Nevoid basal cell carcinoma syndrome



Nevoid basal cell carcinoma syndrome


Patricia Reutemann and Gary L. Peck


Evidence Levels:  A Double-blind study  B Clinical trial ≥ 20 subjects  C Clinical trial < 20 subjects  D Series ≥ 5 subjects  E Anecdotal case reports


image
Multiple basal cell carcinomas arising after radiation therapy of a solitary BCC in a patient with NBCCS.

Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin–Goltz syndrome or basal cell nevus syndrome (BCNS), is characterized by a variety of neoplasms and skeletal anomalies with the universal finding being multiple basal cell carcinomas (BCCs). In addition, more than 50% of patients exhibit palmar and plantar pits, odontogenic keratocysts, rib abnormalities, and ectopic bilamellar calcification of the falx cerebri. Associated neoplasms include medulloblastomas and ovarian fibromas. The chromosomal defect in this autosomal dominant disease is mapped to chromosome 9q22.3-q31, resulting in a mutation of the patched gene (PTCH), which functions as a tumor suppressor gene. The PTCH protein operates in the hedgehog signal transduction pathway and inhibits the activity of smoothened protein. Dysregulation of this transmembrane protein favors subsequent tumor formation.




Specific investigations














First-line therapies






























imageSurgical management B
imageMohs micrographic surgery B
imageProtection against radiation exposure C
imageChemoprevention:  
 –Oral retinoids (isotretinoin, acitretin) A
 –Difluoromethylornithine A
 –Celecoxib A
 –Others B–E













A randomized, double-blind, placebo-controlled phase 3 skin cancer prevention study of α-difluoromethylornithine in subjects with previous history of skin cancer.

Bailey HH, Kim K, Verma AK, Sielaff K, Larson PO, Snow S, et al. Cancer Prev Res (Phila) 2010; 3: 35–47.


Inhibition of ornithine decarboxylase by α-DFMO decreases tissue concentrations of polyamines and prevents neoplastic developments in many tissue types. Patients (n=291) with a history of prior NMSC were randomized to oral DFMO (500 mg/m2/day) or placebo for 4 to 5 years. While there was only a very little difference in the development of new SCCs between groups, there was a significant difference in development of new BCCs in the DFMO group. Compliance with DFMO was >90% and was well tolerated with evidence of only mild ototoxicity.



Basal cell carcinoma chemoprevention with nonsteroidal anti-inflammatory drugs in genetically predisposed PTCH1+/− humans and mice.

Tang JY, Aszterbaum M, Athar M, Barsanti F, Cappola C, Estevez N, et al. Cancer Prev Res (Phila) 2010; 3: 25–34.


In vitro and epidemiologic studies favor the efficacy of NSAIDs in preventing skin squamous photocarcinogenesis. A 3-year double-blinded randomized clinical trial in 60 (PTCH1 +/−) patients with BCNS assessed the effects of oral celecoxib on the development of BCCs. A trend for reducing BCC burden was detected in all subjects (p=0.069). The placebo group had a 50% increase in BCCs per year, whereas the celecoxib group had only a 20% increase (p=0.024). The study was discontinued because of concern of enhanced cardiovascular risks. However, no subjects had a serious adverse event related to the drug.




Second-line therapies









imageElectrodesiccation and curettage B





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Aug 7, 2016 | Posted by in Dermatology | Comments Off on Nevoid basal cell carcinoma syndrome

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