Mehta Anurag, Verma Ajita, Gupta Garima, Tripathi Rupal, Sharma Anurag
Department of Laboratory and Transfusion Services, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, Delhi India.
Molecular Diagnostic Services, Rajiv Gandhi Cancer Institute and Research Centre, Sector-5, Rohini, Delhi 110085 India.
Indian J Hematol Blood Transfus. 2020 Oct;36(4):627-634. doi: 10.1007/s12288-019-01248-w. Epub 2020 Jan 8.
Double hit lymphomas (DHL) and double expresser lymphomas (DEL) are subsets of diffuse large B cell lymphomas (DLBCL) which are being increasingly recognised as cause of treatment failure. This emphasizes the need for their separation from other DLBCL cases in order to prognosticate and administer more aggressive treatment to this set of patients. The present study was conducted with the aim to identify the DHL/DEL patients and study their distinctive clinicopathological profile and overall survival. This retrospective analysis involved 172 cases of DLBCL sub-classified on the basis of cell of origin. Immunohistochemical (IHC) analysis for and CD10 was performed. Rearrangement studies were performed using break apart Fluorescent in situ hybridization. Overall survival (OS) was also evaluated. Distinctive clinical and pathological features of DHL and DEL were identified. Rearrangement study by FISH revealed seven cases of DHL (+ &/or rearrangement). Also, 20 patients (11.6%) showed a concurrent expression of and oncoproteins (DEL) on IHC. Most (6/7) DHL patients were double expressors also. The DHL patients demonstrated a significant association with female gender, high serum LDH levels (> 750 U/L) and GCB phenotype. DEL patients contrarily predominated amongst males, had intermediate LDH levels (251-500 U/L) and non GCB phenotype. The OS of the patients was 63.8% at 4 years. The OS of the DLBCL, DEL and DHL patients was 71.9%, 46.9%, and 0%, respectively at 4 years ( value 0.010). In case of DEL subtype, factors such as age < 60 years (66.7%), male sex (60.8%), nodal localization (52.5%), early disease stage (84.6%), low IPI score (60%), absence of B symptoms (50%), LDH < 250 U/L (80%) and GCB phenotype (53.3%) were associated with better OS. Further, the OS of DHL cases was 0% at 4 years. Double hit and double expresser lymphomas have poor prognostic outcomes and should be separated from DLBCL. All DELs should be tested for DHLs and especially those with immunoblastic morphology. DHL and DEL subtypes delineate the subtypes with inferior OS and reinstate the need for aggressive interventions.
双打击淋巴瘤（DHL）和双表达淋巴瘤（DEL）是弥漫性大B细胞淋巴瘤（DLBCL）的亚型，它们越来越被认为是治疗失败的原因。这强调了将它们与其他DLBCL病例区分开来的必要性，以便对这组患者进行预后评估并给予更积极的治疗。本研究旨在识别DHL/DEL患者，并研究他们独特的临床病理特征和总生存期。这项回顾性分析涉及172例根据起源细胞进行亚分类的DLBCL病例。进行了针对 和CD10的免疫组织化学（IHC）分析。使用断裂分离荧光原位杂交进行重排研究。还评估了总生存期（OS）。确定了DHL和DEL独特的临床和病理特征。FISH重排研究发现7例DHL（ +和/或 重排）。此外，20例患者（11.6%）在IHC上显示 和 癌蛋白同时表达（DEL）。大多数（6/7）DHL患者也是双表达者。DHL患者与女性性别、高血清乳酸脱氢酶水平（>750 U/L）和生发中心B细胞（GCB）表型显著相关。相反，DEL患者在男性中占主导，乳酸脱氢酶水平中等（251 - 500 U/L）且为非GCB表型。患者4年总生存率为63.8%。DLBCL、DEL和DHL患者4年总生存率分别为71.9%、46.9%和0%（P值0.010）。对于DEL亚型，年龄<60岁（66.7%）、男性（60.8%）、淋巴结受累（52.5%）、疾病早期阶段（84.6%）、国际预后指数（IPI）评分低（60%）、无B症状（50%）、乳酸脱氢酶<250 U/L（80%）和GCB表型（53.3%）等因素与更好的总生存期相关。此外，DHL病例4年总生存率为0%。双打击和双表达淋巴瘤预后不良，应与DLBCL区分开来。所有DEL均应检测是否为DHL，尤其是那些具有免疫母细胞形态的病例。DHL和DEL亚型描绘了总生存期较差的亚型，并再次强调了积极干预的必要性。
