Author Information
Satia MN*, Madhavi J**, More V***
(* Professor, ** Third Year Resident, *** Assistant Professor Department of Obstetrics and Gynecology, Seth G.S. Medical College and K.E.M. Hospital, Mumbai, India.)
Abstract
Ovarian tumors in adolescent female is more often benign than malignant. Below the age of 20 years, 60% of the tumors are of germ cell origin. Also, increased incidence of ovarian tumors in reproductive age group is attributed to the improvements in diagnostic modalities and hence, there is more need for fertility preserving surgeries. We report an interesting case of a young girl with a mixed germ cell tumor. It was an embryonal cell carcinoma with yolk sac remnants who underwent a fertility preserving surgery and later had a successful pregnancy outcome twice and then came back to us for medical termination of pregnancy with tubal ligation.
Introduction
Germ cell malignancies account for fewer than 5% of ovarian cancers in western countries and around 15% in Asian countries.[1] Twenty to 25 % of all ovarian neoplasms are of germ cell origin[2], out of which 3% cases are malignant. Mixed germ cell tumors account for 10% of germ cell tumors. They are composed of two or more germ cell elements such as dysgerminoma, teratoma, yolk sac tumor, choriocarcinoma, or embryonal carcinoma. Our patient had a tumor comprising of embryonal cell carcinoma with yolk sac elements. Embryonal cell carcinoma is an extremely rare germ cell tumor, contributing to 3% of all germ cell tumors.[3] It affects very young patients between 4 to 28 years of age. The treatment challenge lies in preservation of fertility, as the tumor affects very young females in the reproductive age group.
Case Report
A 29 year old woman, married for 7 years, gravida 3, para 1 and abortion 1 with 6 weeks of pregnancy came to antenatal outpatient department. At 16 years she had presented with acute abdomen to the emergency department. Ultrasonography done was suggestive of right ovarian mass with torsion. A decision of emergency exploratory laparotomy was taken. Intraoperatively there were two and half turns of torsion, hence right salpingo oophorectomy was performed. The tumor was solid, well capsulated, around 8-10 cm in size. There was no ascites. Patient had an uneventful post operative stay. Histopathology report was suggestive of mixed germ cell tumor; embryonal cell carcinoma with elements of yolk sac tumor. Hence she was referred to an oncologist for further management. Tumor markers were sent. Serum β HCG was 0, α-fetoprotein was 3 ng/ml and CA-125 was 66 IU/ml. CT abdomen and pelvis did not detect any abnormality or any metastatic focus. She had six monthly follow up with the oncologist and her tumor markers were always in the normal range. The table below depicts the regular follow up of the patient over 10 years. No adjuvant therapy was required. She conceived immediately after marriage but had missed abortion for which dilatation and evacuation was done. She conceived spontaneously after an year, continued uneventfully till term and a lower segment cesarean section was performed for breech presentation. During present pregnancy she was antenatally registered at our hospital since 6 weeks of pregnancy. She developed severe pre-eclampsia at 35 weeks of gestation for which antihypertensive therapy was given. Lower segment cesarean section was performed for breech presentation with previous LSCS and impending eclampsia. She delivered a male child of 3.2 kg with apgar at 1 minute of 9/10. Intraoperatively, right sided ligated tubal stump was seen and the left sided fallopian tube and ovary was normal. Cesarean section was uneventful. Post operative course was uneventful and patient was discharged on day 7 of surgery with advise to use depot medroxyprogesterone as contraceptive once in three months. A year after the birth of her second child the patient presented with six weeks of pregnancy. She underwent medical termination of pregnancy and left sided tubal ligation through a minilaprotomy.
Discussion
In the adolescent age group, 80 % of the malignant ovarian tumors are germ cell tumors, and are usually diagnosed between 16-20 years of age.[4,5] According to WHO in 1973, germ cell tumors are classified as dysgerminomas or non-dysgerminomas.[6] Dysgerminomas, considered as the female counterparts of testicular seminomas are the most common (50%) germ cell tumors. Non dysgerminomas include endodermal sinus tumor, embryonal cell carcinoma, polyembryoma, choriocarcinoma, teratomas (immature, mature, and monodermal), mixed and gonadoblastoma. Yolk sac tumors or endodermal sinus tumors are the commonest after dysgerminomas accounting for 20% of the cases, affecting young females around 19 years of age.[7] Embryonal cell carcinoma of the ovary is an extremely rare tumor that is composed of undifferentiated cells. This lesion is a progenitor of other germ cell tumors. As already mentioned these tumors are seen in very young females, the median age at diagnosis being 14 years.[8] These tumor cells synthesize both α fetoprotein and β-HCG, that can be later used to monitor the response to chemotherapy. As compared to slower growing epithelial ovarian tumors, germ cell tumors grow rapidly and are characterized by pelvic pain due to capsular distension, hemorrhage or necrosis. The rapidly enlarging mass can lead to pressure symptoms due to compression on bladder or rectum. Menstrual irregularities have been reported in menarcheal patients. This is attributed to the estrogen secretion seen in embryonal cell carcinoma.[9] Patients can also present with torsion of the ovarian mass, as was seen in our patient and rarely, rupture of the adnexal mass. The primary lesions are large and are usually confined to ovary at the time of diagnosis. Primary modalities of diagnosis include ultrasonography (USG) and computed tomography (CT) of the abdomen and pelvis. CT chest is also recommended as germ cell tumors are known to metastasize to lungs or mediastinum. Tumor markers are also done to evaluate for the nature of the ovarian tumor. As our patient presented with an acute abdomen, these investigations were done retrospectively after confirmation with the histopathological diagnosis. Grossly, embryonal cell carcinomas are poorly defined with areas of hemorrhage and necrosis.[10] Microscopically, they have indistinct cell borders with a variable architecture, composed of solid, glandular and papillary type of cells.
As germ cell tumors affect young reproductive females, preservation of fertility and ovarian function is important, although it is a controversial issue in gynecological oncology. Treatment for stage I cancers is surgical resection alone with a unilateral salpingo-oophorectomy and staging. Ipsilateral tube is removed as there is abundant lymphovascular connection between tube and ovary. Surgical resection requires a diligent follow up care with serial pelvic examinations and follow up with tumor markers is necessary if resection is preferred as the only treatment of choice. The follow up of ovarian germ cell malignancies is usually done with α-fetoprotein (AFP) and β human chorionic gonadotrophin.[11] Our patient had a regular follow up for 10 years (Table 1).
Weinberg et al described 8 patients with spontaneous pregnancies ending in 11 live full-term births in a series of twenty two patients ( fertility rate of 80%).[12] A wedge biopsy of the contralateral ovary was previously recommended to rule out metastasis; but is not recommended now as germ cell tumors are good responders to chemotherapy and also, the fear of adhesions in the ovary after wedge biopsy that might affect future fertility.
Adjuvant treatment in the form of radiotherapy and chemotherapy is recommended for tumors beyond stage Ia. Radiotherapy has been replaced by chemotherapy owing to the long term complications associated such as sterility and early menopause.[13] For those patients requiring chemotherapy, the regimen comprises of Bleomycin, Etoposide and Cisplatin for 3-4 cycles. Germ cell tumors respond well to platinum based chemotherapy regimens. The efficacy of chemotherapy has now allowed conservative surgery including only a unilateral salpingo-oophorectomy preserving fertility in grade I tumors.[14]
Date
|
AFP ng/ml
|
β HCG IU/l
|
10/12/2002
|
2.7
|
0
|
26/3/2003
|
4.0
|
0
|
10/6/2003
|
3.1
|
0
|
23/9/2003
|
3.0
|
0
|
13/1/2004
|
3.1
|
0
|
28/7/2004
|
2.9
|
0
|
8/2/2005
|
3.6
|
0
|
15/9/2005
|
1.84
|
0
|
16/3/2006
|
3.51
|
0
|
8/1/2008
|
4.11
|
<1.20
|
3/6/2008
|
3.99
|
<1.20
|
4/12/2008
|
3.93
|
<1.20
|
2/8/2010
|
5.10
|
<1.20
|
10/8/2011
|
4.98
|
<1.20
|
References
- Berek JS, Friedlander M, Hacker NF. Germ cell and other non epithelial ovarian cancers. In Berek JS, and Hacker NF editors. Berek and Hacker’s gynecologic oncology.5th ed. Philadelphia, PA: Lippincott Williams and Wilkins 2010:509-535.
- Imai A, Furui T, Tamaya T. Gynecologic tumors and symptoms in childhood and adolescence:10 years experience. Int J Gynaecol Obstet 1994; 45:227-234.
- Young RH, Clement PB. Sex Cord- Stromal, Steroid Cell and Germ cell Tumors of the Ovary. In Carter D, Greenson JK, Reuter VE, Stoler MH, Mills SE, editors. Sternberg's Diagnostic Surgical Pathology Volume 1. 5th Ed. Philadelphia, PA: Lippincott Williams and Wilkins. 2009:2309-2341
- Talerman A. Germ cell tumors of the ovary. In: Kurman JR,editor. Blaustein's pathology of the female genital tract. 5th edition. New York: Springer 2002; pp 967–1033.
- Zanagnolo V, Sartori E, Galleri G, Pasinetti B, Bianchi U. Clinical review of 55 cases of malignant ovarian germ cell tumors. Eur J Gynecol Oncol 2004; 25(3):315-320.
- Gershenson DM. Update on malignant ovarian germ cell tumors. Cancer. 1993;71(4 Suppl):1581–1590.
- Koshy M, Vijayananthan A, Vadiveloo V. Malignant ovarian mixed germ cell tumor: a rare combination. Biomed Imaging Interv J 2005;1(2):e10.
- Ueda G, Abe Y, Yoshida M, Fujiwara T. Embryonal carcinoma of the ovary: a six-year survival. Int J Gynaecol Obstet 1990; 31:287.
- Kammerer-Doak D, Baurick K, Black W, Barbo DM, Smith HO.Endodermal sinus tumor and embryonal carcinoma of the ovary in a 53-year-old woman.Gynecol Oncol. 1996;63(1):133-7.
- Abbas AK, Fausto N, Mitchell R. Female Genital System and Breast. In Robbins Basic Pathology. 8th edition. Philadelphia: Elsevier 2011; pp. 696–697
- Eagle K, Ledermann JA. Tumor Markers in Ovarian Malignancies. Oncologist. 1997;2(5):324-329.
- Weinberg LE, Lurain JR, Sing DK, Schink JC. Survival and reproductive outcomes in women treated for malignant ovarian germ cell tumors. Gynecol Oncol 2011; 121(2):285–9
- Schultz KA, Sencer SF, Messinger Y, Neglia JP, Steiner ME. Pediatric ovarian tumors: a review of 67 cases. Pediatr Blood Cancer. 2005;44(2):167-73.
- Gershenson DM. Management of early ovarian cancer: germ cell and sex cord-stromal tumors. Gynecol Oncol.1994;55(3 Pt 2):S62-72.
Citation
Satia MN, Madhavi J, More V. Successful reproductive outcome in a young female following a mixed germ cell tumor. JPGO 2016. Volume 3 No. 6. Available from: http://www.jpgo.org/2016/06/successful-reproductive-outcome-in.html