Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
Pathology Associates Of Lexington, P.A.
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        Colitides, A Linking Classification Outline
      
Colitides

Acute gastroenteritis (AGE) affecting the stomach is unlikely to be biopsied. Transferred through the air or by human contact, it comes on suddenly. When afebrile, without fever, without seriously ill feelings and very primarily nausea and vomiting and stomach cramps, it is likely viral; if it includes a touch of feverish feeling or low grade fever plus general aches and pains, folks refer to it as "stomach flu". If diarrhea, it is almost always non-bloody. Notorious in our area in the winter of 2012-13 is the norovirus GII.4 genotype of the various small round-structured viruses (SRSVs). There can also be bacterial causes and causes by other organisms and toxins. A really-ill, sudden onset with higher fever & bloody diarrhea, a bacterial cause comes into the differential diagnosis. AGE can also come from "food poisoning", norovirus being only one cause. Much of the below has to do with work up of less dramatic situations, except for C. diff. colitis workups.

[on-line endoscopic atlas]
Clinical presentations section
Histological groups section
Endoscopic groups section
Disease entities section

  • clinical presentations: About 15-20% of diarrhea patients who are endoscopically normal will have abnormal biopsy findings3
    1. "watery" diarrhea (without blood, pus, mucous...loose stools):
      • collagenous colitis (CC) .
      • chronic microscopic lymphocytic colitis (CMLC).
      • pericrypt eosinophilic colitis or enterocolitis 22.
      • focal neutrophilic colitis24(Bo-Linn).
      • mastocytic enterocolitis (do mast cell stain)...lamina propria not "inflammed".
      • mast cell rich microscopic colitis23.
      • bile salt diarrhea: post-cholecystectomy syndrome [L09-3721; S10-8641]; Habba syndrome (still have GB which won't accept the hepatic bile...described in 2000)...usually not during night unless late meal. Gallbladder can be so dysfunctional that one has bile-salt diarrhea even pre-operatively & therefore likely to continue postop. [L09-7466]. Around 3,000,000 Americans have bile salt diarrhea (1-2% prevelance).
      • polydipsia (excessive fluid intake): metabolic (such as diabetic mellitus osmotic or diabetes insipidus ADH hormonal insufficiency or ineffective effect on kidneys)), diuretic (such as excessive caffeine intake), stress or anxiety related habit ("habit polydipsia" ), or psychogenic polydipsia of mental disorders.
    2. voluminous (cholera-like) diarrhea:
      • [LMC-02-552 ASLC superimposed on CMLC?]
    3. brief-illness diarrhea:
      • Norwalk epidemic virus (extremely common)
      • E. coli; shigella
      • antibiotic-associated C. diff. associated diarrhea (CDAD).
    4. chronic constipation: see colonic motility disorders.
    5. bloody diarrhea:
      • other diarrheas defecated through bleeding hemorrhoids
      • ischemic colitis
      • true inflammatory bowel disease (IBD)
      • some acute self-limited colitis (ASLC) cases...especially enterotoxigenic (Shiga toxin) E. coli (O157:H7...STEC 0157 [which can become HUS, even proceeding to TTP]); salmonella.
    6. pain and at least occult blood:
      • ischemic colitis
    7. colicky abdominal pain:
      • ischemic colitis.
      • IBS.
      • strictured, stenosing diverticulosis & diverticulitis (which can also contain secondary diverticulogenic active chronic colitis [LMC-04-1055]) & even polyps.
      • many cases of collagenous colitis3.
    8. abdominal pain:
      • almost all colitides.
      • granulomatous appendicitis15: sarcoid, Crohn's, AFB, or fungal.
      • VZV...shingles (affecting a visceral distribution).
      • don't forget porphyria.
  • histological groups:
      • normal histology: the luminal surface epithelial cells should be regularly low columnar. If there begins to be patchy semi-cuboidal shapes & even worse, cuboid to flattened shapes, this is evidence of "injury effect". The lamina propropria cellularity tends mostly lymphocytic but with a few plasma cells and eosinophils. Polys should be absent, but bowel prep may generate a few, even to the point of a little netrophil debris just below the intestinal lumenal surface epithelium.
      • "normal" lamina propria cellularity: normal mucosa vs. mastocytic enterocolitis (do mast cell stain & find =/> 20 mast cells per hpf averaged over about 10 hpfs [do not count cells that touch muscularis mucosae or sides of a crypt...patients may respond to anti-histamine types of therapy20]). Lamina propria has about 13 per 40x hpf & >20 is abnormal, with a diffuse increase (without sheets or nodules) possibly indicating the sort of "functional" entity of "mastocytic enterocolitis" which is not associated with cutaneous or systemic mastocytosis (which, when involving intestine, is likely top be H&E visible with sheets & nodules) and does not have elevated serum tryptase26. Expect to find essentially normal lamina propria in bile salt diarrhea & in polydipsia
      • increased (supraphysiologic) lamina propria cellularity: (increased cellularity is implied when cells seem pressed together, pushing against crypts, rather than loosely situated)3
        • is it "top heavy"? think away from IBD [S09-12662].
        • is it "bottom heavy" or "filling" lamina propria? Consider IBD & consider segmental diverticulogenic colitis [S09-8276].
      • presence of macrophages:
        • pigmented: melanosis coli pigment (implies "laxative abuse") vs. siderotic pigment (implys prior ischemic or nonischemic bleeding).
        • nonpigmented: If increased H&E-visible foamy/granular macrophages, check for (1) d-PAS-positive granular clumps with morphology similar to the d-PAS-positive granular clumps in overlying, intact epithelial goblet cells (therefore, muciphages related to fecal stream stasis [L12-3600 chronic stasis colonopathy], or (2) clear, micro-round-droplet foaminess of xanthomatous or xanthelasmic macrophages, or (3) contain Gram-positive, d-PAS-positive rod organisms named Tropheryma whipplei of Whipple's disease, or (4) contain large quantities of mycobacterial organisms filling the macrophages (likely MAC), mycobacteria being acid fast bacilli (AFB) positive by the acid fast stain & Gram positive, sometimes beaded (but with a lipid coating that tends to significantly impede or block the staining).
      • summit lesion:
        • pseudomembraneous colitis [a dramatic case with pneumoperitoneum, L12-9760]...CDAD.
        • ischemic colitis [LMC-01-5594]
        • ischemic effect of enterotoxigenic bacteria (such as E. coli  O157:H7 & some others...causing HUS and on to TTP)
        • collagenous colitis6, 16
        • in small bowel with adhesion-induced ischemic enteropathy [LMC-01-6486]
      • crypt architectural distortion (implies prior ulceration at that site): (don't be too sensitive in "calling" distortion).
        • IBD...nearly a 100% predictor of IBD; but only noted in 58% of IBD-UC biopsies and 27% of IBD-CD
        • ischemic colitis
        • diverticulogenic active chronic colitis [LMC-04-1055]
      • uneven, interrupted, irregular mucosal microscopic involvement:
        • as to IBD, is a 100% marker of IBD-CD, Crohn's4
      • villous or pseudovillous appearance of biopsy mucosal profile:
        • virtually a 100% predictive marker of IBD
      • basal plasmacytosis:
        • nearly 100% predictor of IBD
      • basal lymphoid aggregates:
        • don't confuse /w 0.5-1.0 mm normally-present (at least in non-elderly adults) mucosal lymphoid nodules.
        • nearly 100% predictive of IBD (in both IBD-UC and IBD-CD)
      • mucosal lining epithelial "injury effect":1
        • be reluctant to diagnose "colitis" without injury, injury being:
          1. mucin depletion (& it can be tiny zones 5-10 epithelial cells in length [S-01-7895])
          2. nuclear enlargement
          3. increased crypt-base mitotic activity
          4. syncytial change of epithelial cells
        • grading injury7:
          1. 0...normal epithelials
          2. 1+...mucous depletion only
          3. 2+...cuboidal epithelials (columnar cell-shape loss) & mucin depletion
          4. 3+...flattened epithelials plus mucin depletion
        • be reluctant...except in basal-predominant lymphoplasmacytosis of lamina propria ([chonic IBD], which should have crypt epithelial injury and crypt distortion)...to diagnose colitis without "injury effect"
        • acute infectious can cause some change3
        • bowel prep can cause slight change [Haggitt]
        • essentially always at least focal change if any true degree of even focal lymphocytic exocytosis [S02-7938]
    1. collagen table thickening3:
        • the sine qua non of collagenous colitis [LMC-02-6009]; but, if non-IBD colitis criteria present and lack unequivolcal table thickening, just generically "stay" at "microscopic colitis" [LMC-01-3499].
        • acute self limited colitis can occur in someone with CC [LMC-05-3073].
        • has also been seen cases of diverticular disease.
        • has also been seen in cases of megacolon.
        • has also been seen in cases of colonic carcinoma.
        • has also been seen in cases of Crohn's disease.
        • amyloidosis (the thickening is smooth & negative for included cells or capillaries)27.
        • has also been seen in cases with pseudomembraneous colitis picture16.
        • some cases of collagenous colitis and enteritis (such as "lymphoplasmacytic enteropathy" [S07-9902]).
        • some cases of collagenous colitis and UC, mostly in males.
        • some cases of collagenous colitis and celiac sprue.
    2. lumenal-surface-intraepithelial lymphocytic (IELs) increase & exocytosis; Protein intolerance, cell mediated type, may be manifested by such lymphocytosis (IELs):
      • normal IEL count: 5 IELs per 100 epithelials8; <1 IEL per 100 epithelials4; <15 IELs per 100 epithelials7; 5-10 per 1009); we use around 1-2 per 20 (5-10 per hundred) as seen with CD3-amplified IHC .
      • IELs much easier to see with IHC for LCA or CD3; but one can usually, on scanning, gain a clue of hypercellular surface epithelium or a lamina proria which seems a little too cellular but turns out to not be collagenous colitis.
      • a high percentage of cases are detected through the highly associated finding of a pattern of lumenal surface epithelial "injury effect" [S10-7502; S10-8323;S10-10996...ave 98 IELS per 100; S10-11179; S10-11222] of loss of columar shapes & decreased cytoplasmic mucus; can see increased IELs in a biopsy without surface "injury effect", though injury be noted in another colonic biopsy site in same case [S-01-7897; LMC-02-7036].
      • one authority suggests that there be a generic category of "colonic epithelial lymphocytosis" with two subheadings10:
        1. "classic lymphocytic colitis" with triad of:
          • chronic non-bloody watery diarrhea
          • normal to near-normal endoscopy
          • increased colonic IELs without subepithelial collagen table thickening (SECT)
        2. "atypical lymphocytic colitis": all other cases (and they may be the ones associated with celiac disease [CG12-5782], or various medications such as NSAIDs, or represent attenuated acute self limited colitis [ASLC]) [S11-5134 25 y/o, 9 cecal to rectal biopsies and colonic "IEL score" of 160 IELs per 100 luminal surface epithelials]
      • don't count over lymphoid follicle and better chance of positive findings in Bxs proximal to the sigmoid7
      • some normals3
      • IBD3; not in IBD...any IBD assoc. is two diseases in one patient7, 10
      • sometimes in [? following?...S-01-7387] infectious colitis3, especially attenuated/resolving [CN09-32] cases.
      • this whole increased-IELs category appears to be a reaction to lumenal-contents antigens or toxins.
      • medications: NSAIDs; Cyclo 3 Forte in France; ranitidine; carbamazepine
      • chronic microscopic lymphocytic colitis (CMLC)
        1. some cases still only "significantly suspicious" after H&E, LCA/CD3, and trichrome stains [S-01-3499;S-01-3461]
        2. some cases need H&E and LCA/CD3 to cinch diagnosis [S-01-3499]
        3. some cases can diagnose on H&E alone [S-01-3713] & CD3 confirm [S-07-4925].
      • focal CMLC pattern in Crohn's disease.
      • nonspecific...not sure why IELs increased [LMC-01-6701; LMC-01-13096].
      • collagenous colitis7 [questionable early CC in a GSE case, S-00-13377].
      • "suspicious for early (CMLC vs. collagenous) colitis"...but not definitely diagnosed...sign-out diagnosis generically as "microscopic colitis, see above" (referring to the differential diagnosis comment in the SP report).
      • duodenal or small bowel (e.g. terminal ileal Bx) involvement in CMLC [LMC-01-2410; LMC-01-7368; LMC-05-4516 & 4634].
      • graft-versus-host disease colitis (GVHD).
      • idiopathic constipation10; some chronic idiopathic constipation cases7.
      • immunodeficiency colitis.
      • "Brainerd chronic epidemic diarrhea" (after an outbreak in Brainerd, Minn. in 1985) which tends not to respond to steroids10 but spontaneously resolves in 3 years (mild IELs and 0-1+injury)7; tends not to have associated epithelial injury10.
      • Brainerd-like histology but not self-limited at 3 years10.
      • drug induced diarrhea7.
      • colonic involvement in celiac disease has been somewhat assoc. with refractory sprue but others refute the refractory part; colonic IEL lymphocytosis cases with classical criteria ought to be tested for GSE/celiac7 & files checked for other biopsies and any history of positive or negative celiac serology [S-06-8460; CG12-5782] celiac & collagenous; celiac & IELs L-05-10215 & S-06-8755] because colonic involvement in about 5% of celiac cases [S09-12662; CG12-5782] .
      • lymphocytic enterocolitis is like combined celiac & CMLC but does not favorably respond to gluten withdrawal.
    3. granulomata (always check for foreign material with polarized light exam):
      • an isolated giant cell is insignificant
      • Crohn's disease, epithelioid
      • reaction to fecal material in erosions of whatever etiology
      • a focal reaction of uncertain etiology: simulating small polyps [S-01-13618];
      • associated with interior cells of a diverticular abscess fistula tract [LMC-01-4414]
      • mucin granuloma of ruptured crypt abscess of such as IBD-UC [S-01-7496c]
      • lymphogranuloma venerium (chlamydial) colitis
      • mycobacterial colitis
      • Yersinia pseudotuberculosis colitis
      • microgranulomas (focal macrophage/histiocyte aggregates) may be seen in Salmonella and Campylobacter colitis.
      • giant cells in CMLC or colagenous colitis18.
      • microscopic colitis, granulomatous (without thickened collagen table or increased IELs18.
    4. increased lamina propria lymphs and plasma cells:
      • these are a normal component of full thickness of cecum and lumenal half, elsewhere9.
      • be very careful about calling colitis on basis of just this and in absence of either increased IELs, definite epithelial injury, or crypt pattern abnormality9,1.
      • also consider mastocytic enterocolitis (do mast cell stain).
      • always try to get colonoscopic "gross pathology" and consider early IBD and diverticulogenic colitis [S09-8276].
    5. mixed-cell lamina propria infiltrate:
      • chronic microscopic lymphocytic colitis (CMLC)
      • possibly a phase of FAC [S08-14618].
      • provided that there is a definite full-thickness increase (filling), is nearly a 100% predictor of IBD [be careful with this!!] (CMLC can heavily fill L07-2183).
      • always try to get colonoscopic "gross pathology" and consider early IBD and diverticulogenic colitis [S09-8276].
    6. polys in lamina propria:
      • focal active colitis (FAC).
      • biopsy in a "skip zone" of IBD-CD.
      • acute self-limited colitis (infectious)
      • pseudomembraneous colitis (superficial & deep)...CDAD.
      • pseudomembraneous-like collagenous colitis (superficial-centered)16.
      • ischemic colitis
      • acute self-limited colitis...protracted cases can also have some increased chronic cells [LMC-04-2679]
      •  (IBS)
      • bowel prep "artifact"
    7. crypt abscesses (polys) in lamina propria:
      • ulcerative colitis, active (IBD-UC).
      • quantitatively "trivial" may be in IBD-C or FAC [S08-14618].
      • infectious (ASLC) colitis: tend all to be at same level, mid to superficial3; & some note that microcystic crypt abscesses with flattened lining cells may be also be seen in acute IBD and ASLC.
    8. polys in crypt epithelium in lamina propria:
      • acute-insult-type colitis:
        1. focal active colitis (FAC)
        2. ischemic colitis
        3. irritable bowel syndrome (IBS)
        4. bowel prep
      • infectious colitis (ASLC): polys in crypt seem disproportionately slight compared to mucous depletion and greater poly presence in lamina propria3. With little surface injury effect or poly presence in lamina propria but some focal cryptitis present = think of attenuated ASLC [L09-76].
    9. inflammation of lamina propria extending into submucosa:
      • IBD-CD is highly likely to do this, but the small biopsies may not show it; if mucosa is OK for IBD & submucosal component is heavier than lamina propria, it is more likely IBD-CD.
      • IBD-UC can do it [S-02-9900].
      • diverticulogenic (diverticular disease associated) colitis can do it [L10-2126].
    10. transmural lymphoid aggregates: especially when away from vicinity of ulcer or fistulae, highly indicative of IBD-CD; IBD-UC and even a post-traumatic ulcerating stricture [LMC-03-6987] can have numerous transmural lymphoid aggregates in the vicinity of the ulceration, especially with severe relapse [LMC-03-5215].
    11. lamina propria hemorrhage:
      • bowel prep or biopsy artifact: negative for any evidence of RBC disintegration or hemosiderin pigment...looks fresh; remember that it only takes 2 hours post injury/hemorrhage to have polys arrive...so, pols there does not r/o bowel prep artifact.
      • hemorrhagic colonopathy: this may be freshly present as blood in lamina propria as mechanical artifact of the endoscopic process and/or a result of intentional (prescribed) or unintentional anticoagulation or antiplatelet therapy [BX prior to L09-2445].
      • ischemic: unless a very fresh lesion from an embolus, you are likely to see ischemic-type lamina propria sclerosis (trichrome stain helps)...possibly some hemosiderin...rather than hemorrhage.
      • venous obstruction: unlikely to see sclerosis because not due to ischemia [LMC-05-8003]...look for vascular dilatation.
    12. ischemic lamina propria eosinophilic color: likely sclerosis if trichrome stain proves is fibrous (& thereby likely due to ischemia). Causes of ischemia:
      • old-age vascular occlusion, possibly newly ischemic due to CHF...decreased cardiac output.
      • medications.
      • thrombophilic situations.
      • vasospasm-inducing substances.
      • recurring extrinsic mechanical obstruction (such as prolapse or impaction)[L11-8288].
    13. eosinophiles increased in lamina propria:
      • marker for increased IELs: eosinophilic exocytosis sometimes combined with lymphocytic exocytosis [S-01-11068] as an expression of chronic microscopic lymphocytic colitis1,10 and noted sometimes in collagenous colitis10[L-01-4369], and could see in a phase of FAC [S08-14618]...all of these tending to show some luminal surface injury effect. And, the eosinophile population is about the sam within that patients proctocolonic tract29.
      • grading: Lamina propria eos are common & the following are eos per 10 40x hpfs = 0, none seen; 1+, occassional eos (1-3); 2+, moderate eos (9-15); 3+ marked increase of eos (greater than 15; 4+, severely increased (greater than 30)29. So-called "normal" lamina propria eosinophile counts vary from less than 10 per high power field in the rectum to less than 30 in the cecum...a reasonable general rule of thumb being that there is eosinophilia when the concentration overall excedes 20 per high power field28.
      • "pericrypt eosinophilic colitis": not sure that this is an actual entity but eos increased in lamina propria and concentrated around crypt bases2. . . (Gastroent. 103:168-176, 1992); not sure a real entity20:
        1. 50% cases assoc. dermatomyositis, scleroderma, MCTD
        2. eosinophilic infiltrate around crypt bases
        3. crypt foreshortening & separation from muscularis by eos.
        4. eos. deep in lamina propria and muscularis mucosae
      • allergic colitis2(AC):
        1. clinical: most infants and children...cows milk.
        2. rectal bleeding...diarrhea sometimes.
        3. histology:
          • mucosal edema and eosinophiles.
          • eos. tend around the mucosal lymphoid nodules.
          • eos. sometimes in crypt abscesses and among muscularis mucosae bundles.
      • Churg-Strauss Syndrome: [probable late manifestation of this rare disease] (Human Path. 10:31-43, 1979).
      • eosinophilic colitis (EC25), primary: a rare disorder, primary eosinophilic gastrointestinal disease (EGID) or eosinophilic gastroenteritis (EGE) was descibed by Kaijser in 193728. Eosinophilic esophagitis has previously been considered part of EGID17; the colon is the least common segment of the GI tract primarily targeted in EGID & tends to bimodally affect neonates and then young adults28; [LMC-02-2108 colonic at Dx & colonic in remission S-02-7598 & duodenal in retrospect]; [not EC = S08-13974].
      • otherwise: lamina propria increase (& even eos crypt abscesses alone and without any other change) is not significant toward a specific DX [S08-14618] in absence of other significant change21, such as associated lumenal surface epithelial injury (see above). Especially if diarrhea-associated, think of medication-induced...drug reaction...(or induced by other ingested allergenic agents [CG12-126]) allergic reaction, IBD, parasites, malignancy, idiopathic hypereosinophilic syndrome (HES) with sustained CBC eosinophilia, and connective tissue disorders28. Medication associated (NSAIDs, antiplatelet, and estrogen) in adults said in another study to (1) have highest eos count is concentrated in the LEFT colon & (2) more likely be found in setting of abdominal discomfort or hematochezia29...in absence of a definite alternative etiology, would the term "eosinophilic colonopathy" be a more fitting diagnostic label [CG12-134]?
    14. capillary/venule prominence in lamina propria: portal hypertension dilates these vessels; and, with constancy & chronicity, they become ectatic and/or thick-walled & appear increased due to tortuosity (by that stage, the patient has portal hypertensive colopathy or colonopathy), the findings said to be more common on the right side & rectosigmoid.
  • submucosal changes:
    • submucosal tiny rings of foamy macrophages: "microvesicular pneumatosis intestinalis" [L07-1499] is said to be present as aggregates of tiny pseudolipomatosis bubbles elswhere in the GI tract & usually in lamina propria. This is the second case I've seen of this histiocytic variant. When the bubbles can be seen with the naked eye, the better name is "pneumatosis cystoides intestinalis" [L07-6907].
  • muscularis propria thickening:
      • muscle hypertrophy:
        1. diverticulosis & diverticulitis
      • thickening other than muscular:
        1. amyloidosis
  • endoscopic categories:
    1. negative mucosa: microscopic colitis entities CMLC & CC (below) are implied but includes any colitide that lacks erythema, hyperpigmentation, obvious paleness, granularity, friability, or ulceration or erosion (see below...and see the watery diarrhea causes, above). "Random biopsies" imply "rule out microscopic colitis".
    2. erythema: implies an acute component & can range from just bowel prep effect to true colitis
    3. erythema and aphthus ulcers: implies an acute component & can range from just bowel prep to true colitis; could be just FAC; could be early IBD.
    4. membranes & pseudomembranes:
      • infectious colitis.
      • pseudomembraneous colitis...CDAD.
      • pseudomembraneous-like collagenous colitis16.
    5. granularity & friability: connotes IBD but can be seen to some degree in 37% of cases of ASLC.
    6. patches: These might be hyperplastic or adenomatous sessile areas. Uncertainty of an adenomatous quailty can be fortified toward that diagnosis if (1) Ki-67 is claerly quite increased in the suspect cells (2) along with the same cells having nuclear p53 positivity (both markers in claerly increased contrast to adjecent epithelials.
    7. ulcers:
      • aphthous ulcer: bowel prep, Yersinia enterocolitic colitis4, or Crohn's4
      • one or a few ulcers: idiopathic colonic ulcer
      • many or large ulcers: Bechet's syndrome (ulcers associated with lymphocytic submucosal phlebitis2)
      • ulcers in a background of definite endoscopic colitis: suggests IBD (strong linearity tends to mean IBD-CD unless is a severe relapse of IBD-UC); diverticular disease associated colitis segmentalized essentially to the area of diverticular disease can do it.
      • stercoral ulcer in background of obstruction or motility disorder & constipation.
      • idiopathic colonic ulcer.
      • patches of yellow white exudate: pseudomembraneous colitis
      • pseudopolyps: IBD-UC or indeterminate or mixed IBD colitis
  • disease classification categories:
    1. colonogenic (colon is primary seat of disease):
      • Vascular hypoperfusion disorders: (lamina propria sclerosis by trichrome stain)
        1. hypoperfusion or ischemic colonopathy
        2. occult hypercoagulopathy situations
        3. athero-embolic or other embolic
        4. ischemic colitis:
          • focal, presenting with perforation in the elderly [LMC-01-6130]
          • zonal, typical
        5. vasculitis-induced ischemic colitis
        6. vasculopathy induced ischemic insult (as with myointimal arterial hyperplasia in women on BCPs)
        7. necrotizing enterocolitis
        8. cocaine users with vasospastic ischemia
        9. caused by Kayexalate-sorbitol enemas (as treatment of hyperkalemia...crystals or crystalline material noted in lamina propria of necrotizing ulcers)13
        10. amphetamine-associated13
        11. mechanically obstructive ischemic (includes functional obstruction as with Hirschsprung's)
        12. evanescent ischemic insults (as with the intensely-competing athlete with focal mucosal hypoperfusion)
      • infectious colitis or acute self limited colitis (ASLC):
        1. medications: NSAIDs13
        2. viruses:
          • herpes (HSV)
          • CMV2: usually ileocecal and in immunocompromised patients, ulcers and hemorrhage [LMC-02-4915]
          • Brainerd colitis
            1. an epidemiological cluster in the town of Brainerd
            2. lymphocytic exocytosis & lumenal surface epithelial injury [looks like CMLC]
        3. chlamydiae:
        4. bacteria:
          • pseudomembraneous colitis: Of C. diff. infections (CDI), this is a worse type progression of antibiotic-induced overgrowth of the anaerobic, spore forming Clostridium difficile associated diarrhea (CDAD) in which the toxin induces colonic surface defects; fecal test for toxin or antigen helps when positive (negative does not rule it out); summit lesion looks like a microscopic "focal explosive mucosal lesion" of fibrino-leukocytic material2; bacteria are Gram positive spore-forming rods with a termianl-end bulge visible on smears; can look ischemic [LMC-01-4278]. Pseudomembraneous colitis [a dramatic case with pneumoperitoneum, L12-9760]
          • acute self-limited colitis (non-specific acute colitis)...many more polys than with FAC in severe cases; but may only manifest as edema and/or hemorrhage (true edema makes crypt bases look "pointy" rather than rounded3); can proceed to fulminantly acute.
            1. Campylobacter: Gram negative short-spiral rod.
            2. Shigella: Gram negative E. coli like rod; can cause HUS.
            3. Salmonella: Gram negative E. coli like rod.
            4. E. coli: Gram negative rod; a strain with bloody diarrhea sometimes assoc. with HUS...O157:H7 [& some others], possibly progressing to TTP.
            5. Vibrio cholera: Gram negative straight or curved rod.
        5. mycobacterial2: TB usually as ileocecal mass with mucosal ulceration and granulomatous morphology.
        6. fungi
        7. parasites:
          • Entameba histolytica2: poly exudate containing amoebae which have engulfed RBCs [S-01-14210; S-02-2996] (macrophages can engulf RBCs, too); acute ulcers and normal intervening mucosa; mass. Amebae have copious (usually) cytoplasm and a small round gray-pink nucleus without chromatin detail [amebae vs. histiocytes].
      • nonspecific colitis:
        1. increased chronic inflammatory cells...particularly plasma cells...in the superficial 2/3rds of lamina propria3 (except in cecum where full-thickness lymphs and plasma cells are normal9).
        2. remember, a rare bifid crypt is normal/OK4.
        3. may see in stasis situations such as chronic pseudo-obstruction.
      • inflammatory bowel disease:
        1. IMPORTANT!!
          • Since advent of pouch, the greatest of care is needed to correctly distinguish IBD-UC from IBD-CD: "There is nothing quite like a pouch to bring out the Crohn's in someone"; IBD SEROLOGICAL DDX ADJUNCT; the pouch for IBD-UC will abscess and fistularize if the patient really has IBD-CD5
          • IBD-UC & dysplasia: low-grade promotes increased rate of surveillance; hi grade warrants strong consideration of colectomy5.
        2. always try to get colonoscopic "gross pathology" and consider diverticulogenic colitis [S09-8276; L10-2126].
        3. Ulcerative colitis (IBD-UC): see below
        4. Crohn's disease (IBD-CD): see below
          • can be very limited [LMC-01-4109]
          • can present for laparotomy as right ileocolic mass (cancer?) with fistulae and localized secondary perifistulous colitis with pseudopolyp formation that looks like a sessile polyp [LMC-03-207]
          • a non-IBD ulcerated stricture can mimic IBD-CD [LMC-03-6987] with transmural lymphoid aggregates
          • granulomatous appendicitis15: sarcoid, Crohn's, AFB, or fungal. There is secondary appendicular inflammation in ileocolic Crohn's; & there is a sort of primary Crohn's appendicitis essentially limited to the appendix [LMC-04-4183] (usually does not behave like a Crohn's case...but should have regular follow up15).
          • IBD-UC in a region of severe diverticulosis & diverticulitis can have associated diverticulitic abscess perforations and fistulae (even come to ER with colovesicular fistual) [LMC-06-10218].
        5. indeterminate/mixed IBD [LMC-01-6097; LMC-03-5215]
        6. table of IBD differential diagnosis factors
        7. flow-chart histo-diagnostic decision tree [here]
        8. generic IBD notes & warnings:
          • crypt distortion reflects healed mucosal pattern after prior ulceration; if Bx from an area never previously ulcerated, you won't see crypt distortion3.
          • the more distorted the crypt pattern, the more likely it is IBD-UC3
          • deep plasma-cell infiltrate...often with lymphocytic band just above the muscularis...takes weeks to accumulate in IBD and won't be seen in an initial acute IBD3.
          • adenomatous polyps in a case of IBD vs. DALM11 (dysplasia associated lesion or mass; that is, is the lesion in the IBD case a relatively harmless sporadic adenoma or the relatively dangerous harbinger of cancer in IBD?).
          • watch out for situation of severe relapse in biopsy diagnosed IBD-UC and you are given the colectomy with prominently linear ulcers...severe relapse of IBD-UC can do this [LMC-03-5215].
          • watch out for diverticular disease associated colitis which can severely ulcerate [LMC-03-5969] but NOT be IBD.
          • infectious colitis can superimpose on IBD, AND an on-going, prolonged infectious colitis can accumulate significant plasma cells and supra-muscularis lymphoid band...but one may be able to discern edema with associated polys of ASLC3.
          • epithelial mucin may become depleted in infectious colitis but polys may be grudging in their attempts to infiltrate and form crypt abscesses3.
          • crypt abscesses of infectious colitis seem to be all at same plane...mid crypt to superficial crypt3.
          • IBD can lead to ascending intrahepatic cholangitis.
          • IBD, especially IBD-CD, may be associated with enteropathic chronic joint disease (arthritis) or even enteropathic chronic recurrent multifocal osteomyelitis 19 (CRMO) [LMC-07-4778; L07-6776].
      • microscopic colitis: term coined in 1980 for chronic diarrhea cases with normal endoscopy and increased inflammatory cells; (1) radiological and endoscopic features almost always normal (remember that bowel prep can cause areas of erythema and even a rare aphthous ulcer...rare cases with slightly/minimal change) and (2) a transmucosal increase in cells (increased cellularity is implied in colorectal biopsies when cells seem pressed together, pushing against crypts, rather than loosely situated)3. Can rarely see colon clearly involved in this fashion in celiac disease [S09-12662].
        • chronic microscopic lymphocytic colitis (CMLC):
          • classical clinical criteria: chronic watery, non-bloody diarrhea, normal to nearly normal endoscopy, normal collagen table, increased colonic IELs7.
          • of those cases of increased IELs meeting all of the above criteria, gender is same as collagenous colitis, have increased eos with the IELs, and have increased prevalence of autoimmune disease7.
          • can have at least focal or zonal collagen table thickening as if transitioning to CC [total colectomy for massive lower GI bleed L07-2183].
          • CMLC associated with HLA-A1.
          • at least an increase of superficial lamina propria cellularity & can be filled [L07-2183]; and,
          • bowel-lumen epithelial "injury" with lymphocytic exocytosis [LMC-03-1148].
          • can rarely have a granuloma18.
          • may see with celiac disease [S-06-8755] or as part of a non-gluten-triggered IEL-increased entercolitis.
          • remember that bowel-prep or infectious FAC can be superimposed on CMLC [S-01-3062].
        • collagenous colitis:
          • described in 1976 by Lindstrom

          • 80% cases middle age to elderly females (50-60 y/o cluster6); chronic watery diarrhea; association with HLA-A2
          • often with extra-intestinal immune disorders such as arthritis and thyroiditis.
          • in some patients, there is a relationship to NSAIDs use and problems stop when meds stopped3.
          • endoscopy: vast majority are unremarkable (microscopic); a minority of cases endoscopically grossly abnormal16, even to the point of linear ulcers and pseudomembrane formations6 [S-01-3062] (but, remember, ASLC can also superimpose on any chronic colitis of another type).
          • may see with celiac disease [S-06-8460].
          • histology:
            1. 82% right colonic bopsies & only 27% rectal collagen table thickening (very spotty finding in biopsies)...with multiple biopsies, thickening can be seen in 80% of cases3; and,
            2. pancolonic increase of superficial lamina propria cellularity, usually including increased plasma cells...will be noted in nearly 100% of cases numerously biopsied3.
            3. bowel-lumen epithelial "injury effect" with lymphocytic exocytosis.
            4. exocytosis may include excessive polys or eosinophiles3.
            5. can rarely be grossly visible, pseudomembraneous-like16[LMC-05-3073].
            6. can rarely have a granuloma18.
        • microscopic colitis with increased mast cells23: [S09-2528 was microscopic colitis of uncertain type and 13 MCs per 40x hpf at most & probably not this entity]
    2. infectious, prolonged or attenuated.
    3. granulomatous with thickened collagen table or increased IELs18.
    4. ischemic colonopathy: especially  noted in low-flow states, there can be lamina propria fibrosis and ectatic capillaries without colitis3
    5. bile salt colitis: may see a diffuse, mostly superficial increase in plasma cells3.
    6. inapparent IBD: subclinical or in colonic areas which are
      endoscopically normal.
    7. medicinal laxative effect colonopathy: melanosis coli
    8. eosinophilia: see above.
    9. focal active colitis (FAC):
      1. histology: lamina propria and/or crypt polys in patchy, mild numbers; can have a few increased eos too [S08-14618] & with maybe very small numbers of both in colonic lumenal surface epithelium. (could this be same as McKenna 200124, above?)
      2. a common finding in biopsies and should probably ignore as an artifact of bowel prep unless clinical or endoscopic reason to believe is true colitis .
      3. seen in: bowel prep., IBS, early ischemia, residual of acute self-limited (infectious) colitis, and as a harbinger of Crohn's disease.
    10. diverticulitis: peristomal mucosa can have microscopic extension of the diverticulitis...usually evident or suspected as such endoscopically.
    11. apoptotic colopathy (McKenna 2001)24...DX if can presume that GVHD excluded and be careful NOT to mistake karyorrhectic poly leukocyte nuclei as apoptotic epithelial debris.
    12. minimal change microscopic colitis25.
    13. intestinal spirochetosis25.
    14. intestinal schistosomiasis25.
    15. Crohn's disease25.
    16. colitis complicating colonic obstruction
  • non-colonogenic (not primarily colonic):
    • ischemic colitis.
    • irritable bowel syndrome (IBS).
    • polydipsia diarrhea (see watery diarrhea causes, above).
    • gallbladder dysfunction [CAUSES] bile salt diarrhea (Habba syndrome..."obstructed gallbladder" or "cholecystopathic bypass syndrome" as in severe chronic impacted cholelithiasis) or in absence of GB (post-cholecystectomy diarrhea[L09-3721]): treated with oral doses of bile-salt-binding resins.
    • bowel prep lesions (such as FAC) and "apoptotic colonopathy" (apoptosis of surface and crypt cells associated with phosphosoda prep13).
    • drug-induced colitis or colonopathy:
      1. chemotherapy-induced: note crypt epithelial apoptosis; can proceed to a full-thickness "neutropenic colitis" which can perforate2
      2. other: NSAIDs ulcers and FAC
      3. antibiotic-associated pseudomembraneous colitis
      4. factitious overmedicated hyperthyroid diarrhea in a patient on thyroid hormone replacement.
    • secondary to radiation therapy.
    • non-specific colon ulcer
    • solitary rectal ulcer syndrome (SRUS).
    • necrotizing enterocolitis in cancer patients.
    • typhlitis: acute colitis centered in, or restricted to, the cecum, usually as a leukemia complication2
    • colitis in chronic granulomatous disease of childhood
    • colitis in immunodeficiency syndromes
    • micro-thrombotic colitis in TTP proceeding from the hemolytic uremic syndrome (HUS), see above.
    • colitis in graft-versus-host disease (GVHD): usually after bone marrow transplant; may see increased colonic lumenal surface IELs (see IELs above); focal crypt epithelial degeneration (apoptosis); may have crypt abscesses worsening to mucosal sloughing2; older lesions may be as segmental fibrosis (biopsies may miss this).
    • colitis in Bechet's disease: multiple ulcers of various sizes, shapes, depths associated with lymphocytic submucosal phlebitis2 which is unlikely to show up on usual colonoscopic biopsy.
    • colitis in celiac disease [S09-12662].
  • REFERENCES:

    1. Taylor, Shari L., acting assistant prof. of path. and attending GI pathologist, U. of Washington Med. Ctr., Seattle, personal letter, 12 Jun 2001 et. seq. (former associate of the late Dr. Rodger C. Haggitt...now in Memphis).
    2. Ackerman's Surgical Pathology, Juan Rosai, vol. 1, 8th Ed., 1996 (pages 729-754).
    3. Robert H. Riddell, GI Pathologist, handout from ASCP workshop 6/1994.
    4. Rodger C. Haggitt, GI Pathologist, handout and notes from workshop, 1991.
    5. R. E. Petras, seminar notes, 1991.
    6. Victoria G. Reyes, M. D., speaking of the Rodger Haggitt training experience at Seattle...personal communication...2 April 2001.
    7. Goldblum, et. al., "Colonic Epithelial Lymphocytosis", AJSP, 23(9):1068-1074, 9/99 Cleveland Clinic.
    8. Dobbins, W. O., Progress Report: Human Intestinal Intraepithelial Lymphocytes, Gut, 27(8):972-985, 1986.
    9. Dayharsh & Burgart, of Mayo Clinic Dept. of Surg. Path, CAP Today, page 104, 7/2001.
    10. Petras RE, et. al., Colonic Epithelial Lymphocytosis Without a Thickened Subepithelial Collagen Table, AJSP, 23(9):1068-1074, 1999.
    11. Petras RE & Ormsby A, "Contemporary Issues in Lower Gastrointestinal Pathology: What You Need to Know to Survive", handout, CAP meeting San Diego, 11 September 2003.
    12. Petras RE, A Practical Approach to Gastrointestinal Pathology: Small Bowel Biopsy Interpretation and Specimen Handling, US & Canadian Academy of Pathology, March 2002 (91st annual meeting) short course handout, 10 pages (online @ USCAP website).
    13. 10 April 2004 GI Path CME, attended by JBC @ UNC.
    14. Ackerman's Surgical Pathology, Juan Rosai, 9th Ed., 2004.
    15. Chandrasoma P (of UCLA), Gastrointestinal Pathology, 1999.
    16. Yaun S, Reyes V, Bronner MP, Psuedomembraneous Collagenous Colitis, AJSP 27(10): 1375-79, October 2003.
    17. Furuta GT, Children's Hosp. Boston, editorial: "Eructations From Eosinophils", Gastroenterology 131(5):1629-30, November 2006.
    18. (granulomas) Histopath. 47(6):644, Dec. 2005.
    19. Bognar M, et. al., "Chronic recurrent...", Am. J. Med. Sci. 315(2):133-5, Feb. 1998.
    20. Shari Taylor , M. D., personal e-communication...12 June 2008.
    21. Shari Taylor , M. D., personal e-communication, speaking of the Rodger Haggitt training experience at Seattle...personal e-communication...12 June 2008.
    22. Clouse R E, Alpers D H, Hockenbery D M, DeSchryver Kecskemeti K, "Pericrypt eosinophilic enterocolitis and chronic diarrhea", Gastroenterology, 103(1): 168-76, July 1992 HERE.
    23. Baum CA, et. al., "Increased colonic mucosal mast cells associated with severe watery diarrhea and microscopic colitis", Digestive Diseases and Sciences 34(9):1462-1465, Sept. 1989 HERE.
    24. Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. Odze, Goldblum, & Crawford, 1067 pages, 2004. [EBS]
    25. de Silva JGN, et. al., "Histologic Study of Colonic Mucosa in Patients With Chronic Diarrhea and Normal Colonoscopic Findings", J. Clin. Gastroenterology 40(1):44-48, Jan. 2006 HERE.
    26. Jakate S, et. al, "Mastocytic Enterocolitis: Increased Mucosal Mast Cells in Chronic Intractable Diarrhea", Archives of Pathology and Laboratory Medicine,130(3):362–367, 2006.
    27. Noffsinger Amy, Postgrad. Pathology Symposium 24 October 2009, Medical College of Georgia, Dept. of Pathology.
    28. Okpara N, Aswad B, & Baffy G [out of Brown University, Rhode Island], "Eosinophilic Colitis", World J Gastroenterol 15(24):2975-2979, 28 June 2009 [HERE].
    29. Caslle G, et. al., "Colonic Left-side Increase of Eosinophils: A Clue to Drug-related Colitis in Adults", Alimentary Pharmacology & Therapeutics, 29(5):535-541, 2009. (on Medscape web site)[HERE]

    30. (posted 2001; latest additions 26 January 2013)

     
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