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Interpretation of Endoscopic
Intestinal Biopsy
Dr.Mrs.Vaidya
Use of Fiberoptic Endoscope
 Direct visualization of GIT
 Taking photographs
 Cytological specimens
 Taking biopsies
 Undertaking therapeutic procedures
Indications for biopsies :
 Small intestine :
1.To know the nature of duodenal ulcer
2. To detect peri-ampullary carcinoma
3. To look for parasites [giardia ,
strongyloides ]
4. Malabsorption study
5. Lymphoproliferative disorders –IPSID &
lymphomas
Indication for biopsies :
 Colo –rectal :
1. Differetiate bet different types of colities
2. Diagnose IBD –UC ,Crohn”s disease , etc.
3. Monitor pt of UC & detect dysplasia or
malignant change
4. Detect the nature polyp & identify early
malignant change
5. To differentiate Ca from Solitary rectal ulcer
6. Detect amyloidosis
Contraindication for biopsies :
 Never performed in uncooperative pt
 Without informed consent
 H/o bleeding disorders
 H/o acute perforation
Endoscopic biopsy forceps :
Forceps Diamete
r of jaw
[mm]
Tissue
wt
ave[mg]
Muscula
ris
mucosa
adequsy
smallest 1.8 3.3 1/3 of bx inadequ
ate
Std.bx.
Forcep
2.4 5.9 2/3 of bx adequat
e
Jumbo 3.4 15.5 All bx BEST
Endoscopic bx forceps :
2 cup shaped jaws – round / elliptical
,serrated / non serrated
Best to use a forcep with central spike to
fix the instrument on mucosa
Other techniques for full thickness bx
specimen –FNAB thr endoscope ,snare
bx technique-electrocoagulation
Gastrointestinal Bx processing
for Light microscopy :
 Essential pre-requisite for HP evaluation
 Careful handling
 Proper orientation –1. Magnifying lens
2. Orienting mucosal surface upward –by mounting bx on Filter
paper/ wire mesh/ plastic mesh/ frosted glass/ vegetable
matrix[ cucumber slice]/ gelfoam,etc.even casette top
 Fixation –10% buffered formalin for 2-3 hr .bouin’s fluid or
halland’s sol.
 Automatic tissue processor or by hand processing in short
cycles
 Ascending grades of alcohol -30 mins each
 Xylol*3 -30 mins each
 Paraffin bath *2 -60 min each
 Orientation is imp while making the paraffin block
 Step sections at 3-4 level
Interpretation of Biopsies :
 It requires good communication bet
endoscopist & pathologist .
 REAL CHALLEHGE : as Bx is very
SMALL
 Pathologist must know :clinical history,
physical findings, result of radiographic & lab studies ,
ind. For scopy, endoscopic findings & site of Bx,etc

So complete scopy report with Bx is necessory.
Interpretation of Jejunal Bx :
 Imp step in
evaluating pt with
MALABSORPTION.
 Normal villous/crypt
ratio -3:1 or 5:1
 Intraepithelial
lymphocytes- 1-5
enterocytes
Dissecting microscopy imp in
interpreting jejunal bx in
malabsorption
 Grade 1 :villi finger or leaf like
 Grade 2 :leaflike with fusion to form
small ridges or convolutions
 Grade 3 :lost with flattening of mucosa
 grade 1 & 2 villi –normal individuals in
India

Patterns of Abnormal SI
Mucosa :
 Severe villous abnormality :flat mucosa , no
villi :villous atrophy
 Variable villous abnormality : villi focally flat or
mild to mod villous shortening
 Crypt hyperplasia or hypoplasia
 Increased intraepithelial lymphocytes : non
specific or with features that suggest sp
diagnosis ie. Numerous eosinophils,
granulomas, parasites .
Enteties ass. With :
 Diffuse severe villous
abn. & crypt hyperplasia
1.Celiac sprue
2.Refractory/ unclassified
sprue
3.other protein allergies
4.Lymphocytic
enterocolitis
 Variable villous abn. &
crypt hypoplasia
1.malnutrition-kwashiorkor
2. Radiation & chemo.
Effect
3.End stage refractory
sprue
4.microvillous inclusion
sprue
Celiac sprue :
 Villous/ crypt ratio :
 Normal – 2.5 or >
 Grade 1: 2 –2.5
 Grade 2: 1- 2
 Grade 3: 1- 0.5
 Grade 4: < 0.5
 Grade 3 & 4 –with
celiac disease
SI bx
 Non specific variable villus abn. , usually not
flat
1. Changes ass. With DH
2. Tropical sprue
3. Infections
4. Mastocytosis
5. Autoimmune enteropathy
SI bx
 Variable villus abn. With specific diagnostic
chahges :
1. Whipple disease
2. Mycobacterium avium intercellulare
complex inf.
3. Parasitic infestation [giardia ]
4. Abetalipoproteinemia
5. Eosinophilia gastroenteritis
6. Lymphagiectasia
7. Intestinal lymphoma
Abetalipoproteinemia
 Apical villous cytoplasm
shows vacuolation –due
bto inability to synthesis
B-lipoprotein
 acanthocytic
erythrocytes-due to lipid
membrane defect
 Failure to thrive,
diarrhea, steatorhea
Eosinophilic enteritis
Lymphagiectesia
Intestinal lymphoma
feature MALT[ IPSID]
{B cell lymph.}
EATCL [T cell
lymphoma ]
age 20 –30 50 –60
ass.
Conditions
Developing
countries
Celiac disease
site Jejunum &
duodenum
same
Intestinal lymphoma
Features MALT [IPSID ] EATCL [T
CELL
LYMPHOMA ]
Microscopy Immunoblastic,
polymorphous,sm
all
cleaved,plasmac
ytoid; R-S-like,
Lymphoepithelial
lesions;
Follicular
Polymorphic,
immunoblast &
R-S-like cell,
Occasionally
eosinophils
Colonic bx  Luminal surface is
straight
 Colonic tubules are
tightly packed,parallel &
nonbranching ,all
closely app. muscularis
mucosae
 Globlet cells numerous .
 Scattered intramucosal
lymphoid aggregates
 Overlying them
flattened surface
epithelial cells –M cells
 Paneth cells- base of
Differential diagnosis of IBD -
 ACUTE SEIF
LIMITED
ENTEROCOLITIS
shigella,c. jejuni
 UNUSUAL FORMS
Collagenous
Lymphocytic
Pseudomembranous
 CHRONIC IDIOPATHIC
COLITIS
Crohn’s disease [CD]
Ulcerative colitis [UC]
Resolving UC
 CHRONIC INF.
TB ,Yersinia ,Spirochete
CMV
Parasites
Why to bother to make DD -
 Majority of cases of diarrhea are self
limited or acute inf.-thus NOT to
mislable them as IBD ,CD or UC
 Surgical therapeutic procedure
interventions can differ in CD & UC
General features
Features Acute Colitis Chronic Colitis
General
architecture of
epithelium &
cyrpts
PRESERVATI
ON
ALTERATION
Lamina propria Mixed
inflammatory
cells –
polymorphs
Inc.cellullarity ,
lympho.,plasm
a
cells,poly.,bas
al lymphoid
follicles
Active colitis pattern :
features Ulcerative
colitis
Crohn’s
disease
Infectious
colitis
Architectural
abnormality
diffuse focal Usually focal
Irregular
luminal surface
diffuse
,undulating or
villous
may be focal Sometime focal
Mucin
depletion
&secretion
yes,diffuse
impaired
Usually focal
,sightly
impaired/
increased
Usually focal
Paneth cell
metaplasia
Common
feature of UC
- - Not seen
Active colitis pattern :
feature Ulcerative
colitis
Crohn’s
disease
Infectious
colitis
Crypt
abscesses &
cryptitis
yes focally ,yes Yes ,luminal
accentuation
Location of
inflam.
Mucosal,
submucosal
transmural mucosal
Basal
plasmacytosis
yes absent Usually absent
Granuloma no yes,28% no
Neutrophils in
lamina propria
no no usually yes
Granuloma :
 Sarcoid granuloma :diagnosis of crohn’s
 Non confluent , non caseating
 Best in submucosa ,rarely present in
endo.ileal bx[3%]
 also in Yersinia enteritis
 C D in absence of granulomas confident in
30-40%, based on patchy inflammation, crypt
& goblet changes & basal lymphoid agg.
 In T B :caseating granuloma
:acid fast bacilli [taken up by M cells ]
Villous surface, distorted crypt
architecture ,mixed LP cellularity :- 100%
predictive of IBD
FEATURE SENSITIVITY % PPV %
Villous mucosal
surface
26.4 100
Paneth cell
metaplasia
75.4 100
Distorted crypt
architecture
1.1 97.2
Basal lymphoid agg. 82.4 93.1
Increase in plasma
cells
86.6 85.2
Granuloma 8.8 66.7
Deliver a diagnosis of Acute-Chronic
colitis :
 Most reliable criteria not always present
 combination of feature hv to be used
 Don’t be afraid to mention your doubt
rather than to deliver a wrong diagnosis
 Remember that clinician often don’t
know & will hv to reevaluate the pt
Psedomembranous colitis :
 Small surface
erosion bet. crypts
covered with luminal
spray of pmn or
mucus
 Shows yellow
plaque on
colonoscopy
Collagenous colitis :
 Normal colonic
subepithelial
collagen layer : 5
microns
 Here, increase to 15
microns or more
 Colonoscopy &
barium enema:
normal
Lymphocytic colitis :

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Interpretation of endoscopic intestinal biopsy

  • 2. Use of Fiberoptic Endoscope  Direct visualization of GIT  Taking photographs  Cytological specimens  Taking biopsies  Undertaking therapeutic procedures
  • 3. Indications for biopsies :  Small intestine : 1.To know the nature of duodenal ulcer 2. To detect peri-ampullary carcinoma 3. To look for parasites [giardia , strongyloides ] 4. Malabsorption study 5. Lymphoproliferative disorders –IPSID & lymphomas
  • 4. Indication for biopsies :  Colo –rectal : 1. Differetiate bet different types of colities 2. Diagnose IBD –UC ,Crohn”s disease , etc. 3. Monitor pt of UC & detect dysplasia or malignant change 4. Detect the nature polyp & identify early malignant change 5. To differentiate Ca from Solitary rectal ulcer 6. Detect amyloidosis
  • 5. Contraindication for biopsies :  Never performed in uncooperative pt  Without informed consent  H/o bleeding disorders  H/o acute perforation
  • 6. Endoscopic biopsy forceps : Forceps Diamete r of jaw [mm] Tissue wt ave[mg] Muscula ris mucosa adequsy smallest 1.8 3.3 1/3 of bx inadequ ate Std.bx. Forcep 2.4 5.9 2/3 of bx adequat e Jumbo 3.4 15.5 All bx BEST
  • 7. Endoscopic bx forceps : 2 cup shaped jaws – round / elliptical ,serrated / non serrated Best to use a forcep with central spike to fix the instrument on mucosa Other techniques for full thickness bx specimen –FNAB thr endoscope ,snare bx technique-electrocoagulation
  • 8. Gastrointestinal Bx processing for Light microscopy :  Essential pre-requisite for HP evaluation  Careful handling  Proper orientation –1. Magnifying lens 2. Orienting mucosal surface upward –by mounting bx on Filter paper/ wire mesh/ plastic mesh/ frosted glass/ vegetable matrix[ cucumber slice]/ gelfoam,etc.even casette top  Fixation –10% buffered formalin for 2-3 hr .bouin’s fluid or halland’s sol.  Automatic tissue processor or by hand processing in short cycles  Ascending grades of alcohol -30 mins each  Xylol*3 -30 mins each  Paraffin bath *2 -60 min each  Orientation is imp while making the paraffin block  Step sections at 3-4 level
  • 9. Interpretation of Biopsies :  It requires good communication bet endoscopist & pathologist .  REAL CHALLEHGE : as Bx is very SMALL  Pathologist must know :clinical history, physical findings, result of radiographic & lab studies , ind. For scopy, endoscopic findings & site of Bx,etc  So complete scopy report with Bx is necessory.
  • 10. Interpretation of Jejunal Bx :  Imp step in evaluating pt with MALABSORPTION.  Normal villous/crypt ratio -3:1 or 5:1  Intraepithelial lymphocytes- 1-5 enterocytes
  • 11. Dissecting microscopy imp in interpreting jejunal bx in malabsorption  Grade 1 :villi finger or leaf like  Grade 2 :leaflike with fusion to form small ridges or convolutions  Grade 3 :lost with flattening of mucosa  grade 1 & 2 villi –normal individuals in India 
  • 12. Patterns of Abnormal SI Mucosa :  Severe villous abnormality :flat mucosa , no villi :villous atrophy  Variable villous abnormality : villi focally flat or mild to mod villous shortening  Crypt hyperplasia or hypoplasia  Increased intraepithelial lymphocytes : non specific or with features that suggest sp diagnosis ie. Numerous eosinophils, granulomas, parasites .
  • 13. Enteties ass. With :  Diffuse severe villous abn. & crypt hyperplasia 1.Celiac sprue 2.Refractory/ unclassified sprue 3.other protein allergies 4.Lymphocytic enterocolitis  Variable villous abn. & crypt hypoplasia 1.malnutrition-kwashiorkor 2. Radiation & chemo. Effect 3.End stage refractory sprue 4.microvillous inclusion sprue
  • 14. Celiac sprue :  Villous/ crypt ratio :  Normal – 2.5 or >  Grade 1: 2 –2.5  Grade 2: 1- 2  Grade 3: 1- 0.5  Grade 4: < 0.5  Grade 3 & 4 –with celiac disease
  • 15.
  • 16. SI bx  Non specific variable villus abn. , usually not flat 1. Changes ass. With DH 2. Tropical sprue 3. Infections 4. Mastocytosis 5. Autoimmune enteropathy
  • 17.
  • 18. SI bx  Variable villus abn. With specific diagnostic chahges : 1. Whipple disease 2. Mycobacterium avium intercellulare complex inf. 3. Parasitic infestation [giardia ] 4. Abetalipoproteinemia 5. Eosinophilia gastroenteritis 6. Lymphagiectasia 7. Intestinal lymphoma
  • 19.
  • 20.
  • 21.
  • 22.
  • 23. Abetalipoproteinemia  Apical villous cytoplasm shows vacuolation –due bto inability to synthesis B-lipoprotein  acanthocytic erythrocytes-due to lipid membrane defect  Failure to thrive, diarrhea, steatorhea
  • 26. Intestinal lymphoma feature MALT[ IPSID] {B cell lymph.} EATCL [T cell lymphoma ] age 20 –30 50 –60 ass. Conditions Developing countries Celiac disease site Jejunum & duodenum same
  • 27. Intestinal lymphoma Features MALT [IPSID ] EATCL [T CELL LYMPHOMA ] Microscopy Immunoblastic, polymorphous,sm all cleaved,plasmac ytoid; R-S-like, Lymphoepithelial lesions; Follicular Polymorphic, immunoblast & R-S-like cell, Occasionally eosinophils
  • 28. Colonic bx  Luminal surface is straight  Colonic tubules are tightly packed,parallel & nonbranching ,all closely app. muscularis mucosae  Globlet cells numerous .  Scattered intramucosal lymphoid aggregates  Overlying them flattened surface epithelial cells –M cells  Paneth cells- base of
  • 29. Differential diagnosis of IBD -  ACUTE SEIF LIMITED ENTEROCOLITIS shigella,c. jejuni  UNUSUAL FORMS Collagenous Lymphocytic Pseudomembranous  CHRONIC IDIOPATHIC COLITIS Crohn’s disease [CD] Ulcerative colitis [UC] Resolving UC  CHRONIC INF. TB ,Yersinia ,Spirochete CMV Parasites
  • 30. Why to bother to make DD -  Majority of cases of diarrhea are self limited or acute inf.-thus NOT to mislable them as IBD ,CD or UC  Surgical therapeutic procedure interventions can differ in CD & UC
  • 31. General features Features Acute Colitis Chronic Colitis General architecture of epithelium & cyrpts PRESERVATI ON ALTERATION Lamina propria Mixed inflammatory cells – polymorphs Inc.cellullarity , lympho.,plasm a cells,poly.,bas al lymphoid follicles
  • 32. Active colitis pattern : features Ulcerative colitis Crohn’s disease Infectious colitis Architectural abnormality diffuse focal Usually focal Irregular luminal surface diffuse ,undulating or villous may be focal Sometime focal Mucin depletion &secretion yes,diffuse impaired Usually focal ,sightly impaired/ increased Usually focal Paneth cell metaplasia Common feature of UC - - Not seen
  • 33. Active colitis pattern : feature Ulcerative colitis Crohn’s disease Infectious colitis Crypt abscesses & cryptitis yes focally ,yes Yes ,luminal accentuation Location of inflam. Mucosal, submucosal transmural mucosal Basal plasmacytosis yes absent Usually absent Granuloma no yes,28% no Neutrophils in lamina propria no no usually yes
  • 34.
  • 35.
  • 36.
  • 37.
  • 38.
  • 39. Granuloma :  Sarcoid granuloma :diagnosis of crohn’s  Non confluent , non caseating  Best in submucosa ,rarely present in endo.ileal bx[3%]  also in Yersinia enteritis  C D in absence of granulomas confident in 30-40%, based on patchy inflammation, crypt & goblet changes & basal lymphoid agg.  In T B :caseating granuloma :acid fast bacilli [taken up by M cells ]
  • 40. Villous surface, distorted crypt architecture ,mixed LP cellularity :- 100% predictive of IBD FEATURE SENSITIVITY % PPV % Villous mucosal surface 26.4 100 Paneth cell metaplasia 75.4 100 Distorted crypt architecture 1.1 97.2 Basal lymphoid agg. 82.4 93.1 Increase in plasma cells 86.6 85.2 Granuloma 8.8 66.7
  • 41. Deliver a diagnosis of Acute-Chronic colitis :  Most reliable criteria not always present  combination of feature hv to be used  Don’t be afraid to mention your doubt rather than to deliver a wrong diagnosis  Remember that clinician often don’t know & will hv to reevaluate the pt
  • 42. Psedomembranous colitis :  Small surface erosion bet. crypts covered with luminal spray of pmn or mucus  Shows yellow plaque on colonoscopy
  • 43. Collagenous colitis :  Normal colonic subepithelial collagen layer : 5 microns  Here, increase to 15 microns or more  Colonoscopy & barium enema: normal