On clinical suspicion of testicular germ cell tumour (e.g. based on testicular palpation and ultrasound), recommended diagnostic procedures include chest X-ray, abdominal ultrasound, and measurement of serum AFP, hCG, PLAP and LDH concentrations. Pre-operative tumour marker determinations can help to confirm diagnosis, both of gonadal and extragonadal (e.g. mediastinal, retroperitoneal, central nervous system) germ cell tumours. [Tumour marker measurements, together with testicular ultrasound, can also help in the differential diagnosis of epididymitis in patients with painless swelling of one testis.]
In clinical Stage I disease following primary surgery, a second marker determination performed 5-6 days post-operatively allows determination of marker half-life. Stage I classification can thus be confirmed retrospectively, if marker concentrations decline according to half-life. For patients undergoing chemotherapy, marker determinations are mandatory prior to each cycle. In addition, following resection, thorough histological analysis of resected tumour specimens according to WHO criteria is obligatory (1).
Elevations of AFP (>10 kU/L) or hCG (>5 U/L) may be encountered in 80% of metastatic and 57% of Stage I NSGCT. Serum PLAP is raised in up to 80% of testicular seminomas (Stage I and metastatic) and hCG in fewer than 20% of these. Elevated serum AFP levels indicate the presence of yolk sac elements, i.e. mixed germ cell tumours (especially embryonal carcinoma and yolk sac tumours), and occur in all stages of disease [sensitivity 50-80% in metastatic disease, 70-72% in undifferentiated malignant teratoma, 60-64% in intermediate malignant teratoma, and 64% of patients with yolk sac or combination tumours]. AFP concentrations >1000 (850 kU/L) m g/L are found in 53% of undifferentiated malignant teratomas, 16% of intermediate malignant teratomas, and 26% of combination tumours (5).
Increased serum HCG concentrations occur in both seminoma and NSGCT, with a diagnostic sensitivity of 40-60% in patients with metastatic NSGCT and 15-20% in those with metastatic seminoma. hCG elevations are predominantly found in patients with tumours containing choriocarcinomatous components, syncytiotrophoblastic giant cells and (more rarely) special round cells also found in pure seminomas.
Trophoblastically differentiated teratomas usually produce hCG, while differentiated teratomas and yolk sac tumours rarely do. In choriocarcinoma, tumour mass correlates reasonably well with the degree of elevation of serum hCG values, which may be as high as several million U/L in advanced disease. A serum hCG concentration of 10 U/L corresponds to approximately 106 tumour cells (4).
Serum hCG is elevated in 55-60% of cases of undifferentiated and intermediate teratomas, 90% of concentrations ranging from 5 to 1000 U/L. The frequency, but not the extent of elevation of serum hCG, is stage-dependent in NSGCT (Stage I, ~45%; Stage II ~55%; Stage III ~85%) (6). Approximately 18% of seminomas have elevated serum hCG (10-2000 U/L) and/or hCGb concentrations. Highly elevated hCG values (>5000 U/L) are suggestive of "mixed" germ cell tumours [see above], and will influence choice of therapy.