Case Report
Laparoscopic Fertility-preserving Treatment of a Pure Nongestational Choriocarcinoma of the Ovary: Case Report and Review of Current Literature Le Xin, MD, PhD*, Anna Beier, MD, Susanne Tiede, MD, Tatiana Pfiffer, MD, Christhardt K€ ohler, MD, PhD, and Giovanni Favero, MD, PhD From the Departments of Operative and Oncologic Gynecology (Drs. Xin, Beier, Pfiffer, K€ohler, and Favero), and Clinical Oncology (Dr. Tiede), Asklepios Clinic Hamburg, Hamburg, Germany.
ABSTRACT This case report demonstrates the feasibility of laparoscopic and fertility-preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure NGCO is a rare malignant condition. In the last decade, only 14 cases have been reported in the literature. The use of laparoscopy and fertility-preserving procedures in nonepithelial ovarian malignancies is extremely controversial. A 23-year-old woman underwent emergency laparoscopy due to acute abdominal pain associated with an 8-cm large adnexal mass. The initial procedure consisted only of a left oophoroplasty, and histology revealed a tumor of high malignant potential compatible with a primary NGCO. Approximately 3 weeks after initial surgery, she was submitted to a laparoscopic staging surgery, including left adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal lymphadenectomy. Final pathology confirmed an International Federation of Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the patient received goserelin for ovarian suppression. Nine months after therapy, the patient presented no signs of recurrence and reassumed normal menstruation cycles with normal levels of gonadotropins and tumor markers. The current report brings new insights into the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO. Journal of Minimally Invasive Gynecology (2015) 22, 1095–1099 Ó 2015 AAGL. All rights reserved. Keywords:
DISCUSS
Fertility-preserving surgery; Laparoscopy; Nongestational choriocarcinoma of the ovary (NGCO); Ovarian suppression
You can discuss this article with its authors and with other AAGL members at http:// www.AAGL.org/jmig-22-5-JMIG-D-15-00180
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Choriocarcinoma of the ovary is a rare and aggressive malignancy, which may be either gestational or nongestational in origin [1]. Epidemiologically, the first pathologic entity is far more frequent than the second one. Nongestational choriocarcinoma of the ovary (NGCO) accounts for less than .6% of all ovarian neoplasms [2,3]. The histopathologic diagnosis of NGCO is very difficult to confirm in women of reproductive age because of The authors report no conflict of interest. Corresponding author: Le Xin, MD, PhD, Asklepios Hospital Hamburg, Department of Advanced Gynecologic Surgery and Oncology, Eissendorfer Pferdeweg 52, 21075 Hamburg, Germany. E-mail: [email protected] Submitted March 21, 2015. Accepted for publication April 27, 2015. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2015 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2015.04.025
the absence of ultrastructural or immunohistochemical distinctive features between the 2 forms of the disease [4]. Currently, there is a notorious paucity of data regarding exact carcinogenesis, tumor biology, clinical course, and standard oncologic treatment of this condition. Particularly in regards to surgical therapy, the possibility of implementing fertility-preserving procedures or the use of laparoscopy are seldom discussed in the literature. Herein, we report a case of NGCO diagnosed in a young woman and discuss the diagnosis and treatment, especially the type and form of surgery, including a brief review of the current literature. Case Report A 23-year-old virgin woman was referred to the Department of Operative and Oncologic Gynecology, Asklepios
1096
Journal of Minimally Invasive Gynecology, Vol 22, No 6, September/October 2015
Clinic Hamburg, Germany, after undergoing emergency explorative laparoscopy due to acute intermittent lower abdominal pain associated with a complex pelvic mass. The diagnostic hypothesis at this point was an adnexal torsion or a hemorrhagic ovarian cyst. During the surgery, an approximately 8-cm tumor arising from the left ovary was observed. The adnexum at this side was partially twisted because of the presence of the expansive lesion. Capsule rupture or peritoneal spread was not identified. At this time, she received only a tumor enucleation at this side. Histology revealed a tumor of high malignant potential compatible with a primary ovarian choriocarcinoma. Postoperative serum tumor marker analysis showed persistent elevated levels of b-human chorionic gonadotropin (b-hCG; 18 000 mIU/mL) and normal levels of CA-125, cardioembryonic antigen, alpha-fetoprotein, and lactate dehydrogenase. Approximately 3 weeks after the initial surgery, the patient underwent a positron emission computed tomography that demonstrated a highly metabolic active residual lesion in the region of the operated ovary, without signs of extragonadal dissemination. Based on these findings (possible residual tumor and inadequate operative staging), the patient was extensively counseled about the therapeutic options, namely conservative versus radical surgery. She decided for the fertility-sparing option, and a laparoscopic staging surgery, including peritoneal washing and biopsies of suspicious areas, unilateral salpingo-oophorectomy (left), pelvic peritonectomy, retroperitoneal lymphadenectomy, and infracolic omentectomy, was performed without intercurrences. Intraoperatively, there were no ascites or clear signs of peritoneal carcinomatosis. However, we observed an approximately 3-cm mass arising from the left ovary (Fig. 1) and a 5-mm large lesion in the cul-de-sac (Fig. 2). The right ovary and fallopian tube were normal in appearance. Optimal debulking was achieved with no macroscopic residual tumor. Final pathology revealed a 2.3-cm large residual choriocarcinoma on the left ovary and a small satellite lesion (3 mm) in the Douglas pouch. All other removed specimens, including 25 pelvic and para-aortic lymph nodes, were negative for malignancy. Further immunohistochemical analysis showed positivity for b-hCG, pancytokeratin, Fig. 1 Laparoscopic appearance of an NGCO.
Fig. 2 NGCO implant in the posterior cul-de-sac.
CK7, and Glypican 3 but negative immunostaining for CD30 and OCT4. Final tumor classification was pT2b pN0 L0 V0–International Federation of Gynecology and Obstetrics stage IIB NGCO. The patient developed no postoperative complications and was discharged 5 days after surgery. Fourteen days after the intervention, the serum level of b-hCG was undetectable. Following the recommendation of our interdisciplinary tumor board, 3 courses of BEP (30 mg bleomycin on days 1, 8, and 15, cycles every 22 days; 100 mg/m2 etoposide on days 1–5; 20 mg/m2 cisplatin days 1–5) in the adjuvant setting were administrated. The patient was informed about potential risks of premature ovarian failure induced by chemotherapy and agreed to receive 10.8 mg goserelin for ovarian suppression before initiation of chemotherapy. The protective therapy and chemotherapy were administrated without major toxicity. Serum concentrations of b-hCG and sexual hormones, thorax and abdominal CT scans, and pelvic and sonographic examinations were then performed every 3 months. Nine months after conclusion of the chemotherapy, the patient had no clinical or imaging signs of recurrence. She reassumed normal menstrual cycles approximately 5 months after the end of the systemic therapy and currently presents normal levels of gonadotropins (follicle-stimulating hormone, 7 mIU/mL; luteinizing hormone, 5 mIU/mL) and estradiol (50 pg/mL). Tumor markers remain negative. Discussion Primary choriocarcinoma of the ovary is a rare condition that affects women of childbearing age more frequently than other women [5,6]. Clinical symptoms are normally nonspecific and may include abdominal pain and vaginal bleeding. Despite its infrequent occurrence, it must be considered, in conjunction with distinct forms of abortion or ectopic pregnancy, a differential diagnosis in women
Xin et al.
Laparoscopy for NGCO: a Case Report
with adnexal mass with increased serum levels of b-hCG. The diagnosis is normally established postoperatively, after the histopathologic analysis of the removed ovarian tumor. The presence of malignant cytotrophoblasts and syncytiotrophoblasts allied with immunohistochemical staining with b-hCG confirm the diagnosis of choriocarcinoma. However, it is very difficult to distinguish a pure nongestational from a gestational form of ovarian choriocarcinoma because of the lack of distinctive immunohistochemical characteristics. More recently, some authors defend the performance of a polymorphic analysis of tumor DNA to clearly distinguish these 2 major variants of the disease. To explain, if the genotype of the tumor tissue in question matches that of the patient at all loci and is different from that of the partner, it would confirm the nongestational origin of the malignancy [4,7,8]. However, this method is very expensive, which limits the application. In the present case, the confirmation of a nongestational form of disease was simplified by the fact that the woman was a virgin. Pure NCGO is a highly aggressive malignancy, characterized by an extremely fast tumor cell growth pattern and frequent development of nodal and systemic metastasis to lung, liver, and brain [9]. Overt bleeding from distant metastases may occur in the gastrointestinal tract, kidney, brain, or lung. In fact, pulmonary manifestations are among the most common presenting symptoms of choriocarcinoma [10]. Presently, because of the paucity of available data in the literature, there is no standard of therapy. The oncologic treatment is mostly derived from other more common forms of malignant germ cell tumors and basically includes optimal debulking surgery and polychemotherapy. Consequently, a number of questions are still open, such as the extension of the surgical procedure (conservative vs radical) mainly in women of reproductive age, the possibility of using endoscopic techniques, and the real impact of systemic therapy in survival versus potential induction of gonadal failure. In addition, it is also not clear if the use of fertility-preserving techniques may negatively influence the prognosis. Up to 2015, only 14 reported cases specifically on NGCO are available in the literature (Table 1). The mean age of the affected women is 28 years (range, 10–55). Conservative surgery could be performed in only 28% of the reported patients (4/14), and its indication was based on age, future desire of pregnancy, and tumor stage. Despite the fact that 75% of these women (3/4) underwent adjuvant chemotherapy, none of them received additional fertility-preserving techniques. The most frequently used chemotherapy schemas are BEP (54%) and etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (27%), but the number of cycles is inconstant among the series, varying from 2 to 6. Laparoscopy was used in only 28% of cases and seems not to have jeopardized the oncologic prognosis. The use of laparoscopy in ovarian malignancies is extremely controversial. Some important concerns, such as
1097
possible port-site metastasis, peritoneal tumor dissemination, inadequate staging, and questionable quality of cytoreduction, have limited the widespread use of laparoscopy in this pathology [9]. The experience in the literature regarding laparoscopy and NGCO is limited to 4 previous case reports [1,12,15,16] and the present description. They have all observed positive oncologic outcomes. It is possible that a key point was the ability to rapidly initiate the adjuvant chemotherapy that is apparently essential for the treatment of this condition. Further advantages observed, such as a short hospital stay, low blood loss, and aesthetics, should be highlighted [10]. Certainly, the oncologic safety of the method needs to be confirmed by larger studies with longer follow-up. Despite the fact that the most important therapeutic prognostic factor is to achieve no residual macroscopic disease at surgery, the magnitude of the interventions is quite different among the published cases. In fact, this is one of the few available reports on a fertility-sparing surgery for this particular sort of germ cell ovarian malignancy. Clearly, the oncologic safety of this strategy must be further investigated, but it reinforces at least the perspective to better counsel patients affected by this condition who deserve to preserve fertility. In these cases, we have to emphasize the importance of the systemic radiologic staging and the complete gonad and extragonad operative staging. This procedure must include, in our opinion, meticulous inspection and execution of multiple biopsies from the peritoneum, regional peritonectomy, omentectomy, and retroperitoneal lymphadenectomy. Currently, it is practically mandatory to discuss with patients the possibility of infertility induced by oncologic treatments during their reproductive years. Gynecologic oncologists should be prepared to offer and explain fertility preservation options before beginning therapy. The gonadotoxic effect of various chemotherapeutic agents is diverse and may involve a number of pathophysiologic mechanisms. The risk of premature ovarian failure depends mainly on the chemotherapy protocol used, the patient’s age, and, in some occasions, the magnitude of the surgical damage to the ovarian tissue. Based on this information, our patient was categorized as intermediate risk and certainly needed an additional fertility protective strategy before adjuvant chemotherapy. The administration of a gonadotropinreleasing hormone analog was an attempt to decrease the insult of the drugs to the remaining follicles by simulating a prepubertal hormonal milieu. Despite insufficient available scientific data, this approach was the best alternative found for maximizing the chances of cure and reproduction in the given scenario [21,22]. The implementation of other fertility-preserving options such as embryo and oocyte cryopreservation were limited by uncertainties regarding the effects of the ovarian stimulation in the primary pathology and the potential delay in the initiation of systemic therapy due to egg collection [22]. Moreover, ovarian tissue cryopreservation for the purpose of future transplantation is currently experimental and has never been clinically used for ovarian malignancies.
1098
Table 1 Pure ovarian choriocarcinoma: summary of reported cases
Age
Initial b-hCG
Outcome
Additional fertility procedure
Diagnosis
Stage
Route
Description
Choi [1], 2013 Exman [7], 2013 Lv [3], 2011
33 24 48
74 612 675 713 7664.3
NGCO NGCO NGCO
NS NS NS
Laparoscopy NS Laparotomy
Gon [11], 2010 Park [2], 2009 Wang [12], 2009 Kong [13], 2009 Mood [14], 2009
21 55 23 10 32
279 000 64 838 26 516 NS 5500
NGCO NGCO NGCO NGCO NGCO
NS NS NS Ic NS
NS Laparotomy Laparoscopy Laparotomy Laparotomy
Chen [15], 2008 Gerson [16], 2007 Koo [17], 2006
23 33 33
NS 564 000 185 000
NGCO NGCO NGCO
Ia NS NS
Laparoscopy Laparoscopy Laparotomy
Bazot [18], 2004 Balat [19], 2004
38 24
2 460 000 8968
NGCO NGCO
NS NS
NS NS
Ozdemir [20], 2004
13
91 028
NGCO
NS
Laparotomy
LO; multiple biopsies TAH; BSO BSO; subextensive total hysterectomy; pelvic lymphadenectomy; omentectomy; appendectomy RSO TAH; BSO; multiple biopsies TAH; BSO; pelvic lymphadenectomy LSO; partial omentectomy TAH; BSO; tumor debulkation; infracolic omentectomy NS RSO; resection of a right adnexal mass AH, BSO, omentectomy, pelviclymphadenectomy TAH, BSO TAH, BSO, PLND, partial omentectomy, stemum mass excision RSO; removal of a single mass
EMA BEP BEP
5 yr NED 1 mo NED 1 yr NED
No No No
NS BEP BEP BVP BEP 1 EMA-CE
NS 20 mo NED NS 2 mo NED 5yr NED
No No No No No
NS EMA-CO MAC
3 yr NED 1 yr NED NED
No No No
NS BEP
7 yr NED Died
No No
MAC
9 mo NED
No
B 5 bilateral; EMA/CE 5 etoposide, methotrexate, actinomycin-D, cisplatin, etoposide; EMA/CO 5 etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine; Ic 5 ; L 5 left; MAC 5 methotrexate, actinomycin-D, cyclophosphamide; NED 5 no evidence of disease; NS 5 not stated; O 5 oophorectomy; PVB 5 cisplatin, bleomycin, vinblastine; R 5 right; S 5 salpingectomy; TAH 5 total abdominal hysterectomy.
Journal of Minimally Invasive Gynecology, Vol 22, No 6, September/October 2015
Chemotherapy scheme
Surgery Author, reference number, year
Xin et al.
Laparoscopy for NGCO: a Case Report
In conclusion, the current report brings new insights about the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO. References 1. Choi YJ, Chun KY, Kim YW, et al. Pure non-gestational choriocarcinoma of the ovary: a case report. World J Surg Oncol. 2013;11:7. 2. Park SH, Park A, Kim JY, et al. A case of non-gestational choriocarcinoma arising in the ovary of a postmenopausal woman. J Gynecol Oncol. 2009;20:192–194. 3. Lv L, Yang K, Wu H, et al. Pure choriocarcinoma of the ovary: a case report. Gynecol Oncol. 2011;22:135–139. 4. Wang Y, Yang Y, Teng F, et al. Pure non-gestational uterine choriocarcinoma in a postmenopausal Chinese woman confirmed with short tandem repeat analysis. Am J Obstet Gynecol. 2014;4:e1–e3. 5. Smith HO, Berwick M, Verschraegen CF, et al. Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol. 2006;107: 1075. 6. Longo R, Battaglia F, Gattuso D, et al. Primary non-gestational choriocarcinoma of the uterine cervix. J Clin Oncol. 2011;29:e301. 7. Exman P, Takahashi TK, Gattas GF, et al. Primary ovary choriocarcinoma: individual DNA polymorphic analysis as a strategy to confirm diagnosis and treatment. Rare Tumors. 2013;5:e24. 8. Tsujioka H, Hamada H, Miyakawa T, et al. A pure non-gestational choriocarcinoma of the ovary diagnosed with DNA polymorphism analysis. Gynecol Oncol. 2003;89:540–542. 9. El-Helw LM, Hancok BW. Treatment of metastatic gestational trophoblastic neoplasia. Lancet Oncol. 2007;8:715. 10. Magrath IT, Golding PR, Bagshawe KD. Medical presentations of choriocarcinoma. Br Med J. 1971;2:633.
1099 11. Gon S, Majumdar B, Barui G, et al. Pure primary non-gestational ovarian choriocarcinoma: a diagnostic dilemma. Indian J Pathol Microbiol. 2010;53:178–180. 12. Wang D, Hu Y, He Y, et al. Pure ovarian choriocarinoma mimicking ectopic pregnancy in true hermaphroditism. Acta Obstet Gynecol Scand. 2009;88:850–852. 13. Kong B, Tian YJ, Zhu WW, et al. A pure nongestational ovarian choriocarcinoma in a 10-year-old girl: case report and literature review. J Obstet Gynaecol Res. 2009;35:574–578. 14. Mood NI, Samadi N, Rahimi-Moghaddam P, et al. Pure ovarian choriocarcinoma: report of two cases. J Res Med Sci. 2009;14:327–330. 15. Chen YX, Xu J, Lv WG, et al. Primary ovarian choriocarcinoma mimicking ectopic pregnancy managed with laparoscopy case report. Eur J Gynaecol Oncol. 2008;29:174–176. 16. Gerson RF, Lee EY, Gorman E. Primary extrauterine ovarian choriocarcinoma mistaken for ectopic pregnancy: sonographic imaging findings. AJR Am J Roentgenol. 2007;189:W280–W283. 17. Koo HL, Choi J, Kim KR, et al. Pure non-gestational choriocarcinoma of the ovary diagnosed by DNA polymorphism analysis. Pathol Int. 2006;56:613–616. 18. Bazot M, Cortez A, Sananes S, et al. Imaging of pure primary ovarian choriocarcinoma. AJR Am J Roentgenol. 2004;182:1603–1604. 19. Balat O, Kutlar I, Ozkur A, et al. Primary pure ovarian choriocarcinoma mimicking ectopic pregnancy: a report of fulminant progression. Tumori. 2004;90:136–138. 20. Ozdemir I, Demirci F, Yucel O, et al. Pure ovarian choriocarcinoma: a difficult diagnosis of an unusual tumor presenting with acute abdomen in a 13-year-old girl. Acta Obstet Gynaecol Scand. 2004;83:504–505. 21. Nezhat FR, Pejovic T, Finger TN, et al. Role of minimally invasive surgery in ovarian cancer. J Minim Invasive Gynecol. 2013;20:754–765. 22. Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2500–2510.
Laparoscopic Fertility-preserving Treatment of a Pure Nongestational Choriocarcinoma of the Ovary: Case Report and Review of Current Literature Le Xin, MD, PhD*, Anna Beier, MD, Susanne Tiede, MD, Tatiana Pfiffer, MD, Christhardt K€ ohler, MD, PhD, and Giovanni Favero, MD, PhD From the Departments of Operative and Oncologic Gynecology (Drs. Xin, Beier, Pfiffer, K€ohler, and Favero), and Clinical Oncology (Dr. Tiede), Asklepios Clinic Hamburg, Hamburg, Germany.
ABSTRACT This case report demonstrates the feasibility of laparoscopic and fertility-preserving approach in nongestational choriocarcinoma of the ovary (NGCO). Pure NGCO is a rare malignant condition. In the last decade, only 14 cases have been reported in the literature. The use of laparoscopy and fertility-preserving procedures in nonepithelial ovarian malignancies is extremely controversial. A 23-year-old woman underwent emergency laparoscopy due to acute abdominal pain associated with an 8-cm large adnexal mass. The initial procedure consisted only of a left oophoroplasty, and histology revealed a tumor of high malignant potential compatible with a primary NGCO. Approximately 3 weeks after initial surgery, she was submitted to a laparoscopic staging surgery, including left adnexectomy, omentectomy, peritoneal biopsies, and retroperitoneal lymphadenectomy. Final pathology confirmed an International Federation of Gynecology and Obstetrics stage IIB NGCO. Before initiation of adjuvant chemotherapy based on 3 courses of bleomycin, etoposide, and cisplatin, the patient received goserelin for ovarian suppression. Nine months after therapy, the patient presented no signs of recurrence and reassumed normal menstruation cycles with normal levels of gonadotropins and tumor markers. The current report brings new insights into the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO. Journal of Minimally Invasive Gynecology (2015) 22, 1095–1099 Ó 2015 AAGL. All rights reserved. Keywords:
DISCUSS
Fertility-preserving surgery; Laparoscopy; Nongestational choriocarcinoma of the ovary (NGCO); Ovarian suppression
You can discuss this article with its authors and with other AAGL members at http:// www.AAGL.org/jmig-22-5-JMIG-D-15-00180
Use your Smartphone to scan this QR code and connect to the discussion forum for this article now* * Download a free QR Code scanner by searching for ‘‘QR scanner’’ in your smartphone’s app store or app marketplace.
Choriocarcinoma of the ovary is a rare and aggressive malignancy, which may be either gestational or nongestational in origin [1]. Epidemiologically, the first pathologic entity is far more frequent than the second one. Nongestational choriocarcinoma of the ovary (NGCO) accounts for less than .6% of all ovarian neoplasms [2,3]. The histopathologic diagnosis of NGCO is very difficult to confirm in women of reproductive age because of The authors report no conflict of interest. Corresponding author: Le Xin, MD, PhD, Asklepios Hospital Hamburg, Department of Advanced Gynecologic Surgery and Oncology, Eissendorfer Pferdeweg 52, 21075 Hamburg, Germany. E-mail: [email protected] Submitted March 21, 2015. Accepted for publication April 27, 2015. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ - see front matter Ó 2015 AAGL. All rights reserved. http://dx.doi.org/10.1016/j.jmig.2015.04.025
the absence of ultrastructural or immunohistochemical distinctive features between the 2 forms of the disease [4]. Currently, there is a notorious paucity of data regarding exact carcinogenesis, tumor biology, clinical course, and standard oncologic treatment of this condition. Particularly in regards to surgical therapy, the possibility of implementing fertility-preserving procedures or the use of laparoscopy are seldom discussed in the literature. Herein, we report a case of NGCO diagnosed in a young woman and discuss the diagnosis and treatment, especially the type and form of surgery, including a brief review of the current literature. Case Report A 23-year-old virgin woman was referred to the Department of Operative and Oncologic Gynecology, Asklepios
1096
Journal of Minimally Invasive Gynecology, Vol 22, No 6, September/October 2015
Clinic Hamburg, Germany, after undergoing emergency explorative laparoscopy due to acute intermittent lower abdominal pain associated with a complex pelvic mass. The diagnostic hypothesis at this point was an adnexal torsion or a hemorrhagic ovarian cyst. During the surgery, an approximately 8-cm tumor arising from the left ovary was observed. The adnexum at this side was partially twisted because of the presence of the expansive lesion. Capsule rupture or peritoneal spread was not identified. At this time, she received only a tumor enucleation at this side. Histology revealed a tumor of high malignant potential compatible with a primary ovarian choriocarcinoma. Postoperative serum tumor marker analysis showed persistent elevated levels of b-human chorionic gonadotropin (b-hCG; 18 000 mIU/mL) and normal levels of CA-125, cardioembryonic antigen, alpha-fetoprotein, and lactate dehydrogenase. Approximately 3 weeks after the initial surgery, the patient underwent a positron emission computed tomography that demonstrated a highly metabolic active residual lesion in the region of the operated ovary, without signs of extragonadal dissemination. Based on these findings (possible residual tumor and inadequate operative staging), the patient was extensively counseled about the therapeutic options, namely conservative versus radical surgery. She decided for the fertility-sparing option, and a laparoscopic staging surgery, including peritoneal washing and biopsies of suspicious areas, unilateral salpingo-oophorectomy (left), pelvic peritonectomy, retroperitoneal lymphadenectomy, and infracolic omentectomy, was performed without intercurrences. Intraoperatively, there were no ascites or clear signs of peritoneal carcinomatosis. However, we observed an approximately 3-cm mass arising from the left ovary (Fig. 1) and a 5-mm large lesion in the cul-de-sac (Fig. 2). The right ovary and fallopian tube were normal in appearance. Optimal debulking was achieved with no macroscopic residual tumor. Final pathology revealed a 2.3-cm large residual choriocarcinoma on the left ovary and a small satellite lesion (3 mm) in the Douglas pouch. All other removed specimens, including 25 pelvic and para-aortic lymph nodes, were negative for malignancy. Further immunohistochemical analysis showed positivity for b-hCG, pancytokeratin, Fig. 1 Laparoscopic appearance of an NGCO.
Fig. 2 NGCO implant in the posterior cul-de-sac.
CK7, and Glypican 3 but negative immunostaining for CD30 and OCT4. Final tumor classification was pT2b pN0 L0 V0–International Federation of Gynecology and Obstetrics stage IIB NGCO. The patient developed no postoperative complications and was discharged 5 days after surgery. Fourteen days after the intervention, the serum level of b-hCG was undetectable. Following the recommendation of our interdisciplinary tumor board, 3 courses of BEP (30 mg bleomycin on days 1, 8, and 15, cycles every 22 days; 100 mg/m2 etoposide on days 1–5; 20 mg/m2 cisplatin days 1–5) in the adjuvant setting were administrated. The patient was informed about potential risks of premature ovarian failure induced by chemotherapy and agreed to receive 10.8 mg goserelin for ovarian suppression before initiation of chemotherapy. The protective therapy and chemotherapy were administrated without major toxicity. Serum concentrations of b-hCG and sexual hormones, thorax and abdominal CT scans, and pelvic and sonographic examinations were then performed every 3 months. Nine months after conclusion of the chemotherapy, the patient had no clinical or imaging signs of recurrence. She reassumed normal menstrual cycles approximately 5 months after the end of the systemic therapy and currently presents normal levels of gonadotropins (follicle-stimulating hormone, 7 mIU/mL; luteinizing hormone, 5 mIU/mL) and estradiol (50 pg/mL). Tumor markers remain negative. Discussion Primary choriocarcinoma of the ovary is a rare condition that affects women of childbearing age more frequently than other women [5,6]. Clinical symptoms are normally nonspecific and may include abdominal pain and vaginal bleeding. Despite its infrequent occurrence, it must be considered, in conjunction with distinct forms of abortion or ectopic pregnancy, a differential diagnosis in women
Xin et al.
Laparoscopy for NGCO: a Case Report
with adnexal mass with increased serum levels of b-hCG. The diagnosis is normally established postoperatively, after the histopathologic analysis of the removed ovarian tumor. The presence of malignant cytotrophoblasts and syncytiotrophoblasts allied with immunohistochemical staining with b-hCG confirm the diagnosis of choriocarcinoma. However, it is very difficult to distinguish a pure nongestational from a gestational form of ovarian choriocarcinoma because of the lack of distinctive immunohistochemical characteristics. More recently, some authors defend the performance of a polymorphic analysis of tumor DNA to clearly distinguish these 2 major variants of the disease. To explain, if the genotype of the tumor tissue in question matches that of the patient at all loci and is different from that of the partner, it would confirm the nongestational origin of the malignancy [4,7,8]. However, this method is very expensive, which limits the application. In the present case, the confirmation of a nongestational form of disease was simplified by the fact that the woman was a virgin. Pure NCGO is a highly aggressive malignancy, characterized by an extremely fast tumor cell growth pattern and frequent development of nodal and systemic metastasis to lung, liver, and brain [9]. Overt bleeding from distant metastases may occur in the gastrointestinal tract, kidney, brain, or lung. In fact, pulmonary manifestations are among the most common presenting symptoms of choriocarcinoma [10]. Presently, because of the paucity of available data in the literature, there is no standard of therapy. The oncologic treatment is mostly derived from other more common forms of malignant germ cell tumors and basically includes optimal debulking surgery and polychemotherapy. Consequently, a number of questions are still open, such as the extension of the surgical procedure (conservative vs radical) mainly in women of reproductive age, the possibility of using endoscopic techniques, and the real impact of systemic therapy in survival versus potential induction of gonadal failure. In addition, it is also not clear if the use of fertility-preserving techniques may negatively influence the prognosis. Up to 2015, only 14 reported cases specifically on NGCO are available in the literature (Table 1). The mean age of the affected women is 28 years (range, 10–55). Conservative surgery could be performed in only 28% of the reported patients (4/14), and its indication was based on age, future desire of pregnancy, and tumor stage. Despite the fact that 75% of these women (3/4) underwent adjuvant chemotherapy, none of them received additional fertility-preserving techniques. The most frequently used chemotherapy schemas are BEP (54%) and etoposide, methotrexate, actinomycin-D, cyclophosphamide, and vincristine (27%), but the number of cycles is inconstant among the series, varying from 2 to 6. Laparoscopy was used in only 28% of cases and seems not to have jeopardized the oncologic prognosis. The use of laparoscopy in ovarian malignancies is extremely controversial. Some important concerns, such as
1097
possible port-site metastasis, peritoneal tumor dissemination, inadequate staging, and questionable quality of cytoreduction, have limited the widespread use of laparoscopy in this pathology [9]. The experience in the literature regarding laparoscopy and NGCO is limited to 4 previous case reports [1,12,15,16] and the present description. They have all observed positive oncologic outcomes. It is possible that a key point was the ability to rapidly initiate the adjuvant chemotherapy that is apparently essential for the treatment of this condition. Further advantages observed, such as a short hospital stay, low blood loss, and aesthetics, should be highlighted [10]. Certainly, the oncologic safety of the method needs to be confirmed by larger studies with longer follow-up. Despite the fact that the most important therapeutic prognostic factor is to achieve no residual macroscopic disease at surgery, the magnitude of the interventions is quite different among the published cases. In fact, this is one of the few available reports on a fertility-sparing surgery for this particular sort of germ cell ovarian malignancy. Clearly, the oncologic safety of this strategy must be further investigated, but it reinforces at least the perspective to better counsel patients affected by this condition who deserve to preserve fertility. In these cases, we have to emphasize the importance of the systemic radiologic staging and the complete gonad and extragonad operative staging. This procedure must include, in our opinion, meticulous inspection and execution of multiple biopsies from the peritoneum, regional peritonectomy, omentectomy, and retroperitoneal lymphadenectomy. Currently, it is practically mandatory to discuss with patients the possibility of infertility induced by oncologic treatments during their reproductive years. Gynecologic oncologists should be prepared to offer and explain fertility preservation options before beginning therapy. The gonadotoxic effect of various chemotherapeutic agents is diverse and may involve a number of pathophysiologic mechanisms. The risk of premature ovarian failure depends mainly on the chemotherapy protocol used, the patient’s age, and, in some occasions, the magnitude of the surgical damage to the ovarian tissue. Based on this information, our patient was categorized as intermediate risk and certainly needed an additional fertility protective strategy before adjuvant chemotherapy. The administration of a gonadotropinreleasing hormone analog was an attempt to decrease the insult of the drugs to the remaining follicles by simulating a prepubertal hormonal milieu. Despite insufficient available scientific data, this approach was the best alternative found for maximizing the chances of cure and reproduction in the given scenario [21,22]. The implementation of other fertility-preserving options such as embryo and oocyte cryopreservation were limited by uncertainties regarding the effects of the ovarian stimulation in the primary pathology and the potential delay in the initiation of systemic therapy due to egg collection [22]. Moreover, ovarian tissue cryopreservation for the purpose of future transplantation is currently experimental and has never been clinically used for ovarian malignancies.
1098
Table 1 Pure ovarian choriocarcinoma: summary of reported cases
Age
Initial b-hCG
Outcome
Additional fertility procedure
Diagnosis
Stage
Route
Description
Choi [1], 2013 Exman [7], 2013 Lv [3], 2011
33 24 48
74 612 675 713 7664.3
NGCO NGCO NGCO
NS NS NS
Laparoscopy NS Laparotomy
Gon [11], 2010 Park [2], 2009 Wang [12], 2009 Kong [13], 2009 Mood [14], 2009
21 55 23 10 32
279 000 64 838 26 516 NS 5500
NGCO NGCO NGCO NGCO NGCO
NS NS NS Ic NS
NS Laparotomy Laparoscopy Laparotomy Laparotomy
Chen [15], 2008 Gerson [16], 2007 Koo [17], 2006
23 33 33
NS 564 000 185 000
NGCO NGCO NGCO
Ia NS NS
Laparoscopy Laparoscopy Laparotomy
Bazot [18], 2004 Balat [19], 2004
38 24
2 460 000 8968
NGCO NGCO
NS NS
NS NS
Ozdemir [20], 2004
13
91 028
NGCO
NS
Laparotomy
LO; multiple biopsies TAH; BSO BSO; subextensive total hysterectomy; pelvic lymphadenectomy; omentectomy; appendectomy RSO TAH; BSO; multiple biopsies TAH; BSO; pelvic lymphadenectomy LSO; partial omentectomy TAH; BSO; tumor debulkation; infracolic omentectomy NS RSO; resection of a right adnexal mass AH, BSO, omentectomy, pelviclymphadenectomy TAH, BSO TAH, BSO, PLND, partial omentectomy, stemum mass excision RSO; removal of a single mass
EMA BEP BEP
5 yr NED 1 mo NED 1 yr NED
No No No
NS BEP BEP BVP BEP 1 EMA-CE
NS 20 mo NED NS 2 mo NED 5yr NED
No No No No No
NS EMA-CO MAC
3 yr NED 1 yr NED NED
No No No
NS BEP
7 yr NED Died
No No
MAC
9 mo NED
No
B 5 bilateral; EMA/CE 5 etoposide, methotrexate, actinomycin-D, cisplatin, etoposide; EMA/CO 5 etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine; Ic 5 ; L 5 left; MAC 5 methotrexate, actinomycin-D, cyclophosphamide; NED 5 no evidence of disease; NS 5 not stated; O 5 oophorectomy; PVB 5 cisplatin, bleomycin, vinblastine; R 5 right; S 5 salpingectomy; TAH 5 total abdominal hysterectomy.
Journal of Minimally Invasive Gynecology, Vol 22, No 6, September/October 2015
Chemotherapy scheme
Surgery Author, reference number, year
Xin et al.
Laparoscopy for NGCO: a Case Report
In conclusion, the current report brings new insights about the possibility of using use minimally invasive surgery and a combination of fertility-preserving methods for the treatment of NGCO. References 1. Choi YJ, Chun KY, Kim YW, et al. Pure non-gestational choriocarcinoma of the ovary: a case report. World J Surg Oncol. 2013;11:7. 2. Park SH, Park A, Kim JY, et al. A case of non-gestational choriocarcinoma arising in the ovary of a postmenopausal woman. J Gynecol Oncol. 2009;20:192–194. 3. Lv L, Yang K, Wu H, et al. Pure choriocarcinoma of the ovary: a case report. Gynecol Oncol. 2011;22:135–139. 4. Wang Y, Yang Y, Teng F, et al. Pure non-gestational uterine choriocarcinoma in a postmenopausal Chinese woman confirmed with short tandem repeat analysis. Am J Obstet Gynecol. 2014;4:e1–e3. 5. Smith HO, Berwick M, Verschraegen CF, et al. Incidence and survival rates for female malignant germ cell tumors. Obstet Gynecol. 2006;107: 1075. 6. Longo R, Battaglia F, Gattuso D, et al. Primary non-gestational choriocarcinoma of the uterine cervix. J Clin Oncol. 2011;29:e301. 7. Exman P, Takahashi TK, Gattas GF, et al. Primary ovary choriocarcinoma: individual DNA polymorphic analysis as a strategy to confirm diagnosis and treatment. Rare Tumors. 2013;5:e24. 8. Tsujioka H, Hamada H, Miyakawa T, et al. A pure non-gestational choriocarcinoma of the ovary diagnosed with DNA polymorphism analysis. Gynecol Oncol. 2003;89:540–542. 9. El-Helw LM, Hancok BW. Treatment of metastatic gestational trophoblastic neoplasia. Lancet Oncol. 2007;8:715. 10. Magrath IT, Golding PR, Bagshawe KD. Medical presentations of choriocarcinoma. Br Med J. 1971;2:633.
1099 11. Gon S, Majumdar B, Barui G, et al. Pure primary non-gestational ovarian choriocarcinoma: a diagnostic dilemma. Indian J Pathol Microbiol. 2010;53:178–180. 12. Wang D, Hu Y, He Y, et al. Pure ovarian choriocarinoma mimicking ectopic pregnancy in true hermaphroditism. Acta Obstet Gynecol Scand. 2009;88:850–852. 13. Kong B, Tian YJ, Zhu WW, et al. A pure nongestational ovarian choriocarcinoma in a 10-year-old girl: case report and literature review. J Obstet Gynaecol Res. 2009;35:574–578. 14. Mood NI, Samadi N, Rahimi-Moghaddam P, et al. Pure ovarian choriocarcinoma: report of two cases. J Res Med Sci. 2009;14:327–330. 15. Chen YX, Xu J, Lv WG, et al. Primary ovarian choriocarcinoma mimicking ectopic pregnancy managed with laparoscopy case report. Eur J Gynaecol Oncol. 2008;29:174–176. 16. Gerson RF, Lee EY, Gorman E. Primary extrauterine ovarian choriocarcinoma mistaken for ectopic pregnancy: sonographic imaging findings. AJR Am J Roentgenol. 2007;189:W280–W283. 17. Koo HL, Choi J, Kim KR, et al. Pure non-gestational choriocarcinoma of the ovary diagnosed by DNA polymorphism analysis. Pathol Int. 2006;56:613–616. 18. Bazot M, Cortez A, Sananes S, et al. Imaging of pure primary ovarian choriocarcinoma. AJR Am J Roentgenol. 2004;182:1603–1604. 19. Balat O, Kutlar I, Ozkur A, et al. Primary pure ovarian choriocarcinoma mimicking ectopic pregnancy: a report of fulminant progression. Tumori. 2004;90:136–138. 20. Ozdemir I, Demirci F, Yucel O, et al. Pure ovarian choriocarcinoma: a difficult diagnosis of an unusual tumor presenting with acute abdomen in a 13-year-old girl. Acta Obstet Gynaecol Scand. 2004;83:504–505. 21. Nezhat FR, Pejovic T, Finger TN, et al. Role of minimally invasive surgery in ovarian cancer. J Minim Invasive Gynecol. 2013;20:754–765. 22. Loren AW, Mangu PB, Beck LN, et al. Fertility preservation for patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2013;31:2500–2510.
