PATHOLOGY CASE 1

PATHOLOGY CASE 1

INTRODUCTION

A 42-year-old policeman has been seen by his family physician for "heartburn" of 5 years' duration. He has been intermittently taking ranitidine, a histamine-2 blocking agent, with some relief. An upper endoscopic examination that was performed recently revealed some reddish discoloration and friability of the lower esophageal region. A biopsy of the lower esophagus was performed, and the microscopic examination revealed columnar cells containing goblet cells.

· What is the most likely diagnosis?

· What is a long-term complication of this process?

· What is the most likely mechanism of this process?

ANSWERS TO CASE 1: Barrett Esophagus

Summary: A 42-year-old man has a 5-year history of heartburn unrelieved by a histamine-2 blocking agent. Upper endoscopy reveals reddish discoloration of the distal esophagus, which on biopsy shows columnar epithelium with goblet cells.

· Most likely diagnosis: Barrett esophagus.

· Long-term complication of this process: Adenocarcinoma of the esophagus.

· Most likely mechanism: Repeated acid reflux to the distal esophagus leading to metaplasia of the normal squamous epithelium into columnar epithelium.

CLINICAL CORRELATION

Introduction

The normal esophagus is lined by nonkeratinized squamous epithelium. The lower esophageal sphincter (LES) prevents reflux of gastric acid from entering the distal esophagus. With gastroesophageal reflux disease (GERD), decreased lower esophageal sphincter tone can lead to acid exposure of the distal esophagus. Through a poorly understood mechanism, the lower esophagus changes (metaplasia) from squamous to columnar epithelium, so-called Barrett esophagus. In fact, the presence of goblet cells in the columnar epithelium is a hallmark of the disease. Barrett esophagus appears reddish and friable on endoscopy and carries an increased risk for developing into adenocarcinoma.

Approach to Esophageal Pathology

Definitions

Esophageal diverticulum: Outpouching of one or more layers of the esophageal wall. When it occurs near the upper esophageal sphincter, it is called a Zenker diverticulum.

Achalasia: Condition of esophageal dilation resulting from lack of esophageal peristalsis and constant contraction of the lower esophageal sphincter associated with a loss of myenteric plexus ganglions. Affected patients complain of dysphagia (difficulty swallowing).

Gastroesophageal reflux: Condition in which gastric acid enters the distal esophagus, usually associated with decreased lower esophageal sphincter pressure. Affected patients often complain of "heartburn" that is relieved by antacids. Long-term complications of GERD include Barrett esophagus, stricture, and ulceration.

Barrett esophagus: Columnar metaplasia of the lower esophageal epithelium, predisposing to esophageal adenocarcinoma.

Esophagitis: Inflammation of the esophagus caused by GERD, infection (Candida, herpes simplex virus, cytomegalovirus), radiation, or uremia.

Hiatal hernia: Gastroesophageal defect in which a part of the stomach protrudes above the diaphragm, usually adjacent to the distal esophagus; may be associated with GERD.

Esophageal carcinoma: Worldwide, squamous cell carcinoma is the most common cell type, but in Western countries, it is divided equally in frequency between adenocarcinoma and squamous cell carcinoma. Patients typically complain of dysphagia, weight loss, and fatigue.

Discussion

Normal Esophagus

The esophagus is a muscular tube that connects the pharynx to the stomach that is lined by squamous epithelium. It has a well-developed submucosa, and the upper third is enveloped by striated muscle, whereas the lower two-thirds is encompassed by smooth muscle. The upper esophageal sphincter is located at approximately the level of the fifth cervical vertebra (C5) level, whereas the lower esophageal sphincter is located below the diaphragm and functions to prevent regurgitation of gastric acid. During the swallowing process peristalsis is initiated in the striated muscle and continues down through the smooth muscle with a coordinated temporary relaxation of the LES. Both sympathetic and parasympathetic nerve fibers innervate the intrinsic myenteric plexus, which is distributed in the striated and smooth muscle.

Congenital Anomalies

Tracheoesophageal (TE) fistulae are congenital disorders that manifest in affected newborns as hypersalivation and difficulty feeding with choking. The most common type (90 percent) involves distal esophageal atresia with a connection to the trachea. Maternal polyhydramnios may be noted in utero, resulting from the fetal inability to swallow amniotic fluid. Less common varieties of TE fistulae may involve a fistula and patent esophagus (so-called H type) or a higher location of the fistula. Recognition and surgical repair are critical.

Achalasia

Achalasia is characterized by progressive dilation of the distal esophagus caused by disturbance of the normal peristaltic process. This nearly always involves a loss of myenteric ganglion cells, although the underlying etiology is unclear. Patients typically have increased LES pressure and complain of progressive dysphagia and vomiting of partially digested or undigested food. The diagnosis is established by endoscopy or upper gastrointestinal barium swallow imaging (so-called bird's beak finding).

GERD and Barrett Esophagus

Esophagitis, or inflammation of the esophagus, has multiple etiologies and often is associated with chest pain, dysphagia, and painful swallowing. By far, the most common cause of esophagitis is gastroesophageal reflux, which may be associated with a hiatal hernia. With chronic acid exposure, the distal esophagus may become hyperemic and ulcerated and develop scars or strictures. Persistent GERD may lead to a benign epithelial change (metaplasia) of the distal esophagus; the normal squamous cell epithelium becomes columnar with the presence of intestinal goblet cells, so-called Barrett esophagus. Barrett esophagus appears reddish and friable on endoscopy and is diagnosed by biopsy; endoscopic surveillance is important because of the increased risk for developing adenocarcinoma.

Esophageal Carcinoma

Esophageal cancers account for about 10 percent of all gastrointestinal cancers in the United States and are largely asymptomatic. Familial influences are not as important as environmental exposures. Chronic alcohol and tobacco exposures significantly increase the risk of esophageal cancer. Other factors may include ingestion of nitrosamine-containing foods, chronic hot and spicy foods, and lye with stricture formation. The most common cell type worldwide is squamous cell carcinoma, usually affecting the upper and middle thirds of the esophagus. In the United States, as a result of decreased tobacco use and an increased prevalence of GERD, adenocarcinoma of the distal esophagus is encountered commonly. Periodic endoscopic surveillance with biopsy for patients with chronic GERD may identify the cancer at an early stage. Regardless of cell type, affected patients generally have few symptoms until late in the course, with those symptoms being progressive dysphagia, weight loss, and fatigue. Because the cancers are usually very large at diagnosis, surgical resection is difficult, and up to 80 percent of affected individuals die within 1 year of diagnosis.

COMPREHENSION QUESTIONS

[1.1] A 55-year-old salesman is noted to have a cancer of the lower third of the esophagus. He is a nonsmoker and occasionally drinks alcohol. Which of the following is the most likely cell type?

A. Adenocarcinoma

B. Melanoma

C. Metastatic cancer

D. Sarcoma

E. Squamous cell carcinoma

[1.2] An 18-year-old man presents with difficulty swallowing over the last 3 days. He denies ingestion of unusual substances and complains of pain even when swallowing liquids. He is an intravenous (IV) drug user and has been taking several medications to "help his immunity." Which of the following is the most likely finding on esophageal endoscopy?

A. Brown blotches scattered throughout the esophagus

B. Normal-appearing esophagus

C. Red patches in the distal esophagus

D. Reddish streaks throughout the pharynx and upper esophagus

E. White patches adherent to the esophagus

[1.3] A newborn male is noted to have difficulty feeding and "turns blue and chokes when drinking formula." The prenatal records reveal that the amniotic fluid appeared normal on ultrasound. A pediatric feeding tube is passed orally to 20 cm without difficulty, with gastric secretions aspirated. Which of the following is the most likely diagnosis?

A. Congenital heart disease

B. Floppy epiglottis

C. Respiratory distress syndrome

D. Tracheoesophageal fistula

E. Zenker diverticulum

ANSWERS

[1.1] A. Adenocarcinoma is the most common malignancy of the lower third of the esophagus and is strongly associated with Barrett esophagus. Squamous cell carcinoma is the most common type of cancer of the esophagus worldwide and usually affects the upper or middle region of the esophagus.

[1.2] E. This patient probably has HIV, and the clinical syndrome of painful and difficult swallowing is consistent with Candida esophagitis. Endoscopy probably would reveal white plaques adherent to the esophagus. Other causes of esophagitis include herpes simplex infection, cytomegalovirus (CMV) infection, and chemical-induced conditions such as those resulting from lye (suicide attempt).

[1.3] D. The vast majority newborns with TE fistulae involve a nonpatent esophagus that is diagnosed by the inability to pass a feeding tube. However, the baby in this case most likely has an unusual type of TE fistula (H type) in which the esophagus is patent but there is a connection between the esophagus and the trachea. When the baby feeds, the formula is aspirated into the tracheobronchial tree, leading to choking and cyanosis. This condition may be diagnosed with a radiologic contrast study and requires surgical correction.

PATHOLOGY PEARLS

· The normal esophagus is lined with nonkeratinized squamous epithelium.

· Gastric acid reflux into the distal esophagus may cause esophagitis, and a patient with gastroesophageal reflux disease typically complains of heartburn.

· GERD usually is treated with histamine-2 blocking agents or proton pump inhibitors, which decrease the gastric acid production.

· Long-standing GERD may lead to columnar metaplasia of the lower esophageal epithelium, so-called Barrett esophagus, which has a propensity for developing into adenocarcinoma.

· Worldwide, the most common type of esophageal cancer is squamous cell carcinoma, whereas in Western countries, adenocarcinoma is increasing in incidence because of the prevalence of GERD and Barrett esophagus.

REFERENCES

Liu C, Crawford JM. The gastrointestinal tract. In: Kumar V, Assas AK, Fausto N, eds. Robbins and Cotran pathologic basis of disease, 7th ed. Philadelphia: Elsevier Saunders, 2005:804-809.

Rubin E. Essential pathology, 3rd ed. Philadelphia: Lippincott Williams & Wilkins, 2001.

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