AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Background

Chondromyxoid fibroma (CMF) is a rare, slow-growing 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.

See also the following topic in eMedicine:
Chondromyxoid Fibroma [Radiology]

Pathophysiology

Grossly, CMFs are firm, grayish-white masses that are sharply demarcated; they are lobulated or pseudolobulated. Their appearance can mimic fibrous tissue or hyaline cartilage. The lesions can destroy trabecular bone and may thin the cortex. Some CMFs may have areas of hemorrhage or cystic degeneration. A liquid, mucinous appearance may increase the suggestion of chondrosarcoma.

Many chondromyxoid fibromas display morphologic features that resemble different stages of chondrogenesis.⁶

A study by Romeo and colleagues examined the DNA microarray of chondromyxoid fibroma (as well as that of chondroblastoma).⁷ The authors found that the differential expression of adhesion and extracellular matrix molecules, including CD166, versican, perlecan, and Col4A2, may interfere with cartilaginous differentiation.

Frequency

United States

CMF accounts for less than 1% of primary bone tumors.

International

As of 2000, approximately 500 cases of CMF had been described in the world literature.⁸

Mortality/Morbidity

Local symptoms of CMF may cause a reduction in activity. CMF may recur locally, especially following a marginal excision. In addition, it may behave in an active or aggressive fashion, but malignant conversion is extremely rare and is difficult to distinguish from misdiagnosed de novo chondrosarcoma. Consequently, mortality from true benign CMF is essentially nonexistent.

Race

No racial predilection has been reported.

Sex

According to most reports, males and females are affected equally, although a few series have reported a male predominance.⁹

Age

CMF primarily affects young adults in their second and third decades of life. Eighty percent of patients are younger than 36 years. The youngest reported patient was aged 3 years at the time of diagnosis, and the oldest patient was aged 87 years at the time of diagnosis.

CLINICAL

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

History

Approximately 70% of patients 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. While typically mild, the pain may become more severe with time, and night symptoms may be present. Patients may also report swelling and, in very rare cases, a limitation of joint motion.

Physical

Approximately 89% of CMFs involve the lower extremity. The proximal tibia is the most common location, followed by the distal femur, pelvis, and foot.¹⁰ Long bones are involved much more frequently than are other bones, especially in younger patients. Flat bone involvement may be observed more often in older patients. Patients may have localized tenderness or swelling over the CMF lesion, and, in rare cases, they may incur a pathologic fracture.

Causes

Although no specific cause is known for CMF, some authors have noted an association with certain chromosomal abnormalities. In a study of 4 patients with CMF, Granter and colleagues found that all of the subjects had a clonal rearrangement of chromosome 6.¹¹ Each of these rearrangements involved band 6q13, which has not been associated with other bone tumors. Thus, band 6q13 may be useful as a cytogenetic marker to distinguish CMF from other histologically similar tumors. The authors suggested that oncogene activation resulting from this clonal rearrangement is likely to be involved in the genesis of CMF.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Other Problems to Be Considered

Chondrosarcoma (conventional)

Although chondrosarcoma may mimic CMF histologically, it typically has distinguishing demographic and radiographic characteristics. The peak incidence of chondrosarcoma occurs in the sixth and seventh decades of life, while CMF develops in the second and third decades. Radiographically, chondrosarcoma tends to be central and to have abundant calcifications. These characteristics also help to distinguish it from CMF. Chondrosarcoma and CMF, however, may each have mild expansion of cortical bone. In higher grade or long-standing chondrosarcoma, a soft-tissue mass may be observed. This mass is uncommon in CMF.^{12, 13}

The histopathologic features of CMF—including a lobular growth pattern, occasional focal deposits of hyaline cartilage, rare mitotic figures, and even cellular pleomorphism—may be similar to those of chondrosarcoma. However, mucinous material, prominent nuclear atypia, and multiple pleomorphic or multinuclear cartilage cells all suggest chondrosarcoma. In addition, chondrosarcoma tends to behave in a more malignant fashion, having more severe symptoms, as well as faster growth, extraosseous invasion, and metastases, than does CMF.

Chondroblastoma

Chondroblastoma and CMF typically occur in individuals of the same age group and may have very similar histologic features, including chondroblastic differentiation, numerous giant cells, and a markedly positive S-100 stain result. Thus, chondroblastoma may be very difficult to distinguish from CMF. However, several features of chondroblastoma vary from those of CMF. The former typically occurs in an epiphyseal location, whereas CMFs are usually 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.¹⁴

Nonossifying fibroma

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

Enchondroma

On radiographs, these lesions are typically central rather than eccentric but also may have associated lucent areas. Mineralization of the hyaline cartilage is generally much 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 atypical cells or myxoid background. Patients with enchondroma are typically older than are patients with CMF.

Unicameral bone cyst

These lesions have a central location and demonstrate absence of cartilage mineralization. They are cystic structures with hemosiderin-laden macrophages, straw-colored fluid, and a thin, fibrous lining.

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, while having a metaphyseal origin, typically extend to involve the epiphysis. They can also have prominent extraosseous extension. The defining histologic characteristic of GCT is the presence of a plethora of multinucleated giant cells, with the background cells containing nuclei that are similar to those in the giant cells.¹⁵

Aneurysmal bone cyst

Although the age range for aneurysmal bone cyst (ABC) and CMF is similar, the former typically demonstrates marked, ballooning cortical expansion and septations radiographically. 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.

See also the following topics in eMedicine:
Aneurysmal Bone Cyst [Orthopedic Surgery]
Aneurysmal Bone Cyst [Radiology]
Enchondroma and Enchondromatosis
Fibrous Cortical Defect and Nonossifying Fibroma
Giant Cell Tumor [Orthopedic Surgery]
Giant Cell Tumor [Radiology]
Unicameral Bone Cyst

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Lab Studies

• CMF does not cause any laboratory abnormalities.

Imaging Studies

• Radiographs^{16, 17}
• • CMFs are well-defined, eccentric, elongated, radiolucent lesions that usually occur in the metaphysis of long bones. A diagnostic feature, when present, is a nearly hemispherical "bite" from the cortical margin without periosteal reaction. The greatest dimension of CMFs is typically 1-10 cm. The margins are often sclerotic with scalloped borders and may demonstrate mild cortical expansion. The lesions can extend into the diaphysis or epiphysis but do not cross the open physeal plate.
  • Trabeculations within the tumor, which reflect bony ridges formed around a lobulated tumor periphery, may be visible on radiographs.
  • Matrix calcifications are unusual, appearing in only 2-13% of lesions.¹⁸
  • When CMF involves the vertebrae (in approximately 8% of cases), radiographs may reveal a more aggressive appearance, with cortical destruction and extension into soft tissue.¹⁹
  • Lesions of the small bones of the hands or feet are more typically central and expansile.
  • CMFs may have associated secondary ABCs, visible on radiographs.
• Computed tomography (CT) scans
• • Mild cortical expansion may be observed on CT scans, and the lesions have a density greater than fluid throughout, except in areas affected by a secondary ABC.
  • CT scans can also reveal the characteristic lack of mineralization within the lesions.
• Magnetic resonance imaging (MRI) scans
• • The 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 images and have a low signal on T1-weighted images. The 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 as well.
  • Secondary ABCs have typical septations and, in many cases, fluid-fluid levels reflecting the blood-filled vascular channels. MRI scans may demonstrate soft-tissue or bone marrow edema extending well beyond the lesion and are helpful in preoperative planning.
• Bone scans - CMFs usually have increased activity on bone scintigraphy.

Procedures

• Biopsy is used for histologic examination. 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.

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.²⁰ None of the cells express desmin.

Staging

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

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Medical Care

No medical care is usually necessary in the treatment of CMFs. Nonsteroidal anti-inflammatory agents or analgesics may be beneficial for pain control.

Surgical Care

CMFs are treated with intralesional curettage or en bloc excision.²¹ Jaffe and Lichtenstein noted in their original description of CMF that "even with incomplete removal, spontaneous regression of the remnants followed."⁵ Subsequent reports have noted recurrence rates of approximately 25% with curettage and bone graft, although this 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.²²

Activity

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 weight bearing should alert one to the possibility of impending fracture. Some patients may limit their activity to control discomfort.

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Nonsteroidal anti-inflammatory agents or analgesics may be used for pain control.

See also the following topics in Medscape:
Resource Center Pharmacologic Management of Pain
CME Improving NSAID Outcomes: Stratifying Risks and Tailoring Treatment (Slides with Audio)
CME Undermanaged Pain in the Orthopedic Surgical Patient: Techniques to Improve Outcomes

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs)

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.

Drug Category: Analgesics

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

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Further Outpatient Care

• The average time to recurrence is typically less than 2 years, but it has been reported to take up to 19 years after the initial tumor presentation.^{12, 23, 24, 25} Patients should be monitored with periodic history and physical examinations and with routine radiographs of the affected site for a minimum of 2 years.

Complications

• 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.

Prognosis

• Patients are generally cured with en bloc excision and have an approximately 25% recurrence rate with usual treatment of curettage. In most cases, radiation therapy should be avoided because of its causative relationship with postradiation sarcoma. Occasional CMFs may be more aggressive, especially when they are located in the axial skeleton.

MULTIMEDIA

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

Media file 1:  Radiograph showing the "bite" out of the metaphyseal cortex that is a diagnostic feature of chondromyxoid fibroma.
	View Full Size Image
Media type:  Image

Media file 2:  Magnetic resonance imaging (MRI) scan of chondromyxoid fibroma (T1 image).
	View Full Size Image
Media type:  MRI

Media file 3:  Close-up of a lobule of a chondromyxoid fibroma.
	View Full Size Image
Media type:  Image

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Multimedia
• References

1. McGrory BJ, Inwards CY, McLeod RA, et al. Chondromyxoid fibroma. Orthopedics. Mar 1995;18(3):307-10. [Medline].
2. Ralph LL. Chondromyxoid fibroma of bone. J Bone and Joint Surg. 1962;44B(1):7-24.
3. Schutt PG, Frost HM. Chondromyxoid fibroma. Clin Orthop Relat Res. 1971;78:323-9. [Medline].
4. White PG, Saunders L, Orr W, et al. Chondromyxoid fibroma. Skeletal Radiol. Jan 1996;25(1):79-81. [Medline].
5. Jaffe HL, Lichtenstein L. Chondromyxoid fibroma of bone: a distinctive benign tumor likely to be mistaken especially for chondrosarcoma. Arch Path. 1943;19:541-51.
6. Baker AC, Rezeanu L, O'Laughlin S, et al. Juxtacortical chondromyxoid fibroma of bone: a unique variant: a case study of 20 patients. Am J Surg Pathol. Nov 2007;31(11):1662-8. [Medline].
7. Romeo S, Oosting J, Rozeman LB, et al. The role of noncartilage-specific molecules in differentiation of cartilaginous tumors: lessons from chondroblastoma and chondromyxoid fibroma. Cancer. Jul 15 2007;110(2):385-94. [Medline].
8. Blackwell JB, Norma M, Curnow P. Benign bone tumours in Western Australia, 1972-1996. Pathology. Dec 2007;39(6):567-74. [Medline].
9. Wu CT, Inwards CY, O''Laughlin S, et al. Chondromyxoid fibroma of bone: a clinicopathologic review of 278 cases. Hum Pathol. May 1998;29(5):438-46. [Medline].
10. Wu KK. Chondromyxoid fibroma of the foot bones. J Foot Ankle Surg. Sep-Oct 1995;34(5):513-9. [Medline].
11. Granter SR, Renshaw AA, Kozakewich HP, et al. The pericentromeric inversion, inv (6)(p25q13), is a novel diagnostic marker in chondromyxoid fibroma. Mod Pathol. Nov 1998;11(11):1071-4. [Medline].
12. Heydemann J, Gillespie R, Mancer K. Soft tissue recurrence of chondromyxoid fibroma. J Pediatr Orthop. Nov-Dec 1985;5(6):725-7. [Medline].
13. Kyriakos M. Soft tissue implantation of chondromyxoid fibroma. Am J Surg Pathol. Aug 1979;3(4):363-72. [Medline].
14. Dahlin DC. Chondromyxoid fibroma of bone, with emphasis on its morphological relationship to benign chondroblastoma. Cancer. Jan-Feb 1956;9(1):195-203. [Medline].
15. Sakayama K, Sugawara Y, Kidani T, et al. Diagnostic and therapeutic problems of giant cell tumor in the proximal femur. Arch Orthop Trauma Surg. Dec 2007;127(10):867-72. [Medline].
16. Marin C, Gallego C, Manjon P, et al. Juxtacortical chondromyxoid fibroma: imaging findings in three cases and a review of the literature. Skeletal Radiol. Nov 1997;26(11):642-9. [Medline].
17. Merine D, Fishman EK, Rosengard A, et al. Chondromyxoid fibroma of the fibula. J Pediatr Orthop. Jul-Aug 1989;9(4):468-71. [Medline].
18. Yamaguchi T, Dorfman HD. Radiographic and histologic patterns of calcification in chondromyxoid fibroma. Skeletal Radiol. Oct 1998;27(10):559-64. [Medline].
19. Cabral CE, Romano S, Guedes P, et al. Chondromyxoid fibroma of the lumbar spine. Skeletal Radiol. Aug 1997;26(8):488-92. [Medline].
20. Nielsen GP, Keel SB, Dickersin GR, et al. Chondromyxoid fibroma: a tumor showing myofibroblastic, myochondroblastic, and chondrocytic differentiation. Mod Pathol. May 1999;12(5):514-7. [Medline].
21. Durr HR, Lienemann A, Nerlich A, et al. Chondromyxoid fibroma of bone. Arch Orthop Trauma Surg. 2000;120(1-2):42-7. [Medline].
22. Hristov B, Shokek O, Frassica DA. The role of radiation treatment in the contemporary management of bone tumors. J Natl Compr Canc Netw. Apr 2007;5(4):456-66. [Medline].
23. Gherlinzoni F, Rock M, Picci P. Chondromyxoid fibroma. The experience at the Istituto Ortopedico Rizzoli. J Bone Joint Surg Am. Feb 1983;65(2):198-204. [Medline].
24. Mikulowski P, Ostberg G. Recurrent chondromyxoid fibroma. Acta Orthop Scand. 1971;42(5):385-90. [Medline].
25. Zillmer DA, Dorfman HD. Chondromyxoid fibroma of bone: thirty-six cases with clinicopathologic correlation. Hum Pathol. Oct 1989;20(10):952-64. [Medline].

Article Last Updated: Jan 18, 2008