Seminars in Diagnostic Pathology (2004) 21, 86 97

Appendicitis and infections of the appendix

Laura W. Lamps, MD
From the Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
KEYWORDS
Acute appendicitis;
Viral appendicitis;
Bacterial appendicitis;
Parasite;
Infectious disease

The pathologic spectrum of the acutely inflamed appendix encompasses a wide range of infectious and
noninfectious entities. The appendix suffers alone in some of these disorders, and in others may be
involved through extension from other areas of the gastrointestinal tract. Although the appendix is the
most commonly resected and examined intraabdominal organ, the pathogenesis and etiology of acute
nonspecific appendicitis (the most common diagnosis made in this organ) remains enigmatic. This
review encompasses the pathology, pathogenesis, and bacteriology of acute appendicitis, as well as
controversial issues such as the diagnosis of chronic appendicitis and the significance of a morphologically unremarkable appendectomy specimen in the clinical context of appendicitis. In addition, the
pathologic features, pertinent diagnostic techniques, and clinical significance of several specific
bacterial, viral, fungal, and parasitic infections affecting the appendix are presented, including adenovirus, cytomegalovirus, Yersinia species, actinomycosis, Mycobacteria species, histoplasmosis, pinworms, schistosomiasis, and Strongyloides stercoralis.
2004 Elsevier Inc. All rights reserved.

The pathologic spectrum of the acutely inflamed appendix encompasses a wide range of infectious and noninfectious entities, some with specific histologic findings, and
others with nonspecific findings that may require an extensive diagnostic evaluation. The appendix suffers alone in
some of these disorders, and in others may be involved
through extension from other areas of the gastrointestinal
tract. Although the appendix is the most commonly resected
and examined intraabdominal organ, the pathogenesis and
etiology of acute nonspecific appendicitis (the most common diagnosis made in this organ) remains enigmatic.

Acute nonspecific appendicitis

Acute appendicitis (AA) remains the most common abdominal surgical emergency. The peak incidence is during the
Address reprint requests and correspondence: Laura W. Lamps,
MD, Dept. of Pathology, University of Arkansas for Medical Sciences,
4301 W. Markham Street, Slot 517, Little Rock, AR 72205
E-mail address: lampslauraw@uams.edu.

0740-2570/$ -see front matter

doi:10.1053/j.semdp.2004.11.003

second and third decades of life, but AA can occur at any

time from infancy to very old age. Perforation is most
common in children and the elderly, and in older patients
the inflammatory process is more likely to be associated
with appendiceal tumors.1 The classical presentation of AA
begins with peri-umbilical pain that is colicky in nature, of
gradual onset, and increasing severity. Nausea, loss of appetite, vomiting, and malaise may be present, as well as a
low fever. Within 6 to 18 hours, the pain typically localizes
to the right lower quadrant and becomes constant, usually
with associated guarding and rebound tenderness.2
Atypical presentations may include a much milder constellation of symptoms, or more generalized signs and
symptoms of peritonitis. If the appendix has an unusual
anatomic location, the symptoms and findings on physical
examination may vary from the norm. The inflamed retrocecal appendix, for instance, may cause pain in the flank or
right upper quadrant, and may produce a positive psoas
stretch sign on physical examination.2
The most common complications of acute suppurative
appendicitis are rupture with peritonitis, wound abscesses,
and pelvic abscesses; the incidence of the latter two is

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Appendicitis and Infections of the Appendix

Figure 1 Gross photograph of early appendicitis, showing a dull

appearance of the serosa, and injection of serosal vessels (photograph courtesy of Dr. George F. Gray, Jr.).

greatly minimized by the use of perioperative antibiotics.

Other less common but well described sites of postappendectomy abscess formation include the subphrenic fossa,
the liver, the lumbar spine, and the cecal wall following
rupture of the appendiceal stump. Rare sequelae include
adhesions, sepsis, gas gangrene of the abdominal wall,
appendico-cutaneous and appendico-vesicular fistulas, and
infective thrombophlebitis, which may also lead to hepatic
abscess.1,2

Pathology
The gross pathology of AA is very variable, and the external
appearance may not correlate with the histologic extent of
inflammation. Inflammatory changes can involve the entire
appendix or only a part; if only one segment is affected, it
is usually the distal tip.1 The earliest grossly visible changes
consist of a dull appearance to the usually glistening serosa,
and dilation of the serosal vessels (Figure 1). As the inflammatory process progresses, the appendix becomes more
edematous, often with luminal dilation and involvement of
the mesoappendix. There may be increasing hyperemia with
or without fibrinopurulent serosal exudates (Figure 2), and
ultimately the gangrenous appendix may show purple,
green, or black discoloration of the wall (Figure 3).1 The cut
surface of the acutely inflamed appendix shows hyperemia
and congestion, with associated narrowing of the lumen and
often intraluminal pus.
The histology of AA is also quite variable. Acute suppurative appendicitis (also known as phlegmonous appendicitis) is defined as neutrophilic infiltration of the appendiceal wall, with associated inflamed and ulcerated mucosa
and often crypt abscesses (Figures 4 and 5).1-3 Vascular
thrombosis is commonly seen. Gangrenous appendicitis has
necrosis of the wall of the appendix in a background of
transmural inflammation, often with extension into the mesoappendix, and perforation will occur if left untreated.

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Figure 2 Gross photograph of acute suppurative appendicitis,

showing a hyperemic appendix with dilation of the tip (right),
serosal purulent exudate, and involvement of the mesoappendix
(photograph courtesy of Dr. George F. Gray, Jr.).

Eosinophils may be present in the inflammatory infiltrate,

the significance of which is unclear.1
The minimal diagnostic criteria for AA are controversial, as some authorities believe that inflammation limited to
the mucosa and submucosa alone may not adequately explain the patients symptoms. Some require extension of the
neutrophilic infiltrate into the muscularis propria for the
diagnosis of AA.1 Others, based on extensive clinicopathologic correlation, believe that the earliest criteria do consist
of mucosal neutrophilic infiltration with superficial ulceration, and that this does correlate with both patient symptoms and usually more extensive inflammation if the appendix is liberally sampled.2 It is important to note that
although patients with symptoms of acute appendicitis may
show only mucosal or mucosal/submucosal acute inflammation, fecaliths and enteric infections (see below) may
produce similar histologic changes. Therefore, the diagnosis
of acute suppurative appendicitis should probably be reserved for those specimens showing neutrophilic infiltration
of the muscularis propria. Cases with inflammation limited

Figure 3 Gangrenous appendicitis showing marked black discoloration (photograph courtesy of Dr. George F. Gray, Jr.).

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Figure 4 Early appendicitis with mucosal and submucosal acute inflammation, and ulceration of the mucosa. (A) (H&E, original
magnification 40). High power view of neutrophilic infiltrate within the wall of the appendix. (B) (H&E, original magnification 400).

to the mucosa or mucosa and submucosa (after adequate

sampling) can be designated acute mucosal or mucosal/
submucosal appendicitis, and assigned a broader differential
diagnosis that includes infection.1 Most authorities are in
agreement that luminal neutrophils alone do not suffice for
the diagnosis of acute appendicitis. The presence of periap-

pendiceal inflammation, in the absence of true appendiceal

inflammation, suggests an extra-appendicular source of the
patients symptoms.1-3

Pathogenesis of acute appendicitis

Figure 5 Acute suppurative appendicitis showing diffuse mucosal ulceration and transmural acute inflammation with extension
into the periappendiceal fat (H&E, original magnification 40).

AA is occasionally caused by foreign bodies, including

straight pins (Figure 6), seeds, small animal bones, intrauterine devices, trichobezoars, and shotgun pellets.2 Although these are the most dramatic and easily identified
causes of AA, these cases are rare.
Historically, obstruction of the appendiceal lumen, with
subsequent secondary infection, has been the most popular
theory of pathogenesis.1,4 Proponents of this theory opine
that obstruction, commonly by fecalith, lymphoid hyperplasia, or adhesions, leads to an increase in intraluminal pressure, which in turn causes vascular compromise, mucosal
ischemia, mucosal ulceration, and ultimately infection by
luminal micro-organisms. Animal studies have supported
this theory. However, although obstruction may account for
the underlying etiology in a percentage of cases, evidence of
obstruction is demonstrable in only a minority of resected
appendices,1,2 and some authors have argued that obstruction is the result, rather than the cause, of appendiceal

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possible contributions that any of these organisms might
make to the pathogenesis of AA remain unclear, but it is
important to be aware of the mixture of anaerobic and
aerobic bacteria that can exist within an inflamed appendix.
If antibiotic therapy is necessary for either wound infections
or peritonitis secondary to perforation, the antimicrobials
selected should cover the variety of organisms that may be
present.2,8

Chronic appendicitis

Figure 6 Acute appendicitis caused by ingestion of a straight

pin with subsequent perforation (photograph courtesy of Dr.
George F. Gray, Jr.). (Color version of figure is available online.)

inflammation.5 Other theories of pathogenesis include compromise of the extramural appendiceal vascular supply;
mucosal ulceration from viral infection, leading to bacterial
superinfection; and low fiber diets with slowing of intestinal
transit time and retention of stool in the appendix that
increases susceptibility to infection.1,2,6,7 No single theory
can explain all cases of acute nonspecific appendicitis, and
it is likely that multiple etiologic factors, varying with the
individual patient, can ultimately lead to invasion of the
appendiceal wall by intraluminal bacteria and associated
mucosal ulceration.1

Microbiology of acute appendicitis

The possible role of gut bacteria in both the development
and the sequelae of acute appendicitis has also been the
subject of great discussion. Bacteriologic studies, usually
performed using microbiologic culture techniques, reveal a
wide variety of anaerobic and aerobic bacteria.8,9 When
correlated with histologic findings, it appears that aerobic
infection predominates in early appendicitis, with a shift
toward a mixture of aerobes and anaerobes later in the
course of disease.2 Bacteroides species are the most common isolate, particularly B. fragilis, and their role in the
pathogenesis of acute appendicitis has been hotly debated.8,10 Some studies have found a higher incidence of B.
fragilis in diseased appendices when compared with normal, whereas others have found no differences.8,9 Studies
examining the immunologic response to commonly isolated
bacteria have shown a greater serologic antibody response
to Bacteroides species than to other isolated organisms in
gangrenous and perforated appendices, but this may reflect
a greater extent of organ destruction and tissue immune
response rather than a true pathogenetic role.8,11 In addition,
other workers showed similar serologic results when patients with noninflamed appendices were studied.11 The

The clinicopathologic existence of chronic appendicitis is

another subject of controversy. It is clear that some patients
may suffer recurrent bouts of acute appendicitis before
appendiceal resection, and patients with adhesions or fecaliths may have recurrent symptoms of acute appendicitis
before resection. In addition, patients with peri-appendiceal
abscesses or specific infections of the appendix (such as
tuberculosis) may have chronic, ongoing symptoms. However, most authorities agree that primary chronic appendicitis is not an entity that should be clinically or histologically recognized.1,2 That being said, the surgical pathologist
may occasionally be faced with an appendix containing a
destructive, predominantly mononuclear or plasmacytic inflammatory infiltrate and scarring. These changes may represent either resolving or ongoing acute appendicitis, and
some authors condone using the phrase chronic ongoing
appendicitis to characterize these findings,2 as long as there
is no evidence of Crohns disease, infectious processes, or
other disease entities within the appendix, and as long as the
patient has not undergone an interval appendectomy following treatment with antibiotics. However, the correlation
between these histologic findings and the patients symptoms remains unclear. Luminal fibrosis without inflammation, scattered lymphocytes outside of lymphoid follicles,
and the normal complement of inflammatory cells within
the lamina propria of the appendix should not be regarded as
histologic signs of chronic appendicitis.1

Negative appendectomy specimens

When an appendix is removed for a clinical diagnosis of
appendicitis, a certain percentage will be histologically normal, and this is accepted by the majority of our surgical
colleagues. Submission of the remainder of the appendix is
recommended to ensure that focal lesions (including fecaliths and other small polyps or masses) are not overlooked.
Several authors have undertaken re-examination of negative
appendectomy specimens in an attempt to find an explanation for the symptoms of appendicitis. Nonspecific findings
including cytokine elevations, flattening of the surface epithelium, and neurogenous hyperplasia have been found in
patients with symptoms of acute appendicitis but morphologically normal appendices; however, the relevance of

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Table 1

Infectious agents involving the appendix

Viruses
Measles
Adenovirus
Cytomegalovirus
EBV
Bacteria
Salmonella sp. (both typhoid and non-typhoid)
Shigella sp.
Yersinia (both enterocolitica and pseudotuberculosis)
Actinomyces sp.
Campylobacter sp.
Clostridium, including C. difficile
Mycobacteria (tuberculosis and atypical)
Rickettsia rickettsii
Fungi
Mucormycosis
Histoplasmosis
Parasites
Enterobius vermicularis (pinworm)
Schistosomes
Entamoeba histolytica
Balantidium coli
Strongyloides stercoralis
Toxoplasma
Cryptosporidium
Echinococcus
Trichuris sp. (whipworms)
Ascaris sp. (roundworms)

these findings to patients symptoms remains unclear.1,2 In

many patients with a grossly and microscopically normal
resected appendix, symptoms will still resolve following
appendectomy.2

Granulomatous appendicitis
Granulomatous appendicitis, including involvement of the
appendix in inflammatory bowel disease, is addressed by
Dr. Bronner in a separate article in this issue.

and ileocecal intussusception,12,13 particularly in children.

Most patients do not have symptoms of appendicitis, and the
adenovirus is found subsequent to laparotomy for intussusception. The virus is thought to contribute to intussusception by producing lymphoid hyperplasia, altering intestinal
motility, or both.13 Morphologic changes are subtle, and
include lymphoid hyperplasia with overlying disorderly
proliferation and degeneration of surface epithelium. Typical viral inclusions are found within the surface epithelium,
consisting either of homogeneous, eosinophilic inclusions
surrounded by halos and distinct nuclear membranes, or the
more common enlarged, basophilic nuclei without a clear
membrane, referred to as smudge cells. Inclusions are
exclusively intranuclear and usually present within the surface epithelium, but rarely the deeper glands (Figures 7 and
8).12,13 Useful aids to diagnosis include immunohistochemistry, stool examination by electron microscopy, and viral
culture; serologic and/or fecal identification of adenovirus
does not necessarily represent current infection, as viral
shedding and elevated serologic titers may persist for
months.12

Cytomegalovirus
CMV is the most common gastrointestinal pathogen in
patients with AIDS, and it is being described in the appendix with increasing frequency.14,15 Patients typically present
with a more prolonged prehospital course than that of immunocompetent patients with appendicitis, consisting of
several weeks of fever, diarrhea, and abdominal pain and
tenderness that ultimately localizes to the right lower quadrant.14 Perforation is a common complication. Histologic
findings include variably ulcerated appendiceal mucosa
with a transmural mixed inflammatory infiltrate, including
numerous histiocytes, plasma cells, and lymphocytes in
addition to neutrophils. The characteristic owls eye in-

Specific infections of the appendix

Numerous viral, bacterial, fungal, and parasitic organisms
may involve the appendix (Table 1); selected entities are
discussed below.

Viral appendicitis
Although the appendix is known to participate in generalized viral infections, actual histologic documentation of
appendiceal viral infection is rare.

Adenovirus
Adenovirus is one of the more common viruses described in the appendix, and it is associated with both ileal

Figure 7 Superficial appendiceal epithelial cells containing

smudge cells indicative of adenovirus are present within neutrophilic infiltrate (H&E, original magnification 600).

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Appendicitis and Infections of the Appendix

Figure 8 Appendiceal epithelial cells infected with adenovirus

(Adenovirus immunostain, original magnification 400).

tranuclear inclusions and basophilic granular intracytoplasmic inclusions can be seen in epithelial, endothelial, histiocytic, and stromal cells.14,15 Useful diagnostic aids include
viral culture, PCR assays, in situ hybridization, and CMV
serologic studies/antigen tests. Isolation of CMV in culture,
however, does not imply active infection, as virus may be
excreted for months to years after a primary infection. The
differential diagnosis is primarily that of other viral infections, particularly adenovirus.

Miscellaneous other viruses

Acute appendicitis may develop during the course of
infectious mononucleosis due to Epstein-Barr virus infection, and changes in the appendiceal lymphoid tissue mimic
those occurring in lymph nodes.16 Characteristic WarthinFinkeldy giant cells may also be seen in the appendix in
patients with measles infection (Figure 9).2,17,18

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Figure 9 Warthin-Finkeldy giant cells within appendiceal lymphoid tissue in measles infection (H&E, original magnification
400; photograph courtesy of Dr. George F. Gray, Jr.).

pertinent to human gastrointestinal disease. These Gramnegative coccobacilli characteristically cause granulomatous appendicitis, which may or may not have associated
enterocolitis and mesenteric adenitis.19,20 The involved appendix has a thickened, edematous wall with nodular inflammatory masses centered on Peyers patches (Figure 10).
Apthoid and linear ulcers may be seen, and perforation is
frequent. Involved lymph nodes may show grossly apparent
foci of necrosis. Both suppurative and granulomatous patterns of inflammation may be seen, and a mixture of the two
is common.19,21,22 Recent studies have shown that there is
significant overlap between the histological features of YE
and YP infection, and that either species may show lymphoid hyperplasia, epithelioid granulomas with prominent
lymphoid cuffing (Figure 11 A and B), transmural lymphoid
aggregates (Figure 12), giant cells, mucosal ulceration,
cryptitis, and concomitant lymph node involvement.19 Gastrointestinal infection with YP often shows granulomatous
inflammation with central microabscesses, usually accompanied by mesenteric adenopathy (Figure 13).19,22 Special
stains are often not helpful in the diagnosis of Yersinia, for

Specific bacterial agents causing appendicitis

Specific bacterial infections may cause appendicitis, with or
without involvement of the surrounding bowel. In many of
these cases, the infectious agent is only determined after
removal of the appendix and careful examination for organisms, using special stains, culture, and/or molecular methods.

Yersinia
Yersinia is one of the most common causes of bacterial
enteritis in Western and Northern Europe, and numerous
cases have been documented in North America and Australia. The reported incidence of Yersinia infection is rising in
both Europe and the United States. Y. enterocolitica (YE)
and Y. pseudotuberculosis (YP) are the two Yersinia species

Figure 10 Gross photograph of appendix with Yersinia infection, showing diffuse nodular thickening of the appendiceal wall.
(Color version of figure is available online.)

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Figure 11 Granulomatous appendicitis due to Yersinia enterocolitica, featuring epithelioid granulomas with prominent lymphoid cuffs
(A) (H&E, original magnification 40). (B) (H&E, original magnification 200). (Color version of figure is available online.)

the organisms are small, may be present in low numbers,

and are difficult to distinguish from normal nonpathogenic
colonic flora. As Yersinia is a fastidious organism that
requires very specific culture conditions, and serologic studies show significant cross-reactivity with other gut pathogens, recognition of the histologic pattern of infection and
molecular confirmation by PCR assay is the most reliable
method of diagnosis.19
The major differential diagnosis of Yersinia infection
includes other infectious processes (particularly mycobacteria and Salmonella) and Crohns disease. Acid fast stains
and culture results should help to distinguish mycobacterial
infection; clinical features and the presence of greater numbers of neutrophils, microabscesses, and granulomas may
help to distinguish yersiniosis from salmonellosis. Isolated
granulomatous appendicitis was historically interpreted as
primary Crohns disease of the appendix; although Crohns
disease and Yersinia infection may be indistinguishable
histologically, patients with granulomatous inflammation
confined to the appendix develop generalized inflammatory

bowel disease less than 10% of the time.23,24 Several recent

comparative histologic studies support the contention that
most cases of isolated granulomatous appendicitis are etiologically different from Crohns disease.19,23,24 Ultimately,
as either species of Yersinia may mimic Crohns disease

Figure 12 Transmural lymphoid aggregates and mural thickening in Yersinia-related appendicitis (H&E, original magnification
100). (Color version of figure is available online.)

Figure 13 Granulomatous inflammation with central irregular

microabscesses in Y. pseudotuberculosis-associated appendicitis
(H&E, original magnification 100).

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93

Figure 14 Actinomycotic granule containing central clusters of

bacteria, peripheral proteinaceous material, and surrounding neutrophilic inflammation in actinomycotic appendicitis (H&E, original magnification 200; photograph courtesy of Dr. George F.
Gray, Jr.).

histologically and clinically, it is important to carefully

consider other potential causes of granulomatous appendicitis before rendering a diagnosis of Crohns disease.

Actinomycosis (Actinomyces israelii)

This filamentous, anaerobic Gram-positive bacterium is a
normal inhabitant of the oral cavity and upper GI tract. It
only rarely causes disease of the alimentary tract, usually as
a chronic, nonopportunistic infection. Infection may be at
any level of the GI tract, and the appendix is one of the most
common organs involved.25,26 Symptoms include fever,
weight loss, abdominal pain, and sometimes a palpable
mass. Grossly, resected appendices are often markedly enlarged, indurated, and adherent to adjacent structures, mimicking malignancy. The inflammatory reaction is predominantly neutrophilic.3,25,26 Palisading histiocytes and giant
cells, as well as frank granulomas, often surround the neutrophilic inflammation. Small sinuses may track from the
lumen into the wall of the appendix, and there is often
marked fibrosis (Figure 14). Involved appendices contain
actinomycotic (sulfur) granules consisting of irregularly
rounded clusters of bacteria bordered by eosinophilic, clublike projections (Splendore-Hoeppli material) (Figure 15).
Gram stains will reveal the filamentous, Gram-positive organisms (Figure 16). Actinomyces are gut commensals that
may be present in the lumen of the appendix without causing an inflammatory process. It is imperative to locate the
organism within the wall of the appendix surrounded by an
appropriate inflammatory infiltrate before making the diagnosis of Actinomyces-related appendicitis, so that long-term
antibiotic therapy is not inappropriately instituted.2 The
differential diagnosis primarily includes other infectious
processes, particularly Nocardia. Unlike Nocardia, Actinomyces are not at all acid-fast. Care should also be taken not
to confuse actinomycosis with fungi or other bacteria that

Figure 15 Transmural chronic inflammation and marked mural

fibrosis in actinomycotic appendicitis (H&E, original magnification 20; case courtesy of Dr. Dianne Johnson).

may form clusters and chains but are not truly filamentous,
such as Pseudomonas and E. coli.

Tuberculous appendicitis
Despite the proximity of the appendix to the ileocecum,
tuberculosis of the appendix is rare, and usually secondary

Figure 16 Tissue Gram stain shows filamentous, Gram-positive

Actinomyces (Gram stain, original magnification 400).

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Figure 17 Numerous macrophages contain H. capsulatum within the mucosa of the appendix. (A) (H&E/methenamine silver, original
magnification 400). (B) (original magnification 1000).

to infection elsewhere in the abdomen.27-29 Although the

ileocecum is involved in over 40% of cases of abdominal
tuberculosis, the appendix is involved in only about 1%.27
In nonendemic countries, many patients with intestinal and
appendiceal tuberculosis are immunocompromised.27
Mechanisms of involvement include extension from ileocecal or genital tuberculosis, hematogenous spread from a
distant focus of infection, and contact with intestinal contents containing bacilli.28 Patients may present with symptoms and signs typical of acute appendicitis, or with milder,
chronic symptoms and nonspecific intermittent right iliac
fossa pain.28 The appendix is usually grossly inflamed with
mural thickening, and is often adherent to the surrounding
bowel with associated lymphadenitis.27-29 Histologically,
involved appendices show lymphoid hyperplasia with associated caseating granulomas.29 Mucosal ulceration may be
present as well. Organisms may be rare, and even multiple
sets of special stains may fail to reveal acid-fast bacilli;
therefore, culture and molecular assays may be invaluable to
diagnosis. The differential diagnosis primarily includes
other granulomatous infectious process, and rarely Crohns
disease. The demonstration of organisms by histochemical,
microbial, or molecular methods, as well as the clinical
context, helps to resolve the differential in most cases.
Atypical mycobacterial infections (particularly MAI)
only rarely cause appendicitis, and this scenario occurs
almost exclusively in immunocompromised patients.30,31
The diffuse histiocytic infiltrate typical of gastrointestinal
MAI infection may be seen, and discrete granulomas are
variably present. Numerous acid fast bacilli are usually
detectable with appropriate acid fast stains.
Other bacterial infections that may cause appendicitis
are listed in Table 1.2,32-37 Salmonella species (both
typhoid and nontyphoid) are rarely isolated from acutely
inflamed appendices; clinical presentation and histologic
findings are identical to acute nonspecific appendicitis.33,34 Patients often remain febrile postoperatively, and
Salmonella infection requires antibiotic treatment follow-

ing appendectomy. Campylobacter species, particularly

C. jejuni, have also been isolated from a minority of
resected appendices using microbiological, immunohistochemical, and electron microscopic methods.35,36 Histologic findings are similar to those of early AA unassociated with bacterial causes, and inflammatory changes
are generally limited to the mucosa without transmural
inflammation or periappendicitis. Appendiceal involvement with C. difficile infection is extremely rare, and the
pathologic findings are identical to those seen in C.
difficile related pseudomembranous colitis.37

Fungal appendicitis
Fungal infection of the appendix is very rare. Mucormycosis
has been reported to cause inflammatory masses of the right
lower quadrant involving the appendix, ileum, and cecum in
patients undergoing chemotherapy.38 Histoplasmosis may
involve the appendix as part of generalized infection of the
gastrointestinal tract, usually in immunocompromised patients (Figure 17).39

Parasitic infection of the appendix

Many parasites can be found in the lumen of the appendix,
including pinworms (most commonly), Ascaris (roundworms), Giardia, and Entamoeba histolytica. Clinicians
must be alerted when parasites are found in the appendix
that could affect other parts of the gastrointestinal tract.

Enterobius vermicularis (pinworms)

Pinworms are one of the most common human parasites,
particularly in the United States and northwestern Europe. The
infective eggs reside in dust and soil, and transmission is

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Figure 18 Numerous pinworms within a resected appendix

(photograph courtesy of Dr. George F. Gray, Jr.). (Color version of
figure is available online.)

believed to be fecal oral. Children and adolescents, especially

those who live in institutions, have the highest prevalence of
infection.40,41 The worms live and reproduce in the appendix,
as well as in the ileum, cecum, and proximal colon, and
females migrate to the anus to lay their eggs and die.
Although pinworms are found in approximately 0.6 to 13%
of resected appendices, their ability to actually cause mucosal
damage has been hotly debated.41 Some believe the lack of
inflammation surrounding even invasive appendiceal pinworms indicates that they invade after the appendix has been
removed, to escape decreasing oxygen tension.40 However,
invasion of the gastrointestinal mucosa has been documented,
and both worms and ova may obstruct the appendiceal lumen
and cause inflammation similar to that caused by fecaliths.2,40,42 It has been suggested that if additional sections
were submitted from appendices containing lumenal pinworms, more cases of invasive enterobiasis would be found.
Grossly, the worms are 2 to 5 mm in length and may be seen
with the naked eye (Figure 18). Although even invasive pinworms usually incite little or no inflammatory reaction (Figure
19), as discussed above, an inflammatory infiltrate composed
of neutrophils and eosinophils may occasionally be seen.42

Figure 19 A pinworm in the lumen of a resected appendix

(H&E, original magnification 40). (Color version of figure is
available online.)

Granulomas, sometimes with necrosis, may be seen as well,

often associated with degenerating worms or eggs. It may be
difficult to distinguish between primary Enterobius infection
and the presence of worms complicating or existing within the
context of preexisting acute appendicitis. Morphologically,
pinworms have lateral ala with easily visible internal organs

Figure 20 Enterobius vermicularis has lateral ala with easily visible organs (A) (H&E, original magnification 400); eggs are ovoid with
one flat side, and a bilayered refractile shell (B) (H&E, original magnification 600). (Color version of figure is available online.)

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Figure 21 Schistosome eggs in the wall of the appendix, with surrounding marked fibrosis and calcification of eggs (A) (H&E, original
magnification 200). (B) (H&E, original magnification 400).

(Figure 20); eggs are ovoid with one flat side, and a bilayered
refractile shell.

Strongyloides stercoralis
Strongyloides stercoralis is a nematode with a worldwide distribution. In the United States, it is endemic in the
southeast, urban areas with large immigrant populations,
and mental institutions. This infection occurs primarily in
adults, many of whom are hospitalized, suffer from chronic
illnesses, or are immunocompromised. S. stercoralis is a
rare cause of appendicitis, and patients may present with
symptoms typical of acute appendicitis.43-45 Affected appendices typically show a marked transmural eosinophilic
infiltrate with granuloma formation. Larvae may be found
within granulomas.43,45 Adult worms typically have sharply
pointed tails that may be curved. Examination of stool may
be an invaluable aid to diagnosis.

(roundworms).2,50 Rarely, coccidians such as Cryptosporidium

have been found in the appendix, primarily in immunocompromised patients.51 Appendiceal involvement by Entamoeba
histolytica, rarely documented, usually represents extension
from infection of the right colon, although isolated appendiceal
involvement has been reported.45,52 When amoebae are found
in the appendix, pathogenic E. histolytica must be distinguished from nonpathogenic amoeba such as Entamoeba coli.2

Acknowledgments
The author would like to acknowledge Dr. George F.
Gray, Jr., who has nurtured her lifelong fascination with the
appendix.

Schistosomiasis

References

Schistosomes, most commonly S. hematobium, are a rare

cause of appendicitis even in nations where Schistosomiasis is
endemic. Patients usually present with signs and symptoms
typical of AA, although some have inflammatory masses on
presentation. Histologically, appendices show transmural inflammation rich in eosinophils, with a granulomatous reaction
to ova (Figure 21). Older granulomas may be fibrotic and
hyalinized.46,47 Arguments similar to those discussed above,
regarding the actual pathogenicity of Enterobius in the appendix, have occurred pertaining to schistosomes as well. However, it has been demonstrated at least in some cases that
schistosomes do cause acute appendicitis, either by inducing
granulomatous inflammation, or by producing such marked
fibrosis that lumenal obstruction leads to signs and symptoms
of acute appendicitis.47
Other parasites that may affect the appendix include Trichuris species (whipworms)48,49 and Ascaris lumbricoides

1. Carr NJ: The pathology of acute appendicitis. Ann Diag Pathol 4:4658, 2000
2. Williams RA, Myers P: Pathology of the Appendix and Its Surgical
Treatment. London, Chapman and Hall Medical Press, 1994
3. Gray GF, Wackym PA: Surgical pathology of the vermiform appendix.
Pathol Ann 21:111-144, 1986
4. Wangensteen OH, Bowers WF: Significance of the obstructive factor
in the genesis of acute appendicitis. Arch Surg 34:496, 1937
5. Arnbjornsson E, Bengmark S: Role of obstruction in the pathogenesis
of acute appendicitis. Am J Surg 147:390-392, 1984
6. Arnbjornsson E: Acute appendicitis and dietary fiber. Arch Surg
118:868-870, 1983
7. Sisson RG, Ahlvin RC, Harlow MC: Superficial mucosal ulceration
and the pathogenesis of acute appendicitis. Am J Surg 122:378-380,
1971
8. Jindal N, Kaur GD, Rajiv SA: Bacteriology of acute appendicitis with
special reference to anaerobes. Indian J Pathol 37:299-305, 1994
9. Roberts JP: Quantitative bacterial flora of acute appendicitis. Arch Dis
Child 63:536-540, 1988
10. Pieper R, Kager L, Weintraub A, et al: The role of Bacteroides fragilis

Lamps

11.

12.
13.
14.

15.

16.

17.
18.

19.

20.
21.
22.
23.
24.
25.
26.
27.
28.

29.
30.

31.

Appendicitis and Infections of the Appendix

in the pathogenesis of acute appendicitis. Acta Chir Scand 148:39-44,

1982
Elhag EM, Alwan MH, Al-Adnan MS, et al: Bacteroides fragilis is a
silent pathogen in acute appendicitis J Med Microbiol 21:245-249,
1986
Reif RM: Viral appendicitis. Hum Pathol 12:193-196, 1981
Yunis EJ, Atchison RW, Michaels RH, et al: Adenovirus and ileocecal
intussusception. Lab Invest 33:347-351, 1975
Neumayer LA, Makar R, Ampel N, et al: Cytomegalovirus appendicitis in a patient with human immunodeficiency virus infection: Case
report and review of the literature. Arch Surg 128:467-468, 1993
Valerdiz-Casasola S, Pardo-Mindan FJ: Cytomegalovirus infection of
the appendix in a patient with the acquired immunodeficiency syndrome. Gastroenterology 101:247-249, 1991
Lopez-Navidad A, Domingo P, Cadafalch J, et al: Acute appendicitis
complicating infectious mononucleosis: Case report and review. Rev
Infect Dis 12:297-302, 1990
Paik SY, Oh JT, Choi YJ, et al: Measles-related appendicitis. Arch
Pathol Lab Med 126:82-84, 2002
Pancharoen C, Ruttanamongkol P, Suwangool P, et al: Measles-associated appendicitis: Two case reports and literature review. Scand
J Infect Dis 33:632-633, 2001
Lamps LW, Madhusudhan KT, Greenson JK, et al: The role of Y.
enterocolitica and Y. pseudotuberculosis in granulomatous appendicitis:
A histologic and molecular study. Am J Surg Pathol 25:508-515, 2001
Natkin J, Beavis KG: Yersinia enterocolitica and Yersinia pseudotuberculosis. Clin Lab Med 19:523-536, 1999
Gleason TH, Patterson SD: The pathology of Yersinia enterocolitica
ileocolitis. Am J Surg Pathol 6:347-355, 1982
El-Maraghi NRH, Mair N: The histopathology of enteric infection
with Yersinia pseudotuberculosis. Am J Clin Pathol 71:631-639, 1979
Huang JC, Appelman HD: Another look at chronic appendicitis resembling Crohns disease. Mod Pathol 9:975-981, 1996
Dudley TH, Dean PJ: Idiopathic granulomatous appendicitis, or Crohns
disease of the appendix revisited. Hum Pathol 24:595-601, 1993
Ferrari TC, Couto CA, Murta-Oliveira C, et al: Actinomycosis of the colon:
A rare form of presentation. Scand J Gastroenterol 35:108-109, 2000
Schmidt P, Koltai JL, Weltzien A: Actinomycosis of the appendix in
childhood. Pediatr Surg Int 15:63-65, 1999
Horvath KD, Whelan RL: Intestinal tuberculosis: Return of an old
disease. Am J Gastroenterol 93:692-696, 1998
Singh MK, Arunabh, Kapoor VK: Tuberculosis of the appendix-a
report of 17 cases and a suggested aetiopathological classification.
Postgrad Med J 63:855-857, 1987
Mittal VK, Khanna SK, Gupta M, et al: Isolated tuberculosis of the
appendix. Am Surg 41:172-174, 1975
Domingo P, Ris J, Lopez-Contreras J, et al: Appendicitis due to
Mycobacterium avium complex in a patient with AIDS. Arch Int Med
156:1114, 1996
Livingston RA, Siberry GK, Paidas CN, et al: Appendicitis due to
Mycobacterium avium complex in an adolescent infected with the
human immunodeficiency virus. Clin Infect Dis 20:1579-1580, 1995

97
32. Randall MB, Walker DH: Rocky Mountain spotted fever. Gastrointestinal and pancreatic lesions and rickettsial infection. Arch Pathol
Lab Med 108:963-967, 1984
33. Kazlow PG, Freed J, Rosh JR, et al: Salmonella typhimurium appendicitis. J Pediatr Gastroenterol Nutr 13:101-103, 1991
34. Golakai VK, Makunike R: Perforation of terminal ileum and appendix
in typhoid enteritis: Report of two cases. East African Med J 74:796799, 1997
35. van Spreeuwel JP, Lindeman J, Bax R, et al: Campylobacter-associated appendicitis: Prevalence and clinicopathologic features. Pathol
Ann 22:55-65, 1987
36. Chan FTH, Stringel G, MacKenzie AMR: Isolation of C. jejuni from
an appendix. J Clin Microbiol 18:422-424, 1983
37. Coyne JK, Dervan PA, Haboubi NY: Involvement of the appendix in
pseudomembranous colitis. J Clin Pathol 50:70-71, 1997
38. ter Borg F, Kuijper EJ, van der Lelie H: Fatal mucormycosis presenting as an appendiceal mass with metastatic spread to the liver during
chemotherapy-induced granulocytopenia. Scand J Infect Dis 22:499501, 1990
39. Lamps LW, Molina CP, Haggitt RC, et al: The pathologic spectrum of
gastrointestinal and hepatic histoplasmosis. Am J Clin Pathol 113:6472, 2000
40. Sinniah B, Leopairut RC, Connor DH, et al: Enterobiasis: A histopathological study of 259 patients. Ann Trop Med Parasitol 85:625635, 1991
41. Wiebe BM: Appendicitis and Enterobius vermicularis. Scan J Gastroenterol 26:336-338, 1991
42. Moggensen K, Pahle E, Kowalski K: Enterobius vermicularis and
acute appendicitis. Acta Chir Scand 151:705-707, 1985
43. Shakir AA, Youngberg G, Alvarez S: Strongyloides infestation as a
cause of acute appendicitis. J Tenn Med Assoc 543-544, 1986
44. Nadler S, Cappell MS, Bhatt B, et al: Appendiceal infection by
Entamoeba histolytica and Strongyloides stercoralis presenting like
acute appendicitis. Dig Dis Sci 35:603-608, 1990
45. Noodleman JS: Eosinophilic appendicitis: demonstration of Strongyloides stercoralis as a causative agent. Arch Pathol Lab Med 105:148149, 1981
46. Adebamowo CA, Akang EEU, Ladipo JK, et al: Schistosomiasis of the
appendix. Br J Surg 78:1219-1221, 1991
47. Satti MB, Tamimi DM, Al Sohaibani M, et al: Appendicular schistosomiasis: A cause of clinical acute appendicitis? J Clin Pathol 1987:
424-428, 1987
48. Kenney M, Yermakov V: Infection of man with Trichuris vulpis, the
whipworm of dogs. Am J Trop Med Hyg 29:1205-1208, 1980
49. Cook GC: The clinical significance of gastrointestinal helminths: A
review. Trans Roy Soc Trop Med Hyg 80:675-685, 1986
50. Sinha SN, Sinha BN: Appendicular perforation due to Ascaris lumbricoides. J Ind Med Assoc 63:396-397, 1974
51. Oberhuber G, Lauer E, Stolte M, et al: Cryptosporidiosis of the
appendix vermiformis: A case report. Z Gastroenterol 29:606-608,
1991
52. Ramdial PK, Madiba TE, Kharwa S, et al: Isolated amoebic appendicitis. Virchows Arch 441:63-68, 2002