Chondrosarcoma of the bone

Arch Pathol Lab Med. 2006 Nov;130(11):1673-9 Abstract quote

CONTEXT: Clear cell chondrosarcoma (CCC) is commonly considered to be a low-grade subtype of chondrosarcoma. However, a few cases of CCC behave as high-grade lesions (with early metastases or multiple/synchronous locations).

OBJECTIVE: To investigate morphologic features that can help predict the aggressiveness of these CCCs.

DESIGN: To investigate possible hallmarks of this aggressiveness, we are presenting the clinicopathologic features of 6 cases of CCC, 4 of which presented aggressive features and 2 low-grade behavior. The patients were 5 men and 1 woman; their ages ranged from 22 to 47 years. Histologic appearance, ultrastructure, and immunohistochemical expression of metalloproteinase 1 and 2 and their inhibitors were evaluated in all 6 cases.

RESULTS: Pain was the most common symptom; the lesions were located in the femur (4), humerus (2), and vertebral body (1), with 1 patient presenting a double/synchronous lesion. Although no major differences were detected using conventional light microscopy, an ultrastructural analysis--at variance with usual cases--showed a lack of superficial microvilli in more than 50% of neoplastic cells in the aggressive cases, therefore suggesting a less differentiated phenotype. In addition, metalloproteinase 2 was more diffusely expressed in the aggressive tumors than in the conventional CCCs, whereas p53 labeling was always negative.

CONCLUSIONS: The aggressive behavior of some CCCs may be, at least in part, correlated to a lesser degree of cell differentiation and to the expression of tumor cell proteins, such as metalloproteinase 2, which are able to favor neoplastic spreading.

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
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EPIDEMIOLOGY	CHARACTERIZATION
INCIDENCE	11% of malignant bone tumors
AGE RANGE-MEDIAN
Central	Range 5-90 years Peak 5-7th decades
Secondary	Peak in 4-5th decades
Juxtacortical	80%>20 years Range 15-63 years of age
Mesenchymal	80% between 10-40 years Range 5-74 years
Clear cell	Most in 3-4th decades Range 14-84 years
Dedifferentiated	Most >50 years Range 19-82 years
SEX (M:F) for classic central tumors	2:1

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Radiographs
Central tumors	Extensive intramedullary spread
Peripheral tumors	Masses that protrude from the cortex

GROSS APPEARANCE/CLINICAL VARIANTS	CHARACTERIZATION
General-Primary chondrosarcomas	Pelvic bones most common site Proximal femur Proximal humerus Distal femur Ribs Usually occur in the diaphysis or metaphysis Cut sections show appearance of hyaline cartilage with blue or white color Lobular pattern with areas of chalky calcifications common Hemorrhagic necrosis in high grade tumors
Secondary	Tumors arising on preexisting benign cartilaginous lesions
Central	Central tumors may have extensive intramedullary spread
Peripheral	Form masses that protrude from cortex
Juxtacortical	<2% of all chondrosarcomas Femur most common site Long bone lesions have a predilection for the metaphysis, less likely the diaphysis Cartilage type, eggshell or popcorn matrix calcifications Underlying cortex is often sclerotic with a saucer shaped defect with a sharply defined border Average size 11 cm
Mesenchymal	2% of all chondrosarcomas Favors the maxilla, mandible, ribs, and vertebrae Pelvis and femur Lytic defect with stippled calcifications Cortex destroyed in 50% of cases with associated soft tissue extension
Clear cell	2% of all chondrosarcomas Epiphyses of long bones Proximal femur and humerus, distal femur, and proximal tibia Expansile osteolytic tumor with sharp interface between tumor and surrounding bone
Dedifferentiated	11% of all chondrosarcomas Bones of the pelvis, proximal femur and humerus, distal femur, and ribs Lytic intraosseous lesion or extraosseous soft tissue mass Usually cortical perforation Abrupt transition between chondroid tumor and dedifferentiated lytic component

HISTOLOGICAL TYPES	CHARACTERIZATION
General-Primary chondrosarcomas	Irregularly shaped lobules of cartilage with variable size, often separated by narrow fibrous bands Chondocytes arranged in clusters or groups, slightly enlarged nuclei and occasionally bizarre nuclei Mitotic figures not found in grade 1 tumors but widely scattered in grade 2 tumors, and abundant in grade 3 tumors Matrix varies from mature hyaline cartilage to myxoid stroma Spindle cells may be present in grade 3 tumors Sections taken from the edge show cartilage invading the marrow between trabeculae of bone-the permeation pattern May have fingerlike extensions into the soft tissue
GRADING
1	Chondrocytes with small, dense nuclei, some with slightly enlarged nuclei, rare multinucleated and binucleated Stroma usually chondroid, with sparse myxoid areas
2	Less matrix with more cellular areas, especially around the periphery of the tumor Chondrocyte nuclei are enlarged and vesicular or hyperchromatic Usually multiple nuclei within lacunae Frequently myxoid stroma Variable areas of necrosis
3	Greater cellularity and nuclear pleomorphism compared to the grade 2 tumors Sparse chondroid matrix and small amount of intercellular material which is myxoid Neoplastic chondrocytes arranged in cords and clumps Individual cells with stellate or irregular shapes Nuclei spindled and vesicular, 5-10x normal
Juxtacortical	Well differentiated cartilaginous lobules, hyaline type Microscopic extension into soft tissue common Grade 3 tumors rare
Mesenchymal	Small round, oval to spindled neoplastic cells with irregular clumping of chromatin and small nucleoli Variable mitotic rate Cartilaginous areas are sparse Vascular with hemangiopericytoma-like pattern
Clear cell	Lobular cartilaginous nests with clear cells Mitotic figures rare Matrix formation sparse with focal calcification
Aggressive clear cell chondrosarcomas: do distinctive characteristics exist?: a report of 4 cases. Corradi D, Bacchini P, Campanini N, Bertoni F. Department of Pathology and Laboratory Medicine, Pathology Section, University of Parma, Via Gramsci 14, 43100 Parma, Italy.	Arch Pathol Lab Med. 2006 Nov;130(11):1673-9 Abstract quote CONTEXT: Clear cell chondrosarcoma (CCC) is commonly considered to be a low-grade subtype of chondrosarcoma. However, a few cases of CCC behave as high-grade lesions (with early metastases or multiple/synchronous locations). OBJECTIVE: To investigate morphologic features that can help predict the aggressiveness of these CCCs. DESIGN: To investigate possible hallmarks of this aggressiveness, we are presenting the clinicopathologic features of 6 cases of CCC, 4 of which presented aggressive features and 2 low-grade behavior. The patients were 5 men and 1 woman; their ages ranged from 22 to 47 years. Histologic appearance, ultrastructure, and immunohistochemical expression of metalloproteinase 1 and 2 and their inhibitors were evaluated in all 6 cases. RESULTS: Pain was the most common symptom; the lesions were located in the femur (4), humerus (2), and vertebral body (1), with 1 patient presenting a double/synchronous lesion. Although no major differences were detected using conventional light microscopy, an ultrastructural analysis--at variance with usual cases--showed a lack of superficial microvilli in more than 50% of neoplastic cells in the aggressive cases, therefore suggesting a less differentiated phenotype. In addition, metalloproteinase 2 was more diffusely expressed in the aggressive tumors than in the conventional CCCs, whereas p53 labeling was always negative. CONCLUSIONS: The aggressive behavior of some CCCs may be, at least in part, correlated to a lesser degree of cell differentiation and to the expression of tumor cell proteins, such as metalloproteinase 2, which are able to favor neoplastic spreading.
Dedifferentiated	Chondrosarcoma component usually grade 1 Sharp junction between cartilaginous and noncartilaginous elements Noncartilaginous component varies from fibrosarcoma, malignant fibrous histiocytoma, osteosarcoma, rhabdomyosarcoma, and angiosarcoma
ADDITIONAL VARIANTS
DEDIFFERENTIATED
Dedifferentiated Clear Cell Chondrosarcoma Ricardo K. Kalil, M.D.; Carrie Y. Inwards, M.D.; K. Krishnan Unni, M.B., B.S.; Franco Bertoni, M.D.; Patricia Bacchini, M.D.; Doris E. Wenger, M.D.; Franklin H. Sim, M.D. From the Division of Anatomic Pathology (R.K.K., C.Y.I., K.K.U., F.B., P.B.), the Department of Diagnostic Radiology (D.E.W.), and the Department of Orthopedic Surgery (F.H.S.), Mayo Clinic and Mayo Foundation, Rochester, Minnesota	Am J Surg Pathol 2000;24:1079-1086 Abstract quote Dedifferentiation, a change in the histologic character and clinical behavior of a tumor to a more immature and aggressive one, occurs in approximately 11% of all chondrosarcomas. The original lesion is usually a low-grade chondrosarcoma. Clear cell chondrosarcoma is a rare cartilaginous tumor of low-grade malignancy with a preference for the ends of long bones. It is usually curable by resection. Recurrence commonly follows inadequate surgery, and metastases to lung, brain, and bones can develop. However, dedifferentiation has not yet been described in association with clear cell chondrosarcoma. Three patients are described who were initially diagnosed as having clear cell chondrosarcoma of the femur. Two were treated with en bloc resection for a clear cell chondrosarcoma. One of these had an undifferentiated sarcoma in a local recurrence after 6 years. In the second, metastasis of the clear cell chondrosarcoma developed 5� years after surgery; autopsy revealed undifferentiated sarcoma in the lung, heart, and lumbar spine. The third patient had dedifferentiated clear cell chondrosarcoma at the time of resection following the biopsy diagnosis of clear cell chondrosarcoma. All three died with metastatic disease. These three patients represent three different manifestations of dedifferentiation�at initial diagnosis, at recurrence, and at metastasis. To our knowledge, this is the first description of dedifferentiation occurring in clear cell chondrosarcoma.
Dedifferentiated chondrosarcoma with a noncartilaginous component mimicking a conventional giant cell tumor of bone. Estrada EG, Ayala AG, Valerie L, Czerniak B. Department of Pathology, Instituto Nacional de Ortopedia, Mexico City, Mexico; and the Departments of Pathology and Orthopedic Oncology, University of Texas, M. D. Anderson Cancer Center, Houston, TX.	Ann Diagn Pathol 2002 Jun;6(3):159-63 Abstract quote We report a case of dedifferentiated chondrosarcoma in which the dedifferentiated component of the tumor shows a close histologic resemblance to a conventional giant cell tumor of bone. The tumor affected a 30-year-old woman with a long history of left shoulder discomfort and limitation of motion. Radiographic studies revealed a biphasic destructive lesion in the left proximal humerus composed of high-signal lobulated component on T2-weighted magnetic resonance image accompanied by a low signal intensity component exhibiting destructive growth with extension into soft tissue. Microscopically, two different areas consisting of the chondroid tissue and nonchondroid giant cell-rich lesion resembling conventional giant cell tumor of bone were found. Considering that the prognosis and survival associated with these two entities are very different, it is important to be aware of this variant of dedifferentiated chondrosarcoma to avoid the misdiagnosis of conventional giant cell tumor of bone.

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Enchondroma
Chondroblastic osteosarcoma