Git pathology m scyear2011 12

GASTROINTESTINAL TRACT

Dr. Jalal A. Jalal

Dept. of Pathology

College of Medicine-HMU

Oral cavity Salivary glands Esophagus Stomach Small bowel Large bowel Appendix

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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

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.

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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.

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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.

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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.

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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

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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

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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.

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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

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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.

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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.

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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.

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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.

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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

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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

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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

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III. DISEASES OF THE ESOPHAGUS

Tracheoesophageal fistula. Esophageal diverticula Achalasia Hiatal Hernia Esophageal varices Inflammatory and related disorders of the esophagus EsophagusTumors

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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.

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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

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HISTOLOGY

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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.

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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.

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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

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.

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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.

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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

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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,

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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.

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REFLUX/GERD• Morphology:

• Inflammatory Cells– Eosinophils– Neutrophils– Lymphocytes

• Basal zone hyperplasia

• Lamina Propria papillae elongated and congested

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REFLUX/GERD

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GASTROESOPHAGEAL REFLUX

What are the major complications of reflux esophagitis?

(a) ulcer;

(b) bleeding;

(c) development of stricture;

(d) development of Barrett esophagus.

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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.

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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

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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

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%.

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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)

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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

ESOPHAGUS SQUAMOUS CELL CARCINOMA

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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%

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ESOPHAGUSMALIGNANT 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

IV. DISEASES OF THE STOMACH

Congenital pyloric stenosis Gastritis: Acute, Chronic Peptic ulcer of the stomach Tumors of the stomach

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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.

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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

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B. GASTRITIS

Acute (erosive) gastritis Causes

Nonsteroidal anti-inflammatory drugs (NSAIDs)Cigarette smokingHeavy alcohol intakeBurn injury; Curling ulcer, an acute gastric ulcer in

association with severe burnsBrain injury; Cushing ulcer, an acute gastric ulcer

in association with brain injury

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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

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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.

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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.

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H. PYLORI GASTRITIS - SILVER STAIN

Bacteria over epithelial cells

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H. pylori–Associated AutoimmuneLocation 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

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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.

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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

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BENIGN, CHRONIC, GASTRIC PEPTIC ULCER

Sharp edges, converging folds of mucosa in the upper half. The ulcer bed is covered by fibrinopurulent exudate.

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ESOPHAGEAL LACERATIONS (MALLORY- WEISS SYNDROME)

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oLongitudinal tears at the gastroesophageal junctionoClinical setting: chronic alcoholics after a bout of severe vomitingoTear may be superficial or deep affecting all layersoClinical picture: Pain, bleeding, superimposed infectionoHiatal hernia is found in 75% of patientsMost 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

D. BENIGN TUMORS- GASTRIC POLYPS

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•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.

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.

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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.

AchlorhydriaChronic gastritis with or without pernicious anemia

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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.

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

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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.

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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."

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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.

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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.

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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.

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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.

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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.

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

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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

V. DISEASES OF THE SMALL INTESTINE

Meckel diverticulum Peptic ulcer Bowel obstruction Malabsorption syndromes Crohn’s disease Tumors of the small intestine

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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.

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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.

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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.

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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.

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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.

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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

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.

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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.

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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

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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).

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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

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 disease99

Infections

Acute infectious enteritis

Parasitic infestation

Tropical sprue

Whipple disease

Lymphatic Obstruction

Lymphoma

Tuberculosis and tuberculous lymphadenitis

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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.

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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.

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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.

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Celiac disease Duodenum, normal

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

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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

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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.

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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.

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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.

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

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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.

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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.

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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.

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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.

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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.

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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).

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Carcinoid syndrome:

Caused by the elaboration of vasoactive peptides and amines, especially serotonin

Manifest clinically by:Cutaneous flushingWatery diarrhea and abdominal crampsBronchospasm Valvular lesions of the right side of the heart

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VI. DISEASES OF THE COLON

A. Hirschsprung disease Diverticula Vascular diseases of the colon Inflammatory disorders of the colon Tumors

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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.

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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

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.

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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.

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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.

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D. INFLAMMATORY DISORDERS OF THE COLON

Ulcerative colitisGeneral 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.

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extraintestinal manifestations:PolyarthritisUveitis and episcleritisSclerosing cholangitis, a chronic fibrosing

inflammatory process of the biliary system leading to chronic cholestasis and sometimes to portal hypertension

SacroiliitisSkin manifestations, including erythema

nodosum and pyoderma gangrenosum

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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.

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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

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

ULCERATIVE COLITIS -CRYPT ABSCESS

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FEATURES THAT DIFFER BETWEEN CROHN DISEASE AND ULCERATIVE COLITIS

Feature Crohn Disease Ulcerative ColitisMACROSCOPIC

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

FEATURES THAT DIFFER BETWEEN CROHN DISEASE AND ULCERATIVE COLITIS

Feature Crohn Disease Ulcerative ColitisFibrosis 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 Yes133

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.

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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.

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E. TUMORS

Benign polypsTerminology. 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.

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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.

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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.

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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.

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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.

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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.

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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.

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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.

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

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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

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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

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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.

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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.

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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.

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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.

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ADENOCARCINOMA OF THE COLON.

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

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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

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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.

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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.

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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.

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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.

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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 esophagus2. Esophageal stricture3. Esophageal lacerations (Mallory Weiss syndrome)4. Esophageal squamous cell carcinoma5. Achalasia

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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

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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

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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 organisms2. Adenocarcinoma3. Non-caseating granulomas4. Diverticulosis

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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. Diverticulitis2. Acute pancreatitis3. Colonic adenocarcinoma4. Peri-rectal fistula5. Appendicitis

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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. Antibiotics2. Anti-Entamoeba therapy3. Corticosteroids4. Gluten-free diet5. Surgical resection 168

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

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