HHV8-positive, EBV-positive Hodgkin lymphoma-like large B cell lymphoma: expanding the spectrum of HHV8 and EBV-associat
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CASE REPORT
HHV8‑positive, EBV‑positive Hodgkin lymphoma‑like large B cell lymphoma: expanding the spectrum of HHV8 and EBV‑associated lymphoproliferative disorders Sandra Sanchez1 · Luis Veloza2 · Luojun Wang2 · Mónica López2 · Armando López‑Guillermo3 · Marta Marginet2 · Antonio Martínez2 · Olga Balagué2 · Elias Campo2 Received: 10 January 2020 / Revised: 26 May 2020 / Accepted: 4 June 2020 © Japanese Society of Hematology 2020
Abstract Human herpesvirus type 8 (HHV8) is a gamma herpesvirus known for its role in lymphoid neoplasms, especially in immunosuppressed patients. We describe the case of a 64-year-old male, without known immunodeficiency, with 1-year-long clinical history of mediastinal and abdominal lymphadenopathies and recurrent pulmonary infections. Histopathological evaluation of a mediastinal lymph node revealed the presence of scattered atypical large cells with Hodgkin and Reed–Sternberg morphology in a background of lymphocytes and extensive areas of fibrosis. The large cells were positive for HHV8 and Epstein–Barr virus (EBV), with a clonal pattern of IGH gene rearrangement. A descriptive diagnosis of “HHV8-positive, EBV-positive Hodgkin lymphoma-like large B-cell lymphoma” was rendered. Interestingly, the retrospective evaluation of a previous biopsy, diagnosed as reactive lymphadenitis, revealed the presence of HHV8- and EBV-positive cells, with a polyclonal pattern and a small peak corresponding to that of the most recent biopsy. This case presents diagnostic challenges due to the presence of particular features not clearly related to current HHV8-associated entities, and also suggests the possibility for disease progression in the spectrum of HHV8- and EBV-associated lymphoproliferative disorders. Keywords HHV8 · EBV · Large B-cell lymphoma · Hodgkin lymphoma · Immune escape · PD-L1 · PD1
Introduction Human herpesvirus type 8 (HHV8) is a gamma herpesvirus known for its role in the development of varied lymphoid neoplasms, such as primary effusion lymphoma (PEL), multicentric Castleman disease (MCD), germinotropic lymphoproliferative disorder (GLPD) and HHV8-positive diffuse large B-cell lymphoma, not otherwise specified [1–4]. Sandra Sanchez and Luis Veloza have contributed equally to this work. * Sandra Sanchez [email protected] 1
Division of Hematopathology, Department of Pathology, University of Miami Hospital, 1400NW 12th Avenue #4062, Miami, FL 33136, USA
2
Hematopathology Unit, Department of Pathology, Hospital Clinic of Barcelona, Barcelona, Spain
3
Department of Hematology, Hospital Clinic of Barcelona, Barcelona, Spain
In addition to these well-characterized HHV8-related entities, occasional cases with atypical and overlapping features, coinfection with Epstein–Barr virus (EBV) and also HHV8related reactive lymphadenitis have been reported [5–9]. However, the clinical implications of these cases are largely unknown. Moreover, they represent diagnostic and therapeutic challenges as most HHV8-positive lymphoproliferative disorders (LPD) present i
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