Background

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 considred a giant-cell variant or a benign cartilaginous tumor. A myxoid element is the defining characteristic.

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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. The authors suggest 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 compared 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%.

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, although 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. The recurrence rate is approximately 25% with the usual treatment of curettage.

In a study of 22 consecutive cases of CMF treated with intralesional curettage,^[15]  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.

Clinical Presentation