Small cell osteosarcoma: clinicopathologic, immunohistochemical, and molecular analysis of 36 cases.
Small round cell osteosarcoma is a very rare type of osteosarcoma, histologically mimicking other small round cell malignancies of bone, most notably Ewing sarcoma. To distinguish small cell osteosarcoma from other primary small cell malignancies of bone, we evaluated the immunohistochemical (IHC) expression of CD99 and SATB2, a marker of osteoblastic differentiation. Second, we analyzed EWSR1 and FUS gene aberrations using fluorescence in situ hybridization and/or reverse transcription-polymerase chain reaction (RT-PCR) techniques to assess whether small cell osteosarcoma and Ewing sarcoma share the same genetic alteration analysis. Thirty-six cases of primitive small cell osteosarcoma of bone were included in this study. All the cases of small cell osteosarcoma showed strong nuclear expression of SATB2 associated with negativity for CD99 antibody or weak, cytoplasmic staining in few neoplastic cells. Reverse transcription-polymerase chain reaction was negative for EWS-FLI1 type 1-2, EWS-ERG type 1, and CIC-DUX4 in the 10 available cases of small cell osteosarcoma analyzed. Fluorescence in situ hybridization analysis was feasible with a readable signal in 13 cases of small cell osteosarcoma, and none of these cases showed any EWSR1 and FUS gene rearrangements. In conclusion, it appears extremely useful to combine IHC analysis of SATB2 and CD99 with molecular analysis of Ewing sarcoma-associated genetic aberrations, to differentiate small cell osteosarcoma from other small round cell malignancies of bone. The strong IHC expression of SATB2 associated with CD99 immunonegativity and the absence of EWSR1 and FUS gene rearrangements in small cell osteosarcoma argues against the existence of a morphologic/genetic continuum with Ewing sarcoma.
*Department of Pathology, Rizzoli Institute †Department of Biomedical and Neuromotor Sciences, University of Bologna ‡Department of Pathology, Villa Erbosa Hospital, Bologna §Section of Pathological Anatomy, Department of Surgery and Translational Medicine, University of Florence, Florence ∥Department of Pathology, Treviso Regional Hospital, Treviso, Italy.
Alberto
A
Righi
Marco
M
Gambarotti
Serena
S
Longo
Stefania
S
Benini
Gabriella
G
Gamberi
Stefania
S
Cocchi
Daniel
D
Vanel
Piero
P
Picci
Franco
F
Bertoni
Antonella
A
Simoni
Alessandro
A
Franchi
Angelo Paolo
AP
Dei Tos
D000328:Adult; D000368:Aged; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology*; D002648:Child; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018228:Sarcoma, Small Cell / Q000235:genetics* / Q000473:pathology*; D046888:Tissue Array Analysis; D055815:Young Adult