The principal objective of the staging evaluation is to ascertain whether the patient has early-stage disease (which is amenable to local therapy) or disseminated disease (which requires chemotherapy).
A chest radiograph can determine whether or not a patient has gross supradiaphragmatic metastases, which would mandate initial chemotherapy.
In patients with a normal chest radiograph, chest CT is recommended in both patients with seminoma and those with NSGCT when abdominal adenopathy is found to rule out occult metastases within the lungs or mediastinum. If such metastases are present, the patient should be treated with primary chemotherapy.
This test provides important information about the retroperitoneal lymph nodes. Usually, periaortic adenopathy is noted on the ipsilateral side of the primary tumor. Patients with primary retroperitoneal germ cell tumors often show an enlarged retroperitoneal mass in the midline. Although hepatic metastases are infrequent, CT is the most viable method of determining the presence of these metastatic lesions.
Positron Emission Tomography
The use of 18F-fluorodeoxyglucose (FDG) is emerging as a significant adjunct in staging and follow-up. Seminomas are FDG-avid. In some cases, nodal and extranodal metastases not appreciated on CT scans may be noted with FDG-positron emission tomography (PET). The optimal use of FDG-PET is in patients with residual masses following systemic therapy for pure seminoma. In such cases, the scans should be performed at least 3 to 4 weeks after the last course of chemotherapy. Because teratoma is not PET-avid, its usefulness in NSGCTs is limited to patients with late recurrences manifested with marker-only disease.
In the absence of symptoms or signs, a CT scan (or magnetic resonance imaging) of the head and radionuclide bone scan are unnecessary. A lymphangiogram is rarely used today to identify microscopic nodal involvement in patients with stage I disease who choose to undergo surveillance. PET scans may be useful in patients with residual disease following chemotherapy for seminoma. If a PET scan is positive in such patients, surgical resection of the residual mass is indicated. Otherwise, the residual mass can be simply followed with periodic radiographic evaluation.
Germ cell tumors are classified into two broad histologic categories: seminoma and NSGCT. Patients with seminoma who have increased AFP levels or any focus of NSGCT components (including teratoma) are considered to have NSGCT.
Seminoma is the most common single histology, accounting for approximately 30% of all germ cell tumors. Up to 10% of seminomas have focal syncytiotrophoblastic cells, which are believed to be the source of β-hCG in some cases. Elevated AFP levels connote NSGCT. Seminomas typically stain positively for placental-like alkaline phosphatase (PLAP), c-KIT, OCT 3, and OCT 4 by immunohistochemistry.
This is a rare subset of germ cell tumors. These tumors often grow to a large size, occur almost exclusively in men older than 50, and rarely, if ever, metastasize. Unlike classic seminoma, immunohistochemical staining is currently negative for PLAP. Other evidence suggests a different cell of origin for spermatocytic seminoma than for other germ cell tumors. Cure rates approach 100% with orchiectomy alone.
This lesion is composed of large pleomorphic cells with different architectural patterns. This tumor may be associated with an elevation in the serum levels of β-hCG and/or AFP. Embryonal cancers typically stain positively for PLAP, CD30, OCT 3, and OCT 4 by immunohistochemistry.
Endodermal sinus tumor (yolk sac carcinoma)
This is the most common testicular tumor seen in infants and young children. Like embryonal carcinoma, the yolk sac tumor has a variety of architectural patterns. This tumor is associated with an elevated serum level of AFP. Yolk sac tumors stain positively for AFP and glypican-3 by immunohistochemistry.
As a pure entity, choriocarcinoma is one of the least common germ cell tumors. These tumors have a great propensity for hematogenous spread, often skipping the retroperitoneum. Choriocarcinoma is associated with an increased serum level of β-hCG. Choriocarcinomas stain positively for hCG and glycipan-3 by immunohistochemistry.
The teratoma is a generally benign tumor with elements from each of the germ layers (ectoderm, mesoderm, and endoderm). Teratoma is uncommonly seen as the sole histology in primary tumors, but it is frequently associated with other histologic elements, including those previously mentioned. Of patients with residual disease following chemotherapy for NSGCT, about 20% to 80% will have evidence of teratoma in resected specimens, depending on whether or not there was evidence of teratoma in the orchiectomy.
A subset of immature teratoma can transform into more malignant tumors, such as primitive neuroectodermal tumor, adenocarcinoma, and sarcoma. These tumors carry a poor prognisis and are generally not curable by chemotherapy, although surgery offers a chance for cure in some patients, if disease remains localized. In addition, late recurrences of both teratoma and carcinoma have been reported in patients with teratoma. Serum markers are normal in patients with pure teratoma.
Testicular cancer spreads in a fairly predictable fashion: from the testicle to the retroperitoneal lymph nodes and, later, hematogenously to the lungs or other visceral sites. Only 10% of patients present with hematogenous metastases (usually in the lungs) in the absence of discernible retroperitoneal adenopathy.
Clinical staging systems (Royal Marsden and TNM systems) for testicular cancer are outlined in Table 2. These staging systems help define the population for appropriate primary therapy.
Good-, Intermediate-, and Poor-Risk Subgroups
For patients with NSGCTs who are candidates for chemotherapy, other staging systems (such as those by Indiana University and the Memorial Sloan-Kettering Cancer Center [MSKCC]) were developed to segregate patients into good- and poor-risk categories. More recently, the International Germ-Cell Cancer Collaborative Group (IGCCCG) formulated a classification that more clearly defines good-, intermediate-, and poor-risk disease (Table 3) and is currently being used to stratify patients for appropriate chemotherapy and in ongoing trials.