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Case Reports

Abstract

Recently, a distinct subtype of epithelioid mesenchymal neoplasms harboring GLI1 genetic alterations (rearrangement or amplification) has been identified in various anatomic locations. Very few cases reported in the literature occurred exclusively in the skin. Here, we describe a GLI1-amplified primary cutaneous case.

A 48-year-old male presented with an isolated nodule on the right ring finger. Histologic sections demonstrated a multinodular proliferation of monomorphic ovoid cells arranged in nests, cords, and nodules in a densely fibrotic stroma with scattered small, well-formed vessels.  The lesional cells have slightly enlarged nuclei, irregular nuclear membranes, conspicuous nucleoli, and abundant clear eosinophilic cytoplasm. There were up to 10 mitotic figures per 10 HPF. Immunohistochemical analysis revealed strong positivity for MDM2, focal positivity for S100 protein, and negativity for STAT6, SOX-10, EMA, SMA, desmin, pankeratin, DUX4, CD99, CD31, CD34, CD45, CD68, and synaptophysin. While next-generation sequencing (NGS) did not reveal a gene fusion, fluorescence in situ hybridization (FISH) was positive for amplification of the GLI1 and DDIT3 gene region, supporting the diagnosis of a GLI1-altered mesenchymal neoplasm.

Considering the morphological overlap of GLI1-altered tumors with other cutaneous round cell neoplasms and their potential for malignant behavior, recognition of this entity is crucial for dermatopathologists. Immunoreactivity for markers such as MDM2 and STAT6 may be a clue to the diagnosis, but molecular studies are required to confirm the diagnosis.  As some cases lack GLI1 fusions, like ACTB::GLI1 and ATP2B4::GLI1, and instead feature GLI1 gene amplification, NGS and FISH techniques may both be necessary to confirm the diagnosis.