Tyrosine kinase‐altered spindle cell neoplasms with EGFR internal tandem duplications

Abstract

In this study, we present two extra‐renal pediatric spindle cell neoplasms with epidermal growth factor receptor (EGFR) internal tandem duplications (ITD). Histologically, these tumors demonstrated the same histologic features seen in other tyrosine kinase‐altered spindle cell neoplasms, with one case showing abundant adipose tissue with cellular fibrous septae resembling lipofibromatosis and the other case showing fascicles of spindled cells resembling infantile fibrosarcoma. There was variable expression of CD34, S100, and SMA, and all cases were negative for panTRK. This case series adds to our molecular understanding of the spectrum of tyrosine kinase‐altered spindle cell neoplasms and represents the first reported examples of EGFR ITDs in extra‐renal tumors. The presence of EGFR alterations in the absence of gene fusions represents a potential therapeutic target and necessitates a broader testing panel for this group of tumors.

FGFR1 tyrosine kinase domain duplication in infantile soft tissue spindle cell tumor

“…[5][6][7][8] Very recently, EGFR TKDD has also been reported in infantile spindle cell tumors. [14][15][16] FGFR1 activation driven by TKDD found in our case further broadens the molecular spectrum of pediatric spindle cell tumors.…”

Expanding the Clinical Utility of Targeted RNA Sequencing Panels beyond Gene Fusions to Complex, Intragenic Structural Rearrangements

“…Similarly, EGFR ITDs are described in the setting of infantile fibrosarcoma and congenital mesoblastic nephroma, particularly in classic or mixed subtype, and aids in diagnostics if the tumor is negative for the more commonly identified ETV6::NTRK3 fusion. This scenario further highlights the utility of broader panel testing and analysis to encompass recurrent events to enable alignment for an integrated diagnosis along with histopathologic characteris-tics [19,20,37,61]. FGFR1 ITDs are commonly reported in the setting of low-grade glial tumors for which the therapeutic significance is still under study [5,8,15].…”