醫師國考複習- 病理學

2009.5/6,5/8,5/15 (update to 98-1 醫師國考)

1. Cellular pathology

Apoptosis
* Distinctive and important form of cell death, programmed cell death
1. Programmed destruction of cells during embryogenesis
2. Hormone-dependent involution in the adult: endometrial cell breakdown
3. Cell deletion in proliferating cell population: intestine crypt epithelia
4. Cell death in tumors: regression in tumors
5. Death of neutrophils during an acute inflammatory response
6. Death of immune cells: B, T lymphocytes after cytokine depletion
7. Cell death induced by cytotoxic T cells: cellular rejection, GVHD
8. Cell injury in certain viral diseases: viral hepatitis
9. Cell death produced by a variety of injurious stimuli
* Morphology (in order)
1. Cell shrinkage: small in cell size, dense eosinophilic cytoplasm
2. DNA fragment
3. Chromatin condensation: aggregates peripherally, karyolysis
4. Formation of cytoplasmic bleb and membrane-bound apoptotic bodies
5. Phagocytosis of apoptotic cells or bodies by adjacent healthy cell

Reversible & irreversible cell injury

* Reversible cell injury
Fatty change: accumulation of lipid droplets, vacuoles, or coalesce to form large
vacuoles
* Irreversible cell injury
Membrane injury  exit of enzyme  calcium in mitochondria  release and
activation of lysosomal enzyme

Hemochromatosis
1. Iron deposition: liver: micronodular cirrhosis
pancreas: DM
skin: pigmentation; heart, endocrine organ
2. Cause: transfusion, liver disease, increased oral take
3. Deposition of hemosiderin, stain blue with Prussian blue stain

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Kernictus
In severe hemolysis, anemia associated with jaundice and the presence of
unconjugated bilirubin, which binds to lipids in the brain resulting in serious damage
to brain (esp. basal ganglion) in infants.

Necrosis
1. Coagulative necrosis (most common): spleen, heart, kidney
* most common type of tissue necrosis
* preservation of basic structural outline of the coagulated cell or tissue
* characteristic of hypoxic death of cells in all tissues except the brain
2. Liquefactive necrosis
* dominant enzyme digestion
* characteristic of bacterial or fungal infection
* hypoxic death in the brain (brain infarct)
3. Caseous necrosis: a special form of coagulative necrosis (tuberculosis)
* cheesy, white gross appearance, structureless amorphous granular debris

Lipofuscin: waste pigment: cell atrophy, free radical injury, heart

Anthracosis: lung & hilar lymph node
Metastatic calcification: kidney, stomach, lung, heart

Cell growth and adaptation

1. Hyperplasia: increase in the number of cells in an organ or tissue
(1) physiologic hyperplasia: proliferation of the ductal epithelium of breast at
puberty and during pregnancy
(2) pathologic hyperplasia: endometrial hyperplasia
2. Hypertrophy: increase in the size of cells
(1) physiologic hypertrophy: hypertrophy of the smooth muscle cell of the uterus
during pregnancy
(2) pathologic hypertrophy: left ventricle hypertrophy of the heart in
hypertension
3. Atrophy: shrinkage in the size of the cell by loss of cell substance
(1) physiologic atrophy: decrease in the size of the uterus after parturition
(2) pathologic atrophy: brain atrophy
4. Metaplasia: a reversible change in which one adult cell type is replaced by
another adult cell type
(1) columnar epithelium of the respiratory tract is replaced by squamous
epithelium in heavy smokers.

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 (2) metaplastic epithelium is often the site of cancer transformation.

2. Inflammation

Morphologic patterns of inflammation

1. Serous inflammation- burn injury- vesicle
2. Fibrinous inflammation
3. Suppurative or purulent inflammation: neutrophil infiltration in brain abscess
4. Ulcer
5. Acute inflammation abscess, chronic inflammation, scar

*Acute inflammation: contraction of endothelium and vascular

hyperpermeability

Granulomatous inflammation
1. Chronic inflammation
2. Infiltration of epithelioid histiocytes, multinucleated giant cells, and lymphocytes
eg. tuberculosis, sarcoidosis, Crohn’ s disease, cat scratch disease, suture
granuloma
TB: mycobacterium tuberculosis
granuloma, epithelioid histiocyte & Langhans’giant cell, central caseous
necrosis, acid-fast bacilli

*Russel body: plasma cell

*Xanthoma cell: foamy histiocyte
*Myeloperoxidase (MPO) in phagocyte: HOCl, antimicrobial agent

3. Repair

Granulation tissue
Proliferation of small blood vessels (neovascularization) and fibroblasts during
tissue repair process

Keloid
Excessive formation of the fibrous scar in wound healing

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 4. Hemodynamic disorders

Forms of edema
* Transudate- low protein content (SG < 1.012)
1. increased hydrostatic pressure
2. reduced plasma oncotic pressure
* Exudate- high protein content (SG > 1.020) with numerous inflammatory cells
* increased vascular permeability

Amniotic fluid embolism

1. Tear in placental membrane and rupture of uterine vein with amniotic fluid infusion
2. Mortality rate >80%
3. Embolus composed of squames and fat

*Caisson disease: air embolism

Shock : hypoperfusion of organs

Type:
a) cardiogenic shock: myocardial pump failure
b) hypovolemic shock: loss of blood or plasma
c) septic shock (endotoxic shock): systemic microbial infection
d) neurogenic shock: loss of vascular tone
e) anaphylactic shock: hypersensitivity reaction
* Failure of multiple organ systems

5. Genetic disorders

Marfan syndrome
1. Disorder associated with defect in structural protein
2. Disorder of connective tissue
Molecular basis of Marfan syndrome
* FBN 1 gene
point mutation on chromosome 15q21.1
defect in synthesis of fibrillin
defect in microfibrillary network, elastic fiber
esp. ligament, aorta, ciliary zonule
3. Skeletal abnormality in Marfan syndrome

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 tall stature: long extremity, spider finger
hyperextension of thumb
dolichocephalic (long-headed)
frontal eminence
prominent supraorbital ridge
kyphoscoliosis
deeply depressed sternum: pigeon-breast (pectus excavatum)
laxation of ligament in hand & foot- double-jointed
4. Cardiovascular lesion- cystic medionecrosis of ascending aorta
aortic incompetence: dilatation of aortic valve
mitral valve prolapse- floppy valve
causes of death: rupture of aortic dissection, heart failure

Glycogen storage disease

1. Hepatic form
type I glycogenosis (von Gierke disease)
* glucose-6-phosphatase deficiency
2. Myopathic form
type V glycogenosis (Mcardle disease)
* muscle phosphorylase deficiency
3. Pompe disease
type II glycogenosis
* acid maltase deficiency
* cardiomegaly

Down syndrome
1. Most common chromosome disorder
major cause of mental retardation
2. Karyotype
trisomy: 47,XX,+21 (95%)
mosaic: 46,XX / 47,XX,+21 (1%)
3. Risk factor: MATERNAL AGE
4. Mongolism: flat face
oblique palpebral fissure
epicanthic fold
5. Mental retardation
* presenile dementia- Alzheimer disease
6. Congenital heart disease (40%)

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 * endocardial cushion defect- cause of death
7. Acute leukemia (10-20X)
8. Simian crease
umbilical hernia
intestinal stenosis

Fragile-X syndrome
* X-linked: triplet repeat mutation in FMR-1 gene on Xq27.3 (fragile site)
* Anticipation- triple repeat amplification

6. Diseases of immunity

NK cell
* 10% to 15% of peripheral blood lymphocytes
* Secret IFN-γ: activates macrophages to destroy ingested microbes. IFN-γa lso
promotes the differentiation of naive CD4+ T-cells into TH1 cells.
* Secret granulocyte macrophage colony-stimulating factor (GM-CSF)
* Surface molecular marker: CD2, CD16 and CD56 to identify NK cells.
* CD2 surface marker present on both NK cells and mature T lymphocytes.

Type I hypersentivity (anaphylactic type)

1. Mechanism: mast cells, T help-2 cells, Ig E, and eosinophils
2. Histamine acts on capillary and venule
3. Atopic dermatitis, urticaria, angioedema, allergic rhinitis, asthma

Type II hypersensitivity (cytotoxic type)

Mediated by antibodies directed toward antigens present on the surface of cells or
other tissue components
transfusion reaction
erythroblastosis fetalis
hemolytic anemia
Pemphigus vulgaris
drug reaction
Goodpasture syndrome
Myasthenia gravis
Gra
ves’disease

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Type III hypersensitivity
Autoimmune disease: SLE, Hashimoto’
s thyroiditis

Type IV hypertensitivity (delayed type, cell-mediated)

Initiated by specifically sensitized T cells.
contact dermatitis
tuberculosis

Systemic lupus erythematosus (SLE)

1. Etiology and pathogenesis
(I) anti-nuclear antibodies (ANAs):
anti-double-strand DNA and anti-Smith antibodies
(II) anti-phospholipid antibody
2 Autoantibodies, VDRL false positive
3 Kidney
WHO classification of lupus nephritis
class I: normal
class II: mesangial lupus glomerulonephritis (mild form)
class III: focal proliferative glomerulonephritis
class IV: diffuse proliferative glomerulonephritis- most severe, wire
loop
class V: membranous glomerulonephritis
4. Skin
(I) erythema- facial butterfly area
(II) liquafactive degenearation of basal layer of the epidermis
(III) immunoglobilin deposition in the dermoepidermal junction
5. Joint: arthritis
6. Central nervous system
7. Pericarditis and other serosal cavity involvement
8. Cardiovascular system: Libman-Sacks endocarditis, onion-skin vasculitis
9. Other organs: lung, spleen

Sjogren syndrome
1. Dry eye (keratoconjunctivitis sicca) and dry mouth (xerostomia)
2. Immunological destruction of lacrimal and salivary gland
3. Anti SS-A(Ro) and anti SS-B(La)
4. Periductal and perivascular lymphocytic infiltration in the lacrimal and salivary
gland

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5. Higher risk of developing lymphoma

Transplant rejection
* Mechanism involved in rejection
(I) T cell-mediated reaction
(II) antibody-mediated reaction: hyperacute rejection: endothelial cell
* Rejection reaction: hyperacute, acute, and chronic

X-linked agammaglobulinemia of Bruton (Bruton disease)

1. Failure of B-cell precursor to differentiate to B cell
2. Absence or remarkable decrease of B cells in the blood
3. Decreased serum level of all classes of immunoglobulin

DiGeorge syndrome (thymic hypoplasia)

1. T cell deficiency deriving from failure of development of the third and fourth
pharyngeal pouches
2. Hypoplasia or aplasia of thymus leads to deficiency of T cell-mediated immunity.
3. Lack of parathyroid glands lead to tetany.
4. Congenital defects of heart and great vessels
5. Abnormal appearance of faces, mouth, and ears

Acquired immunodeficiency syndrome (AIDS)

1. Groups of adults at risk for developing of AIDS
(I) homosexual or bisexual men
(II) intravenous drug abusers
(III) hemophiliacs
(IV) recipients of blood and blood components
(V) heterosexual contacts of members of other high-risk groups
2. More than 90% of pediatric population with AIDS result from transmission of the
virus from mother to child.
3. Three major routes of transmission
(I) sexual contact
(II) parenteral inoculation
(III) passage of the virus from infected mother to newborn
4. Etiology
(I) HIV- HIV1 and HIV2: retrovirus
(II) HIV-1 is the most common type associated with AIDS in USA
5. Pathogenesis

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 (I) HIV target: immune system and central nervous system
(II) infection and severe loss of CD4+ T cell

Clinical features of the crisis phase (AIDS)

I. Opportunistic infection
(1) pneumocytis carinii pneumonia
(2) candidiasis
(3) cytomegalovirus infection
(4) atypical mycobacterial infection
(5) tuberculosis
(6) cryptococcosis
(7) toxoplasma gondii infection- CNS
(8) progressive multifocal leukoencephalopathy caused by JC virus
(9) herpes simplex virus infection
(10) bacillary angiomatosis: G(-) bacilli, vascular proliferation, neutrophil
infiltration
II. Neoplasm
(1) Kaposi sarcoma (human herpes virus 8-related)
(2) non-Hodgkin’ s lymphoma (EBV-associated)
(3) B-cell lymphoma (primary effusion lymphoma) (human herpes virus
8-related)

7. Neoplasia

Cancer suppressor genes

Rb gene (13q14): ‘Two hit’hypothesis of oncogenes
p53 gene (17p13.1)
Both Rb and p53 play a role between G1 to S phases in cell cycle.

*Tumors associated with Rb gene mutation: retinoblastoma, osteosarcoma

*Tumors associated with BRCA-1 and BRCA-2 gene mutation: breast carcinoma,
ovarian carcinoma

Viral carcinogenesis
(1) DNA oncogenic virus
(a) Human papilloma virus (HPV)

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 squamous cell carcinoma of cervix and anogenital regions
DNA sequences of HPV type 16, 18 (31, 33, 35,51) found in about
85% of invasive squamous cell cancer and precursor
(b) Epstein-Barr virus
Burkitt lymphoma
B-cell lymphoma in immunosuppressed individual (HIV infection or
organ transplantation)
nasopharyngeal carcinoma
(c) Hepatitis B virus
200x increased risk of hepatocellular carcinoma
(2) RNA virus: human T-cell leukemia virus type 1 (HTLV-1)-
adult T cell lymphoma/leukemia

*Tumorigenesis of Ras oncogene: point mutation

Choristoma: an ectopic rest of normal tissue

Hamartoma: disorganized but mature specialized cells or tissue
Desmoplasia: collagen fiber proliferation in cancer infiltration of stroma

Tumor invasion
Detachment of tumor cells from each other  Attachment to extracellular
matrix  Degradation of extracellular matrix  Migration of tumor cells

*Carcinoma: lymphatic spreading- lymph node metastasis

*Sarcoma: hematogenous spreading- lung, bone, liver
*Cancer cachexia: cytokine release

8. Infectious diseases

Inflammatory response to infection

1. Suppurative inflammation (neutrophil infiltration)- pyogenic bacteria
2. Lymphocyte infiltration- virus
granulomatous inflammation- TB, fungus
3. Cytopathic-cytoproliferative inflammation- virus
4. Necrotizing inflammation
5. Chronic inflammation and scarring

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Amebiasis
1. Entamoeba histolytica- protozoa
2. Infectious form: cyst
ameboid form: trophozoite- stool contamination
erythrophagocytosis of trophozoite
3. Dysentery
* diarrhea with abdominal cramping pain & tenesmus
* loose stool containing blood, pus, and mucus
4. Involve cecum and ascending colon
5. Flask-shaped ulcer with suppurative inflammation but no obvious necrosis

Lymphogranuloma venereum
1. Chlamydia trachomatis infection
2. Epidermal vesicle, ulceration and granulomatous inflammation on genitalia
3. Swelling of inguinal LN
4. Stellate abscess with suppurative center rimmed by granulomatous inflammation

Staging of syphilis
I. Primary syphilis
chancre
II. Secondary syphilis
skin rash
condyloma lata
generalized lymphadenopathy
III. Tertiary syphilis
gumma
cardiovascular system: syphilic aortitis
neurosyphilis: tabes dorsalis, charcot joint, generalized paresis

Herpes simplex virus infection

* Skin & mucosa (vesicular lesion) → neuron: latency → reactivation →
recurrent skin / mucosa lesion
* Fever blister or cold sore
- bilateral lip & nose
- intraepidermal blister, ulcer, crust
- pain
* Cowdry type A intranuclear inclusion with glassy appearance
- large, pink-purple, multinucleated

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* Viral inclusion: CMV, measles, herpes, rabies

*CMV inclusion: immunocompromised patient, intranuclear inclusion (owl-eye

like with peripheral halo, microphotograph), and intracytoplasmic inclusion

Infectious mononucleosis- Epstein-Barr virus infection

1. Benign self-limited lymphoproliferative disease
2. Late adolescent & young adult
3. Kissing disease- close body contact
4. Infect B lymphocytes and epithelium of nasopharynx, oropharynx, salivary gland
Pathogenesis of IM
1. Latent infection
* polyclonal B cell activation & proliferation → B cell activation
2. Immunoresponse to EBV infection
* atypical lymphocyte (Ts cell) in PB:↓B cell proliferation

Cryptococcosis
1. Cryptococcus neoformans- encapsulated yeast
2. Soil & bird (pigeon) droppings
3. Mucicarmine stain: bright red in tissue
indian ink: negative staining in CSF
4. Solitary granuloma with yeasts in the macrophage &
multinucleated giant cell
5. Meningoencephalitis
immunocompromised
soap-bubble lesion: gelatinous mass in meninges or small cyst in gray matter

*TB meningitis: brain base, hematogenous spreading

*TB epididymitis  orchitis

*Acute suppurative meningoencephalitis in newborn: group B Streptococcus and

E. coli

*Actinomycosis: sulfa granule

*Traveler’
s diarrhea: E. coli

9. Environmental and nutritional pathology

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Radiation injury
* Cellular mechanism of radiation injury: acute effect, fibrosis, carcinogenesis
* Acute injury: bone marrow, skin, lung, GI, brain, NOT thyroid
* Delayed injury of brain: white matter- gliosis

Oral contraceptives
* Venous thrombosis, myocardial infarction, cholestasis, hypertension, and
gallbladder disease
* Increase in risk of cervical cancer, hepatic adenoma
* Decrease in risk of endometrial and ovarian cancers

*Cat scratch disease: suppurative granulomatous inflammation in axillary lymph

node

Thiamine (Vit. B1) deficiency

1. Periventricle and mamillary body petechiae
2. Chronic alcoholism

*Vitamin D deficiency: richet and osteomalacia

*Vit. K deficiency: bleeding tendency
*Ethylene glycol toxicity: oxalate crystal deposition in kidney and brain

10. Diseases of infancy and childhood

Neonatal respiratory distress syndrome (RDS) (hyaline membrane disease)

1. Pathogenesis: immaturity of lung, deficiency of pulmonary surfactant produced
by type II alveolar epithelial cell- airless lung
2. Eosinophilic hyaline membrane composed of fibrin and necrotic debris lining
respiratory bronchiole, alveolar duct, and alveoli

*Intracranial hemorrhage in prematurity: paraventricular germinal matrix

Wilms’tumor
1. Most common primary renal tumor in children, and rare in adults
2. 2-5 y/o
3. Malignant tumor
4. Mutation of WT-1 & WT-2 gene

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5. Triphasic combination
epithelial differentiation
stromal differentiation- skeletal muscle
blastema

Retinoblastoma
* Children
* Rb gene double hit mutation
* Family & sporadic

11. Blood vessel

Hypertension
* Essential H/T (idiopathic) (90-95%)
* Secondary H/T (5-10%)
1) renal disease
2) adrenal disorders (primary aldosteronism, Cushing’
s syndrome,
pheochromocytoma)
3) coarctation of aorta
4) Graves’disease

Atherosclerosis
* Hyperlipidemia: the strongest risk factor for AS in patients under age 45
* Ulcer, calcification, thrombus, hemorrhage

Monckeberg medial calcific sclerosis

1. Calcific deposits in medium-sized muscular arteries in older >50 y/o
2. Irregular medial plaque
3. Second form of atherosclerosis

Burger’
s disease (thromboangiitis obliterans)
1. Intermediate and small arteries of extremities
2. Male, heavy cigarette smokers
3. Mural or occlusive thrombosis of the lumen with small microabscesses

Kawasaki syndrome (mucocutaneous lymph node syndrome)

* Arteritis: large, medium-sized, & small arteries, esp. coronary artery, skin,

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 ocular and oral mucosa
* Young children and infants (80%, < 4 yrs old)
* Fever, lymphadenopathy
conjunctival and oral erythema with erosion
edema of the hands and feet
erythema of the palms and soles

Takayasu’
s arteritis
1. Granulomatous lesion of the aorta and its major branches
2. Common in Asia; female: 15-40 yrs old
3. Weakening of pulses in the upper extremities (pulseless disease)
fibrous thickening of the aortic arch
hypertension
4. Etiology: unknown

Polyarteritis nodosa
* Medium-sized and small arteries
* Panmural acute necrotizing arteritis with fibrinoid necrosis, neutrophil and
eosinophil infiltration and extension into adventitia
* sharply segmental, nodularity
* 30% HBV antigen (+)

Wegener’
s granulomatosis
1. c-ANCA (+)
2. Acute necrotizing granulomas of the upper and /or lower respiratory tract
3. Necrotizing or granulomatous vasculitis (small to medium-sized
vessels) in the lungs and upper airways
4. Renal diseases: focal or diffuse necrotizing, often crescent glomerulonephritis

Aneurysm
* Cause:
1. congenital
2. infectious
3. traumatic
4. systemic disease
* True aneurysm:
- all layers of the arterial wall contribute to the dilatation
- atherosclerotic, syphilitic

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 - two principal causes of aortic aneurysm:
1) atherosclerosis- abdominal aorta 2) cystic medial degeneration

Syphilic (luetic) aneurysm

* Thoracic aorta, commonly in the arch
* Tertiary syphilis: medial layer destruction
* Obliterative endarteritis with lymphocyte, plasma cell
- vasa lumina narrowing => aortic media ischemic injury
- loss of medial elastic fiber and muscle cell  inflammation  scarring 
damaged media (Gross- tree barking)

12. Heart

Right-sided heart failure

Cor pulmonale
1. Acute severe decrease in output - sudden death
．massive pulmonary embolus in outflow tract (RV or main pulmonary artery)
．cardiac tamponade
2. Chronic backward failure
．cause: systemic venous congestion
．hepatomegaly, nutmeg liver
．peripheral edema - ankle, sacrum
Morphologic change of right-sided heart failure
1. Ventricle dilatation and hypertrophy
2. Congestion
3. Liver: chronic passive congestion  nutmeg liver
．central vein congestion  hepatocyte atrophy or hemorrhagic necrosis
．liver diffuse fibrosis  cardiac cirrhosis

Tetralogy of Fallot
* Most common form of cyanotic CHD
* Four features:
VSD
combined with pulmonary valve stenosis or atresia- cyanosis
overriding aorta
RVH

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*Transposition of great arteries: cyanotic congenital heart disease, right
ventricle hypertrophy

Myocardial infarction
* Pathogenesis:
most acute MI caused by coronary artery thrombosis by preexisting atherosclerosis
* Time: within 20-30 minutes of the time of vessel occlusion, and up to 3-6 hours
when full size has developed
* Location: left anterior descending coronary artery branch (40-50%)
anterior and apical left ventricle; anterior 2/3 of interventricular septum
Laboratory evaluation of MI
1. Creatine kinase (CK)
．CK-MM, CK-BB, CK-MB (myocardium)
．total CK
．CK-MB
2. Lactate dehydrogenase (LDH)
．LD-1 isoenzyme (myocardium), more specific for LD-2 isoenzyme
3. Troponin - contractile protein in human skeletal and cardiac muscle
．troponin I (cTnI) - only found in adult heart
．troponin T (cTnT)

Cardiac rupture syndrome

* Free wall rupture (most common)  cardiac tamponade
* Pathology
transmural infarct - most of thickness of the ventricular wall involved

Morphologic change in MI
1. No change in the first 12 hours (grossly)
but few “
wavy”fibers at margin of infarct (1-2 hrs) and early coagulation necrosis
with edema, few PMNs and minimal hemorrhage (4-12 hrs)
2. Pallor change (gross) (18-72 hrs)
coagulative necrosis with nuclear pyknosis, cytoplasmic eosinophilia (18-24 hrs)
* contraction band necrosis at periphery of infarct (18-24 hrs)
* complete coagulative necrosis of myofiber, heavy PMNs with early
fragmentation of PMN nuclei (24-72 hrs)
3. Central pallor with hyperemic border (4-7 days)
Macrophage with phagocytosis of necrotic fibers; granulation tissue at edge of
infarct; PMNs reach a peak on days 5-6

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4. Maximally yellow, soft, shrunken; purple border (10 days)
Well-developed phagocytosis, prominent granulation tissue in the peripheral areas
of infarct
5. End of the 4th week- necrotic myocardium resorbed
6. Firm and gray (7-8 wks)
fibrosis
contraction band
dying cell nearby infarct area with influx of calcium --> hypercontraction
* early reperfusion --> more prominent contraction band
myocytolysis - immediate subendocardial area with vacuolated appearance due to
influx of water
* Complication of MI: sudden death due to ventricular fibrillation (most common)

Cardiac cause of sudden death

A. Coronary artery diseases
1. coronary atherosclerosis
* acute plaque rupture  thrombosis  vasospasm  ventricular arrhythmia
2. developmental abnormalities (anomalous origin, hypoplasia)
3. coronary artery embolism
4. other (vasculitis, dissection)
B. Myocardial diseases
1. cardiomyopathy
2. myocarditis and other infiltrative process
3. right ventricular dysplasia
C. Valvular diseases
1. mitral valve prolapse
2. aortic stenosis and other forms of left ventricular outflow obstruction
3. endocarditis
D. Conduction system abnormalities

Hypertrophic cardiomyopathy
* Asymmetric septal hypertrophy and idiopathic hypertrophic subaortic stenosis
1) myocardial hypertrophy
2) abnormal diastolic filling
3) intermittent ventricular outflow obstruction
* Myocardial hypertrophy, prominent in left ventricle and interventricular system
* Haphazard arrangement of hypertrophied myocytes, myocardial fibrosis

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*Marantic endocarditis (NBTE, non-bacterial thrombotic endocarditis): cancer
at terminal stage

Infective endocarditis
Infection of the cardiac valve or mural surface of the endocardium, resulting in the
formation of an adherent mass of thrombotic debris and organisms (vegetation)
Morphology in infective endocarditis
1. Valvular vegetation containing bacteria
2. Common site: aortic and mitral valves
3. Systemic emboli → multiple infarcts in brain, kidney, heart and abscess

*Bacterial myocarditis: streptococcus, anti-streptolysin and DNAase B,

myocarditis with fibrinoid necrosis

Chronic rheumatic heart disease

* Irreversible deformity of cardiac valve
* Left side valve more than right side- mitral valve (most common)
* Aschoff body: fibrinoid necrosis close to small vessel, surrounded by
lymphocytes, plasma cells, and large histiocyte (Anitschkow cell, caterpillar cell)

Mitral valve prolapse

* Myxomatous degeneration of mitral valve
* Young women, unknown pathogenesis

Aortic stenosis
1. Post-inflammatory scarring (rheumatic heart disease)
2. Senile calcific aortic stenosis
3. Calcification of congenital deformed valve

Tumors of the Heart

1. Adult: myxoma (most common)- left atrium, stellate cells embedded within an
abundant acid mucopolysaccharide ground substance
rhabdomyosarcoma
2. Child: rhabdomyoma
* spider cell, glycogen in tumor cell
* tuberous sclerosis

Cardiac transplantation

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* Complications
a) infection; b) malignancy (e.g. lymphoma)
c) graft vascular disease (or graft arteriosclerosis) d) silent MI
e) rejection: interstitial lymphocyte infiltration and myocyte damage
f) long term complication: coronary artery intimal fibrosis and stenosis
* Monitored by endomyocardial biopsy

13. RBC & platelets

Hydrops fetalis
* Thalassemia
* Erythroblastosis fetalis
* Hemolytic anemia
* Kernicterus

Thalassemia
1. Hereditary hemoglobinopathy: Hb A(α2β2)
2. β-thalassemia
deficient synthesis of β chain- hypochromia
relative excess of α chain
3. α-thalassemia
deficient synthesis of α chain
relative excess of β, γ chain
4. Ineffective erythropoiesis / hemolysis

Megaloblastic anemia
* Impaired DNA synthesis, impaired maturation & differentiation in erythroid series
* Enlarged and hypersegmented neutrophil
* Folate deficiency anemia
* Pernicious anemia: Vit. B12 deficiency due to intrinsic factor deficiency
* Stomach: autoimmune atrophic gastritis, gastrectomy
* Bone marrow: megaloblastic anemia (Vit. B12 deficiency anemia)
* Nervous system: subacute combined degeneration of spinal cord

Iron-deficiency anemia
* Microcytic, hypochromic RBC
* Chronic blood loss

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* Low serum iron, low serum ferritin, low transferrin saturation, high total
plasma iron-binding capacity

*Aplastic anemia: splenomegaly (-), chloramphenicol

*Sickle cell anemia: autosplenectomy
*Sickle cell anemia and hereditary spherocytosis: aplastic crisis, parvovirus

Hereditary spherocytosis
1. Intrinsic red cell membrane defect
2. Vulnerable to splenic destruction: splenectomy
3. Autosomal dominant (85%)
4. Spectrin deficiency
5. Anemia, splenomegaly, jaundice

Hemophilia A
1. Factor VIII deficiency
2. Most common hereditary disease with severe bleeding
3. Reduction in amount or activity of factor VIII
4. X-linked recessive (70%)
5. Massive bleeding after trauma
spontaneous hemorrhage- hemarthroses
6. BT: normal PTT: prolonged
7. Hemophilia B: Christmas disease

Idiopathic thrombocytopenic purpura (ITP)

1. Chronic autoimmune disorder
2. Antiplatelet Ab
3. Childbearing-aged women
4. Splenomegaly (-)
5. BM: increased megakaryocytes
6. Bleeding time prolonged

Disseminated intravascular coagulation (DIC)

1. Acute, subacute, or chronic thrombohemorrhagic disorder
2. Thrombotic diathesis
* activation of clotting system
3. Hemorrhagic diathesis
consumption coagulopathy

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 * activation of fibrinolytic system
4. Fibrin microthrombi in glomeruli

CD34- marker for hematopoietic precursor stem cells in BM

14. WBC

Hodgkin disease
1. A single node or chain of nodes, spreading to anatomically contiguous nodes
2. Diagnostic neoplastic cell: Reed-Sternberg cell (microphotograph)
3. B symptom: fever, night sweats, body weight loss
4. Classification
A. nodular sclerosis
most common form of HD
lacunar cell
collagen bundles dividing the LN into nodules
young women, mediastinal LN
excellent prognosis
B. mixed cellularity
abundant RS cells
polymorphous cell infiltration
C. lymphocyte predominance
rare RS cell
L/H variant (popcorn cell)
Follicular B-cell origin
D. lymphocyte depletion: poor prognosis

Burkitt lymphoma
1. High-grade B-cell lymphoma
2. Children
3. African type & nonAfrican type
4. Small noncleaved lymphoid cells
“starry-sky”appearance- nuclear dusts of lymphoma cells in histiocytes
5. EBV-associated
6. Translocation t(8;14): C-MYC gene

Anaplastic large cell lymphoma

22
1. Peripheral T cell lymphoma
2. Large anaplastic cells, horseshoe-shaped nuclei (microphotograph)
3. Rearrangement of ALK gene (tumor marker) on 2p23
ALK+: children or young adults, soft tissue, good prognosis
ALK-: older adults, poor prognosis

Lymphoblastic lymphoma
1. Childhood in mediastinum
2. Marker: CD3 (T cell), TdT

Follicular lymphoma
1. Low-grade B-cell lymphoma
2. t(14,18): BCL-2 gene expression

Hemophagocytosis-associated lymphoma: NK/T cell lymphoma (most common)

Leukemia
* High incidence in young group
* Basophilia: chronic myelogenous leukemia
* Myelofibrosis with myeloid metaplasia  acute leukemia
* Myelofibrosis: TGF-β from megakaryocyte  fibrosis
* CLL: B lymphocyte in origin

*Lethal midline granuloma: NK/T cell lymphoma in nasal cavity

Multiple myeloma
* Plasma cell neoplasm characterized by involvement of skeleton at multiple sites to
form punched-out lesion on x-ray, vertebra, rib, skull, pelvis in decreased order
* Increased plasma cells in bone marrow: IL-6 associated
plasmablast, multinucleated form
Russell body, Dutcher body
* Production of excessive Ig
hypercalcemia, recurrent infection
renal failure- Bence Jones (light chain) proteinuria: tubular cast with giant
cells
amyloidosis of AL type
* Electrophoresis analysis: increased monoclonal Ig in the blood or Bence Jones
(light chain) protein in the urine- cast nephropathy

23
Waldenstrom macroglobulinemia
1. Serum hyperviscosity caused by high levels of IgM
2. Lymphoplasmacytic lymphoma or rare myeloma that secrets IgM

Langerhans cell histiocytosis

* Clonal proliferation of antigen-presenting dentritic cells with Birbeck granule in
the cytoplasm by EM

Thymic hyperplasia
1. Thymic follicular hyperplasia
2. Predominantly B lymphocytes
3. Most frequently associated with myasthenia gravis

Thymoma
1. Tumor of thymic epithelial cells
2. Adult (> 40 y/o), associated with myasthenia gravis
3. Major location: ant. sup. mediastinum
4. Mixture of neoplastic epithelial cells & nonneoplastic lymphocytes

*Spleen: 150 gm

15. Lung

Brown induration
* Pulmonary congestion and edema caused by heart failure
* Heart failure cell: hemosiderin-laden macrophage

Acute respiratory distress syndrome (ARDS)- diffuse alveolar damage

1. Diffuse alveolar capillary damage
2. Rapid onset of severe respiratory insufficiency
3. Pulmonary edema
4. Clinical and pathologic end result of acute alveolar injury caused by a variety of
insults

Clinical conditions associated with ARDS

* Infection- bact., virus, fungus, sepsis
* Physical injury

24
* Inhaled irritants
* Chemical injury
* Paraquat intoxication  pulmonary fibrosis
* Hematologic conditions- blood transfusion, DIC

Pathology of diffuse alveolar damage

hyaline membrane formation
fibrin exudate
necrotic debris of alveolar epithelium

Chronic obstructive pulmonary disease (COPD)

* Emphysema
* Chronic bronchitis

Emphysema
Pathogenesis: proteinase-antiproteinase hypothesis
Types of emphysema
1. Centriacinar emphysema 95%
A. involvement of respiratory bronchiole
B. favor site: upper lobe
C. associated with cigarette smoking, chronic bronchitis
2. Panacinar emphysema
A. uniform enlargement of acini
B. favor site: lower lobe
C. α1-antitrypsin deficiency
3. Paraseptal emphysema
A. involvement of distal alveoli
B. subpleural location in upper lung
C. associated with spontaneous pneumothorax

Pathology of chronic bronchitis

1. Large airway disease
A. hypertrophy of submucosal gland
↑Reid index = thickness of mucous gland layer
thickness of bronchial wall
B. squamous metaplasia / dysplasia
2. Small airway disease (bronchiolitis)
A. goblet cell metaplasia

25
 B. bronchiolitis obliterans

Asthma
1. Chronic relapsing inflammatory disorder
2. Hyperreactive airway
3. Triggered by dust, pollen, animal dander, food, common cold, exercise
4. Family history of atopy
3. Episodic reversible bronchoconstriction- cough, wheezing, dyspnea
5. Increased responsiveness of tracheobronchial tree to various stimuli, especially in
small bronchi and bronchioles
6. Subepithelial vagal effect in acute phase
7. Influx of eosinophils in late phase
8. Mucus plugging in bronchus and bronchiole
9. Submucosal gland hypertrophy

Bronchiectasis
1. Chronic necrotizing infection of bronchi and bronchioles
2. Gross: abnormal permanent dilation of airway
3. Pathogenesis of bronchiectasis: obstruction, infection

Diffuse interstitial lung disease

1. Heterogeneous group: interstitial pneumonitis, ARDS, pneumoconiosis, drug,
paraquat intoxication
2. Chronic diffuse involvement of interstitium
3. Secondary pulmonary hypertension & right heart failure
4. Pulmonary fibrosis, progression to end-stage honeycomb lung: cystic spaces with
thick fibrous septa
5. Respiratory failure

*Coal worker pneumoconiosis: anthracosis

Silicosis
1. Silicon dioxide (silica, crystalline form, Quartz) - fibrosing pneumoconiosis
2. Most common chronic occupational disease
3. Concentric hyalinized collagen scar surrounded by eggshell calcification
4. Polarized microscopy: birefringent silica particle
5. Favor site: upper zone
6. Associated with fibrosis of pleura & hilar node

26
Sarcoidosis
1. Systemic disease of unknown cause: lymph node, lung, skin, eye
2. Bilateral hilar lymphadenopathy with lung involvement
3. A. noncaseating granuloma
epithelioid cell, Langhans giant cell & foreign body giant cell
B. Schaumann body: laminated concretion with calcium
C. Asteroid body: stellate inclusion in giant cell

Pathologic staging of lobar pneumonia

1. Congestion: red, soft, swelling of lung
intraalveolar edema, bact.(+++)
2. Red hepatization: red, firm, airless
red cells, neutrophil & fibrin exudate in alveolar space
3. Gray hepatization: gray & dry
red cell lysis, fibrinosuppurative exudate
4. Resolution
digestion of intraalveolar exudate

Primary atypical pneumonia

1. Viral and mycoplasmal pneumonia
2. Acute febrile respiratory infection in the pulmonary interstitium- interstitial
pneumonitis
3. Hyaline membrane in early phase

*Farmer’
s lung: hypersensitivity pneumonitis: granuloma

Asbestos-related disease
1. Localized pleural fibrous plaque
2. Pleural effusion
3. Asbestosis: interstitial fibrosis, honeycomb lung
4. Bronchogenic carcinoma
5. Malignant mesothelioma

Pulmonary hypertension
1. Large artery: atherosclerosis, emboli
2. Small artery & arteriole
medial smooth muscle hypertrophy
intimal fibrosis

27
 lumen narrowing
* plexogenic pulmonary arteriopathy:

*Pulmonary infarction: subpleural wedge-shaped lesion in lung base

*Smoking: squamous metaplasia: respiratory epithelium  squamous

epithelium

*Bloody pleural effusion: metastatic carcinoma

Adenocarcinoma of lung
1. Increased incidence in recent years
2. Most common form of lung cancer in women & nonsmokers
3. Peripherally-located
4. Slowly growing
5. Scar →“scar cancer”

Small cell carcinoma of lung

1. Oat cell type:
small round cell with hyperchromatic nucleus and scanty cytoplasm
2. Derived from neuroendocrine cell in bronchial epithelium; neurosecretory
granule in tumor cell
3. Strong relationship to cigarette smoking
4. Centrally-located
5. Most aggressive lung cancer with wide dissemination
6. Response to chemotherapy/radiotherapy
7. Most common lung cancer associated with paraneoplastic syndrome

*Undifferentiated carcinoma: large cell carcinoma, small cell carcinoma

Paraneoplastic syndrome in bronchogenic carcinoma

1. ADH: hyponatremia- small cell carcinoma
2. ACTH: Cushing syndrome- small cell carcinoma
3. Parathyroid hormone-related peptide: hypercalcemia- squamous cell carcinoma
4. Calcitonin: hypocalcemia
5. Gonadotropin: gynecomastia

*Chronic rejection after lung transplantation: bronchiolitis obliterans

28
 16. Head & neck

Pleomorphic adenoma (mixed tumor)

1. Most common tumor in parotid gland
2. Slow-growing, well-defined & well-encapsulated
3. Epithelium-derived benign tumor
epithelial- ductal, acini, strands, squamous
mesenchymal- myxoid, hyaline, chondroid (cartilage), osseous
4. Carcinoma ex pleomorphic adenoma (malignant mixed tumor)

Cholesteatoma
1. Associated with chronic otitis media
2. Not a true neoplasm
3. Epidermal cyst-like, cholesterol, desquamated squames, giant cell reaction

*Acute suppurative otitis media: Hemophilus influenzae

*Vocal cord polyp: singer nodule
*Malignant otitis externa: old patient with DM

Laryngeal carcinoma
* Old men
* Smoking
* Squamous cell carcinoma

*Oral squamous cell carcinoma: betel chewing

17. GI tract

*Esophageal atresia: tracheal bifurcation, choking at first feeding

Barrett esophagus
1. Long-standing & severe reflux esophagitis
2. Squamous epithelium replaced by metaplastic columnar epithelium at distal
esophagus
3. Pathology of Barrett esophagus
red, velvety GI mucosa
metaplastic columnar epithelium

29
 gastric type
intestinal type- goblet cell
dysplasia of glandular epithelium → adenocarcinoma

Mallory-Weiss syndrome
1. Esophageal longitudinal tear at ECJ
2. Alcoholism- excessive vomiting & refluxing
3. Perforation → UGIbl e edi
ng

Esophageal carcinoma
1. Squamous cell carcinoma: 90%
2. M > F
3. Local invasion: tracheoesophageal fistula, pericardium, mediastinum
4. Lymphatic spreading- submucosa & adventitia
lymph node metastasis
5. Poor prognosis

Helicobacter pylori infection

1. Most important etiologic association with chronic gastritis
2. G(-) curvilinear rod-like bacilli, Warthin-Starry stain
3. Antral/antral & body mucosa: chronic active gastritis, chronic atrophic gastritis
with intestinal metaplasia (microphotograph)
4. Bacilli in superficial mucous layer and foveola of epithelial surface
5. Absence in area of intestinal metaplasia
6. High risk to develop peptic ulcer, gastric carcinoma, gastric lymphoma
(MALToma)
7. HP like to bind to gastric epithelium of O blood type

Peptic ulcer
* Chronic, remitting, and relapsing gastrointestinal lesion
* Aggressive action of acid-peptic juice
* Imbalance between mucosal defense mechanism & damaging force
* Location of peptic ulcer
1. duodenal ulcer: 1st portion of duodenum
2. gastric ulcer: esp. antrum
3. esophagocardiac junction
4. gastrojejunostomy
5. Zollinger-Ellison syndrome: duodenum, stomach, jejunum

30
 6. Meckel diverticulum

Stress ulcer
* Small, multiple or single ulceration at stomach & duodenum
* Usually less than 1 cm in diameter
* Curling ulcer: severe burn injury
*Cus hi ngul cer:IICP( i
nc reasedi ntracra nia
lpressure
)→ head injury, brain tumor

Early gastric carcinoma

Confined to mucosa and submucosa, regardless of presence or absence of
regional lymph node metastasis

*Krukenberg tumor: diffuse type gastric adenocarcinoma with bilateral ovary

metastasis

MALToma (mucosa-associated lymphoid tissue lymphoma)

1. Marginal zone lymphoma (low-grade B-cell lymphoma)
2. Extranodal site: GI tract, salivary gland, thyroid
3. Associated with Helicobacter pylori infection in stomach

Gastrointestinal stromal tumor (GIST)

1. Gastrointestinal mesenchymal tumor originated from interstitial cells of Cajal
2. Spindle cells, plump "epithelioid" cells, or a mixture of both
3. Tumor cells positive for c-KIT (CD117), CD34
4. C-KIT mutations and platelet-derived growth factor receptor-α(PDGFRA)
mutations

Hirschsprung's disease (congenital aganglionic megacolon)

* Neonatal period
* Failure to pass meconium
* Obstructive constipation
* Arrest of migration of neural crest to anus
* Aganglionosis: absence of ganglion cell
* Megacolon- dilatation & hypertrophy proximal to aganglionic segment

Meckel's diverticulum
1. Incidence: 2 %
2. Persistence of vitelline duct

31
3. Terminal ileum- 30 cm. proximal to ileocecal valve, antimesenteric border
4. Heterotopic mucosa: gastric mucosa, pancreatic tissue
5. Complication: peptic ulcer, bleeding, rupture

Angiodysplasia in intestine
1. Abnormal tortuous dilation of submucosal and mucosal blood vessels
2. Cecum and right colon
3. Intermittent lower intestinal bleeding

Intussusception
1. Intestinal obstruction
2. One segment of the intestine, constricted by a wave of peristalsis, suddenly
becomes telescoped into the immediately distal segment of bowel
3. Gross

Pseudomembranous colitis
1. Acute adherent inflammatory pseudomembrane
2. Clostridium difficile toxin
3. Antibiotic-associated
4. Severe mucosal injury: ischemic colitis
5. Pseudomembrane- plaque-like adhesion of fibrinopurulent-necrotic debris &
mucus to damaged mucosa
6. Mushrooming cloud- purulent exudate of crypt

Celiac sprue (Gluten-sensitive enteropathy, Nontropical sprue)

1. Diarrhea: sensitive to gluten (gliadin)
2. Whites, rare in orients
3. Genetic susceptibility: HLADQw2
4. Immune-mediated intestinal injury
5. Flat, scalloped or normal mucosa
6. Diffuse enteritis
duodenum & proximal jejunum
mucosal atrophy: villi shortening
7. Surface epithelium
vacuolar degeneration
loss of microvilli
intraepithelial lymphocyte

32
8. Reversible change after gluten-free diet

Whipple's disease
1. Systemic disease: intestine, CNS, joint
2. Tropheryma whippelii, G(-) bacilli
3. Whites, 4th to 5th decades, M:F=10:1
4. Malabsorption, polyarthritis, lymphadenopathy, CNS dysfunction
5. Foamy macrophage: cytoplasmic PAS (+) granule, rod-shaped bacilli by EM
6. Bacilli-laden macrophage in synovial membrane & brain

Crohn’
s disease
1. Mucosal inflammation & ulcer
2. Chronic mucosal damage- atrophy, paneth cell metaplasia
3. Skip lesion
4. Transmural inflammation
* noncaseating granuloma: histiocyte infiltration
5. Fistula

Ulcerative colitis
1. Inflammatory disease limited to colon
2. Mucosa & submucosa lesion
3. Continuous lesion, skip lesion (-)

Hyperplastic polyp of colon

1. < 5 mm, multiple＞single
2. Not neoplastic
3. Proliferative serrated epithelium, infoldings of crowding epithelium
increased goblet cells
4. No malignant change

Villous adenoma
* Mucin diarrhea
* Hypokalemia
* Malignant change

Familial adenomatous polyposis

1. Autosomal dominant
2. Progression to adenocarcinoma (100%)

33
3. 2nd to 3rd decades, 10-15 year-period
4. A minimum of 100 polyps
5. Prophylactic colectomy
6. High risk in sibling & first-degree relatives

*Gardner syndrome: epidermal cyst, osteoma, adenomatous polyposis,

fibromatosis

"Multi-hit" concept for colorectal carcinogenesis

1. Chromosome 5q21: FAP associated gene
* APC (adenomatous polyposis coli) mutation- early event
2. Hypomethylation in DNA
3. Ras gene mutation in adenoma & carcinoma
4. DCC (deleted in colon cancer) allelic loss
5. Loss at 17p in colon cancer

Colorectal carcinoma
* Napkin-ring gross appearance
* Single important prognostic factor: extent of tumor
clinical staging: modified Dukes' classification
* Mucinous adenocarcinoma: poor prognosis

Carcinoid tumor
1. Any age, peak incidence: 6th decade
2. Neuroendocrine cell from gut, pancreas, lung, biliary tree, liver
3. 50 % of small intestinal malignancies
4. Malignant potential: site, depth, and size
5. Favor site: appendix (most common)- tip
intramural or submucosal tumor, small & polypoid

Clinical manifestation of intestinal carcinoid

1. Asymptomatic
2. Gastrin: Zollinger-Ellison syndrome
ACTH: Cushing's syndrome
Insulinoma
3. Carcinoid syndrome- liver metastasis
* flush & cyanosis, diarrhea, asthma
* tricuspid valve stenosis: smooth muscle cells and sparse collagen fibers in an

34
 acid mucopolysaccharide-rich matrix

18. Liver & Gallbladder

Dubin-Johnson syndrome
1. Autosomal recessive, impaired transport of conjugated bilirubin from the
hepatocytes to bile canaliculi
2. Chronic or intermittent conjugated hyperbilirubinemia
"Black liver", coarse iron-free dark brown granules in the hepatocytes

Caroli disease
* Intrahepatic biliary tree is segmentally dilated and contain inspissated bile
* Associated with portal tract fibrosis of the congenital hepatic fibrosis type

Viral hepatitis:hepatit
isvi rusA, B,C,D,E,G…
Hepatitis A: no carrier, no development of chronic hepatitis
Hepatitis B:
* ds DNA virus
* "Serum hepatits"
* Incubation period: 4-26 weeks
* Mode of transmission of HBV
Perinatal (Vertical): HBeAg (+) mothers
Horizontal: children, adults, parenteral
* Serology
HBsAg (+): acute or chronic infection or carrier state
HBsAb (+): past, resolved HBV infection
HBeAg (+): active viral replication
HBeAb (+): lower infectivity
HBc IgM (+): recent infection
HBc Ab(+): recent infection or old HBV infection

Hepatitis C
* ssRNA virus
* Transfusion-associated hepatitis
* Incubation period: 2-26 weeks
* High rate of progression to chronic disease
* Serology: anti-HCV Ab

35
Chronic hepatitis
# Grade
portal inflammation
periportal activity (piecemeal necrosis/bridging necrosis)
lobular activity
# Stage:
portal fibrosis (fibrous expansion, bridging fibrosis, cirrhosis)
* "ground-glass" hepatocytes: HBV infection
* HCV hepatitis: fatty change, lymphoid aggregates, bile duct reaction

Fulminant hepatitis
1. Hepatic failure occurs within 2-3 weeks
2. Fulminant viral hepatitis (50-65%), drug or chemical toxicity (25-30%)
3. Massive to submassive necrosis: liver shrinkage, soft  hepatic failure

Wilson disease (hepatolenticular degeneration)

* Autosomal recessive (ATP7B on Chromosome 13)
* Defect in biliary excretion of copper
liver: fatty change, acute hepatitis, chronic hepatitis, cirrhosis, excess
copper deposition
CNS involvement : basal ganglia, particularly the putaman
Kayser-Fleischer ring: green to brown deposits of copper in cornea
biochemical diagnosis: ceruloplasmin↓, hepatic Cu↑, urine Cu↑

Alcoholic hepatitis
1. Hepatocyte swelling and necrosis
2. Mallory bodies: eosinophilic cytoplasmic inclusions (tangled skeins of
cytokeratin intermediate filaments)
3. Neutrophil, and less lymphocyte and macrophage infiltration

*Liver cirrhosis: collagen produced by sinusoidal stellate cell

*Most common intrahepatic factor of portal hypertension: liver cirrhosis

Primary biliary cirrhosis (PBC)

* Granulomatous inflammation of medium-sized intrahepatic bile ducts
* Middle-aged female
* Autoantibodies (90% antimitochondrial Ab: M2)
* Ductular proliferation, destruction and onion-skin fibrosis

36
* Cholestasis

Focal nodular hyperplasia

1. Young to middle-aged women
2. Fibrous septa and hepatocytic nodules, characteristic central stellate scar

*Liver cell adenoma: oral contraceptives

Hepatocellular carcinoma
* Etiology: HBV (200-fold increased risk), HCV
* Repeated cycles of cell death and regeneration
viral DNA integrated into the host genome and induce instability
* α-fetoprotein
* Trabecular (sinusoid) growth pattern

Cholangiocarcinoma
* Arising form the biliary epithelium
* Peripheral, major bile duct, hilar
* Solitary or multiple
* Adenocarcinoma with markedly desmoplastic stroma

Gallbladder carcinoma
* 60-90% with gallstones
* Adenocarcinoma

Charcot triad of cholangitis

* Jaundice
* Abdominal pain
* Fever & chillness

Cholangitis
1. Bacterial infection of the bile ducts
2. Cause of choledocholithiasis
3. Ascending cholangitis
4. Enteric Gram (-): E coli, Klebsiella, Enterobacter, Clostridius
5. Fever, chills, abdominal pain, and jaundice

*Angiosarcoma of liver: exposure to vinyl chloride, arsenic, or Thorotrast

37
 19. Pancreas

Acute pancreatitis
1. Associated with biliary tree stone and alcoholism
2. Increased serum level of amylase and lipase
3. Initiated
A. pancreatic duct obstruction (biliary stone)
accumulation of enzyme-riched fluid, fat necrosis, edema
B. primary acinar cell injury- drug, trauma, ischemia, virus
4. Fat necrosis, hemorrhage, edema, necrosis

Chronic pancreatitis
* Repeated bouts of mild to moderate pancreatic inflammation
* Continued loss of pancreatic parenchyma and replaced by fibrous tissue
* Alcoholism, hypercalcemia and hyperlipoproteinemia
* Pathology
Interstitial fibrosis after previous episodes of acute pancreatitis
Pseudocyst: develop after inflammation and necrosis of the pancreas
no epithelial lining

Diabetes Mellitus
Classification of DM (based on inheritance pattern and insulin response)
1. Type 1 diabetes
insulin-dependent DM (IDDM) (10%)
juvenile onset
absolute lack of insulin (destruction and reduction in β-cells)
autoimmunity (insulitis)
2. Type 2 diabetes
non-insulin-dependent DM (NIDDM) (80-90%)
adult onset, obesity
deranged β-cell secretion of insulin
amyloid deposition (Congo-red stain under polarized microscope: apple
green)
decreased response of peripheral tissue to respond to insulin (insulin resistance)
* Complication: nephropathy, angiopathy, neuropathy, retinopathy

*Pancreatic carcinoma: pancreatic head (most common)

38
 20. Kidney

Cystic renal dysplasia

* Abnormal metanephric differentiation
* Disorganized architecture, immature tubules and collecting ducts, immature
cartilage

Acute poststreptococcal glomerulonephritis (PSGN)

Acute nephritic syndrome: hematuria, hypertension
Type III hypersensitivity
C3 in serum
Anti-streptococcal Ab (+)
LM: diffuse proliferative GN with many PMNs
EM:s ube pithel
ial“hump”
Prognosis: good, rarely progressive to end-stage renal disease

Rapidly progressive (crescentic) glomerulonephritis (RPGN)

* Glomerular destruction, fibrinoid necrosis of the capillary tufts
epithelial cell proliferation → crescent
grave prognosis
* Goodpas ture’ssyndr ome
lung hemorrhage (hemoptysis): alveolar destruction
crescentic GN: anti-GBM Ab

IgA nephropathy (
Ber
ger
’sdisease)
1. Very common in oriental people
2. Most common presentation: asymptomatic hematuria and/or proteinuria
3. A few cases: nephrotic syndrome
4. LM: mesangial proliferation with/without endocapillary proliferation,
with/without segmental sclerosis
IF: granular deposition of IgA and C3 in the mesangium
EM: electron-dense deposits in para-mesangial matrix
5. Prognosis: variable
10-20% of cases: progression to renal failure 10-20 years later

Minimal change disease (lipoid nephrosis)

* Most common cause of NS in children
* LM: normal glomeruli, lipid in tubular epithelium

39
* IF: no deposit
* EM: foot process effacement

Membranous glomerulonephritis (MGN)

* Most common cause of NS in adults
* C5b-C9 (membrane attack complex of complement)
* Subepithelial immune deposits
* Secondary MGN
carcinoma (lung, colon), SLE, infections (hepatitis B, syphilis),
drugs (D-penicillamine, captopril), inorganic salts (gold, mercury)
* MGN associated with HBV infection in children
serology: HBsAg (+), HBeAg (+)
steroid therapy: not effective
prognosis: usually not progressive to renal failure

Membranoproliferative glomerulonephritis (MPGN)

* Type I: subendothelial deposits and double contour of GBM
* Type II (dense deposit disease)
* Hypocomplementemia

Diabetic glomerulosclerosis (DM nephropathy)

* Diffuse type: GBM thickening, diffuse mesangial proliferation
hyaline thickening of arterioles
* Nodular type: Kimmelstiel-Wilson nodule

Al port’ssyndrome
1. Hereditary nephritis
2. Hematuria or proteinuria, nerve deafness
3. Eye disorders (lens dislocation, cataracts, corneal dystrophy)

*Chronic glomerulonephritis: hyalinization of glomeruli

Hypertensive nephropathy

1. Benign nephrosclerosis
* arterioles: hyaline arteriolosclerosis: fibrosis
* glomeruli: collapse, sclerosis, or ischemic obsolescence
2. Malignant nephrosclerosis
* malignant hypertension (diastolic pressure＞130 mm Hg)

40
 papilledema retinopathy, encephalopathy, renal failure
* arterioles: necrotizing arteriolitis (fibrinoid necrosis) (microphotograph)
ki
hyperplastic arteriolitis (onion-s n”a
ppe
aranc
e)
* glomeruli: necrotizing glomerulitis with hyaline microthrombi

Acute pyelonephritis
1. E. coli (most common)
2. Fever, chillness, pyuria, costovertebral angle pain
3. Suppurative inflammation, abscess
4. Complication
papillary necrosis (mainly in DM patients): acute renal failure
pyonephrosis

Acute tubular necrosis (ATN)

* Most common cause of acute renal failure, reversible
* Ischemic type: shock
pigment-induced ATN:
a) hemoglobinuria: extensive hemolysis
b) myoglobinuria: severe skeletal muscle injury → rhabdomyolysis
* Toxic type: gentamicin, mercury, CCl4
prominent necrosis of the proximal convoluted tubules

Analgesic abuse nephropathy

1. Ingestion of large quantities of phenacetin-containing analgesic mixtures
2. Phenacetin metabolites: direct toxic effect
aspirin: predisposing to ischemia
3. Papillary necrosis→ cortical tubulointerstitial nephritis
4. 50% complicated with UTI
5. Long-term complication: transitional cell carcinoma of the pelvis

Angiomyolipoma
1. Vessels, smooth muscle and fat
2. Perivascular epithelioid cells origin
3. 25-50% of tuberous sclerosis (bilateral): sebaceous adenoma, epilepsy

41
*Aristolochic acid nephrotoxicity: interstitial fibrosis with relative paucity of
inflammation

21. Lower urinary tract and male genital tract

Pyelonephritis and urinary tract infection (UTI)

* Modes of infection
1) hematogenous infection
2) ascending infection
* Most common pathogen: E. coli

Malakoplakia
1. Soft, yellow, slightly raised mucosal plaque
2. Aggregation of foamy histiocytes (granular cytoplasm, PAS +) stuffed with
particulate and membrane debris of bacterial origins and multinucleated giant cells
3. Michaelis-Gutmann body- laminated mineralized concretions
4. Chronic bacterial infection (E. coli, Proteus)
5. Immunosuppressed transplant recipients

*Squamous cell carcinoma of UB- schistosomiasis

*Urinary bladder carcinoma: carcinogen: aromatic amine, azo dye

Urethral caruncle
* Female
* Inflammatory lesion

Cryptoorchidism (undescended testes)

1. 1% of one-year old boys (25% bilateral)
2. Associated with hernia
3. Development of testicular tumor
4. Atrophy and sterility (bilateral)
5. Unknown etiology

42
Nodular hyperplasia (benign prostatic hypertrophy, BPH)
1. Common disorder in men over age 50 (70% by age 60 and 90% by age 70)
2. Transitional zone in the periurethral region
3. (a) androgen: testosterone  dihydrotestosterone (DHT)
(b) estrogen: render cells more susceptible to DHT
4. Proliferation of ducts and fibromuscular stroma

Acute bacterial prostatitis

* Urinary tract infections (UTI)
* E. coli

Prostate carcinoma
1. Age (old, over 50 years), national and race difference
2. White man in Western most common
3. Family history, hormone (androgen) and environmental influence
4. Posterior location (peripheral zone)
5. Adenocarcinoma
6. Metastasis: Bone (axial bone): hematogenous: osteoblastic
7. Lymph nodes
8. Grading of prostate carcinoma (Gleason system)
9. prostate-specific antigen (PSA)
10. Treatment: hormone therapy, surgery

Teratoma
1. Infancy or adult
2. Cystic or solid with cartilage
3. More than one germ layer
4. Mature (benign) v.s. immature (malignant)
5. Most common location of teratoma in infants and children: sacrococcygeal area

Seminoma
1. Most common germ cell tumor in testis
2. 4th decades
3. Secretion of placental alkaline phosphatase (PAP)
4. Termed “ dysgerminoma”in ovary

Yolk sac tumor

43
1. Most common testicular tumor in infants and children
2. Schiller-Duval body:
Lace-like (reticular) network of medium-sized cuboidal or elongated cells with
papillary structures or solid cords of cells
3. Increased Alpha-fetoprotein serum level
4. Malignant mixed germ cell tumor: combined with other germ cell tumor, such as
choriocarcinoma (increased β-HCG serum level)

22. Female genital tract

Clear cell adenocarcinoma of vagina & DES (diethylstilbestrol)

1. Increased frequency of clear cell carcinoma of vagina in young women whose
mothers had been treated with DES during pregnancy.
2. Less than 0.14% of DES-exposed young women develop clear cell
adenocarcinoma.

Table 2000 modification of FIGO staging of carcinoma of the cervix uteri

Stage Definition
0 Carcinoma in situ (preinvasive carcinoma)
I Cervical carcinoma confined to uterus (extension to the corpus should
be disregarded)
IA Invasive carcinoma diagnosed only by microscopy; all
macroscopically visible lesion, even with superficial invasion, are
stage IB
IA1 Stromal invasion no greater than 3.0 mm in depth and 7.0 mm or less
in horizontal spread
IA2 Stromal invasion more than 3.0 mm and not more than 5.0 mm with a
horizontal spread of 7.0 mm or less
IB Clinically visible lesion confined to the cervix or microscopic lesion
greater than IA2
IB1 Clinically visible lesion 4.0 cm or less in greatest dimension
IB2 Clinically visible lesion more than 4.0 cm in greatest dimension
II Tumor invades beyond the uterus but not to pelvic wall or to lower
third of the vagina
IIA Without parametrial invasion
IIB With parametrial invasion
III Tumor extends to the pelvic wall and/or causes hydronephrosis or

44
 nonfunctioning kidney
IIIA Tumor involves lower third of vagina with no extension to pelvic wall
IIIB Tumor extends to pelvic wall and/or causes hydronephrosis or
nonfunctioning kidney
IVA Tumor invades mucosa of bladder or rectum and/or extends beyond
true pelvis
IV Distant metastasis

HPV: E6 protein

Adenomyosis
1. Endometrial tissue present at myometrium with expansion of uterine wall and
multiple small hemorrhagic cysts
2. Menorrhagia, dysmenorrhea and pelvic pain

Uterine leiomyoma
1. Most common tumor in women
2. Estrogen dependent
3. Regression or calcification after menopause
4. Rapid growth during pregnancy
5. Well-defined, round, firm, gray white, variable size
6. Intramural, submucosal, subserosal
7. Whorled pattern of smooth muscle bundles with red degeneration
8. Low or absence of mitotic activity
9. Rarely progress to leiomyosarcoma

Risk factors of endometrial carcinoma

Obesity
DM
Hypertension
Infertility
Endometrial hyperplasia- hyperestrogenism
Endometrial carcinoma: PTEN gene mutation
Polycystic ovarian syndrome

Malignant mixed Mullerian tumor

* Carcinosarcoma- both carcinoma & sarcoma components

45
* Cervix, endometrium, ovary
* Postmenopause women

Polycystic ovaries
1. Numerous cystic follicles in ovaries with anovulation, obesity, hirsutism
2. Stein-Leventhal syndrome- associated with oligomenorrhea
3. Subcortical ovarian cysts with thickened superficial cortex
4. Lack of or inconspicuous corpus luteum
5. Increased risk to develop endometrial carcinoma

*Tumor marker of ovarian carcinoma: CA-125

*Serous carcinoma: most common ovarian malignancy

Ovarian teratoma
1. Mature (benign)-cystic (dermoid cyst) / solid
young women
unilocular cyst containing hair and cheesy sebaceous material and lined by
epidermis
containing skin appendages, teeth, bone, cartilage, thyroid tissue…
2. Immature (malignant)
solid, bulky, necrosis, hemorrhage
immature tissue, esp. neural tissue
3. Monodermal or specialized teratoma
Struma ovarii- composed of entirely mature thyroid tissue
4. Malignant transformation: squamous cell carcinoma (most common)

Yolk sac tumor (endodermal sinus tumor)

1. Second most malignant tumor of germ cell origin of ovary
2. Children and young women
3. Tumor marker: α-fetoprotein
4. Schiller-Duval body

Granulosa cell tumor of ovary

1. Sex cord-stromal tumor, potentially malignant
2. Most in postmenopausal women
3. Solid and cystic encapsulated ovarian tumor
Call-exner body: microfollicles

46
4. Potential production of estrogen
precocious sexual development
endometrial hyperplasia, endometrial ca, cystic disease of breast

Pseudomyxoma peritonei
*Mucinous ovarian or appendiceal cystic tumor (mucinous cystadenocarcinoma)
*Combined with extensive mucinous ascites, cystic epithelial implants on the
peritoneal surface, and adhesion.

Eclampsia in liver
1. Subcapsular and intraparenchymal hemorrhage
2. Fibrin thrombi in portal capillaries with periportal hemorrhagic necrosis

*Complete hydatidiform mole: 46XX/46XY

*Partial mole: 69XXX/69XXY

Hydatidiform mole
1. Cystic swelling of the chorionic villi and variable trophoblastic proliferation
(microphotograph)
2. Vaginal bleeding and usually a larger uterus
3. β-HCG↑
4. 10% invasive mole, 2.5% choriocarcinoma

Choriocarcinoma
1. Epithelial malignant neoplasm of trophoblastic cells
2. Tumor marker: β-HCG
3. Rapidly invasive, widely metastasis: lungs (50%)
4. Abnormal proliferation of both cytotrophoblast and syncytiotrophoblast, villi (-)
5. Metastasis: lung (most common)

*Pelvic inflammatory disease (PID): gonococcus (most common)

Placental site trophoblastic tumor

1. Intermediate trophoblast: found in implantation site and placental membrane
2. Intermediate trophoblast proliferation, deeply invading the myometrium

47
3. Weakly immunoreactive for human placental lactogen
4. Locally invasive, self-limited or cure by curettage

Extramammary Paget’ s disease

1. Vulva, scrotum, and perianal region
2. Pruritic, red, crusted, sharply demarcated, maplike area
3. Large tumor cells singly or in small clusters within the epidermis and appendages
4. Tumor cells: clear and finely granular cytoplasm stained with periodic
acid-Schiff, alcian blue or mucicarmine

23. Breast

Mammary Paget’
s disease
* Eczematous change of nipple
* Involvement of the epidermis of nipple by malignant cell (Paget cell) of ductal
carcinoma in situ or less infiltrating ductal carcinoma of breast
* Extramammary Paget’
s disease- scrotum, vulva:
- a variant of adenocarcinoma
- primary V.S. secondary
* Paget’
s disease of bone: benign

Risk factors of breast cancer

1. Genetic predisposition (family history) BRCA 1, BRCA 2
2. Age
3. Atypical ductal epithelial hyperplasia
4. Carcinoma of contralateral breast or endometrium
5. Radiation exposure
6. Geographic factors
7. Menstrual history
8. No history of pregnancy
9. Exogenous estrogen, obesity, high-fat diet, alcohol consumption, smoking

Breast carcinoma
Bilateral involvement of breast carcinoma- infiltrating lobular carcinoma

48
Comedocarcinoma: ductal carcinoma in situ
Mucinous carcinoma: better prognosis
Infiltrating ductal carcinoma (most common breast ca): ER, PR, arising from
terminal duct
Breast carcinoma after surgery or radiotherapy: angiosarcoma (most common)
Painless metastatic axillary lymph node

Fibroadenoma
1. Most commonest benign tumor in breast
2. Mainly in young women (<30 y/o)
3.Duct-like structures or elongated and thinned ductular structures surrounded by

connective tissue
4. Progressively enlarged during pregnancy

Phyllodes tumor
1. Any age, but the median age is 45 years
2. Fibroepithelial proliferation and stromal hypercellularity, epithelium covers
large, club-like projections which push into cystic spaces
3. Benign (low grade lesion): 90%
4. Malignant (high grade lesion): stromal overgrowth, anaplasia, high mitotic
activity
5. Majority: benign, 10% recur locally
6. Treatment: excision with wide margins

*Acute mastitis: staphylococcus

24. Endocrine

Prolactinoma
1. Most common type of pituitary adenoma
2. Hyperprolactinemia: amenorrhea, galactorrhea
3. Acidophilic cell in origin
4. EM: secretory granules in cytoplasm
5. Treatment by resection or bromocriptine, a dopamine receptor agonist
6. Damage of sella tunica

*Myxedema: hypothyroidism

49
Subacute (granulomatous) thyroiditis (de Quervain thyroiditis)
1. Most common between 30 and 50 years
2. More common in women
3. Viral infection or a postviral inflammatory process
4. Upper respiratory infection just before the onset of thyroiditis.
5. Granulomatous inflammation with multinucleated giant cells: like palpation
thyroiditis
6. Transient hyperthyroidism→ transient hypothyroidism →recovery

*Riedel’
s thyroiditis: fibrosis, as firm as thyroid carcinoma

Hashimoto thyroiditis
1. Most common cause of hypothyroidism in areas of the world where iodine levels
are sufficient.
2. Thyroid failure because of autoimmune destruction
3. Prevalent between 45 and 65 years
4. Clusters in families
5. Both cellular and humoral factors contribute to thyroid injury
6. Autoantibodies in Hashimoto thyroiditis
anti-thyroglobulin and thyroid peroxidase, anti-TSH antibody
7. Diffusely enlarged thyroid
extensive follicular destruction of lymphocytes, plasma cells, germinal centers
Hurthle cells with abundant eosinophilic and granular cytoplasm
8. Increased risk of development of B-cell lymphoma

*Nodular goiter: hemorrhage, fibrosis, calcification, and cystic change

Papillary carcinoma
1. Adult women
2. Previous ionizing radiation of the thyroid
3. Cervical lymph node metastasis
4. Better prognosis
5. Pathology
invasive growing
sclerosing stroma sometimes
papillary architecture
psammoma body
nuclear feature: ground glass, intranuclear inclusion, grooving

50
Thyroid follicular adenoma
1. A solitary, spherical, encapsulated lesion
2. Evaluation of the invasion of capsule and vascular invasion in distinction of
follicular adenoma from well-differentiated follicular carcinoma

Medullary carcinoma of thyroid

1. Neuroendocrine neoplasm derived from the parafollicular cell (C cell)
2. Elevation of calcitonin: hypocalcemia
3. 80% sporadic, 20% in the setting of MEN syndrome II A or IIB
4. Mutation of RET protooncogene
5. Amyloid deposits

Primary hyperparathyroidism
1. Frequency of the various parathyroid lesions underlying the hyperfunction:
(a) adenoma: 75-80% (most common)
hypercalcemia, capsulated tumor, chief cell predominant
(b) primary hyperplasia: 10 to 15 %
(c) parathyroid carcinoma: less than 5%
2. History of irradiation to the head and neck in some patients
3. 95% sporadic, some cases with MEN type I

Secondary hyperparathyroidism
1. Associated with a chronic depression in the serum calcium level because low
serum calcium leads to compensatory overactivity of parathyroid
2. Renal failure: the most common cause of secondary hyperparathyroidism.
3. Parathyroid glands in secondary hyperparathyroidism: hyperplasia of all four
glands

*Bone lesions of hyperparathyroidism: brown tumor, osteitis fibrosa cystica

Cause of Cushing syndrome

1. ACTH-producing pituitary adenoma: Cushing disease
2. Bilateral adrenocortical hyperplasia
3. Adrenocortical adenoma
4. Adrenocortical carcinoma
5. Small cell carcinoma of lung

Conn’
ssyndrome

51
1. Primary hyperaldosteronism
2. 80% by aldosterone-producing adrenocortical adenoma
3. Hypokalemia, hypernatremia, hypertension

Multiple endocrine neoplasia syndromes

1. MEN I
(a) 3 ”P” :pa rathyroid,pa ncr e
as,a
ndpituit
ary
(b) more often by age 40 to 50
(c) pancreas: islet cell tumor
(d) pituitary: prolactinoma
(e) parathyroid : adenoma or hyperplasia
(f) genetic defects in chromosome 11
2. MEN IIA
(a) pheochromocytoma, medullary carcinoma, and parathyroid hyperplasia
(b) mutation of RET gene
3. MEN IIB (or MEN III)
(a) mutation of RET genes
(b) pheochromocytoma, medullary carcinoma,. neuroma or ganglioneuroma

25. Skin

HPV infection of skin

* Verruca vulgaris
* Condyloma acuminatum
* Bowenoid papulosis
* Koilocyte- perinuclear halo

Molluscum contagiosum
* Cup-shaped ingrowth of hyperplastic epidermis
* Intracytoplasmic inclusion bodies (Molluscum bodies)

Halo nevus
Host immune response: lymphocyte infiltration surrounding nevus cells

Vitiligo

52
Partial or complete loss of pigment-producing melanocytes within the epidermis
hypopigmented skin

Psoriasis- arthritis

Bullous disease of skin

I. Pemphigus vulgaris
1. Suprabasal vesicle
2. Eosinophils
3. Immunofluorescent IgG autoantibody to intercellular cement substances

II. Bullous pemphigoid

1. Subepidermal blister
2. Eosinophils
3. Ig and complement autoantibody deposition in basement membrane

Predisposing factors of squamous cell carcinoma in skin

UV light exposure, industrial carcinogens (tar and oil), chronic ulcer & fistula,
draining osteomyelitis, old burn scar, ingestion of arsenicals, ionizing radiation,
tobacco and betel nut chewing

*Bowen’ s disease: carcinoma in situ

*Squamous cell carcinoma: chronic ulcer, fistula
*Basal cell carcinoma: Rodent ulcer
*Urticaria pigmentosa: mast cell

Merkel cell carcinoma

* Skin primary malignancy
* Derived from Merkel cell of epidermis- neural crest
* Small round cell with neuroendocrine type granule

*Langerhans cell: epidermal dendritic cell

26. Bone, joint and soft tissue

Achondroplasia
Growth plate defect causes dwarfism

53
Osteogenesis imperfecta
* Synthetic defect of type I collagen
* Mutation in the genes - code for 1, 2 chains of collagen molecule

Osteitis fibrosa cystica (von Re

ckl
inghaus
en’
sdisease of bone)
* Hyperparathyroidism
* Fracture
* X-ray: a) cortical bone resorption
b) cancellous bone - dissecting osteitis, brown tumor

Osteopetrosis (marble bone disease)

1. Hereditary disease of osteoclast dysfunction
diffuse & symmetrical skeletal sclerosis
brittle & fracture
2. Fracture., anemia, hydrocephaly
3. Carbonic anhydrase II deficiency
4. Treatment: bone marrow transplantation
5. Erlenme ye r
’s flask deformity: bulbous end of long bone

*Brodie abscess: pyogenic osteomyelitis with intraosseous abscess

Osteosarcoma (osteogenic sarcoma)

1. Most common primary bone cancer
2. <20 y/o (75%, primary form); elder (25%, secondary form)
3. Associated with: –Pa g et
’sdise ase,bonei nfarct
,irr
a diat
ion
–osteochondroma, enchondroma, fibrous dysplasia
4. Location: long bone metaphysis (knee 60%), distal femur
5. X-ray: mixed lytic and blastic mass with permeative margins
* Codma n’ st
riang l
e,sunbur st
6. Micro: osteoid & chondroid
7. Metastasis: lung (most common)

*Chondroblastoma: epiphysis

Fibrous dysplasia
* Three patterns:
1) monostotic 2) polyostotic 3) polyostotic + skin lesion + endocrine lesion
* Monostotic type

54
 1. 70% , M=F, early adolescence
2. sites: ribs, femur, tibia, jaw bones, calvarium, humerus
3. bone lesion - local, developmental arrest
4. micro: curvilinear woven bone (lack osteoblastic rimming)
proliferation of fibroblast
* Polyostotic type
1. 3% + café-au-lait skin + endocrine lesion- McCune-Albright syndrome
2. malignant change (osteosarcoma)

*Lipoma: most common soft tissue tumor

Ewing sarcoma (primitive neuroectodermal tumor)

1. Primary malignant small round cell tumor of bone with neural phenotype
2. Second most common bone sarcoma in children
3. 10-15 y/o, diaphysis of femur and pelvis
4. t(11;22)(q24;q12), (EWS-FLI1) fused gene- oncogene
5. Located at medullary cavity invading cortex and periosteum
6. Small blue round cells with scanty cytoplasm
Homer-Wright rosette
necrosis and hemorrhage
7. Onion-skin appearance on x-ray
8. Response to radiotherapy

Osteoarthritis (OA)
1. Degenerative disease, the most common joint disease
2. Clone of proliferative chondrocyte
3. Superficial layer of cartilage is degraded, fibrillation
4. Granular articular surface -> polished ivory (bone eburnation)
5. Subchondral sclerotic bone
6. Subchondral cyst
7. Osteophyte formation

*Gouty tophus: skin, soft tissue, joint, kidney

Ankylosing spondyloarthritis
1. Joint disease of axial joints esp. sacroiliac joint
2. Male, adolescence
3. HLA-B27 (+), 90%

55
4. Severe spinal immobility, low back pain

Ganglion
1. Cystic or myxoid degeneration of tendon sheath
2. Firm, translucent cyst
3. Common in wrists

Rhabdomyosarcoma
1. Most common soft tissue sarcoma in child & adolescence
2. First two decades of life
3. Head & neck, genitourinary tract, retroperitoneum
4. Rhabdoblast
5. Tadpole (strap) cell

Embryonal RMS
1. Most common variant
2. Head & neck
3. Sarcoma botryoides: vagina grape-like tumor in girl
* cambium layer: hypercellular submucosal layer

Synovial sarcoma
1. 3rd to 5th decades
2. Large joint: knee & ankle- extraarticular location
Parapharyngeal region
Abdominal wall
3. Not origin in synovium
4. Biphasic pattern:
epithelial-like cell: solid cord or gland
spindle cell: in fascicle
5. Cytogenetics: t (X ; 18)

Spinal muscular atrophy

1. Autosomal-recessive motor neuron diseases affecting anterior horn cells in the
spinal cord and cranial nerve motor neurons
2. Homozygous deletions of SMN1 (survival motor neuron gene)

X-linked muscular dystrophy- Duchenne muscular dystrophy

1. Most severe form

56
2. Dystrophin gene (Xp21) mutation- X chromosome
3. Boy, 5-10 y/o
pelvic & shoulder girdle
4. Pseudohypertrophy of skeletal muscle
5. Heart failure & arrhythmia
mental retardation
6. Degeneration, necrosis, phagocytosis of muscle fiber

27. Nervous system

Alzheimer type II astrocyte

1. Gray matter astrocyte with a large nucleus, pale-staining central chromatin, an
intranuclear glycogen droplet
2. Hyperammonemia due to chronic liver disease, Wilson disease, or hereditary
metabolic disorders of the urea cycle.
3. Unrelated to Alzheimer disease

*Sclerosis: gliosis (increased astrocytes)

Segmental demyelination
* Dysfunction of Schwann cells or damage to myelin sheath
* No primary abnormality of axon
* Muscular atrophy

Acute disseminated encephalomyelitis (ADEM)

Demyelinating disease that follows either a viral infection

Hydrocephalus
* CSF --- decrease absorption/overproduction --- tumors of choroids plexus
* Hydrocephalus ex vacuo: brain atrophy

Concussion of brain
* Alteration of consciousness
* Transitional neurological dysfunction
* No structure damage of brain

Contercoup contusion

57
* Most common location- frontal lobes along the orbital gyri
* Countercoup-brain surface diametrically opposite to it
* Gross:
Acute: hemorrhage and tissue disruption
Old: depressed, retracted, yellowish brown patches involving the crests of gyri
most commonly located at the sites of contrecoup lesions (inferior frontal
cortex, temporal and occipital poles).

Epidural hematoma
* Middle meningeal artery
* Skull fracture, esp. temporal bone

Subarachnoid hemorrhage (SAH)

1. Berry aneurysm (saccular, congenital)- most common
2. Atherosclerotic (fusiform, basilar artery) aneurysm
3. Mycotic aneurysm
4. Traumatic aneurysm

Cerebrovascular hemorrhage
Charcot-Bouchard microaneurysm in basal ganglion: chronic hypertension

Herniation
1. Subfalcine (cingulated gyrus)
2. Transtentorial (uncal, mesial temporal)- duret brainstem hemorrhage
3. Tonsillar- brain stem compression, vital respiratory center in medulla oblongata

Transmissible spongiform encephalopathies (Prion disease)

* Creutzfeldt-Jakob disease (CJD), Kuru in humans, Mad cow disease
1. neurodegenerative and infectious disease
2. spongiform change, intracellular vacuoles in neurons, progressive dementia
3. sporadic and familiar form
* PrP --- 30KD normal cellular protein present in neuron
* Pathology:
1. spongiform transformation of the cerebral cortex and deep gray matter
2. uneven formation of small empty microscopic vacuoles of varying sizes within
neutrophil and perikaryon of neurons
3. severe neuronal loss
4. gliosis

58
 5. cystic-like lesion

Multiple sclerosis
1. Neurological deficits attributable to white matter demyelination
2. Surface of brain stem or spinal cord reveals multiple well-circumscribed, somewhat
depressed, glassy, gray-tan, irregular shape plaques
3. Micro:
sharply defined, active plaque- myelin breakdown with abundant macrophages
containing lipid-rich
PAS-positive debris
lymphocytes and monocytes perivascular cuffs
relative preservation of axons and depletion of oligodendrocytes
4. Remitting and relapse

Progressive multifocal leukoencephalopathy

1. Polymavirus (JC virus)
2. Infect oligodendrocyte
3. Demyelination
4. Immunosuppressed
5. Morphology: patches of irregular, ill-defined destruction of the white matter
Micro: a patch of demyelination in the center of which are scattered lipid-laden
macrophages and a reduced number of axons.

Idiopathic Parkinson disease

1. Progressive parkinsonism, no toxic or other known underlying etiology
2. Striatal dopamine deficiency, L-dopa
3. Pallor of the substantia nigra and locus ceruleus
4. Loss of melanotic catecholaminergic neurons: Lewy body

Alzheimer disease
* Dementia, insidious impairment of higher intellectual function, alteration in mood
and behavior, memory loss, aphasia, in 5-10 years profound disabled, mute and
immobile
* Pathology
cortical atrophy (gross)
neurofibrillary tangles
senile (neuritic) plaque
amyloid angiopathy,

59
 amyloid

Huntington disease
1. Inherited autosomal disease, progressive movement disorder and dementia
2. 4p16.3 gene
3. Neuronal degeneration
striking atrophy of caudate nuclei, putaman

Meningioma
1. Predominantly benign tumor of adult (female > male), from meningothelial cells of
the arachnoid, well-defined dural base, whorled clusters of cells with round or
ovoid nuclei and indistinct cell border, psammoma bodies
2. Skull bone erosion
3. Progressive during pregnancy
3. Malignant: extremely rare, mitoses, necrosis, infiltration of brain

*Pilocytic astrocytoma: childhood, cerebellum

Glioblastoma multiforme
1. Pseudopalisading necrosis, vascular endothelial proliferation- glomeruloid body
2. Progressed from a low grade to high grade
3. Poor prognosis

Oligodendroglioma
1. Well-circumscribed gelatinous gray masses
2. Spherical nuclei containing fine chromatin surrounded by a clear halo of cytoplasm
3. Delicate network of anastomosing capillaries
4. Calcification

*Cerebellar hemangioblastoma- polycythemia, von Hippel-Lindau disease

*CSF spreading of brain tumor: medulloblastoma, astrocytoma (esp. GBM)

Plexiform neurofibroma
1. Along the extent of a nerve, often multiple
2. Neurofibromatosis type 1
3. Mixture of Schwann cells, perineural cells & fibroblasts in myxoid background
4. Malignant transformation

60
Craniopharyngioma
1. Supracella
2. Squamous epithelium and lamellar keratin

61