Journal of Cancer Therapy, 2010, 1, 174-180
doi:10.4236/jct.2010.14027 Published Online December 2010 (http://www.scirp.org/journal/jct)
Management and Outcomes in Primary Tumors of
the Appendix
Richard K. Englehardt, Noreen K. Durrani, Vijay K. Mittal
Department of Surgery, Providence Hospital and Medical Centers, Southfield, USA.
Received: August 9th, 2010; revised August 15th, 2010; accepted August 23rd, 2010.
ABSTRACT
Primary tumors of the appendix are rare, comprising 1.1% of all appendectomy specimens. Nevertheless, it often pre-
sents in an emergent fashion, creating a need for a well-defined management algorithm that will ensure proper acute
management. We performed a retrospective review of medical charts from 1982-2007 on all charts with a diagnosis o f
appendiceal neoplasm. A cohort of 41 patients was diagnosed with a primary appendiceal neoplasm from a total of
8560 appendectomies over the 25-year period. Several tumors were identified: adenocarcinomas (n = 16), carcinoid
tumors (n = 15), mucinous cystadenocarcinoma (n = 7), and a combination of adenocarcinoma and goblet cell carci-
noid of the appendix (n = 3). Twenty-one patients presented with an acute abdomen. Tumors were discovered intraop-
eratively in eighteen patients while performing other procedures. At diagnosis, metastatic disease was found in 41.5%
of patients (n = 17); average survival ranged from 6 to 21 months based on tumor type. For patients with
non-metastatic disease at diagnosis, all survived longer than 2 years and there were no cases of recurrence or
post-operative metastasis. We devised an operative strategy dictated by initial presenting characteristics of the tumor.
The presence of carcinoma should be suspected and searched for in patients over 40 presenting with acute appendicitis.
Intraoperatively any suspicious mass should undergo frozen sectioning as the finding of a malignancy often necessitates
a larger or repeat operation. The propensity of these neoplasms for presentation in the guise of acute appendicitis
mandates that the surgeon be familiar with the appropriate management algorithm, both in and out of the operating
room.
Keywords: Appendix Cancer, Gastrointestinal Malignancy, Malignant Neoplasms of the Appendix
1. Introduction
Primary tumors of the appendix are rare. However, statis-
tics show that one of the most common surgical emergen-
cies in the United States today is still appendicitis [1].
Since the pathophysiology of appendicitis was first de-
scribed in 1886 by Raymond Fitz, multiple etiologies of
appendicitis have been discovered, ranging from obstruc-
tion via fecalith to obstruction with tumor [2]. Current
management strategies described in the literature advocate
aggressive right colonic resections for most tumor types.
These recommendations are often based on data extrapo-
lated from primary colonic tumors of similar histology.
The objective of our study was to review our experience
with primary tumors of the appendix, compare our man-
agement strategies with the other common management
strategies described in the current literature, and use this
information to better define an accepted management
algorithm for primary appendiceal tumors.
2. Methods
All appendectomies performed at Providence Hospital
and Medical Centers over a 25-year period from March
1982 to December 2007 were reviewed. Those patients
with chart codes positive for appendiceal tumors were
reviewed in detail. Only primary neoplasms of the ap-
pendix were analyzed. Patients with histology consistent
with adenocarcinoma, carcinoid, mucinous cystadeno-
carcinoma, and mixed adenocarcinoid tumors were fur-
ther evaluated. Patients with benign neoplasms and pa-
tients with metastatic disease to the appendix with a sep-
arate primary were not included in the study. Factors
catalogued in the patients incorporated in the study in-
cluded presenting symptoms, method of diagnosis, epi-
demiologic data, preoperative imaging, laboratory studies,
intraoperative findings, operation performed, pathology
results, use of postoperative chemotherapy, and eventual
outcomes.

Management and Outcomes in Primary Tumors of the Appendix 175
Epidemiologic factors analyzed included patient age
at diagnosis, gender, and date of surgery. Patients were
categorized as to whether or not they received preop-
erative imaging, the type of imaging performed, and
whether the imaging was able to detect the presence of
a neoplasm preoperatively, postoperatively on retro-
spective review, or not at all. Laboratory values evalu-
ated including preoperative white blood cell count and
hemoglobin. Intraoperative values recorded including
the presence of gross metastatic disease, whether a neo-
plasm was suspected during the initial operation,
whether a frozen section was performed. The operation
performed as well as whether this was an initial opera-
tion or a completion operation. Patient survival in
months, follow up for a minimum of 2 years, and com-
plications were also noted. Complications which were
looked for included wound infections, abscess forma-
tion, and development of pseudomyxoma peritonei.
Outcomes were determined at surgery by pathologic
examination and by clinical follow-up in all available
patients. All patients were separated out by histologic
classification and compared among those with similar
neoplastic histology.
3. Results
Of the 8560 cases of appendicitis, primary neoplasms of
the appendix were diagnosed in 41 patients, an incidence
of 0.5%. The incidence of diagnosis of primary tumors of
the appendix increased from 0.3% between 1982-2003 to
1.2% between 2003-2008. An investigation of this dis-
crepancy revealed that prior to 2001, cases of grossly
metastatic adenocarcinoma of the appendix with colonic
spre ad wer e cod ed as adeno carc inoma of th e co lon r athe r
than adenocarcinoma of the appendix. It is believed the
true incidence of primary tumors of the appendix is clos-
er to 1.2% within the institution. Two patients were lost
to follow up and records were not available. Twenty-six
patients were female (63%) and 15 were male (37%).
The average age at diagnosis was 53 years. Clinical
presentation was variable (Table 1). As might be ex-
pected, the majority of patients presented with signs and
symptoms consistent with appendicitis. Forty-four per-
cent presented with right lower quadrant abdominal pain
and 7% presented with peritonitis while 22% of patients
presented asymptomatically. Twenty percent of patients
presented with other symptoms secondary to metastatic
disease such as carcinoid syndrome (N = 1), bowel ob-
struction (N = 3), dyspnea (N = 2), upper abdominal pain
(N = 2), and vaginal bleeding (N = 1). The mortality rate
in our series was 2%, with one death secondary to com-
plications of distant metastatic disease in which the fam-
ily opted to withdraw care. The average length of stay
was 8 days.
Table 1. Clinical presentation of primary tumors of the
appendix.
Symptoms Number of
Patients % Pre-operative WBC(K/mcL)
Right Lower Qua-
drant Pain 18 44 10.1
Diffuse Peritonitis 3 7 23.6
Asymptomatic 9 22 10.9
Other 11 27 9.2
CARCINOID
N=15
ADENO-
CARCINOMA
N=15
MUCINOUS
CYSTADENO-
CARCINOMA
N=7
MIXED
N=3
Figure 1. Distribution of primary tumors of the appendix.
Adenocarcinoma (N = 16) and carcinoid (N = 15) we re
the most common pathologic findings. Mucinous cysta-
denoma (N = 7) and mixed adenocarcinoma and goblet
cell carcinoid (N = 3) were also encountered as shown in
Figure 1. Five percent (N = 2) of patients presented with a
synchronous tumor elsewhere in the gastrointestinal tract.
Diagnosis was made on colonoscopy when sigmoid ade-
nocarcinomas were found in two patients with synchro-
nous appendiceal adenocarcinomas. As shown in Table 2,
appendiceal cancer was often discovered incidentally
Table 2. Relationship of the diagnosis of primary appen-
diceal tumor to the initial operation.
Operative Findings Number of
patients %
Incidental finding during
another procedure 18 44%
Appendiceal cancer suspected
prior to operation 10 24%
Tumor discovered while
operating for appendicitis 13 32%

Management and Outcomes in Primary Tumors of the Appendix 176
during operation for other symptoms or during an unre-
lated procedure. Our series found 44% of patients were
diagnosed with a primary appendiceal malignancy after
undergoing routine colonoscopy or surgical exploration
for unrelated symptoms. A large portion of the cohort
(41%) was found to have metastatic disease at the time of
their initial operation. It should be noted that appendiceal
cancer was highly suspected prior to operation in only
24% of the patients who were ultimately found to have
an appendiceal malignancy.
Upon further review of the pathologic subsets as
shown in Table 3, of the 19 patients who pr esented with
either adenocarcinoma or mixed adenocarcinoma and
goblet cell carcinoid, 10 were suspected peroperatively,
either due to preoperative computed tomography (CT) or
while in operating room at the time of the initial opera-
tion. Nine of these patients underwent initial right hemi-
colectomy; one underwent appendectomy with interval
right hemicolectomy. The remaining nine patients were
diagnosed after histologic examination of the pathologic
specimen. Four of these nine returned for right hemi-
colectomy as a definitive operation. Of the remaining
five, one was transferred to another in stitution upon fam-
ily request, three refused further operative intervention
due to distant metastatic disease, and the last had a lesion
located at the tip of the appendix and refused further
surgery (Table 4). On pathologic review of the tumor
grading of the adenocarcinoma tumors, most of the tu-
mors (N = 13) were grade 2 moderately differentiated
tumors (Figure 2).
In contrast to the patients with adenocarcinomas of the
appendix, of the 15 patients diagnosed with carcinoid
tumors of the appendix, four underwent curative appen-
0%
5%
26%
69%
Figure 2. Tumor grad ing of ad eno carcinomas of t he appendix .
dectomy at initial operation, six underwent right hemi-
colectomy at the initial o peration, while five returned for
right hemicolectomy secondary to location of the initial
lesion near the base of the appendix (Table 3). There was
one case of carcinoid syndrome secondary to metastatic
disease to the liver. When looking at the manner of di-
agnosis among patients with carcinoid tumors, four pa-
tients were found carcinoid tumors at the base of the ap-
pendix discovered during colonoscopy. Fifty-three per-
cent (N = 8) of carcinoid patients presented with signs
and symptoms of acute appendicitis. One patient pre-
sented as an incidental mass palpated during another un-
related procedure and one was diagnosed as an incidental
finding on pathologic specimen in a patient undergoing
ileocolectomy for Crohn’s disease. None of the patients
diagnosed with carcinoid tumors subsequently developed
metastatic disease and all survived for a minimal two
years follow up. The one patient with metastatic disease
prior to operation survived 14 months (Table 3).
Seventeen percent (N = 7) of patients in our cohort
were diagnosed with mucinous cystadenocarcinoma. As
seen in Table 3, tumor was suspected preoperatively or
intraoperatively in 71% (N = 5) of these patients. Three
patients underwent initial appendectomy, one of which
was followed with a right hemicolecto my while the other
four patients underwent right hemicolectomy at the initial
operation. The remaining two patients who initially un-
derwent appendectomy developed psuedomyxoma peri-
tonei and did not undergo further surgery. A total of four
patients were found to have pseudomyxoma peritonei at
the initial operatatic disease at the time of operation.
Preoperative CT scans were available in 29 of 39 pa-
tients. The preoperative interpretation of these scans was
obviously suspicious for malignancy in nine of 29 pa-
tients. One additional scan was identified as suspicious
when reviewed retrospectively. The results of these pre-
operative CT scans led to changes in treatment in eight
patients, preventing an unnecessary second operation in
six of these patients and in the institution of non-opera-
tive management in another patient.
At the time of diagnosis of a primary tumor of the ap-
pendix, metastatic disease was found in 17 of the 41 pa-
tients (42%). As shown in Table 4 these were separated
out according to tumor type, and whether or not they
received chemotherapy. Among patients with metastatic
adenocarcinoma of the appendix 5 of the 10 received
chemotherapy with an average survival of 13 months
verses 6 months in those without chemotherapy. There
were 2 patients with metastatic carcinoid who also opted
to receive chemotherapy. Among this group those pa-
tients who received chemotherapy had an average sur-
vival of 11 months as opposed to 13 months among those
who did n ot receiv e ch e mothera py.
Grade 2
Grade 3
Grade 4 Grade 1

Management and Outcomes in Primary Tumors of the Appendix 177
Table 3. Operative results.
Adenocarcinoma%Mucinous cystadenocarcinoma % Carcinoid %
Number 19 467 17 15 37
Tumor suspected
pre-op or intra-op 10 535 71 7 47
Appendectomy alone 2 112 29 4 27
Right hemicolectomy at initial operation 9 474 57 6 40
Right hemicolectomy at second operation 5 261 14 5 33
Refusal of further operation 3 160 0 0 0
Metastatic disease at initial operation 10 534 57 1 7
Twenty four of the 41 patients with primary appen-
diceal cancers were found to have no evidence of metas-
tatic disease at the time of operation. Table 5 demon-
strates the current survival statistics among this group
based on tumor type. At the conclusion of the study all
24 patients without metastatic disease had survived
longer than two years. Seventeen of the 24 patients had
already survived longer than fi ve years (Figure 3). Thr ee
of the 24 patients had deceased, all secondary to non-
cancer related illnesses. There were three patients with
non-metastatic disease who did choose to receive che-
motherapy. Among all patients with non-metastatic dis-
ease at the time of initial operation we have seen no cases
of tumor recurrence or post-operative development of
metastasis.
Table 4. Metastatic disease based on tumor type .
Metastatic disease at
initial operation % Received chemotherapy % Average survival in months with chemotherapy Average survival in months without chemotherapy
Adenocarcinoma (19) 10 53 5 50 13 6
Mucinous cystade-
nocarcinoma (7) 4 57 0 0 N/A 21
Carcinoid (15) 3 20 2 67 11 13
Table 5. Non-metastatic disease based on tumor type.
No metastatic disease at initial
operation %Received chemotherapy %Average survival in
months
with chemotherapy
Average survival in
months
without chemotherapy
Adenocarcinoma (19) 9 473 3360 65
Mucinous cystadenocarci-
noma (7) 3 430 0N/A 104
Carcinoid (15) 102 800 0N/A 139
0
5
10
15
20
25
Number of
patients
012345
Years of survival
Metastatic Disease
Non-metastatic Di s e ase
Figure 3. 5 years post operative survival.

Management and Outcomes in Primary Tumors of the Appendix 178
4. Discussion
Primary malignant tumors of the appendix are rare, oc-
curring in 0.5% of all appendectomies [3]. The four main
types of appendiceal malignancies are carcinoid tumors,
mucinous cystadenocarcinomas, adenocarcinomas and
adenocarcinoid tumors [4]. Common benign tumors in-
clude villous adenomas and mucinous cystadenomas.
Once encountered, the management of appendiceal tu-
mors changes patient management from that of tradi-
tional causes of appendicitis. As the study has shown, the
majority of cases of appendiceal neoplasm are not diag-
nosed pre-operatively, but rather intra-operatively, or on
pathologic review of the specimen post-operatively. The
diversity in treatment strategies for appendicitis creates
the need for a well-defined treatment algorithm for ap-
pendiceal malignancies that will ensure proper treatment
in both the acute setting and retrospectively, when diag-
nosis is made based on the pathologic specimen.
First, gross inspection by the surgeon may reveal
atypical findings. A frozen section should be done
whenever the appendiceal findings are atypical. A diag-
nosis of malignancy can be made during surgery and
appropriate surgery can be done primarily [4]. Treatment
then varies depending on tumor type and location. The
treatment of each type of appendiceal neoplasm is well
described in the literature. All patients with appendiceal
neoplasms should be followed because a second malig-
nancy will develop in 15% to 20% of cases [4].
Consistent with our findings, carcinoid tumors are the
second most frequently encountered malignancy of the
appendix after adenocarcinoma [5]. Appendiceal carci-
noid tumors are typically found in 0.3-0.9 percent of pa-
tients undergoing appendectomy [6]. They tend to pre-
sent with the clinical signs and symptoms of an acute
abdomen and frequently coexist with other intestinal
neoplasms[5]. The size of the tumor is correlated with
prognosis [7]. Diagnosis of a carcinoid tumor less than
one centimeter, or according to some sources between one
and two centimeters is appropriately treated with appen-
dectomy alone [6]. The same tumor, measuring greater
than two centimeters, or associated with mesen-
teric/lymphatic invasion, should prompt right hemicolec-
tomy [8]. Examination of the histological specimen re-
vealing location at the base of the appendix, rather than at
the tip also necessitates right hemi colectomy [6].
Review of the literature reveals that mucinous cystic
neoplasms of the appendix continue to engender con-
siderable debate in their diagnosis and management.
Abdominal pain is the most common presenting
symptom. The recommended treatment of mucinous
cystadenocarcinoma is a right hemicolectomy with
debulking of any pseudomyxoma peritonei [4]. In the
reported literature, an approximately equal number of
patients have been subjected to appendectomy alone
versus right hemicolectomy [9].
Primary appendiceal adenocarcinoma is a rare neo-
plasm that constitutes less than 0.5% of all gastrointesti-
nal neoplasms, yet it is the most common appendiceal
neoplasm. Most patients present with either local inva-
sion or metastatic disease often involving the peritoneu m
or ovaries [10]. In one study, a high frequency of ovarian
metastases in women suggested a role for bilateral oo-
phorectomy [11]. One important prognostic factor of
primary appendiceal adenocarcinoma appears to be his-
tology, with Park et al. [12] reporting improved survival
in those patients with mucinous variants. Adenocarci-
noma is best treated with right hemicolectomy regardless
of size [4]. Survival rate has been shown to be superior
after right hemicolectomy versus appendectomy alone
[13]. In addition, right hemicolectomy performed as a
secondary procedure resulted in the upstaging of 38% of
the patients' tumors [13].
Adenocarcinoid tumors have a dual cell origin, sharing
the histological features of both carcinoids and adenocar-
cinomas, and a predilection for developing ovarian me-
tastases. Size and location of the primary tumor is often
cited as an indication for hemicolectomy rather than ap-
pendectomy. However, other than size greater than two
centimeters and base localization, current studies suggest
that the presence of mucin producing cells, atypical foci,
high mitotic count, or spread beyond the appendix is a
further indication for secondar y r ight hemicolecto my [14,
15]. Adenocarcinoid tumor is appropriately treated by
right hemicolectomy and ooph orectomy in females [4].
Although uncommon, primary appendiceal neo-
plasms often result in clinical symptoms of appendicitis
that may lead to radiographic analysis. As our study
and other studies have shown, acute appendicitis is the
most common manifestation for most tumor types.
Other manifestations include intussusception, a palpa-
ble mass, gastrointestinal bleeding, increasing ab-
dominal girth (from pseudomyxoma peritoneii), and
secondary genitourinary complications [16]. CT can
help rule out or confirm an appendiceal tumor and may
suggest a more specific diagnosis [16].
5. Conclusions
Operative strategy should be dictated by initial presenting
characteristics of the tumor. Tumors should be first differen-
tiated based on pathology. All adenocarcinomas, mixed
adenocarcinoids, and mucinous cystadenocarcinomas
should undergo right hemicolectomy regardless of size or
locatio n on th e append ix. With regards to carcin oid tu mors,
if discovered a t initial surger y as a mass larger than two cm,

Management and Outcomes in Primary Tumors of the Appendix 179
Figure 4. Treatment algorithm for primary tumors of the appendix
a right hemicolectomy should be performed, while tu-
mors less than two cm in size and limited to the tip of the
appendix can be treated with appendectomy alone. Tu-
mors detected post-operatively in the histologic specimen
should be managed according to the location and pathol-
ogy of the tumor. Patients with adenocarcinomas and
tumors found at the base of the appendix should undergo
reoperation with right hemicolectomy or ileocecal resec-
tion. Appendectomy alone can be used for a carcinoid
tumor limited to the tip of th e appendix (Figure 4).
Several key concepts can be gathered from this review.
The initial presentation of the patient often dictates man-
agement. The presence of carcinoma should be suspected
and searched for in patients over 40 presenting with acute
appendicitis. The utility of routine perioperative CT scan-
ning in this age group could not be assessed in our study
given the time frame of the study and changes in CT tech-
nology over this period; however, it may be an important
adjunctive test in this cohort and is worth further evalua-
tion in the future.
In the operating room suspicion of an appendiceal neo-
plasm should prompt a frozen section. Diagnosis of malig-
nancy can be made and the appropriate operation, whether
appendectomy or right hemicolectomy, can be done primar-
ily. The propensity of these neoplasms for presentation in
the guise of acute appendicitis mandates that the general
surgeon be familiar with the appropriate management algo-
rithm, both in and out of the operating room.
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