Robbins - Joints and ST Tumors (Ch. 26)

Question 1

2 synovial cell types in synovial joints (w/ function)

Answer 1

Type A = phagocytic macrophages

Type B = hyaluronic acid producing fibroblasts

Question 2

Why is hyaline cartilage unique?

Answer 2

No blood supply, no lymphatic drainage, no innervation

Question 3

Composition of hyaline cartilage

Answer 3

Water (70%), Type 2 collagen (10%), proteoglycans (8%), chondrocytes

Question 4

How is articular cartilage destroyed pathologically?

Answer 4

Increased IL-1 and TNF that triggers degradation – from chondrocytes, synoviocytes, fibroblasts, and inflammatory cells

Question 5

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?

Answer 5

Osteoarthritis

Degenerative joint disease (DJD)

Degeneration of cartilage and disordered repair that results in structural and functional failure of synovial joints

Question 6

Most common cause of osteoarthritis

It is a disease in which chondrocytes respond to ___ and ___ stresses resulting in the breakdown of the ___

Answer 6

Old age

Biochemical, mechanical
Matrix

Question 7

Men vs. women - most common osteoarthritis locations

Answer 7

Men - Hips

Women - Knees, Hands

Question 8

Early vs. Late OA – what is happening microscopically?

Answer 8

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

Question 9

OA - see what macroscopically? (3)

Answer 9

Polished ivory surface (eburnation) w/ joint mice (as cartilage is sloughed off) and fibrous-walled cysts

Question 10

Heberden nodes

Bouchard nodes

Seen in what?

Answer 10

Osteophytes at the distal IP joints

Bony outgrowths or cysts of the proximal IP joints

Osteoarthritis

Question 11

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?

Answer 11

Rheumatoid arthritis

Hands and feet, then other extremity joints

Question 12

Progression of RA in the joint?

Damage caused by what mediators?

Answer 12

Complete ankylosis – fusion of bones, thus near immobility

IL-1, **IL-17 (Th17), TNF, **IFN (Th1)

Question 13

Characteristic exam/radiograph signs for RA (3)

Answer 13

• Radial deviation of wrist
• Ulnar deviation of fingers
• Flexion-hyperextension of fingers (swan-neck)

Question 14

Diagnosing RA (3)

Answer 14

• Classic radiograph findings
• Sterile, turbid synovial fluid w/ decreased viscosity, poor mucin clots, and inclusion-bearing neutrophils
• Rheumatoid factor and anti-CCP antibodies

Question 15

**Synovial cell hyperplasia, dense inflammatory infiltrates, increased vascularity, exudate on joint surfaces, osteoclastic activity

Answer 15

RA

Question 16

**Mass of edematous synovium, germinal centers, inflammatory cells, granulation tissue, and fibroblasts growing over the articular cartilage, causing its erosion

Answer 16

Pannus - RA

Question 17

RA can look like what other diseases? Why?

Answer 17

SLE or scleroderma

Lesions of skin, heart, BVs, and lungs are common as well

Question 18

Molecular findings in RA (2)

Answer 18

Anti-CCP (citrullinated peptides) autoantibodies

Serum IgM or IgA against the Fc portion of serum IgG (Rheumatoid factor)

Question 19

Genetic susceptibility for RA

Other findings in RA (other organs) (2)

Answer 19

HLA-DRB1

Nontender subQ nodules w/ fibrinoid necrosis, small/medium vasculitis

Question 20

Child under 16, arthritis for 6+ weeks

Which joints most common? Few or many?

Molecular finding?
RF? Rh nodules?

Damage done by what?

Answer 20

Juvenile idiopathic arthritis

Large joints - few (oligo)

ANAs
NO RF or nodules

Cytokines (same as RA)

Question 21

Seronegative spondyloarthropathies - what are they?

Answer 21

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

Question 22

Seronegative spondyloarthropathies - 4 diseases

Answer 22

Ankylosing spondylitis
Reactive arthritis
Enteritis associated arthritis
Psoriatic arthritis

Question 23

4 commonalities w/ all the seronegative spondyloarthropathies

Why are they termed “seronegative”?

Answer 23

• Pathology of ligamentous attachments of the joint, NOT the synovium
• Sacroiliac joint involvement
• NO RF
• HLA-B27 association

No specific autoantibodies

Question 24

Vertebrae + SI joints
10-20, young males - low back pain, spinal immobility
HLA-B27 (90%)

What is it?

Answer 24

Ankylosing spondyloarthritis

Destruction of articular cartilage and bony ankylosis (fusion)

Question 25

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)

Answer 25

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

Question 26

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?

Answer 26

Psoriatic arthritis HLA-B27 and HLA-C Pencil-in-cup deformity RA = proximal IP joints

Question 27

Infectious arthritis - what is it? 4 types?

Answer 27

Class of arthritis diseases caused by various organisms and infections that seed the joint via hematogenous spread - Pyogenic - Mycobacterial (TB) - Lyme disease - Viral

Question 28

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

Answer 28

Suppurative (bacterial) arthritis ``` Kids = H. flu Adults = staph. aureus HbSS = Salmonella Females = Gonococcus ```

Question 29

Gradually increasing joint (LE) pain, confluent granulomas w/ central caseous necrosis, lung mass or osteomyelitis

Answer 29

Mycobacterial arthritis

Question 30

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?

Answer 30

Lyme arthritis Borrelia burgdorferi

Question 31

Causes of viral arthritis (6)

Answer 31

HIV, HBV, HCV, EBV, Parvo, Rubella

Question 32

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?

Answer 32

Gout (acute arthritis) Hyperuricemia (> 6.8 mg/dL) BIG TOE

Question 33

MOST causes of hyperuricemia are (known/unknown) and (primary/secondary) Genetic susceptibility? Causes of 2º gout? (2)

Answer 33

Unknown, Primary HGPRT mutation (can't salvage purines) Chemotherapy (leukemia), Decreased excretion (CKD)

Question 34

Molecular cause of inflammation in gout

Answer 34

MSU crystals --> cytokines and crystal phagocytosis --> proteases and lysosomal enzymes --> injury/inflammation

Question 35

Joints most commonly affected in gout Why?

Answer 35

Peripheral joints MSU crystallizes more at lower temperatures

Question 36

Risk factors for gout (5)

Answer 36

- Prolonged hyperuricemia - HGPRT deficiency (X-linked) - Heavy alcohol consumption - Obesity - Drugs (thiazides) that reduce excretion

Question 37

What happens after many episodes of acute gout?

Answer 37

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

Question 38

Large aggregations of urate crystals surrounded by intense inflammatory reaction of foreign body giant cells When do these form?

Answer 38

Tophi -- hallmark of gout About 12 years after the initial acute attack

Question 39

Gout - non-arthritic association (chronic)

Answer 39

Nephropathy - nephrolithiasis and pyelonephritis

Question 40

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?

Answer 40

Calcium pyrophosphate crystal deposition (CPPD) disease Pseudo-gout Chondrocalcinosis

Question 41

Causes of secondary pseudo-gout (6)

Answer 41

``` Joint damage Hyper-PTH Hypothyroidism Hemochromatosis DM Ochronosis (alkaptonuria) ```

Question 42

Hereditary form of pseudo-gout

Answer 42

Mutation in pyrophosphate transport channel

Question 43

Most cysts and tumors of the joints are due to ____ to trauma or degenerative processes, NOT ____

Answer 43

Reactivity NOT primary

Question 44

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 ____

Answer 44

Ganglion cyst Cystic/myxoid degeneration of connective tissue

Question 45

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?

Answer 45

Synovial cyst Baker cyst (popliteal - RA)

Question 46

Soft tissue tumors are most likely (benign/malignant)

Answer 46

Benign

Question 47

40-60, well-encapsulated mass on the trunk or proximal extremity. Soft, mobile, painless. Yellow adipose tissue.

Answer 47

Lipoma

Question 48

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?

Answer 48

Pleomorphic liposarcoma (12;16) FUS-DDIT3

Question 49

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?

Answer 49

Myxoid liposarcoma (12;16) FUS-DDIT3

Question 50

Irregular or nodular thickening of the palmar fascia, w/ puckering and dimpling. 4th and 5th fingers are partially flexed What is it?

Answer 50

Superficial fibromatosis - Palmar (Dupuytren contracture) Infiltrative fibroblastic proliferation, causing local deformity

Question 51

Palpable mass on dorsolateral penis. Abnormal curvature of the shaft, difficulty urinating. What is it?

Answer 51

Superficial fibromatosis - Penile (Peyronie disease) Infiltrative fibroblastic proliferation, causing local deformity

Question 52

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?

Answer 52

Deep fibromatosis (Desmoid tumor) APC or Beta-catenin mutation FAP (APC mutation)

Question 53

Almost all skeletal muscle tumors are ____

Answer 53

MALIGNANT

Question 54

Child. Infiltrating mass of round and spindle cells in a myxoid stroma. Cells w/ cross striations. Most common locations?

Answer 54

Embryonal rhabdomyosarcoma Sinuses, head/neck, GU tract

Question 55

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?

Answer 55

Alveolar rhabdomyosarcoma Pulmonary alveoli Cross striations (1;13) or (2;13) PAX-FOXO1

Question 56

Small, painful nodules in the skin, fascicles of densely eosinophilic spindle cells that intersect at right angles. Blunt-ended, elongated nuclei.

Answer 56

Leiomyoma (of erector pili mm)

Question 57

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.

Answer 57

Leiomyosarcoma

Question 58

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?

Answer 58

Synovial sarcoma (x;18) SS18-SSX1/2/4

Question 59

Synovial sarcoma -- usually in the synovium?

Answer 59

NO (misnomer) -- can be joint, chest wall, head/neck

Question 60

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?

Answer 60

Undifferentiated pleomorphic sarcoma (UPS) YES - largest category of adult sarcomas