Bone Pathology Flashcards
Characteristics of achondroplasia
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
Characteristics of osteogensis imperfecta (OI) (“brittle bone disease”)
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
Characteristics of osteopetrosis (marble bone disease)
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
Characteristics of autosomal recessive type of osteopetrosis
Malignant
Affects infants and children
Causes multiple fractures and early death due to anemia, infection and hemorrhage
Characteristics of autosomal dominant type of osteopetrosis
Benign
Affects adults
Causes fractures, mild anemia, and cranial nerve impingement
Characteristics of Paget disease (osteitis deformans)
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
What is paget disease associated with?
Paramyxovirus
Mutations of SQSTM1
What are the complications of Paget disease
Arteriovensous shunts in bone marrow
High-output cardiac failure
Increased incidence of osteosarcoma and other sarcomas
What are the 3 stages of paget disease?
Stage 1: Osteolytic stage (osteoclatsic activity predominates)
Stage 2: Mixed osteolytic-osteoblastic stage
Stage 3: Osteosclerotic stage (osteoblastic activity predominates in this “burnout stage”)
What does paget disease look like microscopically?
Haphazard arrangement of cement lines, creating a “mosaic pattern” of lamellar bone.
Characteristics of osteoporosis
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
What are the primary causes of osteoporosis?
Estrogen deficiency (postmenopausal, Turner syndrome)
Genetic factors (low density of original bone)
Lack of excerise
Old age
Nutritional factors
What are the secondary causes of osteoporosis?
Immobilization Endocrinopathies (Cushing disease, thyrotoxicosis) Malnutrition Corticosteroids Smoking/alcohol consumption Genetic disease (Gaucher disease)
Characteristics of osteomalacia and rickets
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
Characteristics of osteomalacia
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
Characteristics of rickets
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
Characteristics of osteomyelitis
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
What are the infecting organisms that cause osteomyelitis?
Most common:
S. aureus
Others: E. coli Streptococci H. influenzae Salmonella (sickle cell) Pseudomonas (IV drug users and diabetics)
Characteristics of tuberculous osteomyelitis
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
Characteristics of avascular necrosis
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
Characteristics of osteitis fibrosa cystica
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
Characteristics of hypertrophic osteoarthropathy
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
Characteristics of Osgood-Schlatter disease
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.
Characteristics of fibrous dysplasia
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
Characteristics of osteoma
Benign neoplasm that frequently involves the skull and facial bones
Osteoma can be associated with Gardner syndrome
Characteristics of osteoid osteoma
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
Characteristics of osteoblastoma
Similar to osteoid osteoma but larger (>2cm) and often involves vertebrae
Characteristics of osteochondroma (exostosis)
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)
Characteristics of osteochondromatosis
Multiple hereditary exostoses
Produces multiple often symmetric osteochondromas
Characteristics of enchondroma
Benign cartilaginous growth within the medullary cavity of bone, usually involving the hands and feet.
It is typically solitary, asymptomatic, and requires no treatment
Characteristics of multiple endchondromas
Enchondromatosis
Can occur as part of Ollier disease (multiple and unilateral) and Maffucci syndrome (with hemangiomas) and carry risk of malignant transformation
Characteristics of osteoclastoma
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
Characteristics of osteosarcoma
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
Characteristics of secondary osteosarcoma
Seen in elderly
Associated with Paget disease, irradiation and chronic osteomyelitis
Characteristics of chondrosarcoma
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
Characteristics of Ewing sarcoma
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
What translocation causes Ewing sarcoma?
t(11;22)
Produces the EWS-FLI1 fusion protein
Characteristics of metastasis to bone
More common than primary bone tumor
Common primary sites: Prostate (often osteoblastic) Breast Lung Thyroid Kidney
Characteristics of thanatophoric dysplasia
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
