Al-Kawaaz Mustafa, Mathew Susan, Liu Yifang, Gomez Maria L, Chaviano Felicia, Knowles Daniel M, Orazi Attilio, Tam Wayne
From the Division of Hematopathology, Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY.
Am J Clin Pathol. 2015 Feb;143(2):288-99. doi: 10.1309/AJCPUIDW2CPTA1JA.
To demonstrate and confirm the existence of cyclin D1-positive diffuse large B-cell lymphoma (DLBCL) with IGH-CCND1 rearrangement and discuss the rationale of differentiating this entity from blastoid and pleomorphic variants of mantle cell lymphoma (MCL).
Two cyclin D1-positive lymphomas with morphologic features of DLBCL and IGH-CCND1 translocations were characterized with respect to clinical features, as well as morphologic, immunophenotypic, cytogenetic, and molecular findings.
The large tumor cells were CD20+, CD5-, CD10-, BCL6+, MUM1+, and cyclin D1+ in both cases. SOX11 was negative. Epstein-Barr virus-encoded RNA in situ hybridization demonstrated diffuse positivity in case 1. BCL6 and IGH-CCND1 rearrangements were identified by fluorescence in situ hybridization in both cases. Specifically, the diagnosis of a relapsed DLBCL with acquisition of IGH-CCND1 was rendered for case 1, molecularly confirmed by the detection of identical monoclonal IGH rearrangements between the initial diagnostic DLBCL and relapse lymphoma.
Our study demonstrates convincingly that IGH-CCND1 rearrangement leading to cyclin D1 overexpression can occur in DLBCL and pose a potential diagnostic pitfall, requiring thorough knowledge of the clinicopathologic findings to allow accurate discrimination from a blastoid or pleomorphic MCL. The coexistence of IGH-CCND1 and IGH-BCL6 rearrangements suggest that BCL6 and cyclin D1 may cooperate in the pathogenesis of DLBCL.
证实并确认存在伴有IGH-CCND1重排的细胞周期蛋白D1阳性弥漫性大B细胞淋巴瘤（DLBCL），并讨论将该实体与套细胞淋巴瘤（MCL）的母细胞样和多形性变体相鉴别的理论依据。
对两例具有DLBCL形态学特征且伴有IGH-CCND1易位的细胞周期蛋白D1阳性淋巴瘤进行临床特征、形态学、免疫表型、细胞遗传学及分子学研究。
两例中的大肿瘤细胞均为CD20阳性、CD5阴性、CD10阴性、BCL6阳性、MUM1阳性及细胞周期蛋白D1阳性。SOX11为阴性。原位杂交检测显示病例1中爱泼斯坦-巴尔病毒编码的RNA弥漫阳性。荧光原位杂交检测发现两例均存在BCL6和IGH-CCND1重排。具体而言，病例1诊断为复发的伴有IGH-CCND1获得性改变的DLBCL，通过检测初诊DLBCL与复发淋巴瘤之间相同的单克隆IGH重排进行分子学确认。
我们的研究令人信服地表明，导致细胞周期蛋白D1过表达的IGH-CCND1重排可发生于DLBCL，这构成了一个潜在的诊断陷阱，需要全面了解临床病理表现以准确鉴别母细胞样或多形性MCL。IGH-CCND1与IGH-BCL6重排共存提示BCL6和细胞周期蛋白D1可能在DLBCL发病机制中协同作用。
