68例肛管直肠黏膜黑色素瘤临床病理特征及预后_赖玉梅.pdf

论著68 例肛管直肠黏膜黑色素瘤临床病理特征及预后赖玉梅1，李忠武1，李欢2，吴艳1，时云飞1，周立新1，楼雨彤1，崔传亮3(1 北京大学肿瘤医院暨北京市肿瘤防治研究所病理科，恶性肿瘤发病机制及转化研究教育部重点实验室，北京100142;2 清华大学附属北京清华长庚医院病理科，清华大学临床医学院，北京102218;3 北京大学肿瘤医院暨北京市肿瘤防治研究所黑色素瘤及肉瘤内科，恶性肿瘤发病机制及转化研究教育部重点实验室，北京100142)摘要目的:总结肛管直肠黏膜黑色素瘤(anorectal mucosal melanoma，AMM)的临床病理特征，分析其预后相关因素。方法:回顾性分析 20102018 年北京大学肿瘤医院收治的原发性 AMM 手术切除标本共 68 例，复阅病理切片评估病理特征，分期采用 Slingluff 分期法。结果:(1)临床特征:患者诊断时中位年龄 61 5 岁，男女比例1 1 62，首发临床表现最常见的是便血(49 例);肿瘤部位最常见的是肛管直肠(66 2%)，其次为直肠(20 6%);诊断时分期为期 28 例(局限期，41 2%)，期 25 例(区域淋巴结转移期，36 8%)，期 15 例(远处转移期，22 1%);5 例行局部扩大切除术，其余为腹会阴联合切除术，48 例术后接受了辅助治疗。(2)病理特征:大体检查88 2%为隆起型肿块，肿瘤中位最大径 3 5 cm，中位厚度 1 25 cm，黏膜肌以下浸润深度 0 5 00 cm(中位1 00 cm);肿瘤浸润达固有肌层者27 例，达肠周脂肪组织者16 例;67 6%为无色素性或色素不明显;细胞形态最常见的是上皮样(45 例，66 2%);89 7%有溃疡形成，35 3%可见坏死，55 9%有血管淋巴管侵犯，30 9%有神经周围侵犯，核分裂象计数中位值 18/mm2;免疫组织化学检测 S100、HMB-45 和 Melan-A 阳性率分别为 92 0%、92 6%、98 0%，Ki-67 增殖指数中位值 50%;53 例进行了 CKIT、BAF 及 NAS 基因突变检测，突变率分别为 17 0%(9 例)，3 8%(2 例)，9 4%(5 例)。(3)预后:66 例患者获得了随访资料，中位随访 17 个月，中位生存时间 17 4个月，1 年、2 年、5 年的总生存率分别为 76 8%、36 8%、17 2%;诊断时淋巴结转移率 56 3%;49 例(84 5%)发生了远隔部位转移，最常见的转移部位是肝;单因素分析显示，肿瘤最大径(3 5 cm)、黏膜肌以下浸润深度(1 0cm)、坏死、血管淋巴管侵犯、BAF 基因突变、术后未行辅助治疗、肿瘤浸润层次深、诊断时分期晚均为总生存期的预后不良因素;多因素分析显示，血管淋巴管侵犯、BAF 基因突变为影响总生存期的独立危险因素，诊断时分期相关的 P 值接近临界值。结论:AMM 患者的总体预后差，血管淋巴管侵犯、BAF 基因突变是独立的预后不良因素;Slingluff 分期法可以有效提示预后，诊断时应详尽评估病理特征，明确分期，并尽可能做基因检测;肿瘤黏膜肌以下的浸润深度可能是比肿瘤厚度更好的预后指标。关键词黏膜黑色素瘤;肛管直肠肿瘤;临床病理特征;预后 中图分类号735 3 文献标志码A 文章编号1671-167X(2023)02-0262-08doi:10 19723/j issn 1671-167X 2023 02 009Clinicopathological features and prognosis of anorectal melanoma:A report of 68casesLAI Yu-mei1，LI Zhong-wu1，LI Huan2，WU Yan1，SHI Yun-fei1，ZHOU Li-xin1，LOU Yu-tong1，CUI Chuan-liang3 1 Key Laboratory of Carcinogenesis and Translational esearch(Ministry of Education)，Department of Pathology，Pe-king University Cancer Hospital Institute，Beijing 100142，China;2 Department of Pathology，Beijing Tsinghua Chang-gung Hospital;School of Clinical Medicine，Tsinghua University;Beijing 102218，China;3 Key Laboratory of Carcino-genesis and Translational esearch(Ministry of Education)，Department of Melanoma and Sarcoma，Peking UniversityCancer Hospital Institute，Beijing 100142，China基金项目:北京大学肿瘤医院科学研究基金(2021-13)、北京大学百度基金资助项目(2020BD036)、首都卫生发展科研专项自主创新项目(首发 2022-02-1024、首发 2018-2-1022)和首都临床特色应用研究(Z141107002514077)Supported by the Science Foundation of Peking UniversityCancer Hospital(2021-13)，the PKU-Baidu Fund(2020BD036)，the Capital s Funds for Health Improvement and esearch(2022-2-1024，2018-2-1022)，the Beijing Municipal Science and Technology Commission Capital Characteristic Clinical Application esearch(Z141107002514077)Corresponding author s e-mail，zhwuli hotmail com网络出版时间:2023-2-1410:15:45网络出版地址:http:/kns cnki net/kcms/detail/114691 202302131323 006 htmlABSTACTObjective:To investigate the clinicopathological characteristics of anorectal mucosal mela-noma(AMM)，and to evaluate the prognostic factors Methods:A total of 68 primary AMM surgical262北京大学学报(医学版)JOUNAL OF PEKING UNIVESITY(HEALTH SCIENCES)Vol55No 2Apr 2023specimens from 2010 to 2018 were retrospectively studied Slides were reviewed to evaluate pathologicalfeatures Slingluff staging method was used for staging esults:(1)Clinical features:The median ageat diagnosis in this group was 61 5 years，with a male-to-female ratio 1 1 62 The most common com-plaint was blooding(49 cases)For anatomic site，anorectum was the prevalent(66 2%)，followed byrectum(20 6%)At the time of diagnosis，28 cases were stage (localized stage，41 2%)，25 caseswere stage (regional lymph node metastasis，36 8%)，and 15 cases were stage (distant metasta-sis，22 1%)Five patients underwent wide local excision，the rest abdominoperineal resection，and 48patients received adjuvant therapy after surgery(2)Pathological features:Grossly 88 2%of the tumorswere exophytic polypoid masses，with the median tumor size 3 5 cm and the median tumor thickness1 25 cm Depth of invasion below lamina muscularis mucosae ranged from 0 5 00 cm(median 1 00cm)The deepest site of tumor invasion reached muscular layer in 27 cases，and perirectal tissue in 16cases Melanin pigmentation was absent or not obvious in 67 6%of the cases The predominant cytologywas epithelioid(45 cases，66 2%)The rate for ulceration，necrosis，lymphovascular invasion，andperineural invasion was 89 7%，35 3%，55 9%，and 30 9%，respectively The median mitotic countwas 18/mm2 The positive rate of S100，HMB-45 and Melan-A were 92 0%，92 6%and 98 0%，re-spectively The median of Ki-67 was 50%The incidences of mutations within CKIT，BAF and NASgenes were 17 0%(9 cases)，3 8%(2 cases)and 9 4%(5 cases)，respectively(3)Prognosis:Survival data were available in 66 patients，with a median follow-up of 17 months and a median survivaltime of 17 4 months The 1-year，2-year and 5-year overall survival rate was 76 8%，36 8%and17 2%，respectively The rate of lymphatic metastasis at diagnosis was 56 3%Forty-nine patients(84 5%)suffered from distant metastasis，and the most frequent metastatic site was liver Univariateanalysis revealed that tumor size(3 5 cm)，depth of invasion below l