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Morphologic Characterization of Mesenchymal Tumors With NTRK Alterations

By: Justine Landin, PhD
Posted: Monday, March 14, 2022

Mesenchymal neoplasms harboring NTRK alterations may be amenable to targeted therapies based on clinicopathologic features, according to Lea F. Surrey, MD, of The Children’s Hospital of Philadelphia, and colleagues. In fact, select morphologic features of mesenchymal tumors appear to be associated with specific kinase alterations and may impact treatment options. The findings of this review were published in the journal Histopathology.

“Mesenchymal tumors with NTRK and other kinase alterations show a relatively broad but recognizable spectrum of morphologies. These histologies should prompt further exploration for the precise kinase alteration to aid in diagnosis as well as correct management and therapeutic options for these patients,” stated the study investigators.

NTRK-rearranged spindle cell neoplasms typically contain stellate to spindle cell tumors, which closely resemble lipofibromatosis-like neural tumors (LPFNTs), peripheral nerve sheath tumors, or fibrosarcomas. LPFNTs are superficial tumors with bland spindle cells that infiltrate the underlying subcutis. A subset of LPFNTs share similar morphology to peripheral nerve sheath tumors, with a more solid pattern; they contain scattered pleomorphic or multinucleated cells and rarely exhibit necrosis. These LPFNTs typically harbor NTRK1 or NTRK3 fusions and rarely other types. Adult-type fibrosarcomas harboring NTRK arrangements are rare but usually found within the cervix and uterus. These sarcomas exhibit a solid pattern, fascicular growth, and extensive infiltration around glandular structures. They typically harbor NTRK3, RAF1, and BRAF fusions.

Pan-TRK immunohistochemistry is recommended as a first-line screening test in soft-tissue tumors suspected of harboring NTRK fusions. The reported specificity of pan-TRK screening is approximately 90%. Following a positive result, fluorescence in situ hybridization may be used to probe for NTRK1-3. A more efficient molecular technology may be next-generation sequencing to target exact genes to ensure adequate coverage of other kinases. Treatment options include complete surgical resection; in situations where this is not possible, kinase inhibition therapy, such as larotrectinib and entrectinib, may be substituted.

Disclosure: For full disclosures of the study authors, visit onlinelibrary.wiley.com.


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