FINAL DIAGNOSIS: -- NEVOID BASAL CELL CARCINOMA SYNDROME
Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin's syndrome or Gorlin-Goltz Syndrome, is an autosomal dominant disorder characterized by a predisposition to cancer, especially multiple basal cell carcinomas, and congenital malformations. The disorder has been linked to chromosome number 9q22.3-q31, results from mutation of a tumor suppressor gene, and exhibits a prevalence of 1 in 56,000 individuals. Diagnosis is based upon identification of at least two major features: jaw cysts, palmar pits, multiple basal cell carcinomas, and a family history of Gorlin syndrome.
The basal cell carcinomas first arise between puberty and 35 years of age, total from a few to several thousand, and involve mainly the face and upper trunk. A small number of these lesions exhibit aggressive behavior. Ninety percent of Caucasians and less than forty percent of African Americans exhibit these carcinomas, although African Americans fully express the other manifestations. This is partially explained by the protective effect of melanin against ultraviolet light.
Seventy-five percent of patients are affected by odontogenic keratocysts (usually parakeratotic type) which are aggressive because of their rapid growth, high recurrence rate, invasive behavior, and in some cases, the occurrence of adjacent daughter cysts or multifocality. Sixty-five percent involve the mandible, and thirty-five percent, the maxilla. These cysts appear in the first decade, peak in the second or third decade, and are classified into two types based on histology. Sixty-five to ninety percent of odontogenic keratocysts are parakeratotic and five to ten percent of these are associated with NBCC. Ten to thirty-five percent of the odontogenic keratocysts are orthokeratotic cysts. (See microscopic description.)
Other skin manifestations include palmar and/or plantar pits in 65% of cases, epidermoid cysts, chalazia, comedones, palmar and plantar keratosis, and dermal calcinosis. The pits are secondary to premature desquamation of most of the horny layer of the skin.
Central nervous system manifestations include calcification of intracranial structures with the falx cerebri affected in 85% of cases. Medulloblastomas, meningiomas, glioblastomas multiforme, astrocytomas, and mental retardation are other possible findings. Sixty percent of patients show splayed, cervical, or bifid ribs. Ocular effects include cataracts, corneal opacities, glaucoma, strabismus, and nystagmus. Ovarian fibromas occur less frequently.
Treatment of the basal cell carcinomas includes surgical excision with skin grafting of the larger tumors or intralesional application of interferon alfa-2b for nodular lesions up to 2 cm. Carbon dioxide laser vaporization is useful in patients with large numbers of lesions and photodynamic therapy with 5-amino-levulinic acid has been suggested as treatment for superficial lesions. Because 35% of odontogenic keratocysts recur, their treatment requires complete removal of the cyst while avoiding fragmentation. Newer treatment modalities include decompression of the cysts prior to enucleation and cryosurgery. Finally, because NBCCS is an inherited disorder with variable manifestation, genetic counseling and evaluation of family members of affected patients should be offered.
Contributed by Debra L. Callahan, M.D. and E. Leon Barnes, M.D.