目的 对一种新命名的人乳头瘤病毒（HPV）相关的宫颈黏液腺癌——宫颈浸润性复层产黏液性癌（ISMC）进行病例分析,为这种罕见疾病提供更多临床和病理数据。方法 回顾性分析3例ISMC,并结合相关文献对其病理学特征、免疫表型、HPV基因分型及预后进行探讨。结果 ISMC肿瘤细胞表现为结构模式和细胞形态的多样性。肿瘤细胞胞质内含多少不等的黏液,瘤巢内外均可见中性粒细胞浸润。3例均发现凋亡小体和有丝分裂。免疫组织化学染色显示p16和CK7呈弥漫强（+）,PAX8、p40和CK5/6巢周少量（+）。结论 ISMC是一种少见、具有广泛形态学谱的HPV相关腺癌。PAX8、CK5/6和p40独特的表达模式使其可以作为ISMC诊断的有效标志物。ISMC预后较差,即便检测到少量ISMC成分也应在诊断中注明其占比,此点尤为重要。
Objective To conduct a case study on invasive stratified mucin-producing carcinoma （ISMC）, a newly named human papillomavirus （HPV）-related cervical mucinous adenocarcinoma, and provide clinical and pathological data for this rare disease. Methods Three cases of ISMC were retrospectively analyzed, and the pathological characteristics, immunophenotype, HPV genotyping, and prognosis were explored in combination with relevant literature. Results ISMC tumor cells exhibited a diversity of structural patterns and cell morphology. The cytoplasm of the tumor cells contained different amounts of mucus, and neutrophil infiltration could be seen around the nests and intratumorally. Apoptotic bodies and mitosis were found in all three cases. Immunohistochemistry showed p16 and CK7 were diffuse and strong （+）, while PAX8, p40, and CK5/6 were slight （+） around the nests . Conclusion ISMC is a rare, HPV-associated adenocarcinoma with a broad morphological spectrum. The unique expression patterns of PAX8, CK5/6, and p40 can be used as effective markers for ISMC diagnosis. ISMC has a poor prognosis, and it is important that even if a small amount of ISMC components are detected, their percentages should be noted in the diagnosis.
[1] Park E, Kim YT, Kim S, et al.Immunohistochemical and genetic characteristics of HPV-associated endocervical carcinoma with an invasive stratified mucin-producing carcinoma (ISMC) component[J]. Mod Pathol, 2021, 34(9): 1738-1749.
[2] Lastra RR, Park KJ, Schoolmeester JK.Invasive stratified mucin-producing carcinoma and stratified mucin-producing intraepithelial lesion (SMILE): 15 cases presenting a spectrum of cervical neoplasia with description of a distinctive variant of invasive adenocarcinoma[J]. Am J Surg Pathol, 2016, 40(2):262-269.
[3] Cree IA, White VA, Indave BI, et al.Revising the WHO classification: female genital tract tumours[J]. Histopathology,2020, 76(1): 151-156.
[4] Stolnicu S, Boros M, Segura S, et al.Invasive stratified mucinous carcinoma (iSMC) of the cervix often presents with high-risk features that are determinants of poor outcome: an international multicenter study[J]. Am J Surg Pathol, 2020, 44(10): 1374-1380.
[5] Stolnicu S, Segura S, Parra-Herran C, et al.Invasive stratified mucin-producing carcinoma (ISMC) of the cervix: a study on morphologic diversity[J].Am J Surg Pathol,2020,44(7):873-880.
[6] Lin T, Wang W, Xu L, et al.Invasive stratified mucin-producing carcinoma (ISMC) of uterine cervix: description of pathological findings and prognosis factors in a series of 15 Chinese patients[J].Arch Gynecol Obstet,2022, 306(5):1703-1709.
[7] Onishi J, Sato Y, Sawaguchi A, et al.Stratified mucin-producing intraepithelial lesion with invasive carcinoma: 12 cases with immunohistochemical and ultrastructural findings[J]. Hum Pathol, 2016, 55: 174-181.
[8] Horn LC, Handzel R, Borte G, et al.Invasive stratified mucin-producing carcinoma (i-SMILE) of the uterine cervix: report of a case series and review of the literature indicating poor prognostic subtype of cervical adenocarcinoma[J]. J Cancer Res Clin Oncol, 2019, 145(10): 2573-2582.
[9] Zhao X,Qin Y,Shen X,et al.The coexistence of invasive stratified mucin-producing carcinoma, mucinous carcinoma and non-specific type and squamous cell carcinoma of the uterine cervix: a case report[J]. Int J Clin Exp Pathol, 2020, 13(8):2187-2191.
[10] Park JJ, Sun D, Quade BJ, et al.Stratified mucin-producing intraepithelial lesions of the cervix: adenosquamous or columnar cell neoplasia?[J]. Am J Surg Pathol, 2000, 24(10): 1414-1419.
[11] Stolnicu S, Hoang L, Chiu D, et al.Clinical outcomes of HPV-associated and unassociated endocervical adenocarcinomas categorized by the International Endocervical Adenocarcinoma Criteria and Classification (IECC)[J]. Am J Surg Pathol, 2019, 43(4): 466-474.
[12] Feng S, Ge Y, Ma X, et al.The genomic landscape of invasive stratified mucin-producing carcinoma of the uterine cervix: the first description based on whole-exome sequencing[J]. J Transl Med, 2022, 20(1): 187.
[13] Sal V, Kahramanoglu I, Turan H, et al.Primary signet ring cell carcinoma of the cervix: a case report and review of the literature[J]. Int J Surg Case Rep, 2016, 21: 1-5.
[14] Bhatla N, Aoki D, Sharma DN, et al.Cancer of the cervix uteri[J]. Int J Gynaecol Obstet, 2018, 143(Suppl 2): 22-36.
[15] Stolnicu S, Hoang L, Hanko-Bauer O, et al.Cervical adenosquamous carcinoma: detailed analysis of morphology,immunohistochemical profile, and clinical outcomes in 59 cases[J]. Mod Pathol, 2019, 32(2): 269-279.
