Diffuse Large B-Cell Breast Lymphoma: A Case Series.
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ABSTRACT:
SUBMITTER: Al Battah AH
PROVIDER: S-EPMC5560510 | biostudies-other | 2017
REPOSITORIES: biostudies-other
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Project description:Primary breast lymphoma is a rare form of extra-nodal lymphoid neoplasm. The most common histological type is the diffuse large B-cell lymphoma, which represents 60-80% of all the cases. Our study analyzes the mutational profile of the primary lymphoma of the breast through targeted massive sequencing with a panel of 38 genes in a group of 17 patients with primary breast diffuse large B-cell lymphoma. Seventy-point-five percent of the patients presented with stage IE and 29.5% with stage IIE. 44% of the cases correspond to lymphomas with germinal center phenotype and 33.3% to activated B-cell. The genes with a higher mutational frequency include PIM1 (in 50% of the analyzed samples), MYD88 (39%), CD79B, PRDM1 and CARD11 (17%), KMT2D, TNFIAP3 and CREBBP (11%). The profile of mutant genes involves mostly the NF?B signaling pathway. The high frequency of mutations in PIM1 compared with other lymphomas may have implications in the clinical presentation and evolution of this type of lymphoma.
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Project description:BackgroundPrimary cardiac lymphoma (PCL) is rare and can present with a wide variety of clinical symptoms, frequently leading to a delay in diagnosis.Case summaryWe report a case of a PCL in an 81-year-old man. Cardiac magnetic resonance imaging showed multiple masses in the right atrium and a mass in the right ventricular outflow tract extending to the pulmonary artery. Biopsy revealed a diffuse large B-cell lymphoma. The patient also had metastases to the liver and lung on the positron emission tomography-computed tomography (PET-CT) scan. He was treated with R-CHOP chemotherapy, with complete remission documented PET-CT scans.ConclusionAlthough most patients with PCL die before chemotherapy can be initiated, a timely diagnosis can result in a favourable outcome.
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Project description:DNA damage is one of the mechanisms of mutagenesis. Sequence integrity may be affected by the action of thermal changes, chemical agents, both endogenous and exogenous, and other environmental issues. Abnormally high mutation rates are referred to as genomic instability: a phenomenon closely related to the onset of cancer. Mutant genotypes may be able to confer some kind of selective advantage on subclonal cell populations, leading them to multiply until dominance in a localized tissue environment that later becomes the tumour. Cellular stress, especially that of oxidative and ionic nature, is a recognized trigger for DNA-damaging processes. A physico-chemical model has shown that high hysteresis rates in DNA denaturation curves may be indicative of dissipative processes inducing DNA damage, thus potentially leading to uncontrolled mutagenesis and genome instability. We here study selectively to what extent this phenomenon may occur by analysing the sequence length and composition effects on the thermodynamic behaviour and the presence of hysteresis in pressure-driven DNA denaturation; pronounced hysteresis in the denaturation/renaturation curves may indicate thermal susceptibility to DNA damage. In particular, we consider highly mutated regions of the genome characterized in diffuse large B-cell lymphoma on a recent whole exome next-generation sequencing effort.
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Project description:IntroductionIn diffuse large B-cell lymphoma, first-line treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone; salvage with cisplatin-based regimens for relapsing patients; and autologous stem cell therapy are standards of care. Treatment approaches are less clear for patients who are refractory or who are not candidates for autologous stem cell therapy. Options may include palliative regimens or clinical trial enrollment. One therapy under investigation in diffuse large B-cell lymphoma is lenalidomide, an immunomodulatory agent with antiangiogenic activity.Case presentationWe present the case of a 55-year-old Caucasian male patient diagnosed with diffuse large B-cell lymphoma who had an early relapse after treatment with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. He then had a subsequent early relapse after cisplatin-based salvage consolidated with autologous stem cell therapy. The efficacy of gemcitabine-cisplatin-rituximab was limited to five months, followed by systemic and central nervous system progression. Fourth-line treatment with lenalidomide plus rituximab and involved-field radiotherapy followed by lenalidomide monotherapy greatly improved this patient's quality of life and performance status, allowing over two years of progression-free survival to date (excluding a brief relapse due to treatment interruption).ConclusionA lenalidomide-based regimen was highly effective in this patient with diffuse large B-cell lymphoma.
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Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11
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Project description:Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history reflects unrecognized molecular heterogeneity in the tumors. Using DNA microarrays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expression among the tumors of DLBCL patients, apparently reflecting the variation in tumor proliferation rate, host response and differentiation state of the tumor. We identified two molecularly distinct forms of DLBCL which had gene expression patterns indicative of different stages of B-cell differentiation. One type expressed genes characteristic of germinal center B cells ('germinal center B-like DLBCL'); the second type expressed genes normally induced during in vitro activation of peripheral blood B cells ('activated B-like DLBCL'). Patients with germinal center B-like DLBCL had a significantly better overall survival than those with activated B-like DLBCL. The molecular classification of tumors on the basis of gene expression can thus identify previously undetected and clinically significant subtypes of cancer. This study is described more fully in Alizadeh AA et al.(2000) Nature 403:503-11 Keywords: other
2002-06-27 | GSE60 | GEO
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