Ovarian Germ Cell Tumor – Histopathological and statistical analysis

Results: A total of 340 cases of ovarian tumors were reported and 150 cases (44%) were of germ cell origin. We had 137 cases of benign and 13 cases of malignant germ cell tumors. Most common subtype was mature cystic teratoma comprising 125 cases. Among the malignant cases, the most common was immature teratoma (5 cases). Age range in our series was from 8 to 82 years (mean 28 years). The most common age group affected was 21-30 years. Most of the malignant cases (76.9%) were in less than 30 years. Among the malignant cases majority (84.6%) were more than 10 cm in size. None of the malignant germ cell tumors were bilateral.

in the same period and among them, 150 cases (44%) were of germ cell origin.The number and percentage of different types as well as 95% confidence interval of all benign and malignant germ cell tumors have been tabulated in Table 1.Benign germ cell tumors were 137 (40.3%) of all ovarian tumors and 91.3% of germ cell tumors.Malignant germ cell tumors constituted 3.8% (n-13) of all ovarian tumors and 8.6% of germ cell tumors.Most common subtype in our series was mature cystic teratoma (n=125).Among the malignant cases, the most common type was immature teratoma (n=5).The age distribution and bilaterality of different types of benign and malignant germ cell tumors have been tabulated in Table 2. Age range in our series was from 8 to 82 years with a mean of 28 years.The commonest age group affected was 21-30 years followed by 31-40 years and 41-50 years.Most of the malignant cases (10/13, 76.9%) were in women of less than 30 years.Out of all 150 cases 11 were bilateral.None of the malignant germ cell tumor was bilateral.Size of all different types of germ cell tumors including bilateral cases are shown in Table 3.The tumor size ranged from 3 cm to 27 cm with 95 cases (63%) in the category 5-10 cm followed by 10-20 cm (n= 51, 34%).Among the malignant cases majority (11/13, 84.6%) were more than 10 cm in size.Statistical analysis of age and size distribution of all the subtypes were carried out and are tabulated in Tables 4 and 5 respectively.

DISCUSSION
Germ cell tumors are a heterogeneous group, majority originating at different stages of development from germ cells. 7Some are composed of undifferentiated cells (dysgerminoma, embryonic carcinoma) while in others there is differentiation towards embryonic (teratoma) all the subtypes including benign and malignant tumors.

Sample size calculation
For 95% confidence interval and, significance level α =5%, P = 50%, Q = 50%, allowable error = 11%, required sample size was 317.P = percentage of germ cell tumor.In the pilot study done prior to the original study with 10 patients. 5

Ethical committee approval
Prior the study, ethical committee approval was taken from the institutional ethical committee, Manipal Teaching hospital, Pokhara, Nepal.The Research was conducted in accordance to latest version of the Declaration of Helsinki.

Data management and statistical analysis
The data collected was analyzed using Excel 2003, R 2.8.0 Statistical Package for the Social Sciences (SPSS) for Windows Version 16.0 (SPSS Inc; Chicago, IL, USA) and EPI Info 3.5.1 Windows Version.The Z test was used to observe the difference between different variables.p < 0.05 was considered as statistically significant. 6

A total of 340 cases of ovarian tumors have been reported
Ghosh A et al. or extraembryonic (choriocarcinoma, yolk sac tumor) structures. 8They account for nearly 30% of all ovarian tumors. 7,9In the current data, they constituted 44% of all ovarian tumors.

Benign germ cell tumors
Mature cystic teratoma is the most common ovarian neoplasm comprising 25% or more. 9In studies by Mondal SK et al and Jha R et al mature cystic teratoma comprised 68.9% and 95.6% of all germ cell tumors. 13,14In Western literature 95% of ovarian germ cell tumors are mature cystic teratoma. 15,16In our study, 125/150 cases were mature cystic teratoma, comprising 83.3% of all germ cell tumors and 36.8% of all ovarian tumors.
Grossly it is mostly unilocular cyst filled with grumous sebaceous material and hair.Microscopy reveals mature adult type tissue derived from two or three embryonic layers, most commonly being ectoderm.Struma ovarii is the most common type of monodermal teratoma. 7However , only 2 cases out of 150 cases were reported as struma ovarii.There were 10 cases of composite tumors where mature teratoma was associated with serous cystadenoma ( n=5), with mucinous cystadenoma ( n=3) and with benign Brenner tumor ( n=2).
Majority of mature cystic teratoma are known to occur in less than 50 years with the peak being between 20 and 29 years. 7,8Similarly, in the present series majority (n=110; 88%) were below 50 years and it was statistically significant with p value 0.001.The peak for mature cystic teratoma was in the age group 21-30 comprising 54 cases (43.2%).Benign teratomas are known to be bilateral in 10-15% cases. 8In our series, 8% ( n=13) benign teratomas where bilateral.Benign teratomas range in size from a few centimeter to large tumor with average being 7-8 cm. 8 We reported cases with a range from 2 cm to 27 cm.Majority were less than 10 cm with significant p value and most common group being 5-10 cm.However though the average size of Struma ovarii is 5-10 cm, the 2 cases we reported were of 8 cm and 15 cm in size.

Malignant germ cell tumors
Immature teratoma is one of the most common malignant germ cell tumors representing 20-30% of these tumors at major cancer centers. 17,18Only 3% of ovarian teratomas are immature. 15,16They occur in young age group and are typically unilateral with average size of 18 cm. 8In our study, 5 cases (3.4%) were immature teratoma.Age and size distribution were statistically significant in the present study, as all were below 30 years of age and majority were more than 10 cm.One case had size of less than 10 cm while rest 4 cases were between 10 and 20 cm.A mixture of mature and immature tissue; mostly in the form of neuroectodermal rosettes and tubules were seen.Histologically, they can be graded into grade 1, 2 and 3 according to extent of neuroectodermal component. 7,8We had 2 cases of grade 1 and 3 cases of grade 2 tumor.
Approximately 1-3% of benign mature teratoma may undergo malignant transformation. 8In a study of 87 ovarian teratomas, Papadias et al reported 5% cases with malignant changes. 19Secondary malignancies are typically Ovarian Germ Cell Tumor seen in postmenopausal women and 85% are squamous cell carcinoma. 7We had only 4 cases of teratomas with secondary malignancy; 2 with squamous cell carcinoma and 1 with undifferentiated carcinoma and 1 with mucinous borderline areas.
Dysgerminoma is a common malignant germ cell tumor of the ovary.10-12Eighty percent of tumors develop in women younger than 30 yrs of age with mean age 21 years.They are extremely rare above 50 years.9Out of 2 cases in our study, 1 case was of 55 years.Microscopically predominantly diffuse pattern of primitive monotonous germ cells with PAS positive cytoplasm are seen (fig.1).The stroma is usually thin with varying number of lymphocytes.
Pure primary ovarian choriocarcinoma of germ cell origin is extremely rare and comprise less than 1% of all ovarian germ cell neoplasms. 7,8We reported only one case in the current study.Diligent search for other germ cell component should be carried out as choriocarcinoma is seen mostly as a component of a mixed germ cell tumor.Grossly they are typically hemorrhagic and microscopy is similar to its endometrial counterpart.
Yolk sac tumors are morphologically heterogenous and may show many epithelial patterns.The only case we had was of 16 years of age and showed classical reticular pattern and Schiller Duval bodies (fig 2 .).
Mixed germ cell tumors are composed of at least two different germ cell component, the most common combination being dysgerminoma and yolk sac tumor. 3All the components with their approximate proportion should be noted in the diagnosis. 7Therapeutic regimen is based on the most malignant element. 20We did not encounter any case under this category.Ovarian Germ Cell Tumor

Table 4 : Statistical analysis and significance of age distribution of different types of germ cell tumor
CONCLUSIONAmong germ cell tumors of ovary, mature cystic teratoma is the most common tumor and malignant subtypes are uncommon.Malignant tumors tend to occur in younger age group.