Infantile fibroblastic and myofibroblastic tumors are the second most prevalent type of soft tissue neoplasms in pediatric patients < 1 years old. Although the majority of these tumors are either benign or low-grade, there are certain subtypes with a higher tendency toward malignancy. Congenital infantile fibrosarcoma (CIFS) is one such high-risk group. CIFS patients present with morphologically ambiguous tumors that can resemble a range of other infantile neoplasms of varying clinical course.
Fortunately, a genetic hallmark of CIFS is the t(12;15)(p13;q25) translocation, with results in ETV6-NTRK3 fusion. This lesion is found in 85% of CIFS patients. Recently, however, several cases of patients with tumors resembling CIFS but lacking ETV6-NTRK3 were identified. These neoplasms fit CIFS’s clinicopathological profile, but were found to harbor different types of NTRK fusions. Of the six patients analyzed, four had TPM3-NTRK1 fusions, one had an LMNA-NTRK1 fusion, and one a variant EML4-NTRK3 fusion.
NTRK gene fusions are emerging as driver mutations in a wide array of solid tumors, with a predisposition for children and young adults, having been described in pediatric gliomas (NTRK1, NTRK2, NTRK3), papillary thyroid carcinoma (NTRK1), spitzoid neoplasms (NTRK1), and infantile fibrosarcoma (NTRK3). However, NTRK1 fusions have only recently been detected in soft tissue tumors, so the discovery of 2 novel NTRK1 fusions in this study is significant.
Results indicate that these neoplasms constitute a new genetic subset of infantile mesenchymal tumors, morphologically and clinically resembling CIFS, but harboring different types of NTRK fusions. The team behind the study recommends labeling this new class of neoplasms as NTRK-associated mesenchymal tumors, in order to highlight their shared molecular and clinical characteristics with CIFS, as well as to emphasize the potential utility of NTRK-targeted therapies for patients with locally aggressive disease.
Source: Davis, Jessica L., et al. "Infantile NTRK-associated mesenchymal tumors." Pediatric and Developmental Pathology 21.1 (2018): 68-78.
Published: December 05th, 2019