While ovarian neoplasms are common, the diagnosis of a malignant tumor of the Fallopian tubes (FTC) is rarely made. The latter term comprises a variety of epithelial and mesenchymal tumors, mixed forms, germ cell tumors, and others. Neither triggers specific symptoms. Suspicion usually arises upon the palpation of an abdominal mass or the detection of abnormal cells in cervicovaginal smears. If this suspicion is confirmed by means of diagnostic imaging, the patients is referred for surgery. Complete surgical tumor resection and postoperative adjuvant chemotherapy achieve good results, particularly in case of low-grade early-stage FTC.
FTC patients usually remain asymptomatic for prolonged periods of time. Still, patients may present with abdominal pain, which may be spasmodic or colicky, or persistent and dull. Abdominal pain may be associated with abdominal distension and ascites [1]. Few women describe urinary urgency, watery or bloody vaginal discharge, and vaginal discharge may temporarily relieve their pain. This phenomenon is known as hydrops tubae profluens and can be explained by the accumulation of fluid in a distended Fallopian tube and by its sudden emptying, which results in an episode of profuse serosanguinous vaginal discharge and possibly shrinkage of an abdominal mass. Less than 5% of affected individuals experience such symptoms, but the presence of an abdominal mass is a clinical hallmark of FTC. Indeed, the combination of colicky lower abdominal pain, watery vaginal discharge, and a palpable mass - designated as Latzko triad of symptoms and first described in 1916 - is often depicted as characteristic of FTC. But it is present in <15% of FTC patients [2]. More commonly, a palpable mass in the lower abdomen is incidentally detected during routine gynecological examinations and represents the only finding indicating the possibility of FTC.
Although those symptoms described in the previous paragraph are much more likely to be triggered by pelvic inflammatory disease, the possibility of FTC should be considered in affected women. Clinical disease allows for an early diagnosis and timely treatment, which improves the patient's prognosis. At the same time, women should be encouraged to regularly undergo gynecological examinations with subsequent analysis of cervicovaginal smears.
Clinical symptoms as well as suspicious findings on palpation or cytological analysis should prompt imaging studies. FTC may be displayed by means of transabdominal and transvaginal sonography, computed tomography, and magnetic resonance imaging. The distinction of ovarian neoplasms from tumors of the Fallopian tubes poses a major challenge, though, and most cases of FTC are preoperatively diagnosed as ovarian cancer. Imaging characteristics of distinct types of FTC vary [3] [4]: They may appear as solid or cystic lesions. Cystic lesions are characteristic of FTC associated with hydrosalpinx, i.e., fluids secreted by the tumor accumulate and distend the Fallopian tube and/or the tumor hinders the drainage of fluid from the oviduct [3]. The neoplasm itself may be of nodular or papillary shape and may constitute an adnexal mass or be contained in the fluid-filled structure [2].
Every attempt should be made to establish that the mass, whether solid or cystic, is separate from the ovary [2]. This conclusion allows for the tentative diagnosis of a tumor of the Fallopian tube. In order to distinguish benign neoplasms from FTC, to determine the type and grade of FTC, tissue samples have to be obtained and examined. It is beyond the scope of this article to describe the histopathological features of all types of FTC, so the interested reader is referred to the specific articles available on this platform and to the appropriate descriptions published by the World Health Organization [5].
With regard to FTC staging, the so-called FIGO staging system is generally applied. This system considers the following tumor stages [5] [6]:
In order to realize a complete tumor staging, all features considered in the FIGO staging system have to be checked. Of note, incomplete surgical staging has been identified as a risk factor for poor prognosis - a fact that highlights the importance of a thorough workup [7].
Surgical resection is the treatment of choice; tissues obtained during surgery have to be examined in order to realize complete tumor grading and staging. Apart from the rare cases where fertility preservation is considered, total extrafascial hysterectomy with bilateral salpingo-oophorectomy is executed to treat FTC. This intervention should be accompanied by pelvic and para-aortic lymph node dissection, omentectomy, biopsies at any area where metastases are suspected, and collection of cytology samples from the diaphragm. In cases of advanced-stage FTC, tumor debulking and removal of all visible tumors is recommended [6].
FTC tend to form lymphogenic metastases. Indeed, the performance of radical lymphadenectomy may increase five-year survival rates by 25% [8]. The high incidence of lymph node metastases is also the reason why affected women should receive postoperative adjuvant therapy, preferentially in form of chemotherapy [8]. With regard to the latter, platinum-based combination regimens are most commonly applied, e.g., carboplatin plus paclitaxel [9]. Due to low efficacy and high complication rates, postoperative radiotherapy is no longer recommended to treat FTC.
If treated accordingly, early-stage FTC is associated with a good prognosis. A study on the outcome of patients with stage 1 FTC showed that five-year disease-free survival rates of 100% can be achieved [7]. Higher tumor grades and advanced-stage disease considerably worsen the prognosis. In fact, the FIGO stage is considered to be the most important prognostic factor in FTC. Median survival times of patients suffering from stage 4 FTC may range between 15 and 29 months, with an estimated five-year survival rate of 20% [10].
FTC is rare and poorly understood. The classification of Fallopian tube neoplasms is derived from that of ovarian tumors and it is generally thought that FTC develops in a manner similar to the better known ovarian cancer. In this context, hormonal, reproductive, and genetic factors may lower or increase the individual risk of FTC. Among those factors reducing the risk of FTC are parity, breast-feeding and the use of oral contraceptives [11] [12]. By contrast, germline mutations in genes BRCA1 and BRCA2 strongly predispose for the development of breast and female genital cancer. BRCA1 mutations are associated with a lifetime risk of 46%-87% for breast cancer and 39%-63% for malignancies of the ovaries; carriers of BRCA2 mutations have a lifetime risk of 38%-84% for breast cancer and 17%-27% for ovarian cancer [13]. Data regarding the likelihood of FTC are not available, but the risk may be assumed to be equally high in patients suffering from the respective hereditary breast-ovarian cancer syndrome. Additionally, long-term estrogen replacement in postmenopausal women may increase the risk of FTC [12] [13].
FTC accounts for 0.1-1.8% of all gynecological cancers, but experts believe its true incidence to be underestimated because the disease may be mistaken for ovarian malignancies [7]. The most common type of FTC is adenocarcinoma [5]. FTC is diagnosed in women with a mean age of 58 years [7], but certain types of FTC, namely trophoblastic neoplasms, arise during ectopic pregnancies and are thus to be expected in younger women [14]. Carriers of BRCA mutations tend to develop cancer before the age of 50 [13].
Although distinct types of FTC vary with regard to their growth behavior, most FTC grow aggressively and invasively. Tumors often penetrate the serosal surface of the Fallopian tube, a condition that largely facilitates the exfoliation of cells and their distribution in the peritoneal cavity. In fact, peritoneal metastases account for the majority of FTC metastases. Lymphogenic spread is also common.
Most tumors - and their metastases - express cancer antigen 125, which is better known as CA125. This is of diagnostic relevance since serum levels of CA125 may easily be assessed. Increased serum levels of CA125 have been reported in 80% of FTC patients [2]. Because serum concentrations of CA125 are more commonly increased in patients with advanced-stage FTC, they have been proposed as an independent prognostic factor for disease-free survival and overall survival [15].
Tumor cells may exfoliate, migrate through the Fallopian tube and reach the uterus or vagina, where they can be detected by means of cervicovaginal smears. A clean background, that disappears when liquid-based cytology is used, small numbers of malignant cells, papillary grouping of overlapping tumor cells, and the absence of tumor diathesis may indicate FTC [2].
As indicated above, BRCA mutations are associated with a very high lifetime risk of developing cancer of the breast or genital organs. In order to lower that risk, women may undergo prophylactic salpingo-oophorectomy [13]. However, infertility and premature menopause, both unavoidable consequences of such an intervention, argue against this surgical procedure. Maintenance of the ovaries until the age of natural menopause may at least alleviate the symptoms of premature menopause. In this context, recent studies point out that high-grade ovarian cancers often originate from the Fallopian tubes and that sole salpingectomy may pose a valuable alternative to salpingo-oophorectomy: The risk of life-threatening ovary cancer would be reduced, but women wouldn't have to suffer the complications of estrogen deficiency [13].
While malignant neoplasms of the female genital are among the most common types of cancer in women [6], FTC is a rare condition. Still, distinct epithelial, mixed epithelial-mesenchymal, mesenchymal, and germ cell tumors may develop in the Fallopian tubes. Trophoblastic neoplasms as well as tumors of hematopoietic or lymphoid origin may also affect these organs. In detail, the following entities are listed in the classification of breast tumors and tumors of the female genital organs, as published by the World Health Organization [5]:
For the sake of completeness, benign tumors of the Fallopian tubes have been added in parentheses.
As can be seen, the term FTC comprises a broad spectrum of malignant neoplasms that differ with regard to etiology, growth behavior, and susceptibility to determined treatment regimens. Additionally, malignant tumors originating from other tissues may metastasize to the Fallopian tubes and such metastases may be associated with distinct clinical presentations and prognoses. The vast majority of secondary neoplasms of the Fallopian tubes has its origin in the ovary.
The Fallopian tubes connect the ovaries with the uterus; in women, they measure up to 15 cm in length. Tumors arising from these organs, whose main functions are to conduce the ovum towards the uterus and to facilitate its fertilization, are rare. Still, the list of tumors that may develop in the Fallopian tubes is long: Some of them are benign tumors, others grow aggressively and invasively. The diagnosis of a malignant tumor of the Fallopian tubes is often made incidentally, during routine gynecological examinations. This is because affected women are usually asymptomatic. They may experience colicky or dull lower abdominal pain, though, and some describe watery or bloody vaginal discharge. Vaginal discharge may temporarily relieve the pain. More commonly, Fallopian tube cancer manifests as a palpable abdominal mass.
Suspicious clinical or cytological findings have to be clarified by means of imaging studies. Transabdominal and transvaginal sonography, computed tomography, and magnetic resonance imaging may be used to display and characterize the tumor. Although it may not always be possible to distinguish ovarian and Fallopian tube cancer, both usually require the complete surgical removal of the tumor. In general, both ovaries, both Fallopian tubes, the uterus, and regional lymph nodes are removed to assure that no tumor cells remain in the body. In order to further improve the patient's prognosis, postoperative adjuvant chemotherapy is often recommended.
Survival rates largely depend on the type of tumor and the stage of the disease at the time of diagnosis. If Fallopian tube cancer is diagnosed early, the prognosis is generally favorable.