(Muscskelint) Objectives For Bone And Joint Pathology

Front 1

Describe the morphologic hallmark of osteoarthritis

Back 1

Erosion of articular cartilage, no evidence of inflammation

Front 2

Name 3 anatomic sequelae which occur after erosion of articular cartilage:

Back 2

Peripheral formation of Osteophytes (lipping)
Cystic degeneration of bone
Sclerosis of subchondral bone

Front 3

Name 3 changes in the composition of articular cartilage with aging:

Back 3

Decrease in proteoglyacans
Increasing water composition
Decreasing the synthesis of type II collagen

Also increased apoptosis of chondrocytes

Front 4

Name 5 organs (besides joints) that can be affected by rheumatoid arthritis:

Back 4

Skin
Heart
Lungs
Muscles
Blood vessels

Front 5

Describe the typical histopathologic features of RA in joints:

Back 5

Inflammation, vasculation, fibrin in joint space, presence of neutrophil, hyperplasia of synoviocytes

Front 6

What is the most common skin lesion seen in Rheumatoid Arthritis and describe its pathology:

Back 6

Rheumatoid nodules (25% of patients with RA have them - especially more severe cases)

They occur in the skin in areas subjected to pressure (ulnar side of forearm, elbow, occiput, lumbosacral area)

Under the microscope: Look like a caseating granuloma (central area of necrosis surrounded by a rim of histiocytes and lymphocytes)

Front 7

Which two aspects of the immunopathogenesis of RA are still unknown:

Back 7

The antigen that triggered the original infection, and the genetic susceptibility

Front 8

Which joints in the hands are typically involved earliest in RA?

Back 8

Generally, small joints affected before larger ones.

MCP and PIPs usually affected first (opposite of osteoarthritis)

Front 9

Compare juvenile and adult forms of rheumatoid arthritis (6):

Back 9

Six findings you seen in the juvenile version more than the adult version:

Oligoarthritis
Large joints affected more often
Has a more systematic onset (fever, fatigue, etc)
Rh factor absent
Rheumatoid nodules tend to be absent
Serum is ANA positive (Although adult form can be too)

Front 10

Which HLA phenotype is more often present in seronegative spondyloarthropathies?

Back 10

HLA B-27

Front 11

Name two mechanisms whereby an infection can involve the joint.

Back 11

Direct invasion (as in trauma, surgery) and systemic spread

Front 12

Name the organism and disease that is frequently associated with migratory arthritis involving the large joints which spontaneously remits:

Back 12

Organism:Borrelia Burgdorferi
Disease: Lyme disease
Disease is spread by ticks

Front 13

Describe the diagnostic microscopic feature of acute gouty arthritis in joint fluid:

Back 13

Monosodium urate crystals found in the cytoplasm of neutrophils.
They are long, slender and negatively birefringent.

Front 14

Describe the metabolic defect in persons with primary gout:

Back 14

The majority of cases happen when the body fails to get rid of uric acid. A minority of cases involve the production of too much uric acid.

According to Robbins page 1311 (the great majority of cases of gout are primary, in which the metabolic defect underlying the increased levels of uric acid is unknown.

Front 15

Describe the pathognomonic histopathologic lesion of chronic gouty arthritis:

Back 15

Not 100% sure on this one …

I think it's tophi which are large aggregations of urate crystals surrounded by an intense inflammatory reaction of macrophages, lymphocytes and large foreign body giant cells.

Front 16

Name the crystalline substance deposited in joints in pseudogout and describe its microscopic features in joint fluid
How do these crystals differ from urate crystals?

Back 16

The crystals are caclium pyrophosphate.

Crystals are rhomboid or geometric shaped and POSTIVELY birefringement. (Gout has needle shaped negatively birefringement urate crystals)

Front 17

Describe the most common location, pathogenesis and treatment of ganglion cyst:

Back 17

Near joint capsule or tendon sheath (especially in joints of wrist, also Baker's cysts).

Pathogenesis = Cystic or myxoid degeneration of connective tissue (cyst wall lacks true cell lining)

Treatment: Surgery cures it if it causes problems

Front 18

Compare pigmented villonodular synovitis (PVS) and giant cell tumor of tendon sheath (GCT) with respect to cell of origin, typical location, size of tumor, and treatment:

Back 18

Both are neoplasms of the synovial lining of joints, sheaths, and bursa.
PVNS affects one or more joints diffusely, while GCT occurs as a discrete nodule.
PVNS usually presents as monoarticular arthritis while GCT affects tendon sheaths along the wrists and fingers.
PVNS can erode into adjacent bones and soft tissues (which allows it to be confused with other forms of neoplasia) while GCT is slow growing and involves mesenchymal.

Surgery recommended in both lesions though PVNS can be difficult to excise and GCT often recurs.

Front 19

Describe how depth and size of an adipose tumor correlates with probability of malignancy:

Back 19

Malignant tumors are bigger in size and occur deeper in the skin

Front 20

Define lipomatosis

What is the most common gender / location?

Back 20

Lipomatosis = Many lipomas

Most affects males and in the neck and shoulder area

Front 21

ID most common age range and gender of patients with angiolipoma

Back 21

Affects children / young adult males

Front 22

Name the most common soft tissue sarcoma in the US and it's 5 most common locations:

Back 22

#1 = Liposarcoma

Affects thigh, trunk, retroperitoneum, arms, and neck

Front 23

Name 3 principal histopathologic types of lipsarcoma

-What is the most common type?
-Which type is associated with rearrangement of CHOP gene?

Back 23

3 types are pleomorphic, Myxoid, and well differentiated

The myxoid type is associated with CHOP

Front 24

Which 3 factors of liposarcoma determine its prognosis?

Back 24

Histologic type, size, and location

Front 25

Describe the typical clinical history associated with nodular fasciitis:

Back 25

A young or middle aged adult presents with a painful solitary mass on an extremity which had been growing for a few weeks but then stopped growing

Front 26

Name one gross and two microscopic features that make surgeons and pathologists concerned about the possibility of sarcoma in patients with nodular fasciitis:

Back 26

Grossly it is concerning that they can occur in subcutaneous regions (liposarcomas can affect the deeper coetaneous regions as well)

Under the microscope they show high cellularity and lots of mitoses which should be concerning for obvious reasons

Front 27

Describe the usual location and predisposing history in patients with myositis ossificans:

Back 27

Location = Skeletal muscle (usually quads and brachialis muscle).
Trauma is a major predisposing factor

Front 28

Name 3 anatomic sites typically involved in benign superficial fibromatosis:

Back 28

Palmar, plantar, and penile (3 P's)

Front 29

Describe the biologic behavior of deep fibromatosis (desmoid tumor) and name the inherited syndrome in which desmoid tumor and adenomatous polyposis of colon co-exist:

Back 29

They are tame looking fibroblasts (specifically myofibroblasts) arranged in broad sweeping fascicles. They can invade local tissue but they cannot metastasize.

Condition of FAP

Front 30

What is a fibrosarcoma and what 3 factor affects its prognosis?

Back 30

Fibrosarcoma = Malignant deep soft tissue fibrous tumor.

3 Factors affecting prognosis is stage, size, and grade

Front 31

What is a leiomyoma and what is the most common location in women?

Back 31

Leiomyoma = Benign neoplasm of smooth muscle.
Most common location in women = myometrium

Front 32

What is a leiomyosarcoma and what are the two most common anatomic sites?

Back 32

A malignant neoplasm of smooth muscle. Affects skin and deep soft tissue (extremities and retroperitineum)

Front 33

Describe the age group and natural history associated with alveolar soft part sarcoma:

Back 33

Affects adolescents (and kids) in the head and neck. Affects adults in the deep mass of legs, hips, pelvis. It is a slow and relentless

Front 34

Why is the 2-year survival in alveolar soft part sarcoma 90% at 2 years but only 20% at 20 years.

Back 34

The cancer is relentless but very slow growing. It eventually metastasizes

Front 35

Name the 4th most common soft tissue sarcoma in US adults:

Back 35

Synovial sarcoma

Front 36

Name the two frequent anatomic locations of synovial sarcoma:

Back 36

Affects large joints (knee, hip)

Front 37

Describe 2 lines of differentiated cells composing a synovial sarcoma:

Back 37

Epithelial and mesenchmal cells

Front 38

Describe the historical basis for the name malignant fibrous histiocytome and why this neoplasm is now believed to arise from myofibroblastic cells

Back 38

It was originally named for the behavior of the tumor cells (like histiocytes) however their phenotype is more in line with myofibrocytes

Front 39

What is the natural history and prognosis of malignant fibrous histiocytoma?

Back 39

Affects muscles of the proximal extremities and retroperitineum.

It is an aggressive tumor that metastasizes in 50% of the time.

Front 40

What is the purpose of the homeobox in bone development?

Back 40

Homeobox provides a blue-print for the skeleton

Front 41

Name two zones in a growing long bone where endochondral ossification is centered:

Back 41

Primary metaphyseal and secondary eepiphyeal centers of ossification.

Front 42

What is the defective mechanism in synpolydactyly?

Back 42

Homeobox problem

Front 43

What is the defective mechanism in achondroplasia?

Back 43

Defective FGFR-3 receptor which is important for coordinating chondrocytes

Front 44

Describe the defective mechanism in thanatophoric dwarfism:

Back 44

Defective FGFR-3 receptor which is important for coordinating chondrocytes (different, more severe mutation than in achondroplasia)

Front 45

Describe the defective mechanism underlying osteogenesis imperfecta?

Back 45

Abnormal type 1 collagen leads to brittle bone formation

Front 46

Describe the defective mechanism underlying mucopolysaccharidoses:

Back 46

Deficiencies in enzymes that degrade mucopolysaccharides

Front 47

Describe the defective mechanism underlying osteoporosis:

Back 47

Reduced osteoclastic activity

Front 48

What's the difference between dysostosis and bone dysplasia?

Back 48

Dysostoses are localized anomalies due to abnormal migration of mesenchyme
Dyslasias are global disorders due to mutations in regulators of skeletal formation which affects bone and cartilage

Front 49

What is craniorachischisis and what is the sequelae involving the spinal cord?

Back 49

Failure of closure of the skull / vertebral column. It results in lethal meningomyelocele and meningoencephalocele

Front 50

Describe 4 features common to all subtypes of osteogenesis imprefecta in terms of genetic mutation, inheritance pattern, deficient protein, and histopathologic changes:

Back 50

Type 1: Autosomal dominant, leads to decreased synthesis of pro alpha 1 chain

Type 2: Mostly autosomal recessive, leads to abnormally short pro-alpha 1 chain (unstable triple helix)

Type 3: Autosomal dominant in 75% of cases (recessive in 25%) leads to altered structure of pro-pepties of pro-alpha-2

Type 4: Autosomal dominant, leads to short pro-alpha 2 chain

Front 51

Identify those subtypes of OI with normal life space, death in utero, and normal sclerae:

Back 51

Type 1 has a normal lifespan; Type II leads to death in utero; Type IV leads to normal sclerae

Front 52

Describe the pathogenesis of multi-organ failure inmucopolysaccharidoses:

Back 52

Accumulation of polysaccharides in the cells of many organs (bone, muscle, cartilage, liver, spleen, heart valves, arteries, brain)

Progressive and eventually fatal

Front 53

How does deficient osteoclast activity lead to hard, brittle bones in osteopetrosis?

Back 53

Lack of carbonic anhydrase means a lack of acidity needed to activate osteoclasts.

This leaves osteoblasts unchecked and tissue remodeling cannot occur

Front 54

What is osteoporosis and what is the most frequent complication?
What is the best method for detecting it?

Back 54

Osteoporosis = decrease in bone mass.

This can lead to fractures

Best detection method = bone density scan by dual-energy absorptiometry

Front 55

Describe the repetitive process leading to abnormal bone quality in Paget disease and ID the pathognomonic feature for the disease.

Back 55

Matrix madness (Repetitive sequences of excessive resorption and formation, leads to burn out sclerotic quiescence).

Pathognomonic feature is mosaic pattern of lamellar bone (crazy cement lines!)

Front 56

What is the typical anatomic distribution of bone disease in Paget's?

Back 56

85% or monostotic (pelvis, spine, skull).

Axial skeleton or proximal femur affected In 80% of cases.

Front 57

Name 4 metabolic disorders in which abnormal mineralization of bone occurs:

Back 57

Rickets, Osteomalacia, Hyperparathyroidism, Renal Osteodystrophy

Front 58

Define and describe histologic features of 3 overlapping stages in the repair of a fracture:

Back 58

Soft tissue callus - Hematoma followed by inflammatory influx, followed by activating cytokines, followed by osteoblast and clast activity

Bony callus - Osteoprogenitor cells deposit bone trabeculae, folllowed by chondroblast production of cartilage which undergoes enchondral ossification)

Remodeling - Bone remodeling and mineralization of callus

Front 59

Name 2 local factors and 3 systemic factors that could inhibit fracture repair:

Back 59

Local factors: Disruption of callus (too much movement) & Infection

Systemic: Calcium or phosphate or vitamin deficiencies; sepsis, ischemia / diabetes

Front 60

Define osteonecrosis and name two common zones of a bone that may be involved:

Back 60

Necrosis of a bone due to ischemia.

Common zones = 1. Subchondral (epiphysis) metaphysis and 2. Medullary cavity (diaphysis or metaphysis)

Front 61

Why is the cortex spared in medullary osteonecrosis?

Why would cartilage remain viable in subchondral osteonecrosis?

Back 61

In medullary osteonecrosis the cortex is spared because of collateral blood supply.

In subchondral osteonecrosis the cartilage is spared because it is avascular and thus not subject to the stresses of ischemia

Front 62

What is the anatomic complication of subchondral osteonecrosis that is often associated with worsening of pain and increased need for joint surgery?

Back 62

When the necrotic bone gets absorbed, cartilage may collapse or get sloughed off (secondary osteonecrosis)

Front 63

What is the most common bacterial etiology in the US for osteomyelitis?

Back 63

Staph Aureus

Front 64

Describe the most common pathogenetic mechanism for acute bone infection.

What are two potential complications that may occur if the periosteum ruptures?

Back 64

Most common mechanism = Seeding of bone after transient bacteremia (due to dental work, minor skin infection, etc)

Rupture of periosteum can lead to soft tissue abscesses and draining of the sinus to the skin.

Front 65

What are two complications of osteomyelitis that are mainly observed in children?

Back 65

Children can get:

1. Supporative arthritis if the epiphysis is involved
2. Spinal deformities if the vertebral body is involved (destruction of vertebral body or discs)

Front 66

Why is osteomyelitis due to M. tuberculosis more likely to cause neurologic deficits than other types of osteomyelits?

Back 66

Because the location of the bone infection. In TB you can see kyphoscoliosis (vertebrae -Pott's disease)
This can lead to compression of the spinal cord.

Front 67

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Osteochondroma

Back 67

#1 benign bone tumor
Cell of origin = Chondrocytes
Age = late childhood & adolescence
Imaging = Pedunculated mass continuous with bone cortex
Hist: Disorganized cartilaginous cap covered by thin fibrous tissue
Prognosis: Cured w/ excision

Front 68

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Chondroma

Back 68

#3 benign tumor
Cell of origin = Hyaline cartilage
Age = young adults
Imaging: Well circumscribed radiolucent lesion surrounded by rim of radio dense bone
Hist: Hyaline cartilage with uniform chondrocytes / endochondral ossification ] Prognosis: Cured by excision

Front 69

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Osteoid osteoma

Back 69

#4 benign tumor
Cell of origin: (not sure)
Age = under 25 (also men outnumber women)
Imaging: Round radiolucency with central mineralization surrounded by reactive bone
Hist: Randomly connected trabeculae of bone rimmed by osteoblasts
Prognosis: Cured by excision

Front 70

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Giant cell tumor

Back 70

#2 benign tumor
Cell of origin: Giant cells
Age group = ? (not sure)
Imaging: Large well define lytic defect (usually affects knee)
Hist: Sheets of giant osteoclasts set in a background of monocytes (sounds poetic)
Prognosis: Unpredictable (Complete resection curative, if not 50% recurrence, 4% metastasis

Front 71

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Malignant Lymphoma

Back 71

#3 Malignant tumor
Cell of origin: Lymph cells (B-cells)
Age group: (Not specified)
Imaging: Poorly defined, lytic destruction
Hist: Diffuse large B-cells
Prog: Depends on stage and subtype (high grade responds to multiagent chemotherapy)

Front 72

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Chondrosarcoma

Back 72

#2 Malignant tumor
Cell of origin: Cartilage
Age group: Adults >40
Imaging: Nodular growth with endosteal scalloping and flecks of calcification
Hist: Wide range of pleomorphism
Prognosis: Stage and grade dependent (5 year: 90% for grade 1, 40% for grade 3)

Front 73

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Osteosarcoma

Back 73

#1 primary bone sarcoma (excluding multiple myeloma)
Cell of origin: Osteoid producing cells
Age: Bimodal distribution (70% < age 20, 20% after age 60)
Imaging: Infiltrative bone mass invades soft tissue, lifts periosteum, and induces reactive bone formation (triangular shelf)
Hist: Many variants, although all show production of osteoid
Prognosis: Stage dependent, 60-70% survival with limb salvage therapy, or chemotherapy + radiation

Front 74

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Chordoma

Back 74

# 5 Malignant tumor
Cell of origin: Notochord
Age: 80% of all cases < 20 years old (mostly teens)
X-ray: Always on midline! Geographic bone destruction
Hist: Cords of neoplastic cells in myxoid matrix, small nuclei and abundant vacuolated cytoplasm
Prognosis: Destructive and tough to resect given location. Many patients have neurologic symptoms

Front 75

Describe the cell of origin, relative frequency among primary bone tumors, age group, imaging features, unique identifying histopathologic features and prognosis for:

Ewing Sarcoma

Back 75

#4 Malignant tumor
Cell of origin: Primitive neuroectodermal tumor (PNET)
Age: Teenagers
Imaging: Lytic destruction w/ tumor invading into soft tissue
Hist: Cells are blue (may resemble malignant lymphoma)
Prognosis: 75% 5-year survival with over 50% in durable remission with use of combined therapy.

Key genetic cause: Fusion of EWS gene on chromosome 22q12 to a family of the ETS transcription factor -> Dominant chimeric protein