Supplementary Material for: Rapid Malignant Transformation of Tubulovillous Adenoma, Initially Presenting as McKittrick–Wheelock Syndrome: a Case-Report

Most cases of colorectal cancer develop from adenomatous polyps, slowly progressing within an average period of 8 – 10 years. McKittrick–Wheelock syndrome (MKWS) is a rare manifestation of tubulovillous adenoma. It generally presents as hypersecretory diarrhea with severe electrolyte and fluid depletion. Roughly 5% of the published cases have reported malignant histopathology associated with MKWS, with little to no data regarding the malignant transformation process of those patients. Our patient was a 53-year-old Asian woman suffering from chronic secretory diarrhea, resulting in severe volume, electrolyte depletion, and pre-renal azotemia, consistent for MKWS. Her symptoms initially improved with sulfasalazine but eventually worsened. She demonstrated signs of systemic (elevated leukocyte, CRP, and LDH) and local inflammation (dense lymphocyte infiltration in colorectal tissue) throughout the course of her disease. Serial pathological results showed rapid neoplastic progression of adenomatous polyp to adenocarcinoma within one year period. Surgical resection resulted in complete symptom resolution. Molecular examination showed a favorable profile of exon 4 KRAS mutation, normal NRAS, BRAF, CDX2, and CK20 expressions. Her molecular pattern did not reflect the profile of an aggressive disease, suggesting the possibility of oncogenic processes outside the major pathways of adenoma to carcinoma progression. Chronic inflammation is a well-established risk factor for colorectal cancer, and PGE2 has been observed as one of the key regulators of tumor initiation and growth. PGE2 is also responsible for hypersecretory diarrhea associated with MKWS.