Why is sigmoidoscopy (examination of the sigmoid colon and rectum using a flexible tube with a camera) recommended in a postmenopausal woman with carcinoma (cancer) of the endometrium (uterine lining)?

Sigmoidoscopy in Endometrial Carcinoma: Screening for Lynch Syndrome-Associated Colorectal Cancer

Sigmoidoscopy is performed in patients with endometrial carcinoma primarily to screen for synchronous or metachronous colorectal cancer when Lynch syndrome (hereditary non-polyposis colorectal cancer) is suspected or confirmed, as these patients have up to 80% lifetime risk of colorectal cancer. 1, 2

Primary Indication: Lynch Syndrome Surveillance

Universal Tumor Testing Requirement

• All endometrial tumors must undergo immunohistochemical staining for DNA mismatch repair (MMR) proteins (MLH1, MSH2, MSH6, PMS2) to identify Lynch syndrome, regardless of patient age, family history, or histologic features 1, 2
• When MMR deficiency is detected (excluding methylated MLH1), patients require genetic counseling and germline mutation testing to confirm Lynch syndrome 1, 2

Colorectal Cancer Risk in Lynch Syndrome

• Women with confirmed Lynch syndrome have a 30-60% lifetime risk of endometrial cancer and up to 80% lifetime risk of colorectal cancer 1, 2
• Annual colonoscopy (not just sigmoidoscopy) is mandatory for all patients with confirmed Lynch syndrome for colorectal cancer surveillance 1, 2
• The NCCN recommends interventions to decrease colorectal cancer risk, including annual colonoscopy, as part of comprehensive Lynch syndrome management 1

Secondary Consideration: Evaluation of Metastatic Disease

Rare but Documented Metastatic Pattern

• Endometrial carcinoma can rarely metastasize to the sigmoid colon and rectum, though this is uncommon in the absence of endometriosis 3
• When colonic metastasis occurs, it typically presents as a solitary lesion that can masquerade as primary colorectal carcinoma on colonoscopy 3
• Immunohistochemistry distinguishes endometrial from colorectal origin: endometrial cancers are cytokeratin-7 positive and cytokeratin-20 negative, whereas primary colon cancers show the opposite pattern 3

Clinical Context for Sigmoidoscopy

• Sigmoidoscopy or colonoscopy may be indicated when patients present with gastrointestinal symptoms (hematochezia, change in bowel habits) or when imaging suggests extrauterine disease involving the bowel 3
• The NCCN guidelines recommend CT, MRI, or FDG-PET/CT to assess disease extent and evaluate for metastatic disease based on clinical symptoms, physical findings, or abnormal laboratory findings 1

Algorithmic Approach to Colorectal Evaluation

Step 1: Universal MMR Testing

• Perform immunohistochemistry for MLH1, MSH2, MSH6, PMS2 on all endometrial cancer specimens 1, 2
• If MLH1 loss detected → perform MLH1 promoter methylation testing 1, 2
  • Methylated = sporadic cancer, no germline testing needed 2
  • Non-methylated = refer for genetic counseling and germline testing 2

Step 2: Risk Stratification

• If Lynch syndrome confirmed: Initiate annual colonoscopy (superior to sigmoidoscopy for complete colonic evaluation) 1, 2
• If strong family history of colorectal/endometrial cancer: Refer for genetic counseling even if tumor MMR testing appears normal, as 9.5% of germline mutation carriers have tumor testing suggesting sporadic cancer 2
• If gastrointestinal symptoms present: Perform colonoscopy to evaluate for synchronous colorectal neoplasia or metastatic disease 3

Step 3: Ongoing Surveillance

• For confirmed Lynch syndrome patients: annual colonoscopy starting at age 25 years or 2-5 years before earliest colorectal cancer diagnosis in family 1
• For patients without Lynch syndrome but with endometrial cancer: follow standard population-based colorectal cancer screening guidelines (FOBT yearly and sigmoidoscopy/colonoscopy per age-appropriate intervals starting at age 50) 1

Critical Pitfalls to Avoid

• Do not skip MMR testing on endometrial cancer specimens—this is now a universal recommendation regardless of age or family history 1, 2
• Do not accept normal tumor MMR testing as definitively excluding Lynch syndrome in patients with strong family history—germline testing may still be warranted 2
• Do not use sigmoidoscopy alone for Lynch syndrome surveillance—colonoscopy is required for complete colonic evaluation, as right-sided colon cancers are common in Lynch syndrome 1
• Do not assume a colonic mass is primary colorectal cancer in patients with prior endometrial cancer—consider metastatic disease and use immunohistochemistry for definitive diagnosis 3

Quality of Life and Mortality Impact

• Early detection of Lynch syndrome through universal MMR testing enables cascade genetic testing of family members, potentially preventing both endometrial and colorectal cancer deaths through intensive surveillance 1, 2
• Colonoscopic surveillance in Lynch syndrome patients reduces colorectal cancer mortality by detecting and removing premalignant adenomas 1
• Prophylactic hysterectomy with bilateral salpingo-oophorectomy after childbearing completion reduces endometrial cancer risk in Lynch syndrome carriers 1, 2