A 62-year-old woman from Mumbai undergoes colonoscopy for iron-deficiency anemia. A 15 mm sessile polyp is found in the right colon. Biopsy shows elongated crypts with a serrated outline, mucin-rich epithelium, and focal low-grade dysplasia. Immunohistochemistry shows loss of MLH1 expression. What is the most likely diagnosis and the recommended management?

Explanation

## Diagnosis: Sessile Serrated Adenoma (SSA) ### Key Histopathological Features **Key Point:** Sessile serrated adenomas are a distinct category of colorectal polyp with high malignant potential and unique molecular features. The clinical presentation is diagnostic of SSA: - **Size 15 mm** — SSAs are typically 5–20 mm - **Right colon location** — SSAs have a predilection for the right (proximal) colon - **Serrated crypt outline** — true serration (not just saw-tooth infolding) - **Mucin-rich epithelium** — characteristic of SSA - **Focal dysplasia** — SSAs often show low-grade dysplasia - **MLH1 loss** — pathognomonic for SSA; caused by BRAF V600E mutation and MLH1 promoter methylation ### Comparison: SSA vs Hyperplastic Polyp | Feature | Hyperplastic | Sessile Serrated Adenoma | | --- | --- | --- | | Size | < 5 mm | 5–20 mm | | Location | Rectosigmoid | Right colon | | Crypt Pattern | Saw-tooth (infolding) | True serration | | Dysplasia | Absent | Often present (low-grade) | | MLH1 Status | Normal | Loss | | Molecular Driver | None (benign) | BRAF V600E + MLH1 methylation | | Malignant Potential | None | High ("serrated pathway") | | Interval Cancer Risk | None | Increased | ### Management Algorithm ```mermaid flowchart TD A[Sessile Serrated Adenoma found]:::outcome --> B{Complete polypectomy?}:::decision B -->|Yes| C[Repeat colonoscopy in 1 year]:::action B -->|No| D[Residual tissue: repeat in 2-3 months]:::action C --> E[If no polyps: return to standard screening]:::action D --> F[Confirm complete removal]:::action ``` ### Clinical Significance **High-Yield:** SSAs are part of the **"serrated pathway"** to colorectal cancer, distinct from the adenoma-carcinoma sequence. They account for 15–30% of colorectal cancers and are associated with **interval cancers** (cancers diagnosed between screening intervals). **Warning:** Hyperplastic polyps < 5 mm do NOT require follow-up, but SSAs ALWAYS require complete polypectomy and surveillance. Failure to recognize SSA is a common cause of interval colorectal cancer. **Mnemonic: SSA Features — "SERRATED BRAF"** - **S**errated crypts (true serration) - **E**longated crypts - **R**ight colon predilection - **R**isk of dysplasia - **A**typical location (proximal) - **T**ypically 5–20 mm - **E**pithelium: mucin-rich - **D**efective MLH1 (loss) - **B**RAF V600E mutation - **R**epeat colonoscopy in 1 year - **A**dvanced surveillance needed - **F**ailure to remove = interval cancer risk **Clinical Pearl:** The loss of MLH1 in SSA is epigenetic (promoter methylation), not genetic. This explains why SSAs can progress rapidly to microsatellite-unstable cancers without a long adenoma dwell time.