Workup of gastrointestinal cases: new tests and biopsy interpretation. Douglas
Palma DVM, DACVIM
For the past few years multiple diagnostic tests have been employed to better
characterize gastrointestinal disease. These tests represent biomarkers of disease,
localization of cytology and/or better characterization of histology.
New blood testing for confirmation gastrointestinal disease:
Over the past few years an emphasis has been made on serum vitamin testing.
Cobalamin is one of these examples. Cobalamin is a vitamin that is from the distal
small intestine (ileum). Disturbances in cobalamin have been documented in patients
with distal small intestinal disease, small intestinal bacterial overgrowth/antibiotic
responsive diarrhea, pancreatic insufficiency and congenital cobalamin deficiency.
In light of the clinical picture. If exocrine pancreatic insufficiency is a possibility, then a
TLI test should be performed. Exocrine pancreatic insufficiency is thought to potentially
result in decreased pancreatic secretions and bacteriostatic effects as well as potentially
reducing production of intrinsic factor necessary for cobalamin absorption within the
intestine. If antibiotic responsive diarrhea is suspected, then appropriate antibiotic trials
should be performed. Recently, a series of dogs with congenital cobalamin deficiency
manifesting with multi-systemic signs have been documented. These patients may not
exhibit clinical histories consistent with gastrointestinal disease but should be a
differential for patients with cobalamin deficiency.
In absence of these conditions, Hypocobalaminemia generally implies that the
absorptive surface of the distal small intestine is dysfunction. This can be a direct result
of inflammatory, neoplastic, infectious and/or noninfectious/noninflammatory conditions
tract. Documentation of low cobalamin should draw the attention of the clinician to,
making sure to procure biopsies, when indicated from this segment.
The presence of a cobalamin deficiency suggests malabsorption and may imply some
quantitative degree of functional impairment. In the author’s opinion, this may provide
us together patient, of chronic enteropathies. It has been suggested that extremely low
cobalamin levels <150 are more supportive of gastrointestinal neoplasia (i.e.
lymphoma) then inflammatory disease in cats.
Furthermore, cobalamin deficiency can result in disruption of gastrointestinal function,
further perpetuating clinical illness. A small subset of the population (predominantly
cats) may have clinical gastrointestinal signs that resolve with cobalamin
supplementation. Therefore, not only does cobalamin represent a diagnostic marker
and localizer disease, it also guides therapeutic intervention.
Supplementation for cobalamin is as follows:
Patients with small intestinal disease or
antibiotic responsive diarrhea
Cats 250 µg subcutaneously once weekly
for six weeks, then every other week for
six weeks, then monthly thereafter.
It is recommended that the cobalamin
checked after therapy has been
implemented (at the monthly dosing
interval) if the level is normal with
treatment, discontinuation could be
considered.
Dogs:
Small dogs: 250 µg; see above
Medium dogs: 500 µg; see above
Medium to large dogs: 750 µg; see above
Large dogs: 1000 µg; see above
Giant dogs: 1500 µg; see above
Exocrine pancreatic insufficiency
see above dosing; give every two weeks
chronically subcutaneously
Congenital cobalamin deficiency
see above dosing; give weekly for six
weeks,,. Then give every other week
thereafter indefinitely
Folate represents an additional vitamin that can as a biomarker for gastrointestinal
disease and essentially provide clues to localization.
Alterations in folate absorption be appreciated with proximal small intestinal disease.
Similar differential diagnoses for these conditions as above should be considered. This
finding is slightly less sensitive than cobalamin for gastrointestinal disease. However, in
the right context, a low folate level suggests proximal gastrointestinal biopsy a position.
Unlike cobalamin in patients with small intestinal bacterial overgrowth/antibiotic
responsive diarrhea, folate is increased from local natural production. While this could
potentially support a bacterial floral alteration, this finding is at times. Therefore, let us
like other diagnostic tests, the findings should be interpreted in the context of the clinical
history and/or physical examination/image changes.
Citrulline:
Recently, work has been performed with Citrulline as a potential biomarker of intestinal
disease. This amino acid is found to be synthesized by intestinal enterocytes.
Alterations in the functional enterocyte mass can result in decreased levels with
gastrointestinal disease.
Future work regarding its utility in screen for gastrointestinal disease. Recent evidence
suggests that it may represent a potential marker of spontaneous and/or acute intestinal
dysfunction. In human medicine, this test has been so good at predicting
gastrointestinal disease patients with inflammatory bowel disease.
Serum 25 hydroxyvitamin D
Vitamin D levels have recently been shown to be decreased with inflammatory bowel
disease. Additionally, these decreased vitamin D levels have related with
hypoalbuminemia and/or disease severity. Furthermore, they may occasionally be
associated with ionized hypocalcemia and/or elevations in parathyroid hormone.
It is uncertain what this assay plays and veteran medicine at this time. However, there
is some suggestion that supplementation may play a role in modifying disease outcome
in the future. Recent suggestion of people suggests that vitamin D may be an
appropriate treatment certain forms Chron’s disease.
Diagnosis of protein losing enteropathies:
This is a group of conditions associated with gastrointestinal loss of protein. The vast
majority of these conditions are associated with the emaciation, weight loss, polyphagia
for inappetence, vomiting and/or third spacing of fluid. It is important to note that some
of these patients have no clinical signs at all and the diagnosis is made based on
biochemical changes alone.
Typically, patients with protein losing enteropathies have panhypoproteinemia, as the
gastrointestinal tract does not discriminate in protein loss. It should be noted that
occasional conditions can be associated with low albumin levels alone. (I.e. fungal
disease or immunoproliferative enteropathy).
Occasionally, the patient presents with hypoalbuminemia at this only clinical finding both
historically and on physical exam. When this occurs, ruling out protein losing
nephropathy (urine proteins: creatinine ratio) and (serum bile acids, liver enzymes,
hepatic imaging, protein C,) is essential to establishing a localization of protein loss from
the gut. In absence of gastrointestinal clinical signs, owner’s may be reluctant to
perform invasive diagnostics (i.e. endoscopic biopsies, full-thickness biopsies).
Therefore, occasionally, documentation of protein loss from the intestines is possible
using an alpha 1 protease inhibitor assay.
It is important to know that a low serum albumin has been associated with more severe
disease process (disease activity; severe) and may correlate with prognosis in dogs and
cats. Additionally, it may be more predictive of certain etiologies (i.e. cats w/ LSA).
Hypoalbuminemia suggests that more aggressive medical management or diagnostics
are indicated.
It is important to note that focal disease can result in a PLE and development of
hypoalbuminemia. In these cases, signs may be minimal based on remaining
gastrointestinal tract being functional. Some common lesions associated with a PLE
may include neoplasia, ulcerations and lymphangectasia.
Alpha 1 protease inhibitor assay
This is a plasma protein, similar in size to albumin that is lost into gastrointestinal tract
at the same rate as albumin and other plasma proteins. Unlike albumin, it is resistant to
enzymatic degradation by bacteria and digestion. It retains its integrity within the
gastrointestinal lumen and ultimately the feces.
The indication for this assay is to screen for protein losing enteropathies, generally in
patients without clinical signs. Positive testing suggests/confirms the presumptive
diagnosis and justifies interventional procedures. Additionally, this test can provide
information regarding breeds at risk of PLE as a screening test (SCWT). Patients with
overt gastrointestinal signs do not need further documentation of disease and therefore,
the assay is not recommended.
Samples are collected on 3 consecutive days on 3 non-hemorrhagic stools obtained by
the owner. Sample handling is crucial with this test. The manufacturers recommend
using specific tubes designed to collect adequate fecal material. These tubes are
provided by the Texas A&M gastrointestinal lab. Following collection of the sample,
each sample must be frozen and held until delivered to the hospital. Following delivery
to the hospital, each sample must be placed in a box and shipped on ice immediately to
the laboratory. Failure to complete the steps, may result in false negatives.
New assays for assessment of intestinal inflammation and/or damage
pANCA (Perinuclear Anti-neutrophil cytoplasmic antibodies)
This serum test has been shown to be a very SPECIFIC test for inflammatory bowel
disease in dogs and may be diagnostic marker for PLE in SCWT. However, the low
sensitivity of this test makes its clinically utility less valuable.
C-Reactive Protein:
Non-specific inflammatory marker/acute phase protein that is release in response to
cytokine mediated hepatic stimulation. This assay has been correlated with moderate
to severe disease using CIBDAIand may be used to track clinical improvement.
Calcium binding proteins:
Fecal calprotectin and other S100 gene proteins (A8/A9 and A12) are calcium binding
proteins present predominantly within neutrophils and other inflammatory cells within
the mucosa. Recently, veterinary studies have documented increased fecal
concentrations of these proteins in the setting of inflammatory bowel disease. In
humans, fecal calprotectin has been associated with activity indices scoring systems,
predicting clinical relapse, biomarker of inflammatory disease and/or certain forms of
colorectal cancer.
Future diagnostic evaluation may aid in differentiation between pathologic processes
within the intestines. Currently, S100 A12 fecal marker appears to have the greatest
sensitivity for the dissection intestinal inflammation and most well correlated with
endoscopic and clinical scoring systems.
Leukotriene concentrations:
Recently, urinary leukotriene for concentrations have been documented in inflammatory
bowel disease suggesting that this pathway may be important in the inflammatory
pathway/pathogenesis.
Future utilization of urinary leukotriene levels may be a marker of inflammation dollars
with chronic enteropathy. Differentiation between diseases and/or utilization of the
assay for cats has not been evaluated.
N-Methylhistamine
mast cells have been documented in inflammatory bowel disease in animals. Local
release of histamine may contribute to the inflammatory cascade locally. NMethylhistamine is a stable metabolite of histamine and has been shown to be
increased in humans within the urine. Preliminary evidence in animals suggests
elevations in fecal N-Methylhistamine levels within certain breeds (Norwegian
Ludenhunds, soft coated wheaten Terriers).
Amino acid profiles:
Disturbances and amino acid metabolism have been documented in with inflammatory
bowel disease. Evaluation of dogs, recently with specific enteritis revealed a
significantly different amino acid profile with many amino acids being decreased relative
to controls some being increased. Additionally, proline and serine were shown to
inversely correlate with the activity indices. The clinical utility of amino acid testing at
this time is uncertain. Future roles may include pharmacologic therapy to correct amino
acid imbalances and/or differences in clinical outcome.
Regulatory T cells
Recently, regulatory T cells have been shown to be decreased within peripheral
circulation and within the tissue of patients with chronic enteropathies. While this may
provide some basis as to potential pathologic mechanisms that contribute to the
expression of disease, it is possible that this could potentially represent a biomarker for
chronic enteropathies (both in peripheral blood and on biopsies) in the future.
Nuclear factor kappa beta
Nuclear factor kappa beta is a transcription factor that results in up
regulation/expression of cytokines involved in inflammatory place. It has been shown in
dogs that nuclear factor kappa ETA is increased in patients with chronic enteropathy
and food response and disease. (FRD >CE). Additionally, it has been shown that
following treatment, tissue activation of nuclear factor kappa beta is produced.
Therefore, future roles of nuclear factor kappa beta may include documentation of
response to therapy, potential predictive this of food responsiveness disease based on
biopsy and expression) and/or help in titration of pharmacologic therapy (i.e.
upregulation of cyclosporine based on lack of nuclear factor kappa beta normalization).
This could particularly be important for ongoing clinical studies, as histologic disease
does not appear to change in many cases despite lack of or complete response to
therapy.
Biomarkers of intestinal neoplasia:
Thymidine kinase is enzyme highly expressed by rapidly dividing cells. It is been shown
to be increased with multicentric lymphoma dogs. Recently investigations of thymidine
kinase into utilization for predicting lymphoma has been utilized and cats. In general,
sensitivity for this assay ranges anywhere from 47 to 78%. In general thymidine kinase
has low sensitivity for neoplasia but high specificity. This test can be utilized in cases
where differentiation between lymphoma and inflammatory disease is needed. This test
is readily available through veterinary diagnostic institutes in California. The author
frequently uses this assay in cases where clinical suspicion for lymphoma exists
(without obvious of masses on ultrasound). A positive asset in getting may warrant
more aggressive therapeutic intervention, potentially without a histologic diagnosis.
Gastrin is a gastrointestinal neuropeptide secreted from intestinal enterocytes and
pancreas. Hypersecretion of gastrin from gastrinomas (a rare neuruendocrine tumor)
can result in chronic vomiting and weight loss. Severe gastrointestinal ulceration can
occur from hyperstimulation of parietal cells within the stomach. Gastrin levels are
readily available to document these tumors. In general these functional tumors are
associated with marked elevations in gastrin, generally >10 times normal controls. It
should be noted that acid suppressive therapy can impact gastrin levels (elevate them),
therefore, if testing is indicated, ideally it would be done in the setting of no acid
suppression.
Clinical Assessment of Disease Severity
The past several years, development of clinical scoring systems to evaluate critically the
response of patients to therapeutic interventions and/or furthered description of disease
severity have been proposed. The initial scoring system was the CIBDAI (Canine
Inflammatory Bowel Disease Activity Indices) and more recently evolved to CCCEAI
(Canine Chronic Enteropathy Activity Indices) and FCEAI (Feline Chronic Enteropathy
Activity Indices).
These activity indices are generally based on one or more of the following parameters:
activity/attitude, appetite, vomiting, stool consistency, stool frequency, weight loss,
albumin levels, ascites/peripheral edema and the presence of pruritus or not. In cats,
similar indices have been proposed however, addition of the presence of endoscopic
lesions, total protein, ALT/ALP and phosphorus have been included.
These scoring systems have been shown to correlate with clinical response to therapy.
Additionally, these clinical scoring systems have been correlated with gross endoscopic
lesions.
New molecular tools: biopsy application
The recent development of newer molecular strategies helps to deal with the chronic
problem of differentiating inflammatory bowel disease from neoplasia (i.e. lymphoma).
This dilemma appears to be a problem particularly cats with small cell lymphoma. It
has been long suspected that inflammatory bowel disease can progress to lymphoma
over time. This progression may occur at some sites, giving rise to a patient with both
inflammatory bowel changes and concurrent foci of neoplasia within the same sections.
PAAR: PCR for antigen receptor rearrangement
This is a PCR-based test that is designed to amplify hypervariable regions of T and B
cell genes. They specifically target e CDR3 region of T-cell receptor gamma and
immunoglobulin heavy chain gene in B cells. By amplifying these hypervariable
regions, a banding pattern can be detected that differentiates a clonal from non-clonal
population of lymphocytes. Clonality is a major differentiating feature between
inflammation and neoplasia. Therefore, application to biopsies may be able to
differentiate a neoplastic process from inflammatory bowel disease. While clonality is
highly associated with neoplasia, it is important to note that, as monoclonal antibody
responses are occasionally seen with nonneoplastic processes, so is clonality on
PARR.
In general, the sensitivity of this test (monoclonal or oligoclonal) is approximately 89%
for feline lymphoma. False-negatives can occasionally occur in these patients. Is
important to note that application of this test to biopsies have a higher yield when areas
of concern are isolated and evaluated. Therefore, if a section of biopsy is more
“suspect” then another section, this is the section that needs to be submitted for
evaluation. Usually, pathologists should hand select which biopsies are chosen
however, it is important to be aware of the potential flaws in submission.
Immunohistochemistry
This is another molecular tool use on tissue to apply primers against common surface
markers on B cells and T cells. A commonly used B cell surface molecule is CD 79,
whereas, a commonly used T cell surface marker is CD 3. Immunohistochemistry
allows for further characterization of cell types presence within a histologic section.
Most lymphocytic neoplastic processes are homogeneous in cell characterization (all B
cells or T cells). Whereas inflammation is characterized by a heterogeneous
inflammatory infiltrate. Therefore, application of immunohistochemistry (more readily
available) to biopsies may further suggests neoplassia as a potential diagnosis.
CD11c Expression:
Surface marker of dendritic cells that have been shown to be reduced in the setting of
inflammatory bowel disease. Additionally, the lack of expression of the surface marker
seems to correlate with a more severe activity indices score. Future considerations
would include evaluation within the feline species, utilization in differentiating disease
processes (food responsiveness vs. nonfood responsive) and/or characterizing potential
responsiveness of disease. Currently, this appears to be more investigational, however
its availability in the future may change.
P glycoprotein
This is a cell membrane pump expressed by the intestinal enterocytes. This pump acts
to eliminate zenobiotics from the enterocytes and displace them into the intestinal
lumen. It is been shown that in animals, P glycoprotein has been upregulated within the
small/large bowel impatience with inflammatory bowel disease. This up regulation both
with in mucosal lymphocytes and enterocytes appears to happen both intrinsically and
is induced with prednisone therapy. There are some suggestions that expression of P
glycoprotein may predict response to therapy, with high expression suggesting poor
response and low expression suggesting good response.
Currently, the availability of this assay limits its utility. Future evaluations and
correlation of P glycoprotein with clinical signs, prognosis and/or response to specific
therapies needs to be established.
FISH: Florescent in Situ Hybridization
This is another molecular tool using a florescent primer added to histologic tissues.
These primers bind to their specific target genes including: 16 S bacterial or 23S rDNA
gene and/or Escherichia coli. This assays predominantly used for patients who are
suspected to have enteroinvasive E. coli. Each individual bacteria are documented
using this technique and allows for pathologists to determine localization of bacterial
and correlation of these bacteria with histologic changes.
The most common utility in this case are patient suspected to have history of histiocytic
colitis (boxers, French Bulldogs). Other potential applications exist for this testing. The
presence of a neutrophilic inflammation within the gastrointestinal tract may further
elucidate the relative association of bacteria with this lesion if not appreciated on this
logic examination. Additionally, atypical inflammatory granulomatous lesions may help
to identify bacteria where traditional staining may not. Veterinary medicine has
commonly used this in the setting of colitis and more recently pancreatic and
hepatobiliary disease (in cats).
New molecular tests for infectious disease:
Recently, new serologic tests have been developed for the diagnosis of atypical fungal
disorders as well as other enteric pathogens.
Pythium
Serologic assay: highly sensitive, highly specific
Indications:
Used to confirm diagnosis of Pythium and/or rule out
other filamentous fungi. Consider in patients in
endemic regions, those with cutaneous lesions and/or
histologic lesions consistent
Lagenidium
Serologic assay: highly specific, moderate sensitivity
Indications:
Used to differentiate from Pythium and/or other
filamentous fungi. Consider in patients in endemic
regions, those with cutaneous lesions and/or histologic
lesions consistent
Blastomycoses/Histoplasmosis Urine antigen testing: Mira Vista Labs.
This test can be performed on blood and urine. The
sensitivities are greater increased on urine. The assay
is highly sensitive for blastomycosis and
histoplasmosis.
Indications:
This is a rare cause of infectious enteropathy and
should be considered with multisystemic disease,
patients in endemic regions and/or to guide therapeutic
treatment
Fecal PCR testing
Interpretation of fecal PCR testing can be difficult and
needs to be correlated with the clinical history,
cytologic findings and/or clinical signs
The presence of DNA does not definitively
documented disease. The presence of the organism
does not definitively document disease.
Indications:
Perform this test in patients with indications suggesting
infection: pyrexia, cytology suggesting infection
(campylobacter, clostridium), leukopenia, exposure to
other dogs, multiple dogs with illness
Heterobilharzia americanum
“Canine” Schistosomiasis is a tremadode located in
the Gulf Coast and the Southern Atlantic Coast. It is
commonly associated with chronic gastrointestinal
signs (diarrhea, vomiting, weight loss) and
multisystemic signs (hypoalbuminemia,
hyperglobulinemia, hypercalcemia, eosinophilia,
hepatopathy).
Indications:
Endemic regions, hypercalcemia with compatible
clinical signs, gastrointestinal and hepatic disease,
access to open water/marshland
Ideal testing:
PCR: highest sensitivity
Samples: collect 2-3 stools over several days and ship
to Texas A&M
Alternative options:
Fecal direct smear: low sensitivity
Sodium chloride sedimentation: moderate sensitivity
Cryptospordium
Diagnostic test of choice:
ProSpecT Enzyme immunoassay
Has highest sensitivity; 89% with one sample
Alternative testing:
Low sensitivities; 1) Acid fast staining 2) IFA testing
Indications:
Immunosuppression, intermittent chronic diarrhea,
malabsorption
Diagnostic of choice:
Fecal ELISA/Immunoassays
High sensitivity and specificity > 90%. It is important to
note that false positives and negative can be present
in some cases.
Indications:
Patients with compatible clinical signs of diarrhea with
exposure, multi-pet illness
Alterative diagnostics:
Zn Sulfate
>90% with 3 fecal samples
Indications:
Patients with persistently positive immunoassays
without signs, routine screening, exposure risk for
zoonosis
Giardia
Diagnostic test of choice:
Fecal ELISA/Immunoassays
High sensitivity > 90% and High specificity > 90%.
Some of th
Standard testing: ZnSO4 centrifugation
Sensitivity
49% if a single fecal sample
> 90% by examining 3 fecal samples from
different days
Direct immunofluorescence assays
Sensitivity and specificity > 90%
Qualitative enzyme immunoassays
Biopsy interpretation:
Is important to note that biopsy interpretation requires not only histologic interpretation
but will that the patient have compatible clinical signs (vomiting, diarrhea, weight loss,
change in appetite, etc.), illumination of other potential factors associated with
symptoms (dietary responsive, antibiotic responsive, infectious disease) in addition to
these biopsies.
Historically, the emphasis of biopsy was the quantity and type of inflammatory infiltrates.
It should be noted that other findings have some significance as well. This may include
changes in villus structure, crypt abscesses and/or lymphangectasia.
Type of inflammatory infiltrates do help to differentiate disease processes. Eosinophilic
inflammation can be a variant form of “inflammatory bowel disease”, however, it may
imply other alternative specific etiologies: food hypersensitivity, parasitic disease,
specific infectious diseases and/or hyperadrenocorticism. Additionally, certain breeds
are predisposed to this type of inflammation (Rottweilers, Siberian Huskies). Dietary
hypersensitivity is definitely the most common cause of eosinophilic inflammation,
therefore diet intervention should be implemented in these cases aggressively.
Occasionally, patients that lack clinical response to diet alone may require a short
course of corticosteroids and ultimately may be able to be managed and died alone in
the future. Less common forms of inflammatory infiltrates include granulomatous
inflammation. These findings are not common to “inflammatory bowel disease” and are
more typical of infectious disorders. The most common infectious etiologies include
enteroinvasive E. coli, fungal disease, canine schistosomiasis, mycobacterium and
feline infectious peritonitis. Granulomatous inflammation can rarely be associated with
idiopathic disease. Therefore, identification of this type of inflammation should
immediately result in an expanded exposure risk/travel history and infectious disease
testing (as deemed appropriate based on geographic area and complementary
biochemical/clinical information). Special stains can be applied to biopsies to evaluate
for acid fast bacteria, fungal elements and/or bacteria. It should be noted that
occasionally, special stains can be negative despite the presence of an organism.
Another form of inflammation, neutrophilic inflammation can be seen with intestinal
disease. Classically, neutrophilic inflammation is associated with a more acute disease
process. This is true of patients with gastrointestinal disease. The majority of the
patients with neutrophilic inflammation have nonspecific gastroenteritis, hemorrhagic
gastroenteritis, and/or other acute enteropathies. Occasionally, patients with chronic
disorders can have a predominantly or secondary population of neutrophilic
inflammation. Explanation for these findings may include ulcerations and/or changes in
bacterial flora (dysbiosis). It is not uncommon to see neutrophils in ulcerative colitis
cases, occasionally associated with tremendous leukocytosis. When neutrophils are
identified, consideration to antibiotic therapy for antibiotic responsive diarrhea, dysbiosis
and/or primary bacterial pathogens, may be considered. Additionally, application of
FISH or other infectious disease testing could be considered. It is always important to
correlate the presence of this type of inflammation with the clinical history. Occasional
findings that complement a more acute disease process might include fibrin and/or
lamina propria edema.
Histologic markers of chronicity:
Recently, emphasis has been placed on alterations in the villus that suggests chronicity
of the disease process. Clearly, alterations in the villi can result in decreased surface
area for absorptive capacity and may represent chronic inflammation over time.
Characteristic changes that may be associated with chronic inflammation and or
disease may include a reduction in villus height, shortening/widening of villi and/or the
fusion of villi. These changes may be more representative of the clinical disease then
the degree of inflammatory infiltrates. In other words, mild inflammation with marked
villus changes may reflect the clinically severe case, while the pathologist may read it
out as “mild lymphoplasmacytic inflammation”. Additional findings associated with
chronicity include alterations within the lamina propria. With chronicity, increased
connective tissue is deposited with in this region this may occur over time. Another
change thoughts likely represent chronicity are changes associated with the crypts.
Hyperplasia of the crypts represents a response to chronic irritation and/or enterocyte
loss. As noted above, the presence of these findings may “trump” the lack of
inflammation in some patients. In other words, histologically “unremarkable” may be
functionally “disastrous”.
Findings suggesting great significance:
The presence of lymphangectasia on a biopsy is often times very significant. While the
presence of this, does not necessarily imply primary lymphangectasia it does suggested
that lymphatic flow is altered. Secondary lymphangectasia is much more frequent and
is generally associated with chronic inflammatory disorders. Chronic inflammation
results in presumptive compression of lymphatics and ultimately secondary dilation,
exudation and potential contribution to protein losing enteropathy. While the primary
disease process may imply an inflammatory process, the presence of this finding may
suggest a complementary role for fat restriction. Occasionally, utilization of novel
proteins that are very lean be appropriate. This may include ostrich, turkey, chicken,
etc., dependent on the patient and their previous exposure history.
Another finding that may be underemphasized on biopsies at times may include crypt
abscesses occasionally, pathologist will describe these findings on biopsies without
terming them crypt abscesses (accumulation of eosinophilic material within crypts or
distention of crypts with eosinophilic, acellular debris) and other pathologist will term this
cryptitis. Interestingly, contrary to what the name would imply, inflammation is not
present within these lesions. However, these findings are almost always correlated with
protein losing enteropathies. And may dominate or be a minor component of the
biopsy. This finding is typical in Yorkshire Terriers with PLE, but can be seen in other
breeds as well. It is important to note that the majority of these cases that respond to
therapy, generally respond to a combination of immunosuppressive therapy. This may
therefore suggest an immunopathogenesis, something that the biopsies may under read
at times.
Intraepithelial lymphocytes are defined as lymphocytes that migrate to the mucosal
surface on biopsies. It has been suggested that presence of epitheliotropism is a
feature of malignancy and therefore supportive of potential developing lymphoma.
Therefore, in cats this finding is always potentially suggestive of lymphoma and certainly
would suggest that application of additional testing to biopsies may be appropriate
(PARR or immunohistochemistry) disease. The significance of this finding in dogs is
less understood. Recent publication suggested that this finding is not correlated with
neoplasia. However, the frequency of small cell lymphoma in this population is
uncommon and therefore, it is hard to know whether or not this feature is seen typically
in dogs with small cell lymphoma. In other words the presence of it is not highly
suggestive per se but is possible that this finding has a higher sensitivity for the disease.
Another finding and biopsies that is sometimes over and/or under interpreted is the
presence of Helicobacter. Helicobacter is often times an incidental finding not exhibiting
any clinical signs. Therefore, interpretation of this organism as potentially being
pathogenic should be made in the context of the clinical history and/or other relevant
biopsy findings. Patients with chronic weight loss, anorexia, diarrhea and/or severe
clinical signs are unlikely to have this is a significant finding. However, patients with
relatively unremarkable biopsies within the remaining gastrointestinal tract with clinical
signs compatible should be considered. Clinical signs commonly associated with
Helicobacter include vomiting or “gastritis” signs disease grueling, decreased appetite,
repetitive/hard swallowing, reluctance to eat occasionally). Concurrent gastric
inflammation on biopsy is further supported this as a definable etiology. However,
occasionally, patients respond to treatment dramatically and completely despite the lack
of concurrent gastritis on histology.