ALL!!! Flashcards
Actinomycosis (acute inflammation)
Caused by actinomyces bacteria, which is present in many places, especially endometrium and subcutaneous tissue.
o Gram positive rod part of normal oral flora
o Sulfur granules
Whole slide is bluish, indicating nuclei of the bacteria
Many PMN, plasma cells, macrophages
This is purulent stage of acute inflammation
Not an abscess because the pus is not well-circumscribed
Bleeding
Acute Appendicitis
Obstruction of orifice (stool, tumor)progressive increase in intraluminal pressure compresses venous outflow ischemic injury and stasis of luminal content bacteria proliferate
Complications: ulceration, peritonitis
Edema, neutrophilic infiltration of lumen and tissue
Mucous membrane is partially missing, indicating ulcer (left side)
Lymphocytes are normal feature, neutrophils are not
Secondary lymph follicles do not have germinal centers
Muscle has abnormal appearance: too many cells, neutrophils present here (contrast with
lymphocytes of pericarditis)
o Transmural inflammation reaching outer layer
This is appendicitis ulcerophlegmonosa (vs. simplex)
Fibrin on the surface is inflamed peritoneum
Endocarditis bacterialis
Endocarditis mostly affects valves
o Exception: Libman-Sachs endocarditis develops on parietal endocardium
Macroscopically, valve has vegetations
This section is from a valve
Note myocardium at bottom of slide
Vegetations are composed of fibrin and bacterial clouds, which stain blue
Endocarditis can be infection (caused by microorganisms) or non-infectious (e.g. rheumatic
endocarditis, Libman-Sachs, marantic)
o Infection endocarditis can be acute or subacute
Acute Rejection
Totally sclerotized glomerulus seen
Tubulitis = lymphocytic infiltration of tubules with mononuclear cells (nuclei larger than normal)
Subendothelitis
Macrophages
Signs of organ rejection. There is Banff categorization for grading rejection
Hyalinosis of vessels = thickening of arteriolar walls with hyaline
Adenocarcinoma coli
Top right corner is normal mucosa
Glands in the tumor are more variable, pseudostratified
Tumor glands are present in and under the muscularis mucosae
o Muscularis mucosa is broken, indicating that the tumor is advanced, malignant
Also see tumor glands in the subserous fat tissue
Pink = stroma
Dark glands = parenchyma
Adenocarcinoma
Well-delineated larger part on the left with acellular elements
Note mucin and cholesterin crystals
Glands are irregular, immature
o Invasive, spreading in neostroma, which is not usually in the lung
Adenocarcinoma, Diffuse Type H&E
Mucosa on left, normal on low power
Upper left = normal foveolar pit
o Lamina propria mucosae has signet ring cells, which are epithelial cells producing mucus that pushes nucleus to the side. “diffuse” type because the border of the tumor is not clearly differentiated
These tumors do not form gland-like structure; they are poorly differentiated
Adenocarcinoma of the prostate
Normally we see smooth muscle and glands
Blank ink at top shows the resection margin
Lymphocytic proliferation
Basal layer: inner columnar, outer flattened
Normal gland structure with some nodular hyperplasia
Tiny holes: just the inner layer is present
Nucleoli seen in the single-layered cells forming gland-like structures
Prostate cancer usually develops at outer margin
Corpus amylacea may rupture gland inflammation
PIN (prostate intraepithelial neoplasm) seen with multilayered glands Seminal vesicle, lipofuscin
Anemic Myocardial Infarction
Myocardium
Infarct = loss of function and necrosis due to ischemia (inadequate blood flow)
o Anemic infarct = pale, white; usually observed in tissues supplied by terminal arteries, and in solid organs (spleen, kidney, liver)
o Hemorrhagic infarct = red, typical in lung because of double blood supply, in loose tissues, and with venous occlusions (e.g. ovarian torsion)
Eosinophilic, necrotic patch. No nuclei are seen in the cardiomyocytes of the infarcted area.
Red discoloration is due to RBCs from damaged capillaries, seen at higher power.
Border of non-infarcted and infarcted area has mild inflammation, e.g. neutrophil
granulocytes.
Signs of necrosis:
- Nuclear changes:
o karyolysis = no nucleus
o karyopyknosis = shrinkage o karyorhexis = breaks up
- Cytoplasm swollen and eosinophilic
White spaces seen between cardiomyocytes are artifacts from edema
Eosinophilic “necrotic bands” are present due to hypercontraction of the sarcomeres
Lipofuscin seen among the healthy myocytes. This is a ‘wear and tear’ pigment that
accumulates in the nuclei with age.
AML – myeloperoxidase
Immunohistochemistry
Brown granulations in cytoplasm contain the myeloperoxidase. These are Auer rods.
o MPO is major constituent of cytoplasmic granules of neutrophilic myeloid cells. Since primary granules appear early in myeloid cell differentiation and are present throughout maturation, myeloperoxidase is a useful marker for detection of myeloid cells.
o MPO+ indicates that they have differentiation towards granulocytes (i.e. not M0 classification.
o In M3 promyelocytic classification, there would be more Auer rods.
AML – H&E
Normally, PMN, lymphocytes, monocytes, RBC, platelets are seen. Blasts and megakaryocytes are not.
o Neutrophils make up 60% of normal WBC
o RBC make up ~45% of peripheral blood (i.e. hematocrit)
Here, we see big, immature leukocytes that are blast equivalents
Instead of normal distribution, there are uniform, immature myeloblasts
Many WBC, few RBC seen
Bone marrow is not producing RBC or platelets, but rather, releases immature WBC that
cannot perform their immune function.
FAB classification is used based on morphology (M0-M6):
o M0: Undifferentiated AML
o M3: promyelocytic leukemia = treat with retinoic acid, otherwise DIC
Adenomatous Polyp
Polyp protrudes into lumen. The polyp is the entire circular structure on the right
Boarder between polyp and tumor:
o Nuclei normally sit at bottom of goblet cell glands. The tumor is pseudostratified with nuclei apically situated.
Mucus secretion decreased
Fewer goblet cells
Disorganized nuclei
Morphological variation about cells
Benign = adenoma; malignant = adenocarcinoma
Observe muscularis mucosae: if the tumor glands don’t infiltrate the muscularis mucosae,
then it is an adenoma (seen here)
Cell line from tumor (apoptosis)
Lymphoid cell line
Lymphocytes have thin ring of cytoplasm surrounding nucleus
Apoptotic cells display karyorhexis or karyopyknosis
o Irregularly shaped nuclei being pushed out
Appendix Carcinoid (H&E)
Blood, PMN, lymphocytes
Normal border
Normal wall with smooth muscle elements
Chronic inflammation through wall into peritoneum. In the bottom of the H&E stain, you can
see salt and pepper nuclei in an island of cells
Neuroendocrine tumor, which used to be described as “carcinoid”
o Neoplasm of APUD (Amine Precursor Uptake Decarboxylase) cells that show differentiation for neuroendocrine elements
Chromogranin A, synaptophysin, and CD56 are neuroendocrine markers that can be used for staining.
o Proves that this is a neuroendocrine tumor
Note infiltration (dispersed spreading of brown cells)
Neuroendocrine Tumors (NET)
o Grade 1
o Grade 2
o Grade 3 = Neuroendocrine Carcinoma
Appendicitis is also seen. Not infrequently, it is found together with the neoplasm.
Arteritis
Frozen section
Lipids in intima can be seen
This is giant cell arteritis. There are 2 types of giant cell arteritis: o Takayasu: affects aorta
o Arteritis temporalis: affects temporal artery and vessels of head and neck
Since this is not in the aorta, this is a slide of arteritis temporalis
Vessels have small lumen
Painful, can cause blindness if it affects the ophthalmic artery
Giant cells are multinucleated. Other examples of giant cells:
o TB granulomas have Langhans cells o Foreign body giant cells
o Anitschkow cells in rheumatic fever
To diagnose arteritis, must take multiple segments of the artery
Aspergillosis H&E
Eosinophilic, dense part vs. airy part
Airy part has thicker septa with eosinophilic material in alveoli
Dense part has no nuclei. This is necrotized tissue
o There are rods with tree-like, septated walls with 45° bifurcation growing in the necrotized tissue
At the left edge, normal structure is recognized better.
Vessels are filled with collection of rods, which then penetrate the vessel rod
o Invasion of vesselinfarctionnecrosis
This infection occurs in immunocompromised patients
Aspergillosis Grocott Stain
Septa are stained by Grocott
Elastic fibers of vessels are also stained
Asthma Bronchiale
Type I Hypersensitivity
Emphysematous parts are called “distensions”
o Septa are destroyed
o Bronchi are dilated and filled with purplish material o Expiratory dyspnea (hyperinflation)
Lymphocytes, mucous gland hyperplasia, and destruction of wall = signs of inflammation
Smooth muscle cells of bronchi proliferate in chronic asthma
Exudate
Denuded epithelium, thickened basement membrane
Deep purple plugs filling the lumens are “Curschmann spirals” = mucin + eosinophils
Arteriosclerosis
Nephrosclerosis arteriolosclerotica
Macroscopically, the kidneys are evenly granulated bilaterally.
Caused by hypertension and/or diabetes
The kidney has 3 units. Damage to one causes secondary damage in the other 2.
o Tubulo-interstitium
o Blood vessels
o Glomeruli
Here, the glomeruli look normal. The tubuli are slightly dilated with eosinophilic cylinders,
but mostly normal.
The arteries have thick walls, narrow lumen
Consequences of hypertension:
o Kidney failure
o Stroke
o Cardiac hypertrophy IHD
In the small arteries:
o Malignant hypertension causes
fibrinoid necrosis
o Benign hypertension causes hyaline
deposition.
o Both are eosinophilic and cannot be distinguished here.
In medium-sized arteries:
o Malignant hypertension makes vessels hyperplastic o Benign hypertension causes fibroelastosis
o Cannot be distinguished here.
Parenchyma has diffuse scarring
o Diminishes functional reverse of kidney
Atherosclerotic Artery – Aorta; Oil Red O stain
Frozen section
Lipids in intima can be seen
Atherosclerotic Artery - Aorta
There are 3 types of arteriosclerosis
- Atherosclerosis – seen here
- Arteriosclerosis
- Monckeberg type media sclerosis
Intima, media, and adventitia can be seen here
Plaques affect the intimal layer
o This is a calcification, so it stains bluish with hematoxylin
o Rhomboid empty white spaces where cholesterol has been washed out.
breast cancer HER-2 immunohystochemistry
HER2 is a member of the human epidermal growth factor receptor family
Membrane becomes brown because tumor has receptors on the cell surface which can be
used as a target for therapy
The presence of HER2 or other epidermal growth factor receptors indicates that this growth pathway is involved, and growth is aggressive. It used to have a bad prognosis, but now, it can be treated with antibody therapy (Anti-HER2)
Carcinoma Ductale Invasivum Mammae
Normal duct with myoepithlial cells can be seen at the top o Terminal ductulolobular unit of normal breast tissue
Black ink is used to see if tumor was completely removed
Island of cells in the middle of the slide show tumor cells of uneven size and shape invading
fatty tissue.
o Many such islands indicate the invasion
o Some have remnants of lumen in the center
Mitotic cells
Breast cancers:
o 90% ductal carcinoma (invasive ductal cancer)
o 10% invasive lobar cancer
This one is a high grade form with low-differentiation
Nottingham Grading Scale/Prognostic Index
o Glands: score 1-3
o Mitotic index: score 1-3
o Heterogeneity of polymorphism of cells: score 1-3
o 6-7 points = grade 2; 8-9 = grade 3 Groups of cells without sharp border
We also use other immunohistochemical methods to determine the grading.
Bronchopneumonia
More common than lobar pneumonia (both occur when there is exudate in the alveolar spaces)
Infection and inflammatory response spreads through bronchial tree lymph as focal adhesions
o Pneumonia originates from bronchioles
o Inflammation occurs in nodular pattern, and the nodules can be felt macroscopically
Tissue is more solid in some regions
Cells in alveoli instead of air
Alveolar structure present, but wall is thick with dilated vessels due to inflammations
PMN cells and fibrin in exudate
Carcinoma basocellular
Carcinomas are cancers with epithelial layers
Upper center: no epidermis (ulcerated)
o Ulceration because the tumor under epidermis cuts off blood supply to epidermis o “ulcus rodens” = crawling ulcer
o Hemolyzed RBC on surface
Trabecule-like structures spread deep into surface o Basophilic
o Islands separated by white line (“retraction”) which is an artifact characteristic for this tumor
Crowded blue appearance due to basal cells making palisading structure. Most of the basal cells are not mature, i.e. do not show squamous differentiation
o However, a squamous pearl is seen here
Malignant, but does not metastasize
Characteristic radial orientation of nuclei
Associated with sun exposure
o Bottom left: solar elastosis
Follicles seen on the right side
Krompecher tumor = slow-growing epithelial tumor derived from basal cells
Tumor spreads in “neostroma”, which is the tumor’s own, more firm stroma.
Resection margin on lower left is close to tumor.
Cervical Carcinoma
This is invasive because it breaks through the basement membrane, and thus gets in contact with the circulation
In situ removal means that the entire tumor can be removed
Staging is important. Use a pap smear
Squamous cell carcinomas are the majority of cervical cancers
o Most occur pre-menopausally
Majority of endometrial cancers are adenocarcinomas
o Most occur post-menopausally
o Hormone-related, not HPV
Surface has thin layer of normal epithelium
Lumen with mucous-producing columnar epithelial cells. This is a dilated gland.
Naboth cysts – normal, present in all females
Squamous epithelium disappears on right edge. This is ulceration/erosion
Inflammation shows that this is not an artifact
Note mitotic figures
This is a squamous cell carcinoma.
Basement membrane is not seen with H&E, but we know it should be above the connective
tissue.
Treatment is conization.
Hepatocellular carcinoma
Hepatocellular carcinoma is a complication of cirrhosis
Common in Africa and Asia, making it the third most common carcinoma worldwide, and it
is increasing in incidence
Metastatic tumors in the liver are general 20x more common.
If the liver is not cirrhotic, it is most likely a metastasis. The exception is HCC in children, who acquire HepB from their mother, which leads to HCC without cirrhosis
The most common primary liver tumor is hepatocellular carcinoma.
Factors that increase HCC: HepB, Aflatoxin from Aspergillus
The capsule is the sharp line in the middle separating the cirrhotic liver below from the
cancer above
HCC are frequently encapsulated
The cancer has polygonal cells with large nuclei and pseudoacinar structure
No portal area seen
Abnormal arrangement
Well-differentiated
If tumor is removed, the cirrhotic liver cannot regenerate, thus transplant is the best option.
Carcinoma lobulare invasivum
Tumor can only be seen with highest magnification in center of slide
Does not form tumor mass. Area appears hypercellular in center of cell
Tends to be bilateral
Less common than ductal carcinoma
Small cells that do not form glands
“Corn seed” arrangement
Metastasis can be to gastric or colonic mucosa
Infiltration between the cysts
Lymph Node Metastatic Carcinoma
Large paler purple mass is the neoplasm. More regular lymph node features can be seen at the periphery
o Encapsulated structure within normal lymph tissue
Trabecules are made up of crowded cells
Islands of eosiniphilic material looks like thyroid gland colloid
o Characteristic of papillary thyroid carcinoma which has spread into LN
Sinus histiocytes at border are a reactive process
Pancreatic Carcinoma
Ductal carcinoma is the most common and most lethal form
Islets, scar tissue with chronic pancreatitis, dysplastic ducts
Peripheral nerve cross-section with cells in capsule. Perineural spreading is typical of pancreatic carcinoma
This causes the symptom of back pain
Ducts with increased basophilia
Caseous Necrosis – Lymphadenitis Tuberculosa
Necrosis (~coagulative + granuloma formation) in infected tissue not related to blood supply o Caused by mycobacterium infection
TNF, hypoxia, free radical injury
Amorphous eosinophilic part in the center is the necrotic core with granular debris
Structure disappears, becomes foamy pink “tuberculitic granuloma”
o Granulomas surrounded by histiocytes (=mononuclear phagocytes), lymphocytes and Langerhans giant cells.
o Activated macrophages surround the necrotic core. The ones with pink, granular cytoplasm and indistinct cell boundaries are epitheloid cells because they resemble epithelia.
Fibroblastic layer surrounds the granuloma in an attempt to “wall off” the microbe from healthy tissue. Lymphocytes (T helper cells) here.
Cervix in situ Carcinoma
Normal squamous epithelium seen on the left
o Vacuoles due to dissolved glycogen
Junction has undifferentiated, disorganized cells
o Lack of maturation
o Polymorphic
Cervical intraepithelial neoplasia
o Border sharpness indicates that tumor cells have not broken through basement membrane. Therefore “in situ”. Tumor can be completely removed.
o Blood and lymph vessels do go through the basement membrane.
Dark island deep in the cervix looks like the neoplasia has spread through the glands, but it is
a “pseudoinvasion” because it still has not broken through the membrane.
Cholecystitis
Infection of the gall bladder, mostly associated with gall stones
Thicker, scarred tissue, uneven surface
Lymphocytes indicate this is chronic
Mucosa is covered by a single layer of columnar epithelium
Note that the wall has lumina covered by surface epithelium. This is not an invasion, but an invagination
Yellow = concentrated bile
Cholestasis – Core Biopsy
Normal lobular structure maintained
Greenish/brown material located between cells in Disse spaces is bile.
Intracellular accumulation in hepatocytes caused by:
o Impaired metabolism
o Extrahepatic bile obstruction
o Reduced excretion due to severe inflammation
Cholestasis (stasis of bile flow) is pathological
Cholestasis in bigger duct = obstruction
Cholestasis in smaller duct = hepatocyte malfunction (as in this case)
Chondroma
2nd most common primary tumor of bone, especially near small joints of the hand Benign
o Chondrosarcoma is malignant and affects axial skeleton No normal bone seen
We see hyaline cartilage, though it is more variable than normal
N.B. We also saw hyaline cartilage in large bronchi of the lungs and pleomorphic adenoma
of the parotid gland
Chorionepithelioma
Germ cell tumor classification:
Seminoma in males, Dysgerminoma is female
o They are undifferentiated, malignant
o Require less intense chemo
Embrionic carcinoma (non-seminoma)
o Totipotent cells
o Malignant
o Can differentiate into somatic cellsteratoma
o Can differentiate into extraembryonic structures: placenta or yolk sac or chorion
Choriocarcinoma is resistant to chemo
Produce hCG
Following pregnancy, a woman can have a gestational choriocarcinoma.
o Looks the same histologically, but has a good prognosis
Uterus seen here
Thick-walled muscles, vessels
Two components:
o Syncytial trophoblasts
o Cytotrophoblasts
High growth rate, so necrosis is common
Angioinvasive
Here is an island with the 2 cell types and necrosis
Chronic bronchitis H&E
Cartilage, mucosa, glands can be seen
Cilia is missing in some parts of the respiratory epithelium
Few goblet cells
Thickened basal membrane
Lymphocyte infiltration
Stratified squamous epithelium
Reid Index is used post-mortally:
o Ratio between the thickness of the submucosal mucus secreting glands and the thickness between the epithelium and cartilage that covers the bronchi (i.e. glands/wall)
o Distance between epithelium and cartilage is >0.5 mm. Glands make up 0.4-0.5 mm. MetaplasiaDysplasiaplanocellular carcinoma
Cirrhosis
Bottom shows islands of hepatocytes separated by CT septa
Liver reconstruction within lobules
Bile duct proliferation (source of the regeneration?)
Mild inflammation in septa
Cirrhosis – picrosirius stain
Collagen I and III stained to demonstrate reconstruction
Regardless of etiology, cirrhosis has this etiology
SCLL/CLL
Here, neutrophils are less than the normal 60% of leukocytes
Relative lymphocytosis
o Higher proportion (greater than 40%) of lymphocytes among the white blood cells
o Absolute lymphocyte count is normal (less than 4000 per microliter). The fluffy cells are Gumprecht shadow cells
o Dead lymphocytes
o Necrotized artifacts
o Not specific for CLL, but helpful for diagnosis
SCLL (=small cell lymphocytic lymphoma) in blood is equivalent to CLL in lymph nodes.
Immunohistochemistry of CLL has a mixture of these characteristics:
o Lymphocytes: CD 5, 20, 23 o T cell: CD 3, 2, 5, 7, 8
o B cell: CD 20, Pax 5
o Follicular DC: CD 23, 24
CML
more nuclei, increased WBC
few Gumprecht cells
cell types: PMN, thrombocytes
mature neutrophils: 10 micrometers with 3-5 lobules connected by fragments. Here, they are
bigger with nuclei that are not separated/lobulated
o jugend and stab forms
Full myeloplastic lineage in in the periphery, not kept in bone marrow. This is pathological
Blasts without mature cells = leukemic reaction/left shift
o AML
o Severe infection
Hiatus leukemicus = only very immature and mature forms are present
CML = persistent leukemic reaction
o Philadelphia chromosome t(9;22)
o BM overproduces WBC
Hyperviscosity
May transform to AML
Hemorrhagic Infarction of Lung
2 sharply different regions
Hemorrhagic infarct (type of coagulative necrosis) due to venous blockage
Infarcted area looks solid, not spongy.
Alveolar cell nuclei are pyknotic
Vessels disappear or contain thrombi, seen by eosinophilic fibrin
Alveoli flooded by blood in greater amount than the interstitial blood of the anemic infarct
Septal structure disappears
Neutrophils at border of infarction
Anthracosis = coal deposits
Foamy purple parts = edema
Celiac Disease, Small Intestine, H&E
No villi or short villi reduce surface area, leading to malabsorption
Increased intraepithelial lymphocytes (IEL): 40+ IEL/100 epithelial cells
T-cell lymphoma may arise
Hyperplastic crypts of Lieberkühn
Crohn Disease, H&E, Large intestine
Not confined to colon, nor to mucosa
Transmural – dark blue spots are the lymphoid follicles in lamina propria and adipose tissues
Ulcer seen on upper left of lumen
Giant cells in granulomas seen on middle right of lumen. These are common in the follicles
cysta dermoides ovarii-germ cell tumor teratoma
Cystadenocarcinoma (papillare serosum) ovarii
Surface epithelial tumors derive from the Müllerian duct o Serous
o Endometrioid o Mucinous
These are the types of tissues in the female genital organs. Mostly, the neoplasms are cystic, i.e. cystadenoma. Serous cystadenocarcinomas are the most common malignancy.
No ovarian tissue can be seen on this slide
These tumors can reach several kilograms
Papillary structure on right side
Invasion of stroma
Cystic Fibrosis (mucoviscidosis)
2 different tissues:
o Round structure with lumen is the small intestine with goblet cells and paneth cells.
Nothing should be in the lumen, but here, they are occupied. This is ileus caused by
meconium.
o Pancreas has exocrine glands with islets of Langerhans
Lots of connective tissue and inflammatory tissue (lymphocytes indicate pancreatitis).
Eosinophilic viscous secretion in lumen of glands remains there and induces inflammation.
Glands are dilated and filled with mucin. Some of the cells atrophy; there is fibrosis and scar tissue.
Digestive enzymes are not sufficient and lead to malabsorption.
Heterozygosity might be advantageous for survival of cholera and tuberculosis
Nephropathia diabetica – PAS
In kidney pathology, H&E, immunofluorescence, PAS, and trichrome, IF (IgA, IgM, IgE) are used
Electron microscopy is still used for nephropathology
This slide is from a biopsy
At least 10-12 glomeruli should be seen to give an overall
impression of a kidney. Here, we have more than this
Normal capillary: tiny wall, small capillaries
Glomerulus is lobulated, fine structure lost
o Fibrotic, sclerotic
o Thickened Bowman membrane PAS material clumps
o PAS stains glycosylated proteins
Swollen epithelial cells
Mesangium enlarged, fused, nodular
o This is Kimmelstiel-Wilson Nephropathy. It is characteristic of DM in about 30%
Totally fibrotic, afunctional glomeruli can be seen
Also affects tubules and interstitium
BM thicker
This is a sign of chronic diabetic nephropathy
Intima of large and small vessels are thickened, PAS+
Atrophy of tubules: flattening of tall cells, loss of cuticle
This is a secondary change to atherosclerosis
Glucose in urine increases the risk of pyelonephritis.
Disseminated Intravascular Coagulation w/ Fibrin Staining (Phosphotungstic acid haematoxylin / Weigert’s Elastic Stain)
Vessels with RBC stain violet/purple (not pathological)
Darker, grape purple is a stain for fibrin
Glomerular capillaries are filled by fibrin and RBC
o Small thrombi
Tubules in cortex lose their nuclear and cytoplasmic differentiation
The pattern of fibrin indicates systemc coagulation, especially in smaller vessels acute
renal failure
Diffuse Large B Cell Lymphoma CD20
CD20 stains B cells
Membrane-bound positivity for CD20 indicates that these are B cells
There is good prognosis with rituximab, which is anti-CD20
Ki67 would show high grade, large proliferation rate
o There is increased mitosis (not decreased apoptosis)
Diffuse Large B Cell Lymphoma H&E
Middle of the slide is crowded. Below that, there are apoptotic cells
Note blast-like cells with vacuoles and nucleoli
Emphysema H&E
Large alveoli made by disrupting smaller
Lack of normal septa
Less place for oxygen exchange
A form of COPD because exhalation is ‘obstructed’
Larger vessels
Macroscopically: white areas at margin
This is panacinar type of emphysema
o destroys the entire alveolus uniformly; predominant in the lower half of the lungs
Liquefactive Necrosis
Structure in center disappears, less eosinophilic
White spaces indicate spongiosis (intercellular) edema
Nuclei of dying neurons disappear
Aka “infarction” because of blockage to cerebral artery
Normally, brain has no neutrophils, macrophages, or fibroblasts. When the BBB is damaged
in infarct, macrophages enter brain tissue
o Appear foamy because of their triglycerol and cholesterol content o Hemosiderin
o Neutrophils not characteristic
In early stage of ischemia, neurons swell and become ‘red giant’ neurons. More sensitive to hypoxia than astrocytes
End stage kidney disease – H&E
Totally sclerotic glomeruli
Irreversible
Atrophic tubules with protein
“Thyroidization” because of proteins
Mononuclear cells in interstitium indicate chronic inflammation
Narrow lumen of vessels indicates decreased blood circulation
Cause cannot be determined from here.
End Stage Kidney – Picro-Sirius stain
Picro stains collagen IV
Glomeruli and vessels are fibrotic
RBC stain cellow
Azothemia, hyperK+, no uremia
Fat Embolization with Oil Red O stain (Sudan Red)
Adipocytes in pyelon are stained by oil red O (frozen section)
o Bright red fat tissue occlusions in the glomerular capillaries are the fat embolization
Orange in vessels = fat plaque accumulation
Glomeruli also have orange staining, delineating capillaries.
Fat embolization obstructs capillaries, leading to glomerular dysfunction
Splinters of bone fracture or trauma to fat can also cause fat embolization
Systemic fat embolization is not caused by fracture; fat will not reach the kidneys because it
remains in the lungs. Fat embolus originates from the arterial system.
Fatty Degeneration
Dark sections: dense septa of CT
Lobular structure maintained
Fibrosis (connective tissue) around portal triad
Holes are artifacts of fatty degeneration
In the cytoplasm of some hepatocytes, there is the beginning of fatty degeneration: pushing
nucleus and cytoplasm to the border
Organs with high fat metabolism can undergo fatty degeneration.
o The other organ is the heart (“tiger heart”)
o If the liver cannot metabolize the fat it receives through the portal vein, the fat will
accumulate in the cytoplasm of the hepatocytes.
o Causes: alcoholism, hypoxia, storage disease, viral infections, obesity, diabetes
Brown pigment fine granulations in the hepatocytes could be: o Bile – no, usually in ducts
o Lipofuscin – yes
o Hemosiderin – in macrophages, except in hemochromatosis, where it would be in the
hepatocytes
Frozen section or Sudan black can be used to see fat accumulations
Fat can be deposited in the hepatic lobules in different patterns:
o Diffuse: vacuoles are evenly spread out within a lobule. Alcoholism produces this pattern, since it reduces fat metabolism in all cells
o Zonular: fat vacuoles appear either peripherally or centrally in the lobules. Stasis causes accumulation in the central zone due to hypoxia there. Acute poisoning (including binge drinking) causes fat to accumulate in the periphery, since there are higher amounts of toxins in the periphery.
Macroscopic: yellow, soft, enlarged
Liponecrosis Pancreatis
Form of coagulative necrosis
Necrosis is not related to blood supply, but rather, enzymes: lipase is activated and acts on
triglycerides. Ca2+ and fatty acids undergo saponification.
o Hypocalcemia leads to tetany
Note the eosinophilic spots where structure of cells has disappeared
Saponified fat of the necrotic adipocytes (anucleated) stains eosinophilic because it is not
removed in tissue processing as normal fat.
Acute inflammatory cells are seen in the border between viable and necrotic tissue
Pancreatitis caused by gall stones, alcohol, infection, injury
Pericarditis Fibrinosa
N.B. “fibrinous” does not mean the same as “fibrous”. Fibrinous means “rich in fibrin”, and is related to acute inflammation. “Fibrous” is a chronic state.
5 types of acute inflammation based on exudate
- Serous: in blisters, burns. Watery, protein-poor fluid from plasma or secretions of mesothelial cells.
- Fibrinous: consequence of more severe injuries resulting in greater vascular permeability. Contains more proteins, including fibrinogen. Extravascular fibrin appears eosinophilic. This type of exudate is characteristic of inflammation in lining of body cavities, and occurs in infection. Two outcomes for the fibrinous exudate are resolution (exudate is degraded by fibrinolysis and debris is removed by macrophages) and organization (exudate is invaded by fibroblasts and blood vessels, leading to scar tissue)
- Purulent: Pus consisting of neutrophils, necrotic cells, edematous fluid, bacteria, 4. Hemorrhagic: Exudate contains proteins and RBC, as in influenza
- Gangrenous: Immune system dysfunctional; tissue necrotic
Effusion = fluid in serous cavity
o Transudate = low protein content effusion
o Exudate = high protein content effusion
o The border is protein content 3 g/L. Rivalta test: sulphosalicylic acid is added and
precipitation indicates high protein content
Here, we see cross-section of heart with subepicardial fat.
Pericardium here is obvious. (Normal mesothelial cells are very thin)
RBC are seen in dilated blood vessels (active hyperemia) of the pericardium, though they are
not usually
Amorphous, eosinophilic material at the edge is fibrin
Lipofuscin is the brown pigment.
Myocardium appears normal
Inflammatory cells present: mostly lymphocytes, plasma cells, macrophages
Macroscopically called “villous heart”/”bread and butter heart”
Can occur locally, e.g. infarctions, or on entire heart, e.g. virus
Fibroadenoma of breast
Benign
Sharply surrounded, capsule
Most common benign tumor
20-30 year-olds
“fibroadenomatosis” = multiple tumors
Fibroma is from mesenchymal (mesodermal), while glands are ectodermal
o Only the mesenchymal component is the origin of the tumor. The glands are not part of the tumor.
o This is unlike adenomafibromatoma of the ovary, where glands are the tumorous part
Stroma is of clonal origin
No breast tissue seen
Lots of connective tissue
stroma with glands pressed together
o “chinese characters”
Diagnose with fine-needle
aspiration biopsy
Low transformation
Phyllode tumor (giant
fibroadenoma) is the malignant counterpart.
Fibrosis Myocardii
Just myocardium, no pericardium
Cardiomyocytes have even extracellular matrix deposition = scar tissue
o MI heals with scar formation
o Could also be caused by chronic ischemia
Macroscopically appears gray
Follicular Hyperplasia – H&E
Capsule is intact
Size of LN is 16,000 micrometers = 16 mm. >5 is pathological.
We should see secondary lymph follicles and paracortical cells.
o There are lymphoid follicles here of variable sizes, some fused
o The marginal zone is not present; we know this is not an abdominal LN
o Follicle germinal center and mantle zone are seen. Germinal center shows normal
asymmetry/polarization
Follicles are site of cell maturation and apoptosis. There are mitotic figures and tingible
histiocytes remove the apoptotic cells.
The cells that are surrounded by lose, white space are the tingible histiocytes.
o Containing phagocytosed, apoptotic cells, i.e. tingible bodies
o “Starry sky” appearance
This is hyperplasia of the follicles, a reactive condition.
Follicular Lymphoma BCL-2 immunohistochemistry
BCL-2+ is in the interfollicular space. Here, it is pathologically expressed in the follicle.
The pathological protein from the Bcl/Ig heavy chain is anti-apoptotic, causing growth
Ki67 is low here compared to normal LN
o Ki67 is a nuclear marker for cell proliferation. This is an indolent, low-grade disease
Follicular Lymphoma H&E
13 mm
Capsule is broken in parts
Germinal centers more monomorphic compared to follicular hyperplasia
Pathological:
o No polarization of follicles
o No starry sky pattern
Lack of apoptosis means that unhealthy cells can proliferate
Chronic Gastritis
Chronic inflammation is characterized by small, round cells, i.e. lymphocytes. It is long-lasting, almost always resulting in scars. Scars are rich in myofibrocytes, which can contract
This is chronic inflammation of stomach mucosa. Biopsy taken from antral mucosa, i.e. glands producing mucous.
There should not be any inflammatory cells in the stomach (whereas they are present in other body parts normally)
Plasma cells have abundant cytoplasm with nucleus pushed to side of the cell
Lymphocytes are dark, bluish clumps in lamina propria
o When lymphocytes are in the interstitium/ (not within glands),
the chronic gastritis is “without activity”
Foveola cells (=surface mucous cells) in the mucous-secreting glands
Goblet cells, bright paneth cells
o indicative of metaplasia in the stomach because they are usual for the intestine (= “intestinal metaplasia”)
Causes of chronic gastritis:
o Autoantibodies against parietal cells o H. pylori
o Chemicals, foods, alcohol
Morbus Gaucher (H&E, PAS)
Autosomal recessive lipid storage disease
Accumulation of fatty substances in cells and certain organs due to enzyme deficiency
Bone marrow section (not a smear) should produce WBC, RBC, thrombocytes
Many elongated, purple PAS-stained cells are macrophages filled with PAS. These are
Gaucher that store cerebroside, a sphingolipid
o Gaucher cells occupy bone marrow, reducing space needed to form cells
Bone marrow failure leads pancytopenia (anemia, thrombocytopenia, and leukocytopenia)
Extramedullary hematopoiesis (i.e. outside of bone marrow) occurs in spleen and liver,
leading to hepatosplenomegally.
When Gaucher cells are in tissue culture with normal macrophages, they disappear. When
co-cultured with Tay Sachs cells, they “cure” one another by sharing enzymes (lysosomal enzymes leak out of the cell)
Stuffed histiocyte
o Tissue paper striations (higher power), which distinguish it from Niemann-Pick storage disease
GIST H&E
GIST is the most common mesenchymal tumor of the GI tract.
o Other types of tumors in the stomach: lymphoma, intestinal type, diffuse type
We do not know if GIST is benign or malignant based on histology
GIST derives from Cajal cells
o Proliferation derived from CD117+/c-KIT+. C-KIT is a receptor for stem cell factor. It is a tyrosine kinase receptor
This is a spindle cell tumor: A type of tumor that contains cells called spindle cells, based on their shape. Under a microscope, spindle cells look long and slender. Spindle cell tumors may be sarcomas or carcinomas.
Treatment is Glivex/Imatinib (also used in CML), which blocks kinase activity.
Derives from wall. Tumor is the darker purple mass on the left of the slide.
Amyloidosis
Congo red stain for amyloid shows up mainly in mesangial matrix of glomeruli and some in interstitium walls of the peritubular vessels.
o Congo will also stain fibrin orange
o To differentiate, another method is to use polarized microscope, under which amyloid
looks apple green (metachromasia)
With H&E, amyloid appears eosinophilic
Amyloid ß sheet structure is insoluble
1st place of accumulation is the small vessels, e.g. in kidney capillaries
Macroscopically: kidneys will appear swollen, and since blood flow is obstructed, the cortex will also be paler. There will be shrinkage eventually.
Amyloid is an inert material, so it does not promote immune response.
Ruins basement membrane, patient will have proteinuria.
Foreign Body Granuloma
Non-immunogenic, from suture
o Giant cells and histiocytes are seen around the fibers, lymphocyte count is lower
White dots seen on high power are the surgical thread fibers
Look like nodules macroscopically
Hashimoto Thyroiditis
Remnant of normal structure at outer parts, though they are a deeper eosinophilic color
Deep blue lymphocytes make secondary follicles
Hürthle cells are enlarged epithelial cells with abundant eosinophilic granular cytoplasm lining the colloid
Entire thyroid gland has been transformed
Stage 1 = hyperfunction
Stage 2 = hypofunction, original structure disappears
This is a chronic autoimmune disease that may progress to papillary thyroid cancer or MALT
Hepatitis B
Most common form of hepatitis, especially in Asia and Africa
Vaccine now used, based on surface antigen
Hepatitis B virus can cause acute, chronic, or acute
chronic hepatitis
Transmission can be vertical from mother to baby
Child is immune intolerant, and more likely to develop chronic form: cirrhosis and cancer
Horizontal spread in adults is usually acute
Needle biopsy
Portal area has mild inflammation
Ground-glass (i.e. opaque) cells, swollen, larger cytoplasm
Derive from the HepBV surface antigen of the Dane particle
Indicated increased of ER, and is not specific for HepB
Here, it has not progressed to fibrosis
Infectious
Hemangioma Capillare Cutis
Hair follicles, normal epidermis
Most common blood vessel tumor
Bluish regions are the stained tumor cells (nuclei are basophilic)
Invasive growth, note infiltration between the adipocytes.
o However, this is a benign tumor o Malignant form is angiosarcoma
Frequently present at birth and disappear spontaneously
Chronic Hepatitis
Needle biopsy
Chronic hepatitis is mostly caused by
Hepatitis C, which begins as chronic (not
acute) form. Histology does not reveal etiology. For that, we use serology.
Increased transaminase levels
Drugs can be used as treatment to kill the virus; they are more efficient the earlier the virus is recognized
With low power, note darker areas. In higher power, we see that these occur in the portal areas due to follicular pattern of lymphocytes
With higher power, note fatty change (steatosis)
Border between inflammation and parenchyma is sharp in some areas.
Characteristic of CPH (Chronic Persistent Hepatitis), which has a benign outcome In other areas, there is interface between spread of inflammatory cells and parenchyma
CAH (Chronic Active Hepatitis)
Together, CPH and CAH have a biphasic pattern. Nowadays, scoring is used to categorize
chronic hepatitis, rather than these terms
In the parenchyma, stellate myofibroblasts (Ito cells, hard to see) are deposited. These lead to cirrhosis.
With highest magnification, one might see apoptotic cells (hard to see)
Councilman (hyaline) bodies = apoptotic hepatocytes; eosinophilic, surrounded by normal parenchyma
Hodgkin Lymphoma
Medulla and capsule are fibrotic
No germinal centers
There are 2 cell types:
o Small cells are lymphocytes
o Big cells with lobulated nucleus are lacuna cells
In HL, B cells don’t express their usual markers
o There is a special immunophenotype of CD15+, 30+ (missing the normal B cell CD20+, 45+)
Reactive T cells surround the lacuna B cells
Types of Sternberg-Reed cells:
o L & H(lymphocytic and histiocytic)/popcorn cells o Mirror cells
o Lacuna cells
H. pylori Gastritis – Undifferentiated Giemsa stain
Biopsy from endoscopy
(differentiated Giemsa is used in bone marrow)
Surface mucosa has curved rods with seagull shape, typical for the bacterium
Can be confirmed with immunohistochem for antibodies.
Myocardial hypertrophy
Hypertrophy of myocardium means that the myocytes increase in size to cope with increased burden.
o These cells cannot divide, so there is no hyperplasia
o Caused by systemic hypertension or aortic valve stenosis which require the L.V. to produce higher pressure
Hypertrophy increases oxygen and energy demands, which may lead ischemia, foci of necrosis
Big, eosinophilic cells and fibrocytes between them.
o Connective tissue is seen among the myocardial cells because necrosis causes
replacement by connective tissue
Cross-striation
Myocytes thickened with irregularity in size and shape of nuclei
Loose and dense parts surrounded by fatty tissue with vessels
Lipofuscin
We can use RBC (7 micrometers) between the myocardial cells as a ruler. Myocardial cells
should not be more than 3 RBC in size.
Sign of ischemia = contour of nucleus becomes sharp instead of round
If we do not see end-to-end anastomosis, think hypertrophy (=same amount of cells, but
bigger)
Induratio brunea pulmonis: H&E and Prussian Blue
In chronic LHF, decrease in contractility develops slowly, allowing the lungs to accommodate to the increase in hydrostatic pressure
o Venous pooling causes pulmonary congestion
o To deal with increased hydrostatic pressure, the lungs constrict their precapillary
arterioles to prevent edema and to keep the capillary pressure constant
o The pulmonary veins will be dilated and filled with blood that is fully oxygenated and
therefore appears dark red.
Capillaries will break due to changing pressure and allow RBC into alveolar lumen
RBC will be digested by alveolar macrophages
Macrophages (large, purple, bean-shaped nuclei) then contain hemosiderin
o “heart failure cells” coughed up
o localized hemosiderosis
o when macrophages are saturated with hemosiderin, they appear on the surface of the
lungs in lymph vessels
Prussian blue stains the macrophage hemosiderin blue. o The black cells are anthracotic cells.
Macroscopically, lungs appear heavier and weigh more due to venous blood.
Infant Respiratory Distress Syndrome (PAS)
Dense lung that looks like a solid organ (pancreas)
PAS (+) regions are stained purple in the alveoli
o This used to be called “hyaline membrane disease”
o Waxy layer of hyaline membrane line the collapsed alveoli. Hyaline is protein and dead cells
Caused by prematurity (insufficient surfactant), diabetic mother, or twin pregnancy
There is poor gas exchange, the pressure increases blood to bypass the lung
Hyaline membranes also caused by Group B Strep or “respirator lung”
Kaposi Sarcoma
Different types of Kaposi sarcoma
o Old age – benign
o Immunocompromised patient – malignant, multifocal
Caused by herpes virus 8 (=Kaposi sarcoma virus)
Epidermis appears normal
Dermis has many blood vessels
o They are small vessels with elongated cells o Brown pigment is hemosiderin.
Kaposi sarcoma – immunohistochemical reaction
Cells that stain brown are positive for KSV
Systemic Lupus Erythrematosus
We should count more than 10 glomeruli to know that we have a representative sample
Subendothelial spaces filled with immune complexes
Increased number of mesangial cells
Note lobulated glomeruli that are widened and in wire-loop formation
Periglomerular fibrosis
Sclerosis
Dilated tubules
With PAS, glomular lobulations and thickened wall are better seen
Lipoma
Most common mesenchymal tumor
Benign
Normal fat tissue
Can be painful, but does not generally undergo malignant transformation
Malignant form is liposarcoma
Liposarcoma
From retroperitoneum
Most common malignant soft tissue tumor
At higher magnification, you can see adipocytes, but it is more cellular than a lipoma
Key feature is the presence of lipoblasts = adipocytes with multiple vacuoles causing imprint
on the nucleus
Mitosis rarely seen
Lobar pneumonia
Lumen of alveoli filled with PMN exudate, not air
Occupies entire lobe (not focal)
o Same stage of inflammation at every location
Firm and solid consistency = “hepatization of lung”
3 stages:
- Hepatization rubra: blood floods lung, it will be reddish
- Hepatization grisa: fibrin in lung turns in gray
- Hepatization flava: leukocytes come
Hepatization preceded by congestion. It is followed by resolution or organization.
Surface of lung has fibrinous pleuritis. This concomitant pleuritis is a complication
Lobar pneumonia can be caused by Strep pneumoniae and Klebsiella
Bronchus: Metaplasia
Columnar, ciliated, pseudrostratified, goblet cells = respiratory epithelium
Here, normal structure is not maintained.
o stratified squamous non-keratinized epithelium (=metaplasia) can bear more irritation, but less clearing abilities
o large, clumped nuclei lacking cytoplasm = dysplasia
Severe dysplasia indicates an in situ carcinoma
o Widening of epithelium Metaplasia Dysplasia
o Breaking through basal membrane = cancer
Fibrocystic Disease of Breast (Mastopathia fibrocystica)
Lump
Mass-forming, but not a tumor because this is not clonal
Most frequent breast disease
Caused by hormonal disbalance
o Less common in women taking contraceptives 2 most typical lesions:
o fibrosis
o cyst formation
Does not increase chance of breast carcinoma, but may lead to proliferations
Note dilated glands
Hardly any fat
Lots of fibrous tissue
Cancer may be present in the fibrous part
Cysts filled with fluid may be painful
Ducts are occupied
proliferative
Apocrine metaplasia (eosinophilic)
Micropapillomatosis
Megaloblastosis – smear from Bone Marrow
Fewer RBC
Adipocytes
Megakaryocytes enlarged
Maturing neutrophils
Bluish cells with round, eccentric nuclei are from the erythroid line (getting rid of nuclei)
Erythroid cells are big
Inefficient RBC development
o Expect anemia in the periphery
Erythroid cells have 120 day lifespan; myeloid has 1⁄2 day lifespan. Normal ratio is 1⁄4; here,
there are more erythroid that myeloid.
Melanoma malignum cutis
Normal skin at top right
Lymphocytic, perivascular infiltration
Solar elastosis (degeneration of elastic fibers)
Hyperparakeratosis = nuclei in the stratus corneum; increased keratin formation, preservation of the nuclei in the superficial cells, and absence of the stratum granulosum
End of normal skin epithelium has necrotic cells, debris
o Crust on ulcer = exoceration
Blue bulge on top is large nodule with brown pigment
o Nests of cells with fibrovascular stroma
Mitotic figures, big nuclei with macronucleoli indicate that these are active o Polymorphic
These are melanocytes, the malignant counterpart of nevus
Nodular, melanin-producing
Melanoma is a ‘great mimic’ clinically
Types:
o Superficial: horizontal spread
o Lentigo malignum: localized to epithelium, good prognosis
o Acral lentiginous melanomas: found in keratinized places, thus hidden until it has
spread
Breslow and Clark stages:
o Breslow gives depth in mm
o Clark gives depth by skin layer
1 = epithelium
2 = below epithelium
3 = vasculature
4
5 = to fatty tissue of dermis
BRAF V600E mutation associated with melanoma o Develops in intermittently sun-exposed skin o Targeted therapy vemurafinib
Meningioma
Meningiomas may be on the meninx, or they may be extrameningial (usually near choroid plexus of ventricles) or extracranial
Mostly benign, but can cause pain and focal epilepsy
Spindle cell arrangement forms fascicles. Depending on the section, they may look appear long, or small, round cross-sections
No normal tissue seen here
Often have progesterone receptors, and grow faster during pregnancy
Mesothelioma from PLEURA H&E
Derives from serous membrane
Mesothelium is from the epithelial covering lining coelom
Very variable histological picture
Asbestos increases mesothelioma risk 1000x
o Asbestos also increases risk of bronchial carcinoma
Slide displays tumor cells
Large polygonal cells with large nuclei
Cell borders well-preserved
Mitotic figures
Diagnosis is based on immunohistochem
o Calretinin
o WT1
Differential diagnosis: a carcinoma that has metastasized to the pleura
o Immunohistochem
o Check for primary tumors
Microcalcification carcinoma ductale in situ
Confined by basement membrane
Duct lumen occupied by tumor cells and necrosis
o Pink is necrosis
o Blue is microcalcification. This is a dystrophic calcification
Calcification can be detected by mammography
Removal at this stage is curative
(Ductal and lobular tumors can be in situ or invasive)
Myelofibrosis – H&E
Bone fragments, adipocytes, fibrocytes, fibroblasts,
Almost no bone marrow
o Expect extramedullary hematopoiesis
Clusters of megakaryocytes with atypical nuclei
Myelofibrosis with reticulin stain
Reticulin stains collagen
Mutation to JAK2 tyrosine kinase V617F in 50% of cases
o PDGF forces fibrotic processes
Myocarditis Rheumatica
This is a non-infectious granuloma because bacteria are no-longer present (it is a post- streptococal disease from Strep pyogenes).
Antibodies against the Strep attack our own cells
Inflammation in all 3 layers of the heart (peri-, myo-, endocardium) = pancarditis
(endocardium not seen here)
Pericardium should be thin layer of mesothelium, but here there is fibrinous pericardititis
Stages of myocarditis:
- Exudative phase – loose, edematous intersitium, fibrinoid necrosis surrounded by neutrophils
- Proliferative phase – Aschoff bodies,
Rheumatic granulomas around blood vessels. They are perivascular granulomas known as “Aschoff nodules” in the myocardium, consisting mainly of T cells, scattered plasma cells, and macrophages (=Anitschkow/caterpillar cells with an intracellular ribbon of chromatin)
Endocardial, i.e. valve, involvement results in fibrinoid necrosis
Virusos Myocarditis
Lymphocytic infiltration
Chronic inflammation
Coxsackie virus (Chagas Disease) is common
Neuroblastoma
Does not develop from neurons, but rather from PNS (neuroblasts of the sympathetic nervous system adrenal)
Tumor cells differentiate into ganglion cells (this one is poorly differentiated)
malignant benign transformation can be accomplished by Coley toxin
Can be congenital
Tumor is small, round cell. No characteristic features, so must be proved by
immunohistochemistry or EM
Nevus intradermalis cutis
Ink seen on right; no remnant seen near resection margin
Hair follicles
Stratum corneum, granulosum, spinosum, basale, dermis
Middle of the top of slide has flattened papilla
Growth is pushing up under surface of dermis, leading to a polypoid structure
Extra tissue composed of cells with ring of cytoplasm, making islands
o Multinucleated cells with nuclear inclusions
Basal layer cells have increased pigment
Towards the bottom, cells are maturing and getting smaller
These are intradermal nevus cells
Nevi may produce melanin (not much seen here)
Benign tumor
Other forms of nevi:
o Intraepidermal
o Compound nevus = intraepidermal + dermal
o Junctional nevus = tip of papilla. Should be examined for malignancy over age 30.
Nutmeg Liver
Backward RHF causes stasis in viscera
o R.V. fails to pump blood into the lungs (due to pulmonary embolism, pneumonia,
etc.), and pools in IVC. This leads to systemic congestion. Three phases of liver congestion:
o Dilation of the central veins
o Central zone fatty accumulation and fatty degeneration in the hepatocytes
surrounding the central veins.
Lipids steatosis hepatis (fatty degeneration). Brown dots surrounded by yellow
o Sinusoids dilate due to increasing pressure, compressing the hepatic cords and causing atrophy of the trabeculae around the central vein. The dying hepatocytes will be replaced by fibrosis (“cardiac cirrhosis”)
Brown spots are hemosiderin-laden Kupffer cells
Rhythmicity in RBC cluster
Lipofuscin is orangy
Here, RBC increase in sinusoids make trabeculae smaller, hepatocytes lose cytoplasm. The
trabeculae are disorganized in atrophied in these regions.
Central veins are dilated. Lighter areas on the section are the parenchymal tissue
surrounding the central veins (3rd stage of congestion)
o These areas appear lighter because the dilated sinusoids have lost their blood.
Around the damaged areas, the hepatocytes show fatty accumulation o karyolysis
Brown pigments could either be lipofuscin or hemosiderin
Osteosarcoma
Most common primary bone tumor
75% occur around the knee
2 peak occurrences: young adults (15-25) and older adults (due to osteomyelitis, Pagets)
sarcoma = malignant neoplasm of mesenchymal origin
Sarcomas are especially pleomorphic
Elongated cells
Mitotic figures
Tumor cells produce bone tissuesislands of bone formation
Higher risk of osteosarcoma in cases of familial retinoblastoma
Chronic pancreatitis
Islets of Langerhans seen, but exocrine acinar part is missing
Results in malabsorption
Secretory ducts are seen
Acute pancreatitis would show fat necrosis
Causes
CF due to mucus plugs
Autoimmune
Alcohol (most common)
Papillary Carcinoma of Thyroid
Normal structure of the thyroid surrounds the papillary mass in the center of the top section
Node is within normal structure. The tumor is encapsulated though the capsule is not entirely intact (upper right, it is broken)
Many papillary structures
3 features:
- Crowded cells
- Groves inside the cells = doubling of nuclear membrane 3. Cytoplasmic inclusions
(2. and 3. are the same feature, depending on which section of the cell is seen)
“Orphan Annie eye” cells with nuclear inclusions
This distinct feature allows papillary thyroid cancer to be diagnosed cytologically
Psamomma bodies may be present (not seen here)
o Concentric, calcified cells
Mutations in RET or RAS oncogenes, or BRAF, or as part of MEN
Can spread to LN
Laryngeal Papilloma
Papilloma – mucus covered by squamous or transitional epithelium
Polyp – covered by glandular epithelium
Stroma has blood vessels spreading like fingers of a hand
Classification based on ratio of stroma to parenchyma
o Medullary tumor e.g. in breast has more parenchyma
o Cirrhotic tumor e.g. in biliary system has more stroma
Thicker squamous epithelium
Differentiated
Sharp border between stroma and parenchyma
No infiltrate, thus a benign papilloma
Symptom – hoarseness
Associated with smokers and HPV
Peptic Ulcer H&E
Mucosa completely missing
Glandular structures also missing
Many goblet cells = intestinal metaplasia is common in region of ulcer
Stomach carcinomas can also be ulcerated, so this must be part of the differential diagnosis
o Biopsy should be taken from border (not the center of the ulcer) because it is more likely representative of the etiology
o Duodenal ulcers do not have malignant transformations
Layers of the ulcer:
o Necrotic tissue on top
o Granulations tissue with inflammatory cells and vessels
o Scar tissue with CT, collaged, few cells
Pheochromocytoma
Growth from the medulla compresses normal structure of cortex
A pheochromocytoma located outside the medulla would be called “paraganglioma”
Normal capsule, fat, and 3 layers of adrenal cortex can be seen on some parts (left side)
Right side: Zellballen of sustentacular cells making up the tumor
o S100+ Schwann cells with round nuclei
o Salt and pepper endocrine cells are positive for the endocrine markers
chromograninA, CD55, and synaptophysin
Rule of 10%: bilateral, malignant, and involved in MEN familiar inheritance
Metastasis is the best way to determine malignancy
Symptoms: sweating, headache, HTN crisis
Pleiomorphic Adenoma of Parotid, H&E
Types of benign salivary gland tumors: o Pleiomorphic adenoma
o Warthin
Types of malignant salivary tumors:
o Mucoepidermoid carcinoma,
o Adenoid Cystic
o Sjögren Syndrome can lead to B-cell lymphoma, a type of extranodal lymphoma
Stomach is the most common site of extranodal lymphoma. H. pylori is a risk factor
Hashimoto’s thyroiditis can lead to T-cell lymphoma
Pleimorphic adenoma can be considered a semi-malignant tumor because it is hard to entirely
remove from facial nerves.
There is inverse relationship between size of gland and malignance, i.e. large parotid gland
rarely has malignant tumors
Encapsulated tumor is seen in the bottom part of the slide below normal salivary gland
Typical components:
- Hyaline cartilage – the pale tissue. This is interesting because cartilage is of mesenchymal origin
- Myoepithelial islands with gland-like appearance. This is labeled as myxoid in the slide (?)
- Myxoid = soft, loose CT not seen here
Pleuritis Carcinamatosa
Smear
Carcinosis is a disseminated cancer
RBC, lymphocytes, mesothelial cells can be seen
Mesothelial cells are big and round with eccentric nuclei and vacolated cytoplasm
o Capable of phagocytosis
Mesothelial cells form darker islands. Here there is a higher nuclei to cytoplasm ratio
Pneumocystitis Pneumonia H&E
Less air
Alveoli are full of eosinophilic material and desquamated, reactive cells
Pneumocystitis is caused by the yeast-like fungus Pneumocystis jirovecii o Foamy eosinophilic material = P. jirovecii
Large cells with deep blue nucleus with a halo are CMV inclusions, “owl eye”
This is a P. jirovecii and CMV coinfection
Note hemosiderin and anthracosis
Pneumocystitis Pneumonia – Grocott staining
Foamy material in alveoli stains place
Grocott + cells are P. jirovecii
o Cell walls of these organisms are outlined
Prostate Hyperplasia
Bluish areas = nuclei from lymphocyte crowding, indicating chronic inflammation
Glandular tissue with basal layer and apical cuboidal layer
Fibromuscular stroma
o Smooth muscle cells are large and eosinophilic
In glandular hyperplasia, glandular tissue increases more than the stroma, giving the prostate
an abnormally large glandular tissue:stroma ratio. Glands appear dilated and crowded, with
small septa separating adjacent glands.
Columnar glandular epithelium of newly formed nodules are generally taller than usual, and
epithelium of older nodules is lower than usual.
o Older nodules undergo pressure atrophy from pressure in the lumen of the glands.
Cells protrude into lumen (flower-like appearance) due to hyperplasia
Atrophic and hyperplastic nodes
o Atrophic part in bottom left
Causes hypertrophy of urinary bladder
Internal part of prostate surrounds urethra, and does not generally give rise to cancer. (Cancer
usually originates from outer part of prostate)
Prostate is testosterone-dependent organ, and when testosterone levels decrease with age, the
prostate enlarges to extract more testosterone from the blood.
Pulmonary Abscess
4 focal lesions with no alveolar septal structure
Consequence of bronchopneumonia
Sharply circumscribed lumen filled by necrotic tissue
Abscess = collection of pus in non-preformed body cavity. Necrotic core.
Core surrounded by neutrophils still in the fluid center
Fibrinous capsule surrounds the focal lesion
Wall of abscess is the pyogenic membrane
Note anthracosis
Pulmonary Edema
Acute pulmonary edema caused by LV insufficiency
o Edema is increased fluid in the interstitium
o Clinical emergency
Increased capillary hydrostatic pressure. Dilated capillaries and blood cells in alveoli indicate congestion in the lung
o Septa will be dark pink
o Congestion is due to passive hyperemia: pooling of venous blood results in dilation of pulmonary capillaries
Homogenous filling of alveoli
o Transudate (lower protein content than exudate) leaks from the vessel due to hydrostatic pressure on membrane wall; Forms the faintly eosinophilic, homogenous filling
o Exudate is the darker eosinophilic spots What causes edema in the lungs?
o L.H.F.
o Mitral stenosis
o ARDS
o Trauma
o Pulmonary hypertension
(Macrophages eat up RBC and become hemosiderin-laden “heart failure cells” in the chronic edema slide)
Inflammatory cells, macrophages, cellular debris of pneumocytes seen in the alveoli
Macroscopically, lungs appear normal but weigh more
Purulent Meningitis
Many granulocytes
Usually, meninges should not be seen, but here they are visible
Dilated vessels
Pus consists of polymorphonuclear cells (=neutrophil granulocytes) in subarachnoid space
Pus has entered into the meninx. Can be a consequence of pneumonia, tumor, or other infections.
Adenicarcinoma renis
Top left rim with irregularities
Lymphocytic infiltration
Panglomerular membrane thickening
Generally normal structure
Below is fibrotic capsule
Round nuclei in empty cytoplasm forming gland-like islands
o Clear-cell renal cancer (CCRC)
o Most common adenocarcinoma of kidney
o Looks like plant cells due to dissolved glycogen. The emptiness is an artifact. In
autopsy, it would be yellow.
o Behaves like malignant tumor because fine vessels allow metastasis o Small nucleilow grade renal cancer
Retinoblastoma
Cross section of the eye
Rare
Led to discovery of Rb gene, 1st tumor suppressor gene discovered
Hereditary vs. sporadic types
Both Rb genes must be mutated in the sporadic form
o Unilateral
Hereditary forms are bilateral (or “trilateral” if also in pineal gland)
Anaplastic, undifferentiated cells of a small, round-cell tumor
Note small necrosis in center of tumor
Rhabdomyosarcoma
Children
Belongs to small, round cell tumors (along with Ewing and Neuroblastoma)
Common in the urogenital and head & neck regions
No normal tissue can be seen here
Pleomorphic cells with mitotic figures suggest malignancy
Tadpole cells appear asymmetric, with nucleus pushed to one side and large, eosinophilic cytoplasm
Usually diagnosed with immunohistochem
Rheumatic Nodule
Related to rheumatic arthritis, a systemic autoimmune disease o Extensor surfaces of upper and lower extremities
Fibrinous necrosis surrounded by epitheloid cells, then fibrous cap, then lymphocytes outermost
o This is the granuloma
Rapidly Progressing Glomerulonephritis – PAS
Atrophic, thick BM of tubules
Glomerulus has bigger cells at border
Structure of glomerulus compressed
Some leukocytes seen
“Crescent type” glomerulus
Patient’s kidney function is destroyed
Occurs in post-streptococcal infection
Also occurs in Goodpasture syndrome and immune complex
Different etiologies, same morphology
Main problem is rupture of BM
Causes nephritisprotein in tubule (Tamm Horsfall protein), proteinuria, HTN, azothemia
Sarcoidosis
“Boeck” sarcoidosis
Granuloma formed
Non-infectious, cause unknown but probably an immune malfunction
Lymph node, lung, and subcutaneous tissue are common sites. Mikulicz syndrome is when
the eyes and lacrimal glands are involved.
Here, the typical structure of the lymph node is lost
High power: dark islands of lymphocytes
No necrosis: sarcoidosis is a non-necrotizing granuloma (unlike tuberculoma)
Langerhans type giant cells
o Contain Schaumann bodies (round laminated concretions of calcium proteins) and asteroid bodies (stellate structures), but these are hard to see here
Most common characteristic is bilateral hilar lymphadenomegaly, in which lymph nodes grow in hilum of lungs. If untreated, will induce lung fibrosis and honeycomb lung.
Schwannoma
Benign tumor of the peripheral nerve. It does not undergo malignant transformation and it is usually encapsulated (capsule not well seen here)
(The other form of benign peripheral nerve tumor is neurofibroma, which is not usually encapsulated and may undergo malignant transformation)
Normal peripheral nerve not seen here
Characteristic pattern are the Verrocay Bodies (“Antoni A”): whirled cellular areas
surrounded by spindle cells and nuclear palisades (like a school of herrings)
Antoni B areas are pale, loosely organized, less cellular
No mitotic figures or necrosis
Thick-walled blood vessels
“malignant schwannoma” (=old name) are now classified as Malignant Peripheral Nerve
Sheath Tumor
Seminoma
Epididymis, cremastor muscle, pampiniform plexus
Glandular, low spermatogenesis
o Outer wall is fibrotic, so this is an older man
Tumor is the bottom part
o Lymphoid cells infiltrate
o Tumor cells make islands, trabecules, there is diffuse structure o Loss of glandular structure
Germ cell cancer with good prognosis despite metastasis
Two peak incidences: ages 30 and 70
cKIT (CD117) is germ cell marker
Respiratory Allergic Polyp
Polypoid structure covered by epithelium, projects towards lumen o Respiratory epithelium covers three sides
Edematous connective tissue structure with dilated mucous glands
Eosinophilic exudate
Eosinophils indicate allergic process
Metaplastic change to stratified squamous epithelium may occur
Sjögren
Immune-mediated destruction of lacrimal and salivatory glands
o Xerostomia
o Keratoconjunctivitis sicca
Glandular structure destroyed
Lymphoid epithelial lesion, end-stage
Round structure with connective tissue capsule
Increased of risk of MALT lymphomas
Microcellular Carcinoma
Hilus with thrombus
Anthracosis
Respiratory epithelium is intact
Basophilic area has a capsule. It resembles a LN
o Higher magnification: lymphocytes, mitotic figures, loose patches of cells with irregular shape and size.
o Immature, polymorphic, highly proliferative tumor Small cell lung cancers are immature and aggressive
o Treatment is chemo rather than operation
It is thought to originate from neuroendocrine cells (APUD cells) in the bronchus called
Feyrter cells. They express a variety of neuroendocrine markers, and may lead to ectopic production of hormones.
Carcinoma Planocellular (squamous cell carcinoma)
Right side looks like normal skin
Left side has invasion of “keratinized pearls” (the islands in the middle with keratinization)
o Differentiation towards center
Invasive lesions
Cells resemble squamous cells, but with disturbed keratinization (they are highly differentiated)
Struma Nodosa Colloides
Follicles make round acini
Paler pink follicles at outskirt = normal colloid
Darker pink follicles are cystically dilated, making macrofollicules.
“nodose goiter” because it appears nodular macroscopically
Hypocellular, hyalinized stroma form border of nodes
Bluish microcalcifications are a sign of regression
Intrafollicular hemorrhage
Synovial sarcoma
Despite the name, this tumor does not arise from the synovial membrane and is not always a part of joints.
Most common in middle-aged adults in extremities and neck
Biphasic appearance:
o Epithelial-looking (not actually epithelium) o Mesenchymal, spindle cells
Translocation can be detected by FISH
FISH is used for diagnosis of sarcomas and hematological disorders
Teratoma
Sperm not seen, but there is otherwise normal testis in upper left Benign
Elements of all germ layers; mature, haphazard structures:
o Cartilage
o Respiratory epithelium
o Large bowel epithelium with goblet cells
Femoral Artery Thrombus
Muscular wall indicates that it is an artery (cut in vessel is postmortal because there is no
bleeding)
o White clot
Internal elastic membrane marks border between tunica media and intima
Tunica intima is widened. Atherosclerotic plaques have darker patches of inflammation
Endothelial cells bordering lumen are absent, replaced by fibrous material and clotting
o Trabeculae of the fibrin mesh present inside the thrombus means that the thrombus is stationary and connected to the wall, unlike post-mortal clots
o Clot attached to wall indicates it was formed on wall plaque, where endothelial surface is ruined.
Arterial clots are rarely occlusive, but emboli are
transitional carcinoma- urothelial carcinoma of the bladder
Tuberculosis Pulmonis
Development of tuberculosis:
o Primary: Mycobacterium infects alveolar macrophages and survives inside, spread to
multiple sites. Induces immune system granuloma formations. Ghon complex is a combination of parenchymal and nodal involvement. T-cell mediated immunity causes spread into lymph nodes (3 weeks after exposure) and causes granuloma formation (Ranke complex)
o Secondary: typically initiated in immunosuppressed patients. Arises from reaction of dormant primary lesions. Necrotic lesions. Bacteria released from airways and ingested.
Patches and nodules similar to pulmonary abscess or tumor on low power, but they are granulomas.
o Granulomas are 0.1-0.5 mm round structures composed of epithloid cells
o Caused by infection, foreign body, or unknown etiology (sarcoidosis, Crohn’s
Disease)
From inside of the tuberculoma to outside:
o Eosinophilic center with causeous necrosis and the bacteria
o Pale blue ring of epitheloid cells (= type of macrophages resembling cuboidal
epithelial cells; abundant cytoplasm and central nuclei), which can fuse to form giant
cells (= multinucleated)
o Dark blue lymphocytes in an amorphous, anuclear substance; caseous necrosis
To confirm that this is a tuberculoma, we use Ziehl-Neelsen (Acid Fast) Stain
Background is pale blue, bacteria are red
Clumped blue areas are granulomas; at higher mag, eosinophilic bacteria are seen there, too
Chronic inflammations can be:
o Specific: e.g. tuberculoma, have characteristic morphology for the etiology
o Non-specific: majority; morphology of inflamed tissue is not characteristic for the etiology
Tuberculosis Pulmonis
Development of tuberculosis:
o Primary: Mycobacterium infects alveolar macrophages and survives inside, spread to
multiple sites. Induces immune system granuloma formations. Ghon complex is a combination of parenchymal and nodal involvement. T-cell mediated immunity causes spread into lymph nodes (3 weeks after exposure) and causes granuloma formation (Ranke complex)
o Secondary: typically initiated in immunosuppressed patients. Arises from reaction of dormant primary lesions. Necrotic lesions. Bacteria released from airways and ingested.
Patches and nodules similar to pulmonary abscess or tumor on low power, but they are granulomas.
o Granulomas are 0.1-0.5 mm round structures composed of epithloid cells
o Caused by infection, foreign body, or unknown etiology (sarcoidosis, Crohn’s
Disease)
From inside of the tuberculoma to outside:
o Eosinophilic center with causeous necrosis and the bacteria
o Pale blue ring of epitheloid cells (= type of macrophages resembling cuboidal
epithelial cells; abundant cytoplasm and central nuclei), which can fuse to form giant
cells (= multinucleated)
o Dark blue lymphocytes in an amorphous, anuclear substance; caseous necrosis
To confirm that this is a tuberculoma, we use Ziehl-Neelsen (Acid Fast) Stain
Background is pale blue, bacteria are red
Clumped blue areas are granulomas; at higher mag, eosinophilic bacteria are seen there, too
Chronic inflammations can be:
o Specific: e.g. tuberculoma, have characteristic morphology for the etiology
o Non-specific: majority; morphology of inflamed tissue is not characteristic for the etiology
Ulcerative Colitis, H&E, Large Intestine
No villi or short villi reduce surface area, leading to malabsorption
Increased intraepithelial lymphocytes (IEL): 40+ IEL/100 epithelial cells
T-cell lymphoma may arise
Hyperplastic crypts of Lieberkühn
Inflammatory bowel disease
When uncertain whether the patient has ulcerative colitis or Crohn disease, it is called
‘indeterminate colitis’
These are endoscopic biopsies
o Only has mucosa. Ulcerative colitis is confined to mucosa.
Disordered mucosa
Crypt abscesses have inflammatory neutrophil granulocytes with mixed infiltrate.
o Plasma cells dominate
o Decreased number of goblet cells
Stroma has mixed infiltrate with plasma cells
Wilms Tumor, Nephroblastoma
Most common malignant kidney tumor
<5 years old; often huge by the time the tumor is diagnosed
Kidney is of mesodermal origin
No normal kidney tissue
Biphasic pattern
3 components:
o Light area represents stroma (mesenchymal component)
o Dark part is blastema
o Epithelial component (secondary epithelium) forms tubular, glomerular structure
Hematogenous spread by renal v. to liver and lungs
