Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com
Research Letter
Primary primitive neuroectodermal tumor of the ovary Ling-Hui Chu a, Wen-Chun Chang a, Kuan-Ting Kuo b, Bor-Ching Sheu a, c, * a
Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan c Centre for Optoelectronic Biomedicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan b
a r t i c l e i n f o Article history: Accepted 27 August 2013
The most common neoplastic ovarian tumor in adolescence is the germ cell tumor. About 58% of primary ovarian neoplasms are germ cell tumors, and most are benign cystic teratomas [1]. Ovarian tumors composed of primitive neuroectodermal elements are extremely rare. We report a case of an ovarian primitive neuroectodermal tumor (PNET) treated with fertility-sparing staging surgery and adjuvant chemotherapy, followed by six courses of chemotherapy. A 16-year-old nulliparous girl presented with a pelvic mass which she had palpated accidentally. The mass grew rapidly over 3 weeks. The patient had experienced intermittent abdominal discomfort and irregular menstruation in recent months, but there had been no bowel habit changes. She visited our clinic and her tumor profile was checked. A detailed sonographic examination showed one huge, solid, 16.5 cm 9.2 cm pelvic tumor with heterogenous echo complex contents including some cystic parts and calcification, with a suspected ovarian origin (Fig. 1). Abdominal and pelvic magnetic resonance imaging revealed a huge mass lesion in the pelvic cavity, which showed low T1 signal intensity and intermediate highT2 signal intensity, with some internal cystic components and good enhancement (Fig. 2).The patient was then referred to our oncology clinic, where tumor markers for suspected malignancy revealed an elevated carbohydrate antigen (CA)-125 level (120.9 U/mL), with normal levels of lactate dehydrogenase, carcinoembryonic antigen, CA-199, alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin. The patient denied a family history of ovarian cancer and teratoma. She also denied symptoms of neuroendocrine activity such as flushing, diarrhea, abdominal cramping, and palpitations.
* Corresponding author. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Number 7, Chung-Shan South Road, Taipei 100, Taiwan. E-mail address: [email protected] (B.-C. Sheu).
An exploratory laparotomy revealed a huge left ovarian solid tumor with an irregular border and central necrosis (Fig. 3). The uterus, bilateral fallopian tubes, omentum, and peritoneal surface were grossly normal. There was a moderate amount of ascites, about 400 mL. In consideration of her fertility at this young age, conservative staging surgery with a left salpingo-oophorectomy, dissection of left side pelvic lymph nodes, and infracolic omental excision was performed. Immediate pathological frozen section revealed a spindle cell tumor. A detailed microscopic pathological examination showed the well-encapsulated ovarian tumor to be composed of grayish tan, solid, fleshy tissue with several small cysts with clear fluid. Marked necrosis was seen. Microscopically, the tumor showed a high cellularity, composed of small cells with hyperchromatic, round to oval nuclei and scanty to small amounts of cytoplasm arranged in lobules separated by fibrovascular septa, patternless sheets incompletely divided by fibrovascular septa or a trabecular/cord-like pattern (Fig. 4). A fibrillary matrix was focally present. Mitotic activity (> 10/10 HPF, high power field) and apoptosis were frequently seen and tumor necrosis was evident. Immunohistochemically, the tumor was relatively diffusely positive for synaptophysin and cluster of differentiation (CD) 56, focally positive for chromogranin, S-100 and glial fibrillary acidic protein, with the latter two particularly predominant in the fibrillary matrix area, but negative for cytokeratin (AE1/AE3), CD99, and AFP. Based on the above findings, the tumor resembled a PNET of the central nervous system with a medulloblastoma/neuroblastoma pattern. In addition, small areas of mature teratoma composed of squamous epithelium, respiratory epithelium, bone, cartilage, smooth muscle, adipose tissue, mature glial tissue, and minor nondescript ducts were also present. Therefore, a primitive ovarian neuroectodermal tumor in association with a teratoma was considered. The patient’s postoperative course was smooth and she was discharged from the hospital after surgery. Under a diagnosis of left ovarian PNET, Stage IC, adjuvant chemotherapy for epithelial ovarian cancer was administered with the PT (carboplatin AUC: 6, paclitaxel 175 mg/m2) protocol six times at 3-week intervals without severe side effects, except for alopecia. She was regularly followed for 13 months at our clinic without evidence of recurrence, with regular menstrual cycles and a normal
http://dx.doi.org/10.1016/j.tjog.2013.08.005 1028-4559/Copyright © 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
410
L.-H. Chu et al. / Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
Fig. 1. Ultrasonography shows a huge, solid, heterogeneous tumor in the pelvic cavity.
Fig. 2. Abdominal and pelvic magnetic resonance imaging reveals a huge mass lesion with low T1 signal intensity. B ¼ urinary bladder; R ¼ rectum; V ¼ vagina.
hormone profile. The tumor makers including CA-125 were all normal during regular monthly follow ups. Follow up with fluorodeoxyglucose-positron emission tomography 12 months after completion of chemotherapy also showed negative findings. Primary neuroectodermal tumors are rare monophasic teratomas composed of immature neuroectodermal tissue. The tumors are separate from other types of teratomas and the incidence is rare. These tumors are classified as ependymoma, astrocytoma, and primitive neuroepithelial tumors such as medulloblastoma, medulloepithelioma and neuroblastoma [2]. PNETs are highly cellular and composed of small cells with hyperchromatic, round to oval nuclei and scanty cytoplasm. Lobules separated by fibrovascular septa are present with prominent areas of necrosis [3]. Based on previous reports, most primary PNETs occur in the second to third decades of life, at a slightly younger age than the well-differentiated form of neuroectodermal tumors. The age range of patients in one study was 13 to 69 years [3]. The prognosis is generally poor with a high mortality rate. Kleinman et al [3] reported 12 PNET cases in Stage IA to Stage III. The duration of posttreatment follow-up ranged from 2 months to 9 years. All patients with Stage IA-IC disease received unilateral salpingo-oophorectomy. Postoperative adjuvant chemotherapy was administered in three of four patients with Stage I disease. No patient had evidence of disease during follow-up. However, nearly all patients (7 of 8) in Stage III died of disease at 2e20 months after diagnosis. Because of the rarity of cases, there is no consensus about the operative method or adjuvant therapies such as chemotherapy and radiotherapy. One case report in 2004 described a patient with PNET Stage IIIC with peritoneal carcinomatosis and extensive lymphadenopathy who received fertility-sparing staging surgery and adjuvant radiotherapy and chemotherapy with carboplatin and paclitaxel. She died after 10 months due to septic shock [4]. The adjuvant chemotherapy regimen varies in reports (Table 1). Some authors used the bleomycin, etoposide, and cisplatin (BEP) regimen as in other germ cell tumors, and some used cisplatin,
L.-H. Chu et al. / Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
411
Fig. 3. Left ovarian tumor revealed during exploratory laparotomy (A) and the cut surface (B).
Fig. 4. The tumor shows lobules of small round cells separated by fibrovascular septa (hematoxylin & eosin stain; original magnification, 400).
etoposide, cyclophosphamide, and doxorubicin as a neuroblastoma treatment protocol [5,6]. In our case, carboplatin and paclitaxel were used, which followed the regimen for epithelial ovarian cancer. Megadose chemotherapy followed by peripheral blood progenitor cell rescue has been reported for metastatic disease [7]. New chemotherapy drugs and drug combinations are being tested for the treatment of ovarian cancer. Drugs such as trabectedin (Yondelis) and belotecan have shown promise in some studies. However, we could find no reports on the effects of these two drugs on ovarian PNET because of the rarity of the disease. In summary, ovarian PNET is a rare type of germ cell tumor. The tumor should be differentiated from a wide variety of primary and metastatic ovarian tumors with similar clinical pictures, and the diagnosis is usually confirmed with pathology. There is no consensus about the treatment strategy for ovarian PNET due to the rarity of the disease, although surgery and chemotherapy are commonly used clinically. More studies are needed to evaluate the response and effectiveness of different chemotherapy regimens.
Table 1 Cases of primary primitive neuroectodermal tumors (PNET) of ovary mentioning chemotherapy regimens. Reference
Pathology
Age (y)
Stage
Residual tumor after surgery
Treatment
Follow-up
recurrence
Demirtas et al, 2004 [6]
PNET
25
IC
Nil
3 y, NED
þ, at lymphocyst
Muhlstein et al, 2010 [8]
Neuroblastoma
17
IC
Nil
6 y, NED
Ostwal et al, 2012 [9]
PNET
28
III
Nil
18 mo, DOD
þ, pelvis
Lawlor et al, 1997 [7]
Neuroblastoma
13
IIIC
Diffuse peritoneal seeding
18 mo, NED
Kim et al, 2004 [4]
PNET
18
IIIC
Diffuse peritoneal seeding, abdominal lymphadenopathy
10 mo, death due to septic shock
þ, para-aortic LN, femur
Clinkard et al, 2011 [10] Ateser et al, 2007 [11]
Medulloblastoma
23
IIIC
6 y, NED
PNET
28
IV
Diffuse peritoneal seeding Lung, adrenal metastases
Surgery þ CT Left SO, pelvic & para-aortic lymphadenectomy BEP 4 VIP 6 (salvage CT) Surgery þ CT Bilateral SO, omentectomy cisplatin þ etoposide 7 Surgery þ CT Left SO, cytoreduction, omentectomy EFT-2001 protocol Surgery þ CT Right SO þ omentectomy Cisplatin þ etoposide þ cyclophosphamide þ doxorubicin Surgery þ CT þ RT RSO, omentectomy, LN biopsy Carboplatin þ paclitaxel VACA Bilateral SO, omentectomy Cisplatin þ etoposide RSO Doxorubicin þ cyclophosphamide þ vincristine Doxorubicin þ actinomycin þ cyclophosphamide þ vincristine
13 mo, DOD
þ
BEP ¼ bleomycin, etoposide, cisplatin; CT ¼ chemotherapy; DOD ¼ died of disease; EFT ¼ Ewing’s family of tumors; LN ¼ lymph nodes; NED ¼ no evidence of disease; RT ¼ radiotherapy; SO ¼ salpingo-oophorectomy; VACA ¼ vincristine, actinomycin, cyclophosphamide, doxorubicin; VIP ¼ vinblastine, ifosfamide, cisplatin.
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L.-H. Chu et al. / Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
Conflicts of interest The authors have no conflicts of interest relevant to this article. References [1] Norris HJ, Jensen RD. Relative frequency of ovarian neoplasms in children and adolescents. Cancer 1972;30:713e9. [2] Morovic A, Damjanov I. Neuroectodermal ovarian tumors: a brief overview. Histol Histopathol 2008;23:765e71. [3] Kleinman GM, Young RH, Scully RE. Primary neuroectodermal tumors of the ovary. A report of 25 cases. Am J Surg Pathol 1993;17:764e78. [4] Kim KJ, Jang BW, Lee SK, Kim BK, Nam SL. A case of peripheral primitive neuroectodermal tumor of the ovary. Int J Gynecol Cancer 2004;14:370e2. [5] Kanbour-Shakir A, Sawaday J, Kanbour AI, Kunschner A, Stock RJ. Primitive neuroectodermal tumor arising in an ovarian mature cystic teratoma: immunohistochemical and electron microscopic studies. Int J Gynecol Pathol 1993;12:270e5.
[6] Demirtas E, Guven S, Guven ES, Baykal C, Ayhan A. Two successful spontaneous pregnancies in a patient with a primary primitive neuroectodermal tumor of the ovary. Fertil Steril 2004;81:679e81. [7] Lawlor ER, Murphy JI, Sorensen PH, Fryer CJ. Metastatic primitive neuroectodermal tumour of the ovary: successful treatment with mega-dose chemotherapy followed by peripheral blood progenitor cell rescue. Med Pediatr Oncol 1997;29:308e12. [8] Muhlstein J, Rodriguez-Dahlhoff S, Marie B, Fouyssac F. Primary ovarian neuroblastoma. J Pediatr Adolesc Gynecol 2010;23:263e6. [9] Ostwal V, Rekhi B, Noronha V, Basak R, Desai SB, Maheshwari A, et al. Primitive neuroectodermal tumor of ovary in a young lady, confirmed with molecular and cytogenetic resultsea rare case report with a diagnostic and therapeutic challenge. Pathol Oncol Res 2012;18:1101e6. [10] Clinkard DJ, Khalifa M, Osborned RJ, Bouffet E. Successful management of medulloblastoma arising in an immature ovarian teratoma in pregnancy. Gynecol Oncol 2011;120:311e2. [11] Ateser G, Yildiz O, Leblebici C, Mandel NM, Unal F, Turna H, et al. Metastatic primitive neuroectodermal tumor of the ovary in pregnancy. Int J Gynecol Cancer 2007;17:266e9.
Contents lists available at ScienceDirect
Taiwanese Journal of Obstetrics & Gynecology journal homepage: www.tjog-online.com
Research Letter
Primary primitive neuroectodermal tumor of the ovary Ling-Hui Chu a, Wen-Chun Chang a, Kuan-Ting Kuo b, Bor-Ching Sheu a, c, * a
Department of Obstetrics and Gynecology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan Department of Pathology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan c Centre for Optoelectronic Biomedicine, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan b
a r t i c l e i n f o Article history: Accepted 27 August 2013
The most common neoplastic ovarian tumor in adolescence is the germ cell tumor. About 58% of primary ovarian neoplasms are germ cell tumors, and most are benign cystic teratomas [1]. Ovarian tumors composed of primitive neuroectodermal elements are extremely rare. We report a case of an ovarian primitive neuroectodermal tumor (PNET) treated with fertility-sparing staging surgery and adjuvant chemotherapy, followed by six courses of chemotherapy. A 16-year-old nulliparous girl presented with a pelvic mass which she had palpated accidentally. The mass grew rapidly over 3 weeks. The patient had experienced intermittent abdominal discomfort and irregular menstruation in recent months, but there had been no bowel habit changes. She visited our clinic and her tumor profile was checked. A detailed sonographic examination showed one huge, solid, 16.5 cm 9.2 cm pelvic tumor with heterogenous echo complex contents including some cystic parts and calcification, with a suspected ovarian origin (Fig. 1). Abdominal and pelvic magnetic resonance imaging revealed a huge mass lesion in the pelvic cavity, which showed low T1 signal intensity and intermediate highT2 signal intensity, with some internal cystic components and good enhancement (Fig. 2).The patient was then referred to our oncology clinic, where tumor markers for suspected malignancy revealed an elevated carbohydrate antigen (CA)-125 level (120.9 U/mL), with normal levels of lactate dehydrogenase, carcinoembryonic antigen, CA-199, alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin. The patient denied a family history of ovarian cancer and teratoma. She also denied symptoms of neuroendocrine activity such as flushing, diarrhea, abdominal cramping, and palpitations.
* Corresponding author. Department of Obstetrics and Gynecology, National Taiwan University Hospital, Number 7, Chung-Shan South Road, Taipei 100, Taiwan. E-mail address: [email protected] (B.-C. Sheu).
An exploratory laparotomy revealed a huge left ovarian solid tumor with an irregular border and central necrosis (Fig. 3). The uterus, bilateral fallopian tubes, omentum, and peritoneal surface were grossly normal. There was a moderate amount of ascites, about 400 mL. In consideration of her fertility at this young age, conservative staging surgery with a left salpingo-oophorectomy, dissection of left side pelvic lymph nodes, and infracolic omental excision was performed. Immediate pathological frozen section revealed a spindle cell tumor. A detailed microscopic pathological examination showed the well-encapsulated ovarian tumor to be composed of grayish tan, solid, fleshy tissue with several small cysts with clear fluid. Marked necrosis was seen. Microscopically, the tumor showed a high cellularity, composed of small cells with hyperchromatic, round to oval nuclei and scanty to small amounts of cytoplasm arranged in lobules separated by fibrovascular septa, patternless sheets incompletely divided by fibrovascular septa or a trabecular/cord-like pattern (Fig. 4). A fibrillary matrix was focally present. Mitotic activity (> 10/10 HPF, high power field) and apoptosis were frequently seen and tumor necrosis was evident. Immunohistochemically, the tumor was relatively diffusely positive for synaptophysin and cluster of differentiation (CD) 56, focally positive for chromogranin, S-100 and glial fibrillary acidic protein, with the latter two particularly predominant in the fibrillary matrix area, but negative for cytokeratin (AE1/AE3), CD99, and AFP. Based on the above findings, the tumor resembled a PNET of the central nervous system with a medulloblastoma/neuroblastoma pattern. In addition, small areas of mature teratoma composed of squamous epithelium, respiratory epithelium, bone, cartilage, smooth muscle, adipose tissue, mature glial tissue, and minor nondescript ducts were also present. Therefore, a primitive ovarian neuroectodermal tumor in association with a teratoma was considered. The patient’s postoperative course was smooth and she was discharged from the hospital after surgery. Under a diagnosis of left ovarian PNET, Stage IC, adjuvant chemotherapy for epithelial ovarian cancer was administered with the PT (carboplatin AUC: 6, paclitaxel 175 mg/m2) protocol six times at 3-week intervals without severe side effects, except for alopecia. She was regularly followed for 13 months at our clinic without evidence of recurrence, with regular menstrual cycles and a normal
http://dx.doi.org/10.1016/j.tjog.2013.08.005 1028-4559/Copyright © 2014, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.
410
L.-H. Chu et al. / Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
Fig. 1. Ultrasonography shows a huge, solid, heterogeneous tumor in the pelvic cavity.
Fig. 2. Abdominal and pelvic magnetic resonance imaging reveals a huge mass lesion with low T1 signal intensity. B ¼ urinary bladder; R ¼ rectum; V ¼ vagina.
hormone profile. The tumor makers including CA-125 were all normal during regular monthly follow ups. Follow up with fluorodeoxyglucose-positron emission tomography 12 months after completion of chemotherapy also showed negative findings. Primary neuroectodermal tumors are rare monophasic teratomas composed of immature neuroectodermal tissue. The tumors are separate from other types of teratomas and the incidence is rare. These tumors are classified as ependymoma, astrocytoma, and primitive neuroepithelial tumors such as medulloblastoma, medulloepithelioma and neuroblastoma [2]. PNETs are highly cellular and composed of small cells with hyperchromatic, round to oval nuclei and scanty cytoplasm. Lobules separated by fibrovascular septa are present with prominent areas of necrosis [3]. Based on previous reports, most primary PNETs occur in the second to third decades of life, at a slightly younger age than the well-differentiated form of neuroectodermal tumors. The age range of patients in one study was 13 to 69 years [3]. The prognosis is generally poor with a high mortality rate. Kleinman et al [3] reported 12 PNET cases in Stage IA to Stage III. The duration of posttreatment follow-up ranged from 2 months to 9 years. All patients with Stage IA-IC disease received unilateral salpingo-oophorectomy. Postoperative adjuvant chemotherapy was administered in three of four patients with Stage I disease. No patient had evidence of disease during follow-up. However, nearly all patients (7 of 8) in Stage III died of disease at 2e20 months after diagnosis. Because of the rarity of cases, there is no consensus about the operative method or adjuvant therapies such as chemotherapy and radiotherapy. One case report in 2004 described a patient with PNET Stage IIIC with peritoneal carcinomatosis and extensive lymphadenopathy who received fertility-sparing staging surgery and adjuvant radiotherapy and chemotherapy with carboplatin and paclitaxel. She died after 10 months due to septic shock [4]. The adjuvant chemotherapy regimen varies in reports (Table 1). Some authors used the bleomycin, etoposide, and cisplatin (BEP) regimen as in other germ cell tumors, and some used cisplatin,
L.-H. Chu et al. / Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
411
Fig. 3. Left ovarian tumor revealed during exploratory laparotomy (A) and the cut surface (B).
Fig. 4. The tumor shows lobules of small round cells separated by fibrovascular septa (hematoxylin & eosin stain; original magnification, 400).
etoposide, cyclophosphamide, and doxorubicin as a neuroblastoma treatment protocol [5,6]. In our case, carboplatin and paclitaxel were used, which followed the regimen for epithelial ovarian cancer. Megadose chemotherapy followed by peripheral blood progenitor cell rescue has been reported for metastatic disease [7]. New chemotherapy drugs and drug combinations are being tested for the treatment of ovarian cancer. Drugs such as trabectedin (Yondelis) and belotecan have shown promise in some studies. However, we could find no reports on the effects of these two drugs on ovarian PNET because of the rarity of the disease. In summary, ovarian PNET is a rare type of germ cell tumor. The tumor should be differentiated from a wide variety of primary and metastatic ovarian tumors with similar clinical pictures, and the diagnosis is usually confirmed with pathology. There is no consensus about the treatment strategy for ovarian PNET due to the rarity of the disease, although surgery and chemotherapy are commonly used clinically. More studies are needed to evaluate the response and effectiveness of different chemotherapy regimens.
Table 1 Cases of primary primitive neuroectodermal tumors (PNET) of ovary mentioning chemotherapy regimens. Reference
Pathology
Age (y)
Stage
Residual tumor after surgery
Treatment
Follow-up
recurrence
Demirtas et al, 2004 [6]
PNET
25
IC
Nil
3 y, NED
þ, at lymphocyst
Muhlstein et al, 2010 [8]
Neuroblastoma
17
IC
Nil
6 y, NED
Ostwal et al, 2012 [9]
PNET
28
III
Nil
18 mo, DOD
þ, pelvis
Lawlor et al, 1997 [7]
Neuroblastoma
13
IIIC
Diffuse peritoneal seeding
18 mo, NED
Kim et al, 2004 [4]
PNET
18
IIIC
Diffuse peritoneal seeding, abdominal lymphadenopathy
10 mo, death due to septic shock
þ, para-aortic LN, femur
Clinkard et al, 2011 [10] Ateser et al, 2007 [11]
Medulloblastoma
23
IIIC
6 y, NED
PNET
28
IV
Diffuse peritoneal seeding Lung, adrenal metastases
Surgery þ CT Left SO, pelvic & para-aortic lymphadenectomy BEP 4 VIP 6 (salvage CT) Surgery þ CT Bilateral SO, omentectomy cisplatin þ etoposide 7 Surgery þ CT Left SO, cytoreduction, omentectomy EFT-2001 protocol Surgery þ CT Right SO þ omentectomy Cisplatin þ etoposide þ cyclophosphamide þ doxorubicin Surgery þ CT þ RT RSO, omentectomy, LN biopsy Carboplatin þ paclitaxel VACA Bilateral SO, omentectomy Cisplatin þ etoposide RSO Doxorubicin þ cyclophosphamide þ vincristine Doxorubicin þ actinomycin þ cyclophosphamide þ vincristine
13 mo, DOD
þ
BEP ¼ bleomycin, etoposide, cisplatin; CT ¼ chemotherapy; DOD ¼ died of disease; EFT ¼ Ewing’s family of tumors; LN ¼ lymph nodes; NED ¼ no evidence of disease; RT ¼ radiotherapy; SO ¼ salpingo-oophorectomy; VACA ¼ vincristine, actinomycin, cyclophosphamide, doxorubicin; VIP ¼ vinblastine, ifosfamide, cisplatin.
412
L.-H. Chu et al. / Taiwanese Journal of Obstetrics & Gynecology 53 (2014) 409e412
Conflicts of interest The authors have no conflicts of interest relevant to this article. References [1] Norris HJ, Jensen RD. Relative frequency of ovarian neoplasms in children and adolescents. Cancer 1972;30:713e9. [2] Morovic A, Damjanov I. Neuroectodermal ovarian tumors: a brief overview. Histol Histopathol 2008;23:765e71. [3] Kleinman GM, Young RH, Scully RE. Primary neuroectodermal tumors of the ovary. A report of 25 cases. Am J Surg Pathol 1993;17:764e78. [4] Kim KJ, Jang BW, Lee SK, Kim BK, Nam SL. A case of peripheral primitive neuroectodermal tumor of the ovary. Int J Gynecol Cancer 2004;14:370e2. [5] Kanbour-Shakir A, Sawaday J, Kanbour AI, Kunschner A, Stock RJ. Primitive neuroectodermal tumor arising in an ovarian mature cystic teratoma: immunohistochemical and electron microscopic studies. Int J Gynecol Pathol 1993;12:270e5.
[6] Demirtas E, Guven S, Guven ES, Baykal C, Ayhan A. Two successful spontaneous pregnancies in a patient with a primary primitive neuroectodermal tumor of the ovary. Fertil Steril 2004;81:679e81. [7] Lawlor ER, Murphy JI, Sorensen PH, Fryer CJ. Metastatic primitive neuroectodermal tumour of the ovary: successful treatment with mega-dose chemotherapy followed by peripheral blood progenitor cell rescue. Med Pediatr Oncol 1997;29:308e12. [8] Muhlstein J, Rodriguez-Dahlhoff S, Marie B, Fouyssac F. Primary ovarian neuroblastoma. J Pediatr Adolesc Gynecol 2010;23:263e6. [9] Ostwal V, Rekhi B, Noronha V, Basak R, Desai SB, Maheshwari A, et al. Primitive neuroectodermal tumor of ovary in a young lady, confirmed with molecular and cytogenetic resultsea rare case report with a diagnostic and therapeutic challenge. Pathol Oncol Res 2012;18:1101e6. [10] Clinkard DJ, Khalifa M, Osborned RJ, Bouffet E. Successful management of medulloblastoma arising in an immature ovarian teratoma in pregnancy. Gynecol Oncol 2011;120:311e2. [11] Ateser G, Yildiz O, Leblebici C, Mandel NM, Unal F, Turna H, et al. Metastatic primitive neuroectodermal tumor of the ovary in pregnancy. Int J Gynecol Cancer 2007;17:266e9.
