Diagnosis and management of nevoid basal cell carcinoma syndrome

Treatment of this autosomal dominant condition is difficult but improving.

Issue: December 1, 2005

ByThad Labbe, MD

ByMark R. Levine, MD, FACS

Nevoid basal cell carcinoma syndrome, also known as Gorlin syndrome, is an autosomal dominant condition transmitted with complete penetrants with variable expressivity. This means that half of the affected person’s children also have the syndrome. It affects one in every 50,000 to 100,000 people. It is due to an abnormal PTCH (patched) gene on chromosome 9q22.3-q31. This gene normally functions as a tumor-suppressor, so when it is not working properly, it may allow cancers to grow (medulloblastoma and meningioma).

Characteristic clinical manifestations include basal cell carcinomas, odontogenic keratocysts, palmar and plantar pits, and ectopic calcifications of the falx cerebri, which are considered major criteria for diagnosis. The disorder is also characterized by congenital skeletal abnormalities — broad forehead, lip abnormalities, cleft lip and/or palate and ocular abnormalities. The ocular abnormalities include congenital cataracts, coloboma of the iris, choroid and optic nerve, strabismus, nystagmus and microphthalmos.

Various low frequency neoplasms such as medulloblastoma, meningiomas, ovarian and cardiac fibromas, melanomas, breast cancer and non-Hodgkin’s lymphoma have been reported.

Presentation

The components comprising the syndrome are expressed at different ages. The skeletal component is the most frequent anomaly present at birth. The skin lesions may be present at birth but generally develop during the first, second or possibly third decade but no later. Only about 15% of patients manifest with skin lesions before puberty.

Patients may have a few to thousands of nevoid basal cell carcinomas arising in any region of the skin but especially on the face, neck and upper trunk (Figure 1). The periorbital areas, eyelid, nose, malar region and upper lip are the facial sites most often affected. The nevoid lesions may be pearly to flesh-colored to reddish-brown and may vary in size from 1 to 10 mm in diameter. The tumors may be papular, pedunculated, pigmented, nodular, erythematous or ulcerative. Microscopically, the nevoid tumors assume a wide spectrum of appearances from benign and adnexal tumors to frank basal cell carcinomas. The histopathology of the nevoid basal cell carcinoma cannot be differentiated from that of ordinary basal cell carcinomas. A full spectrum of basal cell carcinoma may develop from the nodular type to morpheaform (Figure 2). Before puberty, the lesions are harmless, but after puberty into adolescence, the lesions may enlarge, ulcerate and deeply infiltrate, which may lead to loss of one or both eyes and portions of the nose (Figure 3).

A 10-year-old boy with multiple pigmented and nonpigmented papular lesions of the face.	Lower face and neck area shows pigmented nodular and ulcerative basal cell carcinomas.	A patient who had multiple surgeries of the forehead and right lower lid with skin grafts and a reconstructed nose from invasive basal cell carcinomas.
Images: Levine MR

Treatment

Treatment consists of careful surveillance of these tumors after diagnosis, especially between puberty and 35 years of age. It is important to treat basal cell carcinomas when they are small. This may require surgery or one of many treatment modalities including electro-desiccation and curettage, cryotherapy, fluorouracil cream, topical imiquimod cream, 0.1% tretinoin cream and photodynamic therapy. Irradiation should not be used because of the number of lesions, post-radiation skin changes and the ability to provoke the development of more tumors. Recently at Rosewell Park Cancer Institute, 5-aminolevulinic acid photodynamic therapy to treat numerous basal cell carcinomas has shown 85% to 98% success of safely removing tumors.

For Your Information:

Mark R. Levine, MD, FACS, is a clinical professor of ophthalmology in the Department of Ophthalmology, Case Western Reserve University. He can be reached at University Suburban Health Center, 1611 South Green Road, Suite 306A, South Euclid, OH 44121; 216-291-9770; fax: 216-291-0550.

A support group has been formed for patients with basal cell carcinoma nevus syndrome and their families. Kristi Schmitt Burr, executive director at the Basal Cell Carcinoma Nevus Syndrome, Life Support Network, can be reached at P.O. Box 321, Burton, OH 44021; 440-635-0078; fax: 440-635-0078; e-mail: info@bccns.org; Web site: www.bccns.org.

References:

Boonen SE, Stahl D, et al. Delineation of an interstitial 9q22 deletion in basal cell nevus syndrome. Am J Med Genet A. 2005;132(3):324-328.

Gorlin RJ. Nevoid basal-cell carcinoma syndrome. Medicine (Baltimore). 1987;66(2):98-113.

Lo Muzio L, Nocini PF, et al. Nevoid basal cell carcinoma syndrome. Clinical findings in 37 Italian affected individuals. Clin Genet. 1999;55(1):34-40.

Oseroff AR, Shieh S, at al. Treatment of diffuse basal cell carcinomas and basaloid follicular hamartomas in nevoid basal cell carcinoma syndrome by wide-area 5-aminolevulinic acid photodynamic therapy. Arch Dermatol. 2005;141(1):60-67.