Malignant Lesions of the Fallopian Tube and Broad Ligament

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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.

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:

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]

Laboratory Studies

Investigations usually are for postmenopausal bleeding and include the following:

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:

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:

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:

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.

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:

Poor prognostic factors are as follows:

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.

Author

Hetal B Gor, MD, FACOG, Obstetrician/Gynecologist, Private Practice

Disclosure: Nothing to disclose.

Coauthor(s)

John Paulson, MD, Clinical Professor of Obstetrics/Gynecology, Eastern Virginia Medical School; Professor of Clinical Obstetrics/Gynecology, Medical College of Virginia; Associate Director, Residency Program, Riverside Health System

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michel E Rivlin, MD, Former Professor, Department of Obstetrics and Gynecology, University of Mississippi School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Warner K Huh, MD, Professor, Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Senior Scientist, Comprehensive Cancer Center, University of Alabama School of Medicine

Disclosure: I have received consulting fees for: Merck; THEVAX.

Additional Contributors

Karen Loeb Lifford, MD, Director of General Gynecology, Associate Program Director, Department of Obstetrics and Gynecology, Instructor, Brigham and Women's Hospital, Harvard Medical School

Disclosure: Nothing to disclose.

References

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