Chronic Active Epstein-Barr Virus Infection of T/NK-Cell Type Mimicking Classic Hodgkin Lymphoma: Clinicopathologic and Genetic Features of 8 Cases Supporting a Variant With "Hodgkin/Reed-Sternberg-like" Cells of NK Phenotype. (December 2019)

• Record Type: Journal Article
• Authors: Chen, Zihang; Liu, Weiping; Zhang, Wenyan; Ye, Yunxia; Guan, Pujun; Gao, Limin; Zhao, Sha
• Is Part Of: American journal of surgical pathology. Volume 43:Number 12(2019)
• Publication Date: 2019-12
• Subjects: chronic active EBV infection -- HRS-like cells -- genetic features -- classical Hodgkin lymphoma; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001324
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Chronic active Epstein-Barr virus (EBV) infection of T-cell and NK-cell type, systemic form (CAEBV-T/NK-S) is characterized by EBV + T-cell and/or NK-cell proliferation with no changes suggesting malignancy. Therefore, when Hodgkin/Reed-Sternberg (HRS)-like cells are scattered in CAEBV-T/NK-S, it is more likely to be misdiagnosed as classic Hodgkin lymphoma. We encountered a case wherein the patient showed HRS-like cells with typical NK phenotype. Therefore, we further investigated 8 similar cases to provide clinicopathologic and genetic features and discuss their distinction from other related diseases. Clinically, all cases met the diagnostic criteria of CAEBV. Moreover, 4/8 patients had hemophagocytic lymphohistiocytosis. The median survival was 16 months (range, 5 to 35 mo). Pathologically, all lymph node samples had a remarkably similar morphology with scattered HRS-like cells surrounded by a mixture of small-sized lymphocytes, plasma cells, and macrophages that masqueraded classic Hodgkin lymphoma. Besides, erythrophagocytosis was detected in 4/11 samples. The HRS-like cells were positive for CD2, CD3p, CD30, CD56, GrB, and EBER-ISH, but negative for CD20, CD5, PAX-5, and LMP-1. The surrounding lymphocytes were mainly CD8 + cytotoxic T cells, without obvious aberrant expression. In addition, all patients were polyclonal in the T-cell receptor γ rearrangement test. The harbored mutations were mainly in epigenetic modifiers, JAK-STAT signaling pathway, and apoptosis/cell cycle pathway, including SOCS1, DDX3X, and KMT2D, similar to other EBV-associated T/NK-cell lymphoproliferative disorders. Therefore, the evidence indicates that "HRS-like cells of NK phenotype" is a variant of CAEBV-T/NK-S. This study may raise awareness of such confounding CAEBV-T/N-S cases in clinical practice to avoid misdiagnosis and treatment delay. Abstract : Supplemental Digital Content is available in the text.