Borderline Ovarian Tumour

Borderline ovarian tumours (atypical proliferative tumours, tumours of low malignant potential) are epithelial ovarian neoplasms with cellular proliferation and nuclear atypia greater than benign counterparts but without destructive stromal invasion.

They make up 10 to 20 percent of epithelial ovarian tumours. Mean age at diagnosis is 40 to 45 years (about 10 to 15 years younger than invasive cancer), so about one third are diagnosed in women under 40.

Histological types:

• serous (about 55 to 65 percent): BRAF and KRAS mutations; may have micropapillary pattern and non-invasive implants
• mucinous (30 to 40 percent): intestinal type is most common, KRAS mutation; metastasis from the gastrointestinal tract must be excluded
• seromucinous
• endometrioid
• clear cell and Brenner types (rare)

About 70 to 80 percent are stage I at diagnosis. The 10-year survival is over 95 percent for stage I and 65 to 85 percent for advanced stage, though late recurrences occur up to 20 years.

Risk factors for recurrence: residual disease, fertility sparing surgery with cystectomy, micropapillary pattern, invasive implants, and advanced stage.

Invasive implants and invasive low grade serous carcinoma may follow in about 2 to 4 percent of advanced serous cases.

• Asymptomatic in about 25 to 30 percent; found on imaging.
• Abdominal distension, pelvic pain or pressure, urinary frequency, or constipation.
• Acute abdomen from torsion, rupture or haemorrhage; large mucinous tumours (above 20 cm) with pseudomyxoma peritonei in rare cases.
• Ascites is uncommon, found in about 10 to 20 percent of advanced serous disease.
• Infertility is frequent, and a history of ovulation induction is reported.
• Examination: adnexal mass; omental caking in advanced serous types.

• Ultrasound: a cystic mass with papillary excrescences, solid areas, and multilocularity; mucinous tumours are large multilocular cysts with variable echoes. Papillary projections have internal vascularity on Doppler; there is overlap with invasive carcinoma and benign cystadenoma, so the preoperative diagnosis is often uncertain.
• MRI is useful for characterising a complex mass; CT chest, abdomen and pelvis for stage.
• Tumour markers: CA-125 raised in about 50 percent of serous types and in advanced disease; CEA and CA 19-9 raised in mucinous types; combined with an appendix and gastrointestinal evaluation for mucinous tumours (colonoscopy and appendix assessment when the tumour is bilateral, or involves the appendix, or has an abnormal CEA).
• Histological diagnosis is made after surgery; intraoperative frozen section has a sensitivity of about 65 to 75 percent for borderline tumours and underdiagnoses large mucinous tumours, so extensive sampling of the final specimen (one section per cm of tumour diameter) is essential.
• Implant assessment: non-invasive (epithelial or desmoplastic) versus invasive implants, which carry a worse prognosis.

• Surgery is the cornerstone of treatment, and adjuvant chemotherapy is not effective in this disease.
• Women who have completed childbearing: total hysterectomy, bilateral salpingo oophorectomy, omentectomy (infracolic), peritoneal washings, and multiple peritoneal biopsies for full staging; appendectomy for mucinous tumours; lymphadenectomy is not indicated, as it does not improve survival. Surgery is by laparotomy or laparoscopy with intact retrieval in a bag; avoidance of spillage and morcellation.
• Women wanting fertility: fertility sparing surgery with either of the following:
  • unilateral salpingo oophorectomy (preferred; recurrence about 5 to 10 percent)
  • cystectomy (recurrence about 12 to 30 percent, mostly as borderline tumours and treated by repeat surgery)
  Conserve the uterus and the contralateral ovary even in advanced stage, along with staging and removal of all macroscopic disease. Bilateral involvement: bilateral cystectomy with careful follow up.
• Completion surgery (hysterectomy and bilateral salpingo oophorectomy) after childbearing is completed, as recurrence is possible.
• Invasive implants or invasive recurrence: treated as low grade serous carcinoma, with cytoreductive surgery and chemotherapy (carboplatin AUC 5 with paclitaxel 175 mg/m2 every 21 days for 6 cycles; response rates are low, around 10 to 20 percent) and endocrine therapy (letrozole 2.5 mg daily, anastrozole 1 mg daily, tamoxifen 20 mg daily, or fulvestrant 500 mg monthly).
• Recurrence: secondary cytoreductive surgery.
• Pseudomyxoma peritonei from mucinous disease: cytoreductive surgery with hyperthermic intraperitoneal chemotherapy at specialised centres.
• Follow up: clinical examination, transvaginal ultrasound and CA-125 every 3 to 6 months for 2 years, then every 6 to 12 months for at least 10 years because of late recurrences; MRI or CT where suspicion arises.
• Hormone replacement therapy after oophorectomy is acceptable, and fertility drugs are used with caution.
• Pregnancy after fertility sparing surgery is encouraged, with ultrasound monitoring.