Nevoid basal-cell carcinoma syndrome
Published Web Locationhttps://doi.org/10.5070/D393q870v1
Nevoid basal cell carcinoma syndromeDepartment of Dermatology, New York University, New York, New York
Marie Leger MD PhD, Adelle Quintana MD, Julia Tzu MD, Herman Yee MD, Hideko Kamino MD, Miguel Sanchez MD
Dermatology Online Journal 17 (10): 23
Gorlin syndrome is an autosomal dominantly inherited disorder that results in numerous basal cell carcinomas as well as a number of other facial and skeletal findings. We present a patient with many classic features and review some of the treatment options available for these patients.
A 29-year-old man presented to the Dermatology Clinic at Bellevue Hospital Center for evaluation of a lesion on his scalp that had been present for a few years and was enlarging. The patient had a prior history of five basal cell carcinomas on his scalp, face, and upper trunk. The lesion was biopsied, and the patient was referred for excision of the lesion on his scalp and an additional lesion on his left eyelid. Past medical history included a meduloblastoma, which was diagnosed in early childhood and treated with radiation therapy.
On the right parietal scalp was an 8 mm, pink macule with large blue-gray ovoid nests on dermatoscopic examination. A smooth-surfaced, pink papule was present on the postauricular area, two pink patches with dark embedded globules on his upper chest, and an erosion on his left lower eyelid.
Dental radiographs showed a left mandibular cyst. A head computed tomography scan without constrast showed a large cyst in the right maxilla and maxillary sinus as well as smaller bilateral mandibular cysts. There also was calcification of the falx, tentorium cerebelli, and the basal ganglia.
There are aggregates of atypical basaloid cells with foci of pigmentation and peripheral palisading of the nuclei, which are surrounded by a fibromyxomatous stroma. Superficially, there are a few keratinizing cysts.
Nevoid basal cell carcinoma (BCC) syndrome, which also is known as Gorlin syndrome, is the most common inherited disorder that is associated with BCCs. The estimated prevalence ranges from 1/57,000 to 1/256,000, and it affects men and women equally . Gorlin syndrome is an autosomal dominantly inherited disease with high penetrance and variable expressivity that is linked to the human homologue of the Drosophila patched (PTCH1) gene, which is located on chromosome 9q22.3-q31. The inherited inactivation of the PTCH1 gene, when linked with a second hit mutation (often a mutation in p53), leads to the formation of multiple BCCs.
Clinically, the disorder is associated with the development of BCCs at a young age as well as numerous other findings. A study evaluating 105 patients with nevoid basal cell carcinoma syndrome conducted at the National Institutes of Health found that BCCs occur at a mean age of 23 years . The prognosis is good since these tumors are very destructive but very rarely metastasize. Jaw cysts were present in 74 percent of patients, palmar/plantar pits in 87 percent, ovarian fibromas in 17 percent, and meduloblastomas in 4 of the 105 patients . Systemic findings include intracranial calcifications, facial dysmorphism (coarse facies, macrocephaly, hyperteleorism, frontal bossing), and skeletal abnormalities, such as pectus deformity, bifid ribs, and spinal deformities [3, 4]. Although genetic testing is available, Gorlin syndrome remains a clinical diagnosis. Diagnositic criteria have been proposed (Table 1).
There are no evidence-based studies that evaluate the best treatment modalities for patients with Gorlin syndrome. Various treatment options exist for BCCs, which include excision, Mohs micrographic surgery, cryotherapy, photodynamic therapy, ablative laser therapy, and topical 5 percent imiquimod. It has been suggested to treat nodular or aggressive BCCs in low risk areas with surgical excision, to treat lesions on the face with Mohs micrographic surgery, and to consider non-invasive techniques for superficial lesions . Whereas oral retinoids reduce the number of skin cancers in organ transplant patients, this agent is more effective for actinic keratosis and squamous cell carcinomas  than it is for BCCs. In one study, even with high oral isotretinoin mean daily doses of 3.1 mg/kg/day administered for a mean of eight months, only 8 percent of BCCs underwent clinical and histopathologic regression . High-dose oral retinoids can inhibit the development of BCCs in patients with this syndrome, but treatment must be continued indefinitely and most patients cannot tolerate the adverse effects that are associated with such high doses . Radiotherapy should be avoided in these patients because of the high risk of developing further carcinomas. Patients with Gorlin syndrome should be encouraged to use a sunscreen.
A hedgehog pathway inhibitor, the first in its class, also is currently in development. Preliminary phase II data from a trial of 41 patients with Gorlin syndrome randomized in a 2:1 ratio to receive the hedgehog inhibitor or placebo, indicated that patients in the treatment group developed 0.07 BCCs per month compared with 1.74 BCCs per month in the placebo group. However, 20 percent of the patients dropped out of the study because of side effects, such as cramps, taste loss, and hair thinning . Photodynamic therapy with aminolevulinic acid has been effective in treating BCCs since it destroys tumors through oxidative damage rather than ionizing radiation .
While odontogenic keratocysts are rare in the general population, they affect 75 percent to 80 percent of patients with Gorlin syndrome [9, 10]. These cysts tend to be aggressive and have a high recurrence rate. In patients with Gorlin syndrome, keratocysts are often multiple and range in number from 1 to 30 with an average of 5 . At around age 30, the development of new and recurrent cysts tends to decrease . Rarely, ameloblastoma and squamous cell carcinoma have been reported in keratocysts [12, 13].
Managing medulloblastoma in these patients is challenging. Radiotherapy results in an increased number of BCCs [14, 15]. This seems to be the case with our patient, who has BCCs mostly on the scalp, head, and upper body. If the diagnosis of Gorlin syndrome is known, patients should be treated without radiation therapy, if possible, or with a treatment field limited to the posterior fossa.
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