RESIDENT'S CORNER
Appendiceal Neoplasms
Quinton M. Hatch, M.D.
Madigan Army Medical Center, Tacoma, Washington
CASE SUMMARY:  A 50-year-old woman presents with
several months of mild right lower quadrant pain. She has
never had a colonoscopy or prior abdominal operations. Her
white blood cell count is normal. A CT scan of her abdomen
and pelvis with intravenous contrast is shown in Figure 1.
An appendiceal mucocele is suspected. She undergoes
colonoscopy. Figure 2 shows bulging at the appendiceal
orifice. She undergoes laparoscopy, and an enlarged
appendix is identified. It is removed by dividing across
normal bowel at the base of the cecum. Pathology reveals
low-grade appendiceal mucinous neoplasm (LAMN) with
a negative margin and no extra-appendiceal extension.
CLINICAL QUESTIONS
• How do we evaluate appendiceal neoplasms?
• What is the appropriate surgical intervention for the
treatment of these lesions?
• What are the long-term outcomes after surgery?
• What sort of surveillance should we perform?
BACKGROUND
Over 300,000 appendectomies are performed every year in
the United States alone, so it is not surprising that some per-
centage of these specimens will harbor neoplastic pathology.
In such cases, the presence of neoplasia inherently changes
the way we analyze the patient and often shifts the treat-
ment algorithm. Knowledge of the management of neoplas-
tic processes of the appendix is of critical importance to the
surgeon, as appendiceal cancers are often advanced at the
time of diagnosis, and decisions about the surgical manage-
ment can have profound effects on outcome.
Earn Continuing Medical Education (CME) credit online at cme.lww.
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Financial Disclosure: None reported.
Correspondence: Quinton M. Hatch, M.D., 9040 Jackson Avenue, Ta-
coma, WA 98431 Email: qhatch@gmail.com
Dis Colon Rectum 2017; 60: 1235–1238
DOI: 10.1097/DCR.0000000000000983
© The ASCRS 2017
DISEASES OF THE COLON & RECTUM VOLUME 60: 12 (2017)
Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
Neoplasms of the appendix are most commonly iden-
tified incidentally and are found in approximately 1% of
appendectomy specimens.1 The tumors themselves are
broadly classified as either epithelial or nonepithelial,
with mucinous neoplasms, nonmucinous adenocarcino-
ma, and signet ring cell tumors making up the epithelial
variants, and neuroendocrine tumors, lymphoma, and
sarcoma comprising nonepithelial neoplasia. Goblet cell
carcinoids are aggressive tumors that share characteristics
of both epithelial and nonepithelial tumors.
Epithelial Tumors
The majority of the confusion with regard to appendiceal
neoplasia exists within the spectrum of epithelial tumors.
Part of the perplexity is due to shifting terminology over
the years, although a recent consensus report standardized
the reporting (Table 1).2
Mucinous tumors are classified by grade. Low grade
appendiceal mucinous neoplasms (LAMN) are well-
differentiated, slow-growing, and present with gradual
obstruction, appendiceal dilatation, and fibrosis of the
appendiceal wall. Appendiceal adenomas, cystadenomas,
borderline tumors, and mucinous tumors of uncertain
malignant potential all fall under the histologic umbrella
of LAMN. High grade lesions invade beyond the muscula-
ris mucosa and are synonymous with mucinous adenocar-
cinoma or cystadenocarcinoma.
Intraperitoneal rupture of a mucinous appendiceal
neoplasm results in peritoneal surface disease with second-
ary production of mucin with variable cellularity, which
may ultimately result in development of pseudomyxoma
peritonei (PMP). PMP is a descriptive term that means
nothing more than accumulation of mucin within the peri-
toneal cavity. The majority of PMP is caused by low grade
appendiceal primaries but PMP secondary to other mucin
producing primaries such as ovarian colon or pancreas is a
well-documented event. The extent of peritoneal involve-
ment is graded by the peritoneal carcinomatosis index
(PCI), which evaluates the presence and extent of disease in
each of nine abdominal areas and 4 small bowel segments.3
Nonmucinous appendiceal neoplasms are analogous
to colorectal adenomatous neoplasia, with similar natural
history and treatment. They progress via direct extension,
lymphatic metastases and hematogenous metastases.
1235
 1236
FIGURE 1.  Abdominopelvic CT scan demonstrates a blind-ending
tubular structure extending to the right pelvis (top) and no evidence
of surrounding inflammation (bottom).
The current staging system for both types of appendi-
ceal neoplasms is shown in Table 2.4
Non-Epithelial Tumors
The appendix is a common site for gastrointestinal neuroen-
docrine tumors (NETs) (formerly carcinoids). Aptly called
ANETs (appendiceal neuroendocrine tumor), these tumors
arise from neuroendocrine progenitor cells in the submu-
cosa and, in contrast to other gastrointestinal NETs, are fre-
quently hormonally active. Such tumors may secrete growth
FIGURE 2.  Endoscopic view of bulging at the appendiceal orifice.
Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
HATCH: APPENDICEAL NEOPLASMS
hormone, growth hormone releasing hormone, gastrin, cal-
citonin, substance P, insulin, neurotensin, or serotonin. The
symptomatic effects of these substances are generally muted
by first pass hepatic metabolism; however, metastatic disease
to the liver bypasses this mechanism and may result in hor-
monally symptomatic disease. Lymphomas and sarcomas
are exceptionally rare and should be managed on a case-by-
case basis with multidisciplinary input.
Goblet cell tumors, as mentioned previously, share
characteristics of both epithelial and nonepithelial lesions.
They are particularly aggressive and have a poor prognosis
when compared to ANETs.5
PRESENTATION
While the anatomic construct of the appendix shares much
in common with the remainder of the colon, there are some
differences. The most significant of these is the higher per-
centage of lymphoid tissue in the submucosal layer. Addi-
tionally, there is a very high concentration of Goblet cells.
The 2–3 mL/d of secreted mucin must decompress via a
single appendiceal orifice. Not uncommonly, this orifice is
obstructed from fecaliths, lymphoid swelling, or in rare in-
stances a neoplastic process. A common presentation for any
obstruction of the appendiceal orifice is acute appendicitis.
With slowly progressing abnormalities, the present-
ing complaint is subtle, such as vague right lower quadrant
pain. These cases, as well as asymptomatic appendiceal dila-
tion noted on axial imaging, frequently represent mucoceles.
Mucoceles may be a manifestation of any of the previously
mentioned obstructive processes. Rupture of a mucinous tu-
mor of the appendix may lead to PMP and peritoneal carci-
nomatosis, at times present at the initial diagnosis.
Finally, the clinical presentation ANETs can relate to
their hormone production. Any combination of paradoxical
high body temperature, agitation, increased reflexes, tremor,
sweating, dilated pupils, or diarrhea may suggest the “sero-
tonin syndrome” from hormonally active hepatic metastases.
EVALUATION AND WORK-UP
Work-up of appendiceal neoplasms depends on where in
the algorithm the patient presents to the surgeon. Axial im-
aging, usually contrast-enhanced computed tomography
(CT) of the chest abdomen and pelvis, is essential. It pro-
vides an assessment of the primary tumor and a metastatic
evaluation. Mucoceles generally appear as appendiceal
dilation >15 mm in the absence of surrounding inflam-
mation.6 Peritoneal involvement may also be diagnosed
by cross-sectional imaging (extrinsic compression such as
scalloping of the liver, peritoneal reflection, or pouch of
Douglas); however, these are generally late findings.
All patients with appendiceal neoplasia should have a
screening colonoscopy, as synchronous colon lesions are
 DISEASES OF THE COLON & RECTUM VOLUME 60: 12 (2017)
TABLE 1.   Consensus classification for appendiceal neoplasms
and pseudomyxoma peritonei
Classification
Epithelial neoplasms of the appendix
Tubular, tubulovillous, or villous adenoma, low-grade or
  high-grade dysplasia
Serrated polyp
 Without dysplasia
 With low-grade dysplasia
 With high-grade dysplasia
Low-grade appendiceal mucinous neoplasm (LAMN)
High-grade appendiceal mucinous neoplasm (HAMN)
Mucinous adenocarcinoma: well, moderately, or poorly differentiated
 Poorly differentiated (mucinous) adenocarcinoma with signet
   ring cells (<50% of cells)
 Mucinous signet ring cell carcinoma (>50% of cells)
Adenocarcinoma: well, moderately or poorly differentiated
Pseudomyxoma peritonei
Acelluar mucin
Low-grade mucinous carcinoma peritonei
 or disseminated peritoneal adenomucinosis (DPAM)
High-grade mucinous carcinoma peritonei
 or peritoneal mucinous carcinomatosis (PMCA)
High-grade mucinous carcinoma peritonei with signet rings
 or peritoneal mucinous carcinomatosis with signet ring cells
  (PMCA-S)
Adapted from Carr N et al. Am J Surg Pathol 2016;40:14.2
common for both epithelial tumors and ANETs.8 Addition-
al work-up may include baseline tumor markers including
CEA (in cases of adenocarcinoma) and chromogranin A
(for ANETs). Urine 5-HIAA measured over 24 hours may
be used to assess for functional ANETs.
SURGICAL TREATMENT
With the exception of lymphoma, appendiceal neoplasms are
managed surgically. Neoplasms without an invasive compo-
TABLE 2.   Staging for appendiceal neoplasms
Carcinoid
T1: <2 cm
T2: 2–4 cm
T3: >4 cm or extension to the small intestine
T4: Direct invasion of the abdominal wall or nearby organs
Nx: The nodes cannot be evaluated
N0: No involvement of regional lymph nodes
N1: Involvement of regional lymph nodes
M0: No involvement of distant sites
M1: Involvement of distant sites
Stage I: T1, N0, M0
Stage II: T2 or T3,N0,M0
Stage III: T4,N0,M0 or Tany, N1, M0
Stage IV: Tany, Nany, M1
Adapted from Edge, SB, et al. AJCC Cancer Staging Manual, 7th ed, Springer, New York 2010.4 *In the 8th edition, tumor penetrating the visceral peritoneum and including
acellular mucin or mucinous epithelium involving the serosa of the appendix is staged T4a, and tumor which involves adjacent organs and including acellular mucin or mu-
cinous epithelium involving the serosa of the appendix is staged T4b. ^In the 8th edition, intraperitoneal acellular mucin without identifiable mucin is staged M1a, peritoneal
metastases are staged as M1b, and metastases to sites other than the peritoneum are staged M1c.
Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.
1237
nent can be treated with complete appendectomy to negative
margins. Often the diagnosis is not anticipated, and consider-
ation for additional resection is given when additional margin
is needed. When extra-appendiceal spread of mucin is noted at
the time of appendectomy, the best option may be to stop, sam-
ple the mucin for pathologic assessment, take photos, and refer
to a center specializing in management of these tumors. Mod-
erately or poorly differentiated adenocarcinomas of the ap-
pendix and primaries with signet ring cell component require
oncologic resection with right colectomy and lymphadenecto-
my. Due to lack of appendiceal specific adjuvant chemotherapy
outcomes, chemotherapy decisions currently extrapolate from
colon cancer primaries. Patients with accumulation of perito-
neal mucin can be considered for hyperthermic intraperitone-
al chemotherapy (HIPEC), even in cases where there is a high
burden of disease. Options for patients with high-grade appen-
diceal primaries and peritoneal dissemination include chemo-
therapy, cytoreductive surgery, HIPEC, or a combination of all
three. Cytoreductive surgery and HIPEC is most effective when
the PCI is low, tumors are low grade, and complete or near-
complete cytoreduction is achieved.7
Subcentimeter ANETs are also completely treated by ap-
pendectomy, assuming the microscopic margin is negative.
Even larger (1-2 cm) ANETs may be treated with R0 appen-
dectomy alone, assuming there is less than 3 mm of mesoap-
pendiceal invasion, multifocality is not present, and there is
no regional nodal or isolated liver involvement.8 Any lesion
not fitting these criteria requires a right hemicolectomy.
SURVEILLANCE
The surveillance strategy for treated malignant epithelial tu-
mors should generally follow the same guidelines as those
used for colorectal cancer as described in National Com-
Adenocarcinoma
Tis: No invasion of submucosa, LAMN
T1: Invasion into the submucosa
T2: Invasion into the muscularis propria
T3: Invasion through the muscularis propria into the subserosa or mesoappendix
T4: Invasion through the visceral peritoneum or other organs*
N0: No regional lymph node metastasis
N1: 1 to 3 regional lymph node metastases
N2: 4 or more regional lymph node metastases
M0: No involvement of distant sites
M1a: Intraperitoneal metastasis^
M1b: Nonperitoneal distant metastasis^
Stage I: T1 or T2, N0, M0
Stage II: T3 or T4,N0,M0
Stage III: Tany, Nany,M0
Stage IV: Tany, Nany, M1
 1238 HATCH: APPENDICEAL NEOPLASMS

prehensive Cancer Network (NCCN) guidelines including
periodic CT, CEA, and colonoscopy.9 One notable excep-
tion is nonperforated LAMN, which can be followed with a
colonoscopy one year after resection and no further imaging.
LAMN with perforation or extracellular mucin creates a par-
ticular challenge for surveillance. If a CT or MRI done 6–12
months after the appendectomy shows no mucin, additional
follow up may not be needed, but some centers continue to
follow these patients for 5 years or longer. If there is intraperi-
toneal mucin, then debulking or HIPEC can be considered.
Low-risk ANETs less than 2 cm in size are consid-
ered cured after surgery and require no specific follow up.
Tumors >2 cm or with high-risk features, however, ne-
cessitate clinical exam, CT abdomen and pelvis, and con-
sideration of chromogranin A levels every 6–12 months
for at least 7 years after surgery.10
PROGNOSIS
Oncologic outcomes depend heavily on the histologic subtype
and stage of the disease at diagnosis, with five-year disease-
specific survival ranging from 10% to 93%. Current staging
algorithms categorize appendiceal tumors as a distinct entity
from colorectal tumors, with histologic grade factoring heavi-
ly.4 Unfortunately, despite their indolent nature and lower rates
of metastatic disease at diagnosis, 5-year survival is lower than
in other colorectal malignancies.11 This is presumably due to
non specific symptoms and late presentation.
Five-year survival after surgery for ANETs <1 cm is
excellent, approaching 100%. For larger tumors, however,
cancer-related mortality rises exponentially as size increas-
es. Tumors >2 cm at diagnosis already have a 20–30% risk
of nodal metastases, and an average 5-year survival rate as
low as 31%.12
CONCLUSION
Appendiceal neoplasia represents a broad-spectrum of sur-
gical disease within a diminutive vestigial appendage. It is
encountered not infrequently, and clinical decision mak-
ing may have dramatic implications for the patient. It is of
critical importance that every gastrointestinal surgeon be
comfortable navigating the nuanced treatment algorithm
for this spectrum of disease.

EVALUATION AND TREATMENT ALGORITHM

Appendicitis or appendiceal dilation on computed tomography (CT)

Operating room findings

Appendiceal mass or mucocele Appendiceal cancer suspected Extra-appendiceal mucin or

resectable with appendectomy or involvement of the cecum peritoneal dissemination

• Biopsy of implants and mucin

• Low-grade • High-grade neoplasm or
• Appendectomy if freely
neoplasm not adenocarcinoma
perforated
invading serosa OR
• Close and complete staging
OR • Goblet cell tumor
• Adenoma or high- OR
grade dysplasia • Neuroendocrine tumor
OR >1-2 cm, invading Unresectable
• Colonoscopy
• Neuroendocrine mesoappendix, or metastatic
• CT chest, abdomen, pelvis
tumor <1 cm and lymphadenopathy disease
• CEA, CA19-9, CA 125
negative margin

• Colonoscopy if not
High-grade Low-grade
Colonoscopy one done recently Best palliative care
adenocarcinoma adenocarcinoma
year after resection • CEA and/or
chromogranin A

Systemic • Exploratory laparotomy

chemotherapy • Cytoreductive surgery
No further Right colectomy with followed by • HIPEC if complete or near-
treatment lymphadenectomy restaging CT complete cytoreduction

Complete resection not possible Complete resection possible

Surveillance;
consider adjuvant
treatment similar
to colon cancer Best palliative care

Copyright © The American Society of Colon & Rectal Surgeons, Inc. Unauthorized reproduction of this article is prohibited.