Ovarian germ cell tumor

Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma. Ovarian germ cell tumors (OGCTs) are heterogeneous tumors that are derived from the primitive germ cells of the embryonic gonad, which accounts for about 2.6% of all ovarian malignancies. There are four main types of OGCTs, namely dysgerminomas, yolk sac tumor, teratoma, and choriocarcinoma. Dygerminomas are the most common type and are particularly prominent in patients diagnosed with gonadal dysgenesis. OGCTs are relatively difficult to detect and diagnose at an early stage because of the nonspecific histological characteristics. Common symptoms of OGCT are bloating, abdominal distention, ascites, and dyspareunia. OGCT is caused mainly due to the formation of malignant cancer cells in the primordial germ cells of the ovary. The exact pathogenesis of OGCTs is still unknown however, various genetic mutations and environmental factors have been identified. OGCTs are commonly found during pregnancy when an adnexal mass is found during a pelvic examination, ultrasound scans show a solid mass in ovary or blood serum test shows elevated alpha-fetoprotein levels. They are unlikely to have metastasized and therefore the standard tumor management is surgical resection, coupled with chemotherapy. The occurrence rate is less than 3 % worldwide. OGCTs can be classified into dysgerminoma, teratomas, yolk sac tumors, and choriocarcinomas, listed in the order of prevalence. Dysgerminomas are comparable to testicular seminomas and account for approximately 32- 37% of all OGCTs. They are particularly prominent in individuals with dysgenic gonads of 46, XY pure gonadal dysgenesis patients. Based on gross examinations, dysgerminomas are characterized by having a ‘solid, lobulated, tan, flesh-like gross appearance with a smooth surface'. Microscopically, the cellular structure is distinguished by a round-ovoid shape containing ample eosinophilic cytoplasm and an irregularly shaped nuclei. The uniformly positioned cells are separated through the fibrous strands and lymphocytic infiltration is commonly observed. Teratomas can be divided into two types: mature teratoma (benign) and immature teratoma (malignant). Immature teratomas contain immature or embryonic tissue which significantly differentiates them from mature teratomas as they carry dermoid cysts. It is commonly observed in 15 to 19 year-old women and rarely in women after menopause. Immature teratomas are characterized with a diameter of 14-25 cm, encapsulated mass, cystic areas, and occasional appearance of hemorrhagic areas. The stage of immature teratomas is determined depending on the amount of immature neuroepithelium tissue detected. The ovarian yolk sac tumors, also known as endodermal sinus tumors, are accountable for approximately 15.5% of all OGCTs. They have been observed in women particularly in their early ages, and rarely after 40 years of age. The critical pathologic features are a smooth external surface and capsular tears due to their rapid rate of growth. A study consisting of 71 individual cases of ovarian yolk sac tumor provides evidence to the proliferation of the tumor. In one of the cases, the pelvic examination revealed normal activity until a 9 cm and 12 cm sized tumor was discovered 4 weeks later. In another case, a 23 cm tumor was discovered in a pregnant woman who was monitored regularly and had normal findings until oophorectomy became essential. Histologically, these tumors are characterized by mixed solid and cystic components. The mixed solid components are characterized by a soft gray to yellow solid components accompanied with significant hemorrhage and necrosis. The cysts are approximately 2 cm in diameter and populated throughout the tissue which results in giving the neoplasm a ‘honeycombed appearance’. Choriocarcinomas are exceptionally rare which account for 2.1%-3.4% of all OGCTs. Under gross examination, the syncytiotrophoblast cells are aligned in a plexiform arrangement with the mononucleated cytotrophoblast cells surrounding the foci of the hemorrhage. Choriocarcinomas can be divided into gestational choriocarcinomas and non-gestational choriocarcinomas which have immunohistochemical differences. OGCTs are relatively difficult to detect and diagnose at an early stage mainly because the symptoms are normally subtle and nonspecific. They become detectable when as they become large, tangible masses. Symptoms include bloating, abdominal distention, ascites, and dyspareunia. In rare cases where the tumor ruptures, acute abdominal pain can be experienced. The critical indicator of malignancy is usually the appearance of the Sister Mary Joseph Nodule. OGCTs can further give rise to ovarian torsion, hemorrhage, and even isosexual precocious puberty in young children. The exact cause of OGCT is yet to be determined. However, a few factors have been identified which may contribute to increased risk of OGCTs including endometriosis, polycystic ovarian syndrome, and genetic risk factors. Individuals who are more prone to developing OGCTs usually contain the autosomal dominant, BRCA-1/ BRCA-2, mutations. Complications with other cancers such as hereditary nonpolyposis colorectal cancer, also known as the Lynch syndrome, increases the risk of developing ovarian cancer. Pregnancy, breastfeeding, and oral contraceptives are known to have reduced risk for OGCTs.The etiology of OGCT is still under study, however, genetic alterations may contribute to development of OGCTs, such as the classical tumor suppressor genes and oncogenes. Along with genetic modifications, certain environmental factors such as endocrine disruptors, presence of a daily routine that affects the individual’s biochemistry, and exposure to maternal hormones could also contribute to the proliferation of OGCT. A recent study on rats showed the transgenerational epigenetic inheritance supporting the influence of hazardous environmental substances, including plastics, pesticides, and dioxins, on the pathogenesis of OGCT.