Bone Pathology

Question 1

Characteristics of achondroplasia

Answer 1

Most common form of inherited dwarfism

AD mutation in fibroblast growth factor receptor 3 (FGFR3)

Long bones are short and thick, leading to dwarfism with short extremities. Cranial and vertebral bones are spared, leading to relatively large head and trunk.

Intelligence, lifespan and reproductive ability are normal

Question 2

Characteristics of osteogensis imperfecta (OI) (“brittle bone disease”)

Answer 2

Hereditary defect leading to abnormal synthesis of type I collagen

Patients have generalized osteopenia (brittle bones), resulting in recurrent fractures and skeletal deformity

Abnormally thin sclera with blue hue

Laxity of joint ligaments leads to hypermobility

Involvement of inner and middle ear bone produces deafness

Occasional detinogenesis imperfecta, characterized by small, fragile and discolored teeth due to a deficiency of dentin

Dermis may be abnormally thin, and skin is susceptible to easy bruising

Question 3

Characteristics of osteopetrosis (marble bone disease)

Answer 3

Hereditary defect leading to decreased osteoclast function, with resulting decreased resorption and thick sclerotic bones

Xray shows symmetrical generalized osteosclerosis.

Long bones may have broadened metaphyses, causing an “Erlenmeyer flask”-shaped deformity

There are two types AR and AD

Pathology shows increased bone density and thickening of bone cortex. Myelophthisic anemia may result from marrow crowding. Cranial nerve compression due to narrowing of cranial foramina may result in blindness, deafness, and facial nerve palsies. Hydrocephalus may develop due to obstruction of CSF

Question 4

Characteristics of autosomal recessive type of osteopetrosis

Answer 4

Malignant

Affects infants and children

Causes multiple fractures and early death due to anemia, infection and hemorrhage

Question 5

Characteristics of autosomal dominant type of osteopetrosis

Answer 5

Benign

Affects adults

Causes fractures, mild anemia, and cranial nerve impingement

Question 6

Characteristics of Paget disease (osteitis deformans)

Answer 6

Localized disorder of bone remodeling, resulting in excessive bone resorption followed by disorganized bone replacement, producing thickened but weak bone that is susceptible to deformity and fracture

Seen in those age>40
Common in those of european ancestry
Common sites of involvement include the skull, pelvis, femur and vertebrae
Majority of cases are polostotic and mild

Can cause bone pain and deformity, fractures, warmth of the overlying skin due to bone hypervascularity.

Xray show bone enlargement with lytic and sclerotic areas.

Lab studies show highly elevated serum alkaline phosphatase and increased levels of urinary hydroxyproline

Bones are thick but weak and fracture easily
Foraminal narrowing can impinge cranial nerves, often lead to deafness
Involvement of facial bones may produce lion-like facies

Question 7

What is paget disease associated with?

Answer 7

Paramyxovirus

Mutations of SQSTM1

Question 8

What are the complications of Paget disease

Answer 8

Arteriovensous shunts in bone marrow
High-output cardiac failure
Increased incidence of osteosarcoma and other sarcomas

Question 9

What are the 3 stages of paget disease?

Answer 9

Stage 1: Osteolytic stage (osteoclatsic activity predominates)

Stage 2: Mixed osteolytic-osteoblastic stage

Stage 3: Osteosclerotic stage (osteoblastic activity predominates in this “burnout stage”)

Question 10

What does paget disease look like microscopically?

Answer 10

Haphazard arrangement of cement lines, creating a “mosaic pattern” of lamellar bone.

Question 11

Characteristics of osteoporosis

Answer 11

Decreased bone mass (osteopenia), resultin in thin, fragile bones susceptible to fracture.

Most commonly occurs in postmenopausal Caucasian women and the elderly

Dual-energy x-ray absorptiometry (DEXA) can measure bone mineral density to predict fracture risk.

Lab studies may show normal serum calcium, phosphorus, and alkaline phosphatase, but the diagnosis is not based on labs

Microscopically, the bone has thinned cortical and trabecular bone

Patients may experience bone pain and fractures
Common fracture sites include vertebrae (compression fracture); femoral neck (hip fracture); and distal radius (Colles fracture)
Kyphosis and loss of height may result

Question 12

What are the primary causes of osteoporosis?

Answer 12

Estrogen deficiency (postmenopausal, Turner syndrome)
Genetic factors (low density of original bone)
Lack of excerise
Old age
Nutritional factors

Question 13

What are the secondary causes of osteoporosis?

Answer 13

Immobilization
Endocrinopathies (Cushing disease, thyrotoxicosis)
Malnutrition 
Corticosteroids 
Smoking/alcohol consumption
Genetic disease (Gaucher disease)

Question 14

Characteristics of osteomalacia and rickets

Answer 14

Both characterized by decreased mineralization of newly formed bone.

They are usually caused by deficiency or abnormal metabolism of vitamin D. Specific causes include dietary deficiency of vitamin D, intestinal malabsorption, lack of sunlight, and renal and liver disease. Treatment is vitamin D and calcium supplementation

Question 15

Characteristics of osteomalacia

Answer 15

Occurs in adults

Due to impaired mineralization of the osteoid matrix resulting in thin, fragile bones susceptible to fracture.

The patient may present clinically with bone pain or fractures (vertebrae, hips and wrist). X-ray shows transverse lucencies called looser zones.

Lab studies show low serum calcium, low serum phosphorus and high alkaline phosphatase

Question 16

Characteristics of rickets

Answer 16

Occurs in children

Both remodeled bone and bone formed at the epiphyseal plate are undermineralized.

Endochondral bone formation is affected, leading to skeletal deformities.

Skull deformities include craniotabes (softening) and frontal bossing (hardeneing)

The “rachitic rosary” is a deformity of the chest wall as a result of overgrowth of cartilage at the costochondral junction.

Pectus carinatum, lumbar lordosis, bowing of the legs and fractures also occur

Question 17

Characteristics of osteomyelitis

Answer 17

Bone inflammation due to bacterial infection.

The most common route of infection is hematogenous spread this often affects the metaphysis

Other routes of spread include direct inoculation (trauma) and spread form an adjacent site of infection (prosthetic joint)

Characterized by fever and leukocytosis, localized pain and erythema, and swelling.

X-ray may show periosteal elevation followed by a possible lytic focus with surrounding sclerosis after 2 weeks (Xray normal for up to 2 weeks)

Microscopic examination show suppurative inflammation.

Vascular insufficiency can lead to ischemic necrosis of bone

Question 18

What are the infecting organisms that cause osteomyelitis?

Answer 18

Most common:
S. aureus

Others:
E. coli
Streptococci
H. influenzae
Salmonella (sickle cell)
Pseudomonas (IV drug users and diabetics)

Question 19

Characteristics of tuberculous osteomyelitis

Answer 19

See in 1% of cases of TB

Presents with pain or tenderness, fever, night sweats, and weight loss.

Biopsy shows caseasting granulomas with extensive destruction of the bones.

Common sites of involvement include thoracic and lumbar vertebrae (“Pott disease”).

Complications include vertebral compression fracture, psoas abscesses and secondary amyloidosis

Question 20

Characteristics of avascular necrosis

Answer 20

Ichemic necrosis of bone and bone marrow.

Causes include trauma and/or fracture; idiopathic; steroid use; sickle cell; Gaucher disease; and caisson disease

Avascular necrosis can be complicated by osteoarthritis and fractures

Question 21

Characteristics of osteitis fibrosa cystica

Answer 21

Von Recklinghausen disease of bone

Excessive parathyroid hormone (hyperparathyroidism) causes osteoclast activation and generalized bone resorption, resulting in possible bone pain, bone deformities and fractures

Microscopic exam shows excess bone resorption with increased number of osteoclasts, fibrous replacement of marrow, and cystic spaces in trabecular bone

“Brown tumors” are brown bone masses produced by cystic enlargement of bones with areas of fibrosis and organized hemorrhage

Question 22

Characteristics of hypertrophic osteoarthropathy

Answer 22

Presents with painful swelling of wrists, fingers, ankles, knees, and elbows

Pathologically the ends of the long bones show periosteal new bone formations, which can produce digital clubbing and often arthritis of adjacent joints

Question 23

Characteristics of Osgood-Schlatter disease

Answer 23

Common cause of knee pain in adolescents. It develops when stress from the quadriceps during rapid growth cause inflammation of the proximal tibial apophysis at the insertion of the patellae tendon.

Permanent changes to the knees (knobby knees) may develop.

Question 24

Characteristics of fibrous dysplasia

Answer 24

Presents with painful swelling, deformity, or pathologic fracture of involved bone (typically ribs, femur, or cranial bones), usually in children and young adults

GNAS gene mutations cause osteoblasts to produce fibrous tissue (microscopically, irregularly trabelculae) rather than bone

Question 25

Characteristics of osteoma

Answer 25

Benign neoplasm that frequently involves the skull and facial bones

Osteoma can be associated with Gardner syndrome

Question 26

Characteristics of osteoid osteoma

Answer 26

Benign, painful growth of the diaphysis of a long bone, often the tibia or femur

Males are affected more than females, with peak age 5-25.

Pain tends to be worse at night and relieved by aspirin

Xray show central radiolucency surrounded by a sclerotic rim

Microscopically osteoblasts line randomly connected trabeculae

Question 27

Characteristics of osteoblastoma

Answer 27

Similar to osteoid osteoma but larger (>2cm) and often involves vertebrae

Question 28

Characteristics of osteochondroma (exostosis)

Answer 28

Benign bony metaphyseal growth capped with cartilage, which originates from epiphyseal growth plate.

It typically presents in adolescent males who have firm, solitary growths at the ends of long bones. It may be asymptomatic, cause pain, produce deformity, or undergo malignant transformation (rare)

Question 29

Characteristics of osteochondromatosis

Answer 29

Multiple hereditary exostoses

Produces multiple often symmetric osteochondromas

Question 30

Characteristics of enchondroma

Answer 30

Benign cartilaginous growth within the medullary cavity of bone, usually involving the hands and feet.

It is typically solitary, asymptomatic, and requires no treatment

Question 31

Characteristics of multiple endchondromas

Answer 31

Enchondromatosis

Can occur as part of Ollier disease (multiple and unilateral) and Maffucci syndrome (with hemangiomas) and carry risk of malignant transformation

Question 32

Characteristics of osteoclastoma

Answer 32

Giant cell tumor of bone

Benign neoplasm containing multi-nucleated giant cells admixed with stromal cells.

It is uncommon but occurs more often in females than in males, with peak age 20-50.

Clinically the tumor produces a bulky mass with pain and fractures

Xray shows an expanding lytic lesion surrounded by a thin rim of bone, with a possible “soap bubble” appearance

Grossly the tumor causes a red-brown mass with cystic degeneration that often involves the epiphyses of long bones, usually around the knee

Microscopically multiple osteoclast-like giant cells are distributed within a background of mononuclear stromal cells

Question 33

Characteristics of osteosarcoma

Answer 33

Most common primary malignant tumor of bone.

It occurs more frequently in males than in femals, with most cases in teenage years (ages 10-25). Patients with familial retinoblastoma have a high risk

Presents with localized pain and swelling. The classic xray findings are Codman triangle (periosteal elevation), “sub burts” pattern and bone destruction

Prognosis is poor

Grossly osteosarcoma often involves the metaphyses of long bones, usually around the knee.

Produces a large, firm, white-tan mass with necrosis and hemorrhage

Question 34

Characteristics of secondary osteosarcoma

Answer 34

Seen in elderly

Associated with Paget disease, irradiation and chronic osteomyelitis

Question 35

Characteristics of chondrosarcoma

Answer 35

Malignant tumor of chondroblasts which may arise de novo or secondary to a preexisting enchondroma, exostosis, or paget disease

Males are affected more commonly than females, with peak ages 30-60

It presents with enlarging mass with pain and swelling, and it typically involves the pelvic bones, spine, and shoulder girdle

Microscopically there is cartilaginous matrix production

Radiographs show osteolytic destruction and “popcorn” calcification

Question 36

Characteristics of Ewing sarcoma

Answer 36

Malignant neoplasm of undifferentiated cells arising within the marrow cavity.

Males>females teenage years (5-20)

Patients present with pain, swelling, and tenderness

Xray shows concentric “onion-skin” layering of periosteal bone with soft tissue extension

Grossly affects the diaphyses of long bones, with the most common sites being the femur, pelvis, and tibia. Tumor produces a white-tan mass with necrosis and hemorrhage

Question 37

What translocation causes Ewing sarcoma?

Answer 37

t(11;22)

Produces the EWS-FLI1 fusion protein

Question 38

Characteristics of metastasis to bone

Answer 38

More common than primary bone tumor

Common primary sites:
Prostate (often osteoblastic)
Breast
Lung
Thyroid 
Kidney

Question 39

Characteristics of thanatophoric dysplasia

Answer 39

The most common lethal form of dwarfism

Clinical features:
Micromelic shortening of the limbs
Frontal bossing
Relative macrocephaly
Small chest cavity
Bell-shaped abdomen

Microscopically shows dimished proliferation of chondrocytes and disorganization in the zone of proliferation
Mutation in FGFR3 but different from achondroplasia