The appendix is a common specimen in most surgical pathology laboratories.

It may be received as an appendectomy specimen or attached to the cecum as part of a more extensive procedure. In either case, assessment is similar. The length and greatest diameter are measured. Any variation in diameter is recorded. The serosal surfaces are described; they are normally smooth and glistening. The cut surfaces are examined for any areas of hemorrhage, thickening, cyst formation, or tumor. Any fecalith or foreign body in the lumen is noted. A tumor of the appendix requires the same description as a tumor of the colon, with measurement in three dimensions. Dissection of the appendix and selection of tissue for microscopy may proceed by one of several standard techniques. A common method is to bisect the tip longitudinally and make transverse sections at intervals of no more than 10 mm through the remainder; the pathologist then submits half the tip, one or more transverse sections from the middle, and a transverse section from the base.11 Some pathologists prefer to bisect the base to produce longitudinal sections from the base as well as the tip (by using the surgeons clamp mark to distinguish them on the slide). This technique facilitates accurate assessment of the resection margin in the case of neoplasm; the rationale for using it routinely is that some tumors are not identified by gross examination. 12 Alternatively, the entire appendix can be bisected longitudinally. 13 A flexible approach is probably better than slavish adherence to one particular protocol. In particular, the dissection technique needs adjusting in cases of tumors and mucoceles to ensure adequate sampling. Mucocele simple obstruccin Mucocele properly refers to the gross appearance of a dilated, mucin-filled organ.18,19 Most mucoceles are the result of adenomas, low-grade appendiceal mucinous neoplasms, and adenocarcinomas. However, a few are non-neoplastic and are described as simple mucoceles or appendiceal ectasia.They are unusual lesions and are also called obstructive mucoceles on the basis of the putative role of outflow obstruction in their pathogenesis. Sometimes, cystic fibrosis may be associated with mucocele formation. The diameter of an intact simple mucocele is usually less than 2 cm. Except in some cases of cystic fibrosis, an inflammatory infiltrate is virtually always present. 10 The mucosa is atrophic or ulcerated and does not show hyperplastic or neoplastic features. Dissection of the wall by acellular mucin can occur. The principal differential diagnosis is an epithelial neoplasma (cystadenoma, lowgrade appendiceal mucinous neoplasma or mucinous adenocarcinoma). 10 Simple mucoceles may show acellular mucin in the wall or even outside the appendix, so care must be taken not to overinterpret these features as malignant invasion. However, because mucinous adenocarcinomas may be poorly cellular, the other danger is to miss an invasive tumor in a lesion in which the neoplastic cells are scant. In particular, neoplasms with extensive ulceration and granulation tissue formation can mimic a simple mucocele. Helpful in this distinction is (1) adequate sampling of the organ for histology and (2) size, because simple mucoceles are almost always less than 2 cm in diameter. Inflamacion aguda

Pathologic Findings

Inflammation may affect the entire appendix or only part of its length; when only part is affected, it is usually the distal segment. 76 The earliest gross changes are dilation of serosal vessels and dulling of the serosal surface. In assessing serosal vascular dilation, note that some congestion occurs as a result of the surgical procedure. An increase in the diameter may follow, caused by edema or luminal dilation. An inflammatory exudate appears on the surface, and pus may be visible in the lumen. The appendix becomes increasingly congested, and small abscesses may be visible on the cut surfaces. At this stage, the mesoappendix is usually involved in the process. Necrosis of the wall is associated with the development of gangrenous appendicitis, in which the wall becomes friable and shows purple or green discoloration. The cardinal histologic sign of acute appendicitis is neutrophil infiltration of the wall. However, minimal criteria for diagnosing early appendicitis are not well established. In particular, no universally accepted features exist to distinguish mild acute inflammation from normal findings. For some investigators, the minimal criteria for diagnosis are increased mucosal neutrophils and mucosal ulceration.76 This condition has been termed superficial or mucosal appendicitis, and its presence should prompt a careful search for transmural inflammation elsewhere, with submission of more tissue for histologic examination if necessary. When mucosal inflammation is the only finding even after widespread sampling of the appendix, its significance is controversial because the question remains whether the changes were responsible for the patients symptoms, and the possibility of disease outside the appendix may need to be considered; sometimes, the appearances sug - gest acute gastroenteritis or chronic inflammatory bowel disease.11,75 Luminal neutrophils with normal mucosa are encountered in incidental appendectomy specimens and probably do not warrant a diagnosis of acute appendicitis. 72,76,77 Cases in which polymorphs in the lumen are associated with local ulceration from a fecalith could be considered mild appendicitis, but this situation also occurs in incidental appendectomies, and the question again arises whether such changes alone could be symptomatic. In summary, the terminology shown in Table 24-2 is recommended for classifying acute appendicitis. If mucosal inflammation alone is identified despite adequate sampling, the report should alert the surgeon to the possibility that although the changes could represent early acute appendicitis, one may not be able to exclude other causes of the patients symptoms.72 In well-developed cases, the acute inflammatory infiltrate is transmural and consists of neutrophils, usually with eosinophils.72,83 Such cases have been subclassified as suppurative appendicitis, defined as neutrophil infiltration of the muscularis propria. 84 Pus may be present in the lumen, and mucosal ulceration is common. Other findings may include microabscesses, vascular thrombosis, and fibrinopurulent serositis. 76 Gangrenous appendicitis or necrotizing appendicitis may be diagnosed when necrosis of muscle wall is present.11 Transmural necrosis leads to perforation. In practice, the pathologic demonstration of a perforation site may be difficult or impossible, even when clear operative evidence of rupture exists. Periappendicitis is defined as the finding of serosal and subserosal accumulations of inflammatory cells that may extend into the outer muscularis propria but do not involve the mucosa, submucosa, or inner muscularis propria. This condition is caused by intra-abdominal inflammation (e.g., pelvic inflammatory disease).11,73,84 It is important to be aware of periappendicitis because the pathologist can alert the surgeon to the presence of other abdominopelvic conditions. Histologically, one sees widespread neutrophil infiltration of subserosa, an exudate on the serosal surface, reactive changes in mesothelial cells, and usually granulation tissue formation and chronic inflammatory cells in

addition. Periappendicitis needs to be distinguished from changes resulting from intraoperative handling of the appendix that are characterized by subserosal congestion, margination of neutrophils in vessels, and (if the procedure has been prolonged) emigration of neutrophils through vessel walls. Investigators have suggested that serosal fibrin deposition may also occur as a result of intraoperative handling. 65 A few reports have been published on xanthogranulomatous inflammation, characterized by an infiltrate of xanthomatous cells with foamy cytoplasm containing droplets of periodic acidSchiffpositive, diastase-resistant material, together with multinucleated histiocytes, plasma cells, lymphocytes, and eosinophils. This infiltrate contains hemosiderin and may be transmural or confined to mucosa and submucosa, with relative sparing of lymphoid follicles. 85,86 A xanthogranulomatous pattern may be relatively common in interval appendectomy specimens.87 Pathologists and surgeons are familiar with the finding that appendixes removed from some patients with a preoperative diagnosis of appendicitis are morphologically normal.52,74 In some of these cases, other lesions, such as mesenteric adenitis, may be the cause of the clinical features. However, some histologically normal appendixes from patients with a clinical diagnosis of appendicitis show increased cytokine expression, although the relevance of this finding is as yet unclear. 8

Significance of Eosinophils in the Wall

In some appendixes, infiltration of the muscularis propria by eosinophils in the absence of any other abnormality may be observed, but studies addressing this phenomenon are scant. The author of a study from India proposed that eosinophil infiltration could represent an early stage in the development of acute appendicitis,83 and the data suggested that an eosinophil count in excess of 10 per mm2 (25 per 10 high-power fields) could be abnormal. 72 Other authors use the diagnosis of subacute appendicitis when at least five eosinophils per highpower field are present in the wall.84 However, we do not use this diagnosis because this finding is often encountered in incidental appendectomy specimens, and no clinical evidence indicates that it represents a state of subacute inflammation. The differential diagnosis of eosinophil infiltration includes eosinophilic enteritis and infestation by parasites.72

Chronic Appendicitis
This diagnosis is also contentious. Investigators proponed that chronic nonspecific inflammation could cause longstanding symptoms (grumbling appendix), but in practice, a chronic inflammatory infiltrate is normally part of the picture of resolving acute appendicitis or represents a specific infection.65,76 Some cases diagnosed as chronic appendicitis may in reality be examples of recurrent acute appendicitis. Large reactive lymphoid follicles or scattered lymphocytes outside lymphoid follicles are normal and do not represent chronic inflammation.

Healing and Complications

Appendicitis may heal by resolution. Fibrous adhesin formation is usual, and scarring of the wall may occur.73 Histologic features of healing appendicitis may incluye granulation tissue formation, either in the wall or producing a polypoid mass in the lumen, associated with a mixed inflammatory infiltrate.76,85 Extravasation of mucin within the wall into the subserosa may occur; this feature must be differentiated from a mucinous neoplasm. Giant cells of foreign body type may be encountered. The most common serious complication of untreated appendicitis is perforation resulting from necrosis of the wall. Generalized peritonitis may ensue, but the more usual course is for the process to be localized by host defense mechanisms, with a consequent appendiceal or periappendiceal abscess surrounded by granulation tissue and adherent omentum and small intestine. Such lesions may heal by fibrosis or

produce a chronic fistula, either to the skin or to the lumen of an abdominopelvic viscus.53 Pelvic or subphrenic abscess may also occur. Rarely, infection of the veins causes pylephlebitis and hepatic abscess formation. If the appendiceal abscess and the associated host reactions persist, a chronic inflammatory mass that is palpable in the right iliac fossa will result. At gross examination, the lesion can mimic carcinoma of the cecum (ligneous perityphlitis). The histologic findings are usually nonspecific and may include acute and chronic mixed inflammatory infiltrates, foreign body giant cells, abscess formation, granulation tissue, and fibrosis. The differential diagnosis may include Crohns disease, yersiniosis, mesenteric fibromatosis, sclerosing mesenteritis, and inflammatory fibrosarcoma. 85,90 In some cases, the fibrous reaction is characterized by a fibroblastic proliferation exhibiting a whorled, concentric pattern around vessels, with plasma cells, eosinophils, and areas of hyalinization; these features are reminiscent of inflammatory fibroid polyp, and the two conditions should not be confused. If the inflammatory process is localized and only partially penetrates the wall, a diverticulum lined by appendiceal mucosa may develop. Because of the poor drainage of such a structure, the diverticulum can be the source of repeated bouts or persistence of appendicitis, namely, appendiceal diverticulitis.