Keratin‐positive giant cell‐rich tumors of soft tissue with HMGA2::NCOR2 fusions

Abstract

Background: Giant cell tumor of soft tissue (GCT-ST) is a rare soft tissue neoplasm that is morphologically similar to but genetically distinct from giant cell tumor of bone. A novel keratin-positive GCT-ST (KPGCT-ST) harboring HMGA2::NCOR2 fusions was recently discovered. Fewer than 30 cases have been described; herein is reported an additional seven.Methods: Cases diagnosed as GCT-ST were retrieved from institutional archives and consultation files. The histopathologic characteristics were assessed, and the electronic medical record was reviewed.Results: Seven tumors were identified in six women and one man with a median age of 23 years. All patients underwent excision; no recurrences or metastases were noted during a median follow-up period of 7 months. Histopathologically, the tumors were characterized by a multinodular proliferation of keratin-positive mononuclear cells with evenly admixed osteoclast-like giant cells and absent neoplastic bone. A fibrous capsule with lymphoid cuffing was frequently seen. Foamy macrophages, inflammation, hemorrhage, and hemosiderin were variably present. The HMGA2:: NCOR2 fusion was detected in all cases.Conclusions: Our findings support previously reported hypotheses that KPGCT-ST is a spectrum of the same entity as the recently described xanthogranulomatous epithelial tumor. Although follow-up data are limited, to date, KPGCT-ST appears to follow an indolent course.

Giant Cell Tumor of Soft Tissue: An Updated Review

“…KPGCT is an extremely rare, recently described mesenchymal neoplasm which can affect both soft tissue and bone [71][72][73][74][75][76]. In 2021, Agaimy et al described a series of six cases similar to GCTST, but with a subpopulation of keratin-positive cells and a novel high mobility group AT-hook 2 (HMGA2)-nuclear receptor corepressor 2 (NCOR2) fusion [71].…”

“…The authors suggested that these two tumors may represent morphological variants of a single entity. Compared with GCTST, KPGCTST shows a distinct predilection for female and a younger age demographic (a median age of 23 years) [75]. KPGCTST presents as a superficial soft tissue mass of variable size, which frequently occurs in the extremities.…”

“…Due to the limited number of reported cases, the optimal management of KPGCTST is yet to be established. Surgical resection appears to be the primary treatment modality [71,74,75]. The majority of cases show no evidence of disease at follow-up, but available data are unfortunately limited.…”