Biomarker NTRK Coverage from Every Angle

Case Study: Broad Morphologic Spectrum of Mesenchymal Tumors With NTRK Fusions

By: Justine Landin, PhD
Posted: Wednesday, December 1, 2021

The morphologic range of mesenchymal tumors associated with NTRK fusions may be broader than previously reported, according to a case study conducted by João Victor Alves de Castro, MD, of A.C. Camargo Cancer Center, Brazil, and colleagues. In fact, an NTRK fusion was detected in a high-grade, soft-tissue sarcoma with a pure epithelioid morphology. Despite the patient being treated with chemotherapy and the TRK inhibitor larotrectinib, delayed prognosis may have contributed to her death.

“Pan-Trk immunohistochemistry and/or NTRK molecular testing should be performed in all metastatic or locally advanced tumors irrespective of morphologic appearance in order to identify NTRK rearrangements not previously suspected,” stated the study investigators. The details of this case presentation were published in the journal Histopathology.

A 51-year-old woman presented with a history of non-painful swelling of her right thigh. MRI confirmed the presence of a mass involved in the calf muscles with cortical bone erosion and necrosis of the femur. Core-needle biopsy revealed a malignant neoplasm with mixed spindle cell and epithelioid features. Chest CT indicated bilateral metastatic lung cancer. Surgical resection of the tumor confirmed high-grade sarcoma with diffuse epithelioid morphology and scattered neoplastic multinucleated giant cells.

Despite the pure epithelioid morphology, and no hyalinized stromal or perivascular collagen deposition, pan-Trk immunohistochemistry of the tumor was conducted. Targeted RNA sequencing confirmed a SQSTM1-NTRK1 fusion involving exons 5 and 10. Following cycle 6 of chemotherapy, the patient exhibited new metastatic modules in the lungs, and larotrectinib treatment was administered. About 3 months after this targeted treatment, local recurrence led to its discontinuation. The patient died of tumor-related complications 7 months following the start of targeted therapy.

The authors stated that they are “hoping to raise awareness of the possible morphological variations of NTRK-rearranged mesenchymal neoplasms and, ultimately, broaden treatment opportunities for patients with locally advanced and unresectable or metastatic sarcomas.”

Disclosure: The study authors reported no conflicts of interest.

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