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MSK, Rheum, Derm > Gupta - Pathology/Histology > Flashcards

Gupta - Pathology/Histology Flashcards

1
Q

What do you see here?

A
  • Fibrosarcoma: malignant neoplasm of fibroblasts
    1. Adults, typically deep in thigh or retroperitoneal
    2. Local recurrence is common
    3. Hematogenous spread to lungs >25% of case
  • Gross: unencapsulated, w/necrosis and hemorrhage
  • Cytologically: vary from resembling fibromatosis to herringbone patterns to architectural disarray
  • Really hard to get these out (common theme with un-encapsulated soft tissue tumors because they look like the other soft tissue in your body)
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2
Q

What is this?

A

Acute osteomyelitis

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3
Q

What is fibrous cortical defect?

A
  • Aka, non-ossifying fibroma; >5cm, and intramedullary component
  • Teenagers, but no gender preference
  • Benign, typically asymptomatic
  • Probably developmental defect; usually no tx
  • Spindle cells in storiform pattern (black arrow) with scattered giant cells (yellow arrow), histiocytes, cholesterol clefts, and hemosiderin
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4
Q

What is osteomyelitis?

A
  • Infection of bone, typically in children; most often bacterial
    1. Direct inoculation (trauma), contiguous spread (cellulitis), or hematogenous spread
  • Bone pain with systemic signs of infection
  • Lytic focus (abscess) surrounded by sclerosis of bone on x-ray
    1. Lytic focus (inner, old necrotic cortex) = sequestrum (yellow arrow)
    2. Sclerosis (sub-periosteal shell of reactive, viable new bone) = involurum (grey arrow)
  • Get blood cultures before you treat!
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5
Q

What is this?

A
  • Myxoid liposarcoma: abundant basophilic matrix, arborizing (chickenwire) vessels and various stages of adipocyte differentiation reminiscent of fetal fat
  • Intermediate prognosis
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6
Q

What is this?

A
  • Pleomorphic liposarcoma: anaplastic cells, bizarre nuclei and lipoblasts (immature adipocytes)
  • Aggressive
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7
Q

What is this?

A
  • Palmar (dupuytren contracture): irregular nodular thickening of palmar fascia
  • 50% bilateral
  • Progressive contracture of 4th and 5th fingers
  • SUPERFICIAL FIBROMATOSIS
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8
Q

What do you see?

A
  • Humerus showing:
    1) Lytic,
    2) Mixed,
    3) Sclerotic phases of Paget’s disease of bone
  • End result is thick bone that fractures easily
  • See attached image for more details
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9
Q

What kind of bone growth is happening at these two arrows?

A
  • Epiphyseal plate
  • Left: membranous ossification -> cells from periosteum differentiate into osteoblasts and make bone (no cartilage step); occurs in cranial bones and everywhere there is periosteum
  • Right: endochondral ossification -> formation of bone through a cartilage intermediate step; occurs at epiphyseal plates
  • Both forms are involved in fracture healing
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10
Q

What paracrine mechs regulate osteoclast function?

A
  • Osteoclasts derived from same stem cells that produce macrophages
  • RANK ligand + macrophage colony-stimulating factor (M-CSF), the RANK-RANKL interaction drives the differentiation of functional osteoclasts
  • Stromal cells also secrete osteoprotegerin (OPG-a soluable protein), which acts as a decoy; binds RANKL
    1. OPG prevents bone resorption by inhibiting osteoclast differentiation
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11
Q

Achondroplasia

A
  • Activating (point) mutations in fibroblast growth factor receptor 3 (FGFR3)
  • FGFR3 - INH cartilage proliferation -> in disease, FGFR3 always on, suppressing cartilage growth
  • Auto dominant or new spontaneous mutations (80%)
  • Affects all bones that develop by endochondral ossification
  • Most conspicuous changes incl. short stature, dis-proportionate shortening of prox extremities, bowing of legs, and frontal bossing with midface hypoplasia
  • Cartilage of growth plates disorg’d and hypoplastic
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12
Q

What is this?

A
  • Lipoma: benign fat tumor; most common soft tissue tumor in adults
  • Gross: well-circumscribed, yellow, lobulated mass
  • Micro: mature adipose tissue
  • Sometimes can’t even see the distinction between the “normal” fat and the tumor
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13
Q

What are the clinical features of osteopetrosis?

A
  • Fractures
  • Anemia, thrombocytopenia and leukopenia with extra medullary hematopoiesis
  • Vision and hearing impairment
  • Hydrocephalus – narrowing of foramen magnum
  • Renal tubular acidosis – seen with carbonic anhydrase II mutation (decreased tubular resorption of HCO3-, leading to metabolic acidosis)
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14
Q

What do you see here?

A
  • Micro of osteoma
  • Dense, compact bone in paucicellular (sparsely populated w/cells) stroma
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15
Q

What is going on here?

A
  • Giant cell tumor of tendon sheath: often located near joints, and can interfere with function
  • Attached intraoperative picture shows that this is a well-circumscribed tumor -> yellow because it contains many lipid-laden macros
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16
Q

What is this?

A
  • Deep fibromatosis: large infiltrative masses that recur but do not metastasize -> benign, but can cause other problems, i.e., obstruction
  • Teens-30’s, female
  • Association with APC gene or Beta-Catenin, both lead to increased WNT signaling
    1. Association with GARDNERS SYNDROME: if pt has this, have to think about colonoscopies (can get benign epidermal inclusion cysts -> squamous-lined cysts w/keratin debris middle; rupture can cause enormous inflam rxn)
  • Gross: large, firm, white cut surface, infiltrative borders (can make it hard to get out)
  • Micro: broad fascicles amid dense collagen, similar to a scar –> immunostain (+) for nuclear beta-catenin
    1. Histologically will not look very different than superficial fibromatosis
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17
Q

What might this be?

A
  • Osteosarcoma invading normal bone (top arrow), producing poorly formed bone spicules in a hyper-cellular matrix of osteoid (yellow arrow) & numerous pleomorphic malignant cells (bottom arrow)
  • Formation of bone, “MALIGNANT OSTEOID,” by the tumor cells is diagnostic
  • Often described as “lace like”
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18
Q

What do you see here?

A
  • Osteoid osteoma of the femur
  • Coronal CT scan shows a radiolucent nidus (black arrow) with surrounding bony sclerosis and cortical thickening (white arrow)
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19
Q

What is this?

A
  • Micro appearance of osteoid osteoma
  • Randomly interconnected trabeculae of woven bone, prominently rimmed by a single cell layer of osteoblasts
  • Stroma surrounding the neoplastic bone consists of loose connective tissue containing dilated and congested capillaries
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20
Q

What are the 3 types of cartilage-forming tumors?

A
  • Chondroma
  • Osteochondroma
  • Chondrosarcoma
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21
Q

What are some of the possible symptoms of Paget’s?

A
  • Thick skull
  • Deafness
  • Kyphosis
  • Pain
  • Bow legs
  • NOTE: typically localized, not entire skeleton
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22
Q

What do you see here?

A
  • Microscopic pathology of fibrous dysplasia
  • Top image shows the poorly formed islets and trabeculae of woven bone, often with curvilinear shapes resembling Chinese characters, without a rim of osteoblasts
  • Bottom image shows moderately cellular fibroblastic proliferation with lots of collagen surrounding the trabeculae
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23
Q

What is bone composed of?

A
  • Type 1 collagen, aka osteoid
  • Hydroxyapatite: Ca10(OH)2(PO4)6
  • Storehouse for: Ca2+, phosphorous, sodium, and Mg2+
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24
Q

What are the 3 main histologic subtypes of liposarcoma? Why are these important?

A
  • Well-differentiated: adipocytes and scattered spindled cells (left image)
  • Myxoid: abundant basophilic matrix, arborizing (chickenwire) vessels and various stages of adipocyte differentiation reminiscent of fetal fat (middle)
  • Pleomorphic: Anaplastic cells, bizarre nuclei and lipoblasts (immature adipocytes; right image)
  • Affects prognosis: well-differentiated type indolent, pleomorphic type aggressive, and myxoid type intermediate
  • Spindle cells can take over, and tumor becomes d-differentiated (hard to distinguish as fat)
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25
Q

What is an osteoid osteoma?

A
  • Benign tumor of osteoblasts -> produce osteoid (pink stuff); surrounded by rim of reactive bone
  • Young <25, males, and presents as bone pain that resolves with aspirin
  • Arises in cortex of long bones, and imaging shows bony mass (<2 cm) w/a radiolucent core (osteoid)
    1. “Nidus” – usually <1cm (see attached)
  • Treatment usually radiofrequency ablation
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26
Q

What are some of the complications of fractures?

A
  • DVT/PE; in long bone fxs, fat emboli can occur
  • Compartment syndrome: INC pressure compromises vascular supply to extremity
    1. Forearm and leg are the areas most often affected -> pts experience severe pain, and exam reveals a tense, woodlike compartment
    2. Diagnosis can be confirmed by measuring the intracompartmental pressure
    3. Tx is fasciotomy (sx incision of the fascia)
    4. History and physical reveals 5 P’s: Pain, Pallor, Paresthesias, Pulselessness, Paralysis
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27
Q

What is this?

A
  • Stress (hairline fracture)
  • Caused by constant or repeated stress -> often of weight-bearing bones
  • X-ray may not immediately reveal the fracture, so other modalities (e.g., CT) may be necessary
  • Tx or immobilization based on clinical suspicion is often reasonable
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28
Q

What is this?

A
  • Gross appearance of osteoma
  • Sessile (immobile), with a polypoid shape -> usually around 3cm
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29
Q

What is this?

A
  • Gross appearance of fibrous dysplasia
  • Variably sized, circumscribed, medullary, tan-white, gritty mass lesions
  • Bigger ones distort and expand bone, like this one in a femur
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30
Q

What is this?

A
  • Superficial fibromatosis: infiltrative fibroblastic proliferation that causes local deformity
  • Male>female
  • Micro: nodular or poorly defined broad fascicles of fibroblasts in dense collagen
  • Muscle on the right in the left image
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31
Q

What is an this?

A
  • Radiograph of a solitary bone cyst (SBC) in a femur -> lytic lesion, fluid-filled cyst with a thin wall
  • Benign, and typically presents as fracture
  • Usually males, < 20 years
  • Medullary in metaphysis of proximal humerus and femur
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32
Q

What is this?

A
  • Wedge-shaped, pale area of necrosis
  • Causes of ischemic necrosis of bone and bone marrow include:
    1. Fracture/trauma
    2. Steroids
    3. Sickle cell
    4. Alcohol abuse
    5. Decompression sickness (the bends)
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33
Q

What is this?

A

Chondrosarcoma

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34
Q

T1 OI

A
  • Normal lifespan
  • Modestly increased proclivity for FRACTURES (DEC after puberty)
  • Classic finding of BLUE SCLERAE -> attributable to DEC scleral collagen content (can see choroidal vv)
  • HEARING LOSS can be related to conduction deficits in middle and inner ear bones
  • Small MISSHAPEN TEETH are a result of dentin deficiency
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35
Q

What are the types of bone fractures?

A
  • Closed (simple)
  • Open (compound)
  • Displaced
  • Pathologic
  • Spiral
  • Break in the continuity of bone -> should be reduced to anatomic position and immobilized
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36
Q

What do you see in the right, gross image compared to that on the left?

A
  • Paget’s disease of bone
  • Irregular, thick, coarse cortex and replacement of normal cancellous bone with coarse, thick bundles of trabecular bone
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37
Q

What is renal osteodystrophy?

A
  • Collectively describes skeletal changes associated with chronic renal disease –> kidney fails to convert Vitamin D to active form, resulting in:
    1. INC osteoclastic bone resorption, mimicking osteitis fibrosis cystica
    2. Delayed matrix mineralization (osteomalacia)
    3. Osteosclerosis
    4. Growth retardation
    5. Osteoporosis
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38
Q

What do you see here?

A
  • Highly destructive chondrosarcoma at knee joint
  • Bulk of the tumor is distal, invading tibia, but there is some invading proximally across the joint space
    1. Characteristic of malignant bone neoplasms that they do not respect joint spaces
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39
Q

What do you see here?

A
  • Gross appearance of Ewing sarcoma (primitive neuroectodermal tumor, PNET)
  • White, fleshy, ill-defined tumor with extensive involvement of medulla and cortex with periosteal elevation
  • May be necrotic or resemble pus
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40
Q

What syndromes are associated with multiple enchondromas?

A
  • Maffuci syndrome: multiple E’s and soft tissue hemangiomas; ovarian carcinoma, brain gliomas too
  • Ollier disease: non-hereditary disease of multiple E’s of long and flat bones (up to 50% of skeleton) w/assoc skeletal deformities; histologic features of low-grade chondrosarcoma should be ignored if radiographically benign; most lesions regress when skeleton matures; often ovarian sex-cord tumors
  • NOTE: multiple enchondromas may produce severe deformities; assoc w/chondrosarcomatous transformation
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41
Q

What do you see in these images?

A
  • Aneurysmal bone cyst (ABC)
  • Top image is low power: clotted blood in the upper right and a richly vascularized tissue in the lower left
  • Bottom image is high power: sometimes there are giant cells suggesting the misdiagnosis of giant cell tumor -> differentiating feature of aneurysmal bone cyst is the rich capillary bed
  • Left image: large, cyst-like space and hemorrhage in surrounding stroma -> several multi-nucleated giant cells in the stroma that are osteoclasts
    1. In vivo, the cysts, which appear empty here, would be filled with blood
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42
Q

What is the characteristic imaging seen with osteosarcoma?

A
  • Codman triangle
  • Characteristic but not diagnostic -> indicates aggressive tumor
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43
Q

What is a non-accidental trauma?

A
  • In children, handful of fractures highly suspicious for nonaccidental trauma, including:
    1. Rib fractures (see attached image), spiral fractures (other than toddler’s fracture), and multiple fractures at different ages
  • In shaken baby syndrome, subdural hematomas and retinal hemorrhages may also be found
  • Child services should always be notified
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44
Q

What is this?

A
  • Leiomyoma: benign tumor of smooth muscle -> most common neoplasm in women
  • Hereditary leiomyomatosis and renal cell cancer syndrome –> germ line loss-of-function mut in the fumerate hydratase (enzyme in Krebs cycle) gene
    1. Typically younger women (30-40’s): histo a tad different than typical leiomyoma (if you see this, can help catch these and monitor for, or prevent, renal cell cancers)
  • Micro: fascicles of densely eosinophilic spindle cells that often intersect at right angles
    1. There should not be any mitotic figures here
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45
Q

What is this?

A

Bowing of the legs (Rickets)

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46
Q

What do you see here?

A
  • Fibrous cortical defect, aka, non-ossifying fibroma
  • Black arrow shows characteristic storiform pattern
  • Yellow arrow pointing at giant cells
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47
Q

What genese are associated with osteosarcoma pathogenesis?

A
  • Approx 70% have acquired genetic abnormalities
  • RB: critical (-) cell cycle regulator -> pts w/germline RB mutation have a 1000-fold increased risk
  • TP53: guardian of genomic integrity by promoting DNA repair and apoptosis of irreversibly damaged cells (Li-Fraumeni syndrome or sporadic)
  • INK4a, gene that encodes tumor suppressors
  • MDM2 and CDK4: cell cycle regulators that inhibit p53 and RB function, respectively
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48
Q

What is the difference b/t these 2 images?

A
  • Marked reduction in both the marrow space and haversian system in osteopetrosis (bottom image)
  • Note the absence of osteoclasts and cortical-appearing bone
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49
Q

What do you see?

A
  • Micro appearance of Ewing sarcoma (primitive neuroectodermal tumor, PNET)
  • Sheets of small, round, uniform cells; indistinct cell membranes
    1. Glycogen rich cytoplasm may appear clear

2 Little stroma, and no spindling

  • Post-treatment: marked pleomorphism, tumor giant cells
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50
Q

What are these 3 arrows pointing at?

A
  • Top: osteoblast
  • Middle: osteocyte
  • Bottom: osteoclast
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51
Q

What is so important about hip fractures?

A
  • Proximal femoral fractures notable for association with osteoporosis and extremely high mortality in older adults
  • A fall to the side increases risk of hip fracture by about 6 times, compared to falls in other directions
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52
Q

What do you see?

A
  • Micro appearance of osteoid osteoma
  • Randomly interconnected trabeculae of woven bone, prominently rimmed by a single cell layer of osteoblasts (arrow from left)
  • Stroma surrounding the neoplastic bone consists of loose connective tissue containing dilated and congested capillaries (bottom arrow)
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53
Q

What are the common locations of bone lesions (image)?

A
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54
Q

What is the pathophysiology of renal osteodystrophy?

A
  • Decreased vitamin D (failure of kidney to convert to active form) leads to:
    1. Reduced calcium absorption by the intestine, leading to hypocalcemia, which provokes
    2. INC parathyroid hormone secretion -> this increases bone resorption
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55
Q

What is this?

A
  • Diffuse-type tenosynovial giant cell tumor
  • Localized destructive lesion in a single joint, usually knee, with:
    1. Proliferation of synovium
    2. Hemosiderin pigment deposition, and
    3. Destruction of the joint
  • Previously called pigmented villonodular synovitis
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56
Q

What is an undifferentiated pleomorphic sarcoma?

A
  • Undifferentiated pleomorphic sarcoma: malignant high grade waste basket –> these tumors don’t fit anywhere and can’t be ID’d based on histo, IH profile, ultrastructure, or molecular genetics
  • Usually large, grey-white fleshy masses (10-20 cm)
  • Micro: sheets of anaplastic spindled to polygonal cells (see attached image)
    1. Necrosis and hemorrhage common
    2. Atypical mitotic figures, often bizarre nuclei are present
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57
Q

What is McCune-Albright syndrome?

A

Fibrous dysplasia plus café-au-lait skin pigmentations and endocrine abnormalities, especially precocious puberty

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58
Q

Describe the 4 steps in the fracture healing process.

A

A. Hematoma fills fracture gap and surrounding area of bone injury; provides framework and allows platelets and inflammatory cells to do their part

B. End of week one - tissue is primed for new matrix synthesis

C. Wks 2-3: early callus formation –> can’t support weight

D. Bony callus mineralizes to point where controlled weight bearing can be tolerated

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59
Q

What is a pathologic fracture?

A
  • Bones that break after trivial trauma
  • Osteoporosis is often the pathology underlying these fractures, but underlying malignancies or bone cysts should also be considered
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60
Q

What 3 conditions elevate ESR > 100mm/hr?

A
  • Osteomyelitis (in particular Staph aureus)
  • Temporal arteritis
  • Polymyalgia rheumatica: aching and stiffness of upper arms, neck, lower back, and thighs in adults over 50, esp. Caucasians -> worse in the AM, and responds well to corticosteroids
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61
Q

What do you see here?

A
  • Pleomorphic rhabdomyosarcoma: numerous large, sometimes multinucleated, bizarre eosinophilic tumor cells
  • Myogenin (IHC stain) often necessary to prove rhabdomyoblastic differentiation
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62
Q

What is the difference b/t left and right?

A
  • Left: normal, healthy bone
  • Right: osteoporotic bone
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63
Q

What are these 3 stages?

A
  • Proliferation
  • Maturation
  • Mineralization
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64
Q

What is this?

A
  • Leiomyosarcoma metastatic to lung
  • Sarcomas tend to spread hematogenously rather than via lymphatic system, so 1 very characteristic place for them to metastasize to is the lungs
    1. Capillary bed a filter for circulating tumor cells; once filtered, some tumor cells can grow
    2. Can tell this is sarcoma due to hemorrhage and necrosis in some of the masses
  • Pulmonary metastases are generally numerous, tend to be larger, more numerous in basal lower lobes bc of the gradient in pulmonary arterial blood flow, which goes from highest in the bases to lowest in the apices
  • Pulmonary metastases are a major cause of death for patients with sarcomas of all kinds (i.e., also with osteosarcoma)
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65
Q

What is this?

A
  • Well-differentiated liposarcoma: adipocytes and scattered spindled cells
  • Indolent
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66
Q

What is the difference here?

A
  • Normal marrow on the left (w/pink trabeculae)
  • Diffusely congested, hemorrhagic marrow in sickle cell crisis on the right -> osteonecrosis
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67
Q

What is Rickets? What are the associated radiologic changes?

A
  • Defect in matrix mineralization due to vitamin D disturbance (deficiency, abnormal metabolism or calcium deficiency) in children
  • Causes an accumulation of un-mineralized bone matrix
68
Q

What are these signs of?

A
  • Basilar skull fracture
  • Usually secondary to trauma and may present as:
    1. Periorbital ecchymoses (raccoon eyes),
    2. Mastoid ecchymoses (Battle sign),
    3. Cerebrospinal fluid leakage through the ears (otorrhea), or nose (rhinorrhea with salty, metallic taste)
69
Q

What do you see here?

A
  • Osteochondroma
  • Note the prominent cartilage cap of this gross pathologic specimen (also a micro image)
70
Q

What is an osteoma?

A
  • Bone forming tumor composed of compact or mature trabecular bone limited almost exclusively to craniofacial bones, especially paranasal sinuses
  • Adults and children -> M:F = 3:2
  • Prognosis depends on proximity to essential anatomic structures
  • Present with pain, headache, vision changes
  • Associated with Gardner syndrome
71
Q

What is this?

A
  • Myositis ossificans: distinguished by presence of metaplastic bone
    1. Arises in proximal extremities after trauma, typically in young athletes
    2. Can be hard to distinguish from osteosarcoma
    3. Simple excision is usually curative
  • Radiograph: periosteal rxn with eggshell calcification (periosteal rxn) at periphery 3-6 weeks after injury
  • Histo: mature bone at periphery, fibrous tissue resembling nodular fasciitis at center, osteoid between
72
Q

What are the two fibrous dysplasia syndromes?

A
  • Mazabraud syndrome: fibrous dysplasia plus soft tissue myxomas
  • McCune-Albright syndrome: fibrous dysplasia plus café-au-lait skin pigmentations and endocrine abnormalities, especially precocious puberty
73
Q

What is this?

A
  • Alveolar rhabdomyosarcoma: network of fibrous septae that divide cells into clusters or aggregates, creating crude resemblance to pulmonary alveoli
  • Round cells with little cytoplasm
  • t(2:13) and t(1,13) translocations -> t(2;13) has worse prognosis
  • Fibrous network with clusters of malignant cells
74
Q

What do you see?

A
  • Chondrosarcoma: fairly cellular neoplasm
  • Cells that mimic normal chondrocytes in that they appear to float in a chondroid-like matrix (top image)
  • At higher power, however, the tumor cells have:
    1. Large nuclei,
    2. High nuclear/cytoplasmic ratio and
    3. Abundant mitotic figures
75
Q

What is Ewing sarcoma (primitive neuroectodermal tumor, PNET)?

A
  • Malignant proliferation of poorly differentiated cells derived from neuroectoderm
  • 2nd most common in children after osteosarcoma
  • Arises in diaphysis (medullary) of the long bones
  • Usually in white male children (<15 years of age)
  • “Onion skin” on x-ray (see attached).
  • t(11,22) translocation [EWS-FLI1 fusion]
76
Q

What is this?

A
  • Osteomalacia (adults)/Ricket’s (kids)
  • Surfaces of bony trabeculae (black) are covered by a layer of unmineralized osteoid (dark pink)
    1. Von Kossa stain: calcified tissue is black
  • The excess of persistent osteoid is characteristic of osteomalacia
77
Q

What do you see in these 2 images?

A
  • Osteopetrosis (micro images)
  • Irregular bony trabeculae, increased in number and containing residual strips of un-remodeled cartilage (blue-gray within the pink trabecular bone)
  • Osteoclasts are not increased
  • The marrow cavity shows hematopoiesis (dark cells) but the size of the marrow cavity is markedly reduced by the excess, only partially ossified trabeculae
78
Q

What is this? What are the arrows pointing to?

A
  • Micro appearance of rhabdomyosarcoma
  • Usually made up of bizarre cells
  • Left arrow: elongated “strap” cells may recapitulate skeletal muscle cells
  • Right arrow: often have bizarre cells with abundant cytoplasm
  • Some may even have cross striations like muscle
  • Desmin, myogenin are the 2 muscle markers used the most -> panel of stains done on all soft tissue tumors (still do them, even if you know what it is)
79
Q

What is hyperparathyroidism?

A
  • Primary: typically hyperplasia or tumor (adenoma) of the parathyroid gland
  • Secondary: prolonged states of hypocalcemia with resulting hypersecretion of PTH (usually)
  • Increased PTH detected by osteoblasts, which stimulate osteoclasts -> unabated osteoclastic bone resorption
    1. Substantial resorption of bone causes cyst-like brown tumors in the bone, consisting of fibrous tissue and woven bone without matrix
80
Q

What do you see here?

A

Lung cancer metastatic to spine (tan)

81
Q

What is this? Where do they usually arise?

A
  • Leiomyoma: arise almost anywhere in the body, since smooth muscle is ubiquitous (can even wrap around esophagus, and cause dysphagia)
    1. Typically, very well-circumscribed, and pretty homogenous
    2. If you see hemorrhage or necrosis, might be a leiomyosarcoma
  • Uterus is the most common site; the wall of the uterus is made up of smooth muscle -> location a big player here
82
Q

What is a scaphoid fracture?

A
  • Often secondary to a fall on an outstretched hand
  • Patients will have pain at the anatomic snuffbox, but x-ray is usually unremarkable during the first week
  • Patients must be splinted or the proximal scaphoid may undergo avascular necrosis
83
Q

What is an enchondroma?

A
  • Usually asymptomatic
  • Age 20-49, no gender preference
  • Small bones of hands and feet
  • Mostly solitary
  • Treatment = excision or nothing
  • Imaging attached: radiolucent nodule of hyaline cartilage with scalloped endosteal surface -> this one has an associated pathologic fracture
84
Q

Why is Vitamin D important for healthy bone maintenance? Briefly describe the involved pathways (image).

A
85
Q

Thanatophoric dwarfism

A
  • Aka, death-loving dwarfism: lethal variant of dwarfism
  • Small thorax leads to respiratory complications and death
  • Activating point mutation in FGFR3
86
Q

What is Paget’s disease of bone?

A
  • Imbalance of osteoclast and osteoblast function
  • Unknown etiology, possibly viral (paramyxovirus)
  • Familial predisposition linked to chromosome 18
  • Typically localized, not entire skeleton
  • Most common cause of isolated elevated alkaline phosphatase in patients >40 years old
  • Increased risk of osteosarcoma
87
Q

What do you see here?

A
  • Open (compound) fracture
  • Bone is exposed to the environment through the wound so is at risk for infection
  • Procedural washout and antibiotics should be used in the treatment of these fractures
88
Q

What is this?

A
  • Sarcoma botyoides (variant of embryonal) –> devo in wall of hollow mucosa-lined areas (nasopharynx, vagina)
    1. Polypoid or lobulated masses of cells covered by mucosa, with underlying hypercellular zone of poorly differentiated cells (cambium layer -> more cellular along the surface, underneath the squamous epi)
    2. Tumor is beneath and squamous epi on top
89
Q

What is the pathogenesis of osteoporosis?

A
  • Important cytokines: IL-1, IL-6, TNF
  • Important cells: osteoclasts (blasts less active)
  • Roughly half of post-menopausal women will suffer an osteoporotic fracture (compared to 2-3% of men of comparable age)
90
Q

What is going on here?

A
  • Baby on the right has T2 OI
  • Type II variant uniformly fatal in utero or immediately postpartum as a consequence of multiple fractures that occur before birth
91
Q

What differences do you see here?

A
  • Normal, healthy bone on the left
  • Osteoporotic bone on the right
    1. May be shortened by compression fractures, and also exhibits a characteristic loss of horizontal trabeculae and thickened vertical trabeculae
92
Q

What is synovial sarcoma? What are its 2 histological presentations?

A
  • Misnomer bc first recognized near knee synovium
    1. Can present in locations that lack synovium, often deep seated mass for years
  • 10% of all soft tissue sarcomas, ranked #4
  • People in 20’s-40’s; pretty frequently see these
  • Most have characteristic chrom translocation t(X;18)
  • Aggressive tx w/limb-sparing sx and often chemo
  • Mets common to lung and occasional lymph node
  • Monophasic (uniform spindle cells w/scant cyto) and biphasic (classic appearance: spindle cells in white here, but also gland-like structures in purple) histo presentations in attached image
93
Q

What is this?

A
  • Deep fibromatosis: large infiltrative masses that recur, but do not metastasize
    1. Micro: broad fascicles amid dense collagen, similar to a scar
  • Left image: 1400-gram desmoid tumor in lower abdomen 11-y/o boy -> encapsulated mesenteric mass w/sigmoid colon draped over it anteriorly
    1. Micro exam showed a bland, spindle cell proliferation with no mitoses and no necrosis
94
Q

How does an osteochondroma develop?

A
  • Initially, at the epiphyseal plate, there is a small outpouching of cartilage, which grows proximally to the epiphyseal plate
  • Comes to resemble a mushroom growing out of the bone with a cap of cartilage over it
95
Q

What is this cell? Disease?

A
  • Lipoblast, the hallmark cell of the liposarcoma: one of most common soft tissue tumors of adults
    1. Ugly dark nucleus, and bubbly vesicles
    2. People in their 50-60’s
  • Deep soft tissues of the proximal extremities and in the retroperitoneum
    1. Get very large before they are discovered bc in retroperitoneum -> can be very difficult to distinguish b/t malignant and benign fat cells
  • Immunostaining for MDM2 and CDK4 or molecular testing for 12q13-15 amplification
  • Recur locally and repeatedly unless adequately excised
  • Can progress and get away from looking like fat, making them hard to diagnose -> the immunostains help distinguish these as liposarcomas
96
Q

What do you see here?

A
  • Typical, subdermal fat location of nodular fasciitis
  • Rapidly growing, benign, fibroblast proliferation in subcutis, commonly in the arms
    1. Intraoperative view of nodular fasciitis in deltoid area attached
  • 25% have history of trauma (may be more than this)
  • Has been shown to be clonal but self-limited
  • Least rare of the fibrous tumors
97
Q

What are the lab findings in osteomalacia/Ricket’s?

A
  • Inadequate mineralization leads to weak bones and fractures
98
Q

What is an osteoblastoma?

A
  • Similar to an osteoid osteoma, but larger (>2cm)
  • Arises in the vertebrae, and presents with bone pain that doesn’t respond to aspirin
  • 60% female, children and young adults
  • Comprised of anastomosing trabeculae of osteoid and woven bone rimmed by osteoblasts
  • Treatment usually by curettage or it is excised en bloc
99
Q

What is Mazabraud syndrome?

A

Fibrous dysplasia plus soft tissue myxomas

100
Q

What is this?

A
  • Closed (simple) fracture
  • Bone does not pierce the overlying skin
101
Q

What are bisphosphonates?

A
  • Tx for osteoporosis and other bone diseases such as Paget Disease
  • Binds to bone material; released during resorption
    1. INH osteoclast formation, migration, and osteolytic activity -> promote apoptosis (see attached image)
102
Q

What are the chief causes of osteomyelitis?

A
  • Staph aureus – 90% - most common
  • N. gonorrhoeae – sexually active young adults
  • Salmonella – sickle cell disease
  • Pseudomonas – diabetics or IV drug abusers
  • Mycobacterium tuberculosis – typically the spine (Pott disease -> see attached images)
103
Q

What is this? Common cytogenic abnormalities?

A
  • Lipoma: benign fat tumor
  • 55-75% solitary lipomas w/cytogenetic abnormalities have rearrangements of HMGA2/HMGIC at 12q13-15
    1. No clinicopathologic features are associated with the resulting fusion transcripts
  • -Don’t memorize the molecular rearrangements à KEY is to know that they DO HAVE MOLECULAR REARRANGEMENTS
104
Q

What is this?

A
  • Embryonal rhabdomyosarcoma: soft grey infiltrative mass of spindled and round cells in myxoid stroma
  • Sarcoma botyoides (variant of embryonal) –> devo in wall of hollow mucosa-lined areas (nasopharynx, vagina)
    1. Forms cambium layer: underlying hypercellular zone of poorly differentiated cells
105
Q

What is this?

A
  • Plantar superficial fibromatosis: young patients, unilateral and without contractures
106
Q

How do you treat Ewing sarcoma?

A
  • Aggressive malignancies treated with neoadjuvant chemotherapy followed by surgical excision with or without irradiation
  • Advent of effective chemotherapy has achieved 5-year survival of 75% and long-term cure in 50%
  • Amount of chemotherapy-induced necrosis is an important prognostic finding
107
Q

What is going on here? What is the arrow on the right pointing to?

A
  • Osteosarcoma making malignant cartilage, aka chondroblastic osteosarcoma
  • Arrow is pointing to tumor cells forming pink, acellular osteoid
108
Q

What is this?

A
  • Histo of nodular fasciitis: richly cellular
    1. Plump immature fibroblasts in short fascicles (looks like tissue culture)
    2. Abundant mitotic figures
  • Rapidly growing, benign, fibroblast proliferation in subcutis, commonly in the arms
  • Can look really scary and have a high mitotic rate, but BENIGN (history and location are going to help)
109
Q

What is this?

A
  • Brown tumor: resected from rib
  • Shows cystic and hemorrhagic character of this lesion
110
Q

Osteopetrosis

A

uBones are dense, solid, and stone-like.
uTurnover is decreased (poor osteoclast function), bone tissue becomes weak over time, fractures like a piece of chalk.
u Several variants are known, the two most common being an autosomal dominant adult form with mild clinical manifestations, and autosomal recessive infantile, with a severe/lethal phenotype.
uCarbonic anhydrase II deficiency leads to loss of the acidic microenvironment needed for bone resorption.

111
Q

What do you see?

A

Frontal bossing (Rickets)

112
Q

What is this? How can you tell?

A
  • Osteoblastoma: like an osteoid osteoma, but larger (>2cm), and arises in vertebrae
  • Comprised of anastomosing trabeculae of osteoid and woven bone rimmed by osteoblasts
113
Q

What are soft tissue tumors?

A
  • Current evidence suggests these do not arise from mature cells, but pluripotent stem cells
  • Vast MAJORITY ARE BENIGN (going to see lots of lipomas and leiomyomas)
  • Less than 1% of all US malignancies, but 2% of all cancer deaths
  • Some soft tissue tumors are virtually identified based on the associated translocations
  • 40% are on the thigh
114
Q

What is this?

A
  • Biopsy from pt with Paget’s disease of bone
  • Mosaic pattern of lamellar bone
115
Q

What is an osteosarcoma? Where might you get it?

A
  • Malignant proliferation of osteoblasts
  • MOST COMMON 1o bone tumor after myeloma
  • 60% male, ages 10-20
  • Retinoblastoma; Rb gene = risk factor and poor prognosis
  • Assoc w/Paget and post-radiation in older patients
  • 20% have lung metastasis at diagnosis
  • Painful, progressively enlarging fracture of knee, metaphysis of long bones
116
Q

What are the arrows pointing at?

A
  • Black: periosteum
  • Blue: bone marrow
  • Green: residual cartilage
117
Q

What do you see here?

A
  • Spiral fracture -> from torque
  • Significant b/c they may indicate child abuse in the appropriate clinical scenario (e.g., fracture from twisting the child’s arm or leg)
  • Spiral fracture of the distal tibia (toddler’s fracture) is less concerning bc it may occur with rotational force during normal activity
118
Q

What is osteoporosis?

A
  • Reduction in trabecular bone mass
  • Results in porous bone with an increased risk of fracture
  • Most common forms are senile & postmenopausal
119
Q

What do you see here?

A
  • Woven bone: characterized by haphazard org of collagen fibers and mechanically weak -> produced when osteoblasts produce osteoid rapidly
  • It is present in:
    1. All fetal bones initially when bone is laid down, but it is later replaced by lamellar bone
    2. After fxs, the initial bone that unites the fx is woven bone -> replaced by lamellar bone
    3. Paget’s disease
  • Named due to woven appearance of fibrous matrix; basically either immature or pathologic bone
  • Compared to lamellar bone, woven bone has more osteocytes per unit of volume and higher rate of turnover -> weaker and more flexible than lamellar
120
Q

What is going on here?

A
  • Paget’s disease of bone
  • Shown is the cotton wool appearance of bone on a skull radiograph (arrows)
121
Q

What are these?

A

Osteochondromas

122
Q

What do you see here?

A
  • Ewing sarcoma (primitive neuroectodermal tumor, PNET)
  • Periosteal rxn produces layers of reactive bone, aka, “onion skinning”
123
Q

What is fibrous dysplasia?

A
  • Problem of osteoblastic maturation -> fibrous tissue forms instead of medullary bone
    1. Painful, swollen bones prone to fractures
  • Ribs and femur are most commonly affected
124
Q

What is the difference b/t left and right?

A
  • Growing bone on the left
  • Mature bone on the right
125
Q

What are the pits created by osteoclasts (green arrow) called?

A

Howship lacunae

126
Q

Characterize metastatic bone tumors.

A
  • More common than primary tumors
  • Usually “punched out,” lytic lesions radiographically
    1. Prostatic carcinoma classically produces osteoblastic lesions
  • Mnemonic: BLT with a K osher P ickle -> Breast, Lung, Thyroid, Kidney, and Prostate
  • Metastatic breast cancer in attached image
127
Q

What are these?

A
  • Diffuse-type tenosynovial giant cell tumor
  • Localized destructive lesion in a single joint, usually knee, with:
    1. Proliferation of synovium
    2. Hemosiderin pigment deposition, and
    3. Destruction of the joint
  • Pigmented bc they have hemosiderin in them
128
Q

What is a chondroma?

A
  • Benign cartilaginous tumor
  • Either enchondroma (arise in diaphyseal medullary cavity), subperiosteal/juxtacortical chondroma, or soft tissue chondroma
  • IDH1 and IDH2 genes have been identified in the chondrocytes of syndromic & solitary enchondroma
    1. Somatic muts in isocitrate dehydrogenase 1 (IDH1) and IDH2 also occur in gliomas and acute myeloid leukaemia (AML))
129
Q

What is this?

A
  • Micro pathology of chondroma
  • Numerous chondrocytes closely packed near the periphery in a pink ground substance that vaguely resembles normal cartilage
  • Normal hyaline cartilage has light blue ground substance (smaller image in the lower left-hand corner)
130
Q

What do you see here?

A
  • Fibrous cortical defect, aka, non-ossifying fibroma
  • >5cm and intramedullary component (black arrow)
131
Q

What is giant cell tumor of bone?

A
  • Tumor of young adults (20-40s)
  • Arises in the epiphysis of long bones, typically the knee
  • “Soap bubble” on x-ray (see attached)
  • Locally aggressive, and may recur
  • The neoplastic cells express high levels of RANKL, a potential drug target
132
Q

What do you see here?

A
  • Osteomyelitis
  • Top arrows: necrotic bone -> note empty lacunae
  • Bottom arrow: neutrophils
133
Q

What is this?

A
  • Osteosarcoma
  • Tumor cells vary in size and shape and often have large, hyperchromatic nuclei
  • Bizarre tumor giant cells are common, as are mitoses, some abnormal (e.g. tripolar)
134
Q

What do you see here?

A
  • Penile (peyronie) disease: palpable induration or mass on the dorsal penis
  • Eventual curvature of the shaft and/or constriction of the urethra
  • SUPERFICIAL FIBROMATOSIS
135
Q

What is Gardner Syndrome?

A
  • Variant of familial adenomatous polyposis (APC gene on chrom 5q21) -> multiple colon polyps
  • Autosomal dominant
  • Extracolonic tumors include:
    1. Osteomas of the skull,
    2. Thyroid cancer,
    3. Epidermoid cysts (middle left image)
    4. Fibromas, and
    5. Desmoid tumors (CT of any kind, i.e., bone, cartilage, etc.) in approx 15% of affected pts
136
Q

What is an osteochondroma?

A
  • MOST COMMON benign tumor of bone
  • Mostly in males, 10-20 years old
  • Slow growing, can be painful
  • Usually stops growing at puberty and ossifies
  • Rare transformation to chondrosarcoma (5-10%)
  • Treatment = simple excision
137
Q

What is this?

A
  • Osteomyelitis
  • Necrosis, hemorrhage, purulence
138
Q

What is this? How can you tell?

A
  • Enchondroma: note that this is a small bone of the hand (finger)
  • Radiolucent nodule of hyaline cartilage with scalloped endosteal surface -> this one has an associated pathologic fracture
139
Q

What is a displaced fracture?

A
  • The bone is separated in a nonanatomic position
  • It must be reduced before healing
140
Q

What is this?

A
  • Osteoblastic metastatic carcinoma from the prostate
  • Extreme sclerotic changes present in the pelvic bones, femoral heads, sacrum, and vertebrae
141
Q

What is a chondrosarcoma?

A
  • Malignant cartilage forming tumor (NO OSTEOID)
  • Arises in medulla of pelvis or central/axial skeleton
  • Men in 40s -> some variants in younger pts (clear cell and mesenchymal)
142
Q

What do you see?

A

Pigeon chest deformity (Rickets)

143
Q

What is this? Name the characteristic cell type.

A
  • Spider cell of rhabdomyoma: most frequent primary tumor of the pediatric heart (not seen in adults)
  • Most spontaneously regress, may be considered hamartoma rather than true neoplasm
  • May cause valvular or cardiac chamber obstruction
  • 50% are associated with tuberous sclerosis
    1. Mutations of TSC1 (hamartin) & TSC2 (tuberin)
  • This + rhabdomyosarcoma are HIGH YIELD
144
Q

What is going on here?

A
  • Photo-micrographs of brown tumors
  • Show fibroblasts mixed with osteoclasts, and numerous activated osteoclasts at the edge of a trabecula
145
Q

What do you see here?

A
  • Osteochondroma
  • Distal portion of femur in 13-y/o boy with well-circumscribed, knobby surface
  • Lesion forms acute angle w/the cortex of femur, and cartilaginous cap is pointed away from the adjacent epiphysis
146
Q

What is this?

A
  • Foot of a diabetic patient showing a large area of necrosis and ulceration caused by the small vessel atherosclerotic disease, peripheral neuropathy and impaired neutrophil function of diabetes
  • The calcaneus, seen in cross section on the right, has a draining sinus (straight arrow) in which a squamous carcinoma (white tissue indicated by curved arrow) has arisen
147
Q

Osteogenesis Imperfecta

A
  • Brittle bone disease: gp of genetic disorders caused by defective syn of T1 collagen alpha1 or alpha2 chains
  • T1 collagen is major component of ECM in o/parts of body, so extra-skeletal manifestations, incl. skin, joints, teeth, and eyes
  • Four major types, but main ones are Type 1 and 2:
    1. T1: mild bone fragility, rib deformities, blue sclerae
    2. T2: perinatal lethal
148
Q

What is this?

A

Osteoma

149
Q

What are the primary bone tumors in long bones? Where do they occur?

A
150
Q

What is going on here?

A

Rachitic rosary (Rickets)

151
Q

What do you see here? What hallmark of diagnosis is shown here?

A
  • Eosinophilic rhabdomyoblast inclusions, the histo hallmark of rhabdomyosarcoma -> malignant mesenchymal tumor w/skeletal mm differentiation
    1. Sheet of cells with inclusions in a kid
  • 3 subtypes: alveolar, embryonal, and pleomorphic
    1. Alveolar, embryonal: most common soft tissue sarcoma of childhood (patients <20 y/o)
    a. Pediatric form typically arises in sinuses, head and neck, and GU tract
    2. Pleomorphic: predominantly in adults
  • EM shows that rhabdomyoblasts contain sarcomeres (thick and thin filaments) and Z bands
    1. Can stain these to see if they are of skeletal muscle origin (desmin, actin)
152
Q

What is osteitis fibrosa cystica?

A
  • Combined picture of:
    1. Increased bone cell activity
    2. Peritrabecular fibrosis
    3. Cystic brown tumors
  • Rarely seen anymore due to early diagnosis of hyperparathyroidism
153
Q

What might this be?

A
  • Lipoma: benign tumor of fat; MOST COMMON soft tissue tumor in adults
  • Superficial extremity or trunk
  • Most are mobile, slow growing and painless
    1. Angiolipomas can manifest with local pain
  • Complete excision usually curative
154
Q

What is this?

A
  • Ganglion cyst: small, cyst-like spaces with no epi lining containing myxoid material
  • Best thought of as a degenerative phenomenon in tendons or other connective tissue near joints
  • See attached gross image (filled with light, proteinaceous material)
155
Q

What do you see here?

A
  • Leiomyosarcoma: 10-20% of soft tissue sarcomas
  • Women > men
  • Deep soft tissues of extremities & retroperitoneum
  • A particularly deadly form can arise from the great vessels (i.e., IVC)
  • Typically painless and can be large and bulky
  • Eosinophilic spindle cells with blunt-ended, hyperchromatic nuclei in interweaving fascicles
156
Q

What are the 4 types of tumors of bone?

A
  • Osteoma
  • Osteoid osteoma
  • Osteoblastoma
  • Osteosarcoma
157
Q

What is the difference b/t these images?

A
  • Right: non-calcified, hypertrophied growth plate in rickets
    1. Thickened, poorly defined growth plate, particularly on metaphyseal side
    2. Tongues of uncalcified cartilage may extend into metaphysis
    3. Wide osteoid seams
  • Left: normal growth plate
158
Q

Know this.

A

Good job!

159
Q

What do you see here?

A
  • Aneurysmal bone cyst (ABC): like a sponge filled with blood
  • Can cause pathologic fractures, and can be an operative challenge because of extensive bleeding
  • No gender preference; 1-20 years old
  • Benign but grows rapidly
  • 20% recur after curettage
160
Q

What do you see here?

A
  • Micro appearance of giant cell tumor of bone
  • Top image shows regular, uniform distribution of stromal cells (blue arrow) & giant cells (black arrow)
    1. Nuclei of the mononuclear cells and the osteoclasts are similar, ovoid with prominent nucleoli
  • Bottom image shows the fibroblastic activity and formation of reactive bone and osteoid
161
Q

What is the difference between left and right?

A
  • Left: lamellar bone -> cortical bone comprised of osteons (Haversian systems) runs longitudinally
    1. Osteons communicate with medullary cavity via Volkmann’s canals that run horizontally (see attached image)
  • Right: woven bone -> coarse, with random orientation; weaker than lamellar bone, and normally remodeled to lamellar bone
162
Q

What do you see here?

A
  • Gross pathology of a chondroma
  • Gray-white mass with color and consistency similar to normal cartilage (this example is less well circumscribed than typical)
163
Q

What is this?

A
  • Giant cell tumor of bone
  • Tibial tumor from 19-y/o woman w/discomfort in her knee
  • Involves both metaphysis and epiphysis, with extension to articular cartilage
  • Purely lytic defect, confined to normal bone contours, w/sharply defined borders, except for some “blurring” at metaphyseal margin
164
Q

What is this?

A
  • Ewing sarcoma (primitive neuroectodermal tumor, PNET)
  • Sometimes have Homer Wright rosettes (like in this image) composed of dark blue tumor cells surrounding pink fibrillar material resembling neuropil suggestive of neural differentiation
165
Q

What is this?

A
  • Giant cell tumor of tendon sheath
  • Multinucleated giant cells in a background of histiocytes and cells that resemble synoviocytes
  • Localized type of tenosynovial giant cell tumor

MSK, Rheum, Derm (21 decks)

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