The appendix is a small hollow tube attached to the large colon (the large colon is also called large bowel or large intestine). The appendix is approximately 4 inches long and shaped like a worm. The appendix serves no known purpose, although it is thought to possibly play a role in the immune system. Very rarely, the appendix may become cancerous. Since the appendix is attached to the colon, appendix cancer is considered a type of colorectal cancer. Colorectal cancers are also part of a larger group of cancers of gastrointestinal tract, or GI cancers.
Cancer of the appendix may cause appendicitis or cause the appendix to rupture. Sometimes this is the first symptom of appendix cancer. A ruptured appendix may cause a very serious condition called peritonitis, which is an infection of the lining of the abdomen and pelvis. A cancerous tumor of the appendix may also “seed” the abdomen with cancer cells. This may cause more cancerous tumors to develop in the abdomen before it is discovered. Many times there are no symptoms of appendix cancer until it has progressed and is advanced. Abdominal discomfort and bloating of the abdomen can be signs of advanced appendiceal cancer.
Types of Appendix Cancer
Malignant Carcinoid of the Appendix
Carcinoid tumors are the most common of all appendix tumors. They are neuroendocrine tumors, meaning they are tumors that can create and release hormones into the bloodstream, although this usually only happens with metastatic disease (carcinoid tumors that have spread beyond the appendix to other areas of the body). Carcinoids are small yellow tumors usually found in the part of the appendix farthest away from where the appendix attaches to the colon or near the tip of the appendix. The tumors usually do not block the appendix and cause appendicitis. They are most often found unexpectedly during other abdominal or pelvic surgeries, for example surgeries to remove the gall bladder, hysterectomy etc. The tumors are small, slow growing and rarely metastasize (spread to other areas). The term “malignant” is applied to carcinoids that have metastasized to other areas of the body.
Carcinoids usually cause no symptoms. Symptoms of carcinoid syndrome may rarely occur with metastasis, especially metastasis to the liver.
- Tumors less then 1 cm in diameter are treated with appendectomy (surgical removal of the appendix) only. Appendectomy is usually considered 100% curative for these small tumors. Over 95% of carcinoid tumors of the appendix are less than 2 cm in size.
- Tumors 1.5-2 cm may be treated with appendectomy only or with right hemicolectomy (removal of up to half of the right side of the colon); there is disagreement in the medical community in regards to treatment in for carcinoids this size.
- Carcinoids greater than 2 cm are more likely to metastasize. Surgical treatment for these larger carcinoids is appendectomy, right hemicolectomy (removal of up to half of the right side of the colon) and removal of local lymph nodes.
- When carcinoid tumors spread (metastasize), they most commonly spread to the liver or lymph nodes. Chemotherapy is not very successful in this disease, with 30% limited response to chemotherapy reported. These metastatic tumors may be removed surgically.
Appendiceal carcinoids are more common in women by a ratio of 2:1 or 3:1. Average age 4th or 5th decade of life. No other known risk factor.
Overall 5 year survival reported as high as 90% in some medical research.
Mucinous Tumors of the Appendix
Tumors that produce mucous (mucinous tumors) of the appendix are rare. Normally a thin layer of cells lining the inside of the appendix produce mucous in small amounts. These cells normally die off at the same rate they reproduce. In cases of tumors, the cells reproduce faster than they die off and create a mass of cells. These masses of cells, or tumors, can produce large amounts of mucous.
There are different types of mucous-producing tumors that can occur in the appendix. There are both benign and cancerous mucous-producing tumors. Mucinous Adenocarcinoma is a cancerous tumor of the appendix; it is the most common type of appendix cancer. Mucinous Adenoma (also called Mucinous Cystadenoma) is a benign (non-cancerous) or low-grade tumor of the appendix.
Benign tumors differ from cancerous tumors in that benign tumors don’t usually invade normal tissue or spread (metastasize) to other areas of the body, while cancerous tumors often do both. Both mucinous adenocarcinoma and mucinous adenoma tumors can release cells into the abdomen. The released cells travel in the fluid that normally circulates in the abdomen and adhere to the inner surfaces (peritoneal surfaces) of the abdomen. Some tumor cells may also settle in parts of the abdomen and pelvis. These mucous-producing cells that are freed into the abdomen grow into new tumors that create mucous.
Very large amounts of thick mucous can be produced by both the benign and cancerous types of this tumor and can cause the abdomen to become bloated with mucinous ascites. A slang term for the large amounts of this thick mucous in the abdomen is “jelly belly“. Organs in the abdomen can become “squashed” by this mucous, and death can eventually result. In this circumstance the benign cells cause damage in much the same way as cancerous tumors that produce mucous, so are considered in the medical community to be a low-grade cancer.
With treatment, however, survival outcomes from the benign, or low-grade mucous-producing tumors (mucinous adenoma) are much better than outcomes for high-grade cancerous mucous-producing tumors (mucinous adenocarcinoma). See below more information about the different types of mucous-producing tumors of the appendix.
Mucinous Adenocarcinoma (Mucinous Cystadenocarcinoma)
Mucinous adenocarcinoma is the most common cancer of the appendix. It accounts for about 37% of all appendix cancers. This high-grade cancerous tumor produces mucous, but also more commonly invades soft tissues and organs. This tumor may also grow faster and is more likely to metastasize (spread) to the lymph nodes, liver and lung than mucinous adenoma. The medical term for extensive spread of these cancerous mucous-producing tumors into the abdomen is Peritoneal Mucinous Carcinomatosis (PMCA).
Mucinous Adenoma (Mucinous Cystadenoma)
Mucinous adenoma is a slow-growing benign or precancerous cyst-like tumor of the appendix, in which tumor cells produce mucous. If the adenoma ruptures, the mucous producing adenoma cells are released into the abdomen along with the mucous. These cells form mucous producing tumors. Extensive spread of these benign mucous producing tumors into the abdomen is referred to medically as DPAM (Disseminated Peritoneal Adenomucinosis), or just “adenomucinosis”. Though this tumor is considered benign, it is classified as a low-grade malignancy as it can still be fatal if untreated. Because this tumor is less invasive, it is more likely that complete cytoreduction will be achieved with surgical intervention.
Pseudomyxoma Peritonei (PMP)
Pseudomyxoma Peritonei (PMP) is a more common name given to the “jelly belly” syndrome caused by mucinous adenoma and mucinous adenocarcinoma. The term Pseudomyxoma Peritonei means “false mucinous tumor of the peritoneum”. Pseudomyxoma Peritonei (PMP) is commonly used to refer to widespread mucinous disease in the abdomen caused by either mucinous adenoma or mucinous adenocarcinoma. Most currently, though, the label Pseudomyxoma Peritonei (PMP) is starting to be used for DPAM (Disseminated Peritoneal Adenomucinosis), or “jelly belly” that is caused by tumors that are benign or pre-cancerous. Separating the two tumor types when defining PMP is helpful for research purposes as outcomes with the same treatment are much different for the two types of tumors.
Both Pseudomyxoma Peritonei (PMP) and Peritoneal Mucinous Carcinomatosis (PMCA) commonly recur after treatment.
Appendicitis may be the first symptom of both Mucinous Adenocarcinoma and Mucinous Adenoma of the appendix. Both Mucinous Adenocarcinoma and Mucinous Adenoma tumors may cause the abdomen to increase in size, or form masses in the abdomen or in the pelvis. In men the first symptom is sometimes an inguinal hernia, in women it often presents as an ovarian mass.
- Treatment for a benign mucinous adenoma that has not ruptured and that is confined to the appendix is removal of the appendix. If there is any possibility of the cyst being ruptured during laparoscopic removal, the abdomen should be opened surgically to avoid rupture of the cyst into the abdomen. If the cyst does rupture into the abdomen, the cells released may later become tumors and produce large amounts of mucous (adenomucinosis), causing the syndrome Pseudomyxoma Peritonei (PMP). If the appendix is removed laparoscopically, the appendix should be contained in a plastic bag to avoid spilling mucous and cells into the abdomen.
- Treatment for mucinous adenocarcinoma confined to the appendix when the appendix has not ruptured is appendectomy and right hemicolectomy (surgical removal of the appendix and up to half of the right side of the colon).
- Treatment for of mucinous tumors that have spread into the abdomen, either benign or cancerous- Pseudomyxoma Peritonei (PMP) or Peritoneal Mucinous Carcinomatosis (PMCA) is the same: cytoreduction (debulking) surgery to remove mucous and tumor implants in the abdominal cavity followed by intraoperative hyperthermic peritoneal chemotherapy (heated chempotherapy flid placed directly into the abdomen).
- Early postoperative intraperitoneal chemotherapy (EPIC, in which unheated chemotherapy liquid is put into the abdomen using a port or tube soon after the surgery is over), may also be used.
- IV chemotherapy (chemotherapy given into a vein) may possibly be used in addition for treatment of Mucinous Adenocarcinoma, but is not usually used for treatment of Mucinous Adenoma.
Most common 6th decade of life, mean age of occurrence 60 years old. Disagreement in the literature as to male-female ratios.
- Removal of the appendix for Mucinous Cystadenoma that has not spread beyond the appendix is considered curative.
- Prognosis for both Mucinous Adenoma and Mucinous Adenocarcinoma depends on the grade of malignancy of the mucinous tumor and the success of debulking surgeries in removing all tumors that have metastasized into the abdomen.
- For low-grade Mucinous Adenoma that has spread beyond the appendix into the abdomen, and for Pseudomyxoma Peritonei (PMP), 5 year survival has been reported in some studies to be over 75-80% when treated with cytoreduction (debulking) surgery to remove all of the tumors in the abdomen combined with hyperthermic intraoperative peritoneal chemotherapy (HIPEC).
- For high-grade Mucinous Adenocarcinoma that has spread beyond the appendix into the abdomen, and for Peritoneal Mucinous Carcinomatosis (PMCA), 5 year survival has been stated in some studies to be approximately 50% when treated with cytoreduction (debulking) surgery to remove all of the tumors in the abdomen combined with hyperthermic intraoperative peritoneal chemotherapy (HIPEC).
Adenocarcinoma of the Appendix
Adenocarcinoma of the appendix is similar to adenocarcinoma of the colon, and is referred to as “colonic- type” adenocarcinoma of the appendix. This tumor behaves more like colon cancer in that it more commonly metastasizes (spreads) by way of the lymph nodes or bloodstream. Some medical literature states that in 37% of cases the cancer has already spread into the abdominal cavity when it is first discovered.
Most often the first symptom of this cancer is appendicitis. In as many as 50% of cases the tumor perforates (goes through the wall of or “ruptures”) the appendix. In other cases it is first discovered as a mass in the lower right side of the abdomen. In some cases the first symptoms are pain in the abdomen or ascites, a build up of fluid in the abdomen. 10 to 20% of cases are discovered unexpectedly when abdominal surgery is being done for another reason. In cases of appendiceal perforation (rupture), the peritoneal cavity (inside of the abdomen) is assumed to be “seeded” with cancer cells, with a high chance of future tumor growth in the abdomen from these cancer “seeds”. Metastasis to ovaries in females is also common, and in many cases the first sign of this disease in females is a mass on an ovary.
- Treatment for this type of appendix cancer is surgical removal of the appendix (appendectomy) with removal of up to half of the right side of the large colon (right hemicolectomy). There is disagreement in medical literature in regards to recommending preventative surgical removal of the ovaries and fallopian tubes in women to prevent this cancer from occurring there as this is commonly a site to where the cancer spreads.
- In some literature intraperitoneal chemotherapy (chemotherapy liquid directly into the abdomen) is recommended in addition to a right hemicolectomy even if there are no other tumors in the abdomen, especially for intermediate and high grade tumors or in cases of perforation (rupture) of the appendix.
- Cytoreduction surgery and intraoperative hyperthermic chemotherapy is recommended for peritoneal carcinomatosis (cancerous tumors that have spread into the abdominal cavity).
- Treatment with systemic chemotherapy (IV Chemotherapy, or chemotherapy given into the veins) that is commonly used to treat colon cancer is also often used for this “colonic-type” appendix cancer.
Disease is more common in men than women with a 3:1 to 2:1 ratio. Occurs most commonly in people 60-70 years old.
- Overall survival statistics in some literature are stated as 40-50%.
- Other medical journal articles suggest survival rates up to 80% are possible even in cases when the cancer has spread into the abdomen if surgery is able to remove all of the cancer in the abdomen (called complete cytoreduction as all of the visible cancer is completely removed) and is combined with heated chemotherapy solution circulated in the abdomen at the time of cytoreduction surgery (this is called intraoperative hyperthermic peritoneal chemotherapy ). Clinical trials are in progress to evaluate the long-term outcome of this therapy combining surgery with chemotherapy into the abdomen.
Signet Ring Adenocarcinoma of the Appendix (Signet Ring Cell Carcinoma)
Signet Ring Adenocarcinoma, also commonly called Signet Ring Cell Carcinoma, receives its name from the fact that when looking at the cell under a microscope, the cell is so full of mucous that the nucleus of the cell (which would normally be near the cell’s center), is pushed to the edges, or periphery, of the cell. This makes the cell look like signet ring jewelry under a microscope. The signet ring cell type can occur in several different cancers. It is most commonly found in cancer of the lining of the stomach, but can also develop in the bowel, breast, pancreas, bladder, prostate, appendix or lung.
Signet ring cell is a rare type of cancer, and is the rarest of the appendiceal cancers. In the 25 years between 1973 and 1998 there were only 70 reported cases of signet ring appendix cancer in the USA. In one published medical study, 75% of cases of signet ring appendiceal cancer had already metastasized to adjacent organs, lymph nodes or to the peritoneal cavity on discovery. Signet ring is considered a high-grade, or aggressive, type of cancer.
As with other appendiceal cancers, signet ring can present as appendicitis or a perforated (ruptured) appendix. It may also present as an ovarian mass in females as it commonly metastasizes to the ovary. If extensive metastasis to the peritoneal cavity has occurred, it may present with bowel obstruction, abdominal pain or increased abdominal girth and bloating related to ascites. Signet ring adenocarcinoma is frequently in late stages of the disease when it is discovered. It can also progress rapidly.
Treatment is the same as it would be for colonic-type adenocarcinoma.
- Appendectomy with right hemicolectomy. Conflicting views in medical literature in regards to prophylactic removal of ovaries and fallopian tubes as this is commonly a site of metastasis.
- In some literature intraperitoneal chemotherapy is recommended in addition to the right hemicolectomy even without peritoneal surface malignancies, especially for intermediate and high-grade tumors or in cases of appendiceal perforation.
- Treatment with systemic chemotherapy commonly used to treat colon cancer is also used to treat signet ring appendiceal cancer following cytoreduction surgery and HIPEC (heated chemotherapy)
Mean age at discovery 58 years old, slightly more common in females
Signet ring adenocarcinoma has a poorer prognosis than the other varieties of appendiceal cancer. It is felt to be more aggressive and more resistant to chemotherapy than other cell types and is more likely to have metastasized on discovery. In some research 5 year survival is documented at 15-19%.
Adenocarcinoid Tumors of the Appendix (Goblet Cell Carcinoid)
Adenocarcinoid tumors of the appendix are also called Goblet Cell Carcinomas or Crypt Cell Carcinomas. These tumors share features of both adenocarcinoma and carcinoid types of appendix tumors. Adenocarcinoid tumors are more likely to metastasize (spread to other areas) than carcinoid tumors of the appendix. Approximately 20% of these tumors metastasize into the peritoneal cavity (the inside of the abdomen). In females, 90% of adenocarcinoid tumors that metastasize spread to the ovaries. In rare cases, adenocarcinoid tumors can produce mucous and can cause a condition called “mucinous peritoneal carcinomatosis” , which means widespread growth of mucous-producing cancerous tumors in the abdomen (see Mucinous Tumors).
The most common first symptom is appendicitis. In other cases the cancer is most often discovered unexpectedly when the patient is undergoing another surgical procedure.
- For tumors less than 2 cm that have not spread to the lymph nodes or other areas, appendectomy only (surgical removal of the appendix) is all that is recommended in some medical literature
- For tumors at the base of the appendix (near where the appendix attaches to the right side of the colon), spread to lymph nodes or tumor size greater than 2 cm, appendectomy with right hemicolectomy (removal of all or part of the right side of the colon) is the preferred surgical treatment.
- Some literature recommends removal of the ovaries during surgery to prevent them from possibly becoming cancerous later, as this cancer commonly spreads to the ovaries.
- Tumors that metastasize into the peritoneum (spread to the inside of the abdomen) may be treated with cytoreduction surgery and peritoneal chemotherapy.
- In cases of mucous-producing tumors with mucinous peritoneal carcinomatosis (spread of mucous-producing tumors in the abdomen), recommendation has been treatment with cytoreduction (debulking) surgery and intraperitoneal chemotherapy.
Occurs equally in men and women, mean age of occurrence 58.9 years of age. No other risk factors were identified in the literature.
5 year survival rates noted in literature between 60 and 84%. Some literature states 60% ten year survival. Extensive spread of goblet cell carcinoid (adenocarcinoid) into the abdomen is unusual, but when it follows this course, overall 5-year survival is approximately 25% in medical literature.