By Gary M. White, MD
Multiple white scars from the treatment of innumerable BCCs.
Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome, is an autosomal dominant disease characterized by the presence of multiple basal cell carcinomas (BCC), odontogenic keratocysts, palmoplantar pits, and calcification in the falx cerebri caused by mutations in PTCH1, SMO or SUFU genes.
The basal cell carcinomas usually have the same appearance as typical BCCs although they may have a tan or brown appearance like nevi. Pigmented BCCs are not uncommon. The sun-exposed areas are most commonly affected but areas that receive little to no sun (e.g., axilla, groin) may be affected as well [DOJ 2014:20(8):8].
Unilateral mosaic BCNS has been described [Br J Dermatol 2013;169:1342-5].
Rarely the BCCs may metastasize, e.g., lungs [JAMA Dermatol 2014;150:877-9].
The first 94 patients with BCNS in a US registry had the following characteristics: average age 56 years, lifetime mean of 312 BCCs, lifetime mean of 202 surgical procedures, median age of diagnosis at 15 years, jaw cysts in 80%, palmar pitting in 82%, ovarian fibromas in 21%, and meduloblastomas in 4%. 57% had tried vismodegib, but only 15% were on it at the time of the survey (most stopped due to side effects) [Derm Times January 2016, p. 31].
Two major criteria, one major and two minor criteria, or one major criterion and genetic confirmation is required for diagnosis [from BJD 2016;174;68].
Genetic counseling to document the causative mutation should be done. If a SUFU mutation is found, the risk for medulloblastoma is greatly increased (estimated 20 fold). MRI surveillance for children up to 3 years of age with SUFU mutation has been suggested [J Clin Oncol 2014;32;4155].
Strict sun avoidance and close monitoring to detect and treat any new BCCs are all important. The patient may need to be seen every 1-2 months forever. Patients will often have enough BCCs to necessitate treatment of one or two at each visit. A complete skin exam is important as BCCs may develop in areas that have received little sun. Curettage and electrodesiccation may be done on small BCCs (even facial ones) but the cosmetic appearance over time is poor as multiple, white, circular scars are left. Individual BCCs, especially facial ones, may best be treated with Mohs surgery. Nonfacial BCCs may be curetted or excised.
Photodynamic therapy with two porphyrin precursors, aminolaevulinic acid and methyl aminolaevulinate, is approved for treatment in Europe, and is suggested as first line treatment for small BCCs.
Radiation therapy should be avoided as it can induce more BCCs. Some patients have had radiation therapy for medulloblastoma, promoting more skin tumors in the field of therapy [J Neurosurg 1997;86;286].
Vismodegib (Erivedge) can reduce the number of new BCCs [NEJM 2012;366;2180]. Side effects are significant and in the study just referenced, there was a 54% drop out rate. Intermittent therapy with vismodegib may have a place, e.g., 1 month on, 2 months off; or 2 months on, 2 months off [JAMA Derm 2016;152;224].
Keratocystic odontogenic tumors of the jaw affect more than 65% of patients with basal cell nevus syndrome. In one report of 6 patients treated with vismodegib, 4 experienced a size reduction and 2 had no change in the size of their jaw cysts [JAMA Dermatol. 2014 May;150(5):542-5].
Tazarotene showed no benefit when applied topically to prevent BCCs [Cancer Prev Res (Phila). 2014 Mar;7(3):292-9].
Capecitabine, an oral prodrug of 5-fluorouracil, is approved by the US Food and Drug Administration for treatment of metastatic breast cancer resistant to other drugs. In one patient with BCNS, it was well tolerated and caused regression of BCCs [J Clin Oncol 2011; 29:e397–401].
SUBA-itraconazole is an oral investigational drug that inhibits the hedgehog pathway. A clinical trial is being carried out to see if it can help prevent BCCs in BCC nevus syndrome. “SUBA technology” (which stands for “super bioavailability”) is designed to improve the bioavailability of orally administered drugs that are poorly soluble. SUBA-Itraconazole is a patented formulation developed by Mayne Pharma, which has improved absorption and significantly reduced variability compared to generic itraconazole.
Patients that religiously avoid sun are at risk for vitamin D deficiency. Acta Dermato-Venereologica
Multiple pigmented BCCs on the face of a patient with BCNS.
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