Expanding the Spectrum of Pediatric NTRK -rearranged Mesenchymal Tumors

Jessica L. Davis, Christina M. Lockwood, Bradley Stohr, Carolin Boecking, Alyaa Al-Ibraheemi, Steven G. Dubois, Sara O. Vargas, Jennifer O. Black, Michael C. Cox, Mark Luquette, Brian Turpin, Sara Szabo, Theodore W Laetsch, Catherine M. Albert, David M. Parham, Douglas S. Hawkins, Erin R. Rudzinski

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)435-445
Number of pages11
JournalAmerican Journal of Surgical Pathology
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2019

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Keywords

  • infantile fibrosarcoma
  • NTRK
  • pediatric
  • soft tissue sarcoma
  • TRK

ASJC Scopus subject areas

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

Davis, J. L., Lockwood, C. M., Stohr, B., Boecking, C., Al-Ibraheemi, A., Dubois, S. G., Vargas, S. O., Black, J. O., Cox, M. C., Luquette, M., Turpin, B., Szabo, S., Laetsch, T. W., Albert, C. M., Parham, D. M., Hawkins, D. S., & Rudzinski, E. R. (2019). Expanding the Spectrum of Pediatric NTRK -rearranged Mesenchymal Tumors. American Journal of Surgical Pathology, 43(4), 435-445. https://doi.org/10.1097/PAS.0000000000001203