What Is Appendix Cancer?

Are you aware that cancers of the appendix are rare and many people with appendiceal cancer are diagnosed after the appendix is removed? Appendix cancer is often asymptomatic in the early stages and often symptoms appear when the disease is advanced¹.

Appendix cancer is a type of cancer that grows from the appendix cells.

A tumour is an abnormalgrowth of cells that can be either malignant (cancerous) or benign (non-cancerous).¹ The appendix is a small thin bag, connected to your large intestine. It is part of the gastrointestinal tract, which plays a role in absorbing nutrients and removing excess waste from the body.² 

Appendix cancer is rare and has an incidence rate of approximately 1.2 cases per 100,000 people per year in the United States.³ The risk factors of appendix cancer vary from one person to another.¹  It is difficult to detect appendix cancer as it shows no symptoms in its early stages.³

Overview

An appendix is a lingering empty duct that is closed at one end and is attached at the other end to the cecum. (A baglike structure located at the beginning of the large intestine that recieves undigested material from the small intestine). ⁴ However, it is not clear whether the appendix serves any useful purpose in humans.⁵

The appendix is usually 8 to 10 cm (3 to 4 inches) long and less than 1.3 cm (0.5 inches) wide. It has muscular walls that are capable of expelling any of the intestinal contents that have worked their way into the structure and into the cecum. A blockage at the opening of the appendix which prevents it from expelling its contents into the cecum may cause appendicitis (inflammation of the appendenix causing pain and discomfort).⁵

The appendix is a very small organ and surprisingly it gives rise to various morphologic tumour types. ³ The most common type of tumour or cancer that occurs in the appendix is the neuroendocrine or carcinoid tumour.⁶ It may also be called adenocarcinoma. 

Mucin is a jelly-like substance which protects the lining of the abdomen, intestines, and appendix. Most epithelial appendiceal cancers can result in a build-up of mucin, which can cause the appendix to rupture. 

 Below are the types of tumours that can develop in the appendix:

• Mucinous neoplasms: a rare and complex type of epithelial appendiceal cancer that grows from cells that make up the lining of the appendix.  Depending on microscopic images the cells can appear as either low grade (LAMN) or high grade (HAMN) and may spread to other parts of the body⁷
• Low-grade mucinous neoplasms of the appendix are non-cancerous tumours of the appendix. However, due to the delicate nature of the appendix wall, if the appendix ruptures, neoplastic cells (abormal cell growth) may migrate into the stomach. These tumors are formed by mucin-producing cells that line the inside of the appendix, leading to the accumulation of mucin in the abdominal cavity.Mucin build-up can cause abdominal pain, bowel obstructions and bloating⁷
• Adenocarcinomas is a type of cancer caused by gland-forming cells that line the inside of the appendix.⁷ Adenocarcinomas produce mucin producing cells  which  can result in the accumulation of mucin or PMP in the stomach, but may also grow to other body parts, such as the abdominal organs and the local lymph nodes.  Adenocarcinomas are usually categorised depending on their microscopic features starting from low, moderate  or high-grade tumors⁷
• Signet-ring cell are generally considered more hostile than other adenocarcinomas because they grow faster and spread to local lymph nodes thus harder to completely remove in surgery⁷
• Neuroendocrine (Carcinoid) tumours emanate from a group of cells lining the appendix known as neuroendocrine cells. They do not cause PMP since they do not make mucin. Carcinoid tumours are overly regarded as slow-growing and behave very differently from the adenocarcinomas of the appendix⁷
• Goblet Cell Adenocarcinoma is a hybrid tumour of both adenocarcinoma and neuroendocrine tumour. The behaviour of goblet cell adenocarcinoma tumours is closely linked to the behaviour of the adenocarcinoma portion of the tumour.⁷ Therapeutic recommendations are similarfor other types of appendiceal adenocarcinomas. Goblet Cell Adenocarcinoma is generally regarded as a more aggressive tumour type as compared to low-grade or moderately differentiated adenocarcinomas of the appendix. However, they are not as hostile as signet ring cells adenocarcinomas⁷

Causes of appendix cancer

The risk factors for appendix are different for everyone.¹ Many cancerous tumors in the appendix are usually found incidentally when doctors examine tissue samples taken during surgery for acute appendicitis.³ According to John Hopkins Medicine the risk factors for appendix cancer include: 

• Smoking: Smokers have a higher chance of suffering from appendix cancer than nonsmokers
• Family history of appendix cancer: A history of family appendix cancer or multiple endocrine neoplasia type 1 (MEN1) syndrome increases the risk of developing appendix cancer
• Certain health conditions: Medical history of certain medical conditions such as atrophic gastritis or pernicious anaemia can affect the stomach’s ability to produce acid⁹
• Age: Advanced age raises the risk for appendix cancer development⁹
• People assigned female at birth:  have a higher chance of developing appendix cancer as compared to people assigned men at birth⁹

Signs and symptoms of appendix cancer

Many people do not exhibit any symptoms in the early stages of appendiceal cancer. The symptoms are often present when the disease is advanced.³ Symptoms normally manifest when the tumour gets large.tThis includes:

• Pain in the stomach or pelvic area
• Bloating
• Ascites (fluid in the abdomen)
• Pain in stomach or pelvic area³
• Feeling bloated or growing abdominal size
• A mass in the abdomen
• Nausea and vomiting
• Feeling full soon after eating³

Management and treatment for appendix cancer

Treatment for appendiceal tumours and cancers varies depending on the stage (extent) of disease and the subtype. Surgical therapy is the mainstay of therapy for cancers of the appendix; however, advanced cases with distant metastasis may be surgically unresectable.¹⁰ This is due to the fact that the surgery might affect other healthy organs and tissues such as the intestine, colon, and peritoneum in the abdomen and pelvic area.³

However surgical procedures like right hemicolectomy are suggested when there is nodal involvement, a big neuroendocrine tumour whose margins are not clear, and bigger than 3 mm meso-appendiceal invasion.¹⁰

Heated intraperitoneal chemotherapy and cytoreductive surgery are extremely practical in mucinous tumours of the appendix. Surgically unresectable epithelial tumours of the appendix with distant metastasis may be treated with chemotherapy and palliative care.¹⁰ Palliative care is end-of-life care that's  given to individuals to improve their quality of life until death.¹¹

Chemotherapy is used to kill cancer cells if the appendiceal cancer has spread to other parts of the belly. Sometimes, a treatment called hyperthermic intraperitoneal chemotherapy which uses hot chemicals to wash the inside of the abdomen during surgery is used.³

FAQs

How is appendix cancer diagnosed?

Appendix cancer  is difficult to diagnose in its earliest stages due to it being asymptomatic. However, after taking medical history from the patient the doctor may send the patient for some tests, which may include:

Imaging: Your doctor will use scans such as CT and MRI to look at the appendix to confirm the presence of appendiceal cancer.³

Biopsy: A  doctortakes a small sample of your skin with a needle. Afterwards, a pathologist studies the cells from the specimen under the microscope to check if there are any abnormalities.³

Diagnostic Laparoscopy: An instrument is inserted in the abdomen to view the organs in the area. If there are signs of a tumour, doctors may biopsy the tissuewhich lines the organs in the abdomen to see if the cancerous cells have spread.

Lab Tests: If a biopsy confirms that you have appendiceal cancer, lab tests are done to check for protein levels as they determine the stage of your cancer. Knowing how advanced the cancer is, helps determine the treatment plan.³

How can I prevent appendix cancer?

One can lower chances of appendix cancer, as well as other types, with some key lifestyle choices such as avoiding tobacco use and alcohol, being physically active to avoid obesity, and maintaining a certain type of diet to prevent diabetes.¹¹

What are the stages of appendix cancer?

Staging indicates the location of the cancer, where it has spread, and determines if it is affecting other body organs.¹² The following are stages of appendix cancer are:

Stage 0: This means that cancer is confined in only 1 place and has not spread.

Stage I: Cancerous cells have spread to the inner layers of appendix tissue but have not spread to the lymph nodes. 

Stage IIA: The cancer has spread into the connective or fatty tissue near the appendix but has not spread to the lymph nodesor to other parts of the body. 

Stage IIB: The cancerous cells have spread through the inner layers of the appendix but have not spread to the regional lymph nodes or body organs.

Stage IIC: The tumour cells have grown into other body organs, such as the colon or rectum, but have not spread to the lymph nodesor other body organs.

Stage IIIA: The cancerous cells have spread to the lining of appendix tissue and to 1 to 3 l lymph nodesbut have not spread to other body parts. 

Stage IIIB: The cancer has spreadto nearby tissue of the appendix or through the inner layers of the appendix and to 1 to 3  lymph nodesbut has not spread  to other body areas. 

Stage IIIC: The cancer has spread to 4 or more lymph nodesbut hasn't spread to other body areas.

Stage IVA: The cancer has grown to other areas in the stomach but not to the regional lymph nodes l.

Stage IVB: The cancerous cells are moderately or poorly differentiated however they have grown to other parts of the stomach and may be in the lymph nodes. 

Stage IVC: The cancer has grown outside the stomach to distant parts of the body like the lungs.

Recurrent: Both neuroendocrine tumours and carcinomas can recur and other rounds of tests have to be conducted to understand the degree of the recurrence.¹²

Who is at risk of appendiceal cancer?

Advanced age is a risk factor for appendix cancer, the average age of onset is between 50 and 55 years old. Smoking also increases the risk of developing appendix cancer compared to non-smokers. Moreover, patients who have a family history of appendix cancer or multiple endocrine neoplasia type 1 (MEN1) syndrome are at greater risk of getting appendix cancer.² Medical history such as a history of certain medical conditions such as atrophic gastritis or pernicious anaemia, which affect the stomach’s ability to produce acid.⁹ It is also believed that women are more likely to develop appendix cancer than men.⁹

How common is appendix cancer?

Appendiceal cancers are extremely scarce with an estimated incidence of 0.15-0.9 per 100,000 people.⁶ In the US, it has been thought to affect about 1 or 2 people per 1 million per year. However, recent studies show that appendiceal cancer is becoming more common, especially in the older population starting from 50  years old, but can happen at any age.²

When should I see a doctor?

One should see a doctor if showing signs or symptoms that suggest appendix cancer. These include pain in the stomach or pelvic area, bloating, ascites, feeling bloated or growing abdominal size, a mass in the abdomen, nausea and vomiting and feeling full soon after starting to eat.² The doctor will physically examine and take a medical history. Thereafter the doctor may send you for some tests.

Summary

Primary cancers of the appendix vary histologically. Cancers and tumours (neoplasms) of the appendix are sparsely distributed with an estimated incidence of 0.15-0.9 per 100,000 people.⁶ The average age of onset is between 50 and 55 years, and people assigned female at birth are more likely to be affected as compared to people assigned male at birth and the reasons for this are unknown. Appendix cancers usually present either as a hernia filled with mucin, appendicitis, bigger abdominal width, abdominal discomfort, an abdominal mass, during imaging or at the time of surgery.⁶ Treatment for appendiceal tumours and cancers varies depending on the stage (extent) of the disease and the subtypes and it includes surgery, chemotherapy and palliative care.¹⁰