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Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer

Abstract

Epstein–Barr virus (EBV)-positive mucocutaneous ulcer (EBVMCU) is a unifocal mucosal or cutaneous ulcer that is histologically characterized by proliferating EBV-positive atypical B cells. While EBVMCU demonstrates a histology similar to that of EBV-positive diffuse large B-cell lymphoma (DLBCL), their clinical behavior differs. Thus, characterizing distinguishing features of EBVMCU and EBV-positive DLBCL is critical. To identify unique characteristics between EBVMCU and lymphoma, we analyzed the clinicopathological and genetic features of 34 Japanese patients with EBVMCU and compared them to those of 24 EBV-positive DLBCL patients and 25 EBV-negative DLBCL patients. All patients with EBVMCU had localized ulcerative lesions, and 31 patients (91%) were using immunosuppressants, such as methotrexate (MTX) or hydroxycarbamide. All patients that were followed up with exhibited good prognosis following immunosuppressant reduction or chemotherapy. In addition, 17 EBV-positive DLBCL patients, and 15 EBV-negative DLBCL patients, received chemotherapy (P < 0.001, P < 0.001, respectively). Our data showed that EBVMCU did not increase indicators associated with lymphoma prognosis, such as soluble interleukin 2 receptor (sIL-2R) and lactate dehydrogenase (LDH) compared to those in the EBV-positive DLBCL or EBV-negative DLBCL groups (sIL-2R, P < 0.001, P = 0.025; LDH, P = 0.018, P = 0.038, respectively). However, histologically, EBVMCU exhibited EBV-positive, variable-sized, atypical B-cell proliferation. Thus, EBVMCU was histologically classified as: (1) polymorphous; (2) large cell-rich; (3) classic Hodgkin lymphoma-like; and (4) mucosa-associated lymphoid tissue lymphoma-like. Moreover, genetic analysis showed that immunoglobin heavy chain (IGH) gene rearrangement did not differ significantly between EBVMCU and EBV-positive DLBCL (44% vs. 32%; P = 0.377), or between EBVMCU and EBV-negative DLBCL (44% vs. 58%; P = 0.280). Therefore, it is difficult to distinguish EBVMCU from EBV-positive DLBCL using only pathological and genetic findings, suggesting that clinical information is important in accurately distinguishing between EBVMCU and EBV-positive DLBCL.

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Fig. 1: Macroscopic findings of Epstein–Barr virus-positive mucocutaneous ulcer in buccal mucosa (Case No. 31).
Fig. 2: Comparison of sIL-2R and LDH in EBVMCU, EBV-positive DLBCL, and EBV-negative DLBCL.
Fig. 3: Pathologic findings of angioinvasion in EBVMCU.
Fig. 4: Pathologic findings of polymorphous EBVMCU.
Fig. 5: Pathologic findings of large cell-rich EBVMCU.
Fig. 6: Pathologic findings of CHL-like EBVMCU.
Fig. 7: Pathologic findings of MALT lymphoma-like EBVMCU.

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Acknowledgements

This work was partially supported by the Grant-in-Aid for Young Scientists (JSPS KAKENHI grant number 19K16586) and Scientific Research (C) (JSPS KAKENHI Grant Number JP 20K07407), from the Japan Society for the Promotion of Science.

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Correspondence to Yuka Gion or Yasuharu Sato.

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Ikeda, T., Gion, Y., Sakamoto, M. et al. Clinicopathological analysis of 34 Japanese patients with EBV-positive mucocutaneous ulcer. Mod Pathol 33, 2437–2448 (2020). https://doi.org/10.1038/s41379-020-0599-8

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