Dermatomyofibromas harbor PDGFRB mutations - another tyrosine kinase-driven neoplasm.

Abstract

Platelet-derived growth factor receptor beta (PDGFRB) is one of the numerous members of the receptor tyrosine kinase protein family. When altered, it is known to be the driver mutation in different mesenchymal neoplasms, such as pericytic tumors, inflammatory myofibroblastic tumor, and sarcomas with myogenic differentiation. We investigated seven dermatomyofibromas for the presence of a PDGFRB mutation. Patients were 6 females and 1 male. Ages ranged from 2 to 59 years. Neoplasms were located in the shoulder (2), neck (2), upper arm (1), knee (1), and calf (1). Clinically, they appeared as ill-defined plaques. Complete excision was performed in four cases. In three cases, only a biopsy was taken. Histomorphologically, these dermal ill-defined tumors consisted of fascicles of slender myofibroblastic cells oriented often parallel to the epidermis. Their nuclei were monomorphic and elongated, and the cytoplasm was inconspicuous. Involvement of the superficial subcutis was seen in four cases. Immunohistochemically, neoplasms expressed SMA (5/7), focally desmin (1/5), and CD34 (4/6), while S100 was lacking (0/7). By DNA or RNA sequencing, PDGFRB activating mutations were identified in 6/7 tumors. Four neoplasms harbored a mutation in exon 12 encoding for the juxtamembrane domain and 2 neoplasms in exon 14 encoding for the tyrosine kinase domain. Sequencing analyses results highlight that these benign skin tumors belong to the broad spectrum of tyrosine kinase-driven neoplasms.