Abstract

Giant-cell tumor of soft tissue (GCT-ST) is a rare, low-grade neoplasm characterized by a nodular proliferation of bland, histiocytoid mononuclear cells with prominent osteoclast-like giant cells.1,2 A novel subset of keratin-positive GCT-STs harboring an HMGA2::NCOR2 fusion (KGCT-ST) has been recently been described.2 To our knowledge, only six cases arising in soft tissue are reported in the English literature;2 herein we report a series of four additional cases arising in young females (ages 13-40 years). Anatomic sites included the medial scapula, arm, forearm, and eyebrow. Histopathologically, the lesions were characterized by circumscribed collections of osteoclast-like multinucleated giant cells with scattered keratin-positive mononuclear cells within the dermis and subcutis. Lymphoid cuffs, foamy macrophages, and cholesterol clefts were variably present, but metaplastic bone formation was uniformly absent. In one case, next-generation sequencing confirmed the presence of the HMGA2::NCOR2 fusion gene; molecular studies on the remaining cases are underway. HMGA2::NCOR2 fusion has also been rarely described in other benign mesenchymal entities, including neoplasms showing the same morphology arising in bone.3,4 Important differential diagnoses for KGCT-ST include other keratin-positive soft tissue tumors including epithelioid sarcoma and the recently described xanthogranulomatous epithelial tumor, other giant-cell-rich soft tissue tumors, and metastatic carcinoma.2,5,6 Though KGCT-ST appears to exhibit indolent behavior, follow-up data is limited. 2 The one patient in our series with follow-up remains disease free at 24 months. KGCT-ST may be more common than is currently evident, as 5 of 14 GCT-STs retrieved in the initial study were positive for the novel gene fusion.2 Diagnostic knowledge of, and further studies to characterize the epidemiologic and prognostic behavior of this entity will be particularly valuable to dermatopathologists.

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