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Invasive stratified mucin-producing carcinoma (ISMC) is a recently described histologic variant of high-risk human papillomavirus (HPV)-associated endocervical adenocarcinoma, as the putative invasive counterpart of the stratified mucin-producing intraepithelial lesion (SMILE). ISMC can display variable architectural patterns and usually coexists with other more conventional types of HPV-associated carcinomas, which makes diagnosis and differential diagnosis of ISMC is difficult for pathologists. Moreover, the prognosis of ISMC is still controversial. We analyzed 6 ISMCs with detailed pathological and clinical information. Intraepithelial lesion, including 1 high-grade squamous intraepithelial lesion and 1 SMILE, was found. Various architectures were observed (including nest, glandular, solid, trabecular, and single cell). Nuclear peripheral palisading, apoptotic bodies and mitoses, and variable cytoplasmic mucin vacuoles were seen in all of our cases. The predominance of neutrophils infiltration was seen in only 1 tumor. All the tumors infiltrated the cervical stroma in Silva pattern C manner. p63 and/or p40 was characteristically expressed in the peripheral cells in only 2 cases. High-risk HPV infection was observed in 3/3 detected cases. All the patients were alive during the follow-up time. Recognition of this infrequent tumor may help pathologists and oncologists for an accurate diagnosis and a better understanding of the clinicopathological behavior.

Invasive stratified mucin-producing carcinoma (ISMC) of the uterine cervix: An analysis of 6 cases with distinctive clinicopathological features