FINAL DIAGNOSIS: Metastatic seminoma in the duodenum.
Testicular germ cell tumors are divided into two broad categories, seminoma and nonseminomatous germ cell tumors (NSGCT), which are theorized to arise from the seminomatous epithelium (germinal epithelium) of the testis. Tumors containing both of the major types exist, and it is probably best to call these "mixed seminoma and NSGCT," with the type or a list of the types of NSGCT present and their approximate percentages. The type of NSGCT, particularly choriocarcinoma (which has an aggressive course), determines the prognosis in these cases. Seminomas (the male analogue of the ovarian dysgerminoma) comprise 30-40% of all testicular tumors, and are divided into the classic and spermatocytic catagories.
Classic seminoma, far and away the most common of the two categories. Grossly, in the testes, they are solid yellow-tan tumors and may have sharply demarcated zones of necrosis. Cysts and hemorrhage should suggest the presence of a NSGCT component. Microscopically, classic seminomas have noticeable cell membranes surrounding abundant clear cytoplasm with a large central nucleus holding clumped chromatin with variable mitoses. The nucleolus is distinctive, often with a red hue, with irregular contours. Most are nested with fibrous bands containing a mixed inflammatory infiltrate of lymphocytes, plasma cells, and histiocytes. They stain for placental leukocyte alkaline phosphotase (PLAP), which may be positive in the serum in 40% of cases, c-kit, LDH, vimentin, ferritin, and Ki-A10. While generally negative for EMA and high-molecular weight keratins, they may be focally positive for EMA, CD30, and frequently are positive for low-molecular weight and wide spectrum keratins. K-ras mutation is seen in 40% of cases, and on the order of 25% show p53 mutation. Subcatagories of classic seminoma include anaplastic seminoma, whose natural history is now debated and may not be worse than classic seminoma as originally reported. It is defined by more than 3 mitoses per high-power field, but caution is required, as the majority of classic seminomas have more than 3 mitoses per high-power field. As a result, some authors have debated the definition of anaplastic seminoma. Another variant is seminoma with syncytiotrophoblastic features (giant cells), which occur in isolation within the tumor or in sheets and are positive for hCG. Note that granulomatous inflammation can occasionally surround seminomas, and may be confused for this variant. Seminoma with yolk sac elements is yet another variant, and contains foci of cells with hyaline globules and alpha-fetoprotein (AFP) reactivity in microglandular, papillary-alveolar or papillary arrangements.
Classic seminoma is usually unilateral, but can infrequently present bilaterally. Spread is usually local, particularly to the testicular hilum (which may be microscopic only and should be routinely sampled even in the absence of gross involvement), and can be pagetoid to the rete testes. 80% of pure seminomas are confined to the testis at diagnosis (Stage I disease), but up to 15% are metastatic, normally to retroperitoneal nodes. For this reason, seminomas are normally treated by radical orchiectomy with radiation of the retroperitoneal and ipsilateral pelvic nodes irregardless of radiographic or clinical suspicion. Advanced seminomas or patients with post-radiation relapse may receive chemotherapy. Over 90% of patients with any germ cell tumor are cured, including 95% cure rates for Stage I and Stage II (involving subdiaphragmatic lymph node) disease.
Spermatocytic seminoma accounts for 7% of all seminomas, and is typically found in older patients, and unlike classic seminoma has a myxoid gross appearance. Microscopically the tumor cells are highly pleomorphic with abundant granular cytoplasm, round nuclei and scattered, bizarre giant cells. Mitoses are often numerous, and intratubular growth is often found at the periphery. Spermatocytic seminoma is rarely PLAP positive on staining, unlike the classic form. Focal low-molecular weight and wide spectrum cytokeratin staining can be seen in this form as well. In contrast to classic seminoma, spermatocytic seminoma is never associated with NGSCT components, is more commonly bilateral and metastasis in spermatocytic seminoma is vanishingly rare. Orchiectomy alone is frequently curative. However, a highly malignant sarcomatous component of spindle cells, sometimes with skeletal muscle differentiation, is occasionally seen with frequent wide-spread metastasis. Treatment for such cases usually includes adjuvant therapy of some kind.
Contributed by Joey Oakley MD and Scott Owens MD