Biomarker NTRK Coverage from Every Angle

Morphologic and Molecular Characterization of NTRK Fusion Uterine Sarcoma

By: Justine Landin, PhD
Posted: Tuesday, December 21, 2021

NTRK fusion uterine sarcoma has a unique morphologic and immunophenotypic description, according to an update on the pathologic diagnosis of uterine mesenchymal tumors by David B. Chapel, MD, and Marisa R. Nucci, MD, of the University of Michigan, Ann Arbor, and Harvard Medical School, Boston, respectively. In particular, NTRK fusion uterine sarcoma is of low malignant potential and consistent expression of select proteins; unresectable or recurrent tumors are responsive to treatment with the TRK inhibitor larotrectinib. The findings of this article were published in the journal Diagnostic Histopathology.

NTRK fusion uterine sarcoma is a tumor of low malignant potential that mainly affects young women (median age = 30.5 years), with 90% of tumors found in the cervix. Morphologic characteristics of the tumors include tan-yellow to tan-pink polypoid endocervix-based lesions with infiltrative borders, with or without gross necrosis. A fascicular, storiform, or patternless arrangement of fibroblastic spindle cells is often observed with eosinophilic cytoplasm and nuclear atypia. Hyalinization of tumor vessels, necrosis, and lymphocytic inflammation are common manifestations.

Immunohistochemistry indicates that the majority of tumors are negative for desmin and hormone receptors but positive for CD34 and S100. Rearrangement of NTRK1, NTRK2, and NTRK3 and fusion partners led to the overexpression of Trk. NTRK1-TPM3 fusion is the most common, often occurring with CDKN2A deletion. Pan-Trk immunohistochemistry for NTRK-rearranged sarcomas is 75% to 95% sensitive overall for targeting TrkA, TrkB, and TrkC, compared with positive immunostaining in all reported cases of NTRK fusion uterine sarcomas, according to the researchers. 

“Given the imperfect specificity of pan-Trk immunohistochemistry, the novelty and rarity of NTRK fusion uterine sarcoma, and the availability of targeted therapy with the Trk inhibitor larotrectinib, molecular confirmation of NTRK fusion is recommended for diagnosis of NTRK fusion uterine sarcoma,” stated the study investigators.

Disclosure: The study authors reported no conflicts of interest.

By continuing to browse this site you permit us and our partners to place identification cookies on your browser and agree to our use of cookies to identify you for marketing. Read our Privacy Policy to learn more.