GASTROINTESTINAL TRACT PATHOLOGY

Mary Yvonnette C. Nerves, RMT, MD, FPSP

Congenital abnormalities
Atresia/Fistulae/Duplications
Imperforate Anus
Diaphragmatic Hernia/
/Omphalocele/Gastroschisis
Meckel’s Diverticulum
Pyloric Stenosis
Hirschsprung Disease
GIT PATHOLOGY:
Esophagus Stomach Small intestine and colon Peritoneal cavity
Esophageal Acute gastritis Intestinal obstruction Congenital abnormalities
Obstruction Achalasia
Diverticulum Chronic gastritis Ischemic bowel disease Esophagus
Esophageal Mucosal Acute Gastric Ulceration Angiodysplasia Stomach
Web
Esophageal rings Peptic ulcer Infectious enterocolitis Small intestine and colon
Esophagitis/ Gastric polyps Inflammatory bowel disease Peritoneal cavity
Reflux Esophagitis
Hiatal Hernia Hypertrophic gastropathies Sigmoid diverticulitis
Barrett’s Esophagus Tumors Hemorrhoids/anal cancer
Dysplacia Dysplacia Acute
appendicitis/appendiceal
tumors
Esophageal Varices Carcinoma Tumors
Familial syndromes
Esophageal Tumors

CONGENITAL ABNORMALITIES:  Gastric heterotopia: patches of ectopic gastric mucosa in the small
I. ATRESIA / FISTULAE: bowel colon
rd
 Atresia is a condition in which a body orifice or passage in the body is  Most common site of ectopic gastric tissue – upper 3 of the
abnormally closed or absent esophagus  release acid in eso  dysphagia, esophagitis, Barretts
 Fistula is an abnormal connection or passageway between two or adenoCA
epithelium-lined organs or vessels that normally do not connect.
VII. MECKEL DIVERTICULUM:
Type A: pure esophageal atresia (7.6%)  Most common type of true diverticulum
Type B: esophageal atresia with proximal tracheoesophageal fistula (0.8%)  Occurs in the ileum
Type C: esophageal atresia with distal tracheoesophageal fistula (86.5%)  Occurs as a result of failed involution of the omphalomesenteric
Type D: esophageal atresia with proximal and distal tracheoesophageal (vitelline) duct
fistula (0.7%)  RULE of 2s:
Type E: "H-type" tracheoesophageal fistula without esophageal atresia - 2% of the pop’n
(4.4%) - present within 2 feet of the ICV
- approx. 2 inches long
II. IMPERFORATE ANUS: Most common form of congenital intestinal - 2x as common in males
atresia; due to failure of the cloacal diaphragm to involute; - symptomatic by age 2
III. DIAPHRAGMATIC HERNIA: Intestine protruding through hole in  TRUE DIVERTICULUM: blind outpouching lined by mucosa that
diaphragm communicates with the lumen and includes all 3 layers of the
IV. OMPALOCELE (EXOMPHALOS): bowel wall
 Defect of the anterior abdominal wall at the insertion of the
umbilical cord VIII. PYLORIC STENOSIS:
 Occurs in 1 in 5000 to 1 in 20,000 live births  Due to progressive thickening of the circular muscle of the pylorus
 Associated with chromosomal defects,(trisomies 13, 18, and 21),  gastric outlet narrowing
and with other disorders such as Beckwith-Wiedemann  3-4x more common in MALES
nd rd
Syndrome  Generally presents in the 2 or 3 week of life  new-onset
 Closure of abdominal musculature is incomplete  abdominal regurgitation and persistent, projectile, nonbilious vomiting
viscera herniate into a ventral membranous sac  P.E.: hyperperistalsis; ovoid abdominal mass’

Five common features used to define BWS are: macroglossia, macrosomia
(birth weight and length greater than the 90th percentile), midline
abdominal wall defects (omphalocele/exomphalos, umbilical hernia,
diastasis recti), ear creases or ear pits, and neonatal hypoglycemia (low
blood sugar after birth).
V. GASTROCHISIS (LAPAROSCHISIS):
 A small (generally < 5 cm) defect of the abdominal wall just to the
right of the umbilical cord insertion, allowing evisceration of
bowel loops, stomach, and sometimes the gonads
 Prevalence: 1 in 10,000 livebirths
 ventral wall defect involving all layers of the abdominal wall
VI. ECTOPIA (DEVELOPMENTAL RESTS):
 Ectopic gastric mucosa (inlet patch): esophagus
 Ectopic pancreatic tissue: stomach/esophagus
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IX. HIRCHSPRUNG DISEASE
 A.k.a. Congenital Aganglionic Megacolon
 Normal migration of neural crest cells from the cecum to rectum is
arrested prematurely or when the ganglion cells undergo
premature death
 Distal intestinal segment lacks both Meissner submucosal and the
Auerbach myenteric plexus
 Clinical Features: earliest and most common presentation is
delayed (> 48 hrs) passage of meconium in the newborn
 Infants and older children: chronic constipation, abdominal
distention and vomiting
 Pathologic Feature: distal narrow aperistaltic hypertonic segment
(aganglionic) and a dilated proximal segment caused by obstruction
 Aganglionic region may have a grossly normal or contracted
appearance while the normally innervated proximal colon
 May undergo progressive dilation
ESOPHAGUS:
 A muscular tube connecting the throat (pharynx) with the stomach.
 8 inches long, and is lined by moist pink tissue called mucosa.
 Runs behind the windpipe (trachea) and heart, and in front of the
spine. Just before entering the stomach, the esophagus passes through
the diaphragm.
 The upper esophageal sphincter (UES) is a bundle of muscles at the
top of the esophagus. The muscles of the UES are under conscious
control, used when breathing, eating, belching, and vomiting. They
keep food and secretions from going down the windpipe.
 The lower esophageal sphincter (LES) is a bundle of muscles at the
low end of the esophagus, where it meets the stomach. When the LES
is closed, it prevents acid and stomach contents from traveling
backwards from the stomach. The LES muscles are not under voluntary
control.
I. DIVERTICULUM:
An outpouching of the alimentary tract that contains one or more
layers of the wall
ZENKER’S DIVERTICULUM (Cricopharyngeal / Pharyngoesophageal):
located above the UES; results from increased intrapharyngeal pressure in
areas of weakness along the esophageal wall; An outpouching of the
esophageal mucosa at points of weaknesses in the wall of the esophagus at
the junction with the pharynx (inferior constrictor muscle and obliquely
passing fibers of the cricopharyngeal muscles as they descend on the
posterior wall of the esophagus to become longitudinal)
Traction diverticulum: located immediately above the UES; located in
the lower 3rd of the esophagus and in the region of the hilum of the lung;
attributed to fibrosing mediastinal processes or abnormal motility.
Epiphrenic diverticulum: immediately above the LES; located just above
the diaphragm; Cause: unclear
II. ESOPHAGEAL MUCOSAL WEBS
 Ledge-like protrusions of mucosa
 Pathogenesis: unknown
 Paterson-brown-kelly or Plummer-vinson syndrome: webs + IDA
+ glossitis + cheilosis; found in women and associated with IDA
 Most common in upper esophagus
III. ESOPHAGEAL RINGS
A.k.a. Schatzki’s / Lower esophageal Esophagogastric rings
Similar to webs but are circumferential and thicker
Rings include mucosa, submucosa and, in some cases,
hypertrophic muscularis propria
A rings: present in distal esophagus, above the GEJ
B rings: located at the squamocolumnar junction of the lower
esophagus
Treatment: endoscopic dilatation and surgical myomectomy
IV. ACHALASIA:
 A.k.a. Cardiospasm or megaesophagus
 An esophageal motility disorder characterized by an inability of the
LES to relax after swallowing, resulting
 In periodic esophageal obstruction
 Nearly complete loss of myenteric ganglion cells is present in the
lower 3rd of the esophagus
 Generally synonymous with the word “esophagospasm”
 TRIAD: Aperistalsis, Incomplete relaxation of the LES, Increased
LES tone
 Barium swallow: dilated, aperistaltic esophagus with a beak-like
tapering at distal end
 Progressive dysphagia starting in teens
 Pathogenesis: unknown
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V. ESOPHAGITIS:
 LACERATIONS: Mallory-Weiss tears longitudinal tears in the
esophagus near the GEJ assoc with severe retching or vomiting sec to
acute alcohol intoxication
 Boerhaave syndrome: char by distal esophageal rupture and
mediastinitis
VI. REFLUX ESOPHAGITIS:
A.k.a. Gastroesophageal Reflux Disease (GERD)
Reflux of gastric contents into the lower esophagus (most frequent
cause of esophagitis)
Most common clinical symptoms: dysphagia, heartburn,
regurgitation of sour-tasting gastric contents
Pathogenesis: reflux of gastric juices is central to the devt of mucosal
injury
Conditions that decrease LES tone or increase abdominal pressure:
a) alcohol and tobacco use
b) obesity
c) central nervous system depressants
d) pregnancy
e) hiatal hernia
f) delayed gastric emptying
g) increased gastric volume
Gross: marked hyperemia with focal hemorrhage
Morphology: intraepithelial eosinophils and basal zone hyperplasia
VII. HIATAL HERNIA:
 Characterized by separation of the diaphragmatic crura and
protrusion of the stomach into the thorax through the resulting gap
 Of the three major tubes that traverse the diaphragm, the
esophagus has the weakest surroundings, much more muscular and
less fibrous than the aorta and IVC.
 HH can be thought of as a sequela of chronic gastric overdistention.
VIII. BARRETTS ESOPHAGUS:
Can be defined as intestinal metaplasia of a normally SQUAMOUS
esophageal mucosa.
The presence of GOBLET CELLS in the esophageal mucosa is
DIAGNOSTIC.
SINGLE most common RISK FACTOR for esophageal adenocarcinoma
10% of GERD patients get it
Most common in white males; between 40-60 years of age
You can think of Barrett’s as REVERSE squamous metaplasia.
GROSS: patches of red, velvety mucosa extending upward from the
GEJ (You should have, by now, a good feel for squamous (shiny) vs.
columnar (mucoid) surface mucosas anywhere in the body.)
Intestinalized (gastricized) mucosa is AT RISK for glandular dysplasia.
Searching for dysplasia when BARRETT’s is present is of utmost
importance
MOST/ALL adenocarcinomas arising in the esophagus arise from
previously existing BARRETT’s
IX. DYSPLASIA:
 Glandular “dysplasia”: Find the atypical cells. Increased epithelial
proliferation, often with atypical mitoses, nuclear hyperchromasia and
stratification, irregularly clumped chromatin, increased nuclear-to-
cytoplasmic ratio, and a failure of epithelial cells to mature as they
migrate to the esophageal surface are present in both grades of
dysplasia
X. VARICES:
 Dilated, tortuous veins within the lamina propria and submucosa
that bulge into the esophageal lumen because of portal hypertension
and portosystemic; shunting
 Three common areas of portal/caval anastomoses: Esophageal,
Umbilical, Hemorrhoidal
 100% related to portal hypertension
  Found in 90% of cirrhotics
 Massive, sudden, fatal hemorrhage is the most feared
consequence
 Any chronically increased venous pressure phenomenon which
dilates a vein, will also make it more tortuous---legs or esophagus!
Varices appear as tortuous dilated veins lying primarily within the
submucosa of the distal esophagus and proximal stomach.
 FACTORS that lead to RUPTURE:
- inflammatory erosion of thinned overlying mucosa
- increased tension in progressively dilated veins
- increased vascular hydrostatic pressure associated w/ vomiting
XI. TUMORS:
 BENIGN: Leiomyomas, Fibrovascular polyps, Condylomas (hpv)‫ ‏‬,‫‏‬
Lipomas, “granulation” tissue (pseudotumor)‫‏‬
The very BEST way to classify ALL tumors of a major organ is to
remember its basic HISTOLOGY.
You do NOT need to memorize a stupid list from a pathology lecture,
just remember an organ’s native cells!
 MALIGNANT: Squamous cell carcinoma and Adenocarcinoma

ADENOCARCINOMA SQUAMOUS CELL CARCINOMA

Commonest type in US Commonest type worldwide
Risk factor: Barrett esophagus Risk factors: esophagitis, smoking, alcohol, genetics
Distal 1/3 of esophagus Middle 1/3 of esophagus
Symptoms: insidious onset; late obstruction Symptoms: insidious onset; late obstruction
Arises in a background of Barrett esophagus & long-standing GERD Adults over age 45, affects MALES 4x more than females

RISK FACTORS: documented dysplasia, tobacco use, obesity, prior RISK FACTORS: Alcohol and tobacco use, caustic esophageal injury,
radiation therapy achalasia, Plummer-Vinson syndrome or Paterson-Kelly syndrome
presents as a classical triad of dysphagia, iron-deficiency anemia and
esophageal webs; and frequent consumption of very hot beverages
FACTORS that DECREASE RISK: Diet rich in fresh fruits and vegetables, H. Half of SCCs occur in the middle 3rd of the esophagus; Begins as an in-situ
pylori serotypes lesion (SQUAMOUS DYSPLASIA)
Most frequent in CAUCASIANS; M > F Sixfold more common in African-American
Usually occur in the distal 3rd of the esophagus DYSPLASIAIN-SITUNFILTRATION
Pathogenesis: Chromosomal abnormalities & mutation or Pathogenesis: incompletely defined; loss of tumor suppressor genes,
overexpression of p53 are present at early stages; Other genetic changes: including p53 and p16/INK4a
amplification of c-ERB-B2, cyclin D1 and cyclin E genes; mutation of
retinoblastoma tumor suppressor gene; allelic loss of the cyclin-
dependent kinase inhibitor p16/INK4a
Would you call this squamous “dysplasia”? Answer: YES
Would your fear it would develop into squamous cell carcinoma? Answer: YES
Does it always? Answer: NO
Does it usually? Answer: With time, YES, but that time may be years and years.

STOMACH:  NSAID-induced ulcers are related to cyclooxygenase inhibition

I. ACUTE GASTRIC ULCEERATION:
 Focal, acutely developing gastric mucosal defect
 Occur after severe physiologic stress
o Stress ulcers: shock, sepsis, or severe trauma
o Curling ulcers: occur in proximal duodenum; severe burns &
trauma
o Cushing ulcers: gastric, duodenal, esophageal; intracranial
disease
 prevents synthesis of prostaglandins, which enhance HC03
secretion, inhibit acid secretion, promote mucin synthesis, and
increase vascular perfusion
 Intracranial injury: caused by direct stimulation of vagal nuclei
 hypersecretion of gastric acid  systemic acidosis 
contribute to mucosal injury by lowering the intracellular pH
of mucosal cells.

ACUTE GASTRITIS CHRONIC GASTRITIS

A transient mucosal
inflammatory process
Pathogenesis: disruption of the
protective mechanisms:
 Mucin secreted by surface
foveolar cells prevents large
food particles from directly
touching the epithelium
Rich vascular supply to the
 H. pylori gastritis: most common cause of chronic gastritis
 Autoimmune gastritis: most common cause of atrophic gastritis and most common cause of chronic
gastritis in patients w/o H. pylori infection
H. pylori gastritis: Autoimmune gastritis:
H. pylori: spiral shaped or curved bacilli; present in almost ALL Spares the antrum and includes
duodenal ulcers & majority of individuals with gastric ulcers or chronic hypergastrinemia
gastritis; present in 90% of individuals w/ chronic gastritis affecting the
ANTRUM
 Increased acid secretion may result in PUD Characterized by:
 H. pylori infection confers increased risk of gastric Ca a) Abs to parietal cells & IF
 H. pylori transmission: oral-oral; fecal-oral; and environmental b) Reduced serum pepsinogen I
spread concentration
 H. heilmannii: has reservoir in cats, dogs, pigs c)Antral endocrine cell
hyperplasia
d) Vit. B12 def.
e) defective gastric acid secretion
(achlorhydria)
4 Features linked to H. pylori virulence: Pathogenesis:

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 gastric mucosa delivers O2,
HCO3, & nutrients and wash
away acid
a)Flagella: allow motility in viscous mucus  Loss of parietal cells
b)Urease: generates NH3 from endogenous urea & elevates local (responsible for secretion of
gastric pH gastric
c)Adhesins: enhance bacterial adherence to surface foveolar cells acid and IF)
d) Toxins: cytotoxin-assoc gene A (cagA): involved in ulcer & cancer  Loss of gastric acid 
development stimulates gastrin release 
hypergastrinemia &
hyperplasia of antral gastrin-
producing G cells
 Lack of IF  disables ileal vit.
B12 abs.  B12 def. 
megaloblastic anemia
Helicobacter pylori, gastric biopsy, silver stain on left, Giemsa stain on Morphology:
right. As a rule, these bugs ADHERE closely to the gastric mucin rather Diffuse atrophy
than invade the epithelial cells. Intestinal metaplasia
Antral endocrine hyperplasia

Located in the antrum Located in the body

PMNs, subepith plasma cells Lymphocytes, macrophages
Acid production: Increased to sl. decreased Decreased acid prodution
Gastrin: Normal to decreased Gastrin: Increased
Other lesion: Hyperplastic/inflam polyps Other lesion: Neuroendocrine
hyperplasia
Serology: Abs to H. pylori Serology: Abs to H. Parietal cells
Sequela: Peptic ulcer, adenoCA Sequela: Atrophy, PA, AdenoCA,
carcinoid tumor
Associations: Low socioeconomic status, poverty, residence in rural Associations: Autoimmune
areas disease; thyroiditis, DM, Graves
dse
The acute/chronic patterns of gastritis generally conform to the poly/mono principles we so often have referred to. The “oth er” categories of
gastritis are also histologically based.

II.PEPTIC ULCER DISEASE: Penetration, perforation: Pain in BACK, CHEST, LUQ

Most often associated with H. pylori- hyperchlorhydric chronic gastritis
Present in 85-100% persons with duodenal ulcers and 65% with gastric
ulcers
Pathogenesis: imbalances of mucosal defenses and damaging forces
that cause chronic gastritis
 H. pylori & NSAID use: primary underlying cause of PUD
 Gastric hyperacidity:H. pylori infection, parietal cell hyperplasia,
excessive secretory responses or impaired inhibition of stimulatory
mechanisms such as gastrin release
Common co-factors in peptic ulcerogenesis:
- Chronic NSAID use: direct chemical irritation & suppress PG
release necessary for mucosal protection
- Cigarette smoking: impairs mucosal blood flow & healing
- high-dose corticosteroids: suppress PG synthesis & impair healing
Solitary in > 80% of patients
< 0.3 cm: shallow ulcers
> 0.6 cm: deeper ulcers
Round or oval, sharply; punched-out defect – mucosal surface;
overhang the base (heaped up margins  cancer)
Gnawing, burning, aching pain, epigastric
Fe deficiency anemia
Acute hemorrhage
MALIGNANT TRANSFORMATION: very rare
III. MUCOSAL ATROPHY and INTESTINAL METAPLASIA:
 Strongly associated with increased risk of gastric adenoCA
 The risk of adenoCA is greatest in autoimmune gastritis
IV. DYSPLACIA:
 Chronic gastritis  exposes epith to inflam-related free radical damage
& proliferative stimuli genetic alterations
 Morphologic HALLMARKS:
o Variations in epithelial size, shape and orientation
o coarse chromatin texture
o hyperchromasia and nuclear enlargement
V. HYPERTROPHIC GASTROPATHY:
 Rugal prominence (cerebriform)
 No inflammation
 Hyperplasia of mucosa
*Probably better termed “hyperplastic” by the traditional classical
definition, but, conventionally, called “hypertrophic”.

MÉNÉTRIER DISEASE ZOLLINGER-ELLISON SYNDROME

Caused by excessive secretion of TGF-α
Diffuse hyperplasia of the foveolar epith of the body & fundus
& hypoproteinemia due to protein-losing enteropathy
Micro: hyperplasia of foveolar mucous cells
Caused by gastrin-secreting tumors, gastrinomas
Most commonly found in the SI and pancreas
Micro: Doubling of oxyntic mucosal thickness due to a fivefold increase in the number of
aprietal cells; Medium-power view of gastric mucosa in a patient with Zollinger–Ellison
syndrome. Note the large increase in the number of parietal cells
60-90% of gastrinomas are malignant
Note prominence or “cerebrated” appearance of rugae
Hyperplastic gastric mucosa necessitates an increase in surface area

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VI. GASTRIC POLYPS:
 Polyps: nodules or masses that project above the level of the
surrounding mucosa
 Inflammatory and Hyperplastic Polyps:
o approx. 75% of all gastric polyps
o usually develop in assoc with chronic gastritis
o Gross: majority are smaller than 1 cm. & frequently multiple;
ovoid w/ smooth surface
 In general, a “polyp” can be thought of as ANYTHING which
projects as a bump or nodule from a mucosal surface.
 Hyperplastic polyps are considered to be NON-neoplastic, and
therefore NEVER turn into cancers. ADENOMATOUS polyps are
FUNDIC GLAND POLYPS
Occur sporadically and in individuals w/ familial adenomatous polyposis
5x more common in females (ave. 50 y/o)
Occur in the gastric fundus
Gross: well-circumscribed & smooth
Micro: cystically dilated, irregular glands lined by flattened parietal or
chief cells
VII. CARCINOMA:
 Arise from the generative or basal cells of the foveolae, on a
background of chronic atrophic gastritis w/ intestinal metaplasia
and preceded by various stages of dysplasia, CIS, and superficial CA
 Accompanied by hypochlorhydria in 85-90% of cases
 High intragastric ph promotes the growth of bacteria that reduce
dietary nitrate to nitrite and then convert dietary amines, in the
presence of nitrite into carcinogenic N-nitroso-compounds
 Pathogenesis: germline mutations in CDH1 which encodes E-
cadherin (a protein that contributes to epithelial intercellular
adhesion)  loss of E-cadherin function a key step in the devt of
diffuse gastric CA; Mutations in Beta-catenin (a protein that binds
to both E-cadherin & APC), microsatellite instability and
hypermethylation of some genes  sporadic intestinal-type gastric
CA
 (2) Major categories of gastric adenocarcinoma:
a. INTESTINAL-TYPE: arise from metaplastic epithelium
b. DIFFUSE-TYPE: best represented by linnitis plastica or signet
ring (adeno)carcinoma
 Adenocarcinoma growth patterns: These are logical anatomic or
“geometric” descriptions, and NOT exact classifications.
o LINITIS PLASTICA: Most spectacular, and most feared, of
all gastric adenocarcinomas. It grows diffusely through all
layers of the stomach, greatly thickening its wall, and giving
the stomach a classic LEATHER BOTTLE appearance. It has a
horrible prognosis. DIFFUSE WALL THICKENING of ALL
FOUR STOMACH LAYERS IS THE RULE. Not only does it
behave like wildfire but is also poorly differentiated
“signet” cells, diffusely infiltrative.
o Signet ring cells are POORLY differentiated adenocarcinoma
cells, and are OFTEN seen with linitis plastica. Could those
large “holes” in the cytoplasm possibly be mucicarmine
positive” Answer: YES
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true benign neoplasms and MAY turn into carcinomas,
particularly if the exhibit DYSPLASIA on biopsy.
 This SAME general principle, is even MORE true of the colon!
 But in general, you know the drill: 1) Benign, 2) Malignant on one
axis, and 1) epithelial, 2) stromal, and 3) lymphoid on the other
axis.’
 Micro: irregular, cysticaly dilated and elongated foveolar glands
A Gross appearance of gastric polyps of hyperplastic type. Many
of the lesions show central umbilication.
B Low-power microscopic view of gastric polyps of hyperplastic
type. The cystic dilatation of the glands
GASTRIC ADENOMA
Almost always occur on a background of chronic gastritis with atrophy
and intestinal metaplasia
3x more common in males (50-60 y/o)
Most commonly located in antrum
Gross: solitary, < 2 cm.
Micro: ALL GI adenomas have epithelial dysplasia
Increased incidense in pts w/ FAP
Risk of adenoCA is related to the size of the lesion (> 2 cm.)
CA may be present in up to 30% of gastric adenomas
VIII. ADENOCARCINOMA:
 Depth of invasion & extent of nodal and distant metastasis at time
of diagnosis: MOST powerful prognostic indicators for gastric
cancers
 Advanced CA: first detected as mets to the supraclavicular sentinel
LN (Virchow’s node)
 Sister Mary Joseph nodule: marker of metastatic CA; subcutaneous
nodule in periumbilical region
IX. LYMPHOMA:
 5% of gastric malignancies
 Most common are extra-nodal marginal zone B-cell lymphomas
(lymphoma of mucosa-associated lymphoid tissue or MALToma)
 Pathogenesis: Usually arise at sites of chronic inflammation
o pro-lymphomatous inflam: H. Pylori infection
o translocations: t(11;18)(q21;q21) most common 
activation of NF-kB, a transcription factor that
promotes B cell growth & survival
 Micro: dense lymphocytic infiltrate in the lamina propria 
lymphoepithelial lesions; express B cel markers CD19 and CD20
 Clinical Features: most common presenting symptoms 
dyspepsia & epigastric pain
X. CARCINOID TUMOR:
 Arise from the diffuse components of the endocrine system
 Gross: intramural or submucosal masses that create small
polypoid lesions
 Micro: islands, trabeculae, strands, glands, or sheets of uniform
cells with scant, pink granular cytoplasm and a round to
oval, stipples nucleus
 Immuno: (+) for endocrine granule markers (synaptophysin and
chromogranin A)
 The most important prognostic factor for GI carcinoid tumors is
LOCATION
 Foregut carcinoid tumors rarely metastasize
FEATURES OF GASTROINTESTINAL CARCINOID TUMOR:
Feature Esophagus Stomach Proximal Duodenum Jejunum and Ileum Appendix Colorectum
Fraction of GI <1% <10% <10% >40% <25% >25%
carcinoids
Mean patient age Rare 55 50 65 All ages 60
(yr)
Location Distal Body and fundus Proximal third, peri- Throughout Tip Rectum > cecum
ampullary
Size Limited data 1–2 cm, multiple; 0.5–2 cm <3.5 cm 0.2–1 cm >5 cm (cecum);
>2 cm, solitary <1 cm (rectum)
Secretory product(s) Limited data Histamine, Gastrin, somatostatin, Serotonin, substance P, Serotonin, Serotonin,
somatostatin, cholecystokinin polypeptide YY polypeptide polypeptide YY
serotonin YY
Symptoms Dysphagia, Gastritis, ulcer, Peptic ulcer, biliary Asymptomatic, Asymptomatic Abdominal pain,
weight loss, incidental obstruction, abdominal obstruction, metastatic , incidental weight loss,
reflux pain disease incidental
Behavior Limited data Variable Variable Aggressive Benign Variable
Disease associations None Atrophic gastritis, Zollinger-Ellison syndrome, None None None
MEN-I NF-1, sporadic

XI. G.I.S.T.
 Can behave and/or look benign or malignant
 Usually look like smooth muscle, i.e., “stroma”, “spindly”
 tumor cells are derived from the interstitial cells of Cajal, a “neural”
type of cell, similar to the neural plexi found in the intestines
(pacemaker cells for gut peristalsis)
 For as notoriously complex as all this sounds, they look like boring
leiomyomas, and in the days PRE-immunochemistry, they probably
WERE inaccurately called smooth muscle tumors, i.e., leiomyomas.
 Pathogenesis: 75-80% of all GISTS have oncogenic, gain-of-function
mutations of the gene encoding the tyrosine kinase c-KIT (receptor
for stem cell factor)
 Gross: solitary, well-circumscribed, fleshy mass
 Usually form a solitary, well-circumscribed, fleshy mass covered by
ulcerated or intact mucosa
 Recurrence or metastasis is rare for gastric GISTs under 5 cm but
common for mitotically active tumors larger than 10 cm.
 GISTs composed of thin elongated cells are classified as spindle cell
type, whereas tumors dominated by epithelial-appearing cells are
termed epithelioid type; mixtures of the two patterns also occur. The
most useful diagnostic marker is c-KIT, which is
immunohistochemically detectable in 95% of gastric GISTs.
 GIST showing characteristic cytoplasmic vacuoles indenting the nuclear
poles.
 Micro: The tumor cells have a round epithelioid appearance, clear
cytoplasm, and well-defined cell membranes. This corresponds to the
pattern that has been traditionally designated as leiomyoblastoma.
 GIST showing prominent palisading. This feature is not necessarily
indicative of neural differentiation.

SMALL INTESTINES:
I. INFLAMMATORY BOWEL DISEASE:
Features That Differ between Crohn Disease and Ulcerative Colitis
Feature Crohn Disease Ulcerative Colitis Serositis Marked Mild to none
MACROSCOPIC Granulomas Yes (∼35%) No
Bowel region Ileum ± colon Colon only Fistulae/sinuses Yes No
Distribution Skip lesions Diffuse CLINICAL
Stricture Yes Rare Perianal fistula Yes (in colonic No
Wall appearance Thick Thin disease)
MICROSCOPIC Fat/vitamin Yes No
Inflammation Transmural Limited to mucosa malabsorption
Pseudopolyps Moderate Marked Malignant potential With colonic Yes
Ulcers Deep, knife-like Superficial, broad- involvement
based Recurrence after Common No
Lymphoid reaction Marked Moderate surgery
Fibrosis Marked Mild to none Toxic megacolon No Yes

CROHNS DISEASE:
Entire colon is abnormal, and the usual transverse rugal folds have
been almost completely effaced. Although the colon looks redder
along the bottom (this is the proximal one-half), microscopic
examination showed an almost equal degree of inflammation present
throughout. Note that this colon is markedly shortened, measuring
only about 60 cm. in length, relative to the normal length of close to
100 cm.
Microscopically, Crohn's disease is characterized by transmural
inflammation. Here, inflammatory cells (the bluish infiltrates) extend
from mucosa through submucosa and muscularis and appear as
nodular infiltrates on the serosal surface with pale granulomatous
centers.
ULCERATIVE COLITIS:
Microscopically, the inflammation of ulcerative colitis is confined
primarily to the mucosa. Here, the mucosa is eroded by an ulcer that
undermines surrounding mucosa.
II. OBSRUCTION:
Anatomy: Adhesions (post-surgical), impaction, Hernias, Volvulus,
Intussusception, Tumors, Inflammation, such as IBD (Crohn) or

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 diverticulitis, Strictures/atresias, Stones, fecaliths, foreign
bodies, Congenital bands, mecomium, inperf. Anus
Intussusception:
o A length of intestine (intussuscipiens) literally swallows part of
the bowel just proximal to it (intussusceptum)
o Most cases are seen during the first 5yrs of life
o Lymphoid hyperplasia (viral etiology) precedes and is often
the cause of intussusception
Physiology: Ileus, esp. Postsurgical, Infarction, Motility diseases,
esp., hirschsprung disease
Ileus is a disruption of the normal propulsive gastrointestinal
motor activity from NON-mechanical mechanisms. Motility
disorders that result from structural abnormalities are termed
mechanical bowel obstruction. So if you think of the whole
anatomy and physiology of peristalsis, ileus can be defined as any
major problem in the whole scheme of things.
III. TUMORS:
 Non-neoplastic (polyps), Epithelial, Mesenchymal (stromal),
Lymphoid, Benign, Malignant
 ANY mucosal bulging, blebbing, or bump
 Hyperplastic (non-neoplastic)
 Hamartomatous (non-neoplastic)
 Adenomatous (true neoplasm, and regarded by many as
“potentially” PRE-MALIGNANT as well)
BENIGN VS MALIGNANT:
 Usual, atypia, pleo-, hyper-, mitoses, etc.
 Stalk invasion!!!
 Adenomatous polyp showing marked contrast between the
dysplastic glands of the polyp and adjacent normal glands.
 Microscopic appearance of villoglandular polyp. There is an
admixture of villous and glandular structures.
 Gross appearance of multiple hyperplastic polyps. The lesions
are characteristically small, sessile, and pale.
 Microscopic appearance of hyperplastic polyp. The individual
glands show a typical serration of their mid portion.
 Juvenile (retention) polyp. Note the ulcerated, highly
hyperemic surface.
MALIGNANT NEOPLASM:
1) Polyposis (non-neoplastic, hamartomatous)
2) Polyposis (neoplastic, i.e., cancer risk)
3) Hnpcc: (Hereditary Non Polyposis Colorectal Cancer)
THREE types of hereditary or “familial” intestinal glandular tumors.
CANCER RISK FACTORS
 Family history
 Age (rare <50)
 LOW fiber, HIGH meat, LONG transit time, refined carbs
 Whatever dietary carcinogenic influences are for the colon, the
longer they hang around (transit time) the higher the risk!
GROWTH PATTERNS
 POLYPOID Polypoid pattern of growth in a rectal lesion. Cake-like
configuration with central ulceration.
 ANNULAR, CONSTRICTING
 DIFFUSE
 Deeply penetrating and ulcerated tumor.
 Moderately differentiated colonic adenocarcinoma.
 Gross appearance of signet ring carcinoma. This tumor type is highly
malignant, narrows the lumen, and has a pebbly mucosal surface
and thickened muscular wall.
 Does a gland inside of a smooth muscle layer take all the guesswork
out of agonizing whether that gland is benign or malignant? Ans:
YES!

Dukes’ Classification (Astler-Coller modification)

Stage A Tumors invade through the muscularis mucosae into the submucosa but do not reach the muscularis propria
Stage B1 Tumors invade into the muscularis propria
Stage B2 Tumors completely penetrate the smooth muscle layer into the serosa
Stage C Tumors encompass any degree of invasion but are defined by regional lymph node involvement
Stage C1 Tumors invade the muscularis propria with fewer than four positive nodes
Stage C2 Tumors completely penetrate the smooth muscle layer into the serosa with four or more involved nodes
Stage D Lesions with distant metastases
Carcinoma in (may be referred to as high grade dysplasia) – intramucosal carcinoma that does not penetrate the muscularis mucosae
situ

Staging of Prostatic Adenocarcinoma Using the TNM System

TNM Designation Anatomic Findings
Extent of Primary Tumor (T)
T1 CLINICALLY INAPPARENT LESION (BY PALPATION/IMAGING STUDIES)
T1a Involvement of ≤5% of resected tissue
T1b Involvement of >5% of resected tissue
T1c Carcinoma present on needle biopsy (following elevated PSA)
T2 PALPABLE OR VISIBLE CANCER CONFINED TO PROSTATE
T2a Involvement of ≤5% of one lobe
T2b Involvement of >5% of one lobe, but unilateral
T2c Involvement of both lobes
T3 LOCAL EXTRAPROSTATIC EXTENSION
T3a Extracapsular extension
T3b Seminal vesical invasion
T4 INVASION OF CONTIGUOUS ORGANS AND/OR SUPPORTING STRUCTURES INCLUDING BLADDER NECK, RECTUM, EXTERNAL
SPHINCTER, LEVATOR MUSCLES, OR PELVIC FLOOR
Status of Regional Lymph Nodes (N)
N0 NO REGIONAL NODAL METASTASES
N1 METASTASIS IN REGIONAL LYMPH NODES
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 Distant Metastases (M)
M0 NO DISTANT METASTASES
M1 DISTANT METASTASES PRESENT
M1a Metastases to distant lymph nodes
M1b Bone metastases
M1c Other distant sites

IV. COLORECTAL CARCINOMA:  Need neutrophils in the muscularis to confirm the diagnosis
Factors related to prognosis:  Perforationperitonitis the rule, if no surgery
1. Patient’s age – very young and very old: poor px  Why do you need neutrophils in the muscularis?
2. Sex – better px: F > M  Ans: to differentiate from a peritoneal inflammation or luminal pus
3. CEA serum levels > 5.0 ng/ml
from another part of the bowel.
4. Tumor location: favorable px - lesions located in the left colon > lesions
 What is the white junk coating the surface? Answer: FIBRIN
in sigmoid colon and rectum
5. Local extent – focal microscopic CA in a polyp/tumor restricted to  The presence of neutrophils invading the muscularis is the
mucosa & submucosa: good px diagnostic criteria needed to diagnosis or confirm, acute
6. Obstruction – poor px appendicitis!
7. Perforation – poor px
8. Tumor margins & inflammatory reaction – better px VII. Mucus “TUMORS”
9. Vascular/perineural invasion: poor px  Mucocele (common)
10. Microscopic tumor type – Mucinous CA, signet ring CA and anaplastic  Mucinous Cystadenoma (rather rare)
CA: worse px
 Mucinous Cystadenocarcinoma (rare)
11. LN involvement - > 6 LNs: <10% survive >5 yrs.

V. ANAL CARCINOMAS: MUCOCELE

 More likely to be squamous, or “basaloid”  Common cyst on APPENDIX filled with MUCIN
 F > M (3:1)  Can RUPTURE to become:
 Worse in prognosis  Pseudomyxoma peritonei
 HPV – related (HPV16)  (mucinous ascites and mucinous tumor disseminated on
 Factors related to prognosis: peritoneal surfaces)
o Tumor stage– depth of invasion & regional LN
involvement; inguinal LN involvement (grave px sign) VIII. MUCINOUS CYSTADENO(CARCINO)MA
o Tumor size – inversely related to px  A ruptured mucinous cystadenocarcinoma can look exactly like
o Tumor recurrence - tumor recurrence in the pelvic or benign pseudomyxoma peritoneii, but with (malignant) tumor cells
perineal regions following APR: ominous px present. Most adenomas/adenocarcnomas of the appendix are
VERY mucinous!
VI. ACUTE APPENDICITIS
PERITONEAL CAVITY
 A disease of YOUNGER people
 Inflammatory disease
 Obstruction by fecalith: the classic cause but fecaliths present only
 Tumors
about half the time
 Early appendicitis: neutrophilsMucosa, submucosa

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