• 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.
     • 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])
     • 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:
  1. "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 eneterocolitis" 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
  2. 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].
  3. summit lesion:
     • pseudomembraneous colitis...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 colitis^{6, 16}
     • in small bowel with adhesion-induced ischemic enteropathy [LMC-01-6486]
  4. 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]
  5. uneven, interrupted, irregular mucosal microscopic involvement:
     • as to IBD, is a 100% marker of IBD-CD, Crohn's⁴
  6. villous or pseudovillous appearance of biopsy mucosal profile:
     • virtually a 100% predictive marker of IBD
  7. basal plasmacytosis:
     • nearly 100% predictor of IBD
  8. basal lymphoid aggregates:
     • don't confuse /w 0.5-1.0 mm normally-present mucosal lymphoid nodules
     • nearly 100% predictive of IBD (in both IBD-UC and IBD-CD)
  9. 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]
  10. 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.
  11. lumenal epithelial (intraepithelial) lymphocytic increase & exocytosis:
      • 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 IHC for CD3.
      • IELs much easier to see with IHC for LCA or CD3.
      • a high percentage of cases are detected through the highly associated finding of a pattern of lumenal epithelial "injury effect" [S10-7502; S10-8323]; 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 or various medications such as NSAIDs)
      • 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 patient^{7, 10}
      • sometimes in [? following?...S-01-7387] infectious colitis³, especially attenuated/resolving [CN09-32] cases.
      • this whole 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 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 celiac & collagenous; celiac & IELs L-05-10215 & S-06-8755] because colonic involvement in about 5% of celiac cases [S09-12662] .
      • lymphocytic enterocolitis is like combined celiac & CMLC but does not favorably respond to gluten withdrawal.
  12. 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.
  13. 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 abnormality^9,1.
      • also consider mastocytic enterocolitis (do mast cell stain).
      • always try to get colonoscopic "gross pathology" and consider early IBD and diverticulogenic colitis [S09-8276].
  14. 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].
  15. 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"
  16. crypt abscesses (polys):
      • 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.
  17. polys in crypt epithelium:
      • 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].
  18. inflammation 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].
  19. 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].
  20. 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.
  21. 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.
  22. eosinophiles:
      • marker for increased IELs: eosinophilic exocytosis sometimes combined with lymphocytic exocytosis [S-01-11068] as an expression of chronic microscopic lymphocytic colitis^1,10 and noted sometimes in collagenous colitis¹⁰[L-01-4369], and could see in a phase of FAC [S08-14618].
      • grading: 0, none seen; 1+, rare eos; 2+, moderate eos; 3+ marked incr. of eos.
      • "pericrypt eosinophilic colitis": not sure that this is an actual entity but eos increased in lamina propria and concentrated around crypt bases²⁰.
      • Churg-Strauss Syndrome: [probable late manifestation of this rare disease] (Human Path. 10:31-43, 1979)
      • otherwise: lamina propria increase & even eos crypt abscesses alone and without any other change are not significant toward a specific DX [S08-14618] in absence of other significant change²¹, such as associated lumenal surface epithelial injury.
  23. 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].
  24. 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. 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: a worse type of Clostridium difficile associated diarrhea (CDAD); fecal test for toxin or antigen helps when positive; summit lesion looks like a microscopic "focal explosive mucosal lesion" of fibrino-leukocytic material²; can look ischemic [LMC-01-4278].
          • 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
            2. Shigella
            3. Salmonella
            4. E. coli (a strain with bloody diarrhea sometimes assoc. with HUS...O157:H7 [& some others], possibly progressing to TTP)
       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:
     • pericrypt eosinophilic colitis (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
     • colitis in "eosinophilic gastroenteritis" (EGE) :
       1. Eosinophilic esophagitis (EE) is the best described of the eosinophilic gastrointestinal diseases (EGIDs)¹⁷. Increased colonic eosinophiles are a common finding and unlikely to be significant unless,
       2. associated with significant peripheral-blood eosinophilia
          [LMC-02-2108 colonic at Dx & colonic in remission S-02-7598 & duodenal in retrospect]...or, if no gastro-enteric component, maybe,
     • "eosinophilic colitis" (EC)²⁵ [not EC S08-13974].
     • 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.
  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

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.


(posted 2001; latest additions 3 August 2010)