Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)

Abstract

Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

Keywords: Basal cell nevus syndrome; Gorlin syndrome; Keratocystic odontogenic tumor; Nevoid basal cell carcinoma syndrome; PTCH1; SMO; SUFU; Vismodegib.

Fig. 1

This unilocular keratocystic odontogenic tumor is lined by uniform layer of squamous cells with no rete ridges (H&E, original magnification ×20). Image courtesy of Sook-Bin Woo, D.M.D., M.M.Sc., Director of Clinical Affairs, Division of Oral Maxillofacial Surgery, Brigham and Women’s Hospital

Fig. 2

At higher power, this keratocystic odontogenic tumor exhibits basal and parabasal hyperplasia with nuclear palisading and overlying parakeratosis (H&E, original magnification ×200). Basal and parabasal cell hyperplasia should not be mistaken for dysplasia. Image courtesy of Sook-Bin Woo, D.M.D., M.M.Sc., Director of Clinical Affairs, Division of Oral Maxillofacial Surgery, Brigham and Women’s Hospital

Fig. 3

Dyskeratotic palmar pitting (arrows)