Table of Contents  

Nduka: Adenocarcinoma of the fallopian tube and malignancies of the female reproductive system – a review of the literature

Introduction

The fallopian tubes (oviducts) serve to connect the endometrial cavity with the vicinity close to the medial border of the ovaries. They are derived, with the uterus and cervix, from the embryonic mesonephric (Müllerian) duct. Malignancies involving the fallopian tubes could be primary or secondary metastasis. Primary carcinoma of the fallopian tube has been associated with mutations in the BRCA1 (breast cancer 1) and BRCA2 genes.1,2 Fallopian tube involvement in malignancies of the female reproductive system has been generating a lot of interest. It is important to note that the most common variant of ovarian cancer is high-grade serous cancers (HGSCs), accounting for 60–80% of all ovarian cancers.3,4 The most likely site of origin of HGSCs is the fallopian tube.5,6 Malignant precursors, serous tubular intraepithelial carcinomas (STICs), have also been found present in 47% of patients with peritoneal serous carcinoma.7 Primary fallopian tube carcinomas are mostly diagnosed after surgery because they present with non-specific signs and symptoms.8,9 Treatment involves surgery and chemotherapy.

Method

An internet data search using PubMed was carried out for papers published in the last 15 years containing the keywords ‘adenocarcinoma’, ‘fallopian tube’, ‘treatment’ and ‘salpingectomy’, which yielded 179 relevant articles; those not in English were used provided a translated abstract was available.

Discussion/overview

Basic anatomy

The human fallopian tube commences at the apical superolateral borders of the uterus on both sides and ends close to the tubal aspect of both ovaries and is about 10 cm long and 1 cm in diameter.10 It consists of four segments, from lateral to medial: the infundibulum with its fimbrial opening, the ampullary segment, the isthmus and the intramural segment, which connects with the endometrium.10 Histological section of the fallopian tube shows that it has an outer serosal covering, a muscular subserosa, a lamina propria and inner mucosa lined with simple columnar epithelium.11

Epidemiology

Carcinoma of the fallopian tube was first described by Reneaud in 1847.12

The mean age at presentation of primary carcinoma of the fallopian tube is 56.7 years. In a series covering 20 years 27% of affected women were nulliparous, and the mean parity was 1.7.13

Adenocarcinoma of the fallopian tube accounts for more than 95% of all primary carcinomas of the fallopian tube.14 It is, compared with other gynaecological malignancies, rare. Primary carcinoma of the fallopian tube accounts for 0.3–1.9% of all gynaecological tumours.9,1519 Serous adenocarcinoma of the fallopian tube is the most common type, followed by endometrioid adenocarcinoma.20

Pathogenesis

The turning point in the pathogenesis of serous adenocarcinoma would seem to be the appearance of STIC, an immediate precursor of invasive fallopian carcinoma.21 STIC is characterized by a high nuclear to cytoplasm ratio, appearance of mitotic figures, loss of polarity with or without epithelial stratification, pleomorphism and hyperchromasia. The association of STICs with germline BRCA mutation has been documented.1,2 STIC lesions are strongly associated with TP53 mutations, and these mutations are commonly in the form of either a missense or a splice/frameshift mutation. They stain strongly or diffusely for P53, correlating with a TP53 mutation.2226 It has been hypothesized that benign secretory fallopian tubal cells may be the precursor cells from which STICs evolve.27 These secretory cells are termed SCOUTs (secretory cell outgrowths).28 Deregulation of PAX2 (a marker of Müllerian and uroepithelial differentiation) has been seen in most SCOUTs.28 It is also noteworthy that this same deregulation of PAX2 has been associated with serous carcinoma of the distal fallopian tube, hence the hypothesis.27 However, this requires further research.

Clinical features

The presenting clinical features of adenocarcinoma of the fallopian tube may be subtle, and symptoms such as vague lower abdominal pain and non-specific vaginal discharge may be present. These features may lead to a misdiagnosis of tubo-ovarian abscess or ovarian tumour. Abdominal distension, ascites and features of metastasis are usually signs of advanced disease. Pelvic pain and mass combined with serous vaginal discharge (Latzko triad) is noted in less than 15% of patients and this combination of symptoms may be present only with distal fallopian tube blockage.29 Per vaginal digital examination may reveal a mass in the adnexa.

Investigation

Diagnosis is seldom made preoperatively because of the non-specific presentation of clinical features; however, a tumour mass may be found incidentally during imaging for other suspected abdominal and pelvic pathologies. Ultrasound and computerized tomography (CT) are some of the imaging techniques use to aid diagnosis. CT of the abdominopelvis may also be useful in staging disease progression. Salpingectomy via laparoscopy or open laparotomy with histological examination of the specimen is the definitive method of confirming diagnosis. The SEE-FIM (section and extensively examine the fimbriae) protocol has been developed to maximize the detection of occult malignancies in the fimbrial part of the tube.30,31 The protocol involves amputation of the fimbriae at the infundibulum, longitudinal sectioning of the fimbria and extensive cross-sectioning of the remainder of the tube at 2-mm intervals. Because the ovaries and fallopian tube share an embryonic origin, tumours affecting both show clinical and histological similarities. Sedlis’s32 modification of Hu et al.’s33 diagnostic criteria for primary fallopian tube carcinoma includes:

  • tumour arises from the endosalpinx;

  • the histological pattern reproduces the epithelium of the tubal mucosal;

  • transition from benign to malignant epithelium is observed;

  • the ovary should be normal or, at most, contain a smaller tumour.

The tumour marker CA (cancer antigen)-125 has shown promising results in aiding the diagnosis of fallopian tube cancer. Although not specific to tubal carcinoma, it has been used in conjunction with endometrial aspiration cytology. A positive result using both parameters in the absence of endometrial malignancy increases the suspicion of either a tubal or ovarian malignancy.

Treatment/prevention

Treatment of adenocarcinoma of the fallopian tube could be medical and/or surgical with or without radiotherapy, depending on the stage of disease. Worthy of note is that treatment may require a multidisciplinary approach involving the surgical pathologist, oncologist, radiologist, social worker, etc.

There are limited data proving the overall effectiveness of carboplatin and paclitaxel as first-line drug treatments; however, one of the largest series, involving 64 women on the carboplatin and paclitaxel regimen, reported a 93% overall response and excellent 5-year survival rates.34 Gemignani et al.35 reported 1-year survival rate of 96% and 3-year survival rate of 91% in 24 patients, 71% with terminal disease, treated with an adjuvant carboplatin-based regimen after optimal cytoreductive surgery.

Risk-reducing salpingectomy to prevent development of HGSC of the ovary has been suggested.36 This follows various studies showing that HGSC originates from the fallopian tube and not the ovaries, as previously thought.29,37,38 The Society of Gynaecologic Oncology of Canada recommends that the risk and benefit of this option be discussed with patients undergoing hysterectomy and permanent sterilization via tubal surgery.36 Prophylactic salpingectomy is relevant for women in the general population with an average genetic risk for ovarian cancers.

Women with high-risk genetic mutations, such as BRCA mutations, should be offered prophylactic risk-reducing salpingo-oophorectomy (RRSO) as there is evidence that this procedure greatly reduces the risk of developing ovarian and fallopian tube carcinomas.39,40

A detailed histological examination of the whole of the fallopian tube specimen, as in the SEE-FIM protocol, has been shown to detect early cancer in about 4–19% of women with BRCA mutations who have undergone prophylactic RRSO. The variance seems to be associated with the age of patient and the thoroughness with which the specimen was examined.4145 Novel preventative measures include ex vivo optical imaging of the fallopian tube. A study in which reflectance and fluorescence examination of fallopian tube was employed has shown promise for use in the early detection of tubal epithelial abnormality.46 The methods used were also feasible and reproducible; however, further research is required to make this imaging technique in vivo.

Staging

Details of the staging system for carcinoma of the fallopian tube are shown in Table 1.

TABLE 1

An interpretation of the International Federation of Gynecology and Obstetrics staging system for carcinoma of the fallopian tube

Stage Definition
0 Carcinoma in situ (limited to tubal mucosa)
I Growth limited to fallopian tubes
Ia Growth limited to one tube with extension into the submucosa or muscularis, or both, but not penetrating the serosal surface; no ascites
Ib As Ia but growth limited to both tubes
Ic Tumour stage Ia or Ib with extension to serosa or ascites or peritoneal washings containing malignant cells
II Growth involving one or both fallopian tubes with pelvic extension
IIa Extension or metastasis, or both, to the uterus or ovaries, or both
IIb Extension to other pelvic tissue
IIc Stage IIa or IIb with ascites containing malignant cells or positive peritoneal washings
III Tumour involves one or both fallopian tubes with extrapelvic peritoneal implants or retroperitoneal or inguinal nodes containing tumour
IIIa Tumour seems limited to true pelvis but histologically proven malignant extension to the small bowel or omentum
IIIb Tumour grossly limited to the true pelvis with negative nodes but with histologically confirmed microscopic seeding of the abdominal peritoneal surfaces
IIIc Tumour involving one or both tubes with histological confirmed implants of abdominal peritoneal surfaces, none exceeding 2 cm in diameter
IV Abdominal implants greater than 2 cm in diameter or retroperitoneal or inguinal nodes or both, containing tumour
Growth involving one or both fallopian tubes with distant metastases
Pleural effusion cytology must show malignant cells to be stage IV. Parenchymal liver metastases equals stage IV

Conclusion

The place of adenocarcinoma involving the fallopian tube together with the role of precursor lesions such as STIC in the evolution and progression of malignancy involving the female internal genitalia needs further study in order to improve our understanding and, subsequently, management of these conditions.

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