Soft Tissue Tumors Characterized by a Wide Spectrum of Kinase Fusions Share a Lipofibromatosis-like Neural Tumor Pattern

Kao, Y-C., Suurmeijer, A. J. H., Argani, P., Dickson, B. C., Zhang, L., Sung, Y-S., Agaram, N. P., Fletcher, C. D. M. & Antonescu, C. R., 6-Jul-2020, In : GENES CHROMOSOMES & CANCER. 9 p.

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  • Soft Tissue Tumors Characterized by a Wide Spectrum of Kinase Fusions Share a Lipofibromatosis‐like Neural Tumor Pattern

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  • Soft tissue tumors characterized by a wide spectrum of kinase fusions share a lipofibromatosis‐like neural tumor pattern

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  • Yu-Chien Kao
  • Albert J H Suurmeijer
  • Pedram Argani
  • Brendan C Dickson
  • Lei Zhang
  • Yun-Shao Sung
  • Narasimhan P Agaram
  • Christopher D M Fletcher
  • Cristina R Antonescu

Gene fusions resulting in oncogenic activation of various receptor tyrosine kinases, including NTRK1-3, ALK, and RET, have been increasingly recognized in soft tissue tumors (STTs), displaying a wide morphologic spectrum and therefore diagnostically challenging. A subset of STT with NTRK1 rearrangements were recently defined as lipofibromatosis-like neural tumors (LPFNT), being characterized by mildly atypical spindle cells with a highly infiltrative growth in the subcutis and expression of S100 and CD34. Other emerging morphologic phenotypes associated with kinase fusions include infantile/adult fibrosarcoma and malignant peripheral nerve sheath tumor-like patterns. In this study, a large cohort of 73 STT positive for various kinase fusions, including 44 previously published cases, was investigated for the presence of a LPFNT phenotype, to better define the incidence of this distinctive morphologic pattern and its relationship with various gene fusions. Surprisingly, half (36/73) of STT with kinase fusions showed at least a focal LPFNT component defined as >10%. Most of the tumors occurred in the subcutaneous tissues of the extremities (n = 25) and trunk (n = 9) of children or young adults (<30 years old) of both genders. Two-thirds (24/36) of these cases showed hybrid morphologies with alternating LPFNT and solid areas of monomorphic spindle to ovoid tumor cells with fascicular or haphazard arrangement, while one-third (12/36) had pure LPFNT morphology. Other common histologic findings included lymphocytic infiltrates, staghorn-like vessels, and perivascular or stromal hyalinization, especially in hybrid cases. Mitotic activity was generally low (<4/10 high power fields in 81% cases), being increased only in a minority of cases. Immunoreactivity for CD34 (92% in hybrid cases, 89% in pure cases) and S100 (89% in hybrid cases, 64% in pure cases) were commonly present. The gene rearrangements most commonly involved NTRK1 (75%), followed by RET (8%) and less commonly NTRK2, NTRK3, ROS1, ALK, and MET. This article is protected by copyright. All rights reserved.

Original languageEnglish
Number of pages9
Early online date7-Jun-2020
Publication statusPublished - 6-Jul-2020


  • lipofibromatosis-like neural tumor, MET, NTRK, RET, NTRK1 GENE FUSIONS, SUBSET, SARCOMAS

ID: 126876052