General Surgery · Year 3 · from General Surgery

Case 3: Hereditary Cancer Syndrome - Lynch Syndrome

Patient Demographics

• Age: 38 years
• Sex: Female
• Occupation: Elementary school teacher

Chief Complaint

"I was told I have colon cancer, and I'm worried about my family."

History of Present Illness

The patient presented with rectal bleeding and change in bowel habits. Colonoscopy revealed a sigmoid colon mass, and biopsy confirmed adenocarcinoma. Staging workup showed localized disease (T3N0M0). During her oncology visit, the young age of onset raised suspicion for a hereditary cancer syndrome. Detailed family history revealed multiple family members with cancer.

Family History (Three-Generation Pedigree)

• Patient: Colon cancer at age 38
• Father: Colon cancer at age 45, currently alive
• Paternal grandmother: Endometrial cancer at age 52, died age 60 from "stomach cancer"
• Paternal uncle: Colon cancer at age 48
• Paternal aunt: Ovarian cancer at age 55
• Two younger sisters: Healthy, ages 35 and 32

Amsterdam II Criteria Assessment

At least 3 relatives with Lynch-associated cancer:

• 1 is first-degree relative of the other 2 ✓
• At least 2 successive generations affected ✓
• At least 1 diagnosed before age 50 ✓
• FAP excluded ✓
• Tumors verified pathologically ✓

Patient meets Amsterdam II criteria for Lynch syndrome

Tumor Testing

Immunohistochemistry (IHC):

• MLH1: Present
• MSH2: Absent
• MSH6: Absent
• PMS2: Present

Microsatellite instability (MSI) testing:

• MSI-High (MSI-H)

Findings suggest: MSH2 germline mutation likely

Genetic Counseling and Testing

• Pre-test counseling provided
• Informed consent obtained
• Germline genetic testing result: Pathogenic MSH2 mutation confirmed

Diagnosis

Lynch Syndrome (Hereditary Non-Polyposis Colorectal Cancer - HNPCC)

• Autosomal dominant
• MSH2 mutation
• Significantly increased risk of multiple cancers

Cancer Risks Associated with MSH2 Mutation

Management of Current Cancer

Surgical options for colon cancer in Lynch syndrome:

1. Segmental colectomy (standard for sporadic cancer)
2. Subtotal/total colectomy (reduces metachronous cancer risk)

Discussion with patient:

• Risk of metachronous colorectal cancer with segmental resection: ~16% at 10 years
• Total colectomy eliminates colon cancer risk but impacts quality of life

Patient decision: Total abdominal colectomy with ileorectal anastomosis

Surgery

• Total abdominal colectomy with ileorectal anastomosis
• Pathology: T3N0 (0/18 nodes), MSI-H adenocarcinoma
• Stage II with MSI-H (favorable biology)

Adjuvant Therapy Considerations

• Stage II MSI-H colon cancer: Generally favorable prognosis
• 5-FU based chemotherapy may not benefit MSI-H tumors
• Decision: Observation without adjuvant chemotherapy

Risk-Reducing Strategies for Patient

Gynecologic cancers:

• Annual pelvic exam
• Consider endometrial sampling annually starting age 30-35
• Discuss risk-reducing hysterectomy and bilateral salpingo-oophorectomy after childbearing complete
• Patient opted for surveillance initially, planned RRSO after age 40

Remaining rectal surveillance:

• Annual proctoscopy/sigmoidoscopy of remaining rectum
• Consider completion proctectomy if dysplasia develops

Other cancer surveillance:

• Upper endoscopy every 3-5 years (starting age 30-40)
• Urinalysis annually (urothelial cancer screening)
• Annual skin exam

Cascade Genetic Testing for At-Risk Relatives

• First-degree relatives (sisters, children of affected relatives) should undergo genetic counseling and testing
• Predictive testing identifies who carries the mutation
• Allows personalized screening for mutation carriers
• Non-carriers can follow general population guidelines

Family Testing Results

• Father: MSH2 mutation positive (known - colon cancer)
• Sister (35 y/o): MSH2 mutation positive → enhanced screening initiated
• Sister (32 y/o): MSH2 mutation negative → general population screening

Teaching Points

1. Young age at diagnosis (<50) should prompt consideration of hereditary syndrome
2. Lynch syndrome: Most common hereditary colon cancer syndrome
3. Tumor testing (IHC, MSI) can guide germline testing
4. Amsterdam criteria and Bethesda guidelines help identify at-risk patients
5. Extended colectomy may be considered in Lynch syndrome
6. Risk-reducing surgery (hysterectomy/BSO) reduces gynecologic cancer risk
7. Cascade testing identifies at-risk family members
8. MSI-H tumors may respond to immunotherapy in advanced/metastatic setting

Clinical Image

Image Description: Three-generation family pedigree demonstrating the autosomal dominant inheritance pattern of Lynch syndrome. Multiple family members are affected with Lynch-associated cancers including colorectal, endometrial, and ovarian cancers at young ages.

Attribution: Image from Wikimedia Commons, Category:Colorectal cancer. Source: https://commons.wikimedia.org/wiki/Category:Colorectal_cancer

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