Atlas of Appendix Cancer

Introduction

Appendix tumors are unusual, accounting for 0.4% of all of the gastrointestinal tract malignancies. Although rare, the spectrum of malignant disease is complex and has lead to confusion in accurate description of the natural history of these tumors. Consequently, many errors in diagnosis and treatment have occurred. Perhaps the most glaring error in management occurs in women who have ovarian tumors as a result of a perforated primary mucinous tumor of the appendix. Appendiceal tumors present with peritoneal seeding in a majority of patients. Dissemination to lymph nodes or to liver is extremely unusual. Advanced treatments of peritoneal carcinomatosis or peritoneal adenomucinosis have changed these survival rates from zero to approximately 80% for all patients.

Figure 1

Clinical pathway for the treatment of appendiceal tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.

	Carcinoid	Cyst- adenocarcinoma	Adenocarcinoma	Adenocarcinoid	Linitis Plastica* (Signet Ring)
Incidence	66%	20%	10%	Rare	Rare
Location	Tip of appendix	Variable	Base of appendix	Diffuse along appendix wall	Diffuse
Major symptom	Incidental finding	Appendicitis, mucinous ascites	Appendicitis	Appendicitis or right lower quadrant mass	Appendicitis
Prognosis	< 1 cm 100% cure > 2 cm 50% cure	Localized 90% cure Peritoneal seeding- poor prognosis	Follows Duke's stages A - 80% cure B - 50% cure C - 20% cure	84% cure at 5 years	Poor
Clinical syndromes	Carcinoid	Pseudomyxoma peritonei	Peritoneal carcinomatosis
Treayment	< 1 cm appendectomy only > 2 cm right colectomy + cytoreductive surgery	Appendectomy + intraperitoneal chemotherapy + cytoreductive surgery	Right colectomy + intraperitoneal chemotherapy	Appendectomy only unless advanced	Radical surgery + intraperitoneal chemotherapy +

* In separating cystadenocarcinoma, adenocarcinoma, and signet-ring cancer, it must be remembered that these represent a spectrum of these and are not distinct clinical entities. Benign mucocoele is not included as an appendiceal tumor but is rather a cystic process.

Table 1

Survey of appendiceal tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.

	Colon	Appendix
Adenocarcinoma incidence	85%	10%
Carcinoid incidence	< 1%	70%
Mucinous adenocarcinoma	10-15%	20%
Signet-ring adenocarcinoma	1/1,000	10-Jan
Mucinous adenocarcinoid	Not reported	Rare
Differentiation carcinoma	20% Well 60% Moderate 20% Poor	60% Well 20% Moderate 20% Poor
Associated malignancy	Unusual	Common

Table 2

Comparison of colorectal and appendiceal malignant tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.

		Type of distribution of adenocarcinoma
	Proximally random	Redistributed	Fibrin entrapment
Character	Solid	Glazed	Scar encased
Tumor grade	High	Low	Any
Extraabdominal metastases	Likely	No	Any
Tumor texture	Solid or mucinous	Mucinous and layered	Scar encased
Omental cake	No	Yes	No
Diaphragmatic accumulation	No	Yes	No
Bowel surface implantation	Yes	No	Yes
Biophysical mechanism of distribution	Cell surface adhesion	Gravity, peritoneal fluid flow motionless surfaces	Fibrin entrapment at wound site
Adhesion enzymes on cell surface	Yes	No	Either
Treatable tumor volume	Low	Any	Low
Mechanism of implant density	Proximity	Peritoneal fluid flow, gravity	Proximity to surgical margins of resection
Ascites	Unusual	Usual, mucinous	No
Surgical setting: primary vs. reoperative	Both	Both	Reoperative
Transcoelomic progression	Some	Yes	No
Size of cancerous implant	Multiple diameters of plaques	Multiple thickness of layers	Uniform size, depending depending on progression since previous operation.
Tumor character	Plaquelike	Layered	Nodular
Location	Proximal and random	Excludes mobile surfaces	Traumatized sites

Table 3

Figure 2

Survey of appendiceal tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.

Figure 3

Comparison of colorectal and appendiceal malignant tumors. From Sugarbaker PH: Cancer of the appendix and pseudomyxoma (in) Fazio VW: Current Therapy in Colon and Rectal Surgery. BC Decker: Toronto 1998.

Figure 4

Characteristics of three distribution patterns for intraabdominal tumor emboli. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.

Figure 5

Two patterns of natural spread with invasive and non-invasive malignancy. Left: A random and proximal distribution was observed with aggressive tumors. Implants are in close proximity to the perforation site and are randomly distributes on nearby surfaces. Right: Redistributed tumor was observed with non-invasive mucinous tumors. The large volume of implants were within the greater omentum, beneath hemidiaphragms, and within the pelvis. The difference in surface adhesion molecules with invasive and non-invasive malignancy are likely to be the major factor causing the marked differences in the distribution of peritoneal carcinomatosis. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.

Figure 6

Distinguishing clinical features of peritoneal seeding in sarcoma, pseudomyxoma peritonei and adenocarcinoma. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.

Figure 7

Two types of fibrin entrapment. Cancer cells may be traumatically dispersed at the time of a surgical procedure. These cancer cells then become involved in the healing process that inevitably results after a cancer resection. The first phase of the healing process is the flooding of the wound with fibrin. The fibrin entrapment causes two different morphologic types of peritoneal recurrence. Individual tumor emboli that are present on peritoneal surfaces in low density will result in nodular masses distributed throughout the peritoneal surfaces of the abdomen and pelvis. A higher density of tumor seeding will cause fusiform masses. This high density seeding usually occurs along narrow margins of resection, especially those margins that have been surgically traumatized as part of the cancer resection. Fusiform masses result from a layering of tumor within the operative site, especially along vital structures or unresectable anatomic barriers such as bone or major blood vessels. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.

Figure 8

Correlation of distribution pattern and implant morphology. The four distribution patterns of proximal-random, redistribution, generalized, and fibrin entrapment are correlated with a distinct morphology of implants that is observed with each pattern. Adenocarcinoma is an invasive process whose cancer cells contain adhesion molecules on the cancer cell surface. Also, little or no mucus is produced by the tumor that would facilitate widespread dissemination within the abdomen and pelvis. Pseudomyxoma peritonei, in contrast, has no adhesion molecules on its surface and shows no invasive capabilities on peritoneal surfaces or into lymphatics or vascular channels. The tumor cells are suspended in a large volume of slippery fluid. These two properties together account for the widespread dissemination of epithelial cells that arise from ruptured appendiceal adenoma. The mucinous adenocarcinoma presents a hybrid pattern of distribution that shows features of the pattern seen with adenocarcinoma combined with the pattern seen with pseudomyxoma peritonei. Sarcomatosis occurs if there is a perforation of the tumor into the peritoneal cavity. The sarcoma nodules do not migrate, but become wedged into crevices within the abdomen and pelvis where they progress. In most instances, surgical trauma results in sarcoma spillage, and the sarcoma implants are seen on the traumatized peritoneal surfaces. From Sugarbaker PH: Observations concerning cancer spread within the peritoneal cavity and concepts supporting an ordered pathophysiology (In) Sugarbaker PH (ed): Peritoneal Carcinomatosis: Principles of Management. Kluwer: Boston, p79, 1996.

Figure 9

The tissue of origin of a malignancy will control the pattern of progressive intracholehemic dissemination. Sarcoma implants occur in much lower numbers that do adenocarcinoma implants. Sarcoma implants disseminate on peritoneal surfaces if hemorrhagic necrosis and rupture of the primary tumor occurs. These sarcoma implants are limited in number and do not increase in an exponential fashion. Implants of adenocarcinoma reflect the tissue of origin, in that implants will exfoliate malignant cells from their surface early in the progressive growth of the peritoneal nodule. This exfoliation process may rapidly cause a confluence of adenocarcinoma on a peritoneal surface. This causes a "cobblestone" appearance of surfaces involved by adenocarcinoma implants. From Ronnett B, Sugarbaker PH:

Figure 10

Photomicrograph of adenomucinosis after four cycles of intraperitoneal chemotherapy. The tissue shown in this photomicrograph was taken from the surface of this tumor. The tumor shows complete disruption of its architecture, with no viable epithelial cells remaining. (H&E x35).