1 Division of Reproductive Endocrinology and Infertility and 2 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Istanbul University, School of Medicine, 34093 Istanbul, Turkey and 3 Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, St. Lukes-Roosevelt Hospital Center, New York, NY 10019, USA
4 To whom correspondence should be addresssed. e-mail: attar{at}superonline.com
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Abstract |
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Key words: borderline ovarian tumour/conservative surgery/fertility
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Introduction |
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The term micro-papillary serous carcinoma (MPSC) has been introduced recently to define a subset of ovarian serous borderline tumours morphologically characterized by a micro-papillary pattern and clinically associated with a more aggressive behaviour than that of the typical ovarian serous borderline tumours (Burks et al., 1996; Seidman and Kurman, 1996
). Ovarian MPSCs are associated with extra-ovarian invasive peritoneal implants and invasive recurrences much more frequently than typical ovarian serous borderline tumours. In advanced stages of the disease, it is essential to balance the reproductive goals with the necessity for tumour control. Studies in the literature about fertility-sparing surgery and fertility outcomes have focused on the early stages of the typical borderline ovarian tumours. We report a case of a young woman with stage IIIC borderline MPSC of the ovary who underwent conservative surgery followed by a successful IVF pregnancy in spite of high FSH levels. The benefits and costs of conservative surgical approaches to young childless women with advanced borderline ovarian tumour are discussed.
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Case report |
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Surgery resulted in the removal of all visible disease with preservation of the uterus and a small portion of the right ovary. Ascites in the pouch of Douglas was unremarkable. Staging included an appendectomy, partial omentectomy and bilateral pelvic lymphadenectomy. Pathological assessment of the frozen sections showed a borderline serous papillary tumour with a hierarchical branching pattern. Histological examination of the tissues showed MPSC with positive right pelvic lymph nodal involvement. There was no visible implant on the pelvic peritoneum at the time of initial surgery. Seven lymphatic pelvic ganglia were sampled from the left side, with only one of them being tumour positive. Four left pelvic ganglia were tumour free. Slides were reviewed by a group of gynaecological pathologists who all agreed that there was no endosalpingiosis. The peritoneal cytology was positive for malignancy; however, the omentum and appendix were negative for tumour. The stage of the tumour was IIIC according to the International Federation of Gynaecologic Obstetrics (FIGO) classification. No adjuvant therapy was prescribed following the surgery as there is no benefit of this treatment for borderline ovarian cancers (Chambers, 1989).
Following surgery, the patient resumed menstruation after a brief period of amenorrhea. A simple follicle cyst was detected in the remnant ovary. Her basal FSH level was 42.7 mIU/ml and estradiol level was 67.5 pg/ml. She was put on oral contraceptives for 2 months. Her FSH level decreased to 22.3 mIU/ml and she decided to undergo IVF, 5 months after the surgery. A daily dose of 0.1 mg GnRH agonist (Decapeptyl; Erkim, Turkey) s.c. was started on the first day of menstruation and continued until the day of oocyte retrieval. Gonadotrophins were started on the third day of menstruation with a daily injection of six ampoules of Pergonal (Serono, Turkey). Follicular development was monitored by ultrasound with a 5 MHz transvaginal probe. Three follicles developed; the dominant follicle measured 1617 mm in diameter and the estradiol level was 674.7 pg/ml on day 7. We decided to continue the treatment and -HCG 10 000 IU (Pregnyl; Serono, Turkey) was given to induce the follicular rupture when the dominant follicle measured 20 mm. Estradiol reached 845 pg/ml and the other two follicles were 17 and 14 mm in diameter at this time. Transvaginal follicular aspiration was performed 36 h after the HCG injection, under general anaesthesia using propofol (Diprivan; Zeneca, Sweeden). Three metaphase II (MII) oocytes were obtained and ICSI was performed. Two grade I and one grade II embryo developed and were transferred 3 days after the oocyte retrieval. The
-HCG level 10 days after transfer was positive at 61.47 IU/ml. Pregnancy was confirmed by transvaginal ultrasound with one gestational sac and one viable embryo in the uterine cavity in week 7. There was no complication with the pregnancy. The patient delivered by Cesarean section at the 37th week of pregnancy. Exploration of the abdominal cavity during Cesarean section revealed multiple implants on the peritoneal surface and liver. Contralateral ovarian tissue was of normal appearance. Peritoneal washing and multiple sampling from the implants were carried out. Histological examination of implants revealed non-invasive MPSC and endosalpingiosis. Abdominal hysterectomy and right oophorectomy were done as a definitive treatment almost 18 months after the conservative treatment. Multiple sampling from the implants was made and an evolutive tumoural mass was removed from the right abdominal wall. Pathological examination of this tissue revealed serous carcinoma. The rest of the samplings from the peritoneal surfaces of the lower abdomen were assessed as invasive implants. Non-invasive MPSC was detected on the spared ovarian tissue. Adjuvant chemotherapy was prescribed following the surgery after this pathology result. The patient currently is alive with persistent disease and is receiving adjuvant chemotherapy.
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Discussion |
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Controversy over the nature and nomenclature of borderline ovarian tumours is ongoing. There currently is no consensus about the definition of borderline ovarian tumours; and several questions remain about the risk for recurrence associated with conservative management of MPSC. MPSC of the ovary is a recently described neoplasm characterized by long thin micropapillae and cribriform structures that arise directly from large bulbous papillary structures. Burks et al. termed it carcinoma because patients with this neoplasm had a clinical course and mortality rate that was intermediate between typical serous papillary carcinoma and serous borderline tumours without invasive implants (Burks et al., 1996; Seidman and Kurman, 1996
). However, Eichhorn et al. (1999
) proposed that it should remain as a subset within the serous borderline tumour category, with outcome predicated on the presence or absence of invasive peritoneal implants. The largest study of the prognosis and natural history of borderline tumours of the ovary has been published by Kaern and Trope (Kaern et al., 1993
; Trope and Kaern, 1998
). They have evaluated the value of parameters including stage, histological type, age and DNA ploidy status as prognostic factors for long-term survival in 370 patients. In their study, the grade of atypia and extent of surgery or adjuvant therapy did not correlate with survival.
The association between the long-term usage of infertility drugs and development of borderline ovarian tumours has been noticed. In patients with borderline tumour, induction of ovulation or IVF procedures could probably be safely used in those with early stage disease (Navot et al., 1991; Mantzavinos et al., 1994
; Lawal and B-Lynch, 1996
; Beiner et al., 2001
). However, data in the literature are not sufficient to argue about the safety of the use of induction of ovulation or IVF in patients with advanced borderline tumour, particularly in those with peritoneal implants (Nijman et al., 1992
). Gotlieb et al. (1998
) performed conservative surgery for 39 young women who wished to protect their fertility. Fifteen of these patients experienced a total of 22 normal pregnancies. The authors did not experience any apparent prognostic impact of conservative management, despite the ultimate occurrence of three contralateral ovarian serous borderline tumours. Camatte et al. (2002
) reported 17 patients treated with conservative management for a stage II (n = 6) or III (n = 11) borderline ovarian tumour. Six of these patients underwent a unilateral salpingo-oophorectomy with contralateral cystectomy. A total of eight pregnancies were observed in seven patients, with a median delay of 8 months following the surgical procedure. None of these patients had a recurrence in the form of invasive ovarian carcinoma on the spared ovary. Two patients (one with a non-invasive disease and one with an invasive disease) had a recurrence in the form of evolutive invasive implants, but neither woman died. The authors concluded that such management, performed with a close follow-up of the patients, does not affect overall survival. Conservative surgery could be proposed in patients with borderline tumour of the ovary and non-invasive peritoneal implants (Camatte et al., 2002
). The use of IVF has been reported to have been a success in a patient treated for advanced borderline ovarian tumour (Hofman et al., 1999
). In this case report, the authors stated that among patients with advanced stage borderline ovarian tumours of the ovary, those with micro-papillary architecture or invasive implants have the greatest risk of malignant transformation and, in the absence of these patterns, consideration can be given to preservation of reproductive function. However, the exact histogenesis and the prognostic significance of the nodal involvement are still not fully understood. Benign mullerian inclusions, endosalpingioses, occur in approximately one-fifth of patients with gynaecological malignancies in all anatomic regions including pelvic and para-aortic lymph nodes. However, in our case, no endosalpingiosis was seen in the initial surgery. It has not been shown that there are any adverse effects of pregnancy on the course of advanced stage borderline tumours of the ovary. Neither pregnancy status at the time of diagnosis nor occurrence of subsequent term pregnancy has been shown to alter the prognosis (Trimble and Trimble, 1994
).
Conservatively treated patients with borderline ovarian tumours tend to develop recurrent disease earlier than women who had definitive surgery (Darai et al., 1998). However, relapse-free survival is the same for the patients who had surgery after recurrent disease (Tazelaar et al., 1985
). Likewise, tumours do not recur in the form of invasive carcinoma in these patients (Morice et al., 2001a
). The patients in whom there is the most controversy about additional treatment are those who have intra-abdominal spread of the disease. Removal of all implants during definitive surgery is impossible and would not be effective because of their dissemination. There is evidence that MPSCs without invasive peritoneal implants seem to behave as similarly staged non-micropapillary serous borderline tumours without invasive peritoneal implants (Goldstein and Ceniza, 2000
). Therefore, random biopsies from these implants and careful follow-up is a valuable option for these patients (Prat, 1999
). In advanced stages, the use of adjuvant therapy has not consistently led to cures, and complications have been reported (Chambers et al., 1988
). There is now convincing evidence that the only fatal cases of serous borderline tumours are those associated with invasive implants, and chemotherapy is indicated only for these rare tumours. In our case, borderline ovarian tumour showed a rapid progression to carcinoma, and adjuvant chemotherapy was prescribed after the definitive surgery.
Morice et al. (2001a) evaluated the clinical outcome and fertility in patients treated conservatively for epithelial ovarian carcinoma (EOC). In their series, only six of the 27 patients underwent hysterectomy during restaging surgery. Four pregnancies (three spontaneous and one after IVF) were obtained. The authors concluded that conservative surgery for patients with EOC could be considered in young patients with stage IA, grade 1 disease adequately staged and wanting to preserve their fertility potential. Conservative management of very early stage low grade EOC and advanced serous borderline ovarian tumours is an option for those young childless women who would like to preserve their fertility. However, induction of ovulation remains classically contraindicated in EOC and the treatment must be undertaken very cautiously and requires rigorous surveillance.
Borderline tumours remain difficult to diagnose accurately on frozen sections because of the extensive sampling required, and fresh frozen sections cannot indicate the difference between borderline ovarian tumours and ovarian mucinous cancer (Pinto et al., 2001). However, frozen sections are accurate enough to exclude the presence of a benign pathology (Kayikcioglu et al., 2000
). In our case, frozen sections and histopathological results were in accordance.
Tumour markers were within the normal ranges in the case we presented. The role of serum tumour markers in borderline ovarian tumour has not been defined as it has been in the management and detection of invasive ovarian carcinoma. However, the actual CA-125 values are usually lower than those for invasive neoplasms (Chambers et al., 1988; Vinokurov et al., 1992
; Gotlieb et al., 2000
). There is evidence that preoperative CA-125 levels correlate with the stage of disease in patients with serous borderline ovarian tumours (Rice et al., 1992
).
In this case report, treatment options for conservative management of advanced borderline ovarian tumour were discussed with a young childless patient. We showed that pregnancy following high FSH levels is possible after conservative management of bilateral non-invasive borderline stage IIIC MPSC. Current data and our experience revealed that it is no possible to make a definite recommendation for the treatment of the young childless patients with advanced borderline ovarian tumour. However, considering the evolution of this case with invasive implants on the peritoneal surfaces, the use of infertility drugs in patients with a stage IIIC borderline MPSC should not be recommended.
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References |
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Beiner ME, Gotlieb WH, Davidson B. Kopolovic J and Ben-Baruch G (2001) Infertility treatment after conservative management of borderline ovarian tumors. Cancer 92,320325.[CrossRef][Medline]
Bell DA (1991) Ovarian surface epithelial stromal tumors. Hum Pathol 22,750762.[CrossRef][Medline]
Burks RT, Sherman ME and Kurman RJ (1996) Micropapillary serous carcinoma of tha ovary: a distinctive low-grade carcinoma related to serous borderline tumors. Am. J Surg Pathol 20,13191330.[CrossRef][Medline]
Camatte S, Morice P and Pautier P (2002) Fertility results after conservative treatment of advanced stage serous borderline tumour of the ovary. Br J Obstet Gynecol 109,376380.
Chambers JT (1989) Borderline ovarian tumors: a review of treatment. Yale J Biol Med 62, 351365.[Medline]
Chambers JT, Merino MJ, Kohorn EI and Schwartz PE (1988) Borderline ovarian tumors. Am J Obstet Gynecol 159,10881094.[Medline]
Darai E, Teboul J, Fauconnier A, Scoazec JY, Benifla JL and Madelenat P (1998) Management and outcome of borderline ovarian tumors incidentally discovered at or after laparoscopy. Acta Obstet Gynecol Scand 77,451457.[CrossRef][Medline]
Eichhorn JH, Bell DA, Young RH and Scully RE (1999) Ovarian serous borderline tumors with micropapillary and cribriform patterns: a study of 40 cases and comparison with 44 cases without these patterns. Am J Surg Pathol 23,397409.[CrossRef][Medline]
Fox H (1989) The concept of borderline malignancy in ovarian tumors: a reappraisal. Curr Top Pathol 78,111134.[Medline]
Gershenson DM and Silva EG (1990) Serous ovarian tumors of low malignant potential with peritoneal implants. Cancer 65,5359.[Medline]
Goldstein NS and Ceniza N (2000) Ovarian micropapillary serous borderline tumors. Am J Clin Pathol 114,380386.[Medline]
Gotlieb WH, Flikker S, Davidson B, Korach Y, Kopolovic J and Ben-Baruch G (1998) Borderline tumors of the ovary. Fertility treatment, conservative management and pregnancy outcome. Cancer 82,141146.[CrossRef][Medline]
Gotlieb WH, Soriano D, Achiron, R. Zalel Y, Davidson B, Kopolovic J, Novikov I and Ben-Baruch G (2000) CA 125 measurement and ultrasonography in borderline tumors of the ovary. Am J Obstet Gynecol 183,541546.[CrossRef][Medline]
Hofman JS, Laird L, Benadiva C and Dreis R (1999) In vitro fertilization following conservative management of stage 3 serous borderline tumor of the ovary. Gynecol Oncol 74, 515518.[CrossRef][Medline]
Hopkins MP, Kumar NB and Morley G (1987) An assessment of pathologic features and treatment modalities in ovarian tumors of low malignant potential. Obstet Gynecol 70,923929.[Abstract]
Kaern J, Trope CG and Abeler VM (1993) A retrospective study of 370 borderline tumors of the ovary treated at the Norweigan Radium Hospital from 19701982. Cancer 71,18101820.[Medline]
Kayikcioglu F, Pata O, Cengiz S, Tulunay G, Boran N, Yalvac S and Kose MF (2000) Accuracy of frozen section diagnosis in borderline ovarian malignancy. Gynecol Obstet Invest 49,187189.[CrossRef][Medline]
Kennedy AW and Hart WR (1996) Ovarian papillary serous tumors of low malignant potential (serous borderline tumors). A long term follow up study, including patients with microinvasion, lymph node metastasis, and transformation to invasive serous carcinoma. Cancer 78,278286.[CrossRef][Medline]
Lawal AH and B-Lynch C (1996) Borderline ovarian cancer, bilateral surgical castration, chemotherapy and normal delivery after ovum donation and in vitro fertilization-embryo transfer. Br J Obstet Gynecol 103,931932.[Medline]
Mantzavinos T, Kanakas N, Genatas C, Papadias K and Zourlas PA (1994) Five years follow-up in two patients with borderline tumors of the ovary hyperstimulated by gonadotropin therapy for in vitro fertilization. Hum Reprod 9,2032203.[Abstract]
Massad LS Jr, Hunter VJ, Szpak CA, Clarke-Pearson DL and Creasman WT (1991) Epithelial ovarian tumors of low malignant potential. Obstet Gynecol 78,10271032.[Abstract]
Morice P, Camatte S, El Hassan J. Pautier P, Duvillard P and Castaigne D (2001b) Clinical outcomes and fertility after conservative treatment of ovarian borderline tumors. Fertil Steril 75,9296.[CrossRef][Medline]
Morice, P, Wicart-Poque F, Rey A, El-Hassan J, Pautier P, Lhomme C, de Crevosier R, Haie-Meder C, Duvillard P and Castaigne D (2001a) Results of conservative treatment in epithelial ovarian carcinoma. Cancer 92, 24122418.[CrossRef][Medline]
Morris RT, Gershenson DM, Silva EG. Follen M, Morris M and Wharton JT (2000) Outcome and reproductive function after conservative surgery for borderline ovarian tumors. Obstet Gynecol 95,541547.
Navot D, Fox JH, Williams M, Brodman M, Friedman F Jr and Cohen CJ (1991) The concept of uterine preservation with ovarian malignancies. Obstet Gynecol 78,566568.[Abstract]
Nijman HW, Burger CW, Baak JP, Schats R, Vermorken JB and Kenemans P (1992) Borderline malignancy of the ovary and controlled hyperstimulation, a report of 2 cases. Eur. J. Cancer 28A,19711973.[Medline]
Pinto PB, Andrade LA and Derchain SF (2001) Accuracy of intraoperative frozen section diagnosis of ovarian tumors. Gynecol. Oncol. 81, 230232.[CrossRef][Medline]
Prat J (1999) Ovarian tumors of borderline malignancy (tumors of low malignant potential): a critical appraisal. Adv Anat Pathol 6,247274.[Medline]
Rice LW, Lage JM. Berkowitz RS, Goodman A, Muto MG, Knapp RC and Bell DA (1992) Preoperative serum CA-125 levels in borderline tumors of the ovary. Gynecol Oncol 46, 226229.[CrossRef][Medline]
Seidman JD and Kurman RJ (1996) Subclassification of serous borderline tumors of the ovary in to benign and malignant types: a clinico-pathological study of 65 advanced stage cases. Am J Surg Pathol 20,13311345.[CrossRef][Medline]
Seracchioli R, Venturoli S, Colombo FM, Govoni F, Missiroli S and Bagnoli A (2001) Fertility and tumor recurrence rate after conservative laparoscopic management of young women with early-stage borderline ovarian tumors. Fertil Steril 76,9991004.[CrossRef][Medline]
Tazelaar HD, Bostwick DG, Ballon SC, Hendrickson MR and Kempson RL (1985) Conservative treatment of borderline ovarian tumors. Obstet Gynecol 66,417422.[Abstract]
Trimble CL and Trimble EL (1994) Management of epithelial ovarian tumors of low malignant potential. Gynecol Oncol 55,5261.[CrossRef]
Trope C and Kaern J (1998) Management of borderline tumors of the ovary: state of art. Semin Oncol 25,372380.[Medline]
Vinokurov VL, Dudarev AL, Jurkova LE, Lapchenkov VI and Barbanel EJ (1992) Tumor marker CA 125 in diagnosis, monitoring management and follow-up of patients with ovarian tumors. Eur J Gynaecol Oncol 13,205208.[Medline]
Submitted on January 5, 2004; accepted on January 28, 2004.
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