Recurrent activating Gαq mutations in the spectrum of blue nevi have been well studied. However, the clinicopathologic characteristics of the recently described CYSLTR2-mutant and PLCB4-mutant blue nevi remain limited, owing to their rarity. Herein, we present 7 CYSLTR2-mutant melanocytic neoplasms, including 1 cellular blue nevus, 4 atypical cellular blue nevi, and 2 blue nevus-like melanomas. They occurred on the scalp, breast, flank, forearm, thigh, leg, and ankle of 3 male patients and 4 female patients, with a median age of 43 (25 to 81) years at diagnosis. Five exhibited an exophytic growth, and 6 were heavily pigmented. A fascicular arrangement of medium to large spindle melanocytes was seen in 6 cases, but epithelioid cytology was present in only 2 cases, one of them being focal. A junctional component was present in 3 cases. Immunoreactivity for HMB45 was diffusely present, except in 1 cellular blue nevus. BAP1 nuclear immunoexpression was lost in 1 melanoma case. A canonical CYSLTR2 L129Q hotspot mutation was present in all cases. Altogether, these histopathologic findings suggest that CYSLTR2-mutant melanocytic blue neoplasms frequently exhibit a heavily pigmented exophytic tumor with a silhouette resembling “pigmented epithelioid melanocytoma” rather than usual cellular blue nevus. Moreover, most of these tumors were not clinically recognized as blue nevi and not located in the classic topography of cellular blue nevus aside from the scalp. However, a fascicular arrangement of medium to large-sized spindled melanocytes, as well as a lack of epithelioid or nevoid melanocytes, could be potential diagnostic clues to morphologically distinguish CYSLTR2-mutant tumors from “pigmented epithelioid melanocytoma.”
*Department of Pathology, Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital
†Department of Pathology, Itabashi Central Clinical Laboratory, Tokyo
‡Department of Diagnostic Pathology, Shizuoka Cancer Center Hospital, Nagaizumi
§Department of Diagnostic Pathology and Cytology, Osaka International Cancer Institute, Osaka
∥Department of Dermatology, Hyogo Cancer Center, Akashi, Japan
¶Department of Biopathology, Center Le[Combining Acute Accent]on Be[Combining Acute Accent]rard, Lyon, France
#University of Lyon, Claude Bernard Lyon1 University, INSERM 1052, CNRS 5286, Léon Bérard Cancer Care Center, Cancer Research Center of Lyon, Ligue Contre Le Cancer Labellised Team, Lyon, France
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
Correspondence: Arnaud de la Fouchardière, MD, PhD, Department of Biopathology, Center Le[Combining Acute Accent]on Be[Combining Acute Accent]rard, 28, rue Laennec, Lyon 69008, France (e-mail: email@example.com).