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Introduction
  • When answering questions with regard to orthopaedic pathology it is very useful to have an understanding of the different differential groups. This topic is broken down into the following differentials by
    • Age
    • Location
    • Imaging
    • Tumor Grade
    • Histology
    • Treatment
Differentials by Age

Age 
Benign
Malignant
Infants and childres
(0 to 5 years)
 Osteomyelitis
 Osteofibrous dysplasia
 Metastatic rhabdomyosarcoma
 Metastatic rneuroblastoma
 Leukemia
Young patient
(10-40 years)

NOF
Osteoid osteoma
Giant cell tumor
ABC
UBC
Osteochondroma & MHE
Chondroblastoma
Fibrous dysplasia
Osteomyelitis
Eosinophillic granuloma

 Osteosarcoma
 Ewing's
 Desmoplastic fibroma
 Leukemia
 Lymphoma
Older patient
(40-80 years)
Enchondroma
Bone infarct
Bone island
Paget's disease
Hyperparathyroidism
 Metastatic bone disease
 Myeloma
 Lyphoma
 Chondrosarcoma
 MFH
 Secondary sarcoma (Paget's, irradiation)


Differential by Location

Location in Bone
Multiple lesions in Young Patient

EG
Fibrous dysplasia
Leukemia
Lymphoma
Hemangioendothelioma
Enchondroma / Olliers / Marfucci's
Osteochondroma / MHE
NOF / Jaffe-Campanacci syndrome

Multiple lesions in Older Patient 
Paget's
Metastatic bone disease
Multiple myeloma
Lymphoma 
Hyperparathyroidism
Bone infarcts
Epiphyseal / Subchondral Lesions

Chondroblastoma
Giant cell tumor
Clear cell chondrosarcoma

Surface Lesions

Osteochondroma / MHE 
Parosteal osteosarcoma
Periosteal osteosarcoma 
Periosteal chondroma

Post Traumatic Surface Lesions

Florid reactive periostitis
BPOP
Turret exostosis
Subungal exostosis

Location in Body
Sacrum in young patients (10-40)

Giant cell tumor
ABC
Ewing's
Osteosarcoma

Sacrum in older patients (40-80)

Chordoma
Metastasis
Myeloma
Lymphoma
Chondrosarcoma
MFH

Tibial lesions Adamantinoma
Osteofibrous dysplasia
Fibrous dysplasia
Osteomyelitis
Hand and Foot Intramedullary destructive lesions Enchondroma
Giant cell tumor
ABC
Giant cell reparative granuloma 
Metastatic carcinoma (only in older patients)



Imaging Differential

Radiographs
"Bubbly" lesion on xray  

NOF
ABC

UBC

Bone scan is cold Multiple myeloma
Melanoma
Well defined "punched out" lesion

Eosinophillic granuloma 
Giant Cell Tumor                                                                 Multiple myeloma



Differential by Grade

ORIGIN
BENIGN
LOW GRADE
HIGH GRADE
Bone tumors
Osteogenic Osteoid osteoma
Osteoblastoma
Parosteal osteosarcoma • Periosteal osteosarcoma 
• Intramedullary osteosarcoma
Chondrogenic Enchondroma
Osteochondroma
Chondroblastoma
Chondromyoid fibroma
Chondrosarcoma Dedifferentiated chondrosarcoma
Unknown origin • Giant cell tumor
• Histiocytoma
• Adamantinoma • Ewing's tumor
Fibrogenic • Nonossifying fibroma • Desmoplastic fibroma • Fibrosarcoma
Hematopoietic     • Multiple myeloma
• Lymphoma
• Leukemia
Vascular • Hemangioma   • Hemangioendothelioma
Notochordal     • Chordoma
Lipogenic • Lipoma    
Soft tissue tumors
Synovial • Giant cell tumor of tendon sheath x • Synovial sarcoma
• Malignant giant cell tumor of tendon sheath
Fibrogenic & Fibrohistiocytic • Fibroma
• Fasciitis (nodular or proliferative) 
• Fibrous histiocytoma
x

• Fibrosarcoma
• Myxofibrosarcoma
• Malignant fibrous histiocytoma

Lipogenic • Lipoma • Myxoid liposarcoma • Pleomorphic liposarcoma
Muscle tissue • Leiomyoma
• Rhabdomyoma
x • Leiomyosarcoma
• Rhabdomyosarcoma
Vascular • Hemangioma
• Lymphangioma
• Glomus tumor
x • Lymphangiosarcoma
• Hemangiosarcoma
Neurogenic • Neuroma (traumatic or Morton's)
• Neurilemoma (benign schwannoma)
• Neurofibroma (neurofibromatosis)
x • Malignant schwanoma
• PNET tumors




Differential by Histology

Histology
Bone marrow aspiration and biospy required for diagnosis and staging

• Lymphoma
• Ewings

Small round cell tumor

• Lymphoma
• Leukemia
• Ewing's sarcoma
• Metastatic carcinoma (small cell lung) 
• Rhabdomyosarcoma
• Neuroblastoma

Epithelial Glands seen on histology

• Synovial sarcoma (biphasic)
• Metastatic carcinoma
• Glomus tumor

Bimorphic histology

• Dedifferentiated chondrosarcoma
• Synovial sarcoma
• Osteosarcoma with chondroblastic features 

Multi-nucleated Giant cells present

• Giant cell tumor
• Chondroblastoma
• Aneurysmal bone cyst

Hemosiderin pigmentation

• NOF
• PVNS
• UBC

Immunostains
Leukocyte common antigen • Lymphoma
CD138 • Myeloma
CD99 • Ewing's
CD1A • EG
CD31 and 34 • DFSP
• Angiosarcoma
CD20 and CD45 (B cell) • Lymphoma
S100

• EG
• Chordoma
• Melanoma 
• Clear cell sarcoma
• Nerve sheath tumors (Schwanoma) 

Elastin • Elastofibroma
Keratin • Metastatic bone disease
• Synovial sarcoma
• Chordoma
• Epitheloid sarcoma
• Adamantinoma
Factor VIII • Angiosarcoma
Smooth muscle actin • Leiomyosarcoma
Desmin • Rhabdomyosarcoma
Myoglobin • Rhabdomyosarcoma
CK7 • Breast CA
• Lung CA
CK125 • Ovarian CA
CK20 • Colon CA
TTF1 • Lung CA
Vimentin

• synovial sarcoma, rhabodymosarcoma, and leiomyosarcoma

EMA • Synovial sarcoma


Differential by Treatment

NonOperative
Observation 
(if asymptomatic)
Fibrous dysplasia / osteofibrous dysplasia 
Enchondromas / Olliers / Marfucci's 
Osteochondroma /MHE
NOF / Jaffe-Campanacci
Paget's
Eosinophillic Granuloma
Lipoma (soft tissue)
Bisphosphonate therapy Metastatic bone disease (with wide resection and radiation) 
Myeloma (with chemotherapy) 
Paget's disease (with observation) 
Fibrous dysplasia (with observation)
Radiation alone Solitary myeloma
Chemotherapy alone Lyphoma
Multiple myeloma
Operative
Radiofrequency ablation Osteoid osteoma
Aspiration and Injection UBC
Curretage and Bone Grafting 
GCT
ABC 
Chondroblastoma
Chondromyxoid fibroma
Osteoblastoma
NOF(if symptomatic)
Marginal Resection

Periosteal chondroma
Neurilemoma (soft tissue) 
Nodular fasciitis (soft tissue) 
Epidermal inclusion cyst
Glomus tumor

Wide Resection Alone 

• Chondrosarcoma
• Parosteal osteosarcoma
• Chordoma
• Adamantinoma
• Squamous cell (if no mets)

Wide Resection + Irradiation

• Metastatic Bone Disease 
• Soft tissue sarcoma-high grade (angiosarcoma, synovial sarcoma, liposarcoma, desmoid tumor, MFH/fibrosarcoma)

Wide Resection + Chemotherapy

• Osteosarcoma
• Periosteal osteosarcoma
• Ewing's
• MFH / fibrosarcoma 
• Secondary sarcoma
• Dedifferentiated chondrosarcoma
• Rhabdomyosarcoma (exception to soft tissue sarcoma tx)


 
 

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