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Neoplasms of the Appendix

Primary tumors of the appendix are rare; and they are usually diagnosed after pathologic inspection ;( and
histopathological examination) of the appendix that was removed for suspected appendicitis.

Approximately 1%; of all appendectomy specimens will contain a neoplasm.

Classification of Primary Appendiceal Tumors:-

 NETs—(Carcinoid tumors)—the commonest Appendiceal tumor-(88% of all Appendiceal tumors.)
 Adeno-carcinoma:--2- major histologic subtypes:-

Well Differentiated-- Mucinous Adenocarcinoma- --Un-Differentiated Adenocarcinoma- Colonic Type.

 Mixed functional and non-functional tumors—Goblet-cell Adeno-Carcinoid.

 Lymphoma of the Appendix.

Mucinous Neoplasm of the Appendix may be:--

Mucinous- Cyst-adenoma- /Or-- Mucinous Cyst-adenocarcinoma.

Mucinous Cystadenoma and Cystadenocarcinoma—are typically indistinguishable prior to resection

when confined to the appendix and should be resected without rupturing the appendix to reduce the
risk of peritoneal seeding and development of pseudomyxoma peritonei. So- when suspected
Preoperatively or identified Intraoperatively—it is advisable to use open approach/or convert from a
laparoscopic to open approach to avoid potential rupture—and—Rt. Hemicolectomy is appropriate
option and recommended.
Both- Un-Differentiated Adenocarcinoma- Colonic Type- and- Goblet-cell Adeno-Carcinoid - are more
aggressive tumor types and should be treated in a similar fashion as a colon cancer- including Rt.
Hemicolectomy-with lympho-vascular mesenteric clearance-and- Adjuvant Chemotherapy.

Neuro-Endocrine-Tumors-(NETs)—(Carcinoid Neoplasm) of the Appendix:-

NETs)—(Carcinoid Neoplasm)-is the commonest Appendiceal tumor-(88% of all Appendiceal tumors-)

The Appendix is the second common site of GIT- Carcinoid--after SB—(Appendiceal Carcinoid represent
18% of all GIT-Carcinoid.)

(The most common sites of GIT-Carcinoid Neoplasms in Descending order are: SB—Appendix- Colon and
Rectum —Stomach.)

Epidemiological Evidences-- indicate that- Carcinoid tumors- is the most common neoplasm of the
Appendix--(88% of all Appendiceal tumors.)
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Pathology of Appendiceal Carcinoid: ---

Appendiceal Carcinoid Tumors are- Functioning NETs- arise from;  the Entero-Chromaffin Cell –(EC-Cell)
which are separate group of Entero-Endocrine-Cells; situated in the base of intestinal crypts—secrete
Serotonin- and are thought to be derived from un-differentiated Stem Cells.

Size—most-(95%)-of appendiceal tumors are =/or  2 cm.

Gross-appearance--It appears as a submucosal firm, yellow, mass -- the majority of appendiceal

carcinoids--75%) - are located in the tip of the appendix-

Growth—Appendiceal-NETs-tend to grow very slowly—invasion of the muscle wall occurs in 30% of cases.

Histologically: - carcinoids of the appendix are 2-histological--subtypes:-

(a)—Classical Carcinoid.

(b)—Goblet-Cell- Adeno-Carcinoid-(mixed-cell tumors) -- Bad Prognosis than the classical sub- type.

Associated Neoplasm---Appendiceal-NETs—(Like other GIT-- NETs) -- patients with appendiceal carcinoids

may present with second primary tumors, (Synchronous Tumor); especially of the GIT and GUT-- This is
usually a Synchronous Adenocarcinoma (most commonly in the Colon.)

Carcinoid Syndrome—

Appendiceal NETs—(like other mid-gut NETs)--have the ability to secrete numerous Humoral agents—
(Amines and Peptides), the most prominent of which are Serotonin and Substance P. – Bradykinin.

Like other GIT-NETs- Appendiceal tumors are rarely associated with Carcinoid syndrome; unless
metastatic.

Malignant potential

NETs-(Carcinoid) of the Appendix-- are the least aggressive and have the best prognosis- among other
malignant Appendiceal tumors (Adeno-carcinoma; Cyst-adenocarcinoma; and Lymphoma).

At presentation— Most Appendiceal Carcinoids are localized to the appendix-- only approximately 3% of
Appendiceal NETs-are associated with Metastases—(Regional LNs and/ or Distant to Liver mainly.)

Malignant Potential--(ability to Local Invasion and Metastasize) - is related mainly to:--

· Size of the Primary Tumor:--

NETs  1 cm- - almost have-- No risk of associated Lymphatic and hepatic metastases.

NETs-1—2 cm—have only--  5% risk of associated Lymphatic and Hepatic metastases.

NETs--> 2 cm—have 30% risk of associated Lymphatic metastases and—20% risk of Hepatic metastases.
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· Histo-pathological Subtype-- Goblet-Cell Adeno-Carcinoid is more aggressive; and tends to metastasize

to regional L.Ns.
· Grade of Malignancy—which is determined by Tumor Proliferative Index—(Mitotic Count/10 HPF--and
Ki-67 % index—and Degree of Differentiation.

Poorly Differentiated NETs-i.e.—NE-Carcinoma with High Grade Malignancy-has Higher Risk of associated
metastases.

· Staging-- Depth of Local Invasion into the bowel wall and into surrounding structures—and
Angioinvasion.
Classification scheme for Intestinal- NETs—(GEP-Ts)—WHO 2017:--based on Tumor Grading and
Degree of Differentiation:-WHO-2017 Version.

Grade Differentiation Tumor description Mitotic count/10 HPF—-- ki-67-

index %

Low Grade. Well- Differentiated. NE- Tumor OR Neoplasm. 2 AND 3

G--1 (Syn. Carcinoid Tumor)

Intermediate Well- Differentiated. NE- Tumor. 2—20 OR 3--20

Grade. G--2

High Grade. Well- Differentiated. NE- Tumor. 2—20 OR 3--20

G--3

High Grade-G Poorly- Differentiated. NE -Carcinoma. 2—20 OR 3--20

—3-NE It may be- small or large
Carcinoma. cell - NE-Carcinoma.

Staging System of Appendiceal- NETs:-- AJCC—Staging System for GIT-NETs:--

Stage—I: -- Only Local Disease—(Small Tumors-- = /or  2 cm - -And-- without invasion beyond the
Submucosa.

Stage—II: --Only Local Disease—(Larger Primary Tumor - - > 2 Cm -- And/ Or -- deeper depth of invasion
beyond the Submucosa.

Stage—III: -- Advanced Local Disease—(P-T4) -- -Any Tumor Size-- invading through the serosa into
adjacent structures—And/ Or Loco-regional Disease-(presence of LNs-Metastases.)
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Stage—IV: --Evidences of Distant Metastases.

Diagnosis-Appendiceal-Carcinoid:-

Presentation:-

In the Majority of cases—Diagnosis of Appendiceal-Carcinoid is Incidental during/ or after surgery-

(routine Histo-pathological examination of appendix specimen)—and it is uncommon to be Symptomatic
and Diagnosed Pre-operatively by imaging techniques.

It was found that— Approximately 1%; of all appendectomy specimens will contain a neoplasm.

· Usually—the Diagnosis is made- incidentally---During Surgery for Suspected Appendicitis/Or any other
cause- as firm yellowish mass; mostly at the tip of appendix Or/ After Surgery during the Histo-
pathological examination of appendectomy specimens removed for Suspected Appendicitis.
· Occasionally-- if Carcinoid neoplasm arises from base of the appendix; the patient will present as Acute
Appendicitis.
· Picture of Carcinoid Syndrome; Rare; unless; metastasizing neoplasm with hepatic metastases—which
occurs in approximately 3% of cases of Appendiceal tumors.
Management of appendiceal-carcinoid

(I)-- Screening Tests-- to detect any second synchronous primary tumors- according to patient’s age and
presence any additional risk factors—Upper GIT-Endoscopy-- Colonoscopy and may IV Contrast CT-Scan -
for UT.

(II)—Surgical Treatment:--

If—appendiceal carcinoid neoplasm—Diagnosed/ or Suspected- During Surgery as incidental finding:

(A)— Appendiceal Carcinoids--=/ 1 cm -that are located in the tip or the middle of the appendix-(these

tumors have more benign biological behavior; and show No metastatic potential)—So-  Appendectomy-
(ensure that the base of the appendix is included in the specimen) - with Excision of the Mesoappendix--is
curative almost 100%.

Post-operatively—complete Histo-pathological assessment is mandatory to detect tumors with more

aggressive behavior and metastatic potential—and Proceeds according to the Histo-pathology results.

(B)-- Appendiceal carcinoids suspected- to have more aggressive biologic behavior; and show metastatic
potential – - Right Hemicolectomy is indicated.

These are:-

 > 2 cm- or—

 Involve the Base of the appendix-- -or invade the Mesoappendix- -or --With LNs Metastases.-

(C)-- Appendiceal NETs—1.1-2-cm—extent of surgical treatment is controversial-

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Generally- treated with either Radical Surgery-/-or only Appendicectomy-- according to other high risk
features-and Patients should be carefully counseled on the risk for recurrence associated with local
excision-Rt. Hemicolectomy is appropriate option if there is involvement of appendiceal base- or
mesoappendix-

If—appendiceal carcinoid neoplasm--Diagnosed --After Histopathological Examination of

Appendicectomy specimen:-- Proceeds according to Histo-pathological report:--

The Histo-pathological report should include: - tumor dimensions—Depth of Invasion-Grading-(mitotic

index and Ki- 67 proliferation %-index)—degree of Differentiation- the presence or absence of Lympho-
vascular Invasion.

(A)-- Appendiceal carcinoids can be considered Cured with Appendectomy alone when:--

Tumors-- =/  1 cm in Size.

Tumors - confined to the tip of appendix.

Tumors that do not invade the mesoappendix—and-- No LNs-metastases.

well differentiated tumors—with Low-Grad-(G-1).

No evidence of lympho-vascular invasion.

(B)--Appendiceal carcinoid neoplasm found to: -- have more aggressive biologic behavior; and show
metastatic potential – - Formal Right Hemicolectomy is indicated-- when Any One of the following
criteria is present: These are:--

 Large tumor--> 2 cm.

 Tumors Located/ or invading- at the Base of the appendix with positive margins.
 Mesoappendiceal invasion with Ns metastases.
 Poorly-Differentiated tumors-(NET—Carcinoma).
 Intermediate- to- High-Grade malignancy—G-2/3- -tumors-- (with high mitotic index- and- ki-67-
index %)

 Lymphatic and vascular Invasion.

 Goblet cell Adeno-carcinoid tumors.

(C)—Appendiceal NETs-1.1-2 cm are best treated with Right Hemicolectomy- when Any One of the high risk

features are present-

Adenocarcinoma of the Appendix:--

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Appendiceal adenocarcinomas are very rare neoplasm; and mostly diagnosed incidentally during
pathological examination of the resected appendix.

Pathology:--

Adenocarcinoma of the appendix may be either:-

Well-differentiated- mucus-producing tumor --( Mucinous Neoplasm)- Appears as Mucocele.

Poorly differentiated –adenocarcinoma- (colonic type) that; appears as a solid mass.

Both types of adenocarcinoma of the appendix have been reported to metastasize to regional lymph
nodes, although mucinous Adeno-carcinoma has been considered clinically to be less invasive; and has
better prognosis.
Patients with appendiceal adenocarcinoma are at significant risk for both synchronous and
metachronous neoplasms; 50% of which arise from GIT.

Diagnosis:--

Patients are often old-age with long duration of symptoms; and Weight Loss.

Clinical Presentation:--

(a)---Picture of Acute Appendicitis ;( mostly Colonic type; present as a mass obstructing the lumen)  the

commonest presentation.

(The Neoplasm is diagnosed after pathological examination of the appendix that was removed for
suspected appendicitis.)

(b)—Palpable RT.Lower Quadrant Mass ;( mostly Cyst-adenocarcinoma)present as (Mucocele).

(c)—Progressive Abdominal Distension and Diffuse Abdominal Pain. ;( Due to mucinous Ascites);

Treatment:--

(1)---Right Hemicolectomy is indicated in all patients with adenocarcinoma of the appendix.

OR; Less Extensive Surgical Approach:  Surgical Treatment depends upon staging ;( Dukes Staging):--

Appendectomy; in (Dukes A); tumors confined to the mucosa with clear surgical margins.

Formal right Hemicolectomy; in Dukes B and C tumors ;( invasion of the muscle wall/or L.Ns metastases)
and in case of involved resection margins; plus Adjuvant Chemotherapy; similar to colon carcinoma.

(2)---Cancer Surveillance for any; synchronous/or metachronous GIT Neoplasm.

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Mucinous Tumors of the Appendix-(Cystic Neoplasm); It may be:--

Cyst-Adenoma. OR Cyst-Adenocarcinoma.

Appendiceal mucinous neoplasms have unique Pathological characteristics:-

Mucinous Cystadenomas; represent the majority of “Mucoceles, “lead to slow-growing distension of the

appendix; and can grow to 8 cm or more.

Most of these mucinous neoplasms are non-invasive:-

Lymph Nodes and Hepatic metastases are uncommon.

Loco-regional recurrence of mucinous tumors is commoner; which ultimately result in Small Bowel
Obstruction.

Most patients have ruptured Mucocele at the time of diagnosis, and are associated with the spread of
neoplastic epithelial cells within mucoid fluid throughout the peritoneal cavity, pseudomyxoma
peritonei, or mucinous carcinomatosis of appendiceal origin ;( peritoneal dissemination of tumor cells.)

(The appendix is the most common origin of pseudomyxoma peritonei; and mucoid fluid collections in the
abdomen)

The bulk of the peritoneal tumor is an important prognostic factor ;( independent of histologic grade.)

Pseudomyxoma Peritonei ;( mucinous carcinomatosis):--

Pseudomyxoma peritonei is a rare condition in which there is diffuse intra-peritoneal collections of mucoid
gelatinous fluid; associated with mucinous neoplastic cellular implants on peritoneal surfaces and
omentum.

Pseudomyxoma Peritonei is invariably caused by widespread of neoplastic mucus-secreting cells within

the peritoneum.

These Cells are widely scattered, and have a low-grade cytological appearance; and may be difficult to
classify as malignant.

Appendiceal Mucinous neoplasm is the site of origin for the vast majority of cases of pseudomyxoma.

(According to Recent immunocytologic and molecular studies.)

Diagnosis:--

(I)--Presentation:-
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Acute:--Patients usually present with picture of Appendicitis.

Subacute: ---

Insidious onset of RT.I.F.Mass; usually in Cyst-adenoma; as it is slowly growing.

Ruptured Mucinous Neoplasms:-

 Patients present with insidious onset of progressive abdominal distension ;( due to

intraperitoneal accumulation of mucoid material.); and Diffuse Abdominal Pain.

 Ureteral and IVC- obstruction may occur due to increased intra-abdominal pressure;
(Compartment Syndrome)

(II)--Imaging:--

CT-Scan:--

In mucinous Cystadenomas; the Mucocele is large > 2 cm; and may reach to 8 cm or lager; and wall
calcification is characteristic.

In case of Ruptured mucinous neoplasm; there will be focal mucinous fluid collections in the pelvis, left
para-colic gutter, sub-hepatic space, splenic hilum, and/or omentum. There may be enlargement of the
ovaries caused by entrapment of mucinous tumor cells within ovarian tissue.

Treatment:--

Larger Mucoceles; are most likely to be neoplastic: - Treated with 

Appendicectomy; with Wide Excision of mesoappendix with the appendix to determine lymph node status.

Right Hemicolectomy is indicated; if:--

There is invasion of the base of the appendix by tumor; at time of surgery.

Patients with a positive margin at the base of the appendix or positive peri-appendiceal lymph nodes.

(During surgery; effort is made to keep the Mucocele intact during extraction, including placing the
specimen in a bag or converting a laparoscopic procedure to an open procedure, if necessary.)

When a Mucocele is visualized at the time of laparoscopic examination, conversion to open laparotomy is
recommended. This will ensure that a benign process will not be converted to a malignant one through
Mucocele rupture. Also; laparotomy allows for thorough abdominal exploration to rule out the presence of
mucoid fluid accumulations.

In case or ruptured Mucinous Neoplasm ; Pseudomyxoma Peritonei; ( mucinous carcinomatosis):-

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(At Surgery; variable volume of mucinous ascites together with tumor deposits are found involving the
right hemi-diaphragm, right retro-hepatic space, left para-colic gutter, ligament of Treitz, and the ovaries
in women. Peritoneal surfaces of the bowel are usually free of tumor)

Aggressive surgical approach involving:--

(1)--- Right Hemicolectomy should be performed in almost all cases.

If there is simple mucinous ascites contained to the right lower quadrant; without widespread neoplastic
cellular deposits ;( considered localized pseudomyxoma peritonei)  Benign Cystadenomas is likely and
Appendicectomy; and removal of any residual Mucin is curative.

If there is Diffuse (widespread) peritoneal tumor implantation; associated with mucinous ascites; Cyst-
Adenocarcinoma is the most likely diagnosis; so Right Hemicolectomy is indicated.

However; Right Hemicolectomy is appropriate in most cases; as it is difficult to distinguish between benign
and malignant tumors.

(2)---Cytoreductive surgery:--

Extensive excision of the grossly involved peritoneal deposits; and omentum-Omentectomy. Hysterectomy
with bilateral Salpingo-oophorectomy is performed in women.

(De-bulking of the peritoneal tumor is an important prognostic factor); may improve survival for these
patients; especially if performed early in the course of this disease, before tumor cells become trapped in
scar tissue surrounding the viscera.)

Plus

(3)---Perioperative intraperitoneal hyperthermic chemotherapy:-

(Cytoreductive surgery with intraperitoneal hyperthermic chemotherapy is associated with improved

prognosis and survival of these patients.)

Treatment of Loco-regional recurrence:-

Loco-regional recurrence is Common; and patients usually present with Small Bowel Obstruction.

Conservative Treatment ;( NPO (Bowel Rest);IV-Fluids; NG-Decompression);may be tried; as Surgical

Treatment- Repeated Debulking procedures is difficult and associated with much high morbidity; due to
multiple enterotomies; anastomotic leakage and intestinal fistula.
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Lymphoma of the Appendix:-  Present as:-

Primary lymphoma of the appendix; is very Uncommon; accounts for 1% - 3% of GIT-lymphomas.

Extranodal site for non-Hodgkin’s lymphoma; as GIT is the most frequently involved Extranodal site for
non-Hodgkin’s lymphoma.

Diagnosis:-

Usually; the patient presents with picture of Acute Appendicitis; and the diagnosis made after
Histopathological examination of the excised appendix.

Treatment:--

(1)—Neoplasm found to be confined to appendix;  Appendicectomy is sufficient.

(2)—Neoplasm; extends into base of the appendix; onto the cecum or mesentery;  Right Hemicolectomy
is indicated.

(3)--- Postoperative staging workup is indicated to  initiate adjuvant therapy.

(Adjuvant Chemotherapy in not indicated; if the lymphoma confined to the appendix.)

Mucocele of the Appendix:-

Mucocele of the appendix is the result of obstruction of the appendiceal orifice with intraluminal
accumulation of mucoid material; resulting in  distention of the appendix.

(So; Appendiceal Mucocele is not a pathologic diagnosis; but it refers to the macroscopic appearance of an
appendix distended with mucus.)

Pathological Types of Appendiceal Mucocele:--

The spectrum of histologic changes that may be found in the mucosa of appendiceal Mucoceles, ranging
from benign simple epithelium to the invasive mucinous adenocarcinoma.

(Simple cuboidal epithelium Hyperplastic epithelium Cyst-Adenoma Cyst-Adeno-carcinoma.)

(1)--- Simple Mucocele ;( Retention Cyst):-

It results from chronic obstruction of the proximal lumen, usually by fibrous tissue; without subsequent
infection resulting in simple Mucocele that is lined by flattened cuboidal epithelium.
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(2)—Mucosal hyperplasia:--

The Mucocele is lined with hyperplastic epithelium.

Intact Mucocele ≤ 2 cm are almost always benign.

(3)—Neoplastic Mucocele; (Mucinous Neoplasms):--

Cystadenomas.

Cystadenocarcinomas.

Mucinous Cystadenomas; represent the majority of “Mucoceles.

Large Mucoceles >2 cm; are more likely to be neoplastic .

Diagnosis:--

(1)---Picture of Appendicitis; and Appendiceal Mucocele is an incidental finding at surgery;

Appendicectomy.

(2)-- Insidious onset of increasing abdominal distension ;( due to intraperitoneal accumulation of mucoid
material due to ruptured Mucocele.); and Diffuse Abdominal Pain

(2)--- CT-Scan:-

In simple and benign appendiceal Mucoceles; it showed fluid-distended sac without associated
inflammation.

In mucinous Cystadenomas; wall calcification is characteristic.

In case of ruptured mucinous neoplasm; there will be focal mucinous fluid collections in the pelvis, left
para-colic gutter, sub-hepatic space, splenic hilum, and/or omentum. There may be enlargement of the
ovaries caused by entrapment of mucinous tumor cells within ovarian tissue.
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CT scan of the abdomen in a patient with a benign Appendiceal Mucocele. The axial image shows a
distended fluid-filled mass; (10 cm); medial to the appendix (arrow), without associated inflammation.

Treatment:--

Small Mucoceles; ≤ 2 cm; and not ruptured are almost always Benign; and presents no future risk for
the patient. Appendicectomy is sufficient with precaution to prevent rupture of the Mucoceles.

Larger Mucoceles; are most likely to be neoplastic: - Treated with 

Appendicectomy; with wide Excision of mesoappendix with the appendix to include all the appendiceal
lymph nodes, and determine lymph node status.

Collection and cytological examination of all intraperitoneal Mucoid fluid, and careful inspection of the
base of the appendix.

(During surgery; effort is made to keep the Mucocele intact during extraction, including placing the
specimen in a bag or converting a laparoscopic procedure to an open procedure, if necessary.)

When a Mucocele is visualized at the time of laparoscopic examination, conversion to open laparotomy is
recommended. This will ensure that a benign process will not be converted to a malignant one through
Mucocele rupture. Also; laparotomy allows for thorough abdominal exploration to rule out the presence of
mucoid fluid accumulations.

Right Hemicolectomy is indicated; if:--

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There is invasion of the base of the appendix by tumor; at time of surgery..

Patients with a positive margin at the base of the appendix or positive peri-appendiceal lymph nodes.

In case or ruptured Mucinous Neoplasm ;( mucinous carcinomatosis):-

(1)--- Right Hemicolectomy should be performed in almost all cases.

If there is simple mucinous ascites; without widespread neoplastic cellular deposits;  Benign
Cystadenomas is likely and Appendicectomy is curative.

If there is peritoneal tumor implantation; associated with mucinous ascites; Cyst-Adenocarcinoma is the
most likely diagnosis; so Right Hemicolectomy is indicated.

However; Right Hemicolectomy is appropriate in most cases; as it is difficult to distinguish between benign
and malignant Mucinous tumors.

(2)---Cytoreductive surgery:--

Extensive excision of the grossly involved peritoneal deposits; and omentum-Omentectomy. Hysterectomy
with bilateral Salpingo-oophorectomy is performed in women.

(De-bulking of the peritoneal tumor is an important prognostic factor); may improve survival for these
patients; especially if performed early in the course of this disease, before tumor cells become trapped in
scar tissue surrounding the viscera.)

Plus

(3)---Perioperative intraperitoneal hyperthermic chemotherapy:-

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