Lecture 13: Bone Tumors

Osteomas

Skull & facial bones

Young adults or middle years

Solitary

Multiple osteomas → Gardner syndrome

Multiple colon polyps at young age → carcinoma

Familial; APC gene mutation

Benign, slow growing tumor

Asymptomatic but symptoms related to nerve impingement

nasal stuffiness; exophthalmos

Osteoid Osteoma

Benign bone producing tumors

M > F, Young (teens & 20’s)

Malignant transformation is very rare

<2 cm in diameter

Mostly asymptomatic but can present with pain with classic triad

Severe localized pain (due to nerves in tumor & prostaglandins produced by osteoblasts)

Pain occurs at night

Pain relieved by aspirin

Femur or Tibia (mostly in cortex)

Osteoid Osteoma X-ray

Target-like radiolucent lesion (actual tumor or nidus which may be centrally mineralized) which is sharply demarcated with surrounding rim of thick/dense reactive cortical bone

Osteoid Osteoma

Osteoid Osteoma Morphology

Round to oval well circumscribed mass

Hemorrhagic or tan, gritty tissue

Randomly interconnecting trabeculae of woven bone lined by single layer of osteoblasts with benign features & surrounding stroma with loose connective tissue & dilated capillaries

Osteosarcoma

Malignant tumor of osteoblasts producing osteoid matrix or mineralized bone

M > F (1.6 : 1)

Teenagers ( < 20 years ) - classic type

Elderly: secondary osteosarcomas

Primary osteosarcoma

Secondary osteosarcoma (secondary to preexisting disorders in the bone): Paget disease of bone, Bone infarcts, Prior radiation to bone

Familial associations: Hereditary Retinoblastoma with germline mutation in RB gene have greater risk of developing osteosarcoma

Primary Osteosarcoma

Metaphysis of long bones

Distal femur or proximal tibia (knee)

Osteosarcoma Clinical

Painful, present as progressively enlarging mass

Fracture may be the first indication

Radiography:

Large, destructive, mixed lytic & sclerotic mass with infiltrative margins

Extension through the cortex lifts periosteum→ reactive sub-periosteal bone formation → Codman triangle

Sunburst pattern of calcified osteoid

lung metastasis

Osteosarcoma Morphology

Solitary

bulky gritty gray-white tumor with hemorrhage & cystic degeneration

Arises in metaphysis of long bones

Spreads through intramedullary canal

Destroys overlying cortex & “blows through” into surrounding soft tissue

May enter the joint

Formation of osteoid matrix or mineralized bone (fine or lace-like pattern or broad sheets of trabeculae) by malignant pleomorphic (large hyperchromatic nuclei, bizarre giant cells) tumor cells (osteoblasts) with abundant mitosis

Osteochondroma

Arises as lateral projection of growth plate with stalk (disorganized growth plate)

Metaphysis of long bones & knee

Pelvis, scapula, ribs occasionally

Tumor stops growing when patient stops growing (at time of growth plate closure)

M > F

Solitary, sporadic – late adolescent to adulthood

Osteochondroma Clinical

slow growing tumor

non-tender

Painful if impinge on nerve or due to fracture of the stalk

Risk of malignant transformation is rare if solitary

1 to 20 cm in size

Sessile or pedunculated & can be mushroom shaped attached to underlying bone by bony stalk

Medullary cavity of stalk continuous with that of underlying bone from which it arises

Covered with cap of benign hyaline cartilage

Undergoes endochondral ossification with new bone formation

Enchondroma

Benign tumors of hyaline cartilage

Enchondroma arise within medullary cavity of metaphysis of Tubular bones of hand & feet

20 to 50 years age

Usually solitary but can be multiple (enchodromatoses) in Ollier-disease & Maffucci-syndrome (non-hereditary disorders)

Mostly asymptomatic

Occasionally cause fracture → pain

may be numerous & large causing severe deformity

Solitary enchondroma rarely undergoes malignant transformation

Enchondromatoses does undergo malignant transformation

Circumscribed radiolucent lesion with central irregular calcifications, sclerotic rim with 0 ring sign, scalloped/thinned intact overlying cortex

Multiple Enchondromas

frequent sarcomatous (chondrosarcoma) transformation)

Ollier disease: non-hereditary sporadic disorder with multiple enchondromas

Maffuci syndrome:

Multiple enchondromas PLUS spindle cell hemangiomas of soft tissues

Risk for ovarian cancer & brain (gliomas)

Chondroblastoma

benign tumor of teenagers

M > F

Arise in epiphysis of long bones close to joints

Painful; impair joint motility; produce joint effusion

Osteolytic lesion on x-ray

Chondromyxoid Fibroma

benign neoplasm of teenagers

Bones of leg, arms, feet, hands, fingers & toes

Comprised of chondroid, myxoid & fibrous tissue

Radiographic features: Expansile, lobulated, lytic lesion of metaphysis of long bones

Chondrosarcoma

Malignant cartilage producing tumor

Conventional (hyaline cartilage producing), clear cell, dedifferentiated & mesenchymal variants

Primary Conventional: Central (Intramedullary) or peripheral (Juxtacortical)

40s or older

M > F

Axial skeleton – pelvis (hip joint), shoulder, sternum, ribs

Epiphysis of long tubular bones – clear cell variant (younger age)

Distal extremities rarely involved

Secondary chondrosarcoma arise from:

Pre-existing enchondroma (Ollier & Maffucci syndrome; IDH mutations), or osteochondroma (EXT1/2 mutations)

Post radiation

Chondrosarcoma Morphology

Composed of glistening gray white translucent cartilage nodules along with gelatinous or myxoid areas

Neoplastic cartilage/chondrocytes infiltrate marrow space

Spotty calcifications in matrix

Destroy cortex & extend into soft tissue around bone

Chondrosarcoma

Painful, enlarging masses

X-ray:

Radiolucent, nodular mass with poorly defined borders

Foci of flocculent densities (calcified matrix)

Ewing Sarcoma

Malignant/aggressive bone tumor of small round blue cells without differentiation

t(11:22) translocation → fusion of FLI1 gene

<20 years

whites

M > F

Painful enlarging mass

Affected site is often tender, warm & swollen

Fever, anemia, ↑ ESR, leukocytosis

Can spread to lungs, other bones/bone marrow

Giant cell tumor/Osteoclastoma

Benign but locally aggressive

adults in 30 to 50; mostly females

Epiphyses of long bones near joints & may extend to metaphysis 50% around knee

Most are solitary

Neoplastic cells are primitive mononuclear osteoblast precursors

Arthritis like symptoms – joint swelling & pain

Can present as pathologic fracture

Fibrous dysplasia

Benign lesion

Localized area of bone developmental arrest- all components of normal bone present but fail to differentiate into mature structures

Monostotic: single bone involvement → majority

Polyostotic: multiple bone involvement- Disease is evident earlier & more likely craniofacial involvement with deformity

Mazabraud syndrome: mostly polyostotic fibrous dysplasia & soft tissue myxomas

McCune-Albright syndrome

Monostotic Fibrous dysplasia Clinical

Femur, tibia, ribs, jaw bones, calvarium & humerus

Boys = girls; early adolescence; lesions stop enlarging at the time of growth plate closure

asymptomatic

May cause pain or fracture or discrepancies in limb length due to bone enlargement & disfigurement

Polyostotic Fibrous dysplasia Clinical

Disease is evident slightly earlier age than monostotic type

Bones affected: femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible & vertebra

More likely craniofacial involvement with deformity

Crippling bone deformities & fractures

Malignant transformation into sarcoma is rare

McCune-Albright syndrome

Precocious puberty

Hyperthyroidism, pituitary adenomas, primary adrenal hyperplasia

Polyostotic fibrous dysplasia often unilateral

Skin pigmentation: large macules with irregular borders

Dark to Café-au-lait in color

Fibrous dysplasia Morphology

Curvilinear chinese letter or C or W shaped trabeculae of woven bone in cellular fibroblastic proliferation

trabeculae lack prominent osteoblast rim

Radiograph: Intramedullary lytic lesion in diaphysis with well defined margins & thin rim of sclerotic bone & expansion of bone with ground glass appearance

Multiple Myeloma

Most common primary malignancy of bone

Malignant neoplasm of Plasma cells

Plasma cell tumors involving axial skeleton such as skull, vertebra → lytic bone lesions as punched-out defects on x-ray → fractures

Hypercalcemia

Renal failure

Acquired immune abnormalities

Serum & urine “M” spike (high levels of M protein)

↑ levels of monoclonal IgG in the blood

↑ IgA

light chains in urine – Bence jones proteins

Anemia: Rouleaux formation of RBCs on blood smear due to ↑ protein in serum

Amyloidosis AL type due to free light chains deposit in tissue

Multiple Myeloma Pathogenesis

IL-6 is produced by tumor cells & resident marrow stromal cells

IL-6 → plasma cells proliferation & immunoglobulin production

MIP1 alpha derived from myeloma cells regulates RANKL→ osteoclast activation

Wnt pathway modulators released by tumor cells are potent inhibitors of osteoblast function

What tumors comprise the most common sources of bone metastasis?

Adults: Prostate, Breast, Kidney & thyroid- solitary metastasis, Lung

Children: Neuroblastoma, Wilm’s tumor, Osteosarcoma, Ewing sarcoma, Rhabdomyosarcoma

Osteoblastic metastasis

serum alkaline phosphatase (ALP) ↑; normal serum Calcium

Prostate in males

Multiple osteoblastic metastasis of lumbar vertebral bodies & pelvis

Radiodense, sclerotic bone

Growth factors from tumor cells stimulate osteoblasts – TGF beta, FGF, PDGF

Osteolytic metastasis

serum calcium ↑

Kidney & thyroid – single metastasis

Lung, GIT, breast & malignant melanoma – multiple metastasis

Radiolucent bone on radiographs

PTH-rP, cytokines IL-6, MIP1-a (myeloma) activate osteoclasts

Osteoid Osteoma

Osteoid Osteoma

Osteosarcoma

Osteosarcoma

Osteosarcoma

Osteosarcoma

Osteosarcoma

Osteosarcoma

Osteochondroma

Osteochondroma

Osteochondroma

chondrosarcoma

chondrosarcoma

chondrosarcoma

chondrosarcoma

chondrosarcoma

chondrosarcoma

osteosarcoma

osteosarcoma

Fibrous Dysplasia

Fibrous Dysplasia

Fibrous Dysplasia

Fibrous Dysplasia

Fibrous Dysplasia