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2017

Pathological anatomy exam pictures:

4th SEMESTER:

Myocardial hypertrophy: Hypertrophy: A cellular adaptation reaction, that leads to enlargement of cells, causing increased
size of organ/tissue. No new cells are made.
Increased synthesis of structural components. Large darker nuclei because of DNA-synthesis.
 Big nucleus and cytoplasm.
- Causes:
o Physiological:
 Increased functional demand: Muscle hypertrophy
 Hormones/Growth factors: Myometrium during pregnancy
o Pathological:
 Arterial hypertension or valvular disease causing myocardial
hypertrophy.
- Mechanism:
o Mechanical sensors result in increased growth factors.
 TGF-beta, IGF1
- Physiological hypertrophy: Phosphoinositide 3-kinase pathway.
- Pathological hypertrophy: G-protein. This causes changing of myosin from adult to fetal
form (Alpha to Beta), having more slow and ergonomical contraction.
- Outcome:
o Reversible if stress eliminated.
o Enlarged heart, stronger contraction

Fibroatheroma and thrombosis: Thrombus: Local blood clot.

- Pathogenesis: Virchow’s triad:
- Thrombus at the top,. o Endothelial damage: Trauma, atherosclerosis, hypertension.
- Atherosclerotic plaque o Alteration of blood flow: turbulent or slow blood flow.
down, with small calcifications o Hypercoagulability: Primary (mutations) or secondary (aging, smoking).
and fibrosis  Stage 6!!! - Types:
Complications already o Mural (In the heart like arrhythmia, or arteries like plaques) vs. Occlusive
(Occlude the lumen) OR Arterial (Coronary, femoral, brain artieries) vs. Venous
(lower extermities, periprostatic, periuterine plexus)
- Life cycle of a thrombus:
o Propagation: Spread along the blood vessel, accumulation of platelets and fibrin.
o Embolization: Clot detach, sent around in the body.
o Dissolution: Fibrinolysis, removes thrombus.
o Organisation + recanalization: Migration of SM, fibroblasts and SM.
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- Atherosclerosis stages:
1. Fatty droplet: I/C fat inside macrophages, in intima.
2. Fatty streak: Groups of foamy macrophages, mainly intracellular fat. Some T-ly, flat
lesion, no hemodynamic disturbance.
3. Imminent lesion: Fatty streak + small aggregates of extracellular fat.
4. Atheroma: Fatty core: SM, M/ph, Ly, with collagen and elastic fibers. Intracellular +
extracellular fat.
5. Fibroatheroma: Fatty core + fibrosis and calcinosis. Surface has CT and SM fibers.
6. Complications: Fibroatheroma + Thrombosis, rupture, ulceration, erosion,
hemorrhage, aneurysm.
- Pathogenesis: Atherosclerosis happens mostly by chronic endothelial damage, with
accumulation of lipids; activating macrophages and lymphocytes. This leads to increased
cytokines, growth factors, with proliferation of SM.
- Risk factors:
o Age, male, family anamnesis, smoking, little physical activity, fatty meals, alcohol,
stress, DM, hypertension, hyperlipidemia, obesity.

Ischemic myocardial infarction: Myocardial infarction:

- 90% happens due to atherosclerosis. Ischemia is a dysbalance between demand and
supply of oxygen, causing destruction of tissue.
- Myocardial infarction is a coagulative necrosis:
o This necrotic fibers, hypereosinophilic, causes acute inflammation  Reaction of
necrosis.
o Preserved outlines, prevents fast destruction due to inactivation of proteolytic
enzymes.
- Morphology:
1. 0.5-4h: No changes, sarcolemma destruction, mitochondrial changes.
2. 4-12h: Paler heart, with edema and hemorrhages, coagulative necrosis.
3. 12-24h: same as above + neutrophil infiltration.
- Lower part: Necrosis, loss of architecture - White infarction, necrotic area. 4. 1-3 days: pale area, more neutrophils
eosinophilic, no nuclei. 5. 3-7 days: Pale area, rupture of fibres, necrosis. Degradation, Macrophages start to
- Upper part: Chronic inflammation come.
6. 7-10 days: Pale + soft, marked phagocytosis and granulation tissue.
7. 10-14 days: Granulation tissue.
8. 2-8 weeks: Fibrous tissue, with increasing amount of collagen. Scarring.
9. Reperfusion – If started within 4 hours  Decreased infarction size.
- Complications of MI:
o Loss of contractility (systolic dysfunction)  Heart failure.
o Rupture
o Arrhytmias
o Pericarditis
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o Mural thrombus
o Heart aneurysm
o Sudden cardiac death

Breast fibroadenoma:
Breast fibradenoma: Most common benign tumour in female breasts!
- Morphology:
o Single, nodular, multiple or bilateral.
o Painless, firm and slow growing. Grows in size.
o Encapsulated and mobile lump.
o During gravidity: lactational changes (compression of nearby ducts), infarction or
inflammation.
- Pathogenesis:
- Benign clear border of o Fibroepithelial growth and stromal expansion.
gross picture. Encapsulated. o Hormone related growths, that affect during reproductive years  30y mean.
- Epithelium and stroma. Change during menstrual cycle.
o Regress during menopause, causing stromal hyalinosis.

Invasive breast cancer: Ductal breast cancer Ductal breast cancer:

- Most frequent invasive breast cancer (70-80%).
- Gross: Hard, white/yellow
- Microscopic: Tubular, hard complexes of neoplastic cells.
o Show expression of E-cadherin.
o Hyperchromatic anaplastic cells.
o E-cadherin keeps them close together (Stain +)
o Atypical ductal hyperplasia, fibrocystic breast changes.
- Risk factors for breast cancer:
o Age (>50y)
No clear border, desmoplasia. 2-3 layers of cells, anaplastic. o Early menarche, early pregnancy
Hyperchromatic cells. o Late menopause
o BRCA1/2 mutation.
o Radiation
o Endometrial cancer
o Diet
o Adiposity
o Environmental factors
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Melanoma: Melanoma: Most deadly skin cancer.
- Morphology:
o Loss of cell cohesion, lateral growth with irregular borders. Invasion into
Epidermis.
o Variable in size, and shape! Asymmetric.
o Loss of maturation  Anaplastic, with Intranuclear cytoplasmic inclusions. Large
nuclei, hyperchromatic,
Melanoma: Fibrous o Cell atypia, mitosis and necrosis, causing chronic inflammation.
tissue with scar. - Growth: Horizontal and vertical!
- Symptoms: Painless, itching, ulceration, bleeding, change of appearance.
- Primary locations: Eye, skin, anogenital mucosa and mouth mucosa.
- Spread: Very aggressive:
o Lymphogenous
o Hematogenous
- Learn Clark (layers) and Breslow (mm) stages.
- Anti-HMB45+ and Anti-CK-AE1 and 2 +
Lipoma: Lipoma: Benign tumour of adipocytes.
- Most frequent soft tissue tumour of adults.
- Grossly:
o Soft, can be moved, usually not painful (except for angiolipoma).
- Morphology:
o Encapsulated node
o Mature fat cells, resembling normal adipocytes.
o No cellular atypia.
- Spread: Expansive.
- Nodular structure, non painful, smooth surface, encapsulated.
- In intestines it can cause ulceration.

Leiomyoma: Leiomyoma (in uterus: Fibroid): Benign mesenchymal tumour developing from Myometrium.
- Big nodules of smooth - Tumour of smooth muscles, usually in the uterus.
muscles, nodules are - Can develop in M. erector pili (Pilar leiomyoma), skin, breast areola and scrotum.
chaotic with normal cells. - Morphology:
o Skin  1-2 cm
o Uterus: Large
o Spindle cells that are dysplastic (chaotic) without atypia, resemble normal cells.
- Normally it is benign.
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Kaposi sarcoma: Kaposi sarcoma: Endothelial tumour of intermediate grade
- Cause: Human Herpes Virus 8 , with a co-factor of HIV.
- Types:
1. Classic/European: Elderly, skin eruptions, spreading.
2. Endemic/Lymphadenopathy: South-African children, with affected lymph nodes,
visceral spread with aggressive course.
3. Transplant associated: Solid organ transplantation, immunosuppression.
4. HIV-associated: AIDS patients (1/3). Dissemination.
- Morphology:
o Patches: Red/purple macules, dilated and irregular. Endothelium.
o Plaques: Raised skin eruptions, dilated and jagged channels with spindle cells.
o Nodules: plump of spindle cells, containing slit-like spaces with RBCs.
GIST: Gastrointestinal stromal tumour Gastrointestinal stromal tumour (GIST):
- Mesenchymal tumour in the GI-tract, arising from Cajal cells, showing CD-117 +.
- Most common mesenchymal malignancy in GI-tract.
o Male and female ratio equal.
- Morphology:
o Mass inside wall, causing bulging out of the tissues.
o Occlusion of lumen, can cause exulceration on the top.
- Localization:
o Stomach – 60-70%
o Small intestines – 20-30%
o Esophagus
o Large bowel
o Rectum
o Mesentery, omentum
- Morphology:
o Rounded mass lesion, with cystic changes (possible).
o Softer than leiomyoma or cancer.
o White, tan colour.
- Microscopic:
o Spindle cells: 70%
o Epitheloid cells: 30%
o Mixed
-
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Renal clear cell cancer: Malignant renal cell cancer, of clear/eosinophilic cells, with rich
Renal clear cell cancer: vascularisation and delicate network of capillaries.
- Morphology:
o Yellow tumour (contain cholesterol, fats and phospholipids).
o Cystic changes
o Calcification, ossification, necrosis, haemorrhage.
o Unilateral mostly.
o Pseudocapsule
- Microscopically:
o Solid alveolar acini, with delicate capillaries. Optical clear cytoplasm.
o Nuclear atypia, with a high degree of anaplasia.
- Spread:
o Local invasion
o Hematogenous: V. cava, v. testicular, ovarii, lungs, brain,
o Lymphogenous  LN
- Risk factors:
o Smoking, asbestos, cadmimum, adiposity, hypertension, inherited.
- Clinical features: Costovertebral pain, palpable mass, hematuria, general symptoms (fever,
malaise, weakness, etc,) typical for Paraneoplastic syndrome.
Urinary bladder cancer: Urothelial cancer: Urinary bladder cancer: 7th most frequent cancer worldwide. Three types (Urothelial, squamous,
adenocarcinoma)
- Gross view:
o Papillary, polypoid, nodular, solid, ulcerative or transmural! Different shapes.
o Solitary or multifocal.
- Microscopic:
o Cohesive cells, with anaplastic features (hyperchromatic nuclei, polymorphic,
malignancy).
o Wide cytoplasm
Polypus surface, with nuclear atypia (upper o Stromal desmoplasia and inflammation.
right picture). o Can be urothelial Ca. in situ.
Lower picture: Invasion into SM - Growth:
o Papillary, but surface can be smooth.
o Invasion hard to distinguish. Invasive growth.
- Risk factors:
o Smoking, carcinogens, aniline dyes, aliminium factories
- TNM classification: LEARN
TX –no data about the primary cancer
T0 –no primary tumour
Ta –Non-invasive papillary carcinoma
Tis –Non-invasive “flat” Ca in situ
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T1 –tumour invades subepithelial connective tissue

T2 –tumour invades muscle layer
T3 –tumour invades perivesical tissue
T4 –tumour invades prostate, uterus, vagina, pelvic or abdominal wall

Benignprostatic hyperplasia (BPH): Benign prostatic hyperplasia (BPH):

- Nodular hyperplasia of stroma and epithelium, resulting in a weight of gland exceeding 20g, in
average 100g.
 50-70 year males.

Enlargement of prostate, stromal and glandular hyperplasia, secondary cystic atrophy, corpora
amylacea.
- Pathogenesis:
- Cheese like o Hormonal dysbalance
structure, with o Activation of mesenchymal stem cells.
dilated gland. BPH starts in periurethral parts.  Growth starts in periurethral parts (around urethra) in small nodules,
- Hypercellularity in microscopic pictures, 2 layers. compressing the urethra. Can cause urination difficulties.
Corpora amylacea. - Microscopic structures:
- Atrophy due to inflammation and dilation. o Stromal and epithelial hyperplasia.
o Corpora amylacea: Stasis of gland secretion, due to compressed ducts, can
become calcified.
o Cystic atrophy, due to dilation, with secondary inflammation.
- Complications: Prostate infarction, UTI.
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Prostate cancer: Prostate cancer:
- Nodular changes in - Highest prevalence of malignant tumour in males.
subcapsular areas. - Classification by WHO:
- Adenocarcinoma, gland o Epithelial:
like structures, with  Acinar or ductal Adenocarcinoma, intraepithelial neoplasia, Urothelial
atypical cells (green arrow). tumour, squamous tumour, basal cell tumour.
- Nucleomegaly o Neuroendocrine
- Gleason 4: Cribiform o Mesenchymal
- Gleason 3: Infiltrative. o Other
- Morphology: Subcapsular growth of prostate gland, starting with small nodules.
- Microscopic changes:
o Adenocarinoma: Glands
o Single row of malignant cells (BPH has 2).
o Invasive growth, with increased epithelial:stromal ratio.
o Atypical nuclei
o Crystalloid in lumen.
Perineural growth - Gleason grading system:
Gleason 1
Few low-grade tumors
Cancer nodule is rounded
Malignant glands are of equal size and shape

Gleason 2
Rounded malignant glands with some variability

Gleason 3
Most frequent pattern
Marked with infiltrative growth

Gleason 4
Confluent and cribriform glands

Gleason 5
Almost lost glandular differentiation
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- Spread:
o Local spread:
 Periprostatic: Lateral, anterior, perineural (PICTURE).
 Vesical neck
 Seminal vesicle: Direct, along ductus ejaculatorius, perineural or
lymphatic/hematogenous.
 Rectal invasion  Denovilliers fascia.
o Metastatic spread:
 Regional LN: Obturatoic, hypogastric, iliac etc.
 Bones: Pelvis, spine, ribs, sacrum, humerus.
 Visceral metastases: Lungs, liver.

Amyloidosis in the kidney: Amyloidosis in the kidney:

Extracellular deposits of fibrillary proteins, that are misfolded. Made out of Beta-sheets which are
hydrophobic. When they come in contact with hydrophilic substances, then the aggregate more
When they are released, they get misfolded and cause aggregation together with other misfolded
proteins, forming amyloid plaques.
- Beta-sheet secondary structure, instead of alpha.
- Localized amyloidosis: Urinary bl., uretra, ureter, skin, conjunctiva, larynx, heart, pleura,
cartilage etc.
- Systemic amyloidosis: Kidneys, liver, nerves, abdominal fat, spleen, bone marrow.
o Must show amyloidosis in at least 2 different organs/tissues to be systemic.
- Amyloid depositions in kidney glomeruli, between capillaries. - Properties of amyloid: Congo red, apple green affinity, insoluble.
- Congo red.

- Systemic amyloidosis:
1. AL/AH: Ig Light or Heavy chain: Primary, Myeloma  Plasma cell problem.
2. SAA: Serum amyloid A (APR) Secondary, inflammatory  Long standing inflammation
3. ATTR: Transthyretin: Familial, senile systemic  mutation of Transthyretin.
- Local amyloidosis:
1. AL/AH: Ig chains: Primary, myeloma.
2. A-Beta: A-beta protein precuross: Alzheimers
3. APrP: Prion protein: Spongiform encephalopathies
4. AIns: Insulin: Latrogenic
5. ACal: Calcitoninc: C-cell tumour of thyroid gland (Medullary thyroid carcinoma).

- Mechanism of amyloid formation:

Amount reaches a critical concentration, with loss of inhibitors. Start to nucleate and form
large plaques of amyloid that interfere with organ function.
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- Complications: Destroy organ function. Related to kidneys: Causes Nephrotic syndrome.

Crescentic Glomerulonephritis (GN): Extracapillary Crescentic glomerulonephritis:

- Most aggressive GN  Causes progressive Acute renal insufficiency.
Green: Proliferation of glomeruli, - Morphology:
sclerotic. o Extracapillary proliferation, like a half moon.
Yellow: Crescent proliferation, o Genesis of crescents:
contains: M/ph + Epithelial cells.  Proliferation of glomerular epithelium and macrophages.
 Capillaries may rupture.
 Fibrin in Bowmans capsule may stimulate proliferation.
- Pathogenesis:
1. Anti-GBM GN: Antibodies against glomerual basement membrane:
- Pulmo-renal syndrome: Goodpasture syndrome.
2. Immune complexes:
- Deposits of IC in Basement membrane: Post infectious, IgA nephropathy, idiopathic.
3. Pauci-immune crescentic GN: Older patients, better prognosis.
Renal polycystosis (AD type): Polycystic kidney disease:
1. Autosomal Dominant  Adult polycystic kidney disease
- Renal function is normal until 40-50-years are reached.
- Morphology:
o Many cysts
o Bilateral
- Pathogenesis:
o Polycystins, genetic abnormality between intercellular interactions, causing
epithelial proliferation with fluid excretion, forming cysts.
o Genetical disease

2. Autosomal recessive  Childhood polycystic kidney disease

 Perinatal, neonatal, infantile, juvenile!
 Fibrocytin: cell surface receptor, participating in differentiation of renal collecting ducts as
well as liver bile ducts is not normal.
 Morphology: Enlarged kidney, smooth and many cysts in medulla + cortex! Cylindrical +
saccular dilatation of collecting duct, ALWAYS BILATERAL, associated with fibrosis
3. Multicystic renal dysplasia: Sporadic, due to disturbances of metanephric differentiation.
 Morphology: Persistant of immature cartilage, undifferentiated mesenchyma + cysts.
o Typical with anomalies of lower urinary tract, with good prognosis!
4. Acquired renal polycystosis:
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 Dialysis patients, with multiple cortical + medullary cysts: 0.5-2cm
 Usually asymptomatic, can have bleeding + cancer.

Aortic atherosclerosis: Aortic atherosclerosis:

- Atherosclerosis: Intimal damage and formation of atherosclerotic plaque, that narrows vascular
lumen, influences blood flow and weakens tunica media.
- Stages of atherosclerotic plaque described in 2nd picture.
- Architecture of atherosclerotic plaque:
o Shoulder (green arrow): cellular housing: Macrophages, smooth muscles and T-ly.
 Can have neovascularization, calcinosis and growth.
o Surface (blue arrow): CT and smooth muscle
o Detritus (black arrow): Organic debris, fat, fibrin, thrombi, necrotic tissue, foam
cells, plasma proteins.
- Complications: thrombosis, rupture, ulceration, erosion, haemorrhage, aneurysm.
- Atherosclerotic aortic aneurysm:
o Mostly abdominal aorta, below ostia of kidney arteries (T12, L1).
o Can be in aortic arch, thoracic aorta or inguinal arteries.
o Pathogenesis: Severe atherosclerosis, featuring ulcers and granulation tissue with
thrombosis.
o Saccular, fusiform.
o Can become 15-25cm long.
- Pathogenesis: Atherosclerosis happens mostly by chronic endothelial damage, with
accumulation of lipids, activating macrophages and lymphocytes. This leads to increased
cytokines, growth factors, with proliferation of SM. Endothelial damage is done by every
process mentioned, with damage of cells, and inflammation + fibrosis.
- Risk factors:
Age, male, family anamnesis, smoking, little physical activity, fatty meals, alcohol, stress,
DM, hypertension, hyperlipidemia, obesity.

Kidney infarction: Kidney infarction:

White necrosis of kidney. These are referred to as "white" because of the lack of hemorrhaging and
limited red blood cells accumulation. Caused by arterial occlusions.
-
- Necrotic tissue
o Microinfarctions, with necrosis and inflammatory cells at the top.
Armend B. 24.01.2017
Muscle atrophy: Muscle atrophy: Loss of fibers and nuclei, no distinct borders. Lipofuscin accumulation
(degradation)
Atrophy: Shrinkage of cell or organ.
Cause:
 Decreased workload  lowered activity  Osteoporosis is perfect example.
 Denervation  loss of nerve supply
 Decreased blood flow  ischemia
 Lack of nutrients
 Lack of endocrine stimuli
 Aging
 Pressure
Mechanism: Reduced size of an organ or tissue! Biological aim is to ensure survival of the cells in a
difficult time, by decreasing metabolic needs.
 Decreased cell size and number of organelles: Decreased protein synthesis + increased
degredation:
o Ubiquitin-proteasome pathway: Degrade uneeded or damaged proteins, by
proteolysis when Ubiqitin attaches onto the proteins.
o Autphagy: Cell eats/destroys its own components to acquire nutrients. Makes
autphagic vacuoles, which fuse with Lysosomes to digest it.
Lipofuscin related to wear+tear pigment, is typically seen.
Outcome: Change can be reversible, if the factor causing atrophy is removed.
Apoptosis happens if the factor stays for a long time.

Reflux oesophagitis: Irritation of esophagus by gastric juice reflux. Most common cause for
Reflux oesophagitis: oesophagitis.
- Etiology:
Eosinophil in mucosa - Primary - Idiopathic but might be because of weak sphincter
Basal cell hyperplasia
Chronic inflammation - Secondary - Antidepressants, pregnancy, hypothyroidism, alcoholism, smoking,
overeating, axial sliding hiatal hernia
- Morphology:
o Intraepithelial inflammatory cells (Eo, Neu, Ly).
o Basal cell hyperplasia (20%)
o Elongated papillae (Exceeds 2/3 of epithelial layer)
Armend B. 24.01.2017
- Complications:
o Barrets esophagus  Metaplasia into intestinal epithelium, protection.
o Ulcers
o Bleeding

Oesophageal squamous cell cancer: Oesophageal tumours: Benign (lipoma, leiomyoma), malignant (sq. cell cancer, adenocarcinoma),
unknown (GIST).
Oesophageal squamous cell cancer: Malignant epithelial tumour with squamous differentiation,
showing keratinization and intercellular bridging.
- Risk factors:
o Decreased vit. A, C, riboflavin, thiamine
o Nitrite in food
o Mold
o Alcohol
o Hot burning dishes
o Chronic esophagitis, achalasia, celilac
o Smoking
- thickened esophageal wall. Cells (in situ) show anaplastic features to the left, on - Growth:
the right is normal epithelium. The cells have different shapes, hyperchromatic, o Invasive
increased mitosis and can form Keratin bells (right picture) surrounded by o Metastasis
Lymphocytes, chronic inflammation. - Gross:
o Early: Small white elevations, in mucosa.
o Late: Polypoid, flat or ulceration.
- TNM:

T1 – invasion in lamina propria or

submucosa
T2 – invasion in muscle
T3 – invasion in adventitia
T4 – invasion in other organs
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Acute gastritis Infiltration of Neu
Increased capillary permeability
Haemorrhage
Oedema

Causes: NSAID, Alchohol, smoking, ischemia, cold, stress

 Pathogenesis: protective properties of and Pathogenesis of acute gastritis

o gastric pH:
 should deactivate microorganisms
 H. pylori is able to escape gastric acid, increase pH and cause
inflamamtions
o Mucus layer:
 Mechanical and acidic protection
 Layer thickness decreases in age, stomach becomes more sensitive in
age
 Can be damaged by strong acids or bases
o Bicarbonates:
 Filled with alkaline substance: normally can’t be stirred and protects
from acid
 NSAIDs, limit blood supply and interfere in bicarbonate synthesis
 H. pylori; cleaving urea into NH3, increasing pH in lumen, dissolving
bicarbonate layer
o Blood supply:
 Provides nutrients to build up mucosal wall
 Hypoxia, or malnutrition leads to reduced synthesis
o Cell proliferation:
 Maintains level of active cell, to produce gastric acid and mucous
 Can be damaged by alcohol or chemotherapy
Armend B. 24.01.2017
Chronic gastritis:
Chronic inflammation in gastric mucosa, with mucosal atrophy and epithelial metaplasia.
- Causes:
o H. pylori  Chronic gastritis, peptic ulcer, carcinoma, MALT. (immunohistochem
or Giemsa)
o Autoimmune
o Toxins
o Irradiation
- Morphology:
o Starts slowly, long-lasting.
Chronic gastritis: - Morphological components
o Reactions and infiltration of lymphocytes,plasma cells and macrophages
o Proliferation of blood vessels
- Inflmmatory cells in mucosa, star: bv. o Fibrosis, necrosis, tissue injury and repair
Diapedesis and migration. Shows that it is o Epithelial metaplasia and glandular atrophy
active.
- Helicobacter pylori: Immunohisto chem or - Starts during phase of active inflammation
giemsa. - In 48h, m/ph acquire dominant status
- Active secondary follicle in Chronic gastritis. - Activation by:
- Primary lymphoid follicle to the left. o T- and NK ly cytokines
o Bacterial endotoxins
H.pylori adheres to epithelial cells  Uses flagella to move and burrow into the o
tissue  Converts urea to ammonia by urease  Escapes gastric acid by doing this. o Increase in size  Increased conc. of lysosomes  Activated metabolism 
Increased ability of phagocytosis and killing

- Complications:
o Peptic ulcer
o Intestinal metaplasia + atrophy
o Gastric cancer
Gastric cancer: Intestinal type
Adenocarcinoma, characterized by gland like tubular cells, appearing mostly in antrum and
Gastric cancer: Intestinal type curvature minor. Can cause ulcerations.
- Risk factors:
o H. pylori
o Nitrate
o Decreased vegetables
o Low socio-economic status
o Smoking
o Chronic atrophic gastritis
o Gastrectomy
o GAP, HNPCC
Armend B. 24.01.2017
- Morphology: Rough surface, no capsule. Thick mucosa obtrudes the lumen. Large node
causing exulceration of gastric mucosa, can lead to bleeding. The cells are glandular
structure, with anaplastic features. Cells contain apical mucin vacuoles.
o Cohesive cells due to E-cadherin.
- TNM: LEARN + Lauren classification.

- T1 invasion into lamina propria or submucosa

- T2 invasion in muscle layer
- T3 invasion into adventitia
- T4 invasion into adjacent organs

Gastric Gastric cancer: Diffuse type

- Gastric cancer located throughout the whole wall, with minimal exulcerations and normal
cancer: mucosal folds.
Diffuse type - Morphology: Uniform thickening of gastric wall, with decreased volume of gastric lumen.
Looses distensiblity.
- Microscopic: cells are discohesive, lack E-cadherin. They are single cells that infiltrate
individually called Signet cells.
Contain large mucin vacuoles in the mucosa.
- TNM + Risk factors: ABOVE

Celiac disease
Chronic malabsorption disease

Immune reaction to gluten (specifically gliadin, a fraction of gluten which contains the
antigen that induce the celiac disease)

Pathogenesis: T-cell mediated chronic inflammation (autoimmune disease)

 Morphology:
o Intraepithelial lymphocates above 40 per 100 epithelial cells
o Villous atrophy
o Crypt hyperplasia
 Morphological classification:

0: normal mucosa; no pathological findings

Armend B. 24.01.2017
1: infiltrative lesion; visible by increased lymphocyte count
 Above 40/100 epithelial cells
2: hyperplastic lesion; lymphocyte infiltrates and crypt hyperplasia

3: destructive lesion; lymphocyte infiltrates, crypt hyperplasia and villous atrophy

(complimentary factors attach to marked cells and induce apoptosis)
 Most diagnosis are made in this stadium
4: hypoplastic lesions: lymphocyte infiltrates, crypt and villous atrophy

Crohn’s disease

Idiopathic/inflammatory bowel disease: Crohn’s disease:

- Inflammation of GI-tract, that can be from the mouth to the anus.
- Etiology/Pathogenesis: Autoimmune, genetic, intestinal microflora (immune reaction
against it), dysfunctional barrier function, pathological T-cell reaction.
o Mostly affects 15-30 and 50-70 years.
- Morphology:
o Sharp demarcated area of damaged intestinal tissue, alternating from healthy
and affected (skip lesions). UC has continuous lesions.
o Transmural inflammation, with Granulomas. Can be fissures and fistula.
- Gross: Thick wall (edema, fibrosis, muscle hypertrophy), sharp border.
- Microscopic:
o Mucosal inflammation, crypt abscess, ulcers and deep fissures, non-necrotising
granulomas, nerve hyperplasia and vasculitis.
- Localization: Mostly small intestines and large intestines. Can be everywhere of GI-tract.
- Symptoms: GI-symptoms (pain, vomiting, weight loss, malnutrition etc), systemic (fever,
delayed development, weight loss) and extra-GI (Arthritis, skin problems, eye,
neurological).
- Course: Remissions and exacerbations.
- Complications:
o Intestinal obstruction
- Diffuse inflammation in LP, with Giant cells and Granuloma formation (yellow o Fistula and perforation
arrows). Down right pic: Ulcer at top with fissure ulcer. Anal region. o Abscess
o Cancer risk, malnutrition, bleeding
Armend B. 24.01.2017

Necrosis of small intestines due to mesenterial thrombosis: Ischemic bowel disease:

- Ischemia can affect the whole GI-system. From several meters (Truncus coeliacus, A. mesenterica
superior etc.) to small areas (small branches).
- Types:
o Artery or vein.
o Acute or chronic.
o Depth: Mucosal, mural or transmural.
- Predisposing factors:
o Arterial thrombosis: Atherosclerosis, vasculitis, hypercoagulation etc.
o Thromboembolic in arteries: Arrhythmias, endocarditis.
o Venous thrombosis: Hypercoagulation, sepsis, liver cirrhosis.
o Non-occlusive ischemia: Heart failure, shock, vasoconstrictive medication
(digitalis, propranolol etc).
o Various: Radiation, mechanical compression (volvulus), hernia, Amyloidosis, DM.
- Acute transmural infarction morphology:
o Large artery occlusion (T. coelicaus, mesenterica sup, mesenterica inf).
o Gut usually red, with subserosal and submucosal hemorrhages. Edema.
o Gangrene within 1-4 days, with necrosis.
- Acute mucosaland mural infarction morphology:
o Mural: submucosa + mucosa, mucosa: mucosa.
Armend B. 24.01.2017
o Can be unifocal or multifocal. Affected areas are hemorrhagic and edematous,
but lack subseroal hemorrhages or fibrin deposits.
o Limited necrosis, weak inflammation.

Acute appendicitis: Phlegmonous appendicitis Acute appendicitis: Acute inflammation of appendix

- Pathogenesis: Acute inflammation causing purulent exudate and destruction of tissue.
Initiated by increased intraluminal pressure (by inflammation), causing compression of
venous blood vessels, leading to ischemic injury. This facilitates bacterial proliferation and
wall infection.
o Wall obstruction mostly: Fecalith, tumour, worms (appendicular enterobiosis)
o Starts acute appendicitis, with phlegmonous necrosis causing gangerene. Can
lead to perforation and purulent peritonitis.
- Epidemiology: Lifetime risk.
- Risk groups: Adolescents and young adults mostly, small children, elderly and pregnant
women.
- Complicatons: Happen due to spread of infection and inflammation
o Perforation
o Purulent peritonitis
o Sepsis
o Pyelophlebitis (infection of portal vein)
o Portal thrombosis
o Liver abcess

Colorectal adenocarcinoma: Colorectal adenocarcinoma:

Carcinoma of the large intestine.
- Epidemiology:
o Age: 60-80, some before 50.
o Young person mostly due to IBD or hereditary cancer syndromes (FAP, HNPCC).
- Risk factors:
o Geography: Western countries, not in Africa, India etc.
o Diet:
 Little fibers, high carbs + fats, little vitamins, increased fat intake
(increase synthesis of cholesterol and bile acids in liver, increased gut
bacteria, can produce carcinogens).
o Obesity AND No physical activity
- Tumour, with circular stenosis. o Hereditary cancer syndromes: FAP, HNPCC.
Microscopic pictures show mucin - Pathogenesis: Adenoma, turning into a cancerous sequence  Adenocarcinoma.
secretions and anaplastic cells, large - Localization: Mostly Rectosigmoidal area, but also caecum and colon ascendens.
and hyperchromatic.
Armend B. 24.01.2017
- Grossly:
o Mass lesion, with obstructing growth, can cause stenosis. Infiltrative into muscle
and serosa layers. Infiltrative lesions have ulcerative colitis as background.
- Microscopic: Gland formations with mucin secretions.
Grading
G1: high resemblance to original tissue; low grade malignancy

G2: moderate resemblance to original tissue; low grade malignancy

G3: low resemblance to original tissue; high grade malignancy

G4: non-differentiated, resemblance to original tissue; very high-grade malignancy

Can grow with perineural invasion which gives pain and motor control problems.
Chronic hepatitis: Hepatitis B Chronic hepatitis: HBV
Inflammation in the liver causing damage to hepatocytes more than 6 months!
-Sanded nuclei (HBcAg), Grounded - Etiology:
cytoplasm (HBsAg) o Hepatitis virus: B, C, D (+- HIV).
- Apoptotic cell, upper right o Autoimmune
- Lower left: Bile ducts o Drug induced (toxic).
o Cryptogenic
- Pathogenesis: Viral infection presents viral antigens on the surface of Hepatocytes. This
will attract lymphocytes to the area, causing destruction of liver structures. This
eventually leads to fibrosis and cirrhosis, loss of parenchyma. Over time this can cause
hepatocellular carcinoma.
- Morphology:
o Periportal + briding necrosis
o Intralobular degeneration
o Portal inflammation
o Fibrosis
o Cells show:
 Sanded nuclei: HBcAg
 Grounded cytoplasm sER: HBsAg
- Complications:
o Hepatocellular carcinoma
o Liver cirrhosis
o
Armend B. 24.01.2017
Miliary tuberculosis: Look at tuberculosis slides + text further down!

Metabolic liver disease: Liver steatosis Metabolic liver disease: Liver steatosis

Abnormal accumulation of triglycerides in the parenchymal cells.

- Fat accumulation of the liver hepatocytes. Causes destruction of liver.

- Acquired: Non-alcoholic steatosis
o Obesity, Dyslipidemia.
o Hyperinsulinemia, insulin resistance
o DM type 2
o Infections
o Protein Malnutrition
- Inherited: Hemochromatosis, Wilsons disease
o Hemochromatosis: Iron overload disease.
 Hemosiderin deposits, liver cirrhosis and pancreatic cirrhosis. Skin
pigmentation.
o Wilsons disease: AR, Toxic copper levels in the body. Does the same as Fe.
o Amyloidosis.
- Morphology:
o Degree: None, mild (<25%), moderate (25-50%), severe (>50%).
o Types: Microvesicular, macrovesicular, mixed.
o Spread: Focal or diffuse.
Armend B. 24.01.2017
Liver cirrhosis: End stage of many diffuse liver diseases, with loss of lobular architecture. Lobules
Liver cirrhosis: are replaced by connective tissue.
- Causes:
o Diffuse liver diseases: Chronic hepatitis (all types), ethanol, biliary disease,
venous congestion (cardiac cirrhosis), steatohepatitis (alcoholic/non-alc).
o Post-necrotic changes.
- Morphology: Bridging fibrous septa, with pseudo lobules (remaining hepatocyte lobules),
disruption of entire liver structure.
- Pathogenesis: Inflammation causes death of hepatocytes, with activation of fibroblasts to
produce collagen type 1 and 3, along spaces of Disse. This causes proliferation of Stellate
cells  Causing more fibrosis and chemotaxis.  Vascular reorganization and shunting.
Masson trichrome stain. Vascular reorganization, with shunting and capillaries in sinusoids.
- Cause of death in liver cirrhosis:
o Liver failure: Toxics accumulate in the body.
o Portal hypertension  complications
o Hepatocellular carcinoma.
 Complications of P. hypertension  Ascites (increased fluid in
peritoneal cavity), Protocaval shunts (hemorrhoidal plexus causes
haemorrhoids, oesophagogastric venous plexus causes varicose
esophageal veins and periumbilical collaterals causes caput medusa).
Congestive splenomegaly and hepatic encephalopathy is also normal.

Acute cholecystolithiasis: Cholecystolithiasis: Inflammation of the gall bladder due to gall bladder stones.
- Epidemiology: Most adults.
- Types:
o Cholesterol gall stones:
 50% crystalline cholesterol monohydrate  Yellow colour. Most
common (90%).
 Pathogenesis: Increase in cholesterol concentration in bile, exceeding
amount of detergents  Nucleation into cholesterol monohydrate
crystals. Mucous hypersecretion causes trapping into stone masses,
with hypomobility it promotes nucleation.
 Risk factors:
 Geography: Western countries
 Age: Mostly >80y!
 Female sex hormones: Estrogen, oral contac. Pregnancy 
increase HMG-CoA reductase activity, causing more cholesterol
in bile.
 Medication: Fibrates  Reduce blood cholesterol but increase
biliary secretion of cholesterol
 Obesity, Metabolic syndrome, rapid weight loss.
Armend B. 24.01.2017
 Gall bladder stasis: Neuronal, hormonal.
 Hereditary, hyperlipidemia syndromes.
o Pigment stones: Ca2+ + unconjugated bilirubin -> black or brow colour.
 Increase of unconjugated bilirubin due to:
 Infections  Microbial beta-glucoronidases hydrolise bilirubin
Cholesterol stones, with ulcer glucornides. (E.coli, ascaris etc).
 Hemolysis: Increased uncon. Bilirubin.
(black arrow). Angry red mucosa.  Risk factors:
 Geographic areas: Asia
 Rural residents
 Hemolytic sydromes
 Biliary infections
 Crohns
o  Supersaturation of one compound causes nucleation and precipitation,
causing growth.
- Clinical manifestations: Asymptomatic, biliary pain (colic), complications.
- Composition of bile stone: Calcium, cholesterol, calcium bilirubinate, calcium carbonate,
mixed.
- Complications: Choledolithiasis (stone in bile duct), Post-hepatic jaundice, hydrops
vesicae fellae, acute cholecystitis, acute pancreatisis, Mirizzi syndrome, fistula + ileus.

Acute cholecystitis: Acute cholecystitis: Acute inflammation of the gall bladder:

Types:
- Calculous (95% ): Obstruction of neck and cystic duct!
o Chemical irritation + inflammation of gall bladder.
o Gall bladder dysmobility
o Distention + increased intraluminal pressure, compresses bloodvessels, causing
ischemia  inflammation.
o Bacterial infection: Secondary to ischemia.
- Acalculous: 5%
o Cause: Local ischemia  cystic artery is an end artery
o Contributing factors: Inflammation of wall  compromised flow + viscous bile.
o Risk factors: Sepsis, Trauma, Burns, Atherosclersis, Vasculitis, DM, infections.
Armend B. 24.01.2017
Gross picture:
Thick red wall, angry red mucosa! Many ulcerations, with serosal and subserosal changes 
Hemorrhages. Perforation is possible.
Complications:
- Bacterial superinfection  cholangitis  sepsis
- Perforation  peritonitis
- Fistula

Cancer of the Gall bladder: Gall bladder cancer:

- Always (most likely) a Primary tumour. Mostly in females (>50 years)  Correlates with gall
stones.
Risk factors:
- Gall stones
- Cholecystenteric fistula
- Porcelain gall bladder
- UC
- FAP
Clinical manifestations: Local invasion, into muscle layer  pain, similar acute cholecystitis!
General  anorexia.
Gross picture: Diffuse (70%) or polypoid mass (30%).
Types:
- Benign: Adenoma etc.
- Mainly diffuse type
- Malignant: Adenocarcinoma, glandular cells (tubular, papillary, etc), Signet ring cell
cancer, squamous cancer.
- NET: neuroendocrine tumour.
TNM:
T0 – no primary tumour
Tis – Ca in situ
T1 – invasion into lamina propria (T1a) or muscle layer
(T1b)
T2 – invasion into subserosa or adventitia but serosa
and liver are intact
T3 – tumour crosses (perforates) serosa or invades 1
adjacent organ. If liver is affected, invasion depth less
Armend B. 24.01.2017
than 2 cm
T4 – invasion into liver deeper than 2 cm or invasion
into 2 adjacent organs (stomach, duodenum, large
bowel, pancreas, omentum, bile ducts, liver)

Follicular hyperplasia: Follicular hyperplasia: Enlargement of lymph nodes by hyperplasia, which causes variable sizes of
secondary follicles.
Structure:
- Grossly: Enlarged lymph node, that is smooth and normal.
- Microscopic: Increased cellularity inside germinal center, containing hyperplastic cells
such as:
o Macrophages, plasma cells, lymphocytes, some dendritic cells.
o Subcapsular sinus histocytosis and macrophage proliferation.
o Lymphocyte amount does not predominate, such as in Lymphoma.
o Sinusoids can fuse together, normal response  Reactive.
o Different sizes of follicles.
Yellow arrow: Follicular hyperplasia, large o Features showing its not lymphoma:
germinal center.  Normal lymph node architecture
Green arrow:: Mantle zone.  Marked variation in shape and size
Red arrow: CT capsule. Subcapsular sinus  Mitotic activity, phagocytes and dark+light alternating areas.
histiocytosis and macrophage proliferation. Cause:
- Infections, autoimmune diseases, non-specific reactions, acute + chronic lymphadenitis,
HIV, Toxoplasmosis etc.

Diffuse large cell lymphoma (B-cell): Diffuse large B-cell lymphoma: Most common form for Non-Hodgkin’s lymphoma.
- Mostly  60y
- Morphology:
- Gross: Large fast growing mass. Spreads to distant tissues.
o Nodal or extra nodal: Tonsils (Waldeyers ring), spleen, liver, GI, skin.
- Microscopic: Large cells (x4 normal Ly).Diffuse pattern of growth.
o Large rounded cells, with diffuse growth.
o Cytoplasm pale, with large nuclei.
- Clinical manifestations:
- Aggressive, if left untreated, it is fatal.
- Treatment: 60-80% remission.
- Pathogenesis: Genetic, dysregulation of BCL6.
- Immunohistochemistry: CD19 + 20 (Mature B-cell marker), Ki-67  high prolif. Activity
Armend B. 24.01.2017

Large LN with hemorrhage and necrosis.

Large Lymphocytes, x2-3 times size.
Lymphoma in testis, necrosis.

Hodgkin’s Lymphoma: Hodgkin’s lymphoma: Group of lymphatic neoplasms, that are different from Non-Hodgkin’s
lymphomas!
Multinucleated + large nucleoli. Release - Differences:
inflammatory factors - Arise in a single node or chain and spreads to first continuous lymph node (unlike NHL
such as Diffuse large cell lymphoma, spreading to distant tissues).
- Reed-Sternberg cells:
o Large cells, multinucleated
o Cause reactive infiltration of other inflammatory cells (Ly, M/ph, etc).
o Devleop mainly from Germinal B-ly.
- Clinical manifestations:
- Average 30y.
- Painless lymphadenopathy
- Systemic manifestations: night sweating, fever, weight loss.
- Paraneoplastic syndrome: Affected LN can be painful after alcohol ingestion.
- Spread:
- LN.
Ann arbor classification: - Spleen or liver
- Bone marrow
- Extra-nodal involvement is rare.
- Classification:
1. Nodular sclerosis: Most often, affecting mediastinum. Characterized by collagen bands.
Armend B. 24.01.2017
1. 1 LN-regional group OR 1 extra-nodal 2. Mixed cellularity: Mostly young males, with systemic manifestations and wide spread.
organ. Stage 1 + 2 have good prognosis
2. 2 LN groups at one side of the diaphargm 3. Lymphocyte rich: Many Ly + Reed Sternberg cells, classic RS-cells (CD15+30)
with OR without extranodal spread by 4. Lymphocyte depletion: Few Ly + many Reed-Sternberg cells, typical HIV-infected. Wide
invasion. spread and bad prognosis.
3. Both sides of diaphragm affected. 5. Lymphocyte predominance: Change of phenotype of RS-cells (CD20+, 15 and 30 negative)
4. Multiple extranodal foci. - Treatment: Earl stage remission(90%), late (60-70% survive at least 5 y)  Can develop to Acute
myeloid leukemia, lung cancer! Breast, gastric cancer, sarcoma and melanoma risk due to irradiation.
 Each stage + A (no systemic
manifestation) or B(systemic manifestatio) –
night sweats, weight loss and fever.

Bronchopneumonia/Lobular pneumonia: Foci of inflammation in one or several lobes, including

Bronchopneumonia: bronchi.
- Etiology:
- Microbes: Staphyloccocus, H. influenza, Kl. Pneumonia, Pseudomonas etc.
- Pathogenesis:
- Bacteria produces an inflammatory immune response. This response leads to a filling of
the alveolar sacs with exudate (pus)  Loss in air space, replaced with fluid. No normal
wall structure due to edema.

Green arrow: Purulent exudate, with anthracosis to the right.

Yellow arrow: Inflammation in peribronchial site.
Blue arrow: Inflammation in alveoli. - Morphology:
Purulent exudate in alveolar spaces, infiltrated with Neutrophils! - Affects one or more lobes, mostly basally and bilateral.
- Grossly: Foci of consolidation  1-3cm, white circumscribed lesions, separated by normal
lung parenchyma.
- Microscopic: Suppurative+fibrinous exudate rich in neutrophils in the lumen, can be
ulcerations of epithelium. Capillaries are congested!

1. Congestion (24h or less, exudate, m/o, neutrophils)

The affected lobe is heavy, red and boggy; Vascular congestion with proteinaceous fluid and
bacteria accumulation.

2. Red hepatization (2-3 days)

The lung lobe has a liver like consistency: the alveolar spaces are packed with neutrophils, red cells
and fibrin.

3. Grey hepatization - several days

Armend B. 24.01.2017
The lung is now dry, gray, and firm, because the red cells are lysed while the fibrinous suppurative
exudate persists within the alveoli.

4. Resorbtion/resolution 8th-9th day

Exudate in alveoli is enzymatically digested to create debris that can be resorbed.

- Complications:
- Abscess
- Pericarditis
- Pleuritis
- Sepsis
- Respiratory failure
Predisposing factors for pulmonary infections:
- General:
o Chronic infections + immunosuppression/deficiency.
o Hypoproteinemia (loss of albumins and globulins)
o Leukopenia
- Local:
o Decreased cough reflex + activity of macrophages in the lungs (Alcohol, smoking,
CO).
o Damage of cilia: Loss of mucociliary clearance: Smoking, corrosive gases, Viral inf.
Immotile cilia (Kartagener, primary ciliary dysfunction).
o Blood congestion, edema
o Mucous congestion: CF, bronchial obstruction.
Chronic bronchitis: Chronic bronchitis: Chronic inflammation and hypersecretion of bronchial walls.
- Presence of productive cough for at least 3 consecutive months for at least 2 consecutive
years.

- Etiology:
- Long standing irritation: Tobacco, smoke  Direct damage + inflammation
- Infections: Maintain chronic inflammation
- Morphology:
- Mucus hypersecretion, with hypertrophy of submucosal glands. Increased amount of
Goblet cells, secreting mucus  Airway obstruction
- Inflammation  hyperemia, edema, swelling, inflammatory infiltrate.
- Bronchial obstruction  Mucus plug, with muscle hypertrophy  predispose for
infection.
- Epithelial change: Metaplasia, dysplasia, hyperplasia.
- Hyperplasia of Endothelial cells and SM in blood vessels  by inflammation
- Complications:
Armend B. 24.01.2017
Hypersecretion + viscous mucus. - COPS, Respiratory failure, Pulmonary hypertension (bv hyperplasia), Cor pulmonale, HF,
Yellow: hyperplasia. Metaplasia  dysplasia  cancer!
Green: chronic inflammaton. - Clinical manifestations: Productive cough, especially after waking up in the morning, hard to
breath and wheezing.

Metaplasia of cells (upper right), with fibrin

deposits (yellow arrow)

Surface deformity:
Hyperplasia +
muscle
hypertrophy, and
chronic
inflammation

Hyperplastic blood vessels, and chronic inflammation.

Lung emphysema: Lung emphysema: Abnormal permanent enlargement of air-spaces (alveoli), with destruction of
walls without fibrosis (irreversible).
- Etiology:
- Toxic substances: Tobacco, pollutants
- Genetical alpha1-antitrypsin deficiency
o Both lead to inflammation and destruction of alveoli + airways.
- Morphology:
Destruction of alveolar walls, forming large airway spaces, with decreased amount of capillaries
(destroyed too). Loss of Elastic fibers leads to collapse of air-sacs during expiration, making it hard
to inflate them again.
- Types of emphysema:
1. Centroacinar emphysema: Central parts of acini affected, while distal are spared! Normal
+ abnormal acini. Neu are recruited to produce elaste  Elastin is destroyed
2. Panacinar emphysema: All parts of acini affected and are enlarged. Most dangerous, less
diffusion and no breathing! Alpha-1 antitrypsin deficiency --> Does not regulate elastase
anymore --> Elastin gets destroyed
3. Paraseptal emphysema - Associated with previous lung infections that causes
inflammation and recruitment of Neutrophiles
4. Distal acinar emphysema/paraseptal: Located distal to acinus, proximal parts are not
affected. Adjacent to pleura.
5. Irregular emphysema: Irregularly affected.
Armend B. 24.01.2017
6. Bullous emphysema: air sacs > 1cm!! Risk factors are mostly smoking, can also be alpha-1
antitrypsin. Bubble-like cavities filled with air.
- Clinical manifestations:
- Dyspnea, wheezing, Barrel-chest, pink-puffers.
Sarcoidosis (lung): Sarcoidosis (lung): Systemic granulomatous disease, affecting multiple organs, with non-caesating
granulomas in many tissues and organs.
- Etiology:
- Idiopathic
- Contributing factors: Immunological reactions (CD4, TH1, IFN-y, TNF etc), HLA-genes
(A1,B8).
- Infections: Tuberculosis, Rickettsia.
- Morphology:
- Granuloma with giant cell in the middle, surrounded by Epitheloid cells. Accumulation of
monocytes, macrophages and T-lymphocytes. Can have Giant cells as well. Granuloma
surrounded by a fibrous capsule. NO NECROSIS!
Most common: Bilateral hilar lymphadenopathy + Lungs!
- Can also affect: CNS, heart, eyes, skin etc!
- Clinical manifestations: Mostly asymptomatic, but in lungs it causes: shortness of breath, dry
cough, substernal discomfort, fever, fatigue, weight loss and night sweats.

Lung edema/Acute pulmonary congestion: Lung edema: Fluid accumulation in the air-spaces of the lungs, leading to impaired gas diffusion
and respiratory failure.
Classification:
- Localisation: Interstitial VS Alveolar
- Cause + pathogenesis: Hemodynamic edema, Microvascular + alveolar damage,
undetermined origin, might be pneumonia.
- Hemodynamic lung edema:
o Increased hydrostatic pressure: Left side heart failure (congestion), Pulmonary
vein obstruction.  typical with Heart failure cells (mph + hemosiderin).
o Decreased oncotic pressure: Hypoalbuminemia, Nephrotic syndrome, liver
disease
o Lymphatic obstruction: Cancer etc.
- Microvascular + alveolar damage edema:
o Infections
o Gases: O2, SO2.
o Aspiration, Drugs, Shock, Radiation
- Non-cardiogenic lung edema:
o DAD  Diffuse alveolar damage
Alveolar capillaries engorged with blood o ARDS  Acute respiratory distress syndrome
Alveolar septal edema  Endothelial damage: Increased permeability, microthrombi and
ischemic injury.
Armend B. 24.01.2017
Engorged blood vessel  Death of Alveolar cells, with formation of Hyaline membrane due to
and the small capillaries as well inflammation caused by death of alveolocytes.
- increased blood pressure --> RBC will go into the alveoli  Decreased lung perfusion
 Clinical picture: Dyspnea, tachypnea, hypoxemia, Respiratory failure,
bilateral infiltrate
- Undetermined origin lung edema: High altitude, CNS trauma.
Squamous cell cancer – lungs (central): Squamous cell cancer – lungs (central): Malignant epithelial tumour with keratinisation or
presence of intracellular bridges, forming Keratin bells. (CKH 34betaE12 stain)
Origin: Bronchial epithelium (Smokers are known to have metaplastic sq. Cells, can be cancerous)
Localisation: Central
Spread:
- Local:
o Bronchial ep.  endobronchial growth  Obstruction  periphery 
Hematogenous spred
o Lung parenchyma
o LN: Peri-hilar
o Hematogenous
- Intraepithelial spread
- Metastasis: CNS, Liver, Suprarenal glands, Abdominal organs etc.

Etiology for ALL lung cancers:

1. Smoking AND Passive smoking
2. Occupational factors: Asbestos, silicates.
3. Chronic lung disease: TB, alveolitis
4. Outdoor pollution
5. Hereditary: AD, AR
Pathogenesis of main clinical symptoms of ALL lung cancer:
- Systemic manifestations: Fever, fatigue, weight loss, wekaness
- Local manifestations: Genesis  Endobronchial growth, in to bronchial obstruction,
causing Tumour necrosis and chest wall invasion.
Cough, dyspnea, hemtopnea, lung bleeding, pain, exudate
- Medistanial damage: N. Laryngeus reccurens (hoarsness), N. Phrenicus (diaphragma
paresis), Horners triad (Ptosis, myosis, enopthalmos), Brachial plexus invasion, V. Cava
superior syndrome, Myocardial invasion, Esophageal invasion, Medistinal LN.
- Metaststic manifestations
- Paraneoplastic syndrome! Different hormones can be excreted, such as PTH, ACTH etc.
TNM:
T1 – invasion in lamina propria or submucosa
T2 – invasion in muscle
T3 – invasion in adventitia
Armend B. 24.01.2017
T4 – invasion in other organs

N0 – 0
N1 – 1-2 metastases
N2 – 3-6 metastases
N3 - more than 6 metastases in regional
lymph nodes
Small cell lung cancer: Very malignant and aggressive epithelial tumour composed of small cells,
Small cell lung cancer: with high nucleus/cytoplasm ratio and typical chromatin. (CK+, CHR-A+, TTF1+, Ki-67+)
- Very aggressive and fast local growth, with metastasis! Have high intensity mitosis.
Can cause necrosis.
- Common to compress nerves: N. laryngeus + phrenicus.
- Pareneoplastic syndrome typical: PTH secreting cells.
o Neuroendocrine differentiation: TTF1, Chromogranin-A
Etiology + pathogenesis of main clinical symptoms ABOVE!
 Typical cancer for smokers, that can NOT be treated surgically. Almost always FATAL!
TNM: LEARN!

Lung adenocarcinoma:
Lung adenocarcinoma: Malignant epithelial tumour with glandular differentiation or mucus production. (CK7, 20+)
- Mostly in the periphery, but can be central.
- Invasive into: Pleura + chest wall.
Spread:
- Invasive growth
- Aerogenic
- Pleura
- Pseudomesotheliomatous spread (along pleura)
- LN
- Distant metastases: CNS, Bone, Liver, Adrenal gland
Subtype: Colloid cancer: Presented adenocarcinoma with mucus lakes, where over 50% of tumour
tissue is mucous.
Etiology + pathogenesis of clinical manifestations ABOVE!
TNM: LEARN
Armend B. 24.01.2017
Lung hamartoma: Chondroid hamartoma: Lung hamartoma: Chondroid hamartoma:
Pathological tumour, with a microscopically Normal tissue! Benign tumour!
Composition:
- Hyaline cartilage: Common consisten, thus is name.
- Fat, connective tissue, smooth muscle, epithelium!
- Covered by epithelium, in this case: Respiratory epithelium.
o No reccurence or malignisation risk!
Localisation:
Mainly peripheral (incidental finding), 10% endobronchial causing bronchial obstruction.
Size: 4-9cm!
Treatment: Resecetion
Etiology + pathogenesis of clinical manifestations: ABOVE!
TNM: LEARN
Armend B. 24.01.2017
Pulmonary and extrapulmonary Tuberculosis: Pulmonary and extrapulmonary tuberculosis: Infectious disease caused by M. tuberculosis, most
commonly by M. tuberculois – hominis. (8-10mil. New cases every year, with 3 mil. Deaths yearly).
TBC Lymphadenitis: Lymph node Pathogenesis: LEARN GOOD!
tuberculosis: Scrofulosis - Infection aerogenous or alimentary!  10% reach alveoli, phagocytosed by Dust cells (C,
Mostly Neck + Supraclavicular LN, Mannose, IgR, Scavenger receptor A).
with necrotizing granulomatous - Bacterial replication inside m/ph, blocking phagolysosome fusion (decreased Ca2+,
inflammation. Increased size but inhibits Ca2+-calmodulin, autophagy of phagosome, decreases acidity)  For 3 weeks, TB
NOT painful, tupically in children and replicates, can cause Bactermia leading to Miliary tuberculosis and mostly asymptomatic.
HIV-patients. - Replication lyses one m/ph, leading to reqruitment of other m/phs and production of
Langerhans giant cell, chronic TNF-alpha, causing Dendritic cells to present TB-ag to Lymph-node, activating Th1 with IL-
inflammation and caseous necrosis. 16! Th1 secrete IFN-y, activating Macrophages (increases phagolysosome, NO production,
oxidative destruction, increase defensins and autophagy). More macrophages secrete
Granuloma: Caseous necrosis, TNF-alpha, requriting more M/ph, causing activation into Epitheloid cells  Giant cells,
epitheloid cells, Langhans-cells, and Granuloma formation  Caseous necrosis (decreases oxygen for TB).
fibroblasts, T-ly - Granulomas increase in size and amount, causing bronchial and lung destruction, can
cause expectoration, forming cavities and fibrosis.
o Tuberculoma: Necrotic mass surrounded by Fibrotic capsule, seen in TB.
Types of TB:
- Primary TB: New host, no previous infection, non-sensitized! (Children, HIV, Malnutrition)
o Direct infection, mostly children  middle and lower lobes of lung. Can become
Miliary tuberculosis in the liver. dormant or primary disease.
- Destruction of hepatocytes, with o Mostly subpleuraly (Ghon focus, Ghon complex and Ranke complex).
necrotic tissue.  Resembles Acute bacterial pneumonia, hilar lymphadenopathy with
- LH-giant cell, epitheloid cells. Pleurisy (can spread  Meningitis, Miliary)
 Hilar/paratracheal lymphadenopathy  Broncial compression, LN
erosion into bronchi or Bronchioectasis!
o Outcome: 95% Dormant, OR 5% dissemination

- Secondary: Sensibilised host, previous infection or dormant.

o Mostly Apical location in posterior segments of upper lobe, and upper part of
lower lobe, no Lymphadenopathy, but tissue destruction (caverna).
o 1-2cm consolidations, with granulomas.

Risk for TB infection:

1. Exogenous (infection): Contant with TB patient, length of contact, Intimacy and amount of MT
discharge.
2. Endogenous (disease):
- Lowered immune status (DM, transplat)
- Lowered cellular immunity (HIV, inborn immunodef.)
- Lowered general status (malnutrition, malabsorption)
Armend B. 24.01.2017

Squamous cell cancer of Cervix: CIN Squamous cell cancer of Cervix: CIN
Carcinoma of the Cervix of uterus! Squamous cell is most common, followed by Adenocarcinoma.
Most common in 40-45 year old women.
Morphology:
 Atypical cells, with high mitosis and necrosis formation.
 Keratinisation, I/C bridges and Neoangiogenesis!
Risk factors:
1. Early first intercourse + multiple sex partners
2. HPV (type 16,18)
3. High parity
4. Smoking
5. Oral contraceptives
6. Immunosuppresion

Growth:
 Grossly: Exophytic and exulcerative! Infiltrative. Local invasion into vagina, rectum, uterus
and omentum.
Spread: Lymphogenous (LN) + Hematogenous (Liver, lungs, bone marrow) + Invasive.

CIN: Cervical intraepithelial neoplasia:

1. CIN1: Atypical cells in 1/3 of basal layer.
2. CIN2: Atypical cells 2/3 of basal layer
3. CIN3: All 3 layers atypical  Cancer in situ! (Can regress to CIN 1 or 2 in 20% of cases)

Endometriosis: Endometrial gland and stroma outside of uterus, in different locations!

Endometriosis:  Not associated with Malignancy!
Adenomyosis: Gland + stroma of uterus placed in uterus, but NOT in mucosa.

Etiology:
1. Regurgitation + implantation: Menstrual backflow in Fallopian tubes, causing implantation
of glands somewhere else.
2. Post-operative scar
3. Immune system
4. Metaplastic theory: Endometrial differentiation from coelomic epithelium.
5. Vascular/lymphogenous dissemination: Glands spread by blood vessels or lymph!
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Morphology:
 Nodules of parenchyma and stroma of endometrium, forming hemorrhages and fibrous
adhesions at the site.
Multiple hemorrhages make Chocolate cysts (Endometriomas) typically seen.
 Bleed normally with menstrual cycle or intrinsic cycle.
Most common locations:
Ovary  Lig. Latum uteri  Rectovaginal septa  Peritoneum  Appendix/intestines 
vagina/vulva  Laparotomy scars

Endometrial hyperplasia:
Endometrial Defined as an increased proliferation of endometrial glands relative to the stroma, resulting in an
hyperplasia: increased gland-to-stroma ratio, compared to normal proliferative endometrium.
Hormone-induced (e.g breast)
Compensatory - Liver can regain mass after hemihepatectomy
Pathologic:
Hormone disbalance
Induced by virus (HPV)

Types:
Irregular shapes, larger lumen - Simple:
o Changes in glandular architecture, epithelial growth is analogous to the
proliferation phase. Low risk for adenocarcinoma.
- Complex/atypical:
o Crowding of cells (dysplasia) with cellular atypia. Risk for adenocarcinoma is
around 20-30%.

Etiology: Prolonged estrogen stimulation, low Progesterone

o Failure of ovulation.
o Oral contraceptives
o Tumour producing estrogen
o Menopause
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Endometrial adenocarcinoma: Endometrial adenocarcinoma: 85% of them are Adenocarcinomas.

Endometrial cancer is the most frequent gynecological malignancy, present in 7% of females,
mostly post-menopausal women.
Morphology:
- Gland forming mass, with irregular surface, invasion into myometrium and parametrium.
Can be present in all layers.
Endometrial cancerogenesis:
- Type 1 carcinoma:
o Prolonged Estrogen stimulation + Endometrial hyperplasia  Typically produce
low grade tumour
- Type 2 carcinoma:
o Microsatellite instability + Somatic mutation of P53  Typically produce high
grade tumour.
Risk factors:
- Obesity
- DM
- Arterial hypertension
- Infertility
- Endometrial hyperplasia
Leiomyoma: Leiomyoma (in uterus: Fibroid): Benign mesenchymal tumour developing from Myometrium.
Most frequent human tumour  75% of pre-menopausal women (reproductive years).
No malignisation risk  BENIGN

- Tumour of smooth muscles, usually in the uterus.

o Can develop in M. erector pili (Pilar leiomyoma), skin, breast areola and scrotum.
Morphology:
- Grossly: Sharply demarcated white nodule, concentric structure.
o Can me mm  cm!
- Microscopic: Spindle cells that are dysplastic (chaotic) without atypia, resemble normal
cells.
Localisation: Subserosal, intramural or submucosal.
Manifestations + complications:
- Submucosal: vaginal bleeding, can be severe.
- Pressure on urinary bladder if multiple or large.
- Infarction  pain
- Infertility
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- During pregnancy: Increased risk for  spontaneous abortion, ectopic pregnancy, post-
partum bleeding and weak contractions.

Ectopic tubal pregnancy: Ectopic tubal pregnancy:

Implantation outside of uterine cavity!
Morphology:
- Ectopic placenta with fetus, and decidual changes.
o Tubal abortion
o Tubal rupture
o Regression
Location:
1. Fallopian tubes (90%)
2. Ovary
3. Peritoneal cavity
4. Uterine horn (Where uterus attaches to tuba uterina)

Risk factors:
1. PID + Chronic salpingits  Scarring, fibrosis of fallopian tubes may interfere with
transport of ovum.
2. Peritubal adhesions: After appendicitis, operations, Endometriosis.
3. Leiomyoma.

Graves disease: Autoimmune thyroid pathology: F:M (10:1) 20-40y

Graves disease: Autoimmune thyroid pathology: Disease presented with hyperthyroidism, exophthalmos and pretibial myxedema.
- Graves dermopathy: Peau d’ orange – orange peel-like appearance on the skin, causing
itching and burning sensation.
Pathogenesis:
Autoimmune disorder, with abnormal self tolerance against Thyroid antigens.
- Auto antibodies  TSH-receptor (mimicks TSH), Thyroid growth stimulating Ig and
Thyroid inhibiting Ig.
Morphology:
- Gross: Symmetrical enlarged gland, diffuse hypertrophy + hyperplasia of follicular
epithelial cells, with intact capsule.
- Microscopic: Tall columnar cells, forming papillae into the lumen (scallop-shaped), with
lymphoid infiltration and light coloured colloid (little colloid in the follicles, due to
hyperactivity).
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Hashimoto thyroiditis: Autoimmune thyroid pathology: F:M (10:1)  45-65y
Hashimoto thyroiditis: Disease presented with gradual thyroid failure by autoimmune destruction of the thyroid gland.
Autoimmune thyroid pathology: Pathogenesis:
Breakdown of self-antigens of thyroid gland, with self-destruction of parenchyma cells, and
replacement of macrophages and fibrosis.
- Autoantibodies  Auto-thyroglobulin + Auto-thyroid peroxidase
This causes attraction of T-ly, inducing apoptosis of thyrocytes.
Morphology:
- Gross: Diffuse symmetrical enlargement and intact capsule.
- Microscopic: Mononuclear infiltration + inflammation, with T-ly, Plasma cells, which can
for lymph nodes with Germinal centers (Lymphoma complication)!
Follicular cells are low and atrophic  Eosinophilic  Hürthle-cells (too many
mitochondria)
Increased fibrosis and big colloid.
Clinical findings:
Initial hyperthyroidism, followed by hypothyroidism and enlarged gland.
Nodular goiter: Thyroid pathology: Nodular goiter: Thyroid pathology:
Enlargement of the thyroid by different sized nodules, caused by impaired synthesis of Thyroxine.
Most often this is caused by Iodine deficiency  thyroid enlarges to compensate.
Types:
- Endemic: >10%, Iodine deficiency  Diet or too much Cabbage.
- Sporadic: Increased need (high metabolism) for thyroid functions, such as puberty or
young adults.
Clinical manifestations: Enlarged gland (increased TSH), neck deformity, intrathoracic goiter,
hormone disturbances.
Pathogenesis:
On going hyperplasia and hypertrophy causes accumulation of collid, leading to Multinodular
goiter, which is response to follicular stress with uneven growth.
Nodules can produce Thyroxine independently of TSH (Plummer syndrome).
Morphology:
- Multilobular enlarged gland + asymmetric.
- Brown gelatinous colloid, with no capsule around!
- Fibrosis, hemorrhage and calcification (dystrophic).
- Flattened follicular cells.
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Follicular adenoma: Thyroid neoplasm:
Follicular adenoma: Thyroid Benign tumour of the thyroid gland.
neoplasm - Solitary and non-functional
- If functional, can produce Thyroid hormones  Toxic adenoma  Thyrotoxicosis.
Morphology:
- Solitary, well defined capsule.
- Uniform follciles with colloid.
o Can have Hürthle-cells  Hürthle-cell adenoma
- Endocrine atypia: Malignant features without being malignant.
Clinical features:
- Painless nodule, can lead to swallowing difficulties.

Papillary thyroid cancer: Papillary thyroid cancer:

Malignant tumour of the thyroid. Most common Thyroid cancer form (>85%).
- Solitary or mutifocal
- Solid or cystic
- Fibrovascular stalk with cuboidal cells surrounding.
Morphology:
- Papilla formation.
- Nuclei:
o Optically clear nuclei (Orphan annie eye nuclei)
o Intranuclear invagination (Coffe-bean shaped)
o Nuclear overlapping
Clinical manifestations:
Non-painful and non-functional nodule!
Spread: Hematogenous + lymphogenous.
- Distant metastasis: 15%
- Good prognosis: 10y 95%! Best prognosis of thyroid cancers.
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Pheochromocytoma: Pheochromocytoma: Adrenal pathology
Neoplasm of Chromaffin cells, which synthesize Catecholamines (NE + E).
- Mostly a benign tumour
- If outside of Adrenal gland  Paraganglioma.
Morphology:
- Solid mass, 1-4000g
- Zellballen: Chromaffin cell nestles, surrounded by vascular networks!
- Chromogranin-A +
Rule of 10s:
- 10% malignant
- 10% NOT hypertension
- 10% sporadic – bilateral
- 10% extraadrenal
- 10% (25% now) – familial

Clinical findings:
Hypertension, tachycardia, palpitations, sweat, tremor  Paroxysmal episodes!
Osteoporosis: Osteoporosis: Reduced bone mass, in equal ratio between matrix/minerals  osteopenia, with
increased risk for fractures.
Extend: Local (immobilization) OR generalized (Primary, secondary)
Primary osteoporosis:
 Senile osteoporosis: Low turnover
o Aging of osteoblasts, with decreased amount of proliferation and growth factors
in the bone matrix.
o Reduced physical activity, with genetical factors and calcium amount in the body
is the cause.
 Morphology: Decreased amount of Osteoblasts, with thin cortex and
subperiosteal + endosteal bone loss. Widening of Haverisian canals.
 Postmenopausal osteoporosis: High turnover
o Osteoclast activation, with decreased osteoblast activation due to low Estrogen.
o Larger surfaces mostly affected, with increased RANK-L activation of Osteoclasts.
 Morphology: Increased amount of Osteoclasts, with thin, perforated
trabecula and loss of trabecular junction. Typical in large surface bones.
Secondary osteoporosis:
 Endocrine disturbances: Hyper/hypothyroidism, hyperparathyroidism, Hypogonadism,
DM, Cushing syndrome.
 Tumours: Multiple myeloma, carcinomatous dissemination
 GI-tract: Malnutrition, malabsorption (low VIT D + C).
 Drugs + toxins: Anti-coagulants, chemo, GC, alcohol
 Lung pathologies, immobilisation etc.
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Complications: Increased risk for fractures, vertebral deformity, can get pulmonary
thromboembolism, pneumonia. Mostly fracture of femoral neck.

Ewing’s sarcoma/PNET: Ewing’s sarcoma/PNET:

Small blue cell tumour of neural immunophenotype.
Pathogenesis: Mostly translocations, 85% (t11,22), but also other.
Risk age: 10-15 years!

Localisation: Diaphysis of long bones, such as femur and flat pelvic bones.
Morphology: Arising in medullary cavity, eroding bone and invading soft tissue  destructive
tumour
 Contains areas of haemorrhage and necrosis, but tumour has little stroma.
 Forms Onion skin-pattern.
Clinical findings: Painful mass, with the affected site being warm, tender and swollen! Systemic
READ ABOUT OSTEOSARCOMA findings such as: increased ESR, anemia, fever and leucocytosis.
AND COMPARE! Prognosis: Suvival 5y (75%) with intensive treatment! Usually bad prognosis.
 Treatment: irradiation, surgery, chemotherapy.

Chondrosarcoma: Chondrosarcoma:
Malignant mesenchymal tumours producing cartilage, and is 2x less frequent than Osteosarcoma.
Risk age: Teenagers + 30-40 years (bimodal)

Morphology:
 Large bulky tumour, made of nodules of white/gray cartilage matrix!
 Can be central necrosis, making cystic spaces.
 Starts in the medulla mostly, but spreads to cortex and into surrounding muscle or fat.

Localization: Central bones: ribs, shoulders, pelvis and distal extremities.

Spread: Low grade tumours (1-2) are mostly invasive and grow in surrounding tissue, while high
grade tumour (3) mostly spreads haematogenous to the lungs in most cases.

Learn brain infarct – non-haemorrhagic macroscopic and microscopic changes +

hemorrhagic changes!