Spindle Cell Neoplasm

Spindle Cell Neoplasm

35 y/o female athlete present with a growing mass in her right proximal thigh. An MRI with contrast was performed that showed a 9.2 x 7.0 x 8.2 cm right gluteal soft tissue mass with intermediate signal on T1 sequences isointense to muscle, heterogeneously bright signal intensity on T2 and avid contrast enhancement. Some areas of central nonenhancement are present in the anterior half of the mass as may be seen with necrosis.

The lesion involves the right gluteus maximus, right gluteus medius and subcutaneous tissues with signal abnormality along the posterior right iliac wing suspicious for involvement by the mass and extension into the bone.

A biopsy of the mass was performed (see H&E images). A panel of immunohistochemistry showed only CD34 and CD99 positivity; Desmin, S-100, ALK-1, pancytokeratin, EMA, SMA, MyoD1, CD117, STAT6, INI-1, SOX10 and MDM2 are negative. A sarcoma fusion NGS panel was ordered. A fusion was found, and the patient began treatment with Larotrectinib with good clinical response.

Which gene fusion is likely to have been found?

a. ESWR1-WT1
e. MYH9-USP6

Figure 1.

Figure 1

Figure 2.

Figure 2

Figure 3.

Figure 3

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Answer: D

Discussion: NTRK Fusion in sarcoma

The patient was found to have a STRN-NTRK2 fusion. After initial treatment with Larotrectinib the tumor significantly reduced in size, but the patient later developed large pulmonary metastases. The medication was changed to a different TRK inhibitor, and she is now in remission.

Chromosomal rearrangements involving the neurotrophic receptor tyrosine kinase 1, 2, and 3 genes, NTRK1, NTRK2, and NTRK3, which lead to functional gene fusions, have been found to act as oncogenic drivers in a broad range of tumor. Among sarcomas, infantile fibrosarcoma shows NTRK fusion in more than 90% of cases. Many other sarcoma types are also investigated for NTRK fusions.

The ESWR1-WT1 fusion is found in desmoplastic small round cell tumors; NAB2-STAT6 in solitary fibrous tumor; FUS-DDIT3 in myxoid/round cell liposarcoma and MYH9-USP6 in nodular fasciitis.


  1. Siozopoulou V, Smits E, De Winne K, Marcq E, Pauwels P. NTRK Fusions in Sarcomas: Diagnostic Challenges and Clinical Aspects. Diagnostics (Basel). 2021;11(3):478. Published 2021 Mar 9. doi:10.3390/diagnostics11030478
  2. Hsiao SJ, Zehir A, Sireci AN, Aisner DL. Detection of Tumor NTRK Gene Fusions to Identify Patients Who May Benefit from Tyrosine Kinase (TRK) Inhibitor Therapy. J Mol Diagn. 2019 Jul;21(4):553-571. doi: 10.1016/j.jmoldx.2019.03.008. Epub 2019 May 7. PMID: 31075511; PMCID: PMC7456740.
  3. Brčić, I., Godschachner, T.M., Bergovec, M. et al. Broadening the spectrum of NTRK rearranged mesenchymal tumors and usefulness of pan-TRK immunohistochemistry for identification of NTRK fusions. Mod Pathol 34, 396–407 (2021). https://doi.org/10.1038/s41379-020-00657-x


Dario E. Sanabria MD FCAP, Juan C. Santa Rosario MD FCAP FASCP