Browse Day: April 23, 2008

Nonseminomatous Germ Cell Tumors


Nonseminomatous histology comprises about 50% of all GCTs, and most frequently presents in the third decade of life. Most tumors are mixed, consisting of two or more cell types. Seminoma may be a component, but the definition of a pure seminoma excludes the presence of any nonseminomatous cell type. The presence of any nonseminomatous cell type (other than syncytiotrophoblasts) imparts the prognosis and management principles of a nonseminomatous tumor.

Embryonal Carcinoma
Embryonal carcinoma is the most undifferentiated somatic cell type. Individual cells are epithelioid in appearance and may be arranged in glandular or tubular nests and cords or as solid sheets of cells. Tumor necrosis and hemorrhage are frequently observed.


By definition, choriocarcinoma consists of both cytotrophoblasts and syncytiotrophoblasts. If cytotrophoblasts are not present, then the diagnosis of choriocarcinoma cannot be made. Pure choriocarcinoma is an extremely rare presentation usually associated with widespread hematogenous metastases and high levels of hCG. Hemorrhage into the primary tumor is frequent and is an occasional severe complication when it spontaneously occurs at a metastatic site. Elements of choriocarcinoma are frequently found in mixed tumors but appear to have no prognostic importance. Syncytiotrophoblastic giant cells can be seen as a component of any GCT (including pure seminoma). They impart no prognostic value by themselves.

Yolk Sac Tumor

Yolk sac tumor (endodermal sinus tumor) is often confused with a glandular form of embryonal carcinoma. This tumor mimics the yolk sac of the embryo and produces alpha-fetoprotein (AFP). The cells may have a papillary, glandular, microcystic, or solid appearance; and may be associated with Schiller-Duval bodies, which are perivascular arrangements of epithelial cells with an intervening extracellular space. Rarely, embryoid bodies resembling the early embryo can be seen. Yolk sac histology is rarely present as the only histologic subtype except in the mediastinum where pure yolk sac tumors account for a substantial minority of primary tumors. Pure yolk sac histology is the most common histology found in childhood GCT.

A teratoma is composed of somatic cell types derived from two or more germ layers (ectoderm, mesoderm, or endoderm). Mature teratoma consists of adult-type differentiated elements such as cartilage, glandular epithelium, nerve tissue, or other differentiated cell types. Immature teratoma generally refers to a tumor with partial somatic differentiation, similar to that seen in a fetus. Teratoma with malignant transformation refers to a form of teratoma in which one of its components, either immature or mature, develops aggressive growth and histologically resembles another malignancy. These usually take the form of sarcomas (most frequently embryonal rhabdomyosarcoma); and, less frequently, carcinomas (e.g., enteric-type adenocarcinoma), neuroectodermal tumors, or combinations of these. Acute nonlymphocytic leukemias have arisen in the context of mediastinal GCT, but not from other primary sites. Acute lymphocytic leukemia has been described. Although a mature teratoma may be histologically benign, it is derived from a totipotential, malignant precursor cell (embryonal carcinoma or yolk sac tumor). Therefore, a primary testicular tumor in a postpubertal male that displays only teratoma must be considered to be a fully malignant GCT, and management should proceed as if malignant components are present.



Carcinoma in situ (CIS) (intratubular germ cell neoplasia) precedes invasive testicular GCT in virtually all cases of typical and anaplastic seminoma and all nonseminomatous histologies in the adult. CIS is frequently present in retroperitoneal presentations and is rarely, if ever, present in mediastinal presentations. It has not been described in spermatocytic seminoma and rarely in tumors arising in prepubertal patients. Cytologically, CIS preceding seminoma and nonseminoma is identical. The median time for progression of CIS to invasive disease is 5 years. In the general population, the incidence of CIS is very low, while in men with impaired fertility, the incidence is about 0.5%. The incidence of CIS is 2% to 5% in both cryptorchid testes and the contralateral testis in patients with a documented prior testicular GCT.

Seminoma accounts for approximately 50% of all GCT and most frequently appears in the fourth decade of life. The typical or classic form consists of sheets of large cells with abundant cytoplasm and round, hyperchromatic nuclei with prominent nucleoli. A lymphocytic infiltrate or granulomatous reaction with giant cells, or both, is frequently present. Trophoblastic giant cells capable of producing human chorionic gonadotropin (hCG) are present in 15% to 20% of tumors. The presence of syncytiotrophoblastic giant cells in an otherwise pure seminoma does not influence prognosis or treatment. Anaplastic seminoma is an older term used when three or more mitotic figures are seen per high-powered field, and it has no clinical or prognostic importance. Stage for stage, anaplastic seminoma is similar in response and prognosis to classic seminoma.

An atypical form of seminoma has been described with unusual immunohistochemical features. While the cells cytologically resemble classic seminoma, lymphocytic infiltrate and granulomatous reaction are absent, necrosis is more common, and the nuclear: cytoplasmic ratio is higher. These tumors must be distinguished morphologically from solid variants of embryonal carcinoma and yolk sac tumor. Atypical seminoma frequently shows cytoplasmic expression of low-molecular-weight keratin or the type 1 precursor to the blood group antigens, while typical seminoma stains negative. Electron microscopic studies have shown that the individual tumor cells acquire cytoplasmic cytokeratin intermediate filaments, suggesting epithelial differentiation. There has been no specific association of atypical seminoma with an adverse prognosis, and its management is currently the same as any other seminoma.

Spermatocytic seminoma is a rare histologic variant seen almost exclusively in men above the age of 45. The relationship of spermatocytic seminoma to other GCTs is not clear, because it is not associated with CIS or bilaterally, does not express placental alkaline phosphatase (PLAP) (see later), and has not been shown to have the same genetic abnormalities as other GCTs. Metastatic potential is minimal.