Ohata Yae, Tatsuzawa Anna, Ohyama Yoshio, Ichikawa Ayako, Mochizuki Yumi, Ishibashi Sachiko, Itakura Yuri, Sakurai Urara, Sakamoto Kei, Ikeda Tohru, Kitagawa Masanobu, Yamamoto Kouhei
Department of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan; Department of Analytical Information of Clinical Laboratory Medicine, Graduate School of Health Care Science, Bunkyo Gakuin University, 1-19-1, Mukougaoka, Bunkyo-ku, Tokyo 113-8668, Japan.
Hum Pathol. 2017 Nov;69:129-139. doi: 10.1016/j.humpath.2017.09.013. Epub 2017 Oct 6.
Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) is a newly recognized provisional entity included in mature B-cell neoplasm in the latest 2016 World Health Organization Classification. It has a self-limited growth potential with a high predilection for oral cavities and occurs in age-related or iatrogenic immunodeficiency with indolent clinical courses. However, it shares histological features with EBV-positive diffuse large B-cell lymphoma (DLBCL), and this often leads to diagnostic challenges and controversies in patients with an oral EBV-positive B-cell neoplasm. The aim of this study was to better characterize and comprehend the pathophysiology of DLBCL and EBVMCU in the oral cavity. We conducted clinicopathologic and recurrent gene mutation analysis of 49 cases (14 EBV positive, 35 EBV negative), including cases diagnosed as DLBCL or B-cell lymphoproliferative disorders with high-grade morphology in the oral cavity. All EBV-positive cases matched the criteria of EBVMCU, with significantly earlier clinical stages than the EBV-negative group (P=.0006). Besides, histological analysis showed that all EBV-positive cases presented polymorphous features, whereas 91.4% (32/35) of the EBV-negative cases showed diffuse and monotonous proliferation (P<.0001). Furthermore, EBV-positive cases presented favorable clinical outcomes without disease-related death or recurrence. Gene mutation analysis (MYD88, CD79A, CD79B, CARD11, and EZH2) revealed that 33.3% (9/27) of EBV-negative cases harbored at least 1 gene mutation, whereas no gene mutation was observed in the EBV-positive group (0/11). These results suggest that oral EBV-positive B-cell lymphoid proliferation with polymorphous features often fulfill the criteria for EBVMCU, with clinicopathologically and genetically distinctive properties.
爱泼斯坦-巴尔病毒阳性黏膜皮肤溃疡（EBVMCU）是一种新认识的暂定实体，被纳入2016年最新世界卫生组织分类中的成熟B细胞肿瘤。它具有自限性生长潜能，高度好发于口腔，发生于与年龄相关或医源性免疫缺陷且临床病程惰性。然而，它与EBV阳性弥漫大B细胞淋巴瘤（DLBCL）具有共同的组织学特征，这常给口腔EBV阳性B细胞肿瘤患者带来诊断挑战和争议。本研究的目的是更好地描述和理解口腔DLBCL和EBVMCU的病理生理学。我们对49例病例（14例EBV阳性，35例EBV阴性）进行了临床病理和复发性基因突变分析，包括诊断为口腔DLBCL或具有高级别形态的B细胞淋巴增殖性疾病的病例。所有EBV阳性病例均符合EBVMCU标准，临床分期明显早于EBV阴性组（P = 0.0006）。此外，组织学分析显示，所有EBV阳性病例呈现多形性特征，而91.4%（32/35）的EBV阴性病例显示弥漫性和单一性增殖（P < 0.0001）。此外，EBV阳性病例临床结局良好，无疾病相关死亡或复发。基因突变分析（MYD88、CD79A、CD79B、CARD11和EZH2）显示，33.3%（9/27）的EBV阴性病例至少有1个基因突变，而EBV阳性组未观察到基因突变（0/11）。这些结果表明，具有多形性特征的口腔EBV阳性B细胞淋巴增殖通常符合EBVMCU标准，具有临床病理和基因方面的独特特性。
