title: Primary extraskeletal osteosarcoma: a clinicopathological study of 18 cases focusing on MDM2 amplification status.
abstract: Extraskeletal osteosarcoma (ESOS) is an uncommon malignant neoplasm. Most ESOSs are high grade, although some low-grade cases have been reported. A few cases of ESOS with MDM2 amplification have also been reported, suggesting some similarity to skeletal low-grade osteosarcoma such as parosteal osteosarcoma, where MDM2 is often amplified. However, the frequency of low-grade cases and cases with MDM2 amplification among ESOSs remains unknown, and their relationship is unclear. To clarify this, we examined 18 primary ESOS cases clinically, pathologically, and genetically, focusing on their MDM2 amplification status. Our cases comprised 10 men and 8 women whose mean age was 58.6 years; the most common site of the lesion was the thigh and buttock. There were one histologically low-grade case evaluated by biopsy specimen with an aggressive course and 2 relatively low-grade cases whose lesions were of low grade for the most part. MDM2 amplification status was revealed by fluorescence in situ hybridization in all 18 cases; 2 patients-histologically intermediate- and high-grade cases-were found to have MDM2 amplification. In conclusion, this study indicates that histologically low-grade and relatively low-grade cases of ESOS are not always associated with MDM2 amplification. The ESOS case with MDM2 amplification could be high grade, although MDM2-amplified dedifferentiated liposarcoma with osteogenic differentiation should be ruled out in making the diagnosis.
authors.affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan. Electronic address: kyoko@med.nagoya-u.ac.jp.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamashita
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School and School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Orthopedic Surgery, Nagoya University Graduate School and School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Urakawa
authors.affiliation: Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Electronic address: oda@surgpath.med.kyushu-u.ac.jp.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.affiliation: Department of Pathology and Biological Responses, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Toyokuni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics*; D001706:Biopsy; D002454:Cell Differentiation; D003937:Diagnosis, Differential; D005260:Female; D005784:Gene Amplification; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D012516:Osteosarcoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D011237:Predictive Value of Tests; D051736:Proto-Oncogene Proteins c-mdm2 / Q000032:analysis / Q000235:genetics*; D012042:Registries; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: Dedifferentiated liosarcoma with osteogenic differentiation; Extraskeletal osteosarcoma; Low-grade osteosarcoma; MDM2 amplification; Modified FNCLCC grading system