" ( )1-3

Arteriosclerosis

: , .
, :

Monckeberg Medial Sclerosis

( + ) .
.
.
Arteriolosclerosis
, .
.
: ()
.
" , .

- Atherosclerosis .

( , )popliteal ,
( , ).
atheroma
.
, -.
, ,CVA- .
= Atheroma + , .

- - , .
.oxidized LDL
.
.

, , .
.
, .
( 40 ).
" ,"silent killer .
: . (.)multiplicative


: , , .
, .
, ,
.
- familial hypercholesterolemia .
:
- . .
LDL o , .
o 900 LDL-R- familial hypercholesterolemia-
.LDL-
HDL o "" . ,
.
o , -
.
o .
o , LDL- Oxidized LDL . LDL
scavenger receptor .
" 25% - , . .
- .
. .
- , .
, CVA ,MI , .
1

- , ,C-reactive protein
. .
CRP . CRP
.
( - )hyperhomocysteinemia , 10%-
. , B12, B6, B9 .
.
- Metabolic syndrome , " ,
, .
A
: , ,CMV ,
.

, .
, , .
, .
( - )response to injury
.oxidized LDL

1 20% - .


.1

.2

.3
.4
.5
.6
.7
.8

.9

: ,,
, ( ) ,
"
).
( )
= Endothelial Dysfunction :
.
.i
adhesion molecules
.ii
, .-
LDL , .
.
.iii

.
,ECM .
" " .
.
.
, .
,
. LDL- " ,
, , .
.
.
fatty streak-
.

, ""
,
.intra & extra cellular

.
,fatty dot/streak- . ,
.
= .fibrofatty lesion
= .
. , .

Fatty dot/streak .1
.a , .
.b .10 ,
.c foam cells.
.d fatty streak , .
- Fibrous Fatty Plaque .2 , .
.3 - , , , . , ,
.
.a 2- .
.b , ECM- . ,
, , . , ,
. . ,
.
.c , / ( )ostia ,,
, , ,
.
- Complicated Plaque .4 . ,
.

 ,
.fatty streak ,
, ,
75%-
.
- .
75%,

. .

.1 , .
- Atheroembolysm .2 . .
.
.3 , .
.4 ( .)cholesterol embolus
, . .
.5
( )aneurysm . .

- :
, .
: , , , , , :
- - angina pectoris ,
.
- Intermittent claudication , -
.popliteal .
- ( ).
CVA
.
=

,
( ),
( ) . ,
.


<- .
<- .
. ,
( .) cholesterol embolus .
70% .
, .

- emboli-.
- Erosion , - .
' , .
.
- ?
/ - , . ,
. "
,Matrix Metalloproteinase . ,
.
- , .
.

.
- , .

- ,aneurysm . "
.
- " ,liquefactive .CVA
- celiac and mesenteric arteries , ( -,
- SMA - IMA , ).
- , nephrosclerosis- ,
" ( ).

.
1/3- ,
( ).
.
" "- ( .
).
, <- sub-endocardial-
, . ,
.

, :
o , .
o , .
( Angina Pectoris -) , , ".
( ) ,silent ." .
.
, .coagulative necrosis -
, :
, . ,
. . .

90% , .
:
o .
o .
o .
o .

- Myocardial Infarct .1 .
- Angina Pectoris .2 ( )typical (.)unstable
.Chronic Ischemic Heart Disease .3
.Sudden Cardiac Death .4
, ,
.


:
,70% .
.
, ,
,
. ,unstable angina ,MI
.
, MI
.
90% ,
.
,
.

,

25% ,
25%-50% .
50%-75%
75%
MI .
.
, .

Angina Pectoris
, 75%-.
.1 / - .
. . , , .
, () .
.
- Prinzmetal's Angina .2 . ,
. .
- Unstable (crescendo) Angina .3 . .pre-infarction angina
( ) erosion/ulceration , .
, .

.
.
, MI

. ,
, .
.
, .

Chronic Ischemic Heart Disease

, .
.
.dilated cardiomyopathy -
.
.
, .
.
<- <- !
.
subendocard- , .
, .

- Replacement Fibrosis .
- Interstitial Fibrosis .

Sudden Cardiac Death

.
.
, .
:
Aortic valve stenosis o
- Myocarditis o
o
,SCD-
( , ,) . .long Q-T syndrome

, 90% .
40% ,MI- .
.
Cardiac Syndrome X
.
- .
: , , .
o , , .
o , .
o ,micro MI- chronic ischemic heart disease- .
o , " .40

.
Myocardial Infarction ,
.

" 1.5 , 250,000 , " . .

10% 40 45% , .65
- ' .70-80
.

90%- " :
.erosion, ulceration, rupture, fissuring, hemorrhage
.
10%- :
o +.
o () .
o , .
o ( ).

, " +.
- :

.1 .ATP
.2 - : , .
.3 pH <- .

.
.4
.5 .
.6 , . , .

40- , .
- , .
- . ,
.

 , (
); ; ; ,
- , .

( ) , .
/ , .
. .

transmural . , ,
. , .
, .
- Subendocardial infarction , .
,
, ,
.
( )
40%-50%- LAD- ,
2/3- .
30%-40%- ,right coronary artery- 1/3-
, .
,15%-25%- LCA- LAD- 1/3-
.
left circumflex-


().
" .
.
12- , .
.
3- , .
3-10 - .
10-14
- .

6-12
o , .
o ,
.
" 3-4 .
granulation -
,tissue .
, . ,
, . .
,3-4 .

,triphenyltetrazolium- . ,
. , , .

,
.
,
.replacement fibrosis
remodeling
.
,
.
4-10 , -
, ,
- .



20-30- .

.

( )plasminogen activator
" .
- "
.
.
reperfusion
Reperfusion .
,reperfusion :
o , .
:
o bands = = necrosis with contraction bands
.
o ,
o
o hypercontracted sarcomeres .

25% ,
60%- : , , , ( -
.)75%-95%
4-10 , .
(,)fibrinous pericarditis
3-4 ,Dressler's syndrome - .
, , .

.
, , .
, .
, .mitral regurgitation

.
, ,aneurysm , .

- , ,".
- , ,.
- .
- .
, remodelling-
.

, ,
.
troponin- ,
10 .

 , " ( )3-4

- Stenosis.
, .
, ( congenital bicuspid aortic valve 2 ,)3
.
, .
, . .pressure overload
- Regurgitation , .
.
, -.
,mitral incompetence .
, , .volume overload
Pressure overload & volume overload .

o Marfan's ,
, annulus-
.
, , ( ,
, ) . ,
. , ".

Chronic rheumatic heart disease .
Aortic stenosis
.congenital bicuspid-
Calcific Aortic Stenosis
.
- ( 2%).
.
," .60-80

, ".
, .
,

<- ,
.
, ",
afterload . 1-
" 75-100" , :
o , .
o .
o , , .
o .SAD - Syncope, Angina, Dyspnea .
, , .

, , ,
.
, ,
Atrial Fibrillation . , .

, . ,infective endocarditis" ,
, " .
.

- Mitral Valve Prolapse/ /.

.
, .
3%- ," , .
, ' .
, , , annulus-.
.
ECM-' ( )mucin .
, fibrillin 1- .
TGF .satellite cells- .
,aortic stenosis- , ,.
3%- : , ,
- . =< .endocarditis, emboli,
.

Infective Endocarditis
.

/ ,
, ,
.mural endocarditis -
6:100,000 , , .
" - , " .
.
.
, host factors transient bacteremia-
vireulence .

() ( )ABE)SBE( subacute endocarditis-

- ABE , " .Staph aureus"
, .
- SBE , strep viridans . .
, .

.
," .
.
, " tricuspid valve-
, .
.
: , , , , , .

( )50%-60% infective endocarditis SBE " ,strep viridans

<- Staph aureus , 10%-20% ( ,
).
<- enterococci ,
<- Staph epidermidis ,
Candida albicans - .Aspergillus
, .Strep. Viridans

,.

- " , ,.
, .
- transient bacteremia ,
, .
( )NBTE .Bacterial thrombotic endicaditis -BTE
: >- >- >- .
.
.

, . .
.


, . ,ABE-
.
SBE

.
,
,
. ,
,SBE-
.
,
.
: , ,
, . ! , : ,
.
- Supporative Complications .
,
,molecular mimicry .
- , ,
, , ,
constrictive pericarditis .

, ABE .SBE
: ,
( supporative pericarditis- ).
- , , ".
- ,
.
, supporative : , , ,,
, .
- .polyarthritis ,sterile meningitis ,SLE-


- Clubbing , , . ,
,CF- , , . ,SBE- ABE-
.clubbing
- Splinter haemorrhages ,
- Janeway Lesions
- Osler's Nodes , .
.
- Roth spots , .

.
.
, SBE- .
. , .
, . IV
.

Rheumatic Fever and Rheumatic Heart Disease

= Rheumatic Fever

- Immune Mediated .molecular mimicry

. GAS- ,
. . Strep. pyogenes
.
,
,self-limited
,
,
, .
.
- ( !) ,GAS- .
, strep throat .
,strep throat .

, .
.
,5-15 10 6 , 3%
.

-
,rheumatogenic GAS
molecular mimicry
: , ,.


,
.
, .
,pan-carditis - .
, .
( bread&butter pericarditis !),
acute rheumatoid fever- .Aschoff Bodies
, ,
Anitschkow . , , ,
. , - .


<- Aschoff bodies ! ()
,.

- Verrucous Endocarditis ,
-
.H&E- , .
" ,
. .

.
.acute rheumatoid fever-
.

.neovascularization
.SBE-

.regurgitation <- mitral stenosis

.
, .
, .

" .

99% mitral stenosis .RHF

mitral stenosis- "fishmouth stenosis" - .
, , ,
.
, .
Jones Criteria
Major Criteria
,
,
Sydenham's Chorea ,basal ganglia-
,subcutaneous nodules
,Erythema marginatum
.

Minor Criteria
,
.


,elevated CRP - prolonged PR interval".

2 ,major
major + minor .

,self-limited
- ( , !) ,migratory polyarthritis-
.
- Migratory polyarthritis , ," 3
. ( ,)10%-15% .
)!juvenile rheumatoid arthritis (JRA
- Erythema Marginatum , .
ARF . .
. , Aschoff
bodies .

Infective ,
verrucous ,ARF-
non-bacterial thrombotic endocarditis . "
.
- Liebmann-Sachs Endocarditis ,SLE- , .
, .
.

 ' ( )5-7
.
.
" " - .
.
, .
, .

- Bronchus .
Bronchiole
Respiratory Bronchiole
,
- .alveolus
,
" , -.
RB- alveolar duct- <- alveolar sac-
<- .
, respiratory bronchiole-
. .
, ,Trapping .
, RB- .
Acinus ,alveolar duct ,alveolar sac ,RB- .
- Lobule , .acini 3-5
lobule- .pulmonary veins
lobule- , .
, , : , -
.bronchiolar arteries infarction ,
.pulmonary emboli
pulmonary artery- bronchiolar artery- ,
.

, .
,pneumocyte type I .
, pneumocyte type II :
Surfactant alveoli- .
. surfactant .
, .
, ( pneumocytes type 1- )BM- -.
, - perfusion-
. .

Atelectasis
: + ( )
. :
- Resorption .1 , , .
, alveoli- .
.
.
, ,
. ,
.

.
.
, - , , .
. ,
.
,bronchiectasis ,chronic bronchitis ,CF
( ).
, , - .
.
- Compression .2 , .
, ,.
( )effusion .40
, .
- Contraction .3 , , ."
.
- Patchy .4.
, .
.
" .
respiratory distress syndrome of adults-
.
.
: , ,.

Adult Respiratory Distress Syndrome - ARDS

.
() .DAD - Diffuse Alveolar Damage
, , .
.
.
type I- , . "" . ,
( )hyaline membrane .
type II- .

. .

onset- , " ,"white lung .

.
, Type II pneumocytes ,
,alveoli- .
, alveoli- . ,
.
- .

()
<- <- ARDS- multiorgan failure-
, - O2 therapy , ,
. .
- .acute interstitial pneumonia

final common pathway-

" .

.60%
:multiorgan failure- ,ARDS- ARDS- . multi
organ failure .
Pulmonary Infections
, .
.
.
, . .
," , " " : .
.
.

.
.

 -
.1 - , , , .
.
- Mucociliary Reaction .2 , (
) . .
, .cilia-
, .cilia ,primary ciliary dyskinesia
.
- Phagocytic cells .3 , , . ,
. ( O2 toxicity ,
) , ,.
.4 ,bronchiectasis ,CF - . CF-
. ,
.
.5/ -
.6 - humoral immunity- , cell mediated-
intracellular organisms- .
.
Chronic Bronchitis
.
- " .
,
. .

Pneumonia
, .
:

Community acquired Acute Bacterial Pneumonia

- .
( )exudate , .
Consolidation- .
( )
2

Bronchopneumonia
.
patchy ,
" .
,vulnerable host .
, .
lower lobes- .
.
patchy . patchy consolidation -
, .
Lobar pneumonia
, ,patchy .
- Pleuritis .
.
, .
.
consolidation .pleurisy +
heavy load , .Strep. Pneumonia
, , , .
, ,pleuritic chest ,dyspnea ,blood stained (rusty) sputum ,
. pain , , , , ,
, .
4 :
- Congestion . , .
, .
- Red Hepatization .
, , . .
- White Hepatization .
, . alveoli-
, , .
- Resolution .
, .
.

- , - .

Community acquired atypical pneumonia

" ,.
.
.
" , .
" "atypical :
- , .
consolidation.
.
( )lymphoplasmacytic , .
,self-limiting .

-
.
, ARDS .
SARS , .ARDSinfluenza, human metapneumovirus, resp. :
.syncytial virus
, . ARDS .hyaline membrane-

Nosocomial pneumonia

" " " .

.
, - MRSA - .enterobacteriaceae ,pseudomonas

Aspiration pneumonia

debilitated/unconscious patients ,
, .reflux/
, oral flora- .
.
.necrotizing pneumonia-
.

Lung Abscess

= - supporative , ,
" , .
1 - , ,
, .
40 // , , .
emboli .
- Local spread - direct spread , - pyemic spread ,
- Cryptogenic . .

, . " .
" . , posterior .
,segment of upper lobe superior segment of lower lobe- .
, , , ( Clubbing , ) .
, . .
.
, .
- .
:
, / -
. .
fistula ,
.empyema

- Septic emboli
- Amyloidosis .


- Abscess .
- Empyema ,
- Bacteremic Spread , ,.
. ! Staph aureus
Pseudomonas . nosocomial infection . lobar
,bronchopneumonia .
.
, " , ,:
CMV o
Herpes o
Pneumocystis jirovecii o
Aspergillus o
Candida o

, . lavage -
, Pneumocystis . , CMV .
.
, .
CMV cytomegalic inclusion . type II pneumocyte-
- Pneumocystis jirovecii ./ . hyphae 45-.

DVT- , .
Saddle Embolus <- .
" .
,
, , .
"" , . ,
" . , .
, .
.

Pulmonary Hypertension

( . )Pa = CO * TPR
, .
(
).
, .
- " .
<- , <-
.

- left to right shunt .

- "
- " .
Cor Pulmonale
" <- afterload .
" , .
" , . .
pitting edema .

 HTN
- familial HT . left to
right shunt .
- Left heart disease .
/ ,COPD - . 2
. , .
, . .
- ,
" .
HTN
HTN .
:
.
, , <- .
Plexiform Arteriopathy
HTN . . ,
.
, .pinpoint lumen
, .

( internal elastic
.)lamina
plexiform -
.arteriopathy
, ,
( )cor pulmunale .
, .nutmeg liver ,
" ,
.

Chronic Obstructive Pulmonary Disease

- ( .)wheezing-
( ) .
" .FEV1
4
()
()
,bronchiectasis
.

() ,
.
"" . .
, .

Emphysema

alveolar sacs- , "".

terminal bronchionls-
. respiratory bronchioles- .alveolar duct & sac :
: .
3 ()
Centriacinar (Centrilobular) Emphysema .1
, .respiratory bronchiole-
,
() ,respiratory bronchiole-.
( upper lobes- " ").
:
.
lobule- acini 3-5 acini + respiratory bronchiole .
, .
Panacinar .2

, .
, ( ).
.
alpha1-antitrypsin deficiency .
.
Paraseptal .3
, .lobule-
,
, .
, paraseptal emphysema ,bullae 1-"
, .spontaneous pneumothorax-
, .


Elastase .Elastase-
, Elastase , alpha1 antitrypsin- .
<- , .
,Elastase ,alpha1 antitrypsin .
.Elastase
,alpha1 antitrypsin
.

. , . ,
. ,
respiratory bronchiole- - .air trapping-
paraseptal- bullae-.

.
.
, 20 ,
, .

, , wheezing .

- , ( ).
, .
, chronic bronchitis ,
. .
- Pink Puffer , .
.cor pulmunale
cor pulmunale , ,
, .
" .capillary bed-

Chronic Bronchitis
" " .
- , - .
!
3 ( ).
, : .

- .

( 2 ) , , .
- Blue Bloaters , .
cor pulmunale .
<- <- .
.
+ .


, .
" , ,
. .
- ,

.cor pulmonale-
Reid Index

.
, 50% .
, .

Asthma

, .
.
,wheezing chest tightness , , .
10% : 5%- ( ).
" .
, .

() - , IgE ,MAST mast-
.
- () - ,
.

,

, .
- Curschmann's Spirals ( mucus plugs) , .
+Charcot-Leyden Chrystals - .

, , BM- , ,
.
, BM- -
BM

Bronchiectasis

- .
( )
.necrotizing
necrotizing .
, .
bronchiectasis- ,
.

-" , .
, .
, - ,
.
- , ,( Cystic Fibrosis ,
) ,.ciliary dyskinesia ,
,
.bronchiectasis " lower lobes-
upper lobes- Mycobacteria-.

,
,
( H. influenzae ),

.

- Ciliary Dyskinesia .
Bronchiectasis . ,"
- , ( ).

CT- - .
bronchiectasis
( pleura- ).
( " )
,
- , .
,
,
.

,
,
- clubbing ,
.

- hemoptysis . bronchiectasis- massive ,

hemoptysis . cor pulmonale , , ,
pyemic acscesses , .

Restrictive Lung Diseases

cor pulmonale- .

= compliance- = .
2 :
- .
-
.
.

<- <-,
"
.cor pulmonale
. .

- .
" - "honeycomb lung .
.
remodeling- .
.
.
3
- ARDS (.)acute restrictive lung disease

, , .
,UIP- ,collagen vascular diseases , , ( "
).cryptogenic organizing pneumonia ,asbestosis ,
-
.
<- , .
Usual Interstitial Pneumonia
.
.40-70
.
- .

, .
- Temporal Heterogeneity young fibrosis ,colalgen fibrosis- .
( )subpleural ,lower lobes-
upper lobes- , .UIP-

3-5 ." , .
, .
.
.
,honeycomb lung honeycomb lung ,UIP asbestosis
.
, ,clubbing , , honeycomb lung ,.cor pulmonale-

, .remodeling - honeycomb lung-

,pneumocytes- .

Fibroblastic Foci
- , .
.
.collagenous fibrosis

)Non-Specific Interstitial Pneumonia (NSIP

UIP ,temporal heterogeneity ,

.
,UIP NSIP- :temporal heterogeneity
, .

( )
UIP- .
<- <- "honeycomb lung"-
.

-
( Hypersensitivity pneumonitis )
- Collagen Vascular Disease rheumatoid arthritis SLE

- Lymphoplasmacytic Variant .
.
- Fibrotic Variant , .

Hypersensitivity Pneumonitis

.NSIP
- hypersensitivity )antigen-antibody complex( 3.)cell-mediated( 4-
.
.
:
- Farmer's Lung ,
, .chronic hypersensitivity
.
.

.
( ,)ill-formed "" ,
.organizing pneumonia
- Brinchiolar centricity , .
.

.

Pneumoconiosis

.
, .

,
silicosis( silica- ),

3-
- Asbestosis .UIP- UIP- -
,UIP ( .)asbestos bodies UIP
, . , .
, .
. (
) . "" ,
.

.

- ,
,plaque
.

. ,

.
.
.

- Neoplasms .
2 :
- Bronchogenic Carcinoma
. . ,
11 - . 5
. 55 .
.
- Mesothelioma () . ,
. " - , , ,.
," .
1000 , .
,
, , .

Sarcoidosis

-
.
, , .
3 ( caseation ) , " .
-
.
- bilateral hilar lymphadenopathy-
.
, .
, ' .
, interlobular septae- , .
.
: , , , , , .

disordered immune regulation ,

.
<- .
: , salivary glands.
" " .

- bilateral lymphademopathy - .
.
, ,
.hypersensitivity hypersensitivity
honeycomb lung-
.remodeling honeycomb-
UIP
.
alveoli- .

bodies :
body - Schaumann Body .
- Asteroid Body .

.
,

.

bilateral hilar lymphadenopathy .
CT- ,
!
: , ,,
- , , .
.


.
,20% .
10%- pulmonary fibrosis- cor pulmonale- , .

,bilateral lymphadenopathy" .
.
.
( ) , .
, .

)Cryptogenic Organizing Pneumonia (COP

) ,BOOP (bronchiolitis alveolar ducts & sacs- .

, , .pattern of response
- Cryptogenic .

- Lobar pneumonia resolution , organizing pneumonia-

RASLE-

fibroblastic foci- ,UIP-

ducts-.
,
.
-.
.
patchy .
.

Lung Transplantation

, ' .
.
,cor pulmonale , " .
, - cor pulmonale .

.
patchy infiltrates
. .

" ,
. , ,PCP .CMV , .

- Acute - rejection .
(ARDS ) .
.

- Chronic , . ,obliterative bronchiolitis

. . , .
. , .

" ( )8

" .Mycobacterium tuberculosis

" .
, .

, T-cell mediated immunity.
, .
'80-
HIV AIDS .
.
.
.

.
, , .
.

- M. tuberculosis hominis .
- M. tuberculosis bovis , .
- M. Africans ,
- M. kansasii hominis- .
,M. intracellulare - M. avium ,MAC complex- ,
' .
Mycobacterium tuberculosis
,
.
mycolic acids ' .
cord factor .

2- ( - ) 8-10 , 1.6 ,
.
- .
AIDS- 30% : AIDS- .
17-18- , .
predisposing
, , , , ,HIV , , , " .
.Renal Failure ,Silicosis ,Hodgkin's ,
- Infection/
- , ( )Mantaux , ,
, . cell mediated
.immunity
- , , - ,
, , , , .


3%-4% . .
( delayed hypersensitivity type IV" .)T
- .)purified protein derivative( PPD - S.C.
<- .
, .
.
, M. tuberculosis.
PCR .

- False Negative , ,Hodgkin's , , .
- False Positive ( ,)MAC BCG .
-

.1 3 - :
. , .
, . ,
. NRAMP1 .
, ,
, .
.2 - 3 APC , ,IL-12 TH ,1 IFN-
gamma . . TNF
, .-
activated macrophage ,
.
, .)Langhans( multinucleated giant cells
, , .
2
- Hard Tubercle , , .
- Soft Tubercle caseous necrosis , '.
- Langhans Giant Cells .
.

Primary TB

,
,
3% .

- Gohn Focus , -
, 1.5".
3- , .
.
+ Gohn Focus .Gohn Complex

90%- , - .
.
, , . , ,
.

10% ,Progressive primary TB ,Empyema ,

, , .Myliary TB
.

Secondary TB

, /
- reinfection .
, , , (
),
= miliary TB .

,Gohn focus/complex - ( ,)apex ," 2" .

- cavitary lesion .
: .
Gohn focus ,
.
,cavitary lesion" , .

Miliary TB

, .
- "millet" , ,
( ).
( )lung military TB : , ,
, , , , , , .
.

Isolated Organ TB

TB- .
.fulminant
- scrofula .
, ( ) , , ( Potts -
,)Disease.

 miliary-isolated-
miliary- , ,
2" , . .
,isolated- , ( ,
) .
milliary- " hard granuloma .
TB
, , .

pneumonia
- Scrofula
pyuria - Genitourinary , .
- Potts disease .
- Meningitis .
TB
- .
, , , , ,.
Ziel Neelsen .
- .
- PCR ( ) , .

HIV - TB- .
, , .T cells
,T .
:
, , , , ,.
.
.

 " ( )9

Pseudostratified .
, .

,small cell carcinoma- .
, 2
Pneumocytes Type 1
- Pneumocytes Type 2 .
( 2 )

, ( ,) .
.

.Bronchogenic Carcinomas
- ,1900
. .
.

, 50%- .
25%- , 5- ( )13% ,
5-.

4 5 .
,40-70 .50-
2% .40

.1 .
- Squamous Metaplasia .2 " .
,
- Dysplasia .3 , .
: , .insitu carcinoma
, ,
.
" , .
- Invasive Carcinoma .4 .


( )
4

1,200 , .
, .
20 - '20-
, ,'40- .


20 ,RAS
TSG .P53



- , . + =
,
- , .
interstitial lung disease -
, ,squamous cell carcinoma-
. hepatocellular carcinoma
.

70% - - squamous cell -
carcinoma .
30% , .squamous cell carcinoma

.
large cell ,small cell carcinoma ,adenocarcinoma ,Squamous cell carcinoma :
.carcinoma
, adeno ,squamous- small cell.squamous-

)Adenocarcinoma (males 37%, females 47%

)Squamous cell carcinoma (males 32%, females 25%

)Small cell carcinoma (males 14%, females 18%

)Large cell carcinoma (males 18%, females 10%

precursor lesion
squamous cell carcinoma- carcinoma in situ-.
, ,atypical adenomatous hyperplasia .
. ,
.
. . ,
.air trapping - , ( atelectasis) ,
." .small cell
. - .

4 87% , . ,
.

Squamous cell carcinoma

<- ,keratin pearls .

.
- .
- Small cell carcinoma , .
- Large cell carcinoma , poorly differntiated
squamous .
= Precursor Lesion >- carcinoma in situ >-

Small / non-Small Cell Carcinoma

small cell- non-small cell-
.
small cell carcinoma ,
. small cell- , .
...
, .

,
,

, ,
.
,.
- , .
= " " intercellular bridges , .
<- <- <- <-
, (= ).
, , .
- , .
.

sputum cytology " .bronchial cytology

.
.
SSC- , . , 3
:
,SSC .
squamous cell .

Adenocarcinoma

.
.
.interstitial fibrosis
" ,pigmented ,peripheral - "P 3 puckering of pleura
.

.
, .
.
.fine needle aspiration-

, patterns . ,
(.)desmoplastic
, , .
, SSC- ,
, .
Bronchioloalveolar Carcinoma
.
1%-9% .
.
, .pneumonia
, .
,
.
pneumocytes- (
.)lepidic growth
, , .
.
.
, .alveoli-
dyspnea- - - .

Large Cell Carcinoma

, .
,15% -
:.

, , .
sheets- .
- squamous ,poorly differentiated .

Small Cell Carcinoma

, - neurosecretory granules .
.
.
, , ,
.
,neural crest .DNES/APUD -
.neuroendocrine carcinoma = small cell carcinoma
, .

: , .palisading
H&E- .
, , , " salt and
,"pepper .
.
, .
, , . ,
.

12%

,
..

small-cell - 17 ,
-.
: 5 .
( carcinoid squamous cell carcinomas
) Paraneoplastic syndromes -
- ADH
Cushing's - ACTH
- PTH ,
-
- ,
- ( carcinoid syndrome- , ).
)myasthenic syndrome=( Lambert-Eaton syndrome -
.
.
SCC Carcinoid
- ,carcinoid
- .small cell carcinoma
,
carcinoid- ,well differentiated .
Small cell differentiated .

<- Tumorlet <- carcinoid .small cell carcinoma

.

. .

Tumorlet
,small cell carcinoma - " , .
.
Bronchial carcinoid

.
, , , .
, , ,.

1%-5% .
.50%-90%
.
, , , "" .

, ...

Lymphangitis Carcinomatosa

, .
, .dyspnea-
" , , ,
.

_____________________________________________________________________________________

- . effusion- ( )
.
- , ,.
- , , , ,.
,esophagus- .vena cava syndrome-

-
( )atelectasis


bronchiectasis-
Lipid pneumonia . . ,
,foam cells .
- ,pleural effusion .
- - recurrent laryngeal nerve- .
/ - , .
( )superior vena cava syndrome -" .small cell carcinoma
. . , ,
.
- Pancoast's tumor
squamous cell carcinoma( . , )superior sulcus- :
- Horner Syndrome ,enopthalms . , ( )
, .
.brachial plexus-
.


( Hemoptysis ),
( dyspnea ),
, , ,
,
" , .
Tumor Staging
, , .
small cell-:non-small cell-
Non-small cell carcinoma Staging .1 - Tumor - TNM ,Node - N ,
,Metastasis - M , .
.
.
- Small cell carcinoma Staging .2 2- :
- ( )limited
- .
15%-20% ,limited .

" : , , ,needle biopsy , -
, .

80% .
10% .

Metastatic Carcinoma of Lung

.
- ,
( ).
- ," ,multiple nodules
, , , .

, .
, ?
.

 ( ) 11-15


150


25% .
90% .
10% .
afferent <- interlobular arteries -< arcuate arteries <- interlobar arteries-
arterioles .
efferent arterioles , .
efferent arteriole- - vasa recta
.

.
efferent arterioles- - ,
, .

.
proximal convoluted tubule < - proximal straight tubule- descending limb-
,ascending limb-" distal tubule- collecting duct-
.

- .

( - )cortical .
( )juxta-medullary )cortico-medullary junction( deep cortex-
.
800,000-1,200,000-.

, .
.
- - .
200-.
afferent arteriole- .efferent arteriole-
- .
.BM -
, - BM-.
- .



- .
- ,
- .
, BM- -
mesangial matrix.

- .
= slits 70-100.
.
BM
4 ,
- .

.
= foot processes ,BM- .slits

, .
- BM
.
, , , . .BM

- .

.
PDGF .
,BM BM- .
glomerular BM

( lamina rara interna ),
( lamina densa ),
( lamina rara externa
).
300- 4
.
- .
BM- .
3- , ,1-6
.61-3-1
non-collagenous domain7- . triple helix
.
.BM-
Slits
slits- ( )nephrin
, ' '.
.
, CD2 associated protein-
.
" ,
.

.1-2-1...

good-pasture antigen .
.
7


. 70,000-.
. .
. .
Juxtaglomerular Apparatus
Juxtaglomerular cells- afferent arteriole- .
macula densa- distal tubule- juxtaglomerular cells- lacis cells-
.
, -
, -.
,
.1 ,
.2 ,
.3 ,interstitium-
.4 .

Azotemia ( Blood Urea
,)Nitrogen BUN .GFR-
Prerenal azotemia ( , - ,
) .
Postrenal azotemia , .
Uremia , .
Nephritic syndrome
( proteinuria ,)hematuria .
Rapidly progressive glomerulonephritis nephritic syndrome .GFR-
Nephrotic syndrome proteinuria- ( 3.5-
) ,- , ,- (.)lipiduria
Acute renal failure ( ,)
.
Chronic renal failure .
.

- diffused ,
- global ,
- focal ,
- segmental ,
- capillary loop
- mesangial .
- " :
.1 .
.2 .
.3 .
-
(.)in situ immune complex formation
.
.

 in situ immune complex formation

good-pasture antigen
non-collagenous domain- .4
Heymann antigen
cross-reactivity .

planted antigens
,
,
" ( ),
, ,

circulating immune complex deposition

- DNA , .
.
- .

.
<- <-
.
- ,
microangiopathy .intra-vascular coagulation

,
.nephritic syndrome
, .
. .
T . ,
, .

- )DDD( dense deposit disease

, DNA ,
, ,
, . innocent bystander
.

- BM- -.
- " BM- -.
" .
- .
.
:
.1 .
.2 , .
, .
.3
.

 Masugi nephritis :1# nephrotoxic nephritis

.
, .
BM- .
(.)linear pattern
( .)heterologous phase ,
, ,
.autologous phase
Heymann nephritis -2#
" ,proximal convoluted tubule- brush border-
.
cross-reactivity ,BM-
foot processes- BM- ( )
. , .BM-
,
.
Megalin
330- ,Megalin .
.
Good-pasture syndrome
,BM- BM-.
- Good-pasture antigen- non-collagenous domain- 3 .4
.
:
.
.
.
.
-.
30-50% .
.
:
.1 .focal segmental glomerulosclerosis-
.2 .tubulointerstitial fibrosis- ,
.
, ,
.

Focal segmental glomerulosclerosis

.
,
<- <- <- <-
<- .BM-
>- BM- <- ( ).
,
, . vicious cycle .
TGF-

" -
.
<-
.
-Tubulointerstitial fibrosi . -
.


.

- acute nephritic syndrome = nephritis () , .

= nephrotic syndrome 3.5- ,-
, .
-.
( ) ( ,
, ) .
- ,
. .
"
.1 .
.2.
.3 - .
3 ,
.

Acute Proliferative Glomerulonephritis = Acute Post-Infectious Glomerulonephritis

.post-streptococcal
.

- diffused
proliferative
- exudative

, , , ,.urine red blood cell casts-

- 6-10 ( -) ,
.
- " GAS 4 ,12 ,1
M .
<- .

<- 1-4 <-

<- .

- nephritic strain associated protein

( ).
, planted
, .
, ( circulating complex 5-6-) .
, .planted
post-streptococcal ,
, , .

- . " ,

- crescent formation -
.
, , .crescent-
crescents TNF ,IL1.IF-
IGG,IGM-
-humps - .
.
. . .
:starry sky appearance -
post-infectious -
.glomerulonephritis
starry sky
.humps- .
.post-infectious glomerulonephritis-
C3
.


.
.
1% rapidly progressive -
glomerulonephritis
1-2% GN.
15-50% chronic -
.glomerulonephritis
-
.

, .
, .

, .

Rapidly Progressive Glomerulonephritis

- 3 ,
.
.
.
" crescents .
8

anti-GBM antibody - Type 1 .1
Good-pasture syndrome
.anti-GBM antibody disease
immune complex - Type 2 .2
post-infectious glomerulonephritis
glomerulonephritis
Pauci-immune - Type 3 .3
anti-GBM
.

Good-pasture syndrome - Type 1

non-collagenous domain- 3 <- 4 .

.
- BM- ,
( -).
.

Plasmapheresis (" ).

Type 2

.Henoch-Schnlein
.Lupus

post-infectious glomerulonephritis ,
.
post-infectious starry sky ,humps'.

Type 3

- , .
= Anti-Neutrophil Cytoplasmic Antibodies = ANCA
.

C-ANCA .
.1
P-ANCA - -.
.2

= Wegener granulomatosis .C-ANCA +

= Vasculitis9 ,polyangitis- .
= Churg-Strauss syndrome- , .

8 .
9 glomerulonephritis vasculitis Wegener granulomatosis
,Churg-Strauss syndrome- vasculitis- rapidly progressive
glomerulonephritis .

 rapidly progressive glomerulonephritis

= crescents .
,
.
( glomerular tuft-
) ,
.
" .
.
, .

.
,
.
crescents- .
rapidly progressive -
glomerulonephritis 50-80%
.

rapidly progressive- Good-pasture-

,rapidly progressive glomerulonephritis .
,starry sky
.post-infectious
, .type 3
- , ,
. BM-
crescents- .

, .
" , ,nephrotic syndrome .
Good-pasture- , .
, cytotoxica , ,plasmapheresis-
.

Nephrotic Syndrome

Membranous glomerulopathy
Minimal change disease
Focal segmental glomerulosclerosis
Mesangiocapillary (membranoproliferative) glomerulonephritis
IgA nephropathy ,focal mesangial - proliferative glomerulonephritis

Nephrotic Syndrome
3.5 ,- , ,- .
Nephrotic syndrome BM-
.
-- , - .
, , .

- highly selective proteinuria .1 ,
- poorly selective proteinuria .2 , ,
.
Nephrotic Syndrome
.
-.
- renal thrombosis .

Membranous Glomerulopathy

.
.nephrotic syndrome-
85% 15%- nephrotic syndrome .
, .
nephrotic syndrome - nephrotic syndrome- ,
'.
membranous glomerulopathy
,
,
,SLE
, - thyroiditis- .

,
.
.

<- C5-9
<- C5-9 membrane attack complex <-
.

-
.
, .
.
.
-
- . , BM-
( ) spikes .

glomerulopathy glomerulonephritis ,
.BM-
- IgG-.C3-
- , .
,BM-
.spikes- ,
spikes- ( BM- ).
" BM- .
, .

, BM- ( 4-5 )
BM- .membranous glomerulopathy-
1 - BM-
.
3
.
4 .BM-

.
- , , BM-
.

.
3 .
" nephrotic syndrome- .
, , .,
.

20-50%- - .
10%- .
nephrotic syndrome
.
( )
.
10-30% .
, , .

Minimal Change Disease

- Nephrotic Syndrome ( ).
-)2-6( 10 nephrotic syndrome- .

- .

.
- , BM- ,
.
- ,
BM-
.
- -
,
.

, .
:
( ) "
.

90% .
.

)FSGS( Focal Segmental Glomerulosclerosis

Nephrotic Syndrome
, -.
, HIV .

- , .
, IgM.C3-
.
- .

- .

.
.

( { )GFR- MCD- }.
{ .}MCD-

.

10

nephrotic syndrome , membranous

glomerulopathy MCD

 nephrotic syndrome MCD .FSGS-

(+ ) .FSGS

11
.FSGS
. 2 ( FSGS IgM )C3 , .

( FSGS - )nephrotic syndrome .
- juxtamedullary junction-
, .MCD
, .
<- , ,
.

.
, .
,
, .
Collapsing Variant of FSGS

,collapse .
- -
.
collapsing variant .HIV-
.
.
focal segmental glomerulosclerosis- minimal change disease FSGS-
?
- FSGS , .
, ,
.
.
, BM-

slits- .
- .
- Finish type of nephrotic syndrome .
.
, nephrotic syndrome- -
.
. .nephrotic syndrome

{ . MCD "}.

>-"

11

10-12 .

MCD

-++

FSGS

++
- + HTN

Membranoproliferative Glomerulonephritis (MPGN) = Mesangiocapillary Glomerulonephritis

BM- .
( )Membranous .2
nephrotic syndrome-.
.
.
.

MPGN Type 1
. .
.

, .
BM -.

- ( +),
.

.
- .
- . ,
. .
.
BM
.
, BM- , ,BM-
.
BM- , .
. .
)MPGN Type 2 = Dense Deposit Disease (DDD
.Type 1
partial lipodystrophy .
, .
, ,nephrotic syndrome
.
"
C3- , 2:
.1 C3 .
.2 C3.
.C3Nef C3 nephritogenic -
C4 C1q- , .



.
- ,
.BM-
C3
.
C3b <- C3" .convertase convertase- "
I H.properdin-
C3Nef ,
C3 ,C3b- .
70%- C3Nef .


IgA Nephropathy = Berger's Disease

( ).
- .
- 50%- .
- .
.IgA

12 IgA ( , ).
( -
, ).
proteinuria .nephrotic syndrome
, .
- .mesangial dense deposits (
) -

IgA IgA , .
2
- IgA1 ( C3 C1q ,)C4- alternate -
.complement pathway .properdin
- IgA2 .
IgA , -
.alternate complement

- focal segmental glomerulonephritis - .
- .
.

Henoch-Schonlein purpura

, .
( ,)3-8 .
.

- ( )purpura .
.
, nephrotic syndrome ,proteinuria
.

- , .
- .dense
, .IgA nephropahy-
Leucocytoclastic Vasculitis
, .IgA .
immunofluorescence - IgA Nephropathy IgA .
, H-S purpura- .
2 .
H-S purpura . .
. , , .
12 immunofluorescence- IgA-C3.

Chronic Glomerulonephritis

.
( ) , ,
.
,chronic glomerulonephritis- ,
.
( ) ,
,
.
" , .
.
, end-
.stage renal disease
,
.chronic glomerulonephritis

( ,)hyaline obliteration of glomeruli ()

, .
, .
.
- - . , .
, .
. .

intermittent hematuria
- Alport Syndrome

, ( ).
,X-linked , . AD ,AR- .
, .hematuria
" BM
.Alport-
BM- , ,BM- ( -
)lamina densa .
BM - .
immunofluorescence- .alfa3, 4, 5
,Goodpasture .3
, Alport- .3
( focal segmental-.)global sclerosis-
( 4 - ,)5 .
.3+4
hematuria , .

- Benign Familial Hematuria - Thin BM Disease

thin BM .
( )3/4 .4

, 80% .
- .
. EPO
.

.
.
.
.
, .

, , ( 80%-90%).
, .
.

Proximal Tubule
o , .
o
.
o , , , brush border
.
o .
o " .
o - , , brush
.border
o . ,
. - blebs ,".

o - .
o .
Distal Tubule
o .
"fine tuning" o .
o , . ,brush border
.
o .
o .
Collecting Tubule
o fine tuning- .
o .
Juxtaglomerular Apparatus
o ( + Ang2 ).
o .
o macula densa- distal tubule- juxtaglomerular .afferent-

)Acute Kidney Injury (Acute Tubular Necrosis

, .
.

- - ,end arteries
infarction- . ,
.
o -.
o .
o : , , ,
, ( ) ,.
- , - "
,.
- Acute tubulointerstitial nephritis - AKI
, .
- , " .AKI-

,
, .
.

o ,
o (
-),
o
,
o tubuloglomerular -
.feedback
o
' -,
()
NO- (),
o <- GFR-( oliguria-
).

o , .
o ,tubular back-leek , .
o GFR-.

, AKI- straight portion of -
proximal tubules .loop of Henle-
toxic type-
, proximal tubule- . ,
.
AKI
.
-
backleek-
.
.
.
/ , .
- .
.brush border
- patchy .

, , sloughing
( )granular casts .

- .
.

o
( BM- ).
o BM- , .
o - ,
o , .
o -.
,AKI
.
, !
o ( 150).
o , .
o pale cortex - ( afferent-
,)GFR- ,congested medulla- .outer medulla-
recovery phase- .
, .
.
( 50% )... .
3 - AKI
- Initial phase .1 : , , .
36- ( ) ,
. . ,
. 750".
- Maintenance Phase .2 2-6 . - 400"
. .uremia -
( ) . " " .
- Recovery Phase .3 , . " ,polyuria-
. -
. ( ) .
, . - . ".

Tubulointerstitial Nephritis

acute-.chronic-
( ) , / .
.

.
.acute bacterial pyelonephritis
Chronic pyelonephritis .
, .
, ,
- hypersensitivity nephritis- . .
.
mechanic obstruction
- multiple myeloma
- ,
. ,SLE ,Sjorgen's.

Pyelonephritis

.
- .

( )urethritis, cystitits
.Enterobacter ,Proteus ,E. Coli

.infective endocarditis-
Staph E. coli- ().


, .
( ).
- , ,.
- pH .
.
/ ,
.

.
, , self-
.limiting process
cystitis .
, ureter- .
reflux .
.
- .
, " , (.)neurogenic bladder
- vesico-ureteral reflux .
.pyelonephritis-
, . collecting ducts- .
,
.


reflux" .

pyelonephritis- - Enterococcus ,E. coli .

Acute Pyelonephritis

- Urinary tract obstruction

- Vesicoureteral reflux .
.reflux

pyelonephritis - ,
. ,
, .
prolapse , .
" - "
- ,
, .

: ,
(=),
urethra-
dysuria

, ( ).bacteriuria ,
( ) .
<- ,
<- .

,self-limiting
( )obstruction- .

, .
pyelonephritis- .

.
.
-!
, .
" - , " .

- Papillary Necrosis .
,acute kidney injury .
- Pyonephrosis , .
- Perinephric Abscess ,
.

Chronic Pyelonephritis and Reflux Nephropathy

, .calyces & renal pelvis

1/5 .
.urinary tract-

Reflux Nephropathy
,

.vesico-ureteral/renal reflux
reflux-
.
" ,
.
Chronic-obstructive Pyelonephritis

.

.
, .
- .
,
.
chronic glomerulonephritis-
, .

,
, " "patches .
.
, peripelvic fibrosis -.
, ureter- , . ,
( .)urothelium

- patchy , .
.
" .
, .lymphatic nodules
-
.
.
.

Obliterative Endarteritis
chronic pyelonephritis-.
,
.
Super/Mega Tubuli
.
Periglomerular Fibrosis
.
Tubuli Thyroidization
, ( ).
- , , ,
.
.

-" .
, reflux" .
" .
proteinuria- ,hematuria
.proteinuria
proteinuria - ( 3- ) ,
.

Xanthogranulomatous Pyelonephritis

- .
- .
- ' , ,lipfuscin .
.
" Proteus ' , .
.

Acute Drug-Induced Interstitial Nephritis = hypersensitivity nephritis

, /.
.
acute renal injury/failure .acute tubular necrosis, toxic type

.

.
.
( )hapten- .
" IgE - type 1 reaction ,MAST - type 4 reaction , .BM-

.

.uremia -
( )hyposthenuria polyuria, nocturia,
.metabolic acidosia
.
- .
= Acute , = !
- NSAIDs ,cephalosporines ,sulfonamides ,

,acetaminophen - allopurinol ,

" ( )2-40 , .
15%- " "
,

.
, .hematuria & mild proteinuria
.NSAIDs-
, , - tubular dysfunction
polyuria ".

Analgesic Nephropathy

- .Tubulointerstitial Nephritis
, < .

" ( ).
.phenacetin, aspirin, caffeine, NSAIDs
( Phenacetin )acetaminophen ,
.
.

.
.

(.)papillary necrosis

- , , (" ").
proteinuria , hematuria ,.
.
.

,macrohematuria papillary necrosis acute renal failure-

.
.
.papillary urothelial carcinoma of renal pelvis
, !

"
.
fat infiltration( peripelvic fat ),
- . , .
. - demarcation line
.
. dystrophic calcification
.
papillary necrosis- ,acute pyelonephritis-
. acute pyelonephritis " .
, , .



main renal arteries <- <-
interlobar arteries , <-
arcuate arteries- <-
interlobular arteries <-
afferent arterioles <-
peritubular capillaries <- efferent arteriole .vasa recta-
..

vasculitis
HTN-
- ( ,)diabetic nephropathy-
- Chronic Glomerulonephritis .

Benign Nephrosclerosis

" , ,afferent- interlobular.

.
,HTN .
( )autopsy- ".
.

- , <- .
-
hyaline changes<- plasma proteins .
.

benign nephrosclerosis - chronic glomerulonephritis-

.

- afferent , .
.
.hyaline arteriolosclerosis -
afferent arteriole-
( ,)collapse . .
- Obsolent glomerulus , .
tuft- - -
.
collapse- , . focal segmental
.glomerulosclerosis . focal segmental glomerulosclerosis -
,advanced benign nephrosclerosis FSGS- -.
- .

" .
, renal insufficiency -
, , " - .

-" ".
.

Accelerated / Malignant Nephrosclerosis = Malignant Hypertension

, , , - .
" , " proteinuria ,papilledema , ,hematuria , .
" ( 140" )
- Target Organ Damage , , .
proteinuria " .

"
" , (
-).
50%- benign nephrosclerosis.
chronic renal injury- .chronic pyelonehrosis
uremia- .
renal ischemia
<- Ang2 .
NO.
, ( )salt retention
.vicious cycle .
<- <- platelets -
<- subendothelial tissue .

- Flea-bitten kidney -
.
afferent-.glomerular consolidation-
.
bloodless glomeruli - .

wrinkling BM-,
subendothelial space- .expanded lamina rara interna

interlobular arteries-:
, spindle
- - .
, ,
.onion-skinning/hyperplastic arteriolitis -
.
malignant nephrosclerosis :
.ischemic atrophy -

,fibrinoid necrosis
interlobular arteries- onion skinning',
,
.

, : , ,.
( ') , 50%-
.

Renal Artery Stenosis

2%-5% " , .
-
.
renal vascular HT
Goldblatt '30-
" , .
, , ,JGA-
' -Ang2- . .
, " " " .ACEi/ARBs

Atheromatous Plaque
70% ,
.
, , .
Fibromuscular Hyperplasia
, () .
, .
- .

, , .
" " .
, , Ang2.

Thrombotic Microangiopathies

.
, .

, .Malignant HT-
, ,
.

' .
- .

Bacterial Endotoxins
Viruses

-
vin-willebrand factor
. -
. ' . .


Typical Hemolytic-Uremic Syndrome
, ,
- uremia" .
- classic- .
)EHEC( E. coli - ,Shiga-like toxin .
Atypical HUS
.
,diarrhea negative
' - complement- '
. ().
" . .
: atypical HUS- () ,
, , , / ,
,.anti-phospholipid ab's ,
Thrombotic thrombocytopenic purpura (TTP)
" , , ( )purpura.
( )ADAMTS13 von-willebrand factor
.
.

: ,
. (" )
.
," acute .
" , , .

- malignant HT- .
Classic Childhood HUS
, (-").
" E. coli-
verocytotoxin/shiga-like toxin .
.
" sudden onset- hemolytic anemia ,hematuria ,oliguria .
, ,
, " .
- " .plasmapharesis

Idiopathic HUS/TTP
.
von willebrand factor .
, : , ( , ) ,
.
.
- .
.

, , .
( ,)partial necrosis .
, ,interlobular arteries- , renal HT
.
" .

Diabetic Nephropathy

.diabetic glomerulopathy
, , 40%
.
Diabetic nephropathy ,chronic renal failure- 1/3
/ .

, , (
, ) , .
( ,)pyelonephritis -
acute pyelonephritis .papillary necrosis -

/ .
Amadori products
.glycated residues
).advanced glycosylated end-products (AGEs
AGEs cross linking- ,BM- ,4 adhesion-
.
AGEs
AGEs- LDL- .
.ECM-
, turnover .
AGEs ,
<- - <-
, ECM .
:


.reactive oxygen species

.
,
,
.
"
,
.
" -
,GFR
.
.Hyperfiltration
"


.


Early changes
, .
" , , increased mesangial ,
matrix .ECM-
BM - . ( membranous glomerulopathy-
) . .diffuse glomerulosclerosis
- . ,
.
- ,

EM- GBM- ,lamina densa- .
, .
( GBM- )
( ).
minimal change disease-
.
, 30-300( microalbuminuria" ) ,
. GFR- . ,
, .
Advanced Changes
- Nodular glomerulosclerosis = Kimmelstiel Wilson disease
.
,nodules.
, .
ECM.
" .
diabetic nephropathy

( )hyaline arteriosclerosis .benign nephrosclerosis-
collapse- .
, efferent- benign nephrosclerosis-
afferent-.
( )nodular glomerulosclerosis-
.
thickened BM , / .

, , .
, ( )2-5 heavy proteinuria (
. . ).
( GFR- )hyperfiltration
. .

30%-40% ( ).
,Native americans ,- 2 - end-stage disease
.
microalbumineria 1+2
.
80% , 1 20%-40%- 2 - "
".
end stage disease- 20 75%- 1 20%-
.2
type 1
.

Systemic Lupus Erythematosus

, .
.
.
- " , " .
:SLE- , , , , .CNS-

self-tolerance .
( ).
, C2, C4, C1q
activated complement system .

HLA-DQ Anti-sm ,dsDNA.anti-phospholipid abs-
: .

.

UV- , + .IL-2

( 10 ) , .

(' )procainamide ,hydralazine ,drug-induced SLE-like reaction-" .
" .
- / ,
.

- ' - (.)type 3
, ( )type 2 .

4 11 .
.

malar rash . ,discoid ,extensors-

discoid-malar rash ( ).
50% ,
.
minimal change disease.
SLE-
Persistent proteinuria 3+ (more than 0.5 gram/day)
- cellular casts : : , , , .

anti-dsDNA abs titer- , .
.
Lupus nephritis ,
+ . .
" .immunopluorescence


, ... ,
deposits.
- - .
- Whire Loops ,
. .hyaline thrombi -
IgA ,IgM ,IgG .
, ""finger prints
. .
5 lupus nephritis
- Class 1 .1 , " -
,IF . .
Mesangial Proliferative Glomerulonephritis - Class 2 .2 25% . , IF-
.
- Focal proliferative glomerulonephritis - Class 3 .3 50%-20% .
.
. , glomerular tuft-
,
karyorrhexis ( .)nuclear dust .necrotizing lesions 50%-
,3 50%- .4
- Diffuse proliferative Glomerulonephritis - Class 4 .4 50%- . class
3&4 . 35%-40% ..
. . acute
.)?( proliferative glomerulonephritis
- Membranous Glomerulonephritis - Class 5 .5 15% . -
membranous glomerulonephritis IgG C3- , lupus nephritis-
C1q ,C3 ,IgA ,IgG .
.



Renal Papillary Adenoma
Angiomyolipoma
Oncocytoma
, .

- Renal cell carcinoma (adenocarcinoma of kidney) .

Clear Cell carcinoma
Papillary renal cell carcinoma
Chromophobe carcinoma
Collecting duct carcinoma
- Unclassified carcinoma

- Clear Cell Carcinoma , .
- Papillary Renal Cell Carcinoma , .
, .
- Chromophobe Carcinoma " .
.

Renal Cell Carcinoma

( 1%-3% , -),
.
2.
, 50-70 - .
.pediatric renal cell carcinoma
, .
4% , .
, ,
. ,
- .
.

( )

"

, ( )petroleum

10%- , .
.

,
macro-hematuria ,
.
" .
()paraneoplastic syndromes
,hypertension ,hypercalcemia , ,
.
,eosinophilia ,Cushing ( )leukemoid reactions -
.

Clear Cell Carcinoma

.
= hypernephros( Hypernephroma ,
, ).
70%-80% .
95% , 5%- , - von Hippel-Lindau
.
.proximal tubule-

.tumorigenesis-
abnormalities ( 3 ) ,p25-26- protein
).von Hippel-Lindau (pVHL
TSG , .ubiquitin ligase
( HIF-1 .)hypoxia inducible factor 1 -
( GLUT1 ,VEGF ).TGF-beta ,carbonic anhydrase ,
-.
HIF-1 , .IGF
, HIF-1 .
pVHL- .HIF-1
, - pVHL- .VHL

Capillary hemangioblastoma ,
,pheochromocytoma
,
.
, clear cell
.carcinoma " clear cell -
.carcinoma

pseudocapsule ( ).
.
, ( ).

, , .
,clustering ( ).
( ).
"" , .
- clear cell carcinoma "juicy"- .
""the great mimicker
.
,
: .
, "",
.
.
clear cell - .
,PAS .
.


, - .
grading .
.
.
,clear cell carcinoma , .

Papillary Renal Cell Carcinoma

10%-15% .
- - 50%- .
.
clear cell carcinoma-
.

,17 ,16 ,7 Y .
( MET oncogene .)7
papillary renal cell carcinoma oncogenes X.1-
7 - mutated activated MET oncogene-
. hepatocyte growth factor- , , .

(
).
p-RCC .
.
"" - (
).
" , ,
.
.
- Psammoma bodies , .
.

Chromophobe Carcinoma

.
5%-15% , ".
intercalated cells- .collecting ducts-

multiple chromosomal losses

- hypodiploidy .

,clear cell carcinoma- ,

.
, .
clear cell carcinoma
.
, - .
.
- .
.

 2#
25%- .
CCC" ( " ) .
, , , , . ,
.
40%- ( )recurrence , CCC- -
papillary Chromophobe . , .
, 5 .70%
staging
renal vein- .
, 5- - 15%-20% .
Staging- , , .CCC-
,CCC- ( - papillary renal cell
.)carcinoma

Oncocytoma

5%-15% .
: , .
(.)oncocytosis
"-" , .

;1 + Y
DNA-.

, , ,
.

, , .
"" , - .
- , ,"
," .
- " ".
.
.
- . ( ) .
, .

Renal Papillary Adenoma

, .
.VHL
- 5-".
,"
.

- "
.
( papillary renal cell carcinoma- ).

 ' ( )15-17

,cloaca-
<- cloaca-
<- cloaca-' .
( ) -
urethra
- urachus . -
.urachus
, , urachus- median umbilical -
.ligament .

.
.
.
detrusor muscle- .
seminal -
- vesicles.

() .transitional epithelium-
,
.
7 .
-
(,)muscularis mucosa
muscularis propria/detrusor muscle .
.
Transitional Epithelium
,dome/umbrella cells -
tight junctions .
dome cells- intermediate cells
.
-
, .

- squamous cell metaplasia
.
.
. .
- Von Brunn's Nests ,
( . ).
Exuberant Hyperplasia of von Brunn
( Cystititis Cystica ).
, Brunn's nests urothelium-.

Cystitis Glandularis
von brunn -
, .

, .

,
(,)cystitis
.
,pyelonephritis casts .cystitis

- exophytic " ," .
.
- 4 .

- ,
- .
,3
80% .50

50- .
, .

( 50%-80% ) -" .
.
, , .
15-40( arylamines- ).
- ' , ,
analgesic nephropathy .
- cyclophosphamide- .
- schistosoma haematobium .
- .

95%
, .urothelial tumors
- .
Transitional cell papilloma- benign .
.Transitional cell carcinoma (TCC) - malignant
.
- .
.
- , ( ).
.

Papillary Transitional Cell Tumors

Papilloma
WHO grade 0

- "" "
. , , dome cells-
, . -
intermediate dome- .

Papillary transitional cell neoplasm of low malignant potential

WHO grade 1
, .

Papillary Transitional Cell Carcinoma

-low grade/WHO grade 2 .
,"" , ,
.dome cells- ,
intermediate- , "" .
-High grade/WHO Grade 3 .
, , , .

hematuria ,
-
, .
.
" " , . " ,
.
, "
.

Papillary transitional cell carcinoma

- Exophytic .
: " .
.
<- , ,
.invasion into muscular wall -
' (
)
:
( ).
' .
( ) - .


transitional epithelium
,
.
,
.
( low grade ),
.
,
,
dome
intermediate- .
" , ,
polarity , .

.
( high grade )
" ,
- "" ,
,
,
, ( ).
. , .

2
- :
.)umbrella cells=( dome cells
.

low grade carcinoma-

dome , .
.
high grade carcinoma-
clusters , .

= , .
= ( )low grade ,
. ""
. ,
, .
papillary transitional cell carcinoma
.
- . , excision- ,
.
50% low grade TCC- ,
. ,
. , .
, , , ( ,)80%-90%
, . 65%- .
, .

( )
.
, .

Carcinoma in situ

.
(.)high grade
- ( ).
- .

,
: cystitis- , , (
).

" , .
.
( immunotherapy ) - Mycobacteria tuberculosis ,
' . , .

.
urothelium ( ) -
,denudation ( .)denudation cystitis , ,
.

Solid Urothelial Carcinoma

high grade ,
.
combined papillary&solid -
invasive carcinoma
.

- , :
. .muscularis mucosa-
.
- .
high grade solid carcinoma- ?urothelial
" ,
.squamous/glandular differentiation
transitional cell carcinoma
.

Squamous cell carcinoma of bladder

, .
schistosomiasis- .
.
- ,schistosoma- () urinary -
.tract infection
30-40
, SCC
-.

Schistosoma
trematoda
- , .
, ,
" pelvic venous plexus- .
3,000- .
/ ,
.
, .
Schistosoma hebatomium .
squamous cell carcinoma

, , ...
,keratin pearls
.well differentiated-keratinizing
schistosoma
.
,
.

transitional cell carcinoma .
squamous cell carcinoma of bladder
.
, 60%-70%-
,
.

Adenocarcinoma of urinary bladder

2%-5% ( ).
' , .

,predisposing preexisting intestinal metaplasia13-

urachus ( )
- diverticulum .
(
bundles ).
, ( )BHP ,
.
( ) .
.

- neurogenic bladder - , .

30%- .
hematuria
- mucinuria . - 5- .15%-20%

.
- ,mucinous carcinoma .detrusor muscle- .
.
: - " ( ),
. -
.

30%-60%- .
,9 .17p, 13q, 11p, 14p
9

high grade low grade
flat cancers - in situ .
TSG ( P16 )CDK- .P15-
9q- TSG.
17p- p53
/ .invasive urotherlial carcinoma-
p53- .carcinoma in situ-
2
.1 - 9 , p53-
.
P53 .2 - p53-
carcinoma in situ- 9 .tumor progression
.p53-

13

- ' .
7 , .
, .
, 20 -,
( ).
40 .
.ejaculum-

3
- Central Zone
- Transitional Zone ,
. .
- Peripheral zone

.
,
-
.
2-
.1 ,
.2 - .


prostatitis

( , ).

- Acute prostatitis .1 .cystitits
- Chronic prostatitis .2 , , ,
.
prostatitis .
- Abacterial prostatitis .3 , ,
.
- Nonspecific granulomatous prostatitis .4 ,
. , . "
. specific granulomatous prostatitis
, "
, .

Benign Hyperplasia of Prostate

.
40 .
Hyperplasia benign .

<- transitional zone- ,TZ-

,
.urethra-
, , .
20% - 40 90%- .70

:

.

- ,
, " .
.
- Copora Amylacea - ( .)psammoma bodies-
, , Prostatitis-
.
! ,
.

surgical capsule : ,
. .

 BHP
,
.

.
, .BHP
()DHT
, type 2 5-alpha
.reductase
,
.
, .FGF

.
. ,
.
?
( ),
.
BHP-
,
.
.
BHP
, .
, .
.
, 100-200- ( 10).
.
:clinically important hyperplasia , .

50% .
- ,
, .

, .40
BHP , .
( .)DHT-
, .
,
.
, - , 10
( 200 10).
. !
50%- , .
prostatic urethra- , .
, .
. , ,retention of urine , .
BPH- !premalignant -.


BHP- . :
.
- . .
- , ,median lobe hypertrophy-
. , -
, .
BHP

.
,
vesicoureteral
,reflux .
- ." BHP
.
-
. .

. ,
squamous -
.metaplasia ,
.
.

Carcinoma of Prostate

( ).
, , 20- .

.50
familial cancer .
, .
2 .
2
Latent
, post -
.mortem
, PSA-
( ) . .
, .
," .
.clinically important
.


, .
( 3-4 ,)10,000-
.
.
" 50-60 - ,10,000- 10
. - .
, clinically important-
,
.

,
,
- ,
BHP ( ).
- .
, .2
. .
,.

,
Androgen Receptor- .X
,CAG .
! -
.
Germline mutations BRCA2- 20 .
androgen sensitive .
( )loci 8q24 ,
prostate cancer susceptibility gene 1q24-25 .
TSGs .16 ,13 ,10 ,8
. , upregulation-
.ETC .
PCR .
( ) S-
.

,peripheral zone-
( BHP- .)transitional zone- .

.
.
" , . ,
. PSA- -
, " .

- ! . .
- .
prostate specific antigen - serum PSA test .
. PSA- BHP . ,
. cutoff .
.PSA-

PSA
screening-
PSA-.
- , PSA- .
.
PSA cutoff- ,
.PSA

, .
, .
, ,
, .
, .
.

( ) , .
.
- , .needle biopsy
( )6-12 .
.
( ) , !
.
adenocarcinoma , .
: , :
.1 - . ,
.
.2 - " . , .
.3 . , .
.4 .
- .
sheets of malignant cells .

)Carcinoma vs. high grade prostatic intraepithelial neoplasia (PIN

" "carcinoma in situ .

.PIN
, ,
.
carcinoma in situ " ,
.
PIN ,
.
PIN- .
PIN- 3-4.
PIN- , PSA . ,PIN- .
.

Grading
"
.

. " .Gleason
.
5
)1
)2
)3
)4

- Class 1 , "
.
- Class 2 ,"
.
- Class 3 ,

. .
- - Class 4+5 .
, -
. -
class ,
.

( )2
.grade 4 - ,4 " , .grade 4+2 = 6-
,2 .2+4

 - Class 6 gleason grade 6 ,intermediate grade

Class 7 high grade - gleason grade 5 , low grade .
gleason grade 5- .

, PSA , gleason -
grade.
PSA- , .
Gleason grade 7-10 . .
grade- ( ) ," .

( A , ) , ( B
, ).
, - ( BHP
).
( ) .seminal vesicals-
.
C D- pseudocapsule- , , .
, . seminal vesicles- .
, .

( ) 30%-50% - 5.
escape , .
20% , .
. ,
.
,PSA- grading- . ,
, .
.
15 90%- .

, .urinary
.

,BPH .
, , urinary
.symptoms


,perivesical ,obturator - regional lymph nodes-.
, : - , , ,.

 ' ( )18-01
- , .
( )
- , .
- . ,
+ .
/.

- Agenesis ." . ,
.
- Stenosis . ( , , )
. " , ," .
- Atresia , .fistula
- Fistula .

, ( )upper digestive & respiratory tract .
2 2 ,
/ , ' 2 - .

( - )90%-
, (
) ,

.
.
,
.

.

,
.

Achalasia
.
. ,
, .
, .
,Achalasia .

.

(,)dysphagia
(" ),
.
,
= "Bird's Beak"- .
( ) , . ,
. ,

, . " ,
.
, . ,Achalasia
,
. ,.
:Achalasia ( myenteric
) & submucosal , .
. , ,
. , .
Achalasia ,

: . ,
, .

.
, .
, ,

( )
- Chagas .Chagas ,Trypanosoma cruzi
. ) .Assassin bug (kissing bug
, ( ) , , -
.ureter ,megaduodenum ,megacolon- .
- ( ) .
Polio , .
, .
- , : , ,
. Achalasia
"" .

, .

 , ,
.
- , .
"" = , .
= ,
.
.
.
, ,
. .
, , - . ,
.
( - )myotomia .

Rings and Webs

. .
( Webs)
( Rings).
" , .
Plummer-Vinson : .Paterson-Kelly
rings & webs-
.
.

, .
, ,
.
, , ,
. .
( Rings )Shatzki
, .
, .

Hernia
Hiatal hernia
( - )hernia , inguinal hernia
, .inguinal canal-
Hiatus - crus- .
2 :Hiatal Hernia
Sliding Hernia .1
,
.
, .
o ,
.
, .
, ,rugae .
, . , , .
o ,
, ...
Paraesophageal hernia .2
:hiatus- , .
,
, "" ,
.
, .
, ,sliding hernia
o .
o .

o reflux/
:
- , ,
( ,
) .
.
, , ,
. ,
.

Lacerations
Lacerations = Mallory-Weiss syndrome
.
, ( ).
: , ( )
.
, .
.
.

, .
, .
( ) ,
, .
, .
Diverticuli
"" , .
Zenker - = .Zenker Diverticulum
"" .

Zenker
o ( ,)Zenker : ,
,
.
Diverticuli
o /
, ,
, .
o ,traction diverticuli , .
o .
o , .
o .
o .

Esophageal Varices
- , .portal hypertension
( ) , -
.Caput Medusa
, ,
(.)vena cava
" , , Mallory Weiss-
. .
()varix
,
.
.
"
.
, .
40% .

(" , . ),
.
".


Esophagitis
.
.
Reflux esophagitis
: .
reflux
. .
reflux esophagitis
.
' ,
.
- Hypothyroidism ,
.
- : . =
.
- Systemic sclerosing disorders . ,.
.
nasogastric tube .
, .
- Sliding hiatal hernia ,
, .
- ,
.reflux reflux
( ) .
, - .reflux , , .
. ,reflux
. ,
.
reflux esophagitis
. , . , 3:
.1 , , , . -
.reflux esophagitis
.2 , . 2-3
, .
.3 , . ,
,
. .
Reflux esophagitis , .
Reflux esophagitis . ,
.

 Esophagitis
.
.
- irritants / . : ( ) ,
, .
. .
. .
. , .
:
o , , .
o sloughing , .
o
.
. ,
, .
( ) .
: ( .)NaOH
. . ,
, .
. , ,NaOH ,
. . :
, - . ,
.
, , .
, . .
- , ,
: , ,
. .Herpes Simplex, CMV -
. , (" )"punched out
.cookie cutter , CMV-
.
:HSV , . ,
.inclusion bodies , 2-3 .
.
.
,CMV- , "" , .
- , ,
- . Candida-
. , '
2 .Candidiasis - .Aspergillosis ,Mucormycosis
: - , . psudomembrane
, , : , ,
.pseudohyphae- .
, .
- Radiation Injury .
, . , . ,
. ,
.submucosa- ,
, .
- .
- Genetic predisposition .
. , .

 - Graft vs. Host Disease ""

, . GVHD
, .
- Uremia .
.
Barrett's Esophagus
reflux.
, esophagitis -
.
.adenocarcinoma -
.

, . ,
, . -
.reflux esophagitis - .
- .
, . barrett's esophagus
, reflux- .

.
.
, ." 3" ,
.

- ( ,)leiomyoma,
, , ( .)neurofibrimatosis
" -" .

() - , , - .
() -
80-85% squamous cell carcinoma .
,5%-10% - Adenocarcinomas .Barrett's esophagus '50-
,
. .
Barrett's esophagus- .
small cell .

Squamous cell carcinoma of the esophagus

' .
4 - ' .
- , ,"
( ) .

:
.
trace metals- . molybdenum-
- .
. ,
aspergillus . :
aflatoxins . "
" , .
aflatoxins SCC
nitrites - nitrosamines-
, . ,
, ."
SCC
- Betel chewing ,
SCC , .

-
.
, () .
. - .

Esophagitis - ,reflux
.
- Achalasia "" .
- Plummer-Vinson syndrome .
,
- Diverticuli

- .
,SCC .
- .
- .

50% SCC- .
30% .
20% .

, . ,
" , .
. , .

( , )... 3 :patterns
60%- polypoid fungating .1 - .
25% - ulcerating necrotic .2 - , ,
. .
15% - Diffuse infiltrative .3 - , .
, .


SCC , - . = ,
.
" , ""
.
keratinizing pearls - .
Staging SCC
. . :.
.1 - 1 ( 5") , .
.2 - 2 5-" , .
.3 - 3 ( 10-") , ,
.
.4 - 4 3 .

," 4
,
.
-

...

-
.
.
,
3 ,4- .
' , , .
Fistula
,
, fistula .
: - ,SCC
. .
perforation-
.

Adenocarcinoma of the esophagus

5%-10% .

( 40 ),
( ,)5-6
.
, / reflux
. .Barrett's esophagus ,
.SCC-

reflux Barret's esophagus - .

SCC- .
.reflux-
, , .
reflux- Barrett's esophagus .
Barrett's esophagus- .

( SCC- , ) ,.
,
.
, .

 ' ( )01-03

- Cardia transitional zone- .
Fundus-.Body-
- Antrum .
Pylorus .
2
HCl .1" .Parietal Cells
.2 ( ) " .Chief Cells
( !)

Cardia+antrum

Antrum

( G cells )

HCl
Parietal Cells
Fundus
B12
Intrinsic Factor
14
,

Chief Cells

- " , , HCl .
( ).
- , . , " ,
Parietal + Chief Cells.
- .
H2 receptors- Parietal Cells ,HCL.15
.

14

pH- . ,
pH-
15 : ,
, [ ' 49 '].


Diaphragmatic Hernia
( ).
, , -
. , , .
.
,.
.
Pyloric Stenosis
, .
, :
o .
o
.
, .
congenital hypertrophic pyloric stenosis
1:300-900!
".
.4
: ,
, . .
-
.
: , .
. , .
- .
Pylorus - .
" myotomy . , 90-
. , .

- Gastric dilatation .
,
.
: , , .
, ' .
, , .
, .
"" , ("
' , ") .
. , , .
- Gastric Rupture .
.
: ,
.
- Bezoar .
- bezoars
,
. .

' .
.

Gastritis

, :
.1 ,
.2

( )
- Acute gastritis , .
- Acute hemorrhagic gastritis .
- Acute erosive gastritis , .
.
- Acute Stress Erosions . ,
.

Acute Gastritis
( ):
,NSAIDs - .
- ,
.
- .
.
- Uremia .
, , .
- .
, , ( ).16
"
,

- distal gastrectomy , .
.

( )lecithin .

"" .
" ,"back diffusion
.
" tight junctions . tight junctions
.
. ,
, pH- . back diffusion-
.
, "
. ,
. , ,
.
- " .

2 16 acute stress erosions- .


( )
,
,
() -
.
, " " ,
= .
- + ..
, , , ( erosions ).

. ,.
, :
( , )

, , ()hematemesis
- Melena .
( ) , .
.
, .Mallory-Weiss '
, , .NSAIDs- ()
NSAIDs , .
Chronic Gastritis
, ,
.
, .
.
<- ,,
<- .

- Helicobacter pylori .
.
, .
.
,urease urea <-
.
, .
" , .O
- .Parietal Cells
.
,Parietal Cells ( )achlorhydria
. , . .pernicious anemia-
- Pernicious . intrinsic factor B12
10% . .pernicious anemia
Autoimmune Gastritis
.Parietal Cells
: -.intrinsic factor ,
- Achlorhydria , .
, 10%-.
10%- autoimmune gastritis- .pernicious anemia
Addison's, Hashimoto.

 chronic gastritis-
, .NSAIDs
, ".
H. pylori
, - .
, ,
reflux , . ,reflux-
.
: - Bezoars ,
, atony , .
- .
.
- , .
.

GVHD
""
, .
, .Parietal Cells
, .
( )H. pylori , .
reflux-.
,
, "" .
( )rugae , .
, -
, .
( , )
.
- , .
.Helicobacter
( ).
-
. - : gastric pit ,surface mucous cells- -
.gastric gland ,neck- .
, , , - ,
. .
.

- . .
.
- , ( Parietal Cells ) ,
. , .
- G ( ) ,
hypochlorhydria . achlorhydria . .
, , .
- , ( ) ,
. , ,
, . autoimmune gastritis-
, . B12
.
= :Carcinoma in situ " .basal lamina-
.


, , .
, .
, gastric pits
. " .
,atrophic gastritis - ,gastric atrophy-
.

, , : .
.
, - .
.
<- hypergastrinemia 10%-
.pernicious anemia
. ,
.2%-4%

Hypertrophic Gastritis = Hypertrophic gastropathy

"" .
.Hypertrophic gastropathy -
3 :
rugae- ( ) ,
, ,
.
.
.
.1 - Menetrier . Gastric -
.Pits . gastric pits-
. . ,
,
, .
. .
- Hypertrophic Hypersecretory Gastropathy .2
. . , gastric glands- -
.gastric pits , gastric pits-
. ,
.
- Gastric Gland Hyperplasia (Zolinger-Ellison Syndrome) .3
, - ,
G , .
. . hypersecretory -
.gastropathy

Hirschprung's Disease

4 , . .
. .
,"" : .
. , .
.congenital aganglionic megacolon :

.
, .
: .

. Hirschprung , .
,
. .frozen sections
. .
, .

1:5000-8000 .
4.
10% .
/ .

' , ,superimposed enterocolitis .

.
megacolon , colon .
.



HCl-.
" ," .
, .
.
,
. , gastric atrophy- pernicious anemia-
. , .
...

, , ,gastric pits - .
. .
pH- ,1-6 pH- .
, tight junctions ,
.
, .
" , ! , . pH
.

' 80- . ,
- . , , - .
,Cohnhheim ,Virchow
, .
Dragstedt vagotomy- : = .
, .
100%-! , .
,NSAIDs : , reflux ,
, ...
, ,
.
.
, . ,
.
, . Dragstedt
. ,

H. pylori- 4 .

Helicobacter pylori .
, , .
, .
, 50%- ( ).
, .
recurrence .

, <- "" ,
. .
!
.
, , ( -
) . .


( )98% .
.
80% , 4:1 .

(.)cookie cutter
, " .lesser curvature-
(" ").
: ,
buffering
.
- ,
. .

3 :
.A - , , , ,
.
.B - active granulation tissue .
.C - , ,
, . - .
.
.
-
- , .
,
, . , ,
, .
, .


- 2" , " . ,
.
- , , "
" , = " ".
, , , " " .
. , ,
.
- "" ,
. , , , . ,
, , .




2"





""

, .
.
- , . ,
, ,
.


- Perforation . -
omentum , . .
- , .
, .
.
- Obstruction lesser curvature- ,
, .

, . Cancers ulcerate but " :Robbins
'."ulcers rarely 'cancerate
, .

Acute Stress Erosions

acute gastritis , .
, , .
, .erosion
Erosions , .

acute stress erosions

1-2" ,.
"" .

(),
( - )Curling duodenal ulcers
-

- .EICP- erosions" ,Cushing
.

- , " ,Cushing EICP-

, .
" , ,
- .
? ,NSAIDs , .

lipomas
schwannomas
fibromas
.Gastro-intestinal stromal tumor

Polyps
- . ,
. , ,-
20% . ,
. , - .
2-3".
"" - .neoplastic tumors or villous adenomas ,
.

90%-95% -
4% -
.3% - Carcinoid - neuroendocrine tumor Carcinoid .
, .
( ) .2% - "" gastrointestinal stromal tumor
.


: ,' , , ,
. (" , , )... !6 .
.
.
, , ( 2
).

, . ,
.
, , , ( .)aflatoxins-
,.
. ,
.
=

- precursor lesion
- H. pylori . ,
" - .
- Partial gastrectomy ".
-Gastric adenoma 40%- ( ) , 30%-
.
, A . ' A
H. pylori ( ) [ :
O ,H. pylori ]

nonpolyposis colon cancer .

50%-60%
25% ,cardia-
.
lesser curvature- 40%- , greater curvature 12%,
.
.

- Early Gastric Carcinoma .submucosa- , .
- Advanced Gastric Carcinoma .

- Exophytic tumor . papillary adenocarcinoma , .early gastric
( flat - )depressed early .advanced
- Linitis Plastica , ( " ")
. , .
Excavated tumor 2 - . exophytic-
, .


Intestinal
, .
colon- ,
.
Diffuse
,.surface mucous cells-
.

, -
.
Signet Ring Cell
.Adenocarcinoma
.

.
,
,
.
, :
, mucicarmin- .
.
.

' , .
5- 5% 15%-.
( Early Gastric Carcinoma )
.
,early 5- !90%-95%-
( )
- . ,
Cachexia .

,


- Dysphagia ( ).
- .
- melena-

: , 80%-90%- .
20%-40%- : , , - .omentum
- Virchow's Lymph Nodes .supraclavicular lymph nodes- ,
.
Krukenberg Tumor

.
,
" .
, , 10%- ,
.Krukenberg Tumor
!


Gluten-Sensitive Enteropathy = Celiac sprue

3 , . , .
, , .
, .

- - , .
- - " .
, .

- .

() .
, .

gliadin-.
, T .villi-
T- .

Giardia Lambia

12 , ( ) .
: ? , Villi.

.
"" .
"" <- Giardia lambia- , .
- , "
.
.
,blunting- villi-
-.

Inflammatory Bowel Disease

2 ulcerative colitis - ,Crohn's disease- .

.
.
. ,20- .
: , ,
, ,.
- 2 . colon-
,proctocolitis . IBD ,
- IBD- , , , .
.

Ulcerative colitis

"" .
, , .

, . ,
.
, , , .
! "" .
, = . "" .

, .
- , .

.
= .Abscess
.
, ,cryptitits -
- .ulcerative colitis
, ,
, .

- .
( , ,
, ) , , .
, ,
.
.
, , ,
. , .
, , .
. .
.
ulcerative colitis- , .
.
, .
.pseudopolyps/inflammatory polyps - ,
, .
! ,
.

 ulcerative colitis
- .
- ,
.
Megacolon .
.
- Perforation . ,
.
- Benign Stricture (
-) , .
- Malignant Stricture , .
- :

,Sacro-illitis ,
. , ankylosing :
,spondylitis .UC-
- Erythema Nodosum , .
: ,.
.Sclerosing cholangitis -
. .ulcerative colitis
, cholangiocarcinoma .
- . ,
, .

.

, , "" -
ileum , .

Crohn's Disease

UC , ' .
' , - , .
Crohn .

, .ulcerative colitis- .
( )mesentery UC- ,
.
- ileum- , .

Ulcerative Colitis

Crohn's
'

,-


" " ()aphthae
-
Stellate Ulcers
.
,

Pseudopolyps
, .UC-
Aphthoid Lesions

.

, , ,
.
. " ".
, (
) - , .
Crohn
, , , .
.mesentery-
, , - "" ,
.

.
.germinal centers -
: , , , .
.
Crohn UC- , . ,
( UC- ).
( ) :
, . 40%- .Crohn

germinal centers : .
! , " ".
UC-
.Cobblestone Pseudopolyps -

- Ileitis , . .
- String sign .
- Jejunitis , .
, .



, , .
, -
.
, .
Fistula
,
.
.
" " -
, .
Fistula

- .
, .

psoas- -
, , ,ureter-
.
Crohn - UC-
, Crohn .
Crohn

- , .
,
Erythema nodosum - ,
.
UC-
, -
,
, .
'
Crohn ' , !
.UC-
.
Crohn .
IBD "

.

- .ulcerative colitis
- ,

- .Crohn
- ,

.Crohn
- .
IBD- .
, .

, .
- Polyps , .
- .
.

- Non neoplastic
Hyperplastic Polyp

, .
.
Hyperplastic polyp " , 2-" , " " " "
.

, .
.
, - , .
.
, ,
" " .

Hamartomous Polyps

.
.
.
2 :
- Juvenile Polyp .1 ," . , 2-" ,
"
. torsion , . ,
, " ,"autoamputation , .
. .
- Peutz-Jegher Syndrome .2 ,
, , , , , . ,
. , ,
. ,
. , : ,,
, .

Inflammatory Polyp

Pseudopolyp .IBD

Lymphoid Polyp

' (.)GALT
,
.
:
.
.

 - Neoplastic polyps
)Tubular Adenoma (adenomatous polyp

, .
, ( ).
, , .

- .
75%- .
, 60 , .
2.
colon- ( )ascending, sigmoid colon.
, 50%- 50%.
30%-40%- , .
1-2 ," , (.)pedunculated
- .

Villous Adenoma

,Tubular Adenoma- .
" " , , ,Peutz-Jegher
, ,PJ .
, , .

1% , - 50% .villous
,60-65 50 5 , .
.
, .
.
,Tubular Adenoma- 10" , .
" , .
: ( ) ,
.protein losing enteropathy-
,tubular adenoma- ( )40%
, , .precancerous lesion

Tubulovillous Adenoma

- , .
5%-10% .
25%-50% .villous

villous- .
,
, ( )...tubularvillous adenoma-
.tubular adenoma-
1" , .1% 1-2" , 10% ,
45%.

17

)Familial Adenomatous Polyposis (FAP

( )100 .
APC .5q21
.
, 1-".
' .
.
, , , .

Gardner Syndrome

FAP

,osteomas
,
,fibromatosis
,.

)Hereditary nonpolyposis colorectal cancer (HNPCC

.DNA mismatch repair genes ,DNA-

.
, ,
.

Adenoma-Carcinoma Sequence

.
<- <-
<- .
:

17 .

98% , .

".
.

2.
.
.60-80
, 60 .

- , . "" , .
.
- .

<- bulk- <- <-

<- .
, <- <-
.
, , <- <-
.
.

( )60%-70% ( )distal colon ,

, .
()descending colon
- Napkin Rng Constriction .
- Melanosis Coli , .
()ascending colon
- Fungating - .

, - insidious .

, , .
cecum- .

, .
.
classification-

Duke's classification , :Astler-Coller
- Stage A . ,100% . ,
.
Stage B
:1 67% .
5 .
:2 54% . 5 .
- Stage C .
43%( 1 5) - .
23%( 2 5) - .
- Stage D .


80 , .
.
- -
. .IV , .
. ,
,
() .
, pseudomembranous colitis
o , - "".
o , pseudomembrane-
. .
pseudomembranous/antibiotics associated colitis
o .Clostridium difficile
o
.
o , .

 ' ( )05-08

, , .
, .
.
- 25%- .
- 2/3- .
.
, .
/ , 17- ,
,
.
" " - ,
.central vein-
, .
, .

- ( ).
- central vein- .
""
.
""Hepatic Acinus
,
.
:
- Periportal = Zone 1 .1 ,

.
, .
- Zone 2 .2 .
- Pericentral/Perivenular = Zone 3 .3
.
,
.
Masson-trichrome
,
.
2 3 .
: ,
. .

- The Limiting Plate .

()
- .
Space of Disse -

.
- 18Ito cells .
() .
.Kupffer cells -

Bile Canaliculi
.
- Canaliculi - - ,
.
canaliculi- canal of Hering <-

.

( ')
<- , , .)end stage( Cirrhosis <-

Acute Hepatitis
,
,
: , , , .
.
Fulminant Hepatitis
.
, ,.
.
<- .

18

, Ito Stellate cells ,

Chronic Hepatitis

"" 6-.
(
) end stage- .
: , ,non-alcoholic fatty liver disease , .

. , :
) - Aspartate Aminotransferase (AST ( oxaloacetate-).
) - Alanine Aminotransferase (ALT ().
) - Lactate Dehydrogenase (LDH ().
.

( ),
( PTT ),
( ),
(/ ),
.
canaliculi-
- Glutamyl Transferase - GT ;
- Alkaline phosphatase .

:intracellular accumulations ,
- Ballooning Degeneration , , ,
( .) hydropic change , .
.
- Hemosiderosis = . ,H&E-
.
, .
- .
, .Wilson - ,
(.)orcein stain
- Steatosis Fatty Change ,
. .

- , .
Acidophilic bodies . .
-Focal Necrosis , . , .
- Zonal Necrosis , ,
. , - ,zone 3
.
- Bridging Necrosis "" , (
) , .
- Massive Necrosis "" , . ,
,
. ,
.

()inflammation
- Portal Hepatitis .
,
. ,
. , limiting plate- .
.
.
- Interface Hepatitis , ,
"" ( ) .
. , ( ) ,
. .Piecemeal Necrosis
.
- Lobular Hepatitis .

- Hypertrophy , ,
, .
- Regeneration 70%-80% , . ,
. - , . " ,
( ,)DNA ,
.3 . = . 24-48
.
- Cholangiolar Proliferation ,
. .
( ) oval cells ,
. .

- Fibrosis " . .
- Sinusoidal fibrosis , ,
. .
- Bridging Fibrosis ,
Bridging necrosis . , .
.
- Cirrhosis , , .end stage liver disease-
- . ()nodular
.
.

Cirrhosis

<- .

,regenerative nodules
.
.

:
,B+C
,Alcoholic Liver Disease
,Non-alcoholic fatty liver disease (NAFLD)
,

.


<- <- <-
<- .
end stage- .
Ito cells- space of Disse- ECM .
, .

.
<- interface hepatitis limiting plate- <- <-
<- <- end-stage <-
.
.

3
Micronodular .1
- , ( ).
- end stage- , .
, nodules- =
.
, 3" ,
.lobules
: , , .
Macronodular .2
- , 3-" , ".
.
- .
- .
Irregular .3
- ,micronodular cirrhosis (
) , .
,
.
, cirrhosis- :
.i - , .
.ii .irregular-
.iii , irregular
.

portal hypertension-
.
<- <- shunt
.
, , ".
.
" : , , .

 HTN

= - splenomegaly , .
. , congestive
.splenomegaly
( )varices - . ,
, . . .
, .
- Caput Medusae . , hernia ,
,tense ascites = 500" Trans-illumination .
, .
- ascites ( " ) -
. .
, ' - " .
" . 2 :
- Suprahepatic , Inferior vena cava- .
. .
- Prehepatic ,
.perforated appendicitis , , .
.

80%-90% .
,chronic liver disease .acute liver failure -
!
- jaundice , 2 ,
.
- Pruritus , , .
( K) -
- - .
- Spider Angioma , .
- Palmar Erythema , .
- Gynecomastia
( ,)alopecia .
- Encephalopathy ' ,shunt
. , ( )fetor hepaticus .
, ( ,)flapping tremor , ,
. .
- Hepatorenal Syndrome , .
, .
- Hepatopulmonary Syndrome .

()

drug and toxin induced

)Alcoholic liver disease & non-alcoholic fatty liver disease (NAFLD

" .
( ) <- .
, .
B <- , ( ,
).
, , .
.
- staging & grading .
- Grading
.
, , .
- Staging
<- .
<- .
.

Viral Hepatitis

1 12- B - C HIV-
.
1.5 B C -
.

.
,A-G .

.1 - ,
, .
.
.
Acute Viral Hepatitis .2
:
- Incubation (
) - -
.
- Preicteric Stage ( )
- Icteric Stage
- . , .
, ,ballooning degeneration , , Kupffer
( ) , ,
. . - Interface hepatitis
, limiting plate- - Lobular hepatitis . .
.viral hepatitis

Chronic Hepatitis .3
6.
.
, ,interface/lobular hepatitis -
.
, - , .
- .
<-.
hepatomegaly .

remission .
indolent disease .
.end stage disease-
Fulminant Hepatitis .4
- .
, , .
.
- viral hepatitis- , .
, 500 , " " ,
.

, ,
- bridging necrosis .
hemosiderin CYP450
.
oval cells- ( ,)tubular regeneration
.
- . ,
- . ,
.
- ,
.

, , , , . ,
-.

, .
,
( ).

- HAV ,acute viral hepatitis- , .

- HBV , .
- HCV , .
, - , .

HAV

RNA .picornaviridae
- fecal-oral , ().
.
.
.
"" , 6.
( .)fulminant

.
.
,
.
- IgG,
, .
.

- , 5 100%
.
- .

.

5-6" ,
( )
. , .

,Ballooning :HAV- ,.
'
,
99% .fulminant

HEV

HAV-
,)calicivirus( RNA
- fecal-oral .
.
-
unnoticed
.
- .

- .fulminant hepatitis
,
.

HBV

DNA (( )class 7 - hepadnavirus .)DNA

.
B .

2 HBV-,
350
15%-25% .

HBV ,ganglia : , , , , , , ,.
- .
HBV <- HCV .
HBV- ,HCV-
.100%-
.
.HCV ,HBV
- Alcoholic liver disease , .
, .
HBV-
,
,
.
HBV <- HIV- inoculum-
.

3-.

(
).

( )95%,
1% ,fulminant
4% .

( HBs )
.
.

.
, ,
hepatocellular
.carcinoma

.
/
.
.
chronic liver disease hepatocellular carcinoma-
.


- Ground Glass <- HBs
,antigen - .
.
- core antigen- .
HBV- -
- ( )glomerulonephritis
.
, ,.
HBV .

HDV

"" .HBV-
.RNA
HBs antigen- .
" ( )coinfection ,HBV
HBV .superinfection - HDV-
Coinfection .
HBV .
,
HBs- ,
.
, ( 4%-) ,superinfection .
baseline ,HBV ,HDV .
.HDV

HCV

,RNA
( HBV , , ) - .
,HBV- .
- .
, , .
100% 20% , 20% , 60% ,
, , , .
- HCV- ."blue balls" ,
- .
,Sjorgen's syndrome ,glomerulonephritis , Erythema nodosum ,.

- HAV Fulminant Hepatitis,

10% - HBV ,Fulminant Hepatitis ,Ground Glass Cells ,
HCV- - ,Blue Balls ,
- HDV ,HBV
- HEV .

.
- ,.ballooning degeneration ,
, ( ).

Autoimmune Hepatitis

: - .
: .
.IgG
<- - ( )
.
: , <- .
,

3
- Type 1 .1 ," , )anti-nuclear antibodies=( ANA .
. .
- Type 2 .2 ( ) . anti-liver-kidney-microsomal
.antibody = anti-LKM , -
acute .fulminant
- Type 3 .3 , , : .
" .

Drug and Toxin Induced Hepatitis

.
<- iatrogenic .
:
( <- )Herbal life .
<- .

.

, fulminant

Fulminant hepatitis
,HAV
( HBV ,)fulminant hepatitis-
HCV .
15% FH , ,
( 50%!) .acetaminophen -

()hapten

,
- .
parenteral - .

- .
100%- .fatty liver-
30% , 10% .

Fatty liver
, ,
( ).
, 4-6 .
" .
Macrovesicular Alcoholic Steatosis
, .
.
4-6 .
""
- .

"" - 19
.
= Macrovesicular
, .
Microvesicular Hepatic Hteatosis
.
- hepatomegaly- .
- ( ).
- , .

= Microvesicular

focal necrosis ,diffuse steatosischolestasis-

Alcoholic hepatitis

19

ballooning degeneration

- ,

, , .
isolated GT ( canaliculi-) , .
, "" " .

-,
(.)PMNs
, .
- Mallory's hyaline clumping - intermediate -
filaments , - .
, .

ballooning degeneration, acidophilic bodies -
- , ( - )Mallory
!

""

Alcoholic Fibrosis
<- .
, .
: , , portal -
spaces , .
, <-
bridging fibrosis .
, .
.

Alcoholic Cirrhosis

20%-.
<- .
<- , irregular cirrhosis
.
.5%-15% - hepatocellular carcinoma
: , , , , .
- .
. , ,
. - .

100% - 4-6.
<-
,PMNs
,Mallory's hyaline
," .
,
.
.hepatocellular carcinoma

)Non-alcoholic Fatty Liver Disease (NAFLD

, .1980-
.
, :
,
GT .

" 30 - " 8-
.
10%-24% , 58%-74%.obese-
2.6% , =< .

5% - .
- 5% .
, ,2 , .20
.

gold standard- .NAFLD

20

 ""two-hit
= 1st Hit
( centripetal )


= 2nd Hit
- ROS , ,
. ALT , .

- , 20
1%-2% .
( non alcoholis steatohepatitis - NASH - )NAFLD- .
.

,
( - )ballooning degeneration , .mallory's hyaline-
( ).
.

zone 3- ,
.
( ,)centrilobular fibrosis

micronodular cirrhosis -
,
.ballooning degeneration -
- Mallory's hyaline - .

2
" ,
" .
- .
<- : ,
.

, .
, ( Haeme) , .
, () .

Enterohepatic Circulation
ileum-.
, " .
, , .
()cholestasis
, .
()jaundice
( ),
2 .

.
- .
.

-
- .
- Xanthomas , .
/ . , .
- Pruritus , , .
steatorrhea - (
.)K


- hepatocanalicular cholestasis , canaliculi- .
- feathery degeneration- .
- Foam Cells xanthomas , .
- Cholate Stasis canaliculi canals of Hering-
, . ,feathery degeneration - ,
. , .
, , "".
- Mallory's Hyaline limiting plate- .
.Cholestatic Liver Rosettes

- Cholangiolar Proliferation .
, .
,
. , .
, . .
.

,
. . ,
. , .
- Ductopenia . 90%- ,
- 50%
. ,
( ductopenia ).

Extrahepatic .1
, ,.
!
/ right & left hepatic ducts-.
, , .
.
( )hernia .
" / ,
.
- , .
- Bile lakes -
. -!
Intrahepatic .2
.
, , (
) , / , , .

 -
)Primary Biliary Cirrhosis (PBC

.
xanthomas .
.
,anti-mitochondrial antibodies IgM- -
!
, , .

.
-
.
! ,
, cholate stasis .

, ,
.

.

.
,HLA type 1
,HLA type 2

.
<- : , ,steatorrhea ,
, ( ) !
. .hypercholesterolemia ,osteomalacia
, " , .

- Autoimmune Cholangitis ,AMA .
.
- PBC-AIH overlap syndrome ,anti-smooth muscle abs -
.
, , , " PBC ."autoimmune hepatitis
, .

)Primary Sclerosing Cholangitis (PSC

,
-
- ascending cholangitis - ' .
, .
" " - .
, . , ,
.
, .

.
" .

20%-30% ulcerative colitis ,PSC-

70%- PSC- .ulcerative colitis
.

fibro-obliterative cholangitis -
. . " ".
40%-.
.
PSC , .small bile duct PSC

,
.
.
, IBD- , .HLA

. , .
, .
, IBD .
,
.end stage disease-

-Robbins-

,CMV : C.
( .)drug-induced jaundice ,
chronic cholestasis - . : , , , .


inflow -
Chronic Passive Congestion

,
.
, .
- .

,
, /.hypoperfusion/
3 .
"."nutmeg
.
,

,
,
( , cirrhosis )
- cardiac cirrhosis .
.

( )infarcts

.
- , ,
,
( ) . ,
.
.
- , , .
" - " .coagulative necrosis

Portal vein thrombosis

" .
:
.
, .

<- .
<- .

 outflow -
)Budd-Chiari Syndrome( Hepatic Vein-

, , , .

<- ,
<- .
pre-hepatic , , ,
.
fulminant , , ( 50%).
, .

, .
space of Disse-
. .

Veno-occlusive Disease = Sinusoidal Obstructive Syndrome

.

<- (,)hepatosplenomegaly ,
<- .

-
,
.
.
.

- Alpha-1 antitrypsin " .
-
()

Hemochromatosis

Iron overload disorders

.
2
= - Hemochromatosis .
- ( 1:12 ),
,6 hepcidin- .
- .
- , :
, ,pituitary- melanin
stimulating hormone .
= - Hemosiderosis
, , , -
.
, .
Kupffer " .

 3-
.1 -
.2 -
.3 -.
.
testicular atrophy ,pituitary- .

- lipid peroxidation DNA- .
10
, .

.
,
.
- ,iron overload
,Kupffer .
- .
, . , .

, , , .

- , .
. ,
.

Wilson's Disease
. -

. ,
. . primary biliary cirrhosis- ,

Wilson
.) (
. ,copper transporting ATPase-
, ,ceruloplasmin- ,
.21
. ceruloplasmin-

.5 ,
. , , ,
basal ganglia- . -
.
.
"" , ,
. ,parathyroid , , , :
. , ,

,fulminant
,
.
. ,steatosis -

. , "
.
. . - - Kayser Fleischer Ring

21

: 81 ,Robbins-
Normally, 40% to 60% of ingested copper (2 to 5 mg/day) is absorbed in the duodenum and proximal small intestine,
and is transported to the portal circulation complexed with albumin and histidine. Free copper dissociates and is taken
up by hepatocytes. Copper is incorporated into enzymes and also binds to a 2-globulin (apoceruloplasmin) to form
ceruloplasmin, which is secreted into the blood. Excess copper is transported into the bile. Ceruloplasmin accounts for
90% to 95% of plasma copper. Circulating ceruloplasmin is eventually desialylated, endocytosed by the liver, and
degraded within lysosomes, after which the released copper is excreted into bile. This degradation/excretion pathway
is the primary route for copper elimination. The estimated total body copper is only 50 to 150 mg.
The ATP7B gene, located on chromosome 13, encodes a transmembrane copper-transporting ATPase, expressed on
the hepatocyte canalicular membrane. [] Deficiency in the ATP7B protein causes a decrease in copper transport
into bile, impairs its incorporation into ceruloplasmin, and inhibits ceruloplasmin secretion into the blood. These
changes cause copper accumulation in the liver and a decrease in circulating ceruloplasmin. The copper causes toxic
liver injury, through the production of ROS by the Fenton reaction.


4-
-

Focal Nodular Hyperplasia

, .
3-4-.
- .
" /.
, .
, .
<- .
.

, .
.

, .
.
,
focal cirrhosis .

Hemangioma

.
" " , .

, , .
.
:
( ).
.
, .

Hepatocellular Adenoma

.
, .
.
, ,
sub-capsular .
,
,
.

:FNH- , .
,FNH- , .
, , " - "feeding vessels
- .
FNH-
,
.
- , .
, .
, oral contraceptives
.
,FNH- , .
- .

.
- .
.
: ,
(" ").
' ' .
,miliary .

, , :
, , ( cachexia- ),hepatosplenomegaly ,
( alopecia ).
cachexia .

- Large cell dysplasia

- Small cell dysplasia , . .
.

Hepatocellular carcinoma

( 90%- ).
.
,cholangiocarcinoma , ,
.
= .hepatocellular carcinoma
, .
, micronodular- irregular- regenerative nodules

.
,-fetoprotein , .HCC .

, , , .-
nodule .

.
, B , HCC-
( )20-40 .
. , ,85%-
, .60
HCC-
C ,B

.
, .
, .

.
.
.
- ,
( 6 ) , .
" .
, .
, .

<- .
- giant cell type HCC , . poorly
.differentiated
HCC-
- .
.

HCC - ( / ).
, -
( ) "".

, ,cachexia GI/ ,
( ).

Fibrolamelar Type HCC

.hepatocellular carcinoma
, .
( )20-40" .
5% .HCC-
.

Cholangiocarcinoma

.
- , ( )50% - -.
- Klatskin Tumor .
6-7,
- ,cachexia , , .
- HCC-
,-fetoprotein .
,
, .
6.

cholestasis
.
, -.
, -
.

- .
.

- Angiosarcoma , .
.primary liver lymphoma

 ' ( )09

.
20-" , 90-.

- 80%-
90% .
- .


2-7 .
mucin-
.
2-
( -) - - ,

- .

,
ductular cells- ,
ductal cells- .Mucin
2
.1
.2
<- secretin <- CCK-
.
enterokinase- villi-
.
.
, , -
,
.
2
- SPINK1 = Trypsin Inhibitor .
- - PRSS1 .
.

Pancreatitis
Acute Pancreatitis

- <- <- .
, .
self-limiting .

() , , ,,
, .

.
:iatrogenic , - ERCP
.
.
, , , .

, ,.

mumps ,
,Coxsackieviruses
.Mycoplasma Pneumoniae

.
10%-20%-.
.
2 -
.1 ( )35%-60%
.2
Acute Pancreatitis
" ( ,)PRSS1

80% penetrance
.
SPINK1-
.

- <- <-
<- <-.
: , , ,.fat necrosis ,

<- .
= microvascular leakage



,
<- fat necrosis <- calcifications <- .

.
- Hemorrhagic Pancreatic Necrosis necrotizing pancreatitis

- Enzymatic Fat Necrosis , "" .

ascites <- ,
-.
.
.

- acute abdomen - , ,
. .
.

,

24- ,
96- .

- , .
- glycosuria ,
( glycosuria ).
!
:
- , . ARDS-acute -
.renal failure
, - .
, .Pseudocyst
.
5% , .

,.
.
, .

Chronic pancreatitis

.
, .
, .
, .
, ( ).
.

chronic acute-
10%-20% - .
: , , , .
. , .
- Autoimmune Pancreatitis . entity-
IgG4- . .
- : SPINK1- .PRSS1-

- Idiopathic chronic pancreatitis .cystic fibrosis- .
( CFTR- ,)CF- CF , ' ,sweat test-
.
40% -.
( )
- , , plugs
. .
.
- .
<- <- , .
- Necrosis-Fibrosis acute pancreatitis
. .
TGF-beta1 ,IL-8 : <- PDGF- <-
, .

( , ,),
.
, .
.intraluminal concretions
- , .
.

- , .
" , , .
.celiac plexus-
( ) .
," , .
" , , .Oddi
, :malabsorption ,hypoalbuminemia
,steatorrhea ,K . .
50% 20-25 .
, 40% .

Autoimmune chronic pancreatitis

.
,22IgG4- .
( ) , .55
.primary sclerosing cholangitis ,Sjorgen's

.
- .
, , -
.
.
Chronic Pancreatitis
- Pleural effusion .


pancreatic pseudocyst
Pancreatic Pseudocyst
, .
, .
75% pseudocyst
.
pseudocyst- (
) . .
pancreatitis .
, , . ,
, omentum- .
,
( -),
,
<- .

22 IgG4- .

Pancreatic Cystic Tumors

25% .
, .

)Intraductal Papillary Mucinous Neoplasms (IPMN

.2000 , ( mucinous neoplasm).

main duct- , .
.
, , .
.50-60
Peutz-Jegher syndrome.Familial Adenomatous Polyposis-
, .GI tract-
.

.
- , (.)38%-50%
adenoma borderline tumor <- lowgrade dysplasia = carcinoma in situ
.high grade dysplasia

- Ductal Type ,
- Colloid Type .
, . :
colloid type carcinoma .
( )
, , ,.
65%-75% .
.
,pancreatitis ,
.

,
.
, , .
, .
Mucinous Cystic Neoplasms
,2000 IPMN- .
:
IPMN ,
MCN .
MCN ,
.
.
mucinous cyst-.
-
ductal carcinoma .

MCN .
.

.

Solid Pseudopapillary Tumor ,Serous Cystadenoma

.
Solid pseudopapillary tumor . .
Serous Cystadenoma , ,60 (
).

Pancreatic cancer

,ductal carcinoma ,
5 .5%-
,
( .)2
+60.
.
chronic pancreatitis- -
sporadic pancreatitis- .

"" ,
Peutz-Jegher ,BRCA2.
Preneoplastic Lesions 3
- IPMN
- Mucinous cystic neoplasm , .
- Pancreatic intraepithelial neoplasia ,
.

.

Pancreatic intraepithelial neoplasma- .

K-ras 90%-,
p16- ,
SMADA- 55%-.
P53 50-70%-.

60% , .
20% , .

,ductal carcinoma .colloid carcinoma

, ( )desmoplastic , ,
( perineural ) .
.


<- .
.
, - , , , .
, , .
( ) ."Trousseau sign" - migratory thrombophlebitis ,
10%- ,
( thrombophlebitis ) .
- Courvoisier Gallbladder . ,,
.

, .
, CEA ,alkaline phosphatase
.
screening-
.
. 1-"
,CT- .
- .carcinoma in situ
miRNA / .

, " wide
genomic analysis
.
.
10
!
( ) .
.

 ' ( )31

" .
.soft tissue & connective tissue tumors
- , , () ,.
," 2% " - ".
, . 15-16
.

.
. . , /.
. , (
) . .
. - , , .
Hemangioma
.
.
Teratoma
.
" midline , .
, .

,10 .
, .
, ,
.
-

- Wilms tumor .
.hepato-cellular carcinoma ,
Rhabdomyosarcoma .

Neuroblastic Tumors

- neural crest .
( ,)40% ( 25% 15%-)
, .
NC- , .ganglia cells ,chromaffin cells ,satellite

.
, .
- .
- .
18 - cutoff- .

-" .1:700
1%-2%
germline mutation .anaplastic lymphoma kinase - ALK
.
.Gain of Function

-" , .
- ,,
, , .

- Raccoon Eyes ,periorbital spaces- .

- Blueberry Muffin Baby
,
.Langerhans cells histiocytosis -
- ".
- .

poorly differentiated .1 :

.
neuropil - .
.karyorrhexis-
.
- Undifferentiated = small round blue cell tumor .2 , neuropil.
LEMON
( Medulloblastoma ,Ewing ,Lymphoma ) SSC( Oat cell carcinoma ,
) .Neuroblastoma , .small round blue cell tumor -
.
Neuroblastoma ,
.
- ,neuroblastoma in situ .

Ganglioneuroblastoma, ganglioneuroma

.
,
.
.
50%- <- .neuroblastoma
50%- <- .
, .

Staging
- Stage 1 , .
.
- Stage 2 , .
- Stage 3 ,midline- . .
- Stage 4 , , ,.
) - Stage 4S (special (
) , , -,
... .

Very low
Low
Intermediate
High


- , 18 5 , 5

.
children's oncology group- .
" .
very low risk-
.
- Shimada histopathological index .

Schwannian
.Stroma rich
50%- ,
( )nodules , .

50%-
- MKI Mitosis-karyorrhexis index turnover .


, .
.
( N-myc
.)2
neuroblastoma (
).
hyperdiploid .triploid-
N-myc
.double minutes -
homogenously staining region
.
2 .

- risk groups .
3

9000 stage .
"" .
myc-amplified tumor ( .)50%-
.
mitigating factor :amplified Myc- , ( LDH ) , -
turnover , .
, stage 4- myc amplified " ,
.93%
Stage , .

)Wilms Tumor (nephroblastoma

.
, - 8-9- . 13-
, " ( ).
.

- 5%-10% /
, - .
, .
, ,
( )synchronous (.)metachronous
.high-risk

" , - ".
- .
, -

.
" " .
.

, .
.
3 ( )
- blastema ;
;
()

, , ( ) , , ,.
- " .
Anaplasia
.
Wilms tumor-
""
( 3 ),
- multipolar polyploid mitotic figures .
.
.
10%- , .favorable histology
.
,
,
, ,
.

.

 Wilms tumour
WAGR syndrome
( Wilms tumor )( Aniridia , )mental ,Genital Anomalies ,
.Retardation
4 , .
germline deletion WT1 PAX6- - 11p13 .
, .
" "2nd hit , biallelic disturbance WT1-
WT1 .Wilms , , .
.mRNAs
.aniridia ,ambiguous genitalia
WT1- 4 , , +KTS variant--KTS -
.variant ,splicing " .
+KTS 3" ,
( -KTS- , ).
Denys-Drash Syndrome
WT1 ,
gain of function .
splice variants- . ,
.
, .
- Male pseudohermaphroditism :
,
,diffuse mesangial sclerosis
90% Wilms tumor ( gonadoblastoma ).
- dominant-negative missense mutation WT1-
, 2nd hit- WT1 .Wilms
Frasier Syndrome
WT1 , WT1 .-KTS
+KTS- , , .-KTS
,male pseudohermaphroditism .
Wilms .gonadoblastoma
Beckwith-Wiedemann/Hemihypertrophy Syndrome
overgrowth- .
- Organomegaly , (.)macroglossia
.hemihypertrophy -
midline- , .omphalocoele-
cytomegaly , .
Wilms ( , , ).
.

11p15 .
.)Wilms Tumor 2( tumorigenesis-
,IGF2- .
BW- ,IGF2 ( loss of imprinting )
( uniparental disomy ).
.
: Wilms , .

Nephrogenic Rests

precursor lesion - " .Wilms

loss of imprinting , .
," .
40%- -.
<- bilateral Wilms ,Nephrogenic Rests
.

( ) <- 85% .
,Diffuse Anaplasia
.
, ,,
, ' .
, ( )adriamycin
.

 ' ( )39

, .
5.
- ().

, - 2
, , 2 " ".
".
.
--
<- releasing factor
<- )Adrenocorticotropic Hormone) ACTH
.zona fascicula & reticularis- ACTH
.
- !

1" 90% .
.
3
Zona Glomerulosa

, 15% .
.
(.)aldosterone
Zona Fasciculata
70%-80% .
,
.
Zona Reticularis
.
, .lipofuscin
() .

Chromaffin
,
.


Hyperadrenalism23
Hypercortisolism - Cushing Syndrome

- .Zona Fasciculata-

, , Cushing.

ACTH .
/ACTH.

Iatrogenic/
, .
- .
zona glomerulosa- ACTH .
Pituitary Cushing Syndrome
- 70%-80% ' .
- " ,anterior pituitary-
.
ACTH , .
, .
, , , .
zona reticularis & fasciculata-.
100!
Paraneoplastic Cushing Syndome
10% cushing-.
" small cell lung carcinoma .ACTH
- .
.
- 40-50 .
.
.

" ACTH
.ACTH-
,
.
.
( Cushing )
( ,)moon face hump ,
,
( hirsutism ),
,
( cutaneous stria ),
, , .
Cushing
( 24) ,
.
, ( dexamethasone )
, .
23 .

Dexamethasone secretion test

, <- ACTH.
<- Pituitary Cushing syndrome ACTH ,
, .
Dexamethasone , ACTH- .
,Ectopic ACTH production dexamethasone- ,
ACTH .
, ACTH ,
- .

<- pituitary Cushing ACTH-
, ACTH
.
<- ACTH-
<- .ACTH
<- .ACTH-

Hyperaldosteronism

.zona glomerulosa-

( ),
( ).
, , " , .

) = Aldosterone producing Adenoma (Aldosteronoma Conn

.
.
" , .
<-
- .
.
- ( ) , 2-
".
"
.
.
.
Spironolactone-
Spironolactone bodies
( ).
, .

.
( ) ,
( ,)CHF ,.

Androgenital Syndrome

.Zona Reticularis-
congenital- () .

Congenital Adrenal Hyperplasia

.
"" <- <- sex steroids
.
"" , .
. .
,21-Hydroxylase
90% .
,1:13,000 ,1:120
, .6
: , ,
.
shunting
.
<- "" .
<- .
non-classic .late onset
, .
21-hydroxylase-

Simple Virilizing Syndrome

,
,
.
.ambiguous genitalia
, , puberty-
.

""
.
, .
hypoglycemia , ,
.

.
! .

Non-classic Adrenal Virilism

," .
, .
: , , ,
, .

Hypoadrenalism

.
: ( : ).
: .ACTH

Primary chronic hypoadrenalism - Addison's disease

.
( ,) dysgenesis ,
.CAH-
90%- , : , , .
.
, 90%- .

( ,)60%-70% :
- Type 1 , ,
. .21
- Type 2 ( )1 . .
, .
Addison's : , AIDS- . ,
. . , .acid-fast ,
.Addison's
- CMV- .
- , " " .
- , .
.

, ( ).
<- ACTH- melanocyte stimulating hormone -
MSH- .ACTH
, , , .
, , , " .
, .
.

Primary Acute Hypoadrenalism

( " ).
.


( 10%-)
<-
,
.

<- <- .
()
( ) , , ,
- .Waterhouse-Friderichsen syndrome
,Meningococcal meningitis streptococcal
meningitis .Pseudomonas-
.
.
, ,
.
" " , .
" .
.

Secondary Acute Hypoadrenalism

, , - .
<- ACTH .
Addison- , melanocyte
.stimulating hormone .

() 10%- .
(" )"functional neoplasm 10%
( functional).
, .
" ,
, .
, .

Adenocortical Adenoma

" 2.5-3" ," .

, .
- , .
.

Adrenocortical Carcinoma

1 1.7- , .
- .
10-20" , .
.
- .
- , ,
. .

( )Chromaffin.
"" , .Sustentacular Cells -
.Pheochromocytoma -
, multiple endocrine -
.neoplasm

Pheochromocytoma

.
.
" 90% , " ,
0.1-0.3%- ".
, " .
- .
, - .
.

,
.)sustentacular( supporting cells
.Zellballen
" ,"salt and pepper .
.
.
!
:
, .
.

.

sustentacular ,S-100
,
.

,
( )vanillylmandelic acid , .
- .
" "10-
10% -,
10% ,
10% ",
10% ( ),
10%
25% germline mutation 6-.

, .
10% .paraganglioma :
.
, - .
, , , - .

 ' ( )41-41

( ) - .
- - .
. PTH .
- Osteon ( .)haversian system
, . osteocytes . .

= woven bone
.
.
.
24
, .
,osteoid .
remodeling
.
,
.

.
.
( )osteoid (.)hydroxyapatite
!
Osteoclasts

.
.remodeling-

( ),
epiphyseal plate- .metaphysis
,
shaft- (.)diaphysis

24 ( )osteoblasts . .

.
100 .
, .
, , ,
.
.
.
, Ewing's Sarcoma
).t(11;22

- .
( 10-20 ).
metaphysis- .growth plate-
.
+40 osteosarcoma ,metastatic carcinoma ,chondrosarcoma
Paget's disease-.
Giant cell tumor of bone - young adults .20-50

,
giant cell tumor- .

, .
.
- 1# ,osteoid osteoma
.
- 2# . ,
. , .dull ache

metaphysis- .
giant cell tumor : ( chondroblastoma
) . growth plate
.

- chondrosarcoma, enchondroma .
chondrosarcoma
.

Enchondroma ( )
: , .
Osteosarcoma , ( ).
Ewing's Sarcoma / . .

 medulla-

3 " .Geographic ,Moth Eaten ,Permeated :

Permeated
- "
.
Geographic
, .
.
, ""
. .
, . ,
.
. ( ) ,
.
Moth-eaten
.,

Ewing's sarcoma
().
.
, ( osteoid ),
.
.
" .high-grade
,Howship's lacunae .

Cortex-
.
, .
!
Low grade benign .
,endosteum- . ,
.
"" . .
, .
.
,
- .Scalloped Cortex
. fibula-
.tibia-
- Fibrous dysplasia .

,
osteosarcoma periosteum- .soft tissue mass
.

osteosarcoma ewing's sarcoma- .
- Ewing's sarcoma (- )onion skin
.
. ,
. .
- Osteosarcoma ,spiculated
" " . -
periosteum ,
,
.
osteosarcoma- " - Codman
.
, "" .
.
! ,
.osteosarcoma
Matrix

,osteosarcoma -
enchondroma -.
.
, (
) .

- "osteo" , .
- Sarcoma

Osteoid Osteoma

,
,10-20
.
, <- .
, .
( ,).
, sclerosis ( nidus-).
osteoid-/ .
nidus
( )
( ).
- .
".
.

osteoma- , ,
.
.osteoclasts .

Osteoblastoma

osteoid osteoma ,
- 1",
,
",
.

Osteosarcoma

.
( ,)10-20 , .
,
- .
.
peak , Paget's disease25 .

.
- hereditary Retinoblastoma 1000 .
- .
- .
femur - tibia-.

, .osteoid
, .
.
periosteum- . Codman's trianglespiculated periosteal -
.new bone formation

( ) , ,
" .Codman
. growth plate-
.
- , - .
Codman's triangle- !

.
, , , <- osteoma
.
, .

25

Paget . , .


Osteochondroma

.
.
"" , , .
.
-
.
"" , .
, " , .
Multiple Hereditary Exostosis
exostosis .
- .
.

Enchondroma

.
osteochondroma- , = .En
.
, .
.
- , .
, .
, ( ) , ( ) .

Multiple Enchondromatosis

.
.
2 ( )Ollier, Maffucci .
- lobule , .

Chondroblastoma + Chondromyxoid fibroma

.
Chondroblastoma .giant cell tumor-

Chondrosarcoma

, .osteosarcoma
.
.40
chondrosarcoma enchondroma- ( low
,)grade .
, .
- Low grade sarcoma of bone , , . ,
.
, . , , , .

.
() - , ,osteoarthritis-
.
.
.

( ),
," ,
" scalloping : .
, .
.
, , . ,scalloping
.

.
wide excision ,
.

- Grade 1 5 year survival- .90%

.
43% - Grade 3 5- .
- Grade 1 - Grade 2 , , ,
- grade 3 .
,
.

Ewing's Sarcoma

, .osteosarcoma
" ) t(11;22 .EWS-FLI-1
, , .
.small round blue cells
,primitive neutral tumor , .
- 10-20 , .osteosarcoma
.
,
,.
Ewing- : ,pelvis , .
-! periosteum- ,onion skin ,
spiculated .
, ,osteosarcoma osteosarcoma-
( osteomyelitis ) : , , , . osteomyelitis ,
Ewing's , .
,X-ray- ( ) ,
, .soft tissue mass .

.small round blue-cell tumor

,H&E- .CLL-
.
, , small blue round cell
.

,osteosarcoma- .
.
65%-.

Giant Cell Tumor of Bone

.
<- 20-40 ,
( ).
, , ( ).
.mononuclear stromal cell
giant cells- feature , - , .
.
.
- .
, ,
.
, .
giant cell tumor .
, .
,malignant giant cell tumor .

giant cells-
-.
hyperthyroidism .
, , .
, , .
.
.


- epiphysis- . , benign ."
,eccentric . , .
" , .

Fibrous cortical defect & non-ossifying Fibroma

.
fibroma fibrous cortical defect- ( 5-6 -" ).
( 30%-50%- ,)!Robbins
.
, :self-limiting- .
.
, , scalloped
. .scalloped = lobular

:storiform
, "".
-.
giant cell tumor-
,
,
mononuclear stromal cells
,
.

Fibrous Dysplasia

" , .
, .skeletal stem cells
(.)chinese figures
curved woven bone- .
,-.
, .

-
(,)monoostotic
,polyostotic -
+ polyostotic ( + )Caf au lait spots (
" ).
,proximal femur & tibia- ( ) ,.
swelling/deformity - , .
: , .
""Ground Glass

, .

, .fibrous dysplasia-
- , Shepherd's Crook
.Deformity , .

, :
,
,
,
,

,
.
.
,blastic ("
).

 ' ( )41-40

( - )Shunt ( ) .
shunts : foramen ovale- .ductus arteriosus-
, . , shunts-
( ) . ,
.

( - )obstruction .
. , . ,
.

- ( ) . - volume hypertrophy
, - pressure hypertrophy . ,
, .

- Endocardial fibroelastosis
.

- Jet Lesion , .
nidus.infectious endocarditis-

( - )cyanosis 5- 100/" . .
2-:

 - . ,
, . .
. . .
- .extremities-
. , .
-
- Hypertrophic Osteoarthropathy :
o .
o ,
clubbing o .
o . .
.
H.O. o ,CHD : ,
,bronchiectasis .
- Polycythemia - Increased RBC count . .
2-:
- ,low PO2 , , .
.
, .
polycythemia vera - .


- Left-to-Right shunts .1 . , , .
- Right-to-Left shunts .2 .
- Obstructive lesions .3 .

Left-to-Right Shunts
, . 3-:
- Atrial Septal Defect (ASD) .1 .
- Ventricular Septal Defect (VSD) .2 .
- Patent Ductus Arteriosus (PDA) .3 .
.

/ ! right atrium- ,
morphologically right atrium- .
- , '.

,vena cava-
coronary sinus- vena cava
.
,Fossa Ovalis " :septa 2
- Septum Primum .1 inferior vena cava- .valve
.2 , septum primum- -
Septum Secundum .
(
hypoxic vasoconstriction )
. , , ,
,
.
- Ostium Secundum foramen ovale- .
,Ostium Primum ,
" .endocardial cushions-
septum primum- " septum secundum-
.
ASD
- ASD I - ostium primum- , .
- ASD II - osteum secundum- .

ASD type II

foramen ovale- .septum primum-

,
.
, 25%-
, .
ASD <- patent foramen ovale.

, .
= Paradoxical Embolism
septum primum- .

Pulmonary hypertension ,silicosis ,COPD :" . ,
DVT , : , , .
.paradoxical embolism .
ASD type II- ( )
, ,
<- .
, .
: " "
, , . .
,
.

- .
, , ,
< , . ,ASD- , , <- 40
- Eisenmerger Syndrome L-t-R shunt R-t-L shunt- .

ASD type I

, ASD type II- ,

" , .mitral regurgitation-
, volume hypertrophy .
,
.
, .
endocardial cushions- .ostium primum-
persistent AV canal .

VSD

, - chordae tendinae
, .pulmonary artery- outflow- .
,infundibulum- .
, - () .
. - ,
. . 3
.
, " .

,
,
.
VSD-

, , ,
, .
, , " ".

VSD
.
, , ,
.
volume hypertrophy , ,
, pressure hypertrophy- .
ASD- "" ,
volume hypertrophy .

Eisenmenger Syndrome

.
.
, .
VSD- , , ASD-
.
.

Roger

, .
, , .
- ,CHF- , ,
.
- jet lesion - .
.

Common Persistent AV canal

ASD primum ostium .

, atrioventricular canal , "
endocardial cushions .
AV canal- , ,
.
L-t-R shunt- ,
.

Patent Ductus Arteriosus

DA-
.
.
, 2/3 ,
.
<- <-
<- ( ).
.DA-
DA- ,
.

PDA
DA- " ,
DA- ( ) - ,
.
DA
DA <- .
DA "" <- .

<- <- <- .
, volume hypertrophy , ,
( ).
, , -
. ,machinery murmure
( ).

- jet lesion .
.
- .
pressure hypertrophy , - Eisenmenger Syndrome :
.
, ductus arteriosus-
. .

Right to Left Shunts

Tetralogy of Fallot .
Transposition of Great Arteries
Truncus Arteriosus
Tricuspid Atresia

Tetralogy of Fallot
4
- Pulmonary outflow obstruction .1 .
VSD .2 ,
- Overriding Aorta .3 ,VSD- .
- Right Ventricular Hypertrophy .4 .

infundibulum- , outflow-
, .
, VSD "" .
, .
, .
, .
, pressure hypertrophy .
, .
- ,

,
(.)"pink" Fallot
.
, clubbing ,-
,polycythemia .

, ,
:
, (
).

.pulmonary stenosis-
.12
,paradoxical embolization : ,
, . ,
.

Transposition of Great Arteries

, . . ,
, , .
( )AV ,
,AV- .
TGA ! :
- Simple/Complete transposition
.
shunts- , 2
: ,
.
.
, . , ,
- :
,
.

.1 ( )
.2
.3 , .

Viscero-atrial
= S-solitus ,
= I-invertus ,.
ventricular loop-
D-loop ,
= L-loop ,.
- .transposition
.
- D-malposition (
),
L-malposition .

Truncus Arteriosus

: .
- , 2 6-,
.
-
- , ,
CHF .
, - , .

, " .
, .

Tricuspid Atresia

.
- ASD( VSD- ).
, , .
- .
, . ,
...

 - Obstructive Lesions .
- Coarctation of Aorta 2 :
- Post ductal .1 () .ductus arteriosus- . "
.
, .
. " , " .
, " . "
" , intercostal arteries- .internal thoracic artery-
, .
- Pre-ductal/infantile .2 , ,
. right ventricular hypertrophy ,
. .
.hypoplastic left heart

Hypoplastic Left Heart

.
, <- , .
, .
, .
- .

Aortic Stenosis

,
.pressure hypertrophy
3-
, .

.
,
.
, ,
.

Pulmonic Stenosis

," .
, , ,
.

Cardiomyopathies

, .cardiomyopathies
.
.
- .
- , .vasculitis

- Dilated Cardiomyopathy , , ,
" . .
- Hypertrophyic Cardiomyopathy .
- Restrictive Cardiomyopathy , / ,
. ,
.
, .

Hypertrophyic Cardiomyopathy

.
,
, ,outflow tractx-
.
.
outflow tract- , .

, , .
( ) ,
.
stroke volume- , <- ,
, , .
1"!

.
- .
. thrombi
.

.
, ,beta-myosin heavy-chainmyosin binding proteins ,
.
,Fabry's disease .
.

Dilated Cardiomyopathy

, .
, ,
.
, .
, ' ,embolism-
.
, .

- .
, .
, ,
.

30%- ,
( ,)desmin ,titin ,dystrophin
-
.
15%-20%- , . ,
PCR coxsackie .
.
:( adriamycin ,).
Post-partum .
,dilated cardiomyopathy- hypertrophic cardiomyopathy-
( , ).

ARVD Arrhythmogenic Right Ventricular Dysplasia

, - DCM
.
,
.
ARVD- " , ..
, .
, , .
,ARVD . ,
.

, ' , , CHF.

.desmoglein-2 ,desmoplakin :

Ventricular Noncompaction

, , .

looping ,
,
- compaction .
.
compaction - ,
. ,
, .

- ( ) , ,hydrops fetalis- .
- .
- , , thromboemboli
,trabeculated .

,DCM/HCM entity
.
,
.

 ' ( )43-44

Melanotic Lesions

Neural Crest- , .
, , , retina, choroid, iris-,
, .
8 .
( ).

( - )melanin .
, , . ,
.
1 4- 1 10- .
, ,
.

- Eumelanin .1 , .
- Pheomelanin .2 '' , .

, (.)UV
,UVA ,10:00-14:00 9:00- 16:00 .
<- .
, .

.
:
- nevus , - melanoma .

squamous cell carcinoma ,basal cell carcinoma- angiosarcoma
.
- .
, . ,
.
- Nevus : ,
.Melanoma -

Melanoma

.

.
.
- 75%- .
, ( = .)50

, .
, .
" " - , .
50%-80% , precursor lesion.

 , Nevus-
nevi <- .
25-.
nevus , nevi ,
.

Nevus

,
nevus
nevus ,
nevi <- .
5-" , 1 -" 20
" .

Junctional , .
""/ .
Intradermal , dermis- .
- Compound ..

Robbins-
nevi- , .
junctional nevus-
, .
, juctional nevi- , .compound nevi
, ,
.intradermal nevus nevi , junctional nevi-
.

 dermoepidermal junction-
""
nevi- , ,
nevi- , ( ) , cords- .
"" , ()fascicles
( ).

Congenital Nevus

.
Nevus ! nevus.
, .

Blue Nevus

( ).
.
() , .
,dermis- .junctional
, , , ,
.

Halo Nevus

.
," ,multiple lesion .
- .
' .
, .
.
, ,
.
!

Spitz Nevus

, 0.5-".
.
, .
( )Spitz juvenile melanoma .

, .
, 15 , .
.Spitzoid tumor :

Atypical Spitzoid Tumor

.

,10
1",
,
, score .
<- sentinel lymph node-
.
<- - ,20-30
.

.1 - , , - .
.2
- .
- .
.3 - Pagetoid intraepidermal growth
.
.4 - .
.
, , . !
.5 !
, , nevoid melanoma-
.

Dysplastic Nevus Syndrome

" Clark :
nevus- ,
. , .
BK nevus" 2 .

7%-20% (?),
10%-15% ,

- " ,
( ),
.
<- <- .
.

( compound +) - shoulder phenomenon
.
, ,lamellar fibroplasia rete ridges- .
(.)confluence
.
= . ! (
) , .

.
tumor suppressor gene- )P16( CDKN2A ,9p21 Major Melanoma
Gene ( ,
).
, .
.cell cycle-
, germline mutation" deletion
.
56% ,59 .

Melanoma

- 65% . .
Blistering sunburns 20 .
.
, '' - .
.
Dysplastic Nevus Syndrome
- Giant Nevus .
25
P16-

)A
)B
)C - - / , ,

)D 6-"
)E - , , ,
pigmented .

.
. !


- , 56%- nevus -
41% nevus . , " " -
.precursor lesion
- Pagetoid Spreading .
, .



.
( " , 0.7-" , 0.5-" - .
" - .
.
, ,in situ .
, .
Ulceration + Mitoses
.
10% .

.
<- .
,
" .
, ( )Acral .
( ) , .
, .
.

5%-15% - Lentigo Maligna . , ,
.melanoma in situ- .
15%-35% - Nodular , ,
. .
5%-10% - Acral Melanoma . ,
, . .
, ,acral-
, .nevus
.
50%-75% - Superficial Spreading -
. = .
- , , .vulva- .

9% .
.
, .
, .
, ,
.

-
.
.Actinic Keratosis <-
, .
.
- , .
, ( ).
, squamous cell carcinoma-.

 ( )

)Seborrheic Keratoses (S.K.

,
- .
" ( .)40
, .
S.K. ,epidermal growth factor ( -transforming
.)growth factor
Paraneoplastic Syndrome
.
.Leser-Trlat Sign
, , .SK-

Squamous Cell Carcinoma

,
.basal cell carcinoma-
.
5% SCC .
, .well differentiated
SCC , 40%- ,
.

- .SCC
,.
- Marjolin's ulcer ( osteomyelitis
).

- Xeroderma Pigmentosum .)Nucleotide Excision Repair( DNA
, . .

Squamous Cell Carcinoma in situ

" basement membrane .

.Bowen's Disease
.

Invasive Squamous Cell Carcinoma

- Keratinizing , .
-Non-keratinizing .


Basal Cell Carcinoma

.
,
.
.
, .

-
,
,XP
.
<- BCC basal cell nevus syndrome -
, ' , ,' . .

, , ( palisading ) .
- .

Solid Type - . , , .
- Superficial Multifocal BCC- , BCC .
, . , 1"
, . 5" .
. ,rodent ulcer- .
- Morphea Type . . .

 - Chronic Inflammatory Dermatoses

Psoriasis

( 2%).
" .15-35
- ( )salmon color .
- Auspitz Sign <- .
- Koebner phenomena , .

, .
.
.
: - , , .
.

.
() - stratum corneum- 20-30
, , .

4-6 -.

- , .
: .
Pararkeratosis - ( , cornified
).
( .)stratum granulosum
, Acanthosis
, - .
Acanthosis- , -
( epidermal/rete ridges ).
, ( - dermal papaillae- )
- .thinning of suprapapillary plates
" ".
- ,
. acanthosis , , .
.auspitz sign-

( , ).
, .
- Kogoj spongiform pustule .
- Munro Microabscess parakeratotic stratum corneum-.

, , , ,
.

= 2%- ,
= 10% ,
= 10%- .
, .
,
.

10%-30%- .psoriatic arthritis -

. " , .

 Lupus ErythematosusDiscoid Lupus-

( SLE) - , - .
.Butterfly Erythema : ,
.Discoid Lupus

,
infundibulum- plugs .
.basal cell hydropic degeneration
.

,discoid lupus .SLE-

.
( lupus bound test) IgG .basement membrane-
.systemic lupus <-
.discoid lupus <-
( )
, .DL

Bullous Disease

( )Bullae.

Pemphigus

.
: ,
' .

- ( )adherens junctions .Desmosomes -

- Acantholysis , .

,Cadherins
Desmoglin
type 1 ( desmoglin type 1 ).
type 3 ..

3 Pemphigus

Pemphigus vulgaris

80% - .
/ , .
, .
.
.
( ).
40-60 .
, :
suprabasal blister - acantholysis . 2 ,
, (
).
I.F.- - IgG .
pemphigus desmoglin type 3- .

Pemphigus Vegetans

,
acanthosis , .
.
.

Pemphigus Foliaceus

,
( ).
"" ( ) , .
crusts- , <- ,-
desmoglin type 1 . .
.
.
,pemphigus vulgaris- IgG .

 ( )resident
Mycosis Fungoides

T.
.
.40
.
.
" .
,erythroderma , .
- Sezary Syndrome .
, UV .
, . .

,T" helper , .
Sezary Lutzner cells , .
Pautrier Microabscess , -.
.

Panniculitis
- , .

Erythema Nodosum

.
" .

beta-hemolytic Strep.
.
,IBD , , .
.
() , subacute .

.
, subacute .
-.
PCR- .

Erythema Induratum

.
.
: .
.
.
,vasculitis - .
, .
, ( ).

 ' ( )53

4 . 4-5" .
130".
: 12 , ,
.

- - .

- Chief cells .1
- Clear cells .2
- Oxyphil cells .3
, .
. , .

.PTH - parathyroid hormone
, " " .
<- .PTH
PTH
<-
<-
D calcitriol- , ' <-
PTH .
. , .

Hyperparathyroidism

- ,
" . .
- .

" , .
."Painful bones, renal stones, abdominal groans and psychic moans" :
3
- Osteoporosis .1
- Osteitis Fibrosa Cystica .2 . ,
. .
:'20- 20" .
.
- "Brown Tumor" .3 ( ) . .
, . , tumor-like proliferation
. PTH .
- " . ,
. ,
.
- , .
- , - .

PTH , , .

- 75%-80%
primary hyperplasia - 10%-15%
parathyroid carcinoma - 5%

Parathyroid Adenoma

solitary lesion .
, .
- 26 ( 6-8") .
ring , .
,chief cells- .oxyphilc cells
, !
- .

Primary Parathyroid Hyperplasia

4 , 1-1.5".
, .
, - .
- 3.5 ,
.

2-
- 95% .
- 5% - Multiple Endocrine Neoplasia (MEN) Syndrome ,
. ,
.

)Multiple Endocrine Neoplasia (MEN

26

2 ,MEN .
.
- MEN2 ,
.
- . .
" (
) , .
. ,

.

4-5"

Parathyroid Carcinoma

asymptomatic hyperparathyroidism- ,
,PTH- .
,PTH .
, .

, .
, , , , , .
" .
8 6 - = 8 7 , = 8 .
2 - :
- Local invasion .1 ,
- Metastasis .2 , .

Secondary Hyperparathyroidism

- , .
<- <- PTH , <- ,
.
, .
.
Secondary hyperplasia ,primary .

"
.bone anomalies ,
: .
ischemic ulcers- .Calciphylaxis Cutis
secondary hyperparathyroidism - . ,
.

Malignancy-Associated Hypercalcemia

= , .
<-
!
2
- Paraneoplastic Syndrome .1 ,PTH related protein .PTH-
PTH .
- Osteolytic Metastases .2 . :
, , , , multiple myeloma- .

Hypoparathyroidism
.1
.2
.3
.4

- . .
, .
. , - .

Familial Hypoparathyroidism
Idiopathic Hypoparathyroidism

<- . .
-Trousseau sign " .
- Chvostek Sign . .
:
Neuropsychiatric manifestations

Papilledema, cataract
Cardiovascular manifestation
- Dental abnormalities

 ' ( )53-54

, - ,"
.
.
) - Fine Needle Aspiration (FNA .
screening-' .
, .
, .
<- .
. recurrent -
laryngeal nerve . ,
.

(" - )follicles" ,
= .thyrocytes
. ,
,follicle- - .
( -
) .
,
.
.calcitonin
, .
.

(.)Thyroglobulin
( )T4 , T3-
.
, (" ) T3-"
, . T4
.
T3 T4- , ,
, .
, .basal metabolic rate-
T4 T3 ( ) T4 , T3- T3 -
nuclear receptor .

, (" ) , ( 20
).
,
.
" -
T3, T4 , Thyrotropin
) ,Releasing Hormone (TRH Thyroid
) Stimulating Hormone (TSH T3
,T4- .
TSH .


- Euthyroidism .
Hyperthyroidism (=Thyrotoxicosis)
Myxedema <- Hypothyroidism (=Myxedema) .
3-
.1 ( ).
.2
.3

Euthyroidism- Goiter
Endemic Goiter .1
- 27" , ,,
- .
.
, .
: <- TSH <- <-
. ' ,
.

Sporadic Goiter .2
.nontoxic diffuse goiter ,
: ,
, , .
. , .

- , :
.
.
2
.1 - . <- T3, T4 <- TSH- <-
, <- ,
<- <- .pressure atrophy
- Colloid Involution .2 .
.

27

P.O. .

: ,Robbins "" 81%- .endemic goiter-

Multinodular Goiter

, .euthyroidism
- - .
: .colloid involution
,TSH- , uneven <-
follicular hyperplasia.
, <- <- <-
. , , .
, , , ,
. .
, 700 . , .
, . ' , .
- : , , .
, .
- ,PO
.

Hyperthyroidism

, , ++ <- ++
T3+T4
TSH .

3
Grave's Disease - Diffuse Toxic Hyperplasia .1
- Toxic Multinodular Goiter .2
Toxic Adenoma .3

Grave's Disease = Diffuse Toxic Hyperplasia

, ""
.
1:10 ,
.
2%- ".

, .
.

, T-helper B.
B , .anti-TSH receptor antibodies
.
, .
.
TSH-r- , T-
.

30 , 300 .
, <- .
'.
, .
,goiter Infiltrative opthalmopathy , .infiltrative dermopathy-
, Grave's disease- . .


, ,goiter ,exopthalmus ,
.Ophthalmopathy " .T
Grave's Disease . , .20-40
40 apathetic hyperthyroidism .
, .toxic multinodular goiter

Dermopathy
10%-20%-.
Pretibial Myxedema
Myxedema ,Hypothyroidism- .
, , : .
.
- , .
, -
GAGs , .

Ophthalmopathy
- Exophthalmos , .
.extra-ocular-
- T .
.
- / /
. , .
, .

Grave's
, : " - ,,
. . ",
.
, . , ,
. , - Grave's disease
.

( - )thiouracil .
6- , , , .
.

Hypothyroidism
Cretinism

"" -
.
, .
: 4 ,
, , - .myxedema
, ,
.
,T3, T4 TSH .

-
,
.
.
,CNS-
. .

.

2
.1 - , .
.2 inborn errors of metabolism - , .

)Postsurgical Hypothyroidism (myxedema

myxedema- GAGs ,
( ).
- ECM- .
, , <-
.
( 40- ) , . "",
.
: .
,ECM- ECM- , myxedema-
.

.
( ) .
, . .Myxedema coma
: , ( ) , ,
.
, , . 20-
' . ,IV T3 . T3-
.

Hashimoto Thyroiditis

.
, .6
, Sjorgen's syndrome ,SLE.
Grave's .
Grave's Disease- .TSH-
, , .

<- Thelper <- B <- ,

.T-killer
Grave's Disease- T-helper B , .T-killer

.
, .
, , , ,
.thyroiditis , Grave's .T
, , .Hashitoxicosis

.
, germinal centers.
, .oxyphilic metaplasia-
, .
, ' . , , .
, ,
. .
'

) - Oxyphilic (Hurthle Cell .
- Metaplasia . .cherry-red nucleus ,

40% .

( ) , .
. ,
TSH , .

: . .
euthyroidism .
.
. .

( .)SLE
, .
, .


90% solitary nodules- .
/
.1 () , .multinodular goiter
.2 - .
.3 , .
.4 - . Hodgkin's Disease
.' ,
.
.5 , . .
. .
(" ,)"hot nodule . , ,
"" . , FNA .
. , ,frozen section .
, .
:

Follicular Adenoma

, .
.
(" ") , toxic adenomas
.
, - : , .

.

- Microfollicular ,
- macrofollicular ,
- Hurthle cell adenoma .Hurthle
- .
, .
: , . , .
, .
FNA
FNA- .
.
.

<- lobectomy , , .

:
4 () :
75%-85% - Papillary Carcinoma .1
10%-20% - Follicular Carcinoma .2
5% - Medullary Carcinoma .3
<5% - Anaplastic Carcinoma .4

Papillary Carcinoma

.
, ,20-30 ( ) . 2-3 .
rearrangements ,thyrosine kinase receptors RAS-
,BRAF- .

.
, , , , , - " ".
, ' .

.

,
.
" " - , .
.
, .
. , ,
. .
psammoma bodies - .
, " " , .

.
,lamin- ,nuclear lamina-
. ("") , . .
, , . .
.empty nuclei -
( ,)ground glass nuclei Orphan Annie
"."eyes
, Grave's
.

( ).
,
, .
. , nuclear
.pseudoinclusions
viral
.inclusions
: , ( grooves) .nuclear pseudoinclusions

Papillary Carcinoma, Follicular Variant

. .
, , .
.

50%- .
, .lymph node dissection
.
- psammoma bodies .
( 10%-15%) , .
95% 10 .
:
, .
45
4-"
,extrathyroidal extension -

Follicular Carcinoma

.40-50
, multinodular goiter .
( .)RAS-
progression . ,
.
- , -
.

, follicular adenoma : ,
.
,papillary carcinoma-
, .
2
- Minimally Invasive FC ( - )90% ,
.
- Widely Invasive FC . ...
(.)25%-40%

Medullary Carcinoma

.
, = parafollicular- C (
- .)PTH-
.
( ).
" "
VIP - . .
.
, lymph node
,dissection .

( .)80% ,40-50 .
, :
)1 ( MEN2 ) .
. ,20-40 .
MEN2 .C precursor -
lesion ,medullary carcinoma- .precancerous lesions
)2 non-MEN familial medullary carcinoma -
. .50-60

familial .RET protooncogen-

MEN2-
.

( ).
" " ,
...

follicular adenoma- ( ).
.
-
. , congo red- .
EM , .
MC
- 40%-60% 10-.
- , , .
30%-50% 10-.

Anaplastic Carcinoma

.
" .
( 5% ) , goiter.
- .
,debulking .

, , .jugular vein-
multinodular goiter ,recurrent laryngeal nerve- -.
, .

( ) , .
.
, , , ...
.
, poorly differentiated ,
.papillary carcinoma
.
Parathyroid carcinoma , . , follicular -
adenoma .

 ' ( )55-56

, .

- hydroxyapatite .
, , ,.
- 30%
- ( osteoblasts , ,osteocytes ,)osteocytes-osteoclasts-
.
1 .
- Osteocalcin , .

().
, -
bone morphogenic factor.bone binding factor a1-
, -.
3 :
,
lining cells ,
.

" .
,
.canaliculi .

alkaline phosphatase . ,AP

. ,
AP.
,mononuclear phagocytic system- , .
, 6-12 .
.
Howship's Lacuna . .
, remodeling-
() .

" . .
signaling pathways 2 ,
.
pathway receptor activator for nuclear factor - RANK
.Kappa Beta Rank-ligand -
RANK ,
. pathway- "

,osteoprotegerin RANK-L RANK-"
. " beta-catenin
,
.osteoprotegerin
Macrophage specific stimulating
) factor (M-CSF
.
. . multicellular/bone--
, forming unit . ,
, GF-

 . remodeling . osteons- haversian -

.system
Turnover
10%- .
.
,PTH ,D - .
turnover-
,
remodeling .
40- , .0.7%-
.
, 50%- .30
, , .

.

,
- lamellar bone .
.
Woven Bone
.
, .
, .
woven bone , . appositional growth-.
, = Osteoid .
. .
.
, .
: , , ,
, .
Cement line
"" .
remodeling , ,
. , .
.

" .woven bone
. ""
. ,
? .
.

Osteomyelitis

.
3
- Pyogenic OM .1
- Tuberculous OM .2
- Skeletal Syphilis .3

Pyogenic OM

,Staph. aureus 80%-90%!

.
Pseudomonas ,E. coli : - Klebsiella- G.I. infections
.
, .
. H. influenzae GBS- Salmonella .
.
50%- !

.1 - . ' , ,
thrombi- . .
,
.
.2
.3

75% - , .
- .
, : , , ( ) ."
. .
2-
.1
.2 " ( )
, " " . .

,
.
, , ,
.
, .
,
.

. seeding- "
.
,
( Sequestrae .)sequestrum -
. , , . ,
.
, . , .
.
- , , .
- .

Involucrum
- .

,
- ,
.
- . ,
.
.
Brodie's Abscess
" , -
.trabecular bone
" .
.
! sanctuary
.

Chronic OM

.
- , . " , .
.)fever of unknown origin( FUO-
, . ,
.chronic OM
, bone biopsy
. .

Chronic Sclerosing/Garre/Nonsupporative

Chronic OM
.
.
,
.

" , , , .

,debridement .
5%-10%- .
, .

OM
- Sepsis .1 .
- Endocarditis .2 .septic emboli
- Septic or supporative arthritis .3 .
.
.4 , - .
.Ankylosis /
.
.5 - , .
.6 - woven bone , .
.
.7 - Fistula , ,
/ . . .
.

 . . ,
, . ,Pseudoepitheliomatous hyperplasia -
.Squamous cell carcinoma
.8 -
( 0.5% 20) .squamous cell carcinoma

Pseudoepitheliomatous Hyperplasia

, .
, SCC
.
SCC- .

Tuberculous Osteomyelitis

1%-3%- .
.pyogenic OM-
, , ,
.
- .
.

- , , , , .
- .

.Miliary seeding - , .
, , .

,
. ." .
, .

, , .

.central caseating necrosis-
- , palisading ,
, - . .
.
- Pyogenic OM- .
.ankylosis- .
TB Osteomyelitis
- TB arthritis .1
- Skin Sinuses .2 .
- Pott's Disease .3 .
. . .
kyphosis ankylosis- , . .
- Psoas abscess .4 Pott's disease .
TB" .
.5 - .

, , ,.
- Osteoporosis :.Paget's disease-

Osteopenias
.
,osteoporosis-
.
- Osteomalacia , .D
- Hyperparathyroidism .

Osteoporosis

.
, , porosity- , -
, .

,
- Localized Osteoporosis , ,
/ . .
, . , .
- Generalized Osteoporosis , (
).


,senile osteoporosis - Type 2 , .
- Type 1 ( .)40
- ,40
.
,immobilization : , .D
- - , , (
)
multiple myeloma
-
- gastrointestinal tract- , CD-

,osteogenesis imperfecta :

, .
" .

. 40 , .
, .
, :
"" , age-related .
, , .
60%-85% - " ,
. ,D
. , estrogen receptor-- TGF-1 . ,
lipoprotein receptor related protein-5 ,
. .
- . remodeling-
. , .
OP- . ,
, .

 - D .
. puberty- ,OP
.
- . ,
. 10-
, .
RANK-L ,osteoprogeterin- .RANK-L
.
" , ,
porosity- .

, , .
: , , .
, ,
pulmonary emboli- .
.
: .

, , . kyphosis
. ,
.
microfractures , .
.
.

, ( )30%-50% .
- .
,
10- .
" .
, .

,
.D

Paget's Disease of Bone

.
- .
, .

3
.1 - . , .
, 10-100 ( 6-12).
.2 -
. ,
woven .lamellar
.3 - inactive , ,
. . , .
.4
( ) , , .
- - irregular cement lines ,
- .

. , .
:
.1 paramyxovirus ,slow virus - .
Hyperresponsive osteoclasts .2
.3 ,18 . .

, , . - .radiolucent
- ( ) , -
.
( ,monostotic ) (.)polyostotic
: , ," ( ,) , ,
.
: osteoporosis circumscripta - ,
. , , " " .
.porous- . .
: , .porous

.
microfractures , .

foramina- , -
.
: ( Leonine Face - ).
. = .
, .
.arteriovenous shunts high output heart failure- .
1%- , .


Osteoarthritis

, .
, .
, , .

.osteoarthrosis
- ,
.
,50 .
90%- !80

Primary OA
.biological aging -
, " ".
Secondary OA
, .


.
: , overuse tennis elbow.
,congenital disease of bone : , (
28
osteomyelitis septic arthritis) ,
, ( gout
) , - rheumatoid arthritis- .


" " - ,
( ) , ( type 2) " decreased tensile strength.

. generalized disease , .
""
()TNF- ,IL-1

2.
.Chodrolysis .
, , - ""
, .

.
.OA susceptibility genes -
.OA

28 , . synovium ,
. .
, .


, - ,
.
- nests- .
-
.
eburnation -.
, .
- "joint mice"
.
. , .
, ,
.osteophytes
" .
, .
.fibrillation -
- Eburnation , , .
- ,
( )bone spurs -.

( ) - , , , .
interphalangeal- Heberden's Nodes -
[ Bouchard's nodes - !] . -
.carpometacarpal and tarsometatarsal

- ,
, .
, , . .
( crepitation ) , .
, ,
.

- OA- - .
.
- ( )
.

Rheumatoid Arthritis

,
- . , ,OA- ( )synovitis ( ).
, , ankylosis .
: , , , , ,GI tract ,.
.

1%- , 3- 5-.
, ( , -
.)...Autoimmune chronic pancreatitis
- .
, ().
.microbial arithrogen - ,
. .
EBV .

, <- CD4 <-
,RANK-L .
<- B clone B ,rheumatoid factor IgM
Fc portion- .IgG , "
( ) . autoantibody- ,anti-IgG IgM circulating
,immune complex .

- .
.
.
( )exudate .
,
. Pannus . ,
.
Pannus
( ) . ,
:
- .
subluxation -
- Extraarticular Synovitis ,

RA , OA-
.

rheumatoid nodules
25%-.
. .
palisading , . .
. nodules- ,
, ,.
( )
.
, -
.
,Peripheral neuropathy- ,
.


, , .
. .
( ) . ,
. , .
. , .
: Boutonniere .
- deformity proximal interphalangeal joint- extension- Swan-neck .
deformity .
- - .
,/ ( )
.

, .
3 , major criteria.minor criteria-
rheumatoid factor , 20%- .RF-
!RF
, - Cyclic Citrullinated Proteins :
. anti-CCP abs .
: .

.
: NSAIDs , ' . anti-TNF -
abs ( anti-TNF ).

 ' ' ( )57-59

'

2.5-4.5".
, :
- ( ) ,
. . .
.
, ( sex cords- ).
' - ( - coelomic
, .
, ) . .

3 : , .
50 . ,
200 .
- - , .

.
2:
.1 nonkeratinized , .
.2 - .
, .
Endocervix
,
Ectocervix
- .
speculum

.
- , .
cilia ,
. 3 : , .intercalated

- ,
- .primordial, primary, secondary, graafian :
corpus luteum
corpus albicans-.

, coelomic-
.

.

,
.

.

Ovarian Cysts

- Follicular cysts .1 , .
, . , .
" . ,
, . :" . -
US , . .
, ,
.
, 2 : .
.
.
Corpus luteum - Lutein cysts .2 . .
" , . -
, hemoperitoneum . "
. , , .
- Inclusion Cysts .3 ' . ,
. , .

.1
.2
.3
.4
.5

-
80% . .
.
3% . , ".
, .
, .
.
.

.Surface Epithelial Tumors29 - 65%-70% ,
90% , . .
15%-20% - Germ Cell Tumors - germ cells , ()3%-5%
" (.)0-25
- sex cord 5%-10% - Sex-Cord Stromal Tumors - ,
, .
5% - Metastatic Ovarian Tumors - , .
Malignant Tumors, NOS -

, ,
. squamous cell carcinoma ,.

= .
, = .borderline tumors
, , = stromal invasion- .

- , .
29 .coelom- , , .
. .
.

- Serous (tubal) tumors . .

, .
- Mucinous Tumors (
.)goblet
- Endometrioid Tumors .
- Clear cell tumors .
- Transitional tumors . .Brenner tumor -

, , , .
.Brenner

Serous Tumor

30% , .
60% 15% , 25%- .
( ") 40".
-" .unilocular ,
. .
( ,)glistening surface .
. ,
,"primary serous tumor of peritoneum" -
BRCA .

- -.
( nulliparous women ) ," .
( BRCA1&BRCA2- ) , , -
- BRCA1 20%-70% 70 .
2-
- Low Grade (well Differentiated) Carcinoma .1 . KRAS- .BRAF
, . borderline
.
- High Grade Carcinoma .2 ( p53- ) . ,
, . ,borderline .
" ".

, . , .
, . , .

.
, cilia .
, " .serous cystadenoma-
, serous cystadenofibroma
.

, .
,
.
- stratification
- -.
, . .
.
.
borderline , .
, , . .

Serous Carcinoma

- . , , .
- .
.
2/3 , . , ".

.
, , , - .borderline
, .
serous adenocarcinoma of ovary .
,psammoma bodies - ,
.
.
, . .

.

borderline- -
, ,borderline .
, .
sampling ,
( ,)implanting . implants-
borderline- ,borderline implants-
.
()stage 1
5-year survival - 100% borderline
70% .
( ) ,
90%- .borderline , ,
,implants- . .
, 25%- ...
.

Mucinous Tumors

.
25%-30% .
85% 10% , . 5% ,
2- , .
- . ,multicystic .
.
10- 66% - serous carcinoma.
, . .KRAS

- Mucinous cystadenoma ' . .

- Mucinous Borderline Tumor , , . mucinous
. serous- , ( 40"!!!)
. , . "
.
- Mucinous Cystadenocarcinoma , (
.)endocervix- Mucinous carcinoma .
!
5% " pseudomyxoma peritonei
.

, ,
' .
, , .
.

Clear cell tumors

, .
variant .endometrioid carcinoma

Endometrioid Tumor

20% - , .

. 15%-30%- .
endometrioid carcinoma- , .
.mucinous-
, , 2 ".
. ,
2 " . ,
. 2 .
15%- - endometriosis :
, .
. , ,
,15% .
40% .
5 year survival .40%-50%

Transitional Cell Tumors

.
, ." 2 , .
, - ." ,
.
.Brenner Tumor

- Brenner Tumor , . , .
, .
. .
.
-" ,"
. serous- . , .
,cachexia : .ascites , .
,prevention- : CA-125
.serous
, screening- .
( )BRCA .
, ,
. , BRCA
.
.BRCA , , serous carcinoma
. ,
, !

Germ Cell Tumors

15%-20% .
.
' .
, , ,
.

Teratoma

,
3-
- ( - )dermoid cyst ,

.monodermal teratoma

= .benign dermoid cyst
(~ )1%
.
, . - ,
squamous cell carcinoma ,thyroid carcinoma .

.
- Dysgerminoma . !
- choriocarcinoma .
, .immature teratoma -
yolk sac- .yolk sac tumor
, Mixed germ cell tumors .embryonal carcinoma
.

Mature Cystic Teratoma = Dermoid Cyst

.
, , , (" ") ,
.
, .
frozen section .
" - 10%-15% , , .
, .
" .
.
, .
, . -
.dermoid cyst

, . -.
" - keratinized stratified squamous epithelium
. , , , ,.
.

Monodermal Teratoma

, , .
carcinoid tumor( monodermal teratoma- " ' ).
, !
papillary carcinoma of thyroid .
, , .

Immature Teratoma

-.
18 .
.
- , .
. , ,3 ,
!
,
.
:mature teratoma , . .
, .
- .
, , .
grading- .
.
, ,high grade .
" , grade 1 . , ,
.

Dysgerminoma

,.
seminoma .
, ,
, .T
.
.

Yolk Sac Tumor

.
.
, , .
, -fetoprotein .
( )yolk-sac ,embryonal carcinoma ,dysgerminoma mixed germ -
.cell tumors

Embryonal tumors

. .

Sex Cord Stromal Tumors

( ).
.
)adult type( Granulosa cell tumor , .juvenile type
,Sertoli-Leydig cell tumors ,fibrothecoma ,thecoma ,fibroma :.
,granulosa-theca tumor- "
.

Granulosa Cell Tumor

.
, - !
(=) (=) , . 25%
.
25%- , .
.
5% .

, .
:
, coffee bean . . Brenner -
( Tumor transitional epithelium) .coffee bean
, .Call-Exner Body - .
- .

"
.
.
" , 20!

, ,
, .
.

Fibroma

4% .
,
, .
, .
.
, .
, . .

: ,Meigs Syndrome- 3
.1 ( 6-").
.2 ,ascites .serous carcinoma
!ascites
.3 ,hydrothorax . ,
. 40%- , /
.

Metastatic Carcinoma

" .
.serous carcinoma - mucinous carcinoma
, .
mucinous carcinoma ,
( ).
' !
" .
, , (
) - .mullerian-
, , , , .

Krukenberg Tumor

.
- signet ring cell , , '
- .
: , ,signet-ring cells
. .signet ring cells

" .
, ' , .
, ( ).
30% . ,
.ascites ,torsion .
granulosa cell tumor- .

: , .

.1 ()Salpingitis
, .
,ascending infection-
( " ).
.
, . .
N. Gonorrheae , .
,
. . ,
. Staph..Strep.-
, : .
,
- Pyosalpinx . , ,
.
resolution , .
.2
.
: , , .
1:150-.
.
.
, ,
.
, ,
, .
, .
.
.3
, .
serous carcinoma .
, .
, , .
BRCA1 .

.
.
.50-60 -



50 , 200 .
- . ,
. 28-.
2
- Endometrium Functionalis ,
- Endometrium Basalis ( functionalis- )
.
, .
functionalis-
.
,
,
pseudostratification , ,
.
.
.
.
( ,)14 (
16) - (
) , ,
( )18 .
,21-22 , ,
. pseudo-decidual
( ) ,
.
,
- .

2 , .
( - )bifid septate uterous .

Dysfunctional Uterine Bleeding

.
.
, dating
.

-
Anovulatory Bleeding

.
2 - .
, .
. , ,
.unovulatory bleedings
.
, :
. ( , ,
) , - , , .
()inadequate luteal phase
. .
, 21
.18

.
, . .
-.

Endometritis

.
. .
2- :
.1 / - .
.
- .
- IUD .2 .
.
.
: , .

Adenomyosis

, .
nests .
20%!

, . .
.
1.5" , ".
- .
.

, .
.
, , .
2-3" .
, .endometrium basalis-

Endometriosis

.
, , , .
:
- Regurgitation-implantation theory .1 .
, .
- Metaplastic Theory .2 , ,
, . .
.
.3 - .
, .
.4 .
.
: , , . 10%-
( .)... 10% : ,
, . .

, .
! , .Endometrium functionalis-
, .
.
, .

, .
endometrioid carcinoma .
: "" .
.
, .

Chocolate Cyst
, .
.
.
.

Endometrial Polyps

, .
" : - ,.
" .
, .
. .
- , .
, .
.
, .

.
, .
.
. ,
.

" .
, ,anovulation .
. , .
.
, .
obesity .
( HRT - ) .
.

.
, .

, ,
( inactivation of PTEN )TSG .
.
." 1-2".
.

 2
()simple
, .
, .
, , endometrial polyp-
() () ().
.
" , , .
()complex
, .
, .
. , ,
. .

.
.
, .
, -
, .
: .
.

- . .
- 1% .
8% - .
complex 3%-5% - .
complex 25% - .
. , .
, . ,anovulatory cycles - .,
: 50%- , 25%- regression
25%- .
.

Endometrial Carcinoma -

7% ,genital tract- .
, .55-65
" , 4 .
, stage-
, .
,
.
. high grade- . "
. . , ,hobnail
. .
. , . ,Serous papillary carcinoma
serous carcinoma . ,
.
.

.
, .
, .
stage- .
endometroid . , 5- .90% ,-
serous carcinoma .

Type 1 Endometrial Carcinoma

, 80%.
,55-65 ( ).
, ,
.
, , " . .
Endometriod .
precursor lesion- , .PTEN-
.
.endometrial hyperplasia-
.
well differentiated ,.
.
= grade , .
, , .staging-
50%- , .
50%- , omentum ,.
, .stage 2-
, .
.
well differentiated stage-.

Type 2 Endometrial Carcinoma

. 15%-.
, .65-75 " .

serous carcinoma ,
clear cell carcinoma .mixed mullerian tumor
precursor lesion - , - in situ
.endometrial intraepithelial carcinoma
lesion , ,
" .
p53.
" .
high grade carcinoma , Serous carcinoma .grade 3 high
.grade

Malignant Mixed Mullerian Tumor

.type 2 endometrial carcinoma

, "".
2
,
- -
,leiomyosarcoma , , , ,
. , .
, - .
"" .
.
endometrioid carcinoma serous carcinoma .
, ,
. .endometrioid type

( ,)tamoxifen
. !

 Myometrium-
.
- Leiomyoma .1 , . , 75%- .30
. ."
. .
(
) . ,
.
. ." "
-" .
, - .
, ,
. ,
, .

, .
.
. ,
. -
, ,
. , 20" .
. .
, . .
! .
.
- Leiomyosarcoma .2 ."
,
. ,
.
. .,
( ) ,
, .
, ." ,
.
-

.
.precocious puberty -
,anovulatory cycles - .
- . , ,
.
- ,,
.
- - , .

 ()cervix
, . 2 :
.1 ) - )Cervicitis , , .
. gonorrhea ,trichomonas vaginalis ,
salpingitis . ,
, . .
. , ,
. .
.
.2

" squamous stratified non keratinized
.epithelium
.
.external os-
, , ( ) ,
( )transformation zone external -
,os . ,
" . .
-
, squamous epithelium-
.
ectocervix
endocervix .
endocervix transformation zone
. .
.
, = ,ectocervix-
.

" , 5%-.
.
" , , .
, .
.
, .
.

Cervical Carcinoma

, .
" ,Papanicolaou screening - 8 .
: - " .

" , .Human Papilloma Virus-
, , (
) , persistent
infection ,HPV- HPV 16 ,18-
, , .
" , .
HPV
HPV squamous epithelium , .
- transformation zone- .
,immature metaplasia- .
.
- Koilocytotic Atypia- / :
, "" , .perinuclear vacuolization .binucleated
HPV- - Squamous Intraepithelial Neoplasia- -.
low grade .
18 ,16 high grade .

, , .
, , - -
.transformation zone
, <-
- HPV- .HPV
.
HPV
HPV- ," , .
- , , .
( HPV 10%-).
- , . 2
- Low Grade Squamous Intraepithelial Lesion (LGSIL) .1
. , , , .
- High Grade Squamous Intraepithelial Lesion (HGSIL) .2
2/3 : , . ,
. in situ , .
.
-
- LGSIL 60%- .
, . 30%- persistence10%-
.HGSIL-
- HGSIL 30% 60% ,
10%- .

HPV
LGSIL- .
HGSIL- ,
.microinvasion microinvasion , ( 3" 7-" ).

Invasive Carcinoma of Cervix

80%-95% .squamous cell carcinoma

HPV- SCC , , .
( .)HPV-
, ," .
pap smear 3
, .
.

.fungating, ulcerative, infiltrative

.
.

: ureters ,
- .
.
.

.
, .
, .Pap
.LGSIL -
- , HGSIL .

, .

, stage- .
, ( conization -
).
,pelvic exenteration - .
.

 Vulva-

vulva- .
: ( , ") ,
( ) .

Bartholin Cyst

<- Bartholin's glands- .

, .
.
( )excision (.)marsupialization

Vulvar Vestibulitis

.posterior introitus-
" .

)Non-Neoplastic Epithelial Disorders (Vulvar dystrophies

.
, .leukoplakias
, ,
:
- Lichen Sclerosus .1 .thyroiditis
, ,rete pegs- ,
, , .
, . .
(.)1%-4%
- Squamous Cell Hyperplasia .2 .Lichen Simplex Chronicus
. , -
.stratum basale . .

Vulvar Tumors
Benigh Exophytic Lesions

, .
' genital warts - Condyloma Acuminatum :
- )STD( HPV- - (.)11 ,6
, .
" " , -.
, , - Koilocytes
.
- . .

)Vulvar Carcinoma & Vulvar Intraepithelial Neoplasoa (VIN

( ) 3%-
.
90% .60 ,SCC Adenocarcinoma, basal cell
.carcinoma, melanoma

2 SCC :
30% - Basaloid and Warty carcinomas .1 . HPV- ,
. - ,VIN -
. .
() , . , ,10%--
30% / . .
70% - Keratinizing Squamos Cell Carcinomas .2 . lichen sclerosus, lichen -
simplex chronicus ." (
).
,leukoplakia (=) .
, .
, , .

Pagets Disease of Vulva

.Paget's Disease of Breast-

,intraepithelial carcinoma .
- , labia majora-
( ).
- .
( )Paget "" , , , PAS--
.mucin
Paget , 100%- ductal carcinoma
, Paget
.
-
, .
.
, , .

Vulvar Melanoma

5%-10% , .
, 2% .
,50-60 :
.
5- 32% , .
- , 1-
".
( ) ,
.Paget's disease .

, ( ,) , ,cervix :,
, .

 ' ( )31

.trophoblast
2
- cytotrophoblast - ,
syncytiotrophoblast -
, .
( HCG
.)HCG-
- Intermediate/extra-villous trophoblast villi- .
, .-
intermediate trophoblast ).human placental lactogen (hPL
Gestational Trophoblastic Disease -
:GTD
-
Complete Hydatidiform mole
Partial Hydatidiform mole

Choriocarcinoma
Placental site trophoblastic tumor
Invasive Mole
- , , .
, .placenta acretta
, .
" - Persistent GTD"
HCG .
.
germline tumors .HCG
( )HCG
.
Hydatidiform Mole
, .
, ;
, .

- Complete Hydatidiform Mole : 46XX
.46XY , 46XX - ( 46YY -).
, , . , .
- Partial Hydatidiform mole : .
, .
,
,mole .
Mole GTD
complete mole- ,20%-30%
partial mole- 2%-6%.
2%- ,CHM .PHM-
,HCG .

 moles-
, 1-10- 1000.
," ( ).
.40
.
, . ,
.
moles
, CHM- , .
, , .
CHM- .
PHM- .
CHM- , .PHM-
CHM- , ( ,)hydropic
.
,CHM- .
PHM- , 2 :
. .
, ( )trophoblastic inclusions
( "").
: CHM- , . PHM- , -
( )angiectasia .
Syndactyly 3-4 .partial mole

moles .
, .

CHM .PHM- .
CHM- , ,
.
, .extravillous trophoblast ,
.
CHMPHM-
- ploidy- ( ) .
, .CHM
Ploidy analysis :
flow cytometry DNA . ,
.
,
. .
FISH .
, .
partial mole <- triploidy .
<- diploidy .CHM
, . PCR (
).
,P57 .
, .CHM
, .
P57
. .CHM
( ) ,
. ,extravillous trophoblast- .P57
:cytotrophoblast- , . CHM-
.

Choriocarcinoma
.
( molar pregnancy 50% - )CHM , ( 25%) ,
( 22.5%).
mole 1:1000
Mole CHM 1000 .
.
, . intermediate trophoblast.
, , ,
.
- , , .
.
HCG . HCG mole
, .
)Placental Site Trophoblastic Tumor (PSTT
, intermediate trophoblast- .hPL-
,HCG .
, ( -
.)methotrexate
, - , .
, .HCG ,PSTT
.
. ,
( !) . " ,
.
Intra-Uterine Growth Retardation
-.
.
organogenesis- = .
, , ( TORCH , CMV , )HSV-
. , .
, (
) <- .asymmetrical IUGR
.
, , . ( 3 3) .
,IUGR .
.
.
IUGR
) small for gestational age (SGA .catch up growth
, . , , ( SGA
) " , 2 . " "Barker
.
: : ( ) ,
.

.placental barrier- decidua- ,intervillous space-
.

 = Preeclampsia

6%-8% , .
" proteinuria , .edema- vena cava- .
,eclampsia-.
, -.
. Disseminated Intravascular
,Coagulation ( , , )... .
, . (
) . intermediate trophoblast-
, . ,
." , , .
. DIC- " .
,
.

.intermediate trophoblast
, .

.
.acute atherosis
. .
.
.
.
, .
, ( ) ,
.
, , , .
, , , .
. .
HELLP Syndrome
.
low platelets ,elevated liver enzymes , . ,
. , .

- , (
).
- ( ) , -
, .
.
Retroplacental Hematoma
.
.
, . , .
" ".
, .
.

.
, IUGR- , pH
( ).
, .

 ( ?)
,
.
APGAR pH- ,
( ).
. fibrotic avascular villi -
.fetal infarct , sampling
. .
, .
.occlusive -
Twin-twin transfusion syndrome
.IUGR-
,.
, ,
.
,monochorionic diamniotic twins
15%- .
.
- ,- .
.

.
donor- , recepient- .
. ,
-.
, recepient- 107 - 73
! recepient- ,3 6
.
: 6:1 ( sparing- ) , 2:1- .
Confined Placental Mosaicism - IUGR-
, .
- Mitotic CPM CPM- .
-
, "
, .
- Meiotic CPM ,
. ,trisomic zygotic rescue
"" .
. , ,
. ,
.uniparental disomy-
CPM
- mitotic CMP = Type 1 CPM . .
- mitotic CPM = Type 2 CPM . ,
. .7 ,22 ,16
- meiotic CPM = Type 3 CPM -" .IUGR-

 ' ( )30

3-4-" , .
10-14.
, , .spermatic cord-

-
.Seminiferous tubules
, " basement
,membrane ( )sertoli
.
.
, ,Leydig
,
- .

" 5 ,
3-7 -.transabdominal phase-
7 ,inguinal canal- -
(.)scrotum
" .

90%-95% - inguinal canal- .
5%-10%- ,

- Cryptorchidism

.inguinal canal-
1:100 ,.
.

- 50% - .
25%-
- 25% .
' ,hypospadias
(= ) .

BM- .
, , ,
- .
Leydig.

.
.basement membrane-
, - .
- ...
) - intratubular germ cell neoplasia (IGCN ,
. in situ.

.
- ,
.
.hernia = inguinal canal-

.
( ) .
.
, .

-
Atherosclerosis .1
Inflammatory orchitis end stage .2
Hypopituitarism .3
Generalized malnutrition or cachexia .4
Irradiation .5
Prolonged administration of antiandrogens .6
Exhaustion atrophy - persistent stimulation produced by FSH .7
intratubular germ cell neoplasia .

6,100,000-
(.)15-34
10%- .
.

- Germ Cell Tumors .1 95% , . ( ,)15-34
.
- Nongerminal Tumors .2 , 5% . .
, ( 60 ,)40-50
.gynecomastia" .

Germ Cell Tumors

" /.
,
, pineal- - .
90% 10% .extra-gonadal
.

.1 12
.2 - ,genetic predisposition Xq27
. .
.3 - 5 -.
.4 germ-line .
- Testicular Dysgenesis Syndrome .5 ( Hypospadias , ureter-
) , . 10% .
germ cell tumors- .
.6 .XXY - Kleinfelter germ cell tumors"
. germ-line 50 .

germ cell tumors

 seminomatous-.nonseminomatous-
- Seminomatous 3 .typical, spermatocytic, anaplastic :
.
- Non-seminomatous , ,choriocarcinoma
carcinoma ,yolk sac tumor .
( )60% .Mixed germ cell tumors 2
.
IGCN = Testicular Carcinoma in situ
, . , .
, .
50% in situ 5.
, 100% , .
, ".
germ cell seminomatous
.nonseminomatous
.
,
,
.
, : placental ,c-kit ,OCT3/4
).alkaline phosphatase (PLAP
( ) germ cell- IGCN- IGCN .
: IGCN- ( ,)yolk sac tumor, teratoma
.

 - Seminoma.
.ovarian dysgerminoma
50% -.
,30-40 .
" , 10.
, ,spermatic cord- " .tunica albuginea-

( )typical" ,
50% - .
, germ cell.
.
, "" .
, .
" T .

, ,
.
.
.

- oct4 ,c-kit ,placental alkaline phosphatase (PLAP) .
" (.)cytokeratin

.
, .
Spermatocytic seminoma
65,
( ~1% ,)germ cell-
( ).
.
, .
,in situ in situ.
" , .
PLAP .
germ cell.

, - .
, ( ) . 3 :
- Medium size , - , .
- Small size .secondary spermatocytes-
- Large size 10 , -.
Testicular Lymphoma
.spermatocytic seminoma-
.
primary lymphoma .
.
, .diffuse large B cell lymphoma
.

Nonseminomatous Tumor

- stem cell-.

Embryonal Carcinoma
,20-30 , ' .
," .
, .
.
3% "" , 45%
.
, , intratubular germ cell neoplasia
.

" .
- .
,tunica albuginea- .

.
, . ,
. , , .
.
.

" ,CD30- .
PLAP oct3/4- , .c-kit

Yolk Sac Tumor

," .3
,intratubular germ cell neoplasia- .in situ
.
, mixed germ cell tumor- \ .
, .
" , .mucin
().

- Schiller-Duval Bodies
, glomeruli-.
.
, ,microcyst schiller-duval bodies-
yolk sac.
,
.PAS
.-fetoprotein-

Choriocarcinoma
, .
" , mixed germ cell tumor-
( .)trophoblast .
, .
" , .
.
, ,
, .
" . .
- 1%- , .

syncitiotrophoblast , ( )
.
cytotrophoblast .
human chorionic gonadotropin- .

Teratoma

.
" 3 .
, - ,
.
3 : , .
, .yolk sac tumor
" .
in situ ( in situ .)yolk sac-
.
,mixed germ cell tumor-

.
, . ,
embryonal carcinoma- .

()mature
.
, , .
, , , , , ,
.
- ()immature
.
, , ( neuroepithelium ).

.
" - , squamous cell carcinoma .
Mixed germ cell Tumors
60% ,
- .embryonal carcinoma-
,.


, .
, .
. , .
nonseminomatous .
.
Staging
- Stage 1 . , .spermatic cord-
- Stage 2
- Stage 3
non-seminomatous-
1 , , ,
,2 95%- .
non-seminomatous ,stage 2+3- ,
90% . 10% , .
/ . ,
.
- .

Sex Cord/Gonadal stromal tumors

Leydig cell tumors
, , .20-60
gynecomastia .
, 5 .
" 5-" , , .
- ,
.
90% .
Reinke-rod crystalloids - 10% . .
Sertoli cell tumors
" .
10% , .
" , .
- . .

lesions - tunica vaginalis-
:
- Hydrocele . . .
.
- Hematocoele , .
- Chylocele ( )
- Spermatocele
- Varicocele ,spermatic cord- .

,mumps 20%-30% . .
Neisseria gonorrhea- .Chlamydia-
. ( .)gummas Treponema
pallidum.
, caseating granulomas.
( )35 , Pseudomonas.E. coli-

 ' ( )33-34

,terminal ducts-.lobular unit-

.
(" ).
, .
,
10% 6-10 " " :
, lobuli-
.acini terminal duct- -
.acini acini-
.
" , ducts-
lactiferous ducts .

, , 2 .
terminal ducts- .
/ .
.
2 ( 2)
,
: ,
.
2 .

- Interlobular stroma , . .dense CT
- Intralobular stroma , .lobuli-
. .

( ).
- .
.puberty-
, , acini- ,
.
- lobuli , acini 50 lobule-
.
- .

.
, acini- , ,lobuli
" .
acini- , acini-
.
= .
, ,involution , , ,
.
, ( .)35-40
,
, lobuli- , ,
.
, .

milk lines- axilla-

( " 2).
- ,axilla- .axillary accessory breast
- , .
""
"" .
! ,
.
congenital inverted nipple
- 1:100
.
, .
, .
- Amastia , .
- Hypoplasia .
- hypertrophy/premature development .
. , .
.

:
- . ,
. .
. ,
. " .
- . 12%
, .
-
7%- .
,
.

screening- .50 .
, , . ,
80% , , " needle biopsy.
.
, .
2-" . , .
.
, ,
" US .MRI


Acute Mastitis
, .
" - .
.
,Staph. aureus Strep. .
- , , .
- .
" .
Periductal Mastitis
Recurrent subareolar abscess/squamous metaplasia of :
.lactiferous ducts/Zuska disease
, .
90% - .
.
, .
"
, lactiferous ducts- ,
( keratin) ,
.
central calcified keratin plug (.)giant cell
.
Mammary Duct Ectasia
,
50-60 .
.
.
.
.
, .
- ,
. , , .
.
, .
, .

.
" , .

,
,
- foreign body type .
.
, ,
.
,.
Granulomatous Mastitis
( .)1%-
, .
- Granulomatous lobular mastitis , ,
, .

 Benign Epithelial Lesions -

.
.
,
3/. nonproliferative breast changes, proliferative breast disease, atypical hyperplasia:

- Nonproliferative/Fibrocystic Breast Changes .1 , 90%-

. ! ."
,20-40 , .
. , , .
( ,)blue dome cyst , . -
1" 10" .
. , . 20%-
.
, 2 : duct ,

.
, ,oxyphilic -
. .
( ) ,Adenosis
acini- . acini ,lobule -
adenosis .
, . ,
( )blunt-end adenosis .
, ( .)flat epithelial atypia ,
. , .
- , ;
; . .
.2 - density- , .
.papilloma ,complex sclerosing lesions ,sclerosing adenosis ,epithelial hyperplasia : '
1.5 2 .
- Epithelial hyperplasia . 2- .
. , . 2- .
- Sclerosing Adenosis . acini- lobule .
, acini- "" " .
, acini- . ,
. , , ,
, lobuli -
.ducts , lobule , , acini ,
. lobuli- .
, . ,
. . sclerosing adenosis-
, . "
.
. .
- Radial Scar . 10-" , .Complex Sclerosing Lesion ,
.
. .
. , ,
. , - .
. . .
. tubular carcinoma .
( .)p63
. .
. - 2 .large duct, small duct : " .
- Large duct .i . 80%-
.

 , . , "
. . ,
. / . ,
. fibrovascular stalk .
" . .
, . .
- Small duct .ii , .
" , . .
.3 - , carcinoma in situ ,
in situ , 4 5 .
. .
- Atypical Duct Hyperplasia . 2 , 2" . in
.situ .
- Atypical Loblar Hyperplasia . ,acini- acini-
. lobuli- " , "
, .
, .

- screening- , MRI-
.
densities.
( irregular ).
= ,stereotactic core needle biopsy 2".

- 1% -
.
- . ,75-80 1 8-.
menarche - menopause-
." - .
- ...20 ,
. 35 ( " :
!")
- , , .
atypical hyperplasia
-
HRT -
- Breast Density ,
( ) , .Hodgkin's Lymphoma- 20-30
...

- " " 3 - .
- , .
.
- 40- ,
.


- ,
BRCA1&2-
3%- .
- BRCA1 ,
.
- BRCA2 ,
( .)BRCA1-
Carcinoma in situ
.
ductal lobular.
- .
ductal , 70%- .
10% .
)Ductal Carcinoma in situ (DCIS
basement membrane- .
- .
"
.
.
, , .
- ,
.
DCIS
- Comedocarcinoma . . ( ,)""high grade ,
. .
- Cribriform . ,
( )cookie cutter-like " ".
- Solid . , .
- Micropapillary .
- Papillary . . papilloma papillary DCIS-
.
comedocarcinoma- in situ .
- " Paget
1%-4%- .
. .
.DCIS ( )erythematous
.scale crust
DCIS- lactiferous duct- .
basement membrane- .
.
, " ,vacuolated-
. .Paget
" . 7-
.

,DCIS- low grade cribriform DCIS papillary

1% .
DCIS- high grade comedocarcinoma .
DCIS .comedo
,
.

 DCIS-
, .95%-
,
,low grade
5-" ,
3".
. .

Microinvasive carcinoma
1-" . .comedocarcinoma
1-" , invasive carcinoma .
Lobular Carcinoma In Situ
,acini- .DCIS-
, , . 50%- lobule-
LCIS .Atypical Loblar Hyperplasia
." - ,
LCIS . .
, .
DCISLCIS-
LCIS- "" .
E cadherin- LCIS invasive lobular
carcinoma .
high grade ductal carcinoma .E. cadherin-
lobular carcinoma- ,mucin .signet-ring cells
, signet ring carcinoma
.

Invasive Ductal Carcinoma

, .
.
:
.1 .nipple inversion -
.2 , , dimpling .
.
- Peau d'orange .3
.4

screening- ,
. 20%- ,
.
,
. , , " .
.Occult invasive ductal carcinoma MRI- "
.

Inflammatory Carcinoma
, .
, .
.acute mastitis
, inflammatory carcinoma- .
.
.
.

.
Stage 4 .
.

:
DCIS LCIS- .

invasive ductal -
carcinoma - .
invasive lobular carcinoma -
.
Invasive Ductal Carcinoma Non-Special Type
70%-80% .
.
, .
.
. .
.
IDC-NST
,

.
:Low grade malignancy = Grade 1

.
.
,moderately differentiated = Grade 2
.Grade 3 = poorly differentiated

Invasive lobular carcinoma

10% .
, .
( 20%) ().
- , , - .
.signet-ring cells , . E--
.cadherin

.
.
, , , , .
- signet ring cell carcinoma .
, 7- 20- , ,
7 : 20- . .

Medullary Carcinoma
3%-4% .
.special types-
.60
,BRCA 13%- , .
"" / .
, .
, .

,medullary carcinoma- , .poorly differentiated

syncytium like , , , .
.
.
, invasive ductal carcinoma with medullary features
.
DCIS , DCIS invasive ductal carcinoma- DCIS
.
Colloid/mucinous Carcinoma
1%-6% .
( ,)70 .
," .
- ' , .
- "" .
.
85%- , .mucinous carcinoma
,85%- - invasive ductal carcinoma with mucinous features .
Tubular Carcinoma
, .
.
- , .
"apocrine snouts" .
.invasive lobular carcinoma
,radial scar .
- tubular carcinoma- .
.
Papillary Carcinoma
DCIS-.
.
/ .
low grade .
Metaplastic Carcinoma
1%-.
, ,matrix producing carcinoma ,squamous cell carcinoma
.spindle cell , .
".
( )ER ( )PR ."triple negative" - HER-2-
p63 - - .
- .
.


- ( ); ( = ).
- .
- .distant metastasis-
- Locally advanced disease / .stage 4-
- Inflammatory carcinoma .stage 4

o ,
grade o,
o ,
o ( .)HER2/neu ,
4 .
, . ,
.

50%-80% .
HER2 , .Herceptin -

( .)mRNA gene profiling

"
,40%-55% - Luminal Type A .1 well ,moderately-differentiated
. HER2 ,
. .
,15%-20% - Luminal type B .2 . 3 .triple positive -
.
, 13%-20% - Basal-like .3 . . triple-negative
( .)HER2 ,PR ,ER . .
medullary carcinoma , .central fibrotic zone
,BRCA1 .
. - .
,7%-12% - HER2 positive .4 ER, PR- .HER2 positive- HER2-
.17 , , .Poorly differentiated
, , .

Stromal Tumors of Breast

2 :
- Interlobular Stroma , . .
- Intralobular stroma , : -
.Phyllodes Tumor
Fibroadenoma
.
( .)30
"" .
- , , " " .
1" .
.
' , rubbery-.
.
slit ( ) , .

- . , .
" .
polyclonal hyperplasia ( ) ,
.
/ . / .
.

( ) , ,sclerosing adenosis
, .
,complex fibroadenoma .

Phyllodes Tumor
, .50
.
, .
- " " . - .
, .

, .
, .
, .nuclear pleomorphism

, ,
.
.
.low grade lesion-
High grade lesion- . ,
, . , . .
liposarcoma , ,fibrosarcoma .chondrosarcoma .

low grade 3-4" .

.
high grade .
. 30%- , .
.

Pseudoangiomatous stromal hyperplasia
- .
. , .
. 10" , .

, rhabdomyosarcoma, osteosarcoma :.
" .

Angiosarcoma of Breast
( ,)35 .
- , .
- , .
.
. 0.3%-.
Stewart-Treves Syndrome
lymphedema .
, .

- ().
- .

' , .lobules

Gynecomastia
," .
, .
micropapillary epithelial hyperplasia , .
Male breast carcinoma
1% - .
, .
.
,BRCA" BRCA2 4%-14% ,
.
3%-8% .
,
.
' ' .

 CNS' ( )45-51

CNS
' :
- Rhombencephalon hindbrain- ,medulla oblongata- pons- .
- Mesencephalon midbrain- .cerebral aqueduct-
- Prosencephalon forebrain- diencephalon- , ,
- Telencephalon : , basal ganglia- .
, , . , , ,.
CNS-
( ") - ( ,)ICP
.
' :
.
' , - " .
CSF- , .
' .CNS-
CNS ( )1 ( )2 .

( ganglia-) , .
: , C.N. XII
. Calcarine- .
homunculus -.pre&post central gyri-
, 50 ,
( 7-) .
, .
Nissl bodies rER .

:()
apical dendrite [ :
.]...
,spines .
, ,
.
, microtubules ' , Nissl bodies- .rER
, . .perikaryon
: .
.
Neuropil .
H&E .

.

- ' .
- .

Red Neurons
.
.
= .
, 12-24 - .red neurons

,
,
,
,Nissl substance
.
4-8 .
.
.
- Reactive Gliosis , , -
.
-/ - ,
ALS .
, ( )simple atrophy .

= reactive gliosis .
,
.
.
Trans-synaptic Degeneration
, ( lateral geniculate body- ) .
, .
:simple atrophy-
ALS .
.
, , ,Purkinje-
. purkinje- .
, . ,
( ) , , .
Axonal reaction
- ,
- sprouting ,
:central chromatolysis - , ,Nissl bodies-
( ) . ,
' .

.
, .
,CNS-
.

- Neuronal Inclusion Bodies

 senescence .
Lipofuscin - .
- ,- .
- ( )ballooning .
, , .viral inclusion bodies
. .
- Cowdry bodies ,
Negri bodies , .
CMV .
,
. .
- Neurofibrillary Tangles - .
, . .tau
ubiquitin- ( ' ) .
.
Lewy Bodies Substantia Nigra- , -.
Vacuolization , : ,
.
.
Creutzfeldt-Jacob ,
. , . .
. CJ-
" Western blot .prion-
- Proteinopathies ,
, ( ,)intracellular trafficking ('
-).
Axonal Reaction #2
neurofilaments-.
axonal transport- - anterograde , - retrograde .
anterograde- / : , , -
.
retrograde- .
Neuroaxonal Dystrophy
(=) , .
, medulla oblongata- .
.
.
neuroaxonal dystrophy
() .
, .
, '
, , .
:
.

( )
,
.
-
( , ) .
.

)?spheroid=( Retraction Bulb

--
bulb .
, : bulbs
,
.bulbs
.
Diffuse Axonal Injury
( ).
retraction bulbs.

,
- . .
,
, ( )petechial .
.retraction bulbs

influx- , , ,
.
.retraction bulb <-
.

- Macroglia ,ependymal cells ,

Microglia

Macroglia
- ( ) ,
.
, .
- , .
Microglia
, .
= .
.
- .
, , .

-" , 10.
- 8 -.
- ( 5-10) .
- ,H&E- , .brush border/cilia
, - 8-.

Astrocytes

- Protoplasmic Astrocytes
o .
- Fibrous Astrocytes . .
o
) Glial Fibrillary Acidic Protein (GFAP
. .
" " ," , .
.
, .

, .
, / ' (- .)radial glia
:BBB- ( end feet ) .
.

- ( )Gemistocytic ( Alzheimer type II glia )

:
- Cellular Gliosis/Astrocytosis
- Fibrillary Gliosis . = .
/ .

Gliosis30
.
, , H&E-
gemistocytic astrocytes- .GFAP-
, , fibrillary -
.gliosis
- " " .
- .
Piloid Gliosis
"".
, .
pilocytic astrocytes .
Reactive (Gemistocytic) Astrocytes
, , , .GFAP-
.astrocytoma-
Rosenthal Fibers
,/ ,
.
HSP- ( )HSP27 ,-B crystalline.ubiquitin-

.
.Pilocytic Astrocytoma
, ,
, ,craniopharyngioma -.
- Alexander ( ) . GFAP-
, , .pia-
:
.pilocytic astrocytoma
30 CNS-

Leukodystrophy

, .


.GFAP-
.
, , .
macrocephaly.hydrocephaly-
!Rosenthal fibers

Alzheimer type II Astrocyte

, ( 2-3) , , .
.intranuclear glycogen droplets
hyperammonemia .
- " .
- .hepatic encephalopathy-
GFAP- .
Corpora Amylacea
- Polyglucosan Bodies , ,PAS- .
- ( ,)subpial ( )perivascular
.
, , HSP-.
,
.
, adult polyglucosan bodies Lafora
( bodies ).
,polyglucosan bodies :
/ - 4 .branching enzyme-
, , , eccrine-.
.
, .
, .
:
Lafora Body Disease
.
,A.R. , 5-10 , ,
.
.
Adult Polyglucosan Body Disease
.
,
.
,50 CNS- ,PNS-
, MRI- .
.glycogen branching enzyme
: !

Oligodendrocytes

, CNS- , internodes
internode.
" - .H&E-
halo - -
, .
, ( perineural satellites -).
, .

Oligodendrocytes

,multiple sclerosis
( ).
viral inclusions Progressive Multifocal Leukoencephalopathy
( )PML ' . .JC virus
.

Intracytoplasmic Inclusions
.
alpha-synuclein inclusions- -
- . :
.1 Lewy bodies - .Lewy bodies
.2 - ,Multiple System Atrophy (MSA)-
4-6 . ,midbrain ,pons : ,
. ,MSA - . ,
,motor weakness ,cerebellar ataxia , .
. , -
( aspiration pneumonia ).

Ependyma

' , .choroid plexus-

-
( ependymoma).

Sub-Ependymal Gliosis
- Ependymal Granulations- .
: CMV ,HSV .viral inclusions

Microglia

, .
"
() = rod cells- ( ).
= - microglial nodules .
( - )neuronophagia .
, .BBB-
.infarct
.
. .MHC class II

,
: , ',
.

, ( neuronophagia ,)rod cells lipid phagocytosis- .
- Gitter cells .
( ).
- MS .
- Gitter .
___________________________________________________________________________________

2% , 20% .
.
50 -" 100- , .
, CO2- .

- Hypoxemic Hypoxia , .CO - .basal ganglia-
- Stagnant Hypoxia <- cardiac arrest , .
- Histotoxic Hypoxia , .
.

- , .cardiac arrest
( - stroke) - . ,
" " " .

- Red Neurons , . 12-24
. ,
. dark neuron !


31 -
( Cornu Ammonis ) - -,
- Dentate Gyrus .
CA-
CA4 CA3- ,End plate
,CA2
( CA1 - )Sommer sector .
3 5- Laminar Necrosis -
"" .
Purkinje - - red neurons-
: Bergmann glia
.Bergmann gliosis -
- Subacute Purkinje ,
.
, ,
.
CA1-
red neurons .
( liquefactive) , ( ).
CA1- . CA1-.
, .
.

/ CA1 , 3 5- , .Purkinje

.
12 - , gyri- , sulci- , ( )red neurons
12 . .red neurons-
24 - .
24 - .
24 3- - , . ,
.
- / : ,
. , , .

watershed/ .
.
" anterior cerebral artery- middle cerebral artery-
.
.hypotension

31

. , 6- .
)parahippocampus=( Entorhinal- . Subiculum- -
)H1 = CA1( Sommer Sector .


- .

Purkinje
)culiculi( midbrain ( )diencephalon -
.

,
(),
immediate-early genes ( HSP)
.NO

, ( ,
) .
, .
,/

.
:
( 2) , .ATP-
- ( )ATP-.
,
,NMDA
(
).
32
2 , ,
.
, Excitoxic Damage.

.
immediate
early genes C-fos, C-jun
.
NO
, .


.

, .

<- ATP <- <-

NMDA discharge -.
( NMDA )AMPA <- <- .NO synthase-
NO- immediate early .
, .

32

Dentate Gyrus- .Sommer sector-

Dentate Gyrus- .
/ .sulcus-

3 5
sulcus- .

( ).
" .
, .
.
, , . , ,
. "" . .
- , .
3 : , , .
Respirator Brain
, .
.
. ,
, . ,
.
- , , . ,
. . ,
CSF- .
Respirator brain , " " , .
, .

EEG- , , ,
. . .

 CVD
CVA

.
thrombi.emboli-
, , .

"
.
internal carotid- 50%-60% ,
external carotid- .
, .
external carotid- internal carotid- ' ,
.ophthalmic artery- .

- :.MCA-
- : basal ganglia- .
- thrombi .
.

Stroke

24- , " .
( subarachnoid hemorrhage ).
24 , .

(,)80%-
20% (.)Hemorrhagic stroke
" .

Cerebral Infarction

,/ " .
" (/) , -
.
" external carotid- ,
.
( )basal ganglia , ,
.
.NMDA
.

.1 Nonhemorrhagic

80%

.2
20%
.
, .
: ,
. ,
, emboli .thrombi
, (,)reperfusion
.
- .

.1 Nonhemorrhagic
( ").
.2
- .

" - CT , MRI- .
" " , .
<- ,
<- .

/ , , ' ,
, -.
,
- amaurosis fugax " - .
( ).

,oculomotor-
, , .

Non-Hemorrhagic Infract


, ( - ,
).
gyri- .sulci-
MCA- .
MRI- .MCA-

, ( )pallor .
, red neurons - .
24-48 - .
- axonal spheroids . - ,
red neurons- .
Recent infarct
gitter cells , , ,
, .
, .
+ <- .
, .
Micro-infarct
.

.
, , /.33
infarct- .
, .
Resolving infarct
, ,
.
.)liquefactive necrosis( liquefaction -
, /.
, -
. .
( ) .
, -
...

12 ,
24-48 3,
3-5 ,
.
,
.
, .cystic cavity

33

: pseudocyst .

Hemorrhagic infarct

, (.)brain hemorrhage
- - infarct-.
, ( ) .
( ).

-

6 - ,
48 ,
2-10- , .
21- 10 - .

12 ,red neurons ( )
( ) .
48 , .
, .
,
.
, .
.


" atherosclerosis-
( )embolization-
-



( , )

.1 ," ( Emboli , )
.2 -
.3 - -

.1 -
.2
.3
.4 thrombi

- , . ( rheumatic
,infective endocarditis ,endocarditis ) , mural thrombi-
, Rheumatic heart disease . 20%
, 5% . AF-
NSR- .
- myxoma .
/.
.
- ! 2 :
Sudan black .Congo red- .
.brain purpura -
( ) , .

Transient Ischemia Attack TIA

24- .
24- , .
, , .
.
.thromboembolism
TIA- ' , (
) . , .

- TIA ,
.
,
.
-.
,
.
,
.
,endarterectomy .
15%- TIA , 10%- TIA 3 .
.

Lacunar Infarct

.
" ,basal ganglia- ,
.
,arteriolosclerosis34
, , ."lacunar state" = micro-infarcts-
15-" . , .
,
.
, ,
.

Etat Cribl
" , ,
.
, .
Slit Hemorrhage
" " .
.arteriolosclerosis-
, , .
, .
.

34 - Arteriosclerosis :8 , ( )
, " , . .

Acute Hypertensive Encephalopathy

" ( ).
- , , , .
(.)EICP
".
" fibrinoid necrosis ,
herniation .EICP-

Vascular/Multi-Infarct Dementia
() .
,
.

,
"" .
" , .
.Binswanger Disease

)Cerebral A.D Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL

( .)50
Notch3- ,19 .
: , , .
- aura ,TIA vascular dementia
. .
, PAS-
electron dense .
.
.

) - Epidural hemorrhage (EDH ." , .

) - Subdural hematoma (SDH " .
)Subarachnoid hemorrhage (SAH
)Intracerebral hemorrhage (ICH
) - Subependymal germinal matrix/plate hemorrhage (SEH" .
) - Intraventricular hemorrhage (IVH .

ICH = Intracerebral Hemorrhage

",
.basal ganglia-
putamen- - lentiform-
".
.
Lobar hemorrhage
.
( - ) ,
.

- " , basal -
.ganglia
<- <- <-
.
- arteriolosclerosis , microaneursyms"
Charcot-Bouchard .
: <- internal elastic -
<- membrane <- .

(" ) .
Cerebral Amyloid Angiopathy
10%~( 50 ).
.
.
40% 30% , " - .
.
( apolipoprotein E ) , 2, 4
. , .
, .
.congo-red ,A-
. ,
.
Primary Angiitis of the CNS
.
fibrinoid necrosis .
,
.


- Blood dyscrasias
, .
()

( ")

- - , -
. . " ,
( ) . -.
- , ( )Haeme- . "
, , .
,
,BBB- .

 - ()
.
.

-
(
).
<- ,
<- ' .
-
, .
- periventricular leukomalacia - .white matter necrosis -
, .CSF
.
50%-
90%- subependymal plate-
( ).
( .)34 , .
80%- -.

,
( ,) , ,
, .
germinal matrix
- Grade 1 ,
- Grade 2 matrix-
- Grade 3
- Grade 4

- Grade 3 + 4 .
, ,10%-25%
50%-70% .
.

, .
,internal cerebral vein- ( thalamostriate v., choroidal v, vena septa
,)pellucidi .

.
.
, TPA .

SAH = Subarachnoid Hemorrhage

- (" ") , .
EICP , , ( ).
.
( ) , .
.

,blood dyscrasia ,polyarteritis nodosa ,Angiitis

,
,
( ),
, ,arteriovenous malformations ,.
SAH- )congenital (Berry
. 1%-2% , .
5-6 , .
, , 4% - , .
35 " .
, .
, 20%-30%- .
, .
sub-arachnoid space- .


AD polycystic kidney disease
( Ehlers-Danlos Syndrome ) Marfan's disease , - Neurofibromatosis1 .
" ,
, .
" .

.
,
, .

. , .
40% ,
12% ,
33% .
SAH
,
" ( CSF- arachnoid
,)granulations
infarction .
, ( ).

, , clip .
.aneurysm coiling -
35 () , () ,
() . ,Masson-trichrome () ()
- .

Vascular Malformations

- - ,
.
AVM , (.)10-30
.
- ( ).
.MCA-
, ""
" ( shunt '
) .

( 2 )
Arteriovenous Malformation
.
subarachnoid space-
.
, .
Cavernous hemangioma
.
, , .
, , .
.
Capillary telangiectasia
" .
, .Pons
, .
Venous angioma
.
- cavernous -
.hemangioma



.1

- BBB- .
, , .
, .
tight junctions " .
, TJ- .
.
.2 /
: . .
- , . .
" / , .
Gemistiocytic astrocytes .
, .
.3 /
CSF- .
,CSF .
.periventricular white-
, , . TJ-
, .
.

( ,meningioma ) . -
mass effect .
,
( .)diffuse gliomas -
.
Gemistocytic astrocytes - , ( ).

EICP
.elevated intracranial pressure (EICP)-
200" .EICP-
.
.
CSF ,
, .
mass effect- ( )
( , ,).
" , " ( )falx, tentorium.
, ,
.

Herniations
.1

.2

.3
.4

Cingulate/subfalcine Herniation
" - .cingulate gyrus-
.
,cingulate gyrus- .mamillary bodies-
.
.subdural hematoma
Transtentorial/Uncal Herniation
, .
.tentorium cerebelli-
perforating vessels-
/ .
Tonsillar Herniation
cerebellar tonsils- .foramen magnum-
.
<- .

Uncal Herniation
uncal herniation .
.
- Kernohan's Notch <- crus cerebri/cerebral peduncle-
.
, ,
. , ( )hemiparesis
, .

, .pons-
uncus- .
- Duret's Hemorrhage Duret's Hemorrhages .midbrain-
, uncus- pons- midbrain- perforating -
vessels . , ."
, .
PCA- uncus-
( ).
.

, , C.N.III- .
oculomotor- uncus- , uncus-
oculomotor- midbrain- .
Tonsillar Herniation
posterior cranial fossa-.
.
, , .
.foramen magnum-
Diencephalic Herniation
- Greenhall line .mammillary bodies-
, .
- : . ,
Wernicke-Korsakoff mammillary bodies-
.
, mammillary bodies-
.
" , , uncal herniation
.


Meningioma

- .
- .

( )15%-25% .
70%- .
( 10-17 100,000-).

( ).
.posterior cranial fossa-
( )20%- .
____________________________________________________________________________________

, CNS-
, "
.
( -
).
grading-
.grade-
- well-
differentiated poorly-differentiated - staging- ,
.
- grading- .

, .
, .
: (~ 50%) ,( papilledema , ),
"( diplopia ") .C.N.IV .
,
.
, .

- Gliomas
.

( ).
.
- C.N.VIII
( schwannomas .)neurofibromatosis-

.

astrocytomas - medulloblastomas ,.
astrocytomas -.oligodendrogliomas-
- 35-45 .
end-stage - glioblastomas - 50 , , .


- Neuroepithelial tumors "" ,
. = .
- . meningiomas .
(' - )seminomas , .pineal body-
- ( '
) . , .
- sella turcica- , craniopharyngiomas
.
Neuroepithelial
- Gliomas '
- ,
-Oligodendroglioma ,
( )
- Ependymoma .
high .low grade

- Neuronal tumors . neurocytoma , .oligodendroglioma-

.

- Glioneuronal Tumors . low grade

.
.Ganglioglioma / Gangliocytoma
.
, .

- Pineal Parenchymal Tumors . ,

.

" - Embryonal Tumors " ,medulloblastoma posterior fossa-

.

Extra-dural .
Intra-dural
- Extramedullary , .
- Intramedullary , neurilemomas (
).

Glioma

.
- -
.

low grade ,
,

,
. .
, ,
.
,

.

( .)high grade

.
.
( ) high -
.grade
( grade 1- ) high grade-
.

, .
: gamma knife- .
single shot whole brain .
( ,) . , .
,
. ,
. .
- satellitosis . ( - )Scherer
pia- .

[ Scherer : 1940-
. - perineural satellitosis ,perivascular satellitosis :
; - subpial spread ; - Intrafascicular spread -
.corona radiate ].

Astrocytic Gliomas
Grading
- Diffuse Astrocytomas .WHO grade II- grade I !
.
WHO grade II = Astrocytoma
WHO grade III = Anaplastic Astrocytoma
,anaplastic astrocytoma .5
WHO grade IV = Glioblastoma
( microvascular proliferation ) ,
,
grade-
cellularity
- nuclear atypia , , : '.
Mitotic figures
- Microvascular proliferation
Necrosis

Ki-67 .
MIB-1 ,Ki-67- .G1, S, G2, M
G0- .
, ' grading- .
MIB- grade- , .MIB-
: ,
, , -
.inter-rater reliability , MIB- .

( glomeruloid vascular
,)proliferation .
, ( )serpentine necrosis
.pseudopalisading necrosis -
,
, .

, , , .
.

upregulation VEGF .
, , ,pseudopalisading- VEGF
( . ' ) . .
, .
.pseudopalisading-
GFAP- .pseudopalisading-
, MIB- .
confluent .
, . thrombi- .vascular proliferation-
- ,
.

Clone . .
, ,
.

 2
,
secondary glioblastoma <- high-grade
.

Astrocytoma Grade II

.30-40
, , .
, , .enhancement
, .
.

H&E- .
, , , , diffuse -
.astrocytoma WHO grade II
, GFAP- . , .
.
- , .
- . MIB-1 ,Grade II- .

Anaplastic Astrocytoma Grade III

(.)40-49
, , , .
, , , MIB- ( ).
!

Glioblastoma

) glioblastoma multiforme (GBM .

.WHO Grade IV
(.)55%
( ) , .anaplastic astrocytoma-

, , , (
) . .
, ,
- .
, -.
,GFAP- .
, MIB- . "" .
pseudopalisading . .
- ring enhancing , .
, . .
" " - 2 .corpus callosum-
, CSF- ( ) -
.CSF seeding ,- , .CSF-

+.
GFAP- .
CSF .


, .
MRI- .
.
.
.

- primary , ,
- secondary grade- . secondary- ,
.
:
primary glioblastoma
,PTEN36- phosphatidylinositol
.EGFR
.
- p53- p53-
.MDM2
secondary glioblastoma
- p53-
PTEN- .
LOH .10q
Glioblastoma
,
- nitrosurea .
. - ,
.
Therapeutic Resistance-
, .BBB
.
- .
, BBB-
. .
- Cancer stem-cell like cells
.
' DNA- ( )MGMT . ' ,
.

PTEN 36 .3
P53 ,DNA
EGFR RAS . .


Astrocytoma
,
" ' - ( ).
( alkylators ).
Anaplastic astrocytoma
' ,
.
+ " . whole
.brain .
. , .
Glioblastoma
" ,
.

Astrocytomas
Pilocytic astrocytoma .1
.WHO grade I o
o .
o - , ,
.
Pleomorphic Xanthoastrocytoma .2
o , .
WHO grade II o .diffuse astrocytoma .Grade I
Subependymal Giant Cell AStrocytoma (SEGA) .3
o ,tuberosclerosis .
o tubers .WHO grade I
o , .
o .

Pilocytic Astrocytoma

, - .
, ( ,) , .
.
.
/ .
, .

, ( )posterior cranial fossa-.

-.
, CSF-
. ,.papilledema ,
: " ,.

, .
biphasic ,
.
, . .
- . .
. .B-crystallin-
( ).
,
.
, " .
.
.

Oligodendroglioma

.
( ) ,
(.)30-60

, ( ) , , ( ).
oligodendroglioma- ( Grade II- ).
( WHO grade II ) " .
.
, .

.
, " - .grade .
- chicken-wire like vasculature .
- fried egg appearance ,
( ) . .
- GFAP- () . ,
.

,
enhancement- , , - WHO Grade III
.
grade- , , .
MIB1- .
,pseudopallisading Grade-
.III

, glioblastoma with
oligodendroglioma features .grade IV
. " .grade III

LOH 1p - 19q- .
.
, .
P53
.
oligo - astro
(.)oligoastrocytoma
Stem Cell
+ stem cell- <- p53-,
1p LOH <- 19q-.
2- . .
.
,p53- . LOH- , ,
.
stem cell- oligodendrogliomas- astrocytomas-
- )IDH1&2( isocitrate dehydrogenase-
. ,secondary glioblastomas -
.oligodendrogliomas diffuse astrocytomas.oligodendrogliomas-
IDH1&2- , secondary glioblastoma- ,
. . -
diffuse . -
. IDH1- .
.
,primary/denovo- -
.secondary diffuse astrocytoma grades- ,
.

Ependymoma

, .posterior cranial fossa-

.4
.
- myxopapillary ,grade I .grade II
.neurofibromatosis-1

- rosettes .
.
.
, /
. . :
- Homer-Wright Rosette .1 () . .
,PNET- .
- Flexner-Wintersteiner Rosette .2 spikes , - retinoblastoma-
.
- True Ependymal Rosette .3 . ( ) .
.
- Perivascular Rosette )pseudorosette( .4 . GFAP (
).


63% - .
Myxopapillary ependymoma
, cauda equine- ( filum terminale-
) .
,WHO Grade II myxopapillary ependymoma- .WHO Grade I
- / .
( ) .
GFAP , .

 CNS-
)Primitive Neuroectodermal Tumors (PNET

peripheral-PNET ( Ewing Sarcoma- )

.
,central-PNET .
PNET- WHO Grade IV .
. PNET .Medulloblastoma

Medulloblastoma

,posterior cranial fossa- .infratentorial

, .
posterior cranial fossa- ,ependymoma .pilocystic astrocytoma
.
, PNET- " - "Small, Round Blue-Cell Tumor37 ().
- - anaplastic - WHO Grade IV- Grade .
,Molding .
external granular layer- .

" "
- Homer-Wright .
pseudopalisading
.necrosis .
,synaptophysin-
,GFAP- .

- CSF- .
."drop" metastasis -
.

.60%-
" <- .
- Wnt .SHH .
. ( ) ,
, , .

PNET

supratentorial .
basal ganglia- .

, , - .
small blue round cell tumor ,
.
,CSF- .
PNET .

- LEMON 37" -:
( Oat Cell Carcinoma ,Medulloblastoma ,Ewing Sarcoma ,Lymphoma" ) - Neuroblastoma ,
. small round blue cell- .

Non-Glial Tumors

CNS- ,
- intra-cranial (.)extra-axial

Meningioma

.
".
, ( 2:1 10:1 ,") .
- Meningiomatosis ( 10%).
WHO Grade I

+
Atypical Meningioma

Anaplastic Meningioma
1%-2%
, .
, . , ,whorls
,psammoma bodies . -.
Transitional
<- Whorls - , .Psammoma Bodies <-
whorls- , meningothelial-fibrous-
Meningothelial
- Syncytium ( ) , ,
. .
- Fibrous , .
- Cavernous Sinus Meningioma . -
. cavernous sinus . .
. sphenoid sinus- .

Psammoma Body (Whorl)

, , , , . .
arachnoid villi- - psammoma bodies .
' .
!

convexity- ,

,
- .
, ," .
, . / -
grade .
. .
( extracranial extension ).
- en plaque , , .




- recurrence WHO grade I
" - ( )

year survival- .70% recurrence- (.)20.5%
Grading38
WHO grade I -
WHO Grade II atypical meningioma +
- WHO Grade III - Anaplastic Meningioma .

grading- , 10 (.)X40
4 = .WHO Grade I
4-20 = .WHO Grade II
20 = .WHO Grade III
,grade - grade-
.
- .
, -
, .

, - .
Virchow-Robin Space- .
space-
.

)Merlin( NF2 gene- -
.

- Loss of 10q ,
loss of 9p

gamma-knife
( )
.
-
( )Tinea capitis .

.
Basal-Cell Carcinoma low grade radiation-,
Nerve-sheath tumors . CT-
!
Radiation-induced meningioma
, -.
,
(.)meningiomatosis
. ,.
/ ,
. .

38 MIB- . MIB- .WHO grade-

()Nerve Sheath
' ( - ).

- Schwannoma ,
- Neurofibroma + .

malignant peripheral nerve sheath tumor , .

Schwannoma

.
" CN VIII cerbello-pontine angle (CPA) - CN V
(.)85%
Vestibular schwannoma - acoustic neurinoma " / ".
" .incidental finding ,
.
. .gamma-knife-
Bilateral schwannoma .Neurofibromatosis2

( ).
" , .
, , - , ,
.
39
:
- Antoni A , ,palisading .
- Antoni B . , , ,
.

/ , ( "
/).
- Dumbbell - .
sciatic- .

39 Pilocytic astrocytoma ,
" .

Neurofibroma
,
.

,

.
.
, .
,schwannian
, .
,
.
, .

collagen bundles .
.
.Myelin Basic Protein-
patterns
.meissner-like corpuscles
- Plexiform Neurofibroma . .
Neurofibromatosis-1
.

Neurofibromatosis-1

" 2
neurofibromas 2 plexiform neurofibroma;
caf au lait spots 6 ;
- optic glioma " pilocytic astrocytoma ;
Lisch Nodules 2 ,iris- ;
;
.NF1

NF1 ,17
AD .
50% ,
.1:3000
NF1 guanosine-triphosphatase- .

, (" peripheral malignant nerve sheath

- )tumors , .
- .
rhabdomyosarcoma malignant nerve sheath tumor
, .triton tumor

Neurofibromatosis-2

:
;Bilateral Vestibular Schwannoma
vestibular schwannoma , , , -
.
, .

) ,Merlin (NF2 .
- , .NF1-

Malignant Peripheral Nerve-Sheath Tumor

.
( .)thyrosarcoma
.
.
.

15%-25% .
30%- , 50%- .
( )40% .
.
- .
: , , , ( .)clear cell renal carcinoma
.
small cell/oat cell carcinoma PNET-" " .
Squamous Cell Carcinoma .

, -.
,

.
.
.
.
Carcinomatous Meningitis
, .
, PNET , , . , ,
. .
-
.
" , CSF .
- "" . .
. ,CSF- ,choroid plexus-
. ,-
.cauda equina .
leptomeningeal gliomatosis - ,
. GFAP- .

 CNS
- Bacterial Leptomeninges
: , , , , ( )
.

CSF

Bacterial Meningitis

++

41

Aseptic40 Meningitis

TB Meningitis

()

Ziehl-Neelsen

Ventriculitis
CSF- .
"" ( ),
(" ) .
, .

H. influenzae , .
- .
- .
- 50%-60%- - ,
( )GBS .

<- - CSF- . .
- .
- .

40

"
41

 ()Brain Abscess

, :
- , . !
- , SBE .
( .)seeding.septic cerebritis ,
, '.

,
- .
- .
,
. .
.
, ,

( ).

Tuberculous Meningitis

' .
, .miliary TB
.

- .
- - ( .)Langhans
acid-fast bacilli - ZN <- .M. tuberculosis
typical mycobacrteria ,
)atypical mycobacteria( MAC .
- .
- TB- .
.
( caseating granulomas ) , -.
Tuberculoma / - .

 CNS
Meningoencephalitis

- Aseptic Meningitis - Viral Encephalitis .

- Encephalomyelitis .
, ,persistent- ()
. - .

enteroviruses
( herpesviruses )
HIV ,


'
HSV DRG- ;
Poliovirus
Rabies

CMV
olfactory bulb-
HSV- " .
.
Aseptic Meninigitis
- .

( )
- perivascular inflammatory cuffs - ,
- .
( )CSF Virchow-Robin space-
.42
( rod cells )
- Microglial nodules
- Neuronophagia " .
red neurons .
viral inclusions
Cowdry
Negri bodies - Rabies.
JC virus ) ,progressive mulifocal leukoencephalopathy (ML .
" .

- Viral Encephalitis
.1 ,
.2 ,
.3 ,
.4 ,
.5 ,
.6
inclusion bodies .7.

- Subacute Sclerosing Panencephalitis 42 , .


- HSV ,
- Poliovirus anterior horn- .
- VZV ( .)DRG-

- HSV-1 & 2 ,CNS- , .

CNS- .
- VZV .CNS- DRG- ( )shingles
.
EBV - CMV- ,CNS- .

HSV1&2
= ,HSV-2 =
.HSV-1

" ,
" , , "
.
- , , ,
.

PCR .CSF
,CSF- PCR , -
CSF , .
PCR- - ,HSV
.
: - chromatic in situ hybridization( CISH FISH
) , .
EM- .

( ) , .20%
-
.

necrotizing encephalitis - , , , .
- .necrotizing encephalitis-
hemorrhagic necrosis
. .
(= ) .
( )gemystocytic astrocytes .red neurons- " .GFAP-
(.)satellitosis
Neu-N- .
( ) , , -
, .
intranuclear inclusions .
Neonatal encephalitis
HSV-2- , .
( )end-stage .

Slow Virus Diseases

- sub-acute sclerosin panencephalitis (SSPE)
,
.progressive rubella panencephalitis
- .
.
HIV ,
,
.CNS-
)- Progressive Multifocal Encephalitis (PML
JC virus -
.

Subacute Sclerosing Panencephalitis

, ,
( )5-15 .
-
.
- , (
5-10) , .
EEG-
- -
" ' .

intracellular inclusions .
," , ( IgM ) ,CSF- CSF-
panencephalitis ( ).

, , ,.
- = rarefaction - .
intracellular inclusions - ,
.EM-

, , ( ),
inclusions- .

Progressive Multifocal Leukoencephalopathy

" .43JC virus

( , ,).
PML- -.
, ,.PML-

,
.
( ) (
) - .
, MBP- .
( )Gitter cells .
, .
.
:PAS
.PAS-positive
""
. p53- .

nuclear inclusions - .44

JCV- , CISH- .
EM .

43

JC Virus : dsDNA .Polyomavirus

44
ground glass HBV

Demyelinating Diseases

- ( ).
-.
- ,
.

Multiple Sclerosis
,Acute Disseminated encephalomyelitis (ADEM)
PML
Guillan-Barr syndrome
- Experimental autoimmune encephalomyelitis (EAE) .

()Multiple Sclerosis

.
, , , .

=
2 2- - .
- MRI- oligoclonal bands.45CSF-

,MRI- ( )plaques .
, .
,optic neuritis- optic disk- .
.
MS- .
.
( Wlcke ) - .
.
Plaques

.
.
- .Gitter ,PAS-
. CD68- .
.gemistocytic
= Dawson's Finger ,T .
, , . MRI-
Dawson's finger .
,
.
,BBB- T- . molecular mimicry
T . .
, .
. . .
, . .
, . ,-
BBB . .
, .

45

Oligoclonal bands IgG .immunoelectrophoresis bands-

B ,CNS- .

/
( )wasting .
- ,/ -.
.
, , .
( naked axons ) .
"" .
. shadow
plaque .

.
, '.
. .
-
" T <-
<- .
BBB- T-
( ).
.
. .

( ).
MS-
- ,T (
).
, shadow plaques' (
).

PNS- .
tolerance .
,
.
.

.
,
.
DR2 MHC class II .
, .
. ,
. '
. , .

T , , , .
' .
T , .
.
.
. ( )remitting-relapsing secondary -
- progressive . primary progressive
. . .
, . .


Acute MS - Marburg Type

.
, .
.
- .

)Neuromyelitis Optica (Devic's Disease

46

, ' ( ,)optic tract .

AQP4- .
.
, , .
.
.IgM4
MS-.
.

)Concentric Sclerosis (Balo's Disease

-.
"" ,MS .

)Acute Disseminated EncephaloMyelitis (ADEM

, . ,
. . .
- , .
( ) ,
.
.

)Acute Hemorrhagic Leukoencephalopathy (AHL = Weston-Hurst

, .
fat emboli .brain purpura-
,ring and ball - .
, " .
- .
.

Central Pontine and Extrapontine Myelenolysis

46

.
, .
.
, .
, .
. .

optic tract-

.
.
.
.
- GFAP- .

Metachromatic leukodystrophy

arylsulfatase .
.
, , .

Adrenoleukodystrophy

very long chain fatty acid .X-linked

.
.U fibers-
, .
,PAS- very long fatty acids-.EM-

Experimental Autoimmune Encephalitis

.
T .
,ADEM- .

- , .
- , ().
cover story . .
, .
, .
: , .

.
. ,
." , 2040- 81 .

.
.
. .

(,)50%-75
)10%-20%( Vascular Dementia .
- )10%-15%( Lewy , .
- )5%-15%( Frontotemporal Dementia , .
5% .


- B12


- ( ) , .

Alzheimer's Disease

, - grades .
- fMRI .
.
- PET-CT ( uptake ) .

Pittsburgh Compound B - A
.
.CSF-

probable Alzheimer's Disease - , .
.

,
.
, ( ).
.
, , gyri- sulci- ,
.
( ,age-matched control- ).

, midbrain-
substantia nigra- .
.
.
,
. .basal ganglia- , putamen- .
CO MSA- .
multi-infarct dementia .
, , ,basal ganglia , ,calcarine cortex ,
( ,)dentate nuc. midbrain- , ,locus ceruleus- .
.

- progressive supranuclear palsy (PSP) ( locus ceruleus- ,)NA
inclusions , . -
,SN .
- Multiple System Atrophy (MSA) , , dentate nuclei-
, ( -synucleopathy inclusions ) . .
- Pick's Disease - + -
. ( .)PSP-
- Huntington's Disease .Caudate nucleus- triplet expansion
,huntingtin- . grades strial atrophy . ,
.


- MRI- ( - )hydrocephalus ex-vacuo .
<- basal forebrain- .
inclusion bodies : .

-
.
- ,ALS , .
.ALS ,


. ,
. .
.
" .
Neuritic Plaques .
Neurofibrillary Tangles
,tau" , .
.
) Paired Helical Filaments (PHF
.
, PHF- .
neurofibrillary tangles- , .
tau : .
neurofibrillary filaments- .
neurofibrillary tangles , (dementia pugalistica
) , .
.
.
tangles- , , .
, neurofibrillary tangles- ,
plaques-.
Neuropil Threads
.phosphorylated tau-
PHF .neurofibrillary tangles-
.neuropil threads-

Tau

6 , .17
3 4 -
splice alternatives 3 4 .
, .

PSP
Corticobasal degeneration
Pick
frontotemporal dementia- (.)linked to chromosome 17
: , .Lewy bodies
Tau
PHF- .
western blot- , 3 ,
bands 2 . , .
6 , FTDP-17- 4
, Pick's disease- 3 .
.
- ,
.
Neurofibrillary filaments
H&E- established stage- . early stage- H&E-
, .
tangle ,
GFAP- .
Neuritic (senile) Plaques
.
. ' .
, ,
.
, , .
" ( congo red ).
.
.
, ' , .

axonal spheroids .
neurofibrillary tangles (Tau)- .
.
GFAP ( amyloid angiopathy ).
.A
)Amyloid Precursor Protein (APP
A- .
. ...
, ,21
.

organ specific
' ,
.
APP
.
A
apolipoprotein-
E -
,


.


tangles- (
,
,
).

C ,B ,A
=( CERAD ) definite alzheimer's disease .
.'80-
, .tangles- tangles-
, .
3 AD-
- Granulovacuolar Degeneration .1
.olfactory bulb-
.2 - Hirano . , .
.3 / - Status Spongiosus - .
.

APP- ,
4 ApoE- ,
presenilin-1- presenilin-2 .
, ( )21 ,40-50 .
.


4

.