2016, Volume 32, Number 2, Page(s) 082-090
Gastrointestinal Parasitosis: Histopathological Insights to Rare but Intriguing Lesions of the Gastrointestinal Tract
Burçin PEHLİVANOĞLU1, Başak DOĞANAVŞARGİL1, Murat SEZAK1, İlke NALBANTOĞLU2, Metin KORKMAZ3
1Department of Pathology, Ege University Faculty of Medicine, İZMİR, TURKEY
2Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MİSSOURİ, USA
3Department of Parasitology, Ege University Faculty of Medicine, İZMİR, TURKEY
Keywords: Histopathology, Parasitic diseases, Eosinophilia, Infection, Gastrointestinal tract
Gastrointestinal parasitosis is a significant cause of morbidity and mortality. Definitive diagnosis is usually made by stool tests and/or
serology but may require tissue evaluation. Although pathologists are usually familiar with common parasites, it is not well established whether
the diagnosis could be suspected without seeing the parasite itself.
Material and Method: Resection or biopsy specimens of 32 cases with Giardia intestinalis (n=20), Enterobius vermicularis (n=5), Entamoeba
histolytica (n=4), Fasciola hepatica (n=1), Strongyloides spp. (n=1) and Taenia saginata (n=1) infections were retrospectively re-evaluated for
accompanying mucosal changes, and compared with nonparametric tests.
Results: The most common changes were congestion (65.6%) and eosinophilic infiltration (50%). Chronic active mucosal inflammation
accompanied 37.5% of the cases. More than 10 eosinophils/HPF were present in 43.8%. Only one case of G. intestinalis, E. vermicularis, E.
histolytica, and F. hepatica showed more than 50 eosinophils/HPF. Mucosal architectural abnormalities were present in 34.4%. Granulomas,
giant cells and Charcot-Leyden crystals were only seen accompanying F. hepatica. No statistically significant difference was found between
parasite subspecies regarding presence of inflammation, lymphoid aggregates, architectural distortion, congestion, ulceration and increase of
Conclusion: Parasites induce nonspecific inflammation, slight mucosal architectural changes, mild eosinophilic infiltrate or granuloma
formation. They may cause ulceration, bowel obstruction or perforation. Parasitosis should also be considered when evaluating cases mimicking
inflammatory bowel disease, celiac disease or those that do not fulfill diagnostic criteria.
Parasitic infections of the gastrointestinal (GI) tract are
significant causes of morbidity and mortality. Although
they are particularly more common in underdeveloped
regions with poor sanitary conditions, they are prevalent
throughout the whole world. Clinical presentation may
vary depending on the parasite type and the affected parts
of the GI tract. Parasites can survive in the GI tract for years
without causing any symptoms. However, occasionally
they may cause serious clinical presentations. Although
a diagnostic approach can be made on clinical grounds,
they may present important diagnostic challenges as they
can mimic important GI pathologies such as eosinophilic
gluten sensitive enteropathy2
inflammatory bowel diseases3
. The definitive diagnosis
is usually made by stool cultures, stool microscopy and/
or serology. However, some cases may require tissue
evaluation in order to rule out other GI tract pathologies. Therefore, the pathologist should also be aware of the
features of parasitic infections.
In this context, pathologists are usually familiar with
common types of protozoa or at least can identify the
microorganism as a parasite and may refer to a parasitologist
for a more proper identification. On the other
hand, microbiologists/parasitologists generally do not have
adequate knowledge about direct microscopic visualization
of pathogens in biopsy samples4.
Currently, most of the large series on human GI parasites
usually focus on stool microscopy and there is very limited
literature background dedicated to histological features
alone. Besides it is not well known whether there are specific
clues to suspect a parasitic infection or not, especially in
cases where the microorganism is either very sparse or
not visualized on small biopsy material or when there is
no relevant clinical information upon the possibility of a
In this study, we aimed to evaluate the accompanying
histological features seen in tissue samples and to determine
the effectiveness of these features for providing information
to suspect a parasitic infection.
Biopsy or resection specimens of 32 consecutive patients
diagnosed between 2000 and 2011 were included in
the study. The study group was composed of cases with
Giardia intestinalis (n=20), Enterobius vermicularis
(n=5), Entamoeba histolytica (n=4), Fasciola hepatica
(n=1), Strongyloides spp. (n=1) and Taenia saginata (n=1)
infections. Cases with E. vermicularis, T. saginata and
F.hepatica were evaluated with their resection specimens
while the rest of the cases were evaluated with their
endoscopic biopsy materials retrospectively in respect to
accompanying mucosal changes consisting of the presence
of chronic and acute inflammation, increase of eosinophils,
congestion, mucosal ulceration, necrosis, perforation,
lymphoid aggregates, cryptic architectural distortion,
granuloma formation, calcification, hyalinization, and
presence of giant cells and/or Charcot-Leyden crystals.
Eosinophil density was determined as the number of
eosinophils in one high power field (HPF, x40 objective)
and later on dichotomized into two groups as cases
presenting over 10 or 50 eosinophils per one HPF for
statistical purposes. Statistical analysis was performed
using a computer based program, SPSS version 13.0.
Observed changes were correlated with the parasite type
by nonparametric tests (chi-square and Fishers exact test
when appropriate). The protozoon categories with only one
representative case were excluded from statistical analysis. However, the observed changes were provided in the results
and discussed accordingly.
The clinical features of the cases are summarized in Table
and accompanying histological changes according to the
protozoon type are given in Table II
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|Table II: Distribution of histopathological features of the cases according to protozoon type
Fifty-three percent of the cases were female and median
age was 38±19.3 years (range 4-61 years). The median
age was lower in females compared to males (28.7±17.5
versus 42.9±19.2, respectively), and in cases with E.
vermicularis (15±13.8) although statistically insignificant.
Overall 12.5% of the cases had accompanying malignancies
such as lymphoma, stomach and colon cancers and
22% had a chronic disease such as common variable
immunodeficiency (CVID), chronic Helicobacter pylori
(HP) gastritis or Familial Mediterranean fever (FMF).
The taeniasis case (65-year-old male) presented to the
hospital with small bowel perforation due to an obstructing
mass suspicious for malignancy (Figure 1). There was no
known previous history of parasitosis in that case as well
as another case with perforated acute appendicitis with E.
vermicularis infection (15 year-old female). The case with
F. hepatica (46-year-old male) was also complicated with
Click Here to Zoom
|Figure 1: Gross image of ischemic colon containing a pile of
Taenia saginata proglottid.
Apart from the remaining four appendectomies, the rest
of the cases were diagnosed with their biopsy materials by
identification of the parasite itself. Retrospective evaluation
revealed that the most commonly observed mucosal change
was congestion (65.6%) that was accompanied by acute
mucosal inflammation in 37.5% of the cases.
Mucosal erosion and ulceration (18.8%) was a feature
of amebiasis (Figure 2A,B), enterobiasis and giardiasis,
possibly due to complicating acute appendicitis for
enterobiasis (Figure 3A-D) and gastric mucinous
metaplasia in duodenum for giardiasis. Non-Peyer
patch lymphoid aggregates (46.9%) (Figure 4A,B) and
eosinophilic infiltration (50%) were the other common
findings. The gastric mucosa with Strongyloides was
almost normal other than the presence of the parasite
itself (Figure 5A-D). The number of eosinophils differed
between 2 and 75/HPF (median 22.31±22.4). More than
10 and 50 eosinophils were present in 43.8% and 12.5% of
the cases, respectively. Although statistically insignificant,
eosinophilic infiltration was a prominent feature observed
in 85% (n=13) of giardiasis cases as well as faint villous
blunting observed in 7 (35%) of these cases (Table II). None
of them exhibited increased intraepithelial lymphocytosis raising suspicion for gluten sensitive enteropathy (Celiac
disease). G. intestinalis trophozoites were seen between
adjacent villi (Figure 4C,D). Granulomas, giant cells and
Charcot-Leyden crystals were only seen accompanying
F. hepatica (Figure 6A-D). Hyalinization was especially
prominent in enterobiasis (p=0.001) and in sole case
of taeniasis. Two cases with E. vermicularis showed
calcification (p=0.042). However, no significant difference
was found between parasite subspecies regarding presence
of chronic and acute inflammation, lymphoid aggregates,
architectural distortion, congestion, ulceration and
increase of eosinophils.
Click Here to Zoom
|Figure 2: A) Entamoeba spp. in a colonoscopic biopsy (long arrow).
Note the erosion, mixed inflammatory infiltration and mucosal
architectural irregularity mimicking a chronic inflammatory
bowel disease (H&E; x100). B) Engulfed erythrocytes within
trophozoites are seen (short arrow) (H&E; x400).
Click Here to Zoom
|Figure 3: Enterobius vermicularis causing acute appendicitis. E. vermicularis in lumen, A) Cross section image (H&E; x20).
B) Longitudinal section image (H&E; x40). C) Eggs, circled in yellow (H&E; x200). D) E. vermicularis alae (arrow heads) and esophagus
(long arrow) (H&E; x200).
Click Here to Zoom
|Figure 4: A-B) Giardia intestinalis trophozoites in a duodenal biopsy. Note the lymphoid follicle and mild architectural distortion at the
right side of the sample (H&E; x100 and x200). C) Trophozoites between villi (H&E; x200). D) Smiley face like appearance (H&E; x1000).
Click Here to Zoom
|Figure 5: A-D) Strongyloides larvae in gastric biopsy (arrows) (H&E; x40, x200,x400 and x400).
Click Here to Zoom
|Figure 6: Ascending colon resected due to Fasciola hepatica infection. A) Geographic ulcers caused by adult form of the parasite
and granuloma formation (H&E; x40). B) Charcot-Leyden Crystals and histiocytic infiltration at the edge of the ulcers (H&E; x200).
C) Granulomas containing F. hepatica eggs and giant cells (H&E; x100). D) F. hepatica egg with a yellowish shell (arrow), at the center
of a granuloma (H&E; x400).
The correct and timely diagnosis of infectious disease is
essential for immediate onset of the effective treatment.
Stool microscopy is a faster method but is not relevant
in all types of parasites and stool cultures and serological
tests may be useful in supporting diagnosis5,6
. In this
respect, histopathological approach is also informative in
identifying the pathogen but as an invasive method it is
unnecessary in most cases. Thus, biopsies are usually done
for diagnostic purposes and for excluding other entities
while resections are only used in complicated cases.
However, there are incidents where the histopathological
diagnosis precedes the clinical diagnosis, as seen in some
cases of our series. Among the cases presented herein, there
was no prior diagnosis in taeniasis and one of the cases of
enterobiasis until their admission with small bowel and appendix perforation. Strongyloides spp. in the stomach
was also an incidental finding in endoscopic biopsy
performed to rule out recurrent lymphoma. Similarly, G.
intestinalis was a concomitant but clinically unsuspected
finding diagnosed while the cases were being investigated
for other diseases such as gastric adenocarcinoma, colonic
mucinous adenocarcinoma, lymphoma, FMF and CVID
(in four cases).
The tissue diagnosis is usually straightforward when the
causative agent can be easily identified in slides or even
visible in macroscopic materials as seen in taeniasis. The
challenging issue is the identification of the parasite when
there is a very limited number of the trophozoites, cyst, ova,
and larval or adult forms on the slide. Although the role of
the pathologist is usually to confirm the clinical suspicion
in one way or the other, it may even not be possible to make
a differential diagnosis between an infectious pathology
and chronic GI tract disorders.
The initial step for the diagnosis of bacterial, fungal and
viral infections in tissue sections is the identification of
inflammation and determination of the dominant cell type4. Polymorphonuclear leukocyte (PNL) infiltration is
usually more prominent in bacterial and fungal infections
while viral infections usually cause a lymphocytic reaction.
However, although the efficacy of histopathological
examination in the diagnosis of infectious disease has
been well established, there is no specific tissue response
or dominant inflammation type described for parasitic
G. intestinalis was the most common pathogen (62.5%)
in this study followed by E. vermicularis (15.6%) and E.
histolytica (12.5%). Although this cannot be interpreted
as reliable epidemiological data due to limited number
of cases examined, it makes sense as those three parasites
also appear to be the most common cause of GI parasitosis
while the rank of prevalence may show geographical
variations6 and may even vary among different ethnic or
age groups living in the same area5.
In this study, an overall normal appearing mucosa was
only observed in G. intestinalis infections. In almost 40%
of the cases only lymphoid aggregates, and slight villous
blunting which can be attributable to presence of lymphoid
aggregates were observed. Previous reports on the effect of
G. intestinalis on villous architecture are controversial2,7. It causes brush border abnormalities, but recent studies
indicate that the villous architecture is usually preserved
if the concomitant diseases are disregarded7. Although
giardiasis is an important diagnostic consideration in cases with suspected gluten sensitive enteropathy, villous
atrophy, intraepithelial lymphocytosis and/or crypt
hyperplasia are also extremely rare7 and when present
should not be attributed to giardiasis unless all other
diseases are eliminated. We did not observe intraepithelial
lymphocytosis or crypt hyperplasia either. Mild duodenitis
with predominant eosinophilic infiltration was previously
defined but is less prevalent8. This is consistent with our
findings as we also observed active inflammation in 20% of
the cases. However, it was probably due to peptic duodenitis
as it was accompanied by gastric mucinous metaplasia and
erosions, so it is not easy to consider presence of epithelial
infiltrating PNL as a tissue response to giardiasis. In this
context, eosinophilic infiltration is noteworthy as it was
prominent in 60% of the cases even though there was
more than 50/HPF in only one case. Clinical history of diarrhea or CVID, with lack or paucity of plasma cells in
lamina propria, are also important clues for more careful
scanning for possible Giardia colonization. The presence
of CVID in 20% of giardiasis cases in our series is also
noteworthy but not surprising considering the increased
tendency for giardiasis in CVID patients9. However, this
finding should be interpreted with caution since CVID is
a rare disease and this study was conducted at a tertiary
referral center. While the uncomplicated cases are usually
diagnosed and treated in primary care units, cases that may
require further analysis or require endoscopic biopsies are
referred for consultation.
Notably, there were only few G. intestinalis trophozoites in a
small area between two adjacent villi in one of the cases that
were sent for a second opinion to rule out Celiac disease.
Therefore, even though G. intestinalis has very typical pearshaped morphology, it can be easily overlooked especially
in faintly stained slides in cases with fewer trophozoites
because of its resemblance to desquamated surface
E. histolytica is also a 10 to 60 μm parasite and the
trophozoites can easily be overlooked as they usually reside
in the superficial mucosa or in the lumen admixed with cell
debris, and can thus easily be mistaken as desquamated
epithelial cells. Overlooking the trophozoites can be
misleading for the differential diagnosis of the case with
chronic inflammatory bowel disease (IBD) as amebiasis
can mimic the histopathological changes seen in ulcerative
colitis or Crohns disease, the misdiagnosis of which may
result in treatment with steroids that would only exacerbate
the infection6. In this respect, all cases in our series showed
chronic active inflammation on superficial evaluation, while
half of them also presented with ulcero-erosive lesions, mucosal architectural changes and eosinophilic infiltration
that are also common features of IBD. However, none
of them showed basal plasmacytosis, which is a cardinal
feature of IBD or crypt abscess, granuloma formation,
or pseudopyloric or Paneth cell metaplastic changes that
are also encountered in IBD1. One should also keep
in mind that amebiasis can also coincide or complicate
IBD10 and can be more prevalent especially in cases of
ulcerative colitis compared to the normal population11.
In suspicious cases, stool microscopy or rectal swabs can be
very helpful before making the diagnosis or when planning
a therapeutic scheme.
A similar histology with chronic lymphoplasmacytic
infiltration was also observed in our E. vermicularis cases
accompanied by cryptitis, erosion and ulcerations. E.
vermicularis usually resides in the caecum, appendix and
distal ileum and thus can also mimic Crohns disease in this context3. However, no granuloma formation was
observed and mucosal architectural changes such as crypt
distortion were not prominent. Additional findings were
hyalinization and calcification that had probably developed
secondary to ulceration, necrosis and perforation present in
the index cases. Although the clinical history of enterobiasis,
which is commonly referred to as pinworm, is very typical
with anal pruritus, histopathological diagnosis can be
troublesome when the parasite is very sparse, fragmented
or unevenly distributed as it can easily be overlooked in
cases with extensive phlegmonous inflammation especially
in the appendix. In contrast, there may be very limited
inflammation when the worms lie only in the lümen12,
again posing diagnostic difficulties. In cases with limited
amounts of parasite or inflammation, sampling errors are
commonly encountered. However, when provided with
clinical information, it will not be much of a burden for
the pathologist to examine the entire specimen to find areas with more easily identifiable parasites. In this respect,
biopsy materials are much more restrictive and may be
less informative depending on the area where the biopsy
Hyalinization, necrosis and perforation were also observed
in the taeniasis case but probably developed due to
ischemia caused by bowel obstruction while the other
inflammatory changes were even more subtle than in G.
intestinalis infection. Interestingly, the gastric mucosa with
Strongyloides infection was almost normal other than the
presence of the parasite itself. The only mucosal alteration
was eosinophilic infiltration with 17 and 21 eosinophils/
HPF in the small bowel with taeniasis and the gastric
mucosa with Strongyloides, respectively.
The most flamboyant histology was observed in the
fascioliasis case with necrosis, perforation, abscess and
granuloma formation, giant cells and Charcot-Leyden crystals. Interestingly, although many of the cases discussed
herein had eosinophilic infiltration to some extent, only
the fascioliasis case showed prominent Charcot-Leyden
Overall, the most common accompanying histological
findings were nonspecific and included congestion and
non-Peyer patch lymphoid aggregates accompanied by
chronic active mucosal inflammation in 37.5% of the cases.
Even eosinophilic infiltration appeared to be a nonspecific
finding as it did not exceed 10 eosinophils per one HPF
but it was more common with giardiasis among all
agents. Erosion and ulceration were features of amebiasis,
enterobiasis and giardiasis, possibly due to complicating
acute appendicitis and gastric mucinous metaplasia in the
As the study is limited to the observed protozoa infestations
in a 10-years period at a tertiary referral hospital and is
mostly composed of clinically or histologically complicated
cases, some parasites that are more common in some parts
of the world could not be covered under the study due to
the lack of cases. However, despite the nonspecific nature
of the features observed in this study, this is one of the
few studies4,13 dedicated to searching accompanying
histology in parasitic infections.
In conclusion, GI parasitosis should no longer considered
as an exotic disease as it can also be encountered in
industrialized countries14 as well due to various factors
such as increased contact with other cultures, increased
travelling and immigration or increased fresh food imports
from different parts of the world and particularly from developing countries5. Histopathological examination
is crucial not only to diagnose but especially to rule out
other GI diseases. Our results show that parasites usually
induce a nonspecific chronic or active inflammatory
reaction with slight villous or cryptic architectural changes,
mild eosinophilic infiltrate, granulomas or Charcot-
Leyden crystals and they can cause bowel obstruction or
perforation. Thus, a pathologist must consider a parasitic
infection, especially in cases with IBD-mimicking, Coeliac
disease-mimicking areas, which do not fulfill the diagnostic
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