Cancer of the ovary, fallopian tube, and peritoneum
In 2014, the Gynecologic Oncology Committee of FIGO revised the staging to incorporate ovarian, fallopian tube, and peritoneal cancer in the same system. Changing the staging system required extensive international consultation. The primary site (i.e. ovary, fallopian tube, or peritoneum) is designated, where possible. When it is not possible to clearly delineate the primary site, these should be listed as “undesignated” [1,2]. It has been presumed that fallopian tube malignancies were rare [2]. However, histologic, molecular, and genetic evidence shows that from 40% − 60% of tumors that were classified as high-grade serous carcinomas of the ovary or peritoneum may have originated in the fimbrial end of the fallopian tube [3–8]. Therefore, the incidence of fallopian tube cancers may have been substantially underestimated. These new data support the view that high-grade serous ovarian, fallopian tube, and peritoneal cancers should be considered collectively, and that the convention of designating malignancies as having an ovarian origin should no longer be used, unless that is clearly the origination site. It has been suggested that extrauterine tumors of serous histology arising in the ovary, fallopian tube, or peritoneum might be described collectively as “Müllerian carcinomas” [1,2] or “pelvic serous carcinomas” [9]. The latter tumor designation is controversial because some peritoneal tumors might arise in extrapelvic peritoneum. Therefore, the simple term “serous carcinoma” is preferred, and most of these are high-grade serous carcinomas (HGSC). Although there has been no formal staging for peritoneal cancers, the FIGO staging system is used with the understanding that it is not possible to have a Stage I peritoneal cancer. Ovarian epithelial tumors may arise within endometriosis or cortical inclusions of Müllerian epithelium, likely a form of endosalpingiosis. These include low-grade endometrioid carcinomas, clear cell carcinomas, borderline and low-grade serous carcinomas, and mucinous carcinomas. These tumors are thought to evolve slowly from lower-grade precursor conditions (endometriotic cysts, cystadenomas, etc.) and are classified as type I tumors [5]. Fallopian tube carcinomas arise in the distal fallopian tube and the majority of these are high-grade serous carcinomas. These are thought to evolve rapidly from more obscure precursors and are designated as type II tumors [5,6]. This latter group encompasses high-grade endometrioid carcinomas and carcinosarcomas. All of these high-grade carcinomas are nearly always associated with mutations in the TP53 gene [5]. The lymphatic drainage of the ovaries and fallopian tubes is via the utero-ovarian, infundibulopelvic, and round ligament pathways and an external iliac accessory route into the following regional lymph nodes: external iliac, common iliac, hypogastric, lateral sacral, para-aortic lymph nodes and, occasionally, to the inguinal nodes [1,10–12]. The peritoneal surfaces can drain through the diaphragmatic lymphatics and thence to the major venous vessels above the diaphragm. The peritoneum, including the omentum and pelvic and abdominal viscera, is the most common site for dissemination of ovarian and fallopian tube cancers. This includes the diaphragmatic and liver surfaces. Pleural involvement is also seen. Other extraperitoneal or extrapleural sites are relatively uncommon, but can occur [1,10–12]. After systematic pathologic analysis has excluded a tubal or ovarian site of origin, malignancies that appear to arise primarily on the peritoneum have an identical spread pattern, and frequently may involve the ovaries and fallopian tubes secondarily. These “peritoneal” tumors are thought to arise in endosalpingiosis. Although CT scans can delineate the intra-abdominal spread of disease to a certain extent, ovarian, fallopian tube, and peritoneal cancers should be staged surgically. Operative findings determine the precise histologic diagnosis, stage, and therefore the prognosis, of the patient [1,9,10,12–14]. In selected patients with advanced-stage disease, it may be appropriate to initiate chemotherapy prior to surgical intervention, and in these cases, there should be histological or cytological confirmation of the diagnosis prior to starting neoadjuvant chemotherapy (see 5.2.2. below). Chest radiograms may serve as a screen for pleural effusions. As distant metastases are infrequent, there is no requirement for other radiological evaluation unless symptomatic. Serum CA125 levels may be useful in determining response to chemotherapy, but they do not contribute to staging. Fallopian tube involvement can be divided into three categories. In the first, an obvious intraluminal and grossly apparent fallopian tube mass is seen with tubal intraepithelial carcinoma (carcinoma in situ) that is presumed to have arisen in the fallopian tube. These cases should be staged surgically with a histological confirmation of disease. Tumor extension into the submucosa or muscularis and to and beyond the serosa can therefore be defined. These features, together with the laterality and the presence or absence of ascites, should all be taken into consideration [1,3,6,7]. In the second scenario, a widespread serous carcinoma is associated with a tubal intraepithelial carcinoma. A visible mass in the endosalpinx may not be seen but the histologic findings should be noted in the pathology report since they may indicate a fallopian tube primary. Tumors obliterating both fallopian tube and ovary may belong to this group but whether a presumptive assignment of a tubal origin can be made in such cases is controversial given that tubal intraepithelial carcinoma cannot be confirmed. In the third scenario—the risk-reducing salpingo-oophorectomy—tubal intraepithelial carcinoma may be the only finding. It should be reported as originating in the fallopian tube and managed accordingly. The majority of early serous cancers detected are found in the fallopian tube, irrespective of genetic risk [15,16]. The updated, revised FIGO staging system combines the classification for ovarian, fallopian tube, and peritoneum cancer. It is based on findings made mainly through surgical exploration (as outlined above). Table 1 presents the 2014 FIGO staging classification for cancer of the ovary, fallopian tube, and peritoneum. The equivalents within the Union for International Cancer Control (UICC) TNM classification are presented in Table 2. The primary site—that is, ovary, fallopian tube, or peritoneum—should be designated where possible. In some cases, it may not be possible to clearly delineate the primary site, and these should be listed as “undesignated.” The histologic type should be recorded. The staging includes a revision of the Stage III patients and allotment to Stage IIIA1 is based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination, because an analysis of these patients indicates that their survival is significantly better than have intraperitoneal of retroperitoneal lymph nodes be or of tumor from omentum to or liver should be from or liver metastases In to these other of the staging system have been made to better the Stage is divided into three or tumor on ovarian or fallopian tube and in the or peritoneal Stage has been The staging includes a revision of the Stage based on spread to the retroperitoneal lymph nodes without intraperitoneal dissemination, because an analysis of these patients indicates that their survival is significantly better than have intraperitoneal dissemination This is into in and in Stage is extrapelvic peritoneal involvement with or without retroperitoneal lymph The of Stage has been to the lymph Stage includes metastases to the inguinal lymph lymph nodes cannot be regional lymph lymph cannot be distant peritoneal The majority of cases of ovarian cancer are of epithelial FIGO the histological of epithelial ovarian It is that all ovarian epithelial tumors be to the classification given cell carcinomas group of tumors is of epithelial but they are to be in other epithelial tumors tumors are of or more of the major cell of common epithelial The are with high-grade serous carcinoma in the ovaries and fallopian tubes appear to be and not the primary origin can be as peritoneal carcinoma or serous carcinoma of site, the of the cannot be carcinomas are the most common in both the ovary and tube. than of fallopian tube carcinomas are serous or high-grade endometrioid Other cell have been but are rare carcinomas are in a system their serous carcinomas, including both and with and a of mutations in TP53 serous carcinomas are associated with borderline or serous mutations in and and serous carcinomas mutations in TP53 and should be with the high-grade tumors cancers, uncommon, are These include cell cell and are as to the ovary, such as tumors arising in the sites or and cell carcinomas, or mucinous tumors and other are and staged in with their sites of origin [1,2]. tumors of the ovaries occur all with in histological in than of cell tumors borderline tumors occur in in their and or more than in with epithelial ovarian cancers, occur the of The risk of a in the ovarian cancer is 1 in of cancers are ovarian in origin, but of all from cancer of the occur in with ovarian cancer. epithelial ovarian cancer for of all new cancer in and of all The incidence of epithelial tumors from and is in with the of However, this incidence with The of patients with epithelial ovarian cancer is found in the risk for epithelial ovarian tumors include risk have are as likely to this disease. an early early and the of have been associated with of ovarian cancer The of these to fallopian tube cancer is As noted it has been presumed that fallopian tube malignancies were this has been evidence to that tumors that were classified as serous carcinomas of the ovary or peritoneal cancers appear to have their origin in the fallopian tube When the origin is the convention of designating all serous cancers, as originating in the ovary should no longer be used and the term may be the of the mutations in the and the mutations in and have a substantially risk of ovarian, and peritoneal with and with these cancers occur an than cancers, in with a of diagnosis in the mutations in the associated with II these mutations have an risk of a of cancers including and ovarian cancer. the ovarian cancers that occur are endometrioid or clear cell and are Stage in is associated with clear cell and endometrioid carcinomas with a of epithelial ovarian, fallopian tube, or peritoneal cancers, there is a are to have a risk-reducing appropriate and the of All are of a based on or of diagnosis and a high-grade 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endometrioid cancers are early high-grade serous cancers are most Stage III because of early dissemination a more cancer. 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