January 17, 2007

Peritoneal Cancer

Synonyms and related keywords: primary peritoneal cancer, peritoneal malignancy, peritoneum, peritoneal carcinoma, peritoneal carcinoma, malignant mesothelioma, benign papillary mesothelioma, desmoplastic small round cell tumor, peritoneal angiosarcoma, leiomyomatosis peritonealis disseminata, LPD, peritoneal hemangiomatosis, abdominal therapeutic radiation, radiation therapy, asbestos exposure


Background: Since the early years of the last century, the peritoneum has been a topic of considerable interest. Initially, the major focus was on peritoneal infections; however, with the subsequent introduction of antibiotics, the focus of gynecological and nongynecological pathologists shifted to neoplastic and nonneoplastic peritoneal conditions.

Currently, a number of primary cancers have been described to originate from the peritoneum. Knowledge of primary peritoneal cancers is important because these entities have been implicated in many cases of carcinomas of unknown primary origin when no clear explanation for peritoneal carcinomatosis can be documented. The existence of this phenomenon also explains the occurrence of ovarian cancer in women several years after bilateral oophorectomy, as is observed with primary peritoneal carcinoma. Other described primary peritoneal cancers and tumorlike lesions include malignant mesothelioma, benign papillary mesothelioma, desmoplastic small round cell tumors, peritoneal angiosarcoma, leiomyomatosis peritonealis disseminata (LPD), and peritoneal hemangiomatosis.

Pathophysiology: The peritoneum is a serous lining of mesothelial cells with a rich vascular and lymphatic capillary network.

Peritoneal mesothelioma is a primary tumor of the mesothelial lining of the peritoneum. The tumor can be classified as benign, borderline malignant, or malignant. Benign mesothelioma is a circumscribed papillary tumor of considerable firmness, while malignant mesothelioma covers the surface of the mesentery and can obliterate the entire peritoneal cavity.

Both mesotheliomas (solitary and diffuse forms) have a similar growth pattern and 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. In most instances, the tumor is dominated by growth of cells, but very rarely, abundant production of collagen fibers can occur, leading to the fibrous type of peritoneal mesothelioma. Microscopic findings in malignant mesothelioma include extensive cell vacuolization, rare psammoma bodies, the presence of hyaluronic acid, and a lack of mucin.

This tumor tends to spread into the pleural space, leading to pleural plaques observed on chest x-ray films in 50% of patients with primary peritoneal cancer, compared to 20% of patients with primary pleural mesothelioma, which suggests a higher level of asbestos exposure in patients with peritoneal disease. The incidence of asbestos exposure in patients with benign mesothelioma approximates the incidence rate of exposure in the general population, while the association of malignant peritoneal mesothelioma and asbestos exposure has been reported to be as high as 83%. Malignant peritoneal mesothelioma has also been associated with abdominal therapeutic radiation.

A rare syndrome of recurrent peritoneal mesothelial cysts (also termed benign cystic peritoneal mesothelioma) consisting of multiloculated inclusion cysts has been described. Some authors advocate classifying this lesion as reactive proliferation rather than malignancy.

Primary peritoneal carcinoma (also termed serous surface papillary carcinoma) is a malignancy that 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 of the müllerian system, allowing the development of a primary carcinoma.

A desmoplastic small round cell tumor can sometimes be difficult to differentiate from a malignant peritoneal mesothelioma. This tumor demonstrates extensive involvement of the peritoneal surfaces, with rapid multifocal growth and hematogenous metastasis to the liver, lungs, and lymph nodes.

LPD is a condition of small, firm, white-to-gray nodules studding and covering the peritoneal surface. Histologically, these nodules are composed mainly of smooth muscle cells with variable amounts of decidualization and hyalinization. Minimal mitotic activity is observed, with no evidence of atypia or nuclear pleomorphism. The histogenesis of LPD has been a point of debate because of the discrepancy of ultrastructural studies. Regardless of whether the cellular content is decidual cells or smooth muscle cells, embryogenesis involves multipotential mesenchymal stem cells. Excessive hormonal stimulation with estrogen or progesterone has been recognized as a potential stimulus for LPD development. Although once believed to be an unquestionably benign process, cases have been reported of patients with LPD that subsequently evolved into aggressive leiomyosarcomas.

Peritoneal angiosarcomas are rare tumors that appear benign histologically but usually act aggressively. They may arise following previous radiation treatment to the serous membranes. Hemangiomatoses of the peritoneum are rare and are usually associated with hemangiomas of the GI tract or cutaneous hemangiomas.




Age: Patients with primary peritoneal carcinoma are older compared to those with epithelial ovarian cancers.





Ovarian Cysts

Other Problems to be Considered:

The differential diagnosis of primary peritoneal cancers includes peritoneal metastasis (ie, peritoneal carcinomatosis) from primary sites including the GI tract, ovaries, or breast or as part of the syndrome of adenocarcinomas of unknown primary site. Although the primary histology findings dictate the clinical course, important concepts of diagnosis and treatment are common to all forms. The most important risk factor for developing peritoneal carcinomatosis is the depth of invasion of the primary tumor.

Reactive tumorlike lesions of the peritoneum have been described and should be included in the differential diagnosis of primary peritoneal cancers, as follows:

  • Granulomatous lesions

    • Vernix caseosa and meconium peritonitis

    • Granulomatous peritonitis secondary to foreign material, including keratin

    • Necrotic pseudoxanthomatous nodules

    • Postcautery granulomas

  • Nongranulomatous histiocytic lesions

    • Ceroid-rich histiocytic infiltrates

    • Peritoneal melanosis

    • Mucicarminophilic histiocytosis

    • Other histiocytic infiltrates

  • Fibrosing lesions

    • Sclerosing peritonitis

    • Peritoneal fibrosis nodules

  • Mesothelial lesions

    • Mesothelial hyperplasia

    • Peritoneal inclusion cysts
Pseudomyxoma peritonei typically includes any low-grade or benign tumor within the abdominal cavity that produces copious amounts of mucinous ascites. This condition includes peritoneal spread from well-differentiated adenocarcinomas of the GI tract and benign mucin-secreting adenomas of the appendix.


Lab Studies:

Imaging Studies:


Histologic Findings: Primary peritoneal carcinoma is histologically indistinguishable from primary epithelial ovarian carcinoma; however, primary ovarian cancer can be excluded based on certain criteria. First, both ovaries must be of normal in size. Second, the extraovarian involvement must be greater than the involvement on the surface of the ovary. Third, the ovarian component must be smaller than 5 by 5 mm within the ovary or confined to the ovarian surface. Finally, the cytologic characteristics must be of the serous type.


Medical Care:

Surgical Care:


The goals of pharmacotherapy are to induce remission, to prevent complications, and to reduce morbidity.

Drug Category: Chemotherapeutic agents -- Inhibit cell growth and proliferation. Agents used include cisplatin, doxorubicin, cyclophosphamide, carboplatin, and paclitaxel.
Drug Name
Cisplatin (Platinol) -- Inhibits DNA synthesis and thus cell proliferation by causing DNA cross-links and denaturation of double helix.
Adult Dose75-100 mg/m2 q3wk IV; 90-270 mg/m2 IP; retain 4 h before draining with systemic sodium thiosulphate
Pediatric Dose30-100 mg/m2 q2-3wk
ContraindicationsDocumented hypersensitivity; preexisting renal insufficiency, myelosuppression, and hearing impairment
InteractionsIncreases toxicity of bleomycin and ethacrynic acid
Pregnancy D - Unsafe in pregnancy
PrecautionsAdminister adequate hydration before and 24 h after dosing to reduce risk of nephrotoxicity; hyperuricemia, nausea and vomiting, myelosuppression, anemia, peripheral neuropathy, ototoxicity, nephrotoxicity, acute renal failure, bradycardia, arrhythmia, mild alopecia, SIADH, hypomagnesemia, hypocalcemia, hypokalemia, hypophosphatemia, mouth sores, elevated liver enzymes, phlebitis, optic neuritis, blurred vision, and papilledema may occur; symptoms of overdosage include severe myelosuppression, intractable nausea and vomiting, kidney and liver failure, deafness, ocular toxicity, and neuritis; use proper handling and disposal
Drug Name
Doxorubicin (Adriamycin, Rubex) -- Inhibits topoisomerase II and produces free radicals, which may cause the destruction of DNA. Combination of these events can, in turn, inhibit the growth of neoplastic cells.
Adult Dose60-75 mg/m2 as a single dose, repeat q21d; 20-30 mg/m2/d for 2-3 d, repeat in 4 wk; or 20 mg/m2 once wk
Pediatric Dose35-75 mg/m2 as a single dose, repeat q21d; 20-30 mg/m2 once weekly; or 60-90 mg/m2 continuous infusion over 96 h q3-4wk
ContraindicationsDocumented hypersensitivity; severe heart failure; cardiomyopathy; impaired cardiac function; preexisting myelosuppression
InteractionsMay decrease phenytoin and digoxin plasma levels; phenobarbital may decrease plasma levels; cyclosporine may induce coma or seizures; mercaptopurine increases toxicity; cyclophosphamide increases cardiac toxicity
Pregnancy D - Unsafe in pregnancy
PrecautionsExtravasation may result in severe local tissue necrosis; reduce dose in patients with impaired hepatic function; use proper handling and disposal; total dose not to exceed 550 mg/m2 or 400 mg/m2 in patients with previous or concomitant treatment (ie, with daunorubicin, cyclophosphamide, or irradiation of the cardiac region); alopecia, nausea and vomiting, mucositis, ulceration and necrosis of the colon, anorexia and diarrhea, stomatitis, esophagitis, red discoloration of urine, myelosuppression, and cardiac toxicity may occur
Acute arrhythmia, heart block, pericarditis-myocarditis, and chronic cardiac toxicity as congestive cardiac failure may occur; facial flushing, hyperpigmentation of nail beds, erythematous streaking along the vein if administered too rapidly, hyperuricemia, fever, chills, urticaria, conjunctivitis, allergic reaction, and anaphylaxis may occur; radiation recall noticed in patients who have had prior irradiation; symptoms of overdosage include myelosuppression, nausea, vomiting, and myocardial toxicity
Drug Name
Carboplatin (Paraplatin) -- Analog of cisplatin. Has same efficacy as cisplatin but with better toxicity profile.
Dose is based on following formula:
Total dose (mg) = (target AUC) X (GFR = 25), where AUC (area under plasma concentration-time curve) is expressed in mg/mL/min and GFR (glomerular filtration rate) is expressed in mL/min.
Adult Dose360 mg/m2 IV q3wk as monotherapy or 300 mg/m2 q4wk as combination therapy
Pediatric Dose300-600 mg/m2 IV q4wk
ContraindicationsDocumented hypersensitivity; bone marrow suppression
InteractionsNephrotoxicity increases with aminoglycosides and other nephrotoxic drugs
Pregnancy D - Unsafe in pregnancy
PrecautionsMonitor bone marrow function; use proper handling and disposal; high doses have resulted in severe LFT abnormalities; increased risk of allergic reactions if previously exposed to platinum therapy; hypocalcemia, hypomagnesemia, hyponatremia, hypokalemia, nausea, vomiting, stomatitis, myelosuppression, asthenia, alopecia, diarrhea, anorexia, peripheral neuropathy, and ototoxicity may occur; symptoms of overdosage include bone marrow suppression and hepatic toxicity
Drug Name
Cyclophosphamide (Neosar, Cytoxan) -- Chemically related to nitrogen mustards. As an alkylating agent, the mechanism of action of the active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells.
Adult Dose50-100 mg/m2/d PO continuous therapy or 400-1000 mg/m2 PO in divided doses 4-5 d intermittent therapy
Pediatric DoseAdminister as in adults
ContraindicationsDocumented hypersensitivity; severely depressed bone marrow function
InteractionsAllopurinol may increase risk of bleeding or infection and enhance myelosuppressive effects; may potentiate cyclophosphamide-induced cardiotoxicity; may reduce digoxin serum levels and antimicrobial effects of quinolones; chloramphenicol may increase half-life while decreasing metabolite concentrations; may increase effect of anticoagulants; coadministration with high doses of phenobarbital may increase rate of metabolism and leukopenic activity; thiazide diuretics may prolong cyclophosphamide-induced leukopenia and neuromuscular blockade by inhibiting cholinesterase activity
Pregnancy D - Unsafe in pregnancy
PrecautionsRegularly examine hematologic profile (particularly neutrophils and platelets) to monitor for hematopoietic suppression; regularly examine urine for RBCs, which may precede hemorrhagic cystitis; use proper handling and disposal
Adverse effects include alopecia, sterility, nausea and vomiting, diarrhea, stomatitis, mucositis, jaundice, headache, skin rash, facial flushing, myelosuppression, cardiac dysfunction, dizziness, darkening of skin/fingernails, hyperglycemia, hypokalemia, hyperuricemia, SIADH, acute hemorrhagic cystitis, hepatic toxicity, renal tubular necrosis, nasal congestion, interstitial pulmonary fibrosis, and secondary malignancy (alone or in combination with other antineoplastics)
Both bladder carcinoma and acute leukemia are well documented; symptoms of overdosage include myelosuppression, alopecia, nausea, and vomiting
Drug Name
Paclitaxel (Taxol) -- Mechanisms of action are tubulin polymerization and microtubule stabilization.
Adult Dose175 mg/m2 IV over 3 h q3wk; alternatively, 135 mg/m2 IV over 24 h q3wk
Pediatric DoseNot established
ContraindicationsDocumented hypersensitivity to paclitaxel or polyoxyethylated castor oil; peripheral neuropathy; bone marrow suppression; liver failure; severe cardiac disease
InteractionsCoadministration with cisplatin may further increase myelosuppression
Pregnancy D - Unsafe in pregnancy
PrecautionsPremedicate with steroids, H1 blockers, and H2 blockers to decrease risk of hypersensitivity reactions; current evidence indicates that prolongation of infusion >6 h plus premedication may minimize this effect; adverse reactions include hypotension, abnormal ECG tracings, alopecia, nausea and vomiting, diarrhea, mucositis, bleeding anemia neutropenia, thrombocytopenia, abnormal LFT results, peripheral neuropathy, myalgia, bradycardia, and radiation pneumonitis in patients receiving concurrent radiotherapy


Further Inpatient Care:


  • See Mortality/Morbidity.


Medical/Legal Pitfalls:

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