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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

Chen, Zihang MD; Liu, Weiping MD; Zhang, Wenyan MD, PhD; Ye, Yunxia MD; Guan, Pujun MM; Gao, Limin PhD; Zhao, Sha MD, PhD

The American Journal of Surgical Pathology: December 2019 - Volume 43 - Issue 12 - p 1611–1621
doi: 10.1097/PAS.0000000000001324
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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.

Department of Pathology, West China Hospital, Sichuan University, Chengdu, China

Conflicts of Interest and Source of Funding: Supported by the National Natural Science Foundation of China (30900534) and Sichuan Science and Technology Program (2018JY0612). The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Sha Zhao, MD, PhD, Department of Pathology, West China Hospital, Sichuan University, No. 37, GuoXue Xiang, Chengdu, Sichuan 610041, China (e-mail: hxblzhaosha@126.com).

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