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CD20− change after rituximab-containing therapy is considered one of the main reasons of rituximab resistance of B-cell non-Hodgkin lymphomas (B-NHLs). However, the clinicopathological characteristics of B-NHL with CD20− change are not entirely understood. In this study, 252 B-NHL patients who were CD20+ at initial diagnosis, whose diseases relapsed or were refractory after rituximab-containing therapy, and who were re-biopsied between 2000 and 2018, were included. The median number of rituximab administration was 11 (range, 1–48). Completely negative (cCD20−) and partially negative (pCD20−) change of CD20 was observed in 49 (20%) and 16 (6%) cases, respectively. Among cCD20− and pCD20− cases, 74% and 62% of the cases changed to CD20− at the second relapse or later, respectively. Overall survival was significantly shorter in cCD20− follicular lymphoma (FL) cases than in CD20+ FL cases. Seven histopathological patterns, such as CD20− change without histological change, histological transformation (HT) to CD20− diffuse large B-cell lymphoma, and proliferation of plasmablastic/plasmacytoid tumor cells, were associated with CD20− change. HT occurred more frequently in FLs with CD20− change than in FLs continuously expressing CD20 (P < 0.0001), regardless of the timing of HT. Nine out of 25 cases (36%) showed regain or heterogeneous regain of CD20 expression. In conclusion, 20% and 6% of the 252 B-NHL cases show cCD20− and pCD20− changes with 7 histological patterns after rituximab-containing therapy. Because changes in morphology and CD20 expression after rituximab-containing therapy vary, and recovery of CD20 expression is not rare, careful follow-up and re-biopsy in B-NHL patients are recommended. [ABSTRACT FROM AUTHOR]

Epstein‐Barr virus (EBV) infection is associated with pathogenesis of various cancers, including extranodal natural killer/T‐cell lymphoma, nasal type (ENKL). ENKL tumor cells are positive for EBV‐encoded RNA1 (EBER1), which is the most useful marker to identify ENKL tumor cells in histopathology. Currently, EBER1 in situ hybridization (ISH) is recommended to evaluate bone marrow (BM) involvement of ENKL. However, the actual burden of EBER1‐positive cells in normal BM specimens remains unclear. In the present study, we performed EBER1 ISH on 111 BM specimens, which were obtained during an initial staging procedure in patients with EBV‐negative cancers and were also negative for BM involvement. One or more EBER1‐positive cells per whole specimen were observed in 38 specimens (34%). The number of EBER1‐positive cells was distributed as follows: single positive cell, n = 17; two positive cells, n = 13; three positive cells, n = 3; and four positive cells, n = 5. These findings suggest that four or fewer EBER1‐positive cells can be observed in BM specimens of patients with non‐EBV‐related cancers. The clinical implications of a small number of EBER1‐positive cells in BM specimens of patients with ENKL should be evaluated in further studies. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B‐cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network. Methods: We explored the expression levels of PDLs and chromosomal anomalies in 67 cases: 34 cases with cHL, 20 with PMBL, and 13 with GZL, using immunohistochemical analyses and Fluorescence In Situ Hybridization (FISH). Results: Twenty‐one cHL (62%), 3 PMBL (15%), and 6 GZL (46%) cases showed staining to PD‐L1 antibodies in more than 70% of tumor cells. Two cHL (6%), 10 PMBL (50%), and 3 GZL (23%) cases were not stained by PD‐L1 antibodies. Patients over 40 years old manifest more frequent expression of PD‐L1 in cHL. Proportion of tumors stained by PD‐L2 antibody was increased in PMBL. FISH analyses with a PD‐L1/PD‐L2 probe detected 5 amplification, 1 gain, and 7 polysomy cases in cHL, 1 amplification and 1 polysomy case in GZL, and amplification in 1 PMBL case. Conclusion: We identified increased staining of PD‐L1 in cHL and that of PD‐L2 in PMBL. GZL had a pattern similar to that of cHL. [ABSTRACT FROM AUTHOR]

This study analysed incidence, patient outcome, immunophenotype and prognostic factors of histological transformation ( HT) from extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue ( MALT lymphoma) to diffuse large B-cell lymphoma ( DLBCL) in 467 patients (median age, 61 years). The primary sites of MALT lymphoma were the stomach (43%), ocular adnexa (25%), lung (8%), systemic (8%) and other tissues (16%). HT occurred in 8% of MALT lymphomas. Risk of HT by 15 years was 5%: 4% in limited-stage diseases ( n = 385) and 16% in advanced-stage diseases ( n = 56) ( P = 0·02). The median time to HT was 48 months (range, 4-139). Five-year progression-free survival ( PFS) and overall survival ( OS) rates after HT were 80% and 94%, respectively. Immunohistochemical results of DLBCL were as follows: germinal centre B-cell ( GCB)/non- GCB, 37%/63%; CD10, 9%; BCL6, 59%; MUM1, 38%; MYC, 42%; BCL2, 35%; Ki67 ≥ 90%, 23%; and CD5, 3%. The majority (75%, 9/12) of GCB-type DLBCLs exhibited CD10−, BCL6+ and MUM1− immunophenotypes; the remainder had CD10+ immunophenotypes. Multivariate analysis revealed that only advanced stage at HT was a significant adverse factor for PFS ( P = 0·037). Thus, overall risk of HT was low and prognosis after HT was favourable; however, in advanced-stage cases, risk of HT was relatively high and prognosis was unfavourable. [ABSTRACT FROM AUTHOR]

To investigate the clinicopathological and prognostic significance of a nodular pattern and immunophenotypes in primary mediastinal large B-cell lymphoma ( PMBL), histopathological features, including a nodular pattern and immunophenotypes, were analyzed in 58 Japanese PMBL patients. The patients were 23 men and 35 women with a median age of 31 years. The 4-year progression free survival ( PFS) rate was 78%, and the 4-year overall survival ( OS) rate was 89%. Among the histopathological and immunohistochemical features, Bcl6+ ( P = 0.013), MUM1+ ( P = 0.091), and pale cytoplasm ( P = 0.064) were favorable prognostic indicators of PFS, and Bcl6+ ( P = 0.051) and MUM1+ ( P = 0.07) were favorable prognostic indicators of OS. Patients with Bcl2 negativity ( n = 11) had 4-year PFS and OS rates of 100%. Histologically, a nodular pattern, resembling nodular sclerosis classical Hodgkin lymphoma ( CHL), was observed in 22 patients (38%). However, this was not a significant prognostic indicator. In conclusion, Bcl6+, MUM1+, Bcl2-, and pale cytoplasm are candidate favorable prognostic indicators for PMBL and should be further examined in larger studies. We suggest that PMBL with a nodular pattern may belong to the same histological spectrum as nodular sclerosis CHL. [ABSTRACT FROM AUTHOR]