About Appendix Cancer

Appendix cancer is cancer that starts in the cells lining the inside of the appendix. There a number of different types of cancers of the appendix. The different types are determined by which type of cells in the appendix become cancerous and what the cells look like under the microscope. The different types are associated with different behaviors (i.e. likelihood of spreading to other organs or other parts of the body, rate of growth, ability to be completely removed with surgery etc.) and therefore the types of treatment that are offered. Appendix cancers are the most common cause of pseudomyxoma peritonei (or “PMP”) (see below).

• Low grade mucinous neoplasms of the appendix (formerly known as mucinous cystadenomas) are non-cancerous tumors of the appendix. This means that they do not have any potential to spread to lymph nodes or through the blood stream to other organs. However, due to the flimsy nature of the appendix wall, if the appendix ruptures or the tumor grows through the wall, neoplastic cells may spread in the abdominal cavity, because the tumors are created by mucin-producing cells that line the inside of the appendix, and a mucinous substance (a gelatinous material) may accumulate in the abdomen. The build-up of mucin (also known as pseudomyxoma peritonei or PMP) can eventually lead to abdominal pain, bloating, and/or bowel obstructions.
• Adenocarcinomas are cancerous tumors created by gland-forming cells that line the inside of the appendix. They are also frequently mucin-producing cells  and can result in accumulated mucin or PMP in the abdomen, but may also spread to other parts of the body, other organs in the abdomen or to the local lymph nodes.  Adenocarcinomas are usually graded based on their microscopic appearance as either low-, moderate – or high-grade tumors. They can also be categorized by their differentiation (meaning how closely they resemble a normal cell). Well-differentiated and low-grade cancers tend to be slower growing and less likely to spread to other part of the body compared with high-grade or poorly-differentiated adenocarcinomas.
• Signet-ring cell adenocarcinomas (so called because of the physical appearance of the cells under the microscope) are a subset of adenocarcinomas of the appendix. Signet ring cell cancers are generally considered more aggressive than other adenocarcinomas because they are faster growing, more likely to spread to local lymph nodes and harder to completely remove at the time of surgery.
• Goblet Cell Adenocarcinoma (also known as Goblet Cell Carcinoids or Adenocarcinoid cancers) are a hybrid tumor of both adenocarcinoma and a neuroendocrine (or carcinoid cancer) (see below). The expected behavior of goblet cell adenocarcinoma tumors tends to follow that of the adenocarcinoma portion of the tumor.  Consequently, treatment recommendations follow those for other types of appendiceal adenocarcinomas. They are generally considered to be more aggressive than low-grade or moderately-differentiated adenocarcinomas of the appendix, but not as aggressive as poorly-differentiated or signet ring cells adenocarcinomas.  Learn more about goblet cell adenocarcinoma by reviewing the NORD rare disease report for Goblet Cell prepared by ACPMP Medical Advisory Board member Dr. Laura Lambert.
• Neuroendocrine (Carcinoid) tumors arise from a subset of cells lining the appendix known as neuroendocrine cells. They do not make mucin and therefore do not cause PMP. They are generally considered to be slow growing and have a very different behavior than adenocarcinomas of the appendix.

Learn more about appendix cancer by reviewing the NORD rare disease report for Appendiceal Cancer and Tumors prepared by ACPMP Medical Advisory Board member Dr. Laura Lambert, and review the Appendix Cancer: Stages and Grades guide at Cancer.net. The EuroPMP Cost Action group provides an excellent primer on the different types of appendiceal tumors and PMP from pathologist Norman Carr.

The term Pseudomyxoma Peritonei has been and still is used to mean a number of different things. This has created much confusion for patients and physicians. Efforts are underway to better define PMP in the medical literature so that there is a better understanding of the term and communication between physicians and patients. Generally speaking, PMP is a rare condition characterized by the presence of mucin in the abdominal cavity. A number of types of tumors can cause PMP, but the most common cause is appendix cancer – including low grade mucinous neoplasms of the appendix. Learn more about PMP by reviewing Dr. Paul Sugarbaker's report on PMP in the NORD Rare Disease Database. The EuroPMP Cost Action group provides an excellent primer on the different types of appendiceal tumors and PMP from pathologist Norman Carr.

Peritoneal carcinomatosis is the term for cancers that have spread in the abdominal cavity.  PMP is different from peritoneal carcinomatosis in that it refers only to mucinous fluid in the abdominal cavity. It is agreed that the most important aspect of either peritoneal carcinomatosis or PMP is the classification of the cancer cells in the carcinomatosis or any cells that are present in the PMP.  This classification has changed over time (and continues to evolve), but the generally accepted spectrum of classifications of carcinomatosis and PMP are as follows:

1. Mucinous Carcinoma Peritonei Low Grade (MCP), or Disseminated Peritoneal Adenomucinosis (DPAM); this refers specifically to the type of cells present in PMP.
2. “Hybrid” or Peritoneal Mucinous Carcinomatosis with Intermediate Features (PMCA-I). PMP may be present but there is an obvious cancer cell component.
3. Mucinous Adenocarcinoma or Mucinous Carcinoma Peritonei High Grade or Peritoneal Mucinous Carcinomatosis (PMC/PMCA) with or without the presence of signet ring cells. PMP is often not present with these cancers.

Estimates vary, but all tend to be within the category of “extremely rare.” PMP was once thought to be diagnosed in about 1,000 people world-wide each year.  In other words, the lifetime odds of being diagnosed with PMP were thought to be about one in a million. However, specialists now believe it is more common than once thought, closer to one person diagnosed per 500,000 people per year.  Recent research has found the incidence of PMP is estimated to be 3.2 people per million diagnosed per year.

Recent research indicates that the incidence of appendix cancer may be as high as 10 people diagnosed per million per year, taking into account all of the various types of appendiceal tumors. The number of reported cases has increased over the past decade, but it is not certain whether incidence of appendix cancer is actually increasing or the rate has changed due to likely misdiagnosis or misclassification in the past.

Appendiceal cancer and tumors, goblet cell carcinoid tumors, and PMP are listed among the rare or "orphan" diseases acknowledged by the National Association of Rare Disorders (NORD). An orphan disease is generally considered to have a prevalence of fewer than 200,000 affected individuals in the United States.

Orphan diseases such as PMP have such a low prevalence in the general population that a doctor in a busy general practice is unlikely to see more than one case a year (if any). It also means that most pathologists see the disease infrequently and may misinterpret cell pathology, resulting in an incorrect diagnosis. Patients would benefit from improved awareness and diagnostic methods in the medical community through earlier detection and treatment of these diseases.

There are a number of theories about the origins of appendiceal tumors and PMP. It is generally accepted that appendiceal tumors are the most common source of PMP, but there is no known cause of appendix cancer.  Generally, cells from a mucinous tumor (usually in the appendix) leak into the abdominal cavity and implant on the peritoneum or other abdominal organs. These tumors replicate and produce a mucinous byproduct that spreads throughout the abdomen.

Although highly unusual, specialists and researchers have cited the ovary, stomach, colon, pancreas and other abdominal organs as other potential sites of origin for PMP other than the appendix.  It is not known at this time when or why some tumors in those organs would cause PMP while others do not.

Appendix cancer and PMP affect men and women almost equally. The age at diagnosis ranges from late teens to late in life, with most individuals diagnosed in their 40's and 50's.

It is generally thought that there is no genetic (familial) link to appendix cancer and PMP.  Risk factors that might predispose an individual to develop appendix cancer and PMP are unknown.

Many patients lack clearly defined symptoms until the disease has reached a relatively advanced stage. The following are some of the commonly reported symptoms:

• Appendicitis
• Increased abdominal girth
• Bloating
• Pain/discomfort in the abdominal region—can be a dull ache or sharp pains similar to appendicitis
• Hernia symptoms—often initially diagnosed as a hernia, especially in men
• In women, symptoms of an ovarian cyst or tumor—often initially misdiagnosed as ovarian cancer
• Ascites (fluid) buildup in the abdominal cavity

For many patients, appendix cancer and/or PMP are discovered during an unrelated surgical procedure at which time the surgeon observes the mucinous tumors or “studding” on the peritoneum or abdominal organs. The following diagnostic tests are also commonly used in diagnosing appendix cancer and PMP:

• CT scan of the chest, abdomen and pelvis. Note that CT scans are not perfect pictures, and for some patients visible signs of tumor are not present on a CT scan. CT scans also require the judgment of a radiologist who can interpret the scan to identify the signs of appendix cancer or PMP such as fluid buildup or tumor “studding”.

• MRI of the abdomen and pelvis.  There is a growing interest in the use of MRI of the abdomen and pelvis to diagnose and follow appendix cancers and PMP. Special protocols and expertise at reading MRIs are required to get the maximal benefit of this technology. Like CT scans, MRIs are not perfect pictures and they both require tumors to be big enough to be seen on the images.

• Diagnostic laparoscopy. A thin tube with a camera at its tip is inserted through “keyholes” in the abdomen to observe the abdominal cavity. Again, proper diagnosis depends upon the surgeon performing the procedure. Laparoscopic diagnosis of appendix cancer and PMP presents additional challenges in that failure to follow appropriate protocols may result in the spreading or seeding of tumors. If appendix cancer and/or PMP are suspected, a specialist in the disease should be brought in to take the proper precautions.

• Blood tests (tumor markers). Some tumor markers in the blood have been shown to be indicative of appendix cancer and/or PMP activity, particularly CEA, CA-125, and CA 19-9. Unfortunately, tumor markers are not accurate or indicators for everyone. Some patients will have no elevation in their tumor markers despite having extensive, aggressive tumor.