Bone and soft tissue Flashcards
(101 cards)
1
Q
What is the most common primary malignancy of bone?
A
Multiple myeloma
2
Q
Name 3 causes of osteomalacia
A
- Vit D deficiency - X-linked hypophasphatemia - Malabsorption
3
Q
What is the most common type of collagen found in bone?
A
-Type 1
4
Q
Name 3 types of fractures classic for non-accidental injury in children
A
- Bucket handle # (proximal tibial metaphysis) - Complex skull # - String of pearls #s in paravertebral gutters
5
Q
What is the prognosis for granular cell tumors?
A
- Excellent
6
Q
What is the classic IHC staining pattern in chordoma?
A
- Brachyury+, S100+, vimentin +
7
Q
Name 3 factors for local recurrence of chondroblastoma in bone:
A
- Size - Site - Adequacy of resection
8
Q
What is the most common causative organism of osteomyelitis in children > 1yr?
A
- S. aureus
9
Q
Name 3 risk factors/associations with rheumatoid arthritis:
A
- MHC Class II antigens (DR) - Female gender - Certain ethnic groups
10
Q
What is the typical cytogenetic abnormality in low-grade fibromyxoid sarcoma?
A
- t (7;16)
11
Q
Name 3 clinical features of nodular fasciitis?
A
- Rapid growth - Found in subcutaneous tissue - History of trauma
12
Q
The FNC-LCC grading system for soft tissue sarcomas predicts what:
A
- Likely hood of distant metastases
13
Q
Alveolar soft part sarcoma demonstrates what ultrastuctural features?
A
- Rhomboidal crystals
14
Q
Desmoid tumors (aka deep fibromatosis) are associated with which tumor pathway?
A
-APC/B-catenin
15
Q
Give 3 IHC markers positive in leiyomyosarcoma?
A
- Desmin, H-Caldesmon, actin, +/- some keratin
16
Q
How are atypical neurofibromas treated?
A
- Local excision with margin (thin)
17
Q
A palisading granuloma with central mucin deposition is most characteristic of:
A
- Granuloma annulare
18
Q
Name 3 associations with Lyme disease
A
- Borrelia burgdorferi - Arthropod bites - Synovitis
19
Q
Name 3 findings in Carney’s disease
A
- Superficial angiomyxomas - Cardiac myxomas - Spotty skin pigmentation - Endocrine hyperactivity
20
Q
High-grade bone sarcomas most frequently metastatize to which site?
A
-Lung
21
Q
The most common site of extramammary myofibroblastoma is:
A
- Inguinal region
22
Q
How much bone loss before osteopenia shows up on x-ray?
A
- 40%
23
Q
Ochronosis (alkaptonuria) may result in which post-mortem findings:
A
- Black discoloration of tracheal rings - Nephrolithiasis - Vertebral anklylosis
24
Q
What is the most common cause of prosthetic joint failure?
A
-Aseptic loosening
25
Classify cartilagenous tumors of bone
- Osteochondroma - Chondroma (enchondroma/periosteal chondroma) - Chondroblastoma - Chondromyxoid fibroma - Chondrosarcoma (conventional, dedifferentiated, mesenchymal, clear cell)
26
Compare and contrast enchondroma and chondrosarcoma by clinical, radiological, microscopic findings:
Enchondroma: young pts, not painful, 5cm, central (pelvis, long bones), cortical erosiion/destruction & soft tissue extension; micro: hypercellular, cytologic atypia (binucleated, hyperchromatic), Mitoses, necrosis, infiltrative, myxoid matrix
27
Name hereditary risk factors for the development of chondrosarcoma?
- Multiple enchondromatosis (Maffuci, Ollier) - Hereditary multiple osteochondromas (EXT1 gene)
28
Define osteomalacia
- A defect in the mineralization of bone resulting in accumulation of osteoid (non-mineralized bone)
29
List 2 histologic features of osteomalacia
- Increase in osteoid (increased seam thickness, osteoid \>25%) - Decreased minerization (smudging, decreasing space between waves) - Multiple #'s
30
List 3 causes of osteomalacia
- Poor intake (vit D, Calcium or phosphate) - Malabsorption (TPN, no sunlight) - Interfererence/inhibition of mineralization (acidosis, FE, fluoride, aluminum) - impaired reabsorption (x-linked hypophosphatemic rickets, renal tubular defects) - drugs (phenytoin, rifampin, isoniazid, phenobarb) - Hepatobiliary disease (binding by bile acids) - Phosphaturic mesenchymal tumors - Vitamin D resistant rickets (calcitriol receptor defect)
31
Describe handling and processing of bone biopsy for metabolic bone disease
- Fix in 70% alcohol (to preserve tetracycline label) - No decal - Embed in plastic (glycol/methyl methacrylate) - Prepare 5-10 micro sections cut and stained with H&E, von Kossa for measurement of mineralized bone vs osteoid - Do other stains as needed (iron, etc.) - Cut unstained sections for fluorescent microscopy
32
Differentiate gout from pseudogout in tissue sections
Gout: long, needle shaped, brown/white on H&E, negative birefringence (yellow) aligned with red compensator, ++giant cell response CPPD: square/rhomboid, magenta on H&E, positive birefringence (blue), occasionally giant cell response
33
How do you handle a fresh specimen for gout?
- monoSodium urate is soluble in water (formalin has water!), so do touch preps and fix in alcohol - stain as usual - polarize with compensator
34
List 3 findings at autopsy in a patient with gout
- Gouty tophi (soft tissue collections of urate) toes, fingers, ear, elbow - Nephrolithiasis - Uric acid deposits in synovium , menisci - Joint deformities
35
List 3 non-genetic risk factors for gout
- Diabetes - HTN - Lymphoproliferative disease - Obesity - High purine diet +/- ETOH - Renal insufficiency - Hyperparathyroidism - medications (diuretics) - hypothyroidism
36
Describe CPPD findings on a typical knee x-ray
-A linear, radio-opaque deposition in joint space (CPPD dehydrate deposition in the menisci)
37
Define Osteoporosis
- Decrease in the amount of bone, so that microarchitecture is weakened and prone to spontaneous fracture
38
List 5 causes of osteoporosis or conditions associated with osteoporosis
- Postmenopausal/older age - Thins or small framed caucasian women - Endocrine abnormalities (estrogen deficiency, acromegaly, adrenocortical insufficiency, hypothyroidism, hyperparathyroidism, hypopituitarism) - Drugs (steroids, alcohol, anticonvulsants, heparin) - Infiltrative marrow disease (lymphoma, gaucher, mets) - Inactivity, immobilization - Diet (low vit D, calcium, high protein) - Smoking
39
List 3 common sites of # in osteoporosis
- Verebrae (compression #) - Femur (head of, neck of) - Distal radius (colle's) - Proximal humerus
40
Define Paget disease of bone
- Genetic skeletal disorder characterized by the activation of osteoblasts and osteoclasts, resulting in abnormal bone remodelling ('uncoupling", with osteoclasts predominating first then osteoblasts (3 phases)
41
List 4 clinical symptoms of Paget's disease
- None (asymptomatic) - Bone: pain +/- warmth, arthritis, #, deformity, sarcoma "saber shin" - Neurological: cranial/spinal nerve compression, deafness, brainstem compression - Cardiac: high output CHF, hypertrophy - Other: nephrolithiasis, hypercalcemia
42
List 3 stages of Paget disease and their corresponding histology
- Early lytic phase, ++ osteoclast activity (multinucleate), bone resorption - Active, ongoing: increased remodeling of bone (increased osteoclast and osteoblast activity) with bone formation and resorption, thick and thin trabeculae, woven bone, ireegular cement lines, fibrosis - Inactive (burned out): non-specific, marrow fibrosis, thickened irregular cement liens
43
What is the pathogenesis of Paget disease?
- Inherited predisposition as AD trait (chromosome 18, encoding sequestosome 1/p62) - May be initiated by a virus (RSV, parmyxovirus, parainfluenza, canine dystemper)
44
Which bones are most commonly affected in paget's?
- Pelvis, verebrae/sacrum, femur, skull
45
Describe the typical clinical presentation of osteoid osteoma
- Young males (2nd decade) - Present with severe localized pain - Night pain, relieved with ASA/NSAIDS
46
What are the typical findings of osteoid osteoma on plain x-ray?
- Small, circumscribed (~1cm) - intracortical - Common locations: shaft of femur, tibia, distal humerus, fingeres - Nidus: lytic area surrounded by sclerosis +/- targetoid appearance due to central ossification
47
Describe an osteoid osteoma nidus
- Vascular fibroconnective tissue containing thin, irregular trabeculae of benign osteoid rimmed by plump osteoblasts - Outer rim of dense sclerotic bone - May have central ossification
48
What is the ddx of an osteoid osteoma if \>2cm?
osteoblastoma
49
Describe the gross appearance of giant cell tumors of bone:
- Usually epiphysis - Circumscribed, may erode cortex +/- # - Moderate size (4-8 cm) - Sift, hemorrhagic, gritty
50
List 3 characteristic histologic features of giant cell tumors of bone:
- Numerous, evenly distributed multinucleate giant cells (some \>100 nuclei) - Stromal cell component with nuclei identical to those in giant cells - Frequent mitoses, hemorrhage/hemosiderin - No bone (unless periphery sampled)
51
List 3 entities in DDx for giant cell tumor of bone
- Giant cell granuloma - Brown tumor of bone (hyperparathyroidism) - Other tumors containing giant cells (including chondroblastoma, giant-cell rich osteosarcoma)
52
Name 5 tumors that may show EWSR1 breakpoint translocations
- Ewing's sarcoma - DSRCT - Clear cell sarcoma - Angiomatoid fibrous histiocytoma - myxoid liposarcoma (some) - extraskeletal myxoid chondrosarcomas
53
Classify cartilagenous tumors of bone
- Osteochondroma - Chondroma (enchondroma/periosteal chondroma) - Chondroblastoma - Chondromyxoid fibroma - Chodrosarcoma (conventional, dedifferentiated, mesenchymal, clear cell)
54
List 3 common sites of avascular necrosis of bone. Why does this condition occur at these sites?
- Femoral head, proximal scaphoid, posterior talus - Tenuous blood supply with limited or no collateral vessels
55
List 6 risk factors/associations for avascular necrosis of bone
- Trauma - Corticosteroid use - Alcoholism - Gaucher's - Hypercoagulable states - Sepsis - Vasculitis - Idiopathic - Dysbarism - Radiation
56
Describe the classic x-ray appearance of early osteonecrosis in the femoral head
- May be no changes initially - Preserved joint space early on - Cystic and sclerotic change, with subchondral fractures changing the contour of the joint - Subsequent collapse of infarcted area, giving lucent area or crescent sign
57
Describe the classic clinical presentation of osteosarcoma
- young male, 10-20, large stature - painful mass, pathologic fracture - large aggressive tumor in metaphysis of long bones, typically in distal femur/proximal tibia
58
List 3 risk factors for osteosarcoma
- Hereditary RB mutation - Radiation - Long-standing underlying bone abnormality (fibrous dysplasia) - germline p53 mutations - germline p16/INK4a mutations
59
Identify at least 3 important prognostic factors for osteosarcoma
- Location: parosteal\>periosteal\>coventional intramedullary - Stage (most important) - Grade - Site (extremity\>axial) - Histologic subtype (small cell=bad, low-grade fibroblastic=better
60
What is the estimated incidence of osteoarthritis in 20s, 40s, 70s?
- 5% in 20s, 30% in 40s, 70% in 70s
61
List 4 radiologic features of osteoarthritis
- Joint space narrowing - Osteophyte formation - Subchondral pseudocysts and sclerosis - Joint enlargement - Varus deformity
62
Describe 4 gross findings of osteoarthritis
- Cartilage pitting, scoring, fibrillation, erosion - Eburnation and sclerosis of bone - Osteophyte and subchondral pseudocyst formation - Deformity of bone - Secondary osteonecrosis
63
What treatments are available for osteoarthritis?
- Anti-inflammatories - Physiotherapy, exercise - Occupational therapy assistance - WEight loss - Joint replacement
64
In which WHO category does fibrous dysplasia of bone belong?
- Miscellaneous lesions
65
Classify 3 forms of fibrous dysplasia in bone
- Monostotic - Polyostotic, monomelic - Polyostotic, polymelic
66
Describe the microscopic features of fibrous dysplasia of bone
- Well circumscribed, fibro-osseus proliferation; basically all components of bone but disorganized and immature - Fibrous component is bland spindle cells with rare mitoses - Osseus component is uniform, thin curvilinear trabeculae of woven bone with paucity of osteoblasts (chinese letters) - secondary features may include aneurysmal bone cysts, foam cells, giant cells, cartilagenous component
67
List 2 syndromes associated with fibrous dysplasia of bone
- McCune Albright: precocious puberty and other endocrine abnormalties, cafe au lait spots on skin - Mazabraud syndrome-intramuscular myxomas
68
List 3 complications of fibrous dysplasia of bone
- Pathologic fractures - Deformities/cosmetic - secondary ABC formation - malignant transformation (rare)
69
List top four ddx for a small round blue cell tumor (paraverebral) in a 2yr male
- Ewing/PNET - Metastatic neuroblastoma - malignant lymphoma - alveolar rhabdomyosarcoma
70
What IHC can help in the ddx of small round blue cell tumors in children
- CD99, FLI1 - CD45/TdT - Synaptophysin/CHromogranin/GFAP - Desmin, myoD1/myogenin
71
What are 3 ancillary tests that can confirm diagnosis of Ewings/PNET, specify the abnormality.
- Conventional cytogenetics for t (11;22) - FISH for EWS (breakapart probe) - PCR for EWS/FLI1, EWS/ERG fusion transcripts
72
Describe grading of treatment effect in post-chemotherapy resection of Ewings
- Treatment effect based on assessment of tumor necrosis Grade 1: 0% (no effect) Grade 2: \<50% necrosis (low effect) Grade 3: 50-95% necrosis (high effect) Grade 4: 96-99% (scattered foci of tumor only) Grade 5: no residual viable tumor
73
List the most common sites of liposarcoma
- Retroperitoneum - Thigh, buttock, arm, trunk/abdomen - Scrotum/groin (inguinal canal--hernia)
74
List the clinical, microscopic and cytogenetic features of the myxoid liposarcoma
- Clinical: young to middle aged adults, deep seated, large mass \>10cm, found in thigh/buttock/knee/lower leg (never retroperitoneal) - Micro: sheets of uniform, small round-oval cells, some signet-ring lipoblasts. Myxoid matrix and prominent pattern of arborizing, thin-walled capillaries. Mitoses and necrosis rare. - Cytogenetics: t (12;16) DDIT3 gene
75
What is the classification of liposarcoma, and what are the prognostic implications of each category?
- Well differentiated liposarcoma/atypical lipomatous tumor: prognosis depends on location. Peripheral can be cured by local escision, deep recur but don't metastasize unless they dedifferentiate
- Dedifferentiated liposarcoma: local recurrence common, distant mets in 20%
- Myxoid/round cell: Depends on histologic grade (% of round cell). Low-grade has high recurrence rate. High grade with \>5% round cell metastasize in 40%
- Pleomorphic liposarcoma: High metastatic rate and mortality
- Mixed type (too rare to know)
76
Describe the clinical features of synovial sarcoma
- Age: young adults, median 30yrs
- Gender: M\>F
- Presentation: mass +/- pain in lower extremities (knee/thigh, foot/ankle), upper extremities (forearm/upper arm), trunk, head and neck (neck, larynx, parotid)
77
List 3 subtypes of synovial sarcoma, and describe features of biphasic on light microscopy.
- 3 subtypes of synovial sarcoma: biphasic, monophasic spindled, poorly differentiated (can have rhabdoid/high-grade fibrosarcoma pattern)
- Classifcal biphasic: neoplastic spindle cells and epithelial cells.
Spindle cells: hyperchromatic, ovoid, uniform arranged in sheets/fascicles +/- hemangiopericytomatous pattern
Epithelial cells: well-formed glandular structures lined by cuboidal/columna epithelium with PAS+ secretions
Stroma: collagen/myxoid/calcs. or ossification. Mast cells comon. Mitoses and necrosis variable. May be cystic.
78
List the IHC markers expected to be positive in synovial sarcoma and the cytogenetic abnormality.
- Cytokeratins (AE1/AE3), EMA, vimentin, TLE-1
- other non-specific markers: CD99, BCL2, Calretinin, CD56
- cytogenetics: t (x;18) resulting in SYT-SSX fusion
79
What is the classification of rhabdomyosaroma, and what are the most common locations/cytogenetics?
_Classification: _
**Embryonal**
- s**pindle cell, botryoid, anaplastic. IN head and neck/genitourinary. NO consistent abnormalities.**
A**lveolar: extremities, paraspinal, paranasal, perineal. T (2;13) PAX3/FKHR or T (1;13) PAX7/FKHR**
**Pleomorphic: deep soft tissues, no recurrent abnormalities**
80
List 4 prognostic factors in children with rhabdomyosarcoma
- Histologic classification : embryonal best
- Age: younger is better
- Stage
- Site of origin: orbital/paratesticular better, extremity and parameningeal worse
- For alveolar: PAX3/FKHR is worse than PAX7
81
What features is common to tumors in the PEComa group?
- Presence of an HMB-45+ smooth-muscle like element
82
List 3 specific entities in the PEComa group
- Angiomyolipoma
- Retroperitoneal lymphangiomyoma
- Clear cell sugar tumor of lung
- Pulmonary lymphangioleiomyomatosis
- Pecoma of uterus
83
What type of PEComa is most commonly found in the kidney? Describe the inherited condition associated with this lesion. What elements are seen histologically. What features suggest malignancy?
1. Angiomyolipoma is most common in kidney
2. 3 elements are lipomatous, vascular and smooth-muscle like cells which are HMB45+
3. Associated condition: tuberus sclerosis, 20% of AMLs occur in TSC, AD condition. ALso have pulmonary lymphangioleiyomyomatosis, cardiac rhabdomyomas, subependymal astrocytic nodules, angiofibromas.
4. Features suggesting malignancy: size \>5cm, coagulative necrosis, mitoses \>1/50 HPF
84
List 2 gross features of DFSP
- Early lesion is plaque-like, indurated and pigmented
- May form sharply circumscribed pigmented nodule on skin or in dermis
- Firm, fibrous, grey-white on sectionning
85
List the histologic features of DFSP
- Involves dermis and extends to subcutaneous adipose tissue
- Shows infiltrative "string of perls" into fat
- Does not show epidermal hyperplasia
- Shows uniform fibroblasts arranged in tight storiform pattern
- Lacks significant atypia, necrosis, mitotic rate and foam cells
- may show collagen trapping, myxoid change or vascular proliferation
86
What IHC stain can differentiate DFSP from dermatofibroma?
- Dermatofibroma: Factor XIIIa+, negative for CD34
- DFSP: +++ for CD34, negative for Factor XIIIa
87
What is the prognosis for a patient with DFSP?
- Low-grade sar coma
- excellent if completely excised
- high local recurrence rate
- rarely can transform into fibrosarcoma, with attending risk of metastasis.
88
What is the differential diagnosis of myxoid tumors of soft tissue?
- Benign: myxoma, neurofibroma, schwannoma
- Intermediate: aggressive angiomyxoma, ossifying fibromyxoid tumor
- Malignant; low-grade fibromyxoid sarcoma, myxofibrosarcoma (MFH), myxoid MPNST, myxoid liposarcoma, leiomyosarcoma
89
List 3 clinical parameters helpful in distinguishing benign from malignant soft sisue tumors
- Rate of growth, tumor size \>5cm, depth (above vs below fascia)
90
List 3 histologic features helpful in distinguishing benign from malignant myxoid tumors
- Mitotic activity (atypical mitoses)
- Presence of cytologic atypia
- Vascularity
- Infiltrative border
91
Define ischemic fasciitis and give the typical clinical presentation
- Ischemic fasciitis is a pseudoneoplastic, reactive fibroblatic proliferation related to age and ischemic conditions
- Typical clinical presenation is in elderly, bedridden individuals. Predilection for soft tissue overlying bony prominences. Skin overlying lesion is hyperemic.
92
How can you distinguish ischemic fasciits from soft tissue sarcoma on histology?
Ischemic fascitis: can have central fibrinous cavity surrounded by capillaries, mild cytologic atypia, low mitotic rate, zones of arcade-like capillaries
Sarcoma: coagulative tumor necrosis, moderate-marked cytologic atypia, moderate mitotic rate with atypical mitoses.
93
What etiologic factor is implicated in Kaposi sarcoma?
HHV8
94
List 4 clinical/epidemiologic types of Kaposi sarcoma describing lesion location and prognosis
1. Classic: elderly eastern European/Mediterranean men, skin of lower legs, indolent
2. Endemic: children in equatorial Africa, skin of extremities or viscera, indolent in adulst and aggressive in children
3. Iatrogenic: immunosuppressed, skin of lower legs/viscera, unpredictable course
4. AIDS: HIV associated, widespread including face, lower extremities, genitalia, viscera, aggressive
95
Vasclar lesions: List 3 benign, intermediate and malignant lesions
Benign: hemangioma, epithelioid hemangioma, lymphangioma
Intermediate: composite hemangioendothelioma, papillary intralymphatic angioendothelioma, retiform hemangioendothelioma
Malignant: epithelioid hemangioendothelioma, angiosaroma, Kaposi sarcoma
96
What is the characteristic EM finding for alveolar soft part sarcoma?
- Rhomboid crystals
97
What is the typical EM finding for Ewing sarcoma?
- Prominent pools of cytoplasmic glycogen
98
What is the typical EM finding in granular cell tumors?
- lysosomes
99
What is the typical EM finding in Kaposi sarcoma?
Vascular channels
100
What are the EM findings in vascular tumors?
- WEibel-Palade bodies
- BUndles of intermediate filaments, tight and primitive junctions
- Pinocytic vesicles
101
What are the typical EM findings in the following tumors: leiyomyosarcoma, rhadomyosarcoma, schwannoma
Leiyomyosarcoma/smooth muscle tumors: Myofilaments, actin microfilaments, interspermed fusiform dense bodies
Rhabdomyosarcoma: actin (6nm), myosin (15nm) filaments in parallel arrays. Sarcomeres, glycogen, primitive cell junctions, external lamina
Schwannoma: complex entangled long-cell processes, intermediate filaments, microtubules, long-spacing collagen
