Jørgen G. Berthelsen

Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients.

Carcinoma in situ in the contralateral testis was diagnosed in 27 of 500 patients (5.4%) with unilateral testicular germ cell cancer. Eight of the 27 patients received intensive chemotherapy for spread of their initial testicular cancer. Follow up biopsy studies did not detect changes of carcinoma in situ in any of these patients, and none developed a contralateral testicular tumour (observation time 12-88 months). Of the remaining 19 patients with carcinoma in situ, seven developed contralateral testicular cancer. The estimated risk of developing invasive growth was 40% within three years and 50% within five years. None of the 473 patients without carcinoma in situ detected by screening biopsy developed contralateral testicular cancer (observation time 12-96 months). No serious complications arose from the biopsy procedures. All patients with unilateral testicular germ cell cancer should be offered biopsy of the contralateral testis.

Screening for carcinoma in situ of the contralateral testis in patients with germinal testicular cancer.

Two hundred and fifty biopsy specimens from the contralateral testis in patients with unilateral germinal testicular cancer were analysed by light microscopy for carcinoma-in-situ changes. Changes were found in 13 (5.2%) patients. One-third of patients with an atrophic contralateral testis (volume less than or equal to 12 ml) and one-fifth of patients with a history of cryptorchidism had changes in the remaining testis. In the present series 85% of cases with carcinoma-in-situ changes would have been diagnosed if the one-fifth of the patients having an atrophic testis or a history of cryptorchidism or both had been screened. Since the natural course of carcinoma in situ in the contralateral testis of patients with germinal testicular cancer has not been established, the patients are being re-evaluated frequently. To date two patients with carcinoma in situ have developed a second cancer.

Long-term fertility and Leydig cell function in patients treated for germ cell cancer with cisplatin, vinblastine, and bleomycin versus surveillance.

Fertility and Leydig cell function were investigated in 31 patients previously treated for nonseminomatous testicular cancer. Twenty-two patients with metastatic cancer had received cisplatin-based chemotherapy, and the median follow-up was 64 months (range, 42 to 100 months). Nine patients without metastases were treated with orchiectomy alone, and follow-up in this group was a median of 61 months (range, 40 to 77 months). None of the patients have relapsed and retroperitoneal lymph node dissection was not performed in any patient. Both the concentration of spermatozoa and the volume of the remaining testis are significantly reduced in patients who had previously received chemotherapy when compared with patients treated with orchiectomy alone (P less than .05). There were no significant differences between groups when comparing morphology, motility, and penetration of the spermatozoa. Subclinical Leydig cell dysfunction with normal testosterone and elevated luteinizing hormone (LH) was observed in one patient (11%) treated with orchiectomy alone, while 59% of the patients who had received chemotherapy had elevated LH (P less than .05). We conclude that cisplatin-based chemotherapy leads to a persistent impairment of fertility and Leydig cell function in the majority of patients with testicular cancer.

Value of Testicular Biopsy in Diagnosing Carcinoma in Situ Testis

Quantitative histological studies on four testicles removed because of carcinoma in situ (CIS) were performed in order to determine the likelihood of diagnosing carcinoma in situ testis by biopsy. The CIS changes were evenly distributed in the testicles except for the parts adjacent to the epididymis, where the lesion was less frequent. In parts of the testicles where more than approximately 10% of the testicular volume contained tubules with CIS all simulated biopsies measuring 3 mm contained the lesion. The same was true for simulated biopsies measuring 1.5 mm when more than approximately 30% of testicular volume consisted of tubules with CIS. If the distribution of carcinoma in situ generally is similar to that found in the four analysed testicles there seems to be a high probability of detecting the disease by one or two testicular biopsies of 3 mm.

Impaired Testicular Function in Patients With Carcinoma-In-Situ of the Testis

PURPOSE To elucidate the biologic association between germ cell neoplasia and testicular dysfunction, through investigation of Leydig cell function and semen quality in men with carcinoma-in-situ (CIS) of the testis. PATIENTS AND METHODS We examined two groups of men, unilaterally orchidectomized for testicular cancer. Biopsy of the contralateral testis had showed CIS in a group of 24 patients and no evidence of CIS in the other group of 30 patients. Semen quality and serum levels of testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were compared in these two groups of men after orchidectomy but before further treatment for testicular cancer. RESULTS Significantly higher LH levels (median, 8.1 IU/L v 4.8 IU/L; P < .001) and generally lower testosterone levels (median, 12.5 nmol/L v 15.5 nmol/L; P = .13) were found in the CIS group. The proportion of patients with Leydig cell dysfunction was higher in the group of patients with CIS (11 of 24) than in the group of patients without (two of 30) (P = .01). Sperm concentration and total sperm count were significantly lower (P < .001) in patients with CIS (median, 0.03 x 10(6)/mL and 0.10 x 10(6), respectively) than in patients without (median, 9.1 x 10(6)/mL and 32 x 10(6), respectively), whereas the levels of FSH were significantly higher (P < .001) in the former group of men (median, 19.6 IU/L v 9.0 IU/L). CONCLUSION Not only spermatogenesis but also Leydig cell function is impaired in testes with CIS. This impairment could be due to common factors in the pathogenesis of germ cell neoplasm and testicular dysfunction. Alternatively, CIS cells may have a negative impact on Leydig cell function.

Sperm counts and serum follicle-stimulating hormone levels before and after radiotherapy and chemotherapy in men with testicular germ cell cancer

Sperm counts were low (median, 15 X 10(6) per ejaculate) and serum follicle-stimulating hormone (FSH) levels were moderately elevated (median, 31 IU/l) after unilateral orchiectomy and immediately before radiotherapy and chemotherapy in 34 patients with seminomas and 20 patients with nonseminomatous germ cell tumors. The scattered radiation (0.2 to 1.3 Gray [Gy]) reaching the remaining testicle during radiotherapy caused azoospermia in more than two thirds of the patients. A median of 540 days elapsed after the end of treatment before spermatozoa were again found in semen samples, while a median of 1250 days passed before the pretreatment sperm count was reached. One to 5 years after treatment, sperm counts were still low (median, 6 X 10(6) per ejaculate) and serum FSH was elevated (median, 61 IU/l). The adjuvant chemotherapy given to the 20 patients with nonseminomatous tumors did not appear to affect restitution appreciably.

Clinical aspects of testicular carcinoma‐in‐situ

Carcinoma-in-situ germ cells were demonstrated in testicular biopsies from 9 of 826 patients (1.1%) from a selected group of Danish infertile men. A similar observation was noted in testicular biopsies from 9 Swiss patients (representing 0.55% of the total number of infertile patients biopsied in that study). Such changes were also seen in 8 testicular biopsies from the contralateral testis of 180 patients (4.4%) with carcinoma of the teitis. Moreover, carcinoma-in-situ has beer, found in maldecended testes and in gonads of patients with the testicular feminization syndrome although the incidence of carcinoma-in-situ in these two latter groups is unknown. The malignant potential of carcinoma-in-situ of the testis in infertile men has been clearly demonstrated, whereas its clinical significance in other groups of patients remains to be determined.

Incidence of carcinoma in situ of germ cells in contralateral testis of men with testicular tumours.

Biopsy specimens from the contralateral testicle in 50 consecutive patients with germinal testicular cancer were examined for carcinoma in situ. Three out of 21 men with seminomas and one out of 29 with other types of germinal cancer (8%) had carcinoma in situ in the contralateral testicle without any clinical signs. One of these men developed early invasive germ-cell cancer 46 months after carcinoma in situ was first diagnosed. The others have been followed up for less than a year without signs of tumour growth. If these results are confirmed routine biopsy of the contralateral testicle in patients with germinal cancer may be indicated.

Carcinoma-in-situ of the testis and invasive growth of different types of germ cell tumours. A revised germ cell theory

The hypothesis is proposed that seminomas and non-seminomas are histogenetically closely related and both types of germ cell tumours may originate from a common precursor cell: namely the germ cell showing the carcinoma-in-situ pattern. However, it is suggested that the spermatocytic seminoma is an exception as it may originate from spermatocytes.

Distribution of carcinoma‐in‐situ in testes from infertile men

Quantitative histologial studies on 4 testes removed because of carcinoma-in-situ (CIS) were performed in order to determine the distribution of CIS within the testis and to estimate the likelihood of diagnosing testicular CIS by biopsy. The CIS changes were distributed in all parts of the testes but were less frequent in the parts adjacent to the epididymis. In the 4 testes examined 1.4 to 599 of the entire testicular volume contained seminiferous tubules with CIS. In parts of the testes where more than approximately 10% of the testicular volume consisted of tubules with CIS all simulated biopsies measuring 3 mm contained the lesion. The same was true for simulated biopsies measuring 1.5 mm when more then approximately 30% of the testicular volume consisted of tubules with CIS. If the distribution of CIS generally is similar to that found in the 4 analysed testes there seems to be a high probability of detecting the disease by one or two testicular biopsies.