Table 1. Comparison of Diagnostic Criteria for Basal Cell Nevus Syndrome (BCNS) continued...
Odontogenic keratocysts–or keratocystic odontogenic tumors (KCOTs), as renamed by the World Health Organization working group–are one of the major features of BCNS. Demonstration of clonal loss of heterozygosity (LOH) of common tumor suppressor genes, including PTCH, supports the transition of terminology to reflect a neoplastic process. About half of KCOTs from individuals with BCNS show LOH of PTCH. The tumors are lined with a thin squamous epithelium and a thin corrugated layer of parakeratin. Increased mitotic activity in the tumor epithelium and potential budding of the basal layer with formation of daughter cysts within the tumor wall may be responsible for the high rates of recurrence post simple enucleation.[105,106] In a recent case series of 183 consecutively excised KCOTs, 6% of individuals demonstrated an association with BCNS. KCOTs occur in 65% to 100% of individuals with BCNS,[70,107] with higher rates of occurrence in young females.
Palmoplantar pits are another major finding in BCC and occur in 70% to 80% of individuals with BCNS. When these pits occur together with early-onset BCC and/or KCOTs, they are considered diagnostic for BCNS.
Several characteristic radiologic findings have been associated with BCNS, including lamellar calcification of falx cerebri;[110,111] fused, splayed or bifid ribs; and flame-shaped lucencies or pseudocystic bone lesions of the phalanges, carpal, tarsal, long bones, pelvis, and calvaria. Imaging for rib abnormalities may be useful in establishing the diagnosis in younger children, who may have not yet fully manifested a diagnostic array on physical examination.
A 9p22.3 microdeletion syndrome that includes the PTCH1 locus has been described in ten children. All patients had facial features typical of BCNS, including a broad forehead, but they had other features variably including craniosynostosis, hydrocephalus, macrosomia, and developmental delay. At the time of the report, none had basal cell skin cancer. On the basis of their hemizygosity of the PTCH1 gene, these patients are presumably at an increased risk of basal cell skin cancer.