Fibrous, Fibrohistiocytic, and Giant Cell Tumor Malignancies

Hannah D. Morgan

Fibrosarcoma, malignant fibrous histiocytoma (MFH) of bone, and malignancy in giant cell tumor (GCT) are three relatively rare bone sarcomas that tend to be of high grade. All are found primarily around the knee. MFH and malignancy in GCT of bone may be primary or secondary malignancies. Malignancy in GCT is the current World Health Organization (WHO) terminology for what has also been referred to as malignant giant cell tumor or dedifferentiated giant cell tumor. MFH is now referred to as pleomorphic sarcoma not otherwise specified (NOS) as it is thought to
represent a final common pathway toward dedifferentiation for many sarcomas.

Pathogenesis

Etiology

Fibrosarcoma
- Malignant spindle cell tumor with fibroblastic differentiation and a collagenous intercellular background
MFH
- Malignant mesenchymal neoplasm of histiocytic origin
- 72% primary; 28% secondary
- Conditions associated with secondary form: bone infarction, fibrous dysplasia, intraosseous lipoma, Paget’s disease, prolonged steroid use, hematopoietic malignancy, history of radiation therapy, and possibly presence of metallic orthopaedic implant (controversial)
Malignancy in GCT
- Primary malignancy in GCT: high-grade sarcoma arising beside or within a conventional GCT of bone
- Secondary malignancy in GCT: high-grade sarcoma arising at the site of a previously treated conventional GCT (either with surgery alone or with radiation therapy); tumors often multiply recurrent prior to diagnosis of malignancy

Epidemiology

Fibrosarcoma
- <5% of malignant bone tumors; may be lower as more cases are diagnosed as fibroblastic osteosarcoma or MFH
- Male:female 1:1
- Most patients second through seventh decade
- Arises in metaphysis, most commonly around the knee
MFH
- <2% of malignant bone tumors
- Male:female 3:2
- All ages affected, but majority >40 years old
- 75% affect ends of long tubular bones; 50% about the knee
Malignant GCT
- Very rare: 1% to 2% of all GCT of bone
- Primary malignant GCT: male > female
- Secondary malignant GCT: male:female 1:1
- Average age: 45 to 50 years
- Secondary malignant GCTs
  - Typically occur >3 years after treatment of original tumor
  - Average latent period: 9 years
- Majority of tumors occur about knee, as for benign GCT of bone.