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Last updated: 12/2/2024
Years published: 2018, 2024
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders, Laura A. Lambert, MD, FACS, Huntsman Cancer Institute, University of Utah, and the Appendix Cancer/Pseudomyxoma Peritonei Research Foundation, for the preparation of this report.
Summary
Appendiceal cancer is a very rare type of cancer originating from the cells of the appendix, a small pouch attached to the large intestine in the abdomen. While the appendixโs exact role is unclear, it may contribute to the immune system.
Appendiceal cancer spread often occurs within the abdomen, especially if the appendix ruptures. It may also spread via lymph nodes to areas located outside the abdomen.
The average age of onset is between 50โ55 years, affecting males and females equally.
Symptoms often mimic appendicitis and can include hernias containing mucin, increased abdominal girth, pelvic/abdominal masses and abdominal discomfort. It is sometimes found during imaging or unrelated surgeries. In females it frequently spreads to ovaries, sometimes mistaken for ovarian cancer.
Diagnosis requires examination of tumor specimens to confirm cancer type and grade.
This cancer is categorized into two main types: epithelial appendiceal cancer and neuroendocrine appendiceal cancer. Treatment varies based on cancer type and stage and on the subtype classification, as epithelial and neuroendocrine tumors are treated differently due to their unique biology.
Complications of appendiceal cancer spread can include a build-up of mucin in the abdomen (pseudomyxoma peritonei) and peritoneal carcinomatosis, caused by widespread cancer cell growth in the abdominal cavity.
Introduction
The most common type of tumor or cancer that occurs in the appendix is a neuroendocrine or carcinoid tumor. Neuroendocrine tumors (NETs) are derived from specialized cells that reside in the wall of the appendix or another part of the intestine called enterochromaffin (EC) cells. EC cells make chemicals that help facilitate gastrointestinal motility and digestion. NETs (or carcinoid cancers) of the appendix have a unique tumor biology and are treated differently than epithelial tumors or cancers of the appendix which arise from gland-forming cells lining the inside of the appendix. One of the functions of epithelial cells is to make mucin โ a jelly-like substance that helps protect the lining of the intestine.
Epithelial tumors and cancers of the appendix are further categorized based upon how the cells look under the microscope and whether they are invading the wall of the appendix. The main categories include goblet cell carcinoid, low-grade mucinous neoplasm of the appendix (LAMN), high-grade mucinous neoplasm of the appendix (HAMN) and adenocarcinomas. The adenocarcinomas are further classified as well differentiated, moderately differentiated, poorly differentiated and signet ring cell (SRC). These classifications are important for determining prognosis and treatment recommendations.
At the time of diagnosis, appendiceal cancer can be either localized to the appendix or may have spread to other parts of the body โ particularly the abdominal cavity or peritoneum.
Due to the very thin wall of the appendix, finding appendiceal cancer that has already spread at the time of diagnosis is more common than finding it confined to the appendix.
Due to the structure of the appendix (a long, thin-walled, finger-like projection off the right colon), it is easy for tumor or cancer cells to break through the wall and spread in the abdominal cavity.
Consequently, most appendiceal cancers, even the less aggressive ones, tend to present at an advanced stage with peritoneal carcinomatosis.
Once the cancer cells have spread, they continue to grow and may cause abdominal discomfort, distention, a fluid build-up called ascites or pseudomyoma peritonei (mucinous ascites) and intestinal blockage or dysfunction.
Over time this can lead to the following symptoms:
Appendiceal cancer rarely spreads outside the abdominal cavity, and it is most commonly seen in poorly differentiated or signet ring cell (SRC) cancers. However, once the cancer cells escape from the appendix, they can continue to grow in the abdominal cavity, on the surface of other organs such as the omentum, intestines, ovaries, uterus, liver, spleen and peritoneum (lining of the abdominal cavity). This condition is called peritoneal carcinomatosis (see Related Disorders) โ which means growth of cancer cells within the abdominal cavity. Over time, without treatment, this condition can result in blockage of the intestines or loss of intestinal function.
The exact cause of appendiceal cancer is unknown. There are no genetic, familial or environmental factors known to cause this disorder. It does not run in families. One study has shown a correlation with the presence of the intestinal bacterium Helicobacter pylori and pseudomyoma peritonei from appendiceal neoplasms. This has prompted a clinical trial using antibiotic therapy to eradicate the bacteria. This study is still on-going at the time of this report. Recent studies have shown that appendiceal cancers do have a unique genomic profile distinct from adenocarcinomas of the colon which may offer future, appendix-specific and targetable pathways for treatment.
Appendiceal cancer is very rare with approximately 1-2 cases per 1 million individuals. Appendiceal cancers can occur at any age, with the peak occurrence in the 6th decade (average age of 50 at diagnosis). Most studies report that males and females are affected in equal numbers, while a few have suggested a slightly increased frequency in females.
There are no unique features of appendiceal cancer in imaging studies such as ultrasound, CT scan, PET scan or MRI, so the diagnosis of appendiceal cancer cannot be made until a tumor specimen is examined by a pathologist. This is frequently accomplished at the time of appendectomy for appendicitis, surgery for an intestinal blockage or presumed ovarian cancer, or through a diagnostic tumor biopsy performed for an abnormal clinical or radiographic finding such as a palpable tumor or tumors seen on an imaging study. The finding of a dilated, mucin filled appendix on CT scan or MRI should prompt concern for an appendiceal tumor and an appendectomy should be considered. The different types of appendiceal tumors and cancers can be distinguished by the appearance of the cells under the microscope and by staining them for specific markers. Goblet cell carcinoid tumors tend to be easier to identify because of the unique combination of neuroendocrine and epithelial cells.
Once a diagnosis is confirmed, a staging work-up is essential to guide treatment. This involves:
Treatment for localized tumors
Treatment for tumors that have spread in the abdominal cavity
For tumors that have spread within the abdomen, the recommended approach is:
Moderate- or high-grade tumors (poorly differentiated, or signet ring cell cancers):
Advanced disease
For cancers that have spread to lymph nodes or outside the abdominal cavity:
After treatment, close monitoring is crucial to detect recurrence:
For people with a higher risk of recurrence, extended follow-up may be necessary.
Right hemicolectomy is recommended for moderately- or poorly differentiated adenocarcinomas and signet ring cell cancers to ensure full tumor removal and assess lymph node involvement. Debate exists about its utility in well-differentiated cancers, as the risk of lymph node spreading is under 5%.
CRS+HIPEC and other advanced treatments should be performed at specialized centers experienced in these procedures.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the National Institutes of Health (NIH) in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
Information about current clinical trials is posted on this page on the ACPMP Research Foundation website:
https://acpmp.org/clinical-trials
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Carr NJ, Cecil TD, Mohamed F, et al. A Consensus for Classification and Pathologic Reporting of Pseudomyxoma Peritonei and Associated Appendiceal Neoplasia: The Results of the Peritoneal Surface Oncology Group International (PSOGI) Modified Delphi Process. Am J Surg Pathol. 2016 Jan;40(1):14-26.
Marmor S, Portschy PR, Tuttle TM, Virnig BA. The rise in appendiceal cancer incidence: 2000โ2009. J. Gastrointest. Surg. 2015; 19; 743โ750.
Davison JM, Choudry HA, Pingpank JF et al. Clinicopathologic and molecular analysis of disseminated appendiceal mucinous neoplasms: identification of factors predicting survival and proposed criteria for a three-tiered assessment of tumor grade. Mod. Pathol. 2014; 27; 1521โ1539.
Semino-Mora C, Testerman TL, Liu H et al, Antibiotic treatment decreases microbial burden associated with pseudomyxoma peritonei and affects ฮฒ-catenin distribution. Clin Cancer Res. 2013 Jul 15;19(14):3966-76.
van den Heuvel MG, Lemmens VE, Verhoeven RH, de Hingh ICH. The incidence of mucinous appendiceal malignancies: a population-based study. Int. J. Colorectal Dis. 2013; 28; 1307โ 1310.
Chua TC, Moran BJ, Sugarbaker PH et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. J. Clin. Oncol. 2012; 30; 2449โ2456.
Levine EA, Blazer DG, Kim MK et al. Gene expression profiling of peritoneal metastases from appendiceal and colon cancer demonstrates unique biological signatures and predicts patient outcomes. J. Am. Coll. Surg. 2012; 214; 599โ606.
INTERNET
Appendiceal Cancer. National Cancer Institute. https://www.cancer.gov/pediatric-adult-rare-tumor/rare-tumors/rare-digestive-system-tumors/appendiceal-cancer Accessed Dec 2, 2024.
What is the treatment for Appendix Cancer and PMP? ACPMP Research Foundation. https://acpmp.org/about-appendix-cancer/ Accessed Dec 2, 2024.
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