1. GASTROINTESTINAL TRACT
Dr. Jalal A. Jalal
Dept. of Pathology
College of Medicine-HMU

2.  Oral cavity
 Salivary glands
 Esophagus
 Stomach
 Small bowel
 Large bowel
 Appendix
2

3. I.DISEASES OF THE ORAL CAVITY
 A. Inflammatory disorders
 Herpes labialis (fever blisters, cold sores):
 is a common vesicular lesion caused by herpes simplex virus (HSV),
most often type 1 (HSV-1).
 It tends to recur, with activation by febrile illness, trauma, sunshine,
 or menstruation.
 Aphthous stomatitis
 is characterized by painful, recurrent, erosive oral ulcerations.
 Oral candidiasis (thrush, moniliasis):
 is a local white, membranous lesion caused by Candida albicans.
 It occurs most commonly in debilitated infants and children,
immunocompromised patients, and individuals with diabetes.
3

4. B. TUMORS AND TUMOR-LIKE
CONDITIONS
 Benign tumors of the oral mucosa
 Papilloma is the most common benign epithelial tumor of the
oral mucosa. It can occur anywhere in the mouth; the most
common sites are the tongue, lips, gingivae, or buccal
mucosa.
 Fibroma is most often a non-neoplastic hyperplastic lesion
resulting from chronic irritation.
 Hemangioma occurs most commonly on the tongue, lips, or
buccal mucosa.
 Epulis refers to a benign (usually non-neoplastic) growth of
the gingivae. It is most often a reparative growth rather than a
true neoplasm.
4

5. LEUKOPLAKIA AND ERYTHROPLAKIA
 Leukoplakia
 Leukoplakia refers to any whitish mucosal patch or plaque
caused by epithelial thickening.
 Microscopically, leukoplakias show a range of changes, varying
from hyperkeratosis with or without epithelial dysplasia to
carcinoma in situ.
 About 3 to 25% of leukoplakias can progress to invasive cancer.
5

6. 6

7. 7

8.  Erythroplakia
 refers to red, velvety, often granular, circumscribed
areas that may or may not be elevated, having poorly
defined, irregular boundaries.
 Histologically, erythroplakia almost invariably reveals
marked epithelial dysplasia (the malignant
transformation rate is >50%),
 So recognition of this lesion becomes even more
important than identification of oral leukoplakia.
8

9. CANCERS OF THE ORAL CAVITY AND
TONGUE
 Most frequently squamous cell carcinoma.
o The three predominant sites of origin of oral cavity
carcinomas are (in order of frequency) :
(1) Lower lip.
(2) Floor of the mouth.
(3) Lateral borders of the tongue.
9

10. RISK FACTORS FOR ORAL CANCER
Factor Comments
Leukoplakia, erythroplakia Risk of transformation in leukoplakia 3% to
25%
More than 50% risk in erythroplakia
Tobacco use Best-established influence.
Human papillomavirus types 16 and
18
Identified by molecular probes in 30% to
50% of cases; probably have a role in a
subset of cases
Alcohol abuse Weaker influence than tobacco use, but the
two habits interact to greatly increase risk
Protracted irritation Weakly associated
10

11. 11

12. 12

13.  What is the relationship between location and prognosis
for cancers of the oral cavity?
 The prognosis is best for carcinomas of the lip and
poorest for carcinomas of the floor of the mouth and the
base of the tongue
13

14. II. DISEASES OF THE SALIVARY GLANDS
 A. Sialadenitis.
 inflammation of the salivary glands may be caused by infection,
immune-mediated mechanisms, or occlusion of the salivary ducts
by stones (sialolithiasis).
 B. Acute parotitis:
 This condition occurs in mumps, but may also be caused by other
infectious agents.
 Although childhood mumps is self-limited and rarely creates
residual problems, mumps in adults may be accompanied by
pancreatitis or orchitis; the latter sometimes causes permanent
sterility.
14

15.  C.Chronic sialadenitis :
 arises from decreased production of saliva with subsequent
inflammation. The dominant cause is autoimmune sialadenitis, which
is almost invariably bilateral. This is seen in Sjögren syndrome.
 This condition is most likely of autoimmune origin.
 Characteristics include keratoconjunctivitis sicca (dry eyes),
xerostomia (dry mouth), and an associated connective tissue disease,
most often rheumatoid arthritis.
 Sjögren syndrome is associated with an increased incidence of
malignant lymphoma
15

16.  D. Mucocele.
 This cyst-like pool of mucus, lined by granulation tissue, develops
near a minor salivary gland. It results from mucous leakage caused by
rupture of obstructed or traumatized ducts.
 E. Ranula.
 This is a large mucocele, of salivary gland origin, characteristically
localized to the floor of the mouth.
16

17. F. TUMORS OF THE SALIVARY GLAND
 The majority of salivary gland tumors occur in the parotid gland.
 The majority of tumors of the parotid gland are benign.
 In contrast, about half of the tumors of the sub maxillary gland are
malignant.
 Whatever the type, they present clinically as a mass causing a swelling
at the angle of the jaw.
17

18. PLEOMORPHIC ADENOMA (MIXED
TUMOR)
 is the most frequently occurring salivary gland tumor. It occurs with
greatest frequency in women between 20 and 40 years of age
 This is a benign tumor that frequently recurs; it rarely becomes
malignant.
 It has been called "mixed tumor" because of the presence of myxoid
and cartilage-like elements, as well as epithelial cells.
18

19. 19

20. Histologically, pleomorphic adenomas demonstrate irregular
masses or anastomosing strands of stellate or fusiform epithelial
cells, some forming ducts or tubules, all of which are embedded
in a myxoid stroma that may display fibrous, cartilage-like, or
hyalinized areas.
The tumor is most often localized to the parotid gland (~90%).
Usually, the tumor presents as a firm, nontender swelling.
Often, the tumor is difficult to remove completely because of its
proximity to the facial nerve, and it is likely to recur after
resection.
20

21. 21

22.  Other salivary gland tumors
 Papillary cystadenoma lymphomatosum (Warthin tumor):
benign tumor composed of epithelial cells and dense lymphoid
tissue.
 Mucoepidermoid carcinoma:
 most common malignant salivary gland tumor.
 Adenoid cystic carcinoma
22

23. SALIVARY GLAND TUMORS: LOCATION,
HISTOLOGY, AND CHARACTERISTICS
Type Typical Location Histology
Pleomorphic adenoma
(mixed tumor)
Parotid gland Variable mixture of epithelial and
mesenchyme-like elements
Papillary cystadenoma
lymphomatosum
(Warthin tumor,
adenolymphoma)
Parotid gland Cystic spaces lined by double-
layered eosinophilic
epithelium, all embedded in
lymphoid stroma
23

24. Type Typical Location Histology
Mucoepidermoid
carcinoma
Parotid gland Comprised of mucus-producing
and epidermoid components
and cells intermediate
between the two
Adenoid cystic
carcinoma
Minor salivary glands Variable; most characteristic
appearance consists of
cribriform pattern with masses
of small, dark-staining cells
arrayed around cystic spaces
24

25. III. DISEASES OF THE ESOPHAGUS
 Tracheoesophageal fistula.
 Esophageal diverticula
 Achalasia
 Hiatal Hernia
 Esophageal varices
 Inflammatory and related disorders of the esophagus
 EsophagusTumors
25

26. SYMPTOMS OF ESOPHAGEAL
DISORDERS
 Dysphagia (difficulty in swallowing),
which is attributed either to deranged esophageal motor
function or to narrowing or obstruction of the lumen.
o Heartburn (retrosternal burning pain) usually reflects
regurgitation of gastric contents into the lower
esophagus.
o Less commonly, hematemesis (vomiting of blood) and
melena (blood in the stools) are evidence of severe
inflammation, ulceration, or laceration of the esophageal
mucosa.
o Massive hematemesis may reflect life-threatening
rupture of esophageal varices.
26

27. NORMAL ANATOMY
 Extends from C6 to T11 or T12
 Length 25 cm in adult (on average)
 Three points of luminal narrowing:
1. Cricoid cartilage
2. Where left mainstem bronchus crosses anterior to the
esophagus (midway down)
3. Diaphragm
 Upper and lower sphincters defined manometrically; no
mophological landmarks
 Outer longitudinal muscle layer is striated for the first 6-8 cm
 No serosa - lesions can easily spread into mediastinum
27

28. HISTOLOGY
28

29. CONGENITAL ANOMALIES
 A. Tracheoesophageal fistula.
 This congenital disorder is suggested in a newborn by
copious salivation associated with choking, coughing,
and cyanosis on attempts at food intake. It occurs in
three distinct variants:
 In the most common variant (90%), the lower portion
of the esophagus communicates with the trachea near the
tracheal bifurcation. The upper esophagus ends in a blind
pouch (esophageal atresia). Maternal polyhydramnios
(increased amniotic fluid) is a frequently associated
abnormality.
29

30. TRACHEOESOPHAGEAL FISTULA
 The second most common variant is characterized by a fistulous
connection between the upper esophagus and the trachea; the lower
esophageal segment is not connected to the upper esophagus.
 In a third variant, there is a fistulous connection between the trachea
and a completely patent esophagus.
301
2
3

31. B. ESOPHAGEAL DIVERTICULA
 are pouches lined by one or more layers of the esophageal wall.
 Most commonly, false (pulsion) diverticula result from herniation of
the mucosa through defects in the muscular layer.
 Less commonly, true (traction) diverticula consist of mucosal,
muscular, and serosal layers.
 Traction diverticula result from periesophageal inflammation and
scarring.
 Esophageal diverticula occur in three characteristic locations:
Immediately above the upper esophageal sphincter (Zenker
diverticulum).
Near the midpoint of the esophagus.
Immediately above the lower esophageal sphincter (epiphrenic
diverticulum).
31

32. C. ACHALASIA
 The term achalasia means "failure to relax," and here denotes
incomplete relaxation of the lower esophageal sphincter in response
to swallowing.
 This produces functional obstruction of the esophagus, with
consequent dilation of the more proximal esophagus.
 The condition is caused by a loss of ganglion cells in the myenteric
plexus, which leads to the progressive dilation of the esophagus.
32

33. ACHALASIA
 One important source (principally in South America) is Trypanosoma
cruzi infection in Chagas disease.
 In other cases, ganglion cells are lost for reasons that are not known.
 Clinical characteristics include difficulty in swallowing.
 Achalasia can lead to esophageal squamous cell carcinoma in about
5% of subjects.
33

35. HIATAL HERNIA
 Sac-like dilatation of stomach present above the diaphragm
1. Sliding Hernia (90%)
 Congenitally short esophagus or acquired from esophageal
scarring induced with traction on the stomach
 Predisposes to reflux.
2. Rolling (Paraesophageal) Hernia (10%)
 Portion of cardia protrudes through the diaphragm into the
thorax along side the esophagus
 Vulnerable to strangulation and infarction
35

36. E. ESOPHAGEAL VARICES
 These dilated submucosal esophageal veins that occur secondary to
portal hypertension can result in upper gastrointestinal hemorrhage.
 The other important causes of upper gastrointestinal hemorrhage are
 bleeding peptic ulcer
 Mallory-Weiss syndrome,
36

37. F. INFLAMMATORY AND RELATED
DISORDERS OF THE ESOPHAGUS
 Gastroesophageal reflux disease (GERD)
 is reflux of gastric acid contents into the esophagus.
 Characteristic manifestations often include substernal pain (heartburn)
relieved by antacids.
o Most commonly, associated conditions include:
 hiatal hernia
 incompetent lower esophageal sphincter.
 excessive use of alcohol
 tobacco
 increased gastric volume,
 pregnancy,
 scleroderma.
 Assuming a recumbent position.
37

38. REFLUX/GERD
• Morphology:
• Inflammatory Cells
– Eosinophils
– Neutrophils
– Lymphocytes
• Basal zone hyperplasia
• Lamina Propria papillae elongated and congested
38

39. REFLUX/GERD
39

40. GASTROESOPHAGEAL REFLUX
 What are the major complications of reflux esophagitis?
(a) ulcer;
(b) bleeding;
(c) development of stricture;
(d) development of Barrett esophagus.
40

41. BARRETT ESOPHAGUS
 Is columnar metaplasia of esophageal squamous epithelium; the
columnar epithelium is often of the intestinal (specialized) type with
prominent goblet cells.
 Occurring in as many as 5% to 15% of persons with persistent
symptomatic reflux disease.
 Barrett esophagus affects males more often than females (ratio of 4:1)
and is much more common in whites than in other races
 This condition is a complication of long-standing gastroesophageal
reflux and is a well-known precursor of esophageal
adenocarcinoma.
41

42. BARRETT ESOPHAGUS IS APPARENT AS A SALMON-PINK, VELVETY
MUCOSA BETWEEN THE SMOOTH, PALE-PINK ESOPHAGEAL
SQUAMOUS MUCOSA AND THE MORE LUSH LIGHT BROWN GASTRIC
MUCOSA
42

43. 43

44. OTHER CAUSES OF ESOPHAGITIS
 Candida esophagitis (moniliasis)
 Associated conditions often include:
 antibiotic use,
 diabetes mellitus,
 malignant disease,
 immunodeficiency caused by AIDS or immunosuppressive drugs.
 Herpetic esophagitis
 is caused by HSV-1 infection.
 Characteristics include painful, difficult swallowing.
 Less common forms of esophagitis :
 cytomegalovirus (CMV) infection,
 uremia,
 radiation therapy, 44

45. G. Esophagus Tumors
1. Leiomyoma
 Most common benign tumor of esophagus arising from Smooth muscle cells
2. Squamous cell carcinoma
 Incidence: common in China, Rare in US (Adenocarcinoma – MC in USA)
M>F, age >50 yr.
 “Early carcinoma” = upto submucosa ( 90%- 5 year survival good
prognoses even though lymph nodes are involved)
 Spreads locally into mediastinal structures & to lymph nodes
 Clinically:
 Insidious dysphagia, weight loss, anemia.
 Overall 5-year-survival is 5%.
45

46. Risk Factors for Squamous Cell Carcinoma of the Esophagus
Esophageal Disorders
Long-standing esophagitis
Achalasia
Plummer-Vinson syndrome (esophageal webs, microcytic hypochromic anemia,
atrophic glossitis)
Life-style
Alcohol consumption
Tobacco abuse
Dietary
Deficiency of vitamins (A, C, riboflavin, thiamine, pyridoxine)
Deficiency of trace metals (zinc, molybdenum)
Fungal contamination of foodstuffs
High content of nitrites/nitrosamines
Genetic Predisposition
Tylosis (hyperkeratosis of palms and soles)
46

47. MORPHOLOGY
 Squamous cell carcinomas are usually preceded by a long
prodrome of mucosal epithelial dysplasia followed by
carcinoma in situ and, ultimately, by the emergence of
invasive cancer.
 In months to years, these lesions become tumorous, taking one
of three forms:
(1) polypoid exophytic masses that protrude into the lumen.
(2) necrotizing cancerous ulcerations that extend deeply and
sometimes erode into the respiratory tree, aorta, or elsewhere
(3) diffuse infiltrative neoplasms that cause thickening and
rigidity of the wall and narrowing of the lumen.
o About 20% arise in the upper third of esophagus, 50% in the
middle third, and 30% in the lower third. 47

48. ESOPHAGUS
SQUAMOUS CELL CARCINOMA
48

49. Esophagus Tumors
3. Esophageal adenocarcinoma
 Incidence: 25% of esophageal cancers world wide
 up to half of all esophageal cancers reported in US
 Primary risk factor - Barrett’s esophagus
 Most arise in distal 1/3rd of the esophagus.
 Histology: Mucin producing adenocarcinoma.
 present with dysphagia
 Overall 5-year survival - 15%
49

50. 50

51. ESOPHAGUS
MALIGNANT TUMORS
Feature Squamous Adeno
Incidence 75% 25%
Geography Asia USA
Age >50 >40
Site Middle1/3 rd Lower 1/3rd
Risk factors Smoking,
alcohol, foods
Reflux Esophagitis
(Barrett's)
Prognosis 5yr.-5% 5yr.-15%
51

52. IV. DISEASES OF THE STOMACH
 Congenital pyloric stenosis
 Gastritis: Acute, Chronic
 Peptic ulcer of the stomach
 Tumors of the stomach
52

53.  The stomach is divided into four major anatomic
regions: the cardia, fundus, body, and antrum.
 The cardia and antrum are lined mainly by mucin-
secreting foveolar cells that form small glands.
 The antral glands are similar but also contain endocrine
cells, such as G cells, that release gastrin to stimulate
luminal acid secretion by parietal cells within the gastric
fundus and body.
 The well-developed glands of the body and fundus also
contain chief cells that produce and secrete digestive
enzymes such as pepsin.
53

54. 54

55.  A. Congenital pyloric stenosis
 This stenosis is caused by hypertrophy of the circular
muscular layer of the pylorus, often leading to a
palpable mass.
 The resulting obstruction of the gastric outlet causes
episodes of projectile vomiting beginning in the first 2
weeks of life. This condition is much more common in
boys.
 The condition is corrected by surgical incision of the
hypertrophied muscle
55

56. B. GASTRITIS
 Acute (erosive) gastritis
 Causes
Nonsteroidal anti-inflammatory drugs (NSAIDs)
Cigarette smoking
Heavy alcohol intake
Burn injury; Curling ulcer, an acute gastric ulcer in
association with severe burns
Brain injury; Cushing ulcer, an acute gastric ulcer
in association with brain injury
56

57. ACUTE (EROSIVE) GASTRITIS
 Characteristics
Focal damage to the gastric mucosa, with
acute inflammation, necrosis, and
hemorrhage
Manifested as acute gastric ulcers, which are
often multiple
57

58. CHRONIC GASTRITIS
 is characterized by chronic mucosal inflammation and atrophy of the
mucosal glands.
A. Autoimmune gastritis: is associated with:
 Presence of antibodies to parietal cells (and sometimes to intrinsic factor)
 Achlorhydria (lack of gastric acid secretion)
 pernicious anemia
 Autoimmune diseases, such as Autoimmune thyroiditis and Addison disease.
 It is also associated with aging, partial gastrectomy, gastric ulcer, and gastric
carcinoma.
58

59. B. Helicobacter pylori–associated gastritis
is the most common form of chronic gastritis.
There is no association with pernicious anemia, antibodies to
parietal cells, or reduced gastric acid secretion.
Often, increased gastric acid secretion occurs.
H. pylori is also strongly associated with gastric and duodenal
peptic ulcer
Is a high suspect in the causality of carcinoma of the stomach and
gastric lymphoma of the mucosa-associated lymphoid tissue
(MALT) type.
59

60. H. PYLORI GASTRITIS - SILVER
STAIN
Bacteria over
epithelial cells
60

61. H. pylori–Associated Autoimmune
Location Antrum Body
Inflammatory infiltrate Neutrophils, subepithelial
plasma cells
Lymphocytes, macrophages
Acid production Increased to slightly decreased Decreased
Gastrin Normal to decreased Increased
Other lesions Hyperplastic/inflammatory
polyps
Neuroendocrine hyperplasia
Serology Antibodies to H. pylori Antibodies to parietal cells
Sequelae Peptic ulcer, adenocarcinoma Atrophy, pernicious anemia,
adenocarcinoma, carcinoid
tumor
Associations Low socioeconomic status,
poverty, residence in rural
areas
Autoimmune disease;
thyroiditis, diabetes mellitus,
Graves disease
61

62. C. PEPTIC ULCER OF THE STOMACH
 Most often, the stomach ulcer occurs at or near the lesser
curvature, in the antral and prepyloric regions.
 The ulcer is not a precursor lesion of carcinoma of the
stomach.
 Unlike peptic ulcer that occurs elsewhere, peptic ulcer of
the stomach is not dependent on increased gastric acid
secretion; however, acid and pepsin are believed to play
a role, because gastric peptic ulcers rarely occur in
association with absolute achlorhydria.
62

63.  Postulated etiopathogenic mechanisms of gastric peptic
ulcer production include:
 H. pylori–mediated processes, in which bacterial ureases and
proteases break down glycoproteins in gastric mucus, thus
interfering with epithelial protection
 Increased permeability of the gastric mucosa to hydrogen ion,
resulting in back diffusion of hydrogen ion with injury to the
gastric mucosa
 Bile-induced gastritis leading to gastric ulceration
63

64. 64

65. BENIGN, CHRONIC, GASTRIC PEPTIC
ULCER
Sharp edges, converging folds of mucosa in the upper half. The ulcer bed is covered by fibrinopurulent exudate.
65

66. 66

67. ESOPHAGEAL LACERATIONS (MALLORY-
WEISS SYNDROME)
67
oLongitudinal tears at the gastroesophageal junction
oClinical setting: chronic alcoholics after a bout of severe
vomiting
oTear may be superficial or deep affecting all layers
oClinical picture: Pain, bleeding, superimposed infection
oHiatal hernia is found in 75% of patients
Most often bleeding stops w/o intervention, but life-threatening
hematemesis may occur.
Supportive therapy and balloon tamponade. Healing is prompt
with minimal or no residue

68. 68

69. D. BENIGN TUMORS- GASTRIC POLYPS
69
•INFLAMMATORY AND HYPERPLASTIC POLYPS:
o Approximately 75% of all gastric polyps are inflammatory or
hyperplastic polyps.
oThey are most common between 50 and 60 years of age.
o usually develop in association with chronic gastritis, which
initiates the injury and reactive hyperplasia that leads to polyp
growth.
oAmong individuals with H. pylori gastritis, polyps may regress
after bacterial eradication.
oBecause the risk of dysplasia correlates with size, polyps larger
than 1.5 cm should be resected and examined histologically.

70. D. MALIGNANT TUMORS OF THE
STOMACH
 Carcinoma of the stomach
 General considerations
Carcinoma of the stomach is most common after 50 years of age,
with an increased incidence in men. It occurs more frequently in
persons with blood group A, suggesting a genetic predisposition.
Incidence varies greatly from one geographic area to another,
with incidence much higher in Japan, Finland, and Iceland.
The incidence is decreasing in the United States.
70

71. CARCINOMA OF THE STOMACH
 Etiologic factors
H. pylori is a high suspect.
Nitrosamines from dietary amines and nitrites used as food
preservatives may play a role. Incidence of the disease is greatly
increased in populations who eat large amounts of smoked fish
and meat and pickled vegetables.
Increased incidence is also associated with excessive salt intake
and a diet low in fresh fruits and vegetables.
Achlorhydria
Chronic gastritis with or without pernicious anemia
71

72. GROSS MORPHOLOGIC VARIANTS OF
STOMACH CARCINOMA
A-Intestinal type
Often, this variant is manifest as polypoid (fungating)
carcinoma, which forms a solid mass projecting into the lumen
of the stomach. It has a high degree of association with H.
pylori infection.
The intestinal variant can become ulcerated and must be
differentiated from peptic ulcer. Peptic ulcer usually exhibits a
smooth base with nonelevated, punched-out margins. In
contrast, carcinoma tends to form an ulcer with an irregular
necrotic base and firm, raised margins.
72

73. Malignant gastric ulcer.
This ulcerating
adenocarcinoma of the
stomach .
Rolled elevated edges in the
cancer are suggestive signs,
but differentiation by
biopsy is essential.
73

74. B-Infiltrating or diffuse carcinoma (linitis
plastica, leather-bottle stomach)
 is not associated with H. pylori infection.
characterized by a thickened, rigid stomach wall,
caused by diffuse infiltration of tumor cells with
accompanying extensive fibrosis.
74

75. Infiltrating carcinoma (linitis
plastica).
The stomach with stiff rigid
walls caused by infiltrating
tumor cells and extensive
fibrosis has been referred to as
a "leather-bottle stomach."
75

76. 76

77. CLINICAL FEATURES.
 Intestinal-type gastric cancer :
 The mean age of presentation is 55 years, and the male-
to-female ratio is 2 : 1.
 Diffuse gastric cancer is relatively uniform across
countries, there are no identified precursor lesions, and
the disease occurs at similar frequencies in males and
females.
 Notably, the remarkable decrease in gastric cancer
incidence applies only to the intestinal type, which is
most closely associated with atrophic gastritis and
intestinal metaplasia. As a result, the incidences of
intestinal and diffuse types of gastric cancers are now
similar.
77

78.  The depth of invasion and the extent of nodal and distant
metastasis at the time of diagnosis remain the most powerful
prognostic indicators for gastric cancer.
 In advanced cases gastric carcinoma may first be detected as
metastases to the supraclavicular lymph node, also called
Virchow's node.
 Another somewhat unusual mode of intraperitoneal spread in
females is to both the ovaries, giving rise to the so-called
Krukenberg tumor.
78

79. GASTROINTESTINAL STROMAL TUMORS
 GI stromal tumor (GIST) is the most common mesenchymal tumor of the
abdomen, and more than half of these tumors occur in the stomach.
 Epidemiology:
 Overall, GISTs are slightly more common in males.
 The peak age of GIST diagnosis in the stomach is approximately 60 years, with
fewer than 10% occurring in individuals under 40 years of age.
 Pathogenesis.
 Approximately 75% to 80% of all GISTs have mutations of the gene encoding
the tyrosine kinase c-KIT, which is the receptor for stem cell factor.
 GISTs appear to arise from the interstitial cells of Cajal, which are located in the
muscularis propria and serve as pacemaker cells for gut peristalsis.
79

80. MORPHOLOGY (GIST)
 They usually form a solitary, well-circumscribed, fleshy mass
covered by ulcerated or intact mucosa.
 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.
 The prognosis correlates with tumor size, mitotic index, and
location, with gastric GISTs being somewhat less aggressive than
those arising in the small intestine.
 Recurrence or metastasis is rare for gastric GISTs under 5 cm but
common for mitotically active tumors larger than 10 cm.
80

81. GASTROINTESTINAL STROMAL TUMOR (GIST). A, GIST FROM THE
STOMACH WALL. B, HISTOLOGY OF THE TUMOR SHOWING SPINDLE
CELLS WITH ELONGATED NUCLEI WITH FINE CHROMATIN, AND
EOSINOPHILIC FIBRILLAR CYTOPLASM.
81

82. C, KIT STAIN SHOWING STRONG AND UNIFORM REACTIVITY OF THE
TUMOR CELLS.
82

83. GASTRIC LYMPHOMA
 accounts for 4% of malignant gastric tumors.
 They are of the MALT type.
 Gastric MALT lymphomas arise in the setting of mucosal
lymphoid activation, as a result of Helicobacter-associated
chronic gastritis.
 With H. pylori infection, there is an intense activation of T
and B cells in the mucosa. This leads to polyclonal B-cell
hyperplasia and eventually to the emergence of a
monoclonal B-cell neoplasm.
 About 50% of gastric lymphomas can regress with antibiotic
treatment for H. pylori.
 The prognosis is better than it is for denocarcinoma.
83

84. V. DISEASES OF THE SMALL INTESTINE
 Meckel diverticulum
 Peptic ulcer
 Bowel obstruction
 Malabsorption syndromes
 Crohn’s disease
 Tumors of the small intestine
84

85. ANATOMY AND HISTOLOGY
 The adult small intestine is approximately 6 m in length.
 The most distinctive feature of the small intestine is its mucosal
lining, which is designed to provide maximal surface area for the
purpose of food absorption. It is studded with innumerable villi.
 These extend into the lumen as finger-like projections covered by
epithelial lining cells.
 In normal individuals, the villus-to-crypt height ratio is about 4 : 1.
 Within the duodenum are abundant submucosal mucous glands,
termed Brunner's glands. These glands secrete bicarbonate ions,
glycoproteins, and pepsinogen II.
85

86. ANATOMY AND HISTOLOGY
 The surface epithelium of the small intestinal villi
contains three principal cell types.
 Columnar absorptive cells are recognized by the dense
array of microvilli on their luminal surface (the “brush
border”).
 Interspersed regularly between absorptive cells are
mucin-secreting goblet cells,
 Endocrine cells.
86

87. 87

88. A. MECKEL DIVERTICULUM
 is the most common congenital anomaly of the small intestine.
 occurs as a result of failed involution of the vitelline duct, which
connects the lumen of the developing gut to the yolk sac.
 is located in the ilium. It may contain ectopic gastric, or pancreatic
tissue.
“Rule of 2” is used to remember characteristics of Meckel diverticulae:
 Occur in approximately 2% of the population,
 Generally present within 2 feet (85 cm) of the ileocecal valve,
 Approximately 2 inches (5 cm) long,
 are twice as common in males as in females,
 and are most often symptomatic by age 2.
 The condition is usually asymptomatic but complications, including
peptic ulceration in ectopic gastric mucosa with bleeding or
perforation, may occur.
88

89. 89

90.  B. Peptic ulcer
 Occurrence is most frequent in the first portion of the duodenum, the
stomach, or the lower end of the esophagus, all of which are exposed
to acid and pepsin.
 Except for peptic ulcer of the stomach, peptic ulcer is always
associated with hypersecretion of gastric acid and pepsin.
 Ulceration is closely related to gastric H. pylori infection, which
affects essentially all patients with duodenal ulcer and the majority of
patients with gastric ulcer.
 H. pylori increases gastric acid secretion and apparently impairs both
gastric and duodenal mucosal defenses.
90

91.  Frequency of occurrence is increased in persons of blood group O,
suggesting that genetic factors may play a role.
 Peptic ulcer is not a precursor of malignancy.
 Complications often include
 hemorrhage with melena (black stools containing blood).
 Obstruction
 perforation.
91

92. PEPTIC ULCER IS SOMETIMES
ASSOCIATED WITH:
1. Intake of aspirin or other NSAIDs. The ulcerogenic effect of these
drugs may be mediated by inhibition of prostaglandin synthesis.
2. Smoking. The incidence of peptic ulcer is two-fold greater in smokers.
3. Zollinger-Ellison syndrome, increased tendency toward peptic ulcer
formation, which is caused by gastric acid hypersecretion due to
gastrin-secreting islet cell tumor of the pancreas. Recurrent peptic
ulcer or peptic ulcer in aberrant sites, such as the jejunum is
suggestive of the Zollinger-Ellison syndrome.
4. Primary hyperparathyroidism
5. Multiple endocrine neoplasia (MEN) type I (Wermer syndrome):
an autosomal dominant syndrome characterized by pituitary,
parathyroid, and pancreatic islet cell adenomas or hyperplasia.
Associated with hypergastrinemia and peptic ulcer
92

93. C.BOWEL OBSTRUCTION
 Although any part of the gut may be involved, because of its
narrow lumen, the small bowel is most commonly affected.
 Four entities -account for at least 80% of the cases:
 hernias,
 intestinal adhesions,
 intussusception,
 Volvulus
 Tumors and infarction account for only about 10% to 15% of
small bowel obstructions.
o The clinical manifestations of intestinal obstruction include
abdominal pain and distention, vomiting, and constipation.
o Surgical intervention is usually required in cases of mechanical
obstruction or severe infarction.
93

94. 1. Hernias, a weakness or defect in the wall of the peritoneal cavity,
may permit protrusion of a pouch like, serosa-lined sac of
peritoneum, called a hernial sac.
 The usual sites of weakness are anteriorly at the inguinal and
femoral canals, at the umbilicus, and in surgical scars.
 Hernias are of concern because segments of viscera frequently
intrude and become trapped in them.
 The most frequent intruders are small bowel loops, but portions of
omentum or large bowel also may become trapped.
94

95. 2. Surgical procedures, and infection often cause localized or
generalized peritoneal inflammation (peritonitis). With healing,
adhesions may develop between bowel segments or the abdominal
wall and the operative site. These fibrous bridges can create closed
loops through which the intestines may slide and become trapped
(internal herniation). The sequence of events is much the same as
with external hernias.
3. Intussusception (invagination of a proximal segment of bowel into
a more distal segment), causing bowel obstruction.
Intussusception occurs more often without preexisting bowel
pathology and is seen most often in infants and young children.
4. Volvulus (twisting of a portion of the gastrointestinal tract about
itself), often causing bowel obstruction
95

96. 96

97. D. MALABSORPTION SYNDROMES
 Malabsorption is characterized by defective absorption of fats, fat-
soluble and other vitamins, proteins, carbohydrates, electrolytes and
minerals, and water.
 The most common presentation is chronic diarrhea; the hallmark of
malabsorption syndromes is steatorrhea (excessive fat content of the
feces).
97

98. THE MAJOR MALABSORPTION
SYNDROMES
Defective Intraluminal Digestion
Digestion of fats and proteins
Pancreatic insufficiency, due to pancreatitis or cystic fibrosis
Zollinger-Ellison syndrome, with inactivation of pancreatic enzymes
by excess gastric acid secretion
Solubilization of fat, due to defective bile secretion
Ileal dysfunction or resection, with decreased bile salt uptake
Cessation of bile flow from obstruction, hepatic dysfunction
Nutrient preabsorption or modification by bacterial overgrowth
Distal ileal resection of bypass
Total or subtotal gastrectomy 98

99. Primary Mucosal Cell Abnormalities
Defective terminal digestion
Disaccharidase deficiency (lactose intolerance)
Bacterial overgrowth, with brush-border damage
Defective transepithelial transport
Abetalipoproteinemia
Reduced Small Intestinal Surface Area
Gluten-sensitive enteropathy (celiac disease)
Short-gut syndrome, after surgical resections
Crohn disease
99

100. Infections
Acute infectious enteritis
Parasitic infestation
Tropical sprue
Whipple disease
Lymphatic Obstruction
Lymphoma
Tuberculosis and tuberculous lymphadenitis
100

101. CELIAC DISEASE
 Celiac disease is caused by sensitivity to gluten in
cereal products
 Clinical manifestations include weight loss, weakness, and
diarrhea with pale, bulky, frothy, foul-smelling stools. It is
also characterized by growth retardation and general failure
to thrive.
 Disease most often becomes symptomatic in infancy when
cereals are first added to the diet.
 Diagnosis involves documentation of malabsorption, small
intestinal biopsy demonstrating blunting of small intestinal
villi, and clinical improvement and restoration of normal
intestinal morphology on a gluten-free diet.
101

102. Incidence increases in association with human
leukocyte antigens (HLAs) HLA-B8 and HLA-DW3.
 This finding and the presence of antibodies directed
against gliadin (a glycoprotein component of gluten)
and transglutaminase suggest that both genetic and
immune-mediated mechanisms may be involved.
These antibody tests may also be used for screening
prior to definitive diagnosis by biopsy.
Approximately 10%–15% of cases lead to small
intestinal malignancy, most often enteropathy-type
T-cell lymphoma.
102

103. THE HISTOPATHOLOGY IS CHARACTERIZED BY
INTRAEPITHELIAL LYMPHOCYTOSIS, CRYPT HYPERPLASIA,
VILLOUS ATROPHY, AND INCREASED NUMBERS OF PLASMA
CELLS, MAST CELLS, AND EOSINOPHILS, WITHIN THE UPPER
PART OF THE LAMINA PROPRIA.
103
Celiac disease Duodenum, normal

104. Disorder Morphologic Features Comments
Tropical sprue Histologic findings vary from no
changes to abnormalities similar
to those of celiac disease
Tropical disease of
probable infectious origin;
often responds to antibiotics
Whipple disease Distinctive PAS-positive
macrophages in intestinal
mucosa Tropheryma whippelii
bacilli visualized by electron
microscopy
May affect any organ, most
commonly the small
intestine; arthralgias and
cardiac and neurologic
symptoms are common
104

105. Disorder Morphologic Features Comments
Disaccharidase
deficiency
No characteristic histologic
changes
Deficiency of
disaccharidases sited in brush
border of mucosal cells of
small intestine; lactase
deficiency, which leads to
milk intolerance, is most
frequent
Abetalipoproteinemia No characteristic features in the
intestine; circulating
acanthocytes (red cells with
spiny projections) suggest the
diagnosis
β-lipoprotein deficiency is
caused by hereditary
deficiency of apoprotein β
105

106. D. CROHN’S DISEASE
 General considerations
 This chronic inflammatory condition of unknown etiology
may affect any part of the gastrointestinal tract but most
commonly involves the distal ileocecum, small intestine, or
colon.
 Crohn disease tends to affect young people in the second and
third decades of life, although no age group is exempt. It
occurs most frequently in people of Jewish descent.
 The disease can lead to carcinoma involving the small
intestine or colon. However, neoplastic transformation is
much less frequent in Crohn disease than in ulcerative colitis.
106

107. CROHN’S DISEASE
 Morphology
 Chronic inflammation involving all layers of the intestinal wall (transmural
involvement).
 Thickening of involved segments, with narrowing of lumen
 Linear ulceration of the mucosa.
 Submucosal edema with elevation of the surviving mucosa, producing a
cobblestone appearance
 Skip lesions (segments of normal intestine between affected regions).
 Discrete noncaseating granulomas (in about 50% of the cases).
 Submucosal fibrosis.
107

108. CROHN’S DISEASE
 Clinical manifestations
 Abdominal pain and diarrhea.
 Malabsorption.
 Fever.
 Intestinal obstruction resulting from fibrous stricture.
 Fistulas between loops of intestine and between the intestine, bladder,
vagina, and skin.
108

109. Crohn disease. Linear ulcerations and edema result in the
cobblestone appearance shown here.
109

110. E. TUMORS OF THE SMALL INTESTINE
 General considerations
Tumors of the small intestine make up a small percentage of
gastrointestinal neoplasms.
The most common malignant tumors are adenocarcinoma,
lymphoma, and carcinoid.
110

111. Adenocarcinoma
 These tumors grow in a napkin-ring encircling pattern or as
polypoid fungating masses, in a manner similar to colonic cancers.
 Most small bowel carcinomas arise in the duodenum (including the
ampulla of Vater).
 Cramping pain, nausea, vomiting, and weight loss are the common
presenting signs and symptoms, but such manifestations generally
appear late in the course of these cancers.
 By the time of diagnosis, most have already penetrated the bowel
wall, invaded the mesentery or other segments of the gut, spread to
regional nodes, and sometimes metastasized to the liver.
111

112. GASTROINTESTINAL LYMPHOMA
 Any segment of the gastrointestinal tract may be involved
secondarily by systemic dissemination of non-Hodgkin
lymphomas.
 However, up to 40% of lymphomas arise in sites other than lymph
nodes, and the gut is the most common extra-nodal location.
 1% to 4% of all gastrointestinal malignancies are lymphomas.
 By definition, primary gastrointestinal lymphomas reveal no evidence of liver,
spleen, or bone marrow involvement at the time of diagnosis; regional lymph
node involvement may be present.
 Intestinal tract lymphomas can be of B- or T-cell origin.
 The most common form in Western countries is MALT lymphoma.
This is a sporadic lymphoma that originates in B cells of the
mucosa-associated lymphoid tissue (MALT) of the gastrointestinal
tract.
112

113. GASTROINTESTINAL LYMPHOMA
 This type of gastrointestinal lymphoma usually affects adults, lacks
a sex predilection, and may arise anywhere in the gut:
 stomach (55% to 60% of cases),
 small intestine (25% to 30%),
 proximal colon (10% to 15%), and distal colon (≤10%).
 Celiac disease is associated with a higher than normal risk of
intestinal T-cell lymphomas.
113

114. CARCINOID TUMOR
 Cells generating peptide and nonpeptide hormones, are normally
dispersed along the length of the gastrointestinal tract mucosa and
have a major role in coordinated gut function.
 Endocrine cells are abundant in other organs, but most of the
tumors that develop from these cells arise in the gut.
 Tumors arising from these endocrine cells are called carcinoid
tumors; they may develop in the pancreas, lungs, and liver.
 The term carcinoid is an old reference to "carcinoma-like," which
has persisted through the decades. The peak incidence of these
neoplasms is in the sixth decade, but they may appear at any age.
 They compose less than 2% of colorectal malignancies but almost
half of small intestinal malignant tumors.
114

115. CARCINOID TUMOR
 Although all carcinoids are potentially malignant tumors, the
tendency for aggressive behavior correlates with the site of origin,
the depth of local penetration, and the size of the tumor.
 For example, appendiceal and rectal carcinoids infrequently
metastasize, even though they may show extensive local spread.
 By contrast, 90% of ileal, gastric, and colonic carcinoids have
spread to lymph nodes and distant sites at the time of diagnosis.
 As with normal gut endocrine cells, the cells of carcinoid tumors
can synthesize and secrete a variety of hormones.
 Although multiple hormones may be synthesized by a single
tumor, when a tumor secretes a predominant product to cause a
clinical syndrome, it may be called by that name (e.g., gastrinoma,
somatostatinoma, and insulinoma).
115

116. Carcinoid syndrome:
Caused by the elaboration of vasoactive peptides
and amines, especially serotonin
Manifest clinically by:
Cutaneous flushing
Watery diarrhea and abdominal cramps
Bronchospasm
Valvular lesions of the right side of the heart
116

117. 117

118. VI. DISEASES OF THE COLON
 A. Hirschsprung disease
 Diverticula
 Vascular diseases of the colon
 Inflammatory disorders of the colon
 Tumors
118

119. VI. DISEASES OF THE COLON
 A. Hirschsprung disease (congenital megacolon)
 is dilation of the colon due to the absence of ganglion cells of the
submucosal and myenteric neural plexuses; dilation is proximal to
the aganglionic segment.
 Acquired megacolon may result from
 Chagas disease, in which the trypanosomes directly invade the
bowel wall to destroy the neural plexuses.
 Organic obstruction of the bowel by a neoplasm or inflammatory
stricture.
 Toxic megacolon complicating ulcerative colitis or Crohn disease.
119

120. B. DIVERTICULA
 are pulsion (or false) diverticula (pockets of mucosa and
submucosa herniated through the muscular layer) that most
frequently involve the sigmoid colon.
 They are almost always multiple. Diverticula are most common in
older persons.
 Diverticulosis is defined by the presence of multiple diverticula
without inflammation.
Occurrence is most common in populations that consume low-
fiber diets.
The condition is most often asymptomatic or associated with
vague discomfort.
120

121.  Diverticulitis
 refers to inflammation of diverticula.
Older persons are affected.
Complications may include perforation, peritonitis,
abscess formation, or bowel stenosis. Bright red
rectal bleeding is frequent.
Presenting features may include lower abdominal pain
and tenderness, fever, leukocytosis, and other signs of
acute inflammation.
121

122. 122

123. C. VASCULAR DISEASES OF THE
COLON
1. Ischemic bowel disease
The cause is atherosclerotic occlusion of at least two
of the major mesenteric vessels.
Most often affected are the splenic flexure and the
rectosigmoid junction, which lie in the relatively
poorly vascularized regions (so-called watershed
areas) between areas supplied by the superior
mesenteric artery and the inferior mesenteric and
internal iliac arteries.
The result is mucosal, mural, or transmural infarction
involving the wall of the intestine.
123

124. 124

125. 2. Angiodysplasia is tortuous dilation of small vessels in
the intestinal mucosa or submucosa.
Lesions are multiple, most often involving the cecum
or ascending colon.
This condition is an extremely common cause of
otherwise unexplained lower bowel bleeding.
3. Hemorrhoids are dilated internal and external venous
plexuses in the anal canal. They are predisposed by a
low-fiber diet.
125

126. D. INFLAMMATORY DISORDERS OF THE
COLON
 Ulcerative colitis
General considerations
Ulcerative colitis is of unknown etiology.
It is often grouped along with Crohn disease as
inflammatory bowel disease.
Crohn disease and ulcerative colitis share a similar
geographic and racial distribution; some patients
have a family history of either ulcerative colitis or
Crohn disease.
126

127. extraintestinal manifestations:
Polyarthritis
Uveitis and episcleritis
Sclerosing cholangitis, a chronic fibrosing
inflammatory process of the biliary system
leading to chronic cholestasis and sometimes to
portal hypertension
Sacroiliitis
Skin manifestations, including erythema
nodosum and pyoderma gangrenosum
127

128. Morphology:
Mucosal inflammation and ulceration limited to the
large intestine; the rectum is always affected but the
entire colon may be involved.
 Inflammatory changes almost entirely confined to the
mucosa and submucosa; the most characteristic feature
is the crypt abscess, in which there are infiltrates of
neutrophils in the crypts of Lieberkühn.
128

129.  Red, granular appearance of the mucosa; ulceration may be
minimal or quite extensive, with only islands of surviving mucosa
remaining.
 Pseudopolyps, mucosal remnants of previous severe ulceration
 Chronic diarrhea associated with the passage of blood and
mucus; the most frequent clinical manifestation is bleeding.
 Complications
 Toxic megacolon, a medical emergency in which there is a marked
dilation of the colon
 Perforation of the colon
 Carcinoma of the colon
129

130. 130
Ulcerative colitis. In contrast to Crohn disease, which can involve any part of the
gastrointestinal tract, ulcerative colitis is limited to the colon.

131. ULCERATIVE COLITIS -CRYPT
ABSCESS
131

132. FEATURES THAT DIFFER BETWEEN CROHN
DISEASE AND ULCERATIVE COLITIS
Feature Crohn Disease Ulcerative Colitis
MACROSCOPIC
Bowel region Ileum ± colon Colon only
Distribution Skip lesions Diffuse
Stricture Yes Rare
Wall appearance Thick Thin
MICROSCOPIC
Inflammation Transmural Limited to mucosa
Pseudopolyps Moderate Marked
Ulcers Deep, knife-like Superficial, broad-based
Lymphoid reaction Marked Moderate 132

133. FEATURES THAT DIFFER BETWEEN
CROHN DISEASE AND ULCERATIVE
COLITIS
Feature Crohn Disease Ulcerative Colitis
Fibrosis Marked Mild to none
Serositis Marked Mild to none
Granulomas Yes ( 50%)∼ No
Fistulae/sinuses Yes No
CLINICAL
Perianal fistula Yes (in colonic disease) No
Fat/vitamin
malabsorption
Yes No
Malignant potential With colonic involvement Yes
Recurrence after surgery Common No
Toxic megacolon No Yes
133

134. PSEUDOMEMBRANOUS COLITIS
This condition is morphologically distinguished by superficial
grayish mucosal exudates consisting of necrotic, loosely
adherent mucosal debris (pseudomembrane).
The cause most often is overgrowth of exotoxin-producing
Clostridium difficile. Fibrinous necrosis of the superficial
mucosa is caused by the exotoxin, not by bacterial invasion.
Clinical characteristics include fever, toxicity, and diarrhea,
most often occurring in patients on broad-spectrum antibiotic
therapy.
134

135.  Amebic colitis
The cause is infection of the colon with Entamoeba
histolytica.
Flask-shaped ulcers are characteristic.
 Cholera
The cause is infection with Vibrio cholerae, a
noninvasive toxin-producing bacterium.
Characteristics include toxin-mediated loss of fluid
and electrolytes with mucosa of the small bowel and
colon remaining normal in appearance.
135

136. E. TUMORS
 Benign polyps
Terminology. A polyp is a descriptive term for any elevation of the
intestinal surface.
Pedunculated polyps are attached by a narrow stem.
Sessile polyps have a broad-based attachment.
136

137. Non-neoplastic polyps
1. Hyperplastic polyps can occur anywhere in the colon or
small intestine. They have no clinical significance but may
be mistaken for an adenomatous polyp.
2. Inflammatory polyps include benign lymphoid polyps and
inflammatory pseudopolyps consisting of granulation
tissue and remnants of mucosa, caused by chronic
inflammatory bowel disease.
3. Hamartomatous polyps
 Juvenile polyps occur in the small intestine and colon. They
most often occur in children but are also seen in adults.
137

138.  Peutz-Jeghers polyps
 occur as part of the Peutz-Jeghers syndrome, which
includes hamartomatous polyps of the colon and small
intestine and melanotic accumulations in the mouth and on
the lips, hands, and genitalia.
Peutz-Jeghers polyps have no malignant potential
themselves, but the syndrome is associated with increased
propensity for adenocarcinoma of the colon and malignancy
at other sites, such as the stomach, breast, or ovaries.
138

139. NEOPLASTIC POLYPS
 Adenomatous polyps are true neoplasms rather than benign
proliferations of tissue. They are usually asymptomatic but can
result in rectal bleeding.
1. Tubular adenomas
These are the most common type (75%) of adenomatous
polyp.
These polyps are usually small and pedunculated.
They can contain malignant foci; the likelihood of
malignancy is greater in larger polyps.
139

140. 140

141. 141

142. 2. Tubulovillous adenomas
These adenomas account for about 15% of adenomatous
polyps.
Tubulovillous adenomas resemble tubular adenomas but
have a surface covered by finger-like villi. They are similar
histologically to tubular adenomas.
They are intermediate in malignant potential between
tubular adenomas and villous adenomas.
142

143. 3. Villous adenomas
These polyps are much less common than tubular adenomas
and account for approximately 10% of adenomatous polyps.
Villous adenomas are usually larger than tubular adenomas,
usually sessile, and are characterized by large numbers of
finger-like villi.
They have the highest potential for malignancy of all of
the adenomatous polyps; they become malignant in more
than 30% of cases.
143

144. 144

145. 145

146. WHAT VARIABLES DETERMINE THE
LIKELIHOOD OF MALIGNANT CHANGE IN A
POLYP?
 Three interrelated features are determinants of the risk of
cancerous transformation: polyp size, histologic architecture, and
severity of dysplasia.
1) Cancer is rare in tubular adenomas less than 1 cm in diameter.
2) The likelihood of cancer is high (about 50%) in sessile villous
adenomas that are greater than 4 cm in diameter.
3) Severe dysplasia is likely to progress to cancer. Such dysplasias
are found in villous areas.
Of all these, size is the most important factor.
146

147. MULTIPLE POLYPOSIS SYNDROMES
 are associated with a greatly increased risk of malignant
transformation.
1. Familial polyposis is an autosomal dominant condition
characterized by the presence of numerous adenomatous
polyps. The risk of malignant transformation approaches
100%.
2. Gardner syndrome is an autosomal dominant condition
characterized by the presence of numerous adenomatous
polyps along with osteomas and soft tissue tumors.
3. Turcot syndrome is characterized by adenomatous polyps
along with tumors of the central nervous system.
147

148. MULTIPLE POLYPOSIS. THE POLYPS ARE BENIGN, BUT
EACH OF THE INNUMERABLE POLYPS HAS ABOUT A
1% POTENTIAL FOR MALIGNANT CHANGE.
148

149. Type Comments
Non-neoplastic polyps
Hyperplastic polyp No clinical significance
Inflammatory polyps:
Lymphoid polyp Most common site is the rectal mucosa; may be a reaction to
local irritation
Inflammatory
pseudopolyp
Associated with ulcerative colitis and other inflammatory
diseases of the colon; consists of granulation tissue and residual
and regenerating mucosa
Hamartomatous polyps:
Juvenile polyp Occurs most frequently in children
Peutz-Jeghers polyp Associated with Peutz-Jeghers syndrome
149

150. Neoplastic polyps
Tubular adenoma Benign but may undergo malignant change; often
multiple; hereditary multiple polyposis syndromes
associated with greatly increased risk of malignancy
Tubulovillous adenoma Morphologically resembles tubular adenoma with
additional features similar to those of villous
adenoma; greater malignant potential than tubular
adenoma
Villous adenoma Large sessile tumor with velvety surface comprised
of finger-like villi; high potential for malignant
change
150

151. ADENOCARCINOMA OF THE COLON AND
RECTUM
General considerations
Adenocarcinoma of the colon and rectum is one of the most
common neoplasms in the Western world.
The peak age incidence is in the sixth to seventh decades.
This form of cancer is associated with increased serum
concentration of carcinoembryonic antigen (CEA).
Because elevated CEA is not specific for colon cancer, this
laboratory determination is most useful for following the
course of the disease rather than for making the initial
diagnosis.
151

152. The cancer develops through a set of anatomic
changes progressing from normal mucosa to
adenomatous polyp to carcinoma to metastatic
tumor, with a parallel set of molecular
changes in oncogenes and tumor suppressor
genes that have been presented as a
model of tumor progression.
152

153. 153

154. Predisposing factors
1. Adenomatous polyps
2. Inherited multiple polyposis syndromes
3. Long-standing ulcerative colitis
4. Genetic factors; up to a four-fold increase in incidence is
noted among relatives of patients with colon cancer.
5. A low-fiber diet that is high in animal fat; the disease is
less common in much of the Third World, where populations
consume a high-fiber diet that is low in animal fat.
154

155. Characteristics
Adenocarcinoma varies in gross presentation
according to the region of the colon involved.
Carcinoma of the rectosigmoid colon tends to
present in an annular manner, producing early
obstruction.
Carcinoma of the right colon usually does not
obstruct early and often presents (sometimes quite
late) with iron deficiency anemia secondary to
chronic blood loss.
155

156. ADENOCARCINOMA OF THE COLON.
156

157. INVASIVE ADENOCARCINOMA OF COLON
SHOWING MALIGNANT GLANDS INFILTRATING
THE MUSCLE WALL.
157

158. Tumor Stage Histologic Features of the Neoplasm
Tis Carcinoma in situ (high-grade dysplasia) or intramucosal
carcinoma (lamina propria invasion)
T1 Tumor invades submucosa
T2 Extending into the muscularis propria but not
penetrating through it
T3 Penetrating through the muscularis propria into
subserosa
T4 Tumor directly invades other organs or structures
Nx Regional lymph nodes cannot be assessed
N0 No regional lymph node metastasis
N1 Metastasis in 1 to 3 lymph nodes
N2 Metastasis in 4 or more lymph nodes
Mx Distant metastasis cannot be assessed
M0 No distant metastasis
M1 Distant metastasis
158

159. VII. DISEASES OF THE APPENDIX
 A. Acute appendicitis
 Occurrence is most frequent in the second and third
decades of life.
 The disease is thought to be caused by obstruction of the
appendiceal lumen, most often by a fecolith, resulting in
bacterial proliferation and invasion of the mucosa.
 Gross changes include a congested appendix with a
swollen distal half covered by purulent exudate; the
lumen also contains a purulent exudate and often a
fecalith.
159

160.  Histologic characteristics include an acute inflammatory
infiltrate extending from the mucosa through the full
thickness of the appendiceal wall.
 Presenting features include anorexia, nausea, and
abdominal pain, most commonly localized to the right
lower quadrant, and systemic signs of acute
inflammation, such as fever.
 If untreated by surgical resection, appendicitis most
often leads to perforation or abscess, or both.
160

161. B. TUMORS OF THE APPENDIX.
 The most common tumor of the appendix is the carcinoid.
 It is usually discovered incidentally at the time of surgery or
examination of a resected appendix.
 This neoplasm most frequently involves the distal tip of the
appendix, where it produces a solid bulbous swelling up to 2 to 3
cm in diameter.
 Although intramural and transmural extension may be evident,
nodal metastases are very infrequent, and distant spread is
exceptionally rare.
161

162.  Mucocele, a dilated appendix filled with mucin, may simply
represent an obstructed appendix containing inspissated mucin or
be a consequence of mucinous cystadenoma or mucinous
cystadenocarcinoma.
 In the latter instance, invasion through the appendiceal wall can
lead to intraperitoneal seeding and spread.
 In women the resulting peritoneal implants may be mistaken for
mucinous ovarian tumors.
 In the most advanced cases the abdomen fills with tenacious,
semisolid mucin, a condition called pseudomyxoma peritoneii.
162

163.  A 47-year-old man has a history of drinking 1 to 2 liters of
alcohol per day for the past 20 years. He has had numerous
episodes of nausea and vomiting in the past 5 years. He
experiences a bout of prolonged vomiting, followed by
massive hematemesis. Which of the following is the most
likely diagnosis?
1. Barrett’s esophagus
2. Esophageal stricture
3. Esophageal lacerations (Mallory Weiss syndrome)
4. Esophageal squamous cell carcinoma
5. Achalasia
163

164.  All these statements about Barrett’s esophagus are
true, except:
1. It is associated with 30- to 40-fold greater risk to
develop adenocarcinoma
2. It appears as salmon-pink mucosa on endoscopy
3. It is associated with high risk for esophageal
bleeding
4. It represents replacement of the stratified squamous
epithelium by columnar epithelium with goblet
cells
5. It could be a complication of long-standing reflux
esophagitis
164

165.  All these statement about Helicobacter pylori are correct
except:
1. H. pylori organisms are Gram negative bacilli
2. It is associated with intestinal-type gastric
adenocarcinoma
3. It is associated with gastric lymphoma
4. It is associated with diffuse-type gastric adenocarcinoma
5. It is associated with peptic ulcer
165

166.  A 20-year-old man has noted cramping abdominal
pain for the past week associated with fever and
low-volume diarrhea. On physical examination,
there is right lower quadrant tenderness. Bowel
sounds are present. His stool is positive for occult
blood. A colonoscopy reveals mucosal edema and
ulceration in the ascending colon, but the transverse
and descending portions of the colon are not
affected. Which of the following microscopic
findings is most likely to be present in biopsies from
his colon
1. Entamoeba histolytica organisms
2. Adenocarcinoma
3. Non-caseating granulomas
4. Diverticulosis
166

167.  A 35-year-old woman has a 10 year history of
intermittent, bloody diarrhea. She has no other major
medical problems. On physical examination there are
no lesions palpable on digital rectal examination, but a
stool sample is positive for occult blood. Colonoscopy
reveals a friable, erythematous mucosa with focal
ulceration that extends from the rectum to the mid-
transverse colon. Biopsies are taken and all reveal
mucosal acute and chronic inflammation with crypt
distortion, occasional crypt abscesses, and superficial
mucosal ulceration. This patient is at risk for
development of which of the following conditions?
1. Diverticulitis
2. Acute pancreatitis
3. Colonic adenocarcinoma
4. Peri-rectal fistula
5. Appendicitis
167

168.  A 25-year-old man complains of a low volume but
chronic, foul smelling diarrhea for the past year. He
has no nausea or vomiting. On physical examination
there is no abdominal pain or masses and bowel
sounds are present. His stool is negative for occult
blood. Laboratory studies include a quantitative stool
fat of 10 g/day. Upper GI endoscopy is performed
with biopsies of the duodenum. The biopsies reveal
the absence of villi, and increased surface
intraepithelial lymphocytes. Which of the following
therapies is most likely to be useful for this man?
1. Antibiotics
2. Anti-Entamoeba therapy
3. Corticosteroids
4. Gluten-free diet
5. Surgical resection 168

169. REFERENCES
 ROBBINS AND COTRAN PATHOLOGIC BASIS
OF DISEASE, 8/E, 2010.
 Robbins basic pathology 8ed 2007
 OUTLINES IN PATHOLOGY
By John H. Sinard, MD, PhD, May 2006
169