Clinicopathological features of primary diffuse large B‐cell lymphoma of the central nervous system – strong EZH2 expression implying diagnostic and therapeutic implication

Guo, Shuangping; Bai, Qing-Xian; Rohr, Joseph; Wang, Yingmei; Liu, Yang; Zeng, Ke; Yu, Kangjie; Zhang, Xiumin; Wang, Zhe

doi:10.1111/apm.12623

Cited by 11 publications

(10 citation statements)

References 29 publications

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“…The former is positive for CD30 and/or ALK and negative for B-cell markers, whereas primary CNS A-DLBCL expresses B-cell markers with negativity for ALK. Negativity for cytokeratin is helpful in distinguishing this type of DLBCL from undifferentiated carcinoma [14].…”

Section: Discussionmentioning

confidence: 99%

Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma

Jia²,

Wang

et al. 2019

Diagn Pathol

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Background Primary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) is a rare intracranial tumor, defined as DLBCL arising from the brain, spinal cord, leptomeninges and eye, with an overall annual incidence of 5 cases per million. The primary CNS anaplastic variant of DLBCL (A-DLBCL) is even less common; to our knowledge, there are only two other case reports in the literature. The aim of this report is to present rare cases of primary CNS A-DLBCL and study their clinicopathologic and genetic features. Case presentation We report 3 patients, two men and one woman, aged 54, 55 and 67 years old, with primary CNS A-DLBCL. All 3 patients had a high International Extranodal Lymphoma Study Group (IELSG) score; although the patients were treated with methotrexate-based regimens and/or with radiation therapy, the overall survival was only 2, 5, and 8 months. All 3 patients presented with characteristic features of perivascular space infiltration with bizarre-shaped tumor cells, leading to the diagnosis of primary CNS A-DLBCL. Concurrent of MYC and BCL2 and/or BCL6 abnormalities and MYC/BCL2 double-expressor DLBCL occurred in all 3 patients; two patients had MYC / BCL2 / BCL6 triple extra copies, and one patient had MYC extra copy and BCL6 translocation. All 3 patients displayed mutations in MYD88 L265P and nuclear positivity for RELA, RELB and/or c-Rel, indicating constitutive activation of the NF-κB pathway. Conclusions These cases shed light on the unique genetic alterations and biological features of primary CNS A-DLBCL. Patients with primary CNS A-DLBCL may often have a MYC/BCL2 double-expressor and concurrent MYC and BCL2 and/or BCL6 genetic abnormalities, as well as constitutive activation of the NF-κB pathway. Primary CNS A-DLBCL follows a very aggressive disease course and poor prognosis. In the future, a large number of cases should be analyzed, and the evaluation of molecular genetic characteristics could help with practical and therapeutic implications for primary CNS A-DLBCL.

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Section: Discussionmentioning

confidence: 99%

Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma

Jia²,

Wang

et al. 2019

Diagn Pathol

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“…76,77 EZH2 is expressed, but without evidence of gene mutation. 75 PD-L1 is positive in approximately 30% of cases 78 CD10 is positive in less than 20% of cases, CD30 is positive rarely, and CD138, T-cell markers and EBER1 are negative. 1,76 Cytogenetics and molecular Chromosomal alterations involving 9p21.3, 6p, 6q, chromosome 12, 18q21.33-23, and 10q23.2 have been shown.…”

Section: Immunophenotypementioning

confidence: 98%

“…Surrounding reactive gliosis or lymphocytic infiltrates may be noted. 75 Endothelial proliferation or pseudo-palisading necrosis, as seen in glioblastoma, is not a feature.…”

Section: Histomorphologymentioning

confidence: 99%

Diffuse large B-cell lymphoma variants: an update

et al. 2020

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“…[22] In contrast, Guo et al found that MYC expression alone and MYC/BCL-2 co-expression was significantly associated with poor outcome in patients with PCNS-DLBCL. [34] Kim et al summarized that patients with MYC/BCL-2 co-expression exhibited worse progression-free survival (PFS) in the MTX-treated group, and the same conclusion was got in Shi study. [25,23] Similarly, our research found that patients with c-MYC/BCL2 co-expression trended towards a poor prognosis.…”

Section: Discussionmentioning

confidence: 63%

Immunohistochemical overexpression of BCL-2 protein predicts an inferior survival in patients with primary central nervous system diffuse large B-cell lymphoma

Chen

Chen²,

Chen³

et al. 2019

Medicine

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This study was designed to analyze the clinical characteristics and prognostic value of c-MYC and BCL-2 proteins expression in patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL).82 patients newly diagnosed with PCNS-DLBCL, from January 2008 to November 2018, were enrolled in this study. Clinical characteristics, immunohistochemical features, laboratory examinations, and treatment outcome were analyzed among these patients.Among these 82 cases, 45 were males (54.9%) and 37 were females (45.1%). Age ranged from 16 to 78 years old, and 29 patients (35.4%) were elder than 60 years old, with median age at 57 years old. According to Hans classification, 25 were accounted for origin of germinal center B-cell (GCB) subtype (30.5%) and 49 were accounted for non-GCB subtype (59.8%), respectively. Eight patients were unclassified due to lack of detailed pathological results. The median survival of these 82 patients was 30 months, and 1-year, 3-year, and 5-year overall survival (OS) rate was 59.7%, 44.6%, and 34.1%, respectively. Patients treated with sequential HD-MTX based chemotherapies showed a superior prognosis than those without. In combination with rituximab, the outcome was further improved. The median OS was 55 months in HD-MTX + R group, 27 months in HD-MTX group, and 9 months in other groups, respectively. Univariate analysis identified age ≥60, ECOG score ≥ 2 points, and overexpression of BCL-2 protein (≥85%) were adverse prognostic factors for OS. Co-expression of c-MYC (≥40%) and BCL-2 (≥50%) proteins was associated with poor ECOG score, high Ki-67 expression, and trended towards an inferior outcome. Gender, lesion location, number of lesions, lactic dehydrogenase (LDH), cell of origin, BCL-6 protein expression, expression of c-MYC protein alone and Ki-67 ≥85% had no significant impact on OS.In patients with PCNS-DLBCL, age ≥60 years old, ECOG score ≥2 points, and overexpression of BCL-2 protein (≥85%) were associated with a poor survival. HD-MTX based chemotherapies in combination with rituximab could improve the prognosis.

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Clinicopathological features of primary diffuse large B‐cell lymphoma of the central nervous system – strong EZH2 expression implying diagnostic and therapeutic implication

Cited by 11 publications

References 29 publications

Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma

Rare cases of primary central nervous system anaplastic variant of diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma variants: an update

Immunohistochemical overexpression of BCL-2 protein predicts an inferior survival in patients with primary central nervous system diffuse large B-cell lymphoma

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