Serous Carcinomas Initially Diagnosed on Colon Biopsies: A Case Series Highlighting the Role of p53 to Guide Management

This case series highlights the diagnostic challenge of Müllerian carcinoma presenting as colonic metastasis. The morphology, immunohistochemical work-up, and the utility of p53 immunohistochemistry in delineating between high-grade serous carcinoma and low-grade serous carcinomas are reviewed. Four patients initially presented with metastatic tubo-ovarian carcinoma in a colon biopsy between 2012 and 2023. Specimens and immunohistochemical stains were processed following routine clinical workflows. Colon biopsies in all patients showed a malignancy exhibiting papillary morphology (+/-psammomatous calcifications and "bottom-heavy" architecture) or poorly differentiated morphology. All patients were evaluated for metastasis by immunohistochemistry to include keratins (KRT7 and KRT20 or AE1/AE3), CDX2 or SATB2 (for gastrointestinal origin), and PAX8 (for Müllerian origin). Once Müllerian origin was established, further interrogation of the tumor with WT1, p53, and KI67 was essential to establish a diagnosis of high-grade serous carcinoma or low-grade serous carcinoma. Differing clinical management between high-grade serous carcinoma and low-grade serous carcinoma is summarized. Papillary morphology, "bottom-heavy" architecture, and psammomatous calcifications should prompt a metastatic work-up in colon biopsies. When a Müllerian site of origin is identified, a follow-up panel of markers-to include p53-should be used to distinguish between high-grade serous carcinoma and low-grade serous carcinoma to guide initial management options.