EBV‐associated but HHV8‐unrelated double‐hit effusion‐based lymphoma

Abstract

Effusion-based lymphoma is a rare and unique type of large B-cell lymphoma presenting in effusion without a mass lesion. It shares many clinicopathological features with primary effusion lymphoma (PEL), but is distinct from PEL by the absence of HHV8 association. Double hit lymphoma (DHL) is an aggressive B-cell lymphoma, defined by concurrent rearrangement of MYC and BCL2 or BCL6. DHL often presents as lymphadenopathy or an extranodal mass, but rarely occurs in effusion. Here we report a 61-year-old male with alcoholic cirrhosis presenting as massive ascites and left pleural effusion. He has no HIV, HBV or HCV infection and no mass lesion by CT scans. Cytology of both pleural effusion and ascites show large lymphoma cells with plasmablastic morphology characterized by pleomorphic and eccentric nuclei, prominent nucleoli and frequent mitoses. Immunohistochemical study with cell block shows that the lymphoma cells express plasma cell-related markers (CD138, MUM-1 and EMA), but not CD3, CD30, CD45, B-cell markers (CD19, CD20, CD79a, and PAX5), HHV8, ALK or cytokeratin. EBER is positive in most lymphoma cells. Fluorescence in situ hybridization reveals rearrangement at the IGH, BCL2, and MYC loci, but not at BCL6. It is diagnosed as an EBV-associated but HHV8-unrelated double hit effusion-based lymphoma with plasmablastic features. The patient passed away soon after diagnosis without chemotherapy. This is the first reported case of double-hit effusion-based lymphoma with MYC and BCL2 rearrangement. This case illustrates the importance of integrating clinical, cytological, immunophenotypical, and molecular findings to reach a correct diagnosis. Diagn. Cytopathol. 2017;45:257-261. © 2016 Wiley Periodicals, Inc.

Primary effusion lymphoma in Taiwan shows two distinctive clinicopathological subtypes with rare human immunodeficiency virus association

“…IGH , BCL2 , BCL6 and MYC was rearranged in 71% (12 of 17), 11% (two of 18), 12% (two of 17) and 18% (three of 17) cases, respectively. Interestingly, the tumour cells of case 9, an HIV‐negative patient, were EBER‐positive, HHV8‐negative and showed rearranged BCL2 and MYC , the first case of double‐hit effusion‐based lymphoma that we reported recently …”

“…A total of 26 cases with PEL were collected retrospectively from 10 hospitals in Taiwan and from the consultation files of one of the authors (S.‐S.C.). Two cases (cases 4 and 9) had been reported previously . This study was approved by the Internal Review Board of Chi‐Mei Medical Center, Tainan, Taiwan (approval no.…”

“…Two cases (cases 4 and 9) had been reported previously. 20,21 This study was approved by the Internal Review Board of Chi-Mei Medical Center, Tainan, Taiwan (approval no. 10604-002) and was conducted in accordance with the guidelines of the Declaration of Helsinki.…”

“…Interestingly, the tumour cells of case 9, an HIV-negative patient, were EBER-positive, HHV8-negative and showed rearranged BCL2 and MYC, the first case of double-hit effusion-based lymphoma that we reported recently. 20 Table 2 lists the comparison between the HHV8-positive (n = 8) and -negative (n = 16) cases after excluding the single HIV-positive patient to avoid confounding effects. Compared to the HHV8-negative group, the HHV8-positive tumours expressed CD30 (P < 0.001) and CD138 (P = 0.021) more frequently, but less frequently CD19 (P = 0.001), CD20 (P < 0.001), CD79a (P = 0.003) or BCL-2 (P < 0.001).…”

“…In recent years, some HHV8‐negative effusion‐based lymphoma (EBL) cases have been reported, mainly from Japan . These HHV8‐negative EBL cases have been reported to exhibit overlapping clinical presentation and morphology as PEL, but a distinct immunophenotype (often positive for CD20) and lack of association with HIV or EBV.…”