269 Pap Smear as the First Clue: Fallopian Tube High-Grade Serous Carcinoma Presenting as Atypical Glandular Cells on Cervical Cytology

Abstract Introduction/Objective High-grade serous carcinoma (HGSC) of the fallopian tube can rarely disseminate via intramucosal spread along the endometrial and cervical surfaces, mimicking primary endometrial or cervical adenocarcinoma. Intraepithelial extension to the cervix —especially in the absence of a pelvic mass— can lead to diagnostic misclassification as a cervical primary. We present a case of fallopian tube HGSC initially detected on cervical cytology, mimicking a primary cervical adenocarcinoma due to its mucosal spread. This case underscores the critical role of integrated morphologic, immunohistochemical, and clinical assessment in determining the tumor’s true origin. Methods/Case Report A 59-year-old woman undergoing routine cervical cancer screening had atypical glandular cells of undetermined significance (AGUS) on Pap smear. Cervical biopsy, endocervical curettage (ECC), and endometrial biopsy (EMB) revealed rare, detached, highly atypical glandular cells. The degree of atypia and aberrant p53 overexpression raised concern for a carcinoma. Cervical conization showed a small focus of a mucosa-confined atypical glandular proliferation with marked cytologic atypia, brisk mitoses, and high Ki-67. Immunostains demonstrated diffuse p16 and ER positivity, patchy PR expression, and strong aberrant p53 overexpression. High-risk HPV in situ hybridization, CEA, and vimentin were negative—findings that argued against an HPV-associated cervical adenocarcinoma and suggestive of an upper Mullerian primary. Interestingly, the concurrent endometrial curettage showed rare minute strips of atrophic surface endometrium. Subsequent total hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node biopsy revealed bilateral serous tubal intraepithelial carcinoma (STIC) and a microscopic 6 mm focus of invasive HGSC in the left fallopian tube. No carcinoma was found in the cervix, endometrium, or ovaries, all of which were entirely submitted. Results NA Conclusion This case highlights a diagnostically deceptive presentation of fallopian tube high-grade serous carcinoma (HGSC) manifesting as abnormal cervical cytology due to mucosal spread. Negative high-risk HPV in situ hybridization, along with aberrant p53 overexpression, prompted further investigation and ultimately confirmed a tubal origin. Similar “crawling” patterns of superficial spread have been reported and can easily lead to misclassification as a primary cervical neoplasm. Accurate diagnosis requires a high index of suspicion and careful integration of morphology, immunohistochemistry, HPV testing, and complete adnexal sampling to avoid diagnostic error and ensure appropriate clinical management.