BCR-NTRK2 fusion in a low-grade glioma with distinctive morphology and unexpected aggressive behavior

Abstract

A 52-yr-old man was found to have a 6.6-cm left frontotemporal mass. Biopsy revealed a low-grade astrocytic neoplasm with significant infiltration and an unusual morphologic appearance. Only rare mitotic figures were seen and the Ki-67 proliferative index was very low. Unexpectedly, the low-grade astrocytoma showed rapid progression within a short time, but subsequent resection showed similar histologic findings to the original biopsy with only slightly more mitoses and a marginally increased Ki-67 proliferative index. Molecular testing performed on the tumor showed no alterations in the IDH1, IDH2, EGFR, or BRAF genes by sequencing, intact 1p/19q by FISH, and a novel BCR-NTRK2 fusion transcript by reverse transcription and anchored multiplex PCR. The patient underwent standard-of-care therapy, both first and second line, for a high-grade glioma because of the aggressive behavior, but the glioma continued to progress despite treatment, and the patient died within 13.5 mo of the original diagnosis. At the time of diagnosis, the BCR-NTRK2 fusion transcript had not been described in solid tumors; however, a recent publication described this fusion transcript in two glioblastomas. Although no approved therapy was available for this patient, FDA approval has now been given for solid tumors with any NTRK gene family fusions. This unexpected molecular finding in a deceptively low-grade-appearing glioma supports the use of expanded molecular testing in gliomas and solid tumors, particularly in instances where targeted therapies are available.