What is Appendix Cancer?
Cancer of the appendix is a rare type of tumor that is often discovered by accident during appendix removal surgery. In fact, only about 0.5-1% of all tissue samples taken during these surgeries reveal this type of cancer. Usually, this condition shows up as a case of acute appendicitis, which happens when the appendix gets blocked. Like all types of cancer, it’s really important to catch it early. A late diagnosis could potentially lead to worse health outcomes.
What Causes Appendix Cancer?
It’s not entirely clear how cancers of the appendix, also known as appendiceal malignancies, develop. However, some scientists think that a specific type of these cancers, called appendiceal mucinous neoplasms (AMN), may form in a similar way to colorectal cancer. This process might start with a mutation, or genetic change, in a gene called KRAS.
Following this, there could be more mutations or losses in another gene called TP53 on chromosome 17. Changes in other genes, such as the APC gene on chromosome 5 and the beta-catenin gene, may also contribute to the development of the disease.
Another theory suggests that these cancers could be a result of changes in what are known as ‘nucleotide mismatch repair genes’. These include genes like hMSH2, hMLH1, PMS1, PMS2, and GTBP. These genes usually help fix mistakes in our DNA, but when they don’t work correctly, they may contribute to cancer development.
Risk Factors and Frequency for Appendix Cancer
Appendix cancer is rare, being found in less than 2% of appendix samples. However, there has been a recent increase in the number of surgeries to remove the appendix and the occurrence of appendix cancer in the United States. The most common type of cancer found in the appendix is a type of tumor known as gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
Though more common in men in their 60s and 70s, the average age of diagnosis for appendix cancer has been decreasing. Research also shows a link between appendix cancer and colon cancer or chronic ulcerative colitis. The appendix is often the site for neuroendocrine tumors, coming third just after the rectum. Also, by the time it’s diagnosed, over a third of appendix cancer cases have spread to other parts of the body.
- Appendix cancer is found in less than 2% of appendix samples.
- There has been an increase in appendix removal surgeries and appendix cancer cases in the United States.
- GEP-NETs are the most common type of appendix cancer.
- Appendix cancer is often diagnosed in men in their 60s and 70s but the average age at diagnosis is reducing.
- There is a link between appendix cancer and both colon cancer and chronic ulcerative colitis.
- The appendix is often the site of neuroendocrine tumors, following the rectum.
- Over a third of appendix cancer cases spread to other parts of the body by the time they are diagnosed.
Signs and Symptoms of Appendix Cancer
More than half of the time, appendiceal cancer doesn’t show symptoms and is found by chance. However, for about 30% of patients who do show symptoms, it often resembles a condition called acute appendicitis. This has led to acute appendicitis being the most common way appendiceal adenocarcinoma (a type of cancer) is identified. Some things that can make doctors suspect this type of cancer include being over 50 years old with a family history of colon cancer or inflammatory bowel disease, has chronic appendicitis-like symptoms, or unexplained anemia.
Patients may experience symptoms like:
- General abdominal discomfort
- Pain in the lower right part of the belly
- Weight loss
- Lack of appetite
- Fever
- Vomiting
- Signs of a blockage in the intestines
- Fatigue
During a physical examination, doctors might come across things like tenderness in the lower right part of the belly, a feeling of stiffness when the belly is touched, a lump in the abdomen, a buildup of fluid in the abdomen (ascites), and signs of the disease having spread to other places. Patients with a group of tumors known as GEP-NETs who also have liver metastasis might show signs and symptoms related to a condition known as carcinoid syndrome.
Testing for Appendix Cancer
When it comes to initial evaluations, imaging studies are often the first step. An ultrasound might reveal long or round lesions in the right lower part of your belly that show an ‘onion skin’ appearance. This scenario typically indicates the presence of lamellated mucin, an abnormal secretion which is a clear sign of disease. If there’s any sign of a leak in the appendix wall, it might mean a ruptured mucinous tumor, which refers to a tumor that produces mucus.
People showing signs of sudden appendicitis may need either a CT scan or MRI. An enlarged appendix (more than 15 millimeters) that has thick or irregular walls can hint at the presence of a tumor. At times, a CT scan also reveals other signs indicative of Pseudomyxoma Peritonei (PMP), a rare condition characterized by an abnormal buildup of mucus in the abdomen. These signs could include a scalloped appearance, from cancerous deposits on the surfaces and cavities of the organs, and occasionally, there might be a visible ring-like calcification, which means hardened tissue.
If these signs indicate a spread of a mucus-based cancer to the peritoneum, the lining of your abdomen, a needle biopsy might be necessary for confirmation. Regular X-rays of the abdomen generally have little clinical value in these cases, but sometimes they might show a curved calcification in the pelvic area.
It’s worth noting that Carcinoembryonic antigen (CEA) levels can have some diagnostic and prognostic value; normal values of CEA typically indicate a better prognosis. Also, endoscopy may be needed if you are diagnosed with mucinous adenocarcinoma as there’s an increasing occurrence of related polyps and masses. After the tests, a closer look at your appendiceal sample will be needed to confirm the diagnosis.
Furthermore, a detailed examination of the nodes in your ileocolic basin, the potential hepatic metastasis is important when managing appendiceal cancers like GEP-NETs, otherwise known as carcinoid tumors. Patients with goblet cell carcinoma and appendiceal mucinous neoplasm should have their peritoneum evaluated and the findings of the peritoneal cancer index score should be properly documented.
While abdominal radiology readings might not always conclusively diagnose appendiceal cancer, suspicious signs of cancer include an irregular wall and thick soft tissue within a round, well-contained cystic mass in your right lower quadrant. In such cases, additional thorough evaluations may be needed to exclude the presence of abnormal fluid accumulation (ascites), involvement of the peritoneum, and the scalloping of the liver surface.
Treatment Options for Appendix Cancer
Surgery is the main treatment method for appendix cancer. However, in advanced cases where the cancer has spread far from the appendix, surgery might not be possible. Conducting an appendectomy, where surgeons remove the appendix and its surrounding area to check for involved lymph nodes, can both diagnose and treat many appendix tumors. This is because most appendix tumors are diagnosed after doctors examine a removed appendix under the microscope.
Other surgical methods, such as a right hemicolectomy (removing the right side of the colon), might be necessary if the cancer has spread to the lymph nodes, if a large neuroendocrine tumor (a type of tumor that starts in the hormone-producing cells of the body) with unclear edges is present, or if a tumor has spread more than 3mm into the tissue that anchors the appendix to the large intestines.
Two specialized surgical techniques can also be used for mucinous tumors (tumors that produce a thick substance like jelly) of the appendix – cytoreductive surgery (where as much tumor is removed as possible) and heated intraperitoneal chemotherapy (where heated anti-cancer drugs are injected into the abdominal cavity).
If surgery isn’t possible due to widespread appendix tumors, patients may benefit from the use of a chemotherapy regimen that includes a drug called 5-fluorouracil, as well as supportive care to help manage symptoms and improve quality of life.
What else can Appendix Cancer be?
An appendiceal mass is a medical condition that can often be confused with a range of other health issues. These may include:
- Acute appendicitis (sudden inflammation of the appendix)
- Cystic lymphangioma (a cyst that forms in the lymphatic system)
- Mesenteric cyst (a rare, fluid-filled sac in the abdomen)
- Retroperitoneal cyst (a cyst located behind the abdominal cavity)
- Ovarian cyst (a fluid-filled sac in the ovary)
- Ovarian cancer
- Meckel’s diverticulum (a bulge in the small intestine present at birth)
Because these illnesses can mimic the symptoms of an appendiceal mass, a precise diagnosis is essential to ensure appropriate treatment.
Surgical Treatment of Appendix Cancer
In the United States, only around 1.2 in every 100,000 people are diagnosed with appendiceal cancers each year. Interestingly, almost 30% of these people might have acute symptoms. The most common types of these cancers are gastroenteropancreatic neuroendocrine tumors (GEP-NETs), goblet cell carcinoma, colonic-type adenocarcinoma, and mucinous neoplasm.
GEP-NETs are the most common type and they don’t often spread to other parts of the body. But when they do, the liver and lymph nodes are usually affected. When doctors suspect GEP-NETs (also known as carcinoid tumors), they need to examine the liver and lymph nodes. Surgery can get rid of these tumors, and the type of surgery depends on the size. For example, if the tumor is smaller than 1 centimeter, only taking out the appendix is necessary. But if the tumor is larger than 2 centimeters, a more major surgery called a right hemicolectomy may be recommended.
Goblet cell carcinomas is another type of appendiceal cancer that have features of both appendiceal adenocarcinoma and neuroendocrine tumors. Again, thorough examination of the abdominal cavity is crucial. People with a non-spreading cancer that is 2 cm or larger could benefit from a right hemicolectomy. However, there isn’t a complete agreement in the medical community on the best treatment approach for other types of goblet cell carcinomas.
Non-Hodgkin lymphomas, and its specific type called mucosa-associated lymphoid tissue lymphomas could initially have symptoms of acute appendicitis. This type of appendiceal cancer is extremely rare. The surgery mainly involves only removal of the appendix. However, an extensive evaluation is necessary to rule out any possible spread.
Adenocarcinoma of the appendix is another type that often shows up as acute appendicitis. Its treatment typically involves a right hemicolectomy, regardless of the size of the tumor or if it has spread to the lymph nodes.
Appendiceal mucocele could be a benign or malignant condition that could result in acute appendicitis. Some features on imaging, such as a well-capsulated structure on the right lower side of the abdomen, may make doctors suspect this condition. However, a definite diagnosis requires a surgical examination and analysis of the tissue. The preferred treatment is removing the appendix carefully to prevent rupturing the capsule. If there’s a suspicion that it hasspread to the peritoneal covering of the abdominal cavity, a biopsy of the peritoneal tissue might be necessary. Moreover, cases of supposed mucinous neoplasm should be evaluated thoroughly through an abdominal examination. This is particularly important when there is presence of mucin. Deciding whether to use a laparoscopic approach for managing an appendiceal mucocele depends on the appearance of the cyst on imaging.
Pseudomyxoma Peritonei Syndrome can occur in patients with mucinous tumors originating from the appendix or other organs such as the stomach, ovaries, pancreas, and colon. In this syndrome, the tumor spreads to the peritoneal covering of the abdominal organs. The treatment can be either curative or palliative. Cytoreductive surgery along with chemotherapy given directly into the abdomen while it’s being warmed up (hyperthermic intraperitoneal chemotherapy) is the primary approach. This major surgery aims to remove both the peritoneal coverings of the organs and the abdominal wall and after that, chemotherapy is directly administered into the abdomen.
What to expect with Appendix Cancer
The likelihood of recovery from appendiceal cancer varies based on the type of cancer, the stage and grade of the disease, and whether the disease has begun to spread beyond the right lower quadrant of the abdomen. Some additional factors can affect the prognosis, such as the presence of cellular mucin, a type of mucus. Survival rates over five years can range dramatically, from 27% to 93%, depending on the type of tumor involved. For example, signet ring cell tumors have the worst prognosis, with a survival rate of just 27%. On the other hand, neuroendocrine tumors offer the best outlook, with a survival rate of 93%. However, the 10-year survival rate for a specific type of cancer called mucinous adenocarcinoma is less than 10%.
Additionally, the specific type of appendiceal cancer also predicts survival rates and overall prognosis. For instance, goblet cell carcinomas, which display characteristics of both adenocarcinomas and appendiceal neuroendocrine tumors, usually have a better prognosis compared to adenocarcinoma. That being said, their prognosis is not as promising when compared to appendiceal neuroendocrine tumors.
However, it’s important to note that the risk of early onset perforation, which is a rupture within a specific type of appendiceal cancer (including appendiceal adenocarcinoma), doesn’t necessarily mean the overall prognosis will be poorer. This shows that each case is unique and several factors come into play when predicting the outcome.
Possible Complications When Diagnosed with Appendix Cancer
Pseudomyxoma peritonei (PMP) is a condition where abnormal cells that produce a sticky substance accumulate in the lining of the abdomen, resulting in a buildup of this substance. This often presents as the initial symptom in many patients. PMP is classified based on its severity. The first type is disseminated peritoneal adenomucinosis (DPAM) which is linked with LAMN. It is characterized by fewer cell divisions and simple cells. The second type is a more severe type called peritoneal mucinous adenocarcinomatosis (PMAC) which is typically associated with a form of cancer known as mucinous adenocarcinoma.
Adhesions (abnormal bands of scar-like tissue) and intestinal obstruction can often occur when the disease has spread to other areas. It can also spread to the ovaries and to the area behind the abdomen. Additionally, it can lead to hydroureteronephrosis, an uncommon complication where the kidneys and the tubes that carry urine from the kidneys to the bladder become swollen.
Preventing Appendix Cancer
Tumors in the appendix often show symptoms similar to those of acute appendicitis and are usually identified after a detailed study of the appendix tissue removed during an appendectomy. It’s crucial to carefully review this tissue study from the appendectomy to make sure any appendix tumors aren’t overlooked.
