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Recurrence of borderline ovarian tumour after fertility treatment

Junejo, Shabanaa; Welch, Richardb; Ahmed, Ahmed Sekotorya,b

Journal of Evidence-Based Women’s Health Journal Society: May 2013 - Volume 3 - Issue 2 - p 80–83
doi: 10.1097/01.EBX.0000427508.45933.3a
Case report
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Background Borderline ovarian tumours account for 10–20% of all epithelial ovarian tumours. As one-third of these tumours are seen in women less than 40 years of age, fertility remains a major concern in their management. Conservative surgery has been advocated in these cases. Fertility treatment has been successfully used in some of these cases with good results. However, the risk of tumour recurrence cannot be ignored.

Case report A young nulliparous woman had fertility sparing surgery (bilateral salpingo-oophorectomy and omentectomy) for serous borderline ovarian tumours with noninvasive implants (stage IIIc). After 10 years of uneventful follow-up, she decided to undergo an in-vitro fertilization with donor oocytes. She received unopposed oestrogen stimulation for 12 days to prime the endometrium and developed ascites. Subsequent investigations revealed tumour recurrence in the form of low-grade serous adenocarcinoma. The carcinoma proved resistant to chemotherapy and pursued an aggressive course culminating in death within 6 months of diagnosis.

Conclusion Borderline ovarian tumours can recur in an aggressive manner even after a prolonged follow-up. Large clinical trials with longer follow-up are needed to evaluate the safety of controlled ovarian hyperstimulation after conservative surgery for borderline ovarian tumours.

aDepartment of Gynaecological Oncology, University Hospital of South Manchester

bThe Christie NHS Foundation Trust, Manchester, UK

Correspondence to Shabana Junejo, MBBS, MRCOG, Department of Gynaecology Oncology, University Hospital of South Manchester, Moorside Road, Manchester M23 9LT, UK Tel: +44 780 961 4563; e-mail: shjunejo@yahoo.com

Received January 4, 2013

Accepted February 6, 2013

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Introduction

Borderline ovarian tumours account for 10–20% of all epithelial ovarian tumours. As one-third of these tumours are seen in women less than 40 years of age, fertility remains a major concern in their management 1. After conservative surgery, spontaneous conceptions have been reported 2. Some of these patients require fertility treatment such as controlled ovarian hyperstimulation and in-vitro fertilization (IVF) 3.

We present a case of borderline ovarian tumour that recurred in the form of an aggressive, invasive disease after initiation of fertility treatment, more than 10 years after the initial surgery.

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Case report

A 28-year-old nulliparous woman was admitted through accident and emergency with strangulated umbilical hernia. During the operation, she was diagnosed with ascites and bilateral ovarian tumours (17×11×7 and 8.5×7×5 cm) with peritoneal and omental seedlings. About 3 l of ascitic fluid was drained and bilateral oophorectomy and omentectomy were performed, preserving her uterus.

Histological analysis revealed bilateral borderline serous papillary cystadenoma with noninvasive implants on the omentum and hernial sac (FIGO stage IIIc). Postoperatively, her CA-125 level was 86. She was given adjuvant chemotherapy with carboplatin for six doses. The CA-125 level came down to 18 after 6 months.

She had regular follow-ups with the oncology team and remained well. She was on cyclical hormone replacement therapy (HRT) (Prempak-C, Wyeth Medica Ireland, Little Connell, Newbridge, Co. Kildare, Republic of Ireland), which was commenced 4 weeks after her surgery.

After 10 years of uneventful follow-ups, she decided to go for an IVF with donor oocytes.

Preliminary assessments carried out at the IVF unit using transvaginal scans showed revealed an endometrial thickness of 4 mm. She underwent oestrogen stimulation to prime the endometrium with oestradiol valerate (12 mg daily) and Estraderm TTS (Novartis, Basel, Switzerland) (100 μg for 12 days).

Ultrasound scans repeated 2 weeks after oestrogen stimulation revealed pockets of ascitic fluid.

She was referred back to the oncology unit, wherein a computed tomography scan revealed large amounts of ascites, calcified deposits on the uterus and multiple retroperitoneal and retrocrural nodes up to 9 mm in size but no large tumour deposits. The CA-125 level was 45.

She subsequently underwent laparoscopy and was found to have multiple miliary tumour deposits all over the peritoneal surfaces, on remnants of the omentum and on the uterus. A cystic lesion 3 cm in size was seen at left cornu of the uterus, which appeared like a peritoneal cyst. The liver surface appeared generally smooth. Multiple biopsies were obtained from the peritoneum and cystic lesion, and eight litres of ascitic fluid was drained.

The histological analysis revealed low-grade serous adenocarcinoma involving the peritoneum, remnants of the omentum and the broad ligament. Analysis of the ascitic fluid revealed malignant epithelial cells.

The tumour cells were negative for oestrogen receptors.

After discussions at the multi-disciplinary team, she was referred for chemotherapy. She was started with carboplatin and taxol, but unfortunately she failed to respond. She developed massive pleural effusions and ascites, which needed drainage and pleurodesis on multiple occasions. Computed tomography scans confirmed disease progression. After two doses, her chemotherapy was changed to cisplatin. Her condition continued to deteriorate. Multiple tumour nodules appeared at the drainage sites, intestinal obstruction occurred and eventually she died of the disease within 6 months of diagnosis Figs 1 and 2.

Figure 1

Figure 1

Figure 2

Figure 2

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Discussion

The concept of borderline ovarian tumours was proposed by Taylor in 1929, who called them ‘semimalignant’ because the clinical behaviour of these tumours was intermediate between benign and malignant. These tumours were recognized as a separate entity by WHO in 1973 and were named borderline ovarian tumours 4.

The borderline ovarian tumours share some histological features with malignant epithelial tumours but are characterized by the absence of destructive stromal invasion 5. They may be associated with an extraovarian disease (termed implants rather than metastasis). The implants could be invasive or noninvasive. The staging is based on principles same as those for ovarian carcinoma. However, in contrast to their malignant counterparts, borderline ovarian tumours (BOTs) have much better prognosis at every stage 6.

In the past, these tumours were treated aggressively, similar to their invasive counterparts. More recently, after recognition of their intermediate status between benign and malignant ovarian tumours in terms of histology, clinical behaviour, and prognosis, as well as the younger mean age of the patients at the time of diagnosis, conservative therapeutic approaches have been adopted 7.

Approximately 80% of these tumours are diagnosed at stage I or II. The prognosis is better compared with other ovarian malignancies 8.

The detection and nature of extraovarian implants determines to a great extent the prognosis of BOT 9. Noninvasive implants are common, and their presence appears to have no significant influence on survival 10. The prognosis of patients with noninvasive implants is excellent, and conservative surgery can be recommended in such patients. In contrast, prognosis for patients with invasive implants is less optimistic. Therefore, the scope of conservative surgery is limited 11.

In addition to extraovarian extension, the clinical stage, histological type and residual tumour also affect the prognosis 12. HRT is not associated with the development of BOT 13.

The survival rate is not significantly different after conservative treatment as compared with radical surgery 14; however, the recurrence rate varies between 0 and 30% 6.

Zanetta and colleagues studied 339 women treated for borderline ovarian tumours, of which 24 women with peritoneal implants were treated conservatively. The disease-free survival of patients with stage II and III disease was similar, regardless of the type of surgical treatment (conservative or radical). The recurrence rate was however higher for women undergoing fertility sparing surgery (35/189 women, 18.5%) compared with women undergoing hysterectomy and bilateral salpingo-oophorectomy (7/150 women, 4.7%). All but one woman with recurrence of borderline tumour or progression to carcinoma after conservative surgery were salvaged 15.

Conservative laparoscopic surgery for BOT can be safely performed in young patients during early stages of the disease as this reduces the risk of postoperative adhesions and optimizes fertility results. The recurrence rate is same as that after laparotomy. The recurrence is particularly high after cystectomy (30–35%) 16. Therefore, cystectomy, as a conservative treatment for BOT, should only be considered in bilateral tumours (with contralateral adnexectomy) or in cases in which there is only one ovary (history of previous oophorectomy) 17.

Spontaneous conceptions have been reported after conservative surgery. Some patients require fertility treatment. The influence of fertility treatment on the development of ovarian malignancy is controversial. History of infertility increases the overall risk of ovarian cancer. It was suggested that high serum oestradiol levels during ovarian hyperstimulation might promote tumour growth in BOT, especially in oestrogen receptor-positive cases. This risk is very low in patients treated for early-stage BOT 3.

Camatte and colleagues observed eight pregnancies in seven out of 17 (41%) patients with stage II and III BOT and noninvasive implants after conservative surgery. There were six spontaneous conceptions, one occurred after ovarian stimulation and another after IVF treatment. Interestingly, four pregnancies occurred after the second conservative surgery for recurrent BOT of the spared ovary. The recurrence rate was 52% but survival was 100% after a median follow-up of 60 months 11.

In another study, five patients who underwent a previous conservative surgery for BOT (stage Ia–c) received 17 IVF cycles. Six pregnancies were observed in three of the five patients. One patient had three recurrences at 13, 27 and 43 months after the first IVF cycle, all of which remained S-BOT histologically. All patients were without evidence of the disease at the time of last follow-up. The mean follow-up period was 39.2 months 18.

Chan et al. 3 reported 16 patients who underwent IVF after conservative treatment for borderline ovarian tumours. No recurrence was reported during the follow-up period of up to 46 months 3.

Chan et al. 3 reported 10 IVF cycles in five infertile patients after conservative surgery for BOT. Recurrence was not reported in any of these patients after IVF treatment up to a mean duration of 29.6 months (range 14–61 months). This study also showed that prior diagnosis and treatment of BOT have no perceptible negative impact on pregnancy outcomes after IVF treatment, and it can safely be offered to patients with early-stage BOT.

To date, there is no evidence in the literature to restrict the use of artificial reproductive techniques in patients with early-stage BOT after conservative treatment.

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Conclusion

This case appears unusual. The patient had undergone conservative surgery for bilateral borderline serous ovarian tumours with noninvasive implants (stage IIIc). She was on cyclical HRT and remained well up to 10 years of follow-up.

Unopposed oestrogen stimulation for a short period of 12 days precipitated recurrence with progression to low-grade serous adenocarcinoma. The clinical behaviour of the tumour appeared far more aggressive than expected in view of the histology.

This case suggests that borderline tumours may recur in an aggressive manner, and they should not be underestimated.

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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References

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Keywords:

assisted conception; borderline ovarian tumours; fertility

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