Systems Path I exam 2

metastasis to bone

more common than primary bone tumors

primary bone tumors

tumor that starts in bone, can be benign or malignant, asymptomatic, gradually increasing bone pain, mass present, pathologic fracture, fever, fatigue and cachexia present

benign bone tumors are

more common than bone cancers, osteochondroma most common

most common primary bone cancers

osteosarcoma, chondrosarcoma, ewing sarcoma

risks for bone tumors

gene mutations- RB or TP53, inflammation

most bone tumors are

benign, early onset (

if it’s in the knee and patient is 10-20

osteosarcoma

bone-forming tumors

osteoid osteoma, osteoblastoma, osteosarcoma, bone formation is- benign or malignant, osteoid, woven bone, biopsy used to confirm diagnosis

osteoid osteoma

**benign**, smaller/

osteoblastoma

benign, larger/2-6 cm, found in vertebral processes therefore more serious (questionable removal), pain poorly localized and unrelieved by aspirin, treatment is excision or irradiation, 2x more common in males ages 10-20 (open growth plates)

osteosarcoma

malignant, **very aggressive**, **mc primary bone cancer** (20% of all dx), **mc in adolescents- 75%

typical osteosarcoma

60-70% long-term survival rate with amputation or chemotherapy

secondary osteosarcoma

patients 40+ years old, commonly have history with paget disease, irradiation, or AVN, worse diagnosis- responds poorly to therapy, typically lethal

cartilage-forming tumors

most commonly benign but can be malignant, 1- osteochondroma, 2- (en)chondroma, 3- chondrosarcoma

cartilage formation

hyaline cartilage- clear and glass-like, myxoid cartilage- mucus-like

osteochondroma (exostosis)

benign cartilage-capped outgrowth, hyaline cartilage, ages 10-30, 3x more in males, in long bone metaphysis- knee (mc), cortex merges with host bone solitary- sporadic, adolescent/ya onset (rare after maturity), develop slowly, sessile (wider based) or pedunculated (broccoli stalk with narrow base), painful if fractured or compressing other tissues

multiple hereditary osteochondromas

familial mutates TSGs, childhood onset, risk for malignant transformation

enchondroma

benign tumor, **gray-blue nodules of hyaline cartilage**, well-localized/circumscribed lucency, ring of sclerosis present, possible AVN in center, **mc asymptomatic resulting in incidental dx,** **naming is location-based**- enchondroma= medullary, juxtacortical chondroma= cortical; ages 20-50, s**olitary lesions of hand and feet (common in digits)**, multiple results in ollier disease

Ollier disease

multiple enchondromas, result of sporadic genetic mutations

chondrosarcoma

**malignancy, 2nd mc primary bone cancer, 40-60, 2x males**, painful mass, intramedullary (mc) or juxtacortical, **in girdles (proximal not distal- pelvis, shoulder, prox femur) glistening mass** **of neoplastic cartilage**, **high/low grades**, popcorn/stipple calcifications on x-ray, more radiolucency = higher grade, treated with excision and chemotherapy

low-grade chondrosarcoma

most common, slow growing/indolent, small, thickens cortex, favorable prognosis

high-grade chondrosarcoma

large mass, erodes cortex, 70% mets- mc in lungs, poor prognosis

fibrous and fibro-osseous tumors

fibrous cortical defect- nonossifying fibroma, fibrous dysplasia

tumors with unique cells

ewing sarcoma- PNET, giant-cell tumor of bone

fibrous cortical defect (FCD)

benign tumor, proliferation of fibroblasts and macrophages, **reaction to trauma/periosteal injury**, **well-defined radiolucent lesion with** __**thin**__ **sclerosis** **(not a rim)**, most are small, **very common- in 40% of children**, metaphysis/diaphysis near cortex, **mc in knee, mc asymptomatic, self-resolves in few years**- develops into cortical bone

nonossifying fibroma (NOF)

a FCD that is larger than 3 cm, primary concern is weakened bone- may fracture or collapse, requires biopsy if fractured

fibrous dysplasia (FD)

**spontaneous mutations of GNAS**- monostotic, polyostotic, polyostotic + café-au-lait spots; arrested development/**failed osteoblast differentiation**, fibrous tissue is where bone should be

monostotic fibrous dysplasia

most common- 70% cases, ages 10-30, **stops growing at time of growth plate closure**, little-no bony distortion, **asymptomatic, incidental dx mc,** ribs, femur, tibia, jawbones, humerus, calvaria

polyostotic fibrous dysplasia

27% cases, **late childhood/adolescence**, **severe deformation**, fractures common, **craniofacial involvement** in 50% cases, **shepard’s hook deformity**, well-defined borders, **ground glass** appearance, treatment is excision

McCune-Albright syndrome

FD + skeletal + skin + endocrinopathy, 3% FD cases, bony lesions usually unilateral, skin has café-au-lait spots, endocrine hyper-functioning causes **early puberty**, **mc in females**

ewing sarcoma and PNET

both variants of same malignancy- t(11;22) or t(21;22), small round-cell tumors of bone, treatment is excision and chemotherapy

Ewing sarcoma

undifferentiated, 2nd most common pediatric bone cancer, 10% of primary bone cancers, **mc in 10-20 y/o males- 9x in caucasians, diaphysis of long bones, onion-skinning** causes enlarging mass, painful, can become locally invasive, mimics infection (fever, high WBCs, high estrogen), similar to osteosarcoma

Primitive Neuroectodermal Tumor (PNET)

neural differentiation, homer-wright rosettes

giant-cell tumor of bone/osteoclastoma

**multinucleated giant cells**, large and solitary, **mc near knee** (or pelvis/distal radius), **osteolytic, found in epiphysis** more than metaphysis, __overexpression of__ __RANKL on osteoblasts that overstimulate osteoclasts__, arthritis-like pain, ages 20-40, **soap bubble appearance**, thin shell of reactive bone, **uncertainty regarding malignant potential**, treatment is excision and radiation

metastasis to bone (secondary)

**more common than primary bone cancer, spine is mc site**, any cancer may spread to bone, 3 types- direct extension(physical contact), hematogenous (sarcomas) or lymphatic (carcinomas) circulation, intraspinal seeding, occurs in red marrow; can be lytic, blastic, or mixed; occurs in adults and children

blastic bony metastis in adults indicates

prostate cancer

lytic bone metastasis in adults indicates

breast cancer

mixed blastic and lytic bony metastasis in adults indicates

lung cancer

bony metastasis in children can indicate

neuroblastoma, wilms tumor, osteosarcoma, rhabdyomyosarcoma, ewing sarcoma

6 stop signs that indicates low back has cancerous origin

50+ years old, history of cancer, cachexia, LBP is unrelieved with rest, pain lasts over 1 month, failure to improve after 1 month of conservative care

50+ years old + history of cancer + cachexia

100% indicates issue, 60% indicates cancer

space occupying lesion (SOL)

includes blood, pus, tumor, edema

primary joint tumors

rare, mc benign, synovial, vascular, fibrous, or cartilaginous

tumor-like lesions

more common than true neoplasms, reactive or degenerative, ganglion cysts, synovial cysts

ganglion cyst

degenerative connective tissue, small, cyst, mc in wrist, common, asymptomatic, visible often purely cosmetic, not visible cause more pain and issues, treatment is compression, aspiration, and/or surgery (usually cosmetic), may re-accumulate, not neural, no communication with synovium

synovial cyst

synovial herniation, associated with joint degeneration (arthritis), connected to/communicates with joint cavity, popliteal = baker cyst, spinal synovial cyst can lead to radicular symptoms, if in spine MC in L4/L5 because they’re most commonly degenerated

an individual with a spinal synovial cyst is most likely to experience headaches, lumbar spinal stenosis, bilateral UE erythema, or gangrene in the LE?

lumbar spinal stenosis

soft tissue

any non-epithelial tissue

soft tissue tumors

benign 100x mc than malignant, any location- thigh mc, found in- adipose and fibrous tissues, muscles, vessels, PNS

malignant soft tissue tumors are more likely to

be deeper → diagnosed late → more deadly

adipose tumors

lipoma, liposarcoma

lipoma

benign tumor of adipocytes, mc soft tissue tumor, soft, mobile, painless, mostly cosmetic

liposarcoma

malignant adipocyte tumor, adults 50-70, large, variable aggressiveness (mets → lungs), diagnosed via biopsy, treated with excision and radiation

Nodular Fasciitis

benign fibroblast tumor, firm, quick growing, solitary, volar/palm-side of arm on adults, treated with excision, rarely recur

Myositis Ossificans

metaplasia following trauma, mc in adolescent athletes, in proximal extremities, hard and painless, self-limited,

fibromatoses

benign tumor of fibroblasts, invasive, painful and disfiguring, superficial or deep

superficial fibromatosis

superficial fascia, males, peyronie disease mc in 40-70s, dupuytren contrature (viking disease) mc in older males of european descent with adhesions on ulnar-side of palm

deep fibromatosis/desmoid tumors

mc abdominal in females, more aggressive than superficial, locally invasive, can be painful, commonly recur, NOT cancer

fibrosarcoma

**malignant tumor of fibroblasts, notoriously slow growing**, invasive, unencapsulated, herringbone histology, deep- in **thigh or retroperitoneum**, 35-55, **25% have mets at time of dx (mc to lungs**), may invade into bone, treated with excision, recurs in 50%

Rhabdomyosarcoma

aggressive malignancy- nearly 100% malignant, areas of minimal skeletal muscle (small areas of body, mc head/neck), rhabdomyoblasts present, MC pediatric soft tissue sarcoma, treatment- excision, chemotherapy, radiation, 2/3 cured, commonly metastasizes to bone

leiomyoma

benign smooth muscle tumor, common, well-circumscribed, uterine fibroids, small bowel, esophagus

leiomyosarcoma

malignant smooth muscle tumor, mc in adult females, firm and painless mass, deep in extremities or retroperitoneum, spindle cells with cigar-shaped nuclei, better prognosis when superficial or small

synovial sarcoma

soft tissue cancer, nothing to do with synovial, MC in ages 20-40, **notoriously aggressive + firm + painless + immobile, MC near knee**, treatment is limb-sparing surgery, **30% survival rate of 10 years**

PNS damage

anterior horn of spinal cord/peripheral nerves, LMNs, muscle weakness, flaccidity, decreased DTRs, sensory loss common

CNS damage

brain, UMNs, muscle weakness, spasticity, increased DTRs, may include sensory loss but not necessarily

neuropraxia

mild compression/traction axonal injury, overstretch, temporary with good recovery, axon still intact, ‘arm asleep’ after sleeping weird but feeling returns within mins

axonotmesis

moderately severe axonal injury, axon is severed but endoneurium, perineurium, and epineurium all intact (all tools needed to regenerate), regeneration expected 1 mm/day

neurotmesis

severe axonal injury, nerve completely severed, regeneration very unlikely

peripheral nerve injury Seddon classification

neuropraxia → axonotmesis → neurotmesis

peripheral nerve injuries

axonal vs demyelinating, axonal neuropathy, demyelinating neuropathy, mono/polyneuropathies, guillan-barré syndrome, diabetic peripheral neuropathy

axonal neuropathy

direct injury to axon, wallerian degeneration, regrowth and remyelination occur but results in decreased axon density and amplitude on nerve conduction velocity test (NCV)

demyelinating neuropathy

damage to myelin or schwann cells, spares axon, segmental/random demyelination, repair results in thinned myelin and short internodes, altered structure, and decreased velocity on nerve conduction velocity test (NCV)

mononeuropathy

1 nerve affected, entrapment → carpal tunnel syndrome, trauma → shouulder dislocation, axillary nerve palsy

polyneurpoathy

**body-wide**, diffuse/symmetric damage, **stocking-and-glove paresthesia**- most distal extremities affected first, **mc cause for diabetes** then alcoholism and lead

Guillan-Barré syndrome (GBS)

autoimmune demyelinating polyneuropathy, acute motor neuron demyelination, acute ascending paralysis, rubbery legs, respiratory failure, could occur to near anyone- more seen in males 15-35 or 50-60, macrophages near nerve roots, 60% idiopathic, related to C, Jejuni, EBV, CMV, HIV, Zika, 90% cases self-resolve

chronic inflammatory demyelinating neuropathy

chronic relapsing demyelination of motor and sensory nerves, 2x in males, mc 40-60, onion bulb layers, idiopathic with history of SLE (lupus)

diabetic peripheral neuropathy

microvascular injury → nerve injury, begins with decreased sensation (vibration, soft touch, pain), low DTRs, injures myelin and axons, occurs from history of diabetes or hyperglycemia, mc in retina and kidney

neuropathic arthropy (charcot/neuropathic joint)

possible complication of any neuropathy, **mc from diabetes mellitus**, decreased sensation leads to unperceived trauma **mc in feet**

miscellaneous peripheral nerve injuries

enviromental- disrupts axonal transport or cytoskeletal structure, ADRs, chemotherapy, lead, methylmercury (heavy metals); vasculitis; inherited

charcot-marie-tooth disease

group of **inherited** conditions/disorders, PMP22 mutations, axonal or demyelinating neuropathy, **young adulthood,** **mc in feet/muscle innervated by common → deep fibular nerves, ‘steppage’ gait** acquired from lost dorsiflexion of foot to prevent tripping, may need braces or assistive devices, **pes cavus**, motor and sensory interference

myasthenia gravis

**autoimmune attack on post-synaptic ACh receptors, antibody-mediated**, type II hypersensitivity, **mc females age 20-30, worsens as day progresses**, thymic hyperplasia or thymoma, extraocular weakness

lambert-eaton syndrom (LES)

**autoantibodies against pre-synaptic calcium channels,** decreased release of ACh = girdle weakness, **improved by e-stimulation,** 60 y/o, **50% have** **small cell lung ca**

tetanus

**lockjaw**, increased stimulation of skeletal muscle → spasms, may lead to respiratory failure, from **clostridium tetani** in contaminated soil, **blocks release of GABA** results in decreased inhibition of a-motor neurons on anterior horn of spinal cord

botulism

**flaccid paralysis from clostridium botulinu**m, toxin **inhibition of Ach release** by a-motor neurons at pre-synaotic terminals results in muscle inhibition, newborns more vulnerable from underdeveloped gut flora, toxin in **honey**

type I skeletal muscle fibers

slow-twitch, aerobic, fatty, more efficient, fatigue resistant, found in longer distance/continual athletes

type II skeltal muscle fibers

fast-twitch, anaerobic, glycogenic, less efficient, fatigue quickly, found in athletes with quick-bursts of activity

checkerboard appearance of muscle

peripheral axons innervate multiple types of myocytes, everone has variable distribution of fiber types present in muscles

myasthenia

painless muscle weakness

type II skeletal muscle fiber atropy

caused by disuse atrophy (localized = fracture, generalized = quadriplegia) and glucocorticoid atrophy (hypercortisolism/cushing syndrome)

chronic neuropathy and myopathy of skeletal muscle

results in fibrofatty replacement

neuropathic changes of skeletal muscle fibers

grouped atrophy, larger/fewer motor units

cushing syndrome

endocrine disorder of increased cortisol levels, exogenous corticosteroids mc cause, also caused by adenoma increasing ACTH, results in weight gain, moon face, purple striae, buffalo hump, seen in young adults, mc females

muscular dystrophy/dystrophinopathies

group of inherited myopathies, x-linked mutated dystrophin, can be duchenne or becker, females usually carriers not affected, girdle weakness, pseudohypertrophy of calf muscles (invaded by fatty/fibrous tissues)

duchenne muscular dystrophy

progressive ultimately fatal muscle weakness of skeletal and cardiac muscle, begins in childhood w/proximal muscle weakness, gower sign, fatal in late teens/early adulthood, absent dystrophin protein lessens structural integrity of myocytes, x-linked= boys affected, inherited, 1 in 3500

becker muscular dystrophy

inherited myopathy of mutated dystrophin protein increases muscle breakdown, less severe than duchenne md, proximal muscle weakness, possible normal lifespan, x-linked= boys affected

toxic myopathies

thyrotoxic myopathy, ethanol myopathy, drug myopathy

thyrotoxic myopathy

thyrotoxicosis (elevated thyroxine), acute or chronic weakness, necrosis of proximal muscles

ethanol myopathy

binge drinking, acute myalgia, myocyte swelling/necrosis (rhabdomyosis), results in acute renal failure

drug myopathy

ADR of various meds, myopathic signs/symptoms usually without inflammation, statins cause myalgia (diffuse muscle pain/cramps), chloroquine

Graves’ disease

autoimmunity against TSH receptors, MC in females