Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of<i>de novo</i>diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

doi:10.18632/oncotarget.16532

Cited by 30 publications

(26 citation statements)

References 41 publications

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“…This is a key factor in uncontrolled tumor growth and poor clinical outcome in many solid tumors 64 . Several clinical studies have also described the presence of T-cell markers (including CD3, CD4, CD8) in diffuse large B-cell lymphoma (DLBCL), but the prognostic significance of this is not clear 65 . Our data are highly suggestive that the active immune response plays a key role in augmenting tumorigenesis in EμMyc/Casp2 −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

et al. 2019

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Caspase-2 is a highly conserved cysteine protease with roles in apoptosis and tumor suppression. Our recent findings have also demonstrated that the tumor suppression function of caspase-2 is context specific. In particular, while caspase-2 deficiency augments lymphoma development in the EμMyc mouse model, it leads to delayed neuroblastoma development in Th-MYCN mice. However, it is unclear how caspase-2 mediates these differential outcomes. Here we utilized RNA sequencing to define the transcriptomic changes caused by caspase-2 (Casp2−/−) deficiency in tumors from EμMyc and Th-MYCN mice. We describe key changes in both lymphoma and neuroblastoma-associated genes and identified differential expression of the EGF-like domain-containing gene, Megf6, in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2−/− tumors that are strongly associated with neuroblastoma outcome, with roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In contrast, we found that key changes in gene expression in the EμMyc/Casp2−/− tumors, are associated with increased immune signaling and T-cell infiltration previously associated with more aggressive lymphoma progression. In addition, Rap1 signaling pathway was uniquely enriched in Casp2 deficient EμMyc tumors. Our findings suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues.

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Section: Discussionmentioning

confidence: 99%

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

et al. 2019

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“…CD3 expression is very rare in B-cell lymphomas other than plasmablastic and pyothorax-associated lymphomas and more frequent in immunocompromised patients. 10 We routinely include 2 T-cell lineage markers (CD3 and CD5) in our lymphoma workup. The lack of CD5 expression in this case raised a concern for T-cell lymphoma and prompted further workup.…”

Section: Discussionmentioning

confidence: 99%

Primary Central Nervous System T-Cell Lymphoma With Aberrant Expression of CD20 and CD79a: A Diagnostic Pitfall

et al. 2017

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Primary central nervous system T-cell lymphoma (PCNSTCL) is rare, accounting for 2% of CNS lymphomas. We report the first case of PCNSTCL with aberrant expression of CD20 and CD79a in an 81-year-old man with a left periventricular brain mass. A biopsy revealed dense lymphoid infiltrate consisting of medium-sized cells in a background of gliosis and many histiocytes. The lymphoid cells were positive for CD2, CD3, CD7, CD8, T-cell intracellular antigen-1, granzyme B, CD20, and CD79a and negative for CD4, CD5, PAX-5, OCT-2, BOB-1, human herpes virus-8, and Epstein-Barr virus-encoded small RNAs. Molecular studies revealed clonal TCR-β and TCR-γ gene rearrangements and negative immunoglobulin gene rearrangements. The patient was treated with chemotherapy (vincristine and methotrexate) and rituximab, but he died 1 month after the diagnosis. This is a unique case that emphasizes the use of a multimodal approach, including a broad immunohistochemical panel and molecular studies in lineage determination for lymphomas with ambiguous phenotype.

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“…Therefore, it is important to consider this diagnosis in the appropriate settings because patients may achieve durable remission with early diagnosis and rituximab-containing chemotherapy, which has improved the outcome of IVLBCL therapy. 8 - 10 …”

Section: Discussionmentioning

confidence: 99%

Intravascular large B-cell lymphoma with multi-organ failure presenting as a pancreatic mass: a case with atypical presentation and definite diagnosis postmortem

2017

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Intravascular large B-cell lymphoma (IVLBCL) is a very rare extra nodal lymphoma that tends to proliferate within small blood vessels, particularly capillaries and postcapillary venules while sparing the organ parenchyma. The cause of its affinity for the vascular bed remains unknown. Because of its rarity and unremarkable clinical presentation, a timely diagnosis of IVLBCL is very challenging. Here, we describe a case of IVLBCL presenting as pancreatic mass that was ultimately diagnosed at autopsy. A 71-year-old Caucasian female presented with a 3-month history of fatigue, abdominal pain, and weight loss. She was referred to the emergency room with a new diagnosis of portal vein thrombosis and lactic acidosis. During her hospital course she was found to have a 1.9 × 1.8 cm lesion in the pancreatic tail on imaging; The cytologic specimen on the mass showed a high-grade lymphoma. A bone marrow biopsy showed no involvement. The patient’s condition rapidly deteriorated and she, later, died due to multi-organ failure. An autopsy revealed diffuse intravascular invasion in multiple organs by the lymphoma cells. Based on our literature review—and to the best of our knowledge—there are virtually no reports describing the presentation of this lymphoma with a discernible tissue mass and associated multi-organ failure. The immunophenotypic studies performed revealed de novo CD5+ intravascular large B-cell lymphoma, which is known to be aggressive with very poor prognosis. Although it is a very rare lymphoma, it should be considered as a potential cause of multi-organ failure when no other cause has been identified. A prompt tissue diagnosis, appropriate high-dose chemotherapy and stem cell transplantation remain the only viable alternative to achieve some kind of remission.

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Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases ofde novodiffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas

Cited by 30 publications

References 41 publications

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling

Primary Central Nervous System T-Cell Lymphoma With Aberrant Expression of CD20 and CD79a: A Diagnostic Pitfall

Intravascular large B-cell lymphoma with multi-organ failure presenting as a pancreatic mass: a case with atypical presentation and definite diagnosis postmortem

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