醫師國考複習- 病理學
2003.1.11.
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Cellular pathology
Apoptosis
Definition and causes
A 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
1. Cell shrinkage: small in cell size, dense cytoplasm
2. Chromatin condensation: aggregates peripherally, nucleus breaks up
3. Formation of cytoplasmic bleb and membrane-bound apoptotic bodies
4. Phagocytosis of apoptotic cells or bodies by adjacent healthy cell
(parenchymal cells or macrophages)
Specific examples of apoptosis
Signaling by tumor necrosis factor (TNF) family of receptors
Fas-Fas ligand-mediated apoptosis
TNF-induced apoptosis
Cytotoxic T-lymphocyte-stimulated apoptosis
Reversible & irreversible cell injury
Reversible cell injury
Fatty change (foamy cell, xanthoma cell): 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
Iron deposition: liver: micronodular cirrhosis
pancreas: DM
skin: pigmentation; heart, endocrine organ
Anemia due to ineffective erythropoiesis (e.g. thalassemia),
transfusion, liver disease, increased oral take
Morphology: deposition of hemosiderin, stain blue with the Prussian blue stain
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 in infants
Necrosis
1. Coagulative necrosis
most common, denaturation is the primary pattern
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 focal bacterial or sometimes fungal infections
Hypoxic death in the brain (brain infarct)
3. Caseous necrosis: a special form of coagulative necrosis
tuberculous infection; cheesy, white gross appearance, structureless amorphous
granular debris, completely obliterated tissue architecture
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) The columnar epithelium of the respiratory tract is replaced by squamous
cells in heavy smokers
(2) The metaplastic epithelium is often the site of cancer transformation
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Inflammation
Granulomatous inflammation
1. a form of chronic inflammation
2. infiltration of epithelioid histocytes, multinucleated giant cells, and lymphocytes
eg. tuberculosis, sarcoidosis, Crohn’s disease, cat scratch disease,
lymphogranuloma venereum, suture granuloma
TB: mycobacterium tuberculosis
granuloma, epithelioid histocyte & Langhan’s giant cell, central caseous
necrosis, acid-fast bacilli
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Repair
Granulation tissue
formation of new small blood vessels (angiogenesis) and the proliferation
of fibroblasts during tissue repair process
Keloid
excessive formation of the fibrous scar in wound healing
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Hemodynamic disorders
Edema
Definition: an excess of fluid in the interstitial spaces and/or the body cavities.
Mechanisms of edema:
1. Increased intravascular (hydrostatic) pressure - impaired venous return
2. Reduced plasma osmotic pressure (hypoproteinemia) - hypoalbuminemia
(ex. nephrotic syndrome, protein-losing enteropathy, malnutrition, cirrhosis)
3. Increased interstitial oncotic pressure - sodium retention
(ex. renal failure, congestive heart failure)
4. Increased vascular permeability- vasculitis
5. Lymphatic obstruction - inflammatory, neoplastic, postsurgical, postirradiation
Forms of dema
A. transudate - low protein content (SG < 1.012)
1. increased hydrostatic pressure
2. reduced plasma oncotic pressure
B. exudate - high protein content (SG > 1.020) with numerous inflammatory cells
*increased vascular permeability
Types of edema
A. localized
1. tissue or organ - brain, periorbital, pretibial
2. space or cavity - ascites, hydrothorax
B. generalized - anasarca
common site: subcutaneous tissues, lungs, brain
*congestive heart disease
*nephrotic syndrome
Ex: pitting edema
pulmonary edema
edema of the brain
Amniotic fluid embolism
 tear in placental membrane and rupture of uterine vein with amniotic fluid infusion
 mortality rate >80%
 embolism composed of squames
Shock
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
Morphologic change of shock: *failure of multiple organ systems

Genetic disorders
Marfan syndrome
1. disorder associated with defect in structural protein
2. disorder of connective tissue
Molecular basis of Marfan syndrome
 Marfan gene (fibrillin gene)
point mutation on chromosome 15q21.1
defect in synthesis of fibrillin
defect in microfibrillary network, elastic fiber
esp. ligament, aorta, ciliary zonule
Lysosomal storage disease
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Tay-Sachs disease
Niemann-Pick disease
Gaucher disease
Glycogen storage disease
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
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Diseases of immunity
MHC
Structures and function of histocompatibility antigens
human leukocyte antigen (HLA)
(a) function of class I HLA: presentation to CD8+ T cells
(b) function of class II HLA: presentation to CD4+ Tcells
HLA and disease association:
(a) inflammatory disease: HLA-B27 and ankylosing spondylosis
(b) inherited disease: HLA-BW47 and 21-hydroxylase deficiency
(c) autoimmune disease: HLA-DR4 and rheumatoid arthritis
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
autoimmune hemolytic anemia
pemphigus vulgaris
drug reaction
antibody-mediated cellular dysfunction
myasthenia gravis
Graves’ disease
Type IV hypertensitivity (delayed type, cell-mediated)
initiated by specifically sensitized T cells.
contact dermatitis
tuberculosis
tuberculoid leprosy- lepromin test
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
3 kidney
(I) WHO classification of lupus nephritis
class I: normal
class II: mesangial lupus glomerulonephritis
class III: focal proliferative glomerulonephritis
class IV: diffuse prolierative glomerulonephritis
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
6. central nervous system
7. pericarditis and other serosal cavity involvement
8. cardiovascular system: Libman-Sacks endocarditis
9. spleen, lung, and other organs
Sjogren syndrome
(a) dry eye (keratoconjunctivitis sicca) and dry mouth (xerostomia)
(b) immunological destruction of lacrimal and salivary gland
(c) anti SS-A(Ro) and anti SS-B(La)
(d) periductal and perivascular lymphocytic infiltration in the lacrimal and
salivary gland
(e) higher risk of developing lymphoma
Transplant rejection
(a) mechanism involved in rejection
(I) T cell-mediated reaction
(II) antibody-mediated reaction: hyperacute rejection
(b) rejection reaction: hyperacute, acute, and chronic
X-linked agammaglobulinemia of Bruton (Bruton disease)
(I) failure of B-cell precursor to differentiate to B cell
(II) apparent until 6 months of age after materal immunoglobulins are depleted.
(III) predispose to infection of Haemophilus influenza, Streptococcus pneumoniae, or
Staphylococcus aureus, Giardia lamblia or enterovirus.
(IV) B cells are absent or remarkably decreased in the blood
decreased serum level of all classes of immunoglobulins.
Aacquired immunodeficiency syndrome (AIDS)
(a) 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
(b) more than 90% of pediatric population with AIDS result from transmission
of the virus from mother to child.
(c) three major routes of transmission
(I) sexual contact
(II) parenteral inoculation
(III) passage of the virus from infected mother to newborn
(d) etiology
(I) HIV-HIV1 and HIV2: retrovirus
(II) HIV-1 is the most common type associated with AIDS in USA
(e) pathogenesis
(I) HIV target: immune system and central nervous system
(II) infection and a severe loss of CD4+ T cell
impairment in the function of surviving helper T cell
Clinical features of the crisis phase (AIDS)
(I) opportunistic infection
(i) Pneumocytis carinii pneumonia
(ii) candidiasis
(iii) cytomegalovirus infection
(iv) atypical mycobacterial infection
(v) tuberculosis
(vi) cryptococcsis
(vii) Toxoplasma gondii infection
(viii) progressive multifocal leukoencephalopathy caused by JC virus
(ix) Herpes simplex virus infection
(II) neoplasm: Kaposi sarcoma (related with human herpes virus type 8)
non-Hodgkin’s lymphoma
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Neoplasia
Cancer suppressor genes
Rb gene (13q14)
‘Two hit’ hypothesis of oncogenes
P53 gene (17p13.1)
BRCA-1 (17q12-21) and BRCA-2 (13q12-13)
80% of familial cases of breast carcinoma with BRCA-1 and BRCA-2
Viral carcinogeneisis
(1) DNA oncogeic virus
(a) Human papilloma virus (HPV)
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
Choristoma an ectopic rest of normal tissue
Hamartoma disorganized but mature specialized cells or tissue
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Infectious diseases
Amebiasis
1. Entamoeba histolytica- protozoa
2. infectious form: cyst
ameboid form: trophozoite
3. dysentery
* diarrhea with abdominal cramping pain & tenesmus
* loose stool containing blood, pus, and mucus
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
primary syphilis
3 weeks
chancre
secondary syphilis
6-8 weeks
skin rash
condyloma lata
generalized lymphadenopathy
tertiary syphilis
10-15 years
gumma
cardiovascular system: syphilic aortitis
neurosyphilis: tabes dorsalis, charcot joint, generalized paresis
Varicella-zoster infection
1. Varicella-zoster virus
2. air-borne
3. chickenpox / shingles
Infectious mononucleosis- Epstein-Barr virus infection
1. benign self-limited lymphoproliferative disease
2. late adolescent & young adult
3. kissing disease- close body contact
4. epithelium: 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
Legionnaires' disease
1. L. pneumophila, G(-), silver-stained
* cooling system of buildings
2. Legionnaires' pneumonia: smoker & immunocompromized host
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 (cryptococcoma) with yeasts in the macrophage &
multinucleated giant cell
5. meningoencephalitis
immunocompromised: soap-bubble lesion
gelatinous mass in meninges or small cyst in gray matter
Leprosy
1. mycobacterium leprae, acid-fast (+)
2. air-borne
3. slow & progressive chronic disease involving skin and peripheral nerve
4. lepromin test: delayed type hypersensitivity
5. A. tuberculoid leprosy
nerve destruction +++
claw hand
bacilli –
lepromin test +
B. lepromatous leprosy
Leonine face
Lepra cells: lipid-laden macrophages stuffed with bacilli
Lepromin test – (immune response impairment)
 Environmental and nutritional pathology
Vitamine D deficiency: richet and osteomalacia
Radiation injury
Cellular mechanism of radiation injury: acute effect, fibrosis, carcinogenesis
Oral contraceptives
venous thrombosis; myocardial infarction; breast cancer; endometrial cancer;
cervical cancer; ovarian cancer; hepatic adenoma; cholestasis, hypertension and
gallbladder disease
 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
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
5. triphasic combination
epithelial differentiation
stromal differentiation- skeletal muscle
blestema
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Blood vessel
Atherosclerosis
hyperlipidemia is the strongest risk factor for AS in patients under age 45
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
Kawasaki syndrome
．= mucocutaneous lymph node syndrome
．arteritis: large, medium-sized, & small arteries, esp. the coronary artery, skin, ocular
and oral mucosa
．young children and infants (80%, < 4 yrs-old)
．S/Sx:
fever
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. S/Sx:
weakening of pulses in the upper extremities (pulseless disease)
fibrous thickening of the aortic arch
hypertension
4. etiology: unknown
5. microscopically:
early change: adventitial mononuclear infiltration with perivascular cuffing of the
vasa vasorum
later change: intense mononuclear infiltration of the media and sometimes with
granulomatous change
Polyarteritis nodosa
．vessel: medium-sized and small arteries
．morphologic feature: panmural acute necrotizing arteritis with fibrinoid necrosis,
neutrophil and eosinophil infiltration and extension into adventitia
*sharply segmental, nodularity
*30% HBV antigen (+), often with p-ANCA (+)
Microscopic polyangitis (microscopic polyarteritis)
．arterioles, capillaries, and venules => necrotizing glomerulonephritis and pulmonary
capillaritis
．microscopically: leukocytoclastic angiitis (hypersensitivity angiitis)
．p-ANCA (+) in 70% of patients
．few or no demonstrable immune deposits in this type of vasculitis (pauci-immune
injury)
Aneurysm
．cause:
1. congenital
2. infectious
3. traumatic
4. systemic disease
．true aneurysm:
- all the layers of the arterial wall contribute to the dilatation
- e.g. atherosclerotic (abdominal aorta), syphilitic
two principal causes of aortic aneurysm:
1) atherosclerosis 2) cystic medial degeneration
．false aneurysm:
- pseudo-aneurysm
- only a fibrous sac exists
- vascular wall have a leak
- aneurysmal sac is composed of outer arterial layer or periarterial tissue
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
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Heart
Right-sided heart failure
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
．causes: systemic venous congestion
．hepatomegaly, nutmeg liver
．peripheral edema - ankle, sacrum
Morphologic change of right-sided heart failure
1. ventricle dilatation and often 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
subpulmonary stenosis (combined with pulmonary valve stenosis or atresia)
overriding aorta
RVH
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 the interventricular septum
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)
3.
4.
- complete coagulative necrosis of myofiber, heavy PMNs with early
fragmentation of PMN nuclei (24-72 hrs)
- central pallor with hyperemic border (4-7 days)
- macrophage appear, phagocytosis of necrotic fibers; granulation tissue
(fibroblast & capillary) at edge of infarct; PMNs reach a peak on days 5-6
- maximally yellow, soft, shrunken; purple border (10 days)
- well-developed phagocytosis, prominent granulation tissue in the peripheral
areas of infarct
5.
6.
- by the end of the 4th week - necrotic myocardium resorbed
- 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
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. cardiomyopathies
2. myocarditis and other infiltrative processes
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
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
2. systemic emboli -> multiple infarcts in brain, kidney, heart and abscess
Chronic rheumatic heart disease
irreversible deformity of cardiac valve
left side valve more than right side
scarring of valve leaflet:
Chronic rheumatic mitral valvulitis
1. more frequently in female
2. stenosis: valve leaflet and chordae tendinae
“fish-mouth deformity”
3. 10 days to 6 weeks after an episode of pharyngitis by group A streptococcus
4. Pathology: Aschoff body
Tumors of the Heart
1) adult: myxoma - left atrium
rhabdomyosarcoma
2) child: rhabdomyoma
- tuberous sclerosis
Cardiac transplantation
complications:
a) infection;
b) malignancy (e.g. lymphoma);
c) graft vascular disease (or graft arteriosclerosis);
e) rejection: interstitial lymphocyte infiltration
monitored by endomyocardial biopsy
d) silent MI
 RBC & platelets
CD34- marker for hematopoietic precursor stem cells in BM
Thalassemia
1. hereditary hemoglobinopathy: Hb A(α2β2)
2. β-thalassemia
deficient synthesis ofβchain- hypochromia
relative excess ofαchain
3. α-thalassemia
deficient synthesis ofαchain
relative excess ofβ, γchain
4. ineffective erythropoiesis / hemolysis
Megaloblastic anemia
impaired DNA synthesis,
impaired maturation & differentiation in erythroid series
pernicious anemia
Vit. B12 deficiency
folate deficiency anemia
Hemophilia A (Factor VIII deficiency)
1. most common hereditary disease with severe bleeding
2. reduction in amount or activity of factor VIII
3. X-linked recessive (70%)
4. massive bleeding after trauma
spontaneous hemorrhage- hemarthroses
5. BT: normal PTT: prolonged
Disseminated intravascular coagulation (DIC)
1. acute, subacute, or chronic thrombohemorrhagic disorder
2. thrombotic diathesis
* activation of clotting system
3. hemorrhagic diathesis
consumption coagulopathy
* activation of fibrinolytic system
4. fibrin microthrombi
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WBC
Hodgkin disease
1. a single node or chain of nodes, spreading to anatomically contiguous nodes
2. diagnostic neoplastic cell: Reed-Sternberg (RS) cell
3. B symptom: fever, night sweats, body weight loss (>10% of normal body weight)
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
Burkitt’s 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)
Lethal medline granuloma: T/NK cell lymphoma in nasal cavity
Multiple myeloma
1. 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
2. combined with pathologic fracture
3. increased plasma cells in bone marrow
plasmablast, multinucleated form
Russell body, Dutcher body
4. peak age: 50-60 y/o
5. production of excessive Ig
hypercalcemia, recurrent infection
renal failure- Bence Jones (light chain) proteinuria
amyloidosis of AL type
6. electrophoresis analysis: increased monoclonal Ig in the blood or Bence Jones
(light chain) protein in the urine
Waldenstrom macroglobulinemia
1. serum hyperviscosity caused by high levels of IgM
2. lymphoplasmacytic lymphoma or rare myeloma that secrets IgM
Langerhans cell histiocytosis
1. clonal proliferation of antigen-presenting dentritic cells with Birbeck granules in
the cytoplasms by EM
2. A. Letterer-Siwe disease
acute disseminated form- <2 y/o
cutaneous lesion, hepatosplenomegaly, lymphadenopathy, bone involvement
fatal course
B. Eosinophilic granuloma
unifocal/multifocal
admixed with eosinophils
bone destruction, skin, lung
C. Hand-Schuller-Christian triad: skull bone defect, diabetes insipidus,
exophthalmos
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
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Lung
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
B. bronchiolitis obliterans
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. progression to end-stage honeycomb lung: cystic spaces with thick fibrous septa
respiratory failure
Adult 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
Inhaled irritants
Chemical injury
Hematologic conditions- blood transfusion, DIC
Pathology of diffuse alveolar damage
hyaline membrane formation
fibrin exudate
necrotic debris of alveolar epithelium
Emphysema
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 atelectasis, and spontaneous pneumothorax
4. irregular emphysema
A. irregular involvement of acini
B. associated with scarring
Primary atypical pneumonia (viral and mycoplasmal pneumonia)
1. acute febrile respiratory infection in the pulmonary interstitium- interstitial
pneumonitis
Asbestos-related disease
1. localized pleural fibrous plaque
2. pleural effusion
3. asbestosis
4. bronchogenic carcinoma
5. mesothelioma
Adenocarcinoma of lung
1. increased incidence in recent years
2. the 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
* intermediate cell type: larger polygonal or spindle cell
2. derived from neuroendocrine cell in bronchial epithelium
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
Paraneoplastic syndrome in bronchogenic carcinoma
1. ADH: hyponatremia
2. ACTH: Cushing syndrome- small cell ca.
3. parathyroid hormone-related peptide: hypercalcemia- squamous cell ca.
4. calcitonin: hypocalcemia
5. gonadotropin: gynecomastia
Spontaneous pneumothorax
1. young adult
2. rupture of small, peripheral, apical subpleural bleb
3. subside spontaneously
4. recurrent
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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, 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
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GI tract
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
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 → UGI bleeding
Helicobacter pylori infection
1. most important etiologic association with chronic gastritis
2. G(-) curvilinear rod-like bacilli
3. antral / antral & body mucosa
4. bacilli in superficial mucous layer and folveola by H&E, silver stain, Giemsa stain
5. absence in area of intestinal metaplasia
6. high risk to develop peptic ulcer, gastric carcinoma, lymphoma
Peptic ulcer
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
6. Meckel diverticulum
H. pylori & peptic ulcer
1. 100 % of duodenal ulcer associated with H. pylori infection
70 % of gastric ulcer associated with H. pylori infection
Pathology of peptic ulcer
1. duodenal ulcer: duodenum, 1st portion, anterior wall
gastric ulcer: antrum and angle of lesser curvature side
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
Hirschsprung's disease (congenital aganglionic megacolon)
neonatal period
failure to pass meconium
bstructive constipation
abdominal distension
arrest of migration of neural crest to anus
aganglionosis
functional obstruction with pre-obstructive dilatation
megacolon- dilatation & hypertrophy proximal to aganglionic segment
Meckel's diverticulum
1. incidence: 2 %
2. persistence of vitelline duct
3. terminal ileum- 30 cm. proximal to ileocecal valve, antimesenteric border
4. heterotopic mucosa: gastric mucosa, pancreatic tissue
5. complication: ulcer, bleeding, rupture
Angiodysplasia in intestine
1. tortuous dilation of submucosal and mucosal blood vessels
2. cecum and right colon
3. intermittent lower intestinal bleeding
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
mushrooming cloud- purulent exudate of crypt
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. S/S: malabsorption, polyarthritis
lymphadenopathy
CNS dysfunction
5. foamy macrophage: cytoplasmic PAS (+) granule, rod-shaped bacilli by EM
6. bacilli-laden macrophage in synovial membrane & brain
Colonic polyp
Nonneoplastic polyp
Neoplastic polyp (adenomatous polyp)
hyperplastic polyp
Juvenile polyp
Peutz-Jegher polyp
tubular adenoma
tubulovillous adenoma
villous adenoma
Hyperplastic polyp of colon
1. < 5 mm, multiple＞single
2. any age, esp. 6th & 7th decades
3. nipple-like, hemispheric, smooth protrusion
4. proliferive serrated epithelium, infoldings of crowding epithelium
increased goblet cells
Familial adenomatous polyposis
1. autosomal dominant
2. progression to adenocarcinoma (100%)
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
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

Liver
Dubin-Johnson syndrome
autosomal recessive, impaired transport of conjugated bilirubin from the
hepatocytes to bile canaliculi
chronic or intermittent conjugated hyperbilirubinemia
"black liver", coarse iron-free dark brown granules in the hepatocytes
Viral hepatitis: hepatitis virus A, B, C, D, E, G, etc.
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
Chronic hepatitis: mild to severe
#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
Wilson disease (hepatolenticular degeneration)
autosomal recessive (ATP7B on Chromosome 13)
defect in biliary excretion of copper
morphology:
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↑
treatment: long-term chelators (d-penicillamine)
Alcoholic liver cirrhosis
final and irreversible
10-15% of alcoholics develop cirrhosis
micronodular initially
Hepatocellualr carcinoma
Etiology: HBV (200-fold increased risk), HCV, etc.
Pathogenesis:
repeated cycles of cell death and regeneration
viral DNA integrated into the host genome and induce instability

Pancreas
Acute pancreatitis
1. associated with biliary tree disease and alcoholism
2. initiated
A. pancreatic duct obstruction (biliary stone)
accumulation of enzyme-riched fluid, fat necrosis, edema
B. primary acinar cell injury- drug, trauma, ischemia, virus
Chronic pancreatitis
repeated bouts of mild to moderate pancreatic inflammation
continued loss of pancreatic parenchyma and replaced by fibrous tissue
alcoholism, hypercalcemia and hyperlipoproteinemia
1. interstitial fibrosis after previous episodes of acute pancreatitis
2. pseudocyst
develop after inflammation and necrosis of the pancreas
Diabetes Mellitus
chronic disorder of carbohydrate, fat and protein metabolism
defective or deficient insulin secretion response
impairment glucose metabolism- hyperglycemia
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-cell mass)
autoimmunity (insulitis)
2. Type 2 diabetes
Non-insulin-dependent DM (NIDDM) (80-90%)
adult onset
deranged β-cell secretion of insulin
decreased response of peripheral tissue to respond to insulin (insulin resistance)
* Maturity-onset diabetes of the young (MODY)
genetic (AD) defects of β-cell function (5%)
amyloid deposition
 Kidney
Rapidly progressive (crescentic) glomerulonephritis (RPGN)
＃glomerular destruction, fibrinoid necrosis of the capillary tufts
epithelial cell proliferation→crescent
grave prognosis
＃classification of idiopathic RPGN
1. anti-GBM Ab mediated: 2-20%
2. immune complex mediated: 15-50%
3. pauci-immune: 15-50%
anti-neutrophil cytoplasmic Ab (ANCA) mediated
including Wegener’s granulomatosis
＃Goodpasture’s syndrome
lung hemorrhage (hemoptysis): alveolar destruction
crescentic GN: anti-GBM Ab mediated
IgA nephropathy (Berger’s disease)
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
Membranous glomerulonephritis (MGN)
* the most common cause of NS in adults
* 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
Hypertensive nephropathy
1. benign nephrosclerosis
* arterioles: hyaline arteriolosclerosis
glomeruli: collapse, sclerosis, or ischemic obsolescence
2. malignant nephrosclerosis
* malignant hypertension
diastolic pressure＞130 mm Hg, papilledema retinopathy,
encephalopathy, renal failure
* arterioles: necrotizing arteriolitis (fibrinoid necrosis)
hyperplastic arteriolitis (“onion-skin” appearance)
glomeruli: necrotizing glomerulitis with hyaline microthrombi
Acute pyelonephritis
* fever, chillness, pyuria, costovertebral angle pain
* suppurative inflammation, abscess
* complication:
papillary necrosis (mainly in DM patients): acute renal failure
pyonephrosis
Acute tubular necrosis (ATN)
* the 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

Lower urinary tract
Pyelonephritis and urinary tract infection (UTI)
* modes of infection:
1) hematogenous infection
2) ascending infection
the 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

Male genital tract
Seminoma
1. most common germ cell tumor in testis
2. 4th decades
3. secretion of placental alkaline phosphatase (PAP)
 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
0
I
Definition
Carcinoma in situ (preinvasive carcinoma)
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
IB2
Clinically visible lesion 4.0 cm or less in greatest dimension
Clinically visible lesion more than 4.0 cm in greatest dimension
Tumor invades beyond the uterus but not to pelvic wall or to lower
third of the vagina
IIA
IIB
Without parametrial invasion
With parametrial invasion
Tumor extends to the pelvic wall and/or causes hydronephrosis or
nonfunctioning kidney
IIIA
IIIB
Tumor involves lower third of vagina with no extension to pelvic wall
Tumor extends to pelvic wall and/or causes hydronephrosis or
nonfunctioning kidney
II
III
IVA
Tumor invades mucosa of bladder or rectum and/or extends beyond
true pelvis
IV
Distant metastasis
Adenomyosis
1. emdometrial 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. regression or calcification after menopause
3. rapid growth during pregnancy
4. well-defined, round, firm, gray white, variable size,
5. intramural, submucosal, subserosal
6. whorled pattern of smooth muscle bundles with red degeneration
7. low or absence of mitotic activity
Risk factors of endometrial carcinoma
obesity
DM
hypertension
infertility
endometrial hyperplasia- hyperestrogenism
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
Ovarian teratoma
1. mature (benign)-cystic (dermoid cyst) / solid
young women
unilocular cyst containing hair and cheesy sebaceous material and lined by
epidermis
a thin wall 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
Yolk sac tumor (endodermal sinus tumor)
1. second most malignant tumor of germ cell origin of ovary
2. children and young women
3. rich in α-fetoprotein
4. characterized by Schiller-Duval body
Granulosa cell tumor of ovary
1. a sex cord-stromal tumor, potentially malignant
2. most in postmenopausal women
3. solid and cystic encapsulated ovarian tumor
Call-exner body: microfollicles
4. potential production of estrogenprecocious sexual development
endometrial hyperplasia, endometrial ca., cystic disease of breast
Pseudomyxoma peritoni
Mucinous ovarian or appendiceal cystic tumors ccombined 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 peripheral hemorrhagic necrosis

Breast
Mammary Paget’s disease
involvement of the epidermis of nipple by malignant cell (Paget cell) of ductal
carcinoma in situ or less infiltrating ductal carcinoma of breast
Risk factors of breast cancer
1. genetic predisposition (family history) BRCA 1, BRCA 2
2. age
3. proliferative breast disease
4. carcinoma of contralateral breast or endometrium
5. radiation exposure
6.
7.
8.
9.
geographic factors
menstrual history
pregnancy
exogenous estrogen, obesity, high-fat diet, alcohol consumption,
smoking
Bilateral involvement of breast carcinoma- infiltrating lobular carcinoma

Endocrine
Prolactinoma
(1) the most common type of pituitary adenoma
(2) hyperprolactinemia: amenorrhea, galactorrhea
(3) subtle symptoms in men and older women.
(4) treatment by resection or bromocriptine, a dopamine receptor agonist
Hashimoto thyroiditis
(1) the most common cause of hypothyroidism in areas of the world where
iodine levels are sufficient.
(2) thyroid failure because of autoimmune destruction.
(3) most 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) morphology
(a) diffusely enlarged thyroid
(b) extensive infiltration of lymphocytes, plasma cells, germinal centers
(c) Hurthle cells with abundant eosinophilic and granular cytoplasm
(8) increased risk of development of B-cell lymphoma
Thyroid follicular adenoma
morphology
(a) a solitary, spherical, encapsulated lesion.
(b) evaluation of the invasion of capsule and vascular invasion in distinction
of follicular adenoma from well-differentiated follicular carcinoma
Thyroid follicular carcinoma
(1) the second most common thyroid carcinoma
(2) women at an older age than do papillary carcinoma.
(3) nodular goiter and dietary iodine deficiency may be predisposing to
follicular carcinoma
vascular invasion
Spreading to bone, lung, and liver
Medullary carcinoma of thyroid
(1) neuroendocrine neoplasm derived from the parafollicular cell (C cell)
(2) elevation of calcitonin
(3)
(4)
(5)
(6)
in some instances, CEA elevation is noted
80% sporadic, 20% in the setting of MEN syndrome II A or IIB
mutation of RET protooncogene
amyloid deposits
Primary hyperparathyroidism
(1) frequency of the various parathyroid lesions underlying the
hyperfunction:
(a) adenoma: 75-80%
(b) primary hyperplasia: 10 to 15 %
(c) parathyroid carcinoma: less than 5%
(2) a history of irradiation to the head and neck can be obtained 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 is the most common cause of secondary hyperparathyroidism.
3. parathyroid glands in secondary hyperparathyroidism are hyperplastic.
Conn’s syndrome
1. primary hyperaldosteronism
2. 80% by aldosterone-producing adrenocortical adenoma
3. hyperkalemia, hyponatremia
Pheochromocytoma
(1) chromaffin cells: synthesize and release catecholamine
(2) 85% in the medulla of the adrenal.
(3) sporadic or familial (MEN IIA and IIB, von Hippel-Lindau, von
Recklinghausen)
(4) adrenal pheochromocytoma : 10% tumor
10% familial , 10% bilateral ,10% malignancy
(5) Clinical course
(a) hypertension
(b) catecholamine cardiomyopathy
(c) increased urinary excretion of free catecholamine and their metabolites,
such as vanillylmandelic acid (VMA) and metanephrine
Multiple endocrine neoplasia syndromes
(1) MEN I
(a) 3P: parathyroid, pancreas, and pituitary
(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

Skin
Verruca (wart)- HPV infection of skin
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
patial or complete loss of pigment-producing melanocytes within the epidermis
hypopigmented skin
Psoriasis- arthritis
Bullous disease of skin
A. Pemphigus
1. suprabasilar acantholysis
2. eosinophils
3. immunofluorescent IgG autoantibody to intercellular cement substances
B. Bullous pemphigoid
1. subepidermal blister
2. eosinophils
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
Merkel cell carcinoma
1. derived from Merkel cell of epidermis- neural crest
2. small round cell with neuroendocrine type granule

Bone, joint and soft tissue
Achondroplasia
•growth plate defect causes dwarfism
•
Osteitis fibrosa cystica (von Recklinghausen’s disease 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. bone marrow transplantation
5. Erlenmeyer’s flask deformity: bulbous end of long bone
neural foramina: optic atrophy, deafness, facial palsy
no medullary cavity: pancytopenia, hepatosplenomegaly- EMH
osteoclast No.:↓,-,↑
Osteosarcoma(osteogenic sarcoma)
•the most common primary bone cancer
•<20 y/o. = 75% (primary form); elder = 25% (secondary form)
•associated with: –Paget’s disease, bone infarct, irradiation
–osteochondroma, enchondroma, fibrous dysplasia
•location: long bone metaphysis (knee 60%), distal femur
•x-ray: mixed lytic and blastic mass with permeative margins
*Codman’s triangle, sunburst
•Micro: osteoid
Fibrous dysplasia
•bone lesion - local, developmental arrest
•three patterns:
1) monostotic 2)polyostotic 3) polyostotic + skin lesion + endocrine lesion
•micro: curvilinear woven bone (lack osteoblastic rimming)
proliferation of fibroblast
polyostotic type
•3% + café-au-lait skin + endocrine lesion- McCune-Albright syndrome
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
Ganglion
•cystic or myxoid lesion of tendon sheath
•firm, translucent cyst
•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
* cambium layer: hypercellular submucosal layer

Nervous system
Segmental demyelination
Dysfunction of Schwann cells or damage to myelin sheat
(no primary abnormality of axon)
Hydrocephalus
CSF --- decrease absorption/overproduction --- tumors of choroids plexus
Concussion of brain:
alteration of consciousness, transitional neurological dysfunction, no structure damage
of brain
Transmissible spongiform encephalopathies (Prion disease)
Creutzfeldt-Jakob disease (CJD), Kuru in humans, Mad cow disease
neurodegenerative and infectious disease
Spongifrom change, intracellular vacuoles in neural cells, progressive dementia
CJD, sporadic and familiar form
PrP --- 30KD normal cellular protein present in neuron
morphology: spongiform transformation of the cerebral cortex and deep gray matter,
uneven formation of small empty microscopic vacuoles of varying sizes within
the neutrophil and perikaryon of neurons. Severe neuronal loss, reactive gliosis,
cystic-like
Multiple sclerosis
neurological deficits attributable to white matter lesions
Morphology: surface of brain stem or spinal cord reveals multiple
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.
remitting - relapse
Progressive multifocal leukoencephalopathy
Polymavirus (JC virus), infect oligodendrocyte, demyelination, immunosuppressed
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.
Alzheimer disease
dementia, insidious impairment of higher interllectural function, alteration in mood
and behavior, memory loss, aphasia, in 5-10 years profound disabled, mute and
immobile
Morphology: cortical atrophy
Micro: neurofibrillary tangles, senile (neuritic) plaque, amyloid angiopathy, Amyloid
(AB)
Huntington disease
1. inherited autosomal disease, progressive movement disorder and dementia
2. neuronal degeneration
striking atrophy of caudate nuclei, putamen,
Meningioma
1. predominantly benign tumor of adult, 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. malignant: extremely rare, mitoses, necrosis, infiltration of brain
Glioblastoma multiforme
1. pseudopalisading necrosis, vascular endothelial proliferation- glomeruloid body
2. progressed from a low grade to high grade
3. prognosis poor
Cerebellar hemangioblastoma- polycythemia
CSF spreading of brain tumor: medulloblastoma, astrocytoma (GBM)
Plexiform neurofibroma
1. along the extent of a nerve, often multiple
2. neurofibromatosis type 1
3. a mixture of Schwann cells, perineural cells & fibroblasts in myxoid background
4. malignant transformation