Transitional cell carcinoma of the ovary: A rare case and review of literature

<p>Abstract</p> <p>Introduction</p> <p>Transitional cell carcinoma (TCC) of the ovary is a rare, recently recognized, subtype of ovarian surface epithelial cancer.</p> <p>Case presentation</p> <p>A 69-year-old postmenopausal woman presented with a 2-year history of progressive enlargement of an abdominal mass. Abdominal computed tomography showed a pelvic mass. CA-125 was normal. A staging operation with total abdominal hysterectomy, bilateral salpingo-oophorectomy, infracolic omentectomy and pelvic lymph node dissection was performed. After surgery, the pathologic report of the right ovarian tumour was TCC, grade 3, stage IC. The patient underwent 3 cycles of chemotherapy: carboplatin and paclitaxel. She is regularly followed up and has been disease free for 10 months</p> <p>Conclusion</p> <p>Transitional cell carcinoma (TCC) of the ovary is a rare subtype of epithelial ovarian cancer. Surgical resection is the primary therapeutic approach, and patient outcomes after chemotherapy are better than for other types of ovarian cancers.</p

Use of novel serum markers in clinical follow-up of Sertoli-Leydig cell turnours

Background: Sertoli-Leyclig cell tumours of the ovary account for only 0.2% of malignant ovarian tumours. Two-thirds of all patients become apparent due to the tumour's hormone production. Methods: A 41-year-old patient (gravida 4, para 4) presented with dyspnoea, enlarged abdominal girth and melaena. Diagnostic imaging was suspicious for an ovarian cancer. The standard tumour marker for ovarian cancer (CA 125) was elevated to 984 U/mL. Results: Surgical exploration of the abdomen revealed a mouldering tumour of both adnexes extending to the level of the navel. Frozen sections showed an undifferentiated carcinoma of unknown origin. Radical surgery was performed. The final histological report described a malignant sex-cord stroma tumour, a Sertoli-Leydig cell tumour, emanating from both ovaries. Analysis of preoperative blood serum showed elevated levels of CYFRA 21-1 (10.4 ng/mL), neuron-specific enolase (36.2 ng/mL), oestradiol (485 pg/mL) and CA-125 (984 U/mL). Adjuvant chemotherapy and regional hyperthermia were performed due to the malignant potential and incomplete resection of the tumour. Conclusions: Undifferentiated Sertoli-Leyclig cell tumours show a poor clinical course. As only two-thirds of patients with this rare disease present with elevated hormone levels, new markers deserve further investigation to offer more specific, individualised tumour monitoring

Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial

BACKGROUND: Low-grade serous carcinoma of the ovary or peritoneum is characterised by MAPK pathway aberrations and its reduced sensitivity to chemotherapy relative to high-grade serous carcinoma. We compared the MEK inhibitor trametinib to physician's choice standard of care in patients with recurrent low-grade serous carcinoma. METHODS: This international, randomised, open-label, multicentre, phase 2/3 trial was done at 84 hospitals in the USA and UK. Eligible patients were aged 18 years or older with recurrent low-grade serous carcinoma and measurable disease, as defined by Response Evaluation Criteria In Solid Tumors version 1.1, had received at least one platinum-based regimen, but not all five standard-of-care drugs, and had received an unlimited number of previous regimens. Patients with serous borderline tumours or tumours containing low-grade serous and high-grade serous carcinoma were excluded. Eligible patients were randomly assigned (1:1) to receive either oral trametinib 2 mg once daily (trametinib group) or one of five standard-of-care treatment options (standard-of-care group): intravenous paclitaxel 80 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; intravenous pegylated liposomal doxorubicin 40-50 mg/m2 by body surface area once every 4 weeks; intravenous topotecan 4 mg/m2 by body surface area on days 1, 8, and 15 of every 28-day cycle; oral letrozole 2·5 mg once daily; or oral tamoxifen 20 mg twice daily. Randomisation was stratified by geographical region (USA or UK), number of previous regimens (1, 2, or ≥3), performance status (0 or 1), and planned standard-of-care regimen. The primary endpoint was investigator-assessed progression-free survival while receiving randomised therapy, as assessed by imaging at baseline, once every 8 weeks for 15 months, and then once every 3 months thereafter, in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study therapy. This trial is registered with ClinicalTrials.gov, NCT02101788, and is active but not recruiting. FINDINGS: Between Feb 27, 2014, and April 10, 2018, 260 patients were enrolled and randomly assigned to the trametinib group (n=130) or the standard-of-care group (n=130). At the primary analysis, there were 217 progression-free survival events (101 [78%] in the trametinib group and 116 [89%] in the standard-of-care group). Median progression-free survival in the trametinib group was 13·0 months (95% CI 9·9-15·0) compared with 7·2 months (5·6-9·9) in the standard-of-care group (hazard ratio 0·48 [95% CI 0·36-0·64]; p<0·0001). The most frequent grade 3 or 4 adverse events in the trametinib group were skin rash (17 [13%] of 128), anaemia (16 [13%]), hypertension (15 [12%]), diarrhoea (13 [10%]), nausea (12 [9%]), and fatigue (ten [8%]). The most frequent grade 3 or 4 adverse events in the standard-of-care group were abdominal pain (22 [17%]), nausea (14 [11%]), anaemia (12 [10%]), and vomiting (ten [8%]). There were no treatment-related deaths. INTERPRETATION: Trametinib represents a new standard-of-care option for patients with recurrent low-grade serous carcinoma. FUNDING: NRG Oncology, Cancer Research UK, Target Ovarian Cancer, and Novartis

Adult granulosa cell tumor associated with endometrial carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>If strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5%. In patients with granulosa cell tumors, estrogen-dependent endometrial cancers are rarely found, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early.</p> <p>Case presentation</p> <p>We report the case of a 65-year-old post-menopausal Nigerian woman of the Igbo tribe with an adult granulosa cell tumor that was initially treated as endometrial carcinoma. She underwent a total abdominal hysterectomy and a bilateral salpingo-oophorectomy after histopathologic confirmation of a well-differentiated granulosa cell tumor of the ovary and a nuclear grade 1 adenocarcinoma of the endometrium (International Federation of Obstetricians and Gynecologists stage 1B). She had a good post-operative recovery and was discharged 10 days after treatment.</p> <p>Conclusion</p> <p>The association between adult granulosa cell tumors of the ovary and endometrial carcinomas is rare. A high index of suspicion as well as good imaging and histopathologic analyses are important in making this diagnosis.</p

An international, phase III randomized trial in patients with mucinous epithelial ovarian cancer (mEOC/GOG 0241) with long-term follow-up: and experience of conducting a clinical trial in a rare gynecological tumor

Objectives We evaluated four different treatment regimens for advanced-stage mucinous epithelial ovarian cancer. Methods We conducted a multicenter randomized factorial trial (UK and US). Patients were diagnosed with primary mEOC: FIGO stage II–IV or recurrence after stage I disease. Treatment arms were paclitaxel-carboplatin, oxaliplatin-capecitabine, paclitaxel-carboplatin-bevacizumab, or oxaliplatin-capecitabine-bevacizumab. Chemotherapy was given 3-weekly for 6 cycles, and bevacizumab (3-weekly) was continued as maintenance (for 12 cycles). Endpoints included overall-survival (OS), progression-free survival (PFS), toxicity and quality of life (QoL). Results The trial stopped after 50 patients were recruited due to slow accrual. Median follow-up was 59 months. OS hazard ratios (HR) for the two main comparisons were: 0.78 (p = 0.48) for Oxal-Cape vs. Pac-Carbo (each with/without bevacizumab), and 1.04 (p = 0.92) for bevacizumab vs. no bevacizumab. Corresponding PFS HRs were: 0.84 and 0.80. Retrospective central pathology review revealed only 45% (18/40) cases with available material had confirmed primary mEOC. Among these, OS HR for Oxal-Cape vs. Pac-Carbo was 0.36 (p = 0.14); PFS HR = 0.62 (p = 0.40). Grade 3–4 toxicity was seen in 61% Pac-Carbo, 61% Oxal-Cape, 54% Pac-Carbo-Bev, and 85% Oxal-Cape-Bev. QoL was similar between the four arms. Conclusion mEOC/GOG0241 represents an example of a randomized rare tumor trial. Logistical challenges led to early termination, including difficulties in local histopathological diagnosis and accessing drugs outside their labelled indication. There was misalignment between central funders who support clinical trials in rare cancers and the deprioritisation of such work by those managing and funding research at a local level. Rare cancer trials should include centralised pathology review before treatment. Clinical trial registry number: ISRCTN83438782

Clinical management of borderline tumours of the ovary: results of a multicentre survey of 323 clinics in Germany

The aim of this survey was to analyse the standard of care in diagnostic, surgery, chemotherapy and aftercare management for patients with borderline tumours of the ovary (BOTs) in Germany. A structured questionnaire comprising different dimensions was sent to all 1114 gynaecological departments. The questionnaire could be returned anonymously. The overall response rate was 29.0% (323 departments). Most departments were on secondary care (71.8%), tertiary care (23.2%) or university hospital (5.0%) level. Most clinicians performed not more than five BOT operations (89.2%) per year. Most departments (93.2%) used in addition to classical bimanual examination and vaginal ultrasound, tumour marker CA-125 detection, CT scan, MRI or PET-CT techniques. Departments in university and tertiary care hospitals performed more often a fresh frozen section (87 vs 64%). In young women, clinicians performed much seldom unilateral salpingo-oophorectomy (92%) and only in 53% biopsies of the contralateral ovary. Generally, biopsies of the contralateral ovary were performed in 4–53% of the patients. Chemotherapy was mostly favoured in ‘high-risk' patients with tumour residual, microinvasion or invasive implants. Thus, a high grade of insecurity in diagnostic and therapy of BOT exists in some gynaecological departments and underlines the need for more educational and study activities

Endocrine therapy in epithelial ovarian cancer

INTRODUCTION: The estrogen receptor (ER) is expressed at high levels in many epithelial ovarian cancers (EOC) and represents a potential target for endocrine therapy. Both anti-estrogens and aromatase inhibitors have been evaluated in phase II clinical trials. Areas covered: We present an overview of the phase II and phase III trials of anti-estrogens (tamoxifen and fulvestrant) and aromatase inhibitors (letrozole, anastrazole and exemestane) undertaken in epithelial ovarian cancer identified through a Pubmed search. We describe predictive biomarkers that are being investigated to identify responsive cancers. Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents. The low toxicity profile of these agents is favourable although their use is unlicensed and the optimal setting undefined. Prospective clinical trials of endocrine agents in the early relapse and maintenance settings are urgently required to establish their definitive role in the management of epithelial ovarian cancer