P49 A 33-year-old woman with nevoid basal cell carcinoma syndrome presenting with multiple nodular, nodulocystic, ulcerating and superficial basal cell carcinomas predominantly localized in the head and neck region. Case report and review of therapeutic options

Abstract

Case report A 33-year-old woman was referred to our centre for therapeutic advice concerning multiple slow-growing skin lesions on the scalp and face. In 2003, the clinical diagnosis of nevoid basal cell carcinoma (NBCCS) was made based on a history of odontogenic keratocysts, distinct craniofacial features (frontal bossing, hypertelorism and coarse face), calcification of the falx cerebri and dura mater, segmentation defect of cervical vertebrae C5-C6, seizures, cardiac fibroma and mesenteric cysts. Genetic testing with DHPLC technique on leucocytes confirmed a germline mutation in patched 1 (PTCH1) gene on chromosome 9q22.3 in 2007. The first dermatological examination in 2009 revealed multiple lesions in the head and neck region, most of them clinically suspect for nodular or nodulo-ulcerative basal cell carcinomas (BCCs). Lesions suspect for superficial BCCs were predominantly observed on the lower limbs and to a lesser extent in the head and neck region. Patient presented also with dermal naevi, in the face and neck region, which could be differentiated from small nodular BCCs through dermoscopy. We did not observe palmoplantar pits, milia or epidermal cysts. The BCCs, which clinically presented as nodular or nodulo-ulcerative lesions, were treated with surgical excision to ensure optimal cure rate. In total 19 lesions were removed. Histological review showed 17 nodular BCCs and 2 BCCs of the superficial type. Non-surgical treatments, such as topical 5-fluorouracil and topical 5% imiquimod or photodynamic therapy which offer better cosmetic outcome, are treatment options for superficial BCCs. The therapeutic challenge in this genetically impaired patient lies in the expected development of a large number of BCCs with repeated occurrence throughout life. Radiotherapy should be avoided in the treatment of BCC in NBCCS since ionizing radiation may lead to the development of new BCCs in the field of irradiation. In this patient, for whom oral contraception is prohibited due to a history of thrombophilia, oral retinoids are relatively contra-indicated due to their teratogenic effects. In this regard, hedgehog/smoothened inhibitor molecules may provide a long-term option in the treatment of early lesions, in order to avoid surgery with its possible functional defects and unaesthetic consequences. These molecules bind with high affinity to Smoothened protein and substitute for the lost protein PTCH1 function by inhibiting Hedgehog pathway activation. Since available oral molecules are reserved for locally advanced or metastatic BCCs, we opted for inclusion in a clinical trial concerning a topical specific Smoothened inhibitor.