A germ cell tumor (GCT) is a neoplasm derived from germ cells. Germ cells normally occur inside the gonads (ovary and testis). Germ cell tumors that originate outside the gonads may be birth defects resulting from errors during development of the embryo.
Some investigators suggest that this distribution arises as a consequence of abnormal migration of germ cells during embryogenesis. Others hypothesize a widespread distribution of germ cells to multiple sites during normal embryogenesis, with these cells conveying genetic information or providing regulatory functions at somatic sites.
Extragonadal germ cell tumors were thought initially to be isolated metastases from an undetected primary tumor in a gonad, but it is now known that many germ cell tumors are congenital and originate outside the gonads. The most notable of these is sacrococcygeal teratoma, the single most common tumor diagnosed in babies at birth.
Germ cell tumors are classified by their histology, regardless of location in the body.
| Tumor | ICD-O | Peak Age (yr) | Benign or malignant | Histology | Tumor marker |
|---|---|---|---|---|---|
| Germinoma including dysgerminoma and seminoma | 9060/3 | 40-50 | Malignant | Sheets of uniform polygonal cells with cleared cytoplasm; lymphocytes in the stroma | 10% have elevated hCG |
| Embryonal carcinoma | 9070/3 | 20-30 | Malignant | Poorly differentiated, pleomorphic cells in cords, sheets, or papillary formation | Pure tumors do not secrete hCG, AFP |
| Endodermal sinus tumor, also known as yolk sac tumor (EST, YST) | 9071/3 | 3 | Malignant | Poorly differentiated endothelium-like, cuboidal, or columnar cells | 100% secrete AFP |
| Choriocarcinoma | 9100/3 | 20-30 | Malignant | Cytotrophoblast and syncytiotrophoblast without villus formation | 100% secrete hCG |
| Teratoma including mature teratoma, dermoid cyst, immature teratoma, teratoma with malignant transformation | 9080/0-9080/3 | 0-3, 15-30 | Mature teratoma, dermoid cyst usually benign (but follow-up required); others usually malignant | Very variable, but "normal" tissues are common | Pure tumors do not secrete hCG, AFP |
| Polyembryoma | 9072/3 | 15-25 | ? | ? | ? |
| Gonadoblastoma | 9073/1 | ? | ? | ? | ? |
| Mixed | 15-30 | Malignant | Depends on elements present | Depends on elements present |
Germ cell tumors are broadly divided in two classes:
The two classes reflect an important clinical difference. Compared to germinomatous tumors, nongerminomatous tumors tend to grow faster, have an earlier mean age at time of diagnosis (~25 years versus ~35 years, in the case of testicular cancers), and have a lower 5 year survival rate. The survival rate for germinomatous tumors is higher in part because these tumors are exquisitely sensitive to radiation, and they also respond well to chemotherapy. The prognosis for nongerminomatous has improved dramatically, however, due to the use of platinum-based chemotherapy regimens.
Despite their name, germ cell tumors occur both within and outside the ovary and testis.
In females, germ cell tumors account for 30% of ovarian tumors, but only 1 to 3% of ovarian cancers in North America. In younger women germ cell tumors are more common, thus in patients under the age of 21, 60% of ovarian tumors are of the germ cell type, and up to one-third are malignant. In males, germ cell tumors of the testis occur typically after puberty and are malignant (testicular cancer). In neonates, infants, and children younger than 4 years, the majority of germ cell tumors are sacrococcygeal teratomas.
Persons with Klinefelter's syndrome have a 50 times greater risk of germ cell tumors (GSTs). In these persons, GSTs usually contain nonseminomatous elements, present at an earlier age, and seldom are gonadal in location.
The 1997 International Germ Cell Consensus Classification is a tool for estimating the risk of relapse after treatment of malignant germ cell tumor.
A small study of ovarian tumors in girls reports a correlation between cystic and benign tumors and, conversely, solid and malignant tumors. Because the cystic extent of a tumor can be estimated by ultrasound, MRI, or CT scan before surgery, this permits selection of the most appropriate surgical plan to minimize risk of spillage of a malignant tumor.
Germ cell tumors of children are the subject of clinical research by the worldwide Children's Oncology Group (COG), in a number of studies coordinated by Dr. John Cullen, MD.
Intracranial Germ Cell Tumors have been studied through the International CNS GCT Study Group. Under the direction of Jonathan Finlay, the program director, three international treatment studies have been initiated since 1990 with the goal to maintain a high rate of cure while minimizing the late effects of treatment.
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