Skin cancer risk in hereditary mixed cancer syndromes.

The article is a narrative review of skin cancer risk in common hereditary cancer syndromes that are typically thought of as “mixed cancer” syndromes rather than primary skin cancer syndromes.

Key points:

• The review focuses on Li-Fraumeni syndrome, Lynch syndrome, hereditary breast and ovarian cancer (BRCA1/2), ATM‑ and CHEK2‑associated hereditary cancer, BRIP1‑associated predisposition, and hereditary leiomyomatosis and renal cell carcinoma.
• Across these syndromes, the authors highlight biological plausibility (DNA repair/cell cycle defects, treatment exposures, UV sensitivity) and emerging clinical data suggesting increased risk of melanoma, BCC, SCC, and premalignant skin lesions.
• Skin cancers and precancerous lesions appear to be underrecognized and underreported in these syndromes compared with visceral cancers, likely leading to underestimation of true risk.
• The authors conclude that mixed hereditary cancer syndromes—particularly Li-Fraumeni, Lynch, and BRCA1/2‑associated syndromes, and to a lesser extent ATM and CHEK2—likely confer meaningful susceptibility to skin malignancies.
• They recommend incorporating routine dermatologic evaluation and individualized UV protection counseling into the care of affected patients to improve early detection and prevention of skin cancer.