Cervical carcinomas with serous-like papillary and micropapillary components: illustrating the heterogeneity of primary cervical carcinomas

Abstract

Recent changes in the classification of cervical adenocarcinomas have re-categorized serous carcinoma as potentially nonexistent. However, clinical and pathological profiles of cervical adenocarcinomas with serous-like morphological features have not been systematically evaluated using the latest taxonomy and biomarkers. We studied 14 cases of primary cervical carcinomas with serous-like morphologies (papillary and micropapillary patterns). None of these cases exhibited evidence of serous carcinoma involving the upper tracts. Patient ages ranged between 34 and 86 years, most presented with abnormal uterine bleeding. Histologically, ten cases were classified as human papillomavirus (HPV)-associated carcinomas (eight usual-type endocervical adenocarcinomas and two adenosquamous carcinomas), of which six exhibited a papillary pattern and four had a micropapillary pattern. The four remaining cases were HPV-independent gastric-type adenocarcinomas, which displayed a papillary pattern in one case and a micropapillary pattern in three others. All ten HPV-associated carcinomas displayed block positive p16 and wild-type p53 by immunohistochemistry, with nine of them confirmed by HPV testing. Two of the four gastric-type adenocarcinomas had mutation-type p53, one of which also being p16 block positive. HER2 overexpression was demonstrated in 3/14 (21.4%) cases (2 HPV-associated and 1 HPV-independent). PD-L1 expression was identified in 4/10 (40%) cases, all HPV-associated. Targeted next-generation sequencing was performed in two cases with a micropapillary pattern, revealing a missense variant in ATM in an HPV-associated tumor and missense variants in TP53 and SMARCB1 in an HPV-independent tumor. The results demonstrated that primary endocervical adenocarcinomas can mimic the appearance of serous carcinoma, while not representing serous carcinoma. Serous-like papillary and micropapillary patterns may be present in both HPV-associated and HPV-independent cervical carcinomas, but none of the cases studied were unequivocally serous upon detailed analysis. Our findings support the exclusion of “cervical serous carcinoma” from existing classifications of cervical adenocarcinoma.