Practice Essentials
Peritoneal carcinomas are divided into primary and secondary peritoneal tumors. Primary peritoneal carcinomas originate from the cells lining the peritoneum. Secondary peritoneal carcinomas usually invade locally or metastasize into the peritoneum from adjacent or remote organs.
A number of primary cancers have been described to originate from the peritoneum, some of which have been implicated in many cases of carcinomas of unknown primary origin. Ovarian cancer arising in women several years after bilateral oophorectomy is believed to be one of these primary peritoneal cancers. Primary peritoneal cancer has been linked to certain variants of BRCA1/2. Women with higher risk of ovarian cancer also have increased risk of peritoneal cancer. Other described primary peritoneal cancers and tumors include the following:
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Malignant mesothelioma
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Benign papillary mesothelioma
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Desmoplastic small round cell tumors
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Peritoneal angiosarcoma [1]
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Peritoneal hemangiomatosis
Signs and symptoms
Primary peritoneal carcinoma usually manifests as abdominal distention and diffuse nonspecific abdominal pain secondary to ascites. This tumor is described almost exclusively in women.
Patients with malignant peritoneal mesothelioma usually present with symptoms and signs of advanced disease, including the following:
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Abdominal pain
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Ascites
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Weight loss
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An abdominal mass
See Presentation for more detail.
Diagnosis
The workup of peritoneal includes the following steps:
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A pelvic imaging study, if there is clinical suspicion of peritoneal carcinoma.
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Peritoneal lavage, performed using a percutaneous closed technique or at the time of
Pathophysiology
The peritoneum is a serous lining of mesothelial cells with a rich vascular and lymphatic capillary network that covers the abdominal and pelvic walls and organs. The peritoneal cavity, enclosed by visceral and parietal peritonea, is the largest potential space in the body. Any pathologic process involving the peritoneal cavity can easily disseminate throughout this space by means of unrestricted movement of fluid and cells.
Primary malignant diseases arising from the peritoneal cavity include the following:
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Malignant mesothelioma
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Cystic mesothelioma
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Primary peritoneal carcinoma
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Desmoplastic small round cell tumor
Malignant mesothelioma
Malignant peritoneal mesothelioma is a rare but aggressive tumor derived from the peritoneal mesothelium. Although most mesotheliomas involve the pleural surface, 20-30% arise from the peritoneum and are associated with asbestos exposure and abdominal therapeutic radiation. Association of malignant peritoneal mesothelioma and asbestos exposure has been reported to be as high as 83% In a series of 102 cases of asbestosis, approximately 8% of patients were diagnosed with peritoneal mesotheliomas. [5]
Mesotheliomas are composed of strands of connective tissue covered by cells that react positively to periodic acid–Schiff staining in the cytoplasm. These cells grow in multiple layers, forming papillary or tubular formations. Histologically, malignant mesothelioma is classified into epithelial, sarcomatoid, and mixed. Clinical features of malignant mesothelioma include abdominal pain, abdominal or pelvic masses, and thrombocytosis; ascites is the major factor in the disease morbidity and mortality. [6] Rarely, the tumor spreads into the pleural space.
On CT scan, this neoplasm can appear as peritoneum-based masses or abdominal ascites with associated nodular or diffuse peritoneal thickening.
This locally aggressive disease is difficult to treat or palliate. Commonly, treatment regimens combine aggressive cytoreductive surgery with intraperitoneal chemotherapy. Thorough cytoreductive surgery is the cornerstone of current treatment, while hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) is a promising strategy in suitable patients. [7]
Cystic mesothelioma
Cystic mesothelioma is a rare intermediate-grade tumor with a predilection for surfaces of the pelvis. [8] Typically, these lesions consist of multiple grapelike clusters of mesothelium-lined cysts separated by fibrous tissue. The nomenclature for this entity is confusing, and several synonyms (eg, multilocular peritoneal inclusion cyst, cystic mesothelioma) are used interchangeably in the literature.
This rare tumor commonly occurs in young to middle-aged women and typically presents with abdominal pain, tenderness, or distension.
Radiologic tests demonstrate thin-walled cysts containing watery secretions, easily seen on ultrasound, CT scan, and MRI. [9]
Some authors reported effective intraperitoneal chemotherapy, but no clinical study is available about long-term outcome. The short-term prognosis is favorable, although the tumor recurs in 25–50% of cases.
The differential diagnosis includes lymphangioma, mesenteric-omental cysts, ovarian cystadenoma and cystadenocarcinoma, cystic teratoma, pseudomyxoma peritonei, cystic smooth muscle tumors, visceral cysts, and endometriosis.
Primary peritoneal carcinoma
Primary peritoneal carcinoma (ie, serous surface papillary carcinoma) arises primarily from peritoneal cells. The mesothelium of the peritoneum and the germinal epithelium of the ovary arise from the same embryologic origin; therefore, the peritoneum may retain the multipotentiality allowing the development of a primary carcinoma.
This rare malignancy predominantly affects postmenopausal women and typically displays multicentric peritoneal and omental involvement. Pathologically and clinically, it resembles papillary serous ovarian carcinoma. This malignancy is differentiated from its ovarian counterpart by the fact that it involves the extraovarian peritoneum significantly and the ovarian surface minimally or not at all. Extensive calcification or omental caking is present in many cases and is a useful CT finding to exclude mesothelioma. The absence of an ovarian mass is critical for excluding metastatic papillary serous ovarian carcinoma, which otherwise has a similar CT appearance.
Treatment of this malignancy is very similar to that of epithelial ovarian cancer, which includes combination chemotherapy after optimal cytoreductive surgery.
Desmoplastic small round cell tumor
This tumor is a highly aggressive malignancy that has recently been described. It involves the peritoneal cavity in most cases. Unlike the other primary peritoneal neoplasms, desmoplastic small round cell tumor (DSRCT) most often affects young adults. This malignancy extensively and rapidly invades the peritoneal surfaces with hematogenous metastasis to the liver, lungs, and lymph nodes.
Cytologically, DSRCT is a highly cellular tumor composed of small round cells with granular chromatin, nuclear molding, and inconspicuous nucleoli that are arranged singly and in clusters. [10] This tumor exhibits a unique immunohistochemical profile, characterized by coexpression of epithelial (keratin and epithelial membrane antigen), neural (neuron-specific enolase and CD56), mesenchymal (vimentin), and myogenic (desmin) markers. The reciprocal chromosomal translocation t (11; 22)(p13; q12) is also specific for DSRCT.
Radiologic investigation shows multiple rounded peritoneal masses with or without ascites. The omentum and paravesical regions are often involved.
The recommended treatment is a combination of multiagent chemotherapy with adjuvant surgery and radiation. The overall survival for people with this disease is poor despite aggressive treatment.
Leiomyomatosis peritonealis disseminata (LPD)
Although rare, the incidence of leiomyomatosis peritonealis disseminata (LPD) has been increasing in women with a history of laparoscopic myomectomy or subtotal hysterectomy. LPD has a malignancy rate of approximately 7%. [2] The duration from diagnosis to malignancy has been reported from 1 month to 8 years. [3]
The pathogenesis of LPD has not been established. Iatrogenic contamination after morcellation of myoma during laparoscopic surgery is considered the most likely cause. Other proposed etiologic factors include high estrogen levels, peritoneal metaplasia, and genetic mutations related to X chromosome inactivation and abnormal chromosome karyotype. [2, 3]
Other neoplasms
Although clear cell carcinoma is often derived from the ovary and associated with endometriosis, cases of peritoneal origin have been reported. Residual tumor volume appears to determine survival in these patients. These tumors are typically resistant to conventional platinum-based chemotherapy but in one case, adjuvant chemotherapy using irinotecan and cisplatin was effective. [11]
In addition to the above-mentioned primary peritoneal malignancies arising from the peritoneal lining, various types of neoplasms may develop from mesenchymal and lymphatic tissues of the abdominal and pelvic cavities. This includes different forms of sarcomas, histiocytoma, [12] gastrointestinal stromal tumors (GIST), and lymphoproliferative malignancies. Moreover, the differential of peritoneal malignancies includes many benign tumors derived from lymphatic, vascular, neuromuscular, or fatty tissues.
Etiology
A chromosomal translocation, which results in the fusion of the Ewing sarcoma gene with the Wilms tumor gene, has been identified and implicated in desmoplastic small round cell tumors.
Hereditary predisposition may play a role in primary peritoneal carcinoma; patients with the BRCA1/2 mutations have an increased risk. [13]
Susceptibility to mesothelioma may be influenced by genetic makeup. [14] Although conventional wisdom dictates that asbestos is the environmental factor most commonly associated with mesothelioma, asbestos does not transform human mesothelial cells in tissue culture. This suggests that additional carcinogens act in concert with asbestos to cause mesothelioma. Simian virus 40 has been proposed as an etiologic agent; however, the evidence for this hypothesis is weakening. [14, 15]
Epidemiology
All of the peritoneal cancers are rare, with an age-adjusted incidence of 0.65 per 100,000 women in the United States. Primary peritoneal carcinoma is very uncommon. Malignant peritoneal mesothelioma comprises approximately 10 to 15 percent of all cases of mesothelioma in the United States and approximately 600 new cases are diagnosed every year.
Primary peritoneal carcinoma is a rare tumor that occurs almost exclusively in women. Malignant mesotheliomas show extreme male predominance (93% in one series). [16] Desmoplastic small round cell tumors occur in adolescent persons and young men. Although primary peritoneal carcinoma has been reported to occur in older patients than do epithelial ovarian cancers, a United Kingdom study found no statistical difference between the two groups with regard to age (mean 64.43 vs 64.07 years, respectively P = 0.9). [17] Benign cystic peritoneal mesotheliomas are rare and are found predominantly in younger women.
Most cases of leiomyomatosis peritonealis disseminata have been discovered in reproductive-aged women (mean age 37 y), in young pregnant women, and in women who have hormonal excess for any other reason. In most reported cases, nodules either regress or stabilize once the hormonal stimulation has been removed.
Prognosis
Peritoneal cancers traditionally have been associated with significant morbidity and universal mortality, however, significantly improved long-term survival has been reported in patients with resectable disease and complete cytoreduction. [18]
Survival is poor for patients with primary peritoneal carcinoma, with 100% mortality; the median survival reported is 12-25 months, even with extensive surgery and chemotherapy. Benign cystic peritoneal mesotheliomas are associated with prolonged survival, even in patients with bulky disease. Desmoplastic small round cell tumors are associated with a reported median survival of 17 months.
In a multi-institutional data registry that included 405 patients with diffuse malignant peritoneal mesothelioma, overall median survival was 53 months (1 to 235 months), and the 5-year survival rate was 47%. Multivariate analysis showed that the following four prognostic factors were independently associated with improved survival [19] :
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Epithelial subtype (P < 0.001)
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Absence of lymph node metastasis (P < 0.001)
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Completeness of cytoreduction (CC) scores of CC-0 or CC-1 (P < 0.001)
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Use of hyperthermic intraperitoneal chemotherapy (P = 0.002)
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Dr. Oliver Zivanovic, MD, PhD, discusses the role of hyperthermic intraperitoneal chemotherapy in ovarian cancer. Courtesy of Memorial Sloan-Kettering Cancer Center.
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Dr. Oliver Zivanovic, MD, PhD, demonstrates hyperthermic intraperitoneal chemotherapy for ovarian cancer. Courtesy of Memorial Sloan-Kettering Cancer Center.
