Disorders of the Peritoneum

Background

The presence of ectopic decidua in the peritoneal cavity is a relatively common finding in pregnant females, seen in up to 97% of pregnant women and focally involving the omentum in one series. It appears to be associated with a physiologic metaplastic response of the subcoelomic mesenchymal cells to the elevated levels of circulating progesterone hormone during pregnancy. Another possible explanation is that the systemic hormonal response affects preexisting foci of endometriosis and that the ectopic endometrial tissue shows an analogous response to that seen in the uterine endometrium. It usually involutes within 4 to 6 weeks postpartum.

Its occurrence in nonpregnant women is a rare event, and this diagnosis should trigger an active search for a source of hormone production, such as exogenous administration of progesterone or a hormone-producing tumor. In this setting, this benign reaction is best regarded as “pseudodecidualized” tissue.

Clinical Features

Ectopic decidual tissue typically occurs on the surface of the pelvic organs, such as the ovarian or tubal serosal surfaces. However, involvement of the peritoneum, serosa of the gastrointestinal tract, omentum, and mesentery may also be seen. In most cases, it is an incidental finding, usually discovered during cesarean section or during another intra-abdominal operation. However, ectopic deciduosis may occasionally simulate acute abdominal emergencies, such as acute appendicitis, or may cause intra-abdominal bleeding.

Diagnosis

Although usually a microscopic finding, if grossly evident, ectopic decidua typically appears as white, yellowish, or red small nodules located on the serosal surfaces of abdominal organs and peritoneum. Microscopically, decidua shows features similar to decidualized endometrial stroma, being composed of a well-defined collection of bland-appearing large polygonal cells with distinct cell borders, round, centrally placed nuclei, small nucleoli, and abundant eosinophilic cytoplasm ( Fig. 23.1A ).

Immunohistochemistry and Differential Diagnosis

Immunoperoxidase studies are not necessary to make the diagnosis of deciduosis. However, the main differential diagnosis is malignant mesothelioma with deciduoid features (see Fig. 23.1B ). Although the latter entity is malignant, it may show bland cytologic characteristics, closely resembling ectopic decidualized tissue. The presence of areas of the tumor showing nuclear pleomorphism and mitotic activity helps in its distinction from ectopic decidua. Moreover, the neoplastic cells in mesothelioma are positive for keratins, calretinin, and WT-1. A more detailed immunoprofile of mesothelial proliferations is discussed later in the chapter.

The clinical setting of the development of deciduoid mesothelioma is controversial; although the initial descriptions regard this malignant neoplasm as a disease of young women with no history of asbestos exposure, other authors believe that the epidemiology of this tumor follows that of conventional epithelioid mesothelioma; namely, it is a disease of older male adults.

Treatment and Prognosis

The prognosis is excellent for cases of ectopic decidua not complicated by bleeding. Surgical ablation suffices the treatment requirements. The potential for recurrence of this condition is unknown, but presumably it may recur during subsequent pregnancies.

Background

Endosalpingiosis is defined by the presence of foci of epithelium resembling fallopian tube lining outside this anatomic location. It affects approximately 7% of the female population in the reproductive age.

Clinical Features

Although some authors believe that endosalpingiosis may be a source of abdominal pain, it is more often an incidental finding during abdominal surgery and is frequently seen in association with other pelvic pathologic findings, such as endometriosis, leiomyomata, hydrosalpinx, and ovarian neoplasms.

Pathology

Macroscopic evidence of endosalpingiosis is rarely seen involving the peritoneum, omentum, retroperitoneal and abdominal lymph nodes, wall of abdominal organs, and on the surface of pelvic organs. Most commonly, endosalpingiosis is a microscopic finding, consisting of glandular and tubular structures lined by low cuboidal ciliated epithelium ( Fig. 23.2A ).

Immunohistochemistry

Endosalpingiosis, as well as normal fallopian tube epithelium, stains strongly with PAX8, phospho-SMAD2, BCL2, and FOXJ1.

Differential Diagnosis

No endometrial stromal cells, hemosiderin deposition, or desmoplastic tissue reaction is present in association with these nests. Although these findings may raise the concern of metastasis, especially when present in a lymph node, the appearances are bland, with no mitotic figures or necrosis (see Fig. 23.2B ). Endosalpingiosis can vary in complexity (see Fig. 23.2C ) and rarely may assume a florid appearance with large cystic spaces that may mimic metastatic carcinoma.

Treatment and Prognosis

Endosalpingiosis is typically sampled during procedures for other disorders, including malignancy. Other than the fact that this entity appears to have increased in frequency in association with low-grade serous tumors, it is of no clinical consequence.

Background

Endocervicosis is defined by the presence of ectopic endocervical-like glands (i.e., glands lined by columnar cells with mucinous cytoplasm akin to that seen in the endocervix). This condition is encountered in females of reproductive age. Although endocervicosis likely results from a metaplastic process, lesions have been repeatedly associated with a history of cesarean section, raising the possibility of implantation as an etiologic mechanism.

Clinical Features

Endocervicosis most commonly affects the urinary bladder. Most patients present with urinary symptoms such as pain, dysuria, frequency, and hematuria, clinically mimicking a urinary bladder neoplasm or infection. Rare cases of endocervicosis have also been described in the uterine cervix, axillary lymph nodes, rectum, vagina, and small intestine. Although the condition is generally considered benign, there have been two case reports of adenocarcinoma arising in association with endocervicosis.

Pathology

Endocervicosis may form large masses, measuring up to 5 cm, and thus may mimic a neoplasm. The tumor-like prominence is usually located in the posterior bladder wall or dome and may project into the bladder cavity. Microscopically, endocervical-like glands, some of which show cystic dilation, characterize this entity. The cells are columnar in appearance with evidence of mucin production (see Fig. 23.2D ). Mild atypia, as well as cilia, may be seen. In most cases, ruptured glands with extravasation of mucin into the surrounding stroma, eliciting a stromal reaction, are present. Mitoses are rare, if present at all.

Differential Diagnosis

The major differential diagnosis is with metastatic well-differentiated adenocarcinoma or a component of pseudomyxoma peritonei (PP), due particularly to the prominent admixture of glands and stroma. However, appreciable atypia is not present, nor is there extravasated mucin.

Treatment and Prognosis

The prognosis is excellent, and surgical excision should be curative.

Background

Endometriosis is one of the most common gynecologic diseases, affecting 6% to 10% of American women. In patients being treated for infertility, endometriosis is much more common and can be encountered in up to 60% of cases. It is classically defined by the presence of endometrial-like epithelium and stroma outside the endometrial cavity. However, endometrial stroma may also be present in the absence of glands—so-called stromal endometriosis—which accounts for approximately 6% of cases of endometriosis.

Although endometriosis is typically seen in reproductive-age females, it has been documented across the life course, including in premenarcheal adolescents. Furthermore, approximately 70% of adolescents with pelvic pain unresponsive to medical therapy may have endometriosis; however, conservative management therapies in this age group may ultimately delay definitive diagnosis.

Clinical Features

Most cases of endometriosis involve the pelvic organs and are associated with chronic pelvic pain (not related with the menstrual cycle), dyspareunia, dysmenorrhea, and infertility (i.e., ovarian endometriosis). When affecting peritoneal-lined organs, females with endometriosis may be asymptomatic or present with chronic, vague abdominal pain. Diagnosis depends on identification of endometriotic lesions by laparoscopy or laparotomy, with confirmatory biopsy.

Pathology

Classic Criteria

Macroscopically, endometriosis might present as small dark red, black, or bluish cysts or nodules on the surface of peritoneal and pelvic organs ( Fig. 23.3A ); occasionally, the focus of endometriosis may appear whitish and be associated with adhesions. In cases of extensive involvement of the ovary, bleeding may lead to the formation a cystic mass, or endometrioma.

Histologically, endometriosis is characterized by the following:

• The presence of ectopic endometrial-like glands (i.e., pseudostratified columnar glandular epithelium), which may show similar alterations when compared with the glands topically located in the uterine cavity

• Spindled endometrial stroma

• Hemosiderin deposition either within macrophages or in the stroma (see Fig. 23.3B )

In many instances, the classic diagnostic triad of these components is not present or the endometrial glands and stroma may be obscured by hemorrhage, foamy cells, and hemosiderin-laden macrophages such that the diagnosis may be suggested but histologic confirmation may not be possible. In other cases, endometrial stroma may be present in isolation, with no associated endometrial-like glands (“stromal endometriosis”). In some instances, the glands may be situated adjacent to other visceral structures, such as bowel mucosa (see Fig. 23.3C ). Marked (pseudo)decidual changes may obscure endometriosis during pregnancy or hormonal therapy (see Fig. 23.3D ). Histologic features described in association with stromal endometriosis include reactive mesothelial proliferation ( Fig. 23.4A and B ), inflammation, giant cell or granulomata, and myxoid changes.

Adolescent Versus Adult Endometriosis

There is growing evidence that endometriosis in adolescents differs from that seen in adulthood. Adolescent lesions tend to be subtle and transient. Laparoscopically, they frequently appear clear, red, white, or yellow-brown rather than having the classic black/blue “powder-burn” lesions that may be seen in adult endometriosis ( Fig. 23.5 ). Moreover, the histologic features of such biopsies may appear non-descript, consisting of fibrosis, calcification, or macrophages rather than endometrial glands and/or stroma as might be encountered in adults.

Treatment and Prognosis

Treatment of endometriosis, including medical or surgical therapies, is highly dependent on the presence of symptoms, being reserved mainly for symptomatic patients and those with extensive disease. Surgical options include laser coagulation and resection. Medical interventions include the use of drugs that function as estrogen antagonists, such as oral contraceptives, progesterone, danazol, and gonadotropin-releasing hormone (GnRH) agonists. Other newer approaches, such as progesterone receptor modulators, GnRH antagonists, aromatase inhibitors, tumor necrosis factor-alpha inhibitors, angiogenesis inhibitors, matrix metalloproteinase inhibitors, and estrogen receptor β-agonists are under investigation.

The prognosis is variable and related to the extent of involvement of the ovaries and peritoneal cavity by endometriosis and the depth of infiltration. Recurrence may be seen, especially in cases initially associated with extensive peritoneal or ovarian involvement or deeply infiltrating disease. In vitro fertilization may be necessary to overcome infertility associated with extensive endometriosis.

Background

Polypoid endometriosis is a variant of endometriosis that has a tendency to mimic a neoplasm clinically, surgically, and by pathologic examination. The lesions tend to grow as polypoid masses: hence the term polypoid endometriosis , with only a subset of examples showing histologic features of polyps (i.e., prominent thick-walled vessels, fibrous stroma, irregularly spaced and cystic glands). From a historical perspective, the term polypoid endometriosis was first used by Mostoufizadeh and Scully in their description of a variant of endometriosis that shared histologic features with endometrial polyps. Since their original description, there have been only a handful of case reports, with the largest series on the subject reported by Parker et al.

Clinical Features

In a series of 24 women, patients' ages ranged from 23 to 78 years old (median age of 55 years old) with 60% of the patients being older than 50 years old. Slightly fewer than half of the patients were taking exogenous hormones, possibly a contributing factor to the occurrence of endometriosis in older (peri- and postmenopausal) women. Patients most commonly present with symptoms related either to a pelvic mass, vaginal mass (with associated bleeding), or large intestine obstruction. Practically any site of the abdominal cavity may be affected, with involvement of the colon, pelvic structures, vaginal mucosa, omentum, and retroperitoneum having been described in descending order of frequency. In approximately one-third of the cases, multiple sites are affected.

Pathology

On gross examination, lesions may be of varying size, ranging from 0.4 to 14 cm in maximal dimension. They tend to appear as tan/brown, white/gray, or pink/red polypoid masses involving mucosal or serosal surfaces or within an endometriotic cyst ( Fig. 23.6A, C ).

Histologically, the lesions are composed of an admixture of endometriotic glands and stroma, of which the former may show varying degrees of proliferation and metaplastic change (see Fig. 23.6B and D ), including tubal, mucinous, squamous, and papillary syncytial metaplasia. The stroma typically resembles proliferative phase endometrial stroma without stromal cytologic atypia. In the majority of the cases, stromal fibrosis and numerous thick-walled vessels are present, similar to that seen in endometrial polyps. In some, a discrete endometrial polyp is present (see Fig. 23.6C and D ).

The principal differential diagnostic considerations include the distinction of polypoid endometriosis from müllerian adenosarcoma, particularly because the latter can arise from peritoneal endometriosis ( Fig. 23.7 ). Müllerian adenosarcoma can be distinguished from polypoid endometriosis by (1) the presence of stromal papillae and frondlike proliferations that project into glandular or cystic spaces, (2) mild stromal atypia (at least), and (3) periglandular cellular stromal cuffing. Also within the differential diagnosis is endometrial stromal sarcoma (ESS) with glandular differentiation, which can be distinguished from polypoid endometriosis by (1) its characteristic finger-like permeative growth pattern, (2) its propensity for lymphatic/vascular invasion, and (3) its focal presence of usually only endometrioid-type glands.

Treatment and Prognosis

Polypoid endometriosis is benign. In the series by Parker et al., follow-up in 17 (of 24) patients showed that 15 patients were alive without evidence of disease (the range of follow-up was 1 to 20 years with mean of 5.9), one patient was alive with endometriosis at 18 months, and one patient had died of unrelated causes. Similar to typical endometriosis, malignant transformation may potentially occur, with epithelial, mesenchymal, and mixed epithelial-mesenchymal tumors arising out of this lesion. Rarely, polypoid endometriosis can be the source of a well-differentiated endometrioid carcinoma, analogous to that seen in the endometrium ( Fig. 23.8 ).

Adenocarcinoma Arising in Endometriosis

Adenocarcinoma arising in the setting of ovarian endometriosis is seen in pre- or postmenopausal women and is not associated with hormone replacement therapy (HRT), whereas extraovarian adenocarcinoma arising in association with endometriosis tends to occur in postmenopausal females and has a stronger correlation with HRT. The most common histologic subtypes of adenocarcinoma encountered in these patients are endometrioid and clear cell, which account for 90% of the cancers ( Fig. 23.9 ). Similarly, cases of extrauterine ESS arising from endometriotic foci have been reported and show the typical permeative growth pattern and cytomorphologic features of those tumors that arise within the uterus.

Background

There is little argument that extraovarian müllerian serous tumors can arise in the peritoneal cavity. Whether the origin is endometriosis or endosalpingiosis is unclear, inasmuch as it is virtually impossible to document the source, save for the occasional tumor arising in endometriosis. The rather high frequency of concurrent primary serous tumors and endosalpingiosis raises the possibility that the latter predisposes to these lesions. As discussed in later chapters, the absolute percentage of high-grade pelvic serous tumors that can be attributed to the peritoneum is unclear; the fallopian tube has been implicated in the origin of up to 45% of these tumors, including those previously assumed to be peritoneal in origin. The link between a potential extraovarian or extratubal origin for lower-grade serous tumors is more compelling, given the weak connection with the distal tube and the fact that many of these tumors do not have an obvious source in the ovarian cortex or surface epithelium. However, it is still conceivable that most of these tumors are derived from epithelium that originated in the tube, albeit present in the submesothelial mesenchyme at the time of neoplastic transformation. Whether these tumors arise directly from a “müllerianized mesothelium” is virtually impossible to either prove or refute. Thus the term primary peritoneal should not be assumed to connote an origin in mesothelium (as opposed to müllerian epithelium) per se until there is more evidence to support this.

Primary peritoneal papillary serous tumors include borderline or serous tumors of low malignant potential, as well as low- and high-grade papillary serous adenocarcinomas. Similar to the ovarian and tubal serous tumors, the borderline serous tumors afflict a younger group with a median age of 30 years old at diagnosis, whereas most patients diagnosed with papillary serous adenocarcinoma are peri- or postmenopausal, with a median age of 60 years old. Jordan et al. showed women diagnosed with primary peritoneal serous carcinoma to be significantly older than those with papillary serous carcinoma of the ovary. They found that ovarian and tubal serous carcinomas had similar patient profiles; and in contrast, patients with peritoneal carcinoma were more likely to be obese and parity increased risk. However, the expression profiles are similar albeit with differences in frequency of loss of heterozygosity (LOH) at different chromosomal loci.

Interestingly, the reported incidence of primary papillary serous carcinoma has shown a significant increase since the late 1990s, with a most accentuated elevation (more than 13% per year) in non-Hispanic and white females. The reason for this purported increase is uncertain. It is possible that this is an artifact of tumor classification (ovary vs. tube vs. peritoneal), but given the lack of knowledge about this subset of tumors, it bears further investigation.

Clinical Features

The clinical presentation of all the primary peritoneal müllerian neoplasms is quite similar and usually characterized by symptoms related to large, frequently cystic abdominal and pelvic masses that may show involvement of multiple organs at time of diagnosis. Pain, abdominal distention, and intestinal obstruction might develop in the setting of bulky tumors. Malignant peritoneal effusions may be present. In addition, CA-125 is often elevated in patients diagnosed with primary peritoneal serous neoplasms. Radiologically, primary peritoneal serous carcinoma is characterized by the presence of ascites, and peritoneal nodules and masses that enhance with intravenous contrast material on computed tomography (CT) and magnetic resonance imaging (MRI) studies. Occasionally, calcifications, which correspond to psammoma bodies on histologic examination, may be identified. In accordance with the definition of primary peritoneal serous carcinoma, radiologic evidence of ovarian lesions is usually not identified.

Pathology

The pathologist who is confronted with a primary peritoneal serous lesion must exclude several lesions, including the following:

• Endosalpingiosis

• A borderline serous tumor

• Low-grade serous carcinoma, including a variant known as psammocarcinoma

• High-grade serous carcinoma

Papillary serous carcinomas of the peritoneum resemble their ovarian counterparts; by definition, ovaries are uninvolved or show very limited extent of involvement (confined to surface or superficial cortex). These tumors often form large and multifocal cystic, papillary, and solid tumors, typically with seeding, and extensive involvement of the peritoneal lining and omentum may be seen at surgery. Microscopically, papillary serous adenocarcinomas are usually high-grade tumors, characterized by complex and interconnecting papillary formations lined by cuboidal cells showing moderate or marked cytologic atypia, high nuclear/cytoplasmic (N/C) ratio, cellular stratification, increased mitotic activity, including atypical figures, necrosis, and invasion of the underlying stroma ( Fig. 23.10A and B ). A specific histologic source for the tumor is difficult to establish, although careful inspection of the entire fallopian tube is important to exclude a possible total origin (see Chapter 27 ). Rarely, these tumors can be found in association with hemorrhagic cysts, suggesting an origin in endometriosis (see Fig. 23.10F ).

Although most primary peritoneal serous carcinomas are high grade, low-grade carcinomas similar to those in the ovary may be encountered, and a small subset of tumors with extensive psammoma bodies are classified as psammocarcinomas. The latter is a rare variant of papillary serous adenocarcinoma that is characterized by low to moderate nuclear grade, local invasiveness, and a somewhat more indolent behavior. Overall, these tumors appear as invasive or frankly malignant implants (see Chapter 27 )—that is, they have numerous papillary clusters in a dense fibrous tissue reaction with retraction artifact (see Fig. 23.10C and D ). Tumors placed in the borderline or low malignant potential category are distinguished from carcinoma on the basis of blander histologic features and lack of destructive invasive growth, essentially the same criteria for noninvasive implants of borderline serous neoplasia (see Chapter 27 ).

The differential diagnosis of primary peritoneal serous neoplasia includes a serous tumor arising from another site and confusion with benign ( Fig. 23.11A ) and neoplastic mesothelial proliferations (discussed later). Another potential source of confusion is a rare incidental discovery of an epithelioid trophoblastic tumor in the peritoneum. These tumors can mimic epithelial, as well as germ cell, neoplasia in the peritoneum (see Fig. 23.11B ).

Immunoperoxidase studies are ineffective in differentiating between ovarian and primary peritoneal papillary serous adenocarcinomas. In both instances, the neoplastic cells show reactivity for cytokeratins (AE-1/AE-3 and Pan-keratin), epithelial membrane antigen (EMA), B72.3, carcinoembryonic antigen (CEA), WT-1, and Leu-M1. However, immunostains might be extremely useful in the differential diagnosis with malignant mesothelioma ( Table 23.1 ). Although both neoplasms are positive for WT-1 (monoclonal antibody) and cytokeratins, calretinin is almost always exclusively expressed in benign and malignant mesothelial proliferations, whereas Ber-EP4 has 95% sensitivity and 91% specificity for carcinoma, and cytokeratin 5/6 is positive in more than 90% of mesothelioma. In addition, estrogen receptor is typically negative in mesothelioma, whereas it is positive in approximately 95% of primary peritoneal serous carcinoma. Immunostain for progesterone receptor is less reliable for this distinction, with positivity reported in 30% to 65% of serous tumors.

Molecular analysis of papillary serous carcinomas arising from the peritoneal surface has led to the discovery of its association with germline mutations of BRCA-1 gene, in rates similar to those noted in ovarian counterparts. Therefore, women with known mutations of this gene should undergo thorough follow-up not only for breast and ovarian carcinomas but also for primary peritoneal papillary serous carcinomas. Also evidenced by molecular studies is the fact that primary peritoneal papillary serous carcinoma may have a multifocal origin in some cases, as substantiated by LOH at the multiple allelic loci, such as androgen receptor (AR) locus, WT-1 gene, and of 6q. LOH of AR gene is more often seen in patients harboring germline mutations of the BRCA-1 gene. Similarly to papillary serous carcinoma arising in the ovary, serous carcinomas of the peritoneal surface also showed LOH at the p53 loci, located on chromosome 17, in 75% to 100% of cases.

Treatment and Prognosis

Primary papillary serous tumors of borderline or low-grade malignant potential have a good prognosis and require conservative therapy. Biscotti and Hart showed that of 14 patients who underwent treatment, which included surgery and adjuvant chemotherapy, only one patient died of complication related to therapy. None of the patients died of disease.

Primary peritoneal high-grade papillary serous carcinoma is clinically comparable with advanced-stage ovarian papillary serous carcinomas. Therapy options include cisplatin-based chemotherapy and surgery. Surgical approach encompasses cytoreductive technique and less aggressive debulking operations. In one series, patients who underwent cytoreductive surgery appeared to have a longer overall survival, suggesting that the amount of residual disease is a prognostic factor. In another series, combination of chemotherapy and cytoreductive surgical technique had a 5-year survival of 27%. In a recently reported series of patients with advanced and recurrent ovarian and peritoneal surface papillary serous carcinomas, the prior surgical stage, completeness of cytoreduction, and response to chemotherapy before surgery were statistically significant prognostic factors.

Background

Smooth muscle neoplasms of the peritoneal cavity encompass two main entities: leiomyoma and leiomyosarcoma. Another condition that is included under the designation of smooth muscle neoplasms is leiomyomatosis peritonealis disseminata (LPD); this entity is discussed in Chapter 20 .

To be considered a primary peritoneal neoplasm, a thorough examination of the uterus has to be performed to exclude “metastatic” disease. Leiomyomata originating in the retroperitoneum and abdomen are rare, but they unquestionably exist and are more common in females. Most often they are encountered as a tumor mass arising in the wall of the gastrointestinal tract, mainly the colon and rectum. Patients in this latter group are usually within the fifth and sixth decades, and males are more commonly affected than females. Leiomyosarcomas of the abdominal cavity are more often encountered in the retroperitoneum and show female preponderance affecting patients in the sixth and seventh decades of life.

Clinical Features

Smooth muscle neoplasms of the abdominal cavity and retroperitoneum may be asymptomatic or present as a mass that might impinge an abdominal organ, causing obstruction. In addition, when these tumors arise from the gastrointestinal tract, they may protrude into the bowel, cause obstruction, mimic carcinoma, and lead to ulceration of the mucosa with associated gastrointestinal bleeding. Leiomyomata are usually smaller than leiomyosarcomas, which might reach large proportions.

Morcellation and Smooth Muscle Neoplasms

Recently, hysterectomy and myomectomy facilitated by power or hand morcellation have come under scrutiny due to the inadvertent morcellation of malignancies. Inadvertent morcellation of ESS, endometrial carcinoma, uterine serous carcinoma, and leiomyosarcoma have all be reported, with the overall risk of occult cancer on a morcellated specimen approaching 0.73%. When variants of leiomyoma (e.g., cellular leiomyoma, atypical leiomyoma) and STUMP are included, the rate of inadvertent morcellation rises to 1.2%.

Re-exploration in patients with STUMP or leiomyosarcoma reveals disseminated peritoneal sarcomatosis in a significant number of cases with at least one study suggesting the rate may be as high as 72.7%. Furthermore, morcellation of occult uterine leiomyosarcoma has been associated with decreased overall survival, decreased disease-free survival, and a higher risk of abdominopelvic recurrence.

Pathology

Macroscopically, benign smooth muscle neoplasms (leiomyomata) usually have well-defined contours, with a firm, whorled, tan to white cut surface. Foci of hemorrhage may be present, as well as focal cystic degeneration. In cases of leiomyosarcoma, malignant features, such as necrosis and invasion of surrounding structures, are often seen. Occasionally, leiomyomata and leiomyosarcomas can be seen in close association with a vascular structure, such as the inferior vena cava, and the morphologic features are consistent with origin from the vessel wall. When the diagnosis of a leiomyosarcoma is rendered in a retroperitoneal or abdominal mass, origin from a uterine primary should be excluded.

Microscopically, these benign and malignant neoplasms are usually characterized by the typical features associated with smooth muscle neoplasms, being composed of a proliferation of spindle cells arranged in long fascicles with elongated, cigar-shaped nuclei, vesicular chromatin; variably prominent nucleoli, and moderate amounts of eosinophilic cytoplasm ( Fig. 23.12 ). Rarely, cells with epithelioid morphology are present and, exceptionally, this morphology may predominate in the neoplasm, imitating an epithelial neoplasm and often making the histologic recognition challenging. Leiomyomata can undergo several degenerative phenomena, including infarction, cystic changes, hydropic or edematous degeneration, and stromal hyalinization.

The current accepted criterion for malignancy for smooth muscle neoplasms occurring in the abdominal cavity or retroperitoneum of females is the presence of more than 10 mitoses per 50 high-power fields. Although not indicative of malignancy, hypercellularity is a worrisome feature. The presence of atypical hyperchromatic nuclei should also trigger a more extensive search for diagnostic malignant features (e.g., necrosis, mitotic activity).

Immunohistochemistry and Biomarkers

Although the morphologic features of smooth muscle neoplasms may allow for an accurate diagnosis, immunoperoxidase studies are helpful in confirming the smooth muscle origin in less typical cases or small core needle biopsies. Table 23.2 shows the immunophenotypic characteristic of mesenchymal neoplasms of the peritoneum. Smooth muscle tumors are classically positive for SMA, desmin, and h-caldesmon. The extent of expression of these markers by tumor cells varies from diffuse to focal, and this variability in expression, not surprisingly, might affect interpretation of small core needle biopsies. One should keep in mind that the morphology, if characteristic, should govern the diagnosis. Malignant tumors, for example, might have decreased expression or even lose expression of these markers. Other markers that can be expressed by smooth muscle tumors include cytokeratins and EMA, which can be encountered in up to 40% of these tumors. Estrogen and progesterone receptors are often positive in leiomyomata, occurring in reproductive-age females; however, leiomyosarcomas appear to have significantly less expression of estrogen receptor and progesterone receptor. S-100 protein, glial fibrillary acidic protein (GFAP), and c-kit are negative.

Differential Diagnosis and Pitfalls

The differential diagnosis of smooth muscle tumors includes other mesenchymal neoplasms that are often encountered in the abdomen, such as gastrointestinal stromal tumor (GIST), desmoid fibromatosis, and nerve sheath tumors, such as schwannomas and malignant peripheral nerve sheath tumor (MPNST).

In GISTs, the tumor cells are uniform and show a pale eosinophilic cytoplasm with a syncytial appearance. Immunoperoxidase studies in GIST are somewhat overlapping with smooth muscle neoplasms; however, desmin is only rarely positive in GIST (fewer than 5% of the cases), whereas c-kit is characteristically positive in the majority of these tumors and negative in smooth muscle neoplasms (see Table 23.1 ). In addition, GISTs are positive for DOG-1 in more than 90% of cases, whereas smooth muscle tumors are only rarely (0.3% to 10% of cases) positive for this novel marker.

Desmoid fibromatosis shows long hypocellular fascicles composed of cells with tapered ends. Occasionally, this neoplasm may show positivity for SMA and desmin in a very focal pattern, consistent with their myofibroblastic origin; h-caldesmon is negative. In contrast to desmoid fibromatosis, smooth muscle neoplasms are negative for β-catenin.

Neoplasms of nerve sheath origin (schwannoma and MPNST) usually show fascicles formed by elongated cells with tapered nuclei and display variable positivity for S-100 protein and GFAP. They are negative for SMA and desmin. MPNST also may show loss of H3K27me3.

Treatment and Prognosis

The treatment of leiomyomata consists of simple excision. There is a small risk of recurrence. Leiomyosarcomas carry a poor prognosis with high incidence of recurrence and metastasis. The preferential sites of development of metastatic disease include lungs and liver. Therapy should include surgery with adjuvant chemotherapy and irradiation. The 5-year survival is approximately 30%.