Pediatric mesenchymal tumors harboring variant NTRK fusions (ETV6-negative) are being increasingly described; however, the histologic and clinical features of these variant NTRK tumors and their relationship to classic infantile fibrosarcoma are not well characterized. A better understanding of the clinicopathologic features of these tumors is necessary, and would aid in both early diagnosis and treatment. Therefore, the aim of this study was to characterize a series of pediatric NTRK-rearranged mesenchymal tumors, including classic ETV6-NTRK3 fused tumors and tumors with variant (non-ETV6) NTRK fusions. The clinical features, morphology, immunophenotype, and genetics of 12 classic ETV6-NTRK3 fused infantile fibrosarcoma and 18 variant NTRK-rearranged mesenchymal tumors were evaluated. For both classic and variant groups, the age at diagnosis ranged from birth to 15 years (median, 4 mo) with no sex predilection; the most common sites involved were the extremities and trunk. The rate of local recurrence and metastasis were not significantly different (recurrence rate: 11% classic, 40% variant; metastatic rate: 18% classic, 25% variant). Classic and variant NTRK tumors had an overlapping spectrum of histologic features, containing haphazardly arranged primitive cells in a myxoid background and/or spindle cells in long fascicles. Both groups showed diffuse pan-TRK expression by immunohistochemistry. Otherwise, the immunoprofile was nonspecific, but similar between both groups. No statistical difference was seen in any clinicopathologic feature between the classic ETV6-NTRK3 and variant fusion cohorts. Pediatric NTRK-rearranged mesenchymal tumors with both classic and variant fusions likely represent a spectrum of disease with shared, recognizable cliniopathologic features.
Bibliographical noteFunding Information:
Conflicts of Interest and Source of Funding: J.L.D. has received fees for an advisory board role from Loxo Oncology. S.G.D. has received fees for consulting and advisory board roles from Loxo Oncology and has received travel expenses from Roche/Genentech. M.C.C. is an employee of and owns stock in Loxo Oncology, holds a patent 62/318,041 issued to Loxo Oncology, and owns stock in Bayer AG. T.W.L. has received fees for consulting and advisory board roles from Loxo Oncology, Eli Lilly, and Novartis and his institution has received research funding from Pfizer. D.S.H. has received travel expense reimbursement from Loxo Oncology, Bayer, Celgene, and Bristol-Myers Squibb. For the remaining authors none were declared.
© 2018 Wolters Kluwer Health, Inc. All rights reserved.
- infantile fibrosarcoma
- soft tissue sarcoma