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Epithelial Ovarian Cancer:

This type of cancer is the 6th among female cancers and the 2nd among gynecologic cancers. They constitute 4% of the total female cancer and 27% of the gynecologic cancers. It is the gynecologic cancer that leads to death most. Despite advances in surgery and chemotherapy treatment outcomes has not yet reached the desired level. 5-years of  survival ranges from 30-40%.

Incidence and epidemiology:

Malignant epithelial ovarian tumors are especially observed over the age of 50. It is seen approximately at the age of 59, most commonly seen within the age group of 60-64. A woman's risk of developing ovarian cancer during her lifetime is approximately 1.4%. There isn’t a homogenous distribution between countries  in terms of incidence.

Etiology:

The real cause of ovarian cancer is unclear. However, risk factors have been identified in epidemiological studies. These factors can be classified mainly as environmental, endocrine, genetic and other factors. Despite the fact that Most of these factors are promoting the development of ovarian cancer, some are preventive.
 

Ovarian Cancer Etiology

Increased Risk Risk
Talk 1.9
Fatty diet 2.6
Infertility 1.6
Fertility medications 2.8
Hereditary transition
Breast cancer in the family history 1.7
1st grade ovarian cancer 4.5
< age of 55 7.4
≥age of 55 3.7
"Site specific" familial ovarian cancer 39.1
Pregnancy 0.6
Oral contraceptive usage 0.6
Tubal ligation 0.33



The majority of ovarian cancers are seen as coincidental, but 5-13% are are associated with hereditary (hereditary) factors. They are divided into three categories.
1 Specific ovarian cancer family: Epithelial ovarian cancer risk is higher, the rate is increasing depending on the number of ovarian cancer in 1 and 2 degrees relatives. If 1st grade ovarian cancer is present in 2 people in the family, ovarian cancer is  seen at a ratio of 50%. If there is only 1 ovarian cancer in the 1st degree relative in the family history, the risk of cancer is 2 to 4 times more. This type of cancer is seen usually 10 years earlier on average than sporadic cases.
2.Breast-ovarian cancer family: There are members in the family with breast or ovarian cancer. Shows an autosomal dominant inheritance. The BRCA1 and BRCA2 genes have been discovered related to this syndrome. The risk of developing ovarian cancer in women heterozygous for BRCA1 and BRCA2, is between 16% and 60% during their lifetime.

3. Hereditary colorectal cancer family (Lynch II syndrome): Multiple adenocarcinomas are observed in this syndrome. These  are colon, ovarian, endometrial, breast, and other gastrointestinal and genitourinary cancers. These family members will develop cancer 3 times more than in the normal population.

Screening:

In ovarian cancer, screening methods are not safe and sufficient as they are in cervical cancer screenings. screening methods in ovarian cancer are pelvic examination, transvaginal ultrasound examination and tumor markers. Possibility of detecting asymptomatic early stage ovarian cancer with annual pelvic examination is 1/10.000. Especially, CA 125 from the tumor markers, is used in the screening. Necessity of screening by using transvaginal ultrasound and CA125 has been recognized in the literature In women at high-risk groups (who are heterozygous for BRCA1 or BRCA2 and those coming from HNPCC families). Although it is not clearly known whether performing this screening would be beneficial in detection of the ovarian cancer at an early stage, it is known that these reduce mortality. Even if mutation is not detected in women coming from breast-ovarian cancer family, screening should still be performed. Prophylactic is recommended oophorectomy in women belonging to the families of familial ovarian cancer. Depending on the information that ovarian cancer is not seen before the age of 40 in such families, prophylactic oopherectomy can be postponed to the ages after 40 or completing the family.  These patients should be explained that the risk of intra-abdominal carcinomatosis continues despite the removal of ovaries.

Germ Cell Ovarian Tumors

These constitute the 10% of ovarian malignancies. Considering all ovarian neoplasms, this ratio would be 20-25%. They're usually seen at a young age. 70% of the ovarian tumors during the first ages of 20, are compound of germ cell ovarian tumors. Mainly they are examined in several groups. They are aggressive, but chemotherapy-sensitive tumors.

Classification of germ cell ovarian tumors.

A.    dysgerminoma
B. teratoma  
1 Immature teratoma
2 Mature teratoma
i. Solid
ii. cystic
Dermoid cyst (mature cystic teratoma)
Dermoid cyst with malignant transformation
3 Severely specialized and Monodermal
i. Struma ovarii
ii. carcinoid
iii. Struma ovarii and carcinoid
iv. other
C. Endodermal sinus tumor (EST)
D. Embryonal carcinoma
E. Poliembryo
F. Choriocarcinoma
G. Mixed forms

Clinic:

In contrast to the relatively slow-growing epithelial ovarian tumors, germ cell ovarian tumors progress rapidly , and lead to  subacute or acute pelvic pain. This pain may be related to capsular distention, torsion, rupture, hemorrhage or necrosis. Acid and abdominal distention occurs in the further stages.

Most significant examination finding is pelvic mass. Especially solid and semisolid masses are important criteria in terms of malignancy. Tumor markers such as alpha fetoprotein (AFP) (EST), the Human Chorionic Gonadotropin (hCG) (choriocarcinoma and embryonal carcinoma), lactic dehydrogenase (LDH), placental alkaline phosphatase (PLAP) (disgerminomatous for) are helpful in the differential diagnosis of pelvic masses.

Diagnosis:

Diagnosis is made by evaluating the symptoms, findings, tumor markers and risk factors (such as age) together. Masses above 2 cm in pre-menarchial girls and above 8 cm in reproductive ages should be explored surgically.

Complete blood count, liver and renal function tests, chest X-ray are examined in patients for whom surgical exploration is considered.  Considering the possibility of gonadal dysgenesis in pre-menarchial girls, karyotyping is required.

Waiting with oral contraceptive for 2 months in females with a cytic lesion below 8 cm would be appropriate during puberty and reproductive period.

Dysgerminoma

It is the the most common germ cell tumor and responsible for 30-40% of cases. It constitutes 1-3% of all ovarian cancers. A large number of patients are between the ages of 10-30. 20-30% of all ovarian malignancies in pregnancy are dysgerminoma.  Gonadal dysgenesis develops in up to 5% of the cases (streak gonad, 46, XY XY 45X/46, etc.).

The treatment is basically surgery.

Immature treatomas: Immature teratomas contain elements similar to embryonic tissues. It is the second frequently encountered malignant germ cell tumor. It comprises 20% of the tumors below 20 years old.  They usually appear between the ages of 10-20.They are examined in 3 grades according to histopathological characteristics.

Cells are embryonic and show atypical and mitotic activity.

Preoperative and evaluation are similar to other germ cell tumors. Tumor markers are negative, they rarely  include calcifications in radiologic images like mature teratomas.

Endodermal sinus tumor (EST):

 Since they originate from primitive yolk sac, they are also called as yolk sac carcinoma. It is the most common 3rd germ cell malignant tumor. Approximate age is 18. 1/3 of the cases are premenarchial. AFP is released from the tumor and this marker is used in the diagnosis and follow up of the disease. Alpha 1 antitrypsin is a marker released to a lesser extent. The clinical presentation is similar to other germ cell tumors.

Embryonal carcinoma:

It’s a very rare ovarian tumor. It’s approximately seen at the age of 14. By secreting estrogen, they lead to precocious puberty and irregular vaginal bleeding. Presentation is similar to other germ cell ovarian tumors. They generally at early-staged when diagnosed. AFP and hCG are secreted by the tumor and often these markers are used to determine response to therapy.

Choriocarcinoma of the ovary: Nongestational choriocarcinoma of the ovary is an extremely rare tumor. Patients are usually under the age of 20.

Poliembryo: Tumor is composed of early embryonic bodies belonging to all three germ leaves. These are very rare. It may cause pseudopuberty. Usually occurs in the first ten years of age.

Sex Cord Stromal Tumors:

Sex cord stromal tumors of ovary, constitute 5-8% of all ovarian malignancies. These tumors are formed by ovarian  mesenchyme  and sex cord.

Granulosa cell tumors: are seen in reproductive-age. Often secrete estrogen. However, hormone secreting (-)  or androgen-secreting types are also available. They often lead to menstrual disorders.  They cause endometrial cancer in 5% of the patients and endometrial hyperplasia in 20-25% of the patients.  Symptoms and signs are non-specific, similar to other ovarian cancer. They are examined as low-grades malignancy.

Sertoli-Leydig cell tumor: are seen in the 30s and 40s and very rare tumors. Constitute about 0.2% of ovarian cancers. They have low-grade biology. due to androgen secretion, they lead to 70-85% clinical virilization. They rarely secrete estrogen. 1% of cases are bilateral.