Clinical and Dermoscopic Features Associated With Difficult-to-Recognize Variants of Cutaneous Melanoma A Systematic Review Riccardo Pampena, MD; Michela Lai, MD; Mara Lombardi, MD; Marica Mirra, BSc; Margherita Raucci, RN; Aimilios Lallas, MD; Zoe Apalla, MD; Giuseppe Argenziano, MD; Giovanni Pellacani, MD; Caterina Longo, MD, PhD IMPORTANCE The clinical and dermoscopic features of the vast majority of uncommon variants of cutaneous melanoma have been rarely reported, leading to difficulty in making accurate diagnoses. OBJECTIVE To define the main clinical and dermoscopic features of the most frequently reported but uncommon histologic variants of cutaneous melanoma. EVIDENCE REVIEW A 2-step systematic review of the literature was performed (from inception to November 2018) using PubMed, Embase, and Cochrane Central Register of Controlled Trials databases. The first step identified those uncommon variants of melanoma for which at least 1 case reporting dermoscopy was described in the literature. The keywords searched were melanoma, uncommon, rare, dermoscopy, and dermatoscopy. In the second step, each previously identified uncommon variant was searched for in the same databases by combining the following terms with melanoma, dermoscopy, and dermatoscopy: amelanotic, hypopigmented, animal, melanocytoma, balloon, desmoplastic, follicular, nested, nevoid, dermal, spitz*, spindle, and verrucous. The institution’s database was also searched from January 2012 to September 2019 for histopathologically confirmed cases of the same melanoma variants. Each reviewer also assessed the quality of reporting in the included articles based on previously described guidelines. FINDINGS In total, 62 articles met the inclusion criteria, reporting 433 melanoma cases. An additional 56 cases of uncommon melanoma variants were retrieved from the institution’s database for a total of 489 cases: 283 cases of amelanotic superficial spreading melanoma, 18 cases of animal-type and pigmented epithelioid melanocytoma, 7 cases of balloon cell melanoma, 71 cases of desmoplastic melanoma, 3 cases of follicular melanoma, 10 cases of nested melanoma, 33 cases of nevoid melanoma, 2 cases of primary dermal melanoma, 57 cases of spitzoid melanoma, and 5 cases of verrucous melanoma. These variants of melanoma occurred more frequently in women than men (147 cases vs 132 cases). Clinically, these tumors were mainly palpable (162 of 217 [74.7%]) or amelanotic (283 of 489 [57.9%]) lesions that could resemble other benign or malignant skin conditions; dermoscopy typically revealed a homogeneous pinkish background, white structures, and polymorphic vessels. The mean age of all included was 58 years (range, 1-89 years). CONCLUSIONS AND RELEVANCE Uncommon melanoma variants may resemble both inflammatory disorders and other cutaneous neoplasms, representing a diagnostic pitfall even for the most experienced dermatologist. The purpose of this systematic review was to provide an extensive and detailed overview of specific clinical and dermoscopic features of each uncommon melanoma variant, highlighting the main criteria for differentiating these variants from other benign or malignant skin lesions. JAMA Dermatol. 2020;156(4):430-439. doi:10.1001/jamadermatol.2019.4912 Published online February 26, 2020. Invited Commentary page 440 Supplemental content Author Affiliations: Centro Oncologico ad Alta Tecnologia Diagnostica, Azienda Unità Sanitaria Locale–IRCCS di Reggio Emilia, Reggio Emilia, Italy (Pampena, Lai, Lombardi, Mirra, Raucci, Longo); First Dermatology Department, Aristotle University of Thessaloniki, Thessaloniki, Greece (Lallas, Apalla); Dermatology Unit, University of Campania Luigi Vanvitelli, Naples, Italy (Argenziano); Department of Dermatology, University of Modena and Reggio Emilia, Modena, Italy (Pellacani, Longo). Corresponding Author: Caterina Longo, MD, PhD, Department of Dermatology, University of Modena and Reggio Emilia, via del Pozzo 71, 41121 Modena, Italy (longo.caterina@ gmail.com). Clinical Review & Education JAMA Dermatology | Review 430 (Reprinted) jamadermatology.com © 2020 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ by a Università della Campania “Luigi Vanvitelli” User on 10/02/2020