RESUMO
EGFR aberrations are reported in a subset of myofibroblastic lesions with kinase domain duplication (EGFR-KDD) and exon 20 mutations being assigned to infantile fibrosarcomas (IFS), mesoblastic nephroma and fibrous hamartoma of infancy (FHI), respectively. In this retrospective study, we correlated molecular findings with histomorphology of 14 myofibroblastic lesions harboring such genetic changes identified by NGS. We additionally performed DNA methylation profiling (DNAmp) and immunohistochemistry. Lesions were from 10 males and 4 females with a mean age of 3 years (range, 0.3 -14) and occurred subcutaneously in the upper limbs (n = 5), lower limbs (n = 3), back/thorax (n = 5), and the nasal cavity (n = 1). Eleven were cured by surgery, including one relapsed case. Two patients were lost to follow-up. One case was very recent, and the patient was biopsied. Histologically, the lesions showed a wide spectrum varying from classic FHI (n=9) to IFS (n=1) or lipofibromatosis-like tumors (LFT-like) (n=2) or dermatofibrosarcoma protuberans-like (DFSP-like) (n=1) to a predominantly-myxoid spindle cell lesion (n=1). Immunohistochemically, all neoplasms stained with CD34, while S100 was positive in 2/14. EGFR expression was observed in 9/10 cases. Molecularly, the IFS and one LFT-like harbored EGFR-KDD, while an exon 20 mutation was identified in all FHI, one LFT-like and in the DFSP-like and predominantly myxoid spindle cell lesion. By DNAmp, all but two cases formed a well-defined cluster, demonstrating that these lesions are also epigenetically related. In conclusion, EGFR kinase domain aberrations found in FHI, IFS, LFT-like, DFSP-like and a spindle cell lesion with a predominant myxoid stroma of children and adolescents show that these neoplasms with a broad morphological spectrum belong to the group of protein kinase-related lesions with a distinct epigenetic signature. Molecular analyses, including DNAmp, help to identify and characterize this emerging category and become mandatory when targeted treatment is considered.
