Gastrointestinal Pathology

Gastrointestinal Pathology

THE INTESTINE

intestine L. intestinus inward, internal < G. enteron
bowel F. boel > L. botellus sausage, intestine
duodenum L. duodeni twelve in a time; so called because it is about 12 fingerbreadhs in length
jejunum L. empty; 죽으면 텅 빈다고 생각되었던 데서 유래
ileum L. ilium groin, viscera > ilium (os ilii)
colon L. < G. kolon
cecum L. caecum blind, blind gut
rectum L. "straight"
anus L. "ring", "circle" > annular

학습목적

장의 정상구조와 기능을 이해하고 장에 발생하는 각종 질병들의 기전과 형태학적 소견을 임상소견과 연관지어 이해한다.

THE SMALL INTESTINE

CONGENITAL ANOMALIES

Meckel Diverticulum

          True diverticulum
            : All layers of the intestinal wall
          False diverticulum
            : Mucosa, submucosa and serosa layers

Meckel 게실의 발생부위, 형태학적 소견과 임상적 의의를 설명한다. (A)

Meckel Johann Friedrich Meckel (the younger) German anatomist (1781-1833)

　 : Persistence of the proximal portion of
omphalomesenteric duct　

* OMPHALOMESENTERIC (VITELLINE) DUCT: Connects the gut
  to the yolk sac during the first 3 to 5 weeks of
  fetal life. Disappears entirely by week 7 to 8,
  when the placenta replaces the yolk sac as the
  source of nutrition for the fetus.

yolk [jouk, joulk | jэuk] Old English geoloca (geolu yellow + -ca noun suffix) L. vitellus = vit(ulus) + -ellus diminutive suffix

placenta [plэsen'tэ] (pl. -tas, -tae [-ti:]) L. a cake < G. plakoeis flat cake derivative of plax flat

Omphalomesenteric duct. Lateral view of a 4-week-old embryo showing the relationship of the primordial gut to yolk sac.

: 1 - 3 ft. proximal to the ileocecal valve (aver. 80 cm),
antimesenteric

True diverticulum

Heterotopic gastric or duodenal mucosa;
or pancreatic tissue

: The most frequent congenital anomaly of the
digestive tract

　 : Peptic ulcertion
Diverticulitis
Obstruction due to intussusception and volvulus

intussusception L. intus within + suscipere to receive > intussusceptum, intussuscipiens > susceptibility

volvulus L. volvere to twist round

ISCHEMIC BOWEL DISEASE

Transmural Infarction

　: Almost always due to mechanical compromise of
the major mesenteric blood vessels

ischemia G. ischein to suppress + emia

infarction L. infarcire to stuff in

Mucosal and Mural (Mucosal and
Submucosal) Infarction

　: Often due to hypoperfusion, acute or chronic

mural L. muralis, from murus wall

INFLAMMATORY BOWEL DISEASES

  1. Diverticulitis
  2. Ischemic bowel diseases (Ischemic enterocolitis)
       2.1. Common type: Infarct (venous, arterial)
                         Transient ischemia
                         Ischemic stricture
       2.2. Obstructive enterocolitis
       2.3. Neonatal necrotizing enterocolitis
       2.4. Vasculitides
              : Polyarteritis nodosa, Rheumatoid arthritis,
                Systemic lupus erythematosus, Systemic sclerosis,
                Kawasaki disease, Buerger disease,
                Anaphylactoid purpura
  3. Physical and chemical injuries
       3.1. Intrinsic: Uremic enterocolitis
       3.2. Extrinsic: Mercury, Arsenic, Bismuth
                       Antibiotic-associated colitis
                         Hemorrhagic colitis
                       Anti-tumor agents-induced colitis
                       Radiation-induced enterocolitis
                       Oral contraceptives
                       KCl (potassium chloride tablets)
                       Enemas or cathartics
                       Stercoral ulcer
  4. Infections
       4.1. Viral: Cytomegalovirus colitis
       4.2. Bacterial: Nonspecific bacterial colitis
                         (Acute self-limited colitis,
                          Acute infectious-type colitis)
                       Staphylococcal enterocolitis,
                       Typhoid fever, paratyphoid fever,
                       Cholera, Yersinial infection,
                       Bacillary dysentery,
                       Pseudomembranous colitis,
                       Tuberculosis, Syphilis, Actinomycosis
       4.3. Chlamydial: Lymphogranuloma venereum
       4.4. Mycotic: Candidiasis
       4.5. Parasitic: Amebic dysentery, Balantidial dysentery
                       Schistosomiasis, Anisakiasis,
                       Strongyloidiasis, Giardiasis
  5. Immune-mediated
       5.1. Allergic colitis and proctitis
       5.2. Graft-versus-host diseases
  6. Inflammatory bowel diseases
       6.1. Ulcerative colitis
       6.2. Crohn disease
  7. Peptic ulcers
  8. Miscellaneous lesions
       8.1. Behcet disease, simple ulcer
       8.2. Solitary ulcer (mucosal prolapse) syndrome
       8.3. Multiple hemorrhagic (Chronic hemorrhagic, non-specific
            multiple) ulcers of the intestine
       8.4. Idiopathic diffuse eosinophilic enteritis
       8.5. Collagenous colitis
       8.6. Colitis or colonic ulcer, unclassified

INFLAMMATIONS CAUSED BY INFECTION

Typhoid Fever

　: Salmonella typhosa

　 : Fecal-oral route →
      Transcytosis through intestinal epithelial
        cells →
      Bacteremia →
      MPS

장티푸스의 특징적인 임상증상과 형태학적 소견들을 기술한다. (A)

salmonella Daniel Elmer Salmon, American pathologist, 1850-1914)

typhoid G. typhodes smoke-like; delirious

typhus G. typhos stupor arising from fever

INTESTINAL LESIONS

Peyer Johann Conrad Peyer, Swiss anatomist, 1653-1712

　     : Peyer patches and lymphoid follicles of the
           lower ileum and cecum (IMAGE)
           - Macrophages with phagocytosis of
             red cells, lymphocytes, plasma cells
             (= Typhoid cells (IMAGE))
         Necrosis, ulceration (longitudinal), hemorrhage
         Perforation, esp., lower ileum
         Peritonitis

    EXTRAINTESTINAL LESIONS
　    : Spleen, liver, mesenteric lymph nodes,
        bone marrow, gallbladder

mesentery G. mes(o)- intermediate, middle, moderate enteron intestine

       : Endotoxin
         Vascular blockage due to accumulated phagocytic
           cells and hyperreactivity to catecholamines

<Lab.>

　 : Blood culture - 1st week
       Stool culture - 2nd, 3rd weeks
       Urine culture - 3rd, 4th weeks
       Widal reaction - After the 1st week

Widal [vida:l] Georges Fernand Isidore Widal, French physician, 1862-1929

　 : Leukopenia (Neutropenia)

　 : Chronic carriers - GB
- Spleen

Paratyphoid Fever

　 : Shorter, less severe

　    : S. paratyphi A
        S. paratyphi B
        S. choleraesuis

Tuberculosis

　 : Primary - Contaminated milk or food
Secondary

: Lower ileum, cecum

　 - Circumferentially ulcerative form
- Hyperplastic form

장결핵의 호발부위와 형태학적 소견을 기술한다. (B)

　 : Tubercle

INFLAMMATIONS OF UNDETERMINED CAUSE
(INFLAMMATORY BOWEL DISEASE, IBD)

　 : Unknown

     : Genetic predisposition
        Infectious causes
          : Mycobacterium paratuberculosis, measles
       Abnormal host immunoreactivity
　        - Impaired function of small and large intestinal epithelial cells
            as antigen-presenting cells
          - Abnormal elaboration of cytokines
          - Abnormal function of natural killer lymphocytes
          - Induction of cytotoxic antiepithelial antibodies

Crohn Disease (Regional Enteritis)

　 : 2^nd and 3^rd decade; Elderly persons

Crohn Burrill Bernard Crohn, American physician, 1884-1983

　 GROSS (IMAGE)

Crohn병의 형태학적 특성과 합병증을 열거한다. (A)

　     : Small intestine (40%)
         Small intestine and colon (30%)
         Colon (30%)

: Segmental
Skip lesions, sometimes

      : Red, edematous
        Creeping mesenteric fat
        Fibrotic thickening (garden-hose thickening)
          (string sign)
        Proximal dilatation
        Mesenteric lymph node enlargement
      : Mucosal ulceration (aphthous ulcers ->
          serpentine, fissural ulcers)
        Cobble stone appearance
        Fistula and sinus tract formation
        Inflmmatory pseudopolyps

MICRO

　   : Crypt abscess
       Transmural chronic inflammation
         : Noncaseating granulomas (50%)
           Lymphoid aggregates, transmural

aphtha (pl. aphthae) L. < G. aphtha eruption, spot, speck < ? haptein to set on fire, to fasten, to seize, / 글자 그대로의 의미는 점이다. 과거에는 oral candidiasis ( = thrush: candida가 흰 반점을 만듬)도 aphtha라고 하였다. 지금은 구강 점막의 canker sore를 aphtha 또는 aphthous ulcer라고 한다. (우리나라 말로는 oral candidiasis와 canker sore 모두 아구창 (牙口瘡, 鴉口瘡)이다.) 그러나 흔히 원인에 관계 없이 작은 궤양을 표현하기 위해서 사용한다. 그런 경우 구강의 aphthous ulcer와 구분하기 위해 aphthoid ulcer라고 하기도 한다.

       Mucosal metaplasia
          : Pyloric metaplasia
            Paneth cell metaplasia
       Obstructive lymphedema

Paneth Joshep Paneth, Austrian physician, 1857-1890

Chronic and relapsing

　 Intestinal manifestations
       : Mass
         Chronic obstruction
         Fistula
         Abdominal pain
         Weight loss
         Cancer

Crohn병의 임상적 특성과 동반되는 질환들을 열거한다. (B)

abdomen L., possibly from abdere to hide

      Extraintestinal manifestations
        : Migratory polyarthritis, sacroiliitis, ankylosing spondylitis
          Erythema nodosum, clubbing fingers
          Uveitis
          Primary sclerosing cholangitis, pericholangitis
          Systemic amyloidosis

MALABSORPTION SYNDROMES, PRIMARY

Celiac Sprue (Gluten-Sensitive
Enteropathy, Nontropical Sprue,
Celiac Disease)

　 - Immune reaction to gluten (gliadin)

          = CELLULAR
                : T cells sensitized to gliadin
          = HUMORAL
                : Antigliadin, antiendomysial, antireticulin
                    antibodies
                  HLA-DR3, HLA-DQw2

- Toxicity of gluten (gliadin)

흡수장애 증후군을 발생기전에 따라 분류하고 그 예를 열거한다. (B)

celiac G. koilia belly

sprue Dutch spruw, Middle Lower German spru”we tumor-like

gluten, gliadin L. glia glue

tropic G. tropikos turning, trope a turning > tropism, tropic of Cancer (북회귀선), tropic of Capricorn (남회귀선)

　 Jejunal biopsy

: Blunting and flattening of villi
Lymphocytic infiltration

endomysium end(o)- G. endon within + mys muscle

villus L.“tuft of hair”

　     CANCER 1^st. T-cell lymphoma
                    (Enteropathy-associated T-cell lymphoma)
                2. GI and breast carcinomas

TREATMENT: Gluten-free diet

Tropical Sprue (Postinfectious Sprue)

  　: Celiac-like disease, almost exclusively of people
        living in or visiting the tropics, due to
        ? overgrowth of enterotoxigenic organisms (e.g.,
        E. coli and Haemophilus)

Whipple Disease

: Infection of the intestine, CNS, and joints by Gram
(+) actinomycete, Tropheryma whippelii

Small intestinal mucosa

Whipple George Hoyt Whipple, American pathologist, 1878-1976; co-winner, with George R. Minot and William P. Murphy, of the Nobel prize for medicine/physiology in 1934 for their research into the therapeutic value of liver in cases of pernicious anemia and regeneration of hemoglobin

          : Thickened
            Clubbing of villi
            Dilated lymphatics, lipogranuloma
            Large pale macrophages with intra- and
             extra-cellular rod-shaped bacilli

Mesenteric lymph nodes
: Large pale histiocytes

　     SYSTEMIC
          : Fever, polyserositis, migratory polyarthritis,
            diarrhea, intestinal malabsorption, progressive emaciation

TREATMENT
: Antibiotics

TUMORS OF SMALL INTESTINE

　 Benign: Adenoma (1^st.), leiomyoma (2^nd.), ...

   Malign: Adenocarcinoma
           Carcinoid
           Lymphoma ...

* The rarity of tumors, both benign and malignant, of
the small intestine is one of the enigmas of medicine.

Carcinoma - Periampullary Tumor

   : Duodenal mucosa covering and surrounding the
       papilla of Vater
     Ampulla of Vater
     Distal end of common bile duct
     Distal end of pancreatic duct and ductules

Carcinoid Tumors (Argentaffinoma)

papilla [pэpi'lэ] (pl. papillae [pэpi'li:] L. nipple, teat, akin to papula papule < late Middle English pap a baby's call for food, cooresponding L. pappa

ampulla L. "a jug" > ampule

Vater Abraham Vater, German anatomist, 1684-1751

　: Infiltrative, metastasizing neoplasm of
a low grade malignancy

     In contrast to ileal, gastric, and colonic
     carcinoids, appendiceal and rectal carcinoids
     infrequently metastasize.

소장 유암종 (carcinoid tumor)의 기원세포와 임상증상을 설명한다. (B)

　 : Kulchitsky cells

GROSS

Kulchitsky [ku:lt∫i'kski] Nikolai K. Kulchitsky, Russian histologist, 1856-1925

　       1^st. Appendix
               : Tip
                 Locally invasive; but benign
                 No carcinoid syndrome
         2^nd. Small intestine (Ileum); 3^rd. Rectum; 4^th. Stomach; 5^th. Colon
               : Submucosal mass < 3 cm

　 MICRO

　 : Uniform cells, with distinct nuclei and ill-defined cytoplasm
Trabeculae, islands, glands (adenocarcinoid), sheets

　      : Serotonin (5-Hydroxytryptamine, Enteramine),
          bradykinin (← kallikrein), prostaglandins,
          histamine

serotonin sero- + tone + -in

: Urine - 5-Hydroxy-3-indole acetic acid

　 * Carcinoid syndrome

　 : Liver metastasis
Tumor with venous drainage bypassing the liver

            : Vasomotor disturbances - cyanosis
                                     - flushing
              Intestinal hypermotility
              Bronchoconstriction
              Right-sided cardiac involvement

               : Endocardial fibrosis
                   - Tricuspid, pulmonary valves
             Hepatomegaly
             Pellagra-like lesion

pellagra Italian pelle skin + agra rough

THE LARGE INTESTINE

CONGENITAL ANOMALIES

대장 점막의 형태를 기술하고 소장 점막과의 차이점을 설명한다. (B)

Congenital Megacolon
(Hirschsprung Disease)

선천성 거대 결장의 원인과 임상증상, 진단방법을 기술한다. (A)

Hirschsprung Herald Hirschsprung, Danish physician, 1830-1916

     : Migration failure of neuroblasts to
       myenteric Auerbach and submucosal Meissner
       plexuses

Auerbach Leopold Auerbach, German anatomist, 1828-1897

Meissner Georg Meissner, German physiologist, 1829-1905

GROSS

: The rectum is always affected, with involvement
of more proximal colon to variable extents

        : Aganglionic segment - narrowed
            : Functional obstruction,
              pseudo-obstruction
            Proximal dilatation

ganglion G. "knot"

MICRO

: No ganglion cells
Proliferation of nonmyelinated nerve fibers

plexus [ple'ksэs] (pl. plexus, plexuses) L. an interweaving, twining < plectere to turn, akin to plicare fold > plica

Hirschsprung disease

COLONIC DIVERTICULOSIS - Acquired Diverticula

　 : Acquired herniation of the mucosa and submucosa
through a weak place in the muscularis of the
bowel (commonly, arterial vasa recta)

대장 게실의 병인, 형태학적 소견, 임상 소견을 기술한다. (A)

    - Small intestine: Mesenteric border
    - Colon: Along the margins of the teniae
        = Sigmoid (95%)
        = Descending colon

tenia, taenia [ti':niэ| -njэ] (pl. -niae [-nii:]) L. taenia flat band, ribbon > taeniae coli, Taenia saginata, Taenia solium

     : Unless otherwise specified, diverticular disease
        of the colon refers to acquired diverticulosis.
　   : Diverticulitis, peridiverticulitis

ISCHEMIC BOWEL DISEASE

Transmural Infarction

Mucosal and Mural Infarction

　 : Often due to hypoperfusion, acute or chronic

　 : Chronic ischemic colitis may present as an insidious inflammatory
disease, with intermittent episodes of bloody diarrhea interspersed
with periods of healing, mimicking inflammatory bowel disease.

Ischemic disease of the colon. The stippled area of the splenic flexure is more commonly affected because it is the watershed area between the ateries.

INFLAMMATORY BOWEL DISEASES

Acute Self-Limited Colitis

: Campylobacter; Salmonella, shigella, others;
Undetermined

: Self-limited diarrhea

diarrhea G. dia through rhein to flow. An increase in stool mass, stool frequency, or stool fluidity

disentery L. dysenteria, from G. dys- + enteron intestine. Low-volume, painful, bloody diarrhea

Bacillary Dysentery

: Shigella dysenteriae

shigella from Kiuoshi Shiga, Japanese physician, 1870 - 1957

　 : Endotoxin - Intestinal mucosa
Exotoxin - Nervous system

　 : Distal parts of the colon

       Pseudomembranous (Diphtheritic) inflammation
          - Necrosis and shallow ulceration
              of the mucosa
            Fibrinopurulent exudate
            Neutrophilic infiltration,
              most greatly in the submucosa

diphtheria [difθi':riэ, dip- | -θi'эriэ] G. diphthera leather + -ia

Pseudomembranous (Entero-)Colitis

　 : Exotoxin of Clostridium difficile

     : Antibiotics
       Surgery
       Chronic debilitating illnesses

clostridium G. kloster spindle difficile L. difficilis difficult

위막성 대장염의 형태학적 소견과 원인을 나열한다. (A)

　 : Colon; small intestine

      : Mucosal denudation
        Pseudomembrane (IMAGE)
          - Fibrinous exudate
            (volcano-like eruption (IMAGE))
          - Neutrophils, cellular debris

Necrotizing Enterocolitis
(Idiopathic Necrotizing Enterocolitis, Neonatal)

　 : Premature; fullterm
Formula-fed infants

　    : Ischemic injury
        Colonization of pathogenic organisms
        Excess protein substrate in the intestinal lumen
        Functional immaturity of the neonatal gut

　 GROSS

　 : Terminal ileum, ascending colon

　 MICRO

　 : Hemorrhage
Necrosis, ischemic type

　    : Stricture
        Perforation
        Pneumatosis cystoides intestinalis

Amebic Dysentery

　 : Entameba histolytica

ameba L., from G. amoibe change

　 : Cecum, flexures, rectum
Undermined, flask-shaped ulceration

INFLAMMATIONS OF UNDETERMINED CAUSE
(INFLAMMATORY BOWEL DISEASE, IBD)

Ulcerative Colitis

: Early or middle adult life

　 : Rectum and sigmoid; proximal spread
Backwash ileitis (10%)

ACUTE PHASE

특발성 궤양성 대장염을 정의하고 호발부위를 나열한다. (A)

특발성 궤양성 대장염의 병인과 형태학적 소견을 기술한다. (A)

특발성 궤양성 대장염의 동반 질환과 합병증을 기술한다. (A)

　   : Hyperemia of the mucosa
       Infiltration of the mucosa and submucosa by leukocytes
         (lymphocytes, plasma cells, neutrophils) and mast cells
       Crypt abscesses (IMAGE)
       Ulceration of the mucosa and submucosa (IMAGE)
       Psudopolyps
       Mucosal bridges
       Epithelial dysplasia

　 RESOLVING/QUIESCENT PHASE

: (Fibrosis of a limited degree)

Chronic and relapsing　

      Intestinal manifestations
        : Severe hemorrhage
          Fluid and electrolyte disturbances, protein loss
          Toxic megacolon: Sudden cessation of bowel function during acute attack,
                             due to toxic damage to the muscularis propria and neural
                             plexus
          Perforation and peritonitis
          Carcinomatous change - extent and duration

      Extraintestinal manifestations
        : Migratory polyarthritis, sacroiliitis,
            ankylosing spondylitis
          Uveitis
          Primary sclerosing cholangitis, pericholangitis
          Erythema nodosum

Crohn병과 특발성 궤양성 대장염과의 형태학적, 임상적 차이를 기술한다. (A)

The distribution patterns of UC and CD are compared, as well as the different conformations of the ulcers and wall thickenings.

Ulcerative Colitis Crohn Disease

                                     UC                    CD
   PATHOLOGIC FEATURES
     Segmental                       0                     ++
     Transmural involvement          +/-                   ++
     Granulomas                      0                     +/++ (50%)
     Fibrosis                        +                     ++
     Fissuring, fistulas             +/-                   ++
     Mesenteric fat,                 0                     ++
       lymph node involvement
   CLINICAL FEATURES
     Diarrhea                        ++                    ++
     Rectal bleeding                 ++                    +
     Abdominal pain                  +                     ++
     Palpable mass                   0                     ++
     Fistulas                        +/-                   ++
     Strictures                      +                     ++
     Small bowel involvement         +/-                   ++
                                     ("backwash ileitis")
     Rectal involvement              ++ (95%)              +/++ (50%)
     Extraintestinal disease         ++                    ++
     Toxic megacolon                 +                     +/-
     Recurrence after colectomy      0                     +
     Malignancy (with                +                     +/-
       long-standing disease)
                      (0, never; +/-, rare; +, occasional; ++, frequent, common)

TUMORS OF COLON AND RECTUM

대장 용종을 분류하고 각 유형별로 암과의 관계를 기술한다. (A)

Benign - Epithelial: Polyps

Frequency Size Villous Ca. change

Hyperplastic polyp 90% Smallest (-) (-)

      Neoplastic polyp           10%
        - Tubular adenoma            Most                 < 25%         3-5%
        - Tubulovillous adenoma      5-10%                25-50%       Interm
        - Villous adenoma              1%     Largest     > 50%         30%

      Hamartomatous polyp
        - Juvenile polyp
        - Peutz-Jeghers polyp

Malign - Epithelial: Carcinoma

  * The carcinomaous change of a neoplastic polyp is
    correlated with three interdependent features:
    size, villous pattern, and degree of dysplasia.

polyp L. polypus G. polypous a morbid excrescence; 염증세포의 침윤이나 간엽조직의 증식에 의해서도 polyp이 만들어지나 특별히 표기하지 않으면 상피조직의 증식에 의한 병변을 지칭한다.

The hyperplastic polyp sits as a small, hemispheric dome on top of the mucosal fold. The tubular (pedunculated) adenoma has a slender stalk and a knobby, raspberry-like head. The sessile villous adenoma has a broad base and myriad delicate papillae protruding into the lumen.

Sporadic Polyps

Hyperplastic Polyp

     GROSS: Rectosigmoid: 60-80%
            Ascending colon: 20%

          : Sessile
            Frequently multiple
            < 5 mm

MICRO: Mature goblet cells, absorptive cells
Serrate or sawtooth appearance

sessile [se'sil | se'sail] L. sessilis < sedere to sit > sit

peduncle L. pedunculus < L. pediculus little foot pes (gen. pedis) foot + -culus > pedicle, pedal, pedestrian, pedigree (가계도를 두루미의 발모양으로 보고서), pediculosis

serrate [se'rit, se'reit] L. serra saw

: Adenomatous change

Tubular (Glandular) Adenoma (`Adenomatous Polyp')

<Morphology> (IMAGE)

GROSS: Rectosigmoid: 50 - 60%

          : Pedunculated
            More than 1 in 50% of the cases
            A few mm to cm

gland L. glans (gen. glandis) acorn; a general term for a small rounded mass, or gland-like body

aden(o)- G. aden (gen. adenos) gland

      MICRO: Lack of differentiation ( → Atypia)
             Picket fence appearance
             Villous growth < 25%

: Carcinomatous change, 3 - 5%

Tubulovillous Adenoma

GROSS: Rectosigmoid

: Sessile - pedunculated

MICRO: Villous 25 - 50%

: Carcinomatous change, intermediate

Villous Adenoma

      GROSS: Rectum: 50 - 55%
             Sigmoid: 30%
             Descending colon: 10%

           : Broad, sessile
             Usually single
             1 - 10 cm

MICRO: Villous > 50%

: Carcinomatous change (30 - 70 %)

　 * Protein-, mucus-secreting villous adenoma

          : Hypoproteinemia
            Hypokalemia
            Hyponatremia

     * Protein-losing enteropathies
         - Idiopathic
         - Acquired

idiopathic G. idios one's own, separate + pathos disease

              = Gastrointestinal
                  : Menetrier disease
                    Crohn disease, UC, other infl.
                    Lymphangiectasia of small intestine
                    Villous adenoma of the colon
              = Extraintestinal
                  : Chronic constrictive pericarditis

Juvenile (Childhood, Retention) Polyp

: Stromal growth, cystic dilatation

　 * Cronkhite-Canada syndrome

          : Nonhereditary multiple juvenile polyposis
          + Ectodermal changes; Alopecia, nail atrophy,
                                hyperpigmentation

Peutz-Jeghers Polyp

: Hamartomatous polyps

Cronkhite [kro'ŋkit] Leonard Wolsey Cronkhite, Jr., American internist, born 1919

Canada [kæ'nэdэ] Wilma Jeanne Canada, American radiologist, 20th century

Peutz J.L.A. Peutz, [pэ:tz] Dutch physician, 1886-1957

Jeghers [dze'gэ:z] Harold Jeghers, American physician, born 1904

Familial Syndromes

: All autosomal dominant transmission
High malignant potential (except Peutz-Jeghers
syndrome)

- Familial polyposis syndromes
- Hereditary nonpolyposis colorectal cancer (HNPCC,
Lynch syndrome)

Familial polyposis syndromes과 Hereditary nonpolyposis colorectal cancer를 설명한다. (A)

Familial Polyposis Syndromes

- Familial adenomatous polyposis (FAP) (Adenomatous polyposis coli (APC),
Familial polyposis coli)

: Defect of APC gene on 5q21

         GI polyposis
           : Colon; small intestine, stomach
             Tubular adenoma; villous adenoma
         Malignant transformation in 100% (IMAGE)

Var. Gardner syndrome

+ Epidermal cysts, fibromas, lipomas,
osteomas (mandile, skull), ampullary cancer

Var. Turcot syndrome

+ Brain tumor (malignant glioma)

Gardner Eldon John Gardner, American geneticist, born 1909

Turcot [tэ:ko'u] Jacques Turcot, Canadian physician, born 1914

- Multiple juvenile polyposis

: Hamartomatous polyps

- Peutz-Jeghers syndrome

      : Hamartomatous polyps
        GI polyposis: Small intestine;
                      entire GI tract
        Rare carcinomatous change
        Mucocutaneous melanin pigmentation
          : Lips, mouth

Peutz J.L.A. Peutz, [pэ:tz] Dutch physician, 1886-1957

Jeghers [dze'gэ:z] Harold Jeghers, American physician, born 1904

Hereditary Non-Polyposis Colorectal Cancer
(HNPCC, Lynch syndrome)

     1. The presence of three or more relatives with
        histologically documented colorectal cancer, one of
        whom is a first-degree relative of the other two
     2. One or more cases of colorectal cancer diagnosed
        before age 50 in the family
     3. Colorectal cancer involvement at least two
        generations

Lynch Henry T. Lynch, American epidemiologist, the reporter of "Cancer Family G" in 1971

     : High frequency of adenocarcinoma in the
         proximal colon, often multiple
       Association with ovarian or endometrial carcinomas

: Autosomal dominant transmission

     : Defect of DNA mismatch repair genes →
       Genetic instability (RER = replicative error;
                            MIN = microsattelite instability)

         - hMSH2 on chromosome 2p
         - hMLH1 on chromosome 3p
         - hPMS1 on chromosome 2q
         - hPMS2 on chromosome 7p

A mismatch repair model

hMSH2: human MutS homolog 2

hMLH1: human MutL homolog 1

hPMS1,2: homologs of yeast postmitotic segreation genes 1,2

hMSH2 binds specifically to a mismatched base pair, while hMLH1 scans the nearby DNA for a nick which is present in a newly synthesized strand.

Nonepithelial Polyps - Lymphoid Polyp

: Submucosal lymphoid hyperplasia

Carcinoma

    : Most cases occur sporadically, about 1 to 3% occuring
      in patients with familial syndromes or inflammatory
      bowel disease. However, they take the same road to
      colorectal carcinoma.

대장암의 adenoma-carcinoma sequence를 분자유전학적 으로 설명한다. (B)

: Normal epithelium

↓ Germline or somatic mutations of cancer suppresor genes (first hit)

: APC at 5q21, MSH2 at 2p22

Risky epithelium

↓ Methylation abnormalities: Hypomethylation

↓ Inactivation of APC, MSH2 alleles (second hit)

Early adenoma

↓ Protooncogene mutation: K-ras at 12p12

Intermediate adenoma

↓ LOH of additional cancer suppressor genes

: DCC (deleted in colon cancer) at 18q21 (?)

Late adenoma

↓ LOH of additional cancer suppressor genes: p53 at 17p13

Carcinoma

↓ Additional mutations

Metastasis

      SITE: Cecum and ascending colon (38%)
            Transverse colon (18%)
            Descending colon (8%)
            Sigmoid (35%)
            Multiple sites (1%)

GROSS

1. Annular infiltrating type

우측과 좌측에 발생하는 대장암의 차이점을 기술한다. (A)

: Ulcerative, obstructive (napkin-ring constriction)
Left-sided colon

2. Polypoid, fungating form

: Bleeding, anemia
Right-sided colon

MICRO

: Adenocarcinoma

Dukes [du:ks] Cuthbert Esquire Dukes, English pathologist, 1890-1977

      Stage A: Limited to the mucosa
      Stage B1: Extending to the muscularis propria but not penetrating through it;
                uninvolved nodes
      Stage B2: Penetrating through the muscularis propria;
                uninvolved nodes
      Stage C1: Extending to the muscularis propria but not penetrating through it;
                involved nodes
      Stage C2: Penetrating through the muscularis propria;
                involved nodes
      Stage D: Distant metastatic spread

epithelium G. epi- ep- on thele nipple; the covering of internal and external surfaces of the body, including the lining of vessels and other small cavities.

mesenchyma G. mesi(o)- in the middle enchyma infusion; the meshwork of embryonic connenctive tissue in the mesoderm from which are formed the connective tissues of the body, including the blood and lymphatic vessels

polyp G. polypous a morbid excrescence; any nodule or mass that projects above the level of the surrounding mucosa

tubular L. tubulus < tubus

villus L.“tuft of hair”

hamartoma G. hamartia fault + -oma

parenchyma [G. par- beside en- in chein to pour; "anything poured in beside", "visceral flesh": from the belief that the tissue of an internal organ was poured in by the blood vessels of the organ] the essential elements of an organ; used in anatomical nomenclature as a generic term to designate the functional elements of an organ, as distinguished from its framework, or stroma

stroma [G. stroma bed covering, spread, bed] the supporting tissue or matrix of an organ, as distinguished from its functional element, or parenchyma

APPENDIX

INFLAMMATION

Acute Appendicitis

: Adolescents, young adults

    : Luminal obstruction by fecaliths, lymphoid tissue,
         calculus, fibrous thickening,
         parasites (O. vermicularis), tumor

급성 충수염의 발생기전을 설명한다. (A)

Vascular occlusion
Bacterial invasion

1. Early acute appendicitis (Catarrhal appendicitis)

: Scant neutrophilic exudation in
the mucosa, submucosa, and muscularis propria

2. Acute suppurative appendicitis

          : Advanced neutrophilic exudation in all layers
            Mucosal ulceration
            Fibrinopurulent serositis

3. Acute gangrenous appendicitis

: Wall necrosis

      : Pain; periumbilical → RLQ
        Nausea, vomiting
        Tenderness
        Fever
        Leukocytosis

     : Periappendiceal abscess
       Perforation → Peritonitis, localized - generalized
       Pylephlebitis, liver abscess, bacteremia
       False diverticulum

pylephlebitis G. pyle gate + phleps vein + -itis; inflammation of portal vein

Chronic Appendicitis

: Recurrent acute appendicitis, at best (?)

TUMORS

: The most common appendiceal tumor is the carcinoid.

        Benign - (Hyperplasia)
               - Adenoma
                   = (Var.) Mucinous adenoma
        Malign - Adenocarcinoma
                   = (Var.) Mucinous adenocarcinoma

Mucocele

: Appendiceal dilatation by mucinous secretion

1. Mucosal hyperplasia

: Serosal, peritoneal mucinous deposits (-)

2. Mucinous (cyst)adenoma

       : Most common
       : Serosal, peritoneal mucinous deposits
           without neoplastic cells

mucocele L. mucus + G. kele tumor

myx(o)- G. myxa mucus

점액류와 복막가점액종을 정의하고, 점액류를 발생시키는 충수돌기의 병변을 설명한다. (A)

3. Mucinous (cyst)adenocarcinoma

        : Serosal, peritoneal implants with neoplastic cells
          (Invasion by neoplastic cells)
          Spread above diphragm or visceral invasion: exceptional

Pseudomyxoma peritonei

: Implants of mucin-producing adenocarcinoma