No abstract

Serial quantitative measurements of serum alphafetoprotein (AFP) and human chorionic gonadotropin (HCG) have been prospectively studied in 386 patients with testicular germ cell cancer during the past seven years using sensitive and specific radioimmunoassays (RIAS). When HCG and AFP was measured in patients with nonseminomatous testicular tumors (NSTT), about 90% of these patients with active tumors have elevated levels of serum HCG and/or AFP. These markers have proven valuable in reducing the clinical staging errors to 5-14% by measuring their serum levels during the pre- and post-lymphadenectomy periods. The role of these markers have been demonstrated in monitoring the therapy and determining the prognosis of patients with NSTT. Although serum AFP has not been observed in patients with seminoma, serum HCG has been observed in patients with pure seminoma. Although these markers are seen with certain other cancers, their differential diagnosis does not pose a problem. However, since most seminoma and about 10% of NSTT do not produce these markers, their value in differential diagnosis of a scrotal mass is limited. In interpretation of these markers, one should consider their biologic half-lives and their discordant behavior while the patient is under therapy. Concentrating the 24 hour urine and extracting the urinary HCG content by using a carboxy-terminal RIA enhance the potential for a more sensitive monitoring of the tumor burden and for guiding the therapy of certain patients with testicular cancer. Finally, there are a number of potential markers under investigation in our laboratory.

In a case‐control study of testicular cancer, 6 of 269 cases (2.2%) reported a first‐degree relative with testicular cancer, compared to 1 of 259 controls (0.4%). Fathers and brothers of testicular cancer cases had a six‐fold elevated risk of developing a testicular malignancy compared to men in the general population. Cryptorchidism was reported in a first‐degree relative in 1 (17%) of the familial cases versus 7 of 259 (2.7%) controls and 14 of 263 (5.3%) cases with a negative family history for testicular cancer. One half of the 6 familial cases reported a first‐degree relative with a groin hernia (all surgically repaired before age 12), compared to 12.7% of 259 controls and 10.3% of 263 nonfamilial cases. Three familial clusters identified through the case‐control study were selected for clinical evaluation. One of the 6 surviving males with testicular cancer in these 3 families had undergone orchiopexy and inguinal herniorrhaphy at age 6 years, and one had a hydrocele associated with his testicular tumor. Of the 12 living fathers and brothers of these 6 men, 3 reported childhood inguinal hernias, two with coexisting hydroceles. One additional hernia and two additional hydroceles were detected during urologic evaluation of these healthy relatives. The high prevalence of cryptorchidism, inguinal hernias, and hydroceles among men in these families suggests that an underlying alteration in urogenital embryogenesis may be associated with the familial predisposition to testicular neoplasia.

An immunohistologic study of 21 patierits with germ cell tumors of the testis with measured serum levels of chorionic gonadotropin (HCG) and alpha-feto protein (AFP) was undertaken to cerrelatt! the various types of neoplasms with the presence of these tumor markers in the tissue and serum. AFP was demonstrated in mononuclear embryonal cells within embryonal carcinoma and endodermal sinus tumor. HCG was identified within syncytiotrophoblastic giant cells, frequently in association with embryonal carcinoma, and rarely with endodermal sinus tumor and seminoma, as well as in the syncytiotrophoblastic component of choriocarcinoma. Eighteen of the 21 patients (86%) had elevated tumor markers in their serum; serum HCG alone was elevated in five (24%), AFP alone in five (24%) and both were elevated in eight (38%). There was tissue localization of HCG in 12 of the 13 patients (92%) with elevated serum HCG while AFP was identified in the tumor in eight of the 13 patients (53%) with elevated serum AFP levels. Based on these findings, a tentative immunohistologic classification of germ cell tumors utilizing AFP and HCG is proposed. Thus, embryonal carcinoma, adult type, is frequently associated with byth AFP and HCG, endodermal sinus tumor with AFP and choriocarcinoma with HCG, whereas pure seminoma and teratoma are unlikely to be associated with either marker. under a variety of different designations, generally as "teratocarcinoma, " but recently there has been biochemical and immunohistochemical evidence to suggest that the endodermal sinus tumor, also known as yolk sac carcinoma or infantile type embryonal carcinoma, is the specific neoplasm responsible for the synthesis of AFP. 287~10*17~27~28 Elevated levels of HCG have generally been thought to reflect elements of choriocarcinom8, but there has been no systematic attempt to corkelate the various patterns of germ cell tumors with the presence or absence of either AFP or HCG.The present status of histopathology ahd tumor immunology in this area is reflected by the paradoxical situation that HCG is elevated in approximately 72% and AFP in 75% of patients with nonseminomatous germ cell tumors of the testis, 32 yet both choriocarcinoma and endodermal sinus tumor are edtremely rare in adults. In fact, there are only 18 cases of pure choriocarcinoma among 6,000 testis tumors on file in 2136