Malignant Lesions of the Fallopian Tube and Broad Ligament 

Updated: Jan 24, 2019
Author: Hetal B Gor, MD, FACOG; Chief Editor: Warner K Huh, MD 

Overview

Background

In 1847, Renaud first described fallopian tube malignancy. In 1888, Orthmann submitted the first genuine case report.[1]

The broad ligament is a double fold of peritoneum, which is formed by the reflection of the peritoneum off the pelvic floor and the lateral pelvic wall. Most tumors are benign cysts, but malignant tumors are categorized as either primary or secondary.

Primary malignancies of the broad ligament include those of müllerian origin (ie, serous carcinoma, papillary carcinoma, cystadenocarcinoma, endometrioid carcinoma, clear cell carcinoma), urothelium transitional cell carcinoma, mesenchymal sarcoma or histiocytoma, and pheochromocytoma. Some researchers suggest that some primary fallopian tube cancers are misdiagnosed as primary ovarian cancers; however, an experienced pathologist can help to differentiate that.

Secondary malignancies of the broad ligament include metastatic cancers from endometrial, cervical, and ovarian carcinoma.

A primary malignancy is diagnosed based on its location within or on the surface of the broad ligament and by virtue of the complete separation of the tumor from the uterus and ovaries.

See also Fallopian Tube Disorders and Broad Ligament Disorders.

Pathophysiology

Fallopian tube malignancy usually starts as a dysplasia or carcinoma in situ. Typically, transition to adenocarcinoma is observed.

Gilks et al indicate that most cases of incidental nonuterine high-grade carcinomas (HGSCs) arise in the fallopian tube fimbria.[2] In their report, 16 of 21 cases that were incidental microscopic, non-mass-forming serous tubal intraepithelial carcinoma or HGSCs had lesions confined to the fallopian tube (unilateral, 14 cases; bilateral, 2 cases).[3] All 16 had serous tubal intraepithelial carcinoma, and 8 of 16 had invasive HGSC into the underlying lamina propria. In 5 of 21 cases, fallopian tube mucosal and ovarian involvement was found, including 2 cases that also had microscopic peritoneal involvement.[2]

The etiology of malignancies of the broad ligament is unknown, although they are associated with endometriosis.

Epidemiology

Frequency

United States

Fallopian tube carcinomas comprise 1% of all gynecologic cancers. The average annual incidence is 3.6 cases per million women.

Mortality/Morbidity

On average, the 5-year survival rate is 51%; the rate for stage I disease is 65%, stage II disease is 50-60%, and stage III and stage IV disease is 10-20%.

Race

These lesions are more common in whites.

Age

Incidence increases with age but peaks at 60-66 years.

 

Presentation

History

Malignant lesions of the fallopian tube

Patients may present with pelvic pain, a pelvic mass, postmenopausal bleeding, and serosanguineous vaginal discharge.

The classic description of hydrops tubae profluens, which is characterized by colicky lower abdominal pain relieved by a profuse, serous, watery, yellow, intermittent, vaginal discharge, usually is not found.

Malignant lesions of the broad ligament

A clinical history of vague abdominal pain may be present. Upon examination or with abdominal exploration, an adnexal mass is found.

Rarely, it can manifest as an acute abdominal emergency, simulating appendicitis.

Physical

Physical examination findings are not specific; a pelvic mass usually is present, with or without ascites.

Diagnostic criteria include the following:

  • Grossly, the main tumor should be in the fallopian tube.

  • Histologically, the tubal mucosa should be involved, with a papillary pattern.

  • The tubal wall, if involved, and a transition from benign to malignant tubal epithelium should be identified.

  • The lesion is a more advanced stage of tubal tumor than the other tumors.

Causes

The exact etiology is unknown.

Infertility and chronic salpingitis were believed to lead to an increase in incidence, but this theory has not been proven. However, malignancy has been associated with tuberculous salpingitis.

Similar to ovarian malignancy, a BRCA germline mutation and TP53 mutation are associated with fallopian tube malignancy.[4]

 

DDx

Diagnostic Considerations

Fallopian tube and broad ligament malignancies are rare gynecological malignancies. Diagnosing these malignancies at an early stage is difficult because of the lack of symptoms or the presence of nonspecific symptoms. Diagnosis usually is an incidental finding; therefore, medicolegally, it is possible that patients can sue because of a failure to diagnose the cancer at an early stage or preoperatively. In addition, no standardized treatment exists. Usually, these conditions are treated in a manner similar to that used for ovarian cancer intraoperatively. Chemotherapy or radiotherapy after surgery depends on individual preferences.

Differential Diagnoses

 

Workup

Laboratory Studies

Investigations usually are for postmenopausal bleeding and include the following:

  • Papanicolaou smear test, showing malignant glandular cells

  • Endometrial biopsy

The cancer antigen 125 (CA-125) tumor marker assay is performed for follow-up study as a marker of response to therapy.

Imaging Studies

CT scan and MRI help detect location and size of adnexal mass, any metastatic mass, lymph nodes, and other findings for preoperative planning and counseling.

Hysterosalpingography can help detect intraluminal growth; however, spreading the malignancy is a risk.

Color Doppler can help detect arteriovenous shunts, microaneurysms, tumoral lakes, vascular blind ends, dichotomous branching, neovascularization, and low resistance indices.

Three-dimensional (3-D) ultrasonography can help detect papillary protrusions, pseudoseptae, tumoral lakes, microaneurysms, and arteriovenous shunting.

Ultrasonography helps detect an adnexal mass, especially a solid mass corresponding with the expected location of the fallopian tubes in association with normal ovaries or as a sausage-shaped cystic mass with papillary projections.

If symptoms warrant, an upper and lower GI series and barium enema can be performed.

Other Tests

3-D culture models of ovarian cancer, including the fallopian tube fimbriae, show promise in providing a more detailed evaluation of the tumor microenvironment and tumorigenesis.[5, 6, 7, 8]

Histologic Findings

Type of carcinomas found include serous carcinoma (50%), endometrioid carcinoma (25%), transitional cell carcinoma (11.7%), undifferentiated carcinoma (7.8%), mixed carcinoma (3.9%), and clear cell carcinoma (1.9%).

In a retrospective analysis (2001-2011) of 36 Chinese patients with pathology-confirm primary fallopian tube carcinoma (PFTC) who underwent surgical staging, 24 cases were pure adenocarcinoma, 10 cases were mixed.[9] No cases of highly differentiated carcinoma were found, but there was 1 case each of undifferentiated carcinoma and undifferentiated carcinoma/transitional cell carcinoma, 5 cases of moderately differentiated carcinoma, and 29 cases of moderately to poorly differentiated carcinoma. On the basis of multifactor analysis, independent prognostic risk factors included residual tumor diameter larger than 1 cm and the presence of omentum metatastasis.[9]

Immunohistochemistry

Glucose transporter (GLUT1) immunostaining of fallopian tube adenocarcinoma was stronger and more extensive than staining of benign tubal epithelium. GLUT1 positivity is observed in regions most distal from stromal capillaries, suggesting hypoxia-driven GLUT1 induction. On average, GLUT1 staining in primary fallopian tube cancer was less extensive than in primary ovarian adenocarcinomas.[10]

Staging

Although the fallopian tubes are derived from the same embryonic structure as the uterus, histologically and clinically, malignant lesions of the fallopian tubes behave like ovarian tumors. Unlike ovarian tumors, 50% of fallopian tube tumors are stage I and II, whereas more than 50% of ovarian malignancies are usually in stage III and IV. Fallopian tube carcinomas have a predilection for metastasis to retroperitoneal lymph nodes in contrast to intraperitoneal spread of ovarian carcinomas.

International Federation of Gynecology and Obstetrics (FIGO) fallopian tube cancer staging is as follows:

  • Stage 0 - Carcinoma in situ (limited to tubal mucosa)

  • Stage I - Growth limited to the fallopian tubes

  • Stage Ia - Growth limited to 1 tube, with extension into the submucosa and/or muscularis but not penetrating the serosal surface; no ascites

  • Stage Ib - Growth limited to both tubes with extension into the submucosa and/or muscularis but not penetrating the serosal surface; no ascites

  • Stage Ic - Tumor stage 1a or 1b but with tumor extension through or onto the tubal serosa, or with ascites present containing malignant cells, or with positive peritoneal washings

  • Stage II - Growth involving 1 or both fallopian tubes with pelvic extension

  • Stage IIa - Extension and/or metastasis to the uterus and/or ovaries

  • Stage IIb - Extension to other pelvic tissues

  • Stage IIc - Tumor stage IIa or IIb, with ascites present containing malignant cells, or with positive peritoneal washings

  • Stage III - Tumor involving 1 or both fallopian tubes, with peritoneal implants outside the pelvis and/or positive retroperitoneal or inguinal nodes; superficial liver metastasis equals stage III; tumor appears limited to true pelvis but has histologically proven malignant extension to the small bowel or omentum

  • Stage IIIa - Tumor grossly limited to the true pelvis, with negative nodes but with histologically confirmed microscopic seeding or abdominal peritoneal surfaces

  • Stage IIIb - Tumor involving 1 or both fallopian tubes, with histologically confirmed implants on abdominal peritoneal surfaces, none exceeding 2 cm in diameter; lymph node findings negative

  • Stage IIIc - Abdominal implants larger than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes

  • Stage IV - Growth involving 1 or both fallopian tubes, with distant metastases; if pleural effusion is present, positive cytology results necessary to be stage IV; parenchymal liver metastases equal stage IV

Staging for fallopian tube carcinoma is via the surgical pathological system. Operative findings designating stage are determined before tumor debulking.

Modified FIGO staging for fallopian tube carcinoma is as follows:

  • Stage 0 - Carcinoma in situ (limited to tubal epithelium)

  • Stage I - Growth limited to tube

  • Stage IA - Growth limited to 1 fallopian tube, without extension through or onto serosa, ascites containing malignant cells, or positive peritoneal washings

  • Stage IA to 0b - Growth limited to 1 fallopian tube, with no extension into lamina propria

  • Stage IA to 1b - Growth limited to 1 fallopian tube, with extension into lamina propria but no extension into muscularis

  • Stage IA to 2b - Growth limited to 1 fallopian tube, with extension into muscularis

  • Stage IB - Growth limited to both fallopian tubes, without extension through or onto serosa, ascites containing malignant cells, or positive peritoneal washings

  • Stage IB to 0b - Growth limited to both fallopian tubes, with no extension into lamina propria

  • Stage IB to 1b - Growth limited to both fallopian tubes, with extension into lamina propria, but not extension into muscularis

  • Stage IB to 2b - Growth limited to both fallopian tubes, with extension into muscularis

  • Stage IC - Tumor either stage IA or IB, but with extension through or onto tubal serosa, with ascites containing malignant cells, or with positive peritoneal washings

  • Stage I(F) - Tumor limited to fimbriated end of fallopian tube(s), without invasion of tubal wall

  • Stage II - Tumor involving 1 or both fallopian tubes, with pelvic extension

  • Stage IIA - Extension and/or metastasis to uterus and/or ovaries

  • Stage IIB - Extension to other pelvic tissues

  • Stage IIC - Tumor either stage IIA or IIB, with ascites containing malignant cells or with positive peritoneal washings

  • Stage III - Tumor involving 1 or both fallopian tubes, with peritoneal implants outside pelvis, including superficial liver metastasis, and/or positive retroperitoneal or inguinal nodes; tumor limited to pelvis except for histologically proven extension to small bowel or omentum

  • Stage IIIA - Tumor grossly limited to pelvis, with negative nodes but with histologically confirmed microscopic seeding of abdominal peritoneal surfaces

  • Stage IIIB - Tumor involves 1 or both fallopian tubes, with grossly visible histologically confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter; lymph node findings negative

  • Stage IIIC - Abdominal implants larger than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes

  • Stage IV - Growth involving 1 or both fallopian tubes, with distant metastases, including parenchymal liver metastases; if pleural effusion present, fluid must be positive cytologically for malignant cells

  • Modification in terminology - Modifications to accommodate subsets of tumor that otherwise cannot be assigned a stage or to distinguish among subsets that may differ in their associated prognosis

 

Treatment

Medical Care

Medical care for fallopian tube and broad ligament malignancy depends on frozen section and pathology results, as summarized below.

Stage 0 - Carcinoma in situ

Negative cytology results: No further treatment

Positive cytology results: Intraperitoneal platin-based chemotherapy

Stage I

Negative cytology results: No treatment or short-term cisplatin therapy

Positive cytology results: Intraperitoneal cisplatin, but it is associated with more toxicity or short-term platin-based and taxol-based chemotherapy

Stage II-IV

Bulky residual disease or positive nodes: Three cycles of neoadjuvant chemotherapy taxol-based and platinum-based, debulking followed by 3 more cycles of chemotherapy.

No residual disease, negative nodes: Six cycles of taxol-based and platin-based chemotherapy

Treatment of broad ligament malignancy is similar to that for fallopian tube malignancy except in young patients, in whom wide local excision can be adequate.

In a 2012 study, patupilone was not better than standard therapies in treating resistant cases of recurrent ovarian, tubal or primary peritoneal cancer.[11]

Consultations

Consider consultations with the following specialists:

  • Gynecologic oncologist

  • Medical oncologist

  • Surgical pathologist

  • Social worker

Surgical Care

Surgical care includes (1) total abdominal hysterectomy with bilateral salpingo-oophorectomy, (2) omentectomy and peritoneal washing, and (3) selective pelvic and para-aortic lymphadenectomy.

 

Follow-up

Further Outpatient Care

Patients usually are evaluated using the CA-125 assay to monitor response to therapy. If a rise in CA-125 is noted, investigations such as CT scan and laparoscopy can be performed. Any evidence of disease can be treated with chemotherapy, debulking surgery, or both.

Deterrence/Prevention

Carriers of the BRCA gene, especially BRCA2, are recommended to take oral contraceptive pills initially. Once childbearing is over, prophylactic bilateral salpingooherectomy is recommended.

Prognosis

Good prognostic factors are as follows:

  • Negative peritoneal cytology

  • No residual disease at primary cytoreductive surgery

  • Disease limited to the pelvis

  • Abnormal vaginal bleeding as a presenting symptom

  • Negative second look laparotomy

Poor prognostic factors are as follows:

  • Advanced stage of the disease

  • Absence of fimbriated end closure in stage 1 disease

  • The presence of a TP53 mutation

The presence or absence of invasion of tubal wall, the depth of invasion when present, and the location of the tumor within the tube (ie, fimbriated or nonfimbriated) are prognostic variables.

The presence of ascites and the patient's age do not seem to affect prognosis because the prognosis depends on the location of the tumor within the fallopian tube and the depth of invasion of tumor; therefore, Navani suggests modification of the FIGO staging system.