Table of Contents
Definition / general | Essential features | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnosis | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Videos | Sample pathology report | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Chundriger Q, Ud Din N. Chondromyxoid fibroma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonechondromyxoidfibroma.html. Accessed October 3rd, 2023.
Definition / general
- Benign cartilaginous tumor of young adults, arising in proximal or distal parts of long bones, showing zonal architecture
- Local recurrence is common; malignant transformation is extremely rare
Essential features
- Characteristic radiologic appearance; i.e. eccentric lytic lesion with sharp, sclerosed and scalloped intramedullary edges
- Histologically, zonal architecture comprised of lobules of myxoid to chondroid tissue with intervening spindle and multinucleated giant cells, showing variable coarse calcifications
- Complete surgical resection is the treatment of choice, with chances of recurrence following simple curettage but no potential for distant metastasis
ICD coding
- ICD-O: 9241/0 - chondromyxoid fibroma
- ICD-11: 2E82.Z & XH89S0 - benign chondrogenic tumors, site unspecified and chondromyxoid fibroma
Epidemiology
- Rare, benign chondroid tumor
- Wide age range but mostly arises in young adults in second and third decades of life and more commonly in males (J Bone Joint Surg Am 1983;65:198, Hum Pathol 1998;29:438)
Sites
- Most common:
- Long tubular bones; most frequently distal femur and proximal tibia
- Less common:
- Small bones of hands and feet, pelvis, sacrum, spine, et cetera (J Cytol 2018;35:67, Surg Neurol Int 2016;7:S370)
- Skull bones (Cureus 2019;11:e5841, Indian J Ophthalmol 2019;67:2110, Acta Oncol 2005;44:545)
Pathophysiology
- Upregulation of glutamate receptor gene GRM1 coding region of chromosome 6 through recombination with several partner genes in up to 90% of cases (Nat Genet 2014;46:474)
Etiology
- Unknown
Clinical features
- Long bones: present with pain, often of long duration (Korean J Radiol 2011;12:761)
- Flat bones and small bones: swelling sometimes accompanied by pain (Iran J Pathol 2016;11:272, J Clin Diagn Res 2016;10:ED01)
Diagnosis
- Requires integration of radiological and histopathological findings
- Diagnosis can be challenging on a small biopsy specimen (e.g. cytology or needle core)
Radiology description
- Long bones:
- Eccentric, lytic, radiolucent metaphyseal lesions with well demarcated sclerosed and scalloped intramedullary edges; rarely crosses a growth plate
- Associated secondary aneurysmal bone cysts may be seen
- Internal mineralization is better seen with CT as compared with conventional radiology (Br J Radiol 2016;89:20160088)
- CT shows isointense or hypointensity on T1 images, heterogeneous hyperintensity on T2 images (Br J Radiol 2016;89:20160088, World J Surg Oncol 2014;12:283)
- Increased uptake on fluorodeoxyglucose PET (Clin Nucl Med 2009;34:15)
- Small and flat bones:
- Lytic lesions are expansile, loculated and locally destructive
- Lesions in ribs may appear fusiform with thinned out overlying cortices (J Clin Diagn Res 2015;9:XD04)
- Sacral and spinal lesions may appear malignant radiologically with cortical breaks and extension into adjacent soft tissue and spinal canal (Surg Neurol Int 2016;7:S370, Br J Radiol 2016;89:20160088)
Radiology images
Prognostic factors
- Around 15% cases may recur, mostly following simple curettage rather than total resection (World J Surg Oncol 2014;12:283)
- Malignant transformation can occur after radiation therapy
Case reports
- 13 year old girl with painful knee swelling (Tunis Med 2017;95:999)
- 16 year old boy with headache, diplopia and dizziness (Medicine (Baltimore) 2017;96:e9049)
- 47 year old woman with swelling of left side of face (J Educ Health Promot 2017;6:78)
- 63 year old woman with chest pain and swelling (Tex Heart Inst J 2015;42:400)
Treatment
- En bloc resection of the tumor is the treatment of choice
- In cases where complete resection is not possible, radiation following surgery may be helpful (Acta Oncol 2005;44:545)
- Instances of complete tumor disappearance following radiofrequency ablation have been described (J Orthop Surg (Hong Kong) 2017;25:2309499017720830)
Clinical images
Gross description
- Lobulated tumor mass with intact periosteum
- Cut surface is firm, glistening with variable myxoid areas (J Clin Diagn Res 2015;9:XD04)
- Calcifications may not be seen grossly
Microscopic (histologic) description
- Lobulated architecture; lobules separated by mononuclear spindle cells and admixed multinucleated giant cells
- Lobules have hypocellular centers and hypercellular periphery
- Variably myxoid to chondroid stroma, representing various stages of cartilaginous development (Hum Pathol 1998;29:438)
- Lobules have stellate cells in a myxoid background and reside in lacunae in chondroid areas (Am J Clin Pathol 2001;116:271)
- Cells have variable pink cytoplasm, bipolar to multipolar cytoplasmic extensions and oval to spindled nuclei
- Marked nuclear pleomorphism with nucleoli may be seen in some cases
- Periphery of lobules show spindle shaped fibroblast-like cells and scattered multinucleated osteoclast-like giant cells
- Low mitotic rate
- Coarse calcifications may be seen in the stroma, particularly in tumors arising in older age group and unusual sites (Skeletal Radiol 1998;27:559)
- Hemosiderin deposition and lymphocytes may be seen
- Necrosis, cystic change or degenerative changes are rare
- 10% of cases may show associated areas of aneurysmal bone cyst-like appearance (Hum Pathol 1998;29:438)
Microscopic (histologic) images
Cytology description
- Smears are moderately cellular, having fragments of fibrillary myxochondroid tissue, which stains metachromatically (Diagn Cytopathol 2013;41:904)
- Fragments of spindle cells and variable numbers of osteoclast-like giant cells are seen (Iran J Pathol 2016;11:272)
- Nuclear atypia may be variable and result in malignant interpretation
- Calcification may not be seen in cytology smears
Cytology images
Positive stains
- Chondromyxoid fibroma does not require immunohistochemistry for diagnosis
- S100 and SOX9: positive in the cells within chondroid lobules (Hum Pathol 1989;20:952)
- SMA: spindle cells at the periphery of lobules may show some degree of positivity
Negative stains
- CD34
- RUNX2 (Mod Pathol 2012;25:1452)
- Cytokeratins
Electron microscopy description
- Cells show cytoplasmic processes, intracytoplasmic glycogen and thickening of the nuclear membrane
Molecular / cytogenetics description
- Not required for reaching diagnosis
- GRM1 upregulation is highly specific for chondromyxoid fibroma
Videos
Cartilage forming tumors
Sample pathology report
- Left knee and proximal tibia, curettage:
- Benign cartilaginous tumor with features favoring chondromyxoid fibroma (see comment)
- Comment: Correlation with radiological findings is essential.
Differential diagnosis
- Central chondrosarcoma:
- Radiographically destructive, osteolytic lesion with invasion into adjacent bone and soft tissue, moth eaten appearance and foci of calcifications
- Histologically infiltrative lobules of cartilage with variable degree of cellularity and nuclear atypia
- Characterized by IDH mutations
- Chondroblastoma:
- Arises mostly in young patients with immature skeleton
- Epiphyseal location is characteristic
- Islands of mononuclear cells with distinct cell borders, characteristic grooved nuclei; scattered cells may appear epithelioid
- Chicken wire-like calcifications are characteristic
- Harbors mutations of H3.3 (H3F3B gene) on chromosome 17
- Osteochondromyxoma:
- Extremely rare chondroid and osteoid matrix producing benign myxoid tumor, occurring in association with Carney complex
- Tumor arises in the diaphysis of radius and tibia and nasal bone
- Variably cellular tumor of polygonal bipolar to stellate cells arranged in sheets and lobules along with osteoid and chondroid matrix present in myxoid stroma
- Lacks GRM1 upregulation and other chromosome 6 aberrations; instead harbors mutations of PRKAR1A at chromosome 17
- Aneurysmal bone cyst:
- Lytic expansile lesion on radiology with variable fluid levels on MRI
- Composed of cystic blood filled spaces lined by osteoclast-like giant cells
- Solid areas show spindle cell proliferation with blue bone formation
- May be associated morphological finding in a number of benign and malignant bone and cartilaginous tumors
- Giant cell tumor:
- Arises in epiphyses of long bones in adults
- Uniform distribution of osteoclast type giant cells among mononuclear cells
- Shows positive staining for RUNX2, SATB2, H3.3 (G34W)
- Excellent response to denosumab (RUNX ligand inhibitor)
Additional references
Board review style question #1
A 25 year old woman presented with painful swelling of the right knee. Radiology shows a lytic lesion with sclerotic intramedullary margins in the metaphysis of proximal fibula. En bloc resection of tumor was done and microscopy showed the above picture. Which of the statements regarding this entity is true?
- Denosumab is a newly developed drug for nonsurgical treatment
- Diagnosis does not require correlation with radiology
- Most cases of this tumor present clinically as painless masses
- Presence of adjacent aneurysmal bone cyst-like areas is unlikely
- This tumor shows various stages of cartilaginous development
Board review style answer #1
E. This tumor shows various stages of cartilaginous development. The photomicrograph shows a tumor comprised of lobules of myxoid to chondroid appearance with adjacent mononuclear cell population and some osteoclast-like giant cells. These findings are characteristic of chondromyxoid fibroma, which is also suggested by clinical and radiological appearances. The myxochondroid lobules of chondromyxoid fibroma represent various stages of cartilaginous development, from myxoid mesenchyme to well developed hyaline cartilage. Diagnosis always requires radiological correlation, which shows characteristic eccentric lytic lesion in the metaphyseal region of long bones. Painful mass is a common clinical presentation. Adjacent aneurysmal bone cyst-like areas may be seen in up to 10% of cases. Denosumab is a RUNX ligand inhibitor, recently developed for the treatment of giant cell tumor of bone.
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Reference: Chondromyxoid fibroma
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Reference: Chondromyxoid fibroma
Board review style question #2
Board review style answer #2
A. GRM1 upregulation. USP6 rearrangements are seen in aneurysmal bone cysts. IDH1 mutations are characteristic of chondrosarcoma. H3F3B is mutated in chondroblastoma and PRKAR1A mutations are seen in osteochondromyxoma in the setting of Carney complex.
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Reference: Chondromyxoid fibroma
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Reference: Chondromyxoid fibroma