Agminated presentation of fusion‐driven melanocytic neoplasms

Abstract

Background: The conventionally understood pathogenesis of agminated Spitz nevi includes a mosaic HRAS mutation followed by copy number gains in 11p. However, we have recently observed agminated presentations of fusion-driven melanocytic neoplasms.Methods: We retrieved cases from our database of benign fusion-induced melanocytic neoplasms with an agminated presentation. Both the primary lesion and the secondary lesion were sequenced. TERT-promoter mutational testing and the melanoma fluorescence in situ hybridization assay were also performed.Results: Three cases were included. Two had a PRKCA fusion (partners ATP2B4 and MPZL1) and one had a ZCCHC8::ROS1 fusion. None of the cases met morphologic or molecular criteria for malignancy. There was no evidence of tumor progression in secondary lesions. The same fusion was identified in the primary and secondary lesions. None of the patients developed evidence of nodal or systemic metastasis. Conclusions:We present accumulating evidence that fusion-driven melanocytic neoplasms can present with an agminated presentation. The differential diagnosis of an agminated presentation versus a locally recurrent or potentially locally metastatic tumor is critical, and accurate diagnosis has significant prognostic and therapeutic consequences for the patient. As with HRAS mutations, fusion-driven melanocytic tumors may have an agminated presentation.

Diagnostic Imaging of Agminated Blue Lesions and Blue Lesions with Satellitosis: Case Series with a Concise Review of the Current Literature

“…Despite Spitz nevi usually present as solitary cutaneous lesions, multiple Spitz nevi can be divided into agminated (ASN) or disseminated [45]. To date, 20 cases of disseminated (or multiple or eruptive) Spitz nevi [45,[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79][80][81][82] have been reported in the literature, while, regarding agminated Spitz nevi, a total of 39 cases have been reported [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][46][47][48][49][50][51][52][53][54][55][56]…”

Spitz Melanocytic Tumors: A Fascinating 75-Year Journey

“…It appears that the acquisition of HRAS-activating mutations frequently represents one of the hallmark events that can trigger the development of agminated SN, characterized by the emergence of multiple, sometimes hundreds, of morphologically and molecularly identical lesions throughout the body, a clinically concerning situation that may arise from the transformation of a pre-existing nevus spilus [41]. However, case reports of patients with agminated SN lacking HRAS mutations and instead harboring fusions including PRKCA or ROS1 have been published [42,43], including a 30-month-old girl with a recurrent agminated SN of the face, which had a GOPC::ROS1 fusion and responded clinically to treatment with crizotinib [44]. It appears that the acquisition of HRAS-activating mutations frequently represents one of the hallmark events that can trigger the development of agminated SN, characterized by the emergence of multiple, sometimes hundreds, of morphologically and molecularly identical lesions throughout the body, a clinically concerning situation that may arise from the transformation of a pre-existing nevus spilus [41].…”

“…It appears that the acquisition of HRAS-activating mutations frequently represents one of the hallmark events that can trigger the development of agminated SN, characterized by the emergence of multiple, sometimes hundreds, of morphologically and molecularly identical lesions throughout the body, a clinically concerning situation that may arise from the transformation of a pre-existing nevus spilus [41]. However, case reports of patients with agminated SN lacking HRAS mutations and instead harboring fusions including PRKCA or ROS1 have been published [42,43], including a 30-month-old girl with a recurrent agminated SN of the face, which had a GOPC::ROS1 fusion and responded clinically to treatment with crizotinib [44].…”