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.

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