Intrasinusoidal HHV8-EBV–Positive Large B-Cell Lymphoma With Features of Germinotropic Lymphoproliferative Disorder

Abstract

Germinotropic lymphoproliferative disorder (GLPD) is a poorly characterized lymphoproliferative entity, recently included in the World Health Organization classification of hematolymphoid neoplasms. The histological pattern of this disease comprises monotypic plasmablasts that involve the germinal centers of the lymphoid follicles (germinotrophism), forming confluent aggregates positive for both human herpes virus type 8 (HHV8) and Epstein-Barr virus. Currently, after 17 years of its first description, only 18 cases have been reported. In this article, we describe a case of a GLPD presenting in an immunocompetent 79-year-old woman with localized axillary lymphadenopathy, showing a prominent sinusoidal growth pattern, with no evidence of germinotrophism or extrasinusoidal spread. Stinking pleomorphism in tumor cells was also noted. An extension study has not revealed involvement of other groups of lymph nodes or extralymphoid sites. The patient is alive and has shown no relapse after 8 years follow-up (the longest follow-up reported period for this entity). This previously unrecognized pure sinusoidal growth pattern along with the striking pleomorphism in neoplastic cells closely mimics the appearance of an anaplastic large cell lymphoma. GLPD is not usually considered in such a setting, but it should be included in the differential diagnosis of sinusoidal proliferations. Our findings contribute to the expansion of the morphological spectrum of HHV8-associated lymphoproliferative lesions and aids in the characterization of the very infrequent GLPD entity.

Cavity-based lymphomas: challenges and novel concepts. A report of the 2022 EA4HP/SH lymphoma workshop

“…However, the atypical cells were predominantly sinusoidal and paracortical, only partially involving follicles (without appearing focused in germinal centers) and without interfollicular polytypic plasmacytosis. Given the pattern and lack of light chain expression, the panel felt the findings were most in keeping with focal involvement by ECPEL; however, some authors have raised consideration that additional patterns may exist for GLPD [ 18 – 21 ].…”

“…Given the overlap in cytomorphology and immunophenotype, the morphologic pattern is often the most useful diagnostic feature in GLPD: general retention of nodal architecture and involvement of germinal centers by medium to large plasmablastic cells [ 1 ]. When alternative patterns have been reported, such as sinusoidal, mantle, and interfollicular involvement, this is usually in addition to germinal center involvement [ 8 , 18 – 20 ], although not always [ 21 ]. A recent review [ 19 ] found that interfollicular polytypic plasmacytosis was a common feature in GLPD (~37%), which has also been reported as a prominent finding by others [ 18 , 22 ].…”

Epstein–Barr virus reactivation influences clonal evolution in human herpesvirus‐8‐related lymphoproliferative disorders

“…In the second case, we found the entire spectrum of HHV8‐related disorders (MCD, GLPD, and PEL) coexisting in the same lymph node, underlining the variability, the overlap and the possible evolution among these entities. Cases with clinicopathological features of MCD enriched for plasmablastic aggregates and GLPD have been reported, suggesting an overlap with MCD and GLPD in a subset of cases 25,34 . Although GLPD progressing to lymphoma has been reported in HIV‐positive and HIV‐negative patients, 29 definitive association and evolution from MCD to GLPD or EC‐PEL is still not recognised 46 .…”

“…Cases with clinicopathological features of MCD enriched for plasmablastic aggregates and GLPD have been reported, suggesting an overlap with MCD and GLPD in a subset of cases. 25 , 34 Although GLPD progressing to lymphoma has been reported in HIV‐positive and HIV‐negative patients, 29 definitive association and evolution from MCD to GLPD or EC‐PEL is still not recognised. 46 In our case we were able to demonstrate a clonal relationship between the atypical large cells in the germinal centres and in the sinuses from the same lymph node.…”

“…[17][18][19] In humans, occasional cases with atypical and overlapping features among HHV8/EBV-related LPDs have been recognised, such as lesions intermediate between MCD and GLPD in HIV-positive patients, or GLPD that progresses to high-grade EBV or HHV8positive lymphoma. [21][22][23][24][25][26] These cases represent diagnostic challenges, and suggest that the spectrum of HHV8-related lesions and the interaction with EBV infection may not be fully characterised.…”