Osteoclastic giant cell-rich tumors

2022-03-02   Judith VMG Bovée , Paola Dal Cin 

1.Leiden University Medical Center, Leiden, The Netherlands
2.Brigham and Women's Hospital , Harvard Medical School, Boston , MA (USA)

Classification

Definition

Giant cell-rich tumors of bone are a group of rare bone tumors that are all characterized by the presence of osteoclast-like giant cells; however, they harbor different clinical and histological features. Giant cell tumor of bone is a locally aggressive bone tumor characterized by H3F3 p.G34W mutations.

Osteoclastic giant cell-rich tumorsGenetic marker(s)
Aneurysmal bone cyst (ABC)Balanced chromosomal translocations involving USP6 gene at 17p13.1, with the t(16;17)(q22;p13) 1 been the most frequent translocation (~30% of the cases). This rearrangement is associated with CDH11::USPS fusion, driving USPS expression via promoter swapping. 2,3 A variety of partner genes have been reported, including COL1A1,THRAP3,CNBP,OMD, SEC31A, FAT1,SPARC , FOSL2, RUNX2, ASAP1,TNC, SAR1A, EIF1, STAT3 , PAFAH1B1, USP9X, (ZNF9} , CTNNB1, ANGPTL2, and LUM. 4,5
Many other entities are now sharing the same USPS rearrangements, so called USPS-associated neoplasms 4
Giant cell tumor of the boneExclusively alterations in the H3-3A gene (95%) with p.Gly34Trp (~ 92%) followed by p.Gly34Leu, and other rare one. 6,7 Mutations present in both conventional and malignant forms of giant cell tumor. Diploid karyotype with with few structural changes, and with non-random telomeric associations. 8
Non-ossifying fibromaMutually exclusive hotspot mutations in KRAS and FGFR1 (80%) 9,10

Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1105023261999Recurrent t(16;17)(q22;p13) in aneurysmal bone cysts.Panoutsakopoulos G et al
2150263242004USP6 (Tre2) fusion oncogenes in aneurysmal bone cyst.Oliveira AM et al
3287528422017USP6 activation in nodular fasciitis by promoter-swapping gene fusions.Patel NR et al
4326357812020USP6-Associated Neoplasms: A Rapidly Expanding Family of Lesions.Hiemcke-Jiwa LS et al
5328596332020Fusion of the Lumican (LUM) Gene With the Ubiquitin Specific Peptidase 6 (USP6) Gene in an Aneurysmal Bone Cyst Carrying a t(12;17)(q21;p13) Chromosome Translocation.Panagopoulos I et al
6241627392013Distinct H3F3A and H3F3B driver mutations define chondroblastoma and giant cell tumor of bone.Behjati S et al
7317286252020Mutation-driven epigenetic alterations as a defining hallmark of central cartilaginous tumours, giant cell tumour of bone and chondroblastoma.Venneker S et al
8111060782000Cytogenetic-morphologic correlations in aneurysmal bone cyst, giant cell tumor of bone and combined lesions. A report from the CHAMP study group.Sciot R et al
9305490282019Activating mutations in the MAP-kinase pathway define non-ossifying fibroma of bone.Baumhoer D et al
10308097932019Non-ossifying fibroma: A RAS-MAPK driven benign bone neoplasm.Bovée JV et al

External Links

Citation

Judith VMG Bovée ; Paola Dal Cin

Osteoclastic giant cell-rich tumors

Atlas Genet Cytogenet Oncol Haematol. 2022-03-02

Online version: http://atlasgeneticsoncology.org/solid-tumor/208934/osteoclastic-giant-cell-rich-tumors