Neoplasms of Bone and Joint Pathology

Question 1

How does the diagnosis of bone tumors differ from other tissues?

Answer 1

histology comes last

Question 2

What is osteochondroma?

Answer 2

benign cartilaginous lesion and most common benign tumor

contains marrow space contiguous with the underlying medulla of the bone

mutation in suppressor gene EXT1 that affects growth plate kinetics

Question 3

Multiple Hereditary Exostosis

Answer 3

AD disorder resulting in multiple osteochondromas

caused by biallelic inactivation of EXT1 and EXT2

malignant transformation (2-3% of cases) mostly into chondrosarcomas

Question 4

What is the clinical presentation of osteochondroma?

Answer 4

peak is in 1st and 2nd decades

male-female ratio is 2:1

located in the distal femur, proximal humerus, and proximal tibia (>50%)

Question 5

What are the x-ray findings of osteochondroma?

Answer 5

cartilaginous cap on bony stalk that is continuous with medulla of bone

tumor grows away from growth plate (cap size>3cm. suggests malignant transformation)

“arc and ring” calcifications

Question 6

What is the treatment and prognosis of osteochondroma?

Answer 6

no treatment unless symptomatic or there is evidence of possible secondary chondrosarcomatous transformation of the cartilaginous cap

1-2% recur, 1-3% of solitary and up to 5% of multiple osteochondroma undergo malignant transformation

mostly chondrosarcoma

Question 7

What are the histological features of osteochondroma?

Answer 7

cartilaginous “cap” shows features of normal growth plate cartilage

stalk of tumor contiguous with intramedullary portion of bone and composed of normal marrow elements

Question 8

What is osteoid osteoma?

Answer 8

small benign bony process < 2 cm

Question 9

What is the clinical presentation of osteoid osteoma?

Answer 9

increasing nocturnal pain relieved by ASA/NSAID (80% of patients)

any bone except skull/sternum, 50% involve femur and tibia

mostly in 2nd and 3rd decades, rare after 30 years of age

male-female ratio is 2:1

Question 10

What is the radiological findings in osteoid osteoma?

Answer 10

zone of sclerotic bone surrounding a well-demarcated lucent focus (the “nidus”) composed of woven bone in a vascular stroma

Question 11

What is the prognosis of osteoid osteoma?

Answer 11

excellent, but must remove nidus

Question 12

What are the histological features of osteoid osteoma?

Answer 12

the “nidus” (arrows) is the radiolucent central focus of woven bone within a vascular stroma

the surrounding cortical bone is thickened (top)

nidus consists of woven bone with osteoblastic rimming and a highly vascular stroma (right, bottom)

Question 13

What is enchondroma?

Answer 13

benign hyaline intramedullary cartilaginous neoplasm

**periosteal chondroma is located on the cortical surface under the periosteum

Question 14

What is the clinical presentation of enchondroma?

Answer 14

2nd to 4th decades, M=F

located in the finger and toes in 50% of cases

proximal humerus, proximal and distal femur

Question 15

What are the radiologic findings of enchondroma?

Answer 15

well-circumscribed, lucent with cartilage matrix calcification

“arc and ring” due to enchondral bone formation at periphery of tumor nodule

Question 16

What is the prognosis of enchondroma?

Answer 16

observation with serial radiographs

curettage (<5% recurrent state)

Question 17

What are the histological findings of enchondroma?

Answer 17

nodules of mature cartilage within a fatty bone marrow (top)

note low cellularity or lack of pleomorphism (bottom)

benign chondrocytes evenly distributed or arranged in clusters

Question 18

What is multiple enchondromata?

Answer 18

non-hereditable disorder characterized by multiple enchondromas (usually affects same region of body)

incidence of malignant transformation is 15%-50%

unilateral distribution in the appendicular skeleton

Question 19

Ollier’s disease

Answer 19

multiple enchondromata

Question 20

Maffuci’s syndrome

Answer 20

multiple enchondromata + soft tissue/visceral vascular tumor (mainly, hemangiomas)

Question 21

What is giant cell tumor of bone?

Answer 21

locally aggressive neoplasm

tumor composed of osteoclasts and neoplastic spindle cells

Question 22

What is the clinical presentation of giant cell tumor of bone?

Answer 22

peak in 3rd decade (skeletally-mature), F>M (~3:2)

located in the distal femur, proximal tibia, distal radius, proximal humerus (single/multiple GCT in odd sites -> hyperparathyroidism)

Question 23

What are the radiologic features of giant cell tumor of bone?

Answer 23

eccentric, lytic lesion that may involve soft tissue (extends from metaphysis into epiphysis once growth plate closes)

Question 24

What is the prognosis of giant cell tumor of bone?

Answer 24

en bloc excision is prefferred

high recurrence rate (25%-60%) if curetted

<5% of GCT metastasize to lung (histology can’t predict clinical course)

sarcomatous transformation is rare (usually follows radiotherapy)

Question 25

What are the histological findings in giant cell tumor of the bone?

Answer 25

lytic meta- and epiphyseal lesion, ill-defined cellular margins and osteoclast-like giant cells

microscopically, evenly dispersed osteoclasts with numerous nuclei (INSET) and intervening mononuclear stromal cells

Question 26

What is fibrous dysplasia?

Answer 26

developmental fibro-osseous defect due to mutations in GNAS1 gene that encodes the alpha subunit of the G receptor protein (cause decreased GTPase activity)

increased cAMP (affects normal maturation of osteoblasts)

Question 27

What is the clinical presentation of fibrous dysplasia?

Answer 27

mostly diagnosed in first three decades of life (M=F)

located in the femur/tibia, craniofacial, ribs, pelvis

monostotic (80%)

polyostotic (20%)

Question 28

McCune-Albright syndrome

Answer 28

polyostotic disease + cafe au lait spots + endocrinopathies, mostly isosexual precocity

Question 29

What are the radiological findings of fibrous dysplasia?

Answer 29

expansile, lesion with a variable internal density (“ground glass”)

Question 30

What is the prognosis of fibrous dysplasia?

Answer 30

monostotic FD usually stabilizes at puberty

symptomatic lesions treated with biphosphonates

sarcoma is rare (<0.5%; mostly gnathic bones in adults)

may recur if not completely excised

Question 31

What are the histological features of fibrous dysplasia?

Answer 31

expansile, circumscribed lesion within the mid-portion of the rib

irregularly contoured (“C” and “S” shaped) spicules of woven bone with no osteoblastic rimming (INSET) within a spindled and collagenous stroma

Question 32

What is osteosarcoma?

Answer 32

primary malignant tumor in which malignant neoplastic cells produce osteoid and/or bone, even if only in small amounts

develops in metaphysis of long bones of the young

in older patients, presents more often in caniofacial bone or axial skeleton and is usually associated with a predisposing bone condition

Question 33

What is the clinical presentation of osteosarcoma?

Answer 33

peak in second decade, 60% < 25 yrs old

male-female ratio is 3:2 (particularly patients < 20 years)

located in metaphysis of long bones, particularly distal femur, proximal tibia, and proximal humerous

incidence of OS involving pelvis and craniofacial bones increase with age reflecting malignant transformation of benign process like Paget’s disease or fibrous dysplasia

Question 34

What are the radiographical findings of osteosarcoma?

Answer 34

most cases are mixed lytic/blastic + cortical destruction + soft tissue extension

Question 35

What is the prognosis of osteosarcoma?

Answer 35

depends mostly on response to pre-operative chemotherapy (>90% tumor necrosis = survival 80-90%)

whereas <90% necrosis and no change in chemo = survival < 15%

Question 36

What are the histological findings on osteosarcoma?

Answer 36

gross speciment shows OS in metaphyseal region with soft hissue extension

OS defined as a sarcoma in which malignant cells directly produce osteoid/woven bone

note highly pleomorphic cells

Question 37

What is the therapy for osteosarcoma?

Answer 37

preoperative chemotherapy -> 2-6 cycles of chemotherapy -> histologic examination of excised tumor -> fit for prosthesis -> postoperative chemotherapy

if < 90% necrosis after chemo, consider changing drugs and local therapy if margins positive

if >/= 90% necrosis, continue therapy and use local therapy if margins are positive

Question 38

What is the clinical presentation of primary chondrosarcoma?

Answer 38

peaks in 5th to 7th decades

male-femal ratio is 2:1

mostly central (within medullary cavity) and less often peripheral (surface of bone)

pelvis (ilium), proximal femur, proximal humerus, distal femur, and ribs

Question 39

What are the radiologic findings of primary chondrosarcoma?

Answer 39

lobulated, lytic lesion with cartilage matrix calcification

cortical destruction/thickening, no/minimal periosteal reaction

“arc and ring” calcification

Question 40

What is the treatment and prognosis of primary chondrosarcoma?

Answer 40

depends mostly on grade and surgical adequacy

5 yr survival for G1 = 90%, G2 and G3 = 53%

metastases are rare and occur late

Question 41

What are the histological features of primary osteosarcoma?

Answer 41

Question 42

What is Ewing Sarcoma/primitive neuroectodermal tumor (ES/PNET)?

Answer 42

primitive neuroectodermal tumor of bone/soft tissue characterized by a t(11;22) in 90% of cases or t(21;22) in 5-10% of cases

second most common primary malignant bone tumor (behind OS) in children

Question 43

What is the clinical presentation of Ewing Sarcoma/primitive neuroectodermal tumor?

Answer 43

about 80% <20 years

male-femal ratio is 2:1

most common in femur, tibula, fibula, and humerus

followed by pelvis and ribs

Question 44

What are the radiological features of Ewing Sarcoma/primitive neuroectodermal tumor?

Answer 44

Ill-defined lytic lesion in diaphysis or meta-diaphysis

cortical destruction

+/- “onion-skin”/”sunburst” periosteal reaction

soft tissue extension frequent

Question 45

What is the treatment and prognosis of Ewin sarcoma/primitive neuroectodermal tumors?

Answer 45

treated with neoadjuvant multiagent chemotherapy (like osteosarcoma) followed by wide excision and/or radiation

current overall survival for non-metastatic sarcoma is 60% to 80%

metastases in 20-25% of cases and associated with 80% mortality

Question 46

What are the histological features of Ewing sarcoma/primitive neuroectodermal tumor?

Answer 46

sheets/nests of small polygonal cells

metadiaphyseal location of sarcoma with soft tissue component and periosteal reaction

diffuse proliferation of small neoplastic cells with focal necrosis

cells have rounded nuclei and cleared cytoplasm (INSET)

due to glycogen deposition

Question 47

What are type A synoviocytes?

Answer 47

macrophage-like cells found in the synovium of diarthrodial joints

Question 48

What are type B synoviocytes?

Answer 48

cells found in synovium that secrete hyaluronic acid (a large viscoelastic mucopolysaccharide) into the synovial space

Question 49

Where in a joint do inflammatory processes like rheumatoid arthritis first manifest?

Answer 49

the pocket/recess formed by the synovium on one side of the joint space

the bone lacks cartilage here

Question 50

What is the clinical presentation of osteoarthritis?

Answer 50

older aged caucasians with a male:female ratio of 2:1

most commonly affects hip, knee, DIP and PIP of fingers, and spine

Heberden’s nodes in DIP in mostly females

symptoms include pain, stiffness after use (“evening stiffness”), joint effusion, and loss of joint mobility

majority of individuals over age 65 have radiologic and/or clinical evidence of osteoarthritis

5% to 20% of patients have a predisposing condition that compromises integrity of joint and leads to early development of osteoarthritis (secondary osteoarthritis)

Question 51

What happens in the initiation stage of the pathogenesis of osteoarthritis?

Answer 51

chondrocyte injury/death caused by repetive abnormal mechanical loading (ability for joint cartilage to properly dissipate mechanical stress depends on genetic factors, age-related chagnes to cartilage, and anatomy/alignment of the joint)

Question 52

What happens during early OA?

Answer 52

• deeper chondrocytes proliferate and synthesize matrix proteins, proteinases, and growth factors in attempt to remodel the matrix
• endochondral bone formation by by deeply located chondrocyte (with potential to form bone or cartilage)

leads to osteophyte formation, subchondral bone thickening, and bone cyst formation

Question 53

What happens in late OA?

Answer 53

imbalance in matrix synthesis and breakdown during remodeling process eventually leads to loss of cartilage

Question 54

What are the pathologic findings of osteoarthritis?

Answer 54

pale articular cartilage due to loss of glycoaminoglycans and increased water content

vertical cracks in surface cartilage that parallel bundles of collagen type II (fibrillation)

complete loss of cartilage (eburnation)

early thickening of subarticular bone and osteophyte formation result form deepest chondrocytes forming new bone by echondral ossification

microfractures occur in subarticular bone as vessels penetrate bone and thin cartilage during process of echondral bone formation

this allows seepage of synovial fluid and the formation of subarticular (synovial fluid filled cysts)

Question 55

What are the common seropositive noninfectious inflammatory arthritis?

Answer 55

rheumatoid arthritis

juvenile rheumatoid arthritis (ANA-positive)

Question 56

What are the common seronegative (HLA-B27 associated arthridities?

Answer 56

ankylosing spondylitis

reactive arthritis (Gi/GU bacterial and IBD associated)

arthritis (urethritis/cervicitis + uveitis/conjunctivitis = REITER syndrome)

psoriatic arthritis (10%)

Question 57

What is the clinical presentation of rheumatoid arthritis?

Answer 57

affects patients mostly in 5th to 8th decades of life, a lot more females than males (over 2:1)

joints involved include hands (MCP and PIP), feet, wrists, ankles, upper spine, and knees

arthritis is symmetrical , plus the pain and morning stiffness

rheumatodi nodules (palisaded granulomas) in 25% of patients

serology positive for rheumatic factor and/or cyclic citrullinated peptide antibody - 20% of patients remain negative for both

Question 58

What disease are some diseases assocated with rheumatoid arthritis?

Answer 58

Sjogern’s syndrome

amyloidosis

pleuritis and pericarditis

lung fibrosis

aortic valvulitis

vvasculitis

splenomegaly (Felty syndrome)

Question 59

What are the steps in the pathogenesis of rheumatoid arthritis?

Answer 59

1) CD-4 T cells respond to arthritogen and stimulate synoviocytes and macrophages to produce pro-inflammatory molecules and allow for future production of proteases
2) RANKL prootes osteoclastogenesis resulting in bone erosions/osteoporosis
3) B cells produce antibodies that cause imune complex-mediated tissue damage
4) activation of vascular adhesion molecules promoting migration of inflammatory cells into joint

Question 60

What are the usual arthritogen?

Answer 60

infectious organism

collagen

proteoglycans

citrullinated proteins such as fibrin

Question 61

What is the pathology behind rheumatoid arthritis?

Answer 61

1) proliferative synovitis with increased T cells, B cells, plasma cells, macrophages, and synoviocytes
2) increased vascularity (angiogenesis)
3) osteoclastogenesis (osteoporosis)
4) surface fibrin deposition and formation “rice bodies”
5) pannus (inflammatory cells, granulation tissue, macropahges, and fibroblastic synoviocytes - causes chondrolysis that resolves by fibrous ankylosis of joint (scarring of joint space)

Question 62

What are some common radiologic findings of rheumatoid arthritis?

Answer 62

osteoporosis and “ulnar drift”

opera glass deformity