Testicular Neoplasms 1

Testicular Neoplasms 1

Testicular Neoplasms 1
Professor Dr Ali Hassan Altimimi
Professor of Pathology & Histology MSc, PHD, MD(UK)
Testicular neoplasms are the most important cause of firm, painless enlargement of the testis. Such neoplasms occur in roughly 5 per 100,000 males, with a peak incidence between the ages of 20 and 34 years. Tumors of the testis represent a heterogeneous group of neoplasms composed of germ cell tumors and sex cord/stromal tumors. In adults, 95% of testicular tumors arise from germ cells, and all are malignant. Neoplasms derived from Sertoli or Leydig cells (sex cord/stromal tumors) are uncommon and, in contrast to tumors of germ cell origin, usually pursue a benign clinical course. The remainder of this section will focus on testicular germ cell tumors.
The cause of testicular neoplasms remains unknown. As noted previously, cryptorchidism is associated with a 3- to 5-fold increase in the risk of cancer in the undescended testis, as well as an increased risk of cancer in the contralateral descended testis. A history of cryptorchidism is present in approximately 10% of cases of testicular cancer. Intersex syndromes, including androgen insensitivity syndrome and gonadal dysgenesis, are also associated with an increased frequency of testicular cancer. Cytogenetic studies show a wide range of abnormalities in testicular germ cell neoplasms, the most common of which is an isochromosome of the short arm of chromosome 12. However, the role of these chromosomal aberrations in the pathogenesis of testicular neoplasms remains unclear. The risk of neoplasia is increased in siblings of males with testicular cancers, although no consistent hereditary genetic abnormalities have been identified to account for this increased risk. The development of cancer in one testis is associated with a markedly increased risk of neoplasia in the contralateral testis. Testicular tumors are more common in whites than in blacks, and the incidence has increased in Caucasian populations over recent decades.

Classification and Histogenesis

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Table . Simplified Classification of Testicular Germ Cell Tumors
Tumors with One Histologic Pattern Seminoma * Embryonal carcinoma *Yolk sac tumor *Choriocarcinoma *Teratomas Mature Immature With malignant transformation of somatic elements Tumors with More Than One Histologic Pattern Together grouped as non-seminomatous tumors.
Several different classification schemes have been proposed for testicular neoplasms, based on the histologic features of the tumors and on differing theories about their histogenesis. The World Health Organization classification is the most widely used in the United States . In this schema, germ cell tumors of the testis are divided into two broad categories, based on whether they contain a single histologic pattern (60% of cases) or multiple histologic patterns (40% of cases). This classification is based on the view that germ cell tumors of the testis arise from primitive cells that may either differentiate along gonadal lines to produce seminomas or transform into a totipotential cell population, giving rise to nonseminomatous germ cell tumors. Such totipotential cells may remain largely undifferentiated to form embryonal carcinomas, may differentiate along extra-embryonic lines to form yolk sac tumors and choriocarcinomas, or may differentiate along somatic cell lines to produce teratomas. This proposed histogenesis is supported by the high frequency of mixed histologic patterns among nonseminomatous germ cell tumors. The morphology of the more common forms is presented below, along with a discussion of some of their more salient clinical features.

It is now widely believed that most testicular tumors arise from in situ lesions characterized as intratubular germ cell neoplasia. This lesion is present in conditions associated with a high risk of developing germ cell tumors (e.g., cryptorchidism, dysgenetic testes). Furthermore, foci of such in situ lesions are seen in testicular tissue adjacent to a testicular germ cell tumor in virtually all cases.

-Seminoma of the testis appears as a fairly well circumscribed, pale, fleshy, homogeneous mass.


Seminoma of the testis. Microscopic examination reveals large cells with distinct cell borders, pale nuclei, prominent nucleoli, and a sparse lymphocytic infiltrate.
Morphology
Seminomas, sometimes referred to as "classic" seminomas to distinguish them from the less common spermatocytic seminoma discussed below, account for about 50% of testicular germ cell neoplasms. They are histologically identical to ovarian dysgerminomas and to germinomas occurring in the central nervous system and other extra-gonadal sites. Seminomas are large, soft, well-demarcated, usually homogeneous, gray-white tumors that bulge from the cut surface of the affected testis . The neoplasms are typically confined to the testis by an intact tunica albuginea. Large tumors may contain foci of coagulation necrosis, usually without hemorrhage. The presence of hemorrhage should prompt careful scrutiny for an associated nonseminomatous germ cell component to the tumor. Microscopically, seminomas are composed of large, uniform cells with distinct cell borders, clear, glycogen-rich cytoplasm, and round nuclei with conspicuous nucleoli. The cells are often arrayed in small lobules with intervening fibrous septa. A lymphocytic infiltrate is usually present and may, on occasion, overshadow the neoplastic cells. A granulomatous inflammatory reaction may also be present. In as many as 25% of cases, cells staining positively for human chorionic gonadotropin (hCG) can be seen. Some of these hCG-expressing cells are morphologically similar to syncytiotrophoblasts, and they are presumably the source of the elevated serum hCG concentrations that may be encountered in some males with pure seminoma.

Another, less common, morphologic variant of seminoma is the so-called spermatocytic seminoma. These tumors, which tend to occur in older patients than do classic seminomas, contain a mixture of medium-sized cells, large uninucleate or multinucleate tumor cells, and small cells with round nuclei that are reminiscent of secondary spermatocytes. There is no association with intratubular germ cell neoplasia, and metastases are exceedingly rare, in contrast to the behavior of classic seminoma.

Embryonal carcinomas are ill-defined, invasive masses containing foci of hemorrhage and necrosis . The primary lesions may be small, even in patients with systemic metastases. Larger lesions may invade the epididymis and spermatic cord. The constituent cells are large and primitive looking, with basophilic cytoplasm, indistinct cell borders, and large nuclei with prominent nucleoli. The neoplastic cells may be arrayed in undifferentiated, solid sheets or may contain glandular structures and irregular papillae ). In most cases, other patterns of germ cell neoplasia (e.g., yolk sac carcinoma, teratoma, choriocarcinoma) are admixed with the embryonal areas. Pure embryonal carcinomas comprise 2% to 3% of all testicular germ cell tumors. As with other germ cell tumors of the testes, foci of intratubular germ cell neoplasia are frequently present in the adjacent seminiferous tubules.