Dermatology: Practical and Conceptual Research Letter | Dermatol Pract Concept. 2022;12(1):e2022038 1 Gorlin Goltz Syndrome: Beware of Melanoma Filomena Russo1, Flavio Giulio Liso1, Francesco Santi1, Luca Provvidenziale1, Paolo Taddeucci1, Pietro Rubegni1 1 Department of Medical, Surgical and Neurological Science, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy Key words: Gorlin Goltz syndrome, melanoma, reflectance confocal microscopy, dermoscopy Citation: Russo F, Liso FG, Santi F, Provvidenziale L, Taddeucci P, Rubegni P. Gorlin goltz syndrome: beware of melanoma. Dermatol Pract Concept. 2022;12(1):e2022038. DOI: https://doi.org/10.5826/dpc.1201a38 Accepted: July 5, 2021; Published: January 2022 Copyright: ©2022 Russo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License BY-NC-4.0, https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication Corresponding author: Francesco Santi, MD, Dermatology Section, University of Siena, S. Maria alle Scotte Hospital, Siena, Italy. E-mail: santifrancesco90@gmail.com Introduction Gorlin Goltz syndrome, also known as basal cell nevus syn- drome, is a rare autosomal dominant multisystem disorder. The “signature” feature of Gorlin Goltz syndrome is an earlier onset and a higher number of Basal Cell Carcinomas (BCC), median of 160 BCCs in an average lifetime [1]. The genetic base of this syndrome is mainly to be found in pathologic con- stitutive activation of the Sonic Hedgehog signaling pathway. Patients with this syndrome, beyond numerous BCCs, can also present a wide spectrum of manifestations such as: jaw odontogenic keratocysts, palmoplantar pits, lamellar calcifi- cation of the falx cerebri, skeletal abnormalities, childhood medulloblastomas and cardiac or ovarian fibromas. Case Presentation A 60-year-old Caucasian woman was referred to our department because she had been diagnosed with Gorlin Goltz syndrome, with a 20-year history of multiple BCCs predominantly involving her face and upper back as well as multiple jaw cysts. After she had undergone multiple surgical procedures, she started vismodegib with a daily dose of 150 mg from November 2019. Clinical follow-up after 3 months showed progressive improvement in the size of the lesions. On a further follow-up visit in March 2020, the patient continued to show improvement, but a 7-mm pigmented oval-shaped lesion was noted on her scalp (Figure 1A). On 20x polarized dermoscopy regression struc- tures, irregular dark blue pigmented blotches and a brownish peripheral network reminiscent of leaf-like structures were seen, leading to a possible diagnosis of BCC versus mela- noma (Figure 1B). However, reflectance confocal microscopy (RCM, Vivascope 3000, Caliber) examination showed pag- etoid infiltration of round and dendritic atypical cells in the epidermis and irregular meshwork at the dermo-epidermal junction (Figure 1C), suggesting the diagnosis of melanoma. An excisional biopsy was performed, and the histopatholog- ical examination revealed an invasive melanoma with 0.48 Breslow thickness with conspicuous regression (>75%). 2 Research Letter | Dermatol Pract Concept. 2022;12(1):e2022038 Conclusion The presence of melanomas in Gorlin Goltz syndrome is rare and there are only a few documented cases in the literature [2]. Since melanomas of the scalp frequently display non- classic melanoma dermoscopic criteria they can simulate other tumors, amongst which BCC is one. Indeed, typical dermoscopic features of pigmented basal cell carcinomas such as large blue-gray ovoid nests and arborizing vessels can also be found in melanoma. RCM is able to diagnose BCCs mimicking melanoma at dermoscopy as well as mel- anoma mimicking BCCs. Typically, BCCs on RCM display the presence of tight basaloid islands, peripheral clefting and increased dermal vasculature whereas melanoma of the scalp usually, under RCM, has irregular meshwork patterns associated with the presence of nests of atypical melanocytes at the dermo- epidermal junction. The systematic use of RCM on these multiple inconspicuous lesions has enabled clinicians to arrive at a diagnosis of BCC or a melanocytic lesion in few minutes, and with a high level of confidence, since clear-cut confocal criteria can be observed. Our case highlights the ben- efits of using a combined approach between dermoscopy and RCM in Gorlin Goltz syndrome patients to identify ambig- uous lesions in order to discriminate melanoma from BCC, and therefore avoid therapeutical errors and allow clinicians to act promptly. Nonetheless this case highlights the impor- tance of performing a complete body examination. Lesions in areas difficult to explore such as the scalp, in particular in non-bald patient where the presence of hair may hinder a quick examination, could be easily failed to spot resulting in a delayed treatment. References 1. Solis DC, Kwon GP, Ransohoff KJ, et al. Risk Factors for Basal Cell Carcinoma Among Patients With Basal Cell Nevus Syndrome: Development of a Basal Cell Nevus Syndrome Patient Registry. JAMA Dermatol. 2017;153(2):189-192. DOI: 10.1001/jamader- matol.2016.4347. PMID: 27902821.. 2. Briatico G, Moscarella E, Ronchi A, Procaccini EM, Argenziano G. In Situ Melanoma Collision With a Basal Cell Carcinoma in a Patient With Basal Cell Nevus Syndrome: Clinical and Dermoscopic Features. Dermatol Pract Concept. 2019;9(4): 310-312. DOI: 10.5826/dpc.0904a16. PMID: 31723471. PMCID: PMC6830545.. Figure 1. (A) Clinical and (B) dermoscopy aspect. 20x polarized dermoscopy shows regression structures, irregular dark blue pigmented blotches and a brownish peripheral network reminiscent of leaf-like structures. (C) Reflectance confocal microscopy (RCM) examination showed pagetoid infiltration of round and dendritic atypical cells in the epidermis.