Chondrosarcoma Workup

Routine blood investigations are performed as part of preoperative examinations. Tests of liver, lung, and renal function—with bone biochemical analyses—may be used for preoperative assessment and for evaluations of the distant spread of tumors (metastasis).

Otherwise, workup rests primarily on diagnostic imaging modalities (eg, plain radiography, as well as computed tomography [CT] and magnetic resonance imaging [MRI]).

The typical appearance of a cartilaginous lesion on plain radiographs is discrete calcification. The lesion may be radiolucent on radiographs, which may show stippled or punctate calcifications. Appearances vary from lesion to lesion, depending on the amount of mineralization that has occurred.

Characteristic findings

Chondrosarcomas are usually large (>5 cm). The bony contour appears thinned and expanded, and multiple surface erosions (endosteal scalloping) are seen. Chondrosarcomas sometimes produce cortical thickening as well. The extent of bony destruction depends on the histologic grade of the tumor. (See the image below.)

Plain radiograph shows low-grade chondrosarcoma in pelvis (B). Incidental finding is that proximal femur contains benign enchondroma (A).

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The periosteum overlying the tumor may be elevated. This effect leads to new bone formation that results in hazy cortical irregularity and fuzziness or parallel periosteal new bone formation. This process differentiates chondrosarcomas from osteosarcomas, which results in perpendicular periosteal new bone formation that has a sunburst appearance.

Variable amounts of stippled or punctuate calcification are seen. In some cases, calcifications resemble popcorn or commas; in others, arcs and rings of calcification are seen around lobules of cartilage. The typical appearance of an dedifferentiated chondrosarcoma is an area of punctate opacities surrounded by a permeating, destructive lytic lesion.

Endosteal scalloping and thinning may be observed with most lesions. Sometimes, as in clear cell chondrosarcoma, images depict cortical thickening around the lysis with endosteal expansion. High-grade lesions produce permeative lesions as they destroy the cortex.

Findings suggestive of secondary malignant degeneration

Secondary malignant degeneration should be suspected when sequential follow-up radiographs of benign cartilage tumors show the following findings:

• Growth of the lesion
• Decreased calcification and increased lysis
• Endosteal erosion
• Permeative lesions with destruction of the cortex
• Soft-tissue mass
• Growth in a previously stable exostosis or enchondroma in an adult
• Expansion of the cartilaginous cap in exostosis

MRI is the investigation of choice for assessing the extent of a chondrosarcoma; it also helps delineate the extent of soft-tissue involvement (see the images below). Its ability to determine the exact extent of the tumor and the degree to which various soft-tissue compartments are involved make it an important tool for preoperative planning. In addition, MRI is an important study for confirming or diagnosing recurrence at a surgically treated site. Dynamic contrast-enhanced MRI has been reported to be useful and complemetary to standard MRI for distinguishing benign from malignant lesions. ^[22]

T1-weighted MRI shows low-signal-intensity lesion in pelvis: chondrosarcoma.

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T2-weighted MRI shows high-signal-intensity lesion in pubis: chondrosarcoma.

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MRI of chondrosarcoma (B) shows contrast enhancement of lesion. Enchondroma (A) is also present.

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CT may be useful for detecting subtle calcifications in the matrix so as to help diagnose cartilaginous tumors when the findings are in doubt. CT may improve visualization of bony destruction and depict the extent of bony delineation. It has been suggested that positron emission tomography (PET)-CT can help in differentiating between chondromas and chondrosarcomas in the long bones. ^[23]

Bone scanning and chest CT are used for systemic staging of the tumor before surgical treatment. Abdominal CT, abdominal ultrasonography (US), or both may be used for this purpose as well.

Performing a truly representative biopsy of a chondrosarcoma is challenging because the lesion is composed of areas that carry different histologic grades. A tumor should be graded on the basis of its most aggressive component. Hence, the challenge during biopsy is to ensure that the most aggressive part is identified.

Biopsy should be directed at areas that may harbor foci of high-grade tumor, such as areas of endosteal scalloping, soft-tissue components, or diffusely enhancing areas with minimal mineralization. The rationale behind targeting areas with minimal calcification of the matrix is that high-grade areas usually contain myxomatous matrix that is relatively resistant to calcification. By comparison, low-grade areas usually contain chondroid matrix that calcifies.

Biopsy can be performed with either an open or a closed technique. ^[3] Closed biopsy involves fine-needle aspiration (FNA) cytology or core biopsy. Core biopsy through a Tru-Cut biopsy or a core needle biopsy yields results equivalent to those of open biopsy. Image-guided needle biopsy may be more reliable for grading chondrosarcoma in long bones than in the pelvis. ^[24]

Discussion with the radiologist and the histopathologist is essential in obtaining the correct tissue for biopsy. However, with cartilaginous tumors, histopathologic examination of the biopsy specimen alone does not permit accurate classification of the tumor.

Chondrosarcomas are mostly gelatinous. Therefore, the risk of seeding of the biopsy tract with bone-tumor cells is high. Furthermore, because the cartilaginous tumor matrix is avascular, malignant cartilage cells can survive when they are spilled into a wound. For these reasons, biopsy of a chondrosarcoma should be done as meticulously as possible. When a definitive procedure is performed, the whole tract should be completely excised.

In summary, biopsy of a chondrosarcoma is not a benign procedure and must therefore be planned efficiently. The normal principles of biopsy for any tumor should be adhered to, as follows:

• The biopsy should be done by the surgeon who will be providing definitive treatment; if that is not feasible, it should least be done after a detailed discussion with the surgeon
• The path selected for the biopsy should be in the same line as that to be used for the definitive operation, so that the biopsy tract will be excised in the course of surgical treatment
• The biopsy tract should follow a straight line and avoid contamination of joints, uninvolved structures, neurovascular bundles, and bones; preoperative planning is essential, and the biopsy tract should not be placed in the flap that will be used for coverage after excision of the tumor
• Transverse incisions should be avoided
• Appropriate handling of tissue after the biopsy specimen is obtained is essential; this should be decided before the operation in consultation with the histopathologist
• Adequate hemostasis should be achieved before closure
• A suture may be used to mark the skin entry site to facilitate excision of the biopsy tract during definitive surgery

Gross

The cartilaginous nature of chondrosarcomas is apparent on cross-section. The lesion has a grossly lobulated architecture with translucent, gray-black hyaline tissue. Intense mineralization accentuates lobules at the periphery. The myxoid variety may be gelatinous. Two features—tumoral oozing from the cut surface and frank liquefaction—help in differentiating malignant tumors from benign tumors of cartilage. Chondrosarcomas appear as sessile, lobulated masses in the pelvis and have large extraosseous components.

Microscopic

A tumor must be uniformly cartilaginous to be classified as a chondrosarcoma. Chondrosarcomas contain chondroid matrix with increased cellularity, and they have binucleate cells. As noted (see Overview, Pathophysiology), these tumors are classified into low, intermediate, and high grades (grades I, II, and III, respectively).

Low-grade chondrosarcomas typically look like enchondromas. Intermediate-grade tumors contain cartilage cells that have enlarged round nuclei with prominent nucleoli. Their cytoplasm shows prominent rough cytoplasmic reticula, mitochondria, and large amounts of glycogen. High-grade tumors are characterized by high cellularity, prominent nuclear atypia, and mitosis. High-grade tumors constitute 5-10% of all chondrosarcomas.

Immunohistochemical tests show the presence of S-100 protein and vimentin in low- and intermediate-grade chondrosarcomas. However, results for S-100 protein and vimentin are focally negative in high-grade lesions, especially among dedifferentiated areas. Immunohistochemical staining is not routinely indicated for the diagnosis of cartilaginous tumors. These lesions are more readily diagnosed with conventional hematoxylin-eosin stains than with immunohistochemical stains.

Measurements of DNA ploidy reveal that low-grade tumors are diploid, whereas intermediate- and high-grade tumors are aneuploid. Aneuploidy is correlated with the aggressiveness of the chondrosarcoma.

Chromosomal anomalies reveal an accumulation of p53 protein; in high-grade lesions, this finding indicates a poor prognosis.

The Enneking staging system for musculoskeletal sarcomas is applicable to chondrosarcomas, as follows ^[4] :

• Stage I (low-grade tumor) - I-A, intracompartmental; I-B, extracompartmental
• Stage II (high-grade tumor) - II-A, intracompartmental; II-B, extracompartmental
• Stage III (distant metastasis)

The National Comprehensive Cancer Network (NCCN) follows both the tumor-node-metastasis (TNM) classification of the American Joint Cancer Committee/Union for International Cancer Control (AJCC/UICC) and the Surgical Staging System from the Musculoskeletal Tumor Society (MTS) for staging. ^[25]  The European Society for Medical Oncology (ESMO), the European Reference Network for Paediatric Cancers (PaedCan), and the European Network for Rare Adult Solid Cancer (EURACAN) do not provide a specific recommendation for which system should be followed. ^[26]