Bone & joints

Osteoclastic giant cell rich tumors


Nonossifying fibroma

Resident / Fellow Advisory Board: Josephine K. Dermawan, M.D., Ph.D.
Editorial Board Member: Jose G. Mantilla, M.D.
Saba Anjum, M.B.B.S.
Nasir Ud Din, M.B.B.S.

Last author update: 25 October 2021
Last staff update: 18 January 2022

Copyright: 2003-2023,, Inc.

PubMed Search: Nonossifying fibroma[TIAB]

Saba Anjum, M.B.B.S.
Nasir Ud Din, M.B.B.S.
Page views in 2022: 14,182
Page views in 2023 to date: 12,990
Cite this page: Anjum S, Chundriger Q, Ud Din N. Nonossifying fibroma. website. Accessed September 21st, 2023.
Definition / general
  • Benign fibrohistiocytic tumor arising in the metaphysis of long bones of skeletally immature individuals, composed of bland fibroblastic proliferation admixed with osteoclast-like giant cells
  • Local recurrence and malignant transformation are extremely rare
Essential features
  • Characteristic radiologic appearance (i.e. radiolucent eccentric location within the metadiaphysis of long bones with lobulated, well demarcated, sclerotic rim and scalloped borders)
  • Histologically exhibits bland spindle shaped fibroblasts arranged in storiform pattern with interspersed osteoclast-like giant cells
  • Metaphyseal fibrous defect
ICD coding
  • ICD-O: 8830/0 - Benign fibrous histiocytoma
  • ICD-11: 2E85.Y & XH06N0 - Benign fibrohistiocytic tumor of other specified sites and benign fibrous histiocytoma
  • ICD-11: 2E85.Y & XA5GG8 - Benign fibrohistiocytic tumor of other specified sites and bones
  • Accurate incidence is unknown because most of these lesions are asymptomatic and resolve spontaneously
  • Mostly arises in skeletally immature individuals, peaks in second decade of life
  • Up to 40% of children have an occult lesion (Chir Pediatr 1980;21:179)
  • Germline mutations resulting in activation of KRAS-MAPK pathway
  • Unknown in sporadic cases
Diagrams / tables

Contributed by Qurratulain Chundriger, M.B.B.S.

Schematic presentation

Clinical features
  • Requires integration of radiological and histopathological findings; diagnosis can be challenging on a small biopsy specimen (e.g. cytology or needle core)
Radiology description
Radiology images

Contributed by Nasir Ud Din, M.B.B.S. and AFIP images

Distal tibia

Proximal tibia

Proximal fibula

Femur with fracture


Nonossifying fibroma

Images hosted on other servers:

Radius (plain radiograph)

Radius (MRI)

Femur (plain radiograph)

Femur (CT scan)

Vertebral body


Growth stages

Prognostic factors
Case reports
Clinical images

Images hosted on other servers:

Lesion in clavicle

Gross description
  • Well circumscribed, red-brown with areas of yellow discoloration and having sclerotic borders (Niger Postgrad Med J 2018;25:126)
  • Cut surface is firm, can exhibit cystic, hemorrhagic and necrotic areas
Gross images

Images hosted on other servers:

Lesion in clavicle

Lesion in mandible

Microscopic (histologic) description
  • Bland, spindle shaped fibroblasts arranged in storiform pattern, interspersed with osteoclast-like multinucleated giant cells (Ear Nose Throat J 2015;94:E41)
  • Number of giant cells is much fewer than in giant cell tumor of bone
  • Some cases may resemble solid areas in aneurysmal bone cyst
  • Variable amount of foamy and hemosiderin laden macrophages (Head Neck Pathol 2013;7:203)
  • Cystic changes and areas of necrosis if associated with pathological fractures
  • Hemorrhage and inflammatory cells may also accompany necrosis associated with fracture
  • Areas of reactive woven bone formation may be seen (Spine (Phila Pa 1976) 2003;28:E359)
Microscopic (histologic) images

Contributed by Nasir Ud Din, M.B.B.S.

Circumscribed border on resection

Storiform arrangement

Interspersed giant cells

Few giant cells

Resembling ABC

Reactive woven bone

Aggregates of foamy macrophages

Hemorrhage and inflammatory cells

Necrosis after fracture

Virtual slides

Images hosted on other servers:
Hemorrhagic lesion with woven bone

Hemorrhagic lesion with woven bone

Nonossifying fibroma with fracture

Nonossifying fibroma with fracture

Cytology description
Cytology images

Images hosted on other servers:

Lesion in femur

Positive stains
Molecular / cytogenetics description

Bone and cartilage tumors

Sample pathology report
  • Left distal femur, curettage:
    • Benign spindle cell lesion with features consistent with nonossifying fibroma (see comment)
    • Comment: Correlation with radiological findings is essential.
Differential diagnosis
  • Giant cell tumor of bone:
    • Arises in epiphyses of long bones in adults
    • Uniform distribution of osteoclast type giant cells among mononuclear cells
    • Mononuclear cells in GCT are oval shaped and not spindled as seen in NOF
    • Giant cell nuclei are like mononuclear cell nuclei in GCT, which is not seen in NOF
    • Stromal mononuclear cells of GCT are positive for H3.3 G34W
    • GCT may have areas indistinguishable from NOF; positive staining of stromal cells for G34W will help resolve the issue
  • Benign fibrous histiocytoma:
    • Extremely rare, infiltrative lesion of soft tissue which causes destruction of adjacent bones, arising from primitive mesenchymal cells (Medicine (Baltimore) 2019;98:e17144)
    • Primary lesions of bone are even rarer, with cases reported to involve the spine and distal portions of long bones (J Bone Oncol 2018;12:78)
    • Fascicular and storiform growth of spindle cells with interspersed multinucleated giant cells resembles nonossifying fibroma microscopically
    • Extensive excision is required to prevent recurrence, which is common due to infiltrative growth (Medicine (Baltimore) 2019;98:e17144)
  • Solid aneurysmal bone cyst:
    • Arises in the metaphysis of long bones as expansile lytic lesion with circumscribed borders
    • Septal enhancement on contrast; fluid-fluid levels on MRI
    • Solid ABC often shows reactive woven bone formation within tumor and storiform pattern is not prominent
    • USP6 gene rearrangement by FISH, not detected in NOF
  • Fibrous dysplasia:
    • Common fibro-osseous lesion arises in long and craniofacial bones
    • Most cases are asymptomatic but may come to attention due to pain and fracture
    • Radiology shows diaphyseal or metadiaphyseal intramedullary sharply demarcated lesion with ground glass-like appearance, while NOF is eccentrically placed in metaphysis
    • Histology shows irregular curvilinear trabeculae of woven bone in a background of bland spindle cells
    • Multinucleated giant cells may be seen, along with myxoid change and foamy histiocytes but these are not a common feature
Board review style question #1

A 15 year old girl had a fall during marathon practice and sustained a fracture of the distal tibia. Radiological appearance is given in the picture above. Curettage was done and microscopic examination showed a lesion shown in the given photomicrograph. The most helpful feature for establishing the correct diagnosis in this case is

  1. Areas of chicken wire-like calcification surrounding the fibroblasts
  2. Curvilinear trabeculae of woven bone in background of spindle cells
  3. Linear trabeculae of woven bone surrounded by osteoblasts
  4. Pools of hemorrhage surrounded by multinucleated giant cells
  5. Storiform growth of bland spindle cells with scattered giant cells
Board review style answer #1
E. Storiform growth of bland spindle cells with scattered giant cells. The photomicrograph shows a tumor comprised of bland spindle cells growing in a storiform pattern. There are scattered multinucleated giant cells within the tumor. These findings are characteristic of nonossifying fibroma (NOF). The fact that the lesion was asymptomatic and caused pathological fracture due to trauma is another supportive feature in this case. Curvilinear trabeculae of woven bone are a feature of fibrous dysplasia of bone. Linear trabeculae of woven bone may be seen in some cases of NOF but they are not diagnostic of this lesion, per se. Similarly, pools of hemorrhage can be seen in cases of NOF secondary to an associated fracture. This feature, however, is a diagnostic primary finding of an aneurysmal bone cyst.

Comment Here

Reference: Nonossifying fibroma
Board review style question #2
Which of the following genetic mutations has been found to be common in nonossifying fibroma?

  1. BRAF
  2. GNAS
  3. H3F3B
  4. KRAS
  5. TBXT
Board review style answer #2
D. KRAS mutations are seen in up to 80% of nonossifying fibromas. GNAS mutations are a feature of fibrous dysplasia of bone. H3F3B is mutated in chondroblastoma and mutations involving TBXT are a feature of notochordal tumors. USP6 mutations are commonly seen in cases of aneurysmal bone cyst and nodular fasciitis in soft tissues.

Comment Here

Reference: Nonossifying fibroma
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