Tubal epithelial alterations: evolving concepts

The fallopian tube has emerged as a central organ in the pathogenesis of ovarian cancer, particularly high-grade serous carcinoma (HGSC). Detailed histopathological and molecular analyses have revealed a diverse spectrum of tubal epithelial alterations with varying malignant potentials. This review outlines key lesions including secretory cell outgrowth (SCOUT), p53 signature, serous tubal intraepithelial lesion (STIL), serous tubal intraepithelial carcinoma (STIC), β-catenin signatures, endometrioid tubal intraepithelial neoplasia, and papillary tubal hyperplasia (PTH). The p53 signature, STIL, and STIC are changes originating from secretory cells with underlying TP53 alterations. However, recent findings suggest that these lesions do not necessarily represent a continuous sequence in terms of risk of progression to HGSC. Advances in molecular biology have enabled the estimation of malignant potential of individual lesions. SCOUTs, particularly Type II are thought to be precursors of endometrioid carcinoma. While SCOUTs are frequently observed in the general population, endometrioid carcinoma of the fallopian tube remains extremely rare. PTH has traditionally been regarded as a reactive phenomenon; however morphological and molecular overlaps with low-grade serous carcinoma have recently been suggested. These findings underscore the complexity and heterogeneity of tubal epithelial alterations and suggest that not all lesions follow a linear tumorigenic sequence. Continued integration of morphological, molecular, and spatial analyses will be essential for refining our understanding of tubal pathology and its contribution to gynecological carcinogenesis.