Department of Pathology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Division of Pathophysiology, Okayama University Graduate School of Health Sciences, Okayama, Japan.
Mod Pathol. 2020 Dec;33(12):2437-2448. doi: 10.1038/s41379-020-0599-8. Epub 2020 Jun 19.
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.
EB 病毒阳性黏膜溃疡（EBVMCU）是一种局灶性黏膜或皮肤溃疡，组织学表现为增殖的 EBV 阳性非典型 B 细胞。虽然 EBVMCU 的组织学类似于 EBV 阳性弥漫性大 B 细胞淋巴瘤（DLBCL），但其临床行为不同。因此，明确 EBVMCU 和 EBV 阳性 DLBCL 的鉴别特征至关重要。为了确定 EBVMCU 和淋巴瘤之间的独特特征，我们分析了 34 例日本 EBVMCU 患者的临床病理和遗传特征，并将其与 24 例 EBV 阳性 DLBCL 患者和 25 例 EBV 阴性 DLBCL 患者进行比较。所有 EBVMCU 患者均有局灶性溃疡性病变，31 例（91%）正在使用免疫抑制剂，如甲氨蝶呤（MTX）或羟基脲。所有接受随访的患者在减少免疫抑制剂或化疗后均预后良好。此外，17 例 EBV 阳性 DLBCL 患者和 15 例 EBV 阴性 DLBCL 患者接受了化疗（P<0.001，P<0.001）。我们的数据表明，与 EBV 阳性 DLBCL 或 EBV 阴性 DLBCL 组相比，EBVMCU 并未增加与淋巴瘤预后相关的指标，如可溶性白细胞介素 2 受体（sIL-2R）和乳酸脱氢酶（LDH）（sIL-2R，P<0.001，P=0.025；LDH，P=0.018，P=0.038）。然而，组织学上，EBVMCU 表现为 EBV 阳性、大小不一、非典型 B 细胞增殖。因此，EBVMCU 在组织学上被分类为：（1）多形性；（2）大细胞丰富型；（3）经典霍奇金淋巴瘤样；和（4）黏膜相关淋巴组织淋巴瘤样。此外，基因分析显示 EBVMCU 与 EBV 阳性 DLBCL 之间（44% 对 32%；P=0.377）或 EBVMCU 与 EBV 阴性 DLBCL 之间（44% 对 58%；P=0.280）的免疫球蛋白重链（IGH）基因重排无显著差异。因此，仅通过病理和遗传发现很难将 EBVMCU 与 EBV 阳性 DLBCL 区分开来，这表明临床信息对于准确区分 EBVMCU 和 EBV 阳性 DLBCL 非常重要。
