Chondromyxoid Fibroma 

Updated: Sep 16, 2020
Author: Stefanos F Haddad, MD; Chief Editor: Omohodion (Odion) Binitie, MD 


Practice Essentials

Chondromyxoid fibroma (CMF) is a rare, slow-growing, benign bone tumor of chondroblastic derivation.[1, 2, 3, 4]  Jaffe and Lichtenstein first described the condition in 1943.[5]  They differentiated this benign lesion from chondrosarcoma, a much more common, but malignant, tumor. Before 1943, CMF would have been considered a giant-cell variant or a benign cartilaginous tumor. A myxoid element is the defining characteristic.

No medical care is usually necessary, though pharmacologic pain control may be warranted. CMFs are treated with intralesional curettage or en-bloc excision. Radiotherapy may be employed for unresectable tumors, but it should be used cautiously because it increases the risk of a secondary sarcoma.


Grossly, CMFs are firm, grayish-white masses that are sharply demarcated; they are lobulated or pseudolobulated. Their appearance can mimic that of fibrous tissue or hyaline cartilage. The lesions can rarely destroy trabecular bone and often thin the cortex. Rarely, CMFs may have areas of hemorrhagic and cystic degeneration and mimic aneurysmal bone cysts.

Many chondromyxoid fibromas display morphologic features that resemble different stages of chondrogenesis.[6, 7] The most important diagnostic pathologic characteristic is the myxoid element. Without the finding of the myxoid element, the diagnosis cannot be made. Giant cells are frequently present, especially toward the periphery of the lesion. A study by Romeo et al examined the DNA microarray of chondromyxoid fibroma and demonstrated that CMFs could be differentiated from other cartilaginous tumors.[8]


As is the case with most bone tumors, no specific cause is known for CMF.

Some authors noted an association with certain chromosomal abnormalities. In a study of four patients with CMF, Granter et al found that all of the subjects had a clonal rearrangement of chromosome 6,[9]  which had not been associated with other bone tumors. This finding may be useful as a cytogenetic marker to distinguish CMF from other histologically similar tumors. It has been suggested that oncogene activation resulting from this clonal rearrangement is likely to be involved in the genesis of CMF.[10, 11]

Nord et al subjected a series of CMFs to whole-genome mate-pair sequencing and RNA sequencing.[12]  They found that the glutamate receptor gene GRM1 recombines with several partner genes through promoter swapping and gene fusion. The GRM1 coding region remained intact, and 18 of 20 CMFs (90%) showed pronounced (100- to 1400-fold) increases in GRM1 expression levels in comparison with control tissues. These findings demonstrate that direct targeting of GRM1 is a necessary and highly specific driver event for the development of CMF.


CMFs account for fewer than 1% of primary bone tumors in the United States. CMFs are becoming less frequently diagnosed, and thus, the current frequency is much lower than 1%.

As of the end of the 20th century, approximately 500 cases of CMF had been described in the world literature.[13] The frequency of diagnosis seems to be decreasing.

CMF primarily affects young adults in their second and third decades of life. Eighty percent of patients are younger than 36 years. According to most reports, males and females are affected equally, though a few series have reported a slight male predominance.[14] No racial predilection has been reported.


Patients are generally cured with en-bloc excision. After resection both with and without bone grafting, CMFs may recur locally, especially after a marginal excision. 

Curettage alone is associated with a relatively high recurrence rate, about 20-25%. This is probably due to incomplete removal of the tumor. The use of adjuvants lowers the recurrence rate. For example, curettage with bone grafting or cementation is associated with a much lower recurrence rate, about 7%. In lesions where the cortex is found to be involved, a thorough curettage will leave a defect that must be filled with bone grafting to prevent fracture and to facilitate weightbearing.[15]

In a study of 22 consecutive cases of CMF treated with intralesional curettage,[16]  Bhamra et al documented local recurrence in two patients (9%) within the first 2 years after the index procedure. This was treated by recurettage of only the residual defect. Two postoperative complications occurred: a superficial wound infection in one patient, and a transient deep peroneal nerve neurapraxia in the other. The mean postoperative score on the Musculoskeletal Tumour Society scoring system was 96.7%.

In most cases, radiation therapy should be avoided because of its causative relation to postradiation sarcoma.

Occasional CMFs may behave locally in an aggressive fashion after resection, especially when they are located in the axial skeleton.

Malignant conversion is extremely rare and is difficult to distinguish from a misdiagnosed de-novo chondrosarcoma. Consequently, mortality from true CMF is essentially nonexistent.




Approximately 70% of patients with chondromyxoid fibromas (CMFs) have symptoms at the time of diagnosis; the remaining lesions are discovered incidentally. Pain is the most common symptom and may be present for years.[17] Although the pain is typically mild, it may become severe with time, and night symptoms may be present. Patients may also report swelling and stiffness. These symptoms may be especially common around the knee and may cause a reduction in physical activity.

Pathologic fractures have been rarely reported, probably as a consequence of the slow growth of this tumor; the symptom of pain may be due to pending fracture through the lesion.

Physical Examination

Approximately 90% of CMFs involve the lower extremity. The proximal tibia metaphysis is the most common location, followed by the distal femoral metaphysis.[18] Long bones are involved much more frequently than are other bones, especially in younger patients. After the long bones, the pelvis is one of the more common sites.[19] Flat-bone involvement may rarely be seen in older patients. Craniofacial involvement occurs rarely.[20]

Patients may have localized tenderness or swelling over a CMF lesion, and in rare cases, they may incur a pathologic fracture.



Diagnostic Considerations

Chondrosarcoma (conventional)

Chondrosarcoma of low grade may mimic chondromyxoid fibroma (CMF) histologically, except for the lack of a myxoid element. It typically has distinguishing demographic and radiographic characteristics. The peak incidence of chondrosarcoma occurs in the sixth and seventh decades of life, whereas CMF develops in the second and third decades.

Radiographically, chondrosarcoma tends to be central and have abundant calcifications. Chondrosarcoma and CMF, however, may each have mild expansion of cortical bone. In higher grade or long-standing chondrosarcoma, cortical erosion and a soft-tissue mass may be observed.[21, 22]

The histopathologic features of CMF—including a lobular growth pattern, focal deposits of hyaline cartilage, rare mitotic figures, and even cellular pleomorphism—may be similar to those of chondrosarcoma. However, mucinous material, nuclear atypia, and multiple pleomorphic or multinuclear cartilage cells all suggest chondrosarcoma. In addition, chondrosarcoma tends to behave in a more malignant fashion. A myxoid element is not found in chondrosarcoma.


Chondroblastoma and CMF occur in individuals of the same age group and may have similar histologic features, including chondroblastic differentiation, giant cells, and a markedly positive S-100 stain result. Like chondrosarcomas, chondroblastomas lack a myxoid element.

Several features of chondroblastoma differ from those of CMF. Chondroblastomas typically occurs in an epiphyseal location, whereas CMFs are metaphyseal tumors. Moreover, microscopic calcifications, commonly found in chondroblastoma, are usually absent in CMF. Finally, the myxoid pseudolobulations that are noted in CMF are not observed in chondroblastoma.[23]

Nonossifying fibroma

These lesions tend to have a metaphyseal or diaphyseal location and an eccentric lytic appearance. However, nonossifying fibromas have a more demarcated sclerotic border and more cortical expansion on radiographs. On microscopic evaluation, moreover, they show whirling of fibrous tissue without chondroid or myxoid elements


On radiographs, these lucent lesions are typically central rather than eccentric and do not bulge or break the cortex. Mineralization of the hyaline cartilage is generally more extensive in mature enchondromas than in CMFs. Histologically, enchondromas are made up of almost purely chondroid tissue with a bland-looking histologic appearance, and no fibrous or myxoid element is present. Patients with enchondroma are typically older than are patients with CMF. Enchondromas are most common in the hand.

Unicameral bone cyst

These lesions have a more central location and demonstrate absence of cartilage. They are cystic structures with hemosiderin-laden macrophages, straw-colored fluid, and a thin, fibrous lining. Occasionally, unicameral bone cysts can have a radiographic appearance similar to that of CMFs; otherwise, they are easily differentiated.

Giant cell tumor of bone

Patients with giant cell tumor (GCT) of bone are typically older than persons with CMF, and the radiographic and cellular features of GCT differ from those of CMF. GCTs, though of metaphyseal origin, can extend into the epiphysis. The defining histologic characteristic of GCT is the presence of a plethora of multinucleated giant cells.[24] CMFs contain fewer giant cells located near the periphery. GCTs have no myxoid or chondroid elements.

Aneurysmal bone cyst

Although the age range for aneurysmal bone cyst (ABC) and CMF is similar, the former typically demonstrates ballooning cortical expansion. Histologically, an ABC is made up of large, blood-filled vascular spaces and a highly vascular stroma with multinucleated giant cells, hemosiderin deposition, and histiocytes. Both lesions can expand the cortex, but they are easily differentiated radiographically and histologically. The development of a secondary associated ABC within a CMF has been reported.

Differential Diagnoses



Imaging Studies


On radiographs,[25, 26]  chondromyxoid fibromas (CMFs) are well-defined, eccentric, elongated, radiolucent lesions. Like many bone tumors, CMFs occur most frequently in the metaphysis of the proximal tibia and the distal femur. Epiphyseal occurance has not been reported. Other reported locations are the pelvis and the first metacarpal.

A common appearance is a bubbly, expansile, eccentric, elongated, metaphyseal, lytic lesion. A rare diagnostic feature is a eccentric, nearly hemispherical "bite" from the cortical margin without periosteal reaction (see the image below). The greatest dimension of a CMF is less than 10 cm. The margins are usually sclerotic with scalloped borders and may demonstrate mild cortical expansion. The lesions can extend into the diaphysis but do not cross the physeal plate.

Radiograph showing the "bite" out of the metaphyse Radiograph showing the "bite" out of the metaphyseal cortex that is a diagnostic feature of chondromyxoid fibroma.

Trabeculations within the tumor, which reflect bony ridges formed around a lobulated tumor may be visible on radiographs. Matrix calcifications are unusual.[27]

When CMF involves the vertebrae (quite rare), radiographs may show a more aggressive appearance.[28]  Craniofacial CMFs may also have an aggressive radiologic appearance.[20] CMFs of the small bones of the hands or feet (rare) are more central and expansile. CMFs may have associated or secondary aneurysmal bone cysts (ABCs).

Computed tomography

On computed tomography (CT), mild cortical expansion may be observed, and the lesions have a density greater than fluid throughout. CT scans also exhibit characteristic lack of mineralization within CMFs. CT may be superior to conventional radiography for analysing the expansion of the lesion, cortical breakthrough, and internal mineralization.[29]

Magnetic resonance imaging

Chondroid and myxoid tissues, as well as any normal hyaline cartilage within the lesion, have an intermediate-to-high signal on proton-density and T2-weighted magnetic resonance imaging (MRI) and a low signal on T1-weighted images (see the image below).[30, 31, 29] Fibrous tissue components have a variable appearance, depending on their vascularity. Because of their diverse tissue components, CMFs have a heterogeneous appearance. They are typically solid but can have cystic areas. Secondary ABCs have typical septations and fluid-fluid levels.

Magnetic resonance imaging (MRI) scan of chondromy Magnetic resonance imaging (MRI) scan of chondromyxoid fibroma (T1 image).

Bone scanning

CMFs usually have increased activity on bone scintigraphy.


Biopsy is used for histologic examination.[32] A generous tissue sample is required for an accurate diagnosis, because small biopsies may not be representative.

Histologic Findings

Microscopically, CMFs are lobulated or pseudolobulated, with peripheral condensation of more cellular tissue within the lobules. Composed of myxoid or chondroid tissue, the center of each lobule is hypocellular. The surrounding stroma is denser, with spindle-shaped cells, blood vessels, and occasional multinucleate giant cells.

Tumor nuclei may be hyperchromatic, are of moderate size, and may lie in chondroid lacunae. Nuclear atypia can be observed, but mitoses are rare or absent. Microcalcification is present in 15-20% of cases, with an increased incidence in older patients. (See the image below.)

Close-up of a lobule of a chondromyxoid fibroma. Close-up of a lobule of a chondromyxoid fibroma.

Scattered areas of hyalinization, xanthomatous changes, cholesterol clefts, and cystic degeneration may be noted, including secondary ABCs. The tumors have a heterogeneous immunohistochemical staining pattern, with the central chondroid areas staining positively for S-100 protein and the peripheral, hypercellular tissue staining diffusely for muscle and smooth-muscle actin.[33, 34] None of the cells express desmin.


Local staging typically includes plain radiography and MRI or CT. Because CMF does not metastasize, there is no need for routine chest radiography or other systemic staging studies. A total skeletal bone scan is generally advisable during the initial evaluation to assess local activity and to confirm the solitary nature of the tumor.



Medical Care

No medical care is usually necessary in the treatment of chondromyxoid fibromas (CMFs). Nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics may be beneficial for pain control.

Surgical Care

CMFs are treated with intralesional curettage[35] or en-bloc excision.[36] Jaffe and Lichtenstein noted in their original description of CMF that "even with incomplete removal, spontaneous regression of the remnants followed."[5] Subsequent reports noted recurrence rates of approximately 25% with curettage and bone grafting, though this rate may be higher in young children (first or second decade of life) and in patients with tumors that are predominantly composed of myxoid areas.

Wide en-bloc excision may lower the recurrence rate, but it usually adds unnecessary morbidity. Local adjunct treatment agents, such as phenol, methylmethacrylate, and liquid nitrogen, have not been shown to decrease the recurrence rate.

Radiotherapy may be used in tumors that are considered unresectable[37] ; however, caution is required, in view of the increased risk of a seondary sarcoma.


Arrest of growth may occur after aggressive curettage of tumors adjacent to the physis. Malignant transformation has been noted as a possible complication, even in the absence of preceding radiation therapy. However, many authors believe that cases of CMF that have been reported as malignant transformation have not been sufficiently documented and more likely represent a misdiagnosis of chondrosarcoma.


Activity need not be restricted unless the lesion is large enough to create a risk of fracture. This is an unusual occurrence, and pain with weightbearing should alert one to the possibility of impending fracture. Some patients may limit their activity to control discomfort.

Long-Term Monitoring

The average time to recurrence is typically less than 2 years, but it has been reported to be as long as 19 years after the initial tumor presentation.[21, 38, 39, 40] Patients should be monitored with periodic history and physical examinations and with routine radiographs of the affected site for a minimum of 2 years.



Medication Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) or analgesics may be used for pain control.

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Class Summary

NSAIDs have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclo-oxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell membrane functions.

Ibuprofen (Motrin, Ibuprin)

DOC for patients with mild to moderate pain. Ibuprofen inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Naprosyn, Anaprox, Aleve, Naprelan)

Used for the relief of mild to moderate pain. Inhibits inflammatory reactions and pain by decreasing the activity of cyclo-oxygenase, which results in decreased prostaglandin synthesis.

Ketoprofen (Actron, Orudis, Oruvail)

Used for the relief of mild to moderate pain and inflammation. Small dosages are initially indicated in small and elderly patients and in persons with renal or liver disease. Doses >75 mg do not increase the therapeutic effects. Administer high doses with caution and closely observe the patient for his/her response.


Class Summary

Pain control is essential to quality patient care. Analgesics ensure patient comfort and have sedating properties, which are beneficial for patients who experience pain.

Acetaminophen (Aspirin Free Anacin, Tylenol, FeverAll, Tempra)

DOC for pain in patients with documented hypersensitivity to aspirin or NSAIDs, with upper GI disease, or who are taking oral anticoagulants.

Hydrocodone and acetaminophen (Lorcet-HP, Lortab, Norcet, Vicodin)

This drug combination is indicated for moderate to severe pain.