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					                               醫師國考複習- 病理學
                                   Cellular pathology
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
    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

    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

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

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
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

                                      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

                                          Repair
Granulation tissue
formation of new small blood vessels (angiogenesis) and the proliferation
of fibroblasts during tissue repair process

excessive formation of the fibrous scar in wound healing

                                Hemodynamic disorders
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

  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
   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

                                   Diseases of immunity
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
          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

                                        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

                                    Infectious diseases
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
secondary syphilis
    6-8 weeks
    skin rash
     condyloma lata
     generalized lymphadenopathy
tertiary syphilis
     10-15 years
     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

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

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

                                       Blood vessel
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)
     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
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
.microscopically: leukocytoclastic angiitis (hypersensitivity angiitis)
.p-ANCA (+) in 70% of patients
  .few or no demonstrable immune deposits in this type of vasculitis (pauci-immune

 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

                                            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:
       subpulmonary stenosis (combined with pulmonary valve stenosis or atresia)
       overriding aorta

Myocardial infarction
.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
.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 appear, phagocytosis of necrotic fibers; granulation tissue
          (fibroblast & capillary) at edge of infarct; PMNs reach a peak on days 5-6
4.     - maximally yellow, soft, shrunken; purple border (10 days)
       - well-developed phagocytosis, prominent granulation tissue in the peripheral
         areas of infarct
5. - by the 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

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
2) child: rhabdomyoma
           - tuberous sclerosis

Cardiac transplantation
    a) infection;     b) malignancy (e.g. lymphoma);
    c) graft vascular disease (or graft arteriosclerosis);   d) silent MI
    e) rejection: interstitial lymphocyte infiltration
monitored by endomyocardial biopsy

                              RBC & platelets
CD34- marker for hematopoietic precursor stem cells in BM
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

                                           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
          admixed with eosinophils
          bone destruction, skin, lung
   C. Hand-Schuller-Christian triad: skull bone defect, diabetes insipidus,

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

                                         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
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

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
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
                                       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)

1. associated with chronic otitis media
2. not a true neoplasm
3. epidermal cyst-like, cholesterol, desquamated squames, giant cell reaction

                                         GI tract
Barrett esophagus
1. long-standing & severe reflux esophagitis
2. squamous epithelium replaced by metaplastic columnar epithelium at distal
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
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
        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                 tubular adenoma
Juvenile polyp                     tubulovillous adenoma
Peutz-Jegher polyp                 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
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
        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
      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.
        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

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

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
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        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
              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

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
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
     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 estrogen-
      precocious 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.   geographic factors
            7.   menstrual history
            8.   pregnancy
            9.   exogenous estrogen, obesity, high-fat diet, alcohol consumption,

Bilateral involvement of breast carcinoma- infiltrating lobular carcinoma
                                         Endocrine
    (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
         (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)   in some instances, CEA elevation is noted
      (4)   80% sporadic, 20% in the setting of MEN syndrome II A or IIB
      (5)   mutation of RET protooncogene
      (6)   amyloid deposits

Primary hyperparathyroidism
    (1) frequency of the various parathyroid lesions underlying the
         (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

    (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
    (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

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
•growth plate defect causes dwarfism
Osteitis fibrosa cystica (von Recklinghausen’s disease of bone)
•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

•cystic or myxoid lesion of tendon sheath
•firm, translucent cyst
•common in wrists
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)

  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,

 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
         perivascular cuffs, relative preservation of axons and depletion of
 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
 Morphology: cortical atrophy
 Micro: neurofibrillary tangles, senile (neuritic) plaque, amyloid angiopathy, Amyloid

Huntington disease
1. inherited autosomal disease, progressive movement disorder and dementia
2. neuronal degeneration
    striking atrophy of caudate nuclei, putamen,

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

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