INTERPRETATION OF ENDOSCOPIC BIOPSIES OF COLON

Dr. Rajni Yadav, Dr. Prasenjit Das, Prof. S. Datta Gupta

Department of Pathology

All India Institute of Medical Sciences

Ansari Nagar

New Delhi 110029

Endoscopic biopsies of the colon are done routinely for a wide variety of conditions, both

non-neoplastic and neoplastic. The following account emphasizes the interpretation of

biopsies related to non-neoplastic lesions.

Colonoscopy is a diagnostic procedure of choice for certain patients with diarrhoea lasting

several weeks to months, for patients with bloody diarrhoea or to sample any mucosal

abnormalities seen by computed tomography (CT) or by CT-enteroclysis. Endoscopic colonic

biopsies aid in the evaluation of any visual mucosal abnormalities or even normal appearing

mucosa and thus form the basis of diagnosis and management of colorectal diseases (1).

Unfortunately the value of colonoscopy and mucosal biopsy is underestimated. Even when an

accurate histological diagnosis cannot be arrived at, the biopsy provides invaluable direction

in narrowing the clinical or endoscopic differential diagnosis. Nevertheless strategies for

optimal diagnosis have not been clearly established even in areas in which the differential

diagnosis depends on biopsy findings (2, 3, 4).

Colonic biopsy fragments taken from different anatomical locations of colon together, yield

information concerning disease patterns, distribution, extent and/or severity, activity versus

chronicity, clinical state of remission or relapse, and gives information regarding

development of complications (1). However optimal biopsy evaluation is essentially

clinicopathological and interpretation is meaningful only when careful consideration is given

to the historical, clinical, endoscopic, radiographic, microbiologic, and other available data

(5). Inflammatory conditions forma bulk of the reasons for mucosal biopsies of the colon.

Different patterns of inflammation which can be identified in mucosal biopsies include active

or chronic colitides, focal active colitis, ischemic injuries, trauma related changes, apoptotic

colopathy, intraepithelial lymphocytosis, eosinophilic colitis, graft versus host pattern,

chronic mucosal prolapse, portal hypertensive colopathy, nonspecific ulcer of the colon,

etc.(6). Histologic features may suggest an inflammatory condition and provide knowledge

concerning the severity of the underlying lesion or the extent of disease, allowing one to

correlate the clinical impression with histologic findings. One may also be able to diagnose

the presence of specific neoplasms or identify a treatable organism. However one needs to be

acquainted with normal architectural variants, effects of the biopsy procedure, and of the

mucosal events accompanying changes during mucosal repair, to avoid any misinterpretation.

Endoscopic biopsy is utilized to assess normal appearing mucosa, inflammed mucosa, effects

of treatment or follow up or to diagnose the nature of obvious polyps or growths.

Normal Histology of the Colon

In an endoscopic colonic biopsy specimen, usually the full thickness of the mucosa including

the mucosal layer and the muscularis mucosae are included. The superficial portions of the

sub-mucosa may be included but it is rather unusual to expect deeper layers.

In a colonic biopsy in lowest power magnification, the arrangement of glands / crypts should

be the first point to note. The crypts are closely placed The colonic glands, arranged parallel

to each other in the mucosa with an equal amount of intervening amina propria. The crypts

normally extend throughout the thickness of the mucosa and appear to rest on the muscularis

mucosa.

The colonic mucosa comprises of two distinct cells: the absorptive cells and mucus secreting

goblet cells. The absorptive cells are tall columnar with basally situated nuclei. The goblet

cells in contrast show punched out mucin vacuoles, which are positive for alcian blue at

pH2.5 (acidic mucin). Though the distribution of goblet cells does not follow a specific

pattern, the distribution is usually even and gives rise to floret shape in the colonic glands

when cut transversely. Hence areas of loss of goblet cells in a segment of colonic mucosa

should be taken as an abnormality probably due to the effect of inflammatory mucosal injury

or even due to regeneration or a manifestation of preneoplasia.

The lamina propria contains collagen, lymphocytes and plasma cells. Hence before

diagnosing a chronic inflammation in colonic biopsies, this fact should be kept in mind.

These inflammatory cells along with intra-epithelial lymphocytes and lymphoid aggregates in

the submucosa and lamina propria form the mucosal defence mechanism against the invading

organisms. Lymphoid follicles are generally seen up to the level of hepatic flexure. The

mucosal cells above these lymphoid follicles have special characteristics and are called the

M cells. These cells are important in view of transcellular ionic transport in colonic mucosa.

The submucosa is made up of loose areolar tissue, collagen, blood vessels and contain both

nerves and ganglion cells. Inflammatory cells are sparse if at all but lymphiod follicles

described abov may be seen.

The muscular coat comprises of two layers with tenia coli forming bands of thickened

longitudinal layer. The myenteric plexus of ganglion cells and nerves are usually searched for

in the vealuation of Hirchsprung Disease and related conditions.

The serosa is forms a faint but distinct layer that becomes prominent in serositis.

Regional varations in the morphology of the mucosa exists.

Chronic colitis

Although it is customary to describe acute conditions prior to chronic conditions, chronic

colitis will be described first since some of these can have acute exacerbations resembling

acute colitis [active colitis].

The crypt destructive chronic inflammatory pattern in chronic ulcerative colitis (UC) in

remission (quiescent UC) is probably the best representative pattern of chronic colitis. There

is architectural distortion with shortening of crypts, decrease in the number of crypts, loss of

parallel arrangement, branching and irregular glands. Other features include appearance of

paneth cells, a gap between the base of crypts and the muscularis mucosae, hyperplasia of

neuroendocrine cells, islands of lipocytes in the lamina propria and the presence of more than

occasional neutrophils. Basal plasma cells and basally located lymphoid aggregates are also

helpful features to identify chronic colitides. There may be normal colonic mucosal layer or

mucosal atrophy of varying degree with loss of goblet cells may be seen. The muscularis

mucosae is often hypertrophied. However the features described may be seen in varied

chronic colitides, as inflammatory bowel disease (IBD), nonspecific chronic colitis, chronic

ischemic injury, radiation injury, diversion colitis, tuberculosis, schistosomiasis etc (7-10).

Thus the histological features need to be evaluated in conjunction with the clinical

presentation and endoscopic findings.

Active Colitis

The main histological feature is an accumulation of neutrophils in the lamina propria, within

the epithelial cells (cryptitis), or within the lumen of crypts (crypt abscesses). It may be

associated with acute phase of inflammatory bowel disease and acute infectious type colitis.

Diffuse Active Colitis

IBD in the active phase is the classical example of this pattern. One of the most striking

features is the diffuse inflammatory cell infiltrate involving crypts and lamina propria along

with congestion and dilatation of the mucosal capillaries. An early feature is the accumulation

of neutrophils at the base of crypts followed by crypt abscess formation. The mucosal injury

leads to muco-depletion, followed by development of the chronic mucosal changes as

described previously due to the ongoing degenerative and regenerative changes, if the injury

persists. There can be either small mucosal erosions/Apthous ulcers or deep ulcers lined by

mixed inflammatory granulation tissue. Deep fissuring ulcers can be seen in an active

Crohns disease. Intramucosal or rarely submucosal granulomas may be seen in the latter.

The ulcer surface covered with granulation tissue along with inflamed and hyperaemic

mucosa leads to formation of pseudopolypi. Basal plasmacytosis and crypt distortion are the

most helpful features in differentiating active phase of UC from acute self limited/infectious

colitis (11-14).

Focal active colitis

This term is used to describe isolated focal neutrophilic crypt injury. The mere combination

of chronic colitis with patchy acute inflammation does not qualify for it. Thus, some area of

biopsy must be essentially normal. Crohns disease, NSAID induced injury, infectious colitis,

resolving UC, ischemia and bowel preparation may lead to focal active colitis (15-16).

Acute infectious type/self limited colitis

The different patterns which may be observed include: normal colon, non specific increase in

inflammatory cells, diffuse active colitis and focal active colitis. The common histological

features are inflammatory infiltration of lamina propria, edema, hyperemia and hemorrhage.

Severe cases may show crypt abscesses, extensive necrosis and microthrombi. However the

hallmark of this type of colitis is intact crypt architecture. Common etiologic infectious

agents include campylobacter, salmonella, shigella species, viral or parasitic infections. It has

to be differentiated from the acute phase of UC. Crypt distortion and basal plasmacytosis

favour a diagnosis of UC; whereas an acute inflammation out of proportion to chronic

inflammation suggests an acute infective etiology. The definitive diagnosis of infectious

colitis requires laboratory identification of the offending organism (17-20).

Acute mucosal injury with ischemic features and pseudomembrane formation

Pseudomembranous colitis and ischemic colitis share a pathogenic mechanism involving

endothelial damage with disruption of blood flow and tissue oxygenation and, thus, have

similar, occasionally overlapping, histological and endoscopic features.

Acute ischemic colitis

The histological features reflect different stages of the evolution of injury. Early ischemic

lesions consist of mucosal surface necrosis and hemorrhage with minimal or no inflammation

with sparing of deeper portion of the colonic crypts. As the lesions evolve, there are erosions,

areas of acute inflammation and reactive epithelial hyperplasia. A peudomembrane may form

over the ulcerated surface. Other findings include hemorrhage into the lamina propria,

hyalinization of the lamina propria and intravascular thromboses. Acute and chronic

inflammatory cells, especially plasma cells, are typically scant in ischemic type damage and

this feature can help differentiate ischemic type damage from primary IBD. Ischemic colitis

may be a manifestation of vascular disease, hypovolemic state and toxin producing bacterial

infection e.g. verotoxin producing E coli. It may be associated with a variety of drugs,

including vasopressors, oral contraceptives, NSAIDs, cocaine, and glutaraldehyde, which is

sometimes used to clean endoscopes (21-24). The thumb printing pattern of barium enemas

is due to geographical areas of mucosal damage, followed by areas of peudomembrane

formation.

Acute mucosal injury with punctuate pseudomembranes: pseudomembranous enterocolitis/

ischemic enterocolitis/necrotizing enterocolitis

The distinguishing feature is a focal explosive mucosal lesion characterized by the presence

of a mushroom like mass of mucus and neutrophils attached to the surface of mucosal glands.

Initial stage shows numerous minute superficial foci of necrosis which subsequently leads to

bursting of neutrophil rich edema fluid to form characteristic membranes. The

pseudomembranes tend to be diffuse in C. difficile and patchy in ischemia. Hyalinized lamina

propria and atrophic crypts are specific findings in ischemia that are not seen in C. difficile

colitis (25-29).

Traumatic type change

Histologic changes associated with trauma depend on whether the mucosa is examined during

an acute phase or whether a biopsy is taken after repeated traumatic episodes. There is acute

inflammation and hemorrhage in the acute stage. Mucosal distortion, fibromuscular

proliferation in lamina propria, intramucosal capillary ectasia, chronic inflammation and

hemosiderin deposits may be observed in cases of repeated trauma. The trauma pattern can be

seen in the solitary rectal ulcer syndrome, localized colitis cystica profunda, inflammatory

cloacogenic polyp, the mucosa adjacent to orifices of colonic diverticula, and inflammatory

cap polyposis and are frequent findings adjacent to neoplasia and in the vicinity of the

ileocecal valve (30-31).

Apoptotic colopathy

Surface colonic epithelial apoptosis and karyorrhectic debris within the superficial lamina

propria commonly seen in mucosal biopsy are attributed to bowel preparation. Apoptotic

bodies in the deep crypt are only rarely seen (

Read and colleagues in 1980. From this subset of colitides, at least two well-defined

clinicopathologic conditions have been described: collagenous and lymphocytic colitis (37-

39).

Histologically, there is evidence of chronic colitis, but crypt destruction or features of

regeneration are usually not seen. There are increased intraepithelial lymphocytes in crypts

and surface epithelium in lymphocytic colitis (>20/100 epithelial cells [(normal: 5

lymphocytes per 100 ECs]). In collagenous colitis there is deposition of collagen beneath the

surface epithelium in the epithelial basement membrane, making the thickness of the

basement membrane > 10 micrometer [(normal: 2 -3 micrometer thickness]). Histologically,

with aid of Massons trichrome stain thickened basement membrane is identified with

entrapped congested tiny capillaries within the basement membrane (40-43).

Care should be taken to avoid misinterpreting a tangentially cut basement membrane to

interpret as the thickened basement membrane. Surface epithelial damage with increased

intraepithelial lymphocytes are usually present in these cases. Eosinophils are often identified

in areas adjacent to the thickened basement membrane. Cryptitis and crypt abscesses are

unusual (44). Changes morphologically indistinguishable from lymphocytic colitis have been

consistently found in large bowel biopsies of patients with celiac disease suggesting a

pathogenetic relationship between these two disorders (45). A subtype of lymphocytic colitis

containing scattered multinucleated giant cells in the subepithelial region has been described

(46). Sometimes mucosal prolapse, enema, ischemia or radiation may result into similar

histopathological features. Hence a proper clinic-pathological correlation is necessary. The

resolving infectious colitis or in biopsies from right side of colon may show increased intra-

epithelial lymphocytes, hence these should be ruled out before making a diagnosis of

lymphocytic colitis, especially in children.

Brainerd Diarrhoea

The term Brainerd diarrhoea is applied to the syndrome of chronic watery diarrhea

characterized by abrupt onset, marked urgency to defecate, frequent fecal incontinence,

abdominal cramps, weight loss, and fatigue in the absence of other systemic symptoms. Most

cases occur among patients following epidemic exposures to an unknown agent. Colonic

biopsies reveal surface epithelial lymphocytosis without mucosal architectural distortion,

surface degenerative changes, or thickened subepithelial collagen. The disorder can only be

diagnosed in conjunction with epidemiologic data that indicate that the patient is part of an

epidemic colitis with a common point source (47-51).

Chronic mucosal prolapse

The solitary rectal ulcer syndrome, localized colitis cystica profunda, inflammatory

cloacogenic polyp, prolapsing mucosal folds in areas of diverticular disease, and

inflammatory cap polyposis are closely allied conditions that have been linked to large bowel

mucosal prolapse and trauma (52-53).

Solitary Rectal Ulcer Syndrome (SRUS)

The characteristic finding is fibromuscular hyperplasia of the lamina propria. Strands of

smooth muscle lying perpendicular to the colonic crypts are diagnostic (54). There is inter-

cryptal erosion, hyperplasia of the crypts, a tendency towards villous configuration and

thickening of the muscularis mucosae (55).

Colitis Cystica Profunda (CCP) occurs in both localized and diffuse forms. The localized

form usually occurs in the rectum associated with mucosal prolapse or SRUS. The diffuse

form is less common and is usually associated with IBD or radiation injury (56).

The histologic hallmark is the presence of mucin filled cysts lined by benign colonic

epithelium. Misplaced epithelium is usually surrounded by a discrete rim of lamina propria.

Differentiating CCP from a well-differentiated mucinous carcinoma can be extremely

difficult, especially in the setting of chronic IBD (57).

Eosinophilic Colitis

The number of lamina propria eosinophils varies significantly with the geographical locale of

the patient and seasonally. In children, the cecum and appendix have the highest

concentrations of eosinophils. Pure or dominant eosinophilic inflammatory infiltrates, usually

without crypt destruction characterize eosinophilic colitis. Instead of the normal distribution

of eosinophils in the upper lamina propria, clusters or sheets of eosinophils infiltrate deep

lamina propria and crypt epithelium. Eosinophilic colitis may be idiopathic or due to allergies

to foods, drugs, or parasites or to hyper eosinophilic syndrome, leukaemia, or systemic

vacuities. The infiltrates are characteristically patchy and multiple biopsies are essential. In

general, however, more than 60 eosinophils per 10 hpf and eosinophils in the muscularis

mucosae or as the predominant cell in crypt abscesses are diagnostic of this condition (58-

60).

Portal hypertensive colopathy

Portal hypertensive colopathy is characterized by prominent thick-walled venules and

capillaries and occasional superficial superficial venular ectasias. The changes are most

apparent in the right colon. Portal hypertension colopathy occurs in patients with cirrhosis,

hepatic arteriovenous fistulas, or obstruction of the portal vein or its branches by thrombus or

neoplasm (61).

Diversion colitis

It is an inflammatory process that develops in colonic segments excluded from fecal stream.

The most common changes are mild to moderate chronic inflammation in the lamina propria,

crypt abscesses and follicular lymphoid hyperplasia. With time, the muscularis mucosae

hypertrophies, the submucosa shows fatty and fibrous tissue infiltration, the muscularis

propria thickens and the lumen becomes progressively smaller (62-63).

Diverticular disease- associated colitis: ulcerative colitis or Crohns disease-like variant:

A pathologist interpreting the colonic biopsies must be acquainted with these entities, as in

these conditions there can be histological or even gross findings of ulcerative colitis or

Crohns colitis, in absence of the disease elsewhere in the colon. An older person presenting

with hematochezia, often show histological features similar to IBD in biopsies, including

gland distortion, cryptitis or crypt abscesses, in an area adjacent to diverticular only. If not

correlated clinically, an eronious diagnosis of IBD may be given in these cases.

Radiation colitis

Acute radiation damage shows apoptosis with epithelial flattening, loss of mucin content, and

decreased mitoses. Erosions may develop, and eosinophils are typically prominent in the

lamina propria and epithelium. As the mucosa recovers from this insult, marked regenerative

atypia can be seen. Chronic radiation damage may cause occlusive damage to vessels,

strictures, fistulas, ulcers, and serosal adhesions. The key to establishing a diagnosis of

radiation colitis is knowledge of the patient's clinical history (64).

Drug induced colitis

Drug-induced colitis has a wide variety of clinical symptoms and histologic changes.

Chemotherapeutic agents are often associated with ulcerative lesions of the entire GI tract.

Antibiotics are well known to cause pseudomembranous colitis secondary to C. difficile.

NSAIDs have been linked to focal active colitis, chronic nonspecific ulcers, ischemic-type

lesions, collagenous colitis, and increased apoptosis. Oral contraceptives and hormone

replacement therapies have been associated with ischemic type ulcers in the colon.

Mycophenolate mofetil can lead to colitis resembling acute graft versus host disease,

ischemic colitis or IBD. Paediatric patients taking high strength replacement pancreatic

enzymes may show fibrosing colonopathy (65-69).

Preparation artefacts

Enema effect is characterized by flattening of the surface epithelium with edema of the

lamina propria. The surface epithelium may be completely stripped away. Other findings

include extra-vassated lyzed RBCs in lamina propria, mucin depletion in crypts and

neutrophils in epithelium (70).

Changes induced by radiographic substances and venoms

Barium granulomas produce brownish green tumorous masses, fibrosis and structuring (71).

Gastrografin does not elicit an inflammatory response. The crystals can be identified for a

definitive diagnosis. Venoms may lead to ischemic colitis (72).

Neutropenic colitis/typhilitis

Neutropenic colitis traditionally affects children treated for leukaemia and other conditions. A

severe necrotizing colitis is present with marked transmural submucosal edema, vasculitis,

stromal hemorrhage, and patchy to complete epithelial necrosis. A pseudomembrane may

form over the surface. The absence of neutrophils in the face of significant cell injury allows

one to make the diagnosis of neutropenic enterocolitis (73).

Phlegmonous colitis

The mucosa is intact but the folds are thickened due to the submucosal edema. An intense

neutrophilic infiltrate is present in the submucosa, which variably spreads into the muscularis

propria (74).

Disorders associated with granulomas and macrophage collections

Small mucosal macrophage collections are a common nonspecific reaction to low-grade

injury. Occasional small granulomas can complicate almost any infection. Granulomas with

central caseating necrosis constitute the histologic hallmark of tuberculosis or Yersinia

infections. Well-formed granulomas may be found in sarcoidosis and CD. The granulomas in

a CD is usually microgranulomas and mucosal peri-cryptal. Submucosal granulomas or

macrogranulomas may occasionally be seen. While in colonic tuberculosis the granulomas

are mostly macrogranulomas, submucosal, confluent and sometimes necrotizing. (75) Deep

granulomatous lesions may also be seen with invasive carcinomas or diverticulosis.

Xanthogranulomas or foreign body granulomas may also be seen. Diffuse macrophage

collections may be associated with Mycobacterium avium-intracellulare infections, Whipple

disease, histoplasmosis, storage diseases, immunodeficiencys, and even algal infections (76).

In Chronic granulomatous inflammation neutrophilic abscesses surrounded by sheets of

foamy histiocytes are noted. Well formed granuloma formation is usually not noted.

Autoimmune colitis

The colitis presents as a mild intraepithelial lymphocytosis or the epithelium contains large

numbers of degranulating eosinophils and mast cells superimposed on a background of

mucosal atrophy.

Pneumatosis coli

Cysts are found in all bowel layers which may be lined by epithelioid macrophages,

multinucleated giant cells, and variable chronic inflammatory cells infiltrate (76).

Dysplasia and carcinomas in colonic biopsies

Dysplasia in a colonic biopsy may be primary or secondary to an underlying chronic disease.

The most common mistakes performed during interpretation are describing the reparative

atypia as dysplasia. As a practise, dysplasia must be out of proportion to the inflammatory

process undergoing in the mucosal fragment and preferably such changes should be noted in

an area away from the inflammation. If nuclear changes are suspicious in an area of dense

inflammation, the term indefinite for dysplasia would be more favourable.

In case of definite dysplasias, further deeper sections should be examined to rule out at least

superficial infiltration. But, if a definite area of tumor infiltration not seen in a biopsy, the

term carcinoma should not be uttered. To identify the breach of epithelial basement

membrane a simple periodic acid Schiff stain may be performed. A disoriented mucosal

fragment may show transversely cut islands of dysplastic mucosal fragments, which may be

regarded as a carcinoma. Displaced begin mucosal glands in an inflammatory process, may

be difficult to differentiated often from a well differentiated adenocarcinoma and should be

reported carefully.

Algorithms to follow during interpretation of a colon biopsy specimen

As discussed previously interpretation of a colon biopsy should follow a standard protocol, if

not findings may be missed. In the lowest magnification, the mucosal epithelial surface and

the crypt architecture should be observed and noted down. In this power the mucosal ulcers,

exudates, pseudo membrane or altered glandular arrangements are noted easily. Next in 10x

magnification, the definite patterns of glandular disarray are commented. The exudates is

present should also be observed again to see any inoculating fungus. The nuclei should be

seen to rule out any possible dysplasia. After observing all these, the features of chronic

inflammation should be included in description first, as e.g. glandular disarray, loss of glands,

loss of goblet cells, gland branching, lamina propria inflammation, fibrosis, basal

plasmacytosis etc. After mentioning the chronic features, the notes on presence of activity

should be mentioned, in terms of mucosal ulcers, cryptitis, crypt abscesses etc. Any dysplasia

suspected in low power should be confirmed in higher magnification. Any possible viral

inclusion should also be noted in higher power. In case of unexplained chronic inflammation

intra-cellular parasites should also be looked for.

Conclusion

Thus the interpretation of colon biopsies is extremely important as a pathologists report acts

as a window to this immensely important closed organ of body. However, the reporting

should be systematic and protocolized. If not followed a specific pattern of reporting

algorithm, important findings may be missed. There is a general tendency to give less

importance to the small colonic mucosal fragments. A colonic biopsy may be superficial and

representative only the superficial dysplastic mucosal fragment in an adenocarcinoma, and

reporting of the same should be done with caution. Unless a convincing area of tumor

infiltration is seen, the report should be descriptive, mentioning the nature of dysplasia. The

histopathological findings in a colon biopsy must be correlated with clinical, radiologic and

endoscopic features, and the final decision should be in a way to facilitate the patients

management best.

DIAGNOSTIC FEATURES AND CAUSES OF COMMON HISTOLOGICAL PATTERNS

Histological Pattern Diagnostic Histological

Features

Causes and Clinical

Associations

Acute colitis

Neutrophils predominate

Mononuclear cells conned to upper lamina propria

No crypt branching

Self-limited infection

C. difcile Drug reaction

Acute mucosal injury with

punctate pseudomembranes:

Pseudomembranous colitis

pattern

Neutrophils predominate

Other features: edema, focal

surface epithelial necrosis,

pseudomembranes, dilated

crypts with attened epithelium

Early ischemia

C. difcile Verotoxin E. coli 0157:H7

Drug reaction

Acute mucosal injury:

Ischemic colitis

Neutrophils predominate

Other features: edema,

hemorrhage,thrombi,

epithelial necrosis with

preservation of crypt outlines

Hypovolemia/low-ow states

Verotoxin E. coli 0157:H7

Shigella verotoxin

Vasculitis/vasculopathy

Drug reaction

Chronic crypt-destructive

colitis

Predominantly mononuclear

inammatory inltrates with basal plasmacytosis but

neutrophils persist

Cryptitis, crypt destruction,

and branching crypts

Inactive pahse characterized

by empty distorted lamina

propria, crypt branching,

Paneth cell metaplasia

Ulcerative colitis

Crohns colitis Indeterminate colitis

Prolonged enteric

infections

Uncommon chronic

systemic,

venereal, or parasitic

infections

Drug reaction

Diverticular diseaseassociated colitis

Diversion colitis

Idiopathic proctitis

Chronic non-crypt-

destructive colitis

Mononuclear cells

predominate

Basal plasmacytosis but

neutrophils persist

Intraepithelial lymphocytes

increased

Subepithelial collagen in

collagenous colitis

Lymphocytic colitis

Collagenous colitis

Celiac sprue

Drug reaction

Brainerd diarrhea

DIAGNOSTIC FEATURES AND CAUSES OF LESS COMMON HISTOLOGICAL PATTERNS

Histological Pattern Diagnostic Histological

Features

Causes and Clinical

Associations

Eosinophilic Colitis

Eosinophilic infiltrates with or

without crypt destruction

Pericryptal eosinophils, basal

band of mast cell

Food allergy

Drug allergy

Parasitic infestation

Idiopathic eosinophilic enteritis

Hypereosinophilic syndrome

Vasculitis

Pericryptal eosinophilic

enterocolitis

Graft-versus-host/immune-

suppression pattern Mononuclear cells predominate

in lamina propria

Crypt cell apoptosis and lymphocytic infiltration of

crypts

Graft-versus-host disease

HIV infection

Other viral infections Immunosuppression

Chronic mucosal prolapse

Variable combinations of

ischemic change, ulcers, epithelial hyperplasia,

regeneration, or

overgrowth (polyps), hypertrophic smooth muscle

fibers, fibrosis, and sometimes

displacement of epithelium into

submucosa

Occult rectal prolapse

Prolapse in other locations Chronic mechanical trauma

Portal hypertensive colopathy

Mucosal capillaries and venules

prominent with thickened

sclerotic walls, venular ectasia

Portal hypertension due to

cirrhosis, hepatic

arteriovenous fistula, portal

vein or tributary obstruction

Non-specific or idiopathic ulcer

of the colon

Isolated ulcer with granulation

tissue base, epithelial

regeneration on edge but no colitis in surrounding mucosa

Drug reaction, particularly

NSAIDs

Vasculitis Cytomegalovirus

Stercoral ulcers [Tables from Herschel A. Carpenter, and Nicholas J. Talley. Am J Gastroenterol 2000; 95: 878 896]

RECOMMENDATIONS FOR REPORTING INFLAMMATORY BOWEL DISEASE

[British Society of Gastroenterology Working Group]

HISTOLOGICAL ASSESSMENT:

Mucosal Architecture Change of surface topography

Decreased crypt density

Crypt architectural abnormality (distortion, branching, shortening)

Lamina Propria Cellularity

Increase and altered distribution of cell types usually present Granulomas and giant cells

Neutrophil Polymorph Infiltration

Lamina propria Crypt epithelium (cryptitis)

Crypt lumina (crypt abscess)

Surface epithelium

Epithelial Abnormality

The first three relate to Inflammatory Bowel Disease Mucin depletion

Surface epithelial damage

Metaplastic changes

Surface intraepithelial lymphocytes Apoptosis

Subepithelial collagen

REPORTING CATEGORIES:

NORMAL: Directs investigation to functional causes of diarrhoea, but Crohns disease is not excluded

INFLAMMATION UNCLASSIFIED

Definite inflammation present but insufficient features to categorise

CHRONIC IDIOPATHIC INFLAMMATORY BOWEL DISEASE

ULCERATIVE COLITIS TYPE

CROHNS DISEASE TYPE

INDETERMINATE (not possible to make a distinction)

INFECTIVE-TYPE COLITIS

A probability assessment should be given using the standard terms:

Suggestive: Pathologist favours the diagnosis but is not certain Highly suggestive: Pathologist has a definite opinion but full clinical follow-up and/ or correlation

not available.

Regular clinicopathological discussion of cases of suspected CIIBD is to be encouraged and a final

diagnosis should not be made without the necessary supplementary information.

CLASSIFICATION OF DYSPLASIA

[From Harpaz N and Polydorides AD Colorectal Dysplasia in Chronic Inflammatory Bowel Disease Pathology, Clinical Implications, and Pathogenesis. Arch Pathol Lab Med. 2010; 134:876895 & Guidelines from the Bowel Cancer Screening Programme Pathology Group, NHS BCSP Publication

No 1,September 2007]

Colorectal Dysplasia is synonymous with the term intraepithelial neoplasia adopted by the World

Health Organization and Vienna nomenclature systems for gastrointestinal neoplasia but is more

widely used in the United States

Normal / Negative for Dysplasia

No dysplasia

Reactive Changes / Epithelium

In the setting of active or resolving inflammation, the proportions of immature cells tend to expand and to displace the maturation gradient closer to the surface.

Dysplastic epithelium, in contrast, extends uniformly along the crypt axis and surface epithelium with little or no surface maturation. An important exception is villous dysplasia,

which often exhibits maturation along the villous tips.

Other features that favor dysplasia over reactive mucosa include diffuse nuclear hyperchromasia, macronucleoli, atypical mitotic figures, loss of cellular polarity, and dirty

intraluminal necrosis

Low Grade Dysplasia

Low Grade Dysplasia nuclei are confined to the basal half of the epithelial cells whereas High Grade Dysplasia is characterized by nuclei that are stratified randomly between the basal and

apical halves

The epithelium in LGD is simple columnar or cuboidal.

Typically, the nuclei are crowded, elliptical, hyperchromatic, relatively uniform in size and orientation, and have smooth, delicate nuclear membranes, inconspicuous nucleoli, and typical mitotic figures.

In most instances, goblet cells are inconspicuous or pleomorphic, but in some instances they may be hyperplastic or inverted (dystrophic)

High Grade Dysplasia

High grade dysplasia is diagnosed on architecture, supplemented by an appropriate cytology. Hence, its presence is nearly always suspected by the appearance under low power of complex

architectural abnormalities in structures whose epithelium looks thick, blue, disorganised and dirty. The architectural features are:

Complex glandular crowding and irregularity (note that the word complex is important and excludes simple crowding of regular tubules that might result from crushing)

Prominent budding (note that the word prominent is important; there is probably some degree of glandular budding, by definition, in all tubular adenomas)

Cribriform appearance and back to back glands

Prominent intraluminal papillary tufting.

The cytological features are:

Loss of cell polarity or nuclear stratification to the extent that the nuclei are approximately equally,though haphazardly, distributed within all three thirds of the height of the epithelium

Markedly enlarged nuclei, often with a dispersed chromatin pattern

Prominent nucleolus

Atypical mitotic figures Prominent apoptosis, giving the lesional epithelium a dirty appearance.

If a biopsy shows both Low Grade Dysplasia and High Grade Dysplasia, it should be classified as a

High Grade Dysplasia unless the High Grade Dysplasia is focal and in such instances the proportion of High Grade Dysplasia should be indicated in the report.

Indefinite for Dysplasia Definitive diagnosis of dysplasia may be precluded when

Histologic features defy clear-cut distinction between reactive and dysplastic mucosa,

Specimen is technically inadequate, for example, too small or superficial, misoriented, fragmented, or poorly fixed

Changes are ambiguous

In all cases serial sections need to be examined to exclude a definitive classification and

technically suboptimal biopsies must be indicated in the report.

Classification of Colorectal Polyps

The following is a brief classification of polyps for the purpose of completion

Histological

Classification

Polyp Type Malignant Potential

Non-neoplastic Hyperplastic polyps No Hamartomas

Lymphoid aggregates

Inflammatory polyps

Neoplastic (adenomas) Tubular adenomas

(025% villous tissue) Yes

Tubulovillous adenomas

(2575% villous tissue)

Villous adenoma

(75100% villous tissue)

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