Liddy Shriver Sarcoma Initiative on Facebook    Follow Us on Google Plus    Follow Us on Twitter    Sarcoma Videos on YouTube

What is chondrosarcoma?

Prepare. Communicate. Find Support.

Read our Comprehensive Guide for the Newly Diagnosed

Chondrosarcoma is a type of sarcoma that affects the bones and joints. It is a rare cancer that accounts for about 20% of bone tumors and is diagnosed in approximately 600 patients each year in the United States.1 Chondrosarcoma typically affects adults between the age of 20 and 60 years old, and it is more common in men. The disease usually starts in the bones of the arms, legs or pelvis, but it can be found in any part of the body that contains cartilage. Sometimes chondrosarcoma grows on an otherwise healthy bone, and sometimes it grows on a benign bone tumor (an enchondroma or osteochondroma).

There are several types of chondrosarcoma that are named based on the way that they appear under the microscope. These include:

  • Conventional chondrosarcoma
  • Clear cell chondrosarcoma
  • Myxoid chondrosarcoma
  • Mesenchymal chondrosarcoma
  • Dedifferentiated chondrosarcoma

What causes chondrosarcoma?

As with many cancers, the cause of chondrosarcoma is not clear. However, people with certain medical conditions have an increased risk for developing chondrosarcoma. These conditions include:

  • Ollier's Disease
  • Maffucci Syndrome
  • Multiple Hereditary Exostoses (MHE, a.k.a., osteochondromatoses)
  • Wilms’ Tumor
  • Paget’s disease
  • Diseases in children that required previous treatment with chemotherapy or radiation therapy

How aggressive is chondrosarcoma?

Chondrosarcomas behave in different ways, but many are low grade tumors. The cells in these tumors look and behave like normal cartilage with only a small amount of abnormality. In intermediate grade tumors, cells still look like cartilage cells, but they show more malignant changes. In high grade tumors, cells look much less like normal cartilage, and they grow and change rapidly.

Conventional chondrosarcoma and clear cell chondrosarcoma are often low to intermediate grade tumors that are not very aggressive and tend to stay in one place. Dedifferentiated and mesenchymal chondrosarcoma are high grade tumors that behave aggressively and tend to spread. [See the page devoted to mesenchymal chondrosarcoma for more information.]

De-differentiated chondrosarcoma occurs in less than 10% of cases, and it is usually found in the arm, leg or pelvis bones. This tumor is a very different kind of chondrosarcoma that is especially difficult to treat. A part of the tumor appears to be a low to intermediate grade cartilage tumor, and it is located close to a high grade non-cartilage kind of sarcoma.

What are the symptoms of chondrosarcoma?

People with chondrosarcoma usually do not feel sick. They may be able to feel a boney bump, and most patients ultimately will have pain, swelling, or limited movement that is caused by the tumor.

How is chondrosarcoma diagnosed?

A bone tumor is often first discovered on x-ray after a physical exam. It can be difficult to tell the difference between a benign bone tumor and chondrosarcoma on x-ray. Additional tests, including a bone scan, CT scan, MRI and PET scan, can provide more information about the tumor. Ultimately, biopsy of the tumor is the only way to make a definite diagnosis of chondrosarcoma. After the biopsy procedure, a pathologist looks at the tumor’s cells under the microscope to make a diagnosis.

Doctors use the results of the biopsy and imaging studies to develop a patient's treatment plan.

How is chondrosarcoma treated?

Complete surgical removal of the tumor, along with a wide margin of healthy tissue, has historically been the preferred treatment of chondrosarcoma. Limb salvage surgery is a common treatment technique, and amputation is only used occasionally for advanced or recurrent disease.

Studies have been done and are underway to measure the effectiveness of intralesional curettage surgery, which is a less aggressive surgery that removes less tissue, on low grade chondrosarcomas. These studies show that certain low grade tumors respond well to this type of surgery, which has excellent functional results for patients. The issue of how to best deal with low grade chondrosarcoma is controversial and is covered in depth in this article.

Most chondrosarcomas (with the exception of mesenchymal chondrosarcoma) do not respond to chemotherapy or radiation therapy. This makes surgical management crucial in the treatment of chondrosarcoma. In rare situations where the skull is involved, proton radiation therapy may be helpful. 

Chemotherapy or radiation therapy is sometimes considered for patients with recurrent, metastatic or dedifferentiated disease. Unfortunately, these treatments have not been proven to be effective, and there is no standard protocol to follow.

Prognosis for chondrosarcoma patients

Prognosis statistics are based on the study of groups of chondrosarcoma patients. These statistics cannot predict the future of an individual patient, but they can be useful in considering the most appropriate treatment and follow-up for a patient.

The prognosis for chondrosarcoma patients varies by the grade of the tumor and the extent of surgery. In general, low grade tumors have an excellent prognosis, with a small chance of recurrence and virtually no chance of disease spread. Risks increase as the grade of the tumor increases, with de-differentiated tumors having the highest risk of recurrence and metastasis and a poor survival rate.

1: Bovée JVMG . Bone: Chondrosarco. Atlas Genet Cytogenet Oncol Haematol. March 2002.
http://AtlasGeneticsOncology.org/Tumors/chondrosarcID5063.html

Last revision and medical review: 10/2012

By Elizabeth Munroz

Print it

Chondrosarcoma of the Bone : A Detailed Review

What is Chondrosarcoma?

Chondrosarcoma is a malignant cancer whose tumor cells produce a pure hyaline cartilage that results in abnormal bone and/or cartilage growth. People who have chondrosarcoma have a tumor growth, or abnormal bony type of bump, which can vary in size and location. The term chondrosarcoma is used to define a heterogeneous group of lesions with diverse morphologic features and clinical behavior. Primary chondrosarcoma (or conventional chondrosarcoma) usually develops centrally in a previously normal bone. Secondary chondrosarcoma is a chondrosarcoma arising from a benign precursor such as enchondromas or osteochondromas.

Chondrosarcoma is the second most common primary bone cancer. The malignant cartilage cells begin growing within or on the bone (central chondrosarcoma) or, rarely, secondarily within the cartilaginous cap of a pre-existing osteochondroma (peripheral chondrosarcoma). There are several different types of chondrosarcoma, with names based on the type of cells identified when they are examined under a microscope (see next section for detailed descriptions).

It is important to understand the difference between a benign and malignant cartilage tumor. Chondrosarcoma is a sarcoma, or malignant tumor of connective tissue. A chondroma, also called exostosis or osteochondroma, is a benign bone tumor. Benign bone tumors are not sarcomas. Benign bone tumors do not spread to other tissues and organs, and are not life threatening. They are generally left alone or cured by surgical removal if they cause symptoms such as tenderness via pressure on surrounding muscles, tendons or nerves.

Malignant tumors arising from the skeletal system are rare, representing only about half of one percent of all new cancers. Approximately 2100 new cases of malignant bone cancers (sarcomas) occur in the United States each year (Unni, 1996). The most common type of bone cancer is osteosarcoma, which develops in new tissue inside growing bones. About one fourth of malignant bone cancers are chondrosarcomas.

Not all malignant cartilage tumors of bone are chondrosarcomas. For example, chondroblastic osteosarcoma is a bone-forming tumor (osteosarcoma) where production of cartilage (or chondroid) matrix is predominant.

Chondrosarcoma and Osteosarcoma

Chondrosarcoma should not be confused with osteosarcoma, also called osteogenic sarcoma. Osteosarcoma is a malignant tumor arising from bone cells, (not from cartilage) and is the most common primary bone cancer. Although osteosarcoma most often occurs in young people between age 10 and 30, about 10% of cases develop in people in their 60's and 70's. Osteosarcoma is rare during middle age. These tumors develop most often in bones of the arms, legs and pelvis. Conventional chondrosarcoma has a better outcome than osteosarcoma. The treatment options for both these cancers are different; see the section below, "What are the current treatments for chondrosarcoma?"

What are the different kinds of chondrosarcoma?

The single most important factor to consider when evaluating the malignant potential of a chondrosarcoma is its "histologic grade", determined by the appearance of tumor material under the microscope (Donati et al., 2005; Lee et al., 1999; Marcove et al., 1977; Reith et al., 2003; Springfield et al., 1996; Wang et al., 2001). In addition to histologic grade (I-III, dedifferentiated, and mesenchymal, see Table 1), chondrosarcomas can be classified by their location within the bone (i.e., central, peripheral, periosteal) and body (i.e., axial skeleton versus appendicular skeleton), whether they are primary or secondary (i.e., arising de novo versus secondary to a pre-malignant but benign lesion such as an osteochondroma), or whether it fits into a specific histologic variant (i.e., clear cell, myxoid, mesenchymal, dedifferentiated). The lower grade variants of chondrosarcoma can often be quite difficult to differentiate from benign lesions because they have similar appearances on radiographic studies. Benign cartilage tumors, called enchondromas do not usually cause symptoms and never metastasize.

The Skeleton

The axial skeleton and the appendicular skeleton together form the complete skeleton. The axial skeleton consists of the bones in the head and trunk of a vertebrate body. It is composed of three major parts; the skull, the bony thorax (i.e. the ribs and sternum), and the vertebral column. The appendicular skeleton is the part of the skeleton that includes the pectoral girdle, the upper limbs, the pelvic girdle, and the lower limbs. See "Skeleton" on the University of British Columbia's website and "The Bone Box" on the University of Loyola's website.

Molecular techniques to classify tumors, such as cDNA expression arrays may prove useful in the future but have yet to be substantiated in the clinical arena.

Conventional chondrosarcomas are divided into four histologic grades based upon their appearance under a microscope (Table 1). The grading is based primarily on nuclear size of tumor cells, nuclear staining (hyperchromasia, or darker staining of nuclear material) and cellularity (Evans et al., 1977).

Bones

Bone structure can be either woven or lamellar. Woven bone is put down rapidly during growth or repair. It is called woven because its fibers are aligned at random, and as a result has low strength. In contrast, lamellar bone has parallel fibers and is much stronger. Woven bone is often replaced by lamellar bone as growth continues.

Bone is composed of both compact (cortical) and cancellous (spongy) material. Cortical bone (outer layer, or cortex) is synonymous with compact bone. Cortical bone makes up a large portion of skeletal mass. It is dense and has a low surface area. Cancellous bone is trabecular (honeycomb structure); it has a relatively high surface area, but forms a smaller portion of the skeleton. The medullary canal is the central cavity of the bone shaft where marrow is stored. The medullary cavity has walls composed of compact bone referred to as endosteum. Endosteal scalloping refers to erosion of endosteal bone, caused by a tumor, compared to adjacent cortex.

Figure 1

Figure 1: Grade I chondrosarcoma demonstrates increased cellularity...

Grade I (or "low grade") tumors most resemble normal cartilage, but may surround areas of lamellar bone (which is not seen in benign lesions), or show atypical cells including binucleate forms (cells with two nuclei instead of one), see Figure 1.

Grade II (or "intermediate grade") are more cellular with a greater degree of nuclear atypia, hyperchromasia and nuclear size (Schiller, 1985).

Grade III (or "high grade") tumors have significant areas of marked pleomorphism, large cells with more hyperchromatic nuclei than grade II, occasional giant cells and abundant necrosis. Mitoses are frequently detected.

Myxoid changes or chondroid matrix liquefaction is a common feature of chondrosarcomas particularly in Grade II and Grade III lesions. The vast majority of chondrosarcoma are Grade I or Grade II. Grade III is rare (Bjornsson et al., 1998).

The variant known as differentiated chondrosarcoma is less common. It is typically thought of as arising from one of the other three histologic subtypes or from a benign precursor. De-differentiated chondrosarcomas, along with mesenchymal chondrosarcomas, are highly malignant, particularly aggressive (i.e., rapidly growing and disturbing surrounding tissues) and carry with them a poor prognosis.

Chondrosarcoma Tumors
  Tumor Symptoms Prognosis Treatment
Benign Enchondroma Usually no symptoms Excellent Surveillance, intralesional excision if symptomatic
Malignant
(Low grade)
Grade I
Chondrosarcoma
60% are painful Good Controversial: Extended intralesional excision vs. Wide resection
Malignant
(Intermediate grade)
Grade II
Chondrosarcoma
Up to 80% are painful Fair Wide resection
Malignant
(High grade)
Grade III
Chondrosarcoma
Up to 80% are painful Poor Wide resection. Chemotherapy and radiation therapy in select cases
Malignant
(High grade)
Dedifferentiated
Chondrosarcoma
Most are painful Poor Wide resection. Chemotherapy and radiation therapy in select cases
Malignant
(High grade)
Mesenchymal
Chondrosarcoma
Pain and swelling Poor Wide resection. Chemotherapy and radiation therapy in select cases

Enchondromas, which are benign cartilage tumors, are usually found incidentally, most commonly in the bones of the hand and feet (Enneking, 1983). Radiographically they appear as small cartilage nests (usually <5cm in diameter) with multiple intralesional calcifications. Occasionally, very mild endosteal scalloping will occur, however true cortical invasion and the involvement of adjacent soft tissues is rare (Enneking, 1983). Histologically, islands of normal hyaline cartilage are found surrounded by lamellar bone. On rare occasion, enchondromas will become symptomatic, or lead to pathologic fracture, and will require surgical treatment.

Juxtacortical chondrosarcoma arises on the surface of bone and is histologically identical to conventional intramedullary chondrosarcoma.

Chondrosarcomas may also be classified by their histologic sub-type. These sub-types include clear cell, mesenchymal, and de-differentiated. Clear cell chondrosarcomas are low-grade tumors with significant amounts of glycogen. They typically involve the proximal portion of femur, tibia or humerus. Histologically, cells have abundant clear cytoplasm embedded in a loose hyaline cartilaginous matrix and an infiltrative growth pattern. Radiographs show a lytic defect at epiphyseal end of long bones that is sharply demarcated with sclerotic margins. They carry a low recurrence rate and a good prognosis with wide resection.

Mesenchymal chondrosarcomas are highly aggressive tumors that are radiographically and histologically distinct from conventional and dedifferentiated types. They are eccentrically located in bone and commonly extend into soft tissues. This variant of chondrosarcoma is characterized by a bimorphic pattern that is composed of highly undifferentiated small round cells (similar to Ewing’s Sarcoma) and islands of well-differentiated hyaline cartilage. This tumor usually affects young adults and teenagers and shows a widespread distribution in skeleton. The craniofacial bones, the ribs, the ilium and the vertebrae are the most common site (Bertoni et al., 1983). The treatment is radical surgery combined with chemotherapy.

De-differentiated chondrosarcomas represent about 10% of all chondrosarcomas. The most common sites of involvement are pelvis bones, femur and humerus. This tumor is a distinct variety of chondrosarcoma containing two clearly defined components: a well-differentiated cartilage tumor (enchondroma or chondrosarcoma grade I and II) juxtaposed to a high grade non-cartilaginous sarcoma. They are most often found in the femur, pelvis, or humerus bones, although they may also occur in the head, spine, breast, and prostate. Histologically there is a typical abrupt transition between the two components, cartilaginous and non-cartilaginous; both tumor components are evident in varying proportions. The malignant non-cartilaginous component is most frequently malignant fibrous histiocytoma, osteosarcoma or fibrosarcoma, although other malignant tumors have been reported as the differentiated component. The cartilaginous and non-cartilaginous components are often adjacent, and the term "collision of two tumors" has been applied to this lesion. Radiographically the tumor produces an ill defined, lytic, intraosseous lesion associated with cortical disruption and extension into the soft tissues.

Who gets chondrosarcoma?

Most chondrosarcomas are low-grade lesions. They are typically seen in adults in their late 20s to 60s. They occur more commonly in men than women. Chondrosarcoma is not contagious. It cannot be passed on to another person by exposure to a chondrosarcoma patient. Although specialists are not yet certain what causes chondrosarcoma, there are several factors that put people at a higher risk.

Certain hereditary conditions may make people more susceptible to chondrosarcomas. These include Ollier's Disease, Maffucci Syndrome, Multiple Hereditary Exostoses (MHE, a.k.a., osteochondromatoses), and Wilms Tumor. People affected by these conditions are at a higher risk because they usually develop several benign bone tumors (sometimes called bone spurs in the case of MHE), which have a higher chance of becoming malignant. People with these hereditary conditions who experience sudden growth spurts or increases in hormone production, such as pregnancy, have a slight increased risk of a benign bone tumor changing into a chondrosarcoma. These patients should be followed by a bone tumor specialist for all of their lives.

However, most patients with chondrosarcoma do not have any of these genetic conditions. Adults with Paget's disease, a non-cancerous condition characterized by abnormal development of new bone cells, may be at increased risk for chondrosarcoma. When chondrosarcoma occurs in children and young adults, it is often in patients who have had radiation or chemotherapy treatments for other conditions.

Recently, genetic studies have shown that there are specific locations on chromosomes where the genetic information for chondrosarcoma resides (Bovee et al., 2005; Sandberg, 2004). Continuing research of the genes and how the proteins encode for them will offer tremendous insight into the growth of these cancerous cells. This information is important since chondrosarcoma is a problem with the growth of cells. An understanding of the involved gene and the function of its protein may eventually lead to better treatment. It is feasible that, in the future, genetic manipulations may aid in the detection, treatment and/or prevention of chondrosarcoma.

Where in the body are chondrosarcomas usually found?

Chondrosarcomas may develop in any part of the body, but most are commonly found in the pelvis, rib cage, arms (humerus), shoulder blades (scapula) and legs (proximal femur, tibia). Although any bone can be affected, the long bones (legs, arms, fingers, toes,) pelvis and shoulder blades are most commonly involved. Occasionally chondrosarcoma has been found in the spine or skull bones. It is extremely rare to find chondrosarcoma in any internal organs, but this has been described. If chondrosarcoma spreads from its primary site (i.e., metastasizes), it usually spreads to the lungs. Metastasis is rare with low-grade tumors, but has been seen, even up to 10 years after diagnosis (Lee et al., 1999). About half of grade III and nearly all de-differentiated chondrosarcomas will metastasize; see Table 2.

How does someone with chondrosarcoma feel?

People with benign cartilage tumors (i.e., enchondroma or osteochondroma) rarely have pain that is caused by the tumor (Marco et al., 2000b). Most patients with a chondrosarcoma will have pain (Bjornsson et al., 1998; Marco et al., 2000a; Mirra et al., 1985; Murphey et al., 1996) and many will have swelling. It has been reported that in patients with grade I chondrosarcoma, 60% have night pain or rest pain, 21% have vague regional pain, and only 19% have painless tumors (Marco et al., 2000a). People with higher grade tumors (grade II or III chondrosarcoma) have pain up to 80% of the time (Pritchard et al., 1980). Rarely, people will discover they have a chondrosarcoma when they develop a fracture through the tumor (Bjornsson et al., 1998).

Pain associated with chondrosarcoma is usually in the location of the lesion or adjacent joints, muscles, tendons, nerves, blood vessels, or other soft tissues. In addition to pain, patients with chondrosarcoma may notice an enlargement of a bone or limb, changes in their ability to walk normally, or decreased range of motion in joints near the affected bone. Sometimes patients with benign cartilage tumors can have pain caused by something other than the tumor. For example, a rotator cuff injury can be painful at night and an x-ray might show a cartilage tumor in the shoulder. It is very important to determine whether pain is being caused by the tumor or by another process. This difference is vital in the diagnosis and treatment of chondrosarcomas.

Distinguishing between low-grade chondrosarcoma and benign enchondroma is perhaps one of the most challenging endeavors in the field of musculoskeletal oncology because they are difficult to differentiate. Even with diligent clinical practice and advanced radiographic and histologic technologies, the diagnosis may still prove elusive.

What tests are needed to determine if someone has chondrosarcoma?

Figure 2

Figure 2a: Plain radiograph of a low-grade cartilage lesion...

After a doctor asks questions (a history) and performs a physical examination, he/she may order plain x-rays to evaluate the area of concern. It can be very difficult for doctors to tell the difference between benign cartilaginous lesions and low-grade chondrosarcomas on x-rays. Both can demonstrate the classic stippled calcified appearance of cartilaginous bony lesions (Figure 2). If the hard outside covering of the bone (cortex) appears to be getting chewed away (endosteal scalloping) there is an increased likelihood that the tumor has malignant potential, but is not necessarily confirmatory. One helpful analysis of chondrosarcoma had endosteal scalloping of more than 2/3rd of the cortical thickness, whereas only 9% of enchondromas had similar findings (Murphey et al., 1996).

Figure 2

Figure 2b: Plain radiograph of a low-grade cartilage lesion...

More aggressive (malignant) tumors may show more telling signs of malignancy on x-ray. This includes adaptive changes such as expansion and/or thickening of the cortex and expansion of the surrounding soft tissues (Murphey et al., 1996; Unni, 1996). Features typical of lower grade lesions include dense calcifications appearing in rings or spicules, uniformly distributed calcifications and eccentric lobular growth of a soft tissue mass. Findings suggestive of higher grade include faint amorphous calcifications, large areas lacking calcifications and a concentrically growing soft tissue mass.

Perhaps the most reliable radiographic finding when differentiating between benign and malignant lesions is the recognition of change in radiographic appearance over time. In particular, there may be more endosteal scalloping and destruction of the cortex or a decrease in the calcifications with more malignant tumors. If there is no change in the appearance of a benign cartilage tumor on radiographs over time, it is appropriate for the doctor to continue to recommend watchful waiting and repeat x-rays at a later visit.

Figure 3

Figure 3: Bone scan of patient with left distal femoral chondrosarcoma...

bone scan of the entire body can also be helpful in differentiating between benign and malignant tumors, and in identifying whether more than one bone is involved (although multiple bone involvement is rare with chondrosarcomas). This test works by injecting a small amount of radioactive material into the blood stream and taking images using a gamma camera to detect uptake of radioactive material. Lesions demonstrated on bone scan can be compared to internal controls (Murphey et al., 1996). Those lesions demonstrating a higher degree of uptake are more likely to be of higher histologic grade. However, most enchondromas exhibit some radioisotope uptake, and some will erroneously appear as malignancy. Great caution should therefore be used in drawing conclusions from bone scan results, but these results can add to the overall picture, and better inform the decision making process.

Figures 4

Figure 4a: MRI image of distal femoral chondrosarcoma...

Axial computed tomography (CT) can assist in determining the extent of bony destruction, and in better delineating bony architecture. CT will also help in better understanding intralesional calcifications. As with plain radiographs, disappearance or change in the nature of calcifications with repeat scanning can be suggestive of malignancy.

Magnetic Resonance Imaging (MRI) can be helpful in differentiating between benign and malignant lesions in several ways. First, the degree to which the tumor fills the medullary canal can be helpful (Figure 4). Greater than 90% medullary involvement can be suggestive of chondrosarcoma, while the absence of 90% medullary involvement of non-contiguous areas of cartilage within the bone can suggest the presence of an enchondroma (Colyer et al., 1993). In addition, the timing and progression of gadolinium contrast enhancement patterns may help direct a clinician toward or away from a diagnosis of malignancy (Geirnaerdt et al., 2000). Early enhancement (within 10 seconds of arterial enhancement) may be seen in chondrosarcoma but not in enchondroma. Many surgeons consider MRI critical for surgical planning because it can illustrate the extent of tumor involvement in bone and soft tissues.

Figures 4

Figures 4b: MRI image of distal femoral chondrosarcoma...

Recently, there has been some research into the use of a specialized radiographic test called fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) for grading of tumors in patients with chondrosarcoma (Aoki et al., 1999; Brenner et al., 2004). This test is not yet available at all centers, but may become a useful tool for tumor grading and prediction of outcome in chondrosarcoma patients. This may hence allow for identification of patients at high risk for local relapse or metastatic disease.

What if a chondrosarcoma is suspected?

If chondrosarcoma is suspected, two additional (staging) tests will usually be done to determine whether the tumor has spread. These include: 1) a computerized tomography (CT) scan of the lungs; and, 2) a total body bone scan. The results of these staging studies help physicians determine treatments and outcomes (prognosis). Blood tests are generally not helpful in making the diagnosis, although they can be used to make sure that there is not another process going on, such as infection or a different malignant process. After all of these tests are performed, a sample of the tumor (biopsy) is necessary to figure out if the problem is truly chondrosarcoma. Most biopsies for chondrosarcoma are achieved by surgical excision (i.e., complete removal of the tumor) of the lesion rather than through incisional biopsy (i.e., surgery to remove only part of the tumor for diagnostic evaluation).

What will biopsy tell the patient and the doctor?

Figures 5

Figure 5: Grade II chondrosarcoma: Increased cellularity and atypical...

When fresh tissue from a chondrosarcomas is viewed under a microscope after a biopsy, it is generally not difficult to identify a clear distinction between normal host tissue and the malignant tissue. However, with higher-grade tumors, more aggressive margins may have more malignant tissue, and have infiltrating satellite components. They will exhibit heterogeneous gross properties including lobulated areas of chalky calcific admixture, regions of firm translucent unmineralized gray cartilage and relatively low vascularity. Higher-grade tumors tend to have areas of necrosis and degenerative material as well (Enneking, 1983).

Under the Microscope

On microscopic analysis, lower grade chondrosarcomas will exhibit increasing amounts of relatively acellular heavily calcified areas as well as regions of increased activity exhibiting immature cartilage cells with multiple nuclei. By contrast, higher-grade lesions tend to harbor regions of densely packed hyperchromatic malignant looking cells (Figure 5). There may sometimes be difficulty in determining that these cells are truly of cartilaginous origin. In some regions, myxomatous changes, and highly degenerative areas may make identification impossible.

As both benign and malignant cartilage lesions can share certain clinical and histological characteristics, pathologists will often consider the patient’s history when interpreting specimens. Permeation of cortical and/or medullary bone is an important characteristic of conventional chondrosarcoma that the pathologist can use to separate it from enchondroma. The decision by the orthopaedic oncologist for definitive treatment is based upon the areas of highest concern for malignancy. Lesions appearing more aggressive clinically and radiographically must be widely resected without biopsy to avoid contamination of healthy tissue, which would likely necessitate an additional surgery. However, this remains controversial.

What is known about the genetics of chondrosarcoma?

As evolving molecular techniques are available, several genotypic and phenotypic markers for chondrosarcoma have been tested to see if they assist in determining tumor grade prognosis. There is considerable complexity and heterogeneity in the pathologic and clinical behavior of chondrosarcomas. This is reflected in the diversity of cytogenetic and molecular genetic characteristics that have been described in these tumors. Please see Sandberg and Bridge (2003), Sandberg (2004), and Bovee et al. (2005) for a thorough review.

The genetic changes specific to chondrosarcoma continue to be investigated extensively. Although studies have not yet established a specific or recurrent karyotypic feature for any of these tumors, different chondrosarcomas have demonstrated anomalies in several tumor suppressor genes, oncogenes, and transcription factors, including TP53, RAS, EXT1, EXT2, and Sox9. Available cytogenetic and comparative genomic hybridization (CGH) studies reveal changes in some chondrosarcomas, but fail to do so in others. These studies are thus far difficult to interpret.

Chromosomal Changes in Chondrosarcomas

An impressive number of chromosomes have been demonstrated to be affected in chondrosarcomas, by either loss or gain of genetic information, many with implications on prognosis or clinical significance. For example, 6q13~q21 changes in chondrosarcoma appear to be associated with locally aggressive behavior (Sawyer et al., 1998), loss of 13q may be a predictor of metastases (Mandahl et al., 2002), c-MYC amplification and polysomy 8 can be used for prognostic purposes (Morrison et al., 2005), and overexpression of the STK15 gene may play a role in tumor progression, particularly in dedifferentiated chondrosarcoma, and can be used as a prognostic factor for identifying patients who are at high risk for the development of local recurrence or distant metastases (Vakar-López et al., 2001). However, these assays are not routinely performed.

Based on the available studies, it is likely that chondrosarcomas are generated by a coordinated, multi-step process involving primarily tumor suppressor genes. In fact, the complexity and variety of genetic changes seen in chondrosarcomas may indicate several distinct genetic pathways. Some of the same genes may be involved in each, but the order and manner in which they are affected may differ among chondrosarcomas. Establishing the genes that initiate the neoplastic processes, and that are subsequently involved along the pathways leading to chondrosarcoma may lead to therapies addressing these molecular changes, as has been accomplished for several other sarcomas.

What are the current treatments for chondrosarcoma?

For benign-appearing, asymptomatic cartilage tumors (i.e., enchondroma), patients are usually followed with clinical evaluation and sequential x-rays 3, 6 and then 12 months apart. This is continued unless there is a change in clinical examination findings or the radiographic appearance of the lesion at different points in time. Symptomatic enchondromas (i.e., those that cause pain, discomfort, or are disfiguring but do not show indications of malignancy) can be treated with a relatively non-invasive procedure, involving curettage of the lesion within the bone with placement of a bone graft. Fractures through the tumor (called a pathologic fracture) can be treated with either concurrent or staged treatment of both the fracture and the lesion if there is concern over the risk of recurrent pathologic fracture.

Surgical resection remains the primary and most successful means of treating chondrosarcomas. The decision regarding the extent of surgical resection and adjuvant therapy is dependent upon the clinical and histologic characteristics of the lesion. Optimal treatment for low-grade chondrosarcoma remains a dilemma for surgical oncologists, but no chemotherapy or radiation is indicated. For higher-grade tumors, with a worse prognosis for recurrence and metastasis, adjuvant therapies may be considered. Unfortunately, to date, studies have not shown adjuvant treatments such as chemotherapy or radiation to have any significant impact on patient morbidity or mortality in the majority of isolated primary lesions. Proton beam radiation is generally reserved for refractory tumors in high risk anatomic areas such as the skull base and axial skeleton. As these adjunctive modalities are of no proven benefit, the burden of a cure still falls upon adequate initial surgical resection.

Options in Addition to Surgery

Irradiation may be useful in younger patients or those with metastatic disease, where surgery would cause major unacceptable morbidity or be technically impossible (Krochak et al., 1983). This remains controversial. Cytotoxic chemotherapy is ineffective against traditional chondrosarcomas, but may have a role in the dedifferentiated subtype or in stage IV disease (Dickey et al., 2004). There are no established regiments for such cases.

For patients who have developed pulmonary metastatic disease, treatment in a clinical trial at a Sarcoma Center, or with conventional chemotherapy, if appropriate for the patient, may be indicated. ClinicalTrials.gov can be used to view clinical trials that are accepting chondrosarcoma patients.

In the past, wide resection was considered the method of choice for all chondrosarcomas. Unfortunately, these tumors are frequently found in regions such as the pelvis or proximal long bones, where aggressive surgical management may endanger adjacent vital organs and structures or compromise limb function. Thus, less aggressive approaches such as marginal excision and extended intralesional excision with margin expansion using adjuncts such as phenol or cryotherapy have received increasing attention with a national study underway to investigate efficacy. Most surgical oncologists prefer limb salvage techniques with bone graft and prosthetics, preserving the function of the limb. Amputation is still used in advanced disease or as a last option.

While rigorous evidence-based criteria are presently lacking, individual centers may have their own criteria and algorithms for surgical decision-making. In general, benign lesions should be treated conservatively, while high-grade malignancies should be treated aggressively with complete resection. If surgical margins are not clear on histologic evaluation of the tissue after resection of an intermediate- or high-grade lesion, wider surgical resection and possibly bone and/or joint prosthesis may be necessary.

Are there any emerging therapies in the treatment of chondrosarcoma?

During the past several years, substantial new insights have been gained about molecular cell biology, molecular cytogenetics, and immunopathology (Terek, 2006). These have led to a better understanding of chondrosarcoma development at the molecular level and will ultimately lead to the development of targeted treatments. Though they are at present highly experimental, researchers are investigating several new treatments for chondrosarcoma. Examples include agents targeting estrogen receptors (Cleton-Jansen et al., 2005), new chemotherapeutic agents, such as ET-743 (Marchini et al., 2005), and agents effecting cytogenetic pathways (Bovee et al., 2005).

Where is the best place to go to receive appropriate treatment?

Patients with chondrosarcoma are best treated at major Sarcoma Centers with specialized diagnostic and treatment facilities and the availability of musculoskeletal tumor specialists or orthopedic oncologists. Because this disease, like all bone sarcomas, are not common, it is often a good idea to seek an opinion from a major cancer center that has a wide experience in treating bone cancers. A Sarcoma Center will offer an organized group of doctors and other health care professionals who work together to provide the best treatment options and recovery. If your primary care physician suspects chondrosarcoma, a simple referral to an orthopedic doctor may not be adequate. Be sure that you are referred to an orthopaedic oncologist or "bone cancer specialist."

What are the chances for cure and survival from chondrosarcoma?

In general, the prognosis for chondrosarcoma depends on the grade of the tumor and the attainment of complete excision of the tumor and other conditions the patient has such as diabetes, lupus, and clotting and coagulation problems (Table 2). For lower grade chondrosarcomas, prognosis is very good after adequate excision. There is a low incidence of pulmonary metastasis if the primary lesion is widely resected. Metastasis to other bones can occur, but is much less common. Dedifferentiated chondrosarcoma have a uniformly poor prognosis.

Prognosis by Tumor Grade
Five-Year Survival Metastatic Potential Recurrence Rate
Grade I 90% 0% Low
Grade II 81% 10-15% Fair
Grade III 29% >50% High
Dedifferentiated <10% (1 year) Most High

Summary

Cartilaginous lesions of the human skeleton exist on a continuum spanning from the completely benign embryonic inclusion, to the dangerously aggressive neoplastic process. In order to determine the appropriate treatment for each individual lesion, musculoskeletal oncologists must take into account the clinical, radiographic, histologic and soon the microbiologic characteristics of the tumor. It is important for patients to seek treatment for these tumors at a Sarcoma center with availability of specialists possessing a sound understanding of these lesions and a firm grasp of the evolving treatment options. The health care team at these centers will keep patients informed about the details of the treatment course in both the short and long term. Understanding and recognizing the spectrum of appearances of the various types of chondrosarcoma allow improved patient assessment and are vital for optimal clinical management including diagnosis, biopsy, staging, treatment and prognosis. As more advanced molecular tools for predicting tumor behavior are developed, more sophisticated means of diagnosing and treating these tumors will be developed and put into use.

Last revision and medical review: 2/2006

By Peter J. Buecker, MD
Fellow, Orthopaedic Oncology
Harvard Combined Orthopaedic Surgery
Boston, MA

Mark Gebhardt, MD
Frederick W. and Jane M. Ilfield Professor of Orthopedic Surgery
Harvard Medical School
Children's Hospital, Boston
Chief of the Department of Orthopedic Surgery
Beth Israel Deaconess Medical Center

Kristy Weber, MD
Associate Professor, Department of Orthopaedic Surgery and Oncology
Chief, Division of Orthopaedic Oncology
Johns Hopkins University
Baltimore, MD

References and Related Articles

Aoki, J., Watanabe, H., Shinozaki, T., Tokunaga, M., Inoue, T. and Endo, K. (1999). FDG-PET in differential diagnosis and grading of chondrosarcomas. J Comput Assist Tomogr 23, 603-8.

Bertoni, F., Picci, P., Bacchini, P., Capanna, R., Innao, V., Bacci, G. and Campanacci, M. (1983). Mesenchymal chondrosarcoma of bone and soft tissues. Cancer 52, 533-41.

Bjornsson, J., McLeod, R. A., Unni, K. K., Ilstrup, D. M. and Pritchard, D. J. (1998). Primary chondrosarcoma of long bones and limb girdles. Cancer 83, 2105-19.

Bovee, J. V., Cleton-Jansen, A. M., Taminiau, A. H. and Hogendoorn, P. C. (2005). Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment. Lancet Oncol 6, 599-607.

Brenner, W., Conrad, E. U. and Eary, J. F. (2004). FDG PET imaging for grading and prediction of outcome in chondrosarcoma patients. Eur J Nucl Med Mol Imaging 31, 189-95.

Cleton-Jansen, A. M., van Beerendonk, H. M., Baelde, H. J., Bovee, J. V., Karperien, M. and Hogendoorn, P. C. (2005). Estrogen signaling is active in cartilaginous tumors: implications for antiestrogen therapy as treatment option of metastasized or irresectable chondrosarcoma. Clin Cancer Res 11, 8028-35.

Colyer, R., Sallay, P. and Buckwalter, K. (1993). MRI assessment of chondroid matrix tumors, in Limb Salvage: Current Trends. In Proceedings of the 7th International Symposium of Limb Salvage, pp. 89-93. Singapore.

Dickey, I. D., Rose, P. S., Fuchs, B., Wold, L. E., Okuno, S. H., Sim, F. H. and Scully, S. P. (2004). Dedifferentiated chondrosarcoma: the role of chemotherapy with updated outcomes. J Bone Joint Surg Am 86-A, 2412-8.

Donati, D., El Ghoneimy, A., Bertoni, F., Di Bella, C. and Mercuri, M. (2005). Surgical treatment and outcome of conventional pelvic chondrosarcoma. J Bone Joint Surg Br 87, 1527-30.

Enneking, W. (1983). Musculoskeletal Tumor Surgery. New York: Churchill Livingstone.

Evans, H. L., Ayala, A. G. and Romsdahl, M. M. (1977). Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer 40, 818-31.

Geirnaerdt, M. J., Hogendoorn, P. C., Bloem, J. L., Taminiau, A. H. and van der Woude, H. J. (2000). Cartilaginous tumors: fast contrast-enhanced MR imaging. Radiology 214, 539-46.

Krochak, R., Harwood, A. R., Cummings, B. J. and Quirt, I. C. (1983). Results of radical radiation for chondrosarcoma of bone. Radiother Oncol 1, 109-15.

Lee, F. Y., Mankin, H. J., Fondren, G., Gebhardt, M. C., Springfield, D. S., Rosenberg, A. E. and Jennings, L. C. (1999). Chondrosarcoma of bone: an assessment of outcome. J Bone Joint Surg Am 81, 326-38.

Mandahl, N., Gustafson, P., Mertens, F., Akerman, M., Baldetorp, B., Gisselsson, D., Knuutila, S., Bauer, H. C. and Larsson, O. (2002). Cytogenetic aberrations and their prognostic impact in chondrosarcoma. Genes Chromosomes Cancer 33, 188-200.

Marchini, S., Marrazzo, E., Bonomi, R., Chiorino, G., Zaffaroni, M., Weissbach, L., Hornicek, F. J., Broggini, M., Faircloth, G. T. and D'Incalci, M. (2005). Molecular characterisation of two human cancer cell lines selected in vitro for their chemotherapeutic drug resistance to ET-743. Eur J Cancer 41, 323-33.

Marco, R., Lane, J. and Huvos, A. (2000a). Intralesional excision of intramedullary low grade chondrosarcoma of the extremity. In 67th annual meeting of the American Academy of Orthopaedic Surgeons. Orlando, Fla: American Academy of Orthopaedic Surgeons.

Marco, R. A., Gitelis, S., Brebach, G. T. and Healey, J. H. (2000b). Cartilage tumors: evaluation and treatment. J Am Acad Orthop Surg 8, 292-304.

Marcove, R. C., Stovell, P. B., Huvos, A. G. and Bullough, P. G. (1977). The use of cryosurgery in the treatment of low and medium grade chondrosarcoma. A preliminary report. Clin Orthop Relat Res, 147-56.

Mirra, J. M., Gold, R., Downs, J. and Eckardt, J. J. (1985). A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases. Clin Orthop Relat Res, 214-37.

Murphey, M. D., Andrews, C. L., Flemming, D. J., Temple, H. T., Smith, W. S. and Smirniotopoulos, J. G. (1996). From the archives of the AFIP. Primary tumors of the spine: radiologic pathologic correlation. Radiographics 16, 1131-58.

Pritchard, D. J., Lunke, R. J., Taylor, W. F., Dahlin, D. C. and Medley, B. E. (1980). Chondrosarcoma: a clinicopathologic and statistical analysis. Cancer 45, 149-57.

Reith, J. D., Horodyski, M. B. and Scarborough, M. T. (2003). Grade 2 chondrosarcoma: stage I or stage II tumor? Clin Orthop Relat Res, 45-51.

Sandberg, A. A. and Bridge, J. A. (2003). Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: chondrosarcoma and other cartilaginous neoplasms. Cancer Genet Cytogenet 143, 1-31.

Sandberg, A. A. (2004). Genetics of chondrosarcoma and related tumors. Curr Opin Oncol 16, 342-54.

Sawyer, J. R., Swanson, C. M., Lukacs, J. L., Nicholas, R. W., North, P. E. and Thomas, J. R. (1998). Evidence of an association between 6q13-21 chromosome aberrations and locally aggressive behavior in patients with cartilage tumors. Cancer 82, 474-83.

Schiller, A. L. (1985). Diagnosis of borderline cartilage lesions of bone. Semin Diagn Pathol 2, 42-62.

Springfield, D. S., Gebhardt, M. C. and McGuire, M. H. (1996). Chondrosarcoma: a review. Instr Course Lect 45, 417-24.

Terek, R. M. (2006). Recent advances in the basic science of chondrosarcoma. Orthop Clin North Am 37, 9-14.

Unni, K. K. (1996). Dahlin's Bone Tumors: General Aspects and Data on 11,087 Cases. Philadelphia: Lippincott-Raven.

Vakar-López, F., Ito, S., Zhang, R. D. and al., e. (2001). Molecular mechanisms of chromosomal instability and aneuploidy in chondrosarcoma of bone and their clinical significance. Mod Pathol 14, 18A.

Wang, X. L., De Beuckeleer, L. H., De Schepper, A. M. and Van Marck, E. (2001). Low-grade chondrosarcoma vs enchondroma: challenges in diagnosis and management. Eur Radiol 11, 1054-7.

 

Print it

Management in Low-Grade Chondrosarcoma

A Note from Dr. Letson, Coordinating Editor: One of the most controversial subjects in musculoskeletal tumor surgery is how to manage low-grade chondrosarcomas. It is the grading of this disease that makes it so challenging, and the final diagnosis is dependent on clinical, radiologic and pathologic findings. These concepts have been well-presented here in this extended Op Ed piece by Drs. Novais and Randall.

What is Chondrosarcoma?

Chondrosarcoma is a malignant cancer whose tumor cells produce a pure hyaline cartilage that results in abnormal bone and/or cartilage growth. The term chondrosarcoma is used to define a heterogeneous group of lesions with diverse morphologic features and clinical behavior.

Who gets chondrosarcoma? Is it common?

Chondrosarcoma is a rare disease, with an estimated incidence of 1 in 200,000 per year.1 Classically, chondrosarcomas have been described with a slight preference for male patients.4 However in a recent analysis of the SEER Database (Surveillance, Epidemiology and End Results) a higher proportion of appendicular chondrosarcomas was found in women (60.9%) than in men (46.7%) and a lower proportion of axial chondrosarcomas was found in women (30.3%) than in men (40.4%). The age distribution of patients with chondrosarcoma shows a gradual age-related increase, with the peak incidence occurring during the sixth and seventh decades of life. In an analysis of the National Cancer Data Base (NCDB) of the American College of Surgeons over 70% of reported cases were in patients aged 40 years and older.

Chondrosarcoma is not contagious. It cannot be passed on to another person by exposure to a chondrosarcoma patient. Although specialists are not yet certain what causes chondrosarcoma, there are several factors that put people at a higher risk.

Certain hereditary conditions may make people more susceptible to chondrosarcomas. These include Ollier's Disease, Maffucci Syndrome, and Multiple Hereditary Exostoses (MHE, a.k.a., osteochondromatoses), People affected by these conditions are at a higher risk because they usually develop several benign bone tumors (sometimes called bone spurs in the case of MHE), which have a higher chance of becoming malignant. People with these hereditary conditions who experience sudden growth spurts or increases in hormone production, such as pregnancy, have a slight increased risk of a benign bone tumor changing into a chondrosarcoma. These patients should be followed by a bone tumor specialist for all of their lives. However, most patients with chondrosarcoma do not have any of these genetic conditions. Adults with Paget's disease, a non-cancerous condition characterized by abnormal development of new bone cells, may be at increased risk for chondrosarcoma. When chondrosarcoma occurs in children and young adults, it is often in patients who have had radiation or chemotherapy treatments for other conditions.

What are the different types of chondrosarcoma?

Chondrosarcomas are actually a heterogeneous group of tumors. They are classified as primary (or conventional chondrosarcoma) if they are unassociated with a pre-existing lesion and secondary if they develop from a pre-existing chondroid lesion, such as enchondroma or osteochondroma. More than 90% are designated conventional chondrosarcomas. They can be further sub classified as central when they arise from within the medullary cavity and peripheral when they arise from the surface of the bone. Conventional chondrosarcoma are nearly always central; secondary chondrosarcomas can be central but usually they are peripheral. They can also be classified by their location within the body (i.e., axial skeleton versus appendicular skeleton), whether it fits into a specific histological variant (i.e., clear cell, myxoid, mesenchymal, dedifferentiated).

The single most important factor to consider when evaluating the malignant potential of a chondrosarcoma is its cytologic and histologic grade, determined by the appearance of tumor material under the microscope combined with the clinical and radiologic presentation (Table 1).5-10

Table 1: Chondrosarcoma Tumors
Grade Tumor Symptoms Prognosis Treatment
Benign Enchondroma Usually no symptoms Excellent Surveillance, intralesional excision if symptomatic
Malignant (Low Grade) Grade I Chondrosarcoma 60% are painful Good Controversial: Extended intralesional excision vs. rarely wide resection
Malignant (Intermediate Grade) Grade II Chondrosarcoma Up to 80% are painful Fair Wide resection
Malignant (High Grade) Grade III Chondrosarcoma Up to 80% are painful Poor Wide resection. Chemotherapy and radiation therapy in select cases
Malignant (High Grade) Dedifferentiated Chondrosarcoma Most are painful Poor Wide resection. Chemotherapy and radiation therapy in select cases
Malignant (High Grade) Mesenchymal Chondrosarcoma Pain and swelling Poor Wide resection. Chemotherapy and radiation therapy in select cases

While grading is very important in the management of chondrosarcoma, it can be contentious. Although several grading systems have been described, usually they are graded on a scale of 1-3. The grading is based primarily on nuclear size of tumor cells, nuclear staining (hyperchromasia, or darker staining of nuclear material) and cellularity.11 Approximately 90% are low grade to intermediate-grade tumors (grade 1 or 2) and only 5–10% of conventional chondrosarcomas are grade 3 lesions.

  • Grade I (low grade) tumors are moderately cellular and contain hyperchhromatic plump nuclei of uniform size and the cytology is very similar to enchondroma (a benign cartilage tumor). Occasionally binucleated cells may be seen.
  • Grade II (intermediate grade) are more cellular with a greater degree of nuclear atypia, hyperchromasia and nuclear size.
  • Grade III (high grade) tumors have significant areas of marked pleomorphism, large cells with more hyperchromatic nuclei than grade II, occasional giant cells and abundant necrosis. Mitoses are frequently detected.

Chondrosarcomas variants are rare and include the following:

  • Mesenchymal chondrosarcoma is a highly malignant tumor characterized by the presence of solid, highly cellular areas composed of round or slightly spindled primitive mesenchymal cells and is histologically similar to Ewing's sarcoma with foci of cartilaginous differentiation. This is a very aggressive type of chondrosarcoma with a high risk of local recurrence and distant metastasis.
  • Dedifferentiated chondrosarcoma contains two clearly defined components, a well differentiated cartilage tumor, either an enchondroma or a low grade chondrosarcoma, juxtaposed to a high grade noncartilaginous sarcoma. It is typically thought of as a tumor in which a low grade chondrosarcoma or benign cartilage tumor transforms into a high grade sarcoma with features of osteosarcoma, fibrosarcoma, or malignant fibrous histiocytoma. Radiographically the tumor produces an ill defined, lytic, interosseous lesion associated with cortical disruption and extension into the soft tissues. They are aggressive neoplasms and have a dismal prognosis.
  • Clear cell chondrosarcomas are low-grade tumors with significant amounts of glycogen. They typically involve the epiphyseal end of a long bone. Histologically, cells have abundant clear cytoplasm embedded in a loose hyaline cartilaginous matrix and an infiltrative growth pattern. Radiographs show a lytic defect at epiphyseal end of long bones that is sharply demarcated with sclerotic margins. They carry a low recurrence rate and a good prognosis with wide resection.
  • Myxoid chondrosarcoma is a slow-growing tumor characterized by prominent myxoid degeneration histologically and prolonged course, despite a high incidence of local recurrence and metastasis clinically.

What is known about the genetics of chondrosarcoma?

As evolving molecular techniques are available, several genotypic and phenotypic markers for chondrosarcoma have been tested to see if they assist in determining tumor grade prognosis. There is considerable complexity and heterogeneity in the pathologic and clinical behavior of chondrosarcomas. This is reflected in the diversity of cytogenetic and molecular genetic characteristics that have been described in these tumors. Please see Sandberg and Bridge (2003),12 Sandberg (2004), and Bovee et al. (2005)13 for a thorough review.

The genetic changes specific to chondrosarcoma continue to be investigated extensively. Although studies have not yet established a specific or recurrent karyotypic feature for any of these tumors, different chondrosarcomas have demonstrated anomalies in several tumor suppressor genes, oncogenes, and transcription factors, including TP53, RAS, EXT1, EXT2, and Sox9. Available cytogenetic and comparative genomic hybridization (CGH) studies reveal changes in some chondrosarcomas, but fail to do so in others. These studies are thus far difficult to interpret.

Based on the available studies, it is likely that chondrosarcomas are generated by a coordinated, multi-step process involving primarily tumor suppressor genes. In fact, the complexity and variety of genetic changes seen in chondrosarcomas may indicate several distinct genetic pathways. Some of the same genes may be involved in each, but the order and manner in which they are affected may differ among chondrosarcomas. Establishing the genes that initiate the neoplastic processes, and that are subsequently involved along the pathways leading to chondrosarcoma may lead to therapies addressing these molecular changes, as has been accomplished for several other sarcomas.

How can one differentiate a low grade chondrosarcoma from a benign cartilage tumor?

It is important to understand the difference between a benign and malignant cartilage tumor. Chondrosarcoma is a sarcoma, or malignant tumor of connective tissue. An enchondroma is a benign bone tumor. Benign bone tumors are not sarcomas. Benign bone tumors do not spread to other tissues and organs, and are not life threatening. They are generally left alone or cured by surgical removal if they cause symptoms such as tenderness via pressure on surrounding muscles, tendons or nerves. Low grade chondrosarcoma also has relatively little potential to spread but can recur locally if not treated appropriately. If these tumors due recur they can start to behave more aggressively.

Distinguishing chondrosarcoma from its benign counterpart, enchondroma, is crucial to the patient treatment and prognosis but can be difficult at times. The diagnosis of cartilage lesions requires expert evaluation. First, clinical and radiographic features such as the age of the patient, symptoms, localization in the skeleton, and the pattern of bone destruction or mineralization should be scrutinized. The role of biopsy in low grade lesions is quite contentious as sampling errors are a distinct possibility. A wait and see approach is generally recommended at first. If symptoms worsen or there is a progression on radiographic examination then consideration for intralesional surgical treatment may be indicated. Because of the possibility that the tumor is a low grade chondrosarcoma, it should be removed by an experienced musculoskeletal oncologist at a designated sarcoma center with expert pathology and radiology support. The removed specimen must be thoroughly evaluated for features concerning for malignancy.14,15 Distinguishing between enchondroma and chondrosarcoma is one of the most frequent diagnostic dilemmas facing orthopaedic oncologists and their colleagues in diagnostic radiology and pathology.16

Clinical Presentation

Patients with chondrosarcoma experience a wide range of clinical courses, from slow insidious tumor growth over years in low grade lesions to rapid neoplastic progression, metastasis, and death in higher grade lesions. The vast majority of chondrosarcomas is low grade and accordingly is very slow to progress. Clinical symptoms may be helpful in the initial evaluation of a cartilaginous tumor. Pain is more common with chondrosarcoma than with the benign enchondroma. In a review from Murphey et al 95% of patients with chondrosarcoma experienced pain.17 Eefting et al reported that 35% of patients with enchondromas and 62% of the patients with central grade I chondrosarcoma presented with spontaneous pain. It has been reported that in patients with grade I chondrosarcoma, 60% have night pain or rest pain, 21% have vague regional pain, and only 19% have painless tumors.18 This difference is significant, although presentation without pain does not exclude malignancy and should not delay additional analysis.19 Pathologic fractures occur in 3% to 8% of patients with chondrosarcoma.18

Figure 1: Chondrosarcoma X-ray

Figure 1: Radiograph

Imaging

Radiographs - Enchondromas and low grade intramedullary chondrosarcomas of long bones can have similar radiologic appearances. Both types of tumors demonstrate stippled calcifications, and both may display endosteal scalloping on plain radiographs.20 Calcification is manifested by punctuate mineralization or popcorn like calcification (Figure 1).

The margins of the tumor should be examined for osteolysis and endosteal scalloping. Chondrosarcoma can demonstrate adaptive and aggressive radiologic signs. Cortical expansion and thickening are adaptive changes, and cortical disruption and soft-tissue masses are aggressive changes associated with chondrosarcoma. The extent and degree of endosteal scalloping correlate with the likelihood of the lesion being a chondrosarcoma. The imaging characteristics that should suggest chondrosarcoma are endosteal scalloping depth and extent (greater than two-thirds of cortical thickness and along more than two thirds of the lesion), extent of matrix mineralization (within less than two-thirds of the lesion as seen on radiographs), presence of cortical remodeling or destruction and thickening, periosteal reaction, pathologic fracture, and associated soft-tissue mass.17 There is an overlap in the radiographic size of both, however a lesion larger than 5-6 cm in diameter are much more likely to represent a chondrosarcoma.

Anatomic tumor localization is different but should not be considered of diagnostic value. Enchondromas are most common in the hands or feet while chondrosarcomas are common in the axial skeleton (spine and pelvis), typically with large associated soft-tissue masses. The ilium is the most frequently involved bone followed by the proximal femur, proximal humerus, distal femur and ribs.

Advanced Imaging

Computed Tomography (CT) – CT is helpful in detecting more details of the lesion. Enchondromas as a rule should not progress during adulthood and any change in size or radiographic appearance of an enchondroma should be considered as a red flag for the presence of a malignant tumor. CT is superior to radiography for detecting focal areas of scalloping and is considered the best modality to detect mineralization characteristic of a chondroid neoplasm. Murphey et al reported that all enchondromas showed evidence of calcification on CT scans but only 95% revealed these areas on radiographs.17

Figure 2: Chondrosarcoma on MRI

Figure 2: MRI

Magnetic Resonance Imaging (MRI) – MRI is particularly useful in determining the nonmineralized intramedullary extent of the tumor and soft-tissue extension (Figure 2).

The axial and coronal images accurately demonstrate marrow replacement by tumor, providing measurements that can guide the surgeon when either an intralesional or a wide excision is performed. Greater than 90% medullary involvement can be suggestive of chondrosarcoma, while the absence of 90% medullary involvement of non-contiguous areas of cartilage within the bone can suggest the presence of an enchondroma. The relationship of a soft-tissue mass to important paraosseous structures, such as the joint capsule and the neurovascular bundle, is accurately demonstrated on MR images. Fast contrast-enhanced MR imaging has the potential to help differentiation between enchondroma and chondrosarcoma. MR imaging results should be seen as an additive tool and may not be considered alone. The use of gadolinium-enhanced MR imaging adds substantially to the characterization of cartilaginous tumors. The timing and progression of gadolinium contrast enhancement patterns may help direct a clinician toward or away from a diagnosis of malignancy. Early enhancement (within 10 seconds of arterial enhancement) may be seen in chondrosarcoma but not in enchondroma. Differentiation of malignancy on the basis of early and exponential enhancement has been demonstrated to have a sensitivity of 61%, specificity of 95%, positive predictive value of 92% and negative predictive value of 72%.21 Gadolinium-enhanced MR imaging shows septal enhancement in low-grade chondrosarcomas, corresponding to fibrovascular septation between lobules of hyaline cartilage. This feature is usually absent in benign cartilaginous lesions.22,23

Figure 3: Bone Scan

Figure 3: Bone Scan

Bone Scan - This test works by injecting a small amount of radioactive material into the blood stream and taking images using a gamma camera to detect uptake of radioactive material. Bone scintigraphy has limited application in the differential diagnosis of tumors with low biologic activity such as Grade-I chondrosarcoma. A whole-body bone scan with a high degree of radionuclide uptake within the lesion compared with an internal standard, such as the anterior superior iliac spine or acromioclavicular joint, has been considered as more consistent with chondrosarcoma than enchondroma17 (Figure 3). Great caution should therefore be used in drawing conclusions from bone scan results, but these results can add to the overall picture, and better inform the decision making process.

PET Scan - Recently, there has been some research into the use of a specialized radiographic test called fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) for grading of tumors in patients with chondrosarcoma Preliminary studies showed that (FDG PET) could be an objective and quantitative adjunct in differentiating chondrosarcomas from enchondromas and osteochondromas and in assessing the grade of chondrosarcomas.24 In a more recent study FDG PET imaging was found a useful parameter for tumor grading and prediction of outcome in chondrosarcoma patients.25 However, the measurement of glucose metabolism by positron emission tomography alone cannot distinguish between benign and grade-I malignant cartilaginous tumors. It is important to understand the advantages and disadvantages of imaging modalities for accurate interpretation of results. Although positron emission tomography has limitations, it may be useful for predicting high-grade chondrosarcomas from benign chondroid lesions and grade-I chondrosarcoma.26

What if a low grade chondrosarcoma is suspected?

After all of the imaging modalities are obtained an experienced orthopaedic oncologist must decide whether to observe the patient or intervene. If a low grade chondrosarcoma is suspected, then an aggressive curettage is indicated. When a more aggressive lesion is suspected a sampling biopsy is indicated as surgical excision is more extensive and so the diagnosis of a high grade cancer should be established. When fresh tissue from a chondrosarcomas is viewed under a microscope after a biopsy, lower grade chondrosarcomas will exhibit increasing amounts of relatively acellular cartilage stroma as well as regions of modestly increased cellularity. By contrast, higher-grade lesions tend to harbor regions of densely packed hyperchromatic malignant looking cells.

Histologic features to distinguish benign from malignant cartilaginous tumors were advocated in the past although the diagnostic value of individual morphologic criteria or how they are handled in clinical practice is controversial.27 Recent studies have tried to establish a more precise standard method for distinction of cartilage neoplasms in long bones. The American Skeletal Lesions Interobserver Correlation among Expert Diagnosticians (SLICED) Study Group showed that radiologic and pathologic interpretations of cartilaginous lesions in long bones are not optimally reliable, even among specialized experts.28 Another recent study reported that distinction between a high grade chondrosarcoma seems to be less problematic, however differentiation of grade I chondrosarcoma from enchondroma remains a diagnostic challenge. In that study there was considerable interobserver variability, even among expert bone tumor pathologists, in the histologic diagnosis of enchondroma and low-grade chondrosarcoma. In an attempt to distinguish between low-grade chondrosarcoma and enchondroma the authors identified four most important histologic parameters, as following: host bone entrapment, high cellularity, marked nuclear pleomorphism, and irregular distribution of cells. The differential diagnosis could be assessed with a higher great degree of accuracy if the biopsy specimen contained a combination of: presence of host bone entrapment, open chromatin, mucoid matrix degeneration, and the patient’s age was above 45 years.19

What are the current options of treatment for low grade chondrosarcoma?

The management of low grade chondrosarcoma can be a challenge. Grade I chondrosarcomas may not all behave in the same way clinically or radiographically. In some cases a painful cartilaginous lesion in a long bone has the radiologic appearance of a low-grade chondrosarcoma (e.g., lytic areas or high-grade endosteal scalloping without adaptive or aggressive radiographic changes) and the histologic appearance of an enchondroma. This borderline type of lesion has been referred as grade 0.5 chondrosarcomaatypical enchondromagrade 0 chondrosarcoma and chondrosarcoma in situ by different authors.9,13,18 The decision making process about the management of these lesions should involve the following considerations:

  • Intralesional excision grossly removes the tumor but conceivably leaves microscopic and macroscopic tumor in the tumor bed. Intralesional excision with some sort of adjuvant therapy (e.g. liquid nitrogen, argon beam, hydrogen peroxide, phenol) has the potential benefits of adjacent bone and joint preservation and better functional outcome.
  • Wide resection includes a cuff of normal tissue surrounding the tumor completely. Depending on the location, wide resection may cause increased morbidity and require complex reconstruction. Generally, this is reserved for higher grade lesions.

The key for long term successful treatment of these lesions is to adequately identify those patients who would benefit from less aggressive surgical resection without the risks of local recurrence and distant metastasis.

The local recurrence rate and potential for metastasis in low-grade chondrosarcoma are low, so limited surgery (intralesional resection) with adjuvant therapy has been advocated for less aggressive-appearing lesions.5,7,8,14,18 Leerapun et al14 recently report that intralesional excision with adjuvant therapy only works well in confined bony defects. In their series, tumors that had no associated cortical perforation or soft tissue mass were successfully treated with intralesional curettage. Patients with more aggressive lesions (eg, cortical disruption, Stage IB) were selected for en bloc resection and had excellent local control. They excluded lesions of the central skeleton because these historically behave differently from long bone lesions. Marco et al described a subset of patients with low-grade chondrosarcoma that could be treated with intralesional excision with adjuvant therapy without compromise of the oncologic outcome: painful, intramedullary low-grade chondrosarcoma (stage IA) of the appendicular skeleton, which can demonstrate a high degree of endosteal scalloping without adaptive or aggressive radiologic signs. The only local recurrence in their series was in a patient with cortical disruption and expansion, as well as a soft tissue mass. Bauer5 reported on patients with low-grade intramedullary chondrosarcoma of a long bone treated by intralesional excision and followed for 2-25 years. The authors concluded that a central grade I chondrosarcoma of long bones can be treated with curettage and filling with either bone graft or bone cement (methylmethacrylate) but distal more radiographic aggressive lesions requires en bloc resection. Lesions of the pelvis and shoulder girdle should also be treated aggressively since they have a high risk of recurrence. In another recent study Van Der Geest et al29 reported excellent oncological and functional results the use of cryosurgery as an adjuvant in the surgical treatment of active or aggressive enchondromas and chondrosarcomas grade I. Post-operative fracture was seen as the most common complication in their series.

Most authors agree that adequate surgical margins lower the risk of local recurrence in patients with chondrosarcoma.7,8,14,18,30 Wide resection should be implemented for the treatment of low grade chondrosarcoma in a long bone if it shows radiographic signs of adaptive changes (cortical expansion or thickening) or aggressive changes (cortical disruption, stage IB) and if its associated with a soft tissue mass. Wide resection is recommended for virtually all low grade chondrosarcomas of the pelvis and sacrum because in these locations there is a higher chance of local recurrence and metastasis.14,31,32

Is there a need to further treatment of low grade chondrosarcoma by radiation or chemotherapy?

For higher-grade tumors, with a worse prognosis for recurrence and metastasis, adjuvant therapies may be considered. Adjuvant radiation and chemotherapy have been reserved for patients who have a mesenchymal chondrosarcoma or a dedifferentiated chondrosarcoma or for those who have had inadequate operative treatment. Unfortunately, to date, studies have not shown adjuvant treatments such as chemotherapy or radiation to have any significant impact on patient morbidity or mortality in the majority of isolated primary lesions. Proton beam radiation is generally reserved for refractory tumors in high risk anatomic areas such as the skull base and axial skeleton.33

There is no indication for the use of chemotherapy or radiation in the management of low grade chondrosarcoma as adequate initial surgical resection can virtually be successful in all patients.

Clinical Trials and Emerging Therapies

Earlier this decade, a national clinical trial was opened in the United States. However, due to the National Cancer Institute’s budgetary constraints and the relative rarity of chondrosarcoma compared to other cancers, the trial had to be closed prematurely. Investigators hope that the trial can be reinitiated soon.

During the past several years, substantial new insights have been gained about molecular cell biology, molecular cytogenetics, and immunopathology.34 These have led to a better understanding of chondrosarcoma development at the molecular level and will ultimately lead to the development of targeted treatments. Though they are at present highly experimental, researchers are investigating several new treatments for chondrosarcoma. Examples include agents targeting estrogen receptors,35 new chemotherapeutic agents, such as ET-743,36 and agents effecting cytogenetic pathways.13

Where is the best place to go to receive appropriate treatment?

Patients with chondrosarcoma are best treated at major Sarcoma centers with specialized diagnostic and treatment facilities and the availability of Musculoskeletal Tumor Specialists or Orthopedic Oncologists. Because this, like many other bone cancers, are not common, it is often a good idea to seek an opinion from a major cancer center that has a wide experience in treating bone cancers. A major sarcoma center will offer an organized group of doctors and other health care professionals who work together to provide the best treatment options and recovery. If your primary care physician suspects chondrosarcoma, a simple referral to an orthopedic doctor may not be adequate. Be sure that you are referred to an orthopaedic oncologist or "bone cancer specialist." Ideally, the center should be a member of The National Comprehensive Cancer Network.

What are the chances for cure and survival from low grade chondrosarcoma?

In general, the prognosis for chondrosarcoma depends on the grade of the tumor and the attainment of complete excision of the tumor and other conditions the patient has such as diabetes, lupus, and clotting and coagulation problems. Table 2 below shows a comparison between the prognosis based on the tumor grade. Pathological fracture, metastasis, local recurrence, and death are usually more common in patients with a high grade chondrosarcoma.

For low grade chondrosarcomas, prognosis is excellent after adequate excision, with very low rates of recurrence or spread when treated at an established sarcoma center. In a review of 70 patients with low grade chondrosarcoma of the appendicular skeleton only three presented with metastasis.14

Table 2: Prognosis by Tumor Grade
Grade Five-Year Survival Metastatic Potential Recurrence Rate
Grade I 90% 0% Low
Grade II 81% 10-15% Fair
Grade III 29% >50% High
Dedifferentiated <10% (1 year) Most High

Summary

Cartilaginous lesions of the human skeleton exist on a continuum, spanning from the completely benign embryonic inclusion, to the far less common but dangerously aggressive neoplastic process. Differentiating a benign enchondroma lesion from a low grade (grade I) chondrosarcoma is a challenging task even for the more experienced team of Sarcoma specialists. Based upon imaging characteristics, for less aggressive lesions, a wait and watch approach is the best initial management. At follow-up, if there appears to be progression, intervention should be considered.

The majority of patients with less radiographically aggressive low grade chondrosarcoma may be safely treated with a limited surgical interventional (intralesional resection). Patients with any signs of a radiographically aggressive lesion should be treated with a staged biopsy and a more extensive wide resection surgery to keep the local recurrence rate and potential for metastases low. In order to determine the appropriate treatment for each individual lesion, musculoskeletal oncologists must take into account the clinical, radiographic, histologic and soon the molecular biologic characteristics of the tumor.

It is important for patients to seek treatment for these tumors at a recognized sarcoma center with availability of specialists possessing a sound understanding of these lesions and a firm grasp of the evolving treatment options. The health care team at these centers will keep patients informed about the details of the treatment course in both the short and long term. Understanding and recognizing the spectrum of appearances of the various types of chondrosarcoma allow improved patient assessment and are vital for optimal clinical management including diagnosis, biopsy, staging, treatment and prognosis.

Last revised: 6/2009
This article is an editorial and has not been peer-reviewed.

by Eduardo Novais, MD
Instructor
Department of Orthopaedics
University of Utah

R. Lor Randall, MD, FACS
The L.B. and Olive S. Young Endowed Professor for Cancer Research
Director, Sarcoma Services & Chief, SARC Lab
Huntsman Cancer Institute & Primary Children’s Medical Center
University of Utah

References

1. Giuffrida AY, Burgueno JE, Koniaris LG, Gutierrez JC, Duncan R, Scully SP. Chondrosarcoma in the United States (1973 to 2003): an analysis of 2890 cases from the SEER database. J Bone Joint Surg Am. 2009 May;91(5):1063-72.

2. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, et al. Cancer statistics, 2006. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30.

3. Unni KK. Bone Tumors: general aspects and data on 11,087 cases. Dahlin’s Bone Tumors: General Aspects and Data on 11,087 Cases. Philadelphia: Lippincott-Raven; 1996. p. 71-2.

4. Damron TA, Ward WG, Stewart A. Osteosarcoma, chondrosarcoma, and Ewing's sarcoma: National Cancer Data Base Report. Clin Orthop Relat Res. 2007 Jun;459:40-7.

5. Bauer HC, Brosjo O, Kreicbergs A, Lindholm J. Low risk of recurrence of enchondroma and low-grade chondrosarcoma in extremities. 80 patients followed for 2-25 years. Acta Orthop Scand. 1995 Jun;66(3):283-8.

6. Donati D, Yin JQ, Colangeli M, Colangeli S, Bella CD, Bacchini P, et al. Clear cell chondrosarcoma of bone: long time follow-up of 18 cases. Arch Orthop Trauma Surg. 2008 Feb;128(2):137-42.

7. Lee FY, Mankin HJ, Fondren G, Gebhardt MC, Springfield DS, Rosenberg AE, et al. Chondrosarcoma of bone: an assessment of outcome. J Bone Joint Surg Am. 1999 Mar;81(3):326-38.

8. Marcove RC, Mike V, Hutter RV, Huvos AG, Shoji H, Miller TR, et al. Chondrosarcoma of the pelvis and upper end of the femur. An analysis of factors influencing survival time in one hundred and thirteen cases. J Bone Joint Surg Am. 1972 Apr;54(3):561-72.

9. Rizzo M, Ghert MA, Harrelson JM, Scully SP. Chondrosarcoma of bone: analysis of 108 cases and evaluation for predictors of outcome. Clin Orthop Relat Res. 2001 Oct(391):224-33.

10. Wang JW, Ger LP, Shih CH, Hsieh MC. Chondrosarcoma of bone: a statistical analysis of prognostic factors. J Formos Med Assoc. 1991 Oct;90(10):998-1003.

11. Evans HL, Ayala AG, Romsdahl MM. Prognostic factors in chondrosarcoma of bone: a clinicopathologic analysis with emphasis on histologic grading. Cancer. 1977 Aug;40(2):818-31.

12. Sandberg AA, Bridge JA. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: chondrosarcoma and other cartilaginous neoplasms. Cancer Genet Cytogenet. 2003 May;143(1):1-31.

13. Bovee JV, Cleton-Jansen AM, Taminiau AH, Hogendoorn PC. Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment. Lancet Oncol. 2005 Aug;6(8):599-607.

14. Leerapun T, Hugate RR, Inwards CY, Scully SP, Sim FH. Surgical management of conventional grade I chondrosarcoma of long bones. Clin Orthop Relat Res. 2007 Oct;463:166-72.

15. Veth R, Schreuder B, van Beem H, Pruszczynski M, de Rooy J. Cryosurgery in aggressive, benign, and low-grade malignant bone tumours. Lancet Oncol. 2005 Jan;6(1):25-34.

16. Dahlin DC, Henderson ED. Chondrosarcoma, a surgical and pathological problem; review of 212 cases. J Bone Joint Surg Am. 1956 Oct;38-A(5):1025-38; passim.

17. Murphey MD, Flemming DJ, Boyea SR, Bojescul JA, Sweet DE, Temple HT. Enchondroma versus chondrosarcoma in the appendicular skeleton: differentiating features. Radiographics. 1998 Sep-Oct;18(5):1213-37; quiz 44-5.

18. Marco RA, Gitelis S, Brebach GT, Healey JH. Cartilage tumors: evaluation and treatment. J Am Acad Orthop Surg. 2000 Sep-Oct;8(5):292-304.

19. Eefting D, Schrage YM, Geirnaerdt MJ, Le Cessie S, Taminiau AH, Bovee JV, et al. Assessment of interobserver variability and histologic parameters to improve reliability in classification and grading of central cartilaginous tumors. Am J Surg Pathol. 2009 Jan;33(1):50-7.

20. Rosenthal DI, Schiller AL, Mankin HJ. Chondrosarcoma: correlation of radiological and histological grade. Radiology. 1984 Jan;150(1):21-6.

21. Geirnaerdt MJ, Hogendoorn PC, Bloem JL, Taminiau AH, van der Woude HJ. Cartilaginous tumors: fast contrast-enhanced MR imaging. Radiology. 2000 Feb;214(2):539-46.

22. Geirnaerdt MJ, Bloem JL, Eulderink F, Hogendoorn PC, Taminiau AH. Cartilaginous tumors: correlation of gadolinium-enhanced MR imaging and histopathologic findings. Radiology. 1993 Mar;186(3):813-7.

23. Geirnaerdt MJ, Hermans J, Bloem JL, Kroon HM, Pope TL, Taminiau AH, et al. Usefulness of radiography in differentiating enchondroma from central grade 1 chondrosarcoma. AJR Am J Roentgenol. 1997 Oct;169(4):1097-104.

24. Aoki J, Watanabe H, Shinozaki T, Tokunaga M, Inoue T, Endo K. FDG-PET in differential diagnosis and grading of chondrosarcomas. J Comput Assist Tomogr. 1999 Jul-Aug;23(4):603-8.

25. Brenner W, Conrad EU, Eary JF. FDG PET imaging for grading and prediction of outcome in chondrosarcoma patients. Eur J Nucl Med Mol Imaging. 2004 Feb;31(2):189-95.

26. Lee FY, Yu J, Chang SS, Fawwaz R, Parisien MV. Diagnostic value and limitations of fluorine-18 fluorodeoxyglucose positron emission tomography for cartilaginous tumors of bone. J Bone Joint Surg Am. 2004 Dec;86-A(12):2677-85.

27. Mirra JM, Gold R, Downs J, Eckardt JJ. A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases. Clin Orthop Relat Res. 1985 Dec(201):214-37.

28. Group SLICaEDS. Reliability of histopathologic and radiologic grading of cartilaginous neoplasms in long bones. J Bone Joint Surg Am. 2007 Oct;89(10):2113-23.

29. van der Geest IC, de Valk MH, de Rooy JW, Pruszczynski M, Veth RP, Schreuder HW. Oncological and functional results of cryosurgical therapy of enchondromas and chondrosarcomas grade 1. J Surg Oncol. 2008 Nov 1;98(6):421-6.

30. Gitelis S, Bertoni F, Picci P, Campanacci M. Chondrosarcoma of bone. The experience at the Istituto Ortopedico Rizzoli. J Bone Joint Surg Am. 1981 Oct;63(8):1248-57.

31. Ozaki T, Hillmann A, Lindner N, Blasius S, Winkelmann W. Chondrosarcoma of the pelvis. Clin Orthop Relat Res. 1997 Apr(337):226-39.

32. Pring ME, Weber KL, Unni KK, Sim FH. Chondrosarcoma of the pelvis. A review of sixty-four cases. J Bone Joint Surg Am. 2001 Nov;83-A(11):1630-42.

33. Tzortzidis F, Elahi F, Wright DC, Temkin N, Natarajan SK, Sekhar LN. Patient outcome at long-term follow-up after aggressive microsurgical resection of cranial base chondrosarcomas. Neurosurgery. 2006 Jun;58(6):1090-8; discussion -8.

34. Terek RM. Recent advances in the basic science of chondrosarcoma. Orthop Clin North Am. 2006 Jan;37(1):9-14.

35. Cleton-Jansen AM, van Beerendonk HM, Baelde HJ, Bovee JV, Karperien M, Hogendoorn PC. Estrogen signaling is active in cartilaginous tumors: implications for antiestrogen therapy as treatment option of metastasized or irresectable chondrosarcoma. Clin Cancer Res. 2005 Nov 15;11(22):8028-35.

36. Marchini S, Marrazzo E, Bonomi R, Chiorino G, Zaffaroni M, Weissbach L, et al. Molecular characterisation of two human cancer cell lines selected in vitro for their chemotherapeutic drug resistance to ET-743. Eur J Cancer. 2005 Jan;41(2):323-33.

Chondrosarcoma Stories and Support

Sara, a chondrosarcoma survivor, with her little girl

Sara's story

In April 2005, after finishing up an 8th month yoga teacher training program, I saw an orthopedic doctor about a lump on my outer left thigh that had started to cause pain above my knee. The doctor told me I had a tumor and needed to see a specialist in orthopedic oncology. A few weeks later I had scans and an open biopsy at Memorial Sloan Kettering. I had a very large (23cm) low-grade chondrosarcoma that took up ¾ of my femur. The tumor had also bowed my femur. Dr. Morris said my case was unusual and she took it in front of the tumor board at MSKCC. She reported that there were as many opinions on the best course of treatment as there were doctors in the room. Eventually I was given a list of seven options for surgery, and the choice felt impossible. Read more.

Tracy's experience with a skull base tumor

Tracy, a chondrosarcoma survivor

My family and I are from British Columbia, Canada. After many months of pain in my head, burning sensation in my gums, cheek and lip and sporadic eye pain, I was finally diagnosed with having a skull base tumor.

I was rushed for tests (and more tests), and I could see the looks change as the doctors I trusted so much came to talk to me and explain all they could without truly knowing what they were seeing. Something had grown from my skull base and broken through two cavities in my head. It did not look good.

Now the journey that would change my life forever began, and I needed to find someone to save my life. Read more.

Jeanna's story

Tracy, a chondrosarcoma survivor

I was a busy single mom, having just graduated from beauty school, and working on building my life after a divorce. I felt like I was on top of the world and finally making a place for myself. I had just started dating again and didn't see it coming. On a Saturday evening, I went to pick my boys up from their dad's, and I had just done makeup for three weddings. My three-year-old was asleep, and as I carried him down the stairs my leg snapped. I fell catching my son, so he didn't get hurt. It took a second to realize what had happened and as I started to scream I knew I had broken my leg. I mean WTH?! I have never broken a bone in my life!

AFTER SURGERY: I started going through rehab, and I thought my leg was going to explode every single day. It had shriveled down to a toothpick and walking seemed like a far stretch at that point. BUT, I kept going, and kept praying, and kept crying, and healing came. I was eventually able to walk again without a cane. It took me all of six months of seriously pushing it to get there, but I got there and YOU can get there too. Read more.

Brenda, chondrosarcoma survivorBrenda's Race

In 2009, I was diagnosed with a grade 2 chondrosarcoma in my right femur while I was training for the Kansas City half marathon. I had three surgeries in 18 months, one of which was a total knee replacement at the age of 33, and spent nearly two years on crutches. I am proud to say that I finally accomplished my goal and completed the San Antonio Rock & Roll half marathon this past Sunday. I wasn't as fast as I was in 2009 since I can't run anymore, but I worked hard and cried as I crossed the finish line.

Linda writes about advocating for her health

I woke up on 3/7/02 with double vision. That began the first day of the rest of my life. After going through three wrong diagnoses and prognoses of "there is not a way to do a biopsy" to "there is no cure," I survived. My story is one of endurance and being an advocate for my own health. With the help of family, I was able to find the doctor who could do the biopsy, who diagnosed me with chondrosarcoma and then went through the long process of finding the treatment that would save my life. I had to find the right way, or I would not be here to talk to about it. I had to travel out of the box and do the research to find the cure. I found Dr. Liebsch and proton beam radiation. He saved my life.

My story is to tell anyone with a health problem that is not ordinary: do the research, don't just listen to the first doctor. Get a second and third opinion, and find the treatment that you feel is the cure. Be your own advocate. I am now NERD (No Evidence of Recurring Disease) with chondrosarcoma of the skull base.

The Online Chondrosarcoma Support Group

I have been active in creating the online support group for chondrosarcoma patients and their loved ones. I started the group years ago because I had never found another person with this type of cancer, and I didn't want others to feel the same way. In the group, people find comfort knowing they are not alone, that their own cancer is not lost among the many other well known ones. They learn from each other about the little things that are specific to chondrosarcoma treatment and recovery, and they find they have a lot in common with each other.

Some group members read and respond to the stories and insights of others or introduce additional subjects of their own. Some are quiet observers, and many are enthusiastic supporters. Loved ones who are caring for those with chondrosarcoma can get the support and understanding they need among their caregiving peers. Since chondrosarcoma affects people of middle age and older, the support group is geared to their particular additional needs.

When someone has recently been diagnosed and is still in that state of shock and worry, there is immediate comfort and understanding in the group. Facing cancer is daunting. Facing a cancer that nobody has ever heard of is even more so. This group is large enough that most members can find several people who have had a tumor in the exact same location or a tumor of the same type and grade. In the group, we find friendships and camaraderie with those who truly understand the chondrosarcoma journey.

Connect on Facebook

The following Facebook groups provide opportunities to exchange messages with others who are dealing with chondrosarcoma.

Find Treatment and Support Resources

We maintain listings of sarcoma treatment centers, local support groups and organizations that provide financial assistance to sarcoma patients and their loved-ones.

Chondrosarcoma Research

The Liddy Shriver Sarcoma Initiative is pleased to support chondrosarcoma research and has funded a $50,000 study on chondrosarcoma. There is much to be learned about this rare cancer. We hope to fund additional chondrosarcoma studies in the future, and we believe that research will lead to newer and better treatments for those who are diagnosed with chondrosarcoma.

The following research study was funded by the Initiative after experts agreed that it was clinically relevant and scientifically sound:

Identifying the Gene that Causes Solitary & Ollier Chondrosarcomas

The Role of Cytoplasmic p27 in Metastatic Osteosarcoma$50,000 Grant: In this study, Drs. Bovée and Oosting in the Netherlands discovered mutations that are associated with benign cartilage tumors and chondrosarcomas. The investigators plan future studies to assess the role of these mutations in tumor formation.

Help us fund groundbreaking research!

Donate Now

To target your donation to chondrosarcoma research and/or dedicate it to someone, click on the blue "dedicate this donation" link located to the left of the large "proceed" button.

Financial Accountability

This grant was awarded by the Liddy Shriver Sarcoma Initiative in February 2011. It was made possible by generous donations made in honor of Amy Kropp, Gavin Kiener, Brendon Martin, Mary Elizabeth Weigand, Chelsea Byers, Elizabeth Munroz, Sara Alan and Carly Laverty; and by generous donations made in memory of Kenny Allen, Scott Stafford, Tom Hand, and Lorelynn Roat.

Make Research Happen

The Initiative welcomes grant applications for chondrosarcoma research, and it's our intention to support every study that passes our peer-review process. We can only accomplish this goal with the help of generous private donations.

Your donation can be targeted to support the next promising chondrosarcoma study that needs funding. If you would like to invite your family and friends to support this important work with you, consider sharing your story or tribute. We will be happy to include an invitation to support chondrosarcoma research on your page.


  • Figure 1: Grade I chondrosarcoma
    Figure 1: Grade I chondrosarcoma demonstrates increased cellularity, perhaps some hyperchromatism but not necessarily atypical cells.
  • Figure 2: Plain radiographs of a low-grade cartilage lesion in a femur bone
    Figure 2: Plain radiographs of a low-grade cartilage lesion in a femur bone
  • Figure 2: Plain radiographs of a low-grade cartilage lesion in a femur bone
    Figure 2: Plain radiographs of a low-grade cartilage lesion in a femur bone
  • Figure 3: Bone scan of patient with left distal femoral chondrosarcoma
    Figure 3: Bone scan of patient with left distal femoral chondrosarcoma
  • Figure 4: MRI images of distal femoral chondrosarcoma
    Figure 4: MRI images of distal femoral chondrosarcoma
  • Figure 4: MRI images of distal femoral chondrosarcoma
    Figure 4: MRI images of distal femoral chondrosarcoma
  • Figure 5: Grade II chondrosarcoma: Increased cellularity and atypical cells
    Figure 5: Grade II chondrosarcoma: Increased cellularity and atypical cells
  • Figure 1: Chondrosarcoma on Radiograph
  • Figure 2: Chondrosarcoma on MRI
  • Figure 3: Chondrosarcoma on Bone Scan