['Additional sectioning and', 'AI', '-assisted diagnosis reveal underdiagnosis of serous (pre)malignancies in fallopian tube specimen from', 'BRCA', '1/2 carriers']

A. Bouwmeester, T. Gootzen, M. Nobbenhuis, V. Rudaitis, C. van den Berg, H. van Beekhuizen, L. Alcalá, D. Smedts, N. Visser, V. Verhoef, T. Jonges, R. Zweemer, A. Leon-Catillo, C. Lems, J. de Hullu, J. van der Laak, M. Steenbeek and M. Simons

Histopathology 2026.

DOI

Aim

Germline

BRCA1/2

pathogenic variant carriers are at increased risk for high-grade serous carcinoma (HGSC) and are therefore advised to have a risk-reducing salpingo-oophorectomy (RRSO) around the age of 40. A risk of 0.9% to develop peritoneal HGSC (pHGSC) remains, which increases up to 27.5% when serous tubal intraepithelial carcinoma (STIC) is detected at RRSO. The relationship between the detection of STIC and the occurrence of pHGSC is still poorly understood. Here, we investigated the role of tissue sampling by examining deeper sections of the tubal tissue of RRSO specimens.

Methods

Four groups of patients were included: (1) STIC without pHGSC (

n

= 5); (2) STIC with pHGSC (

n

= 4); (3) no STIC and no pHGSC (

n

= 5); and (4) no STIC and pHGSC (

n

= 5). Follow-up time was 10 years or until the development of pHGSC. Deeper sections were cut at 150 mm intervals. A deep learning model was used to support STIC detection.

Results

A focus of isolated STIC or HGSC was found in the deeper sections of all patients who developed pHGSC, while these patients did not have STIC or HGSC at the initial diagnosis. No patients with STIC and pHGSC showed HGSC in the deeper sections. We observed that five STICs presented as serous tubal intraepithelial lesions (STILs) in adjacent slides based on low Ki-67 expression.

Conclusions

Our findings underscore the hypothesis that pHGSC originates in the fallopian tube and confirm that invasiveness is not necessary for disease progression of STIC towards pHGSC. Furthermore, deeper sections might be of additional value when STIL is diagnosed.