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AUTHOR INFORMATION
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Section 1 of 10
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| Author: Hannah
D Morgan, MD, Acting Instructor, Department of
Orthopedics and Sports Medicine, University of Washington
Coauthor(s): Timothy
Damron, MD, Associate Professor, Department of
Orthopedics, Division of Orthopedic Oncology - Joint Reconstructive
Surgery, State University of New York at Syracuse, Upstate Medical
University
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| Editor(s): Howard A Chansky, MD, Associate
Professor, Department of Orthopedics and Sports Medicine, University
of Washington Medical Center; Francisco Talavera, PharmD,
PhD, Senior Pharmacy Editor, Pharmacy, eMedicine;
Sean P Scully, MD, PhD, Senior Associate
Consultant, Department of Orthopedics, Mayo Clinic of Rochester;
Dinesh Patel, MD, Assistant Clinical Professor of
Orthopedic Surgery, Harvard Medical School; Chief of Arthroscopic
Surgery, Department of Orthopedic Surgery, Massachusetts General
Hospital; and Harris Gellman, MD, Clinical
Professor of Orthopedic Surgery, University of Arkansas and
University of Miami; Consulting Surgeon, Broward Hand Center
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INTRODUCTION |
Section 2 of 10   |
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Background:
Chondromyxoid fibroma (CMF) is a rare slow-growing bone tumor of
chondroblastic derivation. The condition was described first in 1948 by
Jaffe and Lichtenstein, who differentiated this benign lesion from
chondrosarcoma, a much more common but malignant tumor.
Pathophysiology: Grossly, CMFs are lobulated or
pseudolobulated firm grayish-white masses that are sharply demarcated.
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 suggestion of chondrosarcoma.
Frequency:
- In the US: CMF comprises less than 1% of primary
bone tumors.
- Internationally: As of 2000, approximately 500
cases of CMF have been described in the world literature.
Mortality/Morbidity: CMF may cause a reduction in
activity due to local symptoms, and it may recur locally, especially
following a marginal excision. CMF 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 predilections have been reported.
Sex: By most reports, males and females are affected
equally, although a few series have reported a male predominance.
Age: This tumor affects primarily young adults in
their second and third decades of life, with 80% of the patients aged less
than 36 years. The youngest reported patient was 3 years old at the time
of diagnosis, and the oldest patient was 87.
History: Approximately 70%
of patients have symptoms at the time of diagnosis, while the remainder of
the lesions are discovered as incidental findings. 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, very rarely, a limitation of joint motion.
Physical: Approximately 89% of CMFs involve the lower
extremity, with the proximal tibia being the most common location,
followed by the distal femur, pelvis, and foot. Long bones are involved
much more frequently, especially in younger patients. Flat bone
involvement may be observed more frequently 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: While 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, all were found to have clonal
rearrangements of chromosome 6 (Granter, 1998). 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. Granter et al
suggest that oncogene activation as a result of this clonal rearrangement
is likely to be involved in the genesis of CMF.
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DIFFERENTIALS |
Section 4 of 10 |
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Other Problems to be Considered:
Chondrosarcoma (conventional)
While chondrosarcomas may
mimic CMF histologically, they typically have distinguishing demographic
and radiographic characteristics. The peak incidence of chondrosarcoma
occurs during the sixth and seventh decades of life, while CMF develops in
the second and third decades. Radiographically, chondrosarcomas tend to be
central and have abundant calcifications. These characteristics also help
distinguish them from CMF. Both chondrosarcoma and CMF, however, may have
mild expansion of cortical bone. In higher grade or long-standing
chondrosarcomas, a soft tissue mass may be observed. This mass is uncommon
in CMF. The histopathologic features of CMF may be similar to those of
chondrosarcoma, with a lobular growth pattern, occasional focal deposits
of hyaline cartilage, rare mitotic figures, and even cellular
pleomorphism. Mucinous material, prominent nuclear atypia, and multiple
pleomorphic or multinuclear cartilage cells all suggest chondrosarcoma.
When compared with chondromyxoid fibromas, chondrosarcomas tend
to
behave in a more malignant fashion, with more severe symptoms, faster
growth, extraosseous invasion, and
metastases.
Chondroblastoma
Chondroblastoma and CMF
typically occur in the 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; thus, they may
be very difficult to distinguish. However, several features of
chondroblastoma distinguish these tumors from CMF. The former typically
occur in an epiphyseal location, whereas chondromyxoid fibromas are
usually metaphyseal tumors. Microscopic calcifications, commonly found in
chondroblastoma, are usually absent in CMF. Finally, the myxoid
pseudolobulations noted in CMF are not observed in
chondroblastoma.
Nonossifying fibroma
These lesions
tend to have a metaphyseal or diaphyseal location with an eccentric lytic
appearance that overlaps that of CMF. However, nonossifying fibromas have
a more marked sclerotic border and more cortical expansion on radiographs.
In addition, they show whirling of fibrous tissue generally without
chondroid or myxoid tissue on microscopic
examination.
Enchondroma
On radiograph, 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 CMF. Histologically,
enchondromas are comprised of almost purely chondroid tissue with a
bland-looking histologic appearance with no atypical cells and no myxoid
background. Enchondroma patients typically are older than patients with
CMF.
Unicameral bone cyst
These lesions have a
central location and demonstrate absence of cartilage mineralization. They
are cystic structures with a thin fibrous lining with hemosiderin-laden
macrophages and straw-colored fluid.
Giant cell tumor of
bone
Patients with giant cell tumor (GCT) of bone typically are
aged older than those with CMF, and the radiographic and cellular features
differ. GCTs, while having a metaphyseal origin, typically extend to
involve the epiphysis. They also can have prominent extraosseous
extension. The defining histologic characteristic of GCT is a plethora of
multinucleated giant cells with the background cells containing nuclei
similar to those in the giant cells.
Aneurysmal bone
cyst
While the age range for aneurysmal bone cyst (ABC) and CMF
is similar, the former classically demonstrates marked ballooning cortical
expansion and septations radiographically. Histologically, ABC is
comprised of large blood-filled vascular spaces and a very vascular stroma
with multinucleated giant cells, hemosiderin deposition, and histiocytes.
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Lab Studies:
- CMF does not cause any laboratory abnormalities.
Imaging Studies:
- 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
chondromyxoid fibromas 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.
- When CMF involves the vertebrae (in approximately 8% of cases),
the radiographs may have a more aggressive appearance, with cortical
destruction and extension into soft tissue.
- Lesions of the small bones of the hands or feet are more typically
central and expansile.
- CMFs may have associated secondary ABC visible on
radiographs.
- Mild cortical expansion may be observed on CT scans, and the
lesions have a density greater than fluid throughout the lesion,
except in areas affected by a secondary ABC.
- Computed tomography can also demonstrate the characteristic lack
of mineralization within the lesions.
- The chondroid and myxoid tissues, as well as any normal hyaline
cartilage within the lesion, all demonstrate intermediate to high
signal on proton-density and T2-weighted images, with low signal on
T1-weighted images. The fibrous tissue components have a variable
appearance depending on their vascularity.
- CMFs have a heterogeneous appearance due to their diverse tissue
components. They are typically solid but can have cystic areas as
well.
- Secondary ABCs show typical septations and, in many cases,
fluid-fluid levels reflecting the blood-filled vascular channels. MRI
images may demonstrate soft tissue or bone marrow edema extending well
beyond the lesion, and are helpful in preoperative
planning.
Other Tests:
- Bone scan: CMFs usually show increased activity on bone
scintigraphy.
Histologic Findings: A generous
tissue sample is required for accurate diagnosis, as small biopsies may be
misrepresentative. Microscopically, the tumors are lobulated or
pseudolobulated with peripheral condensation of more cellular tissue
within the lobules. The center of each lobule is hypocellular, composed of
myxoid or chondroid tissue. The surrounding stroma is more dense, 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. Microcalcifications are 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. None of the cells express desmin.
Staging: Local staging typically includes plain
radiographs and either 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 initial evaluation to assess local activity and ensure
the solitary nature of the tumor.
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TREATMENT |
Section 6 of 10 |
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Medical Care: No medical
care is usually necessary in the treatment of chondromyxoid fibromas.
Nonsteroidal anti-inflammatory agents or analgesics may be beneficial for
pain control.
Surgical Care: Chondromyxoid fibromas are treated with
intralesional curettage or en bloc excision. Jaffe and Lichtenstein noted
in their original description of CMF that “even with incomplete removal,
spontaneous regression of the remnants followed.” However, more recent
reports note 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 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, or liquid nitrogen have not been shown to
decrease the recurrence rate.
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.
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MEDICATION |
Section 7 of 10 |
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Nonsteroidal anti-inflammatory agents or
analgesics may be used for pain control.
Drug Category: Nonsteroidal anti-inflammatory drugs
(NSAIDs) -- Have analgesic, anti-inflammatory, and antipyretic
activities. Their mechanism of action is not known, but 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 Name
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Ibuprofen (Motrin, Ibuprin) -- DOC
for patients with mild to moderate pain. Inhibits inflammatory
reactions and pain by decreasing prostaglandin synthesis.
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| Adult Dose |
200-400 mg PO q4-6h while symptoms
persist; not to exceed 3.2 g/d
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| Pediatric Dose |
6 months to 12 years: 4-10
mg/kg/dose PO tid/qid
>12 years: Administer as in adults
| Contraindications |
Documented hypersensitivity; peptic
ulcer disease, recent GI bleeding or perforation, renal
insufficiency, or high risk of bleeding
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| Interactions |
Coadministration with aspirin
increases risk of inducing serious NSAID-related side effects;
probenecid may increase concentrations and, possibly, toxicity of
NSAIDs; may decrease effect of hydralazine, captopril, and
beta-blockers; may decrease diuretic effects of furosemide and
thiazides; may increase PT when taking anticoagulants (instruct
patients to watch for signs of bleeding); may increase risk of
methotrexate toxicity; phenytoin levels may be increased when
administered concurrently
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| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
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| Precautions |
Category D in third trimester of
pregnancy; caution in congestive heart failure, hypertension, and
decreased renal and hepatic function; caution in coagulation
abnormalities or during anticoagulant therapy | |
Drug Name
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Naproxen (Naprosyn, Anaprox, Aleve,
Naprelan) -- For relief of mild to moderate pain; inhibits
inflammatory reactions and pain by decreasing activity of
cyclo-oxygenase, which results in a decrease of prostaglandin
synthesis.
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| Adult Dose |
500 mg PO followed by 250 mg q6-8h;
not to exceed 1.25 g/d
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| Pediatric Dose |
<2 years: Not
established
>2 years: 2.5 mg/kg/dose PO; not to exceed 10
mg/kg/d
| Contraindications |
Documented hypersensitivity; peptic
ulcer disease; recent GI bleeding or perforation; renal
insufficiency
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| Interactions |
Coadministration with aspirin
increases risk of inducing serious NSAID-related side effects;
probenecid may increase concentrations and, possibly, toxicity of
NSAIDs; may decrease effect of hydralazine, captopril, and
beta-blockers; may decrease diuretic effects of furosemide and
thiazides; may increase PT when taking anticoagulants (instruct
patients to watch for signs of bleeding); may increase risk of
methotrexate toxicity; phenytoin levels may be increased when
administered concurrently
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| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
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| Precautions |
Category D in third trimester of
pregnancy; acute renal insufficiency, interstitial nephritis,
hyperkalemia, hyponatremia, and renal papillary necrosis may occur;
patients with preexisting renal disease or compromised renal
perfusion risk acute renal failure; leukopenia occurs rarely, is
transient, and usually returns to normal during therapy; persistent
leukopenia, granulocytopenia, or thrombocytopenia warrants further
evaluation and may require discontinuation of drug | |
Drug Name
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Ketoprofen (Actron, Orudis,
Oruvail) -- For relief of mild to moderate pain and inflammation.
Small dosages initially are indicated in small and elderly patients
and in those with renal or liver disease. Doses over 75 mg do not
increase therapeutic effects. Administer high doses with caution and
closely observe patient for response.
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| Adult Dose |
25-50 mg PO q6-8h prn; not to
exceed 300 mg/d
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| Pediatric Dose |
3 months to 12 years: 0.1-1 mg/kg
PO q6-8h
>12 years: Administer as in adults
| Contraindications |
Documented hypersensitivity
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| Interactions |
Coadministration with aspirin
increases risk of inducing serious NSAID-related side effects;
probenecid may increase concentrations and, possibly, toxicity of
NSAIDs; may decrease effect of hydralazine, captopril, and
beta-blockers; may decrease diuretic effects of furosemide and
thiazides; may increase PT when taking anticoagulants (instruct
patients to watch for signs of bleeding); may increase risk of
methotrexate toxicity; phenytoin levels may be increased when
administered concurrently
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| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
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| Precautions |
Category D in third trimester of
pregnancy; caution in congestive heart failure, hypertension, and
decreased renal and hepatic function; caution in coagulation
abnormalities or during anticoagulant therapy | | 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.
Drug Name
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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.
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| Adult Dose |
325-650 mg PO q4-6h or 1000 mg
tid/qid; not to exceed 4 g/d
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| Pediatric Dose |
<12 years: 10-15 mg/kg/dose PO
q4-6h prn; not to exceed 2.6 g/d
>12 years: 325-650 mg PO
q4h; not to exceed 5 doses in 24 h
| Contraindications |
Documented hypersensitivity; known
G-6-PD deficiency
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| Interactions |
Rifampin can reduce analgesic
effects of acetaminophen; coadministration with barbiturates,
carbamazepine, hydantoins, and isoniazid may increase hepatotoxicity
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| Pregnancy |
B - Usually safe but benefits must
outweigh the risks.
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| Precautions |
Hepatotoxicity possible in chronic
alcoholic patients following various dose levels; severe or
recurrent pain or high or continued fever may indicate a serious
illness; APAP is contained in many OTC products and combined use
with these products may result in cumulative APAP doses exceeding
recommended maximum dose | |
Drug Name
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Hydrocodone and acetaminophen
(Lorcet-HP, Lortab, Norcet, Vicodin, Margesic) -- Drug combination
indicated for moderate to severe pain.
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| Adult Dose |
1-2 tab or cap PO q4-6h prn pain
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| Pediatric Dose |
<12 years: 10-15 mg/kg/dose
acetaminophen PO q4-6h prn; not to exceed 2.6 g/d
acetaminophen
>12 years: 750 mg acetaminophen PO q4h; not
to exceed 10 mg hydrocodone bitartrate per dose or 5 doses/24 h
| Contraindications |
Documented hypersensitivity; high
altitude cerebral edema (HACE) or elevated intracranial pressure
(ICP)
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| Interactions |
Coadministration with
phenothiazines may decrease analgesic effects; toxicity increases
with CNS depressants or tricyclic antidepressants
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| Pregnancy |
C - Safety for use during pregnancy
has not been established.
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| Precautions |
Tablets contain metabisulfite,
which may cause hypersensitivity; caution in patients dependent on
opiates since this substitution may result in acute
opiate-withdrawal symptoms; caution in severe renal or hepatic
dysfunction | |
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FOLLOW-UP |
Section 8 of 10 |
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Further Outpatient Care:
- The average time to recurrence is typically less than 2 years, but
it has been reported up to 19 years after the initial tumor presentation
(Zillmer, 1989; Gherlinzoni, 1983; Heydemann, 1985; Mikulowski, 1971).
Patients should be tracked 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 feel that cases of CMF reported as
“malignant transformation” have not been documented sufficiently and
more likely represent a misdiagnosis of chondrosarcoma.
Prognosis:
- Patients generally are cured by en bloc excision and have about a
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.
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BIBLIOGRAPHY |
Section 10 of
10 |
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- Cabral CE, Romano S, Guedes P, et al: Chondromyxoid fibroma of the
lumbar spine. Skeletal Radiol 1997 Aug; 26(8): 488-92[Medline].
- Dahlin DC: Chondromyxoid fibroma of bone, with emphasis on its
morphological relationship to benign chondroblastoma. Cancer 1956; 9(1):
195-203.
- Durr HR, Lienemann A, Nerlich A, et al: Chondromyxoid fibroma of
bone. Arch Orthop Trauma Surg 2000; 120(1-2): 42-7[Medline].
- Gherlinzoni F, Rock M, Picci P: Chondromyxoid fibroma. The
experience at the Istituto Ortopedico Rizzoli. J Bone Joint Surg Am 1983
Feb; 65(2): 198-204[Medline].
- Granter SR, Renshaw AA, Kozakewich HP, Fletcher JA: The
pericentromeric inversion, inv (6)(p25q13), is a novel diagnostic marker
in chondromyxoid fibroma. Mod Pathol 1998 Nov; 11(11): 1071-4[Medline].
- Heydemann J, Gillespie R, Mancer K: Soft tissue recurrence of
chondromyxoid fibroma. J Pediatr Orthop 1985 Nov-Dec; 5(6): 725-7[Medline].
- Jaffe HL, Lichtenstein L: Chondromyxoid fibroma of bone: A
distinctive benign tumor likely to be mistaken especially for
chondrosarcoma. Arch Path 1943; 19: 541-551.
- Kyriakos M: Soft tissue implantation of chondromyxoid fibroma. Am J
Surg Pathol 1979 Aug; 3(4): 363-72[Medline].
- Marin C, Gallego C, Manjon P, Martinez-Tello FJ: Juxtacortical
chondromyxoid fibroma: imaging findings in three cases and a review of
the literature. Skeletal Radiol 1997 Nov; 26(11): 642-9[Medline].
- McGrory BJ, Inwards CY, McLeod RA, Sim FH: Chondromyxoid fibroma.
Orthopedics 1995 Mar; 18(3): 307-10[Medline].
- Merine D, Fishman EK, Rosengard A, Tolo V: Chondromyxoid fibroma of
the fibula. J Pediatr Orthop 1989 Jul-Aug; 9(4): 468-71[Medline].
- Mikulowski P, Ostberg G: Recurrent chonromyxoid fibroma. Acta Orthop
Scand 1971; 42(5): 385-90[Medline].
- Nielsen GP, Keel SB, Dickersin GR, et al: Chondromyxoid fibroma: a
tumor showing myofibroblastic, myochondroblastic, and chondrocytic
differentiation. Mod Pathol 1999 May; 12(5): 514-7[Medline].
- Ralph LL: Chondromyxoid fibroma of bone. J Bone and Joint Surg 1962;
44B(1): 7-24.
- Schutt PG, Frost HM: Chondromyxoid fibroma. Clin Orthop 1971; 78:
323-9[Medline].
- White PG, Saunders L, Orr W, Friedman L: Chondromyxoid fibroma.
Skeletal Radiol 1996 Jan; 25(1): 79-81[Medline].
- Wu CT, Inwards CY, O'Laughlin S, et al: Chondromyxoid fibroma of
bone: a clinicopathologic review of 278 cases. Hum Pathol 1998 May;
29(5): 438-46[Medline].
- Wu KK: Chondromyxoid fibroma of the foot bones. J Foot Ankle Surg
1995 Sep-Oct; 34(5): 513-9[Medline].
- Yamaguchi T, Dorfman HD: Radiographic and histologic patterns of
calcification in chondromyxoid fibroma. Skeletal Radiol 1998 Oct;
27(10): 559-64[Medline].
- Zillmer DA, Dorfman HD: Chondromyxoid fibroma of bone: thirty-six
cases with clinicopathologic correlation. Hum Pathol 1989 Oct; 20(10):
952-64[Medline].
| NOTE:
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| Medicine is a constantly
changing science and not all therapies are clearly established. New
research changes drug and treatment therapies daily. The authors,
editors, and publisher of this journal have used their best efforts
to provide information that is up-to-date and accurate and is
generally accepted within medical standards at the time of
publication. However, as medical science is constantly changing and
human error is always possible, the authors, editors, and
publisher or any other party involved with the publication of this
article do not warrant the information in this article is accurate
or complete, nor are they responsible for omissions or errors in the
article or for the results of using this information. The reader
should confirm the information in this article from other sources
prior to use. In particular, all drug doses, indications, and
contraindications should be confirmed in the package insert. FULL DISCLAIMER
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Chondromyxoid
Fibroma excerpt
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