The cecum appears during the fifth fetal week, arising as a diverticulum from the distal primitive intestinal loop before it differentiates into the small and large intestine. The appendix develops from the cecum and matures in the second trimester (1). As the appendix lengthens, the junction between the appendix and the cecum becomes increasingly more distinct. Longitudinal folds and ridges form, producing a segmented appearance; villi form (Fig. 8.1) that eventually involute. The epithelium appears clear due to large amounts of intracytoplasmic glycogen. Endocrine cells develop in the subepithelial connective tissue around the ninth fetal week when the epithelial basement membrane is not fully formed and the muscularis mucosae has not yet developed.

Lymphoid stem cells migrate into the appendiceal mesenchyme. Mature lymphocytes appear when the fetus measures approximately 100 mm in length (2); lymphoid aggregates appear by the 17th week. The apical poles of incipient lymphoid follicles impinge on the surface epithelium by the time the fetus reaches 150 mm in length and lymphoid cells invade the epithelium. Germinal centers develop between the third and sixth postnatal weeks after the introduction of foreign protein (by eating) into the gut. Macrophages appear shortly after the lymphocytes (3). Primitive neural structures develop in the first trimester.

The appendix usually arises from the posteromedial cecal wall, 2.5 to 3 cm below the ileocecal valve at the convergence of the taeniae coli (Fig. 8.2). The adult appendix averages 7 cm in length; lengths up to 20 cm have been reported. The appendix is longer in adults than in children. Its external diameter ranges from 0.3 to 0.8 cm. The appendiceal lumen measures from 1 to 2 mm in diameter appearing round, oval, irregular, or slitlike. The distal tip obliterates in adults. The appendix is suspended from the mesoappendix, and attaches to the cecum in several ways (4). In 65% of adults, the appendix lies behind the cecum with its orifice opening into the cecum near the ileocecal valve. It may also lie to the side of the ascending colon, in front of, or behind, the ileum, lying on the psoas muscle or hanging over the pelvic brim (4). The appendix receives its blood supply from a branch of the posterior cecal artery; its venous drainage is to the portal system, explaining the coexistence of hepatic inflammation in the setting of appendicitis. The lymphatics first drain into the nodes of the mesoappendix and then to the right pericolic lymph nodes as well as to the ileocecal lymph nodes.

The appendiceal mucosa resembles that of the large intestine, except for the prominent circumferential arrangement of lymphoid follicles known as Peyer patches. Peyer patches (Fig 8.3) are most prominent in children, decreasing in size with age. They are markedly diminished or absent in the elderly. The appendiceal epithelium is modified over the dome of each lymphoid follicle to form M cells with a structure similar to that seen in the small intestine (see Chapter 6). Nonbranching crypts are lined by tall mucus-secreting goblet cells that extend from the luminal surface to the crypt bases. The crypts also contain endocrine cells, Paneth cells, and small numbers of intraepithelial lymphocytes. The muscularis mucosae is often absent; it is sometimes difficult to determine the mucosal–submucosal boundary.

The regularly arranged Peyer patches lie at the mucosal–submucosal junction (Fig. 8.3), and a well-defined lymphatic sinus surrounds both the lateral and basal parts of the follicle. These lymphatic sinuses empty into the submucosal-collecting lymphatics. Lymphocytes that proliferate in the gut-associated lymphoid tissues migrate into the surrounding lymphatic sinus or capillaries and enter the systemic circulation to be redistributed to other lymphoid tissues and organs. The endocrine cell population is discussed in Chapter 17.

Congenital appendiceal anomalies are rare (5). They include appendiceal agenesis (6), hypoplasia, duplications, horseshoe shape (7), heterotopia, and diverticula. These

occur in the presence of either a normal cecum or with cecal dysgenesis.

Diverticula affect 0.004% to 2.8% of histologically examined appendices (5,12). They can be congenital or acquired; both types may be single or multiple. Congenital diverticula present as antimesenteric outpouchings with complete muscular walls, contrasting with acquired diverticula that lack the muscularis propria (Fig. 8.6). Some congenital diverticula are attached to the umbilicus by a fibrous band, resembling Meckel diverticulum.

Acquired diverticula are ten times more frequent than their congenital counterparts (5). They affect both sexes equally and develop along the area of the penetrating arteries, often secondary to inflammation or tumors. Associated neoplasms, particularly low-grade mucinous neoplasms, are present in many patients (Fig. 8.6) (13). Diverticula develop due to the increased pressure of the accumulated intraluminal mucin. A similar mechanism may be responsible for the relatively high incidence (14%) of appendiceal diverticula in patients with cystic fibrosis.

Acquired diverticula are commonly multiple (Fig. 8.6), lying along the mesenteric and antimesenteric borders. They usually involve the distal appendix, giving the appendix a beaded appearance. Their size varies from 2 to 5 mm. Like colonic diverticula, they are subject to inflammation or perforation. Inflammation may distort, obliterate, or disrupt a diverticulum. When the inflammatory process spreads into the periappendiceal tissues, an abscess results.

Appendiceal intussusception is rare, usually affecting young boys (14). Patients range in age from 8 months to 75 years. Predispositions to intussusception include the presence of a fetal cone-shaped appendix, an unusually thin mesoappendix, or the presence of mass lesions, most typically endometriosis, adenomas, carcinoid tumors, or the lymphoid hyperplasia associated with viral infections. The presenting signs and symptoms resemble those of acute appendicitis. The lesions may also remain asymptomatic only to be discovered incidentally.

There are four types of appendiceal intussusceptions (Table 8.1). In some cases, the distal appendix intussuscepts into the proximal appendix; in other cases, the proximal appendix intussuscepts into the cecoappendicular opening or the whole appendix intussuscepts into the cecum (Fig. 8.7), presenting as an edematous or infarcted cecal “polyp.” Intussusception can also appear as an umbilicated area at the junction of the taeniae coli on the cecal serosal surface. The mucosa may appear normal, hyperplastic, inflamed, eroded, or ischemic. The latter occurs if the vascular supply has been compromised. If there have been recurrent intussusceptions, the mucosa and muscular layers may become hyperplastic. In intussusception, the histology may also appear to be reversed from normal, with the epithelium lying on the external surface of tissue and the submucosa and muscularis propria lying inside the mucosa (Fig. 8.8). The submucosa becomes edematous and the muscularis propria may appear
hyperplastic, fibrotic, or splayed (Fig. 8.9). The muscular layers maintain a normal relationship with one another and with the submucosa and mucosa. Sometimes the bowel wall appears to have two muscularis propriae. It is important that the appendix be examined carefully in this setting to exclude the presence of an underlying neoplasm or other lesion such as endometriosis that may have been the lead point for the intussusception. Treatment of the intussusception is surgical resection.

Occasionally, the appendix autoamputates following intussusception or volvulus. The presence of cecal scarring and hemosiderin in the absence of other cecal abnormalities provides clues that the appendix was present at birth. Inverted appendiceal stump follows appendiceal autoamputation, and may appear as a cecal polyp grossly or endoscopically. One of the complications of an appendiceal stump is a vascular malformation. Patients may present with massive bleeding from cecal ulcerations. Histologically, massively dilated vessels are present.

Appendiceal torsion is rare, and when it occurs it causes ischemic appendicitis (Fig. 8.10). Histologically, one sees distal inflammation with areas of hemorrhage and necrosis. As with intussusceptions, a careful examination for the presence of an underlying neoplasm, as well as the assessment of the adequacy of the resection of the appendix if a neoplasm is present, is important.

Single or multiple, complete or incomplete septa consisting of mucosa and submucosa may divide in the appendiceal lumen into compartments (Fig. 8.11), predisposing the appendix to develop appendicitis. The inflammation usually remains confined to one compartment of the septated lumen. These lesions present most often in the 15- to 19-year age group with a clear-cut male predominance. They represent residual fetal septations.

The appendix may appear to be absent for several reasons: (a) agenesis; (b) previous resection; (c) obliteration from previous episodes of acute appendicitis, intussusception, or torsion; or (d) its presence in unusual locations. Retrocecal, retrocolic, and retroileal appendices are uncommon but can cause clinical confusion, especially in the individual who presents with acute abdominal pain. Acute appendicitis can resolve, leaving only a thin fibrous cord. Resection of the appendix should be suspected in individuals who have undergone previous surgical procedures. The confluence of the three cecal taeniae is the only consistent landmark for the appendiceal origin.