Primary Extragonadal Germinal Cell Tumors
PKGhatak, MD
Primary extragonadal germinal cell tumors.
The germinal cell produces sperm or ovum. Under normal circumstances, the germinal cells are present only in the gonads (Testicles and Ovaries).
In a rare embryonic mishap, the germinal cells are present in the Pineal gland, Mediastinum and Retroperitoneal areas. Germinal cells in these locations may turn into tumors, both benign and malignant tumors.
A short review of the origin of germinal cells is essential in understanding these aberrant locations of the germinal cells.
Gonads and germinal cells have separate lines of origin. Gonads are mesodermal tissues, whereas germinal cells originate in the Yolk Sac of the developing embryo. At 5 weeks the germinal cells leave the yolk sac and migrate to the developing fetus, and travel along the Allantois behind the hindgut, behind the peritoneum and move all the way to the developing neural tube which later develops into the brain. Most of the germinal cells migrate to the genital ridge and lodge in the gonadal tissue, the rest of the germinal cells disappear.
The allantois is a narrow tube through which placental blood vessels run to and from the fetus and placenta. The fetus and extra fetal tissues (yolk sac) lie submerged in amniotic fluid in the amnion sac, the membrane of the sac is called the coelomic epithelium.
Due to developmental errors, a few germinal cells remain in the brain, mediastinum and retroperitoneal tissues. Tumors that develop at these locations are called extragonadal (non-gonadal) germinal cell tumors.
Histopathological Types.
Germ cell tumors in unusual locations may be benign or malignant. The benign tumors are called teratomas.
Teratoma.
The germ cells are endowed with the power to produce any or all cell lines and are progenitors of the Totipotent stem cells. In teratomas this characteristic is maintained, as a result, the teratomas contain hair, teeth, nails, sweat glands and other tissues. Tumors are generally multicyclic. In males, the tumor though benign by the pathological criteria but behaves like a malignant tumor. Teratomas are diverse in histology and also vary in biological behavior. In women, teratomas are benign multicyclic tumors containing hairs, teeth, nails, glands, bone and cartilage. In males, teratomas are benign looking but may behave like malignant.
Malignant germinal tumors.
The tumors are mixed cell types but one cell line dominates and is named accordingly. The usual varieties are Embryonal cell carcinoma, Choriocarcinoma. Yolk cell Carcinoma, and Seminoma.
Location of tumors.
Germinal cell tumors are midline tumors. In the brain, the usual site is the pineal gland and occasionally appears in the Pituitary gland. In the mediastinum, they are in the anterior mediastinum in between the lungs and behind the thymus gland. The abdominal site is usually in the sacrum behind the hindgut and peritoneum.
Pineal gland germinal cell tumors.
These tumors are generally malignant. Symptoms are of three categories. A growing tumor increases cerebrospinal fluid pressure and produces headaches, nausea, vomiting, and the 6th cranial nerve palsy. Local infiltration of tumor-cerebellar dysfunction affects balance and walking. The hormone of the pineal gland is Melatonin. Disruption of melatonin production results in sleep rhythm change, and difficulty in falling asleep.
The malignant tumors secrete Chorionic gonadotropin and Alpha fetoprotein. The blood levels of these two are elevated in nearly all cases and in 1/3 of cases the CSF levels are also high. It is well known that in raised CSF pressure situation the spinal tap is contraindicated; in this circumstance, the CSF is obtained by the 4th ventricle puncture. Blood chorionic gonadotropin is not specific for gonadal cell tumors, it is elevated in pregnancy and pregnancy related complications and in menopause. Alpha fetoprotein is also elevated in hepatic cell carcinoma and neonatal hepatitis. High chorionic gonadotropin and alpha fetoprotein in addition to an MRI of the brain suggestive of a pineal growth, in non-pregnant women, is as good as biopsy confirmed pineal germinal cell tumors.
In gonadal cell tumors of the brain, matters little, at the time of initial diagnosis, whether the tumor is benign or not. Biopsy of pineal gland tumors is reserved for tumor recurrence. At that time cell types help to direct more specific chemotherapy agents and additional surgery.
Mediastinal germinal cell tumors.
Germinal cell tumors are the second most mediastinal malignant tumors in childhood. Teratomas do not elevate blood fetoprotein and chorionic gonadotropin.
Chest x-ray detects tumors, and most patients are asymptomatic at the time of diagnosis. Biopsy of the tumor can be safely performed by the retrosternal approach. At times teratomas are detected in the thymus gland, rather than behind it.
Symptoms vary from asymptomatic to obstructive symptoms of trachea-bronchi and blood vessels of the mediastinum. Treatment is surgery, and chemotherapy and radiation are added if the tumors are malignant. In certain circumstances, chemotherapy and radiation are followed by surgery.
Ovarian germinal cell tumors are mostly benign cystic. The testicular germinal cell tumors are generally malignant seminoma and non-seminoma, appear in equal frequency. Testicular malignant tumors do not secrete chorionic gonadotropin and alpha fetoprotein.
Retroperitoneal germinal cell tumors are generally benign teratomas. And carry the best prognosis of the three locations.
Extragonadal germinal cell tumors are rare. Tumors are seen in children and young adults. Except for the sacral location, most of the tumors are either malignant or potentially malignant. Intracranial germinal cell tumors pose a diagnostic challenge but blood and CSF markers along with MRI images are virtually diagnostic.
The prognosis of sacral tumors is the best. Mediastinal seminomas have a better prognosis than Non seminomas. Overall, the 5- year survival rate is between 40 to 90 %.
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