Carcinoma in situ of the testis: review of biological and clinical features

Carcinoma in situ of the testis (CIS) is the uniform precursor of testicular germ-cell tumours. Morphologically, CIS consists of large, intratubular, gonocyte-like cells with large nuclei and abundant glycogen. CIS cells are probably derived from primordial germ cells and are supposed to be present in the testis of a future testis cancer patient at the time of birth. CIS cells appear to spread inside the seminiferous tubules until CIS progresses to invasive cancer. Diagnosis is best achieved by surgical biopsy of the testis and subsequent immunohistological staining of placental alkaline phosphatase (PlAP). This enzyme is present in embryonal germ cells, CIS and seminoma as well as several other types of germ-cell tumour but usually not in normal germ cells. CIS is found in testicular tissue adjacent to testicular germ-cell tumours in about 90% of cases, and it is observed in all clinical groups known to be at risk for testicular cancer: cryptorchidism (2% to 4%), infertility (0% to 1%), ambiguous genitalia (25%) and contralateral testis of patients with testicular cancer (5%). Conversely, CIS is found in less than 1% of the normal male population, and this prevalence corresponds well to the life-time risk of testicular cancer in males. If CIS is left untreated, there is a 50% probability of progressing to frank germ-cell neoplasm within 5 years. Localised low-dose radiotherapy to the testis eradicates CIS and germ cells, while Leydig cells are preserved. The patient can thus be spared orchiectomy and hormone supplementation. Currently, dose-reduction studies are looking for the optimal radiation dose, which is expected to be around 14 to 16 Gy. After chemotherapy, there is a cumulative risk of 42% for recurrence of CIS within 10 years. The concept of CIS offers the chance of very early detection of testicular cancer and organ-preserving early treatment.