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 vicinit y 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 (<1 per 20 crypts) outside of pathologic
conditions. Increased deep apoptotic bodies can be seen in ischemic type damage, CMV
infection, chemotherapy or radiation, and in association with mycophenolate mofetil.
Apoptosis is the characteristic form of cell death in graft versus host disease (GVHD), other
immune deficiency syndromes like AIDS and thymic neoplasia. GVHD may result in focal
crypt epithelial cell apoptosis, crypt abscesses, loss of crypts, sloughing of the mucosa and
formation of inflammatory pseudopolypi. There is architectural distortion in the chronic
phase (32-36).
Intraepithelial lymphocytosis/microscopic colitis
Some patients with chronic idiopathic diarrhea have histological evidence of colitis even
though their colons appear normal by barium enema and by colonoscopy; such patients have
the entity known as microscopic colitis. The term microscopic colitis was first coined by
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 disease
associated 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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