Malignant Lesions of the Fallopian Tube and Broad Ligament

INTRODUCTION

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Background: In 1847, Renaud first described fallopian tube malignancy. In 1888, Orthmann submitted the first genuine case report.

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

Müllerian origin - Serous, papillary, cystadenocarcinoma, endometrioid carcinoma (CA), clear cell CA
Urothelium transitional cell CA
Mesenchymal sarcoma, histiocytoma
Pheochromocytoma

Secondary malignancies of the broad ligament - Metastatic from endometrial, cervical, and ovarian CA

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

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

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

Frequency:
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• In the US: Fallopian tube CA comprises 1% of all gynecologic cancers. The average annual incidence is 3.6 cases per 1,000,000 women.

Mortality/Morbidity: On average, the 5-year survival rate was 51%: Stage I (65%), Stage II (50-60%), and Stages III and IV (10-20%).

CLINICAL

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History:

• Malignant lesions of the fallopian tube: Patients may present with pelvic pain, a pelvic mass, postmenopausal bleed, and serosanguineous vaginal discharge. The classic description as 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; on examination or on abdominal exploration, 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

• 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 is not proven, although malignancy has been associated with tuberculous salpingitis.

DIFFERENTIALS

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Other Problems to be Considered:

Benign fallopian tube disease salpingitis (eg, tuberculosis salpingitis)
Benign ovarian disease
Ovarian tumor of low malignant potential
Malignant epithelial ovarian tumors
Broad ligament tumors

WORKUP

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Lab Studies:
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• Investigations usually are for postmenopausal bleeding.

• Papanicolaou smear test, showing malignant glandular cells

• Endometrial biopsy

• CA-125 tumor marker assay is performed for follow-up study as a marker for response to therapy.

Imaging Studies:
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• Hysterosalpingogram - Can detect intraluminal growth

• Color Doppler - Can detect neovascularization and low resistance indices

• Three-dimensional ultrasound - Detects papillary protrusions, pseudoseptae, tumoral lakes, microaneurysms, and arteriovenous (AV) shunting

• Ultrasound - Detects adnexal mass

Histologic Findings:
Serous CA - 50%
Endometrioid CA - 25%
Transitional cell CA - 11.7%
Undifferentiated CA - 7.8%
Mixed CA - 3.9%
Clear cell CA - 1.9%

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 usually, more than 50% of ovarian malignancies are in stage III and IV.

• International Federation of Gynecology and Obstetrics (FIGO) fallopian tube staging

• Stage 0 - CA 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 involves 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 the true pelvis but with histologically proven malignant extension to the small bowel or omentum.
  • Stage IIIa - Tumor is limited grossly to the true pelvis, with negative nodes but with histologically confirmed microscopic seeding or abdominal peritoneal surfaces.
  • Stage IIIb - Tumor involves 1 or both fallopian tubes, with histologically confirmed implants on abdominal peritoneal surfaces, none exceeding 2 cm in diameter. Lymph node findings are negative.
  • Stage IIIc - Abdominal implants larger than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes

• Stage IV - Growth involves 1 or both fallopian tubes, with distant metastases. If pleural effusion is present, positive cytology results must be present to be stage IV. Parenchymal liver metastases equal stage IV.
• Staging for fallopian tube is by the surgical pathological system. Operative findings designating stage are determined before tumor debulking.

• Modified FIGO staging for fallopian tube CA

• Stage 0 - CA 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-0b - Growth limited to 1 fallopian tube, with no extension into lamina propria
  • Stage IA-1b - Growth limited to 1 fallopian tube, with extension into lamina propria but no extension into muscularis
  • Stage IA-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-0b - Growth limited to both fallopian tubes, with no extension into lamina propria
  • Stage IB-1b - Growth limited to both fallopian tubes, with extension into lamina propria, but not extension into muscularis
  • Stage IB-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 are negative.
  • Stage IIIC - Abdominal implants larger than 2 cm in diameter and/or positive retroperitoneal or inguinal nodes

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

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• 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

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Medical Care: Medical care depends on frozen section and pathology results, as follows:

• Stage 0 - CA in situ
• Negative cytology results - No further treatment
• Positive cytology results - Intraperitoneal phosphorous 32 (³²P) or short-term cisplatin therapy

• Stage I
  • Negative cytology results - No treatment or short-term cisplatin
  • Positive cytology results - Intraperitoneal ³²P or short-term cisplatin therapy

  Stage II-IV

  • Bulky residual disease or positive nodes - Cisplatin-containing regimens
  • No residual disease, negative nodes - Short-term cisplatin or intraperitoneal ³²P

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  • Residual disease in pelvis - Cisplatin regimen or whole-abdomen radiation with pelvic boost; however, as with ovarian malignancy, patients with fallopian tube malignancy also have an increase in the 5-year survival rate with Taxol and cisplatin

• Various chemotherapy cycles
  • Cyclophosphamide, doxorubicin, and cisplatin (CAP)
  • Cyclophosphamide and cisplatin (CP)
  • Taxol and cisplatin (TP)
  • Topotecan alone is used for first-line chemotherapy, and it can be used for recurrent disease.

• 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.

FOLLOW-UP

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Further Outpatient Care:
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• Patients usually are observed using 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 and/or debulking surgery.

Prognosis:
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• Prognosis depends on the following factors:

• Stage of the malignancy - Highly significant prognostic factor

• Absence of fimbriated end closure - Adversely affects prognosis

• Stage I disease

• Presence or absence of invasion of tubal wall, depth of invasion when present, location of the tumor within the tube (ie, fimbriated or nonfimbriated)

• Presence of p53 mutation is associated with poor prognosis.

• Ascites and patient 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 FIGO staging.

MISCELLANEOUS

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Medical/Legal Pitfalls:
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• 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 nonspecific symptoms. Diagnosis usually is an incidental finding; therefore, medicolegally, it is possible that patients can sue due to failure to diagnose it at an early stage or preoperatively. In addition, no standarized treatment exists; usually, these conditions are treated in a similar manner to ovarian cancer intraoperatively. Chemotherapy or radiotherapy after surgery depends on individual preferences.