Osteocalcin and osteonectin immunoreactivity in extraskeletal osteosarcoma: A study of 28 cases

Extraskeletal osteosarcoma (EOSA), a rare malignant soft tissue tumor, is b y definition unattached to the skeleton and composed of malignant cells of osteoblastic phenotype which produce osseous matrix tie, neoplastic bone). Because of its location, it can mimic other soft tissue tumors, and its mat rix can be mistaken for hyalinized collagen, Antiosteocalcin (OC) and antio steonectin (ON), antibodies against two abundant human bone proteins, are e xplored in the diagnosis of EOSA. Twenty-eight cases coded as EOSA (n = 24) or probable EOSA (n = 4) a ere identified from the Soft Tissue Registry of the Armed Forces Institute of pathology (Washington DC). All cases had par affin blocks available for immunohistochemistry. OC and ON (Biodesign Inter national, Kennebunk, ME, clones OCl and OST1) immunostaining for tumor cell s and matrix was graded on a four-tiered grading system: 1 = focal (<50%) w eak staining; 2 = focal strong staining; 3 = diffuse (greater than or equal to 50%) weak staining; and 4 = diffuse strong staining. Patient ages range d from 9 to 80 years, with a mean age of 57 years. There were 9 female pati ents and 19 male patients. The tumor sizes ranged from 1.5 to 15 centimeter s, with a mean size of 5.8 centimeters, Locations included the lo ic er ext remity (n = 14, trunk (n = 9), upper extremity (n = 4), and head and neck ( n = I), Subtypes included 12 osteoblastic, 4 fibroblastic, 2 chondroblastic . 2 well differentiated, 1 telangiectatic, 1 small cell, and 6 giant cell r ich EOSAs; the latter resembled giant cell rich malignant fibrous histiocyt omas with neoplastic bone formation. All tumors had both neoplastic cells a nd bony tumor matrix to evaluate. OC was 82% sensitive for EOSA neoplastic cells (1 to 4+), with immunostaining of neoplastic cells away from bone in 91% of cases, and 75% for bony tumor matric (2 to 4+). ON was: 93% sensitiv e for EOSA neoplastic cells (2 to 4+), yet only 39% for bony tumor matrix ( 1 to 4+). In 100% giant tell rich EOSA, neoplastic cells were positive for OC and ON (2 to 4+), OC showed 100% specificity for osteoblasts as it was n onreactive in all nonbone cells, ON was not specific for osteoblasts but co nsistently immunostained other cell types in our EOSA tumors: fibroblasts ( 100%), pericytes (96%), endothelial cells (92%), chondrocytes (5/5), basal layer of skin epithelium (1/4), nerves (2/2), and osteoclastic giant cells (64%). ON also stained scleral other cell types in normal and neoplastic ti ssues in our battery of preliminary stainings; OC was negative in all nonos teoblastic tissues and tumors, Both OC and ON were specific for osteoid mat rix as they were nonreactive in both collagen and cartilage matrix. OC is a sensitive and specific marker for bone cells and would be helpful in ident ifying EOSA, even in the absence of neoplastic bone on small biopsies. ON a nd OC (more sensitive) will both distinguish malignant bone from collagen a nd cartilage matrix, essential to the diagnosis of EOSA.