is an acutely transforming murine retrovirus that induces pre-B and pro-B cell lymphomas. Molecular cloning showed it was generated from the ecotropic Cas-Br-M virus by sequential recombinations with endogenous retroviral sequences and a cellular oncogene. The oncogene sequence shows no homology with known oncogenes but some similarity to the yeast transcriptional activator GCN4. A 100-kDa gag-cbl fusion protein, with no detectable kinase activity, is responsible for the cellular transformation. The cellular homologue of v-cbl, present in mouse and human DNA, is expressed in a range of hemopoietic lineages

Breed prevalence of canine lymphoma in South Africa

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Liesl J. Van Rooyen

2018-03-01

Full Text Available Lymphoma is a common haematopoietic neoplasm in dogs. Several breeds have been shown to have a predisposition to lymphoma; however, very little information exists regarding the South African dog population. This study assessed whether any breed had increased odds of developing lymphoma compared with others, and also investigated the effects of age, sex and neutering status on disease prevalence. Two study populations and their corresponding reference populations were studied retrospectively. Odds ratios (ORs for lymphoma in 49 dog breeds, together with their 95% confidence intervals (CI, were calculated. Age effect was assessed by calculating ORs for different age categories in one of the populations. The chi-square test was used to evaluate differences in the prevalence of the various sex and neutering categories in one lymphoma population compared with its reference population. Fourteen breeds had significantly increased odds of developing lymphoma, and one breed had significantly decreased odds (p < 0.050. The median ages of the two lymphoma populations were 6.5 and 8.0 years, with the 6.1–9.0 year category having significantly increased odds of developing lymphoma (OR 1.61, CI 1.2–2.16, p = 0.002. In one of the lymphoma populations, higher proportions of males (p = 0.033 and neutered females (p = 0.006 were found when compared with the reference population. These findings suggest that certain breeds in South Africa have a higher risk of developing lymphoma, and that sex hormones may play a role in lymphoma pathogenesis. The findings may provide useful information for pet owners and veterinarians.

Concomitant Classic Hodgkin Lymphoma of Lymph Node and cMYC-Positive Burkitt Leukemia/Lymphoma of the Bone Marrow Presented Concurrently at the Time of Presentation: A Rare Combination of Discordant Lymphomas

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Dina S. Soliman

2016-01-01

Full Text Available Discordant lymphoma is rare condition in which different types of malignant lymphomas occurring in different anatomic sites. The two diseases may present clinically as concurrent or sequential disease (10. Herein we are reporting a Pakistani female in her 60s, a carrier of hepatitis B virus with multiple comorbidities presented with cervical lymphadenopathy, diagnosed as Hodgkin's lymphoma, mixed cellularity. During the staging workup, the patient was discovered to have extensive bone marrow (BM involvement by Burkitt leukaemia/lymphoma (BL. Cytogenetic analysis revealed positivity for t(8;14(q24;q32 confirmed by Fluorescence In Situ Hybridization (FISH for IGH/MYC. Epstein-Barr virus (EBV was demonstrated heavily in our case, with (EBV DNA of 24,295,560 copies/ml by PCR at time of presentation, in addition, the neoplastic cells in both diagnostic tissues (cervical lymph node and BM demonstrated positivity for EBV. A diagnosis of concomitant EBV related discordant lymphoma (classical Hodgkin lymphoma (cHL and Burkitt lymphoma (BL in leukemic phase was made. Among all reported cases, this case is highly exceptional because it is the first case of discordant/composite lymphoma, with this combination and concomitant presentation. Since we are dealing with a case with an exceptionally rare combination, we found it significant to elaborate more on its clinical features, contributing factors including EBV role, response to treatment, complications, and prognosis.

J chain and myocyte enhancer factor 2B are useful in differentiating classical Hodgkin lymphoma from nodular lymphocyte predominant Hodgkin lymphoma and primary mediastinal large B-cell lymphoma.

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Moore, Erika M; Swerdlow, Steven H; Gibson, Sarah E

2017-10-01

Although most classical Hodgkin lymphomas (CHLs) are easily distinguished from nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal large B-cell lymphoma (PMBL), cases with significant CD20 expression cause diagnostic confusion. Although the absence of OCT-2 and BOB.1 are useful in these circumstances, a variable proportion of CHLs are positive for these antigens. We investigated the utility of J chain and myocyte enhancer factor 2B (MEF2B) in the diagnosis of CHL; NLPHL; PMBL; T-cell/histiocyte-rich large B-cell lymphoma (TCRLBL); and B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, compared with OCT-2 and BOB.1. J chain and MEF2B highlighted lymphocyte predominant (LP) cells in 20/20 (100%) NLPHLs and were negative in 43/43 (100%) CHLs. Fourteen of 15 (93%) PMBLs and 4/4 (100%) TCRLBLs were MEF2B positive, whereas 67% of PMBLs and 50% of TCRLBLs were J chain positive. Three of 3 B-cell lymphomas, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and CHL, were negative for J chain and MEF2B. J chain and MEF2B were 100% sensitive and specific for NLPHL versus CHL. MEF2B was 100% sensitive and 98% specific for PMBL versus CHL. Whereas loss of OCT-2 and/or BOB.1 expression had a sensitivity of only 86% and specificity of 100% for CHL versus NLPHL, PMBL, and TCRLBL, lack of both J chain and MEF2B expression was 100% sensitive and 97% specific. J chain and MEF2B are highly sensitive and specific markers of NLPHL versus CHL; are particularly useful in highlighting LP cells; and, with rare exception, are of greater utility than OCT-2 and BOB.1 in differentiating CHL from NLPHL and other large B-cell lymphomas. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathology of nodal marginal zone lymphomas.

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Pileri, Stefano; Ponzoni, Maurilio

Nodal marginal zone B cell lymphomas (NMZLs) are a rare group of lymphoid disorders part of the spectrum of marginal zone B-cell lymphomas, which encompass splenic marginal one B-cell lymphoma (SMZL) and extra nodal marginal zone of B-cell lymphoma (EMZL), often of MALT-type. Two clinicopathological forms of NMZL are recognized: adult-type and pediatric-type, respectively. NMZLs show overlapping features with other types of MZ, but distinctive features as well. In this review, we will focus on the salient distinguishing features of NMZL mostly under morphological/immunophenotypical/molecular perspectives in views of the recent acquisitions and forthcoming updated 2016 WHO classification of lymphoid malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Geldanamycin Analogue in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma