Basal Cell Carcinoma
Table 1. Comparison of Diagnostic Criteria for Basal Cell Nevus Syndrome (BCNS) continued...
Of greatest concern with BCNS are associated malignant neoplasms, the most common of which is BCC. BCC in individuals with BCNS may appear during childhood as small acrochordon-like lesions, while larger lesions demonstrate more classic cutaneous features. Nonpigmented BCCs are more common than pigmented lesions. The age at first BCC diagnosis associated with BCNS ranges from 3 to 53 years, with a mean age of 21.4 years; the vast majority of individuals are diagnosed with their first BCC before age 20 years.[67,71] Most BCCs are located on sun-exposed sites, but individuals with greater than 100 BCCs have a more uniform distribution of BCCs over the body. Case series have suggested that up to 1 in 200 individuals with BCC demonstrate findings supportive of a diagnosis of BCNS. BCNS has rarely been reported in individuals with darker skin pigmentation; however, significantly fewer BCCs are found in individuals of African or Mediterranean ancestry.[67,87,88] Despite the rarity of BCC in this population, reported cases document full expression of the noncutaneous manifestations of BCNS. However, in individuals of African ancestry who have received radiation therapy, significant basal cell tumor burden has been reported within the radiation port distribution.[67,80] Thus, cutaneous pigmentation may protect against the mutagenic effects of UV but not ionizing radiation.
Many other malignancies have been associated with BCNS. Medulloblastoma carries the strongest association with BCNS and is diagnosed in 1% to 5% of BCNS cases. While BCNS-associated medulloblastoma is typically diagnosed between ages 2 and 3 years, sporadic medulloblastoma is usually diagnosed later in childhood, between the ages of 6 and 10 years.[63,67,71,89] A desmoplastic phenotype occurring around age 2 years is very strongly associated with BCNS and carries a more favorable prognosis than sporadic classic medulloblastoma.[90,91] Up to three times more males than females with BCNS are diagnosed with medulloblastoma. As with other malignancies, treatment of medulloblastoma with ionizing radiation has resulted in numerous BCCs within the radiation field.[63,76] Other reported malignancies include ovarian carcinoma, ovarian fibrosarcoma,[94,95] astrocytoma, melanoma, Hodgkin disease,[98,99] rhabdomyosarcoma, and undifferentiated sinonasal carcinoma.