Abstract

Cutaneous sarcomatoid squamous cell carcinoma (cSSCC) is well-described with histology resembling pleomorphic undifferentiated sarcoma, having collagenous or myxoid stroma, with or without elements of keratinizing squamous carcinoma. cSSCC should have evidence of epithelial origin or differentiation such as positivity for cytokeratins, p63 or p40. Cutaneous giant cell tumor of soft tissue (cGCT) is exceedingly rare and may have cytokeratin positivity and an HMGA2-NCOR2 fusion. We illustrate two patients with fungating cutaneous tumors composed of sheets of malignant mononuclear cells with malignant osteoclast-like multinucleated giant cells, extravasated blood, and hemosiderin resembling cGCT. Case one was an exophytic facial mass of a 96-year-old woman removed by shave showing extensive cGCT-like tumor but with microscopic elements of squamous cell carcinoma in situ (SCC) and positivity for cytokeratin 5/6 in the malignant spindle cells and SCC. A re-excision had no residual tumor. Case two was a pedunculated penile mass of a 32-year-old removed by shave biopsy that had malignant cytology, resembled cGCT, and had focal staining for cytokeratin AE1/3 and p63. CD68 highlighted the osteoclast-like giant cells. Molecular alterations included CDKN2A, FAT1, SH2B3, TP53, and TERT. Re-excision showed focally invasive keratinizing SCC arising in association with differentiated penile intraepithelial neoplasia and lichen sclerosus, but no residual cGCT-like tumor. Skin specimens with an exophytic mass histologically resembling cGCT but with malignant cytology should be carefully evaluated for elements of SCC. Molecular analysis may also be helpful as H3F3 mutation or HMGA2-NCOR2 fusion would be evidence of GCT bone or GCT soft tissue rather than cSSCC.