Identification of NTRK3 fusions in plaque-like CD34-positive dermal fibroma

Plaque-like CD34-positive dermal fibroma (PDF), previously termed medallion-like dermal dendrocyte hamartoma, is a rare CD34-positive superficial spindle cell fibroblastic tumour that may closely mimic dermatofibrosarcoma protuberans. Recent studies have identified recurrent kinase gene fusions in a subset of congenital and paediatric CD34-positive plaque-like superficial spindle cell tumours with overlapping clinicopathologic features, highlighting an emerging molecular framework for this group. However, the molecular spectrum of lesions meeting classic histopathologic criteria for PDF remains an area of active investigation.

Four cases of PDF were identified retrospectively, and histopathologic and immunohistochemical findings were reviewed. RNA-based next-generation sequencing was performed to evaluate for potential oncogenic gene fusions. All cases demonstrated a superficial, dermal-based proliferation of bland spindle cells with a preserved Grenz zone and diffuse CD34 expression, without S100 expression. Two of four cases harboured in-frame NTRK3 fusions, including a novel SPTBN1::NTRK3 fusion and a PPFIBP1::NTRK3 fusion, both retaining the NTRK3 tyrosine kinase domain. Available clinical follow-up demonstrated indolent behaviour in all patients.

NTRK3 gene fusions occur in a subset of plaque-like CD34-positive dermal fibromas, providing additional molecular insight into this rare superficial spindle cell lesion. Together with emerging literature, these findings support a role for recurrent kinase gene rearrangements in a subset of CD34-positive plaque-like superficial spindle cell tumours, while underscoring the continued importance of clinicopathologic correlation in defining this evolving spectrum.