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Cutaneous Neurotrophic Tyrosine Receptor Kinase-Rearranged Spindle Cell Neoplasm: A Diagnostic Dilemma
Radhika Sudhir1, Su E Low2, Anirban Mandal2
1Royal Liverpool University Hospital, Liverpool, United Kingdom; and.
Abstract:
NTRK (Neurotrophic Tyrosine Receptor Kinase)-rearranged spindle cell neoplasms are a group of molecularly defined tumors with a varied morphological spectrum, displaying overlapping features of infantile fibrosarcoma, lipofibromatosis, and malignant peripheral nerve sheath tumors (Surrey and Davis JL. Cancer Genet. 2022;260-261:6-13). This report discusses a case of an NTRK-rearranged spindle cell neoplasm arising from the left forearm of a 32-year-old patient. The lesion histologically comprised an infiltrative, nodular tumor with heterogeneous stroma displaying myxoid, scar-like and lipofibromatosis-like areas. Areas of hypercellularity with increased mitotic activity were noted. The tumor cells displayed diffuse, strong expression of S100 and CD34. Granular cytoplasmic expression of Pan-TRK immunohistochemistry favored the presence of an NTRK rearrangement. RNA-based next-generation sequencing was performed for confirmation and detected an ETV6::NTRK3 fusion, thereby confirming the diagnosis of an NTRK-rearranged spindle cell neoplasm. The vast morphological spectrum of this entity poses a diagnostic challenge for dermatopathologists, necessitating consideration of a broad range of differential diagnoses. Accurate assessment and reporting of this emerging entity requires correlation of histology and immunohistochemistry, and detection of an NTRK fusion using next-generation sequencing.
Insights
Neurotrophic Tyrosine Receptor Kinase (NTRK)-rearranged spindle cell neoplasms present a diagnostic challenge due to varied morphology. This case highlights the importance of integrating histology, immunohistochemistry, and next-generation sequencing for accurate diagnosis.
Area of Science:
- Oncology
- Pathology
- Molecular Diagnostics
Background:
- Neurotrophic Tyrosine Receptor Kinase (NTRK)-rearranged spindle cell neoplasms are a diverse group of tumors.
- These neoplasms exhibit overlapping features with infantile fibrosarcoma, lipofibromatosis, and malignant peripheral nerve sheath tumors.
Purpose of the Study:
- To report a case of an NTRK-rearranged spindle cell neoplasm in a 32-year-old patient.
- To emphasize the diagnostic challenges and the necessity of integrated diagnostic approaches.
Main Methods:
- Histopathological examination of the tumor from the left forearm.
- Immunohistochemistry for S100, CD34, and Pan-TRK.
- RNA-based next-generation sequencing to detect gene fusions.
Main Results:
- The lesion showed an infiltrative, nodular pattern with heterogeneous stroma and areas of hypercellularity.
- Tumor cells expressed S100 and CD34 diffusely, with granular cytoplasmic Pan-TRK expression.
- ETV6::NTRK3 fusion was identified, confirming the diagnosis of an NTRK-rearranged spindle cell neoplasm.
Conclusions:
- NTRK-rearranged spindle cell neoplasms have a broad morphological spectrum, posing diagnostic challenges.
- Accurate diagnosis requires correlating histology and immunohistochemistry with molecular detection of NTRK fusions.
- Next-generation sequencing is crucial for confirming the diagnosis of this emerging entity.
