25 Clear Cell Change in Tubular Adenoma with High-Grade Dysplasia: A Rare Entity Mimicking Clear Cell Carcinoma and Other Malignancies – A Case Report

Introduction/Objective Clear cell change in colonic tubular adenomas (TAs) is an uncommon phenomenon that presents significant diagnostic challenges due to its resemblance to malignancies such as clear cell carcinoma and other malignancies. Due to the scarcity of cases, the cause, clinical relevance, prognosis, immunohistochemical, and molecular features of this change have largely remained poorly understood. This report describes a case of tubular adenoma with high-grade dysplasia and clear cell change, initially misdiagnosed as clear cell carcinoma. Methods/Case Report A 41-year-old female with anemia underwent colonoscopy, revealing multiple polyps in the transverse, descending, and sigmoid colon. The largest polyp, located in the sigmoid colon, measured 1.5 cm. Histological examination showed a conventional tubular adenoma with areas exhibiting complex glandular architecture, clear cytoplasm, and pyknotic randomly arranged nuclei. Epithelial displacement with associated stromal hemorrhage, hemosiderin deposition and muscular hyperplasia consistent with pseudoinvasion was also observed. No evidence of invasion was noted. Immunohistochemical staining revealed positive results for CK20 and CDX2 in both conventional and clear cell areas, while CK7, SALL4, and PAX8 were all negative, excluding the possibility of gynecologic or germ cell tumor involvement, and enteroblastic differentiation. The initial diagnosis of clear cell carcinoma was later revised by a second facility as tubular adenoma with reactive hypersecretory changes. The final diagnosis, confirmed at our institution, was tubular adenoma with extensive high-grade dysplasia and clear cell change. Results NA Conclusion Clear cell change in tubular adenomas can present a diagnostic dilemma. It is exceedingly rare, observed in less than 0.1% of cases and is considered a precursor to clear cell adenocarcinoma of the colon. The biological and clinical significance of this change remains a subject of debate. Accurate diagnosis is critical to prevent its misinterpretation as carcinoma and avoid unnecessary treatment. This case highlights the importance of distinguishing clear cell change in adenomas from malignancies. Ongoing reporting and thorough documentation of such cases are essential to improve our understanding of this rare entity.