Plexiform Wagner‐Meissner schwannoma with a SH3PXD2A::HTRA1 fusion: a twisted sister?

BACKGROUND: A peripheral nerve sheath tumour composed predominantly of Wagner-Meissner (W-M) bodies is typically regarded as a variant of schwannoma and has been considered rare. Interestingly, a SH3PXD2A::HTRA1 fusion was found which is described in schwannomas with a so-called "serpentine" palisading pattern comprising short palisades of Schwann cells. METHODS: We describe a case of plexiform W-M schwannoma with a SH3PXD2A::HTRA1 fusion demonstrated on RNA-based next generation sequencing and review the relevant histological, immunohistochemical and molecular findings and discuss differential diagnoses. RESULTS: The lesion arose in the distal volar pulp of the right middle finger in a 37-year-old female. It had a plexiform architecture and was composed predominantly of densely packed, repetitive Wagner-Meissner bodies which expressed S100, SOX10, Calretinin and CD56, with intervening S100, SOX10, CD34 and patchy EMA staining. It showed no NF1 expression. A SH3PXD2A::HTRA1 fusion was present. CONCLUSIONS: The case presented suggests that so-called W-M schwannomas may be driven by SH3PXD2A::HTRA1 fusions and that W-M bodies in this context correlate with the 'serpentine' palisading pattern described in schwannomas with HTRA1 rearrangements. Analysis of further cases of W-M rich or predominant lesions including schwannoma, neurilemmoma and perhaps even neurotised melanocytic naevi may warrant consideration.