image: (a) Papillary growth pattern with columnar, pseudostratified tumor cells. This morphology can mimic HPV-associated usual-type endocervical adenocarcinoma. (b) Solid growth composed of round to ovoid tumor cells, with frequent mitotic figures including atypical mitoses. (c) Papillary architecture with hobnailing high-grade tumor cells and clear cytoplasm, which requires distinction from clear cell carcinoma. (d) Infiltrating glandular tumor cells with hyperchromatic, “smudgy” nuclei. Conspicuous mitoses, including atypical forms, and apoptosis are present. (e) Discohesive tumor cells with marked nuclear pleomorphism. (f) Loosely cohesive tumor cells associated with psammoma bodies. Magnification: a-f: 400×.
Credit: Tong Sun
Background and objectives
High-grade serous carcinoma is a rare diagnosis in cervical biopsies. Cervical serous carcinoma is no longer recognized as a primary cervical tumor in the 2020 World Health Organization classification. This study aimed to characterize the clinicopathologic, immunohistochemical, and molecular features of high-grade serous carcinoma identified in cervical or endocervical biopsies, to assess tumor origin and ensure accurate classification.
Methods
Fifty-nine cases originally diagnosed as “serous carcinoma” or “high-grade serous carcinoma” in cervical or endocervical biopsies from 2013 to 2023 were retrospectively reviewed. Clinical data, radiologic findings, and follow-up information were analyzed. Histologic features and immunohistochemical profiles were re-evaluated. Targeted next-generation sequencing was performed on a subset of cases.
Results
The majority of tumors (96%) were determined to originate from the endometrium (n = 47) or the tubo-ovarian region (n = 4), with only one case confirmed as a primary cervical carcinoma. Morphologic patterns varied and could mimic human papillomavirus-associated adenocarcinoma. All tumors showed aberrant p53 expression and diffuse p16 positivity. WT-1 was expressed in all tubo-ovarian tumors but in only 12% of endometrial cases. Estrogen receptor and progesterone receptor were frequently positive in endometrial tumors; human epidermal growth factor receptor 2 was positive in 31% of cases. Molecular analysis confirmed tumor protein p53 mutations and other alterations typical of uterine serous carcinoma.
Conclusions
High-grade serous carcinoma identified in cervical biopsies is overwhelmingly secondary to upper genital tract tumors, most commonly of endometrial origin. A small subset of endocervical adenocarcinomas may mimic serous carcinoma. These findings support the exclusion of primary cervical serous carcinoma from the current World Health Organization classification and emphasize the importance of accurate diagnosis for appropriate management.
Full text
https://www.xiahepublishing.com/2771-165X/JCTP-2025-00023
The study was recently published in the Journal of Clinical and Translational Pathology.
Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.
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Journal
Journal of Clinical and Translational Pathology
Article Title
High-grade Serous Carcinomas Identified in Cervical Biopsies: A Clinicopathologic Study Supporting the Exclusion of Cervical Serous Carcinoma from World Health Organization Classification
Article Publication Date
18-Aug-2025