The Peritoneum

Tuberculosis

Tuberculous peritonitis is still encountered in the peritoneum, usually in immunosuppressed patients. It may also occur as a complication of chronic peritoneal dialysis. It may be secondary to tuberculous salpingitis or result from miliary tuberculosis. Clinically, it may manifest nonspecifically as widespread carcinomatosis. The presence of ascites, a pelvic mass, and marked elevation of serum levels of CA125 may lead to a false clinical suspicion of ovarian cancer. The granulomas are characterized by caseous necrosis and Langhans type giant cells; mycobacteria may be demonstrated by acid-fast stains or immunofluorescence techniques.

Suture Materials

Foreign-body granulomas are most commonly associated with suture material retained from prior surgical procedures. The sutures may consist of dense hyaline material in varying degrees of disintegration, or translucent threads. The foreign-body component of the granulomas can be highlighted with polarizing filters. Cellular reaction consists of macrophages, some multinucleated, and lymphocytes. There is both local fibrosis and serosal adhesions.

Surgical Glove Powder

Surgical glove powder, either talc or starch granules, is a common cause of granulomas. At laparotomy, the peritoneal granulomas may simulate carcinomatosis or tuberculosis. Usually the starch granulomas resolve within a few months, leaving no residua or only adhesions; however, some patients develop fibrosing peritonitis. Commonly, starch granulomas exhibit a typical foreign-body reaction and, less frequently, they appear as sarcoid granulomas, which lack necrosis, or tuberculoid granulomas, with necrosis, that simulate tuberculosis. The polyhedral and translucent starch granules are periodic acid–Schiff (PAS) positive and exhibit the typical Maltese cross under polarized light. Rarely, fat necrosis and rheumatoid-type necrotizing foci are identified as reactions to starch. Talc was once an important cause of granulomatous and fibrosing peritonitis because of its application as a lubricant on surgical gloves; however, its use has been discontinued. Talc is a greater irritant than starch and is poorly absorbed by some patients. Talc granulomas are of the typical foreign-body type. Multinucleated giant cells are numerous and contain pleomorphic crystal spicules readily seen with polarized light.

Contrast Media

Peritoneal granulomas may result from exposure to hysterosalpingographic contrast medium, which can be associated with a lipogranulomatous reaction. These appear as foreign-body giant cell reactions around spherical vacuoles from which lipid has been removed during processing. Lipogranulomas may become confluent and focal necrosis may occur.

Intestinal Contents

Foreign-body granulomas to intestinal contents may be seen following perforation such as in Crohn disease, diverticulitis, or malignant fistulas. These granulomas are generally confined to the serosa, but plant material and barium from a perforated colon may be identified in the wall or subserosal fat.

Cystic Teratoma (Dermoid Cyst) Rupture

Rupture of a mature cystic teratoma (dermoid cyst) is typically associated with widespread peritoneal granulomas and adhesions. The squamous cells, hairs, and sebum trigger a foreign-body reaction. This phenomenon occurs especially when the teratoma is removed by cystectomy during laparoscopic surgery. On occasion the reaction may also appear as sclerosing peritonitis and mimics a neoplasm at operation.

Keratin

Peritoneal foreign-body granulomas to keratin may be found in association with uterine or ovarian endometrioid carcinomas with squamous differentiation, or, less frequently, with squamous cell carcinomas of the cervix or atypical polypoid adenomyomas. Uterine examples are thought to result from retrograde transmission of acellular keratinous debris through the fallopian tubes ( Figure 31.1 ). Granulomas have been seen on the serosa of the adnexa, uterus, colon, and appendix. These granulomas are easily misinterpreted as metastatic carcinoma. Follow-up on these patients indicates that cell-free granulomas lack prognostic significance.

Cauterized Tissue

Foreign-body granulomatous reactions to cauterized tissue in pelvic peritoneal and ovarian biopsies are occasionally encountered in patients who have had endometriotic or other lesions treated in the weeks prior to biopsy. The lesions show central eosinophilic, focally refractile, amorphous material (representing the coagulated tissue and carbonaceous debris) palisaded by large numbers of multinucleated foreign-body giant cells and a peripheral lymphocytic infiltrate ( Figure 31.2 ). Lesions tend to hyalinize with age and may persist for many years.

Cesarean Delivery

Complicating cesarean delivery, the amniotic fluid contents may spill into the peritoneal cavity causing a syndrome clinically similar to bowel perforation. Amniotic fluid contains squamous cells, keratin, and sometimes lanugo hair (vernix caseosa). It may also contain meconium, which itself is composed of bile, pancreatic, and intestinal secretions. Grossly, the amniotic fluid contents appear as cheese-like yellow patches limited to the serosal layer of visceral organs. Meconium peritonitis caused by bowel perforation in utero can also be a problem in newborn infants. The hallmark of meconium peritonitis is calcification, which presumably results from the action of pancreatic enzymes.

Mesothelial Hyperplasia

Mesothelial hyperplasia is a common response to inflammation that occurs in any process that leads to irritation of a serosal surface, such as ascites, hernia sacs, endometriosis, pelvic inflammatory disease, or ovarian tumors. Grossly, the hyperplastic lesions may be seen at operation as multiple small nodules, but more commonly are incidental findings on microscopic examination. Microscopically, the changes range from a mild ( Figure 31.4 ) to a substantial increase in the number of mesothelial cells ( Figure 31.5 ), most of which have transformed from flat and relatively inconspicuous to cuboidal or even columnar. With marked hyperplasia, the mesothelial proliferation appears as sheets, clusters, ribbons, tubules, and sometimes as papillary formations that can be misinterpreted as metastatic adenocarcinoma ( Figure 31.6 ). Psammoma bodies are encountered occasionally and eosinophilic elongated cells resembling rhabdomyoblasts have been described.

Reactive mesothelial cells tend to be uniform in appearance. With minor degrees of reactivity, the nuclei are small, regular, round, or oval, and exhibit central nucleoli. The cytoplasm is eosinophilic or sometimes vacuolated and contains acid mucin (predominantly hyaluronic acid). With increasing degrees of reactivity, the nuclei enlarge and the chromatin increases. Nucleoli become more apparent and, in the extreme case, may become quite large and prominent ( Figure 31.7 ). Cells may become binucleated or multinucleated. In cytologic preparations the large macronucleoli may be mistaken as evidence for malignancy.

The immunoprofile of normal mesothelium differs from that expected of epithelial tissue. As anticipated, it expresses cytokeratin intermediate filaments typical of epithelial cells. But it also expresses vimentin and desmin, which are indicative, respectively, of mesenchymal differentiation and specialization into muscle. In contrast, ovarian surface epithelium is immunoreactive for vimentin and desmin in fewer than half of cases. Ovarian inclusion cysts are nonreactive for vimentin and desmin, as are benign and borderline ovarian tumors. Mesothelial hyperplasia can occur within the superficial ovarian stroma overlying a borderline tumor and in such cases can be misinterpreted as invasive tumor. The differential reactivity of mesothelium (and mesothelioma) and müllerian tissue (and ovarian tumors) is discussed more fully in the following sections.

With greater degrees of injury, a layer of spindle-shaped mesenchymal cells may sometimes appear below the meso­thelial cells. In the resting state, this layer is inconspicuous, but, when stimulated, the cells may proliferate and produce a highly cellular desmoplastic tissue. Cells also express cytokeratin, vimentin, and desmin. These cells simulate myofibroblasts, and are thought to give rise occasionally to the muscular cells in the condition ‘disseminated peritoneal leiomyomatosis’ (see later).

The exuberant and sometimes pseudoinfiltrative growth that mesothelium can show, together with the increased mitotic activity that is frequently observed, may lead to a false impression of primary or metastatic carcinoma, despite the benign cytologic appearance of the cells ( Figure 31.6 ). Carcinoma cells generally demonstrate greater nuclear pleomorphism and more conspicuous mitotic activity. However, clusters of mesothelial cells are easily mistaken for metastatic carcinoma. This is true especially when mesothelial cells extensively involve sinusoids in pelvic lymph nodes either as small papillary clusters or as sheets of somewhat discohesive cells. Exuberant surface proliferations, sometimes forming sessile or polypoid nodules, can also simulate mesothelioma, a problem also encountered in the walls of hernia sacs. A useful morphologic feature that can help distinguish reactive mesothelial cell aggregates from metastatic carcinoma is their orientation at low-power magnification to one another (often in a line that can be traced for some considerable distance) ( Figure 31.6 ) and their relation to the position of the original peritoneal surface (as demonstrated by the presence of the peritoneal elastic lamina).

Organization of surface proliferative lesions and inflammatory exudates may leave adhesions of variable density, ranging from delicate strands of loose connective tissue to broad bands of dense, well-vascularized collagenous fibrous tissue. Entrapped inflammatory exudate within granulation tissue and proliferating sheets of mesothelial cells may lead to mesothelial (peritoneal) cyst formation. These may not become clinically apparent until months or years after the precipitating event.

Mesothelial hyperplasia must be distinguished from malignant peritoneal mesothelioma. The presence of necrosis, marked nuclear pleomorphism, and deep infiltration favors malignant mesothelioma. Immunostains may help in the differential diagnosis. Strong immunoreactivities for p53 and epithelial membrane antigen (EMA; nuclear and cytoplasmic, respectively) are characteristic of the cells of malignant mesothelioma but not reactive mesothelial cells; in contrast, hyperplasic mesothelial cells are usually desmin positive. Proliferative markers such as Ki-67 may also be helpful (approximately 25% vs 5% labeling index for malignant mesothelioma vs mesothelial hyperplasia, respectively). In some cases, however, the distinction between a reactive and malignant mesothelial lesion may be difficult or impossible, particularly in a biopsy samples. An apparently benign mesothelial proliferation occasionally precedes the appearance of a malignant peritoneal mesothelioma.

Mesothelial hyperplasia should also be distinguished from a borderline serous tumor of primary peritoneal origin. Grossly visible tumor, columnar cells with or without cilia, the presence of neutral mucin, and numerous psammoma bodies all favor a serous tumor. Immunohistochemical markers for epithelial differentiation may also be useful in the distinction (see Chapter 25 ).

Peritoneal Inclusion Cysts

Peritoneal inclusion cysts are unilocular or multilocular mesothelial-lined lesions that occur almost exclusively in women in the reproductive age group. They usually involve the pelvis, although may occur in other abdominal locations, including the omentum and mesentery, and are frequently associated with prior abdominal surgery. The origin of peritoneal inclusion cysts remains controversial; some authors consider them reactive lesions that develop in response to injury, whereas others favor their neoplastic nature.

Unilocular peritoneal inclusion cysts are usually incidental findings at laparotomy. Multilocular peritoneal inclusion cysts, also referred to as ‘benign cystic mesotheliomas,’ frequently form large bulky masses ( Figures 31.8–31.11 ) simulating a cystic ovarian tumor. Cysts are thin walled, contain clear proteinaceous fluid, and are lined by a single layer of flat to cuboidal, hobnail-shaped, mesothelial cells ( Figure 31.12 ) with bland nuclear features, although a degree of reactive atypia is occasionally seen. Tubal and squamous metaplasia of the mesothelial lining sometimes occurs. Inflammatory infiltrates, if present at all, are limited to sparse lymphocytic collections. The mesothelial cells are typically immunoreactive for calretinin, and less frequently positive for estrogen (ERs) or progesterone receptors (PRs), or both.

In patients who have had peritonitis, fibrinous adhesions that are superficial to the deeper lining of normal mesothelium may develop and the underlying serosa can be mistaken for invasive serous carcinoma until attention is paid to its regularity and benign histology ( Figure 31.13 ).

Peritoneal inclusion cysts are confused with multilocular cystic lymphangiomas, which typically occur in children, more often in boys. Lymphangiomas are almost always localized in the mesentery of the small intestine, mesocolon, omentum, or retroperitoneum. They contain chylous material and, microscopically, show intramural lymphoid aggregates and smooth muscle, which are absent in peritoneal inclusion cysts.

Although no malignant behavior has been reported in peritoneal inclusion cysts, recurrence occurs in approximately one-half of cases from months to several years postoperatively. GnRH agonists or tamoxifen have successfully been applied to some patients.