Laboratory Studies
Measurements of alpha-fetoprotein (AFP), human chorionic gonadotropin (beta-hCG), and lactate dehydrogenase (LDH) are important in the management of patients with testicular tumors. In fact, these tests are incorporated in the current staging system for testicular tumors (see Staging). [14] Alpha fetoprotein is elevated in over 90% of the cases with yolk-sac origin.
Both AFP and beta-hCG are suggestive of malignancy when elevated before orchiectomy. The rate of decline after orchiectomy indicates the likelihood of residual tumor. Tumor marker levels are used to assess response to treatment and to predict the likelihood of complete remission. In regular follow-up, tumor marker levels indicate recurrence, often in the absence of symptoms, physical findings, or abnormal findings on imaging studies.
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Beta-human chorionic gonadotropin
Beta-hCG is a glycoprotein typically produced by the placenta.
Elevations in beta-hCG levels are found in the serum of approximately 15% of patients with seminoma.
The half-life of beta-hCG is approximately 22 hours.
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Alpha-fetoprotein
AFP is a glycoprotein typically associated with the human fetus and is the fetal equivalent of albumin. AFP is found in nonseminomatous germ cell tumors, as well as in hepatocellular carcinomas, cirrhosis, hepatitis, and pregnancy. It is of note that AFP is normally elevated at birth with gradual decline up to 6-9 months postpartum.
The half-life of AFP is approximately 5 days.
Elevated AFP levels are rare in pure seminomas and indicate that nonseminomatous elements are also present (ie, mixed tumor). [15]
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Lactate dehydrogenase: The LDH level is an independent prognostic factor in patients with germ cell tumors (including seminoma). It is thought to reflect tumor burden.
Imaging Studies
Plain chest radiography and CT scanning of the abdomen and pelvis are the most important radiologic investigations in determining the extent of disease in patients with seminoma. [16]
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Imaging studies of the chest should be done to rule out pulmonary parenchymal metastases.
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CT scanning of the abdomen or MRI are to be performed for identifying the presence and extent of retroperitoneal lymphadenopathy and is necessary in all patients; it has largely replaced bipedal LAG in the radiographic staging of patients with seminoma. Retroperitoneal lymph nodes measuring 1-2 cm are confirmed to be pathologically involved with metastatic tumor in approximately 70% of cases.
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Although radiologists skilled in the technique are increasingly difficult to find, bipedal LAG is uniquely able to define abnormal lymph nodes by both size and internal architecture, unlike CT scanning. In addition, LAG is useful to the radiation oncologist, who is able to minimize irradiation of normal tissues when such a study is available to facilitate portal design. Currently, this test is not widely used because of the difficulty in finding radiologists who are experts in this technique.
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Further radiologic investigation are obtained to rule out metastatic disease (eg, CT or MRI of the primary site as well as brain in select patients).
The typical testicular tumor is intratesticular and may produce one or more discrete hypoechoic masses or diffuse abnormalities with microcalcifications that can be detected using scrotal ultrasonography. Calcifications are more frequent in seminoma than in nonseminomatous tumors.
Histologic Findings
Grossly, seminomas are pale gray–to-yellow nodules that are uniform or slightly lobulated. Pure seminomas are subdivided into 3 subtypes based on histopathologic characteristics.
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Classic seminomas (85%) demonstrate a monotonous sheet 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 hCG are present in 15-20% of tumors. Mitoses are infrequent.
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Anaplastic seminoma (10%) is an older term used to describe seminomas with 3 or more mitotic figures per high-power field. This finding has no clinical or prognostic significance because the response of anaplastic seminomas to standard therapy is equivalent to that of classic seminomas.
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Spermatocytic seminoma (5%) is a rare histologic variant that is not associated with carcinoma in situ. These well-differentiated tumors usually contain cells resembling secondary spermatids or spermatocytes. Spermatocytic seminomas rarely metastasize, and they occur almost exclusively in elderly men. [3] The only recommended treatment is orchiectomy.
Staging
Testicular seminoma is staged according to the American Joint Committee on Cancer (AJCC) 2010 staging guidelines. [17] This is a TNM staging system comprising separate categorizations for the primary tumor, regional lymph nodes, distant metastases, and serum tumor markers; these 4 categories are used to determine the stage of the patient's disease. Modern treatment decisions are based, in part, on the subdivisions of this staging system. Formal staging is a complex process involving particular required and allowable tests and procedures; the following is a quick overview. (For full staging information, see the AJCC Staging Manual.)
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Primary tumor staging
Tis - Intratubular germ cell neoplasia (carcinoma in situ)
T1 - Tumor limited to testis/epididymis without vascular or lymphatic invasion; tumor may invade into the tunica albuginea but not the tunica vaginalis
T2 - Tumor limited to testis/epididymis with vascular or lymphatic invasion or tumor extending through tunica albuginea with involvement of the tunica vaginalis
T3 - Tumor invading spermatic cord with or without vascular/lymphatic invasion
T4 - Tumor invading scrotum with or without vascular/lymphatic invasion
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Regional lymph node staging
N0 - No regional lymph node metastases
N1 - Metastasis with lymph node(s) 2 cm or less in greatest dimension or multiple lymph nodes, none more than 2 cm in greatest dimension
N2 - Metastasis with lymph node(s) larger than 2 cm but not larger than 5 cm in greatest dimension, or multiple lymph nodes, any 1 mass larger than 2 cm, but not more than 5 cm, in greatest dimension
N3 - Metastasis with lymph node(s) larger than 5 cm in greatest dimension
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Distant metastatic staging
M0 - No distant metastases
M1a - Nonregional nodal or pulmonary metastasis
M1b - Distant metastases other than M1a
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Serum tumor marker staging
S0 - Marker studies within normal limits
S1 - LDH level less than 1.5 times the reference range, beta-hCG level less than 5000 mIU/mL, and AFP level less than 1000 ng/mL
S2 - LDH level 1.5-10 times the reference range, beta-hCG level 5,000-50,000 mIU/mL, or AFP level 1,000-10,000 ng/mL
S3 - LDH level more than 10 times the reference range, beta-hCG level more than 50,000 mIU/mL, or AFP level more than 10,000 ng/mL
Children’s Oncology Group Staging System for Testicular Germ Cell Tumors
STAGE I: Limited to testis Completely resected by high inguinal orchiectomy Tumor markers negative Unknown tumor markers at diagnosis -> Need negative ipsilateral retroperitoneal lymph node biopsy if > 2cm on CT
STAGE II: Microscopic residual disease Tumor markers remain elevated Tumor rupture or scrotal biopsy prior to complete orchiectomy
STAGE III: Retroperitoneal lymph node involvement (> 4 cm on CT) RPLN < 4 cm, but > 2 cm need biopsy
STAGE IV: Distant Metastasis
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Radiotherapy fields for stage I seminoma.
