Robbins - Joints and ST Tumors (Ch. 26) Flashcards
2 synovial cell types in synovial joints (w/ function)
Type A = phagocytic macrophages
Type B = hyaluronic acid producing fibroblasts
Why is hyaline cartilage unique?
No blood supply, no lymphatic drainage, no innervation
Composition of hyaline cartilage
Water (70%), Type 2 collagen (10%), proteoglycans (8%), chondrocytes
How is articular cartilage destroyed pathologically?
Increased IL-1 and TNF that triggers degradation – from chondrocytes, synoviocytes, fibroblasts, and inflammatory cells
50+, deep achy pain that worsens with use or early morning, crepitus, limited ROM. Muscle spasms, radicular pain, and neurologic deficits
Other name?
What is it?
Osteoarthritis
Degenerative joint disease (DJD)
Degeneration of cartilage and disordered repair that results in structural and functional failure of synovial joints
Most common cause of osteoarthritis
It is a disease in which chondrocytes respond to ___ and ___ stresses resulting in the breakdown of the ___
Old age
Biochemical, mechanical
Matrix
Men vs. women - most common osteoarthritis locations
Men - Hips
Women - Knees, Hands
Early vs. Late OA – what is happening microscopically?
Early – chondrocytes proliferate into clusters, water content increases, secrete mediators and proteases that cleave proteoglycans and collagen fibers
Late – repetitive injury causes chronic inflammation, chondrocyte death, cartilage loss, and subchondral changes
OA - see what macroscopically? (3)
Polished ivory surface (eburnation) w/ joint mice (as cartilage is sloughed off) and fibrous-walled cysts
Heberden nodes
Bouchard nodes
Seen in what?
Osteophytes at the distal IP joints
Bony outgrowths or cysts of the proximal IP joints
Osteoarthritis
Malaise, fatigue, generalized MSK pains. Joints are swollen, warm, painful, and stiff in morning or after inactivity. Joint enlargement and limited ROM.
Most common joints?
Rheumatoid arthritis
Hands and feet, then other extremity joints
Progression of RA in the joint?
Damage caused by what mediators?
Complete ankylosis – fusion of bones, thus near immobility
IL-1, **IL-17 (Th17), TNF, **IFN (Th1)
Characteristic exam/radiograph signs for RA (3)
- Radial deviation of wrist
- Ulnar deviation of fingers
- Flexion-hyperextension of fingers (swan-neck)
Diagnosing RA (3)
- Classic radiograph findings
- Sterile, turbid synovial fluid w/ decreased viscosity, poor mucin clots, and inclusion-bearing neutrophils
- Rheumatoid factor and anti-CCP antibodies
**Synovial cell hyperplasia, dense inflammatory infiltrates, increased vascularity, exudate on joint surfaces, osteoclastic activity
RA
**Mass of edematous synovium, germinal centers, inflammatory cells, granulation tissue, and fibroblasts growing over the articular cartilage, causing its erosion
Pannus - RA
RA can look like what other diseases? Why?
SLE or scleroderma
Lesions of skin, heart, BVs, and lungs are common as well
Molecular findings in RA (2)
Anti-CCP (citrullinated peptides) autoantibodies
Serum IgM or IgA against the Fc portion of serum IgG (Rheumatoid factor)
Genetic susceptibility for RA
Other findings in RA (other organs) (2)
HLA-DRB1
Nontender subQ nodules w/ fibrinoid necrosis, small/medium vasculitis
Child under 16, arthritis for 6+ weeks
Which joints most common? Few or many?
Molecular finding?
RF? Rh nodules?
Damage done by what?
Juvenile idiopathic arthritis
Large joints - few (oligo)
ANAs
NO RF or nodules
Cytokines (same as RA)
Seronegative spondyloarthropathies - what are they?
Immune-mediated diseases (T-cell response), in a susceptible person, to some environmental antigen, that cross reacts w/ native molecules of the MSK system and causes arthritis
Seronegative spondyloarthropathies - 4 diseases
Ankylosing spondylitis
Reactive arthritis
Enteritis associated arthritis
Psoriatic arthritis
4 commonalities w/ all the seronegative spondyloarthropathies
Why are they termed “seronegative”?
- Pathology of ligamentous attachments of the joint, NOT the synovium
- Sacroiliac joint involvement
- NO RF
- HLA-B27 association
No specific autoantibodies
Vertebrae + SI joints
10-20, young males - low back pain, spinal immobility
HLA-B27 (90%)
What is it?
Ankylosing spondyloarthritis
Destruction of articular cartilage and bony ankylosis (fusion)
Male, 20-30
Urethritis/cervicitis (non-gonococcal) or bloody diarrhea –> LATER arthritis (joint stiffness, low back pain) and conjunctivitis
HLA-B27 (80%)
Symptoms wax and wane for months
What is it?
Organisms?
Common specific joint findings? (2)
Other complications? (4)
Reactive arthritis (Reiter syndrome)
Autoimmune reaction initiated by the GU/GI infection
Chlamydia or bloody diarrhea GI bacteria (4)
Sausage finger/toe
Calcaneal spurs
Balanitis, conjunctivitis, cardiac arrhythmias, aortic regurgitation
30-50, recurrent skin plaques w/ silver scab, joint pains in distal IP joints of hands and feet
Genetic susceptibility?
Common deformity in fingers/toes
How does this arthritis differ from RA?
Psoriatic arthritis
HLA-B27 and HLA-C
Pencil-in-cup deformity
RA = proximal IP joints
Infectious arthritis - what is it?
4 types?
Class of arthritis diseases caused by various organisms and infections that seed the joint via hematogenous spread
- Pyogenic
- Mycobacterial (TB)
- Lyme disease
- Viral
Sudden, acutely painful and swollen joint w/ restricted ROM. Fever, leukocytosis, and elevated sed rate. Purulent fluid on synovial fluid aspiration. Stains positive for an organism.
Most common organism in…
- Kids
- Adults
- Sickle cell
- Sexually active females
Suppurative (bacterial) arthritis
Kids = H. flu Adults = staph. aureus HbSS = Salmonella Females = Gonococcus
Gradually increasing joint (LE) pain, confluent granulomas w/ central caseous necrosis, lung mass or osteomyelitis
Mycobacterial arthritis
Hiking in NE US, skin lesion followed later by arthritis of large joint(s) that migrate every 1-2 months. Anti-organism antibody detected in serum.
Organism?
Lyme arthritis
Borrelia burgdorferi
Causes of viral arthritis (6)
HIV, HBV, HCV, EBV, Parvo, Rubella
30+ male w/ obesity, alcoholic, and/or metabolic syndrome. Transient attacks of acute arthritis w/ redness and warmth in small extremity joint. Dense neutrophilic infiltrate in synovium. Long, slender, needle-shaped crystals found.
Necessary finding on labs?
Common 1st joint?
Gout (acute arthritis)
Hyperuricemia (> 6.8 mg/dL)
BIG TOE
MOST causes of hyperuricemia are (known/unknown) and (primary/secondary)
Genetic susceptibility?
Causes of 2º gout? (2)
Unknown, Primary
HGPRT mutation (can’t salvage purines)
Chemotherapy (leukemia), Decreased excretion (CKD)
Molecular cause of inflammation in gout
MSU crystals –> cytokines and crystal phagocytosis –> proteases and lysosomal enzymes –> injury/inflammation
Joints most commonly affected in gout
Why?
Peripheral joints
MSU crystallizes more at lower temperatures
Risk factors for gout (5)
- Prolonged hyperuricemia
- HGPRT deficiency (X-linked)
- Heavy alcohol consumption
- Obesity
- Drugs (thiazides) that reduce excretion
What happens after many episodes of acute gout?
Chronic tophaceous arthritis…
MSU crystals encrust the articular surfaces, forming visible deposits. Synovium becomes hyperplastic and thickens to form a PANNUS, which leads to articular bone erosions and even bony ANKYLOSIS
Large aggregations of urate crystals surrounded by intense inflammatory reaction of foreign body giant cells
When do these form?
Tophi – hallmark of gout
About 12 years after the initial acute attack
Gout - non-arthritic association (chronic)
Nephropathy - nephrolithiasis and pyelonephritis
50+, asymptomatic or mild arthritis of upper extremity joint(s), crystals within articular cartilage, menisci, and intervertebral discs. Chalky white, friable deposits seen as oval purple-blue aggregates on staining. Rhomboid, birefringent. NOT NEEDLE-SHAPED.
Other names?
Calcium pyrophosphate crystal deposition (CPPD) disease
Pseudo-gout
Chondrocalcinosis
Causes of secondary pseudo-gout (6)
Joint damage Hyper-PTH Hypothyroidism Hemochromatosis DM Ochronosis (alkaptonuria)
Hereditary form of pseudo-gout
Mutation in pyrophosphate transport channel
Most cysts and tumors of the joints are due to ____ to trauma or degenerative processes, NOT ____
Reactivity
NOT primary
Small pea-sized firm, fluctuant, translucent nodule in the wrist. Filled w/ synovial fluid. No cellular lining, no connection to the synovial fluid.
Comes via ____
Ganglion cyst
Cystic/myxoid degeneration of connective tissue
Herniation of synovium through the joint capsule or enlargement of a bursa, producing a fluctuant mass. Hyperplastic synovial lining w/ inflammatory cells and fibrin.
Most common one?
Synovial cyst
Baker cyst (popliteal - RA)
Soft tissue tumors are most likely (benign/malignant)
Benign
40-60, well-encapsulated mass on the trunk or proximal extremity. Soft, mobile, painless. Yellow adipose tissue.
Lipoma
50-60, poorly differentiated mass in deep tissue of proximal extremity or retroperitoneum. Sheets of anaplastic cells w/ bizarre nuclei and immature adipocytes (lipoblasts).
Genetics?
Pleomorphic liposarcoma
(12;16) FUS-DDIT3
50-60, mass in deep tissue of proximal extremity or retroperitoneum. Abundant ground substance and rich capillary network w/ scattered immature adipocytes and primitive round-stellate cells
Genetics?
Myxoid liposarcoma
(12;16) FUS-DDIT3
Irregular or nodular thickening of the palmar fascia, w/ puckering and dimpling. 4th and 5th fingers are partially flexed
What is it?
Superficial fibromatosis - Palmar (Dupuytren contracture)
Infiltrative fibroblastic proliferation, causing local deformity
Palpable mass on dorsolateral penis. Abnormal curvature of the shaft, difficulty urinating.
What is it?
Superficial fibromatosis - Penile (Peyronie disease)
Infiltrative fibroblastic proliferation, causing local deformity
Women 13-30, large poorly-demarcated mass, rubbery and tough, with infiltration of surrounding tissues. Anterior abdominal wall, limb girdle, or mesentery.
Genetics?
Familial disease w/ predisposition?
Deep fibromatosis (Desmoid tumor)
APC or Beta-catenin mutation
FAP (APC mutation)
Almost all skeletal muscle tumors are ____
MALIGNANT
Child. Infiltrating mass of round and spindle cells in a myxoid stroma. Cells w/ cross striations.
Most common locations?
Embryonal rhabdomyosarcoma
Sinuses, head/neck, GU tract
Child, Infiltrating mass of uniform round cells w/ little cytoplasm. Fibrous septae divide the cells into clusters or aggregates. Central cells are discohesive, peripheral cells are adherent to the septae.
Supposed to look like what?
Do NOT see ___
Genetics?
Alveolar rhabdomyosarcoma
Pulmonary alveoli
Cross striations
(1;13) or (2;13) PAX-FOXO1
Small, painful nodules in the skin, fascicles of densely eosinophilic spindle cells that intersect at right angles. Blunt-ended, elongated nuclei.
Leiomyoma (of erector pili mm)
Painless firm mass in the retroperitoneum or deep extremity. Eosinophilic spindle cells w/ blunt-ended hyperchromatic nuclei in interweaving fascicles. Stains w/ actin-myosin antibodies.
Leiomyosarcoma
20-49, deep-seated mass present for several years. Uniform spindle cells w/ scant cytoplasm. Potential gland-like structures w/ cuboidal to columnar epithelioid cells. Keratin-positive (some).
Genetics?
Synovial sarcoma
(x;18) SS18-SSX1/2/4
Synovial sarcoma – usually in the synovium?
NO (misnomer) – can be joint, chest wall, head/neck
Middle age or older. Large mass in deep soft tissue of thigh. Pleomorphic, anaplastic spindle to polygonal cells w/ irregular/bizarre nuclei. Abundant mitotic figures. Lacking differentiation.
Common?
Undifferentiated pleomorphic sarcoma (UPS)
YES - largest category of adult sarcomas
