原位甲下黑色素瘤的临床病理学特征和预后分析

Clinicopathological and prognostic features of subungual melanoma in situ

目的:探讨原位甲下黑色素瘤(subungual melanoma in situ,SMIS)的临床病理学、免疫组织化学、分子生物学及预后。方法:收集复旦大学附属肿瘤医院2018—2022年间SMIS共30例,评估其病理学特征,分析免疫组织化学和黑色素瘤第一代组合荧光原位杂交(FISH)联合9p21(CDKN2A)和8q24(MYC)基因检测结果,并随访患者生存情况。结果:患者30例,男性8例,女性22例,年龄范围为22~65岁(中位年龄48岁)。所有病例均表现为甲纵行黑线,最常受累的部位是大拇指(16/30,53.3%),56.7%(17/30)的病例具有Hutchinson现象。30例都表现为甲母质上皮黑色素细胞的增生,细胞核深染且不规则,细胞密度计数(melanocyte count,MC)范围30~185。29例细胞呈小到中等大小(29/30,96.7%)。30例均有Paget样播散现象,56.7%(17/30)的病例甲母质/甲床上皮内增生的肿瘤细胞中可见核分裂象。19例镜下见皮肤累及,其中4例同时累及附属器。SOX10、PNL2、Melan A、HMB45、S-100蛋白和PRAME蛋白的阳性率分别为100.0%、100.0%、96.0%、95.0%、76.9%和83.3%。9例行FISH检测,其中6例阳性。28例具随访资料,均无病生存。结论:SMIS细胞以小到中等大小为主。MC较高、核深染且不规则、Paget样播散现象、上皮内增生的黑色素细胞出现核分裂象、累及周围皮肤及附属器等都是诊断SMIS的重要线索。SOX10和PRAME等免疫组织化学以及FISH检测可以协助诊断。

ObjectiveTo investigate the clinicopathological characteristics,immunohistochemical profiles,molecular features,and prognosis of subungual melanoma in situ(SMIS).MethodsThirty cases of SMIS were collected in Fudan University Shanghai Cancer Center,Shanghai,China from 2018 to 2022.The clinicopathological characteristics and follow‐up data were retrospectively analyzed.Histopathologic evaluation and immunohistochemical studies were carried out.By using Vysis melanoma fluorescence in situ hybridization(FISH)probe kit,combined with 9p21(CDKN2A)and 8q24(MYC)assays were performed.ResultsThere were 8 males and 22 females.The patients′ages ranged from 22 to 65 years(median 48 years).All patients presented with longitudinal melanonychia involving a single digit.Thumb was the most commonly affected digit(16/30,53.3%).56.7%(17/30)of the cases presented with Hutchinson′s sign.Microscopically,melanocytes proliferated along the dermo-epithelial junction.Hyperchromatism and nuclear pleomorphism were two of the most common histological features.The melanocyte count ranged from 30 to 185.Most cases showed small to medium nuclear enlargement(29/30,96.7%).Pagetoid spread was seen in all cases.Intra-epithelial mitoses were identified in 56.7%(17/30)of the cases.Involvement of nailfold was found in 19 cases,4 of which were accompanied by cutaneous adnexal extension.The positive rates of SOX10,PNL2,Melan A,HMB45,S-100,and PRAME were 100.0%,100.0%,96.0%,95.0%,76.9%,and 83.3%,respectively.FISH analysis was positive in 6/9 of the cases.Follow-up data were available in 28 patients,and all of them were alive without disease.ConclusionsSMIS mainly shows small to medium-sized cells.High melanocyte count,hyperchromatism,nuclear pleomorphism,Pagetoid spreading,intra-epithelial mitosis,nailfold involvement,and cutaneous adnexal extension are important diagnostic hallmarks.Immunohistochemistry including SOX10 and PRAME,combined with FISH analysis,is valuable for the diagnosis of SMIS.