Systemic chemotherapy in patients with peritoneal carcinomatosis from non colorectal origin

Abstract

Peritoneal carcinomatosis (PC) is a malignancy that spreads widely inside the peritoneal cavity, involving mostly the omentum. Different tumour types can present with peritoneal carcinomatosis. The most common cause of PC in women is ovarian cancer. Approximately 75% of patients with ovarian cancer present with FIGO stage III disease (disease spread throughout the peritoneal cavity or involvement of retroperitoneal or inguinal nodes). Serous epithelial ovarian cancer (EOC) however has histopathological, immunohistochemical and clinical similarities with primary peritoneal carcinomatosis (PPC), a far less common malignancy, that has also be encountered in women following bilateral oophorectomy and even in male patients [1-3]. Since first being described in 1959 by Swerdlow [4], primary PC has been the subject of numerous case reports, case series and retrospective reviews [5-9]. However, interpretation of these data is complicated by confusing and varying terminology. A variation in nomenclature has been used to describe the tumour: peritoneal mesothelioma, peritoneal papillary (serous) carcinoma, extraovarian peritoneal serous papillary carcinoma, serous surface papillary carcinoma, multiple focal extraovarian serous carcinoma and small ovarian carcinoma. This is reflective of the diagnostic dilemma faced by pathologists in cases of mllerian carcinomatosis with minimal ovarian involvement [5]. In an effort to better define this patient population and to develop more organized treatment strategies, the Gynecologic Oncology Group (GOG) developed a concise set of criteria for PPC [10]. First, both ovaries must be either physiologically normal in size or enlarged by a benign process (4.0 cm largest diameter). Second, involvement of extraovarian sites must be greater than that on the surface of either ovary. Third, microscopically, the ovarian component must be one of the following: (a) nonexistent, (b) confined to the ovarian surface epithelium with no evidence of cortical invasion, (c) involving the ovarian surface epithelium and underlying cortical stroma but any given tumour size must be less than 5×5 mm, or (d) tumours less than 5×5 mm within the ovarian substance associated with or without surface disease. Fourth, the histological and cytological characteristics of the tumour must be predominantly of the serous type, similar or identical to ovarian serous papillary adenocarcinoma of any grade. Using this clinical definition of PPC, 7-20% of patients previously identified as having primary ovarian papillary serous carcinoma may be reclassified as having PPC [5,7]. However the etiology, pathogenesis, cell of origin, and clinical characteristics of PPC remain obscure. Differential diagnosis may include adenocarcinoma of unknown primary tissue, malignant mesothelioma, and peritoneal adenocarcinoma, as well as metastatic breast cancer (especially lobular cancer of the breast) [11]. In addition to breast and ovarian carcinomas, patients with germline BRCA1 mutations are more likely to develop PPC [12]. Furthermore, PC can be a metastatic site of gastrointestinal malignancies (such as gastric, pancreatic or colorectal carcinomas) [11]. PC is a frequent cause of death in patients with advanced gastric carcinoma. Peritoneal carcinomatosis also commonly originates from colorectal cancer and is present in approximately 10% of patients at the time of first diagnosis and in about 25% of patients with recurrent disease. It is the second most frequent cause of death in colorectal cancer after metastatic disease to the liver. In an estimated 25% of patients, no other tumour locations can be found [13,14]. Another rare tumour type of PC, is peritoneal mesothelioma. In the USA, each year two cases per million are reported. This tumour arises from the serosal lining of the peritoneum. A mesothelioma may involve the pleura, pericardium or peritoneum, and 30-40% has peritoneal manifestations. The tumour can be classified as benign, borderline malignant, or malignant. Benign mesothelioma is a papillary tumour of considerable firmness, while malignant mesothelioma covers the surface of the mesentery and can obliterate the entire peritoneal cavity. Malignant peritoneal mesothelioma is associated with asbestos exposure and is most common in middle age men [15]. Pseudomyxoma peritonei is another distinct subtype of peritoneal carcinomatosis with an approximate incidence of one per million per year. It is caused by rupture of a mucinous cystadenoma of cystadenocarcinoma. The primary tumour usually originates in the ovary or appendix and the mucinous material spreads to the peritoneal surfaces and omentum [16].