INTRODUCTION — Carcinoma of the fallopian tube is a rare malignancy. It is the least common site of origin for a malignant neoplasm of the female genital tract, accounting for 0.2 to 0.5 percent of primary female genital malignancies. The annual incidence in the United States is 3.6 per million women. Secondary carcinoma due to metastatic disease from the ovaries, endometrium, gastrointestinal tract, or breast is more common.
RISK FACTORS — The only identified risk factor for fallopian tube cancer is an inherited mutation in BRCA1 or 2, the breast and ovarian cancer susceptibility genes. In a relatively large cohort study of 483 BRCA1 mutation carriers, there were three cases of fallopian tube cancer, which represented a 120-fold increase when compared to expected incidence rates derived from Surveillance, Epidemiology, and End Results program (SEER) data. By comparison, the relative risk of breast or ovarian cancer in this cohort was 29-fold and 6-fold higher, respectively, compared to the general population. BRCA mutations, primarily BRCA1, have been identified in 16 to 43 percent of women with primary fallopian tube cancer. Therefore, BRCA testing should be offered to women with these tumors.
A history of previous chronic inflammatory changes in the fallopian tubes (eg, old pelvic inflammatory disease or tuberculosis) was considered a risk factor in the past, but subsequent reports have failed to demonstrate such an association. Primary infertility is common in this population, with a 40 to 70 percent incidence of nulliparity reported in some series. Parity may be protective. There is no strong evidence that past history of human papillomavirus or chlamydia infection, sterilization, or hysterectomy are risk factors.
PATHOLOGY AND BIOLOGY — Surgical pathology commonly reveals a dilated fallopian tube. The fimbriated end is closed in about one-half of cases and the lumen usually is filled and dilated by papillary or solid tumor. The left and right fallopian tubes are involved with equal frequency; bilateral involvement occurs in 10 to 26 percent of cases. The mid and distal portions of the tubes are usually affected.
Histologically fallopian tube tumors are most commonly papillary serous adenocarcinomas. Less frequent types include endometroid, clear cell, adenosquamous, squamous cell carcinoma, sarcoma, choriocarcinoma, and malignant teratoma.
Fallopian tube carcinoma spreads predominantly through the tubal ostia and into the peritoneal cavity. Frequent sites for metastasis include the ovaries and uterus. Metastasis to the pelvic and paraaortic nodes is also common, possibly because of the rich lymphatic supply of the fallopian tubes. Metastatic disease was found at presentation in 33 percent of patients presenting with all stages of this cancer in two reports. Synchronous disease in ovaries, uterus, or cervix occurs in 7 to 35 percent of cases.
CLINICAL MANIFESTATIONS — Women with fallopian tube carcinoma often present in the fifth or sixth decades with vague complaints. The classic symptoms and signs associated with this malignancy are:
However, the full triad (Latzko's triad) is noted in fewer than 15 percent of patients. Hydrops tubae profluens, which refers to intermittent discharge of clear or blood-tinged fluid spontaneously or on pressure followed by shrinkage of the adnexal mass, is pathognomonic of the disease.
Women may complain of colicky or dull abdominal pain secondary to forced tubal peristalsis or distention of the tube. Tubal distension produces more intense pain than that associated with ovarian cancer, which may account for the observation that more women with fallopian tube carcinoma present at an earlier stage than patients with ovarian carcinoma.
Preoperatively, most women with a nonmidline pelvic mass are thought to have an ovarian neoplasm since an adnexal mass palpated on physical examination is usually interpreted as an ovarian tumor.
Women can present with findings other than a pelvic mass. A common clinical scenario is presentation with leukorrhea and vaginal bleeding followed by a negative endometrial biopsy. Approximately 10 percent have abnormal cells on Papanicolaou smear and a negative work-up for endometrial or cervical cancer (eg, negative endometrial and endocervical curettage).
DIAGNOSIS AND DIAGNOSTIC EVALUATION — Tissue is required for definitive diagnosis.
There is no consistently reliable noninvasive method to determine the malignant potential of an adnexal mass. The finding of a pelvic mass usually requires surgery for definitive histologic diagnosis. Preoperative evaluation is the same as that for suspected ovarian cancer.
Delay in diagnosis of fallopian tube carcinoma is common, in part because of the rarity of this condition. One study reported a delay of four months between the onset of symptoms to the time of diagnosis in one-half of women. The diagnosis is made postoperatively in the majority of cases.
Laboratory — CA 125 is elevated in most patients. The possibility of fallopian tube cancer should be considered in women with abnormal cells on cervical cytology, but normal colposcopy and biopsies (cervical and endocervical); however, cytology is of limited value in the detection of fallopian cancer as most patients have normal cervical smears.
Routine hematologic and biochemical assessments are obtained prior to surgery.
Imaging — If a pelvic ultrasound is obtained because of the woman's symptoms or after palpation of a pelvic mass, visualization of a solid, cystic, or complex adnexal mass may suggest the diagnosis or the lesion may be attributed erroneously to the ovary or to nonmalignant tubal pathology (eg, hydrosalpinx, tuboovarian abscess). Neovascularization demonstrated on transvaginal color Doppler imaging or ascites suggests malignancy. If malignancy is suspected, a preoperative CA 125 level is useful prognostically and for following the course of disease, but is not diagnostic
Abdominopelvic computerized tomography (CT) or magnetic resonance imaging (MRI) are not helpful in establishing the diagnosis in a patient with a definite pelvic mass; in such patients, surgery is almost always indicated. However, these tests can demonstrate potential sites of metastatic spread, permitting the surgeon to plan the optimal surgical procedure. There also have been reports of the use of positron emission tomography with (flourine-18)-2-deoxy glucose for the detection of metastases
Histopathology — The pathologic diagnosis of primary fallopian tube cancer can be difficult. Criteria that are frequently used include
STAGING — The International Federation of Gynecologists and Obstetricians (FIGO) established an official staging system for fallopian tube carcinoma in 1991
The staging for fallopian tube carcinoma is surgical. A staging operation should be performed in cases where the tumor appears to be well contained. This entails a retroperitoneal lymph node biopsy, infracolic omentectomy, peritoneal washings, and peritoneal biopsies.
This staging system has similarities to the staging for ovarian cancer because of the similarities in pattern of spread, prognosis, treatment, and clinical presentation.
At the time of diagnosis, 33 percent of women have stage I disease, 33 percent stage II, and 34 percent stage III or IV
TREATMENT — Treatment guidelines for fallopian tube carcinoma are very similar to those utilized for epithelial ovarian cancer. Initially surgery is performed, followed by chemotherapy and possibly radiation.
Surgery — Primary surgery consists of total abdominal hysterectomy and bilateral salpingo-oophorectomy, tumor debulking, and full staging. Survival rates are enhanced if the tumor can be removed completely by surgery, similar to the case with ovarian cancer. If optimal cytoreductive surgery cannot be performed in the presence of metastatic disease, removal of as much tumor bulk as possible is important.
Chemotherapy — The data on chemotherapy in fallopian tube cancer are limited by the absence of any randomized controlled clinical trials. It is unlikely that there will be any large-scale randomized trials due to the small number of women with this disorder.
Most fallopian tumors are serous, similar to the most common epithelial ovarian cancers. For this reason, the chemotherapy of primary fallopian tube epithelial tumors is based upon the standard management for ovarian cancer. Patients with residual tumor and those with advanced stage disease are treated with combination chemotherapy using paclitaxel and carboplatin. Many clinical trials for ovarian cancer include patients with fallopian tube cancer because of the similarities in response to chemotherapeutic agents.
There is little experience in clinical trials, with only fallopian tube cancer patients. Several studies have documented the response rate with cisplatin containing regimens:
Adjuvant chemotherapy — The role of chemotherapy in early stage disease is undefined. One study retrospectively reviewed the role of adjuvant treatment in 115 patients with early stage primary fallopian tube carcinoma. They reported five-year survival rate of 53 percent for women receiving radiation versus 27 percent for those receiving cisplatin. They propose that early stage disease is probably better treated with adjuvant radiation therapy.
Radiotherapy — The efficacy of radiation therapy for tubal carcinoma is difficult to assess. This is primarily because of lack of uniformity in published studies in terms of staging, type of radiation, the fraction used, and the radiation field.
The adequacy of pelvic irradiation is questionable since the pattern of spread of this disease includes the upper abdomen. It is possible, however, that whole abdominal radiotherapy might be effective. In one retrospective analysis of 72 patients, patterns of failure included 18 percent pelvic, 36 percent upper abdominal, and 19 percent distant. The majority of these relapses (34 of 40) were within what would be encompassed by the portals of whole abdominal radiotherapy. Further studies are necessary to determine the appropriate candidates for radiation therapy and the dosage and mode of delivery.
Monitoring CA 125 — Monitoring of serum CA 125 levels has value in patients with fallopian tube cancer. The absolute pretreatment serum CA 125 concentration appears to have prognostic value, and following initial treatment, it is a sensitive marker for recurrence and for the response to chemotherapy. This was illustrated in one series of 53 patients with fallopian tube cancer, of whom 43 (81 percent) had an elevated pretreatment serum CA 125 concentration. In a univariate Cox regression model, preoperative serum CA 125 was independently associated with disease free and overall survival. The level of CA 125 also correlated with response to therapy, decreasing in all 20 patients who had an objective response to chemotherapy, and increasing in both patients who had progressive disease. Postoperatively, in 90 percent of patients, an increase in serum CA 125 preceded the clinical or radiologic diagnosis of recurrent disease, with a median lead time of three months.
PROGNOSIS — The single most important factor that correlates with survival is stage of disease. The overall prognosis for fallopian tube carcinoma appears to be better than epithelial ovarian cancer, possibly because patients are diagnosed at an earlier stage of disease. This is illustrated in Table 2, which consists of data derived from the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. The relative five year survival rates are better for every stage of tubal cancer compared to epithelial ovarian cancer. The five year survival rates for fallopian tube cancers in this study are somewhat higher than those reported in single institution series, in which the range of five year survival for stage I, II, III and IV disease is 69 to 73 percent, 37 to 58 percent, 20 to 29 percent, and 12 to 22 percent, respectively.
Stage I disease currently does not take into account the presence or absence of invasion of the tubal wall or the location of the tumor within the tube (fimbrial or nonfimbrial). These also appear to be important prognostic factors
Most recurrences occur outside of the pelvis, within two to three years of diagnosis . Recurrences are common at both extraperitoneal and intraperitoneal sites.
Second look surgery — The role of second look surgery is not well studied in fallopian tube cancer. Second look surgery in women who achieve a complete response to chemotherapy is helpful in determining treatment efficacy and persistent disease. Seventy to 80 percent of patients who have negative second-look surgery following primary cytoreductive surgery and platinum-based chemotherapy remain disease-free . Recurrences after negative second look laparotomy have been reported at distant sites such as the supraclavicular nodes, lung, brain, kidney and axilla . However, second look surgery is not recommended due, in part, to the lack of an effective second-line treatment in patients with persistent disease.
TUBAL SARCOMAS — Tubal sarcomas are considered very rare tumors of the fallopian tubes. The majority of these tumors are malignant mixed mesodermal tumors. One-half are homologous and the others heterologous in nature. Clinical behavior is similar to commonly encountered adenocarcinomas. The prognosis is very poor. Treatment consists of primary surgery followed by cisplatin based chemotherapy.