Tae Won Kim, MD

Chondrosarcoma is amalignant tumor of bone that forms cartilage. Chondrosarcomas are known as “primary”when they arise de novo and “secondary” if they occur following the malignant transformation an underlying lesion such as an osteochonroma or enchondroma.

Chondrosarcomas areclassified histologically as low grade, intermediate grade, or high-grade.Clinical aggressiveness is highly correlated to the histologic grade of the tumor, but lesion size, bone of origin and location within the bone can affectprognosis as well. The vast majority of primary chondrosarcomas are designated“conventional.” Other rare variants, including clear cell chondrosarcoma, dedifferentiatedchondrosarcoma, and mesenchymal chondrosarcoma, can be found as well. (The discussion below applies to “conventional” chondrosarcoma unless note do the rwise.) Most chondrosarcomas are found in the medullary canal and aredesigned “central chondrosarcomas” those originating from the bone’s superficialsurface are termed “juxtacortical” or “periosteal.”

Epidemiology

Chondrosarcomas are the second most common musculoskeletal malignancy, but still have a relatively lowincidence in the general population, about 1 per 100,000. The incidence is roughly equal among males and females. Chondrosarcoma is primarily a disease of patientsin their fifth to seventh decades.

Clinical Features

Chondrosarcomas are most frequently found in the proximal femur, the pelvis and the proximal humerus. Other locations include the distal femur, tibia, ribs and spine. The most common presenting symptom is pain, especially at night. It is not uncommon for chondrosarcomas to also present with a mass, once extraosseous extension ispresent. Grade 1 and 2 chondrosarcomas tend to be fairly slow-growing, where as grade 3 can grow quite rapidly. Rapidly growing lesions may present with apathological fracture.

Radiologic Features

The radiographic hallmark of chondrosarcoma is a mass with calcifiedcartilage and destruction of the nearby bone. In addition, with in the tumor there may be clear areas – so-called “intralesional lysis.” Intralesional lysisis caused by the appearance of younger, more active cartilaginous tissue thathas not yet calcified.

Chondrosarcomas are typically round as they form with in the medullarycanal. As it grows, the tumor will encounter and compress the endosteum of the nearbycortex. This contact might deform the tumor, but also erodes the bone, generatinga scalloped appearance of the endosteum. These scallops are typically 1 centimeteror larger. With continued growth, the tumor can cause progressive cortical reaction. If the growth is slow, as seen with lower-grade lesions, the cortical bone responds to the thinning of the endosteal surface with expansion on the periosteal side and an overall widening of bone. If there is complete erosion of the cortex, extraosseous extension may occur.

Magnetic resonance imaging (MRI) and computerized to mography (CT) are often employed as well. CT is especially adept at detecting matrix mineralization and cortical changes. MRI can assess marrow involvement and soft tissue masses.

Pathology

Cartilage tumors can be classified along a continuum, from benign lesions to high-grade malignancies. This classification is based factors such as cellularity, nuclear size and shape, mitotic activity, and staining pattern.

• Benign cartilage tumors contain hypocellularhyaline cartilage, with one cell per lacunar space. Their chondrocytes havesmall eccentric, crescent-shaped nuclei and are found in a sea of abundant, uniform, high-quality chondroid matrix.
• In lesions of borderline pathology, there is increased cellularity, plump nuclei, binucleate cells, more than one cell perlacunar space, and cells outside of lacunar spaces. The cartilage matrix is typically still abundant and of uniform high-quality.
• With increasing malignancy, the cartilage matrix is replaced by myxoid matrix, as the cells become dedifferentiated. The tumor is very hypercellular, with frank pleiomorphism, atypia, and mitoticfigures.

Intermediate- and high-grade chondrosarcomas are usually recognized histologicallywith ease. Distinguishing low-grade malignancies from benign lesions, however, is more challenging. Moreover, cartilage lesions are defined not only by histologybut also their radiographic and clinical findings. In the case of low-gradehistologic lesions, X-ray and MRI scan may reveal more about the aggressiveness of the lesion than the histology itself.

Note that any malignant tumor that forms osteoid (bone matrix) is classified as an osteosarcoma, even if the osteoid is scant and the cartilage abundant. Thus, the presence of osteoid in what was thought to bechondrosarcoma establishes the diagnosis of chondroblastic osteosarcoma. Chondrosarcomas can demonstrate calcifications, but not ossification, there areno “osteoblastic chondrosarcomas.”

Differential Diagnosis

Enchondroma and a grade 1 chondrosarcoma can have similar radio graphic appearance. (A large size and the presence of a soft tissue mass suggest chondrosarcoma.)

Osteochondromas is a precursor lesion of chondrosarcoma. Thickening of the cartilaginous cap on T2-weighted MRI suggests transformation to a secondary chondrosarcoma.

It is possible to confuse a central cartilage tumor with a bone infarct.

Disease Course: Treatment and Prognosis

Low-grade chondrosarcomas cause local morbidity, but only rarelymetastasize. High-grade chondrosarcomas are associated with high risk ofmortality in light of their propensity for metastatic spread. To a first approximation, grade 1 chondrosarcomas do not metastasize and have a 90% ten-year survival. Grade2 chondrosarcomas metastasize in about 15% of cases and have a 70% ten-yearsurvival. Grade 3 chondrosarcomas metastasize in about 50% of cases and have a 40% ten-year survival. Overall, the prognosis for secondary chondrosarcomas is better than that of primarily lesions, as most secondary chondrosarcomas are low grade malignancies.

The primary treatment for all grades of chondrosarcoma is wide surgicalexcision. While patients with high-grade chondrosarcomas would certainlybene fit from modalities to address systemic disease, there are currently no treatment protocols that have been shown to be effective against high-grade chondrosarcoma.

Chondrosarcoma Variants

Clear Cell Chondrosarcoma

Clear cell chondrosarcoma is a slow-growing tumor, with malignant chondrocytes that show abundant clear cytoplasm and sparse intracellular matrix. Clear cell chondrosarcoma is typically epiphyseal in location and commonly seen in the femoral head. This is a very rare malignancy that occurs predominantly in patients in their third and fourth decades of life. It typically demonstrates low-grade biological potential. Because of the epiphyseallocation, patients with clear cell chondrosarcoma typically present with joint complaints such as pain, stiffness, and decreased range of motion. Plain radio graphs demonstrate a lytic intra-epiphyseal lesion with geographic lysisand focal chondroid calcification. If found in the femoral head, a clear cell chondrosarcoma might be mistaken for avascular necrosis or a femoral. Onhistological examination, the dominant cell in this tumor, as the name implies, is a clear cell chondrocyte, which is said to look like fried egg. These cellsare well-demarcated and associated with a sparse chondroid matrix. Wide-margin surgicalexcision is the standard treatment. No systemic treatment is currently available. Local recurrence and occasional regional or distant meta stases may occur and have been reported up to 15-20 years following initial treatment.

Dedifferentiated Chondrosarcoma

Dedifferentiated chondrosarcoma is tumor with two components side by side: a well-differentiated cartilage tumor, often a low-grade chondrosarcoma, adjacent to a high-grade non- chondroid sarcoma, such as osteosarcoma, fibrosarcoma, undifferentiated pleomorphic sarcoma, or rhabdomyosarcoma. This is a very rare lesionthat occurs most commonly in patients older than 50 years of age. As with most chondrosarcomas, this tumor is typically metaphyseal or diaphyseal. Pain is the most common presenting symptom. Because of its extremely high-grade nature and aggressive behavior, pathologic fracture is also common as a presenting symptom. This tumor appears as a typical high-grade lesion with gross bone destruction, with soft-tissue extension. Matching its biphasic histology, the radio graphic findings of dedifferentiated chondrosarcoma may demonstrate features of both the low-grade cartilage tumor and those of the non-chondroid aggressive lesion. Dedifferentiate dchondrosarcomas are managed with wide-margin surgical resection, though metastases are common, and thus the overall prognosis for these patients is poor. At present, there is no effective drug regimen to treat or prevent metastaticspread, though targeted treatment aimed at the non-chondroid sarcoma may be attempted given the otherwise bleak prognosis.

Mesenchymal Chondrosarcoma

Mesenchymal chondrosarcomas are extremely rare high-grade chondrosarcomas defined by the presence of sheets of small round or oval cells in association with low-grade malignant cartilage. This rare lesion tends to occur in younger adults, typically below the age of 40. The most common skeletal locations are the pelvis, femur, ribs, and vertebrae. Mesenchymal chondrosarcoma is alsofound in extraskeletal soft tissues, including the meninges. Histologic examination typically reveals sheets of small round blue cells immediately juxtaposed to areas of low-grade cartilage. Clinical and radiologic features are similar to that of dedifferentiated chondrosarcoma.

Commonly Tested onExam

1. Precursor lesions that transform to chondrosarcoma

2. Radiography and histology of chondrosarcoma

3. Prognostic factors of chondrosarcoma

4. Treatment protocols

NEEDED FIGURES

• Map of where tumor is found?
• Classic x-ray showing intra-lesional lysis, endosteal scalloping, and cortical thinning and expansion --maybe two?
• MRI and CT if instructive
• Path slides showing normal, low and high grade lesions (eg Pleiomorphism, atypia, mitotic figures, and myxoid matrix production)
• Path of clear cell lesion?
• X-ray and path of dedifferentiated chondrosarcoma showing combined nature of lesion

JB comments

• LINK TO osteochonroma and enchondroma rather than show pictures here
• Author did not speak to indications for biopsy and whether this should be open
• We need a uniform title for “Concepts Commonly Tested on Examinations”