PATHO WEEK 2 - Bones, Joints, and Soft Tissue Tumors

Flashcards about bone, joint, and soft tissue tumors.

What is Osteogenesis Imperfecta?

A group of disorders, also known as 'brittle bone disease', caused by mutations in type 1 collagen genes (eyes, teeth, skin), leading to bone fragility and fractures.

What are classic features of Osteogenesis Imperfecta?

Blue sclerae, hearing loss, and teeth abnormalities.

What is Achondroplasia?

Most common form of dwarfism, an autosomal dominant disorder characterized by reduced endochondral cartilage growth caused by FGFR3 activation, resulting in defective cartilage synthesis at the growth plate.

What are the characteristics of Achondroplasia?

Shortened proximal extremities, a trunk of relatively typical length, and an enlarged head with a bulging forehead, conspicuous depression of the root of the nose

What is Thanatophoric dwarfism?

The most common lethal form of dwarfism, also caused by FGFR3 activation, leading to underdeveloped thoracic cavity and respiratory insufficiency.

Death at birth or soon thereafter.

What is Osteopetrosis?

Marble bone disease, caused by mutations interfering with osteoclast function, associated with dense sclerotic bone, decreased bone turnover, and weak bones.

Tissues become weak and predisposed to fractures

Includes CA2 mutations

What are complications of osteopetrosis?

Cranial nerve palsies and hepatosplenomegaly.

What are the main functions of M-CSF and RANK in osteoclast formation?

M-CSF is crucial for the survival of osteoclast precursors, while RANK signaling is essential for osteoclast differentiation and activation.

What is the difference between osteopenia and osteoporosis?

Osteopenia is reduced bone mass, while osteoporosis is severe osteopenia that increases the risk of fractures.

What are the two main types of Osteoporosis?

Primary (aging and postmenopausal) and Secondary (endocrine disorders, drugs).

What is the typical clinical course of Osteoporosis?

Increased risk of fractures, especially involving the vertebrae and hips, potentially leading to kyphosis, scoliosis.

Pulmonary embolism, and pneumonia are complications of fractures and immobility.

When is osteoporosis detected in X-ray?

X-ray not sensitive until 30%-40% of bone mass has disappeared.

How is Osteoporosis prevented and treated?

Prevention involves adequate calcium and vitamin D intake, and regular exercise; treatment includes bisphosphonates, calcitonin, denosumab, and selective estrogen receptor modulators.

What are the main characteristics of bone affected by Osteoporosis?

Decreased bone mass, cancellous bone, thinned cortices, reduced trabeculae thickness, and larger marrow spaces.

What causes Rickets and Osteomalacia?

Vitamin D deficiency, leading to defects in the mineralization of bone matrix.

What is the difference between Rickets and Osteomalacia?

Rickets occurs in children, affecting the growth plates, while osteomalacia occurs in adults, affecting bone remodeling.

What is Paget Disease (Osteitis Deformans)?

A condition characterized by excessive osteoclast activity followed by structurally unsound osteoblast deposition of bone, resulting in disordered and weak bone.

There is a net gain in bone mass, but newly formed bone is disordered and weak.

What is the pathogenesis of Paget Disease?

Genetic: mutations that increase NFkB, RANK activating mutations, OPS inactivating mutations leading to increased osteoclast resorption.

Environmental: geographic, paramyxovirus infection, infection of osteoclast precursors by measles or other viruses.

What are the three phases in the evolution of Paget Disease?

An initial osteolytic phase, a mixed osteoclastic-osteoblastic phase, and a final sclerotic phase.

What are the clinical manifestations of Paget Disease?

Polyostotic

Bone pain

Headache, visual and auditory disturbances, nerve root compression (lion face)

Back pain, compression fractures, kyphosis

Long bone bowing and fractures.

What is the result of Hyperparathyroidism on bone?

Increased osteoclast activity and bone resorption, leading to fractures, deformities, osteoporosis, brown tumors, and osteitis fibrosa cystica.

What role does PTH hormone play in hyperparathyroidism?

PTH indirectly increases RANKL expression on osteoblasts.

What are brown tumors?

hemosiderin deposits and fibrosis seen due to hemorrhages resulting from microfractures of weakened bones.

What is Osteitis Fibrosa Cystica?

The combination of bone resorption, fibrosis, and cystic brown tumors of severe hyperparathyroidism (von Recklinghausen disease of bone).

What are the different types of Fractures?

Greenstick, simple/closed, open/compound, comminuted, displaced, stress, and pathologic.

What is greenstick (incomplete? fracture?

Type of fracture in which the bone bends and cracks but does not break completely, commonly seen in children.

What is simple/closed fracrure?

Type of fracture where the bone breaks but does not pierce the skin, typically resulting in less risk of infection.

What is open/compound fracture?

Type of fracture in which the bone breaks through the skin, posing a higher risk of infection and complications.

What is comminuted fracture?

Type of fracture where the bone is broken into multiple pieces (fragmented)

What is displaced fracture?

Type of fracture where the bone ends are not aligned and have moved apart.

What is stress fracture?

A small crack in the bone that occurs due to repetitive force or overuse, often seen in athletes.

What is pathologic fracture?

Type of fracture involving bone weakened by underlying disease or conditions such as osteoporosis or cancer.

What are the stages of Fracture Healing?

Hematoma formation, influx of inflammatory cells, formation of soft callus, conversion to bony callus, remodeling, and restoration of the medullary cavity.

What is seen by end of week 1 in fracture healing process?

A mass of predominantly uncalcified soft callus is formed.

What is seen by week 2 in fracture healing process?

Soft callus is converted to a bony callus by deposition of woven bone by osteoblasts.

What happens in the final stages of fracture healing process?

The bony callus matures to response to mechanical triggers where excess tissues is absorbed.

The medullary cavity is restored.

What are potential Complications of Fractures?

Deformity, delayed union or nonunion, infection, compartment syndrome, and fat embolism syndrome.

What is Compartment Syndrome?

Edema and bleeding within a compartment of the limb, causing compression of nerves and vessels, potentially leading to ischemia and necrosis.

What are the treatments for compartment syndrome?

Cast splitting and fasciotomy

What is fat embolism?

Presence of fat globules in the circulation- common with with severe skeletal injuries

What is Fat Embolism Syndrome (FES)?

A constellation of clinical manifestations resulting from fat globules in the small blood vessels of the lung and other organs

Characterized by pulmonary insufficiency, neurological symptoms, anemia, thrombocytopenia, and petechial rashes.

What is the pathogenesis of FES?

When bone is fractured, fat is released into circulation by rupture of venules.

Fat emboli cause occlusion of pulmonary & cerebral microvasculature, aggravated by platelet & erythrocyte aggregates

Free fatty acids released from fat cause toxic injury to endothelium

What are clinical features of FES?

1 to 3 days after injury as the sudden onset of tachypnea, dyspnea, irritability, and restlessness, which can progress rapidly to delirium or coma

What are the treatments for FES?

Correct hypoxemia, corticosteroids Mechanical ventilation may be needed

What is Osteonecrosis?

Ischemic necrosis of bone and marrow in the absence of infection.

Commonly involves proximal femur, distal femur, proximal humerus

Can occur in subchondral epiphysis medullary cavity

Accounts for 10% hip replacements

What are the causes of Osteonecrosis?

Mechanical vascular interruption (fractures), thrombosis or embolism, vessel injury (vasculitis), corticosteroid use, and idiopathic.

What is the clinical course of osteonecrosis?

Subchondral infarcts

Chronic pain, at first at with activity, then at rest

May collapse and cause secondary osteoarthritis

Medullary infarcts may be silent Osteonecrosis of head of femur

Necrosis of spongy bone and marrow

Microscopy: dead bone interspersed with areas of fat necrosis

What is Acute Pyogenic Osteomyelitis?

Inflammation/infection of bone and marrow, commonly caused by staphylococcus aureus.

How is osteomyelitis spread?

Hematogenous spread- is the commonest mode of spread

Extension from an infection in adjacent joint or soft tissue

Traumatic implantation after compound fractures or orthopedic procedures (surgery, joint prosthesis, skeletal traction)

What bacteria cause osteomyelitis?

Caused by staphylococcus aureus- MRSA

Escherichia coli and other gram negative in UTI

H. Influezae and group B streptococci in neonates

What is a sequestrum and an involucrum?

A sequestrum is non-viable necrotic bone, and an involucrum is a shell of living tissue around a sequestrum.

What is a subperiosteal abscess?

Inflammation spread through haversian system that reach periosteum

What is a draining sinus in osteomyelitis?

When the infection ahs spread to soft tissues and skin

What are the clinical manifestations of Acute Pyogenic Osteomyelitis?

Fever, leukocytosis, and throbbing pain.

What are diagnostics and treatment of osteomyelitis?

Blood & bone culture

Radiology- periosteal elevation, lytic area of necrosis

Treatment: Antibiotics, surgical drainage

What is Tuberculous Osteomyelitis?

Osteomyelitis caused by mycobacterium tuberculosis, often involving the spine (Potts disease)

Characterized by bone necrosis and vertebral deformity leading to collapse

What is Pott disease?

Tuberculous osteomyelitis of the spine, leading to vertebral deformity and collapse.

Presence of neurological compromise

The spine is involved in 40% of cases of tuberculous osteomyelitis (Pott disease)

Extensive bone destruction involving mid thoracic vertebrae

How are bone tumors classified?

According to the cell of origin: bone-forming, cartilage-forming, or unknown origin.

What is Osteosarcoma?

A bone-producing malignant tumor

most common primary malignant tumor of bone, mostly seen in patients younger than 20 years of age.

Commonly arises in the metaphyseal region of long bones, mostly about the knee

RB gene mutations occur in most of sporadic tumors, greatly increased risk with hereditary retinoblastomas

What are clinical manifestations of osteosarcoma?

Painful enlarging mass around the knee, pathologic fracture can be the first sign

Triangular shadow on X-ray between the cortex & raised periosteum (Codman triangle) is characteristic

Typically show hematogenous metastasis at the time of diagnosis, esp. to the lungs

What is the morphology of osteosarcoma?

gritty-appearing, gray-white tumors, destroy the surrounding cortices, producing soft tissue masses

Tumor cells show anaplasia, formation of bone (osteoid) by malignant cells is essential for diagnosis of osteosarcoma

What is a Codman triangle?

A triangular shadow on X-ray between the cortex & raised periosteum, characteristic of osteosarcoma.

What is Chondrosarcoma?

A malignant cartilage forming tumor, commonly arising in the pelvis, shoulder, ribs.

Affects 40 or older

What are clinical manifestation of chondrosarcomas?

The tumor manifest as painful, progressively enlarging masses, mostly composed of malignant hyaline and myxoid cartilage

Chondrosarcomas metastasize hematogenously, mostly to the lungs and skeleton

There is a correlation between grade and biologic behavior; most chondrosarcomas are indolent and low-grade, with a 5 year survival rate of 80% to 90%

What is Ewing Sarcoma?

A malignant tumor composed of primitive round cells, mostly in younger than 20 years, affecting boys more frequently.

What are clinical manifestations and treatments of Ewing sarcomas?

The tumors usually arise in the diaphysis of long bones

Most often associated with t(11;22)

They present as painful enlarging masses; extend into soft tissue

Treated with neoadjuvant chemotherapy followed by surgical excision

What is Giant Cell Tumor?

A tumor affecting adults

arising in the epiphyses of long bones, composed of osteoblast precursors, which promotes the proliferation of osteoclasts, which cause destructive resorption of bone

They can be locally aggressive

Cause arthritis-like symptoms, or present with pathologic fractures

What are common metastatic bone tumors?

Metastases from cancers of the prostate, breast, kidney, and lung, typically multifocal and involve the axial skeleton.

What are radiographic appearance of metastatic bone tumors?

Others such as renal cell carcinomas and breast cancers are most often associated with lytic lesions

The presence of bone metastases generally carries a poor prognosis

What is Osteoarthritis?

Most common joint disorder caused by degeneration of articular cartilage.

Primary osteoarthritis occurs in older age- most cases without initiating cause

Secondary osteoarthritis (in less than 5%) occurs in youth, some predisposing condition present- trauma, marked obesity

What are clinical symptoms of Osteoarthritis?

Aching pain, morning stiffness, crepitus & limitation in range of movement.

Osteophytes impinge on spinal foramina causing neurologic deficits

What is the pathogenesis and morphology of OA?

There is an imbalance in the articular cartilage matrix degradation and replacement

Due to an imbalance in the activity, and signaling of cytokines and growth factors (involve genetic factors)

Less proteoglycans & type II collagen network, as a result of decreased synthesis and increased degradation and loss of matrix

Parts of cartilage are lost, the subchondral bone plate is exposed & burnished by friction, (bone eburnation)

Dislodged pieces of cartilage and bone, form loose bodies (joint mice)

Osteophytes develop at the margins of the articular surface

What are locations of OA?

Involves hips, knees, lumbar & cervical vertebrae, proximal and distal interphalangeal joints first carpometacarpal joints, and first tarsometatarsal joints

What are Heberden nodes?

Nodes that occur in DIP joints in osteoarthritis.

What are is rheumatoid arthritis RA?

RA is a systemic, chronic inflammatory autoimmune disease principally attacking joints.

It causes a proliferative synovitis that progresses to destroy articular cartilage and underlying bone

Commoner in women, peak incidence is in the second to fourth decades

What is the pathogenesis of rheumatoid arthritis RA?

Pathogenesis summary: Disease occurs by activation of CD4+ helper T cells responding to microbial, or citrullinated self proteins

CD4+ T cells cause a cytokine-mediated inflammation

Cytokines ( esp. TNF) activate macrophages, whose products cause tissue injury, and activate synovial cells which produce proteolytic enzymes- causing destruction of the cartilage, ligaments, and tendons

Antibodies to citrullinated proteins (anti CCP) e.g. fibrinogen, collagen- may form immune complexes that deposit in the joints & cause injury

These antibodies are a diagnostic marker for the disease

What are clinical features of RA?

symmetric polyarticular arthritis, affecting the small joints of the hands and feet, ankles, knees, wrists, elbows, shoulders, cervical spine

Systemic features: weakness, malaise, low-grade fever, rheumatoid nodules

Warm, painful, swollen & stiff joints, later motion is limited, joints deformed, and in time complete ankylosis

Pursues a chronic, remitting-relapsing course

Anti-CCP and RA (rheumatoid factor) antibodies present in 80% of patients

What key products do synovial cells produce?

Synovial cells produce proteolytic enzymes that cause destruction of the cartilage, ligaments, and tendons

Describe the morphology of RA

Proliferating & inflammed synovial lining forming a pannus

Articular cartilage subjacent to the pannus is eroded, later bony erosions

Joint space filled by fibrosis and ossification may cause permanent ankylosis

Destruction of tendons, ligaments, & joint capsules produces the deformities (radial deviation of wrist, ulnar deviation of fingers, swan-neck deformity

What is juvenile rheumatoid arthritis?

group of disorders of unknown cause that present with arthritis before age 16 and persist for at least 6 weeks

What is a key feature of Juvenile Rheumatoid Arthritis?

Rheumatoid nodules and RA factor are usually absent in Juvenile Rheumatoid Arthritis

What are characteristics of juvenile RA?

oligoarthritis is more common

Systemic disease is more frequent

large joints are affected more often than small joints

rheumatoid nodules and RA factor are usually absent

Antinuclear antibody (ANA) is common Pathogenesis is similar to adult RA; damage appears to be caused by CD4+T cells & is cytokine mediated

Many affected individuals may have chronic disease, only 10% develop serious functional disability

What is gout?

Gout results from increased levels of uric acid in the blood either due to increased production or decreased renal excretion

Monosodium urate crystals precipitate from body fluids supersaturated with uric acid and induce an acute inflammatory reaction mainly in joints

More common in men

What are primary and secondary gout?

Primary gout (90%) results from overproduction of uric acid- basic cause is unknown

Rarely identifiable enzymatic defects are present

Secondary gout, (10%) the cause of the hyperuricemia is known:

Increased production- cell lysis during chemotherapy for lymphoma/leukemia)

decreased excretion (chronic renal insufficiency)

What are risk factors of gout?

Risk Factors: obesity, excess alcohol intake, consumption of purine rich foods, diabetes

What are complications of gout?

Renal complications: uric acid crystals in tubules and renal calculi

What is acute arthritis and its morphology in gout?

Sudden onset, excruciating joint pain with localized erythema, and warmth- first attacks are mostly monoarticular; typically in the first metatarsophalangeal joint (great toe)- may last for hours to weeks; gradually completely resolves

neutrophilic infiltrate in the synovium and synovial fluid, needle-shaped monosodium urate crystals in the synovium

What is chronic tophaceous arthritis and its morphology?

Happens a decade or so

Crystal deposits in joint tissues with bone erosion & loss of the joint space

Urates encrust the articular surfaces and form visible deposits in the synovium

Inflamed thickened synovium forming a pannus that destroys cartilage, & leads bone erosions; in severe cases, ankylosis of joint

What are tophi?

large aggregates of urate crystals surrounded by an inflammatory reaction- seen in articular cartilage, ligaments, tendons, and soft tissues, and elsewhere

What is the most common pathogen that causes Suppurative Arthritis?

Staphylococcus aureus is the most common pathogen in adults and children

In neonates, group B Streptococcus and Neisseria gonorrhoeae

Infection with gram-negative bacilli and Pseudomonas is generally seen in patients who are immunocompromised

What are the clinical features and treatments of suppurative arthritis?

Sudden onset- acutely painful and swollen joint & restricted range of motion

Usually involves only a single joint, most commonly the knee, hip, shoulder, elbow, wriest

Fever, leukocytosis, and elevated ESR

Treatments/diagnostic:

Joint aspiration- yields purulent fluid in which the causal agent can be identified

Antimicrobial therapy