Cancer Predisposition Syndromes

A 50-year-old woman is diagnosed with breast cancer. Her mother had breast cancer at 55, and her maternal uncle had colorectal cancer. Genetic testing reveals a _CHEK2_ c.1100delC pathogenic variant.

A 38-year-old woman is diagnosed with triple-negative breast cancer. Her mother died of ovarian cancer at age 52, and her maternal aunt had breast cancer at 45. Genetic testing reveals a _BRCA1_ pathogenic variant.

A 42-year-old woman is diagnosed with invasive ductal breast cancer. Her sister was diagnosed with breast cancer at 39, and her maternal aunt died of pancreatic cancer at 58. Multi-gene panel testing identifies a pathogenic variant in _PALB2_.

A teenager is found to have hundreds of colonic polyps on colonoscopy. His father had colon cancer at age 35 after being diagnosed with FAP. Extracolonic findings include osteomas and dental abnormalities.

A child with rectal bleeding is found to have multiple juvenile polyps throughout the colon. A family history of colon cancer and possible HHT features are noted.

A 42-year-old is diagnosed with colorectal cancer. His tumor shows microsatellite instability (MSI-high) and loss of _MLH1_/_PMS2_ on IHC. Family history reveals colon cancer in his father at 48 and endometrial cancer in his sister at 45.

A 45-year-old presents with iron-deficiency anemia. Colonoscopy reveals 30 adenomatous polyps and a colorectal adenocarcinoma. Family history shows no affected parents but two affected siblings. Genetic testing reveals biallelic _MUTYH_ pathogenic variants.

A child with mucocutaneous pigmentation (lips, buccal mucosa, fingers) has recurrent episodes of abdominal pain from intussusception. Colonoscopy reveals hamartomatous polyps.

A patient presents with numerous fundic gland polyps in the proximal stomach. Family history reveals gastric cancer in multiple relatives. No colonic polyps are found.

A family has multiple members with diffuse (signet ring) gastric cancer at young ages. Women in the family also have lobular breast cancer.

A patient with a paraganglioma in the head and neck is found to have a pheochromocytoma. His father had similar tumors. Genetic testing reveals an _SDHB_ variant.

A 35-year-old woman presents with recurrent kidney stones and is found to have elevated calcium and PTH. Further workup reveals a prolactinoma on brain MRI. Her father had a pancreatic neuroendocrine tumor resected at age 40.

A 25-year-old woman presents with a thyroid nodule. Biopsy shows medullary thyroid carcinoma. Calcitonin is markedly elevated. Genetic testing reveals a _RET_ pathogenic variant. Her 5-year-old son tests positive for the same variant and is referred for prophylactic thyroidectomy.

A child with severe growth restriction has sun-sensitive facial erythema in a butterfly distribution. He has frequent infections and develops leukemia.

A child with café-au-lait macules develops a brain tumor at age 6 and colorectal cancer at age 12. Both parents are found to have Lynch syndrome.

A 30-year-old appears much older, with gray hair, skin atrophy, and cataracts. He has developed type 2 diabetes and has a sarcoma.

A child develops severe sunburns after minimal sun exposure and has freckling in sun-exposed areas by age 2. By age 10, he develops multiple skin cancers.

A patient with a spontaneous pneumothorax has numerous skin-colored papules on the face and neck (fibrofolliculomas). Imaging reveals bilateral renal tumors.

A 35-year-old patient presents with a newly diagnosed melanoma on the upper back. Physical exam reveals more than 50 dysplastic nevi. Family history is significant for melanoma in his father (age 40), paternal uncle (age 45), and paternal grandmother (age 55), with his paternal uncle also diagnosed with pancreatic cancer at age 62. Genetic testing identifies a pathogenic variant in _CDKN2A_.

A child with macrocephaly has palmar pits and odontogenic keratocysts of the jaw. He later develops multiple basal cell carcinomas as a teenager.

A young woman with numerous painful skin nodules (leiomyomas) and uterine fibroids requiring early hysterectomy is found to have an aggressive renal tumor. Genetic testing reveals a _FH_ variant.

A patient is diagnosed with bilateral papillary type 1 renal cell carcinoma. Several family members have had similar kidney tumors.

A 4-year-old is diagnosed with adrenocortical carcinoma. Her mother had breast cancer at 32 and her maternal grandmother died of a brain tumor at 40. A _TP53_ pathogenic variant is identified.

A 42-year-old woman with macrocephaly (head circumference >97th percentile) presents with multiple facial trichilemmomas and oral papillomas. Mammography shows breast cancer. She has a history of follicular thyroid cancer at 35 and a cerebellar mass on brain MRI (Lhermitte-Duclos disease).

A 25-year-old with a history of retinal hemangioblastoma presents with headache and ataxia. MRI shows a cerebellar hemangioblastoma and multiple pancreatic cysts. Abdominal imaging reveals clear cell renal cell carcinoma.