For the basics of the GI viruses, click here.

ESOPHAGUS

Esophagus "Pathology Outlines" Nat Pernick MD

Esophagus Exhibit Virtual Pathology Museum University of Connecticut

Esophageal Pathology Sampurna Roy, MD Lots of photos and good text

The "gullet" begins at the cricophagyngeus (the short "upper esophageal sphincter" starts here) and ends at the diaphragmatic hiatus or thereabouts ("lower esophageal sphincter"). Solid food may hang up at either site, or where the esophagus passes behind the left main-stem bronchus or between enlarged hilar nodes. Neither sphincter is fool-proof (or even anatomic). Considerable coordination is required for a proper swallow (the big word for "swallowing" is "deglutition"). Most of the time, the esophagus performs its simple but important task well.

Throat Ed's Histology Notes

You remember that the upper esophagus (i.e., the first inch or so) has mostly skeletal muscle (and is thus subject to diseases of nerve and skeletal muscle), the middle esophagus (i.e., maybe another inch) has both skeletal and smooth muscle, and the distal esophagus (i.e., most of the esophagus) has mostly smooth muscle. Unlike most of the rest of the gut, the esophagus has no serosa to help limit the spread of rips or cancers.

Problems with the esophagus manifest as difficulty and/or pain on swallowing, and/or problems with regurgitation.

BIRTH DEFECTS of the esophagus are relatively common.

AGENESIS of some or all of the esophagus is uncommon. ATRESIA of the esophagus, as elsewhere, is failure of a normally-hollow organ to develop its lumen. An atretic esophagus is represented, over part or all of its length, by a fibromuscular cord without a lumen. Less severely, portions of the esophagus may be congenitally STENOTIC (i.e., too narrow).

{20073}    esophageal atresia, from behind. Lungs at the sides, stomach at the bottom

TRACHEO-ESOPHAGEAL FISTULAS of several varieties are common neonatal surgical problems. The proximal esophagus may enter the trachea or bronchus, producing coughing upon feeding (* original movie of M*A*S*H). The proximal esophagus may end blindly and the distal esophagus arise from a large airway, preventing feeding and causing the stomach to fill with air (the most common version). Or there may simply be a window between the two organs.

THROAT PROBLEMS: A little bit higher than the real esophagus, but worth mentioning here:

GLOBUS HYSTERICUS ("globus syndrome", "globus pharyngeus"), a "lump in the throat", is spasm of the back of the throat and perhaps the upper esophagus. It creates the feeling of a mass in the hypopharynx. Sometimes the cause is organic (i.e., a reflex from something wrong nearby, perhaps reflux from the esophagus spilling into the larynx; or a thyorid nodule that was missed -- J. Laryngol. Otol. 121: 242, 2007); often it's psychosomatic. Psychiatrists attribute it to "swallowed tears", and the cure is to cry. (Despite its banal nature, the sensation of a mass may frighten a patient. "Spontaneous cures of non-biopsy-proven throat cancer" sound like globus.)

ZENKER'S "PULSION" DIVERTICULUM: Adjacent to the cricophagyngeus muscle. A hiding-place for last week's spaghetti and last month's pills (so THAT'S why they didn't work....) The smell alone may create a serious social problem.

* A Zenker's can be a true or pseudodiverticulum.

* An EPIPHRENIC DIVERTICULUM, also of mysterious origin, occurs just above the diaphragm. It can harbor large amounts of fluid that are disgorged back to the mouth shortly after the patient goes to bed.

ACHALASIA means "failure of a sphincter to relax when it should". Usually, this means the lower esophageal sphincter.

In the U.S., the problem is usually idiopathic failure of the lower sphincter to relax. The etiology is just now becoming clarified; the cause is usually inflammation of the myenteric plexus (Am. J. Surg. Path. 24: 1153, 2000; Histopathology 35: 445, 1999; Gastroenterology 111: 648, 1996), with eventual nerve damage, but nobody knows why this happens. In other cases, the ganglion cells are simply lost instead; no one knows why.

The esophagus remains filled with food. The patient (typically a young adult) will notice regurgitation and bad breath. The situation may become really nasty as more and more food accumulates in a mega-esophagus. Fortunately, most patients are cured by a single endoscopic dilatation of the sphincter; there's also "botox", or laparoscopic myotomy and partial fundoplication for the hard cases (Am. J. Surg. 181: 471, 2001.)

Untreated, achalasia is a life-threatening problem (carcinoma, aspiration pneumonia).

* Pseudo-achalasia usually results from cancer obliterating the myenteric plexus (Am. J. Surg. Path. 26: 784, 2002).

You remember that Chagas' disease (T. cruzi) is an important cause of mega-esophagus worldwide.

GLYCOGEN PLAQUES are acanthotic (i.e., thick spiny layer) epithelium with extra glycogen. The most common lesion of the esophagus, and of no consequence. You'll see it frequently if you do endoscopies.

* Occasionally, endoscopists see a very dark-pigmented esophagus without any other pathology. This is esophageal melanocytosis (Arch. Path. Lab. Med. 130: 552, 2006); its significance remains unknown.

WEBS are contracted, localized fibrous scars that form little shelves ("ledges") that may obstruct the lumen.

They are most common in the upper esophagus, and most common in women. Their etiology is usually obscure; some are congenital, some result from reflux, graft-vs-host disease, and pemphigus.

* No one knows quite what to make of a supposed association between upper esophageal webs, iron deficiency anemia, and a risk for squamous cell carcinoma in the proximal esophagus. Whether or not this really exists, it's called "Plummer-Vinson syndrome". Current thinking is that somehow iron deficiency causes the webs to form just beyond the cricoid (Am. J. Gastro. 97: 190, 2002).

SCHATZKI'S RING is a washer-shaped partially-obstructing fibrous ring at the squamo-columnar junction just above the gastroesophageal junction. It is a radiologist's delight and may be seen in any adult; long a mystery, cases that occur in the absence of reflux may be due to pill enlodgement (Am. J. Surg. 158: 563, 1989). A-RING is the same, at the gastro-esophageal junction.

A big chunk of solid food (i.e., poorly-chewed beef) may hang up on a web or ring. In bad cases, softer food may have trouble negotiating the obstruction.

{09433}    Schatzki ring
{09434}    Schatzki ring
{09435}    web

HIATUS HERNIA is said to be present whenever a portion of the stomach pooches up through the diaphragmatic hiatus. Said to be present in up to 10% of adults (typically the overweight), they are most often sub-clinical.

SLIDING HIATUS HERNIA (the usual kind) is present when a short (congenital, fibrous scarring from years of reflux, diaphragm pulled low by obesity) pulls the proximal stomach into the chest. As the esophagus contracts during swallowing, radiologists watch the stomach slide further up through the diaphragm. As with "reflux esophagitis", the distal esophagus is likely to become inflamed and damaged as a result of exposure to pepsin and acid.

PARA-ESOPHAGEAL ("ROLLING") HIATUS HERNIA (the less common kind) is present when a portion of the stomach rolls up through the diaphragm alongside an esophagus of normal length. This is typically a non-problem, but the herniated portion of stomach may become strangulated.

Future pathologists: Don't expect to see either type of hernia (or, for that matter, a Schatzki's ring, or an intestinal hernia) after death, when the muscles of the body relax / go into rigor mortis.

TRACTION DIVERTICULUM, illustrated without comment in "Big Robbins", probably result from scar contraction in the mediastinum (i.e., TB). They are uncommon.

* APHTHOUS ULCERS, the familiar painful white "canker sores" that most people have experienced on the oral mucosa, may be a serious problem in the esophagus for people with HIV infection. No one knows why. Thalidomide for this problem: J. Inf. Dis. 180: 61, 1999.

GASTROESOPHAGEAL REFLUX (GERD, formerly, "peptic esophagitis") is THE common esophagal problem, the result of an incompetent lower esophageal sphincter.

Everyone has probably experienced sudden, unexpected reappearance of a little bit of lunch in the back of the mouth. But sustained or frequent reflux starts a vicious cycle that becomes a major threat to the health of the esophagus and lungs.

The sphincter is inflamed, scars, and becomes further damaged. The epithelium keeps getting digested and regrowing, with much more opportunity to select for mutated cells. Pathophysiology Am. J. Med. Sci. 326, 274, 2003.

Update for clinicians: JAMA 287: 1972 & 1982, 2002. The correlation between clinical symptoms and endoscopy is remarkably poor. Only about half of the patients with severe "GERD" on endoscopy even have heartburn (Dig. Dis. Sci. 48: 2237, 2003.)

* Like most other diseases of children, pediatric GERD has been blamed on cow's milk. Since the disease also occurs in children who do not drink cow's milk, it cannot be the sole cause. And since the only test is an elimination diet and response to challenge (still true Arch. Dis. Child. 92: 902, 2007), and since strongly-held emotionally-based beliefs are involved, getting at the truth will be difficult. A pop claim that eosinophils in the upper GI mucosa correctly identified the subset of cases caused by milk allergy failed a scientific study miserably (J. Clin. Path. 59: 89, 2006),

Peptic esophagitis ulcers

WebPath Photo



The cause of common "reflux" remains obscure. Mechanical problems (including overweight and sliding hiatus hernia) must contribute, and the problem is more severe if there's "excess stomach acid / pepsin / bile" or the gastric contents stays for some reason within the esophagus. Other things that irritate the esophagus (swallowing spicy food, alcohol (Gut 34: 727, 1993, others), very hot beverages, and/or tobacco juice) will not help either. Pregnancy, benzodiazepines, intubation, and tobacco use are all implicated as well. Lying flat makes matters worse (tip: try propping the head of the bed up on cinder blocks).

The diagnosis of GERD is made clinically on endoscopy (Dig. Dis. Sci. 45: 217, 2000), but pathology may be obtained for confirmation. Pathologists diagnose reflux based on the following criteria (older review: Gast. Clin. N.A. 19: 631, 1990; update Am. J. Surg. Path. 20(S1): S-31, 1996):

• More than 20% of the thickness of the epithelium is taken up by basal cells (i.e., cuboidal ones with scanty cytoplasm, i.e., nuclei at least half the diameter of the cells.

Future pathologists: Be sure you've got that specimen properly oriented, and consider asking the clinician to send it up on cardboard;

Why the thickness of the basal cell layer? In reflux, the surface cells get digested and the basal cells are multiplying overtime to replace them.

• papillae with visible cores more than 2/3 of the way up the epithelium;
• eosinophils in the epithelium (we used to teach that this is more sensitive and specific than it really is, but it's still a fairly good marker: Am. J. Surg. Path. 26: 1032, 2002; Am. J. Gastro. 96: 984, 2001).
• polys in the epithelium (this just means there's an ulcer, which is what you'd expect if reflux is severe)
• balloon cells (hydropic change in injured cells)

{19451}    histopathology of reflux (basal cell hyperplasia)

Barrett's esophagus WebPath Photo

Barrett's esophagus. WebPath Photo

Barrett's WebPath Photo

Barrett's esophagus Joel K. Greenson MD U. of Michigan

If replacement of the normal squamous epithelium by a columnar epithelium has occurred, you may have a BARRETT'S ESOPHAGUS. All about Barrett's: Gastroenterology 122: 1569, 2002; NEJM 346: 836, 2002; Med. Clin. N.A. 86: 1423, 2002.

Today's definitions of Barrett's usually require goblet cells, and for the truly hardcore, the non-goblet cells are both absorptive and secretory. Older definitions of Barrett's allowed any columnar epithelium type.

Ignore hamartomas of gastric-type mucosa; cancer probably only occurs if there is metaplasia with goblet cells, so perhaps one day Barrett's will be redefined as limited to this.

There are at least 2 million "Barrett's" patients in the U.S. In Sweden, 1.6% of the population is affected, with alcohol and tobacco being risk factors (Gastroent. 129: 1825, 2005).

As you'd expect ("Nowell's law triumphant"), finding a Barrett's esophagus means there's been some hits on the genome, and the genetically damaged cells have had a chance to overgrow the area because of repeated healing from reflux. This is a fertile breeding ground for adenocarcinoma of the esophagus.

The molecular biology of transformation to cancer is now fairly clear: Lancet 360: 1587, 2002.

* Anti-reflux therapy may be helpful, but don't count on it to reverse the process. This includes the new, popular procedure of laparoscopic fundoplication (Ann. Thor. Surg. 77: 393, 2004).

In today's cost-conscious era, it seems reasonable to screen adults who complain of heartburn once for Barrett's, with follow-up if and only if there is dysplasia (numbers Ann. Int. Med. 138: 176, 2003).

More on mutations in Barrett's: Arch. Surg. 132: 728, 1997. Deciding on therapy (lasers, electrocoagulation, mechanically removing the mucosa, surgery) based on how bad the dysplasia is: Br. J. Surg. 84: 760, 1997, Am. J. Med. 111 S 8A: 147A, 2001; lasers see Gut 51: 776, 2002. Some pathologists recommend waiting to resect until there is "superficial adenocarcinoma", but the truth is that pathologists can't seem to distinguish this reliably from high-grade dysplasia (Gut 51: 671, 2002).

Future pathologists: You'll look at dysplasias from Barrett's biopsies frequently, and there are likely to be further refinements that will help you let the surgeons know when to operate (laser, scrape, etc). All Barrett's have some hyperchromasia of the nuclei in the lower portions of the glands. Low-grade dysplasia features loss of mucus production, stratified nuclei in the crypts, and elongated nuclei in parallel. High-grade dysplasia features stratification on the surface, branching glands, and/or cribriform stuff in the crypts. Be careful about calling "severe dysplasia" if there is inflammation; it might be better to treat the reflux and repeat the biopsy. One major criterion that says "operate" is loss of the basal orientation of the nuclei, i.e., this is more than just the kind of atypia that one finds in an adenomatous polyp. Grading updates: J. Clin. Path. 55: 910, 2002; J. Clin. Path. 59: 1029, 2006. Biomarkers Mayo Clin. Proc. 76: 438, 2001. Does screening really save enough lives to be worthwhile? It's still a tough call (Am. J. Gastro. 98: 1931, 2003; Gastroenterology 127: 310, 2004 from KU).

* HCA, an immunostain to help spot the aggressive dysplasias: Am. J. Clin. Path. 122: 747, 2004.

{15428}    Barrett's esophagus (note tan columnar, rather than white squamous, mucosa)
{15429}    Barrett's esophagus
{15427}    acute reflux esophagitis (one heck of a case of heartburn; stomach is on the left)

Reflux Eosinophils, slight atypia KU Collection

Reflux leads to fibrosis (scarring, shortening, perhaps narrowing) of the esophagus, difficulty on swallowing ("DYSPHAGIA"), pain in swallowing ("ODYNOPHAGIA"), retrosternal pain ("heartburn") and/or slow GI bleeding leading to iron-deficiency. In severe cases, massive GI bleeding (hematemesis, melena) can occur.

Other noteworthy causes of ESOPHAGITIS include candida, CMV, herpes, radiation, generalized diseases of stratified squamous epithelium (* pemphigus, other) or keeping a stomach tube down for more than a few minutes. All the above can give some nasty ulcers.

Herpes esophagitis
Joel K. Greenson MD
U. of Michigan



CMV Esophagitis
Joel K. Greenson MD
U. of Michigan



You also remember the esophageal changes ("rubber hose") in scleroderma (review for pathologists Gut 55: 1697, 2006) and graft-vs.-host disease.

Scleroderma Trichrome stain WebPath Photo

Candida in the esophagus WebPath Photo

Candida of the esophagus Urbana Atlas of Pathology

{11096}    candida esophagitis (scrapes off, unlike glycogen acanthosis)
{11099}    candida esophagitis
{49128}    candida esophagitis

Herpes esophagitis Sharp borders WebPath Photo

Herpes esophagitis WebPath Photo

Herpes esophagitis WebPath Photo

Herpes esophagitis Nice herpes nuclei and inclusions WebPath Photo

{19449}    herpes, histology
{25910}    herpes, pap smear

* Future pathologists: Herpes of the esophagus is often relatively devoid of good herpes-inclusion cells. Look instead for clusters of macrophages (Hum. Path. 22: 541, 1991).

Drinking lye (Drano, etc., an extremely painful and unreliable method for would-be suicides) or some other caustic substance leads to corrosive esophagitis, strictures, etc., etc.

{11772}    lye burn of stomach
{15554}    lye burn of stomach

PERFORATED ESOPHAGUS can result from swallowing the wrong thing. Chicken bones are infamous (AJFMP 19: 166, 1998) -- these can pierce the heart or cause other dreadful problems.

LACERATED ESOPHAGUS usually results from heavy-duty vomiting during which the esophagus fails to relax (alcohol abuse, pregnancy, post-anesthesia; MALLORY-WEISS SYNDROME). Endoscopists and pathologists see little longitudinal tears, usually in the distal esophagus. They are a problem only if bleeding is massive, or if the esophagus actually ruptures (BOERHAAVE'S SYNDROME; at these sites of rupture, the muscularis mucosae is apparently absent: Am. J. Surg. 158: 420, 1989).

{15420}    lacerated esophagus

ESOPHAGEAL VARICES are dilatations of the esophago-gastric venous plexus. These result from portal vein hypertension from any cause, as the blood from the stomach and intestines seeks the low-pressure pathway back to the heart.

You won't know varices are there until they bleed. And they bleed massively when their attenuated overlying mucosa is rubbed away, or they just pop from pressure. This is the fast way out of life for many problem drinkers.

Esophageal varices WebPath Photo

Esophageal varix WebPath Photo

Esophageal varix Inflamed after rupture WebPath Photo

{38629}    varices, gross
{38632}    varices, gross
{15419}    esophageal varix, histology
{24406}    varices, histology
{40724}    varix with clot, histology

Portal hypertension patients will also commonly exhibit hemorrhoids and dilated veins around the umbilicus ("caput medusae", why?) Remember that portal hypertension will greatly accelerate GI bleeding from non-variceal causes (gastritis, peptic esophagitis, ulcer, Mallory-Weiss) as well.

Learn now: THE CAUSES OF PORTAL HYPERTENSION....

PRE-HEPATIC


Thrombosis of the portal vein


Hypercoagulability
Polycythemia vera, sickle cell, others
Invasion by tumor (usually hepatocellular carcinoma)


Tumor compressing the portal vein


INTRA-HEPATIC


Cirrhosis from any cause
Other obstructive disease


Bad alcoholic liver disease without cirrhosis
Schistosomiasis even without cirrhosis
Central hyaline sclerosis in alcoholism
Various birth defects


POST-HEPATIC
Budd-Chiari (thrombosis of hepatic veins)


Causes as for thrombosis of portal vein






BENIGN TUMORS OF THE ESOPHAGUS: Banal, and relatively uncommon. For example, fibrovascular hamartomas: AJR 166: 781, 1996.

CARCINOMA OF THE ESOPHAGUS strikes around 8000 people each years and kills most of them.

Esophageal Tumors From Chile In Spanish

Esophageal Carcinoma Text and photomicrographs. Nice. Human Pathology Digital Image Gallery

SQUAMOUS CELL CARCINOMA has historically been the most common esophageal cancer in the United States, but is becoming less common.

Most patients are males (more than 4:1), black men are at higher risk than others, and in the U.S., the large majority are both smokers (cigarets, cigars) and drinkers.

Old lye strictures are also frequent sites for esophageal cancer, as is the Chagas-disease ridden mega-esophagus (Digestion 47: 138, 1990).

The epidemic of highly-aggressive squamous cell carcinoma in Mainland China (Cancer 73: 2027, 1994; Cancer 74: 573, 1994) has been attributed to aspergillus fungus contamination, nitrosamines, vitamin deficiency, zinc deficiency, molybdenum deficiency, ethnic teas, and ethnic delicacies that are pickled (i.e., rendered rich in certain fungi).

* Dysplasia precedes the lesion (Gut 54: 187, 2005).

* The South Carolina lowlands have a great excess of squamous cell carcinoma of the esophagus, and these cancers have a distinctively high rate of p53 mutations, suggesting some chemical in the environment (J. Thor. Card. Surg. 108: 148, 1994). Still a mystery: South. Med. 95: 900, 2002. In West Kenya, it is a common disease of teens and young adults (Lancet 360: 462, 2002).

Any portion of the esophagus can be involved; the middle third is slightly more common than the others.

Like most squamous cell carcinomas, esophageal cancer arises in squamous dysplasia (update Gut 54: 187, 2005), is often multifocal (Cancer 73: 2687, 1994), grows as a fungating lesion (less often, just an ulcer), and produces symptoms (dysphagia, food "sticking") only late. Because of its location, the later stages of this disease are particularly cruel.

* Biomarkers: Surgery 127: 552, 2000.

* A claim from the 1990's that many esophageal carcinomas contained HPV remains unconfirmed.

* Honesty or the impact of managed care? The surgeons finally tell it like it is: radiation and chemotherapy for cancer of the esophagus have little or no impact beyond making life more miserable for these patients (Arch. Surg. 133: 722, 1998).

Esophageal cancer WebPath Photo

Esophageal cancer Squamous cell carcinoma WebPath Photo

Squamous cell carcinoma WebPath Photo

{15423}    carcinoma of the esophagus, exophytic growth
{15421}    carcinoma of the esophagus, growing as ulcer
{15422}    carcinoma of the esophagus, annular growth
{15424}    squamous carcinoma of the esophagus, histology
{15552}    carcinoma of esophagus invaded aorta
{19345}    yet another squamous cell carcinoma of the esophagus (x-ray)
{26876}    and another
{42231}    and still another

ADENOCARCINOMA is now almost as common as squamous cell carcinoma, and is probably increasing in frequency. It arises most often arising in a Barrett's esophagus. Again, the male predominance is marked (more than 6:1) and as you'd expect, symptomatic reflux is a strong risk factor (NEJM 340: 825, 1999). Tobacco and obesity are risk factors, alcohol consumption is not. It's basically the same lesion as cancer of the gastric cardia: Br. J. Surg. 529: 529, 1999. The longer the Barrett's region (Gut 33: 1155, 1992), the higher the risk, and smoking also increases risk: Cancer 72: 1155, 1993 (big study). Histopathology of Barrett's cancer: Hum. Path. 19: 942, 1988.

Barrett's esophagus with cancer
Joel K. Greenson MD
U. of Michigan



Other tumors of the esophagus are banal (little leiomyomas) or curiosities (sarcomas; melanomas, Am. J. Clin. Path. 92: 802, 1989, others).

{49132}    leiomyoma, gross

Histopathology and cell-of-origin of cancers of the esophagus: Cancer 75(S6): 1440, 1995.

* ESOPHAGEAL ANGINA: Spasm simulating myocardial infarct (including "crushing chest pain radiating to the left arm and jaw", etc., etc.) Once said to be common, we hear little about this now.

STOMACH

Stomach Exhibit Virtual Pathology Museum University of Connecticut

Gastric Pathology
Sampurna Roy, MD
Lots of photos and good text

{11889}    stomach with biscuit
{09332}    normal gastric rugae
{11740}    normal stomach fundus histology
{50459}    normal stomach fundus histology

Normal stomach WebPath Photo

Normal gastric antrum WebPath Photo

Normal gastric fundus mucosa WebPath Photo

Stomach "Pathology Outlines" Nat Pernick MD

Most stomach problems start with the mucosa. Review of the healthy mucosa:

Surface, pits ("crypts" / "foveolae") in all areas... Tall surface mucous cells (make "neutral mucus")

Deep in pits, all areas... Neck cells (reserve cells for both above and below; "the proliferative zone")

Cardiac glands... More neck-type cells

Gastric glands... Parietal cells (eosinophilic, packed with mitochondria; make acid and intrinsic factor); Chief cells (pale, granular)

Pyloric glands... Neck-type cells; G-cells (gastrin producers)

In 1999, Lancet 354: 134, 1999 published a short report on biotech-enhanced potatoes thickening the mucosa of the stomach and elongating the crypts of rats to which they were fed. A small-sample study with a conclusion that didn't make sense... and the small differences could easily be explained by differences in the angles produced by hand-cutting and hand-embedding, as happens on human biopsies routinely. Did the author compare the heights of the villi to the depths of the crypts for control purposes? Or for that matter, the relative thickening of crypt layer and gland layer? Of course not! Your instructor wrote to Lancet (who turned down my letter) and to the author (Arpad Pusztai, who had gone on TV and made inflammatory statements about the public being used as guinea pigs; he didn't respond either and is now a leading antibiotechnology activist and celebrated "persecuted genius"). Lancet ended up admitting (May 29, 1999) that it knew the paper was junk science when it was published but that if it hadn't published it, it would have been smeared for "suppressing information" by anti-biotechnology militants. I am not making any of this up. Regrettably "environmental activism" thrives on this kind of stuff. Greenpeace USA's website (2005) is still citing the paper as proof of the dangers of bioengineered food ("damaged immune systems and stunted growth of vital organs").

* The mucosa protects itself with a host of protease-inhibitors, phospholipids, glycoproteins, etc., etc.; neutrophils and lots of other things damage it (Dig. Dis. Sci. 39: 138, 1994), etc., etc. You'll go crazy trying to keep them all straight.

* CURIOSITIES

It's not rare to find a bit of ectopic pancreas.

You may also find lung, complete with bronchus -- the famous "pulmonary sequestrum." It's harmless.

DIEULAFOY'S MALFORMATION is an extra-large artery running along the mucosa of the lesser curvature. It can cause severe bleeding, even into the chest (Chest 110: 567, 1996; Ann. Thorac. Surg. 80: 1126, 2005).

INTESTINAL METAPLASIA (review Gut 52: 1, 2003):

A common finding. Most often it's caused by helicobacter; you might see it in autoimmune atrophic gastritis with achlorhydria (perhaps due to the associated bacterial colonization); bile reflux and previous radiation.

An experienced endoscopist can spot areas of intestinal metaplasia by their slightly more whitish color.

Intestinal metaplasia is clearly the precursor lesion for "intestinal type" stomach cancer.

* Some pathologists distinguish subtypes of worsening severity:

TYPE I:

Straight crypts, regular architecture, mature enterocytes, Paneth cells, and goblet cells, neutral mucin

{15432}    type I intestinal metaplasia (right)
{15534}    type I intestinal metaplasia

TYPE II:

Mild distortion of glands, few enterocytes or Paneth cells, many mucin-producers and goblet cells, neutral mucin, * carboxymucin

TYPE III:

Variable degrees of glandular distortion, cells less differentiated, mostly sulfo-mucin ("colonic differentiation").

Any kind of stomach cancer can harbor any kind of mucin. In case somebody (not me) asks:

SULFOMUCIN... Very acid... Intestine; if in stomach, the epithelium is atrophic-metaplastic and is likely to turn nasty (?)

CARBOXYMUCIN... Acid... Intestine (also called "acid sialomucin")

NEUTRAL MUCIN... Neutral... Stomach (also called "neutral sialomucin").

Future pathologists: Use alcian blue to stain the acid mucins!

I am almost sorry to have to add that newer work indicates that all three types may represent either multistep-mutations-of-carcinogenesis or just tissue regeneration (Cancer 74: 556, 1994); the distinction is of no importance (J. Clin. Path. 54: 679, 2001). This is sad because for the past decade, we pathologists have been honing our color-vision to distinguish normal gastric neck cells from "small-intestinal type" intestinal metaplasia, etc., etc.

* Stay tuned for prognosticating "intestinal metaplasia", judging whether it is reversible upon eradicating helicobacter (consensus is now that this is the norm: Gut 54: 1536, 2005), based on gene studies (Gut 52: 1, 2003) and/or immunostaining and/or repeat endoscopy (Dig. Dis. Sci. 45: 1754, 2000). "Das-1 positive is premalignant": Gut 52: 80, 2003).

BIRTH DEFECTS

DIAPHRAGMATIC HERNIAS result from failure of the diaphragm to form properly. Portions of stomach, intestines, and other organs end up in the chest.

{15607}    diaphragmatic hernia, left leaf never formed
{49138}    diaphragmatic hernia, left leaf never formed

Diaphragmatic hernia WebPath Photo

Diaphragmatic hernia WebPath Photo

Congenital PYLORIC STENOSIS is probably a hereditary defect of variable penetrance in which the pylorus of the stomach is hypertrophic, and the gastric outlet may become fully obstructed, typically at the end of the first month of life. The infant experiences projectile vomiting, and the surgeon feels a mass ("feels like an olive") in the upper abdomen. Surgical splitting of the pylorus effects a cure.

It is more common in boys, and Turner's XO is also a risk.

* A claim that some of these kids lack nitric oxide synthetase (NEJM 330: 969, 1994) has failed to find additional support (Clin. Genet. 53: 421, 1998).

* More recently, the understudied "interstitial cells of Cajal", little cells that have a lot to do with gut motility, have been found to be somewhat lacking both in numbers and a key enzyme in the pylorus in these kids (Arch. Path. Lab. Meed. 127: 1182, 2003). Stay tuned.

Pyloric stenosis
WebPath Photo

DILATED STOMACH Often impressive. Causes include beer chug-a-lugging, bowel obstruction, misplaced endotracheal tubes, gastroparesis (think of diabetic autonomic neuropathy), and (in the dead) inept CPR attempts. (Amateurs first blow air into the stomach, then rupture it by pressing in the wrong place. See Ann. Int. Med. 30: 343, 1997.) {49141}    gastric dilatation

Gastroparesis
Spectacular x-ray
Brazilian Medical Students

BEZOARS

These are swallowed goodies that remain permanently in the stomach.

Hairballs (TRICHOBEZOARS) are seen in people who enjoy nibbling their long hair ("Rapunzel syndrome"). Or ask a pet cat. Review Mayo Clin. Proc. 73: 653, 1998.

Trichobezoar
Rapunzel syndrome
AFIP


PHYTOBEZOARS may be chunks of ill-chewed vegetable matter, or (worst) persimmon remnants. The latter contain a substance that, complexed with acid, turns into cement and may require surgery.

Treating a gastric phytobezoar with meat tenderizer: Dig. Dis. Sci. 46: 1013, 2001.

Things that interfere with gastric emptying (diabetes, other dysautonomias, post-vagotomy, anti-cholinergic medicines) enhance one's ability to personally experience a bezoar.

{49150}    bezoar
{10160}    trichobezoar

ACUTE GASTRITIS: Acute damage to the gastric mucosa from any cause.

Pathologists define this to be neutrophils in the epithelium above the basement membrane.

If there is necrosis of any epithelial cells, it is "erosive gastritis" -- you remember that an erosion is inflammation plus necrosis of an epithelium without necrosis of the underlying connective tissue (at least not yet).

Pathogenetic mechanisms include:

• compromise of the mucosal defenses
• killing of epithelial cells
• increased acid production / decreased bicarbonate production
• ischemic injury

"Big Robbins" listed, or could have listed, these important causes:

• alcohol consumption
• aspirin use (remember this one; even the "minidose aspirin" that is supposed to be so good for you gives about half of users gastric erosions: Dig. Dis. Sci. 50: 78, 2005)
• caffeine use
• chemotherapy for cancer
• food allergy (it's for real, and endoscopy is much more accurate than skin-tests or RAST; Am. J. Gastro. 83: 1212, 1988). Probably causes at least some of the cases of the mysterious "eosinophilic gastroenteritis".

Eosinophilic / allergic gastroenteritis
Joel K. Greenson MD
U. of Michigan



• helicobacter (see below)

Helicobacter pylori
Joel K. Greenson MD
U. of Michigan



• radiation injury
• reflux of lysed lecithin ("lysolecithin") from the duodenal bile
• shock
• spicy foods
• staph food poisoning
• "stress" (maybe)
• tobacco use
• viruses (Norwalk calicivirus winter "stomach 'flu", others; all about viral gastroenteritis JAMA 269: 627, 1993)

You can figure out for yourself what the mechanisms might be in each case. Anatomically, you may see anything from mild edema and a few polys to bloody sloughing of chunks of the upper mucosa, and symptoms can range from "upset stomach" to vomiting blood by the pint.

AUTOIMMUNE ("FUNDIC", "CHRONIC ACTIVE", "DIFFUSE ATROPHIC", "TYPE A") CHRONIC GASTRITIS is an autoimmune process that attacks primarily the fundic glands.

You'll see loss of mucous secretion, striking shortening of the glands, and usually loss of the parietal cells.

Patients usually (60+%) have autoantibodies against parietal cell H⁺/K⁺ ATPase (and usually others against intrinsic factor). This is the usual cause of the achlorhydria (i.e., greatly diminished or no stomach acid) and Addisonian pernicious anemia. JAMA 278: 1946, 1997; update Gastroenterology 120: 377, 2001.

Around 10% of these patients go on to develop stomach cancer.

Many of these patients have other autoimmune endocrine diseases as well. The three to remember are Addison's disease of the adrenals, Hashimoto's disease of the thyroid (Arch. Int. Med. 159: 1726, 1999), and insulin-dependent diabetes.

* Future pathologists: Since there is no acid and no feedback, the G-cells undergo hyperplasia in the antrum. They are a single layer of clear cells. This is a breeding-ground for carcinoids supposedly.

Work on autoimmune gastritis is overshadowed nowadays by helicobacter, but the finding of anti-parietal cell autoantibodies seems solid. Perhaps those lacking the antibody were really helicobacter-induced atrophy (see below). And helicobacter itself can supposedly trigger the autoantibodies (you think?: Gastroent. 115: 340, 1998). Update: Blood 107: 1673, 2006.

Pernicious anemia
Immunoglobulin on parietal cells
WebPath Photo

{15426}    "atrophic gastritis", gross
{15434}    "atrophic gastritis"
{15561}    early atrophic gastritis, starting on surface

HELICOBACTER GASTRITIS is a serious problem worldwide.

The vast majority of the old "unexplained chronic gastritis" ("type B gastritis") cases are caused by helicobacter. You'll have no trouble recognizing the familiar wiggly creatures on the surface of (often obviously damaged) gastric mucosa. Giemsa, immune, or silver stains show them to advantage.

* Much confusion is being generated right now by talk of various gross patterns on helicobacter gastritis. Usually the antrum gets it worst ("antral predominant", often with hyperacidity), or the whole stomach is involved ("pangastritis"). A minority of patients with helicobacter have the antrum spared ("corpus predominant"), and these people supposedly have atrophy and a low stomach acid that returns to normal after helicobacter is eradicated; obviously this has a lot in common with autoimmune gastritis without helicobacter. Wait to try to figure this out until the matter is more settled.

Helicobacter flourishes in the stomach because it cleaves urea to ammonia under acid conditions (Science 287: 482, 2000). Helicobacter's virulence factor, CagA protein, actually gets inoculated into the stomach cells (Science 287: 1497, 2000). Nobody knows yet exactly what it does to cells after it enters, though it deregulates at least one growth control gene (J. Inf. Dis. 187: 334, 2003). The other virulence factor, VacA (vacuolizing cytotoxin A) is even more mysterious.

There's a chronic infiltrate with both lymphocytes and neutrophils. Lymphoid follicles in the mucosa suggest "Helicobacter". Pyloric metaplasia advances from the antral area into the fundus, perhaps decreasing acid production, and the fundic glands may atrophy as well. You may see intestinal metaplasia, especially near any ulcers that may be present. Acid production may be increased, decreased, or normal.

When the fundus is involved, the fundic glands become shallow ("patchy atrophic gastritis", to be distinguished from autoimmune atrophic gastritis), and typically exhibit intestinal metaplasia (i.e., enterocytes, goblet cells; it's especially pre-malignant -- type III -- when they are filled with "acid mucus/sulfomucus" as in the real intestine) and/or antral metaplasia (neck cells, G-cells). In advanced autoimmune gastritis only, the parietal cells are completely gone.

* The atrophy caused by helicobacter, from the molecular point of view: Dig. Dis. Sci. 49: 1615, 2004.

In any portion, the rugae are likely to flatten and vanish. The process begins at the surface and work downward into the glands. Lesions of various stages are present simultaneously in different parts of the stomach. Eventually, the surface will come to exhibit at least some intestinal metaplasia and probably some degree of dysplasia.

Helicobacter gastritis involving most of the stomach is the precursor lesion to the epidemic stomach cancers seen in much of the world.

Removing helicobacter cures this illness (J. Clin. Path. 4: 22, 1994). Most people with significant duodenitis (i.e., polys) have helicobacter gastritis (Am. J. Clin. Path. 90: 711, 1988, kids Am. J. Clin. Path. 102: 188, 1994 & Dig. Dis. Sci. 39: 1488, 1994), etc., etc.

Helicobacter KU Collection

Helicobacter KU Collection

Acute gastritis Me after beer, pizza, and aspirin WebPath Photo

Nasogastric tube erosions WebPath Photo

Acute gastritis WebPath Photo

Helicobacter WebPath Photo

Helicobacter pylori Stained black New England Journal of Medicine

{11728}    Helicobacter in gastritis (look close)
{15440}    Helicobacter
{19492}    type B, antrum
{19491}    type B, antrum
{26903}    type A
{26906}    type A
{26909}    type A, some atypia

Gastritis I From Chile In Spanish

Gastritis II From Chile In Spanish

OTHER FORMS OF GASTRITIS:

REACTIVE GASTROPATHY, without helicobacter but with loss of / changes in the antigens of mucin (different changes from helicobacter cases), is today the second-most-common diagnosis made by pathologists on stomach biopsy today (Arch. Path. Lab. Med. 131: 86, 2007). Often the cause is obscure; NSAIDS and bile reflux supposedly are often responsible.

MENETRIER'S DISEASE ("idiopathic hypertrophic gastritis"; "enlarged fold gastitis"): Idiopathic hyperplasia of the surface mucous cells, with corresponding atrophy of the glands. Makes for some big folds, and a lot of protein loss in the excessive mucus. Intestinal metaplasia and neoplasia may form (nice case: NEJM 1/14/88).

Menetrier's is caused (at least sometimes) by helicobacter, and resolves when you clear the bacteria (Gut 35: 701, 1994). Growth factors producing the huge folds: Gut 39: 787, 1996.

{19486}    Menetrier's, gross
{19487}    Menetrier's, histology

Menetrier's disease Pittsburgh Pathology Cases

Watermelon Stomach Joel K. Greenson MD U. of Michigan

* HYPERTROPHIC HYPERSECRETORY GASTROPATHY: Idiopathic hyperplasia of the stomach glands themselves, with excessive numbers of parietal and chief cells.

ZOLLINGER-ELLISON SYNDROME: Gastrinoma (often in the pancreas) causing hyperplasia of the gastric glands. Makes for a very upset, ulcerated stomach.

* GRANULOMATOUS GASTRITIS: Sarcoid, Crohn's, idiopathic (for the latter see Dig. Dis. Sci. 39: 1649, 1994). All are non-caseating, of course.

STRESS ULCERS (the usual "acute erosions") are small (less than 1 cm) areas of loss of some (or all) the mucosa. Note that nobody really knows where "acute gastritis" leaves off and "stress ulcers" begin; probably they're part and parcel of the same reaction pattern.

Nomenclature: If the patient has burns, they are "Curling's ulcers" (* think of a hot curling iron). If the patient has intracranial trauma, they are "Cushing's ulcers" (attributed to vagal stimulation of gastric acid secretion, named for famous neurosurgeon Harvey Cushing).

Their pathogenesis constitutes a major mystery of medicine. Except in Cushing's ulcers, hyperacidity does not seem to be the problem. Most of the factors that produce "acute gastritis" can also help produce stress ulcers. Some workers now favor catecholamine effect (i.e., ischemia) and/or some glucocorticoid effect.

Pre-pyloric erosions are due to stress (Scan. J. Gastr. 24: 522, 1989).

{15425}    "stress ulcer", gross
{18711}    "stress ulcers", gross
{19350}    "gastric erosion", histology
{39426}    hemorrhagic gastritis, nasogastric tube erosions
{07184}    hemorrhagic gastritis, nasty case

Curling ulcers KU Collection

* A sweet-and-simple test for the integrity of your gastric mucosa: swallow some sucrose and test for sucrose in the blood! Lancet 343: 998, 1994.

PEPTIC ULCERS

Peptic Ulcer
Text and photomicrographs. Nice.
Human Pathology Digital Image Gallery

Peptic Ulcer I From Chile In Spanish

Peptic Ulcer II From Chile In Spanish

Peptic Ulcer Text and pictures From "Big Robbins"

Peptic ulcer Photo and mini-review Brown U.

Stomach ulcer WebPath Photo

Stomach ulcer WebPath Photo

Stomach ulcer WebPath Photo

Stomach ulcer WebPath Photo

Stomach ulcer Bleeder WebPath Photo

Gastric Ulcer With a malignant one for comparison Ed Uthman

{10471}    benign stomach peptic ulcer
{15438}    benign stomach peptic ulcer
{15439}    benign stomach ulcer, with clot
{15560}    histology of ulcer, arrow marks bleeding point
{19372}    peptic ulcer
{26888}    peptic ulcer, stomach

Ulcers resulting from the digestive action of acid-pepsin ("no acid, no ulcer") on the gastric mucosa. A common problem, somewhat more common in men, usually subclinical, prone to remit and relapse ("once an ulcer, always an ulcer"). "Ulcers" can occur anywhere along the GI tract. Frequency:

80% duodenum

19% stomach

1% elsewhere

The early wisdom was that almost all patients with either gastric or duodenal ulcer patients have helicobacter on board (Gut 35: 19, 1994), and eliminating the creature eliminates the disease. Of course that was an exaggeration; a large minority of stomach ulcer patients are helicobacter-negative (Gastroent. 128: 1845, 2005).

Other risk factors for ulcer include...

• being under physical or emotional stress (maybe; Gastroent. 99: 1628, 1990)
• smoking
• taking aspirin or NSAID's
• boozing
• a family history
• blood type O (* blood group factors, notably Lewis B, mediate attachment of helicobacter: Science 262: 1892, 1993; a factor BabA binds to blood group O though the link to Lewis B is clearly more important Scand. J. Gastro. 32: 16, 1997)
• having a job that requires you to be physically active (Gut 32: 983, 1991)
• * non-secretor status (ask a blood banker or criminologist, these people keep Lewis B on board)
• hypercalcemia from any cause (enhances gastrin secretion)
• cirrhosis and/or emphysema (make life stressful)
• ... and having a stomach tube down (Surgery 111: 274, 1992).

  None of these are overwhelmingly powerful.

  You WILL get an ulcer, and probably several, if you develop a gastrinoma.

  Ask a gastroenterologist about the differences among ulcer patients.

  Those with duodenal ulcers tend to secrete acid too abundantly when stimulated, and to empty their stomachs too readily.

  Gastric ulcer types tend to have low-normal levels of acid, and tend either to have chronic gastritis or take lots of aspirin or other substances noxious to the stomach. People with longstanding gastric ulcers almost all have "chronic gastritis" in the antrum, and intestinal metaplasia near the ulcer.

  NSAID Gastritis
  Joel K. Greenson MD
  U. of Michigan
  
  

  * Whether or not helicobacter is on board, gastric ulcers seem to be preceded by abnormalities of the phospholipids in the gastric epithelium, with loss of their normal protective function. This may be a common pathway by which helicobacter, atrophic gastritis, cirrhosis, certain animal models, and others produce ulcer (Gastroent. 107: 362, 1994).

Most (almost all) patients with duodenal ulcers, and a majority of those with gastric ulcers, now are known to have helicobacter on board, and the bug is thought to be an important part of the pathogenesis.

In the duodenum, there appears to be a vicious cycle between helicobacter infection and antral metaplasia (J. Clin. Path. 43: 981, 1990, Am. J. Clin. Path. 102: 188, 1994) that permits the bugs to thrive. This is not surprising, considering the abrupt appearance and disappearance of ulcers. Antral metaplasia is a common finding in normal duodenum (Am. J. Clin. Path. 90: 711, 1988), and perhaps this how duodenal ulcers begin.

The rare helicobacter-negative duodenal ulcer patient may have Crohn's, Zollinger-Ellison, taking steroids or NSAID's (review Gut 35: 891, 1994; nobody knows how it works), or just be unlucky (Gut 34: 762, 1993; Am. J. Med. 91: 15, 1991).

Peptic ulcers are usually single, and most are less then 3 cm across. They look sharply punched-out (as you'd expect, rolled borders suggest malignancy). However, they may penetrate deeply. The base is always keep clean by digestive juice. Gastric ulcers are usually on the lesser curvature, and the favorite site is near or in the antrum. Duodenal ulcers are usually in the first portion, but may be anywhere. As scar contracts, the mucosal folds radiate from the ulcer.

Peptic ulcers may cause pain (relieved when food or antacid neutralizes stomach acid, recurring after a meal stimulates stomach acid), hemorrhage, perforate (call the surgeon!) and/or cause fibrosis leading to obstruction (notably of the pylorus). We believe they do not undergo malignant transformation ("cancers often ulcerate, but ulcers seldom/never cancerate").

Future surgeons: You may "CHOP" out the ulcer if it is Chronic, Hemorrhaging uncontrollably, Obstructing the gastric outlet, or Perforated.

BENIGN TUMORS

HYPERPLASTIC POLYPS ("inflammatory polyps") are extremely common and thought to result from exuberant regeneration of the mucosal epithelium. They usually look like multiple little rice grains, but may be larger. Microscopically, they are composed of dilated glands lined with pit-type cells.

The big ones (over 1.5 cm) can turn cancerous (Dig. Dis. Sci. 41: 377, 1996).

{09292}    hyperplastic polyps of stomach
{38656}    hyperplastic polyps of stomach

* INFLAMMATORY FIBROID POLYP is a mass of vessels and stroma looking like granulation tissue, plus a lot of eosinophils.

* JUVENILE POLYPS resemble those we'll meet later in the colon.

ADENOMATOUS POLYPS ("neoplastic polyps", "adenomas") tend to be pedunculated, with villi and/or crypts, and the current definitions require some dysplasia. They are premalignant, there is a link to syndromes and a familial tendency, and maybe half would turn into cancer if left alone (but who wants to do that study?)

* Patients with familial adenomatous polyposis of the colon are especially likely to get these (morphology and genes Am. J. Path. 161: 1735, 2002).

{09333}    adenomatous polyp
{09312}    adenomatous polyp
{09331}    adenomatous polyp

Adenomatous colon polyp Ed Uthman's Pathology Gallery

Adenomatous colon polyp WebPath Photo

GASTROINESTINAL STROMAL TUMORS are the common spindle-cell neoplasms of the stomach, usually bearing a trademark c-kit mutation and stainable antigen, and responding to Gleevic (imatinib). They range from totally benign to highly malignant (South. Med. J. 96: 512, 2003).
The cell of origin is probably most often the interstitial cell of Cajal, in the nerve plexus (Lancet 369: 1731, 2007). Most "leiomyomas", "leiomyoblastomas", and "leiomyosarcomas" are probably "GIST"'s.

Leiomyoblastoma Bryan Lee

Leiomyosarcoma WebPath Photo

{09299}    leiomyoblastoma

GASTRIC CARCINOID is worth mentioning here because of the big medicolegal flap about long-term gastric acid suppression perhaps causing gastric carcinoids. High levels of gastrin causes enterochromaffin cell hyperplasia, and most people who get gastric carcinoid have high gastrin levels (atrophic gastritis or Zollinger-Ellison). And rats actually get such tumors after lifetime omeprazole. Stay tuned.
* Gastric carcinoinds that produce ghrelin: J. Clin. Endo. Metab. 86: 5052, 2001).

* Subclassifying them: Ann. Surg. 242: 64, 2005. Those resulting from atrophic gastritis almost never kill, other types are more aggressive.

GASTRIC ADENOCARCINOMA (common "stomach cancer"; Lancet 362: 305, 2003; Ann. Surg. 241: 27, 2005)

While its prevalence in the U.S. has decreased strikingly in recent decades, this continues to be an important cancer killer in every country. Around 15,000 people per year die of stomach cancer in the U.S. Rates in the rest of the world are also declining.

Risk factors include:

• diet -- smoked food, ethnic pickled delicacies, lack of green vegetables, liking your meat well-done (Int. J. Cancer 71: 14, 1997), lack of meat / animal fat (Int. J. Cancer 93: 417, 2001; studies are contradictory), nitrates/nitrites (obviously a lot of this is junk science)
• status post partial gastrectomy (the old ulcer operation)

• helicobacter
• blood groups A and AB (* for some mysterious reason, helicobacter that produces cytotoxin associated gene A are more prevalent in people with a dose of blood group A)

Diet and environment are evidently much more important than ethnic background. First-generation immigrants have the risk of their home countries; second-generation immigrants the risk of their new countries (Ann. Surg. 241: 27, 2005).

There are two major types of gastric adenocarcinoma, with different cells of origin.

(1) DIFFUSE INFILTRATIVE GASTRIC ADENOCARCINOMA arises from the neck cell.

It exhibits small glands made of polyhedral cells with round, tame-looking nuclei, or cells infiltrating singly. The most common subtype Is the signet-ring cancer.

Helicobacter, autoimmune gastritis, and intestinal metaplasia are not risk factors.

The frequency of this cancer is actually increasing dramatically in the US (CDC: Arch. Path. Lab. Med. 128: 765, 2004). No one knows why.

* Hereditary diffuse gastric adenocarcinoma, an anti-oncogene deletion syndrome, is caused by mutated E-cadherin (CDH1): Gut 53: 814, 2004; JAMA 297: 2360, 2007. Signet-ring cancers begin at the body-antral junction, and are already invading the upper mucosa long before they are visible on endoscopy. Prophylactic gastrectomy seems like a good idea.

(2) INTESTINAL TYPE GASTRIC ADENOCARCINOMA typically arises in the setting of longstanding "atrophic gastritis" or other "chronic gastritis", usually in the presence of helicobacter and/or autoimmune gastritis and/or intestinal metaplasia and/or bile reflux.

It features large glands made of tall cells with rod-shaped nuclei (as in the more common, more familiar primary carcinomas of the colon). This is the common type of stomach cancer in the high-risk countries.

How we discovered the link to helicobacter: Am. J. Clin. Path. 100: 236, 1993); Cancer 73: 2691, 1994; Cancer 75: 2203, 1995; Dig. Dis. Sci. 41: 950, 1996. Does eradicating helicobacter prevent progression of intestinal metaplasia to cancer? Yes! (Gut 53: 1244, 2004. No! JAMA 291: 187, 2004.

* News: Around half of stomach cancers arising in the gastric cardia (but not elsewhere) probably arise from Barrett's esophagus (Arch. Surg. 129: 609, 1994).

* Some cancers, espsecially after partial gastrectomy, are rich in lymphocytes and these are almost always packed with Epstein-Barr virus (Cancer 74: 805, 1994). Similar tumors are common in the Far East regardless of previous surgical procedures. Stomach cancers "with lymphoid stroma" are less aggressive than common gastric cancers (Arch. Surg. 129: 615, 1994), even if they are not the result of previous surgery, and regardless of Epstein-Barr positivity (the virus is usually present). Histopathology 36: 252, 2000; molecular biology Gastroent. 121: 612, 2001; Am. J. Path. 161: 1207, 2002; Am. J. Clin. Path. 121: 237, 2004.)

The gross is the usual for a cancer (a cauliflower, an ulcer, or diffuse invasion). The histology is what you'd expect. In either case, you may see invasive glands, papillae, signet-ring cells, mucus lakes, desmoplasia, and most anything else, though when you see signet ring cell invasion, it is usually the "diffuse" type rather than the "intestinal" type. Terms: LINITIS PLASTICA: "leather bottle" stomach from a diffusely-infiltrating, desmoplastic cancer. KRUKENBERG TUMOR: Drop-metastases causing enlargement of the ovaries. SISTER MARY JOSEPH'S NODE: metastasis to the umbilicus (named for the Mayo brothers' scrub nurse). RECTAL SHELF ("of Blumer"): Drop-metastases to the lowest place on the peritoneum (remember the "pouch of Douglas"?)

* Grading stomach cancer is based on whether the cancer makes tubules and/or mucus (Goseki I-IV): Gut 35: 758, 1994; some studies claim this gives no useful prognostic information beyond the stage; Cancer 88: 2114 & 2426, 2000 did find it to be of some help.

Symptoms are also what you'd expect -- nausea, vomiting, early satiety, GI bleeding. As you'd also expect, there are usually no symptoms until it's too late. (If you have an extra cauliflower in you stomach, you'd never know it.) There is so much stomach cancer in Japan that people get endoscoped routinely in search of it, and there are many cures (unlike in the US). (For some reason that no one understands, the Japanese have a tremendously high rate of atrophic gastritis, conceivably from the local strains of helicobacter, and this is where most of these cancers arise: Gut 55: 1545, 2006). Biopsy all stomach ulcers you see -- even a cancer may shrink on a regimen of H2-blockers and antacids.

Stomach Tumors I From Chile In Spanish

Stomach Tumors II From Chile In Spanish

Gastric Adenocarcinoma Text and photomicrographs. Nice. Human Pathology Digital Image Gallery

Gastric Carcinoma Text and photomicrographs. Nice. Human Pathology Digital Image Gallery

Gastric carcinoma Ed Uthman's Pathology Gallery

Stomach cancer Pittsburgh Pathology Cases

Stomach cancer WebPath Photo

Stomach cancer WebPath Photo

Stomach cancer Linitis plastica WebPath Photo

Stomach cancer at autopsy WebPath Photo

Stomach cancer Adenocarcinoma WebPath Photo

Stomach cancer Adenocarcinoma WebPath Photo

Stomach cancer Anaplastic adenocarcinoma WebPath Photo

Stomach cancer Signet ring adenocarcinoma WebPath Photo

Stomach carcinoma Positive cytokeratin stain WebPath Photo

{17511}    Stomach cancer, exophytic
{10472}    Stomach cancer, ulcerated
{15509}    Stomach cancer, linitis plastica, gross
{15562}    Stomach cancer, linitis plastica, histology
{08818}    Stomach adenocarcinoma, intestinal type
{17517}    Stomach adenocarcinoma, intestinal type
{10473}    Stomach adenocarcinoma, diffuse type
{39380}    Stomach adenocarcinoma, diffuse type
{39392}    Stomach adenocarcinoma, diffuse type
{15510}    Signet ring stomach cancer
{19346}    Stomach cancer, superficial
{35258}    Stomach adenocarcinoma, Pap smear

Most gastric adenocarcinomas are probably preceded by high-grade carcinoma-in-situ/dysplasia (see Arch. Surg. 140: 644, 2005; dysplasia usually invades the mucosa soon, and until it penetrates the muscularis propria, it's called "early gastric cancer" (EGC). It can stay in the mucosa for a long time (Arch. Path. Lab. Med. 114: 1046, 1990).

Some diffuse-infiltrating cancers may start de novo, without dysplasia.

{15443}    early stomach cancer

Detected late (and it still usually is), stomach cancer has a generally poor prognosis.

{15441}    non-metaplastic dysplasia
{15444}    non-metaplastic dysplasia

The mainstay of therapy for stomach cancer is still surgery.

* Serum tumor markers: CA 19-9, CA 72-4. Am. J. Surg. 169: 595, 1995.

STOMACH LYMPHOMAS (and other GI lymphomas) are less common than carcinomas but have a better prognosis. Since they tend to be bulky, patients present with obstruction.

WESTERN ("American") LYMPHOMAS are usually familiar B-cell lymphomas. Helicobacter seems to be the big risk factor: J. Clin. Path. 47: 437, 1994, J. Clin. Path. 47: 436, 1994; Lancet 345: 26, 723, 724 & 798, 1995 (no surprise, since helicobacter makes lymphoid follicles grow). However, many gastric lymphomas are helicobacter-negative and different genetically (Gut 52: 641, 2003).

* MEDITERRANEAN LYMPHOMAS occur especially around the Near-East, and usually feature plasmacytoid differentiation. A subset is alpha-heavy chain disease.

* SPRUE-ASSOCIATED LYMPHOMA exhibits T-cell markers (reviews Gut 49: 804, 2001; Am. J. Clin. Path. 127: 701, 2007; the more anaplastic primary small bowel lymphomas tend to be preceded by celiac sprue while the less anaplastic ones don't);

* PSEUDOLYMPHOMA of the stomach is an old term that has no meaning in light of today's molecular diagnostic techniques (Cancer 79: 1656, 1997). You can't always tell severe chronic inflammation from true lymphoma just on histopathology, but today's biotech resolves even the toughest calls by demonstrating clonality (Gut 55: 782, 2006).

Helicobacter lymphoma
Joel K. Greenson MD
U. of Michigan