Template:Bone and cartilage mass differential diagnosis

Disease Name	History & Symptoms	Physical Exam	Lab Findings	Imaging Findings	Histologic Findings	Genetic Studies
Adamantinoma	20-30 yo males Gradual dull bone pain at the tibial area	Leg swelling and tenderness	No specific lab findings	Well-demarcated, eccentric/epicenteric, expansile, osteolytic, cortical lesion on X ray Located at the tibial diaphysis Areas of lysis interspersed with areas of sclerosis Lack of periosteal reaction	Biphasic tumor Islands of epithelial cells found in a fibrous stroma Fibro-osseous component includes spindle cells Epithelial component includes nests of basaloid cells	p53 gene mutations CK14 +ve CK19 +ve
Ameloblastoma	30-50 yo patients Unerupted teeth Oral ulcers	Painless mandibular mass Lower jaw crepitus on palpation Facial deformity	No specific lab findings	Multilocualted, expansile "soap-bubble" lesion, with well demarcated borders on X ray Mixed solid and cystic pattern on MRI Thick irregular wall, often with papillary solid structures projecting into the lesion on MRI	Tall columnar cells with a palisaded nuclei and reverse polarization Subnuclear vacuolization Giant cells Subepithelial hyalinization	BRAF V600E
Aneurysmal bone cyst	10-20 yo patients Gradual onset of bone pain	Limb swelling, tenderness, and warmth Palpable lump Restricted range of motion	No specific lab findings	Sharply defined, expansile osteolytic lesion on CT Thin sclerotic margins Air-fluid levels Doughnut sign on bone scan	Bony trabeculae or osteoid tissue Osteoclast giant cells Benign spindle cells Blood-filled spaces of variable sizes	Translocation t(16;17)(q22;p13)
Unicameral bone cyst	10-20 yo patients Asymptomatic Pathologic fractures	Often unremarkable	No specific lab finding	Well defined geographic lucent lesions on Xray Sclerotic margin No periosteal reaction Thinning of the endosteum and pseudotrabeculation	Cysts contain clear serosanguineous fluid Fibrous membranous lining	TP53 mutations
Brown tumor	40-50 yo females History of hyperparathyroidism	Often unremarkable	Hyperparathyroidism	Well-defined, purely lytic lesions on X ray Little reactive bone lesion Solid, cystic, or mixed component on MRI	Fibrosis Giant cells with round to oval nuclei and nucleoli Elevated number of osteoblast and osteoclast	MEN1 gene RET oncogene
Chondroblastoma	<20 yo males Joint pain and muscle wasting	Bone tenderness and swelling	No specific lab finding	Well defined lucent lesions located at the epiphysis Lobulated margins with a thin sclerotic rim Internal calcifications Joint effusion	Abundant extracellular material Eosinophilic cytoplasm Calcifications surround cells nests Chickenwire appearance	S100+ve Vimentin +ve
Chondromyxoid fibroma	Progressive bone pain Bony swelling Restricted range of movement in affected limb	Bone tenderness and swelling	No specific lab finding	Metaphyseal region of long bones Lobulated, eccentric radiolucent lesion with a well defined sclerotic margin No periosteal reaction Presence of septations, pseudotrabeculation, and geographic bone destruction	Chondroid, myxoid, and fibrous tissue components Spindle cells or stellate cells in a myxoid or chondroid stroma Pseudolobulated architecture Lobules with hypocellular centers and hypercellular peripheries Scattered calcifications	SOX9 +ve
Chondrosarcoma	50-70 yo males Deep, achy, dull pain Night time bone pain Limited range of joints motion Pathologic fracture	Palpable bony lump or local mass effect	No specific lab finding	Lytic intralesional calcification Endosteal scalloping Moth eaten appearance Cortical remodelling, thickening and periosteal reaction	Bi-nucleation Nuclear atypia with a hypochromatic enlarged nucleo Infiltration of lamellar bone ("invasion") Increased cellularity	S-100 +ve Collagen II +ve
Desmoplastic fibroma	20 yo patients Painless, slowly growing mass	Palpable bony lump	No specific lab finding	Lytic bone lesions with geographic pattern of bone destruction on X ray Located at metaphysis of long bones Narrow zone of transition Non-sclerotic margins Internal pseudotrabeculation	Mature, bland fibroblasts Little cellularity, no pleomorphism Abundant collagenous stroma Thin walled, dilated vascular channels	CD117 Beta-catenin
Enchondroma	10-30 yo patients Asymptomatic Pathological fracture Maffuci syndrome and Ollier disease	Widening of the bone Limb-length discrepancy Angular deformity	No specific lab finding	Located in the medullary cavity at the metaphyseal region of the hand bones Small lytic lesions, sharply defined scalloped margin, and narrow zone of transition Expansion of the overlying cortex with rings and arcs of calcifications	Lobules of hyaline cartilage Surrounded by fibrous tissue and bone Bony extension into the cartilage Myxoid change, hypercellularity, and binucleation Calcification, endochondral ossification, and necrosis	Ki-MCM6
Ewing sarcoma	10-20 yo males Extreme bone pain Intermittent fever	Localized tenderness and swelling	Anemia and leukocytosis Increased sedimentation rate	Large, poorly marginated tumor, located at the metaphysis Destructive bone lesions on X ray "Onion-skin" periosteal reaction	Sheets of round, uniform, PAS +ve, small cells with a scant clear cytoplasm Round nuclei with indentations Homer-Wright rosettes Necrosis and hemorrhage Prominent vasculature and variable mitotic figures	EWS/FLI-1 fusion gene t(11;22)(q24;q12) CD99 +ve FLI-1 +ve
Fibrosarcoma	30-60 yo males Bone pain, progressive swelling, decreased range of motion Pathologic fracture Positive history of radiation exposure or bone infarct	Fixed, firm mass to a localized area of tenderness Neurologic or vascular defect	No specific lab finding	Highly destructive with a wide zone of transition Expansile large soft tissue mass extending from the bone Periosteal reaction is uncommon	Elevated mitotic activity Highly cellular fibroblastic proliferation Herring bone pattern and spindle cell lesions Long dark nuclei with increased granular chromatin Scant cytoplasm	Vimentin +ve
Fibrous dysplasia	10-20 yo patients Asymptomatic Incidental finding on imaging studies	Facial asymmetry, rib deformities, and leg-length discrepancy as late complication	No specific lab finding	Located at the craniofacial bones, ribs, and proximal femur Ground-glass matrix Completely lucent or bubbly cystic expansile benign lesion Well circumscribed with no periosteal reaction	Fibrocellular matrix of immature collagen Contains small irregularly shaped trabeculae of woven bone "Chinese characters" appearance Trabeculae not rimmed by osteoblasts Cartilaginous islands	GNAS1 gene
Giant cell tumor	20-30 yo female Bone pain and swelling Pathologic fracture Paget disease of bone	Localised bone tenderness	No specific lab finding	Epiphyses of the femur Solitary expansile eccentrically-placed lytic lesion Intratumoral hemorrhage present Tumor extends into the subchondral plate	Uniform and regular distribution of multinucleated giant cells and mononuclear stromal cells Hemorrhage, necrosis, and hemosiderin deposition Elevated mitotic figures	Acid phosphatase +ve Alpha-1-antitrypsin +ve Alpha-1-antichymotrypsin +ve Ki-67 +ve
Ossifying fibroma	1-5 yo children Asymptomatic Minority of cases may have bone pain, swelling, and pathological fractures	Painless, firm, swelling located at the anterior tibia Anterior bowing of the tibia	No specific lab finding	Well-circumscribed lesion Intracortical osteolysis Sclerotic band (osteoblastic rimming) Cortical expansion Homogeneous lesion matrix	Fibrous proliferation of polyhedral, round, or spindle cells Myxamatous matrix with calcifications Psammomatoid growth patterns	Over expression of Runx2
Osteoblastoma	20-30 yo males Gradual, dull, and achy pain Neurological deficit (cord compression)	Scoliosis and torticollis	No specific lab finding	Mainly located in the spine Expansile lytic lesions with a rim of reactive sclerosis Internal calcification Cortical destruction, surrounding sclerosis, and periostitis Secondary aneurysmal bone cyst	Trabeculae of woven and osteoid bones Surrounded by a single layer of osteoblasts Multiple osteoclasts Loose fibrovascular stroma Intralesional hemorrhage	p53 protein expression and high PCNA index.
Osteochondroma	< 20 yo males Asymptomatic found incidentally on imaging May have adjacent muscle soreness, pressure, or irritation with heavy exercising Pathological fractures	Hard, immobile, painless palpable mass Limited range of movements	No specific lab finding	Sessile or pedunculated lesion located at the metaphyseal region of the femur Cartilage cap Irregular subchondral bone Projecting away from the epiphysis	Composed of bone, cartilage, and perichondrium Pink fibrous capsule Normal bony trabeculae Absence of spindle cells	8q24.1 11p11-12
Osteoid osteoma	10-35 yo males Deep, constant, aching, localized bone pain Pain worse at night Pain relieved by aspirin	Restricted range of motion	No specific lab findings	Well circumscribed lucent cortical lesion located at the femur Less than 2 cm in diameter with cortical thickening Surrounded by reactive sclerosis Ovoid central region of mineralisation	Anastomosing bony trabeculae Sclerotic nidus of woven bone with variable mineralization Osteoblast rimming Highly vascularized, fibrous stroma	PTEN mutation
Osteosarcoma	10-20 yo males Bone pain and swelling Pathologic fracture History of Paget disease of bone or irradiation	Tender, warm, palpable mass Limited range of motion	No specific lab findings	Metaphyseal regions of femur and tibia Medullary and cortical bone destruction Wide zone of transition with a moth-eaten appearance Sunburst and codman triangle Tumor matrix ossification/calcification	Hemorrhage, fibrosis and cystic degeneration Areas of bone formation Poorly formed trabecular bone Cellular pleomorphism and mitoses	RB1 tumor suppressor gene
Plasmacytoma	55-60 yo males Back pain Pathological fracture Palpable vertebral mass	Palpable bony lump	Elevated monoclonal antibodies	Well-defined, “punched-out” lytic lesions Marked erosion, expansion, and destruction of bone cortex Thick ridging around the periphery “Soap bubble” appearance	Atypical plasma cells	Unregulated expression of cMYC with KRAS12V in T2 B cells
Eosinophilic Granuloma	5-10 yo males Local bone pain Failure to thrive Spontenously resolve	Localized swelling and tenderness	ESR may be elevated	Ill-defined border, cortical destruction with aggressive periostitis Punched out lytic lesions without sclerotic rim "Hole within a hole" sign Common locations include femur, skull, iliac bone, rib, vertebra	Langerhans cells histiocytes - key feature.	Elevated expression of p53, c-myc, and H-ras
Brodie abscess	5-15 yo males Nocturnal pain Rapid response to analgesics Mimics osteoid osteoma	Tender, localized and painful mass Limited range of motion	Leukocytosis Increased sedimentation rate	Lytic lesion often in an oval configuration Surrounded by thick dense rim of reactive sclerosis Lucent tortuous channel extending toward growth plate prior to physeal closure (pathognomonic) Common location is the epiphysis long axis of long bones	Neutrophils, lymphocytes and plasma cells with bone necrosis and reactive new bone formation	There are no genetic studies associated
Osteoma	20-35 yo females Facial pain and headache Related to familial syndromes (eg. Gardner syndrome)	Facial tenderness and cosmetic deformity	No specific lab findings	Well-defined, circumscribed mass with varying amounts of central lucency Lobulated mass occupying frontal or maxillary sinus Common location is facial skeletal bones	Presence of dense compact mature bone in paucicellular fibrous stroma.	APC gene mutation, present in multiple forms
Intraosseous lipoma	5-85yo, males Bone pain Incidental finding	Localized tender mass in affected limb	No specific lab findings	Benign-appearing osteolytic bone lesion with well-defined margins. Common location is the calcaneal bone, if found in long bones is located in the metaphysis	Mature adipocytes without admixed hematopoietic tissue or bony trabeculae	Translocation t(3;12)(q28;q14)
Enostosis	No age or gender predilection Asymptomatic Incidental finding	Often unremarkable	No specific lab findings	Bone-islands, typically less than 1 cm, "fingers" at the margins that blend with the surrounding trabeculae is a classic finding Common predilection for diaphysis of long bones, pelvis, spine and ribs	Dense cortical like bone complete with haversian canals located within the spongiosa	Associated mutation is LEMD3 gene
Chordoma	30-70 yo, no gender predilection Slow growing tumor, commonly found in caucasians Originate from embryonic remnants of the primitive notochord	Often unremarkable	No specific lab findings	Well-circumcised, lytic lesion with marginal sclerosis. Intratumoral calfications Distrubtion is along the axial skeleton Common locations, include: sacrococcygeal, spheno-occipital: 30-35% vertebral bodies	Cords and lobules of physaliferous (having bubbles or vacuoles) cells separated by fibrous septa with extensive myxoid stroma	Associated with the duplication of T gene
Bone metastasis	No age or gender predilection Often asymptomatic Initial presentation may be a pathological fracture	Often unremarkable	Increased serum calcium and alkaline phosphatase Increase in hydroxyproline excretion may also be present	Three-patterns may be observed: lytic, sclerotic, and mixed Morphological characteristics may vary: expansile, focal or diffuse Common locations, include: axial skeleton, and long bones	Stromal bone formation, descruction and ostoclast activation	Associated mutation will vary depending on primary tumor
Intraosseous ganglion	30-50, no gender predilection Mild localized pain Origin due to a synovial herniation Can be multiple or single	Often unremarkable	No specific lab findings	Subchondral radiolucent lesion without degenerative arthritis, often localized in the epiphyses of long bones (medial malleolus, femoral head, proximal tibia, carpal bones)	Uni-/multilocular cysts surrounded by a fibrous lining, containing gelatinous material	There are no genetic studies associated