Although primary appendiceal malignancies make up only about 0.5 per cent of all intestinal tumours, they are important because they are rarely diagnosed preoperatively or intraoperatively.

The four main types of appendiceal neoplasms are carcinoid, mucinous cystadenocarcinoma, colonic adenocarcinoma, and adenocarcinoid tumours (Table 1) 348. They have different clinical presentation and prognosis and require different therapy, but are alike in that they all carry a 15 to 20 per cent chance of a second malignancy developing, concurrently or subsequently, usually in the gastrointestinal tract.

Although the vast majority of appendiceal carcinoids behave in a benign fashion, they are considered malignant because they all have the potential for invasion, metastasis, and production of physiologically active substances.

Carcinoids occur in about 0.5 per cent of appendectomy specimens and account for about 85 per cent of appendiceal malignancies. At least 50 per cent of all carcinoid tumours originate in the appendix. They are most common in young adult women, probably because they are discovered accidentally among the large number of incidental appendectomies performed in association with hysterectomies and cholecystectomies.

At least 80 per cent of carcinoid tumours are incidental findings discovered during surgery for other indications. Sometimes they are found as coexisting disease in patients with acute appendicitis, and occasionally they are actually the cause of the acute appendicitis. Rarely do they present as metastatic disease or the malignant carcinoid syndrome.

Carcinoids are small, yellow-white firm, well circumscribed, but unencapsulated tumours. Most are spheroidal or elliptical; some diffusely involve the appendiceal wall. Many carcinoids are unrecognized grossly being seen only on microscopic section. About 70 per cent are located in the tip of the appendix, 22 per cent in the body of the appendix, and 8 per cent in the base of the appendix.

Seventy per cent of carcinoids are less than 1.0 cm in diameter, and only about 15 per cent are larger than 2.0 cm in diameter before fixation: larger tumours tend to occur in younger patients. Since size is the most important factor in determining treatment, measurements should be recorded in vivo, because after fixation shrinkage of 35 per cent can occur.

Carcinoids are composed of nests of small, uniform, argyrophilic cells with occasional acinar formation. The different microscopic patterns are of little practical importance because there is little correlation between the microscopic appearance and the biological malignancy of the tumour. Debate exists as to whether the cells arise in the base of the crypts of Lieberkuhn or from neuroendocrine cells in the lamina propria beneath. Although mitoses are infrequent, the muscularis and subserosal lymphatics are often invaded. The mesoappendix is frequently involved, but spread to regional lymph nodes and distant sites is rare. Spread to the liver may be associated with the carcinoid syndrome.

Size is the most important guide in considering the malignant potential of appendiceal carcinoids. Distant metastases and death occur only in patients with tumours larger than 2.0 cm in diameter (1.5 cm in a fixed specimen). Treatment for good risk patients is outlined in Table 2 349. Carcinoids in the base of the appendix should have enough caecum removed to leave margins free of neoplastic disease but a right hemicolectomy is not required merely because of the location of the tumour.

Controversy exists with regard to proper treatment for patients with carcinoids between 1.0 and 2.0 cm in diameter. Moertel feels that an appendectomy with removal of the mesoappendix is adequate for nearly all patients in this group. Others are more aggressive and advise a right hemicolectomy if lymphatic permeation and mesoappendiceal invasion are present since regional lymph node involvement is more likely. Sufficient data to enable this question to be settled are not available.

The 5-year survival for patients with appendiceal carcinoids is 99 per cent. Recurrences are found only in those patients with large tumours or in those who had intra-abdominal spread at the original surgery. All intra-abdominal disease should be resected if possible, primarily or at a later operation if there is a recurrence. In patients in whom all recurrent disease can be resected the 5-year survival rate is about 75 per cent.

Metastatic disease in the liver is rare with appendiceal carcinoid tumours, but when present in association with the carcinoid syndrome medical treatment with 5-hydroxytryptamine (serotonin) antagonists or debulking of the tumour mass, either at laparotomy or by hepatic arterial embolization, is indicated.

Although mucinous cystadenocarcinoma is included with colonic adenocarcinoma as adenocarcinoma, it is considered separately here because of its different behaviour. Cystadenocarcinoma is both the second most common appendiceal malignancy and one of the few that can be diagnosed preoperatively, allowing elective preoperative preparation.

There is no sexual predilection; patients are usually younger than the typical adenocarcinoma patient. Cystadenocarcinoma is nearly always symptomatic, causing a variant of acute appendicitis and a palpable right lower quadrant mass. A barium enema may show a non-filling appendix with a globular mass; computed tomography shows a mass of near water density with calcium in its wall. About 50 per cent of patients have intra-abdominal metastases, with concomitant ascites, intestinal obstruction, and pseudomyxoma peritonei.

Mucocele is a term used to describe an appendix with a diffuse globular swelling, a dilated lumen with large amounts of mucus, and occasional mucinous intraperitoneal collections. A mucocele can be caused by obstruction of the appendiceal lumen, by mucosal hyperplasia, by mucinous cystadenomas, and by mucinous cystadenocarcinomas. Because the term has no aetiologic or prognostic significance, it is gradually being discarded from current classifications.

Mucinous cystadenomas and cystadenocarcinomas may be indistinguishable grossly, and resemble each other microscopically. Both neoplasms contain mucus-secreting epithelial mucosal cells with varying degrees of atypia, mitoses, and papillary configuration. As the intraluminal mucus secretion continues, the wall becomes thin, ulcerated, and calcified. The mucin eventually penetrates the wall and appears in the periappendiceal and retroperitoneal areas.

The distinction between malignant mucinous cystadenocarcinoma and its benign counterpart is based on two histological features: the first is the invasion of the appendiceal wall by atypical glands; the second is the identification of epithelial cells in any intraperitoneal mucinous collection.

Rupture of appendiceal mucinous cystadenomas and cystadenocarcinomas accounts for about 33 per cent of pseudomyxoma peritonei cases. Although gelatinous ascites per se is innocuous, the implanted mucin-producing malignant cells cause peritoneal irritation, recurrent ascites, and intestinal obstruction.

The distinction between mucinous cystadenomas and mucinous cystadenocarcinomas is important. Cystadenoma is cured by simple appendectomy, even in the presence of periappendiceal fluid collections, while a right hemicolectomy is the best treatment for a malignant mucinous cystadenocarcinoma in a good risk patient.

Since many cystadenocarcinomas are associated with intra-abdominal metastases, aggressive debulking, omentectomy, drainage of mucin collections, and oophorectomy are often needed. Multiple surgical procedures are more beneficial for recurrences than are chemotherapy and irradiation.

Because mucinous cystadenocarcinomas are slowly progressive, patients have a better prognosis than do those with an adenocarcinoma. Both appendectomy and right hemicolectomy are used for curative therapy: 5-year survival rates are about 70 per cent with both methods. When 10-year survival is considered however right hemicolectomy proves itself clearly superior, yielding a 65 per cent survival rate compared to 37 per cent after appendectomy. Even patients with metastases and pseudomyxoma peritonei have 50 per cent 5-year and 20 per cent 10-year survival rates.

Colonic adenocarcinomas are much less common than carcinoids, occur in older patients, and are nearly always symptomatic. Most patients present with acute appendicitis, frequently with a peri-appendiceal abscess. The correct diagnosis is almost never made preoperatively, only occasionally intraoperatively, but commonly after the microscopic examination is complete. Further operative therapy must then be considered.

There are no distinctive gross features of this type of carcinoma. Most are near the base of the appendix and appear as a firm nodularity or diffuse swelling that quickly occludes the appendiceal lumen. A few have been reported in a previously invaginated appendiceal stump. Microscopically the picture is a typical colonic adenocarcinoma. Since the appendiceal muscle walls are thin, any malignancy that involves the submucosa is essentially subserosal. Mesenteric and lymphatic involvement is common, most tumours being Dukes' B and C stages.

Since the lymphatic drainage of the appendix is identical to that of the caecum, only a right hemicolectomy can accomplish a wide removal of the tumour with an adequate dissection of the regional lymph nodes. Although a rare Dukes' A tumour may be cured by an appendectomy, a right hemicolectomy is preferred for all good risk patients with localized disease, even if the appendix has perforated. If the correct diagnosis is known intraoperatively, a right colectomy is performed primarily. If not, a secondary right hemicolectomy must be undertaken within several weeks. An accompanying oophorectomy may be added in postmenopausal women.

The outlook is less favourable for patients with the colonic type of adenocarcinoma than for those with mucinous cystadenocarcinoma and similar to the prognosis of other colonic carcinomas, stage for stage. Survivors are few if regional lymph nodes contain cancer. Adjunctive therapy with 5-fluorouracil and levamisole will improve the prospects.

This recently described tumour is a rare appendiceal malignancy that has both carcinoid and adenocarcinoma features. It is also called goblet cell carcinoid, mucinous carcinoid, and crypt cell carcinoma. Because it is more aggressive than the typical carcinoid but less so than an adenocarcinoma, the term adenocarcinoid seems to describe it best. Adenocarcinoids are mixtures of tubuloglandular structures and goblet cells that arise from the base of the glands and spare the luminal mucosa. They stain positively for acid mucin and argyrophilic granules and commonly invade perineural and lymphatic structures.

Adenocarcinoids are nearly always symptomatic, show no sexual preference, and usually present as acute appendicitis. Since this tumour has an unusual propensity to spread to the ovaries, the patient may present with ovarian masses (Krükenberg tumour).

Adenocarcinoid tumours are inconspicuous and do not have a characteristic gross appearance. They are usually less than 2.0 cm in diameter involve all parts of the appendix equally, and are diffusely infiltrative. Unlike the situation with ordinary carcinoids, size is not a reliable guide to their clinical behaviour.

Debate exists about the histogenesis of adenocarcinoid tumours. Adenocarcinomas derive from primordial endodermal elements, while carcinoids develop from neural crest cells. There might be a simultaneous malignant transformation of the two stem cell types. Alternatively crypt base stem cells may be the origin, since they have the potential to differentiate into either cell type.

Metastatic disease may or may not be of the same type as the primary tumour. Frequently, the ovarian metastases will be pure signet ring carcinoma.

A right hemicolectomy is the best treatment for nearly all patients with localized disease. Because the diagnosis is nearly always made postoperatively, right hemicolectomy is performed as a secondary procedure, along with an oophorectomy in most cases. If the patient has intra-abdominal metastases, aggressive resection is usually helpful.

Some patients with a Krükenberg tumour (usually bilateral) will have no obvious gastrointestinal source. A concomitant appendectomy should be undertaken to avoid overlooking a small primary appendiceal adenocarcinoid.

Adenocarcinoids lie between ordinary carcinoids and adenocarcinoma in malignant potential. Adenocarcinoids with a primarily tubular pattern fare better than those with a goblet cell pattern. The overall 5-year survival is about 80 per cent. Nearly all survivors are those with the tumour localized to the appendix. Patients with intra-abdominal spread and ovarian metastases have a poor prognosis.

1.A frozen section examination should be performed whenever the appendiceal findings are atypical. A diagnosis of an appendiceal malignancy can then be made intraoperatively, allowing appropriate surgery to be performed primarily.

2.All patients with an appendiceal malignancy should be followed, since 15 to 20 per cent of them develop a second malignancy.

3.Although surgery has been the main treatment for appendiceal malignancies, chemotherapy and radiation therapy should be helpful in the future.

4.Appendectomy is recommended for patients whose appendiceal carcinoids are 1.0 cm in diameter, before fixation and for many whose tumours are between 1.0 and 2.0 cm in diameter. Right hemicolectomy is recommended in good risk patients whose tumours are 2.0 cm or more in diameter, or between 1.0 and 2.0 cm if there is evidence of lymphatic permeation and mesenteric invasion.

5.Benign mucinous appendiceal tumours are treated by appendectomy while a right hemicolectomy is best for mucinous cystadenocarcinoma. Aggressive surgical treatment for intra-abdominal metastases and pseudomyxoma peritonei can allow long survival.

6.Most of the colonic forms of appendiceal adenocarcinomas are Dukes' C stage, require a right hemicolectomy, and have the same prognosis as do other colon adenocarcinomas.

7.Adenocarcinoids are a rare appendiceal malignancy of dual cell origin that have a predilection for producing ovarian metastases and have a malignant potential between that of carcinoids and adenocarcinomas. A right hemicolectomy, with concomitant oophorectomy in postmenopausal women, is the recommended therapy.

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