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Xanthogranulomatous epithelial tumors and keratin-positive giant cell-rich soft tissue tumors: two aspects of a single entity with frequent HMGA2-NCOR2 fusions

Abstract

Xanthogranulomatous epithelial tumor (XGET) and keratin-positive giant cell-rich soft tissue tumor with HMGA2-NCOR2 fusion (KPGCT) are two recently described neoplasms with both distinct and overlapping clinical and histopathologic features. We hypothesized that XGET and KPGCT may be related and represent a histologic spectrum of a single entity. To test this, we sought to characterize the clinical, radiographic, immunohistochemical, ultrastructural and molecular features of additional tumors with features of XGET and/or KPGCT, which we refer to descriptively as keratin-positive xanthogranulomatous/giant cell-rich tumors (KPXG/GCT). The archives were searched for potential cases of KPXG/GCT. Clinical and imaging features were noted. Slides were assessed for histologic and immunohistochemical findings. Ultrastructural and next generation RNA sequencing-based analysis were also performed. Nine cases were identified arising in seven women and two men [median age of 33 years (range: 12–87)]. Median tumor size was 4 cm (range: 2.4–14.0 cm) and tumors presented in the thigh (2), buttock (1), forearm (2), groin (1), cranial fossa (1), ilium (1), and tibia (1). Morphologically, tumors were most frequently characterized by a fibrous capsule, with associated lymphoid reaction, enclosing a polymorphous proliferation of histiocytes, giant cells (Touton and osteoclast-types), mixed inflammatory infiltrate, hemorrhage and hemosiderin deposition, which imparted a variably xanthogranulomatous to giant cell tumor-like appearance. One case clearly showed mononuclear cells with eosinophilic cytoplasm characteristic of XGET. All cases expressed keratin and 7 of 9 were found to harbor HMGA2-NCOR2 fusions including cases with xanthogranulomatous appearance. One patient developed local recurrence and multifocal pulmonary lesions, which were radiographically suspicious for metastases. Shared clinical, histologic and immunohistochemical features, and the shared presence of HMGA2-NCOR2 fusions supports interpretation of KPXG/GCT as a single entity which includes XGET and KPGCT. Given limited clinical follow-up to date and rare cases with apparently aggressive findings, we provisionally regard these tumors as having uncertain biologic potential.

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Fig. 1: Gross and imaging features of soft tissue tumors.
Fig. 2: Imaging features of bone tumors.
Fig. 3: Spectrum of histomorphology.
Fig. 4: Additional histologic features.
Fig. 5: Case 1 with typical histologic features of xanthogranulomatous epithelial tumor.
Fig. 6: Histologic and immunohistochemical features of tumors without identified fusion.
Fig. 7: Immunohistochemical features.
Fig. 8: Ultrastructural features.

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Available upon request.

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Funding

Washington University School of Medicine Department of Pathology and Immunology; Mount Sinai Hospital Department of Pathology and Laboratory Medicine.

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C.A.D. and J.S.A.C.—project conception and design, data gathering, data analysis, paper drafting, paper review/revision; J.C.B.—data gathering, data analysis, paper drafting, paper review/revision; R.B.—data analysis, paper drafting, paper review/revision; B.C.D.—data gathering, paper review/revision; R.E.S.—data gathering, data analysis, paper drafting, paper review/revision; E.G.D.—data gathering, data analysis, paper drafting, paper review/revision.

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Correspondence to John S. A. Chrisinger.

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Dehner, C.A., Baker, J.C., Bell, R. et al. Xanthogranulomatous epithelial tumors and keratin-positive giant cell-rich soft tissue tumors: two aspects of a single entity with frequent HMGA2-NCOR2 fusions. Mod Pathol (2022). https://doi.org/10.1038/s41379-022-01115-6

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