Laboratory Studies
The tumor markers serum alpha fetoprotein (AFP) and/or the beta subunit of human chorionic gonadotropin (β-hCG) are elevated in extragonadal nonseminomatous germ cell tumors. These tumor markers provide diagnostic, staging, and prognostic information. Check these levels before and then at regular intervals after therapy.
Choriocarcinoma, embryonal carcinoma, and a minority of seminomas (< 10%) produce β-hCG. Neoplasms with which β-hCG elevation can be seen are prostate, bladder, ureteral, and renal cancers. The levels of β-hCG in the cerebrospinal fluid of patients with primary intracranial germ cell tumors (ICGCT) are elevated more frequently than in the plasma before treatment and become detectable prior to any increase of the serum values in case of relapse.
Serum AFP elevations are seen in yolk-sac tumors and embryonal carcinoma. Pure seminomas and pure choriocarcinomas do not produce AFP. Pregnancy, hepatocellular carcinoma, cirrhosis, and hepatitis also may be associated with increased levels of serum AFP.
The half-life of β-hCG is 24 hours, and that of AFP is 4-6 days.
AFP, β-hCG, or both are elevated in approximately 85% of extragonadal nonseminomatous germ cell tumors. Small increases in serum β-hCG can be seen in up to 50% of patients with disseminated seminoma.
Lactate dehydrogenase (LDH) is a nonspecific marker. Its level correlates well with the tumor burden and with the number of copies of the i(12p) isochromosome of the short arm of chromosome 12.
Placental alkaline phosphatase is used in some centers as a marker and is useful in the immunohistochemical characterization of midline tumors.
Cytogenetic analysis of patients with mediastinal germ cell tumors (MGCTs) reveals trisomy 8 in 16% of cases and Klinefelter syndrome (XXY) in 14-20% of cases. However, the most common karyotype abnormality is i(12p), present in 38% of patients. The presence of this abnormality helps identify midline germ cell tumors presenting as poorly differentiated carcinomas with atypical features.
Obtain baseline evaluation of pituitary function (ie, thyroid-stimulating hormone, cortisol, growth hormone, follicle-stimulating hormone, luteinizing hormone, prolactin) before treatment and then at regular intervals in patients with intracranial germ cell tumors.
Evaluation of blood counts, liver function, and kidney function before therapy and after recovery is necessary.
Imaging Studies
Testicular ultrasound
This should be ordered whenever a malignant germ cell tumor is diagnosed to rule out a gonadal primary site. [21]
Computed tomography of the chest, abdomen, and pelvis
On computed tomography (CT) scans, mature teratomas appear as heterogeneous cystic, well-defined, anterior mediastinal masses with walls of different thicknesses. Calcifications are present in approximately one quarter, with a bone or a tooth rarely identifiable. The combination of fluid, soft tissue, calcium, and/or fat attenuation in an anterior mediastinal mass is highly specific for mature teratoma.
Seminomas present as bulky, lobulated, homogeneous, anterior mediastinal masses. Although invasion of adjacent organs is uncommon, metastases to regional lymph nodes and bone can be seen. Calcifications are rare.
Nonseminomatous mediastinal germ cell tumors (NS-MGCTs) appear as irregular, anterior mediastinal masses, often with extensive, central heterogeneous areas of low attenuation caused by necrosis, hemorrhage, and/or cyst formation. Adjacent organ involvement and metastases to regional lymph nodes as well as to distant sites may occur.
Chest x-ray
Chest x-ray films show enlargement of the mediastinum on the anteroposterior view. The lateral view reveals the anterior location of the mass.
Brain Imaging
CT scan or magnetic resonance imaging (MRI) of the brain shows pineal seminoma as a discrete mass that usually reaches 3-4 cm in diameter. It compresses the superior colliculi and sometimes the superior surface of the cerebellum and narrows the sylvian aqueduct. Obstructive hydrocephalus may be evinced by the presence of dilated ventricles and interstitial edema.
Positron emission tomography (PET)
Early published studies that compared positron emission tomography (PET) with CT for the evaluation of patients with newly diagnosed disease or residual germ cell neoplasms after chemotherapy suggested that PET may be more sensitive than CT, although PET did not detect tumors smaller than 0.5 cm. [22, 23, 24] In patients with nonseminomatous germ cell tumors (NSGCT), PET has not been consistently able to identify residual viable malignant germ cell tumors (GCTs) and also does not detect teratoma. One study has shown that PET is useful in the detection of residual viable seminoma in patients with masses larger than 3 cm in diameter after chemotherapy. [25]
Other Tests
Biopsy of the tumor mass
Histologic confirmation of germ cell tumors (GCTs) may be obtained by open biopsy of an abdominal mass, anterior median sternotomy of a mediastinal mass, and neuroendoscopy of a pineal tumor. Fine-needle aspiration frequently establishes the diagnosis, obviating open biopsy. [26] Pathologic studies help determine the histologic subtype, the presence of non–germ cell elements, or the rare cases of marker-positive non–small cell lung cancer.
Tumor marker elevation in the appropriate clinical setting makes the diagnosis of germ cell tumors highly likely. [27] Chemotherapy can be initiated in these cases without tissue diagnosis if a need for immediate treatment is present.
Histologic Findings
Extra-gonadal germ cell tumor (EGGCTs) show the same histologic features as gonadal germ cell tumors (GCTs).
Staging
Clinical staging of mediastinal germ cell tumors (MGCT) is as follows:
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Stage I - Well-circumscribed tumor with or without focal adhesions to the pleura or pericardium but without microscopic evidence of invasion into adjacent organ
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Stage II - Tumor confined to the mediastinum with macroscopic and/or microscopic evidence of infiltration into adjacent structures
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Stage III - Tumor with metastases; stage IIIA is with metastases to intrathoracic organs, stage IIIB is with extrathoracic metastases
Pediatric Oncology Group/Children's Cancer Group Staging for Malignant Extragonadal Germ Cell Tumors is as follows:
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Stage I - Complete resection at any site; coccygectomy for sacrococcygeal site; negative tumor margins; tumor markers positive or negative
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Stage II - Microscopic residual; lymph nodes negative; tumor markers positive or negative
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Stage III - Gross residual or biopsy only; retroperitoneal nodes negative or positive; tumor markers positive or negative
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Stage IV - Distant metastases, including liver
