Appendiceal tumours and pseudomyxoma peritonei

• Tumours of the appendix are uncommon, forming about 0.5% of all gastrointestinal neoplasms and being detected in 0.9 to 1.7% of appendicectomy specimens, usually by accident after operations for appendicitis. ^[4]
• The main families are neuroendocrine neoplasms (a quarter to about two-thirds of primary malignant appendiceal tumours), low-grade and high-grade mucinous neoplasms (LAMN and HAMN), conventional adenocarcinoma (non-mucinous or mucinous) and goblet cell adenocarcinoma. ^[1][4]
• An appendiceal neuroendocrine tumour under 2 cm without risk features rarely needs more than appendicectomy, but one over 2 cm, or a smaller lesion with risk features at the base of the appendix, is managed with oncological right hemicolectomy. ^[1][4]
• Pseudomyxoma peritonei (PMP) is treated in specialist centres with cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC), with the best results when cytoreduction is complete (CC-0 or CC-1) and the disease is low grade. ^[2][6]
• There is no population screening. Every appendicectomy specimen must be examined histologically, and mucinous lesions need carefully documented follow-up and multidisciplinary review. ^[3][4]

By the end of this page you should be able to:

1. Classify appendiceal neoplasms using the 2019 WHO framework and explain why a mucinous neoplasm can be dangerous.
2. Describe how appendiceal neuroendocrine tumours present and choose management from size, grade and risk features.
3. State the criteria that move a patient from appendicectomy to right hemicolectomy.
4. Explain the diagnosis, pathological classification and staging of pseudomyxoma peritonei.
5. Outline cytoreductive surgery and HIPEC, including operability and the disputed regimens.
6. Counsel on prognosis and follow-up for the main tumour families.

A neoplasm of the appendix is any primary tumour arising in the vermiform appendix. Most are epithelial or neuroendocrine, found incidentally at microscopy after an appendicectomy. The current framework is the World Health Organization classification, 5th edition, 2019, harmonised with the Peritoneal Surface Oncology Group International (PSOGI) consensus of 2016 and the 8th edition of the American Joint Committee on Cancer (AJCC) staging system. ^[3][4]

The main families are:

• Sessile serrated lesions and adenomas - rare mucosal lesions with a serrated architecture; their importance is the association with colorectal neoplasia, hence colonoscopy after they are found. ^[3][4]
• Mucinous neoplasms - low-grade (LAMN) or high-grade (HAMN). They form mucinous epithelium that pushes rather than invades the wall. They are tumours of uncertain malignant potential and are staged by grade and by how far the mucin has spread. LAMN carries ICD-O behaviour code 8480/1 and HAMN 8480/2. ^[3][4]
• Adenocarcinoma - an invasive glandular tumour, non-mucinous or mucinous (mucinous when over half the tumour surface is extracellular mucin; signet-ring when over half of the cells are signet cells), including undifferentiated variants. ^[4]
• Goblet cell adenocarcinoma - an amphicrine tumour mixing goblet-type mucinous cells with endocrine and Paneth-like cells; formerly called goblet cell carcinoid. It behaves like adenocarcinoma, not like a neuroendocrine tumour, and is graded by the proportion of its high-grade component. ^[4][5]
• Neuroendocrine neoplasms - neuroendocrine tumours (NET) in grades 1 to 3, poorly differentiated neuroendocrine carcinomas (NEC) and mixed neuroendocrine - non-neuroendocrine neoplasms (MiNEN, in which both components must account for at least 30% of the tumour). ^[1][4]

Older terms such as mucocele, mucinous cystadenoma and mucinous cystadenocarcinoma are no longer recommended, because they blurred the line between indolent mucin-producing lesions and disseminated disease. ^[3]

Appendiceal neoplasms are rare overall: about 0.5% of all gastrointestinal neoplasms and detectable in 0.9 to 1.7% of appendicectomies. ^[4] LAMN alone is diagnosed in only 0.13% of appendicectomies, so under-diagnosis is likely. ^[4] Neuroendocrine tumours of all sites occur at about 0.2 to 0.3 per 100,000 person-years. ^{[4] [1]}

Appendiceal cancer in general has an incidence of about 1 to 2 per 1,000,000. ^[6] Incidence rose by roughly 54% between 2000 and 2009, with mucinous adenocarcinoma now the commonest subtype. ^[3]

Neuroendocrine neoplasms are the commonest malignant appendiceal neoplasm, making up 25 to 60% of primary malignant appendiceal tumours. ^[1] They are found in 0.16 to 2.3% of appendicectomies done for acute appendicitis, usually present at age 20 to 50 (most often in the 40s, younger than other gastroenteropancreatic neuroendocrine neoplasms) and are more common in women, partly because incidental appendicectomy is commoner in women undergoing pelvic surgery. ^[1]

Pseudomyxoma peritonei is the clinical syndrome of extensive mucinous peritoneal disease, mostly of appendiceal origin. Its incidence is roughly 1 to 4 per 1,000,000 people (about 2 to 4 in some series, 1 to 2 in others) and it develops in about 20% of patients with mucinous appendiceal neoplasms. ^[2][3]

Most appendiceal tumours are sporadic and the cause is unknown. ^[1][4]

• Age and sex. Most appendiceal neuroendocrine tumours present in the second to fifth decades; goblet cell adenocarcinoma peaks in the sixth decade; LAMN and HAMN are most often found from the fifth to seventh decades, with a female excess. ^[1][3][4][5]
• No established modifiable risk factor. No lifestyle or environmental factor is specifically linked to appendiceal tumour, and family history is not a major factor. ^[4]
• Serrated lesions. These lesions share KRAS changes with mucinous neoplasms but are largely BRAF-negative, and their biology appears distinct. After an incidental appendiceal serrated lesion is found, some reports describe a several-fold higher yield of advanced colorectal neoplasia and recommend complete colonoscopy. ^[3]
• Cancer syndromes. MEN1, von Hippel-Lindau disease, neurofibromatosis type 1 and tuberous sclerosis predispose mainly to pancreatic and duodenal neuroendocrine tumours and only occasionally to appendiceal ones; a young patient with multiple tumours should prompt syndromic screening. ^[1]

Appendiceal neuroendocrine tumours arise from mucosal neuroendocrine cells, usually at the (distal) tip; only about 10% are at the base, where they can obstruct and cause appendicitis. ^[1] Most are EC-cell (enterochromaffin) serotonin-secreting tumours; a smaller L-cell group produces glucagon-like peptide, pancreatic polypeptide and peptide YY. ^[1] Base-of-appendix and larger tumours are more likely to cause obstruction and nodal or distant spread. ^[1]

They are graded by mitotic count and Ki-67 labelling index into grades 1 to 3; poorly differentiated NEC and MiNEN are aggressive and usually present with metastasis. ^[1][4]

Size strongly predicts spread. Nodal metastases occur in up to 33% of 2 cm lesions and 64% versus 31% of lesions over 2 cm versus 1.1 to 2 cm; distant metastasis occurred in about 12% in one SEER analysis. ^[1] The 5-year survival rate falls from 89.9% for lesions of 2 cm or less, to 70.6% for 2 to 4 cm, to 58.2% for lesions over 4 cm. ^[1]

Low-grade and high-grade appendiceal mucinous neoplasms replace the mucosa with mucinous epithelium, distend and thin the wall, and can leak through it. Growth is pushing rather than infiltrative, which is why they are tumours of uncertain malignant potential that usually become dangerous when the wall is breached. ^[3][4]

Molecular studies show that about 90% of LAMN carry KRAS mutations, about 70% carry GNAS mutations, and TP53 mutations are usually absent, matching the indolent behaviour. ^[3] HAMN has high-grade cytology, higher proliferation and abnormal p53 expression, and is more likely to progress. ^[3]

When the wall ruptures, two outcomes follow. Acellular mucin alone has a much more favourable course, with very high progression-free survival after complete cytoreduction. Cellular mucin, containing viable tumour epithelium, seeds the peritoneum and becomes pseudomyxoma peritonei. ^[3][4] For LAMN confined to the appendix, appendicectomy alone is curative, with reported disease-specific survival close to 100%. ^[3]

Pseudomyxoma peritonei is not a single cancer but a syndrome: copious mucin accumulates in the abdomen through repeated transcoelomic seeding from a mucin-producing appendiceal neoplasm, progressing slowly but relentlessly to obstruction, malnutrition and cachexia if untreated. ^[2][3] Mucin collects mainly in the greater omentum and under the right hemidiaphragm, producing scalloping of the liver edge, an omental cake and central displacement of bowel loops. ^[2]

Histology is the key. The 2016 PSOGI consensus splits peritoneal mucinous disease into acellular mucin, low-grade mucinous carcinoma peritonei (LMCP, previously known as disseminated peritoneal adenomucinosis), high-grade mucinous carcinoma peritonei (HMCP, previously called peritoneal mucinous carcinomatosis) and high-grade disease with signet-ring cells (HMCP-S). ^[2] The AJCC 8th edition (2017) uses M1a for acellular peritoneal mucin and M1b, grades 1 to 3, for cellular mucin; the 2019 WHO classification is similar. ^{[2] [3]}

Non-mucinous and mucinous adenocarcinomas of the appendix behave like colorectal cancers: they invade, spread to lymph nodes and, in signet-ring variants, are aggressive. ^[4][5][6] Goblet cell adenocarcinoma looks like a mixed neuroendocrine and adenocarcinoma but behaves as an adenocarcinoma. Reported five-year disease-specific survival is 58 to 81%, against over 90% for appendiceal neuroendocrine neoplasms. ^[5]

Most are completely asymptomatic and are found in specimens removed for appendicitis. ^[1][4] Only tumours at the base are likely to obstruct and cause appendicitis. ^[1] Carcinoid features such as flushing, diarrhoea, wheezing and right-sided heart fibrosis are uncommon at presentation and usually point to liver metastasis. ^[1] High-grade NEC and MiNEN present with metastatic disease: pain, nausea, fatigue, anorexia, weight loss, abnormal liver enzymes or bowel obstruction. ^[1]

These are often silent and noticed as a mucin-filled distended appendix (mucocele) on imaging, as right lower quadrant discomfort, or as acute appendicitis. Large lesions can cause obstruction. ^[3][4] Rupture produces pseudomyxoma peritonei.

PMP evolves slowly. The typical patient has insidious abdominal distension ("jelly belly"), vague abdominal pain, a change in bowel habit, or an umbilical or inguinal hernia that contains mucin. ^[2][3] On examination there may be ascites of a dough-like consistency, a firm upper abdominal feel from subcapsular mucin, or a palpable mass. CT typically shows an enlarged cystic appendix, diffuse mucinous ascites that may be septated, omental thickening, scalloping of the liver and central displacement of bowel. ^[2][4]

These present with appendicitis or a right lower quadrant mass; advanced disease causes obstruction, perforation or peritoneal spread. Goblet cell adenocarcinoma accounts for about 10 to 23% of primary appendiceal neoplasms and affects both sexes equally, with a mean age in the sixth decade. ^[4][5]

Two questions need to be separated: which tumour is present when a patient has appendicitis or a mass, and what else could mimic a mass on imaging or a peritoneal collection at surgery.

The LAMN versus serrated-lesion distinction deserves care, because over-calling LAMN leads to over-treatment. The lamina propria and muscularis mucosae are lost in LAMN but preserved in serrated lesions; mural mucin, fibrosis and a pushing pattern favour LAMN. ^[3]

Most patients are diagnosed incidentally after appendicectomy; investigations then split into three strands: accurate pathology of the appendix, biochemical follow-up and staging.

Pathology. The whole appendix should be submitted for histology, including margin and mesoappendix size. The report must state the WHO 2019 family, grade (mitoses and Ki-67), margin status (R0/R1), lymphovascular and perineural invasion, mesoappendiceal invasion depth and mucin cellularity beyond the wall, because these drive every subsequent decision. ^[1][3][4]

Biomarkers. Chromogranin A is used for neuroendocrine surveillance, but is non-specific: it can be raised by proton pump inhibitors, renal or hepatic impairment and uncontrolled hypertension. A 24-hour urinary or plasma 5-hydroxyindoleacetic acid (5-HIAA) supports serotonin-producing disease, particularly with liver metastasis. For mucinous tumours, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and CA 125 reflect tumour burden and are measured every 6 months in follow-up. ^[1][2][4]

Imaging. For neuroendocrine tumours larger than 2 cm, or where resection was incomplete with positive nodes or margins, a contrast-enhanced triple-phase CT or MRI of chest, abdomen and pelvis is recommended. ^[1] For mucinous neoplasms and suspected PMP, CT (often with 3D reconstruction) is the workhorse: cystic appendiceal dilation with wall calcification, mucinous ascites, septations, omental cake, scalloping and bowel displacement. MRI helps with small-volume disease and liver deposits; laparoscopy may be needed when imaging cannot define extent. ^{[2][4] [3]}

For well-differentiated neuroendocrine tumours, somatostatin receptor imaging (68Ga- or 64Cu-labelled DOTA-analogue PET-CT) is the gold standard for metastatic staging and receptor assessment; it is not routine after complete resection of small localised disease. Poorly differentiated NEC and high-grade tumours are staged with 18F-FDG PET plus CT or MRI, because they usually lack somatostatin receptor expression. ^[1][4]

Colonoscopy. Mucinous appendiceal tumours and epithelial disease should prompt a complete colonoscopy to exclude synchronous colorectal cancer; this is built into the PSOGI preoperative evaluation. ^[2][4]

Diagnosis is ultimately histological. Several frameworks are in use:

• WHO 2019 / PSOGI 2016 / AJCC 8th edition for mucinous lesions and adenocarcinoma. ^[3][4]
• UICC / TNM / ENETS for neuroendocrine neoplasms. ^[4] For LAMN, tumour categories pT1 and pT2 are not assigned, because expansion into the muscle layer is regarded as herniation; pTis means tumour limited to the appendix with acellular mucin or mucinous epithelium extending into muscle; pT4 indicates perforation or spread beyond the serosa, including mucinous spread into the right lower quadrant. ^[4]
• Mucinous PMP staging (AJCC 8th edition) uses M1a for acellular peritoneal mucin and M1b (grades 1 to 3) for cellular mucin. ^[2]
• Neuroendocrine staging uses size and depth of mesoappendiceal invasion; in the Köhler summary, T1a is 1 cm or less, T1b 1 to 2 cm, T2 2 to 4 cm and T3 over 4 cm, with over 3 mm of mesoappendiceal invasion counting as T3. ^[4]

PMP operative staging uses two tools: the peritoneal cancer index (PCI), scoring 13 intra-abdominal regions from 0 to 3 by largest implant size (total score 0 to 39), and the completeness of cytoreduction (CC) score after surgery (CC-0 no visible residue, CC-1 under 2.5 mm, CC-2 2.5 mm to 2.5 cm, CC-3 over 2.5 cm or unresected disease). ^[2]

Many patients present as appendicitis; the appendix is removed and the diagnosis follows. If histology then shows a tumour, re-operation or staging proceeds once local inflammation settles. ^[4] Perforated or obstructed tumours, or those with peritonitis, need emergency exploration. ^[4]

Handling matters: any appendix that is unusually dilated, firm or cystic at operation, or that ruptures with mucin, should be removed carefully, because spilled mucin worsens outcome. ^[3][4] If PMP is obvious, biopsy and close the abdomen, then refer to a peritoneal surface malignancy unit for planned CRS rather than incomplete debulking, which can make later surgery harder. ^[2][6]

Appendicectomy alone is sufficient in all guidelines when the tumour is under 1 cm, and in the absence of risk factors when it is 1 to 2 cm. ^[1][4] Recognised risk factors for nodal spread are tumour over 2 cm, mesoappendiceal invasion over 3 mm, angioinvasion, incomplete (R1) resection and Ki-67 over 2%. ^[4]

A comparison of how the major neuroendocrine guidelines treat localised disease (from Mohamed et al.) is:

This table names the North American and European societies (NANETS, ENETS, UK NETS) and NCCN. The ESMO gastroenteropancreatic neuroendocrine guideline (Pavel et al., 2020) and a 2023 ENETS guidance paper dedicated to appendiceal neuroendocrine tumours (Kaltsas et al., 2023) belong to the same consensus landscape; both agree that small, completely resected lesions need no further surgery and that radical resection is reserved for larger or high-risk lesions. ^[1]

High-risk features for these positions are mesoappendiceal invasion over 3 mm, lymphovascular or perineural invasion and grade 2 differentiation. Right hemicolectomy also requires full colonoscopy before operation, inspection of the bowel at operation and systematic lymphadenectomy. ^[1]

Two newer points soften this algorithm. First, NCCN allows appendicectomy alone for all tumours under 2 cm, even with high-risk features. ^[1] Second, a retrospective multicentre evaluation of 278 patients with 1 to 2 cm appendiceal neuroendocrine tumours found no significant overall survival benefit from right hemicolectomy in that selected group (hazard ratio 0.88, 95% confidence interval 0.44 to 1.75). ^[4] Nodal involvement in small lesions also does not clearly worsen overall survival in several series, so many centres are moving to de-escalation. ^[1][4]

Right hemicolectomy technique requires clearing the ileocolic lymphatic field; the appendix base and margin status must be documented. ^[1][4]

Confined LAMN. Complete appendicectomy is curative when the tumour is confined, with reported disease-specific survival close to 100%; neither radiotherapy nor systemic chemotherapy has benefit. ^[3][4] Avoid rupture. If the tumour perforates but there is no distant spread and final histology shows pT4 disease without extra-appendiceal mucin beyond the right lower quadrant and R0 margins, extended resection and right hemicolectomy are not indicated, because LAMN does not spread through lymphatics or blood. ^[3]

Limited extra-appendiceal mucin. If acellular or cellular mucin is found on the appendiceal surface or in the right lower quadrant, management is unsettled. Multidisciplinary review, and consideration of CRS, with or without HIPEC, are appropriate when cellular mucin is present. ^[3][4]

HAMN. For HAMN without perforation or imaging evidence of PMP, appendicectomy alone suffices; with perforation or peritoneal spread, right hemicolectomy plus CRS with HIPEC is recommended (PSOGI, 2021). ^[4]

Incidental appendiceal adenocarcinoma is managed like colorectal cancer. Appendicectomy alone may suffice for completely resected pTis or pT1 disease without risk factors; pT1 with risk factors (grade 3 differentiation, angioinvasion, R1 resection) or pT2 and above should have oncological right hemicolectomy with systematic lymphadenectomy. ^[4] Mucinous adenocarcinoma (over 50% mucin) or signet-ring carcinoma (over 50% signet cells) is managed in the same way. ^[4]

Adjuvant systemic chemotherapy for stage III and higher is recommended by analogy with colorectal cancer, but prospective randomised trials in appendiceal cancer are lacking. ^[4] At stage IV, palliative systemic therapy also follows colorectal guidance; biological agents (anti-VEGF or anti-EGFR, depending on RAS and BRAF status) are not specifically validated in appendiceal adenocarcinoma, although mutation profiling can guide expectations of response. ^[4] If disease is confined to the peritoneum, CRS with HIPEC can be considered in fit patients. ^[4][6]

Despite their neuroendocrine cells, these are managed as adenocarcinoma. Oncological right hemicolectomy is standard for pT3 and pT4 disease, which gave a small but statistically significant improvement in five-year survival (85.4% versus 82.0%, p = 0.028) in a meta-analysis of over 1,220 patients; for pT1 and pT2 disease with negative appendicectomy margins, omitting right hemicolectomy may be reasonable because nodal involvement is uncommon. ^[4][5] Adjuvant chemotherapy (FOLFOX or FOLFIRI) is associated with improved five-year survival in stage III (77.1% versus 42.8%), though not clearly in stage II (96.9% versus 89.1%). ^[5] CRS with HIPEC is the proposed treatment for peritoneal carcinomatosis from goblet cell adenocarcinoma: where complete cytoreduction was achieved, five-year survival was 67% and progression-free survival 59% in one institutional series. ^[5]

PMP is treated as a whole, not as discrete metastases. Cytoreductive surgery (CRS) is radical peritonectomy and organ resection to leave as little tumour as possible; hyperthermic intraperitoneal chemotherapy (HIPEC) bathes the cavity with heated cytotoxic solution after maximal cytoreduction. ^[2][6] The standard reference is the PSOGI/EURACAN guideline of 2020, regarded by many centres as the most authoritative source for PMP. ^[2]

Patient selection. Preoperative assessment includes serum CEA and CA 19-9 (always), CA 125 (consider), triple-phase CT (always), MRI when needed, colonoscopy and careful histological review; laparoscopy may be needed to assess resectability. ^[2] The PCI defines tumour burden and the operative plan; the CC score is the strongest prognostic factor. ^[2]

Relative or absolute contraindications include age over 75 (relative), aggressive histology (such as high-grade PMP with signet-ring cells, mucinous adenocarcinoma with signet-ring cells, or goblet cell adenocarcinoma) with PCI over 20 (relative), extensive small bowel serosal involvement (absolute), mesenteric retraction (absolute), liver hilum involvement, lesser sac infiltration, ureteric obstruction and the need for complete gastric resection, the last group being relative and usually combined with a high PCI. ^[2]

Residual disease targets (CC). Complete cytoreduction means CC-0 (no visible tumour) or CC-1 (residue under 2.5 mm). CC-2 and CC-3 carry much worse outcomes. ^[2][6]

HIPEC regimens are debated. No single drug, duration (30 to 120 minutes), temperature or delivery method has consensus support at the 51% level used by PSOGI/EURACAN 2020. Regimens in common use include oxaliplatin-based (Elias high dose 460 mg per m2 for 30 minutes; Glehen medium dose 360 mg per m2 for 30 minutes; Wake Forest 200 mg per m2 for 120 minutes) and mitomycin C-based (Dutch triple-dosing 35 mg per m2 over 90 minutes; Sugarbaker with mitomycin C and doxorubicin 15 mg per m2 each over 90 minutes; ASPSM low dose 40 mg in 3 litres over 90 minutes). Temperatures around 42 to 43 degrees Celsius are typical. ^[2][4] One randomised trial comparing mitomycin C-based and oxaliplatin-based HIPEC (Levine) found no difference in 3-year survival, though mitomycin C was more haematologically toxic; it was underpowered for a superiority claim. ^[2][6]

Systemic therapy. In PMP, palliative systemic chemotherapy can be used for unresectable disease, and combining it with bevacizumab may prolong progression-free survival; where neoadjuvant or adjuvant systemic chemotherapy is used, a combination of a fluoropyrimidine and an alkylating agent is recommended. Adjuvant and neoadjuvant chemotherapy, in contrast, have no proven survival advantage in low-grade disease and remain controversial, although they are not abandoned outright for high-grade PMP and high-grade PMP with signet-ring cells. ^[2]

EPIC (early postoperative intraperitoneal chemotherapy, days 1 to 4 or 5, unheated) is debated on safety grounds and is not routine; it is used in some centres where HIPEC is unavailable. ^[2]

Evidence base. CRS with HIPEC is the standard of care for appendiceal cancer with peritoneal disease; registry and cohort series report 5-year survival of roughly 50 to 96% depending on grade and completeness, compared with about 50% after debulking alone. ^[6] A randomised trial of CRS with HIPEC against systemic chemotherapy (Verwaal) showed benefit but included only 17% appendiceal cancers, so the specific contribution of HIPEC remains uncertain. ^[6]

Because LAMN does not metastasise through lymphatics or blood, lymphadenectomy is not required when it is pT4 without right-lower-quadrant mucin and R0; appendicectomy alone then suffices. ^[3] Complete colonoscopy before any resection, and inspection of the bowel at operation, are repeated themes in the guidelines above. ^[1][2]

Management of metastatic appendiceal NET follows the broader midgut NET evidence: surgical cytoreduction of liver metastases is favoured when tumour burden is mostly hepatic, with a commonly quoted threshold of at least 90% cytoreduction, although no clear benefit was proved above roughly 70% in observational data. ^[1] Long-acting somatostatin analogues - octreotide LAR 30 mg intramuscularly every 4 weeks, or lanreotide depot 120 mg deep subcutaneously every 4 weeks - control carcinoid symptoms and slow progression; everolimus, PRRT (177Lu-DOTATATE, where 68Ga-DOTATATE uptake is seen) and liver-directed embolisation or ablation are used for refractory or progressive disease. ^[1]

Follow-up for neuroendocrine tumours. Small (under 1 cm), completely resected low-grade NET needs no active surveillance, although patients with symptoms of hormone excess do. For NET of 1 to 2 cm after right hemicolectomy without residual disease, no surveillance imaging is usually required, whereas incompletely resected or higher-grade lesions need biochemical markers (chromogranin A, 5-HIAA) and anatomical imaging, often 6 months to 1 year after operation and yearly thereafter, up to 10 years. ^[1][4]

Follow-up for mucinous neoplasms. LAMN follow-up is with CT (preferably MRI) every 6 months for 5 years together with CEA, CA 19-9 and CA 125. ^[4] PMP follow-up after CRS with HIPEC: every 6 months for the first 2 years (physical examination, chest, abdomen and pelvis CT and tumour markers), then yearly imaging with tumour markers every 6 months; examination frequency from year 2 is not settled. ^[2]

Refer any suspected PMP, goblet cell adenocarcinoma, high-grade NET, NEC, MiNEN, or appendiceal adenocarcinoma beyond low-risk pT1 to the appropriate specialist team: a peritoneal surface centre for PMP or peritoneal dissemination, and neuroendocrine and oncology teams for NET-related disease. ^[1][2][4]

• In PMP - bowel obstruction, malnutrition, cachexia and eventually death; high-grade disease and incomplete cytoreduction carry the worst outcomes. ^[2][6]
• After CRS with HIPEC - anastomotic leak, bleeding, infection, venous thromboembolism and, rarely, re-operation; morbidity is substantial and reported in up to 30 to 40% of procedures, with mortality under 3% in modern series. ^[2][6]
• Perforated mucinous neoplasm - seeding across the peritoneum and subsequent PMP; recurrence is predicted by cellular rather than acellular mucin. ^[3][4]
• High-grade NEC - early metastasis and carcinoid features only when disease reaches the liver. ^[1]
• Peritoneal carcinomatosis generally behaves more aggressively than PMP itself. ^[5][6]

Prognosis is dominated by three things: histological family, grade and completeness of treatment.

• Appendiceal neuroendocrine tumours have the best prognosis of the families, with a five-year survival of about 89.9% for lesions 2 cm or less falling to 70.6% (2 to 4 cm) and 58.2% (over 4 cm). Regional lymph node metastasis does not reliably change survival in these indolent tumours. ^[1][4]
• PMP is a chronic, slowly progressive disease. Five-year survival with CRS and HIPEC ranges from about 50 to 96% in older series, against about 20 to 50% after incomplete cytoreduction. Completeness of cytoreduction (CC-0 or CC-1) is the single most important variable. ^[2][6]
• Goblet cell adenocarcinoma has five-year disease-specific survival of 58 to 81% in reported series. ^[5]
• Appendiceal adenocarcinoma has survival similar to colorectal cancer matched by grade and stage; stage IV non-mucinous tumours benefit from fluoropyrimidine-based chemotherapy in registry analyses. ^[4][6]
• High-grade PMP (HMCP, HMCP-S, signet-ring) carries a much worse outcome than LMCP, and young patients with advanced histology should be counselled accordingly. ^[2][5]

Where sources differ - for example on the benefit of right hemicolectomy for 1 to 2 cm neuroendocrine tumours, and on the precise threshold for HIPEC benefit - the honest statement is that no randomised trial settles the question and multidisciplinary judgement is required. ^[1][4][6]

No population screening exists for appendiceal tumours. Primary prevention is not possible because no modifiable risk factor is established. ^[4] The practical preventive measures are:

• Submit the entire appendicectomy specimen for histology, with named sections and margin status. ^[1][3][4]
• Avoid rupture at operation, especially of a mucin-filled appendix. ^[3][4]
• Make histopathology of any mucinous or atypical appendix a routine reporting item in low-resource laboratories, so that rare lesions are not missed in partially sampled specimens. ^[3][4]
• When a serrated lesion is present, arrange complete colonoscopy because of the excess of colorectal neoplasia. ^[3]
• For appendiceal NET in syndromic patients (rare), use the appropriate inherited tumour surveillance protocol. ^[1]

• Pregnancy. Appendiceal neoplasms in pregnancy are usually handled like appendicitis; appendicectomy is safe and should not be delayed for presumed appendicitis. Systemic therapy in pregnancy needs oncological review.
• Children and adolescents. Neuroendocrine tumours of the appendix occur in younger patients than most other gastroenteropancreatic tumours; hereditary syndromes should be considered in the young or with multiple tumours. ^[1][4]
• Older adults and frail patients. Age over 75 is a relative contraindication to CRS with HIPEC, but not an absolute one; many older patients complete treatment with careful perioperative care. ^[2]
• Immunocompromised patients. These need early infection control around CRS.

• Diagnosis rests on careful histology of every appendicectomy specimen. If a laboratory cannot process whole specimens, fix and transport the appendix, or at least the tip, base and mesoappendix, to a larger centre. ^[3][4]
• Imaging. CT of abdomen and pelvis is the most useful staging and follow-up tool where 68Ga-DOTATATE PET-CT and MRI are unavailable. ^[1][2]
• CRS with HIPEC is not available in most district hospitals; early referral of suspected or confirmed PMP to a peritoneal surface centre is the single most cost-effective intervention. ^[2][6]
• If CRS is inaccessible, palliation with a fluoropyrimidine-based regimen and symptomatic treatment may be appropriate; local regimens vary and discussion with the nearest oncology unit is advised. ^[6]
• Pathology at the bench - confirm the clinicopathological correlation before committing to radical surgery; a second opinion can up-stage or down-stage a mucinous neoplasm materially. ^[3][5]

• Acute appendicitis
• Neuroendocrine tumours (gastroenteropancreatic)
• Colorectal cancer (staging and adjuvant therapy)
• Ovarian mucinous tumours and peritoneal disease
• Cancer staging, screening and tumour markers
• Palliative care and oncologic emergencies