Match each patient's clinical presentation and associated gynecologic neoplasm with the most likely underlying genetic mutation and hereditary syndrome.
- A 45-year-old woman with endometrioid endometrial adenocarcinoma; her family history is notable for a brother with colon cancer at age 42 and an aunt with urothelial cancer.Defect in DNA mismatch repair genes (e.g., MLH1, MSH2) leading to microsatellite instability.
- A 52-year-old woman with ascites and a pelvic mass, diagnosed with high-grade serous carcinoma of the fallopian tube. Her maternal grandmother died of breast cancer.Defect in homologous recombination repair genes (e.g., BRCA1, BRCA2).
- A 35-year-old woman with a history of macrocephaly and multiple trichilemmomas, who is now diagnosed with early-onset endometrial carcinoma.Defect in a tumor suppressor gene on chromosome 10 (PTEN) regulating the PI3K/AKT/mTOR pathway.
- A 22-year-old woman with dark blue macules on her buccal mucosa and lips, presenting with a sex cord tumor with annular tubules (SCTAT) of the ovary.Defect in a serine/threonine kinase gene on chromosome 19 (STK11/LKB1).
Answer
The correct matches align Lynch syndrome with mismatch repair defects, Hereditary Breast and Ovarian Cancer (HBOC) with homologous recombination defects, Cowden syndrome with PTEN mutations, and Peutz-Jeghers syndrome with STK11 mutations, based on their classic syndromic presentations.
Each patient presentation provides classic phenotypic and familial clues that define a specific hereditary cancer syndrome with high risk for gynecologic malignancies. Recognizing these unique patterns allows for the precise matching of the clinical syndrome to its underlying genetic defect.
Step-by-Step Solution
Key Concept
Hereditary cancer syndromes and their associated genetic mutations in gynecologic oncology.