Extensive Foamy Cell Change in Serous Tubal Intraepithelial Carcinoma and Tubal High-grade Serous Carcinoma

High-grade serous carcinoma (HGSC) and its precursor, serous tubal intraepithelial carcinoma (STIC), usually exhibit cytologic features reminiscent of fallopian tube secretory cells, their presumed cell-of-origin. While it is not uncommon to encounter focal areas of cytoplasmic clearing in HGSC, we have occasionally observed extensive foamy change in STIC and tubal HGSC, which morphologically mimics mucinous differentiation, and to a lesser extent, clear cell carcinoma. In this report, we describe the histologic, immunophenotypic, and ultrastructural features of STIC/tubal HGSC with extensive foamy cell change. From 5 tubo-ovarian HGSC resections (chemotherapy-naive, n=4; post-neoadjuvant chemotherapy, n=1), STIC (n = 2), or tubal HGSC (n = 3) with extensive foamy cytoplasm were identified. Mucicarmine and Periodic acid Schiff/Alcian blue pH 2.5 stains were negative in the foamy cells, excluding mucin and glycogen accumulation. By immunohistochemistry, the tubal lesions retained Müllerian (tubal) differentiation (PAX8+, n=5; ER+, n=5; WT1+, n=4; PR+, n=3), along with aberrant p53 expression (n=5; concordant with somatic TP53 mutations detected by targeted next-generation sequencing). CDX2 and Napsin-A were absent, while HNF-1β and racemase showed variable staining. Adipophilin showed patchy expression in 2 cases, suggestive of lipid content. Ultrastructurally, foamy STIC/HGSCs contained numerous empty micro-vacuoles and macro-vacuoles, with occasional dilated rough endoplasmic reticulum. In contrast, fallopian tubes with true mucinous metaplasia (n=3) were highlighted by mucin stains and showed reduced or absent Müllerian marker expression. Foamy cell change is a distinctive cytoplasmic alteration in STIC and HGSC. The presence of this histologic feature should prompt immunohistochemical studies to confirm serous differentiation.