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Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors
- Source :
- Modern Pathology
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Giant cell tumors of soft tissue (GCT-ST) are rare low-grade neoplasms that were at one time thought to represent the soft tissue counterparts of GCT of bone (GCT-B) but are now known to lack the H3F3 mutations characteristic of osseous GCT. We present six distinctive giant cell-rich soft tissue neoplasms that expressed keratins and carried a recurrent HMGA2-NCOR2 gene fusion. Patients were five females and one male aged 14–60 years (median, 29). All presented with superficial (subcutaneous) masses that were removed by conservative marginal (3) or wide (2) local excision. The tumors originated in the upper extremity (2), lower extremity (2), head/neck (1), and trunk (1). Five patients with follow-up (median, 21 months; range, 14–168) remained disease-free. Grossly, all tumors were well-demarcated but not encapsulated with variable lobulation. Histologically, they were composed of bland plump epithelioid or ovoid to spindled mononuclear cells admixed with evenly distributed multinucleated osteoclast-type giant cells. Foci of stromal hemorrhage and hemosiderin were seen in all cases. The mitotic activity ranged from 2 to 14/10 high power fields (median: 10). Foci of necrosis and vascular invasion were seen in one case each. The mononuclear cells were immunoreactive with the AE1/AE3 keratin cocktail and less frequently/less diffusely for K7 and K19 but lacked expression of other lineage-associated markers. RNA-based next-generation sequencing revealed an HMGA2-NCOR2 fusion in all tumors. None of the keratin-negative conventional GCT-ST showed the HMGA2-NCOR2 fusion (0/7). Metaplastic bone (4/9) and SATB2 expression (3/4) were frequent in keratin-negative conventional GCT-ST but were lacking in keratin-positive HMGA2-NCOR2 fusion-positive tumors. The distinctive immunophenotype and genotype of these tumors strongly suggest that they represent a discrete entity, differing from conventional GCT-ST and other osteoclast-rich morphologic mimics. Their natural history appears favorable, although a study of additional cases and longer follow-up are warranted.
- Subjects :
- Adult
Male
0301 basic medicine
Pathology
medicine.medical_specialty
Stromal cell
Soft Tissue Neoplasm
Adolescent
Soft Tissue Neoplasms
Diseases
Pathogenesis
Biology
Article
Pathology and Forensic Medicine
Young Adult
03 medical and health sciences
0302 clinical medicine
Immunophenotyping
Keratin
medicine
Humans
Nuclear Receptor Co-Repressor 2
Oncogene Fusion
Giant Cell Tumors
Child
Aged
chemistry.chemical_classification
HMGA2 Protein
Soft tissue
Middle Aged
030104 developmental biology
chemistry
Giant cell
030220 oncology & carcinogenesis
Hemosiderin
Keratins
Female
Subjects
Details
- ISSN :
- 08933952
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Modern Pathology
- Accession number :
- edsair.doi.dedup.....284dfee9535b735bd9781f034f28b109