Original StudySpitz Tumors With ROS1 Fusions A Clinicopathological Study of 6 Cases, Including FISH for Chromosomal Copy Number Alterations and Mutation Analysis Using Next-Generation SequencingDonati, Michele MD*; Kastnerova, Liubov MD†,‡; Martinek, Petr PhD†,‡; Grossmann, Petr PhD†,‡; Sticová, Eva MD§; Hadravský, Ladislav MD, PhD¶; Torday, Tomas MD‖; Kyclova, Jitka MD**; Michal, Michal MD†,‡; Kazakov, Dmitry V. MD, PhD†,‡Author Information *Department of Pathology, University Hospital Campus Bio-Medico, Rome, Italy; †Sikl's Department of Pathology, Medical Faculty in Pilsen, Charles University in Prague, Pilsen, Czech Republic; ‡Bioptical Laboratory, Pilsen, Czech Republic; §Clinical and Transplant Pathology Centre, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; ¶Department of Pathology, First Faculty of Medicine and General University Hospital, Charles University in Prague, Prague, Czech Republic; ‖Medicyt Laboratory, Kosice, Slovakia; and **Department of Pathology, University Hospital, Brno, Czech Republic. Correspondence: Dmitry V. Kazakov, MD, PhD, Sikl's Department of Pathology, Charles University Medical Faculty Hospital, Alej Svobody 80, 304 60 Pilsen, Czech Republic (e-mail: Kazakov@medima.cz). Supported in part by a Charles University project (SVV 260 391/2019). The authors declare no conflicts of interest. The American Journal of Dermatopathology: February 2020 - Volume 42 - Issue 2 - p 92-102 doi: 10.1097/DAD.0000000000001499 Buy Metrics Abstract Spitz tumors represent a heterogeneous group of melanocytic neoplasms with a spectrum of biological behavior ranging from benign (Spitz nevus) to malignant (spitzoid melanoma). Prediction of the behavior of these lesions based on their histological presentation is not always possible. Recently, mutually exclusive activating kinase fusions, involving ALK, NTRK1, NTRK3, RET, MET, ROS1, and BRAF, have been found in a subset of spitzoid lesions. Some of these genetic alterations were associated with specific morphological features. Here, we report the histological presentation of 6 Spitz tumors with ROS1 fusion. The age of the patients ranged from 6 to 34 years, with strong female prevalence (5:1). All neoplasms were compound melanocytic proliferations with a predominant dermal growth but a conspicuous junctional component displaying atypical microscopic features qualifying them as atypical Spitz tumor. FIP1L1 and CAPRIN1 were identified as 2 novel 5′-fusion partners of ROS1 along with the known PWWP2A–ROS1 fusion. FISH for copy number changes of 9p21, 6p25, and 11q13 was negative in all but 1 neoplasm harboring isolated gain of 8q24. TERT-promoter hotspot mutation analysis was negative in all tumors. All patients are disease-free after a mean follow-up period of 30 months. It is concluded that ROS1-fused spitzoid neoplasms seem to have no distinctive histopathological features although consistent findings were spindled melanocytes arranged in confluent whorling nests, prominent transepidermal elimination of melanocytic nests, and myxoid/mucinous changes. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.