Esophagus

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Embryology of esophagus

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· notocord induces formation of foregut from endoderm

· at day 21 (end of week 3), lateral walls of foregut develop septa that fuse and divide foregut into esophagus and trachea

· at week 4, myenteric plexus develops

· at weeks 5-6, septation of walls ends; initial lining is stratified columnar epithelium, which proliferations and almost occludes the lumen

· at weeks 6-7, submucosal plexus develops, circular muscular layer develops

· at weeks 6-7, epithelial vacuolization appears, vacuoles coalesce to form a single esophageal lumen

· at week 8, ciliated cells appear and extend to almost entire columnar epithelium

· at week 9, longitudinal muscle layer develops; interstitial cells of Cajal appear

· at week 10, a single layer of columnar cells covers entire esophagus

· at month 4, submucosal glands appear due to downward growth of columnar cells, extend distally to cardiac mucosa

· at month 5, stratified squamous epithelium initially appears in mid esophagus, and replaces ciliated epithelium cephalad and caudally; proximal esophagus may retain ciliated epithelium at birth

· at month 5, upper esophagus has both striated and smooth muscle

Drawings: 4 weeks-relation of gut to yolk sac

References: GI Motility online

Normal anatomy of esophagus

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Also called gullet

Muscular tubular structure 25 cm long in adults; connects pharynx and stomach; has cervical, thoracic and abdominal segments

Main purpose is to propel food from pharynx to stomach via peristalsis; secretes mucin for lubrication, but has no other significant secretory or absorptive functions

Extends from cricopharyngeus muscle in pharynx (level of C6) to lower esophageal sphinchter at gastroesophageal junction (T11/T12); diagram

Regions:

· cervical (lower border of cricoid cartilage to suprasternal notch / thoracic inlet, 3 cm long, begins 15 cm from incisors); contains striated muscle

· upper thoracic (suprasternal notch to tracheal bifurcation, 6 cm long, begins 18 cm from incisors); has striated and smooth muscle

· mid-thoracic (tracheal bifurcation to diaphragmatic hiatus, 8 cm long, begins 24 cm from incisors); has striated and smooth muscle

· lower thoracic and abdominal (8 cm long [AJCC says 3 cm-this appears to be an error], begins 32 cm from incisors); extends past diaphragm to its junction with stomach; has smooth muscle only

Usual points of narrowing (possible sites of food / pill lodging): cricoid cartilage (due to cricopharyngeus muscle), aortic arch, anterior crossing of left main bronchus and left atrium, where it passes through diaphragm

Gastroesophageal junction: traditionally defined as macroscopic point of flaring of tubular esophagus or proximal limit of gastric rugal folds (diagram; gross image); endoscopic definition is Z (“zigzag”) line at irregular boundary of squamous and columnar mucosa in distal esophagus, which is usually 2-3 cm proximal to macroscopic GE junction (Z line; micro image); proposed definition is proximal limit of gastric oxyntic (fundic) mucosa (micro image), defined by histology (Hum Path 2006;37:40)

The distal 1-2 cm of esophagus is often composed of cardiac or cardiac-oxyntic type of mucosa; whether this is normal or due to reflux esophagitis is debatable

Esophageal sphincters: two areas of high pressure at rest; upper esophageal sphincter at cricopharyngeus (diagram) and inferior pharyngeal constrictor muscles and lower esophageal sphincter at 2-4 cm proximal to esophagogastric junction at level of diaphragm (composed of intrinsic esophageal muscles, sling fibers of proximal stomach and crural diaphragm, diagram)

Vagotomy does NOT affect tone of lower esophageal sphincter; tone is affected by gastrin, acetylcholine, serotonin

Arterial blood supply: cervical region-inferior thyroid artery; upper thoracic-bronchial and intercostal arteries; lower thoracic-aortic branches; abdominal-left gastric and inferior phrenic arteries; infarction is rare due to numerous anastomoses; diagram

Venous drainage: extensive submucosal venous plexus communicates with periesophageal veins; flows into inferior thyroid (upper 1/3), azygous (middle 1/3) and gastric veins (lower 1/3);

azygous vein empties into superior vena cava and gastric veins into portal system; this connection between caval and portal venous systems explains esophageal varices due to portal hypertension; diagram

Normal anatomy of esophagus (continued)

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Nerves: left and right vagus nerves run lateral to esophagus, form plexi along anterior and posterior surfaces, then reunite to form anterior and posterior vagal trunks to stomach; parasympathetic and sympathetic innervation

Lymphatic drainage: freely anastomosing networks in submucosa, muscularis propria and occasionally lamina propria; facilitate lengthwise tumor dissemination; upper third drains into paratracheal and internal jugular nodes, middle third to mediastinal nodes, lower third to nodes around aorta and celiac axis; diagram

Adjacent structures: cervical esophagus lies in posterior mediastinum, posterior to trachea and thyroid gland; is bounded by left and right recurrent laryngeal nerves and carotid sheaths; distal esophagus is posterior to left atrium and bounded by azygous veins; passes through opening in diaphragm called the hiatus; diagram

Incisura / angle of His: left side of esophagus forms sharp angle where it joins the stomach

Gross images: transverse section at level of aortic arch

Normal histology of esophagus

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Layers (similar to GI tract): mucosa, submucosa, muscularis propria, adventitia

Mucosa: epithelium, lamina propria and muscularis mucosae

epithelium: nonkeratinized stratified squamous epithelium with melanocytes, endocrine cells, Langerhans cells, Merkel cells, T cells with convoluted nuclei (“squiggle cells”); basal zone has basophilic proliferative cells with minimal cytoplasm, usually 3-4 cells thick, 15% or less of epithelial thickness except distally; suprabasal zone (with prickle and functional [anucleated] cell layers) has glycogen-rich squamous cells that flatten and mature as they approach lumen / surface

lamina propria: fibrovascular connective tissue between epithelium and muscularis mucosae; folds into slender papillae that project into epithelium, usually less than 2/3 of epithelial thickness; may contain gastric cardia-like mucus glands lined by foveolar-like cells with neutral mucin (PASD positive, Alcian Blue at pH 2.5 negative), particularly in distal esophagus, and scattered inflammatory cells

muscularis mucosae: smooth muscle bundles oriented longitudinally; begins at cricoid cartilage and becomes thickened distally, where it may resemble muscularis propria (important to remember for accurate AJCC staging of adenocarcinoma in this region)

Submucosa: loose connective tissue with vessels, lymphatics, occasional white blood cells and lymphoid follicles, Meissner’s plexus (sparse ganglia) and nerves, submucosal glands lined by mucinous cells that produce acid mucin (continuation of minor salivary glands of oropharynx) that drain through cuboidal or squamous lined ducts; glands are PASD+, Alcian Blue+ at pH 2.5 (indicates acidic mucin) and also produce bicarbonate; ducts are positive for CK7, CK8/18, CK14, CK19

Muscularis propria: inner circular and outer longitudinal layers; proximally includes skeletal muscle from cricopharyngeus and inferior pharyngeal constrictor muscles (thus, skeletal muscle disorders cause esophageal dysfunction); contains Auerbach (myenteric) plexus

Note: longitudinal muscle originates as two bands from cricoid cartilage that incompletely digitate and leave bare a V shaped region (area of Laimer) that exposes the underlying circular muscle and creates area of weakness where Zenker’s diverticulum (a pharyngeal diverticulum due to outpouching of posterior pharyngeal wall, just above upper esophageal sphincter) may occur;

longitudinal muscle distally is continuous with longitudinal muscle of stomach; esophageal circular muscle continues as middle circular and inner oblique muscles of stomach

Adventitia: loose connective tissue; no consistent serosa, so tumors and infections spread readily; majority of esophagus is surrounded by fascia

Drawing: various layers

Normal histology of esophagus (continued)

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Micro images: transverse section #1; #2; #3; #4; full thickness #1; #2; #3; #4; #5; #6; #7-esophageal fold (trichrome); #8-upper third

squamous epithelium - #1-thin basal zone, prickle cell zone has glycogen rich-flattened cells which occupy most of epithelium, functional zone consists of a few flattened cells on surface without nuclei #2; #3; #4; #5-with intraepithelial lymphocytes (normal finding); #6-with lymphocytes and squiggle cell (center)

mucosa and submucosa - mucosa and submucosa; muscularis mucosae-thin layer; muscularis mucosae-thick layer; submucosal glands and ducts #1; #2; #3 (just above GE junction); #4-Alcian blue; submucous gland with squamous metaplasia

muscularis propria - smooth muscle-middle third

Virtual slides: normal esophagus #1; #2

Biopsy of esophagus

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For tumors, 5-6 biopsies recommended, including edge of ulcers, base of ulcer, other non-necrotic areas

Cytology samples may pick up additional cancers missed by biopsies

Limit a cassette to 3-4 biopsy fragments so they will be properly embedded

Recommend embedding on edge and cutting perpendicular to mucosa, although difficult to do with small biopsies

Immediate fixation is particularly important for lymphoid lesions

Common stains are Alcian Blue pH 2.5 (detects acidic mucin), mucicarmine (detects acidic mucin), PAS with and without diastase (detects acidic and neutral mucin)

Congenital anomalies of esophagus

Atresia of esophagus

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Definition: esophageal segment is usually a thin, noncanalized cord with a proximal blind pouch connected to pharynx and a distal pouch leading to stomach

Present in 1 per 2500 live births, etiology unknown but not genetic (recurrence risk in siblings is only 1%)

Discovered shortly after birth due to immediate regurgitation after feeding

Usually near tracheal bifurcation; fistula present in >80% (see topic below) connecting the upper or lower pouch with the trachea or a bronchus; also associated with congenital heart disease, neurologic disease, GI or GU malformations in 50%; also single umbilical artery

Most common is a blind upper segment, fistula between blind lower segment and trachea

Diagrams: common types of atresia; classification of Esophageal Atresia/TracheoEsophageal Fistula (EA/TEF) #1; #2

Diagnosis: inability to pass a nasogastric tube

Case reports: due to diverticulum of Kommerell (very rare, Pediatr Cardiol 2007;28:303)

Treatment: surgery (diagram, early since incompatible with life) is usually successful, but complications are GERD, esophagitis (J Pediatr Surg 2007;42:370) and tracheomalacia

References: Orphanet J Rare Dis 2007 May 11;2:24 (review), Chest 2004;126:915 (complications), eMedicine #1 (includes classification systems), #2

Ectopic gastric tissue in esophagus

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Also called gastric heterotopia, cervical inlet patch

Most common form of heterotopia

Usually in postcricoid region (may be difficult to examine endoscopically, South Med J 2006;99:865), found in 1-4% endoscopically (J Gastroenterol Hepatol 2004;19:891, Int J Clin Pract 2007 May 29 [Epub ahead of print])

May be due to rests of gastric precursor cells that remain after original esophageal mucosa is replaced by stratified squamous epithelium

May cause dysphagia or heartburn

Associated with H. pylori (29-77%, Am J Gastroenterol 2003;98:1266), esophagitis and Barrett’s esophagus (20%, Archives 2004;128:444); Barrett’s has similar mucin profile (Hum Path 1988;19:1301) and keratin expression (AJSP 2005;29:437)

Classified based on symptoms and morphologic changes (Am J Gastroenterol 2004;99:543)

Complications: ulceration, bleeding, stricture or perforation from acid secretion; rarely adenocarcinoma

Endoscopy: circular, red-orange flat area referred to as “inlet patch”

Endoscopy images: salmon colored patch

Case reports: with hypopharyngeal squamous cell carcinoma (Auris Nasus Larynx 2007;34:135), with adenocarcinoma (Am J Clin Oncol 2004;27:644, Dig Dis Sci 1998;43:901)

Gross: resembles gastric mucosa with sharp border from normal squamous epithelium; deep pink and velvety

Micro: usually cardiac-fundic glands with parietal and chief cells, often extensive inflammation causing reactive changes; may ulcerate

Micro images: mucosal biopsy shows antral type mucosa and a small fragment of squamous epithelium; various images

Ectopic pancreatic tissue in esophagus

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Also called pancreatic heterotopia

At gastroesophageal junction in 16% of pediatric/young adult patients

May be congenital and independent of Barrett’s esophagus (AJSP 1996;20:1507)

Usually no clinical significance, but may exhibit pathologic changes of pancreatic tissue including ductal carcinoma (Archives 1994;118:568), other malignancy (Ann Thorac Surg 2000;69:259) or pancreatitis (Surg Laparosc Endosc Percutan Tech 2005;15:345, Dig Dis Sci 1995;40:2373)

Micro: benign appearing pancreatic ducts and acini

Cytology: clusters of benign appearing ducts and small acini mixed with inflammatory cells (Diagn Cytopathol 2004;31:175)

Micro images: esophageal squamous mucosa overlying pancreatic type parenchyma, immunostaining for trypsin, lipase and amylase

Positive stains: trypsin, chymotrypsin, amylase, lipase (AJSP 1995;19:1172)

References: Archives 2000;124:1165

Ectopic sebaceous glands

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Approximately 2% of adult autopsies

May be multiple (Am J Gastroenterol 1994;89:1884); occurs at any level of esophagus

Case reports: 53 year old woman with > 100 minute polyps of mid-lower esophagus (Dig Dis Sci 1995;40:287), 50 year old man with reflux esophagitis (The Internet Journal of Gastroenterology 2007;5(2)), 69 year old woman with multiple esophageal nodules

Micro: sebaceous glands in lamina propria; may be metaplastic submucosal gland ducts

Micro images: ectopic sebaceous glands in lamina propria surrounded by lymphocytes; squamous epithelium with sebaceous glands #1; #2; #3; cuboidal/squamoid cells with foamy lipid filled cells

Fistula (congenital) of esophagus

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Associated with atresia; also tracheomalacia, Auerbach plexus abnormalities, cardiovascular abnormalities

May be due to abnormality during foregut separation phase or fixation during elongation of trachea (Texas Medical Center)

Gross’s classification:

Type A: no connection with trachea (i.e. atresia but no fistula, 8%)

Type B: upper segment connects with trachea (1%)

Type C: lower segment connects with trachea (87%)

Type D: both segments connect with trachea (1%)
Type E: both segments join to connect with trachea (H type-4%)

Tracheobronchial remnants often persist in lower esophageal segment as dilated epithelial clusters of seromucous glands and cartilage (Archives 2003;127:1523)

Treatment: surgical repair, possibly through thoracoscopy (Ann Surg 2005;242:422)

Drawings: various types of fistulas #1; #2 (has different Type designations since Netter’s drawings were before Gross’s publication)

Gross images: blind sac of esophagus above (left) and continuation of esophagus from carina inferiorly #1 (right); #2; #3; apparent perforation of membranous portion of trachea into esophagus

Micro images: tracheobronchial remnants - fig 1: GERD with cardiac-type metaplasia; fig 2-3: plates of mature cartilage and acini of minor salivary glands; fig 4: branchial cleft-like cysts

References: Orphanet J Rare Dis 2007 May 11;2:24-review, Chest 2004;126:915 (complications), eMedicine #1 (includes classification systems), #2, Am Fam Physician 1999;59:910

Paterson-Brown-Kelly or Plummer-Vinson syndrome of esophagus

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Also called sideropenic dysphagia

Very rare; decreased incidence may be due to better diets (J Gastroenterol Hepatol 1994;9:654)

Occurs mostly in Scandinavia and Great Britain

Usually women ages 30+ years

Pathogenesis not known, may be due to iron and nutritional deficiencies, genetic predisposition, and autoimmune factors.

Upper esophageal web, iron deficiency anemia and dysphagia; also glossitis, cheilitis (scaling and fissures at corners of mouth due to riboflavin deficiency), nail changes; at risk for postcricoid squamous cell carcinoma

Case reports: patients requiring balloon dilation for webs (Turk J Gastroenterol 2005;16:224), post-cricoid carcinoma leading to diagnosis of syndrome (Am J Otolaryngol 2007;28:22), with stomach cancer (rare, World J Gastroenterol 2005;11:7048)

Treatment: iron supplements, mechanical dilation, monitor for upper GI carcinoma

Micro: thin layer of squamous mucosa and submucosa

References: Orphanet J Rare Dis 2006 Sep 15;1:36, eMedicine

Rings of esophagus

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Definition: concentric, smooth, thin (3-5 mm) protrusions of normal esophageal tissue (with mucosa, submucosa and muscularis propria) into the lumen

Usually in distal esophagus

May be congenital, or a scar from drinking caustic liquids

Type A: lower muscular ring; rare; thickened circular smooth muscle with overlying squamous mucosa; usually 1.5 cm proximal to squamocolumnar junction, usually asymptomatic (Am J Gastroenterol 2000;95:43)

Type B: lower mucosal ring / Schatzki’s ring; 5% of normal esophagi; upper surface is lined by stratified squamous epithelium, undersurface is lined by columnar-type epithelium; ring contains connective tissue and fibers of muscularis mucosae; located at squamocolumnar junction at proximal margin of hiatal hernia; associated with meat impaction (“steakhouse syndrome”, Surg Endosc 1989;3:195), “swallow syncope” (Dysphagia 2005;20:273), and a reduced incidence of Barrett’s esophagus (Dig Dis Sci 2004;49:770)

Initially described as a constant, symmetrical, diaphragm-like narrowing at the GE junction associated with a small sliding hiatus hernia (Amer J Roentgenol 1953;70:911)

Type C: rare; refers to indentation on radiographic studies caused by diaphragmatic crura; usually asymptomatic

Diagrams: Netter drawings of A and B rings

Case reports: 16 year old boy with dysphagia and Schatzki’s ring (J Postgrad Med 1987;33:99), 54 year old man with dysphagia (Dis Chest 1968;54:465)

Treatment: dilation, possibly anti-reflux medical therapy or surgery (Ann Thorac Surg 1984;37:103)

Micro images: Schatzki’s ring-various images; hypertrophied squamous mucosa, hyperplasia of gastric glandular elements and increased submucosal fibrous connective tissue (fig 2)

References: eMedicine #1, #2 (Schatzki’s ring), GI motility online, Wikipedia

Stenosis of esophagus-congenital

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Fibrous thickening of esophageal wall, particularly the submucosa, with atrophy of muscularis propria; thin and ulcerated lining epithelium

Incidence of 1 per 25-50,000 live births

Congenital cases defined as intrinsic alteration of esophageal wall due to ectopic tracheobronchial tissue, membranous diaphragm, muscular hypertrophy or diffuse fibrosis of submucosa (Pediatr Surg Int 2001;17:188)

Associated with esophageal atresia or other congenital malformations in 17-33%

May occur in adults (AJR Am J Roentgenol 2001;176:1179)

Case reports: 1 month old boy (J Pediatr Surg 2006;41:E5), due to tracheobronchial remnants with cartilage (Arch Pediatr 2006;13:1043), due to membranous diaphragm with tracheoesophageal fistula (J Pediatr Surg 2005;40:e11)

Treatment: dilation and resection plus anastomosis (J Pediatr Surg 2002;37:1024)

Acquired cases due to severe esophageal injury with scarring (reflux, radiation, scleroderma, caustic injury); associated with progressive dysphagia, may cause total obstruction

Webs of esophagus

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Uncommon, ledge like, semi circumferential protrusions of mucosa into lumen

In upper esophagus are called webs, are covered by squamous mucosa and have vascularized fibrous tissue core; associated with Paterson-Kelly syndrome above

In lower esophagus are called Schatzki’s rings (just above squamocolumnar junction), have gastric epithelium on their undersurface

Rarely protrude more than 5 mm into lumen

More common in women over 40 years

Etiology uncertain, but may be associated with gastric heterotopia (South Med J 1997;90:554)

Cause episodic dysphagia associated with “bolting” solid food

Acquired cases due to radiotherapy or graft vs. host disease

Endoscopic images: various images

Treatment: myomectomy, dilation

References: eMedicine, Wikipedia

Esophagitis

Esophagitis-general

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Defined as epithelial damage and inflammation

5% incidence in US (all types, although reflux symptoms in 33-44% of general population), higher incidence in northern Iran and China

Most common cause is gastroesophageal reflux (reflux of gastric contents into lower esophagus); infectious causes are much less common

Histologic changes may be severe (erosion, ulcer, exudates) or subtle

References: eMedicine #1; #2

Allergic esophagitis

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See also eosinophilic esophagitis

Children with eosinophilic esophagitis often have allergic cause

Increasing incidence, perhaps due to increasing recognition

Diagnose based on esophageal pH probes (not acidic), failure to respond to antireflux therapy, allergic history and biopsy

Associated with dysphagia, strictures, failure to thrive (Dig Liver Dis 2006;38:245), peripheral eosinophilia, eosinophilic infiltration elsewhere in GI tract and abnormal allergen skin test results; is some seasonal variation (J Clin Gastroenterol 2007;41:451)

Patients may have enhanced production of cytokines against both food and environmental allergens (Dig Dis Sci 2006;51:1934)

Endoscopy: white flecks in esophageal mucosa (Gastrointest Endosc 2004;59:835)

Case reports: due to pulses (peas, beans and lentils) and chicken (Digestion 2006;74:49), egg allergy (Allergol Immunopathol (Madr) 2006;34:79)

Treatment: antiallergic therapy (An Pediatr (Barc) 2005;62:333) or dietary modification (Indian J Pediatr 2006;73:919); biopsy for follow up (Curr Opin Pediatr 2004;16:560)

Micro: >20-24 eosinophils per high power field, presence of eosinophil aggregates / microabscesses and superficial intraepithelial eosinophils

Micro images: large number of eosinophils and eosinophilic microabscesses

DD: gastroesophageal reflux disease (acidic pH in esophagus, fewer eosinophils and no eosinophil aggregates, no allergic history, responds to anti-reflux therapy)

References: AJSP 1999;23:390, AJSP 1986;10:75, AJSP 1985;9:475, Children’s Memorial Hospital

Aspergillus esophagitis

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Also called aspergillosis

Poor prognosis

Case reports: AML patients (Diagn Cytopathol 2004;30:347)

Treatment: intravenous amphotericin B

Cytology: scattered three dimension groups of fungi with 45 degree angle branching

Gross images: multiple confluent ulcers; focal yellow granular lesions in bone marrow transplant patient

Bacterial esophagitis

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Associated with immunocompromise (Arch Intern Med 1986;146:1345, Dig Dis Sci 1995;40:183), Chagas disease (J Gastrointest Surg 2007;11:199), reflux esophagitis (some bacteria are similar to normal flora, World J Gastroenterol 2005;11:7277), Barrett’s esophagus (possibly, Dig Dis Sci 2004;49:228)

Phlegmonous esophagitis: rare; due to suppurative bacterial infection; high mortality; most common pathogens are Streptococcus, Staphylococcus, Escherichia coli, Hemophilus influenzae, Proteus, Clostridia

Necrotizing infectious esophagitis has a high mortality due to sepsis (Ann Thorac Surg 2003;75:342)

Case reports: Actinomycosis (J Infect 2005;51:E39), staphylococcus (Abdom Imaging 1993;18:225)

Micro: clusters of bacteria invade esophageal wall and blood vessels; may be epithelial necrosis

Micro images: reflux esophagitis associated (fig 1)

References: Current Treatment Options in Gastroenterology 1998;1:56

Candida esophagitis

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Usually due to Candida albicans or Candida tropicalis

Most common cause of infectious esophagitis

Associated with antibiotic use in non-immunocompromised; also acid suppressive therapy, carcinoma, corticosteroids, diabetes mellitus, esophageal motility disorders, gastric surgery, HIV, rheumatic disease (Dis Esophagus 2003;16:66)

Note: fungal invasion is a requirement for diagnosis since Candida is normal flora in GI tract

Often associated with CMV or HSV esophagitis (case report at Hum Path 1982;13:760); also esophageal stricture

Poorer prognosis in the elderly (Dis Esophagus 2006;19:189)

Case reports: 70 year old healthy woman (The Internet Journal of Infectious Diseases 2006;5:1)

Treatment: fluconazole

Endoscopy: gray-white pseudomembrane or plaque in mid to distal esophagus; mucosa is erythematous, edematous, ulcerated or friable

Gross images: tan-yellow plaques with mucosal erythema #1; #2; #3; leukemic patient has pseudomembrane #1; #2; necrotic appearing ulcers; focal erosion; diffuse involvement

Micro: densely matted pseudohyphae and budding spores in squamous debris, fibrinopurulent exudate or necrotic debris; underlying active esophagitis; invasion into muscularis propria and adventitia in HIV patients in past (Mycoses 1997;40 Suppl 1:81)

Micro images: pseudohyphae #1; #2; GMS #1; #2; PAS #1; #2; #3; #4; #5; #6; #7; #8; neutrophilic infiltrate; pregnant woman (figs 1 & 2); various images

Virtual slides: Candidiasis

Positive stains: PAS, GMS

Chemical (corrosive) esophagitis

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Children or adults

Causes: ingestion of strong alkalis (see lye stricture below), acids or nonphosphate detergents (may be suicide attempts); cytotoxic chemotherapy

In Taiwan, commonly due to ingestion of alkaline oil (Pediatr Surg Int 2004;20:207)

Complications: stricture, Barrett’s esophagus, rarely squamous cell carcinoma

Treatment: dilation, often surgery (Int J Pediatr Otorhinolaryngol 2001;57:203)

Gross images: reaction to caustic injury

Micro: mucosal or transmural injury with hemorrhage, necrosis and possible bacterial infection

References: Int J Pediatr Otorhinolaryngol 2005;69:1257

CMV - cytomegalovirus esophagitis

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Usually immunocompromised patients; up to 30% of AIDS patients have CMV, Candida or Herpes esophagitis; rarely occurs in immunocompetent patients

Inclusions are numerous but may be atypical in HIV patients (Hum Path 1992;23:1019)

Histology is necessary to confirm diagnosis; repeat biopsy may be necessary

Case reports: dialysis patient (Nefrologia 2005;25:201), CMV esophagitis in renal transplant recipient presenting as black esophagus (Transpl Infect Dis 2007;9:42)

Treatment: anti-CMV drugs or reduction of immunosuppression (J Clin Virol 2005;34:219)

Gross: punched out mucosal ulcers with normal surrounding mucosa (similar to herpes simplex), but may lack ulcers (Hepatogastroenterology 2005;52:1236)

Micro: virus present in enlarged endothelium and stromal cells at ulcer base; basophilic cytoplasm often has coarse intracytoplasmic granules; prominent intranuclear basophilic inclusions surrounded by clear halo; macrophage aggregates in perivascular distribution are somewhat specific for CMV or HSV (Hum Path 1997;28:375); features are less obvious in patients receiving antiviral therapy

Micro images: intranuclear inclusions (H&E and EM); H&E and CMV immunostain; CMV and leishmaniasis #1; #2; various images

Positive stains: CMV immunostain or in situ hybridization

References: eMedicine

Crohn’s disease of esophagus

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Cannot diagnose on biopsy, need resection specimen

Associated with GI Crohn’s disease; esophageal involvement in 0.2-13% with ileocolic Crohn’s disease; isolated esophageal involvement is extremely rare

Usually extraesophageal Crohn’s disease at time of presentation in esophagus (Inflamm Bowel Dis 2001;7:113)

Case reports: 31 year old man with isolated esophageal involvement (Eur J Gastroenterol Hepatol 2003;15:1123)

Gross: early - mucosal hyperemia and aphthous ulcers; late - discrete ulcers of lower 2/3, fibrosis, stenosis, fistulas

Micro: deep and aphthoid ulcers, transmural inflammation, non-necrotizing granulomas, epithelioid non-necrotizing granulomas in 7-9% (Am J Gastroenterol 1997;92:1467)

Positive stains: often HLA-DR in all layers (AJSP 1999;23:970)

References: J Pediatr Gastroenterol Nutr 2003;36:454 (children)

Eosinophilic esophagitis

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Also called allergic esophagitis by some authors (Curr Opin Gastroenterol 2006;22:429)

Children are likely to have a clinically identifiable allergic cause (Curr Opin Allergy Clin Immunol 2007;7:274), see allergic esophagitis above

Adults typically don’t have a clinically identifiable allergic cause (Allergy 2006;61:1480), although may have allergen mediated pathophysiology (Dig Dis Sci 2006;51:1934)

Dysphagia in 63% (World J Gastroenterol 2006;12:2328); onset in second or third decade is suggestive; often presents with food impaction (J Clin Gastroenterol 2007;41:356); also part of the rare anticonvulsant hypersensitivity syndrome (Dig Liver Dis 2007 Mar 27 [Epub ahead of print])

May occasionally be familial (Gastrointest Endosc 2007;65:330)

May be part of spectrum of eosinophilic gastroenteritis or associated with peripheral eosinophilia or reflux esophagitis

No actual increase in incidence in past 15 years according to one study (Archives 2007;131:777)

Pathogenesis: systemic CD4+ Th2-cell-mediated immunity and an enhanced eosinophil-CCR3 chemokine receptor 3/eotaxin-3 pathway play a role (J Pediatr Gastroenterol Nutr 2007;45:22)

Endoscopy: white plaques, stipple-like exudates, linear fissures, trachealization (ringed esophagus), strictures

Case reports: 24 year old man with dysphagia (the DAVE project)

Treatment: topical fluticasone propionate (a steroid), allergen elimination if allergic, dilation (Curr Gastroenterol Rep 2007;9:181), possibly anti-IL5 antibody (Allergy Clin Immunol 2006;118:1312)

Micro: prominent intraepithelial eosinophils (15 or more in 2 or more high power fields or 25 or more in any HPF), microabscesses (42%), often with large clusters near surface; also increased intraepithelial CD8+ T cells, intercellular edema, lamina propria fibrosis; peripapillary eosinophils may represent an early stage

Micro images: reflux esophagitis and eosinophilic esophagitis; large number of intraepithelial eosinophils and eosinophilic microabscess #1; #2; #3; #4; GERD features plus extensive eosinophils #1; #2; #3; moth-eaten appearance due to intercellular edema; GERD-like changes; various images

Positive stains: major basic protein (indicates eosinophil activation and degranulation, AJSP 2007;31:598)

Molecular: associated with eotaxin 3 expression (J Clin Invest 2006;116:536

DD: GERD (may have extensive eosinophils-Am J Gastroenterol 2006;101:1666 but see Am J Gastroenterol 2007;102:1301-may not be clear distinction)

References: Mod Path 2006;19:90, GI motility online

Food granuloma of esophagus

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Micro images: food granuloma #1; #2

Graft versus host disease (GVHD) esophagitis

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Common after allogeneic stem cell transplantation (Ann Hematol 2004;83:101)

Case reports: causing bullous esophagitis (Am J Gastroenterol 1997;92:529), stricture (Bone Marrow Transplant 1988;3:513)

Gross: desquamative esophagitis with web formation

Micro: increased intraepithelial lymphocytes, dyskeratotic squamous cells and apoptosis of individual squamous cells in non-inflamed background is diagnostic; also have increased submucosal fibrosis associated with mucosal esophagitis and ulceration (Gastroenterology 1981;80:914)

Micro images: apoptotic squamous cells; with lymphocytic infiltrate #1; #2

DD: scleroderma (fibrosis, but no apoptotic squamous cells, different clinical history)

Granulomatous esophagitis

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Case reports: chronic granulomatous disease of childhood (Radiology 1991;178:189), Crohn’s disease (J Pediatr Gastroenterol Nutr 1988;7:451), tuberculosis (Ann Trop Med Parasitol 1987;81:129), Wegener’s granulomatosis (Arthritis Rheum 1994;37:1404)

Micro images: various Crohn’s disease images

Herpes simplex esophagitis

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#2 most common cause of infectious esophagitis after Candida

Usually an opportunistic infection in immunosuppressed / AIDS patients, but also affects young immunocompetent children (J Pediatr Gastroenterol Nutr 2004;39:560)

Self-limited in healthy patients; may cause esophageal perforation or disseminate in immunocompromised patients

May have secondary bacterial or fungal infections

Must rule out HSV infection as cause of esophageal ulcers, particularly from immunocompromised patients

Diagnosis: histology, culture, PCR

Case reports: peritoneal dialysis patient with herpes and Candida infections (Am J Med Sci 2007;333:191), immunocompetent host with Mallory-Weiss syndrome (Dis Esophagus 2005;18:340)

Gross: shallow vesicles and ulcers; may coalesce into extensive areas of erosion

Gross images: punched out ulcers #1; #2; #3

Micro: ulcers contain necrotic debris and exudate with neutrophils; viral inclusions are present in multinucleated squamous cells at margin of ulcer; inclusions are usually Cowdry type A (dense eosinophilic intranuclear and cytoplasmic) with thickened nuclear membrane and clear halo; also ground-glass inclusions that fill the nuclei and nuclear molding; aggregates of macrophages with convoluted nuclei are adjacent to inflamed epithelium; inclusions may be absent in endoscopic biopsy specimens

Micro images: ulcer has sharp margin where squamous epithelium is lost and replaced by necrotic tissue; ground glass intranuclear inclusions #1; #2; #3; #4; #5; multinucleated giant cells #1; #2; various images

contributed by Dr. Nilesh Patel, California - 70 year old immunocompentent man with candida and herpes esophagitis - image

Virtual slides: herpes esophagitis

Positive stains: CD68 (large cells with convoluted nuclei)

References: Hum Path 1991;22:541

HIV / human immunodeficiency virus esophagitis

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Associated with idiopathic esophageal ulcers and opportunistic infections (Candida, CMV, herpes, TB, J Gastroenterol Hepatol 2005;20:722)

Diagnosis: histology with immunostains is best, viral culture and cytology are not helpful (J Gastroenterol Hepatol 2005;2:564)

Case reports: acute primary HIV esophagitis (Endoscopy 1990;22:184), leishmaniasis infection in HIV+ patient (Mod Path 1996;9:966)

Gross: large ulcers, severe active inflammation

EM: HIV-like viral particles in idiopathic ulcers

DD: CMV esophagitis

Infectious esophagitis

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Usually restricted to patients with immunocompromise (HIV-J Int Assoc Physicians AIDS Care (Chic Ill) 2002;1:53), diabetes, antibiotic therapy or scleroderma (Semin Arthritis Rheum 2006;36:173)

Most cases due to Candida, herpes simplex virus, cytomegalovirus

Should consider infectious causes if ulcer or exudate is present

Treatment: in immunocompromised, initially systemic fluconazole for presumed Candida (Curr Treat Options Gastroenterol 2003;6:55)

References: eMedicine

Leishmaniasis of esophagus

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Case reports: leishmaniasis infection in HIV+ patient (Mod Path 1996;9:966)

Micro images: leishmaniasis in HIV+ patient #1; #2; CMV and leishmaniasis #1; #2

Lymphocytic esophagitis

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Recently described subset of chronic esophagitis (AJCP 2006;125:432)

Often age 17 years or younger (55%)

May have no upper GI symptoms

Associated with Crohn’s disease (40%), gastroduodenitis (30%), GERD (20%), carcinoma of esophagus or elsewhere (20%), celiac disease (10%); also achalasia (AJSP 1994;18:327)

Micro: frequent intraepithelial lymphocytes around peripapillary fields; no/rare intraepithelial granulocytes

Micro images: various images; figures 1 & 2

Positive stains: lymphocytes - CD3, CD4 (42%), CD8 (36%)

Negative stains: lymphocytes - granzyme B, TIA

DD: reflux, Candida or postradiation esophagitis (show increased intraepithelial lymphocytes in interpapillary areas)

Pill induced esophagitis

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Pills sticking in esophagus cause local injury, often in mid-esophagus

Often doxycycline and other antibiotics, aspirin and NSAIDs, slow-release potassium, ferrous salts, alendronate (Fosamax, Mod Path 1999;12:1152)

Associated with diabetes and ischemic heart disease (Endoscopy 2005;37:740), advanced age; more common in women

May rarely cause strictures

Prevention: take pills when upright and with adequate fluids (Curr Treat Options Gastroenterol 2004;7:71)

Endoscopy: erosions, kissing ulcers, multiple small ulcerations with bleeding, mainly in mid-esophagus

Case reports: alendronate and doxycycline (Rom J Gastroenterol 2005;14:159), Cal-Ban 3000 diet pill (Am J Gastroenterol 1992;87:1424), oral contraceptive Diane-35 (Int J Clin Pract Suppl 2005;147:79), procardia-extended release (J Assoc Acad Minor Phys 1997;8:38), rifampin (Ann Pharmacother 1999;33:27), tamsulosin for prostatic hypertrophy (Dig Liver Dis 2004;36:632), telithromycin (Turk J Gastroenterol 2006;17:113)

Micro: inflammatory exudate, ulceration, inflamed granulation tissue, prominent eosinophils, necrotic squamous epithelium, polarizable crystalline foreign material, multinucleated giant cells; fungi or viral inclusions present in 20% of cases due to alendronate

Micro images: various images; diffuse inflammation infiltrate and ulceration (figs 1b & 2b)

References: Drug Saf 2000;22:237, J Clin Gastroenterol 1999;28:298

Radiation esophagitis

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Complication of treatment for cancer of lung, mediastinum or esophagus with doses of 30 gray or higher

Is primary dose limiting acute toxicity for radiation therapy of thoracic neoplasms (Semin Radiat Oncol 2004;14:280)

Use of cytotoxic chemotherapy has an additive effect (World J Gastroenterol 2005;11:2626)

Acute damage: mucosal necrosis, submucosal edema

Chronic injury: due to fractionated doses of 60 gray or more; submucosal fibrosis, capillary telangiectasia, thick-walled arterial vessels, mucus glandular atrophy, atypical fibroblasts; grossly are ulcers, strictures or fistulas

Gross images: esophageal squamous cell carcinoma - radiation has destroyed tumor, resulting in sharply circumscribed erosion with deep ulcer, presumably where tumor had penetrated the deepest; deep ulcer with necrotic base due to destruction of large, deeply invasive tumor

Micro: variably sized cells in all layers, often increased cytoplasm, enlarged nuclei with bizarre shapes, may be hyperchromatic or smudged; may have large eosinophilic nucleoli; usually no mitotic figures

Micro images: normally oriented epithelium is thinner than normal, but contains bizarre cells at all levels #1; #2; radiated esophageal squamous cell carcinoma has clumps of keratin without epithelium but with foreign body giant cell reaction #1; #2; fibrosis and giant cells; neovascularization (highlighted with CD31)

Reflux esophagitis / gastroesophageal reflux disease / GERD

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Most common cause of esophagitis

Due to reflux of gastric or duodenal contents into lower esophagus

Affects 3-4% in general population, usually mild or moderate disease

Usually adults over age 40, occasionally children

May be erosive or nonerosive (Clin Gastroenterol Hepatol 2007;5:690)

Causes: alcohol and other central nervous system depressants (clomipramine-Am J Gastroenterol 2007 May 19; [Epub ahead of print]), delayed gastric emptying, hypothyroidism, nasogastric tube, pregnancy, sliding hiatal hernia, systemic sclerosing disorders, tobacco; often unknown

Symptoms: heartburn, dysphagia; severity of symptoms is NOT related to histology (Dig Dis Sci 2002;47:2565); pain may be mistaken for myocardial infarction

Physiology: chronic exposure to gastric juices impairs reparative capacity of esophageal mucosa; gastric acid injury to mucosa is critical (Med Clin North Am 2005;89:219); bile reflux may also contribute (J Pediatr Gastroenterol Nutr 2003;36:266)

Diagnosis: clinical (heartburn, regurgitation), intraesophageal pH monitoring to detect acid, Bernstein acid infusion test to assess mucosal sensitivity to acid, endoscopic and histologic examination (multiple biopsies since changes are non specific, Archives 2005;129:159); methods may not correlate, and no “gold standard” exists for diagnosis

Endoscopy: linear ulcers at distal esophagus, often with exudate; also erythema or edema; normal in 50-60% of symptomatic patients - thus biopsy required if clinically suggestive of reflux esophagitis even if normal endoscopy

Endoscopic images: linear ulcers

Treatment: motility promoting drugs, H2 receptor antagonists, proton-pump inhibitors, surgery to reduce hiatal hernia

Long term consequences are bleeding (almost never massive), stricture, Barrett’s esophagus with possible Barrett’s ulcer

Gross: severe cases have hyperemic mucosa with focal hemorrhage

Gross images: longitudinal ulcers

Reflux esophagitis (continued)

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Micro: inflammatory cells in epithelial layer (eosinophils, neutrophils, excess T cells); basal cell hyperplasia exceeding 15-20% of epithelial thickness, elongation of lamina propria papillae into upper 1/3 of epithelium; ballooned squamous cells in 65% (resemble glycogenic acanthosis but PAS negative and positive for immunoglobulin or albumin, Mod Path 1988;1:175), vascular dilatation in 60% (usually at superficial papillae, also associated with varices), also multinucleated squamous epithelial giant cells simulating viral cytopathic effect (AJSP 1998;22:93)

No interstitial cells of Cajal at GE junction (Med Sci Monit 2005;11:BR452)

Eosinophils: seen early in 30% but (a) uncommon in infants (J Pediatr Gastroenterol Nutr 2007;44:27); (b) present in 52% of adults (AJSP 1984;8:899) - correlates best with endoscopic findings; (c) difficult to identify with Bouin’s or Hollande’s fixative, (d) occasional eosinophils are also present in normal lamina propria and in non-GERD esophagitis, (e) rarely large numbers mimic eosinophilic esophagitis (Am J Gastroenterol 2006;101:1666), (f) rare eosinophils in 1/3 of normal adults, so not a reliable diagnostic criterion but, (g) eosinophils not normally present in children, so presence is important in this population

Neutrophils: present in 15%; indicates more severe injury including ulceration and erosion; search for fungi if prominent neutrophils or purulent exudate

Lymphocytes: normal component of squamous mucosa (T cells), no diagnostic significance

Cardiac mucosa at GE junction: GERD causes H. pylori like changes with neutrophils, plasma cell or eosinophilic infiltrates

Micro images: intraepithelial eosinophils; basal cell hyperplasia and elongated papillae; elongated papillae; moderate basal cell hyperplasia; various images; marked neutrophilic infiltrate

DD: normal esophagus (epithelial hyperplasia is present in normal individuals in distal esophagus; tangential artifacts), infectious esophagitis, pill esophagitis, eosinophilic esophagitis, radiation or chemotherapy induced esophagitis

References: AJSP 1984;8:899, J Clin Pathol 1985;38:1265, Wikipedia

Sclerotherapy / sclerosing agent related esophagitis

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Treatment for esophageal varices, but is being replaced by endoscopic band ligation (Curr Opin Gastroenterol 2006;22:442)

Sclerotherapy may cause a chemical esophagitis, which may coexist with reflux esophagitis (J Nucl Med 1995;36:1363)

Case reports: causing mucosal bridges (Trop Gastroenterol 2001;22:94)

Gross: superficial and deep mucosal ulceration

Micro: variable necrosis and vascular thrombosis, ulceration and fibrosis (Gastroenterol Jpn 1986;21:99); thrombi may recanalize (Jpn J Surg 1985;15:30)

References: Semin Liver Dis 2002;22:73, Gut 1982;23:615

Tuberculosis (TB) of esophagus

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Not that rare in developing countries with high incidences of TB (Am J Gastroenterol 2002;97:287)

Usually direct spread from adjacent structures, associated with mediastinal lymphadenopathy (Gastrointest Endosc 2003;57:588)

Latent infections may be reactivated by HIV

Recommended to treat for TB if clinically suspect, even if cultures or PCR are negative (J Gastroenterol 2003;38:477)

Case reports: spread from mediastinal lymphadenitis resembling carcinoma (Hong Kong Med J 2006;12:473), death due to esophageal hemorrhage from aortoesophageal fistula with aortic aneurysm (Archives 1986;110:965), 48 year old Pakistani woman with primary esophageal disease (Eur J Gastroenterol Hepatol 2005;17:435), 14 year old boy with mid-esophageal ulcer and hilar / mediastinal adenopathy (Indian J Pediatr 2004;71:457)

Gross: fistulas common

Micro: epithelioid granulomas (usually caseating), Langhans giant cells

Micro images: granulomatous inflammation with necrosis; non-caseating epithelioid granuloma beneath squamous epithelium (fig 2)

Non-neoplastic disorders of esophagus

Achalasia of esophagus

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Also called cardiospasm, megaesophagus

Esophageal motor disorder characterized by lack of progressive peristalsis and partial/incomplete relaxation of lower esophageal sphincter (LES), preventing passage of food into stomach

Preferentially involves circular layer of muscularis propria, which is hypertrophied

Due to T cell mediated destruction or complete absence of myenteric ganglion cells in lower third of esophagus (Am J Gastroenterol 2005;100:1404)

Most cases are idiopathic, usually young adults with progressive dysphagia, nocturnal regurgitation and aspiration of undigested food; can occur in children

Specific causes: Allgrove’s syndrome (World J Gastroenterol 2006;12:4764), amyloidosis, Chagas’ disease (Trypanosoma cruzi destroys myenteric plexus of esophagus, duodenum, colon, ureter; common in South America), diabetic autonomic neuropathy, polio, sarcoidosis, surgical ablation of dorsal motor nuclei, thyroid disease (World J Gastroenterol 2007;13:594), tumor

Patients with achalasia may also have GERD (Eur J Gastroenterol Hepatol 2006;18:369)

5% risk (33x normal) of esophageal squamous cell carcinoma, at mean 21-28 years after diagnosis of achalasia (Anticancer Res 2000;20:3717)

Also increased risk of Candida, lower esophageal diverticula, aspiration, peptic ulceration, stricture, gastroesophageal reflux and Barrett’s esophagus (Ann Surg 2006;243:196)

Treatment: esophagomyotomy (World J Gastroenterol 2006;12:5921, GI Motility Online), dilation (World J Gastroenterol 2006;12:5763)

Gross: progressive dilation of esophagus above LES, variable wall thickness

Gross images: dilated esophagus #1; #2; massive dilation

Micro: early - Auerbach/myenteric plexus lymphocytic inflammation (cytotoxic T cells, eosinophils) with germinal centers and submucosal glandular atrophy, late - marked depletion / absence of ganglion cells in myenteric plexus (middle of esophagus, may be normal at LES) and replacement of nerves by collagen with muscular hypertrophy; squamous mucosa markedly hyperplastic with papillomatosis and basal cell hyperplasia resembling GERD (J Gastroenterol Hepatol 2006;21:727)

Micro images: various images

Achalasia of esophagus (continued)

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Positive stains: p53, T > B cells (AJSP 2001;25:1413)

EM: smooth muscle cells have nuclear and cytoplasmic inclusions, marked loss of small nerve fibers, paucity of granules in nerve fibers; also nonspecific filament disarray, mottling of myocyte fiber density, thick and long cytoplasmic dense bodies, long dense plaques (AJCP 1983;79:319)

DD: visceral neuropathies, normal aging, pseudoachalasia (see below)

References: AJSP 1994;18:327, Wikipedia, eMedicine, GI Motility Online

Atypical regenerative hyperplasia of esophagus

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Associated with chronic esophagitis, not with neoplasm

Micro: immature and relatively monotonous small/medium keratinocytes mixed with inflammatory cells; pleomorphism and atypia are common in keratinocytes and endothelial cells; also mitotic figures

Micro images: squamous cell carcinoma versus atypical regenerative hyperplasia; various images

DD: squamous cell carcinoma (stromal infiltration by nests, cords or thin prongs of malignant keratinocytes; also desmoplasia, in situ carcinoma, atypical mitotic figures)

References: Archives 2005;129:899

Black esophagus

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Also called acute esophageal necrosis

Somewhat rare (~ 100 cases reported, 0.2% of endoscopies); endoscopic finding of black, diffusely necrotic esophageal mucosa, primarily in distal third

80% men, mean age 67 years (J Gastroenterol 2007;42:29)

Due to ischemic injury from atherosclerosis, thrombus or aortic dissection; also associated with alcoholic hepatitis (Endoscopy 2005;37:268) and poor general health (Gastrointest Endosc 2002;56:213)

Patients present with GI bleeding or cardiovascular shock / events

Case reports: after severe alcoholic vomiting in a healthy young man (Surg Endosc 2003;17:521), with cholangiocarcinoma (J Natl Med Assoc 2002;94:735), 79 year old woman with no known cause (CTSNet), herpes simplex esophagitis (Endoscopy 2007 Jul 5; [Epub ahead of print])

Treatment: supportive therapy; usually resolves, although patient may die of other causes (Endoscopy 2004;36:411)

Gross: darkly pigmented esophageal mucosa with ulcerations

Gross images: perforated esophagus (1) with intraluminal hematoma (2); extensive esophageal perforation with distal perforation

Micro: severe acute inflammation with mucosal necrosis; hemosiderin and siderophages, but no melanin; necrosis may extend into muscularis propria and be overlooked at autopsy (APMIS 2003;111:591)

Micro images: extensive ulceration and necrosis

DD: tellurium poisoning in children (found in metal-oxidizing solutions, causes vomiting, blacking of mucosa and garlic odor to breath, Pediatrics 2005;116:e319), activated charcoal deposits (Am J Gastroenterol 1997;92:1359), dye ingestion, melanoma

Celiac disease and esophagus

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Present in 10% with lymphocytic esophagitis (AJCP 2006;125:432) but see AJSP 1996;20:865 (no increase in intraepithelial lymphocytes)

Associated with increased incidence of Barrett’s esophagus (Dig Dis Sci 2005;50:126) and esophageal motility disorders (Neurogastroenterol Motil 1995;7:239)

Case reports: with glycogen acanthosis (Acta Paediatr 2004;93:568)

Cricopharyngeal dysphasia

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Also called cricopharyngeal spasm or achalasia

Cricopharyngeus muscle is part of inferior pharyngeal constrictor

Prominent clinical findings but subtle microscopic findings

May have multiple etiologies (Eur Arch Otorhinolaryngol 1992;249:216-free full text), may be due to diverticulum

Drawings: cricopharyngeus muscle #1 (drawing on left, near bottom); #2

Treatment: cricopharyngeal myotomy, botulinum toxin

Micro: degeneration and regeneration of cricopharyngeal muscle fibers, interstitial fibrosis (Histopathology 1979;3:223)

Micro images: various images (figs 1-3)

EM images: figs 1-6

References: eMedicine (myotomy), PowerPoint presentation

Cysts of esophagus

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Considered developmental unless due to cystic degeneration of tumor or otherwise

Rare

Simple cysts are epithelial lined

Duplication cysts have 2 muscle layers

Either intramural or attached to outer layers of esophagus

Often asymptomatic, even if large; may cause obstructive symptoms

See also retention cysts below

References: eMedicine, Archives 1977;101:136

Bronchogenic cysts of esophagus

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Often young women with dysphagia or chest pain during exercise (Clin Imaging 2006;30:309)

Developmental cysts with cartilage and mucus glands, smooth muscle and ciliated columnar epithelium

Case reports: 26 year old man with cystic lesion at lower esophagus (Dig Surg 2006;23:209)

Micro images: cyst #1 lined by respiratory epithelium overlies collagen, small vessels and smooth muscle; #2; #3 (respiratory epithelium, cartilage, two layers of smooth muscle - fig 4-5)

Duplication cysts of esophagus

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Also called gastroenteric cyst, foregut cyst

Congenital anomaly, usually lower esophagus

Most are intramural; duplications external to esophageal wall are associated with vertebral anomalies

90% do not communicate with esophagus

Case reports: with squamous cell carcinoma (Br J Radiol 2003;76:343), posterior mediastinal cyst with pulmonary anomaly (Radiat Med 2001;19:161), 22 day old infant (Indian J Pathol Microbiol 2006;49:396), 52 year old woman (Yonsei Med J 2005;46:859), causing respiratory distress in infants (Pediatr Emerg Care 2005;21:854), with fistula to lung (Eur J Cardiothorac Surg 2000;18:117)

Treatment: surgery (if symptoms) or possibly observation (Endoscopy 2005;37:870)

Micro: mucosa, submucosa and muscular layers similar to GI tract; lined by either esophageal squamous, gastric, primitive, ciliated columnar or small intestinal epithelium

Micro images: respiratory epithelium and two muscle layers #1 (fig 4); #2 (fig i, also squamous epithelium); #3 (fig D)

Inclusion cysts of esophagus

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Lined by squamocolumnar epithelium, may be ciliated

Diverticula of esophagus

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Outpouching of alimentary tract containing all visceral layers

May cause obstruction, aspiration pneumonia, abscess, infection, hemorrhage or be associated with malignancy

Zenker’s diverticula: also called pharyngoesophageal or pulsion diverticula; more common in elderly; above upper esophageal sphincter, usually posterior wall; due to disordered cricopharyngeal motor dysfunction or weakness in esophageal wall at junction with pharynx; may accumulate food, cause regurgitation or aspiration pneumonia or simulate a neck mass; malignancy in 0.3%

Mid-esophageal/traction diverticula: near mid esophagus at level of tracheal bifurcation; previously thought to be due to TB, mediastinal lymphadenitis and scarring; may be due to motor dysfunction, congenital or alkali ingestion (Med Hypotheses 2004;62:931); better prognosis than distal disease (Dysphagia 2006;21:198)

Epiphrenic diverticula: rare; immediately above LES; due to lack of coordination of peristalsis and LES relaxation (Am J Surg 2005;190:891); may cause nocturnal regurgitation of massive amounts of fluid, obstruction, aspiration; contains mucosa, submucosa and muscularis mucosae; lined by squamous epithelium, often markedly inflamed; case report of fatal hemorrhage (Archives 2006;130:867)

False diverticula: mucosa and submucosa only

Case reports: squamous cell carcinoma in Zenker’s diverticula (Dis Esophagus 2007;20:75)

Drawings: Zenker’s

Gross images: Zenker’s #1; #2; epiphrenic diverticula #1; #2; #3-defect in esophageal wall causes arterial perforation (rare)

Micro images: diverticulum #1; #2

Virtual slides: Zenker’s diverticula

References: eMedicine (Zenker’s)

Enteryx polymer of esophagus

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Injectable polymer deposited into esophageal muscularis propria to treat reflux esophagitis (Gastrointest Endosc 2006;63:468) and reduce use of proton pump inhibitors

Now withdrawn due to safety concerns (US FDA, December 2005)

Case reports: causing abscess (Am J Gastroenterol 2004;99:1856)

Fistula of esophagus (acquired)

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Aortoesophageal fistulas are usually due to thoracic aortic aneurysm, foreign body ingestion or esophageal malignancy

Case reports: aortoesophageal fistula due to a penetrating atherosclerotic ulcer (J Cardiothorac Surg 2007;2:12), 71 year old woman with nasogastric tube and aortic-esophageal fistula (Hum Path 1989;20:709), tracheoesophageal fistula #1 in HIV+ man with Candida and CMV infections (Chest 1994;106:284), #2 presumably due to tuberculosis (J Postgrad Med 1994;40:83)

Gross images: aortic arch aneurysm that perforated in esophagus; orifice of fistula (fig 3); aortoesophageal fistula due to tuberculosis (fig 2)

Glycogenic acanthosis of esophagus

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Common endoscopic finding (25%), often in lower esophagus

Extensive glycogenic acanthosis may be associated with Cowden’s disease (Am J Gastroenterol 1997;92:1038), but otherwise no clinical significance

Gross: multiple white mucosal plaques < 1 cm; may resemble leukoplakia

Gross images: numerous white islands with background of hyperemic mucosa; white nodules; slightly elevated longitudinal plaque of lower esophagus

Micro: epithelial thickening by large squamous cells of prickle cell layer packed with glycogen; no atypia, no inflammation

Micro images: large squamous cells with abundant cytoplasm; thickened superficial squamous epithelium with enlarged squamous cells containing abundant pale to clear cytoplasm #1; #2

Positive stains: PAS (glycogen), diastase sensitive

References: Wikipedia

Hiatal hernia

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Due to separation of diaphragmatic crura and widening of space between muscular crura and esophageal wall

Associated with reflux esophagitis, both erosive and nonerosive (BMC Gastroenterol 2005 Jan 9;5:2)

May be axial or nonaxial

Axial (sliding): 95%, protrusion of stomach above diaphragm creates bell shaped dilation

Nonaxial (paraesophageal): 5%, separate portion of stomach enters thorax, usually along greater curvature; may be due to surgery for sliding hernias, but cause often unknown, associated with reflux, but compromise of LES is probably due to the hernia

Incidence: 1-20% of adults, increases with age, also seen in children

Only 9% with sliding hernias have heartburn or regurgitation of gastric juices into the mouth; accentuated by bending forward, lying supine, obesity

Rarely is familial (autosomal dominant, Gut 1999;45:649)

Complications: ulceration, bleeding, perforation; strangulation of paraesophageal hernias; increased risk of esophageal and gastric adenocarcinoma (Cancer 2003;98:940)

Case reports: 11 year old with congenital paraesophageal hernia (Indian J Pediatr 2007;74:310)

Drawings: axial (sliding) hernia #1; #2; nonaxial (paraesophageal) hernia

Gross images: autopsy findings

References: eMedicine #1, #2, Wikipedia

Idiopathic muscular hypertrophy of esophagus

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Diffuse thickening of the lower esophageal and upper gastric musculature, luminal diameter usually preserved

Often asymptomatic; incidental finding at autopsy (Chest 1978;73:28)

May present with dysphagia

Case reports: with superficial esophageal carcinoma (Tokai J Exp Clin Med 2003;28:103)

Gross: wall is 0.6 to 0.9 cm thick (normal is 0.25 cm)

Gross images: thickened wall (fig 2); uniform thickening of wall and narrowing of lumen (fig 1)

Micro: marked uniform thickening of muscularis propria, usually the inner circular layer, with variable lymphocytes; no nodules

Micro images: thick fibrous septum divides muscle fibers of circular layer of muscularis propria (fig 3); hypertrophy of muscularis propria and lymphocytic infiltration (fig 3-4)

DD: leiomyomatosis (nodules are present)

Kayexalate damage of esophagus

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Kayexalate (sodium polystyrene sulfonate) in sorbitol is used to treat hyperkalemia, may crystallize in the esophagus and produce endoscopic ulcers and erosions resembling carcinoma or Candida

Micro: crystals are lightly basophilic with a faint crystalline mosaic pattern, better seen with PAS/Alcian blue; crystals are refractile but not polarizable, luminal and adherent to intact surface epithelium or mixed with inflammatory exudate in patients with ulcer or erosion

Micro images: crystals in colon

References: AJSP 2001;25:637

Lacerations (Mallory-Weiss syndrome) of esophagus

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Longitudinal tears at GE junction or proximal gastric mucosa

Usually due to severe retching associated with alcoholism

Tears may be mucosal or full-thickness

Cause 5-10% of upper GI bleeds, usually limited, surgery not necessary

Rarely causes sudden unexpected death (Arch Kriminol 2002;209:36, Srp Arh Celok Lek 2001;129:257, J Clin Pathol 1991;44:787)

Rare in children; has various etiologies (Dis Esophagus 1999;12:65)

Boerhaave syndrome: esophageal rupture, may be lethal

Case reports: due to pseudodiverticulosis (Surg Today 2002;32:519)

Treatment: support, vasoconstrictors, transfusions, occasionally balloon tamponade

Gross images: laceration at GE junction #1; #2

References: eMedicine

Lichen planus of esophagus

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Subacute to chronic mucocutaneous disorder of unknown etiology that involves skin, nails and mucosal surfaces

Mucosal surfaces affected are usually perineum, oral mucosa and pharynx

Rarely involves esophagus, usually upper or mid esophagus

All esophageal cases reported to date are in women, usually ages 40+ years

Tends to be chronic and cause dysphagia due to esophagitis and stricture formation

May be underdiagnosed and a risk factor for squamous cell carcinoma (Eur J Gastroenterol Hepatol 2006;18:1043)

Case reports: isolated esophageal involvement (Z Gastroenterol 2004;42:379)

Treatment: systemic corticosteroids, retinoids, cyclosporine or azathioprine; may relapse when therapy is stopped

Micro: lichenoid, T cell rich lymphocytic infiltrate, basal epithelium degeneration, Civatte bodies (degenerated epithelial cells); often parakeratosis and atrophic epithelium; usually no hypergranulosis

Micro images: skin - sawtoothing of rete pegs, chronic inflammatory infiltrate at dermoepidermal junction; various images

DD: gold therapy, thiazides or antimalarials (cause lymphocytic infiltrate), gastroesophageal reflux disease (clinical symptoms, intraepithelial eosinophils, usually lower esophagus)

References: AJSP 2000;24:1678

Lye stricture of esophagus

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Also called corrosive or caustic stricture

Usually at bifurcation of trachea

Mean age 6 years at time of ingestion

Associated with motility disorders in children (Braz J Med Biol Res 2004;37:1623)

Treatment: stenting, dilation or surgical resection

Complications: carcinoma, mean 40 years later, usually at tracheal bifurcation

Gross images: stricture (cause unknown)

Micro images: stenosis of lumen and extensive fibrosis

References: Sao Paulo Med J 2001;119:10, eMedicine

Lymphoid hyperplasia of esophagus

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Associated with chronic stenosing ulcerating esophagitis and Barrett’s esophagus (AJSP 1985;9:141)

DD: follicular lymphoma (Korean J Pathol 1995;29:393)

Pseudoachalasia of esophagus

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2-4% of patients with achalasia-like syndrome

Difficult to diagnosis

Resembles achalasia, but has different pathology; usually associated with a neoplasm, often adenocarcinoma at/near the esophagogastric junction invading into myenteric plexus

Rarely due to a paraneoplastic process (Dis Esophagus 2007;20:168), documented by anti-neuronal antibodies

Reversal of achalasia-like symptoms after treatment of underlying disorder

Case reports: due to metastatic cervical carcinoma to esophagus (JSLS 2001;5:57), due to neurofibromatosis of esophagus (Ann Thorac Surg 2006;81:1138), due to vagotomy (World J Gastroenterol 2006;12:5087), due to other neoplasms (Dis Esophagus 2007;20:168)

References: AJSP 2002;26:784, Scand J Gastroenterol 2005;40:378.

Pseudodiverticulosis of esophagus

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Also called diffuse intramural esophageal (pseudo) diverticulosis

See retention cysts below

May be due to retention cysts (AJCP 1976;65:314)

More numerous in upper third of esophagus

Usually no clinical findings, rarely dysphagia with markedly enlarged cysts

Case reports: 74 year old woman with dysphagia and vomiting (Archives 1993;117:848), 57 year old man with dysphagia for 2 years (J Postgrad Med 2005;51:328, free full text)

Treatment: dilate strictures (if any), reduce inflammation as needed

Gross: numerous 1-3 mm flask shaped diverticula with a pinpoint mouth

Gross images: thickened esophageal wall due to expanded submucosa that contains numerous collapsed cysts, which may appear grossly as irregular slits

Micro: squamous lined, resemble dilated excretory ducts of submucosal mucus glands; often surrounded by chronic inflammatory infiltrate

Micro images: two dilated ducts in superficial submucosa lined by thick metaplastic squamous epithelium

References: Hum Path 1988;19:928

Retention cysts of esophagus

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Also called mucocele

Derive from obstructed submucosal gland ducts

Small, usually in lower esophagus

May cause intramural pseudodiverticulosis, with multiple flask like invaginations into esophageal wall (AJCP 1976;65:314)

Associated with chronic esophagitis and fibrosis; also surgically isolated segments of esophagus (Dis Esophagus 2002;15:96)

Micro: saccular or flask-shaped dilation of submucosal gland excretory ducts; rarely reaches muscularis propria; in large lesions, muscularis does not accompany the lesion, so are not true diverticula

Sarcoidosis of esophagus

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Rare; usually associated with pulmonary sarcoidosis (GI Motility online 2006)

Rarely associated with scleroderma (Ann Med Interne (Paris) 1996;147:590)

Case reports: causing achalasia (J Clin Gastroenterol 2002;34:54), with dysphagia and esophageal dysmotility disorder (Am J Gastroenterol 1996;91:1423), with dysphagia and muscle weakness (Am J Gastroenterol 1991;86:1679)

Micro images: granuloma in lamina propria

DD: sarcoid-like reaction of regional lymph nodes in malignancy (Surg Today 1999;29:260), TB or fungi

Scleroderma (systemic sclerosis) of esophagus

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Involves esophagus in 75%+ patients, usually distal 2/3, with aperistalsis and reduced tone of lower esophageal sphincter

Commonly causes reflux esophagitis (Semin Arthritis Rheum 2006;36:173), strictures, Candida esophagitis, Barrett’s esophagus (J Clin Gastroenterol 2006;40:769, but similar prevalence as other reflux esophagitis patients-Arthritis Rheum 2005;52:2882)

Case reports: with CMV esophagitis (J Clin Rheumatol 2001;7:384), with achalasia (Dtsch Med Wochenschr 2006;131:1799)

Treatment: no treatment for underlying disease; proton pump inhibitors for reflux esophagitis, dilation for strictures

Micro: resection specimens - atrophy and replacement fibrosis of inner circular layer of muscularis propria and resulting stenosis; longitudinal layer is usually involved; also submucosal fibrosis, mild inflammation, intimal proliferation of arterioles (Gut 2006;55:1697)

biopsies - ulcers or erosions resembling reflux esophagitis, Candida or Barrett’s

Micro images: fibrosis of muscularis propria; trichrome stain shows fibrosis in submucosa and muscularis propria

EM images: collagen between degenerate muscle fiber (left) and necrotic muscle fiber (right); muscle fibers (M) separated by collagenous fibers with widened intermyofibrillar space

DD of muscularis propria fibrosis: Sjogren’s syndrome, systemic lupus erythematosus, primary visceral myopathy, cricopharyngeal dysplasia

Ulcer of esophagus

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Usually caused by chronic gastroesophageal reflux

Consider infectious causes if exudate is present

Case reports: Barrett’s ulcer with perforation (Ann Thorac Surg 2002;73:302), Behcet's disease (World J Gastroenterol 2006;12:2622, Yonsei Med J 2002;43:457), CMV (South Med J 2000;93:818), doxycycline (Gastroenterol Hepatol 2001;24:390), HIV in child (Pediatr Radiol 2002;32:907), metronidazole (Rev Gastroenterol Mex 1998;63:106), myeloma (World J Gastroenterol 2006;12:2305), NSAID (Surg Endosc 1997;11:143), radiotherapy (Dis Esophagus 2002;15:266), tuberculosis (Eur J Gastroenterol Hepatol 2005;17:435)

Gross images: multiple healed ulcers; ulcers related to unspecified tube #1; #2 (Blakemore tube); ulcers (cause unknown)

Micro: granulation tissue with large, atypical mesenchymal cells resembling carcinoma; adjacent epithelium has reactive changes and prominent hyperplasia (pseudoepitheliomatous hyperplasia) that appear as uniformly thick, parallel prongs of primitive squamous cells that penetrate the granulation tissue of the ulcer bed; cells have minimal cytoplasm, large pleomorphic and hyperchromatic nuclei and prominent nucleoli; mitotic figures common; may appear invasive with tangential sectioning

Micro images: surface of healing ulcer (top) shows primitive squamous cells penetrating granulation tissue; cells are large with dark, pleomorphic nuclei #1; #2; base of ulcer shows large abnormal spindle cells #1; #2 with capillary buds; granulation tissue overlying submucosal glands; long prongs of undifferentiated cells in parallel penetrate the granulation tissue at base and edge of ulcer, cells have high N/C ratio, hyperchromasia, pleomorphism and large nucleoli #1; #2; #3; #4; myeloma ulcer (figs 1-4); necrotic epithelium

Negative stains: atypical cells in ulcer bed are keratin negative

Varices of esophagus

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Dilated tortuous vessels, usually submucosal, that develop due to portal hypertension (prolonged or severe), which induces formation of collaterals between portal and caval systems

Collaterals in lower esophagus divert flow from portal vein, through coronary veins of stomach, into esophageal veins, then azygous veins, then into vena cava

Present in 90% of cirrhotic patients, usually due to alcoholism; acute alcohol intake may cause death, often outside the hospital

May rupture and cause massive hemorrhage (cause of death in 50% with advanced cirrhosis)

40% die in first episode of bleeding varices; rebleeding occurs in 50% of survivors within 1 year with 40% mortality

Blood stains at death scene and unusual body positions of deceased are clues to fatal esophageal variceal hemorrhage

#2 cause of bleeding varices worldwide is hepatic schistosomiasis

“Downhill” varices occur in upper esophagus from other causes (Rev Esp Enferm Dig 2006;98:359)

Treatment: repeated sclerotherapy (injection of thrombotic agents, Ann Surg 2006;244:764), banding/ligation (Arq Gastroenterol 2005;42:72), balloon tamponade

Gross: varices may protrude into lumen, mucosa may be normal or inflamed

Gross images: linear, dark blue, submucosal dilated veins #1; #2; #3; #4; #5; ruptured varices #1; #2; #3; #4 (esophagus turned inside out); partially thrombosed after sclerotherapy #1; #2; at gastroesophageal junction

Micro images: dilated veins #1; #2; #3; #4; #5; #6; #7; focal rupture; inflamed varix; sclerosed varix

Virtual slides: ruptured varices

DD hematemesis: gastritis, esophageal laceration, peptic ulcer

References: Archives 2002;126:1197 (fatal cases), Wikipedia, eMedicine #1; #2

Benign tumors of esophagus

Benign tumors of esophagus - general

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Rare, usually small, polypoid and asymptomatic, but may be confused with malignancy

Treatment: endoscopic resection of small superficial tumors (Semin Thorac Cardiovasc Surg 2003;15:27)

DD: mediastinal bronchial artery aneurysm (J Vasc Surg 2003;38:1125)

Adenoma of esophagus

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Derived from submucosal gland/duct system, parathyroid or thyroid tissue

Benign ductal or glandular neoplasms of the esophagus unrelated to Barrett’s esophagus are very rare

Case reports: with superficial squamous cell carcinoma (Cancer 1993;71:2435), parathyroid adenoma (Archives 1978;102:242), pleomorphic adenoma (Ann Thorac Surg 1987;44:653)

Amyloid tumor of esophagus

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Very rare

May cause perforation and hematemesis

Amyloid (not necessarily in tumor form) may cause achalasia (J Clin Gastroenterol 1990;12:447)

Case reports: with systemic disease (Laryngoscope 1976;86:850)

Blue nevus of esophagus

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Very rare

Case reports: 58 year old Chinese woman (Head Neck 2001;23:506)

Micro: dendritic melanocytes in subepithelial connective tissue; no junctional melanocytes, no atypia

Esophageal gland duct adenoma

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Very rare

Immunohistochemistry is similar to normal esophageal gland submucosal duct cells

Usually lower half of esophagus

Case reports: 75 year old Japanese man with incidental finding (AJSP 2007;31:469), 81 year old man with 1 cm mass (AJSP 1995;19:1191)

Treatment: excision

Gross: usually polypoid or pedunculated; rarely flat

Micro: no capsule but well demarcated; tubulopapillary and cystic structures with eosinophilic granular cells but no atypia; basal cell layer present; interstitial lymphocytic infiltrate

Positive stains: duct cells - strong and diffuse CK5/6, CK7, CK19 and high molecular weight cytokeratin; weak CK17 and CK18; myoepithelial cells - S100, alpha smooth muscle actin

Negative stains: CK20, mucin

EM: numerous mitochondria

DD: adenocarcinoma

Fibrovascular polyp of esophagus

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Also called fibroma, fibrolipoma, fibromyxoma, lipoma, giant fibrovascular polyp

Uncommon submucosal tumor (1-2% of benign esophageal tumors) that arises in upper esophagus from cricopharyngeal region; may be due to redundant folds that get pulled down by force of swallowing

Lesion is unique to esophagus

Presents with dysphagia or weight loss of ~10 kg

Benign, but may cause death from asphyxia secondary to laryngeal obstruction or be regurgitated into oral cavity

Usually men (75%) age 45+ years

May actually be an acquired malformation or hamartoma

Case reports: giant polyp causing death by asphyxiation (Archives 2006;130:725), 5 month old infant girl (Yonsei Med J 2001;42:264)

Treatment: excision, possibly endoscopically (Laryngoscope 2007;117:944); rarely recurs (South Med J 1991;84:1370), 44 year old man with tumor extending into stomach

Gross: soft, elongated, pedunculated mass up to 20 cm with narrow point of attachment; overlying mucosa may be ulcerated; cut surface is yellow-tan, edematous

Gross images: giant polyp causing asphyxiation; giant tumor is mobilized through esophagotomy incision (top); cut surface has white glistening tissue (bottom); yellow tumor with smooth surface; core is composed of fibrous and adipose tissue (fig 1); 4 cm mass with stalk (fig 2); various images (fig 4-7)

Micro: squamous epithelial lining with frequent ulceration; core of mature fibromyxoid tissue with scattered thin-walled blood vessels and variable adipose tissue; also stromal edema and occasional lymphocytic infiltrate; may have prominent mast cells

Micro images: adipocytes form lobules of different sizes; myxoid area contains spindle cells and vessels; core contains fibroadipose tissue; figures 2-6; loose fibrous tissue with fatty and myxomatous change (fig 3); various images (fig 8-10)

DD: inflammatory fibroid polyp (near GE junction, granulation tissue with prominent inflammatory infiltrate)

References: Archives 2003;127:485

Gangliocytic paraganglioma of esophagus

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Very rare

Usually periampullary and solitary

Case reports: 58 year old woman with simultaneous occurrence in esophagus and superior mediastinum (Hum Path 2004;35:1288)

Micro: neuroectodermal and neuroendocrine differentiation; nests of epithelioid cells with interspersed ganglion cells

Positive stains: epithelioid cells - CAM 5.2, chromogranin, synaptophysin; ganglion cells - S100, neurofilament; spindle cells - S100, neurofilament, GFAP

Glomus tumor of esophagus

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Very rare

Case reports: 28 year old woman with glomangioma (Dis Esophagus 2006;19:208), synchronous tumors of esophagus and lung (Hepatogastroenterology 2003;50:687)

Micro: round glomus cells have pale to clear cytoplasm, are arranged around vascular spaces; frequent stromal liquefaction and hyalinization

Micro images: sheets and strands of round glomus cells with clear cytoplasm and hyalinized stroma with dilated vessels #1; #2

Positive stains: smooth muscle actin, calponin, collagen type IV (envelops the cells)

Negative stains: S100, keratin

Granular cell tumor of esophagus

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Also called Abrikosoff's tumor, myoblastoma

Most common site in GI tract for these tumors

#2 most common stromal tumor of esophagus after leiomyoma

Usually incidental, in lower esophagus, 90% solitary

May cause obstruction if large

May be of Schwannian origin

Commonly women in 40’s, blacks

May be underdiagnosed on superficial biopsies that lack lamina propria

Endoscopy: sessile, yellow-white, firm, intact epithelium

Case reports: esophageal tumor 7 years after bronchial tumor (APMIS 2006;114:659), associated with esophageal leiomyomas (Dig Liver Dis 2004;36:292), multiple tumors (J Gastroenterol 2003;38:776), with squamous cell carcinoma (Dis Esophagus 2002;15:88)

Treatment: local excision

1-3% are malignant (locally recur) - associated with rapid growth, > 4 cm, tumor necrosis, increased cellularity, atypia, > 2 mitotic figures/HPF

Gross: intramural nodule(s), poorly circumscribed, up to 2 cm

Gross images: multifocal tumor

Micro: identical to granular cell tumors elsewhere; sheets or packets of uniform epithelioid cells with abundant eosinophilic granular cytoplasm and small nuclei that interdigitate with overlying epithelium; often pseudoepitheliomatous hyperplasia; often involves superficial lamina propria; may extend into muscularis propria

Micro images: tumor fills lamina propria; tumor extends to base of squamous epithelium, which has spike like rete pegs; tumor cells have fine cytoplasmic granules; granular cells infiltrate between muscle fibers; various images; PAS and S100

Positive stains: PAS, S100

EM: myelin like tubules, cytoplasmic processes surrounded by basal lamina in layers reminiscent of Schwann cells

EM images: numerous intracytoplasmic autophagic vacuoles containing fragmented cell organelles

References: Ann Thorac Surg 1996;62:860

Hemangioma of esophagus

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May present with severe bleeding or dysphagia

May be cavernous or capillary or pyogenic granuloma (lobular clusters of small capillaries)

Case reports: 58 year old man with endoscopic mucosal resection of hemangioma (J Med Invest 2006;53:177), pyogenic granuloma (Virchows Arch 2004;444:590)

Micro images: cavernous hemangioma (fig 7)

Hyperplastic polyp of esophagus

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Also called inflammatory esophagogastric polyp

Rare, near gastroesophageal junction

May represent an exaggerated mucosal response to esophageal injury, including reflux associated ulceration and repair, protracted vomiting, Crohn’s disease, sclerotherapy for varices, heterotopic gastric mucosa

Usually men

48% associated with GERD; 15% with Barrett’s esophagus; not associated with carcinoma

Case reports: 13 year old boy with hyperplastic polyp and ulcerative colitis (Acta Paediatr Jpn 1993;35:53)

Treatment: endoscopic mucosal resection or other excision (World J Gastroenterol 2006;12:5699)

Micro: hyperplastic gastric-type foveolar epithelium or squamous epithelium with granulation tissue, edematous lamina propria, inflammatory infiltrate; 67% have ulceration or erosion

Micro images: cardiac epithelium with foveolar hyperplasia and cystic dilation of pits (fig 2); adenomatous villous type polyp with low grade dysplasia (fig 3); various images

References: AJSP 2001;25:1180

Inflammatory fibroid polyp of esophagus

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Similar to lesions elsewhere in GI tract, but rare in esophagus (<20 reported cases)

Considered to be reactive, with benign behavior

Mid to lower esophagus

Case reports: rapidly growing tumor (World J Surg Oncol 2005;3:30), 76 year old woman with submucosal tumor (Dis Esophagus 2000;13:75), HIV+ man (Dysphagia 1995;10:59)

Treatment: excision

Gross images: 9 cm soft slimy tumor

Micro: submucosal proliferation of fibroblasts and small vessels in a fibromyxoid background with diffuse infiltrate of eosinophils and other inflammatory cells

Micro images: muscularis propria (at bottom) is partially replaced by vascular tumor; tumor contains inflammatory cells, plump stromal cells, blood vessels and collagen; various images; thick and thin walled blood vessels, fibroblasts, lymphocytes and eosinophils

Positive stains: CD34

Negative stains: CD117

DD: fibrovascular polyp (core of fibrovascular tissue, no prominent eosinophils), hyperplastic polyp (hyperplastic epithelium)

References: Am J Dig Dis 1975;20:475

Leiomyoma of esophagus

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Most common benign tumor of esophagus; 8% incidence in autopsy studies (Hum Path 1981;12:1006)

Median age 35 years, 2/3 men

Usually arises from inner circular muscle; most common in distal esophagus

Minute (1-2 mm “seedling”) tumors are often near the gastroesophageal junction and are asymptomatic

Multiple tumors are associated with MEN1 syndrome (Am J Pathol 2001;159:1121)

Large tumors may cause obstructive symptoms

Case reports: multinodular growth pattern simulating carcinoma (Dis Esophagus 2007;20:187), with early squamous cell carcinoma (Jpn J Clin Oncol 2004;34:751), with coexisting leiomyosarcoma (J Exp Clin Cancer Res 2005;24:487)

Treatment: excise if significant symptoms, endoscopic enucleation for small tumors (Singapore Med J 2006;47:901), esophagectomy for large tumors (World J Gastroenterol 2005;11:4258); benign behavior (Ann Thorac Surg 2005;79:1122)

Gross: circumscribed, mural, solitary mass, 2-5 cm (surgical specimens), bulges into lumen, may be polypoid; pink-gray-white with whorled cut surface; mucosal surface is only rarely ulcerated

Gross images: 5 cm lobulated leiomyoma has bulging, white, whorled cut surface; submucosal tumor #1; #2; #3; #4; #5

Micro: similar to classic endometrial leiomyoma; circumscribed lesion of circular muscularis propria or muscularis mucosae composed of intersecting fascicles of bland spindle cells with abundant cytoplasm; variable fibrosis in center of large leiomyomas; occasional calcification; no/rare mitotic figures; no atypia, no cellular foci

Micro images: incidental leiomyoma; leiomyoma of muscularis propria; cluster of seedling leiomyomas within muscularis propria forms a single multilobular mass; seedling (small) leiomyoma of muscularis propria is distinct from surrounding muscularis, although cells are identical; leiomyoma with overlying squamous epithelium; fascicular growth pattern; seedling leiomyoma composed of mature, hypertrophic smooth muscle cells with abundant fibrillary cytoplasm and elongated nuclei

Cytology images: groups of spindled cells with low cellularity #1; #2

Positive stains: desmin, alpha smooth muscle actin

Negative stains: CD34, CD117, S100

DD: GIST (very rare; solid, myxoid and perivascular patterns; more cellular by H&E and cytology, CD117+, CD34+, variable desmin and actin immunoreactivity)

References: AJSP 2000;24:211, Ann Thorac Cardiovasc Surg 2007;13:78, eMedicine

Leiomyomatosis of esophagus

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Uncommon

Some cases may be familial and associated with Alport’s syndrome and deletions of COL4A5/A6 genes (Am J Med Genet A 2003;119:381, Nephrol Dial Transplant 2002;17:70, Orphanet)

Usually children or young adults

May be associated with vulvar, uterine or respiratory tract leiomyomas

Case reports: 22 year old with vulvar leiomyoma and pseudoachalasia (Dis Esophagus 2000;13:165