Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

Management Strategy

Despite advances in molecular understanding, the diagnosis of GS currently generally depends on identification of clinical abnormalities, most commonly for those patients seen by dermatologists the development of multiple BCCs or of at least one BCC before the age of 20, the presence of three or more palmoplantar pits, and by jaw cysts. Dermatologic management of GS patients focuses on patient education, tumor prevention, and treatment of BCCs while optimizing cosmesis and minimizing discomfort and cost.

Patient education should include information on avoidance of sun exposure and the necessity of avoiding unnecessary ionizing radiation (IR) exposure, as GS patients are especially susceptible to the development of BCCs in areas of IR, as well as genetic counseling. Patients who avoid sunlight should be tested regularly for vitamin D deficiency and given D ₃ supplements as needed. Complete skin examinations should be performed at least annually and more frequently after the development of the first BCC. Dermatologists can advocate and provide resources including referrals to other specialists for diagnosis and treatment of extracutaneous manifestations of GS, e.g., annual ophthalmologic and dental examinations. Pediatric GS patients especially should be monitored for development, vision, speech, and hearing. A baseline echocardiogram can identify the rare cardiac fibroma. Pelvic ultrasound of girls who have reached puberty can assess for ovarian fibromas. Magnetic resonance imaging (MRI) is preferable when possible, e.g., for assessing for jaw cysts. An annual MRI of the head is recommended until the age of 8, when medulloblastoma becomes less common.

Genetic testing generally can be limited to the following situations: (1) when future prenatal testing is likely; (2) for establishing the diagnosis in patients whose clinical criteria are ambiguous; and (3) for screening an asymptomatic patient who is at risk because of an affected family member.

Patients with GS need emotional support as they undergo multiple treatments that may result in scarring and deformity. They may benefit from regular screening for depression and referral to a support network (e.g., https://gorlinsyndrome.org ; https://gorlingroup.org ).

The size and numbers of BCCs, especially in those with type I and II skin, the often young age at presentation, and the distribution on the head and neck, pose challenges greater than those associated with sporadic BCC. Nonetheless, with the notable exception of radiotherapy, which should be avoided, treatment generally is based on the same modalities as are used for sporadic BCCs including surgery; photodynamic therapy (PDT); and topical, injectable, and systemic therapy, including vismodegib and sonidegib, HH pathway inhibitors that bind SMO protein, and, if all else fails, chemotherapeutic drugs.

The role of chemoprevention (prophylactic therapy to reduce the incidence of new BCCs) is still unclear. Evidence for its efficacy in GS is inconclusive, except for vismodegib, which may be useful in severe cases, if patients tolerate its common side effects.

This chapter focuses largely on literature specific to GS; that on BCC gives a broader review of the management of this tumor. One difference is that in some GS patients much of the skin, at least near BCCs, has BCC-like budding from the base of the epidermis, making a ‘clear surgical margin’ essentially impossible.