Invasive Stratified Mucin-producing Carcinoma (ISMC) of the Cervix

Abstract

Invasive stratified mucin-producing carcinoma (ISMC) is a recently described tumor with similar morphology to the stratified mucin-producing intraepithelial lesion. Stratified mucin-producing intraepithelial lesion and ISMC likely arise from human papillomavirus (HPV)-infected reserve cells in the cervical transformation zone that retain their pluripotential ability to differentiate into various architectural and cytologic patterns. This is important, as small studies have suggested that ISMC may be a morphologic pattern associated with more aggressive behavior than usual HPV-associated adenocarcinoma. We sought to study the morphologic spectrum of this entity and its associations with other, more conventional patterns of HPV-associated carcinomas. Full slide sets from 52 cases of ISMC were reviewed by an international panel of gynecologic pathologists and classified according to the new International Endocervical Criteria and Classification system. Tumors were categorized as ISMC if they demonstrated stromal invasion by solid nests of neoplastic cells with at least focal areas of mucin stratified throughout the entire thickness, as opposed to conventional tall columnar cells with luminal gland formation. Tumors comprising pure ISMC, and those mixed with other morphologic patterns, were included in the analysis. Twenty-nine pure ISMCs (56%) and 23 ISMCs mixed with other components (44%) were identified. Other components included 13 cases of usual-type adenocarcinoma, 6 adenosquamous carcinoma, 3 mucinous-type adenocarcinoma, 1 high-grade neuroendocrine carcinoma. ISMC displayed architectural diversity (insular, lumen-forming, solid, papillary, trabecular, micropapillary, single cells) and variable cytologic appearance (eosinophilic cytoplasm, cytoplasmic clearing, histiocytoid features, glassy cell-like features, signet ring-like features, bizarre nuclei, squamoid differentiation). Awareness of the spectrum of morphologies in ISMC is important for accurate and reproducible diagnosis so that future studies to determine the clinical significance of ISMC can be conducted.

Tumor Typing of Endocervical Adenocarcinoma: Contemporary Review and Recommendations From the International Society of Gynecological Pathologists

“…ISMC can occur in pure form or it can be associated with usual or mucinous differentiation, and as adenosquamous or neuroendocrine carcinoma. ISMC displays a wide range of architectural diversity, including insular, glandular, solid, papillary, trabecular, micropapillary, and single-cell formations 38 . Their cytologic appearance can also vary, with variable amounts of mucin (mucin-rich to mucin-poor), cytoplasmic clearing, histiocytoid-like features, “glassy cell”–like features, signet-ring–like features, bizarre nuclear atypia, “squamoid differentiation” in the form of cells with dense eosinophilic cytoplasm lacking intercellular bridges, and keratinization.…”

“…Intraepithelial neutrophilic infiltrates, apoptotic bodies, and frequent mitotic figures are commonly easily identified. These features are important to recognize when making a diagnosis of ISMC, as it can mimic other tumor subtypes 27 , 38 .…”

Online Training and Self-assessment in the Histopathologic Classification of Endocervical Adenocarcinoma and Diagnosis of Pattern of Invasion: Evaluation of Participant Performance

“…The subtypes of HPVA are not associated with differences in prognosis, with the exception of invasive stratified mucinous carcinoma (iSMILE/iSMC), which has been shown to be associated with a worse prognosis 19 – 21 and those adenocarcinomas showing a mucinous or micropapillary pattern of invasion, which are associated with more or less favorable prognoses, respectively 12 . It will be important to ensure that there are robust diagnostic criteria for these entities so that appropriate treatment decisions can be made.…”

Invasive Stratified Mucin-Producing Carcinoma (ISMC) of The Uterine Cervix: A Clinicopathological Study of 8 Cases

“…The ve cases were preoperatively misdiagnosed as mucinous adenocarcinoma and squamous cell carcinoma. As described by Stolnicu et al [12] , ISMC can display a wide morphologic spectrum that can impart an ambiguous appearance and make it di cult to classify the tumor, especially to distinguish it from traditional poorly differentiated HPV-associated usual-type and mucinous-type adenocarcinoma.…”