Appendix Tumours and Cancers

Appendix cancer is rare and symptoms often appear late. It is frequently discovered unexpectedly after an appendectomy. Unlike colorectal cancer, appendix tumours can be several different types, and their behaviour and treatment can be very different.

If your appendix pathology report shows neuroendocrine, LAMN, HAMN, goblet cell adenocarcinoma or adenocarcinoma, the next step depends on the exact tumour type, grade, margin status, stage and whether the disease has spread beyond the appendix.

The appendix is a small tube attached to the beginning of the large intestine. Tumours arising from the appendix include neuroendocrine tumours and cancers, low-grade appendiceal mucinous neoplasms (LAMN), high-grade appendiceal mucinous neoplasms (HAMN), goblet cell adenocarcinoma and appendiceal adenocarcinoma.

LAMNs are low-grade, mucus-producing tumours usually confined to the appendix. If they leak, they can cause pseudomyxoma peritonei. HAMNs also produce mucus but have higher-grade features. Mucinous, non-mucinous and goblet cell adenocarcinomas are invasive cancers. Neuroendocrine tumours are often small and slow-growing, but larger or higher-grade tumours may behave more aggressively.

The tumour type, grade, pathological features and extent of disease determine the appropriate treatment.

What Is a Mucocele of the Appendix?

A mucocele of the appendix is an appendix enlarged by a buildup of mucus. It can result from blockage, benign changes or mucinous tumours. Because a mucinous tumour can rupture and spread through the abdomen, suspected mucoceles require careful assessment and surgical planning.

Many appendiceal tumours cause no specific symptoms and are discovered unexpectedly after surgery for suspected appendicitis.

When symptoms occur, they may include persistent or recurrent abdominal pain, abdominal bloating or increasing abdominal swelling, changes in bowel habits, loss of appetite or early satiety, unexplained weight loss, and a feeling of abdominal fullness or, occasionally, an abdominal mass.

These symptoms are common and usually have causes other than cancer. Persistent or progressive symptoms, however, should be evaluated.

After an appendectomy, an unexpected tumour may be found in the pathology specimen. The pathology report should be reviewed by a specialist team. Further treatment or surveillance depends on the tumour type and grade, whether it has invaded the appendix wall or nearby tissues, whether the appendix has ruptured, whether lymph nodes are involved, whether the surgical margins are clear, and whether any tumour remains or there is disease in the peritoneum. In other cases, the diagnosis is made after a person develops symptoms and undergoes appropriate investigations.

Staging assesses whether the tumour is confined to the appendix, has spread to nearby lymph nodes, or has involved the peritoneum or other organs. It may include the following tests:

• CT is usually the first imaging test. MRI can be particularly useful for assessing mucinous and peritoneal disease. PET-CT has a more selective role, particularly in higher-grade disease.
• Tumour markers, including CEA, CA 19-9 and CA-125, to support assessment but not diagnose cancer alone.
• Biopsy when peritoneal disease is suspected or identified, to confirm the tumour type and grade.
• Colonoscopy may be recommended after an appendiceal adenocarcinoma or goblet cell adenocarcinoma diagnosis to check for additional abnormalities.
• Diagnostic laparoscopy may be recommended when staging information is unclear or other diagnostic tests are inconclusive. This allows the surgeon to examine the abdominal cavity directly and assess for peritoneal disease.

Yes. Some appendiceal tumours, particularly mucinous tumours, can spread within the abdominal cavity.

When mucin-producing tumour cells spread across the lining of the abdomen and mucus builds up inside the abdomen, this is called pseudomyxoma peritonei (PMP). It may cause increasing abdominal swelling, discomfort, reduced appetite and bowel symptoms.

Importantly, PMP is not always advanced or incurable cancer. Its outlook depends mainly on the type and grade of the original tumour, and how much disease is present and where it has spread.

Treatment depends on the tumour type, grade, stage, margins and spread. It should be planned by a specialist multidisciplinary team.

For a LAMN confined to the appendix and removed intact, appendectomy is usually sufficient. HAMN requires more careful assessment because its behaviour can be more aggressive. Further treatment or surveillance depends on perforation, extra-appendiceal mucin or tumour cells and other pathological risk factors.

For appendiceal adenocarcinoma, goblet cell adenocarcinoma and neuroendocrine cancers, a right hemicolectomy with lymph-node removal is generally recommended.

For pseudomyxoma peritonei, selected patients may undergo cytoreductive surgery (CRS) to remove all visible disease, combined with hyperthermic intraperitoneal chemotherapy (HIPEC), which circulates heated chemotherapy through the abdomen. Suitability depends on the tumour type, extent of disease, likelihood of complete removal and overall health.

For appendiceal adenocarcinoma and goblet cell adenocarcinoma that are advanced or have spread to the lymph nodes or other organs, systemic treatment is used. The exact treatment depends on the tumour type, grade, molecular features, previous treatment and overall health. Chemotherapy may be used before surgery to shrink the tumour or control the disease, or after surgery to reduce the risk of recurrence. In some cases, chemotherapy is used as the main treatment when surgery is not possible or when the cancer has spread extensively.

Molecular testing may be recommended, particularly in advanced disease, to identify mismatch-repair deficiency, microsatellite instability or other potentially actionable changes. Treatment usually involves standard chemotherapy, with targeted treatment added when appropriate based on the molecular test results. Tumours with mismatch-repair deficiency or high microsatellite instability may be treated with immunotherapy.

Because these are uncommon tumours and decision-making is complex, treatment should be planned at a specialist centre experienced in appendiceal and peritoneal surface malignancies.

Some appendiceal tumours, particularly low-grade tumours that are completely removed, have an excellent long-term outlook.

Other tumours, especially high-grade disease or disease with extensive peritoneal involvement, can be more challenging.

Prognosis depends on the tumour type, grade, stage, peritoneal involvement and completeness of treatment rather than simply on the diagnosis of "appendix cancer."

The pathway varies depending on how the tumour is discovered and what the pathology shows.

1. Discovery

Appendicitis, an incidental scan finding, abdominal swelling, or occasionally a pelvic/ovarian mass.

2. Pathology

The appendix or biopsy is examined to determine the exact tumour type and grade.

3. Staging

CT or MRI, tumour markers and, when appropriate, PET-CT, colonoscopy or diagnostic laparoscopy are used to assess the extent of disease.

4. Specialist review

A multidisciplinary team reviews the pathology and scans and determines whether further treatment is needed.

5. Treatment

Depending on the diagnosis: appendectomy, right hemicolectomy, CRS-HIPEC, systemic therapy, surveillance, or a combination.

6. Follow-up

Surveillance with imaging, tumour markers and clinical review is tailored to the tumour type and risk of recurrence.

Key Message

Appendix cancer is not a single disease. The pathology determines the biology, and the biology determines the treatment. An incidental diagnosis after appendectomy does not automatically mean that major surgery or HIPEC is required. Conversely, patients with peritoneal disease may benefit from assessment at a specialised centre where CRS and HIPEC can be considered when appropriate.