Fallopian Tube Cytology for Exploratory Detection of Adnexal Malignancy: Prospective Evaluation of the CytoSaLPs Score in an Ex Vivo Surgical Cohort.

Objective: Ovarian, fallopian tube, and primary peritoneal cancers remain among the deadliest gynecological malignancies, largely because most cases are diagnosed at an advanced stage and no effective screening strategy is currently available. Increasing evidence suggests that many high-grade serous ovarian carcinomas originate from the fallopian tube. We aimed to explore the diagnostic performance of ex vivo fallopian tube cytology and the CytoSaLPs score for detecting tubal and adnexal malignancies in women undergoing salpingectomy or salpingo-oophorectomy. Methods: We conducted a prospective single-center observational study including 304 women undergoing salpingectomy or salpingo-oophorectomy for benign, premalignant or malignant gynecological indications between 2020 and 2023. Ex vivo cytological brushing of the distal fallopian tube was performed before fixation, followed by histopathological examination using the SEE-FIM protocol where appropriate. The primary analysis was performed at the specimen level. Of 544 paired specimens initially available for cytology-histology correlation, 53 non-diagnostic cytological specimens were excluded from the primary diagnostic performance analysis, leaving 491 evaluable paired specimens. Fallopian tube cytological findings were compared with histopathology as the reference standard. The discriminatory ability of the CytoSaLPs score was explored using receiver operating characteristic analysis. Results: Fallopian tube cytology demonstrated high sensitivity for histologically confirmed tubal malignancy, although specificity was moderate. Based on the primary specimen-level analysis, sensitivity was 94.4% and specificity was 71.0%. When fallopian tube cytology was compared with ovarian histology, sensitivity was 72.9% and specificity was 72.4%. For the adnexa considered as a single anatomical entity, sensitivity was 76.5% and specificity was 70.7%. The CytoSaLPs score showed good discriminatory ability for fallopian tube malignancy (AUC 0.8534), moderate discrimination for ovarian malignancy (AUC 0.6790), and fair discrimination for adnexal malignancy (AUC 0.730). The optimal score thresholds were derived from the same dataset and should therefore be considered provisional. Three serous tubal intraepithelial carcinoma lesions were identified histologically; two showed cytological abnormalities and elevated CytoSaLPs scores, whereas one specimen was non-diagnostic. Conclusions: This exploratory proof-of-concept study suggests that ex vivo fallopian tube and the CytoSaLPs score may provide a structured approach for detecting cytological abnormalities associated with tubal and adnexal malignancy. However, the findings were obtained in a tertiary gynecologic oncology population under ex vivo conditions, non-diagnostic specimens occurred in approximately 10% of samples, and the scoring system was developed and evaluated within the same cohort. Independent external validation and evaluation using clinically applicable in vivo sampling methods are required before any clinical implementation can be considered.