Fallopian Tube Carcinoma

Fallopian tube carcinoma is a malignant epithelial tumour of the tubal mucosa, usually high grade serous in type (about 80 percent). It is now recognised as the origin of most high grade serous carcinomas previously attributed to the ovary or peritoneum. These start as serous tubal intraepithelial carcinoma in the fimbria.

Pure primary tubal carcinoma is rare (0.3 to 1.1 percent of gynaecological cancers), with a peak age of 55 to 65 years. Associations are BRCA1 and BRCA2 mutations, Lynch syndrome, nulliparity, and infertility. About 3 to 10 percent of mutation carriers undergoing prophylactic salpingo oophorectomy have occult tubal cancer, with the fimbria involved in most.

Other types are endometrioid, clear cell, transitional, mucinous and carcinosarcoma.

Diagnostic criteria for primary tubal origin:

• The main tumour is in the tube.
• The mucosa is involved with a papillary pattern.
• A transition from benign to malignant epithelium is demonstrable.
• The ovary and endometrium are normal or contain less tumour than the tube.

Staging is as for ovarian cancer: stage I confined to the tubes, II pelvic extension, III peritoneal or retroperitoneal nodal spread, IV distant metastases. About 50 percent are stage I or II at diagnosis (higher than ovarian cancer because of earlier symptoms).

• Classic triad (in under 15 percent): watery or serosanguinous vaginal discharge (hydrops tubae profluens), colicky pelvic pain relieved by the discharge, and a pelvic mass.
• Abnormal vaginal bleeding (postmenopausal or intermenstrual), pelvic pain or pressure, abdominal distension, and an adnexal mass.
• Ascites, bowel symptoms and weight loss in advanced disease.
• Often misdiagnosed as ovarian carcinoma, pelvic inflammatory disease, or ectopic pregnancy.
• Cytology with abnormal adenocarcinoma cells in an otherwise normal cervical smear (a malignant glandular cell on cytology with normal hysteroscopy and endometrial biopsy raises suspicion).

• Transvaginal ultrasound and MRI: a sausage shaped adnexal mass or dilated tube with solid papillary projections that are vascular on Doppler, and a mass separate from the ovary with no hydrosalpinx pattern.
• CA-125 raised in about 80 percent and used for monitoring; CEA and CA 19-9.
• Hysteroscopy and endometrial biopsy to exclude uterine primary tumours when there is vaginal bleeding or malignant cells on a smear; cervical cytology.
• CT chest, abdomen and pelvis for staging; PET-CT for suspected recurrence.
• Definitive diagnosis is histological after surgery; frozen section is useful intraoperatively.
• Germline BRCA1, BRCA2 and mismatch repair testing; the tumour is tested for homologous recombination deficiency.

Management is identical to that of epithelial ovarian cancer.

• Surgery: total hysterectomy, bilateral salpingo oophorectomy, omentectomy, peritoneal washings and biopsies, and pelvic and para aortic lymph node assessment. Nodal metastases occur in about 30 to 50 percent, including in early stage. In advanced disease, aim for maximal cytoreduction with no residual macroscopic tumour.
• Adjuvant chemotherapy for all stages except low risk stage IA (and IB) grade 1: carboplatin AUC 5 to 6 with paclitaxel 175 mg/m2 every 21 days for 6 cycles.
• Use neoadjuvant chemotherapy for unresectable stage III or IV disease, with interval cytoreduction. Give bevacizumab 15 mg/kg every 3 weeks in high risk disease.
• Maintenance therapy with PARP inhibitor (olaparib 300 mg twice daily or niraparib 200 to 300 mg once daily) after response in BRCA-mutated or homologous recombination deficient tumours.
• Recurrence, platinum sensitive: platinum based doublets, secondary cytoreduction in selected patients, and PARP inhibitor maintenance.
• Recurrence, platinum resistant: weekly paclitaxel, pegylated liposomal doxorubicin, topotecan, or gemcitabine, with or without bevacizumab.
• Early stage (I) disease: 5-year survival 65 to 90 percent. Stage III to IV: about 20 to 40 percent. Survival is similar to or slightly better than ovarian cancer stage for stage.
• Surveillance: examination and CA-125 every 3 months for 2 years, then every 6 months for 3 years, then yearly. Image when symptoms or marker rise.
• Genetic counselling and cascade testing. Offer prophylactic salpingectomy for tubal fertility sterilisation and risk reducing bilateral salpingo oophorectomy in carriers. The fimbria must be fully examined with the SEE-FIM protocol, with whole tube sectioned.
• Hormone replacement therapy decision is individualised after oophorectomy for early stage disease.