SURGICAL PATHOLOGY

1.01 Gastrointestinal Pathology P1

September 9, 2020 | Dr. Arnel Bayotas
OUTLINE  Type C - Esophageal atresia with distal
I. Congenital Anomalies esophageal fistula (most common: 86%)
A. Atresia, Fistula & Duplication  Type D (blind pouch)
B. Ompalocele & Gastrochisis  Type E - No esophageal atresia with double
C. Meckel’s Diverticulum tracheoesophageal fistula (proximal and
II. Esophagus
distal) H type
A. Esophageal Diverticulum
B. Esophageal Mucosal webs
C. Esophageal Rings
D. Achalasia
E. Hiatal Hernia
F. Reflux Esophagitis/GERD
G. Barret Esophagus
H. Squamous Cell Carcinoma of the Esophagus
I. Adenocarcinoma of the Esophagus
III. Stomach
A. Pyloric Stenosis
B. Gastritis Figure 1. Esophageal atresia & tracheoesophageal fistula
C. Stress-Related Mucosal Disease
D. Peptic Ulcer Disease  IMPERFORATED ANUS
E. Gastric Malignancies o Most common form of congenital intestinal
IV. Small Intestine
atresia
A. Neoplasm
B. Inflammatory Bowel Disease o Due to failure of the cloacal diaphragm to
C. Intestinal Obstruction involute
V. Large Intestine o Treatment: (purely surgical)
A. Neoplasm  Perineal anoplasty
B. Sigmoid Diverticular Disease
C. Hirchsprung Disease
 Colostomy and pull-through operation
VI. Small/Large Bowel Polyps
B. OMPHALOCELE (EXOMPHALOS) & GASTROSCHISIS
A. Hyperplastic
B. Inflammatory (LAPAROSCHISIS)
C. Hamartomatous
Table 1. Opmpalocele vs. Gastrochisis
D. Neoplastic
E. Adenomatous Polyposis Omphalocele Gastroschisis
I. CONGENITAL ANOMALIES

A. ATRESIA, FISTULA AND DUPLICATION

 May occur in any part of the GI tract
 Agenesis - absence of organ
 ATRESIA
o A condition in which a body orifice or passage in
the body is abnormally closed or absent
o Occurs most commonly at or near the tracheal Incomplete closure of the abdominal musculature and the
bifurcation (esophagus) abdominal viscera herniates
o Usually associated with a fistula connecting the Has a ventral membranous No ventral membranous
upper and lower esophageal pouches to a sac sac (Allowing evisceration
bronchus or the trachea of bowel loops, stomach
o Atresia can occur without fistula and sometimes the
 FISTULA gonads)
o An abnormal connection or passageway Does not involve all layers of Involves all the layers of
between two epithelium-lines organs or vessels the abdominal wall the abdominal wall (from
that normally do not connect peritoneum to the skin)
o 2 types of fistula:
 Fistula with atresia Associated with Small (generally <5 cm)
 Fistula without atresia chromosomal defects: defect of the abdominal
o Most common: Tracheoesophageal Fistula Trisomies 13 (Patau), 18 wall just to the right of the
o 5 types of TEF (Edward) & 21 (Down) and umbilical cord insertion.
 Type A - Isolated esophageal atresia (pure with other disorders such as
atresia) Beckwith-wiedemann (Prevalence: 1 in 10,000
 Type B - Esophageal atresia with proximal syndrome live births)
tracheoesophageal fistula

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 1.01 GIT Surgical Pathology SEM 1 PRELIMS

Can be encountered also in  Attributed to fibrosis, esp. in the

other cardiac anomalies mediastinum.
(ASD, VSD)  Lined by stratified squamous
epithelium non-keratinized.
C. MECKEL DIVERTICULUM Epiphrenic  Immediately above the lower
 Due to failed involution of vitelline duct esophageal sphincter
 Located in the ileum  Transition of stratified squamous
 Solitary; anti-mesenteric side of bowel epithelium non-keratinized and
 Most common true diverticulum columnar.
 Rule of 2’s:
o 2 % of population
o Within 2 feet of ileocecal valve
o Approximately 2 inches long
o 2x as common in males
o Usually symptomatic by the age of 2 years old

Figure 2a & 2b. Meckel’s diverticulum (gross & micro)

Same histology with normal wall, only difference is the outpouching Figure 3. Esophageal diverticula based on location

II. ESOPHAGUS B. ESOPHAGEAL MUCOSAL WEBS

A. ESOPHAGEAL DIVERTICULUM
 TRUE DIVERTICULUM
o Traction (True = Traction)
o Due to inflammation
o Outpouching of alimentary tract lined by mucosa
o Communicates with the lumen
o Contain all 3 layers of the wall
 FALSE DIVERTICULUM
o Pulsion (Pulsion = False yun)
o Due to defect in associated sphincter muscles
o Diverticula wall lacks muscle layer
Table 2. Esophageal diverticula based on location
Zenker  Immediately above the upper
(Pharyngo- esophageal sphincter
esophageal)  Impaired relaxation and spasm of the
cricopharyngeus muscle
swallowing → ↑ pressure within the
distal pharynx → Zenker
 Lined by stratified squamous
epithelium non-keratinized
 Small → asymptomatic
 Large → mass, regurgitation &
halitosis
Traction  lower third of the esophagus
(region of the hilum of the lungs)
 Involves the 3 layers of the
esophagus
 Idiopathic, ledge-like protrusions (semi-
circumferential) of mucosa that may cause
obstruction.
 Most common in Upper Esophagus
 Main symptom: nonprogressive dysphagia associated
with incompletely chewed food.
 Paterson-Brown-Kelly or Plummer-Vinson
Syndrome:
○ Webs
○ Iron-deficiency anemia
○ Glossitis
○ Cheilosis
C. ESOPHAGEAL RINGS/ SCHATZKI RINGS
 aka lower esophageal esophago-gastric rings
 Similar to webs, but are circumferential, thicker
after  Include mucosa, submucosa, and ocassionally,
hypertrophic muscularis propria
 A rings – Present in the distal esophagus, above the
gastroesophageal junction
 B rings – Present at the squamocolumnar junction of
the lower esophagus and may have gastric cardia-
type mucosa

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E. HIATAL HERNIA
 Characterized by separation of the diaphragmatic
crura and protrusion of the stomach into the thorax
through the resulting gap

Figure 4. Esophageal Rings

D. ACHALASIA Figure 6. Types of Hiatal Hernia

 aka Cardiospasm or Megaesophagus
 Pathogenesis: Unknown  Treatment: Nissen fundoplication
 Characterized by dysmotility and inability of the LES
to relax after swallowing. F. REFLUX ESOPHAGITIS/ GERD
 Due to complete loss of the myenteric ganglion cells
 Reflux of gastric contents into the lower
 Failure of the cardiac mechanism to open when
esophagus → called gastroesophageal reflux
peristaltic waves conveying food through the
disease (GERD)
esophagus reach it
o Due to conditions that increase abdominal
 Progressive dysphagia starting in teens
pressure or decrease lower esophageal
 Primary Achalasia
o Nearly complete loss of ganglionic cells in the sphincter tone
Auerbach’s plexus in the lower 3rd of the  Most common cause of GERD → transient lower
esophagus esophageal sphincter relaxation.
 Secondary Causes o Mediated via vagal pathways, and can be
o Chagas Disease triggered by gastric distention, by gas or food,
 Trypanosoma cruzi infection causes mild pharyngeal stimulation that does not trigger
destruction of the myenteric plexus, failure swallowing, and stress.
of peristalsis and esophageal dilatation  Can also occur following swallow-induced LES
o Varicella Zoster Infection relaxations or due to forceful opening of a relatively
 Achalasia Triad hypotensive lower esophageal sphincter by an abrupt
o Aperistalsis increase in intraabdominal pressure, such as that due
o Incomplete relaxation of the LES to coughing, training, or bending.
o Increased LES tone
 Risk factors
 Barium Swallow
o Alcohol and tobacco use
o Dilated, aperistaltic esophagus with a beak-like
o Obesity
tapering at distal end
o Central nervous system depressants
o Pregnancy
o Hiatal hernia
o Delayed gastric emptying
o Increased gastric volume.
 24 hours pH study - gold standard for diagnosis.
 Morphology
o Mild GERD → histology unremarkable
o Severe GERD:
 Intraepithelial eosinophils & neutrophils
 Basal zone hyperplasia > 20% of the total
epithelial thickness
 Elongation of lamina propria papillae
Figures 5a. Barium Swallow 5b Achalasia  Gross appearance
o Marked hyperemia with focal hemorrhage is
 Management: present in the area of reflux
o Botulinum Neurotoxin Injection - To inhibit
LES cholinergic neurons
o Pneumatic Dilation

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 Classification if with dysplasia in Barrett

esophagus:
o Negative dysplasia: repeat endoscopy in 3-5
years
o Indefinite dysplasia: same risk for malignant
progression as low grade dysplasia, re-biopsy in
3-6 month
o Low grade dysplasia: repeat endoscopy in 6-12
months
o High grade dysplasia: surgical or endoscopic
resection of the lesion
 Microscopic scenarios qualify for a diagnosis
o Indefinite Dysplasia
 Insufficient cytologic atypia
Figures 7a. Gross Appearance of GERD 7b. Histology of GERD
 Dysplasia-like epithelium in the background
 Clinical features of marked inflammation or mucosal erosion
o Most common in adults >40 years old  Subsquamous extension of “dysplastic
o Most common clinical symptoms: glands”
 Dysphagia or odinophagia  Dysplastic glands that mature to the surface
 Heartburn  Biopsies without surface epithelium or other
o Other symptoms may include: regurgitation of obscuring factors
sour-tasting gastric content; attacks of severe
Table 3. Dysplasia Features
chest pain (chronic)
 Complications Feature Low Grade High Grade
o Esophageal ulceration Dysplasia Dysplasia
o Hematemesis
Architecture Preserved crypt Architectural
o Melena
architecture or distortion:
o Stricture development
villiform surface  Crowding
o Barrett esophagus
 Branching
 Treatment: Proton pump inhibitors or H2 histamine
receptor antagonists → symptomatic relief  Budding
 Cribriforming
G. BARRET ESOPHAGUS Nuclei  Preserved  Lack polarity
 Complication of chronic GERD polarity  Stratification
 American College of Gastroenterology definition:  Stratification  Prominent
o Change in the esophageal epithelium of any  Enlargement enlargement
length (>3 cm long segment, ≤ 3 cm short  Hyperchromasia  Irregular
segment) that can be recognized on endoscopy  Crowding membrane contour
and confirmed to have intestinal metaplasia by  Less  More
biopsy pleomorphic pleomorphism
 Histologic basis: Characterized by intestinal
metaplasia within the squamous mucosa → (+) Cytoplasm  Diminished Mucin absent
goblet cells (highlighted by Alcian blue/PAS) = mucin
necessary for diagnosis  Dystrophic
 Increased risk of esophageal adenoCA → pre- goblet cells
malignant condition
 Microscopic  Identified only through endoscopy and biopsy: evidence of
o (+) goblet cells metaplastic columnar mucosa above the
o Gland architecture: budding, irregular shapes, gastroesophageal junction
and cellular crowding  Usually prompted by GERD symptoms
o Non-goblet columnar cells, like gastric type  Complications
foveolar cells may also be present, but are o Reflux esophagitis & aspiration pneumonia
insufficient for diagnosis. o Malignancy
 When dysplasia is present it is classified as low or high o Esophageal stricture
grade o Esophageal ulcer & perforation
o Esophageal bleeding
 Treatment options
o Photodynamic therapy

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o Laser ablasion I. ADENOCARCINOMA OF THE ESOPHAGUS

o Endoscopic mucosectomy  Arises in a background of Barrett esophagus & long-
o esophagectomy standing GERD
 Risk factors
H. SQUAMOUS CELL CARCINOMA OF THE o Barret’s (most important)
ESOPHAGUS o Tobacco exposure
 4x more common in males; > 45 y/o o Radiation
 Risk factors o Obesity
o Alcohol and tobacco use → synergistic o GERD
 In areas where alcohol & tobacco use o Scleroderma
uncommon, risk factors include: nutritional o Alcohol
deficiencies, polycyclic hydrocarbons, o Meds: Long term use (>5 years) of Theophylline
nitrosamines, fungus-contaminated foods, & Beta-agonist
HPV infection  Risk is reduced by:
o Caustic esophageal injury o Fresh fruits & vegetables
o Achalasia o Some serotypes of H. pylori infection reduce the
o Plummer-Vinson syndrome risk due to atrophy of the gastric mucosa
o Frequent consumption of very hot beverages  Most frequently: Caucasians , M > F, distal 1/3 of
o Previous radiation therapy to mediastinum esophagus
 Clinical features  By the time symptoms appear, the tumor usually
o Onset insidious spread to the submucosal lymphatic vessels
o Dysphagia, odynophagia (pain on swallowing),  Over-all 5-year survival is less than 25%
and obstruction  Microscopically: Most are mucin producing glandular
o Extreme weight loss & debilitation tumors with intestinal type features
o Tumor ulceration → (+) hemorrhage and sepsis  Pathogenesis: Progression of Barret’s to AdenoCA
o Overall 5-year survival = 9% occurs through the stepwise acquisition of genetic &
 Morphology epigenetic changes
o 50% occur in middle third (or upper 3rd) o Early stages: Mutation of TP53 &
o Begins as in-situ lesion called squamous downregulation of p16/INK4a
dysplasia o Late stages: Amplification of EFGR, ERB2, Met,
o Grows into polypoid, or exophytic tumor, and cyclin D1 & cyclin E genes
protrude into and obstruct the lumen  Morphology
o Most are moderately to well differentiated o Usually occurs in the distal third of the
o LN metastases vary with tumor location: esophagus and may invade adjacent gastric
 Upper 3rd → cervical LN cardia
 Middle 3rd → mediastinal, paratracheal, and o Initially appearing as flat or raised patches in
tracheobronchial nodes otherwise intact mucosa, large masses of 5 cm or
 Lower 3rd → gastric & celiac nodes more in diameter
 Morphologic patterns o Commonly produces mucin and form glands,
o Exophytic protruding lesion in the lumen (60%) often with intestinal-type morphology
o Flat, diffuse infiltrative form spreading in the  Clinical features
esophageal wall (15%) o Commonly present with pain, difficulty in
o Ulcerative lesions swallowing, progressive weight loss,
hematemesis, chest pain, & vomiting

Figures 8a. Ulcerating Squamous cell carcinoma 8b. Malignant tumor

Figure 9. Adenocarcinoma of the esophagus
of the esophageal squamous mucosa, strongly associated with
tobacco and alcohol use

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III. STOMACH Mic: Presence of neutrophils Mic: Lymphocytes &

in direct contact with plasma cells along with
A. PYLORIC STENOSIS
epithelium intestinal metaplasia &
 Progressive thickening of the circular muscle mucosal injury
(hyperplasia of the muscularis propria) of the Focal damage to the gastric
pylorus → gastric outlet narrowing mucosa, with acute
 Edema and inflammatory changes in the mucosa and inflammation, necrosis, and
submucosa → aggravate the narrowing. hemorrhage
 May be congenital or acquired RF: Heavy smoking, RF: Drugs-NSAIDs, H.
o Acquired pyloric stenosis occurs in adults: excessive alcohol, excessive pylori, alcohol and
consequence of antral gastritis or peptic ulcers NSAID-aspirin, ibuprofen, smoking, radiation,
close to the pylorus. naproxen, Uremia, Ischemia gastrectomy with
o Carcinomas of the distal stomach and pancreas
and shock, Stress (major gastroenerostomy, uremia,
→ narrow the pyloric channel due to fibrosis or
surg.. burns, infections) pernicious anemia
malignant infiltration.
 3-4x more common in males  CHRONIC GASTRITIS
 At risk for congenital hypertrophic pyloric stenosis: o Characterized by chronic mucosal inflammation
o Monozygotic twins (if one twin is affected) and atrophy of the mucosal glands
o Diizygotic twins and siblings of affected o Less common causes of chronic gastritis:
individuals radiation injury, chronic bile reflux, mechanical
o Turner syndrome and Trisomy 18 injury (e.g.an indwelling nasogastric tube), and
o Erythromycin and azithromycin exposure (via oral involvement by systemic diseases, (e.g. Crohn
or mother’s milk in the first 2 weeks of life) disease, amyloidosis, or graft-versus-host
 Generally presents in the 2nd or 3rd week of life disease)
(Previous trans: 3rd and 6th weeks of life ) → new- o Complications
onset regurgitation and persistent, projectile, non-  Peptic Ulcer Disease
bilious vomiting after feeding and frequent demands  Mucosal atrophy and intestinal metaplasia
for re-feeding  Gastritis cystica
 Physical exam: a firm, ovoid, 1 to 2 cm abdominal  Dysplasia
mass
Table 5. Chronic gastritis
 Abnormal left to right hyperperistalsis is evident during
With H. pylori (Type B) Without H. pylori (Type
feeding and immediately before vomiting.
A)
 Treatment: Surgical splitting of the muscularis
90% 10%
(myotomy) → curative
Most common type Autoimmune gastritis:
most common type of
B. GASTRITIS
Not Associated with intestinal gastritis without H. pylori
 Maybe acute or chronic metaplasia & duodenal
 ACUTE GASTRITIS epithelium
o Pathogenesis Body-Fundic
 Gastric lumen pH: close to 1 (contributes to Predominant: Spares
digestion and has the potential to damage Antrum
the gastric mucosa)
 Protective factors of the gastric mucosa: H. pylori causes gastritis in 2 Associated with
surface mucus secretion, bicarbonate patterns: hypergastrinemia
secretion into mucus, mucosal blood flow,
epithelial barrier function, epithelial Associated with other
regenerative capacity and elaboration of autoimmune disease (e.g.
prostaglandins pernicious anemia,
o Clinical features Hashimoto’s Thyroiditis,
 Asymptomatic or have persistent epigastric T1DM)
pain Antral Pangastritis Characterized by diffuse
 May be accompanied by occasional bilious predominant followed by atrophic gastritis
vomiting gastritis: multifocal (mucosal damage of the
Table 4. Acute vs. Chronic Gastritis Low pro- atrophic oxyntic (acid-producing)
ACUTE GASTRITIS CHRONIC GASTRITIS inflammatory gastritis: mucosa w/in the body and
Transient mucosal Ongoing mucosal cytokines: High pro- the fundus.
inflammation inflammation with mucosal TNF & IL-1B. inflam
atrophy cytokines:

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Associated TNF & IL-  Dieulafoy lesion : caused by a

with ↑ acid 1B. submucosal artery that does not branch
production & ↑ properly within the wall of the stomach
risk of Associated  Gastricantralvascularectasia (GAVE) :
duodenal with ↓ acid responsible for 4% of non-variceal upper
ulcer production & GI bleeding; longitudinal stripes of
↑ risk of edematous erythematous mucosa that
adenoCA alternate with less severely injured, paler
Screening: Characterized by: mucosa, and is sometimes referred to
• Serum ELISA for  Antibodies to parietal as watermelon stomach
antibodies cells and intrinsic
• UREA breath test – factor D. PEPTIC ULCER DISEASE
radiolabeled urea is  Reduced serum  Most often associated with H. pylori- hyperchlorhydric
broken down to pepsinogen I chronic gastritis
radiolabeled CO2 by concentration  Present in 85-100% persons with duodenal ulcers
urease, detected by  Endocrine cell and 65% with gastric ulcers
breath analyzer. hyperplasia  Location (decreasing order of frequency)
• Silver staining or  Vitamin B12 o Duodenum (1st part) pyloric ring
warthin starry stain - deficiency o Stomach (lesser curvature near the junction of
gold standard for H. pylori  Defective gastric acid the body and the antrum
detection secretion o GEJ in GERD or Barret’s Esophagus
• Culture done in (achlorhydria) o Margins of jejunostomy
Skirrow’s medium – o Stomach, duodenum and/or jejunum of patients
most specific with Zollinger-Ellison syndrome
investigation o In ileal Meckel’s diverticulum containing ectopic
gastric mucosa
C. STRESS- RELATED MUCOSAL DISEASE
Table 6. Duodenal vs. Gastric Ulcer
 Occurs in patients with severe trauma, extensive
Features Duodenal Ulcer Gastric Ulcer
burns, intracranial disease, major surgery, serious
Site 1st part of Along lesser
medical disease, and other forms of severe
duodenum curvature
physiologic stress.
Incidence More common Less common
 Given specific names based on location and clinical
Age 25-50 yrs, M>F Beyond 6th
associations
decade, M>F
o Stress ulcer: most common in individuals with
Etiology Almost all have Less stronger
shock, sepsis, or severe trauma
H. pylori infection assoc
o Curling ulcers: occur in the proximal duodenum
Acid Level High Usually normal; ↑
and associated with severe burns or trauma
o Cushing ulcers: gastric, duodenal, and if
hypergastrinemia
esophageal ulcers arising in persons with
intracranial disease and carry a high incidence of Pain after food Relieved Aggravated
perforation intake
 Pathogenesis Clinical features Night pain & No night pain,
o Stress-related gastric mucosal injury is most melena more hematemesis
often related to local ischemia common more common
o Upregulation of inducible NO synthase and ↑
release of endothelin-1 No vomiting/ no Vomiting
o Direct stimulation of vagal nuclei → wt/ loss common/ weight
hypersecretion of gastric acid loss is present
o Systemic acidosis Complications No malignant Malignant change
 Morphology change (rarely)
o Ranges from shallow erosions caused by  Pathogenesis
superficial epithelial damage to deeper o Imbalances of mucosal defenses and damaging
o Lesions that penetrate the depth of the mucosa forces that cause chronic gastritis
 Clinical features  Primary underlying cause: H. pylori & NSAID use
o Gastric mucosal damage  Gastric hyperacidity: H. pylori infection, parietal cell
o Other, non-stress-related causes of gastric hyperplasia, excessive secretory responses or
bleeding include: impaired inhibition of stimulatory mechanisms such as
gastrin release

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 Common co-factors in peptic ulcerogenesis: bleeding in gastric  More  Incapacitating,

o Chronic NSAID use: direct chemical irritation & ulcer common in crampy
suppress PG release necessary for mucosal  May be life- anterior abdominal
protection threatening wall pain
o Cigarette smoking: impairs mucosal blood flow  Accounts for 25% duodenal  May lead to
& healing of ulcer deaths ulcers total
o High-dose corticosteroids: suppress PG  May be the first obstruction
synthesis & impair healing indication of an with
 Solitary in > 80% of patients ulcer intractable
o < 0.3 cm. – shallow ulcers vomiting (fluid
o > 0.6 cm. – deeper ulcers & electrolyte
 Round or oval, sharply, punched-out defect – mucosal imbalance –
surface overhang the base (heaped up margins → metabolic
cancer) alkalosis)
 Gnawing, burning, aching pain, epigastric
Table 8. Benign vs. Malignant Gastric Ulcer
 Fe deficiency anemia
BENIGN GASTRIC ULCER MALIGNANT GASTRIC
 Acute hemorrhage ULCER
 Penetration, perforation:
 Lesser curvature  Greater curvature
o Pain in back
 Smooth radiating folds  Interrupted nodular,
o Pain in chest
with Hampton line & clubbed folds (malignant
o Pain in LUQ
collar ulcers with no mass)
 Malignant transformation – very rare
 Overhanging margins  Eccentric with heaped up
showing regeneration and everted margins
 Mucosal rugae projects  Mucosal rugae stop far of
outwards from the the ulcer
margins of ulcer  Necrotic base
 Huge base  No peristalsis
 Preserved peristalsis  No healing
 Heals within 8-10 weeks

Figures 10a & b. Ulcers include layers of necrosis (N), inflammation

(I), and granulation tissue (G), but a fibrotic scar (S), which takes time J. GASTRIC MALIGNANCIES
to develop, is only present in chronic lesions.
 Adenocarcinoma, GIST, Lymphoma
Table 7. Complications of PUD
Table 9. Genes in Gastric Cancer
Complications of peptic ulcer disease (BPO)
Familial Gastric Sporadic gastric cancer
Bleeding Perforation Obstruction
Cancer Intestinal type Diffuse type
 Occurs in 15% to  Occurs in  Occurs in
Loss of CDH1 Most common Loss of CDH1
20% of patients about 5% of about 2% of
gene which overall loss of
 Most frequent patients patients
encodes for E p53
complication  Accounts  Mostly in
cadherin o ↑ wnt pathway
 More common in for 2/3 of chronic ulcers
o Loss of fxn
posterior wall ulcer deaths  Most often APC
duodenal ulcers – MC cause due to pyloric o Gain of fxn of
 Gastroduodenal of death in channel B catenin
artery – MC PUD ulcers
source of bleeding  Rarely the  May also
in duodenal ulcer 1st occur with ADENOCARCINOMA
 Left gastric artery indication of duodenal  Most common gastric malignancy (90%)
– MC source of an ulcer ulcers  Based on Macroscopic pattern:
o Protruding mass or exophytic (Type I lesion)

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o Flat or depressed: No obvious mass in the mucosa signaling via the Wnt pathway. These include
(Type II lesion) loss of-function mutations in the adenomatous
o Excavated: Erosion is present in stomach wall polyposis coli (APC) tumor suppressor gene and
(Type III lesion) gain-of-function mutations in the gene encoding
\
β-catenin.
Table 10. Classification of Gastric Adenocarcinoma
o Loss-of-function mutations or silencing of a number
Based on Depth of Invasion Based on Lauren’s
of other tumor suppressor genes have also
Histological classification
been identified, including those involved in TGFβ
 Early gastric cancer  Intestinal type
signaling (TGFβRII), regulation of apoptosis
(superficial spreading o Composed of the
(BAX), and cell cycle control (CDKN2A).
type) neoplastic intestinal
 Morphology
o Involvement of the glands
o Most common location: antrum of the stomach
mucosa and the o Arise from metaplastic
o Cancer of the gastric cardia is on the rise
submucosa epithelium
especially due to Barrett’s esophagus
irrespective of the
o Lesser curvature: involved more often than
involvement of
greater curvature
perigastric lymph
o Diffuse gastric cancer: no definite lump, strong
nodes
desmoplastic reaction that stiffens the gastric wall.
o Associated with best
These tumors show diffuse rugal flattening and a
prognosis
rigis, thickend wall-leather bottle appearance
 Late Gastric Cancer
(linnitis plastica)
o Involvement of the
 Clinical features
muscle layer
o Intestinal-type gastric cancer predominates in
o Poor prognosis
high-risk areas and develops from precursor
 Diffuse type: linitis plastica lesions, including flat dysplasia and adenomas.
o Non-cohesive cells o The depth of invasion and the extent of nodal and
which do not form distant metastases at the time of diagnosis
glands remain the most powerful prognostic indicators.
o “signet ring” appearance  Investigaton of choice
(because mucin pushes o Endoscopy with biopsy of lesion
nucleus to the  Metastasis
periphery) o First organ affected: liver
o Worst prognosis o Followed by: lungs, bone, ovary (Krukenberg’s
o E-cadherin mutation tumor)
frequently associated o Peiumbilical lymph node: Sister Mary Joseph
Nodule
o Peritoneal cul-de-sac: Blumer’s (palapable on
rectal and vaginal exam)
o Left supraclavicular node: Virchow’s lymph node
o Axillary: Irish Nodes

GASTROINTESTINAL STROMAL TUMOR (GIST)

 Arise from pacemakers of the GIT (intestinal cells of
Cajal)
 GIST: most common mesenchymal tumor of the
abdomen
 Pathogenesis
 Most common location: Stomach
o Majority of gastric cancers are not hereditary
 Associated with neurofibromatosis 1
o The loss of E-cadherin is a key step in the
 Microscopically: epitheloid cells, spindle cells or mixed
development of diffuse gastric cancer.
(both epitheloid and spindle cells)
o Individuals with BRCA2 mutations are at increased
 Useful diagnostic markers: DOG (detected on GIST) and
risk of developing diffuse gastric cancer.
c-kit (CD117)
o Mutation of TP53 is also found in the majority of
 Carney triad (Carney–Stratakis syndrome)
sporadic gastric cancers of both diffuse and
o A nonhereditary syndrome seen primarily in young
intestinal types.
females that includes:
o In contrast to diffuse gastric cancers, sporadic
 Gastric GISTs
intestinal-type gastric cancers are strongly
 Paraganglioma
associated with mutations that result in increased
 Pulmonary chondroma

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 1.01 GIT Surgical Pathology SEM 1 PRELIMS

 Morphology  Among malignant small intestinal tumors,

o Large size; solitary, well-circumscribed, fleshy adenocarcinomas and well-differentiated
o If with thin elongated cells → spindle cell type neuroendocrine (carcinoid) tumors have roughly
o If with epithelial-appearing cells → epithelioid type equal incidence, followed by lymphomas and
 Clinical: sarcomas.
o Mass effects  In primary adenocarcinoma, the duodenum is the
o If with mucosal ulceration → blood loss → anemia most common site.
Prognosis correlates with tumor size, mitotic index
and location (more aggressive in SI) CARCINOID TUMOR
 Most common small bowel neoplasm
 Arise from the diffuse components of the endocrine
system and are now properly referred to as well-
differentiate neuroendocrine tumors.
 May be associated with endocrine cell hyperplasia,
autoimmune chronic atrophic gastritis, MEN-I, and
Zollinger-Ellison syndrome.
 Gastric endocrine cell hyperplasia has been linked to
Figure 11a GIST (gross) 11b GIST (micro) Spindle cell lesion with proton pump inhibitor therapy, but the risk of progression
pseudopalisading pattern reminiscent of a schwannoma. Inset - lesional cells to a neuroendocrine neoplasm in this circumstance is
highlighted with CD117 (c-kit) immuno-histochemical stain. extremely low.
 Gross
LYMPHOMA o Intramural or submucosal masses → small polypoid
 5% of gastric malignancies lesions
 Most common are Extra-Nodal Marginal Zone B-cell o In the intestines the tumors may invade deeply to
Lymphomas (lymphoma of mucosa-associated involve the mesentery
lymphoid tissue or MALToma) o Yellow or tan, very firm (intense desmoplastic
 Kinds of Lymphoma reaction) → kinking and obstruction of the bowel.
o Gastric MALT lymphoma- replacing much of the  Histology
gastric epithelium. Inset shows lymphoepithelial o Islands, trabeculae, strands, glands, or sheets of
lesions with neoplastic lymphocytes surrounding uniform cells with scant, pink granular cytoplasm
and infiltrating gastric glands. and a round to oval stippled nucleus.
o Disseminated Lymphoma- within the small o Minimal pleomorphism
intestine with numerous small serosal nodules.  Clinical features
o Large B-cell lymphoma- infiltrating the small o Peak incidence → 6th decade, but they may appear
intestinal wall and producing diffuse thickening at any age
 Pathogenesis o Gastrin may cause Zollinger- Ellison syndrome
o Usually arise at sites of chronic inflammation o Ileal tumors may cause carcinoid syndrome
o They can originate in the GI tract at sites of o Strongly associated with metastatic disease in the
preexisting MALT, (Peyer patches of the SI), liver
but more commonly arise within tissues that are  Types
normally devoid of organized lymphoid tissue. o Foregut
o MALT is induced, typically as a result of chronic  Stomach, duodenum proximal to the ligament
gastritis. of Treitz, and esophagus
o H. pylori eradication results in durable remissions  Rarely metastasize
with low rates of recurrence in most MALToma  Generally cured by resection
patients. o Midgut
 Morphology  Jejunum and ileum
o Dense Lymphocytic Infiltrate in the Lamina Propria  Multiple
lymphoepithelial lesions ○ Express B Cell Markers  Tend to be aggressive.
CD19 and CD20  Greater depth of local invasion, increased size,
 Clinical features: most common presenting symptoms and the presence of necrosis and mitoses →
dyspepsia and epigastric pain worse outcome.
o Hindgut
IV. SMALL INTESTINE  Appendix and colorectum
A. NEOPLASM  Discovered incidentally
 Carcinoid Syndrome
 Least common site for primary malignancy in the GIT
o Systemic fibrosis (affects cardiac valves,
endocardium, retroperitoneal & pelvic fibrosis)

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o Hepatomegaly (bec. of metastasis) o Extraintestinal manifestations: Uveitis,

o Intestinal hypermotility (vomiting, diarrhea,
cramps, nausea)
o Vasomotor symptoms (flushing & cyanosis of the
skin)
o Asthma like features (Cough, wheezing, dyspnea)
B. INFLAMMATORY BOWEL DISEASE
 Chronic condition resulting from inappropriate
mucosal immune activation
 Pathogenesis: combined effects of alterations in host
interactions w/ intestinal microbiota, intestinal
epithelial dysfunction, aberrant mucosal immune
responses, and altered composition of the gut
microbiome.
 Two conditions: Chron’s Disease & Ulcerative Colitis
CHRON’S DISEASE
 Hallmark: Non-caseating granulomas
 Most common sites: terminal ileum, ileocecal valve,
and cecum
 Typically transmural
 Skip lesions – multiple, separate, sharply delineated
areas
 Aphthous ulcer - first ulcer that can be seen ( may
coalesce into elongated, serpentine ulcers )
 Marked inflammatory changes and the formation of a
fissure between mucosal folds
 In extensive transmural disease, mesenteric fat
frequently extends around serosal surfaces (Creeping
Fat)
 crypt abscesses - Abundant neutrophils that infiltrate
and damage crypt epithelium
 Paneth Cell metaplasia may also occur in the left
colon
 Cutaneous granulomas form nodules that are
referred to as Metastatic Crohn disease.
 Gross appearance
o Segmental nature of inflammation
o Rigidity of the wall
o Flattening of the mucosa
o Cobblestone appearance (multiple granulomas)
 Clinical features
o Intermittent attacks: mild diarrhea, fever, and
abdominal pain
o 20% experience RLQ pain, fever, and bloody
diarrhea
o May mimic acute appendicitis or bowel perforation
o Periods of active disease are typically interrupted
by asymptomatic periods
o Iron deficiency anemia may develop
o Extensive small bowel disease → protein loss
and hypoalbuminemia
o Malabsorption of B12 and Bile Salts
o Fibrosing strictures → terminal ileum
Polyarthritis, Acroilitis, Ankylosing Spondylitis,
Clubbing of fingers
ULCERATIVE COLITIS
 Severe ulcerating inflammatory disease
 Closely related to Crohn disease; they share the same
extraintestinal manifestations like migratory
polyarthritis, sacroiliitis, ankylosing spondylitis, uveitis
and skin lesions
 Limited to the colon and recum
o Pancolitis: disease of the entire colon
o Ulcerative proctitis or ulcerative
proctosigmoiditis: limited distal disease
 Small intestine is normal
 Backwash ileitis, or mild mucosal inflammation of the
distal ileum, can be seen in severe cases of pancoilitis
 Morphology
o Mucosa: slightly red and granular or have
extensive, broad based ulcers
o Abrupt transition between diseased and uninvolved
colon
o (+) pseudopolyps → tips of polyps fuse → mucosal
bridges
o (-) mural thickening, NORMAL serosal surface, NO
stricture
o Inflammation → damaged muscularis propria →
disturb neuromuscular fxn → colonic dilation and
toxic megacolon (at risk for perforation)
o Microscopic: inflammatory infiltrates, crypt
abscesses, crypt distortion and pseudopyloric
epithelial metaplasia
o Inflammatory process is diffuse and generally
limited to mucosa and superficial submucosa
o (-) granuloma
o Acute form with marked hyperemia
o Chronic form → mucosal ulceration with residual
foci of elevated and hyperemic mucosa.
 Clinical features
o Relapsing disorder characterized by:
 Bloody diarrhea with stringy mucoid material
 Lower abdominal pain
 Cramps that are temporarily relieved by
defecation
 Infectious enteritis precedes disease onset in
some cases
 Ulcerative colitis patients tend to lack antibodies to
Saccharomyces cerevisiae
 Treatment: colectomy

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Clinical findings
Perianal fistula
No Yes (in colonic
Malabsorption disease)
Malignant No Yes
potential Yes With pancolitis,
early age onset,
Recurrence after duration > 10 yrs
surgery Toxic No Common
megacolon
Yes No

Radiography “Lead pipe” “String” sign in

appearance in terminal ileum;
chronic fistulas
disease

INDETERMINATE COLITIS
 Due to extensive pathologic and clinical overlap
between ulcerative colitis and Crohn disease, definitive
Figure 12. Crohn’s vs. Ulcerative colitis diagnosis is not possible in approximately 10% of IBD
patients
Table 11. Chron’s vs. Ulcerative Colitis  Do not involve the small bowel
Ulcerative Crohn’s disease  Have colonic disease in a continuous pattern that would
colitis typically indicate ulcerative colitis
 (+) perinuclear anti-neutrophil cytoplasmic antibodies
Epidemiology Whites > black Whites > black
Americans Americans;
No sex Jews > non- COLITIS-ASSOCIATED NEOPLASIA
predilection Jews  Risk factors for dysplasia:
Young adults Women > men o Duration of the disease: risk increases sharply 8 to
Young adults 10 years after disease onset
Extent Mucosal & Transmural ○ Extent of the disease: patients with pancolitis are at
submucosal greater risk than those with only left-sided disease
○ Nature of the inflammatory response
Location Mainly rectum 30% - terminal  Diagnosis
Extends ileum alone
continuously 50% - ileum o For early detection of neoplasia, patients are
into left colon and colon enrolled in surveillance programs 8 yrs after
(may involve 20% - colon diagnosis of IBD
entire colon) alone o Goal of surveillance biopsies: identify dysplastic
Does not Involves other epithelium (precursor to colitis associated
involve other areas of GIT carcinoma
areas of GIT (mouth to anus)
 Chromoendoscopy and confocal endoscopy: used to
Gross feature increase the sensitivity of detection of dysplasia
Bowel region Colon only Ileum + colon  IBD-associated dysplasia is classified histologically as
Distribution Diffuse Skip lesions o High-grade dysplasia: invasive carcinoma at the
Stricture Rare Yes
same site or elsewhere in colon
Wall Thin Thick
appearance o Low-grade dysplasia
● Other causes of chronic colitis
Microscopic o Diversion colitis
Inflammation Limited to Transmural o Microscopic Colitis
mucosa
o Lymphocytic Colitis
Pseudopolyps Marked Moderate
Ulcers Superficial, Deep, knife-like
broad-based C. INTESTINAL OBSTRUCTION
Lymphoid rxn Moderate Marked
Fibrosis Mild to none Marked HERNIA
Serositis Mild to none Marked  Any weakness in the wall of the peritoneal cavity that
Granulomas No Yes (~35%)
Fistula/sinus permits protrusion of a serosa-lined pouch of
No Yes
peritoneum (hernial sac)

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 Acquired hernia
o Most commonly occur anteriorly via the femoral
and inguinal canal or umbilicus or sites of
surgical scars visceral protrusion (external
herniation)

Figure 14. Four major causes of intestinal obstruction

Figure 13. Types of hernia

V. LARGE INTESTINE

VOLVULUS A. NEOPLASM
 Complete twisting of a loop of bowel about its  Risk Factors
mesenteric base of attachment o Age older than 50 years
 Produce both luminal and vascular compromise o Low fiber/high saturated fat diet
 Sigmoid colon > cecum > small bowel > stomach or o Cigarette smoking
transverse colon o Familial polyposis syndrome, family history,
ulcerative colitis.
ADHESIONS  Locations
 Surgical procedures, infection or other causes of o Rectosigmoid – 50% of cases
peritoneal inflammation (e.g. endometriosis) → o Ascending colon – 15% of cases
adhesions between bowel segments, abdominal wall & o Descending colon – 15% of cases
operative sites → fibrous bridges create closed loops → o Transverse colon & cecum – 10% each
internal herniation  Screening tests
o Fecal occult blood test – not very sensitive or
INTUSSUSCEPTION specific
 Most common cause of intestinal obstruction in children o Colonoscopy – gold standard
< 2 years of age o Barium enema
 2 portions of intussusception  Clinical findings
o Intussuscipiens: pinasukan na intestine o Left-sided cancers tend to obstruct
o Intussusceptum: pumasok na intestine  Lesions with annular, “napkin-ring”
 Infants & children: viral infection & rotavirus vaccine appearance
(Reactive Hyperplasia of the Peyer’s patches/MALT  Change in bowel habits – constipation and
Leading Edge of intussusception) diarrhea with or without bleeding; change in
 Older children and adults: Intraluminal mass or tumor caliber, change in consistency; stools with
serves as point of traction mucus
o Right-sided cancers tend to bleed
 Tumors are more polypoid in appearance
 Blood in the stool and iron deficiency are
more likely
 Anemia, with symptoms such as dizziness,
malaise, and palpitation.
o Symptoms due to metastasis
 Sites of metastasis: liver (most common),
lungs, bone, and brain

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 1.01 GIT
 Shortness of breath (lung metastasis)
 Jaundice (liver metastasis)
HEREDITARY NON-POLYPOSIS COLORECTAL CANCER
(HNPCC)
 aka lynch syndrome
 Familial clustering of cancers at several sites including:
o Colorectum
o Endometrium
o Stomach
o Ovary
o Ureter
o Brain
o Small bowel
o Hepatobiliary tract
o Pancreas
o Skin
 Most common syndromic form of colon cancer (2-4% of
all colorectal cancer)
 Tend to occur at a younger age than sporadic colon
cancer
 Pathogenesis: inherited mutations in genes that
encode proteins responsible for the detection, excision,
and repair of errors that occur during DNA replication
 There are at least five mismatch repair genes but a
majority of HNCC patients have a mutation in MSH2 or
MLH1 genes
 HNPCC patients may inherit one mutant gene and one
normal gene
 Silencing of the normal gene through mutation →
extremely high mutation in microsatellites →
microsatellite instability (prone to developing into
colorectal cancer)
ADENOCARCINOMA
 Adenocarcinoma of the colon is the most common
malignancy of the GI tract and is a major cause of
morbidity and mortality worldwide
 Location: approximately 50% of all carcinomas occur in
the rectosigmoid area
 Risk for development
o Environmental Factors
 Low dietary fiber content: may alter the
composition of intestinal flora and increased
synthesis of toxic oxidative by-products of
bacterial metabolism that would be exposed to
colonic mucosa for extended periods of time
 High content of refined carbohydrates
 High fat: enhances hepatic synthesis of
cholesterol and bile acids which can be
converted into carcinogens by intestinal
bacteria
 Decreased intake of micronutrients
 Aspirin, or other NSAIDS: have protective
effect by causing polyp regression in AP
patients in whom the rectum was left in place
after colectomy
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Surgical Pathology SEM 1 PRELIMS
 Mediated by inhibition of the enzymes of
COX-2 which is highly expressed in 90%
of colorectal carcinomas and 40%-90% of
adenomas
 Recall: COX-2 is necessary for production
of PGE2 that promotes epithelial
proliferation, particularly after injury
o Genetic factors
 APC gene mutation
 Adenomatous polyposis
 Hereditary Nonpolyposis Colorectal Cancer
 Morphology
o Microscopic findings: crowding or formation of
cribriform pattern of tubular glands
o Gross findings
 “Napkin Ring” deformity
 Can be distinguished as:
o Polypoid: presents as a bulky mass with
well-defined, rolled margins, and a sharp
dividing line with the normal bowel
o Ulcerative/Infiltrative: less elevated
surface and is certainly ulcerated
 Microscopic differences
o Tubular: with space in between glands
o Villous: vertical elongation of glands
o Adenocarcinoma: no space in between glands due
to the fusion of adjacent glands creating a cribriform
pattern
 Growth Pattern
o Polypoid/exophytic: proximal portion of large
intestine (right side)
o Annular, constricting (napkin ring): distal portion of
the large intestine (left side)
o Diffuse
 Pathogenesis
o APC/B-catenin pathway
 Classic adenoma-carcinoma pathway
o Microsatellite instability pathway
 Defects in DNA mismatch repair and
accumulation of mutations in microsatellite
repeat regions of the genome
 aka MSI high or MSI-H tumors
 Mutations in TGF-B receptors may contribute
to uncontrolled cell growth due to the inherent
activity of TGF to inhibit colonic epithelial cell
proliferation
o Activating mutations in the oncogene BRAF are
common in these cancers
o KRAS and TP53 are not typically mutated
 Microsatellite instability + BRAF mutations +
methylation of specific of targets (e.g. MLH1) =
signature of pathway of carcinogenesis
 Clinical significance
o Right-sided colon cancer: fatigue and weakness
due to iron deficiency anemia
o Left-sided colorectal adenocarcinomas: occult
bleeding, changes in bowel habits or cramping, and
left lower quadrant discomfort
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o Most important prognostic factors: depth of invasion o May be missed during casual inspection because it
& +/- LN metastasis is compressible, easily emptied of fecal contents,
 Diagnosis and often surrounded by the fat-containing epiploic
o Screening for high-risk individuals appendices
 Fecal Occult Blood Test  Has a thin wall composed of a flattened or atrophic
 Annual Colonoscopy for both men and women mucosa, compressed submucosa, and attenuated or,
over 40 years old most often, totally absent muscularis propria
o Diagnostic tools  Hypertrophy of the circular layer of the muscularis
 CBC and PBS: microcytic and hypochromic propria in the affected bowel segment
anemia, low RBC, Hgb, and Hct  Obstruction of diverticula → inflammatory changes →
 Occult blood: positive diverticulitis and peridiverticulitis
 Barium Enema: “Apple core appearance”,  Inflammation and ↑ pressure within an obstructed
shouldering diverticulum → perforation (why? kasi muscularis
o Prognosis mucosae and subserosal tissue lang ang nakasupport
 Mucinous Adenocarcinoma sa wall ng diverticulum so imagine kapag sobrang taas
 Factors: depth of invasion and presence of ng pressure)
lymph node metastases o Perforation → pericolonic abscesses, sinus tracts,
 The most common metastatic sites are the peritonitis
liver, lungs, and bones  With or without perforation, diverticulitis may cause:
o Segmental diverticular disease-associated colitis
o Fibrotic thickening in and around the colonic wall
o Stricture formation
 Clinical feature: most patients are asymptomatic

C.
Figure 15. Histologic appearance of colorectal carcinoma.. A, Well-
differentiated adenocarcinoma. Note the elongated, hyperchromatic
nuclei. Necrotic debris present in the gland lumen. C, Mucinous
adenocarcinoma with signet-ring cells and extracellular mucin pools
B. SIGMOID DIVERTICULAR DISEASE
DIVERTICULAR DISEASE
 Acquired pseudo-diverticular outpouchings of the
colonic mucosa and submucosa
 Not invested by all three layers of the colonic wall
 Rare in persons <30 years old
 Diverticulosis: multiple diverticula
 Most diverticula in Asia and Africa occur in the right
colon; right-sided diverticula are uncommon in Western
countries
 Pathogenesis
o Result from the unique structure of the colonic
muscularis propria
o ↑ intraluminal pressure in the sigmoid colon
 Due to exaggerated peristaltic contractions
with spasmodic sequestration of bowel
segments
 Enhanced by diets low in fiber → reduce stool
bulk
 Morphology
o Small, flask-like outpouchings occur in a regular
distribution alongside the taenia coli
HIRCSHPRUNG DISEASE
 aka Congenital Aganglionic Megacolon
 May be isolated or occur in combination with other
developmental abnormalities
 1 of 5000 live births
 10% of cases: children with Down syndrome
 5% of cases: with serious neurologic abnormalities
 More common in males
 When present in females, tends to involve longer
aganglionic segments
 Defect ALWAYS begins at the rectum
 Pathogenesis
o Results when the normal migration of neural crest
cells from cecum to rectum is prematurely
arrested OR when the ganglion cells undergo
premature death.
o Distal intestinal segment lacks both Meissner’s
and Auerbach plexuses (aganglionosis) →
absent peristalsis on distal segment → functional
obstruction → dilation proximal to the affected
segment.
o Genetics: heterozygous loss-of-function
mutations in receptor tyrosine kinase RET
o Pathologic feature: Distal narrow a peristaltic
hypertonic segment (aganglionic) and a dilated
proximal segment caused by obstruction.
 Clinical features
o Failure to pass meconium in the immediate
postnatal period.
o Obstruction or constipation often with ineffective
peristalsis.

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o Earliest and most common presentation is  “Sawtooth appearance”

delayed (> 48 hrs) passage of meconium in the  Serration is typically restricted to the upper
newborn third (or less) of the crypt
o Infants and older children: chronic constipation,
abdominal distention and vomiting.
 If few cm of rectum is affected, occasional passage of
stool may occur. Most cases limited to rectum and
sigmoid colon.
 (+) megacolon → stretch and thin the colonic wall to
the point of rupture (usually cecum)
 Major threats to life
o Enterocolitis
o Fluid and electrolyte disturbances
o Perforation
o Peritonitis
 Diagnosis
o Requires documenting the absence of ganglion
cells within the affected segment
 H&E stain
 Immunohistochemical stain for Figure 16. Hyperplastic polyp. A, Polyp surface with irregular tufting
acetylcholinesterase of epithelial cells. B, Tufting results from epithelial overcrowding. C,
 Intraoperative frozen-section analysis: Epithelial crowding produces a serrated architecture
confirmatory
 Treatment: Surgical resection of the aganglionic B. INFLAMMATORY POLYPS
segment followed by anastomosis of the normal ● Form as part of the solitary rectal ulcer syndrome
proximal colon to the rectum ● Clinical triad
o Rectal bleeding
 VI. SMALL & LARGE BOWEL POLYPS o Mucus discharge
 Most common in the colo-rectal region but may occur in o Inflammatory lesion of the anterior rectal wall
the esophagus, stomach, or small intestine ● Pathogenesis: impaired relaxation of the anorectal
 Begin as small elevations of the mucosa (sessile) sphincter → sharp angle at the anterior rectal shelf →
o Sessile: polyps without a stalk recurrent abrasion and ulceration of the overlying
o Pedunculated: polyps with stalks rectal mucosa
 Intestinal polyps can be grouped into neoplastic and non- o Result of chronic cycles of injury and healing
neoplastic ● Entrapment in fecal stream → mucosal prolapse
o Neoplastic: with dysplasia; example is adenoma ● Microscopic: mixed inflammatory infiltrates, erosion,
o Non-neoplastic can be further further classified as and epithelial hyperplasia + lamina propria
inflammatory, hamartomatous, or hyperplastic fibromuscular hyperplasia

A. HYPERPLASTIC POLYPS C. HAMARTOMATOUS POLYPS

● Occur sporadically or as components of various
 Benign epithelial proliferations that are typically
genetically determined or acquired syndromes
discovered in the 6th and 7th decades of life
● Pathogenesis: caused by germline mutations in
 Pathogenesis: result from decreased epithelial cell
tumor suppressor genes or protooncogenes
turnover and delayed shedding of surface epithelial
● Some are associated with increased cancer risk
cells → “piling up” of goblet cells and absorptive cells
 NO malignant potential
JUVENILE POLYPS
 Histologically similar with sessile serrated adenomas
 Focal malformations of the epithelium and lamina
 Morphology
propria
o Found in the left colon
 Occur in children <5 y/o but they can present at older
o Smooth, nodular protrusions of the mucosa, often
ages
on the crests of mucosal folds
 Located in the rectum
o May occur singly but are more frequently multiple,
 Clinical manifestations: rectal bleeding,
particularly in the sigmoid colon and rectum
intussusception, intestinal obstruction, or polyp prolapse
o Microscopic: mature goblet and absorptive cells
(through the anal sphincter)
o Delayed shedding of these cells → crowding →
serrated surface (morphologic hallmark)  May be sporadic or syndromic

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o Sporadic (retention) polyps: usually solitary
lesions, dysplasia is extremely rare
o Syndromic polyps: may require colectomy to limit
the chronic and sometimes severe hemorrhage
associated with polyp ulceration, associated with
dysplasia
 Extraintestinal manifestation of juvenile polyposis
include pulmonary arteriovenous malformations and
other congenital malformations
 Morphology
o Gross: pedunculated, smooth-surfaced, reddish
lesions with characteristic cystic spaces
o Microscopic: dilated glands filled with mucin and
inflammatory debris
 Remainder of the polyp is composed of lamina
propria expanded by mixed inflammatory
infiltrates
 Muscularis mucosae may be normal or
attenuated
 Initiating event: hyperplasia of the mucosa
 Pathogenesis: mutations in SMAD4 (encodes a
cytoplasmic intermediate in the TGF-β signaling
pathway) and BMPR1A (kinase that is a member of the
TGF-β superfamily) → autosomal dominant juvenile
polyposis
Figure 17. Juvenile polyps. Note the surface erosion and cystically
dilated crypts.
PEUTZ-JEGHERS SYNDROME
 Rare autosomal dominant syndrome
 Clinical features
o Median age of 11 years
o Multiple GI hamartomatous polyps
o Mucocutaneous hyperpigmentation (dark blue to
brown macules on the lips, nostrils, buccal mucosa,
palmar surfaces of the hands, genitalia, and
perianal region)
o (+) family history
 Can initiate intussusception (occasionally fatal)
 Associated with a markedly increased risk of several
malignancies
o At birth: sex cord tumors of the testis
o Late childhood: gastric and SI cancers
o > 2nd and 3rd Decades of life: colon, pancreatic,
breast, lung, ovarian and uterine cancers
 Pathogenesis: germline heterozygous loss-of-function
mutations in the STK11 (Recall: STK11 is a tumor
suppressor gene that encodes a kinase that regulates
Transcribers Damian, Ng, Perez, Santos
Surgical Pathology SEM 1 PRELIMS
cell polarization and acts as a brake on growth and
anabolic metabolism)
*The function of the second normal copy of STK11 is lost
through somatic mutation in cancers
 Morphology
o Seen in small intestine (most common), stomach,
colon, bladder and lungs
o Gross: large and pedunculated with a lobulated
contour
o Microscopic: arborizing network of connective
tissue, smooth muscle, lamina propria, and glands
lined by normal-appearing intestinal epithelium
*The arborization and presence of smooth muscle
intermixed with lamina propria can be used to distinguish
Peutz-Jeghers from Juvenile polyps.
D. NEOPLASTIC POLYPS
● Neoplastic mass lesions in the GI tract may produce a
mucosal protrusion, or polyp
o Adenocarcinomas, neuroendocrine (carcinoid)
tumors, stromal tumors, lymphomas, and
metastatic cancers from distant sites
● Colonic Adenoma: Most common neoplastic polyp.
Precursors to majority of colorectal adenocarcinoma
o Recommended colonoscopy surveillance :
■ General population: 50 y/o
■ With family hx of colorectal adenoCA: at
least 10 years before the youngest age at
which a relative was diagnosed
o Risk factors for malignancy
■ Adenomas > 2 cm size (40% risk)
■ Multiple polyps
■ Polyps with increased villous component
■ High grade dysplasia
o Size is the most important characteristic that
correlates with risk  40% of lesions > 4 cm
contain foci of cancer
● Adenomas are intraepithelial neoplasms that range
from small pedunculated polyps to large sessile
lesions. Characterized by presence of epithelial
dysplasia.
o Most are clinically silent, with the exception of:
■ Large polyps that produce occult bleeding
and anemia
■ Rare villous adenomas that cause
hypoproteinemic hypokalemia by secreting
large amounts of protein and potassium
o Can be classified into:
■ Tubular adenomas (adenomatous
polyps)
 Small, smooth, pedunculated polyps
 Solitary, usually stalked
 Most common (60% of polyps)
 Sigmoid colon most common site
 Composed of small rounded, or tubular,
glands
 Microscopic: circular glands, crowding
of the tubular formations on dysplastic
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colonic glands, pseudostratification of E. ADENOMATOUS POLYPOSIS

the lining, dysplastic changes as
FAMILIAL COLONIC POLYPS AND CARCINOMA (FAP)
exhibited by hyperchromasia
 Autosomal dominant disorder
■ Villous adenomas
 Often larger  Caused by mutations of the Adenomatous polyposis
 Covered by slender villi coli (APC) gene
 Most cases present as a single mass in o Key negative regulator of the Wnt signaling pathway
the rectum  At least 100 polyps are necessary for diagnosis
 Papillary villous projections, usually  Polyp growth are indistinguishable from sporadic
attached by a wide base adenomas except for their remarkable number
 Gross: The lesion is characteristically  (+) Large central dominant polyp surrounded by multiple
large and flat and has an arborescent smaller polyps
architecture. Multiple villous projections  Flat or depressed adenomas are also prevalent and
ramify on a long papillary crown like microscopic adenomas are frequently observed in
growth “carpet” like normal-appearing mucosa
 Microscopic: Epithelial dysplasia,  Colorectal adenocarcinoma develops in 100% of
hyperchromasia, vertical elongation of untreated AP patients
villi, finger like projections. Long villi are  Treatment: prophylactic colectomy
arranged in parallel, perpendicularly to o Prevents colorectal cancer
the mucosa. o Remain at risk for neoplasia at other sites
■ Tubulovillous adenomas o Adenomas may develop elsewhere in the GI tract,
 Mixture of tubular and villous elements particularly adjacent to the ampulla of Vater in the
 20 – 30% of polyps stomach
 Usually pedunculated  Extraintestinal manifestation: congenital hypertrophy of
● Colorectal adenomas are characterized by the the retinal pigment epithelium
presence of epithelial dysplasia.  Subtypes of FAP
o Prevalence of colorectal adenomas correlates o Classic FAP syndrome
with that of colorectal adenocarcinoma ■ The patient has a large number of
● Morphology adenomatous polyps and retinal pigment
o Can be pedunculated or sessile, with the surface epithelial hypertrophy. There should be a
of both types having a texture resembling velvet minimum of 100 polyps to make a diagnosis
or a raspberry
of this syndrome. Most adenomatous polyps
o Microscopic: nuclear hyperchromasia,
are tubular polyps.
elongation, and stratification (all of which are o Gardner Syndrome: Intestinal polyps + epidermal
hallmarks of epithelial dysplasia); prominent
cyts + fibromatosis + osteomas (of the mandible,
nucleoli, eosinophilic cytoplasm, and ↓ goblet
long bones & skull)
cells o Turcot Syndrome: Adenomatous colon polyposis
+ CNS tumors ( medulloblastoma in 2/3 and gliomas
in 1/3 patients).
o Noncolonic causes of death in patients with
FAP
 Thyroid adenocarcinoma
 Pancreatic carcinoma
 CNS tumors
 Complications of therapy

MYH-ASSOCIATED POLYPOSIS
 Autosomal recessive disorder
 Some polyposis without APC loss have bi-allelic
mutations of the base-excision repair gene MYH
 Similar to attenuated AP with polyp development at later
Figure 18. Histologic appearance of colonic adenomas. A, Tubular adenoma with a ages, presence of fewer than 100 adenomas, and
smooth surface and rounded glands. Active inflammation is occasionally present in delayed appearance of colon cancer.
adenomas, in this case, crypt dilation and rupture can be seen at the bottom of the
field. B, Villous adenoma with long, slender projections that are reminiscent of small
REFERENCE:
intestinal villi. C, Dysplastic epithelial cells (top) with an increased nuclear to
cytoplasmic ratio, hyperchromatic and elongated nuclei, and nuclear Lecture PPT, Lecture Notes, Systemic Pathology Transes 2022,
pseudostratification. D, Sessile serrated adenoma lined by goblet cells without Robbin’s 9th ed.
cytologic features of dysplasia. This lesion is distinguished from a hyperplastic polyp by
extension of the neoplastic process to the crypts, resulting in lateral growth

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 SURGICAL PATHOLOGY
1.01 Gastrointestinal Pathology P1
September 9, 2020 | Dr. Arnel Bayotas
APPENDIX

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