Published on 19/03/2015 by admin
Filed under Dermatology
Last modified 19/03/2015
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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
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.
Affected individuals usually present with multiple primary BCCs that pose a therapeutic challenge because of their number, size, and location. The goal of therapy is to achieve adequate cancer control while minimizing cosmetic disfigurement. Therapy should also include emotional support and genetic counseling. The treatment of BCCs in NBCCS is similar to that of sporadic BCCs and includes multiple modalities such as surgery, lasers, and topical, injectable or systemic therapy; it also highlights the role of chemoprophylaxis, sun protection, and radiation avoidance. Furthermore, in the last several years, research has focused on the hedgehog signaling pathway with the development of smoothened protein inhibitors for metastatic or locally advanced BCCs.
Radiologic studies
Genetic studies
Dermatoscopy
Mirowski GW, Liu AA, Parks ET, Caldemeyer KS. J Am Acad Dermatol 2000; 43: 1092–3.
Radiologic studies detect the various skeletal and soft tissue anomalies associated with NBCCS including odontogenic keratocysts, lamellar calcification of the falx cerebri, macrocephaly, cleft lip and/or palate, rib and vertebral anomalies, and short fourth metacarpal (Albright sign).
Lo Muzio L. Orphanet J Rare Dis 2008; 25: 32.
PTCH1 gene mutation analysis is the definitive diagnostic test to demonstrate NBCCS, although it is labor-intensive as there are 24 exons. Newly designed high-resolution oligonucleotide microarrays with a much smaller median distance between the probes have been used to detect gene deletions that could not have been detected by conventional chromosomal analysis.
Zedan W, Robinson PA, High AS. Diagn Mol Pathol 2001; 10: 41–5.
Zalaudek I, Kreusch J, Giacomel J, Ferrara G, Catricalà C, Argenziano G. J Am Acad Dermatol 2010; 63: 377–86.
Under dermoscopy, branched arborizing vessels are a specific finding of nodular, cystic or sclerodermiform BCC, while fine arborizing vessels of a smaller diameter, either alone or associated with dotted vessels and whitish streaks are characteristic of fibroepithelioma of Pinkus, an unusual variant of BCC. Superficial BCC frequently has the presence of fine ‘microarborizing’ vessels, shiny red-white structureless areas, and multiple small erosions.
Goldberg DP. Clin Plast Surg 1997; 24: 673–86.
Surgical excision, with a 2–5 mm margin of normal skin depending on tumor size, has a cure rate as high as 95–99% for primary tumors. Low-risk sporadic BCCs located on the neck, trunk, and extremities are associated with recurrence rates of 1–10%, while BCCs on the ear, nasolabial groove, scalp, or forehead exhibit higher recurrence rates.
Telfer NR, Colver GB, Bowers PW. Br J Dermatol 1999; 141: 415–23.
Mohs micrographic surgery has an overall 5-year cure rate of 99%, and is the treatment of choice for high-risk BCCs, such as those tumors located on the eyelids, nose, lips, and ears, and those malignancies exhibiting infiltrative, morpheic, and micronodular growth patterns.
Frentz G, Munch-Petersen B, Wulf HC, Niebuhr E, da Cunha Bang F. J Am Acad Dermatol 1987; 17: 637–43.
Radiation therapy should be avoided in patients with NBCCS since these patients develop BCC as a consequence of radiotherapy within 6 months to 3 years, in contrast to the usual 20- to 30-year lag period for radiation-induced tumors seen in patients with sporadic BCC.
Peck GL, Gross EG, Butkus D, DiGiovanna JJ. J Am Acad Dermatol 1982; 6(Suppl 2): 815–23.
Goldberg LH, Hsu SH, Alcalay J. J Am Acad Dermatol 1989; 21: 144–5.
Campbell RM, DiGiovanna JJ. Dermatol Ther 2006; 19: 306–14.
Lens M, Medenica L. Expert Opin Pharmacother 2008; 9: 1363–74.
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.
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.
Amini S, Viera MH, Valins W, Berman B. J Clin Aesthet Dermatol 2010; 3: 20–34.
While primary prevention of NMSC includes strict sun-protective behaviors, several topical agents can serve as secondary prevention. Topical retinoids have demonstrated efficacy in decreasing the risk of developing NMSCs, and other topical agents such as perilly alcohol, T-4 endonuclease, DL-α-tocopheral, DFMO and COX-2 inhibitors have shown positive results. Furthermore, a recent study showed that short-term (<5 years) non-aspirin NSAID use had significant protective effects against BCC.
Treatment of Skin Disease Comprehensive Therapeutic Strategies 4e
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Surgical management
Mohs micrographic surgery
Protection against radiation exposure
Chemoprevention:
Electrodesiccation and curettage
