title: USP6 gene rearrangements occur preferentially in giant cell reparative granulomas of the hands and feet but not in gnathic location.
abstract: Giant cell reparative granulomas (GCRGs) are lytic lesions that occur predominantly in the gnathic bones and occasionally in the small bones of the hands and feet. They are morphologically indistinguishable from, and are regarded as synonymous with, solid variant of aneurysmal bone cysts (ABC) in extragnathic sites. Identification of USP6 gene rearrangements in primary ABC has made possible investigating potential pathogenetic relationships with other morphologic mimics. USP6 gene alterations in giant cell-rich lesions (GCRG/ABC) of small bones of the hands and feet have not been previously studied. We investigated USP6 gene alterations in a group of 9 giant cell-rich lesions of the hands and feet and compared the findings with morphologically similar lesions including 8 gnathic GCRGs, 22 primary ABCs, 8 giant cell tumors of bone, and 2 brown tumors of hyperparathyroidism. Overall, there were 49 samples from 48 patients including 26 females and 22 males. Of the 9 lesions of the hands and feet, 8 (89%) showed USP6 gene rearrangements, whereas no abnormalities were identified in the 8 gnathic GCRGs, 2 brown tumors, or 8 giant cell tumors of bone. Of the 22 primary ABCs, 13 (59%) showed USP6 gene rearrangements. In conclusion, most GCRGs of the hands and feet represent true ABCs and should be classified as such. The terminology of GCRG should be limited to lesions from gnathic location. Fluorescence in situ hybridization for USP6 break-apart is a useful ancillary tool in the diagnosis of primary ABCs and distinguishing them from GCRGs and other morphologically similar lesions.
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065. Electronic address: agaramn@mskcc.org.
authors.forename: Narasimhan P
authors.initials: NP
authors.lastname: Agaram
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065.
authors.forename: Francois V
authors.initials: FV
authors.lastname: LeLoarer
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065.
authors.forename: Sinchun
authors.initials: S
authors.lastname: Hwang
authors.affiliation: Department of Orthopedic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, 10065.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Athanasian
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065.
authors.forename: Meera
authors.initials: M
authors.lastname: Hameed
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065. Electronic address: antonesc@mskcc.org.
authors.forename: Cristina R
authors.initials: CR
authors.lastname: Antonescu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017824:Bone Cysts, Aneurysmal / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005528:Foot; D015321:Gene Rearrangement; D006101:Granuloma, Giant Cell / Q000235:genetics* / Q000473:pathology; D006225:Hand; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007573:Jaw Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*; D055815:Young Adult
chemical_list: D011518:Proto-Oncogene Proteins; C473330:USP6 protein, human; D043222:Ubiquitin Thiolesterase
keywords: Giant cell reparative granuloma; Solid ABC; USP6
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