Chapter 18 Skeletal System, Bone Tumors, Soft Tissue Tumors Flashcards
What defect is apparent in Achondroplasia? What is it a common cause of?
Impaired cartilage proliferation in the growth plate; common cause of dwarfism
What is Achondroplasia due to? and what is the inheritance pattern?
Due to an activating mutation in fibroblast growth factor receptor 3 (FGFR3); AD
What does overexpression of FGFR3 cause?
Inhibits growth of cartilage
Are most mutations in achondroplasia sporadic or inherited and what are they related to?
most are sporadic and related to increased paternal age
What are the clinical features of achondroplasia?
Short extremities with normal sized head and chest- due to poor endochondral bone formation; intremembranous bone formation is not affected
Describe Endochondral bone formation? What type of bones are formed this way?
Is characterized by formation of a cartilage matrix, which is then replaced by bone; it is the mechanism by which long bones grow. Starts with cartilage matrix, cartilage dies and gets calcified and mineralized into bone.
Describe Intramembranous bone formation?
is characterized by formation of bone without a preexisting cartilage matrix; it is the mechanism by which flat bones (skull, ribs, wrist) develop. Produced from a connective tissue matrix
Describe the effect of achondroplasia on mental function, life span, and fertility?
Not affected
What defect is apparent in Osteogenesis Imperfecta?
Congenital defect of bone formation resulting in structurally weak bone
What is OI most commonly due to? what is the inheritance pattern?
Due to an AD defect in collagen type 1 synthesis (type found in bONE)
What are 3 clinical features of OI?
1 Multiple fractures of bone (can mimic child abuse, but bruising is absent)
2 Blue Sclera - Thinning of scleral collagen reveals underlying choroidal veins
3 Hearing loss - bones of the middle ear easily fracture
What defect is apparent in Osteopetrosis?
Inherited defect of bone resorprtion resulting in abnormally thick, heavy bone that fractures easily.
What is osteopetrosis due to?
Due to poor osteoclast function
Multiple genetic variants of osteopetrosis exist, what is the most common?
Carbonic anhydrase II mutation leads to loss of the acidic microenvironment required for bone resorption
What are 5 clinical features of osteopetrosis?
1 bone fractures
2 pancytopenia with extramedullary hematopoeisis due to bony replacement of the marrow (myelophthisic process)
3 Vision and hearing impairment - due to impingement on cranial nerves
4 hydrocephalus due to narrowing of the foramen magnum
5 Renal tubular acidosis - seen with CAII mutation (lack of CA results in decreased tubular resorption of HCO3 leading to metabolic acidosis
What is the treatment for osteopetrosis?
Treatment is bone marrow transplant; osteoclasts are derived from monocytes which come from hematopoiesis
What defect is apparent in Rickets and Osteomalacia?
Defective mineralization of osteoid and abnormal deposition of osteoid
What is osteoid and what cell produces it?
Osteoblasts normally produce osteoid, which is then mineralized with calcium and phosphate to form bone
What is Rickets/Osteomalacia due to?
Due to low levels of vitamin D, which results in low serum calcium and phosphate
What are the two normal sources of vitamin D?
Normally derived from the skin upon exposure to sunlight (85%) and from the diet (15%)
What does activation of vitamin D involve?
25-hydroxylation by the liver followed by 1 hydroxylation by the proximal tubule cells of the kidney
How does active vitamin D raise serum calcium and phosphate?
1 Intestine - increases absorption of calcium and phosphate
2 Kidney - increases reabsorption of calcium and phosphate
3 Bone - increases resorption of calcium and phosphate
What scenarios is vitamin D deficiency seen?
decreased sun exposure, poor diet, malabsorption, liver failure, and renal failure
What is rickets due to and what does it cause?
Rickets is due to low vitamin D in children, resulting in abnormal bone mineralization
What demographic does rickets most commonly present in?
Most commonly arises in children <1 year old
How does rickets present? (4)
1 Pigeon breast deformity - inward bending of the ribs with anterior protrusion of the sternum
2 Frontal bossing (enlarged forehead) - due to osteoid deposition on the skull
3 Rachitic rosary - due to osteoid deposition at the costochondral junction
4 Bowing of the legs may be seen in ambulating children
What is Osteomalacia due to?
Low vitamin D in adults
What does low vitD in osteomalacia lead to?
Inadequate mineralization results in weak bone with an increased risk for fracture in weight bearing bones
What laboratory findings are seen in osteomalacia? Serum calcium, serum phosphate, PTH, Alkaline phosphatase
decreased calcium and phosphate
increase PTH and alkaline phosphatase
What is osteoporosis and what does it result in?
Reduction in trabecular bone mass, results in porous bone with an increased risk for fracture
What is risk of osteoporosis dependent on?
Peak bone mass (attained in early adulthood) and rate of bone loss thereafter
When is peak bone mass achieved and what is it dependent on?
Achieved by 30 years of age and based on;
1 genetics (VitD receptor)
2 Diet
3 Exercise
How fast is bone lost after peak bone mass is achieved and what is this rate based on?
Lost at lightly less than 1% of bone mass per year and is based on exercise, diet, and estrogen
What are the 2 most common forms of osteoporosis?
Senile and postmenopausal
What are the clinical features of osteoporosis and the lab values seen for calcium, phosphate, PTH, alkaline phosphatase
1 Bone pain and fractures in weight bearing areas such as the vertebrae (leads to loss of height and kyphosis), hip, and distal radius
2 Serum calcium, phosphate, PTH and alkaline phosphatase are normal
How is bone density measured?
DEXA scan
How can Osteomalacia and Osteoporosis be differentiated?
By lab values.
What does treatment of osteoporosis involve? (4)
1 Exercise, Vitamin D, and calcium - limit bone loss
2 Bisphosphonates - induce apoptosis of osteoclasts
3 Estrogen replacement therapy is debated (Currently not recommended)
4 Glucocorticoids are contraindicated (worsen osteoporosis)
What defect is seen in Paget Disease of Bone?
Imbalance between osteoclast and osteoblast function
Who is paget disease of bone normally seen in?
usually seen in late adulthood (Average age >60)
What normally controls the function of osteoclasts and what happens in paget disease?
Osteoblasts normally manage osteoclasts, in paget disease the osteoclasts go off on their own
What is the etiology of paget disease?
etiology is unknown, possibly viral (infection of osteoclasts)
Describe the bone involvement of paget disease?
Localized process involving one or more bones; doe snot involve the entire skeleton
What are the 3 distinct stages of paget disease?
1 osteoclastic
2 mixed osteoclastic/osteoblastic
3 osteoblastic
What is the end result of the three stages of paget disease and what does biopsy show?
End result is thick, sclerotic bone that fractures easily. Biopsy revelas a mosaic pattern of lamellar bone
What are 5 clinical features of paget disease?
1 Bone pain - due to microfractures
2 increasing hat size - skull is commonly affected
3 Hearing loss- impingement on cranial nerve
4 Lion-like facies
5 isolated elevated alkaline phosphatase - most common cause of isolated elevated alkaline phosphatase in patients >40 years old
What effects does paget disease have on serum calcium, phosphate, and PTH?
All are normal
What does treatment of Paget disease include?
1 calcitonin - inhibits osteoclast function
2 bisphosphonates - induces apoptosis of osteoclasts
What doe complications of paget disease include?
High output cardiac failure- due to formation of AV shunts in bone
Osteosarcoma
What is osteomyelitis?
Infection of marrow and bone
Is osteomyelitis more common in adults or children?
children
What is the most common cause of osteomyelitis and how does it reach the bone?
Most commonly bacterial; arises via hematogenous spread
What etiology and area of long bones is osteomyelitis seen in adults and children?
transient bacteremia in children seed metaphysis. Open-wound bacteremia in adults seeds epiphysis
What is the most common cause of osteomyelitis?
Staph Aureus
What is a common cause of osteomyelitis in sexually active adults?
N Gonorrhoeae
What is a common cause of osteomyelitis in sickle cell disease?
Salmonella
What is a common cause of osteomyelitis in diabetics or IV drug users?
Pseudomonas
What is a common cause of osteomyelitis resulting from cat or dog bites?
Pasteurella
What is a common cause of osteomyelitis in TB patients?
Mycobacterium Tuberculosis usually involves vertebrae (pott diesease)
What are the clinical features of osteomyelitis? What does it look like on Xray?
Bone pain with systemic signs of infection (eg fever and leukocytosis). Lytic focus *Abscess) surrounded by slerosis of bone on x-ray; lytic focus is called sequestrum, and sclerosis is called involucrum
How is diagnosis of osteomyelitis made?
Blood culture
What is avascular necrosis?
Ischemic necrosis of bone and bone marrow
What do causes of avascular necrosis include?
Trauma or fracture (most common), steroids, sick cell anemia (Dactylitis), and caisson disease; gas emboli of N2 precipitates out of the blood and lodges in the bone
What are two major complications of avascular necrosis?
Osteoarthritis and fracture are major complications
What is an osteoma, where does it most commonly arise? and what is it associated with?
Benign tumor of bone, most commonly arises on the surface of facial bones, associated with Garner Syndrome
What is Gardner syndrome?
Familial adenomatous polypopis, Fibromatoiss in the retroperitoneum, and osteomas of facial bones
What is fibromatosis?
Nonneoplastic growth of fibroblasts that locally destroys tisssue
What is an osteoid osteoma?
Benign tumor of osteoblasts (that produce osteoid) surrounded by a rim of reactive (sclerotic) bone
Who does osteoid osteomas occur in?
Occurs in young adults <25 years of age (more common in males)
Where does osteoid osteoma arise?
Arises in the cortex of long bones (e.g. femur) usually arises on the diaphysis
How does osteoid osteoma present?
bone pain that resolves with aspirin
What does imaging reveal in osteoid osteoma?
reveals a bony mass (<2cm) with a radiolucent core (osteoid)
What is an osteoblastoma and how does it relate to osteoid osteoma?
similar to osteoid osteoma but is larger (>2cm), arises in vertebrae, and presents as bone pain that does not respond to aspirin
What is an osteochondroma?
Tumor of bone with an overlying cartilage cap; most common benign tumor of bone
Where does osteochondroma arise?
Arises from a lateral projection of the growth plate (metaphysis); bone is continuous with marrow space
What can the overlying cartilage of an osteochomdroma transform into? How common is this transformation?
Can transform into a chondrosarcoma. this is rare
What is an osteosarcoma?
Malignant proliferation of osteoblasts
What demographics are peak incidences of osteosarcoma seen in?
Teenagers; and less commonly in the elderly
What are 3 risk factors of osteosarcoma?
familial retinoblastoma, paget disease and radiation (last two in elderly)
How does osteosarcoma arise?
Arises in the metaphysis of long bones, usually the distal femur or proximal tibia
How does osteosarcoma present?
Presents as a pathological fracture or bone pain with swelling
What does imaging reveal in osteosarcoma?
Reveals a destructive mass with a ‘sunburst’ appearing and lifting of the periosteum (Codman triangle)
What does biopsu reveal in osteosarcoma?
pleomorphic cells that produce osteoid
What is Giant Cell Tumor?
Tumor comprised of multinucleated giant cells and stromal cells
Who does Giant cell tumors occur in?
Young adults
Where do Giant cell tumors arise?
arise on the epiphyis of long bones, usually the distal femur or proximal tibia
What appearance is seen on xray in giant cell tumors?
‘soap-bubble’ appearance
How does a giant cell tumor behave?
Locally aggressive tumor; may recur
What is a Ewing Sarcoma?
Malignant proliferation of poorly differentiated cells derived from neuroectoderm
Where does Ewing sarcoma arise and in who?
Diaphysis of long bones; usually in male children <15 years old
What does biopsy reveal in Ewing sarcoma?
small, round blue cells that resemble lymphocytes
What can Ewing sarcoma be confused with?
Can be confused with lymphoma or chronic osteomyelitis (Some can present with fever)
What is the characteristic translocation of Ewing sarcoma?
t(11;22)
What is a chondroma and where does it arise?
Benign tumor of cartilage that usually arises in the medulla of small bones of the hands and feet
What is a chondrosarcoma and where does it arise?
Malignant cartilage-forming tumor that usually arises in the medulla of the pelvis or central skeleton
What is more common in bone, metastatic or primary?
metastatic
What do bone mets usually result in, what is the one exception?
Result in osteolytic (punched out) lesions. The one exception is prostatic carcinoma classically produces osteoblastic lesions (sclerosis)
What is a lipoma?
Benign tumor of adipose tissue
What is the most common benign soft tissue tumor in adults?
lipoma
What is a liposarcoma and what is the characteristic cell?
Malignant tumor of adipose tissue. Lipoblast is the characteristic cell
What is the most common malignant soft tissue tumor in adults?
liposarcoma
What is a rhabdomyoma?
Benign tumor of skeletal muscle
What is cardiac rhybdomyoma associated with?
tuberous sclerosis
What is a rhabdomyosarcoma, what is the characteristic cell, and what marker is it positive for?
malignant tumor of skeletal muscle. Rhabdomyoblasts are the characteristic cell; desmin positive
What are the most common sites for rhyabdomyosarcomas?
Head and neck; vagina is the classic site in young girls
What is the most common malignant soft tissue tumor in children?
rhyabdomyosarcoma
