ADHESIONS are fibrous bands that follow peritonitis from any cause (most typically, peritoneal irritation during surgery). These can snare loops of bowel and require re-entry into the abdomen.

{40680}    adhesions
{40681}    adhesions

INTUSSUSCEPTION is a telescoping of the bowel into itself, often because of a bump in the wall (big Peyer's patch, polyp, Meckel's) and the gut mistakes it for dinner.

Most common in kids, you can see it at any age. Future radiologists: Here's one you can sometimes both diagnose and cure with a barium enema!

* Philologists: The trapped part is the "intussusceptum". The enclosing part is the "intussuscipiens".

{09832}    intussusception
{38677}    intussusception, colonic, with gangrene
{39391}    intussusception

Intussusception Great photos Pittsburgh Pathology Cases

VOLVULUS: Twisting of a loop of bowel 360 degrees around its stalk (or Meckel's). Rare, but don't miss it. When it occurs in the colon (most often sigmoid, but anyplace is possible), the lowest-level medical student is given the privilege of untwisting it, while everyone else stands way back (why?)

{07210}    volvulus

Cecal volvulus WebPath Photo

{24441}    meconium ileus and volvulus (cystic fibrosis)
{46271}    volvulus, sigmoid colon ("chronic")

CARCINOID TUMORS: Cancers arising from the endocrine (paracrine, Kulchitsky, enterochromaffin, APUD, neuroendocrine, neurosecretory, chromaffin, etc., etc.) cells of the gut or elsewhere. Most look and act relative non-aggressive, but they are often discovered only when metastatic disease has already appeared. Reviews Lancet 352: 352, 1998; NEJM 340: 858, 1999; Gastroent. 128: 1717, 2005; Am. Fam. Phys. 74: 429, 2006.

The histology looks like a non-secreting adenoma. The cells are monotonous, and the architecture is is often like simple shapes from geometry / an arabesque. Depending on the site, carcinoids tend to secrete various hormones (check "Big Robbins" for the list, which is long).

You'll see neurosecretory granules, if you stain for them or use EM. As you know, they'll be at the bottoms of cells to synapse with the nerve twigs. Synaptophysin is a good stain to use to see them; it helps make the call.

Carcinoids are very common in the appendix (1 in 300 autopsies). Here, and in the rectum, they have only limited ability to metastasize.

Carcinoids elsewhere may be more aggressive.

* The molecular biology is only now starting to be worked out. There seems to be no trademark mutation yet (Cancer 109: 2420, 2007); the little that's known does not support the WHO's idea that carcinoids and islet cell tumors should be classified together as "gastroenteropancreatic neuroendocrine tumors" (Cancer 104: 2292, 2005; this isn't going to affect clinical care in any case).

Today's pathologists distinguish tame "carcinoids", nastier "well-differentiated neuroendocrine carcinoma", and the nastiest "poorly-differentiated neuroendocrine carcinoma" based on mitotic counts and cellular atypia.

When the liver cannot detoxify the secretory products of the carcinoid (i.e., it is not in the portal system, or there are liver metastases), patients are prone to symptoms.

The classic carcinoid syndrome (blamed in part on serotonin) involves (1) wheezing; (2) flushing; (3) fibrosis of the right-sided endocardium (lung detoxifies whatever does this).

* The truth is that nobody knows which tumor product causes the fibrosis of the right-sided endocardium, though serotonin is once again a "usual suspect".

Prolonged survival is common in carcinoid disease, even with liver metastases. (Surgeons: You may de-bulk them -- and this helps; see Arch. Surg. 141: 1000, 2006; arterial embolization often helps as well Cancer 104: 1590, 2005.)

Future clinicians: Suspecting a carcinoid? Check the urine for the serotonin metabolite, 5-HIAA (5-hydroxy-indole-acetic acid). Even better... if you really think this might be carcinoid, an isotope scan using 111-In-pentetreotide (an octreotide analogue) will light up carcinoids (good for other neuroendocrine tumors too; in high doses it can used for radiotherapy).

By the time you are in practice, the standard may be blood chromogranin A as screen (Ann. Surg. 243: 273, 2006). Several circulating tumor markers are known including chromogranin A (Cancer 10: 459, 2003. Watch blood neurokinin A as a marker for carcinoid, especially as a marker for its continued presence after resection / responsiveness to octreotide therapy (Gut 55: 1581, 2006).

Carcinoid Nice argentaffin stain Pittsburgh Pathology Cases

Carcinoid WebPath Photo

Carcinoid WebPath Photo

Carcinoid WebPath Photo

Carcinoid Tom Demark's Site

{19521}    carcinoid, appendix, gross
{19522}    carcinoid, appendix, gross
{19508}    carcinoid, small bowel, histology
{49187}    carcinoids, small bowel, gross
{24678}    carcinoid, small intestine
{26348}    carcinoid, ileum
{09175}    carcinoid, electron micrograph
{09176}    carcinoid, electron micrograph

Future pathologists mostly:

* ARGENTAFFIN: Capable of reducing silver (and thus having the granules stain black) without a separate reducing agent.

* ARGYROPHIL: Capable of reducing silver (and thus having the granules stain black) so long as a separate reducing agent is supplied. All argentaffin cells are also argyrophil.

CHROMOGRANIN, now a tumor marker in clinical use, is a classic immunostain for carcinoid, adrenal medulla, and generally for "neuroendocrine" stuff. SYNAPTOPHYSIN is also in widespread use to confirm that a GI tumor is carcinoid or at least shows "neuroendocrine differentiation."

* Foregut carcinoids are almost never argyrophil. (NOTE: This includes lung, duodenal, and biliary carcinoids. These are not usually serotonin / "carcinoid syndrome" producers, but might make something else.) All about gastric carcinoids: Cancer 73: 2053, 1994.

* Midgut carcinoids are almost always argyrophil. (NOTE: This includes small intestinal, appendiceal, and most colonic carcinoids. These are usually hormonally active.)

* Hindgut carcinoids are variable. (NOTE: Descending colon and rectum.)

ADENOCARCINOMA OF THE DUODENUM / SMALL INTESTINE is thankfully rare. Known risk factors include Lynch's, familial adenomatous polyposis, Peutz-Jegher's, Crohn's and celiac sprue (Gut 52: 1211, 2003).

* "Autistic enterocolitis" is still under discussion, the idea being that the measles-vaccine virus causes both a characteristic gut lesion and regressive autism. Whatever is going on with the measles virus, the gut lesion is hard (at best) to distinguish from "no pathology" (Histopathology 50: 371, 2007). More than a decade after a truly terrible article in "Lancet" began the whole business, your lecturer believes (pending further evidence) that "autistic changes in the bowel mucosa" are either normal histology (as in the "Lancet" article) or the effects of these kids' retaining stool.

Small bowel biopsy can be performed using standard endoscopy, or a swallowed device ("Watson capsule", "Storz capsule") that is monitored on fluoroscopy and then retrieved (Scand. J. Gastro. 36: 1230, 2001). "Wireless capsule endoscopy" is an exciting new technology. The patient swallows a capsule containing a tiny video camera, a transmitter, and an antenna. Using it to confirm the diagnosis of Crohn's: Gut 52: 390, 2003.

Tiny camera setup

APPENDIX

Appendix Exhibit Virtual Pathology Museum University of Connecticut

Worm in appendix Or perhaps a Meckel's? KU Collection

There's less "mystery" to our having the appendix than "Big Robbins" would have you believe. Many animals have a large pouch here that they need for digestion. We've still got it, but it's no asset. (* Darwin's world; the imperfections of nature tell stories of our origins. Pseudoscience fans: Ignore what you've heard about the appendix being essential for the developing immunity of the unborn child. It's only one of many sites where B-cells can mature. It's also handy for us in this day of modern antibiotics -- perhaps it's a reservoir for the "nice" bacteria which can repopulate the gut. I look forward to a study showing that people who have had appendectomies do worse after bacterial colon infections generally.)

ACUTE APPENDICITIS

A familiar, common surgical problem, mostly of young people, caused (in most cases, we think) by obstruction of the lumen (usually a fecalith or hyperplastic lymphoid tissue, less often a tumor, gallstone, or maybe pinworms).

Probably impaction by a fecalith is most important, since appendicitis is rare in countries with high-bulk eating habits.

Two percent of healthy children have a fecalith in the appendix on imaging studies, so this finding alone is not proof of appendicitis.

In folks older than 30 with acute appendicitis, about 10% have obstruction by a serrated adenoma, far more than random. You do have to look thoroughly (Am. J. Clin. Path. 126: 875, 2006).

The neurons in an acutely-inflamed appendix are likely to be hypertrophied, indicating that there's been obstruction for a long time before things got really nasty (Arch. Path. Lab. Med. 124: 1429, 2000).

Measles was once famous for causing appendicitis that exhibits the classic Warthin-Finkeldey giant cells. Two cases from contemporary Korea: Arch. Path. Lab. Med. 126: 82, 2002.

{20088}    appendicitis with fecalith

Appendix pinworms

Wikimedia Commons


As mucus continues to be secreted behind the obstruction, the pressure builds, the epithelial barrier breaks, the bacteria can penetrate the wall, and true infection quickly begins.

As the osmotic pressure within the pus builds up to tremendous levels, the appendix becomes gangrenous (vascular compromise) and/or bursts (nasty, you'll get peritonitis or worse).

Early symptoms are a poorly-defined belly-ache (typically referred to the umbilicus) and no appetite ("Would you like some ice cream?" "NO!!"), with maybe fever and leukocytosis. Later, when the appendix presses against peritoneum, the pain becomes knife-like and peritoneal signs appear. Call a surgeon.

The pathology is what you'd expect. Early, there's the obvious hyperemia. Later, there's fibrin on the outside, pus on the inside. At the end, there's gangrene. Again, the weakened wall may rupture, spreading the infection.

{13283}    acute appendicitis, gross
{10196}    acute appendicitis, gross
{11445}    acute appendicitis, gross
{19526}    acute appendicitis, histology
{17558}    acute appendicitis, histology
{17562}    acute appendicitis, polys

Acute Appendicitis Australian Pathology Museum High-tech gross photos

Acute Suppurative Appendicitis Text and photomicrographs. Nice. Human Pathology Digital Image Gallery

Acute appendicitis Urbana Atlas of Pathology

Future surgeons: If fewer than 20% of your operations for "appendicitis" don't reveal a normal appendix, your index of suspicion is low. Once in there, you may find mesenteric adenitis (Yersinia enterocolitica), an inflamed Meckel's, the GI 'flu, gonococcal salpingitis, etc., etc.

GRANULOMATOUS APPENDICITIS, which looks histologically like Crohn's but is limited to the appendix, has a benign follow-up (J. Am. Coll. Surg. 185: 13, 1997).

* I got a chuckle from a surgeon's claim (Lancet 347: 1076, 1996) that a "histologically normal appendix" removed at surgery for suspected appendicitis often exhibits widespread immune activation. The "immune activation" looks like the result of overstaining the sections.

MUCOCELE of the appendix is an appendix transformed into a bloated, tense-walled bag of mucus.

The cause may be (1) a hyperplastic polyp of the appendix; (2) a mucin-producing adenoma; (3) a mucinous cystadenocarcinoma.

Of these:

• the hyperplastic polyp is slimy and harmless;
• the cystadenoma is likely to perforate and spew cell-free mucus around the area;
• the cystadenocarcinoma is likely to perforate and spread its cells around the peritoneum, resulting in PSEUDOMYXOMA PERITONEI, a patient's and surgeon's nightmare where loops of bowel are frozen together in a desmoplastic slime.

More about the spectrum of mucinous tumors of the appendix: Arch. Path. Lab. Med. 134: 871, 2010.

CARCINOID is the common tumor of the appendix. It is a very low-grade malignancy.

* There are two varieties: Arch. Path. Lab. Med. 134: 871, 2010. Common carcinoid generally has a good prognosis, but if the pathologist finds a goblet cell carcinoid, it's good to do a right hemicolectomy after.

COLON AND RECTUM

Colon Exhibit Virtual Pathology Museum University of Connecticut

Colorectal Images University of Washington Pictures and comments

{49202}    melanosis coli from cascara laxatives, the terminal ileum is normal color

Lymphocytic colitis
Joel K. Greenson MD
U. of Michigan



Terms:

TENESMUS is the continuous, painful urge to defecate, whether or not you really need to do so. Any inflammatory problem in the anus or rectum is likely to lead to tenesmus, which is very unpleasant.

DYSENTERY is the passage of bloody-mucoid stools, usually not voluminous, usually painful.

BIRTH DEFECTS

MALROTATION may first become apparent when the inflamed appendix isn't where it should be. REDUPLICATION may produce double-barreled portions of the colon or rectum. One kid in 5000 has an IMPERFORATE ANUS (failure of the cloacal diaphragm to open; there are several varieties, including those with fistulas to nearby organs).

{49199}    imperforate anus ("atresia of the anus")

* There are normally some white cells (mostly lymphocytes, plasma cells, and some eosinophils) in the colonic mucosa, but they are not so numerous as in the small bowel, and if they extend all the way to the muscularis mucosae, there is probably some real inflammation here.

* ACUTE TYPHLITIS today describes bacterial ulcers of the cecum, a potentially deadly hazard in those who lack neutrophils. Update Cancer 104: 380, 2005.

DIVERSION COLITIS ("pouchitis") results from depriving mucosal cells of the short-chain fatty acids they need to get from the fecal stream. This can happen when a diverting colostomy is performed proximal to a portion of bowel; we treat it with fatty acid enemas.

HIRSCHSPRUNG'S DISEASE ("congenital megacolon"; Am. Fam. Phys. 74: 1319, 2006; seven consonants in a row) results from failure of Auerbach's and Meissner's plexuses to develop over a stretch of bowel, usually rectosigmoid. If the entire colon is involved, it's AGANGLIONOSIS.

This isn't rare. Around 1 in 6000 people suffer from Hirschsprung's.

* Down's children have an increased rate of Hirschsprung's.

Every once in a while, it develops in an older child or adult.

Future pathologists: You will make the diagnosis on RECTAL SUCTION BIOPSY, which samples the mucosa without any need to get the ganglion cell layer itself. In the absence of proper ganglia, the unmyelinated nerve fibers in the mucosa are thicker and more abundant (Arch. Path. Lab. Med. 122: 721, 1998), and distinguishing this from normal is usually easy.

{20090}    aganglionic megacolon

Hirschsprung's WebPath Photo

* The first Hirschsprung's gene turned out to be an allele at the RET receptor (MEN-IIb locus, for GI tract ganglioneuromas.) See Nature 367: 319, 1994; good RET product seems to be required to prevent apoptosis of neurons, at least in an animal model (J. Clin. Inv. 118: 1890, 2008). More recently, both endothelin 3 and endothelin receptor have proved to be Hirschsprung loci.

* INTESTINAL NEURONAL DYSPLASIA is a Hirschsprung's variant with an okay Auerbach's plexus but lots of giant ganglia in the submucosa instead of the hypertrophic nerve trunks and excessive adrenergic and cholinergic fibers seen in the submucosa in Hirschsprung's. See Gut 48: 671, 2001. Slow-transit chronic constipation ("colonic inertia") might perhaps be a forme fruste of IND, with malformations of the ganglionic plexus. One report: Eur. J. Gastro. 12: 755, 2000.

For an adult, there are many causes of megacolon, including damage to the nerve tissues from inflammatory disease. Pretty much the only thing that destroys ganglion cells is Chagas' disease.

{49197}    acquired megacolon

DIVERTICULAR DISEASE ("ticks")

This common problem is the result of the mucosa pooching out through the weak spots where vessels penetrate the muscularis propria 120 degrees on either side of the mesentery.

At least a few diverticula are present in most older people eating a "western diet". The cause, of course, is high intra-lumenal pressures necessary to propel these peoples' hard little feces. As you would expect from the etiology, diverticula are most numerous distally.

Purists: Of course, these are really "pseudo-diverticula".

Usually asymptomatic (the bowel complaints are a result of the high intraluminal pressures), uncomplicated DIVERTICULOSIS may result in copious bleeding if a feeder artery gets nicked.

{42227}    colonic diverticulosis, gross (inflated specimen)
{08086}    colonic diverticulum, histology (this is all mucosa, protruding out into adventitia)
{10514}    colonic diverticulum with bleeding point
{19702}    diverticulosis coli, x-ray
{24425}    diverticulosis coli, x-ray
{39995}    diverticulosis; barium fills the "ticks"

DIVERTICULITIS ("left-sided appendicitis") results from one diverticulum getting infected, probably when a fecalith occludes its mouth and lets bacteria proliferate.

Suppuration may result, and nearby diverticula may become involved when bacteria spread and edema narrows their mouths.

The process usually subsides, but surgery may be required. Severe diverticulitis may cause scarring and chronic problems.

FUNCTIONAL BOWEL SYNDROME ("spastic colon") is cramping, constipation, and/or diarrhea without a good anatomic correlate.

Long attributed to "emotional causes", and then to "inadequate fiber in the diet", at least part of the problem is uncoordinated peristalsis, resulting in a portion of the bowel trying to push feces through a distal portion that is clamped shut ("segmentation").

This may also be a mechanism underlying diverticular disease.

* "The mind and the gut": The "emotional causes" business may reflect the common experience that anxiety speeds transit time, and depression slows it; some enterprising psychiatrists actually quantitated this in 1996, and found that anxious psych patients averaged a 14 hour transit time, depressed psych patients averaged a 49 hour transit time, and controls averaged a 42 hour transit time (Br. Med. J. 1996).

* Future pathologists: Ignore anything anybody tells you are determining post-mortem interval from how far dinner (eaten at a known time) has passed along the gut.

* Amoebas probably are not an important cause of functional bowl syndrome symptoms (Lancet 349: 89, 1997).

* Type 3 serotonin receptor blocker (alosetron) for spastic colon: Lancet 355: 1035, 2000. The medicine was approved too fast and killed people by producing ischemic colitis: Lancet 357: 1544, 2001. It's now back, but be careful.

HEMORRHOIDS are dilated perianal venous plexi.

The causes are (1) constipation and straining at stool; (2) venous stasis of pregnancy; (3) portal hypertension.

Rectal problems attributed to hemorrhoids may simply be due to constipation. However, a thrombosed or twisted-infarcted hemorrhoid can be very painful. Bleeding hemorrhoids in portal hypertension can be fatal (Dr. Livingstone, of "I presume" fame, died this way; he may have had portal hypertension due to schistosomiasis).

Please don't forget that an anal carcinoma can look like a prolapsed hemorrhoid.

Hemorrhoids Text and photomicrographs. Nice. Human Pathology Digital Image Gallery

ANGIODYSPLASIA of the colon is a dilatation of vessels, usually in the cecum of older people, that can bleed slowly or copiously.

Angiographers see this lesion more readily than do pathologists, since the lesion collapses on removal from the body.

Angiodysplasia Endoscopic photos.

{08088}    angiodysplasia of cecum; the glands are normal

INFECTIOUS COLITIS

The bacteria that cause infectious colitis are already familiar to you, and include shigella, salmonella, campylobacter, yersinia, and some E. coli.

In the unlikely event that this is biopsied, the pathologist will see neutrophils in the epithelium and lamina propria. The glands will not be disrupted, and there will not be plasma cells; the latter is very helpful in being sure this is not ulcerative colitis.

IDIOPATHIC ULCERATIVE COLITIS (Lancet 359: 331, 2002).

Ulcerative Colitis Text and photomicrographs. Nice. Human Pathology Digital Image Gallery

Ulcerative Colitis Gross and Microscopic Wikimedia Commons

Inflammatory Bowel I From Chile In Spanish

Inflammatory Bowel II From Chile In Spanish

Inflammatory Bowel III From Chile In Spanish

Inflammatory Bowel IV From Chile In Spanish

An inflammatory disease of unknown etiology but predictable pathology.

The disease begins in the rectum and may extend up as far as the cecum. The pathology is continuous, without the "skip lesions" of Crohn's. (* Well, sometimes it's patchy, but usually it's continuous up from the rectum. Am. J. Gastro. 92: 1247, 1997; J. Clin. Path. 49: 319, 1997.)

Involvement of the terminal ileum is called "backwash ileitis" (review for pathologists, with criteria: Am. J. Clin. Path. 126: 365, 2006; focus on how to tell it from Crohn's; not surprisingly, bachwash ileitis is continuous and confined to the mucosa). Otherwise, the small bowel is spared.

There may be systemic problems, most notably enteropathic arthritis, erythema multiforme, and uveitis, as well as sclerosing cholangitis and even the dread, necrotizing skin lesion "pyoderma gangrenosum".

* An interesting finding is that, if your assay is super-sensitive, a large majority of ulcerative colitis and/or primary sclerosing cholangitis patients have small amounts of anti-neutrophil cytoplasmic antibodies on board (Am. J. Clin. Path. 99: 277, 1993). These antibodies seem to be directed against lactoferrin, cathepsin, lysozyme, and/or beta-glucuronidase, but not proteinase 3 (Wegener autoantigen) or myeloperoxidase (polyarteritis autoantigen).

The pathology is inflammation (predominantly plasmacytic), hemorrhage and tissue loss. Except in the most severe cases, the damage is strictly limited to the mucosa.

Look for "crypt abscesses", accumulations of neutrophils in the dilated bases of surviving colonic crypts. These are fun to find, and are usually abundant in ulcerative colitis, but not pathognomonic of anything.

As the ulcers coalesce, the surviving mucosa sticks up as PSEUDOPOLYP. These may grow long and look like worms. Or they may tunnel under a "bridge" of intact mucosa.

In the most severe cases (as with any severe, extensive inflammatory colonic disease), "toxic megacolon" may develop, with the bowel wall paralyzed and the lumen filled with incredibly nasty stuff. Call a surgeon.

In milder cases, lesions in various stages of healing are common.


{26822}    ulcerative colitis, gross
{08113}    ulcerative colitis
{08809}    ulcerative colitis with atypia (worse on the bottom)
{26825}    ulcerative colitis, good pseudopolyps
{10172}    ulcerative colitis, histology
{10175}    ulcerative colitis, crypt abscess
{10178}    ulcerative colitis
{11554}    ulcerative colitis, crypt abscess
{49203}    ulcerative colitis
{24809}    ulcerative colitis, pseudopolyps, gross
{24422}    pseudopolyp, histology; there has been substantial healing of the mucosa between the pseudopolyps, which in a better case would be ulcerated

Ulcerative colitis, acute lesions
Classic drawing
Adami & McCrae, 1914


Pseudopolyp and ulcer Tom Demark's Site

Crypt abscess Tom Demark's Site



The cause remains obscure.

By now, there is a consensus that the disease is caused by some immune reaction between the gut mucosa and the contents of the large intestine. Beyond this, there's still no unifying a large number of observations (Lancet 369: 1025, 2007).

It's easiest to think that some bacterial product in the gut of specially-vulnerable people damages the colonic epithelium, shutting down metabolism of fatty acids (Gut 35: 73, 1994; Lancet 343: 35, 1994). The best candidate right now is a fusobacterium that produces butyric acid (Gut 52: 79, 2003).

Or perhaps it's the immune response to the product of some bacterium. One interesting new finding in ulcerative colitis is that administration of the "kinder, gentler" colon bacterium Bifidobacterium longum brings about impressive relief (Gut 54: 242, 2005). Stay tuned.

* A genetic disease with mutated interleukin-10 receptor produces an ulcerative-colitis-like picture beginning early in life. Perhaps this is a clue to the etiology of the idiopathic disease (NEJM 361: Nov 4, 2009.)

Whatever the cause, the disease is increasing in prevalence in the U.S. The disease waxes and wanes, though the talk about "stress" as a precipitator hasn't held up.

Smoking is supposed to make the disease less severe. It's not worth it though.

* The 1997 media hoopla about measles vaccine causing ulcerative colitis (refuted): Lancet 350: 764, 1997.

As you would expect, patients are troubled with bloody diarrhea, and may have systemic symptoms. The most serious complication is the development of adenocarcinoma of the colon.

Gastroenterologists follow patients with this disease, and if the mucosal cells begin to look dysplastic, colectomy is probably advisable (Lancet 343: 71, 1994). If the crypts are involved but the surface spared, the pathologist is required to call "indefinite for dysplasia." The cancer risk continues even when the disease is quiescent (Gastroent. 103: 431, 1992), and historically was said to approach 100% in thirty years. Thankfully, this is no longer the case.

* A group at Stanford has a fluorescent protein that binds selectively to dysplastic epithelium. Watch this one: Nat. Med. 14: 454, 2008).

The worse the ongoing inflammation, the greater the cancer risk (Gastroent. 133: 1099, 2007). But all these patients need cancer surveillance, and for this you need your pathologist.

Today's risks for cancer in all patients, without regard to histology, are 2% at 10 years, 8% at 20 years, and 18% at 30 years (Br. J. Surg. 92: 928, 2005).

Dysplasia is recognized as hyperchromatic nuclei, and scored as low- or high-grade primarily based on whether the nuclei are lined up evenly or not.

High-grade dysplasia calls for colectomy. Right now, a pathologist's call of "low grade dysplasia" probably does not justify colectomy, and pathologists can't agree among ourselves whether it is present in particular specimens: Gut 52: 1127, 2003. But "low grade dysplasia on flat epithelium", has a 50% chance of going malignant in five years (Gastroenterology 125: 1311, 2003).

* Future pathologists: "Special malignant stains" to detect dysplasias: Intracytoplasmic sucrase (Hum. Path. 23: 774, 1992); TAG (Int. J. Cancer 43: 810, 1989). Dysplastic cells have p53 hit: Gastroent. 107: 369, 1994, and src hit: J. Clin. Inv. 93: 509, 1994.

* This is an exciting time for the medical therapy of ulcerative colitis. You'll learn about this, and the colon cancer surveillance these folks require, on rotations. If the sulfa and the steroid enemas fail, and you elect "no surgery", consider cyclosporine by vein (NEJM 330: 1841, 1996). Newer remedies include epidermal growth factor per rectum (NEJM 349: 350, 2003), infliximab (Gastroent. 128: 1805, 2005), rebamipide enemas (Dig. Dis. Sci. 50 S1: S-119, 2005), and the anti-CD3 monoclonal antibody visilizumab (Gastroent. 133: 1414, 2007), and rosiglitazone (Gastroenterology 134: 688, 2008). There are others underway. A more mundane approach may simply involve giving oral phosphatidylcholine (Ann. Int. Med. 147: 603, 2007).

Removal of the colon at any time cures ulcerative colitis.

Future clinicians beware: Shigellosis and amebiasis can mimic ulcerative colitis pretty well. Future pathologists:

• Amebiasis tends to be more severe in the proximal colon.
• In other inflammatory bowel diseases, including shigellosis and salmonellosis, the crypt abscesses tend to be superficial, while in ulcerative colitis, they are deep.
• Salmonellosis usually features only a scanty inflammatory cell infiltrate
• * Someday, we may check stool for fecal S100A12, a neutrophil product that fairly sensitive and specific for inflammatory disease (Crohn's, ulcerative colitis, nasty infections) from irritable bowel syndrome (Gut 56: 1706, 2007).