A 28-year-old woman from rural India presents with multiple colonic polyps detected on colonoscopy. Genetic testing reveals a germline APC mutation. Which feature best distinguishes familial adenomatous polyposis (APC mutation) from Lynch syndrome (mismatch repair gene mutation)?

Explanation

## Distinguishing FAP from Lynch Syndrome ### Key Discriminating Feature **Key Point:** Familial adenomatous polyposis (APC mutation) is characterized by **pathognomonic extracolonic manifestations** (osteomas, desmoid tumors, congenital hypertrophy of retinal pigment epithelium [CHRPE], jaw cysts), whereas Lynch syndrome (mismatch repair defects) has **minimal extracolonic features** and primarily affects the colon and other internal organs (stomach, ovary, ureter). ### Comparative Table | Feature | FAP (APC) | Lynch Syndrome (MMR) | |---------|-----------|---------------------| | **Polyp count** | Hundreds to thousands | 10–100 adenomas | | **Polyp type** | Adenomatous (uniform) | Adenomatous (scattered) | | **CRC risk** | ~100% by age 50 | ~70–80% by age 70 | | **Osteomas** | Yes (jaw, skull) | No | | **Desmoid tumors** | Yes (10–15%) | No | | **CHRPE** | Yes (75%) | No | | **Jaw cysts** | Yes (common) | No | | **Extracolonic cancers** | Stomach, duodenum, pancreas, thyroid, brain (Turcot variant) | Stomach, ovary, ureter, biliary tract, brain | | **Inheritance** | Autosomal dominant | Autosomal dominant | | **Age of CRC onset** | 40–50 years | 45–65 years | ### Why This Matters **High-Yield:** APC mutations cause a **polyposis phenotype** (hundreds of polyps) with **skeletal and soft tissue manifestations** that are absent in Lynch syndrome. These extracolonic features are the **clinical hallmark** of FAP. **Clinical Pearl:** A patient with multiple colonic polyps + jaw osteomas + CHRPE on ophthalmology exam → **FAP**. A patient with scattered adenomas + family history of endometrial cancer and ovarian cancer → **Lynch syndrome**. ### Mnemonic **FAP = "Familial Adenomatous Polyposis" (polyps + bones + desmoids)** vs. **Lynch = "Lynched by internal cancers" (no extracolonic skeletal features)** [cite:Robbins 10e Ch 7]