title: Immunohistochemical and FISH analysis of MDM2 and CDK4 in a dedifferentiated extraskeletal osteosarcoma arising in the vastus lateralis muscle: differential diagnosis and diagnostic algorithm.
abstract: Extraskeletal osteosarcoma is a rare neoplasia within the broad differential diagnostic spectrum of calcifying intramuscular lesions. We present a case of a slowly increasing mass within the left vastus lateralis muscle. At first presentation the patient showed a partially calcified well defined mass with a diameter of 5 cm and with no direct contact to the femur. A biopsy from the periphery revealed an ossifying lesion compatible with myositis ossificans. The patient returned 18 months later with the lesion having increased to a diameter of 25 cm. The resection specimen revealed a well delimitated tumor with a central core of partially necrotic neoplastic bone. Besides, histology showed high mitotic areas with pleomorphic spindle cells and regions with cartilaginous differentiation. Immunohistochemistry demonstrated: vimentin+, CD34-, desmin-, actin-, EMA- and pancytokeratin- with focal S100 protein positivity and a Ki-67 index of 20%. Comparative genomic hybridization (CGH) revealed a gain of chromosomal material on 12q; FISH analyses for the CDK4 and MDM2 region showed high level amplifications. Consequently, a high-grade dedifferentiated extraskeletal osteosarcoma was diagnosed. In conclusion, analysis of the MDM2 and CDK4 status is a powerful and discriminating diagnostic tool to distinguish dedifferentiated extraskeletal osteosarcoma from other benign/malignant ossifying lesions in the skeletal muscle.
authors: Department of Trauma and Orthopaedic Surgery, University of Ulm, Germany.
authors: Alexandra
authors: A
authors: von Baer
authors: Department of Radiology, University of Ulm, Germany.
authors: Alexander
authors: A
authors: Ehrhardt
authors: Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel, Switzerland.
authors: Daniel
authors: D
authors: Baumhoer
authors: Department of Internal Medicine III, Germany.
authors: Regine
authors: R
authors: Mayer-Steinacker
authors: Department of Trauma and Orthopaedic Surgery, University of Ulm, Germany.
authors: Markus
authors: M
authors: Schultheiss
authors: Institute of Pathology, Hospital of Memmingen, Germany.
authors: Thair
authors: T
authors: Abdul-Nou
authors: Institute of Dermatopathology, Friedrichshafen, Germany.
authors: Thomas
authors: T
authors: Mentzel
authors: Institute of Pathology, University of Tübingen, Germany.
authors: Falko
authors: F
authors: Fend
authors: Institute of Pathology, University of Ulm, Germany.
authors: Peter
authors: P
authors: Möller
authors: Bone Tumor Reference Center at the Institute of Pathology, University Hospital Basel, Switzerland.
authors: Gernot
authors: G
authors: Jundt
authors: Institute of Pathology, University of Ulm, Germany. Electronic address: Thomas.barth@uniklinik-ulm.de.
authors: Thomas F E
authors: TF
authors: Barth
mesh_terms: D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001706:Biopsy; D001859:Bone Neoplasms / Q000175:diagnosis / Q000473:pathology*; D055028:Comparative Genomic Hybridization / Q000379:methods; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism*; D003937:Diagnosis, Differential; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000175:diagnosis / Q000473:pathology*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism*; D052097:Quadriceps Muscle / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
keywords: Differential diagnosis; Extraskeletal osteosarcoma; Histology; Molecular pathology