26 Bones Joints And ST Flashcards
Causes osteoarthritis
Not an inflammatory process, but rather due to chondrocytes breaking down matrix in response to biochemical and mechanical stressors
Often an aging phenomenon (idiopathic/primary)
Oligoarticular (few joints)
Secondary to joint deformity or injury, or underlying systemic disease that puts joints at risk (obesity, diabetes mellitus, hemochromatosis, etc.)
Environmental: aging + biomechanical stress & a small genetic component
Tuberculosis spondylitis pott disease
Spinal involvement (40%) via hematogenous spread usually infection breaks through intervertebral discs, affecting multiple vertebrae and extends into soft tissue Destruction of discs and vertebra → permanent compression fractures = scoliosis or kyphosis and neurological deficits secondary to spinal cord and nerve compression (paraplegia can happen) 75% of patients develop soft tissue infection, commonly in Psoas muscle If untreated, degeneration of vertebrae can herniate into cord space May also have: sinus tract formation, psoas abscess, tuberculosis arthritis, amyloidosis
Monosodium urate
Synovial fluid is a poor solvent (vs. plasma)
Lower Temp favors precipitation
Precipitation depends on nucleating agents (insoluble collagen fibers, chondroitin sulfate, proteoglycans, cartilage fragments
Seronegative spondyloarthropathies
Immune mediated (T-cell response) & unified by changes in ligamentous attachments (not synovium), involvement of SI joints +/- other joints, absence of rheumatoid factor, and HLA-B27 association
Types:
P - Psoriatic arthritis – less associated with SI joint involvement than the others
A - Ankylosing spondylitis
I - Enteritis associated arthritis (inflammatory bowel disease: ulcerative colitis or Crohn’s disease + arthritis)
R - Reactive arthritis
Viral arthritis
Causes Alphavirus Parvovirus B19 Rubella EBV Hep B, Hep C Many reactions occur due to autoimmune reaction generated by the infection (reactive or post-infectious arthritides) HIV: rheumatic conditions may develop, likely autoimmune. ↓ incidence due to antiretroviral therapy
Juvenile idiopathic arthritis
Heterogenous group of disorders of unknown cause
Arthritis occurs < 16 year olds and persists 6+ weeks
Long term prognosis is very variable
many individuals may have chronic disease
Only 10% develop serious functional disability
Due to TH1 & TH17 cells and mediators (IL1, IL17, TNF, IFNγ) – just like rheumatoid arthritis
Risk factors
HLA, PTPN22 – just like rheumatoid arthritis
Versus Rheumatoid
Presentation of bone metastasis
Significant pain Bone marrow suppression Hypercalcemia Pathological fracture Spinal cord/nerve root compression Significant impact on quality of life
Types of renal osteodystrophy
High turnover: characterized by increased bone resorption and bone formation, with resorption predominating Low turnover or aplastic: manifested by adynamic bone (little osteoclastic and osteoblastic activity), and, less commonly, osteomalacia Mixed pattern (area dependent: high/low turnover
Location aneurysmal bone cyst
Metaphysis of long bones (proximal tibia, distal femur) + posterior vertebral bodies
Morphology paget
Initial lytic phase: waves of osteoclastic activity and lots of resorption pits. Osteoclasts are large and have many more nuclei than the 10-12 normally seen
Mixed phase: osteoclasts persist, but there are many more osteoblasts
Marrow next to the bone-forming surface is replaced by loose connective tissue with osteoprogenitor cells and lots of vessels
hallmark is a ahem mosaic pattern of woven and lamellar bone, seen in the sclerotic phase
“Jigsaw puzzlelike” due to unusually prominent cement lines orienting lamellar bone
Bone eventually exhibits coarsely thickened trabeculae with soft, porous cortices that lack structural stability = vulnerable to deformation under stress → easy fractures
“Cotton wool” appearance
Postmenopausal osteoporosis
characterized by an acceleration of bone loss
up to 2% per year for cortical bone and 9% per year for cancellous bone
Females may lose up to 35% of cortical bone and 50% of cancellous bone within 30-40 years
↓ estrogen
= ↑ secretion of inflammatory Cytokines (IL6, TNFα, IL1)
= ↑ RANKL
= ↓ osteoclast proliferation & ↓ osteoclast apoptosis
= resorption > formation
Penile
Palpable mass on dorsolateral aspect that can cause abnormal curvature, constriction of urethra or both
Uterine leiomyoma
Most common neoplasm in female
Cartilage forming tumors
30% (majority) of primary tumors involving bone (both malignant and benign)
osteosarcoma == most common primary malignant bone tumor
cartilage tumor == majority of primary bone tumors (both benign and malignant)
Benign
Osteochondroma (exostosis) == EXT1 or EXT2
Chondroma == IDH1 and IDH2
Ollier disease
Maffucci syndrome
Chondroblastoma
Chondromyxoid fibroma
Bone forming tumors
2-6% of primary tumors involving bone
All tumors produce unmineralized osteoid matrix or mineralized woven bone
Benign: identical histologic features but differ in size, sites of origin, and symptoms; malignant transformation is rare
Osteoid osteoma
Mycobacteria osteomyelitis
Typically seen in developing countries
1-3% of patients with tuberculosis have osseous infection
Blood borne organisms that originate from a focus of active visceral disease during primary infection
May persist for years before diagnosis
Localized pain, low grade fever, chills, weight loss
Solitary infection unless immunocompromised
histology: caseous necrosis and granulomas (same as tuberculosis elsewhere)
Tends to be more destructive and resistant to control
Sarcoma of st generalizations
Origin is unknown
Simple karyotype (15-20%): Euploid tumors with single or limited number of chromosomal changes, that serve as tumor markers. Common in younger patients and have a monomorphic appearance.
Complex karyotype (80-85%): Aneuploid or polypoid with multiple severe chromosome gains and losses (none that are recurrent)
More common in adults
most adult sarcomas have complex karyotypes, tend to be pleomorphic and genetically heterogenous with a poor prognosis
Subtype IV
Subtype IV Short proα2(1) chain Unstable triple helix Autosomal dominant Compatible with survival Postnatal fractures Moderate skeletal fragility Short stature Normal sclera (+/-) dentiginogenesis imperfect
Epidemiology
Youngest age at presentation (80% are < 20)
Slightly more males are affected
Predominantly affects whites (rarely African Americans or Asians
Diagnosis and treatment osteomyelitis
nosis and Treatment
Lytic bone lesion surrounded by sclerosis on radiograph
Some untreated cases may have (+) blood culture
Pathogen identification requires biopsy and bone cultures
Treatment: antibiotics and surgical drainage = curative
Clincla osteopetrosis
autosomal recessive mutations (infantile form): fracture, anemia, and hydrocephaly may cause death shortly after birth surviving infants (autosomal dominant): Mild form presenting with cranial nerve defects (optic atrophy, deafness, facial paralysis). Recurrent infections (often fatal) due to leukopenia. Extramedullary hematopoiesis → hepatosplenomegaly
Diagnosis
other forms of chronic arthritis == lupus, scleroderma, and Lyme disease
Characteristic radiographic findings
Sterile, turbid synovial fluid with ↓ viscosity, poor mucin clot formation and inclusion-bearing neutrophils
Rheumatoid Factor and anti-CCP antibody (80%)
Anti-CCP: diagnostic
increased erythrocyte sedimentation rate (happens faster)
rheumatoid factor present in 80% of rheumatoid arthritis cases (IgM antibody against the Fc portion of IgG)
anti-citrullinated cyclic peptide (CCP) is more specific
Pathoma: rheumatoid arthritis == synovitis + pannus
Risk factors
Age (appears after 20-30 years of hyperuricemia)
Mutations of: X-linked HGPRT, URAT1, GLUT9
Heavy alcohol consumption
Obesity
Drugs (thiazides) or renal failure that reduce urate excretion
Lead toxicity (saturnine gout
Superficial fibromatosis
Infiltrative fibroblastic proliferation → local deformity
Nodular or poorly defined broad fascicles of fibroblasts in long, sweeping fascicles surrounded by abundant, dense collagen
Innocuous (not harmful) clinical course
Male predominance
Treat osteopetrosis
HSC transplant
Osteoclasts are produced from donor stem cells and may reverse many of the skeletal anomalies
Location osteochondroma
bones of endochondral origin, most commonly at the metaphysis of long bones (especially near the knee)
If they arise from the pelvis, scapula, or ribs they are sessile and have short stalks
Mutations chondrosarcoma
Sporadic: CDKN2A, IDH1/2 mutations
Syndromic: EXT, IDH1/2 mutations
Softtissue
Non-epithelial tissue excluding the skeleton, joints, CNS, hematopoietic and lymphoid tissues
Benign tumors»_space; malignant sarcomas (100x), exception: skeletal muscle neoplasm
sarcomas == 2% of cancer mortality in the US (ie they are highly aggressive)
majority of sarcomas are sporadic
Tumors often occur in extremities (thigh)
15% occur in children, incidence ↑ with age
Fracture healing: infection nutrition
Common with open fractures
Malnutrition and skeletal dysplasia hinder healing
Treat fibromatosis
Cox-2 inhibitors, trk inhibitors tamoxifen
Diagnosis and treatment osteoporosis
Diagnosis: DEXA, or quantitative CT measure bone density. NO LABS for diagnosis
Treatment: exercise, Ca++/vitamin D intake, prescription (bisphosphonates, denosumab (anti-RANKL)
bisphosphonates reduce osteoclast activity and induce apoptosis
HRT → DVT, stroke
Disorders chondroma
Ollier disease and Maffucci syndrome
non-hereditary disorders characterized by multiple enchondromas
Maffucci syndrome is, in addition, distinguished by presence of spindle cell hemangiomas and patients are at increased risk of developing ovarian carcinomas and brain gliomas
enchondromas are sometimes more cellular than sporadic enchondromas and exhibit cytologic atypia
Tumors may be numerous and large → severe deformities
Patients are mosaics (IDH1/2 mutations)
increased potential for sarcomatous transformation
most likely site of metastasis with malignant transformation == lung
Synovial cyst
Herniation of synovium through a joint capsule OR massive enlargement of a bursa
eg Baker Cyst of the popliteal fossa in rheumatoid arthritis
Synovial lining may be hyperplastic and contain inflammatory cells and fibrin
Morphology skeletal syphilis
Morphology
Edematous granulation tissue containing lots of plasma cells and necrotic bone
Spirochetes are seen with silver stains
Gummas can also form
Well differentiated liposarcoma
Definition Malignant tumor of adipose tissue Scattered atypical spindle cells 50-60 year olds Relatively indolent Location Deep extremity, retroperitoneum Mutations Amplification of 12q13-q15 = MDM2 encodes an inhibitor of p53
Morphology
Ewing Sarcoma: arises in the medullary cavity, invades the cortex, periosteum, and soft tissue
Sheets of primitive round cells without much differentiation, rich in glycogen
small, round blue cells with scant cytoplasm
Tumor contains areas of hemorrhage & necrosis
Homer Wright rosettes: Round groupings of cells with central fibrillary core.
indicate neuroectodermal differentiation
Periosteal reaction: layers of reactive bone deposited in an “onion-skin” fashion
characteristic
Psoriatic arthritis
Chronic inflammatory arthropathy associated with psoriasis that affects peripheral and axial joints and entheses (tissue connecting ligaments and tendons to bones)
Develops in 10% of patients concurrently or after onset of skin disease
HLAB27, HLA-Cw6 confer susceptibility
30-50 years old when signs and symptoms manifest
Tumor like conditions paget
Benign: giant cell tumor, giant cell reparative granuloma, extraosseous hematopoietic tissue
Sarcoma: osteosarcoma or fibrosarcoma of the long bones, pelvis, skull, spine
RA
systemic, chronic, autoimmune etiology (females > males) 20-40 year olds, HLA-DR4
Chronic inflammatory disorder of autoimmune origin that may affect many tissues/organs, primarily affects small joints → non-suppurative proliferative and inflammatory synovitis
Skin, heart, vessels, lungs (can resemble other autoimmune diseases)
Can progress to destruction of articular cartilage and ankyloses
Commonly happens after an infection (trigger
Osteoblasts
On the matrix surface
Synthesize, transport and assemble matrix, regulating mineralization
May become inactive over time which is indicated by ↓ cytoplasm
Some may remain on the surface of trabecula, others become embedded in the matrix (osteocytes)
produce monocyte colony stimulating factor (M-CSF) that activates osteoclast precursors to become osteoclasts
Adamanntinoma
amantinoma from the table
Malignant, primary bone tumor of unknown origin
Cortical, fibrous bone matrix with epithelial islands
Location: tibia
30-40 year olds
Pathogenesis chondrocytes
Lesions occur due to degeneration of articular cartilage + disordered repair in weight bearing joints
Three phases
Chondrocyte injury (genetics, biochemical)
Early OA: proliferation for remodeling of cartilaginous matrix and secondary inflammatory changes
Late OA: chondrocyte drop out due to repetitive injury and chronic inflammation → extensive subchondral bone changes
All extracellular components are affected
Proteoglycan composition is altered
Sparse inflammatory cells, but many other inflammatory factors are present: TGFβ (induces MMPs), TNF, prostaglandins, and nitric oxide
Location
Diaphysis of long bones (femur + flat bones of pelvis) and shoulder
Pathogenesis osteopetrosis
Mutations affect acidification of the osteoclast resorption pit, which is necessary for the dissolution of calcium hydroxyapatite within the matrix
ahem CA2 (carbonic anhydrase 2) autosomal recessive: acidification of urine is blocked with the lack of acidification of the pit –> metabolic acidosis
CLCN7: encodes the proton pump on the surface of osteoclasts
Undifferentiated pleomorphic sarcoma
Definition
Malignant tumor of uncertain histology
40-70 year olds
largest category of adult sarcomas
no reproducible genetic changes
Location
Thigh, deep soft tissue of extremities
Morphology
Sheets of high grade anaplastic polygonal, round or spindle cells
Bizarre nuclei, atypical mitoses, necrosis
Treatment and prognosis
Aggressive malignancies treated with surgery and chemo +/- radiation
Poor prognosis; 30-50% rate of metastases
Bacterial causes osteomyelitis
Staph Aureus: 80-90% of culture positive cases of osteomyelitis.
Cell wall proteins bind bone matrix components (collagen) facilitating adhesion
staph == coagulase positive (aureus only), catalase positive
coagulase positive == staph aureus and nothing else
strep == coagulase negative, catalase negative
E. Coli, Pseudomonas, Klebsiella: patients with genitourinary infections or IV drug users
Mixed infection: Direct spread or inoculation of organisms during surgery or into open fractures
Neonatal: H. Influenzae, group B strep
Sickle cell: Salmonella typhi
50% of cases = no organism can be isolated
Morphology
Formation of bone by tumor cells is diagnostic
Large, destructive, grey-white, gritty +/- hemorrhage and cystic degeneration
Large, hyperchromatic, pleomorphic, mitotically active tumor cells
Neoplastic bone has a fine, lace-like pattern
Osteoblastic, chondroblastic, or fibroblastic differentiation
Chondrosarcoma
Malignant tumors producing cartilage
Conventional (90%): hyaline cartilage producing
2nd most common malignant matrix producing tumor of bone (half as common as osteosarcoma)
patients older than 40 years, males 2X
Osteoporosis risk factors
Age: Diminished capacity to form bone (senile form aka low turnover variant)
Reduced physical activity: Mechanical forces stimulate bone remodeling.: Weight training (load magnitude) exercise is better
Genetics: RANKL, RANK, OPG, HLA locus, estrogen receptor
Calcium nutritional state: impacts the bone density peak that can be achieved, especially affected are adolescent females
Hormones
Treat nodular fasciitis
Typically regresses spontaneously
If excised: rarely recurs
Clincial presentation type 1 collagen disease
fundamental abnormality == too little bone → extreme skeletal fragility
Blue sclera: ↓ collagen = translucent sclera and partial visualization of the underlying choroid
Hearing loss: related to both sensorineural deficit and impeded conduction due to bone abnormalities in the middle and inner ear
Dental imperfections: Small, misshapen, blue-yellow teeth secondary to deficiency in dentin
Mccune Albright sydnrome
Polyostotic disease
unilateral bone disease, with café-au-lait pigmentation ipsilateral dark, irregular serpiginous borders on neck, back, chest, shoulder, and pelvic areas
skin pigmentation is usually limited to the same side of the body
Precocious puberty is the most common clinical presentation, especially in girls
treat with aromatase inhibitors
Endocrinopathies: hyperthyroidism, growth hormone excess, primary adrenal hyperplasia
GNAS1 mutation
Rhabdomyoma
Benign tumor of skeletal muscle frequent in individuals with tuberous sclerosis
Polygonal rhabdomyoblasts, “spider cells”
Location: head & neck
0-60 year olds
Liposarcoma
One of the most common sarcomas of adulthood
Sarcoma Botros DES
Variant of embryonal rhabdomyosarcoma
Develops in the walls of hollow, mucosal lined structures: Nasopharynx, common bile duct, vagina, bladder
Form cambium layer (submucosal zone of hypercellularity) on organ mucosa
Best outcome of all subtypes
Osteosarcoma
Adolescents knee
Location of tumors
Typically multifocal
Kidney, thyroid cancers may be solitary
Most involve the axial skeleton: Red marrow has rich capillary network and slow blood flow allowing implantation and growth of tumor cells
Hand or foot involvement is uncommon (lung, kidney, colon
Leiomyoma smooth msucle
Definition
Benign tumor of smooth muscles
20 year olds
uterine leiomyomas are the most common neoplasm in women
Location
Extremities, uterus, erector pili muscles (pilar) of skin, nipples, scrotum, labia, gut
Pilar = multiple & painful
Morphology
Uniform, plump, eosinophilic cells in fascicles intersecting at right angles
Blunt ended elongated nuclei
Minimal atypia, few mitotic figures
Treatment
Solitary = easily cured
Multiple: complete surgical removal may be impractical
Pathogenesis osteosarcoma
RB (70% of sporadic) 1,000x ↑ risk
TP53: the guardian of the genome
Li-Fraumeni patients have ↑ risk
INK4a: encodes p16 (negative regulator of CDKs) and p14 (augments p53 function)
MDM2 (inhibits p53) & CDK4 (inhibits RB): overexpressed in low grade osteosarcomas via amplification of 12q13-q15
Osteoclasts
Originate from HSCs rather than mesenchymal stem cells
Specialized multinucleated macrophages derived from circulating monocytes
Responsible for bone resorption
Attach to bone matrix via integrins → resorption pit (sealed extracellular trench)
Dissolution of bone components occurs due to secretion of acid and neutral proteases (MMPs) into the pit
Hyperparathyroidism
Excess levels of this hormone occur due to autonomous secretion (primary) OR
Renal disease (secondary): inadequate 1,25(OH)2D synthesis (altered GI absorption) & hyperphosphatemia suppression of α1-hydroxylase
Secondary hyperPTH is typically milder
Significant skeletal change due to unabated osteoclast activation
Entire skeleton affected
Bone changes are completely reversible with reduction of hormone levels
Polyostotic
Manifests somewhat earlier and may cause problems into adulthood
May require corrective orthopedic surgeries, bisphosphonates
Affects femur, skull, tibia, humerus, ribs, fibula, radius, ulna, mandible, vertebra
50% with craniofacial involvement, 100% in patients with extensive skeletal disease
Progressive deformities & fractures when involvement of the shoulder or pelvic girdles occurs
Rare complication == malignant transformation of a lesion into sarcoma can occur
Dedifferentiated type
Malignant tumors producing cartilage, more aggressive
Low grade tumor with a second, high grade component that does not produce cartilage
Treatment: widely excised + additional chemotherapy because of more aggressive course
Osteoarthritis
efinition
Most common type of joint disease
Degeneration of articular cartilage and disordered repair→structural and functional failure of synovial joints
biomechanical causes == wear and tear (eg increased age, obesity, and trauma)
biochemical causes == injury to chondrocytes or abnormal matrix formation
Females: knees & hands
Males: hips
Alveolar rhabdomyosarcoma
Definition Malignant tumor of skeletal muscles 5-15 year olds Location Extremities, sinuses Genetics Genetically heterogenous FOXO1 fusion to PAX3 or PAX7 t(2;13) or t(1;13) Morphology Uniform, round, discohesive cells with little cytoplasm between septae (look like alveoli) Discohesive center with peripheral cells adherent to the septae No cross striations
Common joint affected osteoarthritis
Hips, knees, lower lumbar & cervical vertebra, proximal & distal interphalangeal joints of fingers, 1st carpometacarpal & 1st tarsometatarsal joints
Wrists, elbows and shoulders are spared
Skeletal syphilis
Bone involvement is infrequent due to earlier diagnosis and treatment
Bone lesions appear in the 5th months of gestation and are fully developed at birth
Spirochetes localize to areas of active enchondral ossification (osteochondritis) and in the periosteum (periostitis)
Saber shin: massive reactive periosteal bone deposition on the medial & anterior surfaces of the tibia
(don’t forget about Hutchinson teeth)
If acquired, bone disease manifests 2-5 years after initial infection and involves the nose, palate, skull and extremities (long bones
Hormonal control of bone growth
ormonal Control of Bone Growth
Growth hormone stimulates chondrocytes to induce and maintain proliferation
Thyroid hormone (T3) stimulates chondrocyte proliferation
Indian Hedgehog coordinates chondrocyte proliferation and differentiation and osteoblast proliferation
PTHrP activates PTH receptor and maintains proliferation of chondrocytes
Wnt activates β-catenin signaling; can promote both proliferation and maturation of chondrocytes
Wnt proteins produced by osteoprogenitor cells bind to the LRP5 and LRP6 receptors on osteoblasts and trigger the activation of β-catenin and the production of OPG
sclreostin (produced by osteocytes) inhibits WNT/β-catenin signaling
SOX9 is essential for differentiation of precursor cells into chondrocytes
RUNX2 controls terminal chondrocyte and osteoblast differentiation
Fibroblast Growth Factors act on hypertrophic chondrocytes to inhibit proliferation and promote differentiation
Bone Morphogenic Proteins have diverse effects on chondrocyte proliferation and hypertrophy
Osteodystrophy osteoma
Benign, bone forming tumor < 2cm
Severe nocturnal pain due to osteoblast production of PGE2, relieved by ASA
metaphysis of long bones (femur, tibia = 50%)
Thick rind of reactive cortical bone radiographically
10-20 year olds, male predominance
Presentations: severe nocturnal pain that is relieved by aspirin
Treatment: radiofrequency ablation
Osteochondroma (exostosis)
Most common benign bone tumor
Benign, cartilage capped tumor attached to the underlying skeleton via a bony stalk
Slow growing solitary masses
Painful if impinge on a nerve or stalk is fractured, but generally found incidentally
Male predominance
Late adolescence and early adulthood
Pyogenic osteomyelitis causes
Due to bacterial infection reaching the bone via hematogenous spread (most common in children), extension from a contiguous site, direct implantation
Skeletal muscle tumors
Mostly malignant
Treatment and prognosis Ewing
Neoadjuvant chemotherapy and surgical excision +/- irradiation
because ESFT are aggressive malignancies
75% 5 year survival, 50% long term cure
Chemotherapy induced necrosis = important prognostic factor
Myxoid liposarcoma
Definition
Malignant tumor of adipose tissue
Myxoid matrix, ‘chicken wire’ vessels, round cells, lipoblasts
Abundant basophilic extracellular matrix, arborizing capillaries and primitive cells at various stages of differentiation (fetal fat)
30 year olds
Intermediate malignant behavior
Location
Thigh, leg
Mutation
t(12;16) – chromosome 12q == MDM2 gene (potent inhibitor of p53
Types of rhabdomyosarcoma
Alveolar
Embryonal (most common)
sarcoma botyroides == variant embryonal rhabdomyosarcoma with the best prognosis
Pleomorphic: seen predominantly in adults
often fatal
Fracture healing maturation
Areas not physically stressed are resorbed, reducing the callus in size and shape
The outline of the fractured bone is reestablished as lamellar bone
Healing is complete with restoration of the medullary cavity
Thanatophoric dysplasia
most common lethal form of dwarfism
micromelic shortening of the limbs, frontal bossing, relative macrocephaly, a small chest cavity (–> respiratory insufficiency), and a bell-shaped abdomen
gain-of-function mutations in FGFR3 that differ from those in achondroplasia
Presentation osteoarthritis
morning joint stiffness, worsens with use
Insidious disease that presents >50 years old. Young patients likely have an underlying condition
Deep, achy pain in 1-2 joints that worsens with use
Morning stiffness, joint crepitus, limited range of motion, joint swelling
Osteophytes may impinge on spinal foramina → cervical & lumbar nerve root compression = radicular pain, muscle spasms, muscle atrophy, and neurological deficits
X-ray: joint narrowing
Heberden nodes: prominent osteophytes at distal interphalangeal joints that are common in females
Bouchard nodes more proximal than Heberden nodes
Deformity may occur but fusion does not occur (rheumatoid arthritis == fusion/ankylosis
Presentation osteosarcoma
Painful, progressively enlarging mass, may present as a fracture
Extends from medulla to lift periosteum = reactive periosteal bone formation
Radiographically: large, destructive, lytic & blastic mass with infiltrative margins
Codman triangle: triangular shadow between the cortex & raised ends of the periosteum; indicates an aggressive tumor; non-specific (characteristic but not diagnostic)
Location osteosarcoma
Can occur in any bone, but most commonly occur in the metaphysis of distal femur or proximal tibia, especially in the growth plate since there is faster cell proliferation there
Joint morphology
symmetric arthritis principally affecting the small joints of the hand and feet
Synovial hyperplasia and proliferation
Dense inflammatory infiltrates of CD4 T helper cells, B cell, plasma cells, dendritic cells, and macrophages
↑ vascularity due to angiogenesis
Fibrinopurulent exudate on the synovial & joint surfaces
Osteoclast activity in underlying bone = synovium penetration of bone → periarticular erosions and subchondral cysts
pannus: mass of edematous synovium, inflammatory cells, granulation tissue, and fibroblasts that grows over the articular cartilage and causes its erosion
in time, the pannus bridges the apposing bones to form a fibrous ankylosis, which eventually ossifies and results in fusion of the bones, called bony ankylosis
pannus == granulation tissue –> bony ankylosis
blood vessels
fibroblasts
myofibroblasts
contract and lead to joint deviations/deformity
Joint Deformity == Rheumatoid Arthritis
ulnar deviation of the fingers, radial deviation of the wrist
Swan Neck and Boutonniere deformities
Morphology osteopetrosis
Subchondral infarction: triangular/wedge shaped segment of tissue that has the subchondral bone plate as its plate undergoes necrosis
The overlying articular cartilage remains viable from nutrients in the synovial fluid
Dead bone is recognized as empty lacunae that are surrounded by ruptured adipocytes, which can have associated fat saponification (may remain for life)
Creeping substitution with new bone occurs from the margin of the infarct, but is too slow and collapses upon itself
Morphology osteopetrosis
due to deficient osteoclast activity, bone lacks a medullary canal
ends of long bones are bulbous (Erlenmeyer flask deformity)
neural foramina are small, compressing exiting nerves II, VII, and VIII
primary spongiosa is not removed, filling the medullary cavity leading to no hematopoietic marrow and preventing the formation of mature trabeculae
woven architecture of newly deposited bone
diffuse skeletal sclerosis (bones look wider but they are brittle because increased woven bone) = fractures
Pathogenesis fibrous dysplasia
Somatic GNAS1 gain-of-function mutation
same gene is mutated in pituitary adenoma
Constitutively active GS protein, activating cAMP→ cellular proliferation
Extent of phenotype depends on stage in which the mutation occurs and the fate of cell harboring the mutation
McCune Albright occurs when mutations happens during embryogenesis
monostotic fibrous dysplasia happens when mutation occurs in one osteoblast precursor during or after skeletal formation
Deep fibromatosis
Large, infiltrative masses that frequently recur (no metastases)
Benign fibrous tumor
Teens-30s
Female predominance
Clincla course paget
Variable clinical presentation based on extent and site of disease
Most are asymptomatic and discovered incidentally
85% of cases are poly-ostotic (involve more than one bone)
80% involve the axial skeleton (head/trunk) or proximal femur
Pain localizes to the affected bone due to microfractures or bone overgrowth compressing spinal and cranial nerve roots
Bone pain/deformity (bowing of tibia) and/or nerve entrapment
Leontiasis ossea (lion face): enlargement of craniofacial skeleton (frontal bone) and a cranium so heavy that it is difficult to hold up
Platybasia: invagination of the skull base → compression of the posterior fossa
Weight bearing = anterior bowing of femurs and tibia → distortion of femoral heads –> 2˚ osteoarthritis
in the absence of malignant transformation, Paget disease is usually not a serious or life-threatening disease
Osteoblast OA
Benign, bone forming tumor >2cm (larger) No bony reaction involves the posterior spine (laminae & pedicles) 10-20 year olds Pain is not responsive to aspirin Treatment: curetted or excised in bloc
Pathogenesis tenosynovial
t(1;2)(p13;q37): Type VI collagen α-3 promoter with M-CSF = M-CSF overproduction –> proliferation of macrophages (similar to giant cell tumor of bone
Morphology fibrous cortical defect
Sharply demarcated radiolucencies with a long axis of bone parallel to the cortex, surrounded by a thin rim of sclerosis
Fibroblasts are arranged in a storiform (pinwheel) pattern
Macrophages are clustered together with foamy cytoplasm or giant cells
Limited growth potential, and spontaneously regress
Chondrosarcoma
Older adults pelvis and proximal extremities
Subtypes of chondrosarcoma
Conventional
Clear cell
Dedifferentiated
Mesenchymal
Bone sarcoma
< 1% of all bone disease
50% are lethal
Found from bone pain or pathological fractures
Treatment is often disfiguring
Goal: optimize survival & maintain function of affected body parts
bone tumors are classified according to the normal cell or matrix they produce
lesions that do not have normal tissue counterparts are grouped according to their clinicopathologic features
Risk factors
Chronic injury and inflammation: bone infarcts, chronic osteomyelitis, Paget disease, radiation, metal prostheses
Clincal course of non joint structures
Arthritis may be accompanied by inflammation of tendons, ligaments and adjacent skeletal muscles
Radial deviation of wRist, ulNar deviation of fiNgers – RR and NN
Swan-neck deformity: PIP extension + DIP flexion
Boutonniere deformity: PIP flexion + DIP extension
Characteristic rheumatoid nodules that can present in places like the lung or skin
Calcium pyrophosphate crystal deposition disease
AKA pseudogout or chondrocalcinosis
patients > 50 years old, incidence increases with age
Sporadic (idiopathic) or hereditary
Causes
Autosomal dominant mutation of pyrophosphate transport channel
Secondary form: previous joint damage, hyperparathyroidism, hemochromatosis (HFE mutation), hypothyroidism, diabetes, ochronosis
Pathogenesis
Proteoglycans (normally inhibit mineralization) are likely degraded, allowing crystallization around chondrocytes
Inflammation is caused by activation of inflammasome in macrophage
Morphology
Crystals first develop in the articular cartilage, menisci, intervertebral discs
Crystals are chalky, white, friable deposits
Crystals are rhomboid and positively birefringent
Palmar fibromatosis
Palmar Fibromatosis (Dupuytren Contracture)
Irregular or nodular thickening of the palmar fascia uni- or bi-laterally
Puckering and dimpling of the skin may occur over years
Slow, progressive flexion contracture affects the 4th and 5th digits of the hand
25% do not progress
Intramembranous ossification
Intramembranous ossification is responsible for the development of flat bones and facial bones
unaffected in achondroplasia
Synthesis gout
Purine catabolism → uric acid
↑ uric acid likely due to abnormal purine production
Most primary causes are due to this
Monostotic
Occurs during early adolescence
Stops enlarging at the time of growth plate closure
Asymptomatic lesion of a single bone, incidentally discovered
Femur, tibia, ribs, jaw, calvarium, humerus
Can cause pain, fracture, limb length discrepancies
Radiographic: ground glass appearance, well defined margins
If symptomatic: treat with curettage (curative
Pleomorphic liposarcoma
Contain complex karyocytes without reproducible genetic abnormalities
Sheets of anaplastic cells
Bizarre nuclei
Variable number of immature adipocytes (lipoblasts)
Aggressive tumor that frequently metastasizes
Liposarcoma treatment
Causes osteopetrosis
Mechanical injury to blood vessels: thromboembolism, external pressure on vessels, venous occlusion
Often due to fracture or corticosteroid administration
Alcohol abuse, Bisphosphonates (especially jawbones), pregnancy
Rickets
Rickets (children)
Vitamin D deficiency or abnormal metabolism
Impaired mineralization → accumulation of under-mineralized matrix
disease of children (called osteomalacia in adults)
Interferes with deposition of bone in the growth plates
Osteopenia
Osteopenia
↓ bone mass
Bone mass 1-2.5 standard deviations below mean peak bone mass in young adults
Treatment and spread giant cell
Curettage (40-60% recur)
4% metastasize to lungs, but spontaneously regress – do not usually undergo malignant transformation
RANKL inhibitor (denosumab) as adjuvant therapy
Dysostosis
ocalized problems in the migration and condensation of mesenchyme; transcription factors, homeobox genes, cytokines and cytokine receptors
aplasia: complete absence of a bone or entire digit
supernumerary digit: extra bones or digits
syndactyly, craniosynostosis: abnormal fusion of bones
