Recommendations for diagnosing STIC: a systematic review and meta-analysis

Area of Science:

• Gynecologic Pathology
• Oncogenesis
• Cancer Precursor Lesions

Background:

• High-grade serous ovarian cancer (HGSOC) understanding has advanced, including precursor lesions like serous tubal intraepithelial carcinoma (STIC).
• Accurate STIC diagnosis is crucial for patient prognosis and guiding risk-reducing surgical strategies (e.g., salpingectomy with delayed oophorectomy).
• Current STIC diagnosis faces challenges with moderate reproducibility among pathologists.

Purpose of the Study:

• To review diagnostic approaches for STIC.
• To analyze factors influencing STIC diagnosis, including grossing protocols, morphology, pathologist training, and immunohistochemistry.
• To propose a framework for improving STIC diagnostic adequacy and reproducibility.

Main Methods:

• Literature search identifying 39 studies on risk-reducing salpingo-oophorectomy in BRCA1/2 carriers.
• Meta-analysis of pooled STIC proportion.
• Analysis of reported grossing protocols, morphological criteria, pathologist training, and immunohistochemistry use.

Main Results:

• A pooled STIC proportion of 2.8% (95% CI, 2.0-3.7) was estimated in 6833 patients.
• Key morphological features of STIC include loss of cell polarity, nuclear pleomorphism, high nuclear-to-cytoplasmic ratio, mitotic activity, pseudostratification, and prominent nucleoli.
• Studies fully embedding specimens showed a higher STIC incidence (3.2%) than those not fully embedding (1.7%), though not statistically significant (p=0.24).

Conclusions:

• A structured diagnostic framework is proposed to enhance STIC diagnosis.
• This framework includes the SEE-FIM grossing protocol, evaluation by a subspecialized gynecopathologist, judicious use of immunohistochemistry, and second opinions.
• Implementing this framework aims to improve diagnostic accuracy and reproducibility for STIC.