Final Diagnosis -- Mixed Germ Cell Tumor of Testes



Contributor's Note:

Approximately 95% of all testicular neoplasms are of germ cell origin. For unclear reasons, there has been a worldwide increase in the incidence of these tumors (1). The current incidence in the United States is 6 per 100,000. Germ cell tumors tend to occur in the 15- to 34-year age group. The most well documented risk factor for the development of germ cell tumors is cryptorchidism. Testicular dysgenesis, a prior contralateral tumor, and genetic factors also play a role. The most consistent chromosomal abnormality is an isochromosome of the short arm of chromosome 12, i(12p), which is present in 56% of seminomas and in83% of nonseminomatous tumors (2). Approximately 1.35% of patients also have a first degree relative with germ cell tumor of the testis. The relative risk for first degree relatives is increased 3-10 fold (3). Patients with germ cell tumor in one testicle have a 500-1000 fold greater chance of developing a contralateral testicular carcinoma. 0.5-7% of patients will develop a contralateral testicular tumor. 80-85% of bilateral tumors occur metachronously, at a mean of 65.1 months after the first tumor (4).

WHO classification divides germ cell tumors into two categories. About 40% of the tumors are composed entirely of a single histologic pattern such as seminoma, spermatocytic seminoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and teratoma (mature and immature). The remaining 60% contain a mixture of two or more histologic patterns, known as a mixed germ cell tumor. The most frequent combination is that of embryonal carcinoma, yolk sac tumor, teratoma, and choriocarcinoma, which constitutes 14% of testicular germ cell tumors. Choriocarcinomas are highly malignant and carry a poor prognosis. Grossly, they are small, red-brown, friable lesions with extensive hemorrhage and necrosis. Microscopically, choriocarcinomas contain both multinucleated syncytiotrophoblasts and polygonal cytotrophoblasts. The syncytiotrophoblasts stain positively with human chorionic gonadotropin (HCG). Intratubular germ cell neoplasia, unclassified type, represents the common precursor to most testicular germ cell neoplasms. The majority of germ cell neoplasms stain positively with placental alkaline phosphatase (PLAP) and negatively with epithelial membrane antigen (EMA).

Seminomas represent approximately 50% of germ cell tumors and tend to occur in the fourth decade. Grossly, they are circumscribed, gray-white to tan, with a bulging cut surface. Necrosis and hemorrhage are uncommon. Microscopically, seminomas consist of sheets of large clear cells, divided by delicate vascular septae with lymphocytic infiltration. Granulomatous areas and multinucleated giant cells can occur.

Spermatocytic seminomas are uncommon and usually affect men over age 60. Grossly, they are larger then classic seminomas. Microscopically, these tumors are composed of three cell types: the majority are medium sized with a round nucleus and eosinophilic cytoplasm; small cells with condensed chromatin; and scattered multinucleate giant cells.

Embryonal carcinomas tend to show gross necrosis and hemorrhage. They usually occur in the third decade. Microscopically, embryonal carcinomas are large, pleomorphic cells, most commonly glandular but also tubular, alveolar, papillary and solid patterns. The neoplastic cells contain basophilic cytoplasm with large pleomorphic nuclei and solitary prominent nucleoli. Cell borders are usually indistinct. Mitoses are common.

Yolk sac tumors are the most common testicular tumor in children under the age of three years. Grossly, these tumors are yellow-white and multinodular. The most common microscopic pattern seen is a reticular (lace-like) network of medium elongated cells. Schiller-Duvall bodies are seen in 50% of tumors. Most tumors also contain intra- and extracellular hyaline globules. The yolk sac tumor cells as well as the hyaline globules stain positively with alpha-fetoprotein (AFP).

Teratomas are divided into mature and immature subtypes based on the degree of histologic differentiation. Tissues derived from all three germ cell layers may be seen. The gross appearance is heterogeneous, composed of solid, cartilaginous, and cystic areas. Hemorrhage and necrosis are common. They tend to be larger than other germ cell tumors. They may occur at any age.

Testicular tumors tend to metastasize through the lymphatics, with para-aortic nodes the first to be involved. Hematogenous spread is often to the lungs and liver. The histology of the metastasis may be different than that of the primary tumor. Seminomas are monomorphic and necrosis is uncommon. They tend to remain localized to the testis for a longer period of time and thus present at an earlier clinical stage. They are extremely radiosensitive and have cure rates greater than 95%. Nonseminomatous germ cell tumors, including mature and immature teratomas, have a varigated appearance and often display hemorrhage and necrosis. These tumors are biologically more aggressive and radioresistant. These tumors still carry a relatively high rate of remission with aggressive chemotherapy, including 60-75% remission with clinical stage III disease. The histologic subtype does not influence prognosis. Biologic markers, including AFP, HCG, PLAP, and lactate dehydrogenase (LD) are valuable in continued follow up of the patient.


  1. Cotran, Ramzi S, et al. The Male Genital Tract: in Robbins Pathologic Basis of Disease, 6th edition, W.B. Saunders Co, Phil. 1999.
  2. Ulbright, Thomas M. Germ Cell Neoplasms of the Testis. Am J Surg Pathol 1993; 17:1075-1091 .
  3. Brodsky, Gilbert L. Pathology of Testicular Germ Cell Tumors. Hem/Onc Clinics N Am 1991; 5:1095-1125.
  4. Murphy, Patrick, and Johnson, David H. Staging and Prognostic Factors in Nonseminomatous Testicular Cancer. Hem/Onc Clinics N Am 1991;5:1233-1243.
  5. Bartlett, Nancy L, et al. Serum Markers in Germ Cell Neoplasms. Hem/Onc Clinics N Am 1991; 5:1245-1258.
  6. Ilson, David H, et al. Genetic Analysis of Germ Cell Tumors: Current Progress and Future Prospects. Hem/Onc Clinics N Am 1991; 5:1271-1280.
  7. De Jong, Bauke, et al. Cytogenetics of the Progression of Adult Testicular Germ Cell Tumors. Cancer Genet Cytogenet 1997; 95:88-95.
  8. Oosterhuis, J. Wolter, et al. Chromosomal Constitution and Developmental Potential of Human Germ Cell Tumors and Teratomas. Cancer Genet Cytogenet 1997; 95:96-102.
  9. Sandberg, Avery A, et al. Reviews of Chromosome Studies in Urological Tumors. III. Cytogenetics and Genes in Testicular Tumors. J Urol 1996; 155:1531-56.

Contributed by Melissa B. Halpern, MD, Jason C. Fowler and Uma Rao, MD


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