Precursors of High-Grade Serous Carcinoma

Knowledge of the molecular/genetic alterations and of the natural history of the cancer precursors that precede high-grade serous carcinoma continues to evolve. Comprehensive examination of the fallopian tubes removed from women at high genetic risk of ovarian cancer, usually carriers of germline mutations of BRCA1 or BRCA2, led to the discovery of serous cancer precursors in the distal end of the fallopian tube. Controversy about the cell of origin of high-grade serous carcinoma still exists. The presence of serous intraepithelial carcinoma (STIC) in the fallopian tube in the absence of invasive disease and the coexistence of STIC with high-grade serous carcinoma in sporadic as well as in hereditary HGSC strongly support the tubal epithelium as cell of origin. The consistent and reproducible diagnosis of STIC and related lesions depends on both careful processing of the fallopian tube following a SEE-FIM-like protocol and the application of a diagnostic algorithm incorporating morphology and immunohistochemistry. STIC and HGSC share common molecular and genetic alterations. Other lesions considered to be latent cancer precursors, the p53 signature and secretory cell outgrowth (SCOUT), have been described.