Recurrent alterations in receptor tyrosine kinase (RTK) and downstream effectors are described in infantile fibrosarcoma (IFS)/cellular congenital mesoblastic nephroma (cCMN) and a subset of spindle cell sarcomas, provisionally designated “NTRK-rearranged” spindle cell neoplasms. These two groups of tumors demonstrate overlapping morphologies and harbor alterations in NTRK1/2/3, RET, MET, ABL1, ROS1, RAF1, and BRAF, although their relationship is not fully elucidated. We describe herein a cohort of pediatric tumors with clinicopathologic features not typical for inflammatory myofibroblastic tumor, but rather with similarities to cCMN/IFS harboring ALK fusions.

Clinicopathologic features were assessed and partner agnostic targeted RNA sequencing on clinically validated platforms were performed. Tumors occurred in patients from 2 to 10 years (median age 2 years) with a 2:2 male to female ratio and an average size of 8.4 cm. Two tumors arose in soft tissues and 2 in the kidney. Morphologic features included spindle to ovoid cells arranged in long fascicles or haphazardly within a myxoid to collagenized stroma; a subset of cases had either dilated, ectatic vessels or focal perivascular hyalinosis. By immunohistochemistry, all cases tested showed cytoplasmic expression of ALK and one case demonstrated co-expression of CD34 and S100.

This series of ALK rearranged IFS-like tumors expands the spectrum of targetable kinases altered in these tumors and reinforces the potential overlap between IFS/cCMN-like tumors and the provisional entity of “NTRK-rearranged” spindle cell neoplasms.