Pathology

Question 1

What are the characteristics of benign bone forming tumours?

Answer 1

Examples:
-osteoid osteoma
-osteoblastoma

Osteoid osteoma and osteoblastoma are benign bone producing tumours that have similar histological features but differ clinically and radiographically

Question 2

What are the characteristics of osteoid osteomas?

Answer 2

-Common locations: metaphysis of long bones
-Age: 10-20 years
-morphology: cortical interlacing microtrabeculae of woven bone
-less than 2 cm in diameter
-most common in young men
-50% of cases involve the femur or tibia, where in they typically arise in the cortex.
-has a thick rim of reactive cortical bone that may be the only cue radiographically
-present with severe nocturnal pain that is relieved by aspirin and other non-steroidal anti-inflammatory agents
-osteoblasts produce prostaglandin E2 which causes pain

Question 3

What are the characteristics of osteoblastomas?

Answer 3

-common locations: vertebral column
-age: 10-20 years
-morphology: posterior elements of vertebra, histology similar to osteoid osteoma
-larger than 2 cm
-involves the posterior components of the vertebrae (laminae and Pedicles) more frequently
-pain is unresponsive to aspirin
-the tumor does not usually induce a marked bony reaction

Question 4

What are the characteristics of osteosarcomas?

Answer 4

-common locations: metaphysis of distal femur and proximal tibia
-age: 10-20 years
-morphology: extends from medulla to lift periosteum, malignant cells producing woven bone
-produces osteoid matrix or mineralised bone
-excluding hematopoietic tumours (myeloma and lymphoma) it is the most common primary malignant tumour of bones
-has a bimodal age distribution: 75% of osteosarcomas occur in people younger than 20 years
-also common in older adults who suffer from conditions which predispose to osteosarcoma such as : Paget’s disease, bone infarcts, and previous radiation. (These are referred to as secondary osteosarcomas)
-men are more commonly affected than women
-they present as painful, progressively enlarging masses
-sometimes a pathological fracture is the first indication of osteosarcomas
-they are bulky tumours that are gritty, gray-white and often contain areas of hemorrhage and cystic degeneration
-the tumours frequently destroy the surrounding cortices and produce soft tissue masses. They spread extensively in the medullary canal, infiltrating and replacing the marrow

Question 5

How are osteosarcomas identified under a light microscope?

Answer 5

• the formation of osteoid matrix or mineralised bone by malignant tumour cells is diagnostic of osteosarcoma.
  -The neoplastic bone usually has a fine, lace like configuration but also may be deposited in broad sheets or as primitive trabeculae.
  -The tumor cells vary in size and shape (pleomorphic) and frequently have large hyper chronic nuclei.
  -Bizarre tumor giant cells, vascular invasion and necrosis are common. -Mitotic activity is high, including abnormal forms (e.g. tripolar mitosis)

Question 6

What is the clinical course of osteosarcomas?

Answer 6

-The aggressive neoplasms spread hematogenously to the lungs
- in patients with detectible metastases, the prognosis has improved with 5 year survival rates reaching 60% to 70% with chemotherapy
-for patients with metastases, recurrent disease or secondary osteosarcoma the prognosis is poor.

Question 7

What are the characteristics of osteochondromas?

Answer 7

-A benign cartilage-capped tumor
-common locations: metaphysis of long bones
-age: 10-30 years
-morphology: bony excrescence with cartilage
-known clinically as exostosis
-it is attached to the underlying skeleton by a bony stalk
-85% are solitary
-solitary osteochondromas are unusually first diagnosed in late adolescence and early adulthood, but multiple osteochondromas become apparent during childhood
-men are affected three times more often than women
-develop in bones of endochondral origin and arise from the metaphysis near the growth plate of long tubular bones, especially near the knee
-they present as slow-growing masses, which can be painful if they imping on a nerve or if the stalk is fractured. In many cases they are detected incidentally

Question 8

What are the characteristics of chondromas?

Answer 8

-Benign cartilage forming tumours of hyaline cartilage
-common locations: small bones of hands and feet
-age: 30-50 years
-morphology: circumscribed hyaline cartilage in medulla
-usually occur in bones of endochondral origin
-arise within the medullary cavity (enchondroma) or on the cortical surface (juxtacortical chondroma)
-enchondromas are usually diagnosed in individuals 20 to 50 years of age
-typically, endochromas appear as solitary metaphysical lesions of the tubular bones of the hands and feet
-the radiographical features consist of a circumscribed lucency with central irregular calcifications, a sclerotic rim and an intact cortex
-enchondromas are usually smaller than 3 cm and are grey blue and translucent. They are composed of well-circumscribed nodules of hyaline cartilage containing benign chondrocytes

Question 9

What are the characteristics of Ewing sarcoma?

Answer 9

-Common locations: diaphysis of long bones
-age: 10-20 years
-morphology: sheets of primitive small round cells
-a malignant unknown origin tumor composed of primitive round cells with varying degrees of neuroectodermal differentiation and a characteristic molecular signature
-Ewing sarcoma accounts for approximately 10% of primary malignant bone tumours and follows osteosarcoma as the second most common bone sarcoma in children
-80% of patients are younger than 20 years
-Boys are affected slightly more frequently than girls
-the tumours usually arise in the diaphysis of long tubular bones but 20% are extra skeletal.
-they present as painful enlarging masses, and the affected site is frequently tender, warm and swollen
- plain radiographs show a destructive lytic tumor with permeating e margins that extends into the surrounding soft tissues. The characteristic periosteal reaction produces layers of reactive bone deposited in an onion-skin fashion

Question 10

What is the clinical course of Ewing sarcomas?

Answer 10

-they are aggressive malignancies treated with neoadjuvant chemotherapy followed by surgical excision with or without radiation
- with chemotherapy, 5-year survival of 75% and long term cure in 50% of patients is possible

Question 11

What are the characteristics of giant cell tumours?

Answer 11

-common locations: epiphysis of long bones
-age: 20-40 years
-morphology: destroys medulla and cortex of osteoclasts
-it is so-named because multinucleated osteoclast-type giant cells dominate the histology
-it is a locally aggressive neoplasm that almost exclusively affects adults
-giant cell tumours arise in the epiphyses of long bones, most commonly the distal femur and proximal tibia
-the typical location of these tumours near joints frequently causes arthritis-like symptoms. Occasionally, they present with pathological fractures
-giant cell tumours often destroy the overlying cortex, producing a bulging soft tissue mass delineated by a thin shell of reactive bone
-grossly, they are red-brown masses taht frequently undergo cystic degeneration
-microscopically, the tumor conspicuously lacks bone or cartilage, consisting of numerous osteoclast-type giant cells with 100 or more nuclei with uniform , oval mononuclear tumor cells in between

Question 12

What are the characteristics of metastatic bone tumours?

Answer 12

-metastatic tumours greatly outnumber primary bone cancers
-the pathways of tumor spread to bone include:
Direct extension
Lymphatic or hematogenous dissemination
Intraspinal seeding (via the batson plexus of veins)

-any cancer can spread to bone, but in adults more than 75% of skeletal metastases originate from cancers of the prostate, breast, kidney and lung
-in children, metastases to bone originate from neuroblastoma, Wilms tumor and rhabdomyosarcoma
-Skeletal metastases are typically multi focal and involve the axial skeleton, especially the vertebral column
-the radiographic appearance of metastases may be purely lytic (bone destroying), purely blastic (bone forming), or mixed

Question 13

Answer 13

Osteoid osteoma

Question 14

Answer 14

Osteoblastoma

Question 15

Answer 15

Osteosarcoma

Question 16

Answer 16

Osteosarcoma

Question 17

Answer 17

Osteosarcoma

Question 18

Answer 18

Osteosarcoma

Question 19

Answer 19

Osteochondroma

Question 20

Answer 20

Enchondroma

Question 21

Answer 21

Enchondroma

Question 22

Answer 22

Ewing sarcoma

Question 23

Answer 23

Giant cell tumor

Question 24

Answer 24

Giant cell tumor

Question 25

Answer 25

Skeletal metastases

Question 26

Differentiate between the different types of arthritis (inflammation of the joint)

Answer 26

Mono arthritis: affecting one joint
It might be acute (traumatic or septic) or chronic (tuberculosis or osteoarthritis)

Poly arthritis: affecting more than one joint at the same time. It may be acute (acute rheumatic fever or infectious fevers) or chronic (rheumatoid disease, gout or degenerative Articular conditions)

Question 27

Describe how acute suppurative arthritis spreads

Answer 27

It usually affects a big joint

Caused by:
-Staphylococcus aureus
-Streptococci
-H.influenza

Spreads through:
-Hematogenous spread
-Spread from a neighbouring infection
-Direct from perforating wound

Question 28

What are the lesions caused by acute suppurative arthritis in mild cases?

Answer 28

In mild cases, the synovial membrane is red, congested, edematous, covered by fibrin and polymorphs. The joint cavity is filled with turbid fluid.

If treatment is effective, the exudate is resolved and resolution is complete

Sometimes the condition becomes chronic with thickening if the synovial membrane

Question 29

What are the lesions caused by acute suppurative arthritis in severe cases?

Answer 29

There is intense congestion, swelling, ulceration, fibrin and pus which may be sanguinous

Articular cartilage is destroyed producing severe pain. If the ligaments are affected dislocation of the joint may occur and the condition may end by fibrous adhesions and stiffness or ankylosis of the joint

Question 30

Describe the morphology, clinical features and how tuberculosis arthritis (chronic arthritis) spreads

Answer 30

It spreads hematogenously from tuberculosis of the the lungs or a nearby osteomyelitis

Morphology: joints of vertebral column (from Potts disease), followed by hip, knee, elbow, wrist, ankle and sacroiliac joints are characterized by:
-Confluent granulomas
-Central caseous necrosis
-Exudation
-Severe destruction of joint structures
-Fibrous ankylosis
-Obliteration of the joint space

Clinical features: onset of arthritis is gradual with progressive pain

Question 31

Describe rheumatoid arthritis (chronic arthritis)

Answer 31

It is a systematic chronic inflammatory disease that affects principally the joints, blood vessels, skin, heart, lungs, nerves and muscles

It is a common disease. About 1% of the worlds population suffers from rheumatoid arthritis

Women are affected 3 times more than men
It’s peak prevalence is in the third to fourth decade of life
There is a familial association

Question 32

What is the morphology of rheumatoid arthritis?

Answer 32

Symmetric arthritis affecting principally small proximal joints of the hands and feet.

Wrists,elbows,ankles,knees, shoulders and vertebral column especially the upper cervical spines may be affected

Grossly: the synovium is oedematous and thickened. It changes from a smooth contour to one covered by delicate finger like processes (villi)

Question 33

How does rheumatoid arthritis appear microscopically?

Answer 33

It is a severe form of chronic synovitis

The synovial membrane appears hyperaemic, the synovial lining cells are proliferated and hypertrophied resulting in the formation of finger- like processes (villous projections)

The sub synovial connective tissues is heavily infiltrated by lymphocytes, macrophages and plasma cells with formation of lymphoid nodules

Prominent neovascularization with plump endothelial cells and fibrin deposits are also seen.

At this stage, the joint space contains turbid synovial fluid, poor in mucin and contains neutrophils

Question 34

What happens at a later stage of rheumatoid arthritis?

Answer 34

The inflamed hyperaemic and hypertrophied synovial membrane creeps over the Articular surface forming a pannus (mantle)

This pannus causes erosion of the underlying cartilage. In time , the pannus also causes erosion of the subarticular bone leading to its destruction and rarefaction

At the end, the pannus fills the joint space, with subsequent fibrosis and calcification leading to permanent ankylosis of the joint

Tendons and ligaments may be involved in the inflammatory process of the joint. The inflamed synovial sheathes cause irreversible damage of the tendons and ligaments, sometimes may cause their rupture. Occasionally, the inflammation extends to the adjacent muscles

Question 35

What is the pathogenesis of rheumatoid arthritis?

Answer 35

It is an autoimmune disease so joint inflammation is immunologically mediated

The immunologic reaction is initiated and triggered by an arthritogenic microbial injury in an immunologically susceptible individual

After initial injury, continuing autoimmune reactions follow, in which CD4+T cells release cytokines and inflammatory mediators that ultimately destroy the joint

Question 36

What are the clinical features of rheumatoid arthritis?

Answer 36

Slowly progressive disease leads to destruction of the Articular cartilage and progressive disabling arthritis ending in ankylosis of the joint

It presents as symmetric poly arthritis, affects first the small proximal joints of the hands and feet. At this stage, there is association of weakness, malaise and low grade fever

Later on there is gradual aching and stiffness of the affected joints, especially noticed in the morning

As this disease is advanced, the joints affected become enlarged with limited motion and permanent complete ankylosis associated with deformity

Question 37

What criteria is required for diagnosis of rheumatoid arthritis?

Answer 37

Requires presence of 4 of the following criteria:
Morning stiffness
Arthritis in 3 or more joint areas
Arthritis in hand joints
Symmetric arthritis
Rheumatoid nodules
Serum rheumatoid factor
Typical radiographic changes

Question 38

What is the fate of rheumatoid arthritis/ what does it develop into?

Answer 38

Systemic amyloidosis

Question 39

Describe what is gout

Answer 39

It is marked by transient attacks of acute arthritis initiated by irate crystals deposited with and around joints

Whether gout is primary or secondary to some other underlying disease, the common feature is excessive Utica acid in tissues and body fluids

In the primary form (90% of cases), gout is the major manifestation of the disease and the cause is usually unknown

Question 40

What is the pathogenesis of gout?

Answer 40

Hyperuricemia (plasma urate level above 6.8 mg/dL) is necessary, but not sufficient, for the development of gout

Question 41

Describe the difference between primary and secondary gout

Answer 41

Primary gout:
Elevated uric acid most commonly results from reduced excretion, the basis of which is unknown in most patients.

A small minority of primary gout is caused by uric acid overproduction as a result of identifiable enzymatic defects

Secondary gout:
Can also be caused by increased production (rapid cell lysis during chemotherapy for leukemia, so- called tumour lysis syndrome) or decreased excretion (chronic renal disease)

Question 42

Describe the pathogenic of gout

Answer 42

-The inflammation in gout is triggered by precipitation of urate crystals in the joints, stimulating the production of cytokines that recruit leukocytes
-Macrophages and neutrophils phagocytise the crystals, which activate a cytosolic sensor, the inflammasome leading to the production of active IL-1b.
IL-1 is pro inflammatory and promotes accumulation of more neutrophils and macrophages in the joint. These cells, in turn, release other cytokines, free radicals, proteases and arachidonic acid metabolites
-Activation of complement by the alternative pathway may contribute to more leukocyte recruitment. The result is an acute arthritis, which typically remits spontaneously in days to weeks. Repeated attacks of acute arthritis lead eventually to the formation of tophi, aggregates of urate crystals and inflammatory tissue in the inflamed synovial membranes and periarticular tissue
-this causes severe damage to the cartilage development and the function of the joints is compromised

Question 43

What is the morphology of gout?

Answer 43

-Acute arthritis
-Chronic tophaceous arthritis
-Tophi in various sites
-Gouty nephropathy

Question 44

What is the acute arthritis caused by gout characterized by?

Answer 44

It is characterised by a dense inflammatory infiltrate that permeates the synovium and synovial fluid. Urate crystals are frequently found in the cytoplasm of the neutrophils and are arranged in small clusters in the synovium

They are long, slender and needle-shaped and are negatively birefringent

The synovium is edematous and congested and it also contains scattered lymphocytes, plasma cells and macrophages

Question 45

Describe what is chronic tophaceous arthritis

Answer 45

It evolves from repetitive precipitation of urate crystals during acute attacks. The crystals encrust the Articular surface and form visible chalky deposits in the synovium

The synovium becomes hyperplastic, fibrotic and thickened by inflammatory cells and destroys the underlying cartilage

Question 46

Describe what is tophi

Answer 46

In the Articular cartilage, ligaments, tendons and bursae are pathgnomonic of gout

They are formed by large aggregations of urate crystals surrounded by an intense foreign body giant cell reaction

Question 47

What are the complications of gouty neuropathy?

Answer 47

Uric acid nephrolithiasis
Pyelonephritis

Question 48

What is the clinical course of gout?

Answer 48

Only about 10% of patients with hyperuricemia develop clinical gout. Other factors contribute symptomatic gout:
-Age of the individual and duration of the hyperuricemia. Gout usually appears after 20-30 years of hyperuricemia
-Genetic predisposition
-Alcohol consumption
-Obesity
-Drugs (e.g. thiazides) that reduce excretion of urate

Question 49

What are the 4 clinical stages of gout that are recognised?

Answer 49

-Asymptomatic huleruricemia
-Acute arthritis: most first attacks are monoarticular; 50% occur in the first metatarsophalangeal joint; untreated, acute gouty arthritis may last for hours to weeks but gradually there is complete resolution
-Asymptomatic intercritical period: resolution of the acute arthritis leads to a symptom-free interval; in the absence of appropriate therapy, the attacks recur at decreasing intervals and frequently become poly Articular
-Chronic tophaceous gout develops on average about 12 years after the initial acute attack

Question 50

Describe what is osteoarthritis (degenerative joint disease)

Answer 50

It is the most common type of disease
It occurs at old age and in both sexes
It is characterized by progressive erosion of the Articular cartilage
Joints affected are: knees and hand hands in females and hips in males
The shoulders, vertebrae or the sacroiliac joints may be affected

Question 51

Describe the types of osteoarthritis

Answer 51

Primary (idiopathic): it occurs de novo, without apparent initiating cause. It occurs in men in midlife somewhat later in women. It’s prevalence increases beyond the age of 50 years

Secondary: it occurs secondary to some predisposing conditions (the joint is previously damaged or is congenitally abnormal). Such conditions are: trauma to the joint, abnormal stresses on the joint (obesity) congenital deformity of a joint, some metabolic disorders (diabetes mellitus and haemochromatosis)

Question 52

What is the pathogenesis of osteoarthritis?

Answer 52

A disease of cartilage, in which there is intrinsic biochemical and metabolic changes that occur resulting in its breakdown. The cause remains unknown, but it is clearly related to aging and injury (multi factorial)

-With aging, capacity of chondrocytes to maintain cartilaginous matrix slows
-Also with aging, there is alteration in the proteoglycans and collagen within the Articular cartilage, which decrease resilience and increases vulnerability to injury
-Under stress of injury, chondrocytes release cytokines which initiates matrix breakdown
-Secondary mediators enhance release of lytic enzymes that inhibit matrix synthesis, precise signals inducing release of cytokines and enzymes are still unknown

Question 53

What is the morphology of osteoarthritis?

Answer 53

In early stages of the disease:
-The biochemical changes will lead to increase in the water content of cartilage matrix and a decrease in the proteoglycans
-This biochemical change will lead to degeneration of the superficial layers of the cartilage with fibrillation and cracking of the matrix

Grossly: the Articular surface appears granular and softer than normal

Question 54

What occurs in later stages of osteoarthritis?

Answer 54

-Full thickness portions of the Articular cartilage are sloughed with exposure of subchondral bone plate that becomes the new Articular surface
-Joint motion and friction smoothens the exposed bone plate giving it the appearance of polished ivory (bone eburation)
-At the same time there is thickening of the subchondral cancellous bone leading to its sclerosis
-Small fractures through the articulating bone are common
-Dislodged pieces of cartilage and bone fall into the joint space forming free-floating bodies (joint mice)
-Synovial fluid may leak through fracture gaps into the subchondral regions and form cysts with the bone
-Mushroom-shaped bony outgrowths (osteophytes) develop at the margins of the Articular surface

Question 55

What occurs in advanced stages of osteoarthritis?

Answer 55

The synovial membrane is congested, fibrotic and may show scattered chronic inflammatory cells

Question 56

What are the clinical features of osteoarthritis?

Answer 56

-Signs and symptoms of osteoarthritis develop very gradually and usually affect one or more joints
-Osteoarthritis by joint stiffness and deep, aching pain particularly in the morning. Repeated use of the joint tends to aggregate the pain
-In severe cases, there is some effusion and swelling of the joint affected, associated with crepitus ( a crackling sound caused by exposed surfaces of the bone rubbing against each other)
-limitation of of movement may occur
-Compression on spinal foramina by osteophytes results in cervical and lumbar nerve root compression
-prominent osteophytes in distal interphalangeal joints of women lead to appearance of Herberdens nodes