하부위장관비종양성질환의 감별진단 주미인제의대일산백병원

Transcription

1 하부위장관비종양성질환의 감별진단 주미인제의대일산백병원

2 Solutions for diagnostic problems in Colitis : Please ask yourself five questions Normal or Inflamed? Acute or Chronic? IBD or Other chronic colitis? Ulcerative colitis or Crohn s disease? Another form of inflammation? Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic IBD J Clin Pathol. 1997;50(2):

3 Ulcerative colitis Colon Bx Inflammation Chronic (idiopathic) IBD Acute (infective) Crohn s disease Indeterminate colitis Acute self-limited colitis Pseudomembranous colitis Enterohemorrhagic E.coli Ischemic colitis Normal Specific (Unclassified) Collagenous colitis Lymphocytic colitis Eosinophilic colitis Others Focal active colitis Drug-induced colitis Guidelines for the initial biopsy diagnosis of suspected chronic idiopathic IBD J Clin Pathol. 1997;50(2):

4 Normal versus Abnormal It is important to understand normal variations and preparation effects

5 Normal colonic mucosa Architecture of crypts - Rack of Test Tube or Daisy flower - Mild architectural distortion Epithelial cells - Colonocytes : Goblet cell = 5:1 (Rt), 3:1 (Lt) - Paneth cells: Normal in Rt colon Paneth cell metaplasia in Lt colon Lamina propria inflammatory cells - Normal: 30%~50% of free lamina propria - Normal gradient

6 Normal colonic mucosa Architecture (Surface), Lamina propria

7 Histology for Pathologists, 3rd Edition Mills, Stacey E.

8 Preparation effects or Artifact Focal active colitis Surface neutrophilic infiltration Stromal edema & Fresh hemorrhages Pseudolipomatosis (Gas effect, No fat)

9 병리진단에 Normal 이라고써도될까? Some pathologists may argue that such comments is unnecessary, even insulting, to clinician. Biopsy Pathology in Colorectal disease 2 nd Ed. Pathologists should not be afraid to render a diagnosis of normal colon. Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas 3 rd Ed. Colonic mucosa with no significant pathologic changes

10 Significance of the normal biopsy Stating This is a normal biopsy help to Highlight other more important diagnoses Make a differential diagnosis : UC vs CD (skip lesion) Determine the extent of disease : Left sided UC with cecal patchy Evaluate treatment effects (Normalization) : Rectal sparing of UC

11 Abnormal.. So, what s the diagnosis?

12 Q: What is it? A: It s a kind of Q: IBD? A: Moderate chronic active colitis Q: What disease, specifically? A: Pattern of injury, at best

13 Pattern of injury 에의한진단은어떻게? Inflammatory Disorders of Colon Surgical Pathology of the GI Tract, Liver, Biliary Tract & Pancreas 3 rd Ed. Acute Chronic Eosinophilic Paucicellular Ischemic/ hemorrhagic Non-ischemic/ Non-hemorrhagic Preserved Architecture Abnormal Architecture Ischemic Radiation Microscopic colitis DDAC Some infections DDAC Chronic ischemia Radiation Tuberculosis Healed injury IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

14 Look for a pattern of injury One of the biggest challenges in mucosal biopsy pathology is to recognize a specific morphologic pattern of injury, which is often best performed at low magnification. Archtecture & Lamina propria

15 Guidelines for biopsy diagnosis of chronic colitis (IBD) (J Clin Pathol 1997;50:93 105)

16 필수요건, 적어도둘중하나는있어야.. Activity 와관련.. 필수적이지않음 있으면도움이되는소견..

17 Active (Acute) Colitis Architecture: Normal Lamina propria: Neutrophils only Chronic Colitis with Preserved Architecture Architecture: Normal Lamina propria: Abnormal Chronic Colitis with Abnormal Architecture Architecture: Abnormal Lamina propria: Abnormal Chronic Injury Pattern Architecture: Abnormal Lamina propria: nearly Normal

18 Active (Acute) Colitis

19 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Acitve colitis only + ischemia/ hemorrhage Preserved Architecture Abnormal Architecture Ischemic Radiation Microscopic colitis DDAC Some infections DDAC Chronic ischemia Radiation Tuberculosis Healed injury IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

20 Acute (Active) Colitis only Architecture: Normal Lamina propria: Normal Neutrophilic infiltration: Superficial-predominant pattern Epitheliotropic (Cryptitis, Crypt abscess) Most often caused by infections >>> drugs or IBD Acute self-limited colitis: Salmonella, Shigella, Campylobacter & Yersinia

21 Useful information Acute (Active) colitis (1) Drug-associated Colitis: NSAID : Can mimic almost any type or pattern of colitis, including infectious colitis, IBD, ischemic colitis, microscopic colitis, and even eosinophilic colitis. Older individuals, Stool culture (-) History of NSAID consumption for a period of at least 1 months before illness (or 1 to 2 weeks after high dose NSAID) Erythema, friability, erosions or ulcer (Right > Left) Bleeding, diarrhea, IDA or rarely perforation Microscopic findings Typical features of active colitis ± mild cryptal apoptosis, some eosinophilic infiltration, mild intraepithelial lymphocytosis

22 Acute (Active) colitis (2) Rarely IBD, mild form or early phase of disease Endoscopic impression: R/O IBD, R/O UC Microscopic findings: Active colitis without well established features of chronicity Diagnosis: Colon, endoscopic biopsy: - Active colitis - No features of chronicity is seen (see Note) Note: Definite features of chronicity are not identified. However, an early phase of IBD cannot be excluded. Clinical correlation and follow-up are needed.

23 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Acitve colitis only + ischemia/ hemorrhage Ischemic Radiation Preserved Architecture Microscopic colitis DDAC Some infections Abnormal Architecture DDAC Chronic ischemia Radiation Tuberculosis Healed injury IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

24 Acute Ischemic/Hemorrhagic Colitis Architecture: Normal Lamina propria: Normal Neutrophilic infiltration: Usually not prominent, Pseudomembrane Fibrohyalinized lamina propria, withering crypts, hemorrhages, regenerating epithelial changes, with or without intravascular thrombi Most often caused by ischemia, infections (E.coli O157:H7 and Clostridium difficile), radiation injury, and drug reactions. From Diagnostic Pathology Gastrointestinal, Amirsys

25 From Diagnostic Pathology Gastrointestinal ( Histologically indistinguishable colitis: Enterohemorrhagic E. coli colitis versus Acute ischemic colitis DDx points - Patient age, anatomic distribution, Clinical history

26 Differential Diagnosis of Active (Acute) ischemic/hemorrhagic colitis Feature Ischemia Infection (E. coli) Radiation Anatomic distribution Watershed Right > Left Left > Right Edema/hemorrhage Withered crypts ++ ± ± Fibrin thrombi ± + ± Neutrophils ± ++ ± Atypical cells ± Dilated blood vessels ± ++ LP hyalinization ++ ± ±

27 Chronic colitis

28 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Ischemic/ hemorrhagic Non-ischemic/ Non-hemorrhagic Preserved Architecture Abnormal Architecture Ischemic Radiation Microscopic colitis DDAC Some infections DDAC Chronic ischemia Radiation Tuberculosis Healed injury IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

29 Chronic colitis with preserved architecture Architecture: Normal Lamina propria: Abnormal (basal plasmacytosis, lymphoid aggregates) Neutrophilic infiltration: Diffuse pattern Predominantly Neutrophilic Predominantly Lymphoplasmacytic Infectious colitis (Delayed resolution) Early phase IBD (NSAIDs) Microscopic colitis Resolving IBD Diverticulosis Some infections (Shigella)

30 Chronic Colitis with Preserved Architecture Predominantly neutrophilic Architecture: Normal Lamina propria: Increased cellularity, Mild basal plasmacytosis Neutrophilic infiltration: Prominent, Diffuse pattern Differential diagnoses include delayed resolution of infectious colitis >> early phase of IBD or drug reactions ( 감별어려움 ) Colon, endoscopic biopsy: - Colonic mucosa with diffuse neutrophilic infiltration & mild basal lymphoplasmacytosis, but no architectural abnormality (see Note) Note: Differential diagnoses include delayed resolution of infectious colitis, early phase IBD & drug-induced colitis. Clinical correlation & F/U are needed.

31 Chronic colitis with preserved architecture Predominantly lymphoplasmacytic Architecture: Normal Lamina propria: Abnormal, dense lymphoplsamacytic infiltration basal plasmacytosis, basal lymphoid aggregates Neutrophilic infiltration: Not prominent - Microscopic colitis? Lymphocytic colitis, Collagenous colitis - Others? Resolving IBD, Diverticulitis, Drugs, Infections.. The major difficulties in this category of inflammatory disorders involves differentiating microscopic colitis from IBD.

32 Chronic Colitis with Preserved Architecture predominantly lymphoplasmacytic (1) Lymphocytic colitis Chronic watery, nonbloody diarrhea Normal endoscopy (sometimes minor changes, rarely ulceration) Intraepithelial lymphocytosis ( 20/100 epithelial cells) Surface epithelial injury (flattening, regeneration, mucin depletion) + Increased cellularity (lymphoplasmacytosis) in lamina propria

33 Chronic Colitis with Preserved Architecture predominantly lymphoplasmacytic (2) Collagenous colitis Chronic watery, nonbloody diarrhea Normal endoscopy (sometimes minor changes, rarely ulceration) Immunologic response to intraluminal dietary or bacterial elements Presence of irregular thickened subepithelial collagen layer (Type IV collagen, >10 μm, usually 20 to 60 μm) Entrapment of inflammatory cells and vessels + Increased cellularity (lymphoplasmacytosis) in lamina propria

34 The IBD-like features are seen in 30% of collagenous colitis, usually focal & mild. Typical histologic features are readily seen in the majority of the serial biopsies. Focal IBD-like changes should not alter the diagnosis if all other features are C/W collagenous colitis.

35 Chronic Colitis with Preserved Architecture predominantly lymphoplasmacytic (3) Longstanding infectious colitis - 40-year-old man - Abdominal pain & diarrhea lasting > 1 year - No response to UC medication Dx: Amebic colitis mistaken for UC 소화기병리연구회삼성서울병원제출 case

36 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Ischemic/ hemorrhagic Non-ischemic/ Non-hemorrhagic Architecture preserved Abnormal Architecture Ischemic Radiation Microscopic colitis DDAC Some infections DDAC Chronic ischemia Radiation Tuberculosis Healed injury IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

37 Chronic Colitis with Abnormal Architecture Architecture: Abnormal Lamina propria: Abnormal + Neutrophils: Chronic active colitis (mild, moderate, severe) With lamina propria fibrosis or hyaline-like material Without lamina propria fibrosis or hyaline-like material Chronic ischemia Chronic radiation colitis Mucosal prolapse Posttreatment IBD Inflammatory bowel disease Diverticular diseaseassociated colitis (DDAC)

38 Chronic Colitis with Abnormal Architecture With lamina propria fibrosis or hyaline-like material Architecture: Abnormal (loss or atrophy of crypt) Lamina propria: Abnormal Neutrophlic infiltration: Not prominent Vascular ectasia, thrombi formation

39 Chronic Colitis with Abnormal Architecture with Lamina Propria Fibrosis or Hyaline-like Material (1) Chronic radiation colitis History of Radiation Frequent rectal involvement Predominantly hyalinization & fibrosis Vascular ectasia with hyalinization Atypical stromal cells From Diagnostic Pathology Gastrointestinal, Amirsys

40 Chronic Colitis with Abnormal Architecture with Lamina Propria Fibrosis or Hyaline-like Material (2) Rectal mucosal prolapse (solitary rectal ulcer syndrome) Rectal Mucosal prolapse with or without ulcer Common in younger adults or older than 60 yo Chronic constipation & strenuous defecation Hyalinization in LP & Fibromuscular hyperplasia Crypt elongation with Glandular hyperplasia

41 Differential Diagnosis of Chronic Colitis with Abnormal Crypt Architecture and Lamina Propria Fibrosis or Hyaline-like Material Feature Radiation Prolapse Chronic Ischemia Polyp/mass formation Rare + Rare Primarily rectal involvement Rare IBD-like mucosal inflammation ± ++ Withering crypts ± ± ± Pseudomembrane ± Hyalinization Fibromuscular hyperplasia ++ ± Vascular dilatation/proliferation ++ ± Atypical stromal/epithelial cells ++ Hyperplastic changes ++ Thrombi ± ± ++

42 Chronic Colitis with Abnormal Architecture Without lamina propria fibrosis or hyaline-like material Architecture: Abnormal Lamina propria: Abnormal (basal plasmacytosis, lymphoid aggregates) + Neutrophils: Chronic active colitis (mild, moderate, severe) Inflammatory bowel disease Diverticular disease-associated colitis Generally, two diseases are histologically indistinguishable. - DDx points: Presence of diverticulosis, Involvement of rectum

43 Inflammatory Bowel Disease

44 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Ischemic/ hemorrhagic Non-ischemic/ Non-hemorrhagic Preserved Architecture Abnormal Architecture Ischemic Radiation Microscopic colitis DDAC Some infections DDAC Chronic ischemia Radiation Tuberculosis Healed injury IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

45 Biopsy pathology of IBD Index (First) biopsy - Early phase of IBD - Typical IBD Follow up biopsy - Resolving IBD (Healing period) - Posttreatment IBD (Resolution period) - Flare up - CMV infection UC versus Crohn s disease

46 Index (First) biopsy Early phase of IBD (DDx Acute colitis) Active(Acute) Colitis Chronic Colitis with Preserved Architecture Typical IBD Chronic Colitis with Abnormal Architecture

47 Follow up biopsy Resolving IBD (Less activity and crypt injury) Chronic Colitis with Preserved Architecture predominantly lymphoplasmacytic Chronic Colitis with Abnormal Architecture Less inflammatory activity Posttreatment IBD Chronic Inactive Colitis Abnormal Architectural only Chronic Colitis with Abnormal Architecture + Fibrosis Normal (Normalization)

48 Microscopic features of untreated UC and Crohn s disease Ulcerative Colitis Diffuse, continuous disease Rectal involvement Disease worse distally No fissures No transmural aggregates No ileal involvement (except in backwash ileitis) Upper GI tract involvement less common Crypt-rupture (mucin) granulomas Crohn's Disease Segmental disease, skip lesion Variable rectal involvement Variable disease severity Fissures, sinuses, fistulous tracts Transmural lymphoid aggregates Ileal involvement Upper GI tract involvement common Epithelioid granulomas unrelated to ruptured crypts The distinction may be impossible on biopsies & always requires clinical correlation.

49 Diffuse colitis seen in every Bx: Favor Ulcerative colitis Left-sided UC Subtotal UC Total (Pan) UC Left-sided UC with cecal patch Backwash ileitis Patchy colitis + Normal (Skip) Favor Crohn s disease Chronic ileitis: ileocolic type

50 Terminal ileal biopsy Normal Active ileitis ( Active colitis): infection, nonspecific Chronic ileitis ( Chronic colitis): Crohn s disease, Tuberculosis, rarely UC Aphthous (incidental) ulcer (Erosion with active ileitis): Drugs, CD Colonic disease Site of ileitis Length involvement Histology Pyloric metaplasia, a histologic marker of chronicity Backwash ileitis in UC Severe pancolitis, Usually cecal involvement Distal few (1 2cm) of terminal ileum Short, patchy, discontinuous Mostly active ileitis Sometimes chronic ileitis May be present Ileal involvement in CD Segmental disease, CD-like features > 3cm proximal from IC valve Long (> 5cm) Frequently chronic ileitis Sometimes granuloma Usually present

51 Colon biopsy shows CC versus UC Biopsy from ileum (> 3cm proximal from IC valve) Endoscopy: Large healing ulcer - Widening of lamina propria with villous blunting, Architectural distortion, Pyloric metaplasia (Chronic ileitis) Favor ileal involvement of CD than BWI of UC

52 Granulomas in Crohn s disease, Ulcertive colitis, and intestinal tuberculosis True granuloma Crohn s disease Crypt rupture granuloma (pseudo) Ulcerative colitis True granuloma Intestinal Tuberculosis Histologic features Crohn s disease Intestinal tuberculosis Granuloma size < 100μm > 200μm Mean No. of granulomas 1 > 5/section Shape of granuloma Small, pericryptal Confluent Other helpful findings Aphthous ulcer Focally enhanced colitis Necrosis, Lymphocytic cuffing around granuloma Ulcer lined by histiocytes Am J Gastroenterol 2010;105(3):642-51

53 Feautures of typical IBD But, No granuloma, No chronic ileitis NOTE for UC versus Crohn s colitis These findings are consistent with idiopathic IBD. Distinction between ulcerative colitis & crohn's disease cannot be made on the basis of these biopsies. Clinical correlation is advised.

54 Others Eosinophilic, Paucicellular colitis

55 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Ischemic/ hemorrhagic Non-ischemic/ Non-hemorrhagic Architecture preserved Architecture NOT preserved Ischemic Radiation Microscopic colitis DDAC Some infections IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis DDAC Chronic ischemia Radiation Tuberculosis Healed injury Allergic Eosinophilic gastroenteritis Mastocytosis GVHD Systemic dx

56 Eosinophil-Predominant Colitis Architecture: Usually normal Lamina propria: Usually normal Eosinophilic infiltration: Prominent Differential diagnoses include Allergic colitis, Eosinophilic GE Parasitic infection, and Mast cell disorder. From Diagnostic Pathology Gastrointestinal, Amirsys Eosinophilic infiltration in all compartment including muscularis mucosa Usually localized to lower third of the mucosa 6 ~ 20 Eos/HPF, up to 60/10HPFs Cryptitis, Crypt abscess (Eosinophilic microabcess), degranulation No features of chronicity

57 A 32-year-old man with abdominal pain & diarrhea Mastocytosis CD117 Lamina propria infiltration by round cells with metachromic cytoplasm & eosinophils Colonic involvement of systemic mastocytosis or Mastocytic enterocolitis Positive for CD117 & mast cell tryptase, CD25 (+) only in systemic mastocytosis

58 Inflammatory Disorders of Colon Acute Chronic Eosinophilic Paucicellular Ischemic/ hemorrhagic Non-ischemic/ Non-hemorrhagic Architecture preserved Architecture NOT preserved Ischemic Radiation Microscopic colitis Early IBD DDAC Some infections DDAC Chronic ischemia Radiation Tuberculosis Healed injury GVHD Systemic dx IBD, inflammatory bowel disease; DDAC, Diverticular disease-associated colitis Allergic Eosinophilic gastroenteritis Mastocytosis

59 Paucicellular Colitis Architecture: Variable, dilated crypt Lamina propria: Minimal infiltrates Commonly associated with increased apoptosis (Apoptotic colonopathy) Differential diagnoses include Graft-Versus-Host Disease (GVHD), & Drug reactions (Chemotherapy, Mycophenolate mofetil). Increased epithelial apoptosis Dilated damaged crypt

60 Take home message Don't be afraid of diagnosing Normal Colon Look for a pattern of injury Identify specific features Otherwise, put a descriptive diagnosis (+ Note)