Pathology Flashcards
RANKL (RANK ligand)
located on osteoblast/ stromal cells
binds RANK receptor on osteoclasts and activates ir
M-CSF (macrophage- colony stimulating factor)
located on osteoblast/ stromal cells
helps RANKL activate osteoclast
osteoprotegerin (OPG-a soluble protein)
located on osteoblast
binds RANKL and prevents bone resorption by inhibiting osteoclast differentiation
parathyroid hormone (PTH)
increases RANKL
enchondral ossification
formation of bone through cartilage
occurs at epiphyseal plate
membranous ossification
no cartilage intermediate step
cells from periosteum differentiate into osteoblasts and make bone
flat bones
osteogenesis imperfecta
mutations in alpha 1 or 2 chains of TYPE I COLLAGEN
achondroplasia dwarfism
AD or spontaneous
activating mutation in FGFR3
affects only bones that develop by enchondrial ossification
cartilage of growth plates disorganized and hypoplastic
Sx: frontal bossing with mid face hypoplasia, short limbs, bowing legs, trident hands, lordosis
thanatophoric dwarfism
FGFR3
lethal variant of dwarfism
small thorn leads to respiratory complications
osteopetrosis
AD (mild, adult)
AR (lethal, infantile)
dense solid bones that fracture easily
poor osteoclast function
CARBONIC ANHYDRASE II deficiency: loss of acidic microenvironment needed for bone resorption
Sx: metabolic acidosis, anemia, thrombocytopenia, extra medullary hematopoiesis (hepatosplenomegaly), vision and hearing impairment, hydrocephalus, infections
osteogenesis imperfecta type I presentation
normal lifespan mild bone fragility rib deformities BLUE SCLERAE hearing loss small misshapen teeth (dentin deficiency)
osteogenesis imperfecta type II
perinatal lethal
FGFR3
fibroblast growth factor receptor 3
inhibits cartilage proliferation
ACHONDROPLASIA
carbonic anhydrase II
generate protons from CO2 and water
rickets
VITAMIN D (deficiency, abnormal metabolism or Ca2+ deficiency): defect in bone mineralization
Xray: distal end of long bones flared, frayed, and cupped; increased distance between radius and metacarpals
Sx: pigeon chest deformity, frontal bossing, bowing of legs, rachitic rosary
increase: PTH, alkaline phosphatase
decrease: Ca, Pi
osteomalacia
VITAMIN D deficiency in adults
inadequate mineralization of bone
increase: PTH, alkaline phosphatase
decrease: Ca, Pi
vitamin D
mineralizes osteoid matrix
stimulates osteoblast to synthesize osteocalcin
osteocalcin
deposition of Ca in bone development
calcium hydroxyapatite
inorganic part of bone
Ca, Pi, Na, Mg
strength and hardness of bone
osteomyelitis
bone infection
cause: direct inoculation (trauma), contiguous spread (cellulitis), hematogenous spread
Sx: bone pain, sequestrum surrounded involurum on X-ray
Tx: blood culture first
osteoporosis
reduction in trabecular bone mass
porous bone with increased risk of fracture
causes: aging, inactivity, decreased estrogen, genetics, nutrition
Sx: hip fracture (side fall, high mortality), kyphosis
Tx: bisphosphonates
Pagets
imbalance of osteoclast and osteoblast function: thick bone that fractures easily
predisposition: chromosome 18
LOCALIZED
Sx: isolated elevated ALAKALINE PHOSPHOTASE, thick skull, deafness, kyphosis, pain, bowed legs
COTTON WOOL skull
complication: OSTEOSARCOMA
Tx: bisphosphonates
hyperparathyroidism
primary: tumor or hyperplasia
secondary: prolonged state of hypocalcemia with hyper secretion of PTH
PTH -> osteoblasts -> osteoclasts
bone resorption
Sx: brown tumor
renal osteodystrophy
skeletal changes associated with chronic renal disease
kidney fails to convert Vitamin D to active form
reduced Ca -> increased PTH -> bone resorption
avascular (aseptic) necrosis
ischemic necrosis
causes: fracture/trauma, STEROIDS, sickle cell, alcohol abuse, decompression sickness (the bends)
osteoid
unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue
type I collagen
How does menopause play a role in the pathogenesis of osteoporosis?
- decreased estrogen
- increased IL-1, IL-6, TNF
- increased RANK, RANKL
- increased osteoclast activity
How does aging play a role in pathogenesis of osteoporosis?
- decreased replicative activity of osteoprogenitor cells
- decreased synthetic active of osteoblasts
- decreased biologic activity of matrix-bound growth factors
- reduced physical activity
bisphosphonates
inhibit osteoclasts and promote apoptosis
Tx: Paget, osteoporosis
sequestrum
lytic focus (abscess)
involurum
sclerosis
Causes of osteomyelitis:
- most common
- sexually active young adults
- sickle cell disease
- diabetics or IV drug abusers
- Pott disease (spine)
- staph aureus
- N. gonorrhoeae
- salmonella
- pseudomonas
- mycobacterium tuberculosis
Conditions that elevate ESR > 100 mm/hr
- osteomyelitis
- temporal arteritis
- polymyalgia rheumatic
Osteitis fibrosa cystica (von Recklinghausen disease of bone)
RARE
increased bone cell activity, peritrabecular fibrosis, cystic brown tumors
end result of hyperparathyroidism
simple fracture
closed
does not pierce overlying skin
compound fracture
open
bone is exposed to environment through the wound
risk of infection
displaced fracture
separated in non-anatomic position
pathologic fracture
break after trivial trauma
pre-existing problem
ex: osteoporosis, bone cysts, cancer
spiral fracture
may indicate child abuse
toddler’s fracture
spiral fracture of distal tibia usually from normal activity
NOT indicative of child abuse
stress (hairline) fracture
caused by constant or repeated stress
Xray may not reveal fracture
scaphoid fracture
fall on outstretched hand
pain at snuffbox
xray: unremarkable
PROXIMAL scaphoid may undergo avascular necrosis
basilar skull fracture
secondary to trauma periorbital ecchymoses (RACCOON EYES), mastoid ecchymoses (BATTLE SIGN), CSF leakage through ears (otorrhea) or nose (rhinorrhea with salty, metallic taste)
fractures that are highly suspicious for child abuse
multiple fractures of different ages
rib fractures
spiral fratures (not toddler’s fracture)
*need to ensure not osteogenesis imperfecta
shaken baby syndrome
subdural hematomas
retinal hemorrhages
compartment syndrome
increased pressure compromises the vascular supply to extremity
Sx: WOODLIKE compartment, severe pain
Dx: measure intracompartmental pressure
Tx: fasciotomy
PAIN, PALLOR, PARESTHESIA, PULSELESSNESS, PARALYSIS
complications of fractures
deep vein thrombosis
pulmonary emboli
fat emboli
compartment syndrome
steps of a healing fracture
- hematoma: fills gap; platelets and inflammatory cells enter
- end of week one: tissue is primed for new matrix synthesis
- week 2-3: early callus formation
- bony callus: can now bear weight
osteoma
adult/child
bone tumor: compact or mature trabecular bone
CRANIOFACIAL bones, PARANASAL sinuses
Sx: pain, headache, vision change
prognosis: depends on proximity to essential structures
GARDNER SYNDROME
osteoid osteoma
young male:
osteoblastoma
children/young adults bone tumor (similar to osteoid osteoma) benign > 2 cm vertebrae Sx: bone pain that does NOT respond to aspirin Tx: curettage or excised en bloc
chondroma
benign cartilage tumor: CHONDROCYTES
enchondroma, subperiosteal/juxtacortical chondroma or soft tissue
IDH1/IDH2 genes: enchondroma
osteochondroma
male 10-20 MOST COMMON benign tumor of bone epiphyseal plate: cap of cartilage Sx: pain, slow growth, stops after puberty and ossifies rare transformation to: CHONDROSARCOMA Tx: excision imaging: MUSHROOM (nuclear blast)
chondrosarcoma
male in 40’s
malignant cartilage tumor (NO osteoid)
medulla of pelvis or axial skeleton
fibrous cortical defect (non-ossifying fibroma)
teens benign > 5cm and intramedullary component asymptomatic developmental defect Tx: none PINWHEEL
fibrous dysplasia
fibrous tissue forms instead of medullary bone
problem with osteoblast maturation
rib, femur
Sx: painful swollen bones, fracture
giant cell tumor
young adults (20-40s) epiphysis of long bone, knee xray: SOAP BUBBLE locally aggressive, reoccurrence express RANKL
Ewing sarcoma
white male children
solitary bone cyst
male
aneurysmal bone cyst
1-20 yrs
benign, fast growing: like sponge filled with blood
Tx: curettage (can be a challenge due to extensive bleeding)
reoccur
metastatic bone tumors
more common that primary
lytic lesion: punched out (exception: prostatic is white osteoblastic lesion)
BLT with a Kosher Pickle: breast, lung, thyroid, kidney, prostate
tumors located at epiphysis
benign
chondroblastoma
giant cell tumor
tumors located at diaphysis
benign 1. enchondroma 2. fibrous dysplasia malignant 1. Ewing's sarcoma 2. chondrosarcoma
tumors located at metaphysis
benign 1. osteoblastoma 2. osteochondroma 3. non-ossifying fibroma 4. osteoid osteoma 5. chondromyxoid fibroma 6. giant cell tumor malignant 1. osteosarcoma 2.juxtacortical osteosarcoma
osteosarcoma
male 10-20yrs MOST COMMON (after myeloma) bone tumor malignant: OSTEOBLASTS knee, metaphysis Rb gene: retinoblastoma: poor prognosis TP53: Li-Fraumeni syndrome or sporadic older patients: Paget, post radiation Sx: pain, enlarging, fracture, 20% lung metastasis at Dx imaging: CODMAN TRIANGLE micro: LACE LIKE
gardner syndrome
familial adenomatous polpyosis AD APC gene chromosome 5q21 Sx: colon polyps, osteoma, thyroid CA, epidermoid cysts, fibromas, desmoid tumors association: deep fibromatosis, osteoma
codman trianble
OSTEOSARCOMA
tumor destroys periosteal new bone before it ossifies and lifts the periosteum
chondroblastic osteosarcoma
osteosarcoma making malignant cartilage
RB
OSTEOSARCOMA and retinoblastoma
neg. regulator of cell cycle
TP53
OSTEOSARCOMA and others
gene whose product functions as guardian of genomic integrity by promoting DNA repair and apoptosis of irreversibly damaged cells
LI-FRAUMENI syndrome
INK4a
OSTEOSARCOMA
tumor suppressor gene
MDM2
OSTEOSARCOMA, LIPOSARCOMA
cell cycle regulator that inhibits p53
CDK4
OSTEOSARCOMA, LIPOSARCOMA
cell cycle regulator that inhibits RB
enchondroma
20-49 yrs small bones of hands and feet solitary usually arise from diaphyseal medullary cavity asymptomatic Tx: excise or nothing IDH1/2
IDH1/IDH2
isocitrate dehydrogenase 1/2
CHONDROMA, AML, glioma
multiple enchondromas
may produce severe deformities
transformation to chondrosarcoma
Maffuci syndrome
- multiple enchondromas
- soft tissue hemangioma
- ovarian cancer, brain gliomas
Ollier disease
non-hereditary disease of multiple enchondromas of long bones and flat bones with skeletal deformity
if imaging benign: ignore low grade chondrosarcoma features on histo
most lesions regress when skeleton matures
often: ovarian sex cord tumors
mazabraud syndrome
- fibrous dysplasia
2. soft tissue myxomas
McCune Albright syndrom
- fibrous dysplasia
- CAFE AU LAIT skin
- endocrine abnormalities (precocious puberty)
lytic lesion
punched out (dark) on X-ray ex: metastatic bone cancer, cysts
osteoblastic lesion
white on X-ray
ex: metastatic bone cancer from prostate
soft tissue tumors
arise from pluripotent stem cells
most benign
most on THIGH
ganglion cyst
joint
small cyst-like spaces with no epithelial lining, contain mixed material
degenerative phenomenon in tendons or CT near joint
giant cell tumor of tendon sheath
near joint
interfere with function
well circumscribed tumor
YELLOW: lipid laden macrophages
tenosynovial giant cell tumor
joint
HEMOSIDERIN depostion: brown
localized destructive lesion in a single joint, usually knee
lipoma
benign tumor of fat MOST COMMON soft tissue tumor in adults trunk or superficial extremity mobile, slow growing, painless (angiolipoma can manifest with pain) YELLOW HMGA2/HMGIC rearrangement at 12q13-15 Tx: complete excision cures
liposarcoma
50-60’s
malignant tumor of fat
deep soft tissue of proximal extremities, RETROPERITONEUM
MDM2, CDK4 stain
12q13-15 amplification
recur locally and repeatedly if not adequately excised
LIPOBLAST
HMGA2/HMGIC rearrangement at 12q13-15
lipoma
lipoblast
liposarcoma
12q13-15 amplification
liposarcoma
histologic subtypes of liposarcoma
- well differentiated: indolent
- myxoid: intermediate (CHICKENWIRE vessels)
- pleomorphic: aggressive (LIPOBLAST)
nodular fasciitis
fibrous RAPIDLY GROWING, benign fibroblast proliferation in subcutis ARMS 1/4 Hx of trauma clonal but self limited
myositis ossificans
fibrous
presence of metaplastic bone after trauma of proximal extremities in young athletes
Tx: cure with excision
fibromatosis: superficial
male
fibrous
fibroblastic proliferation that causes local deformity: CONTRACTURE
fibrosarcoma
adults fibrous malignant neoplasm of fibroblasts deep in thigh, retroperitoneal local recurrence common hematogenous spread to LUNGS HERRINGBONE gross: unencapsulated with necrosis and hemorrhage
fibromatosis: deep
young females
benign fibrous
large infiltrative mass that recur but do not metastasize; can impinge abdominal structures
APC, BETA-CATENIN: increase WNT signaling
association: GARDNERS SYNDROME
Beta-catenin
increase WNT signaling
deep fibromatosis
APC gene
increase WNT signaling
deep fibromatosis, Gardners
rhabdomyoma
muscle PEDIATRIC HEART (hamartoma): can obstruct valve or chamber SPIDER cells spontaneously regress association: TUBEROUS SCLEROSIS TSC1/2 mutation
rhabdomyosarcoma
muscle
malignant mesenchymal tumor with skeletal muscle differentiation
pediatric forms: sinus, head, neck, GU
RHABDOMYOBLASTS: on EM can see sarcomeres
TSC1
hamartin
rhabdomyoma
TSC2
tuberin
rhabdomyoma
tuberous sclerosis
seizures, angiomyolipomas of kidney
child with RHABDOMYOMA
types of rhabdomyosarcoma
- embryonal (child)
- alveolar (child): t(1:13), t(2:13)
- pleomorphic: myogenin (IHC stain)
sarcoma botyoides
variant of embryonal rhabdomyosarcoma
nasopharynx, vagina
from cambium layer
t(1:13)
alveolar rhabdomyosarcoma
t(2: 13)
alveolar rhabdomyosarcoma
worse prognosis
myogenin (IHC stain)
pleomorphic rhabdomyosarcoma
prove rhabdomyoblastic differentiation
leiomyoma
sm. muscle benign tumor most common neoplasm in women uterus common associaiton: renal cell CA syndrome FUMERATE HYDRATASE: germline loss of function mutation
leiomyosarcoma
women more than men sm. muscle painless, large, bulky deep soft tissue tumor of extremities and retroperitoneum great vessels: deadly metastasis: LUNG
fumerate hydratase
Kreb’s cycle
germline loss of mutation function: hereditary leiomyomatosis, renal cell cancer syndrome
synovial sarcoma
20s-40s misnomer can present in locations without synovium, deep seated mass for years t(X: 18) Tx: surgery and chemo mets: to LUNG monophasic and biphasic
t(X: 18)
synovial sarcoma
undifferentiated pleomorphic sarcoma
cannot be identified on hits, immunohistochemical profile, ultrastructure, or genetics
large, white, grey-white fleshy mass
necrosis and hemorrhage common
