Long Xinyuan, Ma Xiaoting, Xiao Wei, Lv Jinghuan
Department of Pathology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, P.R. China.
Int J Gynecol Pathol. 2025 May 1;44(3):268-273. doi: 10.1097/PGP.0000000000001075. Epub 2024 Oct 30.
Invasive stratified mucin-producing carcinoma (ISMC) is a specific type of adenocarcinoma of the cervix, which is associated with human papillomavirus infection and often coexists with other types of carcinomas. However, given its rarity, understanding of this disease remains insufficient. We present a unique case of ISMC of the cervix coexisting with a high-grade squamous intraepithelial lesion (HSIL). In addition to histologic and immunohistochemical feature observation, genomic profiling of the 2 lesions was performed. Histologically, the ISMC and HSIL lesions were independent of each other. Aside from the typical morphology, various architectural features of ISMC were observed. Immunohistochemically, the ISMC and HSIL lesions were strongly and diffusely positive for p16 and exhibited high Ki-67 expression. The ISMC lesion was also positive for CK7, MUC5AC, and MUC6, while it was negative for PAX-8. The HSIL lesion was positive for CK5/6 and p40. The combined positive score of PD-L1 was 55. The other markers were all negative in both lesions, and the p53 was wild-type. Next-generation sequencing analysis revealed multiple gene mutations in the ISMC and HSIL lesions. A total of 88 gene mutations were identified in the ISMC lesion, while 20 gene mutations were identified in the HSIL lesion. Three mutations ( ERBB2 , histidine decarboxylase gene [ HDC ], and BSN ) were detected in the ISMC and HSIL lesions. Both lesions had a low tumor mutation burden and microsatellite-stable status. No copy number-associated variants or structural variations were identified in either lesion. These results suggest that patients with ISMC may benefit from PD-L1 immunotherapy and targeted therapy.
浸润性分层黏液腺癌（ISMC）是子宫颈腺癌的一种特殊类型，与人类乳头瘤病毒感染相关，且常与其他类型的癌共存。然而，鉴于其罕见性，对该疾病的了解仍然不足。我们报告了一例子宫颈ISMC与高级别鳞状上皮内病变（HSIL）共存的独特病例。除了观察组织学和免疫组化特征外，还对这两种病变进行了基因组分析。组织学上，ISMC和HSIL病变相互独立。除了典型形态外，还观察到ISMC的各种结构特征。免疫组化方面，ISMC和HSIL病变对p16呈强弥漫性阳性，且Ki-67表达高。ISMC病变对CK7、MUC5AC和MUC6也呈阳性，而对PAX-8呈阴性。HSIL病变对CK5/6和p40呈阳性。PD-L1的联合阳性评分是55。其他标志物在两种病变中均为阴性，且p53为野生型。二代测序分析揭示了ISMC和HSIL病变中的多个基因突变。在ISMC病变中总共鉴定出88个基因突变，而在HSIL病变中鉴定出20个基因突变。在ISMC和HSIL病变中检测到三个共同突变（ERBB2、组氨酸脱羧酶基因[HDC]和BSN）。两种病变的肿瘤突变负荷均较低且微卫星稳定。在任何一种病变中均未鉴定出与拷贝数相关的变异或结构变异。这些结果表明，ISMC患者可能从PD-L1免疫治疗和靶向治疗中获益。
