Diagnostic Challenges in Sessile Serrated Lesions: Progression to Adenocarcinoma in a High-Risk Patient

BACKGROUND Sessile serrated lesions (SSLs) are precursors in approximately 20-30% of colorectal cancer (CRC) cases, often characterized by B-Raf proto-oncogene (BRAF) mutations and CpG island methylator phenotype (CIMP), and follow the serrated neoplasia pathway. Histopathological differentiation between SSLs with dysplasia and conventional adenomas is diagnostically challenging because their visual and pathologic features often overlap. SSLs with dysplasia carry a high malignant potential and can progress rapidly to invasive carcinoma, underscoring the need for accurate classification and timely intervention. CASE REPORT A 78-year-old man with a history of acute myeloid leukemia (treated with bone marrow transplant), Barrett's esophagus, and ulcerative colitis in remission underwent colonoscopy, which identified an 11-mm polyp. It was resected piecemeal and initially reported as showing features of both a sessile serrated adenoma (SSA) and a tubular adenoma (TA). Given the mixed histology, a follow-up colonoscopy was performed 6 months later, revealing an invasive, moderately-differentiated adenocarcinoma with mismatch repair deficiency (loss of MLH1 and PMS2) and a BRAF V600E mutation. Surgical resection confirmed stage III CRC with lymph node involvement. Retrospective pathological review reclassified the original lesion as an SSL with dysplasia (SSL-D). CONCLUSIONS This case highlights the diagnostic challenges of SSLs, particularly when lesions are resected piecemeal. For accurate diagnosis and optimal patient management, it is essential that there is effective communication between pathologists and endoscopists about the morphological characteristics of the polyp, and the reading pathologists should communicate with endoscopists for any clarification. A multidisciplinary, collaborative approach is crucial for high-risk lesions.