Citation, DOI, disclosures and article data
At the time the article was created Frank Gaillard had no recorded disclosures.View Frank Gaillard's current disclosures
At the time the article was last revised Craig Hacking had the following disclosures:
- Philips Australia, Paid speaker at Philips Spectral CT events (ongoing)
These were assessed during peer review and were determined to not be relevant to the changes that were made.View Craig Hacking's current disclosures
Non-ossifying fibromas (NOF) are benign and generally self-limiting osteoclastic giant cell-rich bone tumors typically found in the metaphyses of long bones. They are classified as osteoclastic giant cell-rich bone tumors 1,2.
NOFs account for the 'N' in the popular mnemonic for lucent bone lesions FEGNOMASHIC.
On this page:
The terms ‘fibrous cortical defect’ (confined to the cortex), ‘metaphyseal fibrous defect’ or ‘benign fibrous histiocytoma' are no longer recommended 1.
Non-ossifying fibromas are very common in children and adolescents and are considered the most common benign tumor 1-5. The true incidence of non-ossifying fibromas is not known because most lesions are not detected due to the absence of clinical symptoms and the benign natural history of the lesions 1. Their frequency has been estimated at around 30-40% of all normal children with a peak in the second decade 1-4. They are about twice as common in boys than in girls 1,3. They are usually not seen beyond the age of 30 as they heal spontaneously after puberty and ossify gradually 2-5.
Non-ossifying fibromas have been found in association with the following 1,3:
The diagnosis of non-ossifying fibromas is mainly based on characteristic radiographic or imaging features 1. They are considered as ‘do not touch’ or ‘leave me alone lesions’ 4.
Diagnostic criteria according to the WHO classification of soft tissue and bone tumors (5th edition) 1:
The essential feature is:
bone tumor with typical imaging findings
The following additional criteria are desirable:
metaphyseal location in long bones in skeletally immature individuals
storiform proliferation of plump spindle cells
interspersed giant cells, haemosiderophages and clusters of foamy histiocytes
Non-ossifying fibromas are usually asymptomatic 1,2 and incidentally found in imaging studies 3. Larger tumors can have an impact on the biomechanical properties of the affected bone and cause pain 1.
Non-ossifying fibromas might cause a pathological fracture if large.
Non-ossifying fibromas are benign spindle cell tumors of bone containing osteoclast-like giant cells 1-3.
They are biologically active and can grow initially become more polycyclic and regress after puberty filling up gradually with bone from the diaphyseal side 3.
The irony of non-ossifying fibromas appearing to ossify has not been lost on generations of radiologists, although strictly speaking the lesion itself does not ossify, rather being filled in by normal bone from the periphery 4.
Indeed, it is believed that many bone islands are healed non-ossifying fibromas ref.
The etiology of sporadic non-ossifying fibromas is not known 1. They might occur in the background of germline mutations resulting in the RAS-MAPK pathway 5 or postzygotic mutations in neurofibromatosis type 1 or Jaffe-Campanacci syndrome 1.
Most non-ossifying fibromas are found in the metaphysis of long bones of the lower extremities such as the distal femur and the distal lateral and proximal medial tibia 1,2,6. They can also occur at multiple locations 1,3.
Non-ossifying fibromas are far less common in the mandible or the flat pelvic bones in the mandible 7 and might then represent a giant cell tumor of bone with regressive changes 1.
Macroscopically non-ossifying fibromas have been described as usually well-circumscribed reddish-brown tumors with yellowish areas and sclerotic borders. They have a firm cut surface and can display cystic areas and hemorrhagic or necrotic changes, especially in the setting of pathologic fracture 1.
Histologically non-ossifying fibromas are characterized by the following 1,2,6:
arrangement of spindle-shaped cells in a storiform pattern
diffusely scattered osteoclast-like giant cells
focal cystic changes and reactive bone formation
Non-ossifying fibromas show mutations in KRAS and FGFR1 genes in > 80% of cases 1,2,5.
Plain radiograph / CT
Characteristic radiographic appearances of non-ossifying fibromas include 3,4:
polycyclic, multiloculated, lucent lesion
eccentrically located in the metaphysis near the physis
long axis parallel to the axis of the bone
thin sclerotic rim
with increasing age, they seem to migrate away from the physis 6
The natural course of non-ossifying fibromas can be radiographically classified by the Ritschl stages 3,4,8 of which the duration seems to be variable 3:
eccentric bone lesion near the growth plate
small oval with smooth outlines and no sclerotic border
variable distance from the growth plate
progressively polycyclic shape
thin sclerotic border, thin sometimes protruding cortex
no periosteal reaction
stage C: progressively sclerotic with ossification beginning at the diaphysis
stage D: homogeneous sclerosis or disappearing lesion
MRI appearances of non-ossifying fibromas are variable and depend on when along with the development and healing phase the lesion is imaged.
Initially, the lesion has a high or intermediate T2 signal, with a peripheral low signal rim corresponding to the sclerotic border. As it matures and begins to ossify, the signal becomes low on all sequences 9,10. They might show septa of variable signal intensity.
Contrast enhancement is also variable 9,11.
T1: low signal intensity
initially heterogeneously high or intermediate signal with a low signal peripheral rim
later low signal intensity
T1 C+ (Gd): variable
Appearance on bone scan depends on the phase of the lesion:
non-ossifying fibromas are usually not associated with increased activity
mild to moderately increased activity can be seen during non-ossifying fibroma "healing", corresponding to mild hyperemia and osteoblastic activity
note that extensive uptake or hyperemia should prompt consideration of a superimposed fracture or alternative diagnosis 12
The radiological report should include a description of the following 13:
location and size
tumor margins and transition zone
relation to the growth plate
degree of sclerosis
Treatment and prognosis
Non-ossifying fibromas are considered as “leave alone” or “do not touch” lesions.
Due to their benign self-limiting natural history, they do not require biopsy or follow-up in the setting of characteristic imaging features 1.
As long as biomechanical stability is not affected they do not require treatment. If they are large (involving >50% of the diameter of the parent bone) then prophylactic curettage and bone grafting may be prudent to avoid a pathological fracture 1. Recurrence is rare and malignant transformations have not been reported 1.
History and etymology
Non-ossifying fibromas were first described by the American bone pathologists Henry Louis Jaffe and Louis Lichtenstein in 1942 3,14.
Non-ossifying fibromas have been also known as fibroxanthoma in the past a term considered synonymous with 'benign fibrous histiocytoma' (see above) and rarely used nowadays 15.
General imaging differential considerations include:
aneurysmal bone cyst (solid version)
eccentric lytic metaphyseal lesion
MRI differentiates aneurysmal bone cysts by fluid-fluid levels
- 1. WHO Classification of Tumours Editorial Board. WHO Classification of Tumours, 5th Edition. Soft Tissue and Bone Tumours. (2020) ISBN: 9789283245025 - IARC Publications
- 2. Choi J & Ro J. The 2020 WHO Classification of Tumors of Bone: An Updated Review. Adv Anat Pathol. 2021;28(3):119-38. doi:10.1097/PAP.0000000000000293 - Pubmed
- 3. Herget G, Mauer D, Krauß T et al. Non-Ossifying Fibroma: Natural History with an Emphasis on a Stage-Related Growth, Fracture Risk and the Need for Follow-Up. BMC Musculoskelet Disord. 2016;17(1):147. doi:10.1186/s12891-016-1004-0 - Pubmed
- 4. Błaż M, Palczewski P, Swiątkowski J, Gołębiowski M. Cortical Fibrous Defects and Non-Ossifying Fibromas in Children and Young Adults: The Analysis of Radiological Features in 28 Cases and a Review of Literature. Pol J Radiol. 2011;76(4):32-9. PMC3389949 - Pubmed
- 5. Bovée J & Hogendoorn P. Non-Ossifying Fibroma: A RAS-MAPK Driven Benign Bone Neoplasm. J Pathol. 2019;248(2):127-30. doi:10.1002/path.5259 - Pubmed
- 6. Goldin A, Muzykewicz D, Dwek J, Mubarak S. The Aetiology of the Non-Ossifying Fibroma of the Distal Femur and Its Relationship to the Surrounding Soft Tissues. J Child Orthop. 2017;11(5):373-9. doi:10.1302/1863-2548.11.170068 - Pubmed
- 7. Bowers L, Cohen D, Bhattacharyya I, Pettigrew J, Stavropoulos M. The Non-Ossifying Fibroma: A Case Report and Review of the Literature. Head Neck Pathol. 2013;7(2):203-10. doi:10.1007/s12105-012-0399-7 - Pubmed
- 8. Ritschl P, Karnel F, Hajek P. Fibrous Metaphyseal Defects--Determination of Their Origin and Natural History Using a Radiomorphological Study. Skeletal Radiol. 1988;17(1):8-15. doi:10.1007/BF00361448 - Pubmed
- 9. Jee W, Choe B, Kang H et al. Nonossifying Fibroma: Characteristics at MR Imaging with Pathologic Correlation. Radiology. 1998;209(1):197-202. doi:10.1148/radiology.209.1.9769832 - Pubmed
- 10. Stacy G & Dixon L. Pitfalls in MR Image Interpretation Prompting Referrals to an Orthopedic Oncology Clinic. Radiographics. 2007;27(3):805-26; discussion 827-8. doi:10.1148/rg.273065031 - Pubmed
- 11. Dumitriu D, Menten R, Clapuyt P. Pitfalls in the Diagnosis of Common Benign Bone Tumours in Children. Insights Imaging. 2014;5(6):645-55. doi:10.1007/s13244-014-0356-y - Pubmed
- 12. Hod N, Levi Y, Fire G et al. Scintigraphic Characteristics of Non-Ossifying Fibroma in Military Recruits Undergoing Bone Scintigraphy for Suspected Stress Fractures and Lower Limb Pains. Nucl Med Commun. 2007;28(1):25-33. doi:10.1097/MNM.0b013e328012e3de - Pubmed
- 13. Chang C, Garner H, Ahlawat S et al. Society of Skeletal Radiology- White Paper. Guidelines for the Diagnostic Management of Incidental Solitary Bone Lesions on CT and MRI in Adults: Bone Reporting and Data System (Bone-RADS). Skeletal Radiol. 2022. doi:10.1007/s00256-022-04022-8 - Pubmed
- 14. Jaffe H & Lichtenstein L. Non-Osteogenic Fibroma of Bone. Am J Pathol. 1942;18(2):205-21. PMC2032933 - Pubmed
- 15. Bauer T. Letter to the Editor: Fibroxanthoma: A Complication of a Biodegradable Screw. Clin Orthop Relat Res. 2011;469(1):300-1; author reply 302. doi:10.1007/s11999-010-1601-4 - Pubmed