MSK PATH Flashcards
What can ABC arise from ?
2/3 Primary
1/3 Secondary
**- GCT
- Chondroblastoma
- NOF
- Osteoblastoma
- Fibrous Dysplasia
**
What malignant lesions have ABC components ?
- Osteosarcoma
- Chondrosarcoma
- MFH
A
ABC microscopics ?
- Plump fibroblasts
- Multinucleated Osteoclast-like giant cells
- Reactive woven bone
- “Blue cone” - cartilage like matrix
ABC prognosis
- Non-malignant
- Recurrence rate 20-30% (if incomplete resection)
Most common causes of AVN
- Trauma (most common): due to vascular occlusion
- Steroids (next common)
- Sickle cell
- Alcohol
- Infection
- Pancreatitis
- Gauchers
- Caissons
- Bisphosphonate for the jaw!
Chondrosarcoma can arise from ?
- Enchondroma
- Osteochondroma
- Pagets
- Fibrous dysplasia
Types of Chondrosarcoma
- Conventional (90%)
- Clear cell: special – only originates in epiphyses of tubular long bones
- Mesenchymal
- De-differentiated
Chondrosarcoma histologically graded based on ?
- nuclear size, hyperchromasia, and cellularity.
Histologic grade is most important predictor for prognosis
Associated syndromes of Chondrosarcoma
- Maffuci
- Ollier
- Multiple Hereditary Exostosis
Pathology findings of Ewings
- Small round blue cell tumor
- Recurrent t(11;22) (q24;q12) chromosomal translocation.
- EWS/ETS gene fusion.
- Homer-wright pseudorosettes indicates neuroectodermal differentiation (PNET)**
–> also found in pPNET, Askin tumour, and neuroepithelioma
Clinical presentation of Ewing sarcoma
- Pain (most common)
- Fever
- Raised ESR, LDH
- Femur shaft most common site
Which site of Ewing sarcoma will mets most commonly ?
- Pelvis (mets most common compared to extremities) - mets very important prognostic factor
- Spine is the most common BONE site to mets
- Lung most common site of mets
Which site of Ewing sarcoma has the best prognosis ?
- Spinal Ewing (best prognosis site)
Monostotic FD vs Polyostotic FD
Monostotic
- Adolsecent and stops growing with skeletal maturity
- Frequently asymptomatic
- Proximal Femur (most common site)
- Leg-length differences and impingement or nerve compression syndromes
Polyostotic
- Younger age and causes problem in adulthood
- Rarely sarcomatous transformation
- Craniofacial, Skull base and mandible (most common site)
- Unilateral and monomelic: one limb
- Femur most common
Pathophysiology of FD
- GNAS1 mutation
What are the associated syndromes of FD
McCune Albright
- endocrinopathy: precocious puberty
- polyostotic fibrous dysplasia: more severe than in sporadic cases**
- ‘café au lait’ spots
Mazabraud syndrome
- fibrous dysplasia and intramuscular myxomas
GCT most common site
- Distal femur Epiphysis*
GCT consists of what cells
- Non-neoplastic osteoclasts* (majority of cells)
- Neoplastic cells (minority of cells - high RANK-L)
Epidemiology of GCT ?
- F (slightly more common)
- M (more common in malignant GCT)
GCT associations
- Pagets
- Gorlin-Goltz
- Jaffe-Campanacci
- Phaeochromocytoma-paraganglioma and giant cell tumour syndrome
Recurrence rate of GCT ?
40-60% recur locally
Prognosis of GCT mets ?
- lungs mets (4%)
- rarely fatal
- can regress spontaneously
Classifications of Gout ?
Primary (95%)
- Enzyme defect: abnormalities in purine metabolism
- reduced renal excretion of urate (90%)
Seconcary (5%)
- Secondary to increased serum uric acid levels resulting from associated disorder
- Leukemia, neoplasm, lymphoproliferative disease, end-stage renal disease, drugs (diuretics, ethanol, cytotoxics)
- Congenital: Lesch-Nyhan
Aetiology of Gout
Undersecretion of Uric acid by kidneys (90%)
- CKD
- HTN
- Hyperparathyroidism
- Drugs (frusemide, thiaizde, diuretics)
- Lead poisoning (saturnine gout)
- Obesity
Overproduction of Uric acid (10%)
- Myeloproliferative disorders
- Haemolysis
- Extreme exercise
- Lesch-Nyhan syndrome
Gout uncommon in premenopausal woman due to estradiol having urate lowering effect
Most common organism in Osteomyelitis due to Sickle cell disease ?
- Salmonella
Most common organism in Osteomyelitis due to IVDU ?
- E-Coli, Steph aureus (most common overall)
OM locations in:
Neonates
Children
Adults
Neonates
- Epiphysis
Children
- Metaphysis
Adult
- Epiphysis
Most common location of OM ?
- Lower limb medulla (most common)*
- Vertebra: Lumbar > Thoracic > Cervical
Complications of OM
- develops into SCC (Marjolin Ulcer)
- secondary sarcoma (eg. osteosarcoma) rare
- secondary amyloidosis
- pathological fracture
Primary vs Secondary causes of Osteoporosis
Primary
- Post menopausal
- Senile
- Idiopathic
Secondary
- Hyperparathyroidism
- Multiple Myeloma
- Malabsoprtion, Malnutrition
- Chemotherapy, Steroids
- Immobilisation
2 Variants of Osteoporosis
Low turnover variant
- Elderly with low functioning osteoblasts
High turnover variant
- Post menopausal
- Reduced estrogen stimulates osteoclasts by increasing RANK-L
Osteosarcoma Epidemiology
- <25 yo (mostly)
- Seen in older patients if secondary to a pre-existing lesion
Secondary Osteosarcomas arise from ?
- Bone infarct
- Infection
- Osteoblastoma
- Osteochondroma
- Paget disease
Osteosarcoma associations
- Paget disease
- Retinoblastoma
- Li-Fraumeni syndrome
- Irradiation
- Rothmund-Thomson syndrome
- Fibrous Dysplasia (rare)
- Mazabraud syndrome (rare)
Classification of Osteosarcoma
Intramedullary/Central (80%)
- Conventional (80%): osteoblastic type (most common)
- Telangiectatic
- Small cell
- Low grade central
Surface
- Periosteal
- Parosteal
Most common mets site for Osteosarcoma
- Lung > Bone and Nodes
Epidemiology of Paget disease
- Caucasian
- > 55yo (90%)
- M > F
Paget disease Polyostotic or Monostotic more common
Polyostotic more common
Paget clinical presentation
- Asymptomatic when diagnosed, usually incidental (majority)
- high ALP with normal Ca and PO4
- Bone pain (most common symptom)
- Bone deformity: Kyphosis, Protrusio, Bowing*, spinal stenosis, big skull, hearing loss, fracture
- high output cardiac failure (rare)
Pathophysio of Paget
- a disease of OSTEOCLASTS*
- associated with PARAMYXOVIRUS
Lab markers of Paget disease
- High ALP
- Normal Ca and Phosphorus
- High urine Hydroxyproline
Which type Osteogenesis is lethal ?
- Type 2 (death in utero)
Clinical features of Osteogenesis imperfecta by type
Type 1 and 3:
- blue sclera
- hearing impairment
RA epidemiology
- 1% in developed country
- Female (3x)
- peak 20-50
Pathophysiology of RA
- T-helper cell activate macrophages
- TNF and IL-2* stimulates synovial cells to release proteases to break down hyaline cartilage
- RANK-L activates to stimualte bone resoprtion
- ** Fibrinoid necrosis = immune complex (antigen-antibody) deposition in vessels walls
Extra-articular involvements of RA
- Skin RA nodules
- lung necrobiotic nodules
- vasculitis
RA lab findings ?
- Anti-CCP
- RA
RA syndromes
- Felty syndrome: RA + splenomegaly + neutropenia
- Caplan syndrome: RA + pneumoconiosis
Treatment and prognosis of RA
- 20% complete remission
- TNF targeted drugs and Steroids
Complications
- Amyloidosis and opportunistic infection
Rickets and Osteomalacia pathophysio
- defect in bone mineralization due to Vitamin-D deficiency or defect in metabolism
- Reduced GI and renal absoprtion of calcium and phosphate
- Increased PTH which increases calcium resorption in kidney, but this comes at the cost of losing
phosphate - Reduced osteoblast stimulation
Clinical presentation of Rickets / Osteomalacia
- Basilar invagination
- Scoliosis
- Acetabular protrusio
- Leg bowing
- Rachitic rosary ribs due to osteoid accumulation at costochondral junction
- Looser zones are pseudofractures
Aetiology of Rickets / osteomalacia
- Vit-D deficiency
- Reduces Vit-D synthesis: renal failure, liver cirrhosis (liver converts vit D to soluable form)
- Vit-D receptor defect
- Phosphate metabolism defect: X-linked hypophosphatemia
MFH (pleomorphic undifferentiated sarcoma) Risk factors ?
- Radiotherapy**
- Arise from Paget disease**
- can also arise from FD, GCT, enchondroma, OM, Osteonecrosis
MFH (pleomorphic undifferentiated sarcoma) imaging features ?
- T2 dark to intermediate (half the time) - think about “fibrous” like scar
- Spontaneous hemorrhage common “history is old lady stood up from chair ends with big proximal hematoma - under that hematoma is MFH
Synovial sarcoma mimic
- Baker cyst: if it’s not located in its typical location / looks too complex or has flow in it, think synovial sarcoma*
3 imaging appearances of Synovial sarcoma
1) “triple sign”, high, medium and low signal all in same mass (prob in knee) on T2
2) “bowel of grapes” bunch of fluid-fluid level in a mass
3) xray with soft tissue component and calcifications (least likely way shown)
Clinical features of Synovial sarcoma
- Most sarcomas don’t attack bones; Synovial sarcoma Can
- Most sarcomas present as painless mass; Synovial sarcomas Hurt
- Soft tissue calcifications + Bone erosion is highly suggestive
- Slow growing, mislead people to think its benign
- 90% have X-18 translocation
- Most common malignancy in teens/young adults of the foot, ankle and lower extremity*
Earliest sign of Gout ?
- Joint effusion
Myossitis Ossificans vs. Parosteal Osteosarcoma calcification pattern ?
Myossitis ossificans
- Ossifies from peripheral to central
Parosteal osteosarcoma
- Ossifies from central to peripheral
What happens to phosphate in Hyper PTH ?
- “Phosphate retention”
What view to do for SLE hand ?
Norggard view
- Shows reversible ulnar deviation
- No articular erosions
- Show hands with ulnar deviation on Norggard view, but reduces on AP view (because hands are flat)
- The ligamentous laxity also increases risk of patellar dislocation
SLE hand DDx ?
Jaccoud’s Arthropathy
- very similar to SLE in the hand (ppl often say them together)
- History is Post Rheumatic Fever
JIA features
- <16yo
- carpals are jacked and ankylosed (premature fusion of growth plates)
- Serology often negative (85%)
- Enlargement of epiphysis in knees** (Epiphyseal overgrowth BUZZWORD)
- Widened interocondylar notch (like hemophilia)
Amyloid Arthropathy features
- Seen in dialysis patients after 10 years of treatment
- Bilateral involvement of shoulders, hips, carpals, and knees (distribution key*)
- Carpal tunnel syndrome common manifestation**
- Joint space preserved until late***
What is the normal pattern of marrow conversion?
- Epiphysis / apophysis > diaphysis > distal metaphysis > proximal metaphysis
- Red marrow converts to Yellow marrow from distal to proximal
- Adult has yellow marrow everywhere except axial skeleton and proximal metaphysis
- Red marrow can be found in adult femoral head or humeral head as variant
Yellow marrow on MRI
T1 is money sequence: Yellow is bright, Red is darker than yellow (iso-intense to muscle almost)
Red marrow should never be darker than disk on T1
What is the normal pattern of REconversion of marrow ?
- Occurs in reverse order:
- Axial skeleton > peripheral
- The last to go are distal long bones
- Typically epiphysis are spared unless hematopoietic demand is very high*
How to differentiate Giant cell tumor of tendon sheath from a ganglion cyst on imaging ?
GCT of tendon sheath will
- show doppler flow
- T1 and T2 low to intermediate (c.f. ganglion cyst T2 hyperintense)
- Otherwise: Both can be non compressible, both can be homogeneous or heterogeneous
- GCT can mimic cancer on PET
Pathology marker of GCT of tendon sheath ?
- CSF-1 hyperexpression
“popeye” bulge in the arm
Biceps tendon tear
RF factors + or - in JIA ?
RF usually negative and ANA usually positive (Robbins)
RF 20-30% positive and ANA 40% positive. If RF + then anti CCP + (StatDx)
Nodular fasciitis location ?
- Volar aspect of the forearm** (c.f. Palmar fibromatosis aka. Dupytrens contracture seen in PALMAR hand, Female) - most common
- The lower extremity, and the chest and back.
Nodular fascitis clinical presentation ?
- typically manifests as a rapidly growing mass
- The lesions tend to be small (<4 cm).
Nodular fascitis causes ?
- Trauma