Lymphocyte-rich classical Hodgkin's lymphoma: distinctive tumor and microenvironment markers

Abstract

The existence, diagnostic features, and the biological and clinical relevance of lymphocyte-rich classical Hodgkin's lymphoma remain controversial. A comparative marker analysis of lymphocyte-rich classical Hodgkin's lymphoma, nodular lymphocyte-predominance Hodgkin's lymphoma, and of other subtypes of classical Hodgkin's lymphoma was carried out. Markers were selected focusing on B-cell lineage and transcription program (OCT.1, OCT.2, BOB.1, BCL6, PAX-5, GCET1, KLHL6, and BLIMP1), the NF-jB signaling pathway (REL-B, C-REL, TRAF-1, p-50, and MUM-1) and the T-cell microenvironment (CD3, CD57, PD-1, CXCL-13, and CD10, BCL-6, CD23). Lymphocyte-rich classical Hodgkin's lymphoma cases displayed features intermediate between those of classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma. The expression of B-cell transcription factors such as OCT.1, OCT.2, BOB.1, and BCL6 was more frequent in lymphocyte-rich classical Hodgkin's lymphoma than in classical Hodgkin's lymphoma. A follicular T-cell microenvironment was also identified in 50% of lymphocyte-rich classical Hodgkin's lymphoma cases. NF-kB markers were expressed at frequencies comparable with those observed in classical Hodgkin's lymphoma. The neoplastic cell immunophenotype and microenvironment in lymphocyte-rich classical Hodgkin's lymphoma closely mimic that which are observed in the outer zone of the germinal center, where B-cell blasts with germinal-center markers co-express CD30 and the B-cell transcription program, surrounded by follicular T-cell rosettes. Lymphocyte-rich classical Hodgkin's lymphoma seems to be characterized by a stronger expression of the B-cell transcription program by the neoplastic cells and by a follicular T-cell background, occupying an intermediate position between classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma.

Analyzing primary Hodgkin and Reed-Sternberg cells to capture the molecular and cellular pathogenesis of classical Hodgkin lymphoma

“…Conversely, LR-cHL appeared to be very close to nLPHL, suggesting that it has features intermediate between cHL and nLPHL not only in the microenvironment but also in the tumor cells themselves, as already appreciated regarding their morphology (smaller nuclei, less atypia) and phenotype (less frequent down-regulation of B-cell markers). 44,45 It is also intriguing that the 2 cHL subtypes closest to PATHOGENESIS OF CLASSICAL HODGKIN LYMPHOMA 4617 BLOOD, 29 NOVEMBER 2012 ⅐ VOLUME 120, NUMBER 23…”

“…Conversely, LR-cHL appeared to be very close to nLPHL, suggesting that it has features intermediate between cHL and nLPHL not only in the microenvironment but also in the tumor cells themselves, as already appreciated regarding their morphology (smaller nuclei, less atypia) and phenotype (less frequent down-regulation of B-cell markers). 44,45 It is also intriguing that the 2 cHL subtypes closest to PATHOGENESIS OF CLASSICAL HODGKIN LYMPHOMA 4617 BLOOD, 29 NOVEMBER 2012 ⅐ VOLUME 120, NUMBER 23For personal use only. on April 29, 2019. by guest www.bloodjournal.org From nLPHL (ie, LR-and MC-cHL) are also the closest to TCRBL, a variant of DLBCL into which nLPHL can transform and whose reactive background (rich in T cells and histiocytes) and neoplastic cell population (sometimes cytologically indistinguishable from HRS cells and sometimes expressing CD30) can make TCRBL mimick MC-cHL.…”

The 2016 revision of the World Health Organization classification of lymphoid neoplasms

“…147,149 The revision will also acknowledge that lymphocyterich CHL has some features that are intermediate between other CHL and NLPHL. 150 …”

Shades of gray between large B-cell lymphomas and Hodgkin lymphomas: differential diagnosis and biological implications

“…9 In one study, the B-cell expression program (Oct2, Bob1) was more often preserved in LRCHL compared with other CHL subtypes, and had infrequent expression of REL compared with other CHL but comparable expression of TRAF1, suggesting that LRCHL may be a distinct entity from either CHL or NLPHL. 10 LRCHL comprises about 5% of the cases of HL. 11 The clinical features at presentation similar to those of NLPHL: similar to NLPHL, patients have early stage disease, lack bulky disease or B-symptoms, lack mediastinal disease and have a predominance of males, and a median age higher than that for NSCHL.…”