Pathology Laboratory Slides



Pathology Laboratory Slides

Cell/Tissue Injury

#212: Fatty Liver

1. darker red areas of normal hepatocytes

2. pale bubbly areas of fatty change

3. nuclei of fat cells pushed to the side

4. causes of fatty liver: alcohol, diabetes, malnutrition

[pic]

[pic]

[pic]

#234: Spleen: Gaucher’s disease

1. Gaucher’s disease: defective glucocerebrosidase, results in the accumulation of glucocerebrosides in lysosomes of cells (“lysosomal storage disorder”)

2. red pulp filled with aggregates of pink, fluffy looking Gaucher cells

a. these nuclei are not pushed to the edge like in fatty liver cells

3. high power: Gaucher cells have granular cytoplasm

|[pic] |

|Spleen, Gaucher's Disease; Hi Mag. |

|Here is a field of white pulp with it's artery and lymphoid cells. A pocket of Gaucher cells is seen to the left (white arrows). Most of |

|these cells are found in the red pulp areas, because that is where the phagocytes are normally most active. As Gaucher cells form, they tend|

|to occupy more and more volume, "crowding out" white pulp, as in our specimen. |

#1: Liver, various stages of necrosis

1. Normal

-large stores of glycogen (look like ragged clear spaces)

-cytoplasm is basophilic

-large hepatocytes with distinct cell boundaries

-sinusoids are hard to appreciate

2. 2 hours – mostly normal!

-glycogen stores have disappeared

-tissue looks paradoxically better than the control

- cells are smaller, less vacuolated, more uniform in appearance

- cell borders more distinct, shrinkage has made sinusoids and triads more apparent

- no clear spaces readily apparent

3. 8 hours – loss of basophilia

-basophilia lost due to enzymatic digestion of RNA

-cytoplasm looks more pink

-sinusoidal borders become ill-defined

-nuclei start to look pale due to breakdown of RNA/DNA

4. 24 hours – RED IS DEAD!

-loss of basophilia gives cytoplasm distinct pink appearance

-surrounding blue band of inflammatory cells – neutrophils rushing in to digest the dead tissue

-some nuclei are shrunken and dark (“pyknotic”), others are pale and ghostlike

-nuclear dust from karyorrhexis can be seen

-some nuclei disappear due to karyolysis

|[pic] |

|Normal Liver; Medium Mag. |

|Here we see a triad at the right. The hepatocytes look ragged, and cell borders and sinusoids are ill-defined. |

|[pic] |

|Ischemic liver, 2h, (Medium Mag.) |

|A triad is indicated by the black arrow and the central vein by the white one. As mentioned in the manual, the depletion of cytoplasmic |

|glycogen over the 2h ischemic interval is apparent, but such findings are often seen in tissue harvested and left sitting for a short time |

|unfixed. Even the expert would be hard put to declare this liver to be morphologically abnormal. |

|[pic] |

|Ischemic liver, 8h; (HI Mag.) |

|This field is taken from an area adjacent to a central vein. Cell morphology is still apparent although the careful observer would begin to |

|suspect that the cells were injured before the sample was harvested and fixed. There are no "zonal" gradations to be seen, unlike what is |

|observed in patients who suffered chemical or ischemic liver damage, because here the circulation was abruptly cut off to all parts of the |

|organ at once. Likewise, the complicating elements of inflammatory infiltrates, congestion and hemorrhage, and bile stasis are not seen |

|here. Later on you will encounter much more interesting Images of liver injury than this. |

|[pic] |

|Ischemic liver, 24h; (Medium Mag.) |

|Here there is a triad at the lower left. The hepatic cords look like irregular pink ribbons streaming radially from the triad. Nuclei are |

|mostly gone. Cells show necrotic changes more quickly if their basal activity level is higher to start with. There are more nuclei in the |

|triad than among the hepatocytes, because those triad nuclei belong to fibroblasts and smooth muscle cells that tolerate ischemia better. |

|They are probably dead at this point too, but they have not been dead as long as the hepatocytes. |

|[pic] |

|Ischemic Liver, 24h; (Hi Mag. #2) |

|This is the outer rim of the 24h specimen, showing the polys infiltrating the dead tissue. The black arrow shows the interface between |

|omentum and liver fragment, while the white arrow shows the interface between the wave of advancing polys and uninvolved necrotic liver. In |

|the abdominal cavity omentum often functions as a sort of emergency patch, covering an area of inflammation or limiting the spread of |

|infection if the source is relatively localized. |

#207: Liver with centrilobular necrosis

1. example of zonal necrosis of the liver – certain areas of the liver more susceptible to particular types of insults

2. centrilobular necrosis – spares triads, involves cells around central veins, farthest from inflowing blood

a. common causes: portal hypertension, ischemia/hypoxia, and chemical injury (toxic metabolites)

3. tissue looks mottled – pale and darkly staining areas = “nutmeg liver”

a. pale areas – around central veins, hepatocytes here have lost their nuclei, see inflammatory cells, sinusoidal architecture lost

b. darker areas – contain portal triads, healthy

| |

|[pic] |

|Nutmeg Liver; Gross Specimen |

|In this slice from a gross specimen we can easily recognize that the liver has patterned areas of light and darker-colored tissue. |

|Experience tells the pathologist that this indicates a "zonal" effect, with hepatocytes affected differently when they are periportal vs |

|centrilobular. |

|[pic] |

|Centrilobular necrosis; Hi Mag. |

|At high Mag. in a hemorrhagic area we can recognize a central vein (black arrow), and now we can see pale hepatocytes and an infiltrate of |

|polys, consistent with necrosis. What is a plausible sequence of events to explain these observations? |

#220: Liver, biliary cirrhosis

1. Periportal inflammatory pattern (vs. centrilobular like last slide)

2. bile duct obstruction, neoplasms, autoimmune biliary disease can block bile ducts causing jaundice

3. periportal zones: darkly staining areas with lots of inflammatory cells

4. Greenish-brown spots: accumulations of bile

5. In the liver, you can see the following colors

a. Red cell remains – hemosiderin

b. Browinish, yellowish pigment – bilirubin

c. Brownish remains – lipofusin

|[pic] |

|Biliary Cirrhosis, Medium Mag. |

|The black arrow indicates a bile duct, surrounded by inflammation and early fibrosis; white arrows indicate pools of bile. |

#210: Liver, viral hepatitis

1. can see periportal patchy areas of blue, corresponding to cytotoxic T-cell infiltration

2. “Councilman bodies”: pink anucleate blobs of dead hepatocytes, swollen and bloated

|[pic] |

|Viral Hepatitis, Medium Mag. |

|Here is a field in which the upper half is inflammatory infiltrate, mostly lymphocytes. Most hepatocytes have been destroyed in this area. |

|The lower part of the field shows some residual hepatocytes, one of which is degenerating (black arrow). |

|[pic] |

| |

|Viral Hepatitis, High Mag. |

|Here is an area showing patchy loss of hepatocytes with edema and chronic inflammation. An eosinophilic Councilman body is |

|shown by the black arrow. Many of the hepatocytes are stained with accumulated bile. |

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| |

Inflammation

#192: Lung with lobar (pneumococcal) pneumonia

1. aveoli still well-defined, just full of exudate

2. Uniform filling of alveoli by exudates

a. Can see lots of PMNs – hallmark of acute inflammation

b. Also see blood in the alveoli

c. Can see fibrin strands in the exudates – comes from leakage of plasma proteins from capillaries (fibrin is a plasma protein)

3. anthracotic pigments – black carbon particles from inhaled soot, present in any lung

|[pic] |

|Lobar Pneumonia, Low Mag. |

|The compartments are alveoli filled with pus. The red lines outlining the compartments are the congested septal capillaries. Collections of |

|anthracotic pigment can be seen to the left of the Image. |

|[pic] |

|Lobar Pneumonia, Medium Mag. |

|In this field one sees an airway space with desquamating epithelium (black arrows) beside pulmonary artery branches. Lymphatics run adjacent|

|to the airways and vessels, and pigmented macrophages form the black deposits visible even at this relatively low Mag. Note the uniformity |

|of the filling of the alveoli by the exudate; characteristic of lobar pneumonia. |

#49: Lung with bronchopneumonia

1. alveoli not well defined, not a uniform field of lung tissue

2. tissue looks patchy, lung architecture is damaged

3. areas that are solid=injury, areas that have lots of holes=healthy

|[pic] |

|Bronchopneumonia, Medium Mag. |

|Here is an area of inflammation where the underlying architecture seems destroyed. The black arrows point at opaque pigment that is probably|

|anthracotic (carbon), but other small foci of blue amorphous material are indicated by the white arrows, and these are probably microbial |

|colonies surrounded by pus. |

|[pic] |

|Bronchopneumonia, Medium Mag., II |

|In this field are an airway space and a couple of pulmonary artery branches (white arrows) and an airway (black arrow)for orientation. This |

|region of lung would contribute nothing to ventilation. |

#6: Nasal polyp

1. identify different inflammatory cells:

a. RCs

b. Activated endothelial cells (become thicker)

c. Lymphocytes – nucleus occupies almost entire cell

d. Plasma cells –

i. Look like lymphocytes but have extra cytoplasm

ii. have off-center nucleus and round eccentric darker nuclei with pale “clear zones” (golgi apparatus)

iii. Russell bodies – huge red plasma cells that make Igs w/o secreting them

e. Macrophages – nuclei are off-center, less regularly round, lighter than lymphocytes

f. Eosinophils – are bilobed

|[pic] |

|Nasal Polyp, Hi Mag. IV |

|In this field the differences between plasma cells (green arrows) and macrophages (purple arrows) can be appreciated. The fact that the |

|macrophages have internalized some pigmented substance makes it easier to recognize them. Note they are larger than plasma cells, with a |

|less regular shape. The nuclear chromatin pattern is more homogeneous, without the clockface clumps at the nuclear membrane. Plasma cells |

|never exhibit cytoplasmic granularity or contain exogenous pigment. A stromal fibroblast (black arrow) is present to the left. |

|[pic] |

|Nasal Polyp, Hi Mag. |

|At higher Mag., one can see a venule with endothelium and smooth muscle cells of the wall. Neutrophills (black arrows) and an eosinophil |

|(red arrow) are sticking to the lining. In the interstitium, most of the cells we see are lymphocytes (blue arrows). |

|[pic] |

|Nasal Polyp, Hi Mag. II |

|In this field, most of the cells are plasma cells (green arrows); they have abundant basophilic cytoplasm and eccentric round nuclei with |

|chromatin that is slightly stippled. The large pink cell with the pycknotic nucleus is a Russell body (large green arrow). These are plasma |

|cells, possibly defective, that accumulate immunoglobulin in their cytoplasm without secreting it; eventually they undergo degeneration. |

|Such cells are commonly observed wherever plasma cells accumulate, and are incidental findings only. A few lymphocytes (blue arrows) can |

|also be identified. |

#15: Skeletal muscle with injected agar

1. forms a granuloma – 3 defining characteristics

a. fibrous capsule (fibroblasts wall off area)

b. macrophages! (chronic inflammation, vs PMNs)

c. multinucleated giant cells! – macrophages attempt to increase their engulfing ability

|[pic] |

|Foreign Body Reaction, Low Mag. |

|The arrow indicates a good sort of area to choose for high Mag. examination, since there seems to be some breakup of the agar into smaller |

|fragments there. |

|[pic] |

|Foreign Body Reaction, Medium Mag. |

|The arrows indicate some giant cells. These are so large that the plane of section could not include the whole thing; how much you see of |

|any given one depends upon chance. By studying a number of examples you can form an estimate of their average size. Some of these can be |

|observed to probably contain foreign material, while others seem to be simply "plastered" against much larger aggregates. When the |

|pathologist encounters giant cells such as these, the possibilities to be considered include foreign material, infectious diseases with |

|robust organisms such as mycobacteria and certain fungi and diseases such as sarcoidosis (of uncertain pathogenesis). |

Repair

#7: Rabbit cornea – 24 hours after incision

1. inflammatory cells next to wound – migrated from blood vessels at outer edge of avascular cornea!

2. epithelial cells have begun to proliferate near wound edge in preparation for bridging the gap

|[pic] |

|Corneal Laceration, 24h; Low Mag. |

|On the upper surface is the corneal epithelium; the arrows indicate collections of rabbit heterophiles caught in the act of migration into |

|the area of injury. |

#8: Rabbit cornea – 48 hours after incision

1. Injury has been re-epithelialized

2. collagen bundles separated by edema?

|[pic] |

|Corneal Laceration, 48h; High Mag. |

|The arrow indicates the cornea with the area of injury; a tiny area in a slide that also shows many interesting normal ocular structures |

|beautifully prepared. |

|[pic] |

|Corneal Laceration, 48h; Medium Mag. |

|Here there has been restoration of the continuity of the epithelium, but there is still increased epithelial thickness and disorder among |

|the collagen fibers. These abnormalities would ordinarily resolve completely over a period of days to weeks following the injury. |

#9: Rabbit ear: 48 hours after incision

1. example of a skin wound

2. because skin is vascularized see edema, infiltration by acute inflammatory cells, vascular congestion

3. wound filled with clotted blood

4. more complicated wound, see mixture of acute and chronic inflammation

5. can see granulation tissue

|[pic] |

|Skin Incision, 48h; Low Mag. |

|The wound is wedge-shaped in cross section, and is filled with a clot. The arrows indicate the approximate extent of the proliferating |

|epithelium as it is spreading out to reestablish continuity. |

|[pic] |

|Skin Incision, 48h; High Mag. |

|In this example there is more activity than we saw in cornea. The bleeding must be stopped and cells must be mobilized to clean up and |

|prevent infection. There is a mixture of acute and chronic inflammation, with proliferation of endothelial and fibroblastic cells. |

|[pic] |

|Skin Incision, 48h; High Mag., II. |

|Granulation tissue is edematous stroma with inflammatory cells secreting a stew of mediators that drive proliferation and direct cell |

|movement. Here we can identify blood vessels, but individual cells can be difficult to sort out because most appear relatively |

|undifferentiated at this stage. |

#41: Kidney; staphylococcal abscesses

1. example of an abscess

a. large numbers of PMNs

b. congested blood vessels

c. central zones are EMPTY, were filled with pus that was lost in processing

d. example of liquifactive necrosis!

|[pic] |

|Kidney abscesses, Medium Mag. |

|Here is another focal abscess, showing loss of underlying structure and accumulation of pus. Adjacent areas can be virtually normal or can |

|exhibit secondary changes related to damaged tubules and collecting ducts. |

[pic]

|In the lower pole of this kidney is a 1 cm pale yellow abscess. Infections can reach the kidney either by |

|ascending up the urinary tract (from a bladder infection, for example) or by hematogenous spread with sepsis. |

|This lone abscess was probably hematogenous in origin. |

#13: Heart; organizing fibrinous pericarditis

1. Demonstration of organization

2. Outer layer: fibrous exudates from injury of vessels surrounding pericardium and outpouring of plasma. Looks like an amorphous sheet of pink, netlike material without nuclei (but not as wavy as collagen fibers, looks more organized).

3. Pale zone between fibrin and myocardium: organizing zone, example of granulation tissue

a. Look for proliferating capillaries – look like the bright red spots in the pale zone. Capillaries are the HALLMARK of granulation tissue

b. With time, fibroblasts infiltrate and lay down new connective tissue – mild scarring results.

|[pic] |

|Fibrinous Pericarditis, Medium Mag. |

|The new blood vessels (white arrows point to two examples) stand out prominently in the pale organizing zone, while the exudate on the right|

|is red with condensed fibrin and entrapped erythrocytes. |

#82: Lung silicosis

1. Example of functionally significant scarring due to repair process.

2. Scarring is due to disorderly fibrous proliferation, it is harmful rather than helpful in this case.

3. Dense fibrous scars: amorphous acellular pink tissue

4. Can also see some persistent inflammation and less dense fibrosis in the patchy lighter areas

a. These inflammatory cells are chronic ones: lymphocytes, plasma cells and macrophages!

b. Plump pink cuboidal cells: specialized macrophages – hyperplastic type II alveolar lining cells

|[pic] |

|Silicosis, Low Mag. |

|This field shows the edge of a fibrotic nodule adjacent to recognizable but abnormal lung. Such interface areas are the best for going over |

|the changes described in the manual. The central portions of the scar nodules show little or nothing that is useful to see. |

|[pic] |

|Silicosis, Medium Mag. |

|In this view of the edge of one of the fibrotic nodules we can see the actively proliferating fibroblastic cells mixed up with pigmented |

|cells that are probably macrophages (blue arrows). Pure silica has no color of its own, but dust has other pigments in it and erythrocyte |

|breakdown in congested tissues leads to hemosiderin deposition; macrophages take up all these substances. The black arrows indicate clusters|

|of cuboidal epithelial cells that are probably hyperplastic surfactant-producers. |

|[pic] |

|Silicosis, High Mag. |

|Here we see several pigment-laden macrophages (blue arrows) loose in an alveolar space along with ribbons and nests of detached Type II |

|lining cells (black arrows). The septum is inflamed and beginning to become fibrotic. |

#102: Skin, keloid

1. example of unregulated scarring/fibrosis

2. see lots of disorderly collagen fibers – thick, glassy, randomly arranged

|[pic] |

|Keloid Scar, Low Mag. |

|This is a disagreeably "too pink" slide, but the epithelium is visible at the top; all the rest is fibrous connective tissue with thick |

|collegen fibers and few vessels. |

|[pic] |

|Silicosis, High Mag. |

|Here we see several pigment-laden macrophages (blue arrows) loose in an alveolar space along with ribbons and nests of detached Type II |

|lining cells (black arrows). The septum is inflamed and beginning to become fibrotic. |

Thrombosis

#40: Heart valve simple thrombus

1. irregular red and pink throbmus attached to the leaflet – example of a simple layered thrombus

a. pale layers – platelets and fibrin

b. dark layers – have trapped RBCs

c. known collective as the “Lines of Zahn” – telltale sign of a thrombus vs. a postmortem clot

2. Thrombus is not organized, can easily embolize

3. Simple thrombus because it is not infected

|[pic] |

|Nonbacterial Thrombotic Endocarditis, Low Mag. |

|In this section the thrombus' attachment to the valve leaflet is not apparent, but it can be seen in other planes. The lines of Zahn are |

|more easily appreciated, and these tell us at a glance that this was a thrombus rather than a postmortem clot. |

|[pic] |

|Nonbacterial Thrombotic Endocarditis, Medium Mag. |

|The black arrows indicate fibrin-rich areas, while the pale zones are rich in platelets. The arrangement is irregular, reflecting the |

|turbulence in the blood passing around the vegitation. |

#160: Heart valve, septic thrombus

1. Thrombi are favored sites of growth for some bacteria, this slide is an example of bacterial endocarditis

2. Still see the lines of Zahn, but see many irregular dark blue areas in the thrombus itself.

a. Dark blue areas = inflammation, calcifications, collagen and ground substance, even microbial colonies

b. Microbial colonies - granular-looking masses of lighter blue

c. Calcification – more amorphous magenta clumps

3. Causes of basophilic areas on slides:

a. Inflammatory cells

b. Collagen and ground substance

c. Calcifications

d. Microbial colonies

e. Tumor cells

|[pic] |

|Bacterial Endocarditis, LowMag. |

|Here we see the more normal valve tissue to the left and the vegitation to the right. This thrombus has undergone some organization, so it |

|is firmly attached by fibrous connective tissue to the valve. At the surface, however, regions of recent thrombus can be found (black |

|arrow). |

|[pic] |

|Bacterial Endocarditis, Hi Mag., II |

|At the surface of the vegitation, we can see colonies of cocci (black arrows) mixed with fresh thrombus . PMNs are infiltrating below, but |

|it is difficult for them to reach all the organisms. |

|[pic] |

|Bacterial Endocarditis, Medium Mag. |

|The vegetation is a mass of fibrin, platelets and entrapped cells, with ingrowing granulation tissue; once it becomes infected it is covered|

|with PMNs and other inflammatory cells as well as the microorganisms themselves. New thrombus with PMNs and microorganisms is indicated by |

|blue arrows. Calcifications are indicated by black arrows. |

#37: Artery and Veins with organized thrombi

1. These are examples of organized thrombi

a. Thrombus is replaced by fibrous tissue = organization

b. Thrombi do not look layered

c. In the pale areas of organization, can see chronic inflammatory cells, new capillaries (irregular endothelium lined channels), and fibroblasts laying down collagen

2. organized thrombi cannot embolize

3. Pigment deposits in the centers of occluded lumens = hemosiderin deposits

|[pic] |

|Thrombosed vessels, Low Mag. |

|In this image, the vessel on the left is exhibiting recanalization of a previous thrombosis. The vessel to the right appears relatively |

|normal, but the material in the luman looks like the contents of an atheromatous plaque: is that an embolus from an upstream plaque rupture?|

|[pic] |

| |

|Thrombosed vessel, Medium Mag. |

|The organized thrombus has been penetrated by vascular spaces of various sizes |

| |

| |

| |

|[pic] |

|Thrombosed vessel, Hi Mag. |

|Hemosiderin deposits are visible as brown pigment, along with nuclei of fibroblasts, endothelial cells and some residual lymphocytes and |

|macrophages. |

Atherosclerosis

#24: Aorta 19 year old male

1. should see structure of a normal large elastic artery

a. endothelium

b. tunica intima

c. tunica media (collagen and elastic fibers)

2. even at this age, however, can see fatty streaks (intimal thickening that can regress or develop into a full-blown plaque)

|[pic] |

|Normal Aorta, Medium Mag. |

|The intima is at the top (black arrows). Most of the media is occupied by collagen and elastic fibers. Note the relative thinness and |

|uniformity of the intima. Adventitia is not seen. |

|[pic] |

|Normal Aorta, Medium Mag. |

|In this field from our example of normal aorta, we have a region of intimal thickening (black arrows) that consists of some plump, pale |

|cells, probably carrying cytoplasmic lipid accumulations, and some more cellular areas of proliferation. This is a fatty streak, and these |

|are found from adolescence on in most persons subsisting on a Western diet. Some of these lesions may regress, while many progress to |

|full-blown atherosclerotic plaques. |

#172: Aorta, atheromatous plaque

1. note the intimal thickening between the endothelial surface and the tunica media

2. pinker regions: fibromuscular areas including the fibrous capsule

3. lighter pale zones: central core of the plaque containing lots of lipids

4. cholesterol clefts: jagged, spindle-shaped empty areas

5. foam cells: may be either macrophages or SMCs that are bloated with lipids

a. have centralized nuclei with whitish puff around them

b. found throughout the expanded intima

6. dark purple spots are lymphocytes, nuclei are about the same size are RBCs

|[pic] |

|Atheromatous Plaque, Low Mag. |

|The red arrow on the right indicates the transition from thickened intima to plaque proper; the black arrow indicates the thickest part of |

|the plaque. Deep to where the black arrow is pointing, one can see a paler area of cholesterol deposition. |

#178: Blood vessels from the leg; atherosclerosis, thrombosis

1. Arteries show sever narrowing of the lumen due to complicated plaues

|[pic] |

|Leg vessels with atherosclerosis and thrombosis, L |

|Here are six large vessels exhibiting different degrees of luminal occlusion. The one on the right seems to contain a recent thrombus, while|

|others exhibit multiple small irregular luminae of the sort that develop when old thrombi become recanalized. |

|[pic] |

|Recanalizing thrombus, Medium Mag. |

|This image is a higher Mag. of the vessels on the right hand side of the lower Mag. image. The recent thrombus is seen on the right of this |

|view. White arrows indicate a vessel with evidence of recanalization; the original lumen of this vessel is filled with connective tissue, as|

|happens when thrombi become organized. |

#180: Aorta: dissecting aneurysm

1. aneurism: partial failure of the wall of the heart or an artery, outpouching of the wall leads to further weakening of the wall, such that the wall stretches out like an inflated balloon

a. when occur in the heart, commonly due to injury or death of the muscle following an infarction

b. in arteries, common causes

i. atherosclerosis b/c plaques weaken arterial walls (most common)

ii. hereditary disorders of collagen or elastin (Marfan’s syndrome)

2. dissection: intima tears and blood forces its way between the layers of the wall

3. in our slide, look for dissection through the outer intima

4. can also see the true lumen with an atherosclerotic plaque

|[pic] |

|Scanning Image, Dissecting Aneurism, |

|The black arrows indicate the lumen of the aorta: cross section on the right, long section on the left. An atheromatous plaque is visible on|

|the luminal surface to the left. The colored arrows indicate the false lumen of the aneurism, where blood forced a new channel by tearing |

|into the vessel wall along a plane of weakness. In the cross section we can appreciate that the true lumen was narrowed at the expense of |

|the false lumen. Blood flow in the true lumen may be severely compromised, and outflow to branching arteries in the region reduced. |

Infarction

#176: Coronary artery; atherosclerosis, complicated plaque

1. lumen narrowed by recent thrombus

2. fibrous roof of the plaque has ruptured

3. thrombus itself may contain cholesterol crystals from the ruptured plaque

|[pic] |

|Coronary artery occlusion, Low Mag. |

|The arrow points to the occluded coronary artery, with epicardial fat around it and cardiac muscle toward the bottom of the Image. |

|[pic] |

|Coronary artery occlusion, Medium Mag. |

|Here we can see the lumen of the vessel with a pink-staining thrombus. In this slide, the thrombus can be seen to contain some light |

|staining, angular foci of cholesterol crystals from a ruptured atheromatous plaque. Not all the slides show such inclusions in the thrombus.|

|The actual site of plaque rupture would presumably have been upstream. |

|[pic] |

|Coronary artery occlusion, Medium Mag. |

|In this section the cholesterol deposit in the thrombus is not seen, but the area of initiation at the focus of plaque rupture is apparent |

|(orange arrow). The blue arrow points to the thrombus and the black arrow to areas of calcification and lipid deposit in the vessel wall. |

#165: Heart, recent transmural infarct

1. represents first stage of repair process: acute inflammation to remove debris

2. can see large pools of blood in the myocardial wall

3. endocardium still alive b/c it receives oxy from blood in the heart chamber

4. patchy looking myocardial tissue

a. pinker areas are healthy myocardium

b. red areas are dead (look darker b/c nuclei are pycnotic)

i. cells have lost distinct borders

ii. cells are swollen

iii. nuclei and striations are lost

5. this is an example of coagulation necrosis – outlines of cells and nuclei remain intact

6. can also see inflammatory response

a. see PMNs b/c it is a recent infarction

b. brown areas – hemosiderin indicative of dead RBCs due to hemorrhage

|[pic] |

|Slide 165a: Myocardial Infarct border, Medium Mag. |

|This Image is photographed from the larger 165 section; on this example it is possible to find areas of more viable myocardium. Here is an |

|interface between acute M.I. on the left and bottom and living heart muscle at 1 o'clock. The infarcted area is glassy pink and infiltrated |

|with PMNs, some of which are indicated by the dark arrows. |

|[pic] |

|Normal Myocardium, Medium Mag. |

|This is for comparison with the infarct. Note that the nuclei are evenly distributed and there is little apparent space between the fibers. |

|The staining is pale pink. Many of the smaller, dark irregular nuclei seen between the fibers are probably capillary endothelium. The |

|myocyte nuclei are larger, ovoid, and located within the fibers. |

|[pic] |

|Slide 165: Myocardial Infarct, Medium Mag. |

|This field is from the middle of an infarcted area, and the nuclei of the fibers are mostly gone. The spaces between the fibers are filled |

|with exuded fluid and PMNs. |

#161: Heart; myocardial infarct 2 weeks old

1. represents second stage of repair process: formation of granulation tissue

2. irregular pale areas: dead myocardial granulation tissue

a. bright red dots: ingrowing blood vessels

b. can also see fibroblasts

c. can see nuclear dust – tiny purple spots around the cells that are disintegrated nuclei that underwent karyorrhexis

d. inflammatory cells that are present are of the chronic variety: macrophages (with hemosiderin), lymphocytes

3. this granulation tissue will turn into a scar as fibroblasts lay down collagen

|[pic] |

|Slide 161: Myocardial Infarct, 2 weeks old; Scanni |

|The black arrow points to the endocardial surface, while the blue arrow indicates areas of granulation tissue replacing destroyed heart |

|muscle. |

|[pic] |

|Slide 161: Myocardial Infarct, 2 weeks old; Low Ma |

|Residual muscle fibers can be seen to the left, with loose, vascular connective tissue in the center of the field. Hemorrhagic foci are seen|

|to the right. |

#166: Heart; myocardial old infarct, fibrosis

1. represents third and final stage of repair: scarring

2. pale areas interspersed with heart muscle – can see mature fibrous tissue w/ fibroblast nuclei

3. can also see that cells closest to the endocardium took the biggest hit (except the endocardial cells themselves), those closest to the epicardium took the least hit.

|x[pic] |

|Myocardial Fibrosis, Low Mag. |

|Here we see scar tissue (black arrows) infiltrating between the myofibers in a fashion similar to the acute exudates in the recent MIs seen |

|earlier. In patients who survive, infarcts eventually heal with fibrosis replacing destroyed myofibers. |

#186: Kidney; infarct

1. classic shape of an infarct: WEDGE-shaped

2. pale zone: area of coagulation necrosis

3. dark zone: borders the pale zone, area of acute inflammation and hemorrhage

|[pic] |

|Gross Specimen, Kidney Infarct |

|Here is a bisected fresh kidney showing a wedge-shaped infarct with the apex pointing toward the renal pelvis and the base on the cortex. It|

|is outlined by a hemorrhagic border. |

|[pic] |

|Kidney Infarct, Low Mag. |

|The arrow indicates the border between the pink infarct on the right and relatively normal kidney on the left. |

|[pic] |

|Kidney Infarct, Medium Mag. |

|At higher Mag. in the infarcted area, one can recognize that the nuclei of the tubule cells are lost, and the tissues exhibit the familiar |

|amorphous pinkness we have seen in other infarcted organs. As in other acute ischemic infarcts we have seen, this is coagulation necrosis. |

Benign Proliferations

#248: Vulva, condyloma acccuminatum

1. epithelial proliferation driven by HPV

2. papillary architecture: squamous epithelium surrounding cores of connective tissue

3. orderly maturation sequence of 3 layers within the epithelium still seen

a. basal to

b. spinous to

c. squamous layer

4. cells within each layer also resemble each other (all cells are the same horizontally)

5. in the upper spinous layers, can see highly vacuolated cells – these contain large amounts of the virus

|[pic] |

|Scanning Image, condyloma accuminatum |

|The black arrow indicates the epithelium and the blue arrow points to the connective tissue core of one of the finger-like projections. Some|

|of the "fingers" of tissue pass through the plane of section and are cut off so as to appear as isolated islands of connective tissue |

|completely surrounded by epithelium. |

|[pic] |

|Condyloma accuminatum, Medium Mag. |

|The black arrows point to some of the the vacuolated cells that are full of HPV. The tiny dots in the epithelium that are more numerous |

|toward the surface are nuclei of polys; this specimen exhibits acute inflammation, probably due to local irritation. The connective tissue |

|shows edema and congestion of vessels, as expected in this setting. |

#203: Rectum, adenomatous polyp

1. polyp: outgrowth into a body cavity that arises from the lining mucosa, usually has abnormal proliferation of the epithelium with folding and development of CT stalks. Looks like a little tree.

2. epithelium is quite blue b/c the nuclei are large and numerous. However, this doesn’t represent the hyperchromatism you see with dysplasia because the nuclei themselves are just densely packed, but otherwise normal.

3. dark intense pink stuff within the CT of the stalks: blood vessels

4. some mucin can be seen - looks clear, within the gland lumen

|[pic] |

|Scanning Image, Adenomatous polyp |

|This is a small segment of the wall of the colon, with the polyp projecting like a tree on the left. The arrow indicates a common type of |

|folding artifact seen in large fragile specimens; such folds are often noted to be parallel to one another and to the edge of the microtome |

|blade used in cutting the section. Once recognized, such artifacts may be ignored. |

|[pic] |

|Adenomatous polyp, Medium Mag. |

|Here the epitheium can be seen to be simple columnar, with densely packed but relatively normally arranged nuclei. As noted in the manual, |

|such a polyp is considered to be neoplastic but benign. |

#153: Jaw, ameloblastoma

1. Class of neoplasms called odontogenic tumors.

2. exhibits a “plexiform” growth pattern – tumor forms a network of interconnected epithelial strands with large cavities in-between.

a. Some cavities are filled with CT

b. Some cavities are empty are would normally be filled with pus

3. hard to see distinct cell borders.

|[pic] |

|Ameloblastoma, Low Mag. |

|This is a mass of tumor tissue that is difficult at first to orient. The epithelim in some areas forms cysts (white arrows) that would be |

|fluid-filled in situ. In other areas there is loose connective tissue with vascular spaces (black arrows). The interlacing ribbons of |

|epithelium look netlike or "plexiform". |

#101: Fibroma (benign spindle cell tumor)

1. solid mass of light-staining tissue filled with small spindle-nuclei cells

2. cells look exactly like normal fibroblasts, but have indistinct cell borders

a. not cancer because the nuclei are largely the same size, mitotic figures are rare

3. Blood vessels evenly spaced

|[pic] |

|Fibroma, Medium Mag. |

|To the left of the field is an area of elongated nuclei in parallel; to the right is an area where a fascicle was cut across. Cytoplasmic |

|borders are indistinct, but the shape of the cell generally coincides with the shape of the nucleus, so we describe these cells as |

|spindle-shaped or fusiform. The tissue looks benign in that the nuclei are pale-staining and uniform in appearence, with no mitotic activity|

|evident. |

#20: Uterus; leiomyoma (uterine fibroid tumor)

1. leiomyoma = benign smooth muscle tumor, extremely common benign tumors of the uterus

2. fibroid is visible at one side as well-demarcated, hemispherical, deeply eosinophilic nodule

3. tumor cells look like SMCs

a. blunt-end nuclei

b. pale chromatin

c. even spacing

d. “corkscrew” twists when viewed longitudinally

4. SMC fibers look disorganized – will see fibers cut longitudinally and in cross-section right next to each other

5. not leiomyosarcoma because little or no mitotic activity, cells are extremely uniform in appearance

|[pic] |

|Scanning Image, Leiomyoma |

|In this scanning image, the endometrial surface is seen at the bottom, with the arrow in myometrium, pointing to the fibroid. Note the |

|sharply circumscribed border between the nodule and its surroundings; this suggests a benign process. |

|[pic] |

|Leiomyoma, Medium Mag. |

|These smooth muscle tumors are very bland-appearing, with fascicles of uniform cells. There is little to be gained from high magnification, |

|as the major cues for the diagnosis are the circumscribed borders and the homogeneity of the tumor that is readily apparent here. |

#52: Breast, fibroadenoma

1. epithelium and stroma proliferate in tandem: can see both neoplastic glandular epithelium as well as marked proliferation of the supporting CT

a. only the epithelial component is clonal however

2. encapsulated nodule with inner plexiform arrangment

a. pale empty looking areas: connective tissue

b. dark staining “cords”: ductal epithelium

|[pic] |

|Scanning Image, Fibroadenoma |

|Here the arrow points to the well-circumscribed tumor. Such a low-mag appearence of encapsulation suggests a benign tumor in most cases. |

|[pic] |

|Fibroadenoma, Medium Mag. |

|This field shows the basic pattern of the tumor, with strands of ductal epithelium proliferating in tandem with "immature" connective |

|tissue. Note the orderly spacing of epithelium, connective tissue, blood vessels and fibrous septae; these relationships suggest that the |

|tissue is responding to signals that modulate growth to some degree. |

Carcinomas

#25: Cervix, Squamous cell carcinoma

1. sharp transition point between normal stratified squamous epithelium to invasive tumor

2. deeply basophilic epithelium can be seen invading the cervical stroma

3. epithelial nests have weird looking tumor cells!

a. Big N/C ratio

b. Pelomorphic nuclei

c. Prominent nucleoli

d. Mitotic figures found

4. some epithelium nests are necrotic in the center, have outgrown blood supply

5. can also see epithelial cells invading lymphatics

a. find an artery and look close to it, will see a lymphatic duct

b. cancerous ducts look like a little cluster of tumor cells separated by a white clear circle

6. example of a moderately differentiated tumor: some keratinization present (indicating epithelial origin), but many tumor cells malignant but otherwise nondescript.

|[pic] |

|Cervical cancer, Low Mag. |

|This field shows the area where normal cervical epithelium on the left gives way to squamous carcinoma toward the right. Irregular islands |

|and strands of dark-staining tumor epithelium can be observed invading into connective tissue. There is a dense infiltrate of inflammatory |

|cells associated with the tumor; at higher mag these can be recognized as mostly lymphocytes. Such a host response is relatively common |

|around malignancies, and sometimes carries with it a better prognosis. |

|[pic] |

| |

|Medium Mag., Cervical cancer |

|Here is a closer view of the hyperchromatic, disorderly tumor cells. The black arrow points to tumor cells inside a lymphatic|

|vessel. |

| |

| |

| |

|[pic] |

| |

|Cervical cancer, Hi Mag. |

|The black arrow points to a pocket of squamous differentiation; the cell borders are distinct and at higher mag intercellular|

|bridges could probably be seen there. On the other hand, the cells exhibit abnormally large nuclei and a moderate degree of |

|pleomorphism and hyperchromaticity. These cytologic features of malignancy correlate with the invasive growth pattern visible|

|at low Mag. to confirm the diagnosis of cancer. |

| |

| |

| |

#22: Endometrium, adenocarinoma

1. this slide is well-differentiated glandular carcinoma (adenocarcinoma)

2. tumor is deeply basophilic, growing in papillary projections both outward and inward

3. tumor cells are growing as cords:

a. two rows of columnar cells “back to back” against stromal CT

b. can see RBCs within each CT strip

4. carcinoma because

a. no apparent mucus production (= loss of fxn)

b. nuclei appear more “open”

c. mitotic figures readily apparent

|[pic] |

|Scanning Image, Endometrial CA |

|In this scanning Image, the tumor is the basophilic part indicated by the arrows. Myometrium is to the left. |

|[pic] |

|Endometrial CA, Medium Mag. |

|The arrow points to one of the gland-like spaces formed by the tumor; residual "normal" glands can be seen to the left. The microscopic |

|diagnosis of malignancy depends on the growth pattern and cytology of the neoplastic cells, and this tumor is invasive and disorderly in its|

|growth pattern, although it is quite well differentiated cytologically. |

#119 Esophagus: Squamous cell carcinoma

1. pink-staining tissue with central blue area

2. this tumor has ulcerated – epithelium lost its integrity, exposing CT to outside world

3. tumor is slightly more pink than normal because cancer cells are producing keratin

4. look for foci of necrosis with pynotic tumor cells and PMNs

|[pic] |

|Scanning Image, Esophageal CA |

|The arrows indicate the region of the tumor. The muscularis externa of the esophagus is visible at the right arrow, and there it seems to be|

|"pushed" by the mass; on the other hand it seems to disappear beneath the middle portion of the tumor, where it is invaded and perhaps |

|destroyed. |

|[pic] |

|Esophageal CA, Low Mag. |

|The black arrow points to an invasive nest of tumor cells, perhaps in a vessel. The white arrow indicates a tumor island with a focus of |

|central necrosis, a prominent feature in this example. Necrosis is seldom a feature of benign neoplasms. |

#120: Breast carcinoma

1. look for discrete expanded clusters of larger, pale-staining cells that break the basement membrane and disperse into the stroma

2. desmoplastic stromal reaction: stromal reaction in response to tumor invasion, stromal cells surround tumor nests with collagen

3. Small basophilic calcified bodies: “psammoma bodies”

|[pic] |

|Breast CA, Low Mag. |

|The arrows point to areas of tumor; the tumor masses contain stromal fibroblasts and inflammatory cells in addition to the tumor cells |

|themselves, so they appear rather solid on low-mag exam. The ductal structures visible at this power are residual gland elements. |

|[pic] |

|Breast CA, Medium Mag. |

|All the round nuclei in clusters belong to the tumor cells. Comparison of the stroma with the area of more normal fat at the lower right |

|highlights the degree of desmoplasia evoked by the cancer. |

#112: Colon, adenocarcinoma

1. can see that the tumor has penetrated and abolished muscular layer, extends all the way through the fat

2. can see columnar tumor cells arranged in glandular spaces

3. see inflammatory reaction around tumor cells

|[pic] |

|Scanning Image, Colon CA |

|In this scanning view, the arrow points to the area of tumor where invasion of the muscularis is apparent. To the right and lower is the |

|area of extention into adventitia. |

|[pic] |

|Colon CA, Low Mag. |

|The black arrows outline an area of tumor, with normal mucosa for comparison below (white arrow). Tumor cells grow here in a papillary |

|configuration, and the cells can be seen to be much darker-staining than their benign counterparts. |

#184: Lung, squamous cell carcinoma

1. starts as metaplasia: pseudostratified columnar epithelium gets replaced by squamous epithelium

2. progresses to dysplasia (disorderly growth) – can find atypical cells with disordered stratification

3. look for squamous differentiation, central necrosis in the tumor nests, cellular anaplasia

4. look for keratin pearls: hard pink, dense balls, little bigger than a normal cell

a. sign of a carcinoma because epithelial cells make keratin

|[pic] |

|Lung CA, Low Mag.,II |

|This is another view of transition from relatively normal epithelium (on the left) to invasive carcinoma. The white arrows indicate the |

|smooth muscle layer. Invasive nests of cancer cells are indicated by black arrows. Some have penetrated the muscularis. |

|[pic] |

|Lung CA, Medium Mag |

|At the top is dysplastic epithelium with squamous differentiation, pleomorphism and loss of orderly stratification. A few invasive nests are|

|seen above the muscularis, but many malignant nests and cords of epithelium are visible in the submucosa (black arrows). |

|[pic] |

|Lung CA, High Mag |

|Here much of the field is taken up by nests of squamous CA (black arrows) that were found deep to the bronchiolar cartilage. The nests have |

|undergone central necrosis amd PMNs fill areas of liquifaction degeneration. The squamous differentiation is easy to appreciate, but the |

|epithelial cells no longer form a sheet on the surface but rather proliferate unchecked through the connective tissue. |

Other malignancies

#103: Fibrosarcoma

1. compared to the fibroma, can see

a. pleomorphic nuclei and cells

b. mitotic figures

c. tumor giant cells

i. arise from multiple nuclear divisions without division of the cell cytoplasm

2. typical of a spindle cell malignancy

|[pic] |

|Fibrosarcoma, Low Mag. |

|At this Mag.nification one can appreciate that this is very abnormal-looking connective tissue; the nuclei are too numerous, there is too |

|little extracellular matrix, and the pleomorphism of the cells is obvious even at low Mag.. Usually tumors like this arise in deep soft |

|tissue, are quite large, and exhibit gross evidence of infiltrative, destructive growth. |

|[pic] |

| |

|Fibrosarcoma, Medium Mag. |

|Here the tumor cells can be seen to be wildly anaplastic; at the microscope numerous mitoses, many of them atypical, |

|reinforce the impression of malignancy. |

| |

| |

| |

#106: Osteosarcoma

1. Tumor sitting in the medullary cavity, is invading the surround soft tissues

2. Can see the tumor forming bone directed both inward and outward: radiating trabeculae that correspond to “sunburst” opacifications on radiographs

|[pic] |

|Scanning Image, Osteosarcoma |

|The black arrow indicates the residual cortical bone. To the right, the marrow is filled with tumor, but there is not much tumor bone |

|production. The white arrow shows where tumor is extending beyond the cortex, and there are radiating spicules of tumor bone which would |

|look like a "sunburst" on a radiograph. This is the area easiest to identify as osteosarc. |

|[pic] |

|Osteosarcoma, High Mag. |

|Here one can see malignant mesenchymal cells associated with the osteoid in a tumor area. The black arrows indicate a few good examples, but|

|most of the cells in this field are malignant ones. The diagnosis of osteosarcoma is made when malignant cells are demonstrated to be making|

|bone. |

#151: Ewing’s sarcoma

1. rare, aggressive childhood bone malignancy of unknown origin

2. tumor sits in the bone marrow cavity, causes enhanced bone resorption

3. between the tumor cells and the bone cortex – “halo” of reactive lamellar bone formed in response to the lifting of the periosteum by the tumor growth.

|[pic] |

|Ewing's sarcoma, Low Mag. |

|To the right is the original cortex of the bone, with reactive bone in the middle of the field, to the left of the white arrow. The black |

|arrows point to areas of infiltrating tumor cells all through the specimen. |

|[pic] |

| |

|Ewing's sarcoma, Medium Mag. |

|Here the arrows point to an area of cellular tumor outside of the reactive bone. The tumor cells are relatively densely |

|packed and undifferentiated. |

| |

| |

| |

#152: Bone, myeloma

1. bone marrow tumor that produces immature plasma cells

a. large amounts of monoclonal Igs released into the circulation

2. you see only plasma cells in the bone marrow, then there should be many different types

|[pic] |

|Scanning Image, Myeloma |

|One can appreciate that this is a cross section of a tubular bone that has the marrow cavity filled up with basophilic cells. The arrows |

|indicate an area where the cortex is eroded from within. |

|[pic] |

|Myeloma, Medium Mag. |

|In this image the homogeneity of the tumor to the right of the bone is striking; this is a clonal expansion of plasma cells, so it should |

|not be surprising that all the tumor cells look similar to one another. |

|[pic] |

| |

|Myeloma, High Mag., II |

|In this field one can appreciate the plasmacytoid look of the myeloma cells; they have circumscribed borders, basophilic |

|cytoplasm and some show nuclei with peripheral chromatin clumping to produce the "clockface" look. |

| |

| |

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