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.
Pathophysiology
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]
Etiology
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.
Epidemiology
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.
Prognosis
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.
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Radiograph showing the "bite" out of the metaphyseal cortex that is a diagnostic feature of chondromyxoid fibroma.
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Magnetic resonance imaging (MRI) scan of chondromyxoid fibroma (T1 image).
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Close-up of a lobule of a chondromyxoid fibroma.
