结外鼻型NK／T细胞淋巴瘤117例临床病理分析

Clinicolpathological characteristics of 117 cases of extranodal NK/T cell lymphoma, nasal type

目的分析结外鼻型NK／T细胞淋巴瘤（NKTL）的临床病理特点，探讨其与疾病预后的关系，为临床个体化治疗提供依据。方法回顾117例确诊为NKTL患者的病理临床资料。病理诊断均采用常规组织学、免疫组织化学、T细胞重排和原位杂交方法检测EB病毒（EBV）编码小RNA（EBER）。EBVDNA拷贝数检测采用PCR方法。所有患者经过国际预后指数（IPI）和Ki-67等指标临床评估后均采用化疗和放疗联合治疗。随访患者并对临床指标与2年总生存（OS）率和无进展生存（PFS）率的关系进行单因素分析。结果免疫组织化学结果提示各指标阳性率：CD3为90．6％，CD56为94．0％，CD。R0为92．9％，TIA为97．9％，GranzymeB为97．7％，EBER为100．0％。117例患者中位年龄为43．2岁（14—77岁），原发鼻者95例（81．2％），Ki．67平均值为（48．3±2．6）％；原发非鼻者22例（18．8％），包括原发咽喉、舌、扁桃体、淋巴结、皮肤、肝、肠、中枢神经系统和睾丸。与原发鼻的NKTL患者相比，原发肝和肠者Ki．67值较高，且瞄．67值大于80％的NKTL患者均在1年内死亡。Ki-67值为60％～80％的45例2年0s率为60．0％，与Ki．67值为30％-60％的33例OS率（86．3％）和Ki．67值小于30％的8例0S率（100．0％）分别相比，差异均有统计学意义（P=0．047、0．011）。Ki．67值为60％-80％者2年PFS率为36．0％，与Ki．67值为30％。60％者PFS率（57．5％）相比，差异无统计学意义（P=0．07），与Ki-67值小于30％者PFS率（78．0％）相比，差异有统计学意义（P=0．02）。CD。阴性的8例CD3表达阳性，TCR重排均为阳性，提示为T细胞来源，原发部位均为鼻部，无全身症状，2年0s率和PFS率分别为100．0％和70．0％，高于CD。阳性患者，差异均有统计学意义（P=0．03、0．02）。13例检测了EBVDNA拷贝数，5例高于正常值者Os率为60．0％，余8例OS率为100．0％。结论除了IPI外，NKTL原发部位和病理特征，尤其是Ki-67、CD56、EBER和EBVDNA拷贝数与其临床预后的关系不容忽视，也是NKTL预后判断的独立因素。

Objective To improve the understanding of clinical and pathological features of extranodal NK/T cell lymphoma, nasal type （NKTL） with poor prognosis and provide experiential references via a retrospective analysis. Methods 117 NKTL cases in a single center were retrospectively analyzed of their pathologic diagnoses and clinical manifestations, especially primary sites. Pathological examinations were mainly depended on morphology, immunohistochemisty for immunophenotype, and in situ hybridization for Epstein-Barr virus （EBV） encoded small RNA （EBER）. Polymerase chain reaction （PCR） for whole-blood EBV DNA and T-cell receptor （TCR） gene rearrangement was performed. Chemotherapy and radiotherapy were the main treatments. International prognostic index, Ki-67, 2 years overall survival （OS） rate and progressive free survival （PFS） rate according to the clinical characteristics were included in the univariable analysis. Results The positive rate for CD3 was 90.6 %, 94.0 % for CD56, 92.9 % for CD45ao, 97.9 % for TIA, 97.7 % for Granzyme B and 100.0 % for EBER, respectively. The median age was 43.2 （14-77） years old. The primary nasal NKTL was 95 cases （81.2 %） and their average Ki-67 was （48.3±2.6） %. Other primary extranodal NKTL was 22 cases （18.8 %）, including primary posterior pharyngeal wail, tongue, tonsil, laryngeal, lymph nodes, skin, liver, intestinal, central nervous system and testis. Patients with primary liver or intestinal NKTL or Ki-67 greater than 80 % died in the first year. Patients with primary liver and intestinal NKTL had higher Ki-67 than patients with primary nasal. Compared to the 2 years OS rate 60.0 % and PFS rate 36.0 % of patients with Ki-67 from 60 % to 80 %, the OS rate （86.3 %） and PFS rate （57.5 %） of patients with Ki-67 from 30 % to 60 % were higher （P = 0.047,0.070）, and the OS rate （100.0 %） and PFS rate （78.0 %） of patients with Ki-67 less than 30 % were also higher （P = 0.01, 0.02）. 2 years OS rate of 8 CD56 negative patients whose T cell rearrangement was positive and primary sites were nasal was higher than that of 109 CD56 positive patients （P = 0.03, 0.02）. Among the 13 EBV DNA samples detected, 8 samples were normal and OS rate was 100.0 %. 5 samples had more than 6.1×10^7 opies/ml and OS rate was 60.0 %. Conclusion It is implied that Ki-67, CDs6, EBER, EBV-DNA and primary site are related with the prognosis of NKTL.