So-called Fibrohistiocytic Tumors
2022-03-01 Paola Dal Cin, PhD Affiliation1.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)
Classification
Definition
A group of heterogeneous lesions that share morphological features of histiocytes and fibroblasts on light microscopy. The “fibrohistiocytic” designation does not necessarily denote lineage differentiation in all cases. Distinguishing among the fibrous and "fibrohistiocytic" tumors can be a diagnostic challenge, given their sometimes-similar histologic appearances and confusing nomenclature. A subset of fibrohistiocytic neoplasms, have unique genetic aberrations. 1,2
| So-called fibrohistiocytic tumors | Genetic event(s) |
|---|---|
| Tenosynovial giant cell tumor (TGCT) | t(1;2)(p11-13;q37)1 associated to COL6A3::CSF1 gene fusion is the the most frequent translocation resulting in CSF1 overexpression via promotor swapping. 2-4 Several other 1p13 translpcation have benn descibed. 5 Several novel fusion partners have ben reported : ARID4A, CDH17, GSTM5,CD101, TGFBR3, NBPF20 , NOTCH2, PDGFRN,CENPFS,C100A1,VCAM1,FN1 and CDH1. 6-8 However, all these rearrangements have in common a replacement of the 3'URTR of CSF1 with other sequencing, e.g. 3'UTR deletion. 6-8 However, there is a consistent presence of CSF1 overexpression in translocation negative lesions. 2,4 CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking like lesions. 9 |
| The morphologic and immunohistochemical features of malignant tenosynovial giant cell tumors and the the presence of CSF1 rearrangements support origin of such aggressive sarcoma from synoviocytes. 10 Loss of the CDKN2A and CDKN2B also present.11 | |
| Atypical TGCTs harbor gene fusions not implicating CSF1 e.g. NIPBL::ERG, FN1::ROS1, and YAP1::MAML2 and suggest that non-CSF1 fusions potentially confer greater propensity to recurrences and local aggressiveness. 12 | |
| Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, strong selectivity against CSF1R. 13 | |
| CBL missense mutations, in exon 8 or 9, affecting the linker and RING finger domain with some of them recurrent mutations (C404Y, ML380P and R420), and not mutually exclusive to CSF1 fusions. 7,8 | |
| Trisomies 5 and 7 are recurrent chromosome finding only in diffuse type. 14 | |
| Deep fibrous histiocytoma (DFH) | Several cytogentic reports, with t(3;11)(p21;q13) as the only recurrent translocation.15 FISH analysis and NGS revealed either PRKCB at 16p12 or PRKCD at 3p21 rearrangement, sofar partners genes : PDPN, CD63 and LAMTOR1.15,16 Single KIRREL1::PRKCA gene fusion. 15 Single case with t(16;17) (p13.3;q21.3). 17 |
| This lesion can occur in soft tissue (so-called deep benign fibrous hystiocytoma ), often in the skin (so-called dermatofibroma), but may also appear in the skeleton (so-called non-ossifying fibroma). ALK rearrangement/ ALK protein overexpression by immunohistochemistry has been shown consistently in epithelioid fibrous histiocytoma, rare and distinctive cutaneous neoplasms. 18-20 | |
| Plexiform fibrohistiocytic tumor (PFHT) | Only 3 published cytogenetic studies, showing a variety of non-recurrent abnormalities, and a single case demonstrating a GNAQ mutation, of unknown signifcance. 21 |
| Giant cell tumors of soft tissue (GCT-ST) | Although giant cell tumors of soft tissue are similar in histological appearance to giant cell tumors of the bone, they are genetically distinct because they lack H3-3A (HEF3A) mutations as well as the related genes. 22-24 |
| Single case in the breast with H3-3A mutation 25 | |
| HMGA2::NCOR2 fusion was detected in GCT-ST, 26 , but also in giant cell tumor of the bone 27 and xanthogranulomatous epithelial tumors. 28 |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 8033128 | 1994 | Cytogenetic characterization of tenosynovial giant cell tumors (nodular tenosynovitis). | Dal Cin P et al |
| 2 | 17527089 | 2007 | Translocation and expression of CSF1 in pigmented villonodular synovitis, tenosynovial giant cell tumor, rheumatoid arthritis and other reactive synovitides. | Cupp JS et al |
| 3 | 16407111 | 2006 | A landscape effect in tenosynovial giant-cell tumor from activation of CSF1 expression by a translocation in a minority of tumor cells. | West RB et al |
| 4 | 30152874 | 2019 | Does CSF1 overexpression or rearrangement influence biological behaviour in tenosynovial giant cell tumours of the knee? | Mastboom MJL et al |
| 5 | 10392632 | 1999 | Analysis of 35 cases of localized and diffuse tenosynovial giant cell tumor: a report from the Chromosomes and Morphology (CHAMP) study group. | Sciot R et al |
| 6 | 24604026 | 2014 | Novel CSF1-S100A10 fusion gene and CSF1 transcript identified by RNA sequencing in tenosynovial giant cell tumors. | Panagopoulos I et al |
| 7 | 31107544 | 2019 | Massively parallel sequencing of tenosynovial giant cell tumors reveals novel CSF1 fusion transcripts and novel somatic CBL mutations. | Tsuda Y et al |
| 8 | 31469468 | 2020 | Detection of CSF1 rearrangements deleting the 3' UTR in tenosynovial giant cell tumors. | Ho J et al |
| 9 | 36320082 | 2022 | Diagnostic utility of CSF1 immunohistochemistry in tenosynovial giant cell tumor for differentiating from giant cell-rich tumors and tumor-like lesions of bone and soft tissue. | Sugita S et al |
| 10 | 30206409 | 2019 | Malignant Tenosynovial Giant Cell Tumor: The True "Synovial Sarcoma?" A Clinicopathologic, Immunohistochemical, and Molecular Cytogenetic Study of 10 Cases, Supporting Origin from Synoviocytes. | Al-Ibraheemi A et al |
| 11 | 27989786 | 2017 | Malignant tenosynovial giant cell tumor with CDKN2A/B genomic alteration: a histological, immunohistochemical, and molecular study. | Alexiev BA et al |
| 12 | 31906059 | 2019 | Molecular Profiling of Atypical Tenosynovial Giant Cell Tumors Reveals Novel Non-CSF1 Fusions. | Vougiouklakis T et al |
| 13 | 30825104 | 2020 | A phase I study of pexidartinib, a colony-stimulating factor 1 receptor inhibitor, in Asian patients with advanced solid tumors. | Lee JH et al |
| 14 | 1382569 | 1992 | Trisomy 5 and trisomy 7 are nonrandom aberrations in pigmented villonodular synovitis: confirmation of trisomy 7 in uncultured cells. | Fletcher JA et al |
| 15 | 26121314 | 2015 | Gene fusion detection in formalin-fixed paraffin-embedded benign fibrous histiocytomas using fluorescence in situ hybridization and RNA sequencing. | Walther C et al |
| 16 | 24721208 | 2014 | Fusions involving protein kinase C and membrane-associated proteins in benign fibrous histiocytoma. | Płaszczyca A et al |
| 17 | 20804915 | 2010 | Deep fibrous histiocytoma with a clonal karyotypic alteration: molecular cytogenetic characterization of a t(16;17)(p13.3;q21.3). | Frau DV et al |
| 18 | 29327718 | 2018 | Epithelioid fibrous histiocytoma: molecular characterization of ALK fusion partners in 23 cases. | Dickson BC et al |
| 19 | 30289773 | 2019 | Epithelioid Fibrous Histiocytoma: A Concise Review. | Felty CC et al |
| 20 | 32379091 | 2020 | Epithelioid Fibrous Histiocytoma With Dot-Like Perinuclear ALK Expression and PRKAR2A-ALK Fusion. | Dawson K et al |
| 21 | 36071257 | 2022 | Plexiform fibrohistiocytic tumor: a clinicopathological and immunohistochemical study of 39 tumors, with evidence for a CSF1-producing "null cell" population. | Thangaiah JJ et al |
| 22 | 28084336 | 2017 | Giant cell tumor of soft tissue is genetically distinct from its bone counterpart. | Lee JC et al |
| 23 | 28477388 | 2017 | Phenotypic and molecular differences between giant-cell tumour of soft tissue and its bone counterpart. | Mancini I et al |
| 24 | 28899740 | 2017 | Histone 3.3 mutations in giant cell tumor and giant cell-rich sarcomas of bone. | Righi A et al |
| 25 | 31784095 | 2020 | Giant cell tumor of soft tissue of the breast: Case report with H3F3A mutation analysis and review of the literature. | Luangxay T et al |
| 26 | 33742141 | 2021 | Recurrent novel HMGA2-NCOR2 fusions characterize a subset of keratin-positive giant cell-rich soft tissue tumors. | Agaimy A et al |
| 27 | 35181586 | 2022 | Recurrent Fusion of the Genes for High-mobility Group AT-hook 2 (HMGA2) and Nuclear Receptor Co-repressor 2 (NCOR2) in Osteoclastic Giant Cell-rich Tumors of Bone. | Panagopoulos I et al |
| 28 | 35690644 | 2022 | Xanthogranulomatous epithelial tumors and keratin-positive giant cell-rich soft tissue tumors: two aspects of a single entity with frequent HMGA2-NCOR2 fusions. | Dehner CA et al |
Citation
Paola Dal Cin, PhD
So-called Fibrohistiocytic Tumors
Atlas Genet Cytogenet Oncol Haematol. 2022-03-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/208953/so-called-fibrohistiocytic-tumors
