BONES AND JOINTS PATHOLOGY



BONES AND JOINTS PATHOLOGY

The long bone is divided into three main regions: the epiphysis, the metaphysis, and diaphysis (the shaft)

The surface of the long bone’s end is covered by articular cartilage and there is a secondary ossification center (subarticular bone) that forms early in life

The growth plate is where all the growth in the length of a long-bone occurs

If the growth plate is somehow lost, the bone will be abnormally short

There is medullary bone in the medulla (also called trabecular bone or endoesteal bone – these are all the same tissue at the center of the bone and contain the marrow)

The cortex is the hard outer portion of the shaft and on the outside is the periosteum – it has haversian systems with blood vessels

The growth plate is a very fast growing, self-replicating tissue – especially in the young. It is arranged such that the function of cells in this tissue can be determined by their location in layers, each of which has specific functions

First zone at the top is the resting zone where not much goes on, but the chondrocytes are alive

Toward the bottom of the proliferative zone the cells undergo maturation and then hypertrophy. They become much bigger as they are displaced toward the base of the growth plate or metaphysis. Typically, in a fast growing animal, such as a rat, the entire lifecycle of a cell is about 2-3 days

Mineralization (cartilage undergoes calcification) occurs at the base of the growth plate in the longitudinal septum

Levels of growth plate

o Resting zone: area of lesser metabolic activity but it is the home to the stem cells that give rise to proliferating cartilage cells in the proliferating zone. The proliferation of this zone is evident by the coin-like stacking of the stone. This is an area of lesser metabolic activity

o Proliferative zone – cell division, columnation

o Hypertrophic zone

o Calcifying zone – chondrocytes die, calcification of longitudinal septum

o Metaphysis

Cells and traverse septa resorbed

Calcified cartilage persists as lattice

The trip from PZ to M takes about 2 days

Three major components of cartilage matrix

o Water

o Collagen – mostly type II

o proteoglycan – metachromatic and composed of 500 A granules, add elastic properties, fill space between collagen fibrils

o growth plate cartilage-thin randomly arranged collagen fibril separated by leaf like proteoglycans

The first deposits of mineral in growth plate are discrete spherules which fuse

Mineral is restricted to LS. (Therefore there is something special about LS which allows its preferential calcification). Mineral deposits mainly on vertical bars of matrix. It spares the transverse bars b/c matrix vesicles bud from lateral edges of proliferating cells like viruses.

Matrix vesicles are

o Extracellular, 100-200 nm

o Double layer membrane-invested

o Distribution: restricted to cartilage matrix which will calcify

o The first mineral deposits occur inside MVs

o Matrix vesicles bud from lateral edges of proliferative cells which are polarized cells

First evidence of mineralization is seen inside the Mvs and it is by deposition of needle-like crystals of calcium phosphate: hydroxyapatite

Mineral crystals in extracellular fluid serve as nuclei for formation of new crystals- self propagating once initiated in matrix vesicles

Calcium concentrated by lipids and Ca-binding proteins

Phosphate is released by phosphatases at the vesicle membrane (the “trigger”)

High calcium + high PO4 locally allows the deposition of the first crystalline CaPO4 (apatite); precipitation occurs at inner leaflet of matrix vesicle membrane (area of highest Ca binding ability and phosphate deposition by phosphatases)

Mineralization is biphasic: Phase I and Phase II

Phase I: formation of 1st crystal inside matrix

o Vesicles are high in enzymes, proteins, and lipids

o Therefore, binding of Ca and liberation phosphate inside vesicle

o Over time, Ca and phosphate exceed solubility and precipitate out, usually along inner leaflet of matrix vesicle membrane because it is the highest Ca binding ability and site of phosphate deposition by phosphatases (alk phos)

Phase II: exposure of crystal to EC fluid( brush fire extending beyond matrix vesicles into surrounding matrix

o When apatite crystals are exposed to the Ca+2 and PO4-3 of cartilage fluid they multiply

o Except in rickets where there isn’t enough Ca+2 and PO4-3 to allow crystal growth

o MV’s are present in many calcifying tissues including cartilage, bone and teeth

Intramembranous Bone Growth

o Bone also forms in the absence of cartilage

▪ During development of “membrane” bone of the skull

▪ At growing surfaces of the cortex and endosteal trabeculae

▪ Osteoblasts at bone surfaces secrete osteoid and become enveloped in matrix

▪ Matrix vesicles initiate calcification in newly-formed matrix

▪ The mature bone matrix is composed of type I collagen fibrils

• Intramembranous bone growth = bone growth at surfaces covered by periosteum (bone growth not initiated by cartilage)

• Endochondral bone growth = bone formed in association with cartilage

• Osteoid = bone matrix not yet been calcified

• Osteoblasts secrete matrix and age as they become encased in secretions ( osteocytes

• Osteocytes are metabolically active

• 1st bone formed and new bone forms by intermediation of matrix vesicles

• Cartilage matrix = made of randomly assembled fibrils

• Bone matrix = forms layers of type I collagen

• In slices of non-decalcified bone the blue/green color is calcified bone matrix and the red color is uncalcified osteoid

METABOLIC BONE DISEASES – (a euphemism for bone-losing conditions)

|Disease |Pathogenesis |Clinical Features |Morphology |Notes |

|Scurvy |In scurvy less collagen is |Large discolored spots, swollen legs, putrid gums, overwhelming | |Definition: a disease of all connective |

| |synthesized |lassitude, syncope, shivering, depression and unaccountable terrors, | |tissues, resulting from a deficiency of ascorbic|

| |-collagen is under hydroxylated |the reopening of old wounds, dissolution of callus in healed fractures,| |acid (Vitamin C), which leads to a failure of |

| |-less triple helix is formed |jaundice, indolent ulcers with luxuriant granulation tissue, and | |collagen synthesis |

| | |pleurisy(ulcers due to failure of Type I collagen secretion | | |

| |In scurvy there is less | | |Due to a deficiency of vitamin C ( poorly formed|

| |intermolecular crosslinking |A major problem is breakdown of vascular connective tissues with | |type I collagen in bones |

| | |hemorrhage – weakness and fragility of blood vessels | | |

| |And insufficient cartilage and bone |-into joints | |Type I collagen is a tri-peptide formed in ER or|

| |matrix is formed, leading to fragile |-at epiphyseal/metaphyseal junctions there is hemorrhage and separation| |osteoblasts |

| |bones |-subperiostic hemorrhage (under periosteum of calverium) | | |

| |-where cartilage meets bone- common | | |Collagen is synthesized in the RER where |

| |site for hemorrhage and fracture |Occurs when women give only breast milk or unfortified milk to a baby | |tri-peptides are hydroxylated by proline and |

| | |(black populations of northern cities) babies breast fed over a | |lysine residues by ascorbic acid then secreted |

| | |year/long period of time | | |

| | | | |After secretion, telopeptide removed ( collagen |

| | |Also in those with deficient diets (e.g., alcoholics, elderly) | |fibrils |

| | | | | |

| | |People not exposed to sunlight | |Cross link in rows in a staggered array = |

| | | | |periodicity of collagen molecule |

| | |Low dietary green leafy vegetables | | |

|Rickets |Dietary deficiency of vitamin D3 |Protruding forehead, pigeon chest, depressed ribs, enlarged epiphysis |The “rachitic rosary” results from |A disease of childhood with failure of |

| |(most common) leads to reduced |at wrist, protruding abdomen, large head, curved humerus, kyphosis, |enlargement of poorly mineralized |mineralization of bone due to insufficient Ca |

| |synthesis of 1, 25-OH, D3 |curved radius and ulna, curved femur, curved tibia and fibula, enlarged|costochondral growth plates |and PO4 |

| | |epiphysis at ankle | | |

| |Impaired absorption of Ca and PO4 | |The rachitic growth plate is devoid |Rickets is still a problem in infants of |

| |(sprue) |Lack of calcification in growth plate ( enlargement |of calcification |vegetarian black mothers who breast feed |

| | | |-no calcification ( ineffective |(avoiding cow milk) |

| |Impaired tubular reabsorption of |Very widened and uncalcified growth plate on x-ray |osteoclasts ( unresorbed cartilage (| |

| |PO4-3 (secondary hyperparathyroidism)|-a reversible lesion |debris accumulates at junction |Softening of bone ( curvature of bone and pigeon|

| | |-add vitamin D back to the diet, calcification is re-established as a |between the two tissues |breast |

| |Growing bones can’t get enough |line across the plate: so-called “line test” | | |

| |Ca+2and PO4-3 to support | |Hypertrophic zone enlarges – due to |Failure of calcification of bone |

| |mineralization. They become soft and|With low vit D, bones soften and set in curvature. When calcification |impaired resorption of unmineralized| |

| |flexible |of restored, they set in curved shape. |cartilage matrix |Mineralization is based on ion product of Ca+2 |

| | | | |and PO4-3 -need both |

|Osteomalacia |Causes of Osteomalacia: |Often a history of persistent diarrhea |Marked increase in osteoid – but no |Rickets in adults |

| |-impaired absorption of vitamin D due| |decrease in bone spicule size | |

| |to sprue, persistent mild diarrhea, |ALP is frequently elevated and there is bone pain | |Most commonly results from a failure of Ca, PO4 |

| |or inadequate dietary intake of | |Decreased calcification of matrix |absorption |

| |vitamin D |Osteopenia = bone loss | | |

| |-dietary deficiency of Ca or PO4 | |Lots of osteoblasts trying to |Therapy is very effective |

| |-hyperphosphaturia in Vitamin D |There are pseudofractures (Looser’s zones) |mineralize matrix but can’t, which | |

| |resistant rickets ( selective loss of|-these are characteristically painful |is why the alk phos is elevated |Elevated ALP in rickets and osteomalacia |

| |PO4-3 and failure of bone |-pseudofractures are transverse areas of decalcification | |-ALP is produced by osteoblasts |

| |calcification |-not actual fractures | | |

| |-aluminum toxicity ( coating of | | |Osteopenia is caused by osteomalacia and |

| |mineralization front of bone ( |Treatment: give exogenous vitamin D and calcium, phosphate | |osteoporosis – and you must separate malacia |

| |prevent further mineralization | | |from porosis |

| |-malignant tumors (oncogenic | | | |

| |osteomalacia) cause hyperphosphaturia| | | |

|Osteoporosis |Cause(s) of osteoporosis is poorly |Often occurs after menopause |Spicules are thin and far apart |Often confused with osteomalacia |

| |understood | | | |

| | |Classic picture: shrinking post menopausal female |There is no failure of |Definition: a diffuse reduction in bone mass |

| |The pathogenesis involves a negative | |mineralization |and bone density (not due to a failure of |

| |balance between bone formation and |Middle-aged to old-age | |calcification) |

| |bone resorption | |Bone metabolism is in a negative | |

| |-amount of overall bone present is |Usually in women |balance with resorption exceeding |Results in 350,000 vertebral and hip fractures |

| |not sufficient to replace bone lost | |formation |annually in U.S. – at a cost of more than $1 |

| | |Sclerosis and Kyphosis, loss of height, and frequent real fractures | |billion (also 2nd most frequent cause of death |

| |Porosity of bone is increased | |Increase in osteoid because the bone|in females after age 45 = 5% (Heart disease = |

| | |Vertebral compression fractures are common and shorten the stature |matrix that is present is calcified |38%, breast cancer = 4%) |

| |Leading to crush fractures of | |(normal mineralization) | |

| |vertebra |Osteoporotic fractures: 350,000/year (rib, femoral neck, humeral head | |There are definite risk factors |

| | |and across the wrist) |There is more marrow of the bone and|-hereditary (defective vitamin D receptor gene);|

| | | |the bone trabeculum is thinner and |multifactorial |

| | |Serum calcium, phosphate and ALP levels are normal |fragile |-loss of ovarian endocrine function (estrogen |

| | | | |promotes bone growth) |

| | |Increased morbidity | |-diet deficiency in calcium, vitamin D |

| | | | |-smoking |

| | | | |-prolonged steroid therapy (corticosteroids) |

| | | | |-inactivity or weightlessness |

| | | | | |

| | | | |There are two major approaches to treatment |

| | | | |currently |

| | | | |-estrogen replacement to promote bone formation |

| | | | |(ERT increases incidence of uterine and breast |

| | | | |cancer) |

| | | | |-anti-osteoclast agents (bisphosphonate) to |

| | | | |inhibit bone resorption |

|Paget’s disease |Etiology unknown – familial with |A disease of the elderly |Excessive osteoclastic resorption |The end result is a bone with very thick bone |

|(osteitis |geographic “hot spots” | |and excessive osteoblastic activity |spicules and increased x-ray density, but not |

|deformans) | |There is increased warmth to touch over affected bones due to increased|on the other (earliest change is |very mechanically strong |

| |Course: slowly progressive, |vasculature |lytic) causing increased bone | |

| |spreading to involve multiple bones | |formation |Complications of Paget’s: |

| |(typical: enlarging hat size-femurs |High ALP (greater osteoblastic activity) but normal Ca and PO4 | |-cardiac failure due to extra oxygen demand of |

| |bow outwards) |-high osteoblastic activity is associated with a release of alkaline |Frantic cellular activity at cross |newly formed, highly vascularized bone |

| | |phosphatase |purposes – first lytic and later |-fractures (paradoxically); PD bone is not well |

| | |-high bone formation |osteoblastic |organized ( decreased strength |

| | | |-early in PD: increased osteoclasts|-osteogenic sarcoma in an older age population |

| | |Build up of bone in shins and head (“saber shins” and enlargement of |( bone loss | |

|Paget’s disease | |head) |-later in PD: increased osteoblasts|possibly associated with a measles-like virus |

|(cont) | |-overgrowth of calvarial bones | |changing the osteoclast |

| | |-disorderly thickening (hyperostosis frontalis interna) |The osteoclasts of Paget’s are the | |

| | | |largest and most bizarre in any | |

| | |The rapid breakdown of collagen leads to the appearance of |disease state (can have as many as | |

| | |hydroxyproline in the urine |100 nuclei) | |

| | | |-since Paget’s usually begins as | |

| | | |excessive resorption, something may | |

| | | |be intrinsically wrong with | |

| | | |osteoclasts | |

| | | | | |

| | | |Decal sections show mosaic cement | |

| | | |lines where osteoclastic resorption | |

| | | |stopped and bone formation filled in| |

| | | | | |

| | | |End result: hyperdense zone which | |

| | | |blocks out marrow | |

| | | | | |

| | | |Extra osteoid is seen = too much | |

| | | |bone formation is taking place | |

FRACTURE HEALING

48 hours after a fracture:

o A blood clot is present between the fractured ends (latest evidence says it is a good thing – platelets have growth factors that will help bone growth – like bone morphogenic protein)

o Cortical osteocytes die in Haversian systems near the broken ends – probably because of disrupted blood supply

o Osteogenic cells in periosteum and endosteum are already beginning to proliferate (osteoblasts precursor cells)

o Ends are unhealed but they are opposed to each other

o Ends of bone are necrotic – not osteocytes, empty lacunae

o Callus is seen: repaired bone tissue (but not a lot)

o Periosteum cells multiply ( callus

7 days after fracture (beginning of “reparative phase”):

o The periosteum is elevated by the presence of many new cells in the external callus

▪ Callus = new growth of incompletely organized bony tissue surrounding the broken ends of a fracture

▪ Full callus joins the ends of the fracture

▪ Callus has cartilage (sign that the repair occurs by endochondral bone formation)

▪ Healing via callus is a form of endochondral bone formation- recapitulation of embryonic bone growth

o Endosteal cells proliferate to form an internal callus

o Mesenchymal cells of overlying muscle probably contribute to the external callus

o The clot is mostly resorbed

o New bone formation evident in endosteum

o All cartilage will be replaced by bone

3rd stage of repair = reformation of bone that closes ends of injured bone (months to years later)

o Osteoclasts resorb old bone (primary callus) and osteoblasts lay down new bone spicules

o new bone stronger than original bone – new fractures will rarely come back to the same area

Early callus contains central cartilage

o Perhaps because of reduced blood supply

o Bone forms at periphery

Remodeling phase: the final stage of fracture repairs requires months to years

o During remodeling, the dead bone ends, and mechanically inefficient spicules of new bone are resorbed

o Replacement occurs by coordinated osteoclastic and osteoblastic action producing new trabeculae which are oriented to best withstand mechanical forces at the fracture site

o It is amazing that bone cells know how to align themselves and their matrix to resist mechanical stress

DISEASES OF BONE GROWTH (bone dysplasias)

These are usually hereditary disorders

Typically, either endochondral or membranous bone formation is disordered due to a genetic mutation

|Disease |Pathogenesis |Clinical Features |Morphology |Notes |

|Achondroplasia |Genetics: a simple Mendelian dominant trait |The result is a circus dwarf with |The long bones are very short because of a|Failure of endochondral bone formation as it occurs at the |

| | |very short arms and legs (were court |failure of longitudinal growth |growth plate |

| |In 1994, the gene causing achondroplasia was |jesters in olden days) |-have wide ends at epiphyses | |

| |identified – autosomal dominant |-normal sized heads |-growth plates vary (sometimes thin) |Endochondral bone growth is diminished |

| |-the condition results from one of several | | | |

| |possible mutations in the FGFR3 gene, causing |The flat bones of the skull and jaw |Growth plates contain masses of disordered|Disease is compatible with life |

| |a failure of endochondral ossification |are normal sized looking overgrown |cartilage | |

| |-FGFR mutations inactivate FGF receptor ( |causing: |-chondrocytes not in normal columnar array|Skull and jaw formed by membrane bone formation (not |

| |impair growth at growth plates (endochondral |-bulging forehead |and there is marked shortening of |endochondral formation) |

| |bone formation) |-proganthism (i.e. protruding jaw) |metaphysis | |

| | |-achondroplastics often become circus|-hinders normal lengthening of bone | |

| |Failure of growth at the epiphyseal growth |dwarfs!?!?! | | |

| |plate (intramembranous bone growth is normal) | | | |

|Osteogenesis imperfecta |Hereditary: may be autosomal dominant or |Clinical evidence of poor collagen |Extremities are very deformed |AKA “brittle bone disease” |

| |recessive. The recessive, congenital form is |formation: | | |

| |most severe and common |-thin skin |X-rays show irregular small bones lacking |A hereditary disease characterized by abnormally fragile |

| | |-blue sclerae (thin sclerae) |mineralization |bones and frequent fractures |

| |Inadequate osteoblasts making insufficient |-hypermobile joints |-with many fractures | |

| |matrix but no defect in mineralization |-early tooth loss (dentinogenesis |-deficient mineralization of bone ( won’t |Results from a failure of membrane bone and cortical bone |

| | |imperfecta) |show up on x-ray |formation |

| |Since there is no defect in endochondral | | | |

| |ossification, fracture callus tends to be |Weight bearing joints suffer |Microscopically, cortex and medulla |X-rays in this disease can be deceptive: hypertrophic |

| |excessive | |contain very little bone |fracture callus can be confused with osteogenic sarcoma |

| | |Long bones grow normally but most |-thin cortex, no bone spicules in | |

| |Etiology: mutations of the gene for collagen |damaged because bear the most weight |medullary cavity |Failure of bone matrix formation |

| |type I, causing insufficient bone matrix |and fracture the most |-trabeculum fully calcified but lacking in| |

| |synthesis | |matrix and very thin |In fractures, callus well formed (endochondral bone |

| | | |-osteocytes close together because not |formation) but doesn’t get filled in with normal bone |

| |Pathogenesis: a reduction in bone matrix, | |enough matrix to push away |(matrix formation) ( generates lots of callus (can be |

| |which although fully calcified, results in | | |misdiagnosed as osteosarcoma) |

| |fragile bones that are more prone to fracture | |Bone spicules show many osteoblasts but |-outside callus, bone is thin and demineralized |

| | | |they look anemic, not much cytoplasm, poor|-sunburst appearance (confused for osteosarcoma) |

| | | |Golgi formation, too close together – |-lots of cartilage b/c Type II isn’t affected |

| | | |unable to secrete enough collagen Type I | |

|Osteopetrosis |Mutations causing impaired osteoclastic bone |Flask-shape to bones with increased |X-rays show very dense bones with no |A hereditary deficiency of bone resorption characterized by |

| |resorption |density |detectable endosteum, plus widened |abnormally dense bones |

| | |-cortex cannot be distinguished from |diaphyses (“Erlenmeyer flask deformity”) | |

| |There are two major forms |medulla | |Disease in which the bones becomes hard as rock (sometimes |

| |-the severe congenital form which is | |Long bones show a curious |called marble bone disease) |

| |transmitted as a Mendelian recessive |Bone overgrows the marrow space ( |“bone-within-a-bone” phenomenon | |

| |-and a less severe form which appears during |anemia, thrombocytopenia and |-resulting from failure of resorption at |In osteopetrosis, the balance between osteoblastic bone |

| |later childhood or adolescence, is transmitted|increased vulnerability to infection |the metaphyses |formation and osteoclast-mediated resorption is distributed |

| |as a Mendelian dominant (Albers Schoberg |w/ bleeding tendency |-pile-up of metaphysical bone on both |– literally means “bones made of stone” |

| |disease) | |sides of growth plates | |

| |-Impaired remodeling results in bone that is |Bone spicule: | |Normally, osteoclasts are multi-nucleated and have ability |

| |very dense, but its basic structure is |-several inclusions of cartilage |Bone has: |to resorb bone matrix and bone mineral with ruffled border |

| |disordered. Thus, osteopetrotic bone does not|matrix because abnormal resorption |-thin cortex |(seals cell to bone spicule and releases enzymes and |

| |resist mechanical forces well, and is |-osteoclasts present but not |-piling up of bone containing cartilage |proteins that dissolve mineral and collagen) but in |

| |frequently fractured |functioning |inclusions in the central shaft |osteopetrosis you can’t find ruffled borders in their |

| |-Etiology: mutations of genes that govern |-fragile bone because lacks |-medullary space compression causing loss |osteoclasts |

| |osteoclast formation and function |architectural patterns of normal |of marrow (death often results from | |

| |-Pathogenesis: impaired osteoclastic |bones and very resistant to |Pancytopenia and intercurrent infections) |Recessive type is very severe |

| |resorption leads to excessive bone formation |mechanical stress | |Cartilage persists so not like Paget’s |

|Myosites ossificans |The pathogenesis of the disease is poorly |Usually begins in childhood – the |Microscopically: endochondral bone |Disease in which bone is formed at abnormal locations in |

|(fibrodysplasia ossificans|understood, but probably is hereditary in |back and shoulder girdle are |formation occurs in muscles |muscle |

|progressive – FOP) |childhood cases |affected first |-as we have seen with fractures, | |

| | |-early signs of FOP: ossicle in SCM;|osteoprogenitor cells in muscle can |Disease is not compatible with life |

| |Etiology: in some cases, genes for bone |surgical removal ( even larger bone |generate cartilage and bone | |

| |morphogenetic proteins (BMPs) are mutated or |develops | |There are other forms of myosites ossificans |

| |overexpressed | | |-myositis ossificans circumscriptor may follow local trauma |

| | |Victims of this hereditary disease | |-occurs in the lower extremities of about 4% of paraplegics |

| |Pathogenesis: in childhood, osteoprogenitor |usually have inwardly bent great toes| |with spastic paralysis |

| |cells of muscle begin progressive endochondral|(hallux valgus) | | |

| |bone formation, in one muscle group after | | |Starts at neck (SCM) ( upper extremities, chest ( lower |

| |another. |In childhood cases of FOP, | |extremities |

| | |circulating WBCs express high levels | | |

| |Phenotype: “Petrified man” |of BMP-4 | |No treatment |

| | | | | |

| |Bone formed as endochondral bone (1st |The childhood form of FOP is | |BMP induce new bone formation; stimulate osteoprogenitor |

| |cartilage ( bone by osteoblasts) |relentlessly progressive: group | |cells to form new bone |

| |-bone formed never goes away |after group of muscles and tendons | |-sm mol wt proteins |

| | |“freeze” | | |

| | |-victims are exhibited in carnivals | |BMP will grow bone under skin if placed there in an |

| | |as “petrified men” | |experimental animal (ectopic bone formation) |

| | |-death results from a failure to chew| | |

| | |food or breathe | | |

| | | | | |

| | |Late stage of FOP: bone forms across| | |

| | |joints | | |

| | |-cause of death: respiratory | | |

| | |infections | | |

|Hypertrophic |Bulbous enlargement of the tips of the fingers|Tumors release a factor leading to | |Clubbing of the fingers – distal phylanges |

|osteoarthropathy |results from cortical overgrowth of bone |abnormal growth | | |

| | | | |Usually associated with an intrathoracic neoplasm |

| |The process is one of periosteal inflammation |When tumor is removed, returns to | |(bronchogenic CA, thymoma or mesothelioma) |

| |followed by periosteal new bone formation |normal | | |

| | | | |Periosteal overgrowth of distal phalanges |

| |The cause is obscure – hypoxia is suspected | | | |

|Avascular necrosis |3 main causes: |Bone infarcts occur in children |Subarticular bone collapses ( overlying |3 major types |

| |1. steroid therapy: not dose-dependent; |-at the head of the femur |articular cartilage loss with arthritis | |

| |block sm vessels at end of long bones |(Legg-Calve-Perthes or Perthe’s) | |Associated with Caisson disease in divers, due to |

| |2. Bends (or caisson disease) – in divers who|-in subarticular bone at diverse |Bone fragment may fall off to form a |hyperbarism or in sickle cell anemia |

| |have not properly resolved the CO2 and N gas |sites (osteochondritis dessicans) |“loose body,” or “joint mouse.” | |

| |bubbles when return from depth ( bubbles to | |-bone fragment coated with reactive, |Bone infarcts are often associated with steroid therapy |

| |end of long bones ( infarcts |Most frequent in pre-adolescent or |repair cartilage | |

| |-also tunnel building construction workers |adolescent males, 4:1 vs. females |-once encased, cause squeakiness in joint | |

| |3. Legg syndrome (or Legg-Calve-Perthes): | |( joint mouse | |

| |infarcts in upper femur of teenagers; infarct |Often associated with trauma and/or | | |

| |( weakening of growth plates and break apart (|sports injuries | | |

| |slipped femoral epiphysis | | | |

| |-weakened bone under articular surface and |Very painful | | |

| |falls into joint space | | | |

| |-bone loss at distal end of bones | | | |

| |-unknown cause | | | |

| |4. Sickle Cell disease | | | |

|Osteomyelitis |Usually caused by hematogenous Staphylococci |Characteristically seen in childhood |acute phase- marrow replaced by polyps |Chronic progressive infection of bone which begins in bone |

| |aureus | | |marrow |

| |-E. coli, Pseudomonas, and Klebsiella are more|Sudden onset of pain and swelling |Center of osteomyelitis- pus filled with | |

| |frequent in patients with urinary tract | |neutrophils, surrounded by dead bone. |Infection of bone in ends of long bones |

|Osteomyelitis (cont) |infections or who take intravenous drugs |More often in children: 4:1 male |Osteocytes empty- dead | |

| |-Salmonella is more common in sickle cell |predominance | |Remains a problem because sequestered organisms can escape |

| |anemia | |With time there is chronic inflammation |antibiotics |

| | |Metaphyses of long bones most |and fibrosis |-difficult to treat because decreased blood flow for |

| |Hematogenous disease from non-bone site |frequently affected |-the vascular supply to some areas of bone|antibiotics to reach |

| | | |may be compromised causing bone infarction| |

| |Osteomyelitis starts in metaphysic and form |Characteristic smoldering infection |(sequestrum) |Infection may penetrate the growth plate, slow bone growth, |

| |ankylosing bone where articular surfaces no |often persists for months or years |-dead bone spicules have empty lacunae |and even enter the joint space. The result is limb |

| |longer slide, but are frozen |(with progressive destruction of |(and no nuclei) |shortening (interruption of long bone growth in kids). And |

| | |bone) | |it can move onto other bones |

| | | |Reactive new bone formation is present at | |

| | | |the cortical surface (involucrum) |Osteomyelitis can break out of the bone at any time to form |

| | | |-cortical bone reacts to osteomyelitis by |a draining sinus to surface of the body |

| | | |formation of new bone (closeness of | |

| | | |osteocytes) = WOVEN bone |A final complication: Brodie’s abscess – burned out, |

| | | | |non-infective bone cyst at site of previously active |

| | | |End result: dead bone w/in a live bone |osteomyelitis |

| | | | |-burned out focus of osteomyelitis that is no longer |

| | | | |harboring bacteria but did not fill in after the infection |

BENIGN BONE TUMORS

Growth in length occurs at the epiphyseal plate and metaphysis

Growth in width occurs at the cortex

Metaphysis = very active area of bone growth and site of origin of bone tumors in adolescents

Pain = indication that tumor is active

Reasons why tumor in bone hurt:

o Increased activity ( ↑ tumor cells and edema ( overfill space ( stimulate nerve endings causing pain

o Tumor weakening bone ( micro fractures ( pathological fracture

Systemic complaints: fever, chills, loss of appetite; indicate metastasis, rare

Expansile lesion = width of bone wider and tumor has been there for awhile. Ground glass- b/c made of fat, tissue, minerals- not completely dense bone or cartilage

Bone scan: pts injected with lipid phosphate and scanned. Active osteoblasts take up radiolabeled phosphate ( nonspecific bone activity

Transition zone = zone differentiating bone from lesion

3 borders to look for at transition zone: geographic borders, permeative borders (non-distinct borders between bone and bone tumor), and moth-eaten borders (multiple holes in transition zone)

|Disease |Clinical Features |Morphology |Notes |

|Fibrous dysplasia |Typically with onset before puberty, usually originate in metaphysis |Lesions show typical features of fibrous dysplasia against |McCune Albrights Syndrome in 5% of cases |

| | |a background of fibrous tissue |of polyostotic fibrous dysplasia |

| |Osteoblastic activity ( alkaline phosphatase elevated |-dysplasia because bone is malformed |-fibrous dysplasia |

| | |-weak bone and abnormal haversian structure |-café au lait spots on skin |

| |Distribution: |-disorganized bone with lining of fibroblast that release |-precocious puberty |

| |-50% craniofacial |ALP |-often disappears at puberty |

| |-70% monostotic | | |

| |-30% polyostotic (occur in several bones at the same time) |Irregular, weak-looking bone spicules |Fibrous dysplasia is considered |

| | | |non-neoplastic (more like a hamartoma or |

| |It often disappears at puberty |The new bone is said to be dysplastic. There is disordered|malformation) |

| | |maturation. Irregular woven bone without lamellae or | |

| |Cortical allograft is used b/c seen as foreign and not destroyed |haversian systems |Specific genetic defect |

| | | | |

| |Pain intermittent, increased with activity and decreased with rest |As the bone weakens, muscles cause cortex to crack and |High recurrence if scrape out and fill |

| | |reform, crack and reform, etc. to bow the bone |with allograft-dysplastic cells eat away |

| |Only bone tumor seen in kids that can continue to grow in adulthood. |-shepard’s crook deformity- hip, bowing of the bone inward |away graft |

| | | | |

| | |Lab: alkaline phosphatase mildly elevated. |No risk of metastasis unless treated |

| | |Bone scan – area of fibrous dysplasia lights up (so does |w/radiation |

| | |bladder!) | |

|Osteoid osteoma |Typical age of onset (5 to 25 years) – often in diaphysis |Gross: cylinder of dense bone |Tumor = nidus (hole) incenter that has |

| | | |caused bone proliferation by producing |

| |Typical history of pain relieved by pain relievers (aspirin) |X-ray: peripheral sclerotic bone and central lucent nidus |growth stimulants |

| | |-nidus: tiny bone spicules | |

| |-this is a tumor that makes prostaglandins, which causes inflammation and pain, more at |-dense bone spicules at periphery |Removal of nidus should cause dissolution |

| |night when kids are not as active. |-dense region at uptake |of proliferative growth |

| | | | |

| |Treatment = aspirin for pain for 3-6 months before surgical removal; removal of nidus by |Bone spicules in the nidus are mostly osteoid (i.e. |Location of lesion in shaft; translucent |

| |drilling holes around demarcated nidus and chiseling out lesion; repeat CT |uncalcified bone matrix) |nidus |

| | |-woven bone spicules with osteoid material (uncalcified | |

| |Bone is not at risk of fracture, so you would only go after them surgically if the |bone matrix) |Tumor produces high prostaglandins( bones |

| |medication does not help the pain. Usually after using medication for a while, the pain | |swell( stimulate nerve endings( pain |

| |stops, although the lesion doesn’t go away. |Special stains show many nerve endings entering the nidus (| |

| | |pain |MRI useless b/c edema makes tumor look |

| | | |worse |

| | |Center has very small malformed bone spicules surrounded by| |

| | |dense trabeculae |Often have posterior spine muscle spasms |

| | | |-take xray standing w/ spasm and then the |

| | |Extra bone gets remodeled in cotical bone (diaphysis) |spasm will go away when pt lays down for |

| | | |2nd xray |

|Giant cell tumor |Diagnosed clinically, so no biopsy taken |Giant cell tumors are usually cystic, rapidly growing, but |Malignancy is rare |

| | |without reactive bone formation at the edges | |

| |Typical age of onset 30-50 years | |Usually arise in the epiphysis – spread to|

| | |Micro: fibroblasts, histiocytes, and a variable number of |metaphysic |

| |In epiphysis usually (or metaphysis) |giant cells | |

| | | |Rule out hyperparathyroid “brown tumor” |

| |Aggressive nature (soft tissue expansion) |Giant cells probably represent fused marrow monocytes |(Osteitis fibrosa cystica) |

| |-some go through the bone, cartilage and metastasize |-have features of osteoclasts (osteoclastoma) | |

| | |-many mitochondria |Clinical follow-up |

| |Erosions of cortex on outside of tumor |-high tartrate-resistant acid phosphatase (TRAP) | |

| | | |Benign but very active |

| |High rate of recurrence b/c it is so active. The more they come back, the more bone and |lesion eroding bone from inside (endosteal scalloping) | |

| |joint they destroy. (ones in distal radius are more aggressive and likely to return and |bone is trying to wall off |Metastasis ~1% |

| |metastasize) | | |

| | |Tumor mass filled with gelatinous fluid, cortex thinned and|Radiolucent- no mineralization |

| |Treatment is difficult; resection of tumor exposes to soft tissue (these tumors can grow |pushed to side. Looks very cystic on gross specimen. | |

| |in soft tissue) | |Can be in kids- highly metastatic because |

| |-Make hole in bone, scrape out the tumor and use something to kill whatever tumor is left |X-ray – solitary expansile radiolucent lesion – strongly |high metabolic activity |

| |(ie: peroxide), fill hole with bone cement (decreased risk of lung metastasis and |positive on bone scan. Very sharp border (benign) | |

| |recurrence). Bone cement gets very hot and helps kill off any remaining tumor. |Lab: all normal (Ca, P, alk phos, PTH) | |

| |-If in distal radius, cut it out and put in a piece of frozen bone radius. | | |

|Osteochondroma |First appears in kids |Gross: cauliflower mass, with hard smooth, bosselated |The most common benign bone tumor that |

| | |(bumpy) outer surface. Attached to cortex of bone. |arise from the surface of the bone |

| |Autosomal dominant transmission - hereditary | | |

| | |Not very active on bone scan. |Caused by a defect on perimeter of growth |

| |Arises at metaphysic of long bones | |plate |

| | |May be pedunculated or cessile. | |

| |More common in lower extremities | |Growth plate rotates 90º; during growth |

| | |Cross section showed direct communication between the tumor|spurts, grows to side |

| |Bowing in arms and legs because composed of 2 bones |and normal medullary bone. | |

| | |-there was a cartilage cap (growth plate) |Autosomal dominant |

| |Treatment: removal of tumor only when symptomatic, usually do nothing. | | |

| | |Cartilage cap is where lateral growth occurs as if a |These almost never become malignant but |

| |May also be multiple lesions – multiple oseochondromatosis |metaphyseal growth plate gets turned 90º to the long axis |must be completely removed to prevent |

| | |of the bone and grows out like a mushroom |recurrence |

|Osteochondroma (cont)|Often seen in kids when they go through growth spurts. |-chondrocytes aligned in parallel columns; lower | |

| |After kid stops growing, usually it stops growing as well and causes no other problems, |proliferative zone |1% risk for malignancy; lesions in adults |

| |Sometimes in 30s and 40s it can undergo malignant degeneration. |-tumor arising below or at level of growth plate |concerning |

| | |-neck connected with medullary cavity of bone |-Telangiectasia and Malfuchi Syndrome? |

|Multiple enchondromas|Not hereditary – 20’s to 50’s |Gross: ovoid, smooth surfaces; semitranslucent (typical of|Also called Ollier’s disease |

| | |cartilage) | |

| |Solitary enchondromas are much more frequent |-well-demarcated with no characteristics of malignancy |Very mildly malignant |

| | | | |

| |Rule out Matucci syndrome: multiple enchondromas and cavernous hemangioma of skin |Tumor is composed entirely of nodular masses of hyaline |Pathogenesis: displaced cartilage nests |

| |-hereditary, 100% rate of developing metastasis |cartilage |in metaphysic which start to grow |

| | |-small fields of small nodules of well-differentiated |endosteally |

| |x-ray – punctate (popcorn) calcifications are a sign of a cartilaginous lesion. |hyaline cartilage |-small inclusions of cartilage which |

| | | |persist in bone as they develop |

| |Lesions may undergo malignant transformation and become a chondrosarcoma. |Some chondrocytes were “stretched out” – slightly atypical |-not limited to any region of bone |

| | |-a few have double nuclei (a suspicious sign of | |

| | |chondrosarcoma) | |

| | |-must be vigilant for malignant transformation (this is | |

| | |BORDERLINE) | |

| | |-2 nuclei in one lacuna | |

| | | | |

| | |Rounded “popcorn calcification” in femur heads | |

| | | | |

| | |Lucent center and surrounding mineralization | |

| | | | |

| | |Fields of sm nodules of well-differentiated hyaline | |

| | |cartilage | |

MALIGNANT TUMORS

sarcoma- malignancy of mesenchymal tissue

Best drugs for sarcomas: adriomycin (cardiotoxic) and aphosphamide (renal toxic)

Most common primary malignant tumor of bone is multiple myeloma

|Disease |Pathogenesis |Clinical Features |Morphology |Notes |

|Osteosarcoma |Arises in metaphysis of long bones, 60% |Bimodal peak age of incidence (teens, |Gross: a bony mass in the metaphysic expanding to involve |Is the most common primary malignant tumor of|

| |around the knee |70-80’s) |the cortex |bone |

| | | |-can penetrate the cortex lifting the periosteum to form | |

| |Aggressive, spread by blood |Age of onset: 10 to 20 |“codman’s triangle”; bad prognostic sign ( indicates |Malignancy of mesenchymal tissue |

| | | |aggressive tumor | |

| |No hx of trauma |1.6:1 male: female ratio |-railroad track sign at cortex; bad prognostic sign |Osteoblasts also secrete alkaline phosphatase|

| | | |-permeative border | |

| |Pain about 4 months prior to radiographic |Pagets disease and radiation are linked|-sunburst pattern – tumor is growing out into soft tissue. |The tumor metastasizes by blood stream |

| |activity |to later onset, 40’s to 70’s | |-in recent years prognosis has been improved |

| | |-secondary lesion in older pts |Micro: characterized by the formation of irregular bone |by chemotherapy and advanced surgical |

| | | |spicules that are partially mineralized, partially |techniques |

| | |Treatment: surgical resection, bone |unmineralized. | |

| | |graft + chemo |-there may be cartilaginous areas |making bone, but not from bone- can be in |

| | |-tumor not sensitive to radiation |-spicules formed by malignant cells |soft tissue |

| | |-after surg, CT and bone scan | | |

| | |-chemo 10 wk later |The feature common to all osteosarcomas is the presence of |Often seen in people who’ve had high dose |

| | |-surg- wide resection- only leave a |atypical, malignant osteoblasts secreting a calcifiable bone|radiation of paget’s |

| | |little normal tissue |matrix | |

| | |Survival 90-95% | |Uptake of technetium on bone scan |

| | | |Very hot in bone scan. | |

| | |Spread in blood- lung 95% |MRI – tumor mass is dark (calcified) | |

| | |-rule out lung metastasis w/ chest Xray| | |

|Chondrosarcoma |Commonly arises in the central skeleton, |Occurring in an older age group (40’s |Gross: outer surface of upper humerus with clavicle |Usually an indolent tumor |

| |i.e. pelvis, shoulder and ribs |to 70’s) |attached | |

| | | |-cross section shows a central cystic area surrounded by |Grossly malignant |

| |Indolent tumor which grows and metastasizes|High uptake on bone scan |slightly translucent tumor | |

| |(by blood) more slowly | |-punctate “popcorn” calcification- lesions with circles of |Benign and malign can be right next to each |

| | |Treatment = surgery |calcification – pushing cortex out. |other- make sure to Bx malign |

| | |-has proteins that pump toxins (chemo) |-centrally necrotic, hemorrhagic, and translucent | |

|Chondrosarcoma (cont) |Predisposing factor: previous enchondroma |out of cell so poor response to |cartilaginous appearance |If pain, check elsewhere and if nothing else,|

| |(1%) |chemotherapy |-high soft tissue component indicates malignancy |check for malign |

| | | | | |

| |Low or high grade |x-ray – expansile lesion w/ |Micro: nodular, disorderly, well differentiated hyaline |Low grade, asym- no Tx. |

| | |characteristic punctate calcifications.|cartilage with typical chondrocytes separated by cartilage |If pain, scrape- 3% recur |

| | | |matrix |High grade- tx like other bone cancer, remove|

| | |Bone scan – intense uptake in region of| | |

| | |tumor. |Close inspection shows subtle evidence of malignant atypia: | |

| | | |nuclear variation, two cells/lacuna, rarely mitoses | |

|Ewings sarcoma |Arising in the medullary cavity of long |Intramedullary, diaphyseal malignancy |Micro: a malignant small cell tumor resembling |Chemotherapy has greatly improved the |

| |bones (only slightly more frequently than |of childhood (usually under age 15) |neuroblastoma |prognosis |

| |other bones) |Ages 5-25 | | |

| |-frequently invades the cortex, and | |Tumor cells are small, with poorly differentiated atypical |Most common type of sarcoma in 7.0 mg |Articular surfaces covered by crystals |The effect can be very destructive |

| | |%) | | |

| |Etiology: multifactorial hereditary | |Nodular deposition in peri-articular connective |Complications: |

| |disease, most common in males |Affects small joints |tissue in joint capsule |-most serious is chronic renal disease requiring |

| | | | |dialysis |

| |Pathogenesis: abnormal uric acid |Most common: 1st metatarsophalangeal joint |Nodules = tophi (an extra-articular deposition |-accelerated atherosclerosis |

| |metabolism leads to hyperuricemia with |between great toe and 1st metatarsal |of monosodium urate crystals) |-deformity due to destruction of articular surfaces|

| |deposition of monosodium urate crystals | | |-Lesch Nyhan syndrome: congenital absence of |

| | | |Crystals = needle-shaped deposits |hypoxanthine-guanine phosphoribosyl transferase |

| | | | |(HGPRT) causes hyperuricemia with mental |

| | | |Chronic inflammation with foreign-body giant |retardation, severe neurodegeneration, and |

| | | |cells resorbing these crystals, surrounding them|choreoathetosis (shaking tremor) |

| | | | | |

| | | |Deposits outside of great toe in soft tissues: | |

| | | |tophi | |

|Chondrocalcinosis |Unknown |Usually there are no symptoms |X-ray: linear calcium deposits in articular |More common than gout but can be confused |

| | | |cartilage |Sometimes called “pseudogout” or calcium |

| | |Sometimes there may be very severe joint pain | |pyrophosphate deposition disease, CPDD |

| | |-usually in the major weight-bearing joints |Micro: | |

| | | |-deposition of a crystalline material in |Calcium pyrophosphate crystal deposition into |

| | |Older-aged individuals |articular cartilage |articular cartilage |

| | | |-usually there is no inflammation | |

| | | |-CaPPi is not solubilized by ordinary fixation |Calcium pyrophosphate = insoluble and crystalline |

| | | |and histological processing, and appears as |form of pyrophosphoric acid |

| | | |small rhomboids | |

| | | |-crystals are rhomboid/rectangular and resistant|Not very inflammatory |

| | | |to various forms of solubilization | |

|Calcium hydroxyapatite |Resistant to solibilization by normal |Tiny crystals of hydroxyapatite find their way|it may develop as a periarthritis with calcific |Highly inflammatory |

|deposition arthritis |conc of ECF |into the synovial fluid (10 x 100 nm) |deposits in the periarticular tissues | |

| | |-experiments have shown that these crystals |-or it may mimic osteoarthritis (with excessive |Most commonly encountered form of CaPO4 in body |

| | |are highly inflammatory |HA deposits near tidemark) | |

| | | |-when in shoulder called “Milwaukee shoulder” |Typical crystals deep in bone |

|Septic arthritis |Hematogenous spread of organisms from a |There is pain, redness, swelling of a single |PMNs infiltrate the articular cartilage surface |Is usually monoarticular involving one of the large|

| |primary site of infection, most often |joint (monoarticular) |and accumulate in the synovial fluid |joints and can be caused by staphylococci, |

| |from pneumonia, bacterial endocarditis or|-can be any joint | |streptococci, pneumonococci, gonococci or |

| |gonorrhea | | |tuberculous organisms |

| | |The diagnosis is made by culture and | | |

|Septic arthritis (cont) |Salmonella infection is frequent in drug |identifying the characteristic TB granulomas | |TB is one of the most destructive forms of septic |

| |addicts |in biopsy of the synovium | |arthritis |

| | | | |-more common in children |

| | |Treatment: antibiotics | |-it tends to affect weight bearing joints and the |

| | | | |spine, in which case it is referred to as (Pott’s |

| | | | |disease)- white death |

| | | | |-very destructive and difficult to eradicate |

| | | | |-TB granuloma: central area of caseous necrosis |

| | | | |surrounded by typical cellular components of |

| | | | |granuloma, including giant cells and histiocytes |

|Reiter syndrome |Etiology unknown; probably not related to|Urethritis, arthritis, and conjunctivitis | |Most common cause of monoarticular arthritis in |

| |gonococcus. May be autoimmune-stimulated| | |young males |

| |by Chlamydia |Autoimmune arthritis that mimics septic | | |

| | |arthritis | |Recently shown to be associated with HLA-B27 |

| | | | |antigen in 60% of cases |

|Osteoarthritis |Cause is unknown |Seen in most people after the age of 50 |Focal degeneration of articular cartilage with |Degenerative joint disease |

| | |>65y/o- 100% |reactive outgrowth of the articular margins to | |

| |Loss of proteoglycan seems to be the |more severe in younger indiv |form bone spurs called “osteophytes” |Causes a loss of 68 million work hours/yr in the |

| |first step in the development of the | | |U.S. |

| |lesion |Affects large weight bearing joints |The earliest microscopic changes seen are a loss| |

| |-this reduces the mechanical resistance | |of metachromatic polysaccharides from the |Often appears to be related to repetitive |

| |of articular cartilage and makes it more |This is a very big disease problem, causing |cartilage matrix and a breaking up of the |mechanical trauma |

| |susceptible to the destructive effects of|much pain and disability among the elderly |cartilage surface into bundles, i.e. |Wearing away of articular cartilage |

| |ordinary mechanical stress | |fibrillation | |

| | |Risk factors: |-causes deep grooves in articular cartilage |Herberden’s nodes are a variant of osteoarthritis |

| |Proteoglycan is lost because of lysosomal|-hereditary, gender |-circular cluster of cells = ineffective attempt|-osteophytes (bone spurs) which form at the distal |

| |proteases, particularly cathepsins B and |-repeated mechanical trauma |at repair |interphalangeal (DIP) joints ( fusiform enlargement|

| |D, and MMPases | | |of joint |

| |-are released from cartilage cells and |multifactorial, multigenic |Not an inflammatory lesion |-they are mostly seen in middle-aged women and show|

| |this dissolves the proteoglycan | | |a hereditary pattern of inheritance |

| |-the result is fibrillation | |Later in the course of the disease there is | |

| | | |characteristic proliferation of new bone at the | |

| |Pathogenesis: | |edges of the articular surfaces to form bony | |

| |-proteolytic degradation of cartilage | |spurs: the so-called osteophytes | |

| |matrix | |-uneven wearing away of cartilage | |

| |-loss of resilience of articular | | | |

| |cartilage | |The final result of all this grinding away is | |

| |-surface irregularity of subchondral bone| |eburnation. Cartilage is lost and underlying | |

| | | |bone hardens to form a dense bony articular | |

| | | |surface | |

| | | |-hydroxyapatite worn away and released into | |

| | | |joint space and cause periodic acute | |

| | | |inflammation | |

| | | | | |

| | | |Circular clusters- ineffective attempt at repair| |

| | | |Fibrillation of articular cartilage- deep | |

| | | |grooved( change in cellular structure on either | |

| | | |side of fibrillar cleft | |

| | | |-cells clustered( matrix lost | |

|Rheumatoid arthritis |Etiology unknown: for several reasons it|3:1, females:males |At first there is an acute inflammation in the |A systemic, autoimmune arthritis of multiple small |

| |appears to be an autoimmune disease | |synovium, followed by chronic inflammation. The|joints (esp. fingers, wrists, and temperomandibular|

| | |Hereditary predisposition |synovial enlarge and project into the synovial |joints) |

| |Auto-antibodies, characterized by | |cavity. | |

| |rheumatoid factor (RF), cause chronic |Perhaps because of the severe pain associated | |A systemic inflammatory disorder which leads to |

| |synovitis |with rheumatoid arthritis, the muscles |This produces a pannus – i.e. papillary |destructive changes in articular cartilage of |

| |-RF is an immunocomplex composed of an |associated with an affected joint undergo |projections of inflamed synovium |multiple small joints: fingers, temperomandibular |

| |IgM associated with IgG |spasms and can actually dislocate the bones of|-the word pannus comes from the Latin word for |joints and wrists |

|Rheumatoid arthritis | |a joint |apron – the sort that Roman bakers wore | |

|(cont) |Inflammatory cytokines, released from |-this is called “subluxation,” i.e. |-pannus spreads, apron-like, over the articular |Risk factors |

| |inflamed synovium, signal |over-riding of articulating bones |surface |-hereditary (HLA-DR genotype) |

| |complement-mediated destruction of | |-when it does, it causes extensive destruction |-EBV infection |

| |articular cartilage |Subluxation of the metacarpo-phalangeal joint |of the articular surfaces, probably due to the | |

| | |= Boutonnier deformity |release of lysosomal enzymes |Rheumatoid variants: |

| |Rheumatoid factor is often tested for by | | |-Still’s disease: RA in children (RF usually |

| |latex agglutination (latex spheres or |Often there is ulnar deviation |Rheumatoid nodules develop in the subcutaneous |absent) |

| |sheep RBCs coated with normal human IgG –|-uneven tension of flexor vs. contractor |tissues near the joints (Rheumatoid nodules may |-Rheumatoid ankylosing spondylitis (eponym: Marie |

| |then reacted with RF to cause |muscles in forehand, fingers forced outwards |also be present in aorta, large arteries or |Strumpell disease) |

| |agglutination) | |sometimes in lungs, i.e. Kaplan’s syndrome) |-Felty’s syndrome: RA with splenomegaly and |

| |-usually the RF titer correlates well |Erosion of the articular cartilage causes |-these nodules are comprised of central |leukopenia |

| |with the severity of rheumatoid |fusion |fibrinoid necrosis surrounded by palisades of |-Sjogrens: RA is associated with salivary gland |

| | | |histiocytes and fibroblasts |enlargement and dryness of eyes and mouth (there is|

| |Additionally there is often an |The last stage is a bony union across what | |chronic inflammation of lachrymal and salivary |

| |anti-nuclear antibody, similar to the one|used to be a joint (ankylosis) | |glands) |

| |seen in Lupus |-when 2 normally articulating bones come | | |

| | |together and form one bone | |What causes rheumatoid hypersensitivity and immune |

| | |-no joint space | |complex formation remains is unknown |

| | | | | |

| | |Spastic contraction of muscles around joints (| | |

| | |overriding of joints (subluxation) | | |

| | | | | |

| | |Flipper hand = subluxation of several knuckles| | |

| | |of hand | | |

| | |Characteristic ulnar deviation | | |

|Lyme disease |etiologic agent is Borrelia burgdorferi |characteristic rash called erythema chronicum |serologic testing is currently unreliable; a |serious complications: myocarditis, cardiac |

| |carried by loxodes damani |migrans (ECM) |characteristic rash is perhaps the most |arrhythmias, and encephalitis |

| |-tick borne spirochete | |definitive way of making the diagnosis | |

| | |late sequelae include arthritis, neuropathy | |has many features of rheumatoid arthritis |

| | |and cardiac arrhythmias | | |

| | | | |self-limited |

TUMORS OF THE JOINTS

|Disease |Clinical Features |Morphology |Notes |

|Ganglion cyst |Most common on the extensor surface of |Microscopically it is a fibrous-walled cyst |Not neoplastic |

| |the wrist, between tendons | | |

| | |Often there is no lining epithelium. Some believe that it is a displaced bursa which has lost its |Very common benign tumor, no pain |

| |Develops close to joint surface in wrist|lining | |

| |-fluid-filled | |Therapy: surgical removal (in olden days –|

| | | |hitting it with a hammer) |

|Benign giant cell tumor |Often arising in the hands and fingers |Both tenosynovitis and giant cell tumor are similar histologically, showing: |Related to “pigmented villonodular |

|of tendon sheath | |-giant cells |tenosynovitis” |

| |Occur in articular capsule |-fibrous stroma | |

| | |-variable number of histiocytes |-These benign tumors are thought not to be |

| | |-variable old hemorrhage |neoplastic but to be inflammatory |

| | |-Gross: brownish pigment due to hemosiderin spilled out |-Never becomes malignant |

|Synovial sarcoma |Primary is small, usually arising in the|The histology varies considerably but usually there are two components |Sometimes called “synovioma” (a misnomer) |

| |lower extremities, 18-25 year olds |-most commonly encountered are malignant spindle cells- malig fibroblasts | |

| |-Diagnosed by lung metastases (via |-malignant cuboidal lining cell – the malignant counterpart of the synovial lining cell –epithelial |Very aggressive |

| |blood) |component- trying to make synovial space (deceptively benign looking – it kills the pt by blood-bourne | |

| | |metastasis) | |

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