J. Comp. Path. 2008, Vol. 138, S1eS43
Available online at www.sciencedirect.com
www.elsevier.com/locate/jcpa
Histopathological Standards for the Diagnosis of
Gastrointestinal Inflammation in Endoscopic
Biopsy Samples from the Dog and Cat: A Report
from the World Small Animal Veterinary
Association Gastrointestinal
Standardization Group
M. J. Day*, T. Bilzer†, J. Mansell‡, B. Wilcockx, E. J. Hall*, A. Jergensk,
T. Minami{, M. Willard‡ and R. Washabau#
*
University of Bristol, Bristol, UK, † University of Düsseldorf, Düsseldorf, Germany, ‡ Texas A&M University,
College Station, TX, USA, x Histovet, Guelph, Canada, k Iowa State University, Ames, IA, USA, { Pet-Vet, Yokohama,
Japan and # University of Minnesota, St Paul, MN, USA
Summary
The characterization of inflammatory change in endoscopic biopsy samples of the gastrointestinal mucosa is
an increasingly important component in the diagnosis and management of canine and feline gastrointestinal
disease. Interpretation has hitherto been limited by the lack of standard criteria that define morphological
and inflammatory features, and the absence of such standardization has made it difficult, if not impossible,
to compare results of retrospective or prospective studies. The World Small Animal Veterinary Association
(WSAVA) Gastrointestinal Standardization Group was established, in part, to develop endoscopic and
microscopical standards in small animal gastroenterology. This monograph presents a standardized pictorial
and textual template of the major histopathological changes that occur in inflammatory disease of the canine
and feline gastric body, gastric antrum, duodenum and colon. Additionally, a series of standard histopathological reporting forms is proposed, to encourage evaluation of biopsy samples in a systematic fashion. The
Standardization Group believes that the international acceptance of these standard templates will advance
the study of gastrointestinal disease in individual small companion animals as well as investigations that compare populations of animals.
! 2008 Elsevier Ltd. All rights reserved.
Keywords: cat; diagnostic standards; dog; gastrointestinal biopsy; gastrointestinal inflammation
Introduction
The diagnosis and treatment of gastrointestinal disease
in the dog and cat are increasingly based on the
collection and interpretation of mucosal biopsy samples
obtained endoscopically from one or more gastrointestinal sites. There are many stages in this process in
which error may be introduced, thereby influencing
the clinical outcome. These stages include the endoscopic biopsy procedure, the processing and embedCorrespondence to: M.J. Day (e-mail: m.j.day@bristol.ac.uk).
0021-9975/$ - see front matter
doi:10.1016/j.jcpa.2008.01.001
ding of the small and fragile tissue samples, and the
microscopical interpretation of the tissue changes by
the diagnostic pathologist (Willard et al., 2001, 2002).
For many clinicians and pathologists, the histopathological interpretation has proved to be the most
contentious and frustrating step in the diagnostic
sequence. This interpretation may be complicated by
inadequacies in the number and quality of the tissue
samples, by fragmentation and unfavourable orientation of these samples during processing, and by the
lack of an internationally accepted set of standards for
evaluating microscopical changes present in the tissues.
! 2008 Elsevier Ltd. All rights reserved.
S2
M.J. Day et al.
The aims of the pathologist are to distinguish normal
from diseased tissue, to characterize the nature and
severity of tissue changes, and to provide an accurate
morphological or aetiological diagnosis, thus facilitating formation of a prognosis and appropriate therapy.
Some histopathological diagnoses, for example, the
identification of adenocarcinoma or overt alimentary
lymphoma, can be made relatively simply. By contrast,
the interpretation of mucosal inflammatory change has
proved to be far more complex. Characterization of
gastrointestinal inflammation has been hampered by
the lack of standard criteria for measuring the histopathological changes within a sample of mucosal tissue.
Over the past two decades, several independent
groups have developed and applied classification systems for characterizing the nature and severity of gastrointestinal inflammatory changes (Jergens et al.,
1992, 1996, 1999, 2003; Wilcock, 1992; Hart et al.,
1994; Yamasaki et al., 1996; Stonehewer et al., 1998;
Baez et al., 1999; German et al., 2000, 2001; Kull
et al., 2001; Zentek et al., 2002; Waly et al., 2004; Peters
et al., 2005; Wiinberg et al., 2005; Münster et al., 2006;
Allenspach et al., 2007; Garcia-Sancho et al., 2007). In
most of these studies, the nature of gastrointestinal inflammation is portrayed primarily by the dominant
population of inflammatory cells (e.g. lymphoplasmacytic, eosinophilic or pyogranulomatous); it is recognized, however, that such populations may overlap
and occur in various combinations. The severity of gastrointestinal inflammation has most often been graded
with a simple four-point scale: normal, mild, moderate
or marked. Although this approach would appear logical, the specific criteria defined by various groups have
differed to the point at which it has become impossible
to relate with certainty the histopathological changes
described in different studies. Even when specific criteria are applied, there may be significant variation between pathologists in the interpretation of changes in
gastrointestinal tissue samples. Thus, Willard et al.
(2002) reported lack of uniformity in the assessment
of 50% of biopsy samples examined by five veterinary
pathologists. This interpretive variation may pose
problems for the routine diagnosis of gastrointestinal
disease or for monitoring the progress of patients receiving post-therapeutic endoscopy. Moreover, such
variation impedes progress in the performance of
multi-centre diagnostic or therapeutic clinical trials
in small animal gastroenterology.
With this background, a Gastrointestinal Standardization Group was convened with the support
of the World Small Animal Veterinary Association
(WSAVA), and with the purpose of developing standards for the diagnosis and treatment of gastrointestinal disease in the dog and cat. One of the first tasks of
this group was to develop a set of histopathological
standards for characterizing the nature and severity
of mucosal inflammatory and associated morphological changes. The current monograph presents the outcome of these deliberations, in what we hope will
become an internationally accepted standard for the
description of microscopical changes affecting the mucosa of the canine and feline gastric body, gastric antrum, duodenum and colon.
Materials and Methods
The WSAVA Gastrointestinal Standardization
Group developed the standards presented herein
over several face-to-face meetings (American College
of Veterinary Internal Medicine [ACVIM] Forum,
2004, St Paul; ACVIM Forum, 2005, Baltimore; British Small Animal Veterinary Association [BSAVA]
Congress, 2006, Birmingham; European College of
Veterinary Internal Medicine [ECVIM] Congress,
2006, Amsterdam; ACVIM Forum, 2007, Seattle;
ECVIM Congress, 2007, Budapest) and by electronic
communication in between these meetings. The scope
of the project was first defined by identifying the four
most commonly sampled anatomical regions of the
gastrointestinal mucosa: the gastric body, gastric antrum, duodenum and colon. For each of these regions,
tissue changes were defined by (1) morphological abnormalities, and (2) the major types of inflammatory
cell infiltrating the epithelium and lamina propria of
that region. The Group included in these evaluations
only those microscopical changes considered to be of
greatest relevance to the inflammatory process. Minor
changes that could equally be artefactual (e.g. small
capillary haemorrhage, tissue oedema) were not incorporated into the standards.
The Group adopted pictorial ‘‘templates’’ of histopathological images to demonstrate the particular
morphological or inflammatory change being presented. It was proposed that for each of these changes,
four images would be presented, namely (1) the normal tissue morphology or baseline numbers of leucocyte subpopulations, (2) mild manifestation, (3)
moderate manifestation, and (4) marked manifestation. The Standardization Group recognized that development of a single pictorial template applicable to
samples taken from both the dog and the cat would be
of greatest value. The fundamental inflammatory
changes that occur within the stomach and intestine
of these two species are in general sufficiently similar
to allow this approach. A major exception, however,
is the density of intraepithelial lymphocytes in the duodenum, which is significantly greater in the cat than
in the dog (German et al., 1999; Waly et al., 2001). It
was agreed that, for this variable, a separate template
would be presented for each species.
Gastrointestinal Histopathology Standards
With these objectives defined, one member of the
Group (MJD) assembled an archive of digital images
by retrospectively screening canine and feline endoscopic biopsy samples from the pathology database at
his institution (Division of Veterinary Pathology, Infection and Immunity, School of Clinical Veterinary
Science, University of Bristol). Images were captured
by a Leica DMLS microscope and associated Leica
DC300 digital camera with IM50 image-management
software. The most representative of these images were
assembled into draft pictorial templates, which were
distributed to the remainder of the group for comment
or replacement by alternative images. By this process
the Group arrived at an agreed set of images, which
now form the basis of the current template.
In addition to developing the pictorial template, the
Group recognized that it would also be useful to
develop a parallel textual description of the key features displayed by each image. This description should
be sufficiently succinct to be applied in the setting of
day-to-day microscopical analysis undertaken by veterinary histopathologists. The aim of the text would
be to complement the image by providing simple
guidelines for assessment and interpretation of each
morphological or inflammatory criterion. These descriptors would be generally based on the ‘‘unit’’ of
a microscopical field examined with a !40 objective,
this being considered the magnification most likely to
be used by diagnostic histopathologists to reach a morphological diagnosis. The proposed text was initially
drafted by MJD and then circulated to the Group
for discussion and editing.
The Group recognized that several studies had
been published in which computer-aided analysis of
immunohistochemically labelled sections had made
possible the precise enumeration of leucocyte subpopulations within the normal canine and feline stomach
and intestine (Roth et al., 1992; Kolbjørnsen et al.,
1994; Jergens et al., 1996, 1999; Elwood et al., 1997;
Stonehewer et al., 1998; German et al., 1999, 2000; Sonea et al., 1999; Roccabianca et al., 2000; Waly et al.,
2001; Paulsen et al., 2003; Southorn, 2004). Although
these data were valuable, they lacked immediate applicability to the simple pictorial template we had
aimed to develop for international use by pathologists
evaluating haematoxylin and eosin (HE)-stained sections of gastrointestinal mucosa. However, for completeness we extracted from these data, for inclusion
in the present monograph, key information on tissue
morphology and on leucocyte numbers in lamina
propria and epithelium, derived from HE-stained
and immunohistochemically labelled sections.
The final section of this monograph presents three
standard reporting forms, devised by the Standardization Group for use in parallel with the templates.
S3
The group proposes that pathologists should be
encouraged to examine endoscopic biopsy samples
taken from the alimentary tract in a systematic fashion and to record the major findings by means of a simple ‘‘tick-box’’ format. Accordingly, the three forms
provide for evaluation of samples taken from the
gastric body, gastric antrum, duodenum and colon.
The forms encourage recording of the number of
tissue samples present on the microscope slide and
an assessment of whether these are adequate for interpretive purposes. Samples may be considered entirely
inadequate (and therefore not interpretable), too superficial but still adequate for limited interpretation,
or adequate. The number of tissues considered abnormal is also recorded. The completed forms then make
possible (1) an assessment of the severity of the morphological and inflammatory changes defined by
the templates, and (2) determination of the final morphological diagnosis. Additional space is provided for
further tissue-specific comments.
Results and Supplementary Information
The pictorial and textual templates for assessment of
inflammatory and associated morphological changes
in the gastric body, gastric antrum, duodenum and
colon of the dog and cat are presented in Tables 1e
4. In each case, a single page of this monograph
presents four images associated with one particular
morphological or inflammatory criterion. The first
(uppermost) image shows the expected appearance
of normal tissue, and the remaining images depict
mild, moderate and marked changes. Accompanying
each image is the associated text that verbally defines
the key features shown by the photomicrograph.
The templates presented herein relate to adult animals with fully mature gastrointestinal tracts, which
will most frequently be the subject of clinical endoscopic
examination. Developmental morphology of the canine
and feline gastrointestinal tract has not been investigated extensively, but it is likely that age-related changes
occur. We would therefore caution that some aspects of
the templates presented here may not be directly applicable to samples taken from other age groups.
Additional supplementary information on normal
morphometry and key resident leucocytes derived
from published literature is presented below for each
of the four anatomical regions under consideration.
Gastric Body Mucosa
A single study (Southorn, 2004) characterized the leucocyte subpopulations within the superficial region of the
normal canine gastric body mucosa. A ‘‘mucosal unit’’
was defined by a 250 mm length of mucosa, in which
S4
M.J. Day et al.
the CD3+ intraepithelial lymphocytes (mean 0.93,
range 0e2), CD3+ lamina propria lymphocytes (mean
4.2, range 0.5e13), lamina propria eosinophils
(mean 0.45, range 0e2) and lamina propria plasma
cells (mean 1.59, range 0e5.83) were enumerated.
The samples were derived from eight dogs, in which
considerable inter-animal variation in cell counts occurred.
plasm and express the molecule perforin as shown by
immunohistochemical labelling with cross-reactive antisera (Konno et al., 1994). This observation suggests that
the cells are granular lymphocytes with cytotoxic function. In general, these cells do not appear to increase in
number in feline inflammatory enteropathy, but neoplasia of this lineage is documented (Roccabianca et al.,
2006). Future studies will be needed to clarify the role
of such cells in the intestinal inflammatory response.
Gastric Antral Mucosa
Colonic Mucosa
Again, a single study (Southorn, 2004) characterized
the leucocyte subpopulations within the superficial
region of the normal canine antral mucosa. A ‘‘mucosal unit’’ was defined by a 250-mm length of mucosa,
in which the CD3+ intraepithelial lymphocytes
(mean 4.4, range 1.5e8), CD3+ lamina propria lymphocytes (mean 10.7, range 2.5e16.5), lamina propria eosinophils (mean 2.7, range 0e6) and lamina
propria plasma cells (mean 6.8, range 0.5e15.5)
were enumerated. The samples were derived from
eight dogs, in which considerable inter-animal variation in cell counts occurred.
German et al. (1999, 2000) assessed the number of
goblet cells in normal canine colonic cryptal epithelium (25.6 " 7.32 per 100 colonocytes). However,
the Standardization Group recognizes that measurement of goblet cells in colonic epithelium is not
straightforward and that the number of such cells
may be artefactually reduced by discharge of mucus
content during the biopsy process. For that reason, assessment of alteration in goblet cell number (specifically goblet cell hyperplasia) was not incorporated
into the standard template.
There are, on average, 7.7 " 3.7 intraepithelial
lymphocytes per stretch of 100 colonocytes in the normal canine basal crypt epithelium (German et al.,
1999). In the lamina propria between the basal crypts
of the canine colon there are approximately
5.5 " 4.29 plasma cells and 3.8 " 3.72 eosinophils
per 10,000 mm2 (German et al., 1999, 2000).
Duodenal Mucosa
Several studies have evaluated, morphologically and immunohistochemically, the normal canine and feline duodenal mucosa. The normal villus length for an adult
dog is 722 " 170 mm, the normal crypt depth is
1279 " 203 mm, and the normal villus to crypt ratio is
0.68 " 0.30 (Hart and Kidder, 1978; Hall and Batt,
1990; Paulsen et al., 2003). Normal dogs have a mean
number of 3.6 " 3.56 goblet cells per stretch of 100 villous enterocytes, and 9.3 " 3.09 goblet cells per stretch
of 100 cryptal enterocytes (German et al., 1999). Villous
intraepithelial lymphocytes are less numerous in the
dog (20.6 " 9.5 per 100 enterocytes) than in the cat
(47.8 " 11.7 per 100 enterocytes), but the number of
cryptal intraepithelial lymphocytes in the dog
(5.2 " 2.33 per 100 enterocytes) is similar to that in the
cat (4.6 " 1.7 per 100 enterocytes) (Hall and Batt,
1990; German et al., 1999; Waly et al., 2001). In the
dog, the total leucocyte count is greater in the cryptal
lamina propria (156.3 " 24.91 per 10,000 mm2) than
in the lamina propria of the base (128.3 " 26.64 per
10,000 mm2) or tip (100.7 " 43.89 per 10,000 mm2) of
the villus (German et al., 1999). Similarly, there are
more eosinophils in the canine cryptal lamina propria
(9.8 " 7.51 per 10,000 mm2) than in the lamina propria
of the villus base (3.7 " 3.52 per 10,000 mm2) or tip
(3.8 " 6.06 per 10,000 mm2) (German et al., 1999). In
cats, a population of globular leucocytes is sometimes
recognized within the intestinal epithelium. These cells
have distinctive eosinophilic granules within the cyto-
Discussion
We believe this is the first attempt to create a histopathological standard for the characterization of inflammatory
and associated morphological abnormalities of the stomach, intestine and colon of dogs and cats. The WSAVA
Gastrointestinal Standardization Group presents these
templates in the hope that they will be accepted by our
peers as the current international standard in the definition of inflammatory change in the canine and feline gastrointestinal tract. The group recognizes that simply
producing such a template does not necessarily mean
that its availability will immediately address all of the current problems related to the microscopical interpretation
of endoscopic biopsy samples. The Group encourages
and welcomes the testing of this model in retrospective
and prospective studies of disease.
To test the utility and validity of the template, we are
performing a validation study that will be presented
elsewhere on completion. It is based on the collation
of a large slide set of several hundred endoscopic biopsy
samples derived from the pathology archives of nine institutions in six different countries. These slides have
been coded and reviewed by four pathologist members
of the Standardization Group. Each pathologist has
Gastrointestinal Histopathology Standards
been asked to use the current templates to score the
changes in each biopsy sample and to record these on
the standard reporting forms. These data points have
been entered into a computer spreadsheet and will be
subject to searching statistical analysis, which will
form the basis of subsequent presentations. This analysis may help us to refine further the templates presented
in this monograph.
These templates and reporting forms have been designed to have ready applicability to retrospective or
prospective research investigations, in which a numerical histopathological score may be correlated with
clinical or therapeutic outcome parameters. The
simple numerical addition of grades of histopathological change (where normal ¼ 0, mild ¼ 1, moderate ¼ 2 and marked ¼ 3) may provide an overall
histological score for the tissue of interest.
The WSAVA Gastrointestinal Standardization
Group hopes that the availability of these template
documents will prove of value to clinicians and pathologists working in the field of dog and cat gastroenterology and will facilitate the reporting of microscopical
changes in biopsy samples, reducing variation between
the interpretations of different pathologists and, consequently, between different published studies.
Acknowledgments
The members of the Standardization Group gratefully acknowledge the financial sponsorship from
Hills Pet Nutrition, which has enabled this project
to be undertaken. Although this commercial funding
underpins our efforts, the Group consists entirely of
independent academic scientists and there is no commercial representation. No member of the Group has
declared having personal or research funding from
Hills Pet Nutrition. The group also acknowledges
the support and encouragement of the WSAVA Executive Board and Scientific Advisory Committee. This
monograph has been subject to the normal peerreview process of the Journal of Comparative Pathology.
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Gastrointestinal Histopathology Standards
Table 1
Histopathological standards for inflammation of the gastric body
Surface epithelial injury
Normal surface epithelium
Single layer of columnar epithelium. HE. Bar, 500 µm.
Mild surface epithelial injury
Attenuation, degeneration, vacuolation or separation of focal
areas of superficial epithelium. HE. Bar, 50 µm.
Moderate surface epithelial injury
More pronounced degenerative changes with focal loss of
some epithelium. HE. Bar, 50 µm.
Marked surface epithelial injury
Widespread ulceration of surface epithelium. HE. Bar, 500 µm.
(Continued on next page)
S8
M.J. Day et al.
Table 1 (continued)
Gastric pit epithelial injury
Normal epithelium
Single layer of columnar epithelium in neck of gastric pit. HE.
Bar, 50 µm.
Mild epithelial injury
Attenuation, degeneration, vacuolation or separation of focal
areas of epithelium of the gastric pit (within area indicated).
HE. Bar, 200 µm.
Moderate epithelial injury
More pronounced degenerative changes, with focal loss of
some epithelium. HE. Bar, 50 µm.
Marked epithelial injury
Widespread disruption and loss of the epithelial structure of
the gastric pit. HE. Bar, 200 µm.
S9
Gastrointestinal Histopathology Standards
Table 1 (continued)
Fibrosis/glandular nesting/mucosal atrophy
Normal mucosa
Glandular tissue closely packed but separated by narrow bands
of connective tissue, 1–2 fibrocytes in width. HE. Bar, 200 µm.
Mild mucosal atrophy
Glands individualized and separated by broader bands of
connective tissue, up to 5 fibrocytes in width. HE. Bar, 200 µm.
Moderate mucosal atrophy
Variably sized lobules of glandular tissue isolated (“nested”)
within connective tissue, separated by matrix up to 10
fibrocytes in width. HE. Bar, 200 µm.
Marked mucosal atrophy
Nested, atrophic and sparse lobules of glandular tissue
separated by collagenous matrix-filled spaces >10 fibrocytes in
width. HE. Bar, 200 µm.
(Continued on next page)
S10
M.J. Day et al.
Table 1 (continued)
Intraepithelial lymphocytes
Normal intraepithelial lymphocytes
Sparse population of approximately 1–2 cells per stretch of 50
epithelial cells. HE. Bar, 50 µm.
Mild increase in intraepithelial lymphocytes
Individual lymphocytes, up to 10 per stretch of 50 epithelial
cells. HE. Bar, 50 µm.
Moderate increase in intraepithelial lymphocytes
Lymphocytes may cluster in groups of up to 4 cells. There may
be up to 20 per stretch of 50 epithelial cells. HE. Bar, 50 µm.
Marked increase in intraepithelial lymphocytes
Epithelium is more diffusely infiltrated by lymphocytes (up to
50 per stretch of 50 epithelial cells). HE. Bar, 200 µm.
S11
Gastrointestinal Histopathology Standards
Table 1 (continued)
Lamina propria lymphocytes and plasma cells*
Normal mucosa
Sparse individual lymphocytes and plasma cells beneath
surface epithelium and between glands; <20 cells per ×40 field.
HE. Bar, 200 µm.
Mild increase in mucosal lymphocytes and plasma cells
Aggregates of lymphocytes and plasma cells beneath
epithelium and between glands; 20–50 cells per ×40 field.HE.
Bar, 200 µm.
Moderate increase in mucosal lymphocytes and plasma cells
Aggregates of lymphocytes and plasma cells present in lamina
and may infiltrate glands; 50–100 cells per ×40 field. HE.
Bar, 200 µm.
Marked increase in mucosal lymphocytes and plasma cells
Diffuse infiltrate of cells occupies much of the area of lamina
propria and may infiltrate and disrupt glandular structure;
>100 cells per ×40 field. HE. Bar, 200 µm.
(Continued on next page)
S12
M.J. Day et al.
Table 1 (continued)
Lamina propria eosinophils*
Normal mucosa
One or two eosinophils per ×40 field within lamina propria are
normal. HE. Bar, 50 µm.
Mild increase in mucosal eosinophils
Clusters of eosinophils within lamina propria; up to 20 cells
per ×40 field. HE. Bar, 50 µm.
Moderate increase in mucosal eosinophils
More widespread infiltration of eosinophils within lamina
propria; up to 50 cells per ×40 field. HE. Bar, 50 µm.
Marked increase in mucosal eosinophils
Diffuse infiltration of lamina propria and sometimes glandular
structure; up to 100 cells per ×40 field. HE. Bar, 200 µm.
S13
Gastrointestinal Histopathology Standards
Table 1 (continued)
Lamina propria neutrophils
Normal mucosa
Neutrophils should not be present. HE. Bar, 200 µm.
Mild increase in mucosal neutrophils
Scattered neutrophils within superficial lamina propria; 10–20
cells per ×40 field. HE. Bar, 200 µm.
Moderate increase in mucosal neutrophils
More widespread infiltration by neutrophils within lamina
propria; up to 50 cells per ×40 field. HE. Bar, 200 µm.
Marked increase in mucosal neutrophils
Diffuse infiltration of lamina propria and sometimes glands; up
to 100 cells per ×40 field. There may be a concurrent
macrophage infiltrate. HE. Bar, 200 µm.
(Continued on next page)
S14
M.J. Day et al.
Table 1 (continued)
Gastric lymphofollicular hyperplasia
Normal mucosa
Small lymphoid aggregates or follicles occupying <10% of
biopsy area are normal, usually in the deep mucosa. HE. Bar,
1 mm.
Mild hyperplasia
Lymphoid aggregates or follicles occupying 10–30% of biopsy
area. HE. Bar, 1 mm.
Moderate hyperplasia
Lymphoid aggregates or follicles occupying 30–50% of biopsy
area. HE. Bar, 1 mm.
Marked hyperplasia
Lymphoid aggregates or follicles occupying >50% of biopsy
area. HE. Bar, 1 mm.
*Mixed inflammatory responses showing both lymphoplasmacytic and eosinophilic infiltration are not uncommon.
S15
Gastrointestinal Histopathology Standards
Table 2
Histopathological standards for inflammation of the gastric antrum
Epithelial injury
Normal mucosa
Single layer of columnar epithelium over surface and lining
gastric pits. Deep tubular pyloric mucous glands. HE.
Bar, 500 µm.
Mild epithelial injury
Attenuation, degeneration or vacuolation of focal areas of
superficial epithelium. HE. Bar, 200 µm.
Moderate epithelial injury
More marked degenerative changes, with focal detachment or
loss of some epithelium. HE. Bar, 200 µm.
Marked epithelial injury
Widespread ulceration of surface epithelium. HE. Bar, 200 µm.
(Continued on next page)
S16
M.J. Day et al.
Table 2 (continued)
Epithelial hyperplasia
Normal mucosa
Single layer of columnar epithelium over surface and lining
gastric pits. Deep tubular pyloric mucous glands. HE. Bar,
200 µm.
Mild epithelial hyperplasia
Uniform increased thickness of gastric pit epithelial lining.
Mild dilation of pit lumen, with some folding of epithelium.
HE. Bar, 500 µm.
Moderate epithelial hyperplasia
Increased thickness of gastric pit epithelial lining, with
distortion and variation in pits. Dilation and folding of
epithelium. Epithelium may be more basophilic. HE. Bar,
500 µm.
Marked epithelial hyperplasia
This change was recognized as an uncommon accompaniment
to inflammatory change and no image or descriptor was
prepared.
S17
Gastrointestinal Histopathology Standards
Table 2 (continued)
Mucosal fibrosis/glandular atrophy
Normal mucosa
Gastric pits and glands uniformly arranged and separated by
bands of connective tissue, up to 10 fibrocytes in width. HE.
Bar, 500 µm.
Mild mucosal atrophy
Gastric pits separated by broader bands of connective tissue.
Mucous glands individualized by narrow but distinct
connective tissue bands. HE. Bar, 500 µm.
Moderate mucosal atrophy
Gastric pits separated by broader bands of connective tissue.
Mucous gland acini reduced in number and more widely
separated by connective tissue. HE. Bar, 500 µm.
Marked mucosal atrophy
Atrophic and sparse lobules of gastric pit/glandular tissue
nested within a more extensive collagenous matrix. HE.
Bar, 500 µm.
(Continued on next page)
S18
M.J. Day et al.
Table 2 (continued)
Intraepithelial lymphocytes
Normal mucosa
Sparse population of approximately 1–2 cells per stretch of 50
epithelial cells. HE. Bar, 200 µm.
Mild increase in intraepithelial lymphocytes
Individual lymphocytes, up to 5 per stretch of 50 epithelial
cells. HE. Bar, 200 µm.
Moderate increase in intraepithelial lymphocytes
Individual lymphocytes, up to 10 per stretch of 50 epithelial
cells. HE. Bar, 200 µm.
Marked increase in intraepithelial lymphocytes
Individual or small clusters of lymphocytes, up to 20 per 50
epithelial cells. HE. Bar, 200 µm.
S19
Gastrointestinal Histopathology Standards
Table 2 (continued)
Lamina propria lymphocytes and plasma cells*
Normal mucosa
Scattered individual lymphocytes and plasma cells beneath
surface epithelium and between gastric pits; <20 cells per ×40
field. HE. Bar, 500 µm.
Mild increase in mucosal lymphocytes and plasma cells
Aggregates of lymphocytes and plasma cells beneath
epithelium and between gastric pits; 20–50 cells per ×40 field.
HE. Bar, 500 µm.
Moderate increase in mucosal lymphocytes and plasma cells
Aggregates of lymphocytes and plasma cells in lamina may
separate gastric pits; 50–100 cells per ×40 field. HE. Bar, 200 µm.
Marked increase in mucosal lymphocytes and plasma cells
Diffuse infiltration of cells occupies much of the area of lamina
propria and may infiltrate and disrupt gastric pit structure;
>100 cells per ×40 field. HE. Bar, 200 µm.
(Continued on next page)
S20
M.J. Day et al.
Table 2 (continued)
Lamina propria eosinophils
*
Normal mucosa
Generally no eosinophils within lamina propria. Up to 1–2 per
×40 field considered normal. HE. Bar, 200 µm.
Mild increase in mucosal eosinophils
Clusters of eosinophils within lamina propria; up to 10 cells
per ×40 field. HE. Bar, 50 µm.
Moderate increase in mucosal eosinophils
More widespread infiltration of eosinophils within lamina
propria; up to 50 cells per ×40 field. HE. Bar, 50 µm.
Marked increase in mucosal eosinophils
Diffuse infiltration of lamina propria, which may distort gastric
pit structure; up to 100 cells per ×40 field. HE. Bar, 50 µm.
S21
Gastrointestinal Histopathology Standards
Table 2 (continued)
Lamina propria neutrophils
Normal mucosa
Should be none present. HE. Bar, 200 µm.
Mild increase in mucosal neutrophils
Scattered neutrophils within superficial lamina propria; up to
10–20 cells per ×40 field. HE. Bar, 200 µm.
Moderate increase in mucosal neutrophils
More widespread infiltration of neutrophils within lamina
propria; up to 50 cells per ×40 field. HE. Bar, 50 µm.
Marked increase in mucosal neutrophils
Diffuse infiltration of lamina propria, which may distort gastric
pit structure; up to 100 cells per ×40 field. There may be a
concurrent macrophage infiltrate. HE. Bar, 200 µm.
(Continued on next page)
S22
M.J. Day et al.
Table 2 (continued)
Gastric lymphofollicular hyperplasia
Normal mucosa
Small lymphoid aggregates or follicles occupying <5% of
biopsy area are normal, usually in the deep mucosa. HE.
Bar, 500 µm.
Mild lymphofollicular hyperplasia
Lymphoid aggregates or follicles occupying up to10% of biopsy
area. HE. Bar, 1 mm.
Moderate lymphofollicular hyperplasia
Lymphoid aggregates or follicles occupying up to 25% of
biopsy area. HE. Bar, 1 mm.
Marked lymphofollicular hyperplasia
Lymphoid aggregates or follicles occupying up to 50% of
biopsy area. HE. Bar, 1 mm.
*Mixed inflammatory responses showing both lymphoplasmacytic and eosinophilic inflammation are not uncommon.
S23
Gastrointestinal Histopathology Standards
Table 3
Histopathological standards for inflammation of the duodenum
Villous stunting
Normal mucosa
Long, slender uniform villi when sectioned longitudinally.
Note that the accurate assessment of villous height is only
possible with well-oriented endoscopic biopsy samples. HE.
Bar, 1 mm.
Mild villous stunting
Villi reduced to approximately 75% of normal length; some
may be increased in width and non-uniform. HE. Bar, 1 mm.
Moderate villous stunting
Villi reduced to approximately 50% of normal length
(stunted); most are increased in width and some may be fused.
HE. Bar, 1 mm.
Marked villous stunting
Villi reduced to <25% of normal length and often fused;
intestinal surface may be flat in severe cases. HE. Bar, 1 mm.
(Continued on next page)
S24
M.J. Day et al.
Table 3 (continued)
Villous epithelial injury
Normal mucosa
Single layer of columnar epithelium. In dogs, normal number
of goblet cells is approximately 3 per 100 enterocytes. HE.
Bar, 50 µm.
Mild villous epithelial injury
Attenuation, degeneration, vacuolation or separation of focal
areas of superficial epithelium. HE. Bar, 50 µm.
Moderate villous epithelial injury
More marked degenerative changes, with focal loss of some
epithelium. HE. Bar, 50 µm.
Marked villous epithelial injury
Widespread ulceration of surface epithelium. HE. Bar, 50 µm.
Gastrointestinal Histopathology Standards
S25
Table 3 (continued)
Crypt distension
Normal mucosa
Uniform crypts aligned perpendicularly to surface, with narrow
luminal area. Columnar epithelial lining with occasional
goblet cells (normal in dog is approximately 9 per 100
enterocytes). Dilation or “abscessation” of individual crypts is
within normal limits. HE. Bar, 200 µm.
Mild crypt distension
Up to 10% of crypts in section are dilated, distorted or contain
luminal eosinophilic material/degenerate neutrophils (“crypt
abscess”). HE. Bar, 200 µm.
Moderate crypt distension
Up to 25% of crypts in section are dilated, distorted or present
as crypt abscesses. HE. Bar, 1 mm.
Marked crypt distension
Up to 50% of crypts in section are dilated, distorted or present
as crypt abscesses. HE. Bar, 500 µm.
(Continued on next page)
S26
M.J. Day et al.
Table 3 (continued)
Lacteal dilation
Normal mucosa
Central lacteal represents up to approximately 25% of width of
the villous lamina propria when sectioned longitudinally. HE.
Bar, 200 µm.
Mild lacteal dilation
Central lacteal represents up to approximately 50% of width of
the villous lamina propria when sectioned longitudinally. Villi
are generally wider than normal. HE. Bar, 1 µm.
Moderate lacteal dilation
Central lacteal ballooned, representing up to 75% of width of
the villous lamina propria when sectioned longitudinally.
Affected villi are wider than normal. HE. Bar, 1 µm.
Marked lacteal dilation
Central lacteal markedly dilated to occupy up to 100% of the
villous lamina propria. Surrounding lamina propria (where
apparent) is oedematous. Villi are markedly distended –
particularly at tips, giving a “club-shaped” appearance. HE.
Bar, 500 µm.
S27
Gastrointestinal Histopathology Standards
Table 3 (continued)
Mucosal fibrosis
Normal mucosa
Narrow band of stroma, up to 1 to 2 fibroblasts in width,
separates crypts. HE. Bar, 100 µm.
Mild mucosal fibrosis
Crypts separated by a band of stroma, up to 5 fibroblasts in
width. HE. Bar, 200 µm.
Moderate mucosal fibrosis
Crypts separated by a band of stroma, up to 10 fibroblasts in
width. Crypts may vary inwidth, some being atrophic. HE.
Bar, 200 µm.
Marked mucosal fibrosis
Crypts separated by an extensive area of collagenous matrix,
>10 fibroblasts in width. Crypts may be atrophic or lost and
replaced by fibrotic matrix. HE. Bar, 200 µm.
(Continued on next page)
S28
M.J. Day et al.
Table 3 (continued)
Canine intraepithelial lymphocytes
Normal mucosa
Normal number in villus, approximately 5–10 per ×40 stretch
of epithelium. HE. Bar, 50 µm.
Mild increase in intraepithelial lymphocytes
Mild increase in number equates to approximately 20–30 per
×40 stretch of villous epithelium. These will generally be
individual cells. HE. Bar, 50 µm.
Moderate increase in intraepithelial lymphocytes
Approximately 30–50 per ×40 stretch of villous epithelium.
These may be focally clustered. HE. Bar, 50 µm.
Marked increase in intraepithelial lymphocytes
Approximately 50–100 per ×40 stretch of villous epithelium.
These may be clustered and occur at all levels of the
epithelium. HE. Bar, 50 µm.
S29
Gastrointestinal Histopathology Standards
Table 3 (continued)
Feline intraepithelial lymphocytes
Normal mucosa
Normal number in villus is approximately 10 – 20 per ×40
stretch of epithelium. HE. Bar, 50 µm.
Mild increase in intraepithelial lymphocytes
Approximately 40 – 60 per ×40 stretch of villous epithelium.
These will generally be individual cells. HE. Bar, 50 µm.
Moderate increase in intraepithelial lymphocytes
Approximately 60 – 100 per ×40 stretch of villous epithelium.
These may be focally clustered. HE. Bar, 50 µm.
Marked increase in intraepithelial lymphocytes
Approximately >100 per ×40 stretch of villous epithelium.
These may be clustered at all levels of the epithelium. HE.
Bar, 50 µm.
(Continued on next page)
S30
M.J. Day et al.
Table 3 (continued)
Text
Lamina propria lymphocytes and plasma cells*
Normal mucosa
Within the villous lamina propria, approximately 25% of the
area of one ×40 field may be occupied by lymphocytes and
plasma cells. Between crypts, there may be 1–2 lymphocytes or
plasma cells. HE. Bar, 200 µm.
Mild increase in lamina propria lymphocytes and plasma cells
Lymphocytes and plasma cells may occupy 25–50% of the area
of the villous lamina propria in a ×40 field. Crypts may be
separated by up to 5 lymphocytes or plasma cells. HE. Bar, 50 µm.
Moderate increase in lamina propria lymphocytes and plasma
cells
Lymphocytes and plasma cells may occupy 50–75% of the
villous lamina propria in a ×40 field. Crypts may be separated
by up to 10 lymphocytes or plasma cells. HE. Bar, 100 µm.
Marked increase in lamina propria lymphocytes and plasma
cells
Lymphocytes and plasma cells may occupy 75 - 100% of the
villous lamina propria in a ×40 field. Crypts may be separated
by up to 20 lymphocytes and plasma cells. HE. Bar, 50 µm.
S31
Gastrointestinal Histopathology Standards
Table 3 (continued)
Lamina propria eosinophils*
Normal mucosa
Normal number of eosinophils may approximate 2–3 cells per
×40 field. Eosinophils may be more numerous in young animals.
HE. Bar, 50 µm.
Mild increase in lamina propria eosinophils
Mild elevation in number of eosinophils to approximately
5 − 10 per ×40 field. Mononuclear cells still dominate the tissue
population of leucocytes. HE. Bar, 50 µm.
Moderate increase in lamina propria eosinophils
Moderate elevation to 10 - 20 per ×40 field. Mononuclear cells
still dominate the tissue population of leucocytes or may occur
in a number similar to that of the eosinophils. HE. Bar, 50 µm.
Marked increase in lamina propria eosinophils
Eosinophils dominate the tissue population of leucocytes and
are not easily enumerated within a ×40 field. HE. Bar, 50 µm.
(Continued on next page)
S32
M.J. Day et al.
Table 3 (continued)
Lamina propria neutrophils
Normal mucosa
Neutrophils should not be present. HE. Bar, 50 µm.
Mild increase in lamina propria neutrophils
Mild infiltrate (5 – 10 neutrophils per ×40 field) in lamina
propria may spread into epithelium. Mononuclear cells still
dominate. HE. Bar, 50 µm.
Moderate increase in lamina propria neutrophils
Moderate infiltrate (20 – 30 neutrophils per ×40 field); may be
accompanied by macrophages. Neutrophils and mononuclear
cells may be present in equal numbers. HE. Bar, 50 µm.
Marked increase in lamina propria neutrophils
Neutrophils are the dominant population in a ×40 field and
are not easily enumerated. May be accompanied by
macrophages. HE. Bar, 50 µm.
*Mixed inflammatory responses showing both lymphoplasmacytic and eosinophilic inflammation are not uncommon.
S33
Gastrointestinal Histopathology Standards
Table 4
Histopathological standards for inflammation of the colon
Surface epithelial injury
Normal mucosa
Single layer of columnar epithelium over surface and lining
crypts. Goblet cells within surface epithelium. More goblet
cells in crypt lining. HE. Bar, 200 µm.
Mild surface epithelial injury
Attenuation, degeneration or vacuolation of focal areas of
superficial epithelium. HE. Bar, 50 µm.
Moderate surface epithelial injury
More marked degenerative changes, with focal separation and
loss of some epithelium. HE. Bar, 200 µm.
Marked surface epithelial injury
Widespread ulceration of surface epithelium. HE. Bar, 100 µm.
(Continued on next page)
S34
M.J. Day et al.
Table 4 (continued)
Crypt hyperplasia
Normal colon
Crypts of uniform length, diameter and perpendicular
arrangement. HE. Bar, 500 µm.
Mild crypt hyperplasia
Crypt lining more basophilic and thickened (particularly
basally), resulting in mild distortion and lack of uniformity. HE.
Bar, 500 µm.
Moderate crypt hyperplasia
Crypt lining diffusely thickened, sometimes resulting in
increased width of crypts, with mild distortion. May be some
folding of lining epithelium into lumen of crypt. HE. Bar, 500 µm.
Marked crypt hyperplasia
Crypt lining markedly thickened; may appear multilayered and
basophilic. Associated with crypt dilation and distortion.HE.
Bar, 500 µm.
S35
Gastrointestinal Histopathology Standards
Table 4 (continued)
Crypt dilation and distortion
Normal mucosa
Crypts of uniform length, diameter and perpendicular
arrangement. HE. Bar, 500 µm.
Mild crypt dilation and distortion
Crypts generally perpendicular but of increased diameter, with
more prominent lumen. HE. Bar, 500 µm.
Moderate crypt dilation and distortion
Crypts irregularly oriented and may be branching. Increased
diameter, with prominent lumen. HE. Bar, 200 µm.
Marked crypt dilation and distortion
Crypts widely dilated and distorted, with no normal
perpendicular orientation. HE. Bar, 500 µm.
(Continued on next page)
S36
M.J. Day et al.
Table 4 (continued)
Mucosal fibrosis and atrophy
Normal colon
Narrow band of stroma separates crypts uniformly. HE.
Bar, 500 µm.
Mild mucosal fibrosis and atrophy
Crypts separated by wider band of stroma, or crypt structure
focally disrupted by localized zone of mild fibrosis. HE.
Bar, 500 µm.
Moderate mucosal fibrosis and atrophy
Loss of crypts. Surviving atrophic crypts are seen within a
prominent collagenous matrix that replaces much of the
mucosal architecture. HE. Bar, 500 µm.
Marked mucosal fibrosis and atrophy
More extensive fibrosis, with almost complete loss of cryptal
structure. HE. Bar, 500 µm.
S37
Gastrointestinal Histopathology Standards
Table 4 (continued)
Lamina propria lymphocytes and plasma cells*
Normal colon
Lymphocytes and plasma cells in lamina propria between
crypts. Five or fewer cells are regarded as normal. Scattered
individual intraepithelial lymphocytes are present in surface
and cryptal epithelium. Increase in the number of
intraepithelial lymphocytes appears to be a rare change in the
colon. HE. Bar, 500 µm.
Mild increase in mucosal lymphocytes and plasma cells
Lymphocytes and plasma cells may fill inter-cryptal region and
mildly increase separation of crypts, but they do not disrupt
normal perpendicular cryptal architecture. HE. Bar, 500 µm.
Moderate increase in mucosal lymphocytes and plasma cells
Lymphocytes and plasma cells fill inter-cryptal region and
moderately increase separation of crypts. May cause some
distortion of cryptal architecture. HE. Bar, 500 µm.
Marked increase in mucosal lymphocytes and plasma cells
Lymphocytes and plasma cells are diffusely distributed in the
lamina propria, disrupting, distorting or obliterating cryptal
micro-architecture. HE. Bar, 500 µm.
(Continued on next page)
S38
M.J. Day et al.
Table 4 (continued)
Superficial lamina propria eosinophils*
Normal colon
One or two scattered eosinophils may be present per ×40 field
of superficial lamina propria. HE. Bar, 100 µm.
Mild increase in mucosal eosinophils
Mild elevation in number of eosinophils to approximately
5 – 10 per ×40 field. HE. Bar, 50 µm.
Moderate increase in mucosal eosinophils
Moderate elevation to 10 - 20 per ×40 field. HE. Bar, 50 µm.
Marked increase in mucosal eosinophils
Eosinophils dominate the tissue population of leucocytes and
are not easily enumerated within a ×40 field. HE. Bar, 100 µm.
S39
Gastrointestinal Histopathology Standards
Table 4 (continued)
Lamina propria neutrophils
Normal colon
Neutrophils should not be present. HE. Bar, 200 µm.
Mild increase in mucosal neutrophils
Mild infiltrate (5 – 10 neutrophils per ×40 field) in lamina
propria or spreading into epithelium. Mononuclear cells still
dominate. HE. Bar, 200 µm.
Moderate increase in mucosal neutrophils
Moderate infiltrate may be 20 – 30 neutrophils per ×40 field;
may be accompanied by macrophages. Neutrophils may be
equal in number to mononuclear cells. HE. Bar, 200 µm.
Marked increase in mucosal neutrophils
Neutrophils are the dominant population in a ×40 field and
are not easily enumerated. May be accompanied by
macrophages. HE. Bar, 50 µm.
(Continued on next page)
S40
M.J. Day et al.
Table 4 (continued)
Lamina propria macrophages
Normal colon
Occasional scattered macrophages within lamina propria. HE.
Bar, 200 µm.
Mild increase in mucosal macrophages
Macrophages increased in number (up to 20 per ×40 field)
and may form small clusters. HE. Bar, 100 µm.
Moderate increase in mucosal macrophages
Macrophages increased in number (up to 50 per ×40 field)
and may focally aggregate. HE. Bar, 100 µm.
Marked increase in mucosal macrophages
Macrophages are dominant population, forming a diffuse
sheet of cells within the lamina propria and displacing cryptal
microarchitecture. HE. Bar, 200 µm.
*Mixed inflammatory responses showing both lymphoplasmacytic and eosinophilic inflammation are not uncommon.
S41
Gastrointestinal Histopathology Standards
STANDARD FORM FOR ASSESSMENT OF THE
GASTRIC BODY OR ANTRAL MUCOSA
Pathologist_______________________
Case number_____________________
Number of pieces of gastric tissue on slide_________
Tissue present
Inadequate
Too superficial
Adequate depth
Number of tissues abnormal______________
MORPHOLOGICAL FEATURES
Normal
Mild
Surface epithelial injury
Gastric pit epithelial injury
Fibrosis/glandular nesting/
mucosal atrophy
INFLAMMATION
Intraepithelial lymphocytes
Lamina propria
lymphocytes and plasma cells
Lamina propria eosinophils
Lamina propria neutrophils
Other inflammatory cells
Gastric lymphofollicular hyperplasia
FINAL DIAGNOSIS
Normal tissue
Lymphoplasmacytic inflammatory
Eosinophilic inflammatory
Neutrophilic inflammatory
Mucosal atrophy/fibrosis (non-inflammatory)
Other
OTHER COMMENTS
Moderate
Marked
S42
M.J. Day et al.
STANDARD FORM FOR ASSESSMENT OF DUODENAL MUCOSA
Pathologist_______________________
Case number_____________________
Number of pieces of duodenal tissue on slide_________
Tissue present
Inadequate
Too superficial
Adequate depth
Number of tissues abnormal______________
MORPHOLOGICAL FEATURES
Normal
Mild
Villous stunting
Epithelial injury
Crypt distension
Lacteal dilation
Mucosal fibrosis
INFLAMMATION
Intraepithelial lymphocytes
Lamina propria
lymphocytes and plasma cells
Lamina propria eosinophils
Lamina propria neutrophils
Other
FINAL DIAGNOSIS
Normal tissue
Lymphoplasmacytic inflammatory
Eosinophilic inflammatory
Neutrophilic inflammatory
Lymphangiectasia
Mucosal atrophy/fibrosis (non-inflammatory)
Other
OTHER COMMENTS
Moderate Marked
Gastrointestinal Histopathology Standards
STANDARD FORM FOR ASSESSMENT OF COLONIC MUCOSA
Pathologist_______________________
Case number_____________________
Number of pieces of colonic tissue on slide_________
Tissue present
Inadequate
Too superficial
Adequate depth
Number of colonic tissues abnormal______________
MORPHOLOGICAL FEATURES
Normal
Mild
Surface epithelial injury
Crypt hyperplasia
Crypt dilation/distortion
Fibrosis/atrophy
INFLAMMATION
Lamina propria
lymphocytes and plasma cells
Lamina propria eosinophils
Lamina propria neutrophils
Lamina propria macrophages
FINAL DIAGNOSIS
Normal colon
Lymphoplasmacytic inflammatory
Eosinophilic inflammatory
Neutrophilic inflammatory
Histiocytic/granulomatous inflammatory
Mucosal atrophy/fibrosis (non-inflammatory)
Other
OTHER COMMENTS
Moderate Marked
S43