Alpha fetoprotein determinations in germ cell tumors of testis.

Alpha fetoprotein was demonstrated in 15 of 115 patients with histologically proved germinal testicular neoplasms. Alpha fetoprotein was detected in patients only with embryonal carcinoma and teratocarcinoma; determinations were negative in all cases of pure seminoma, teratoma, and choriocarcinoma. Of 15 patients having detectable alpha fetoprotein, 14 had Stage III disease and one had Stage II disease. When alpha fetoprotein is present, it usually heralds progression of the disease and therefore may serve as a valuable biologic marker to monitor response to therapy.     

Significance of DNA quantification in testicular germ cell tumors

A cytophotometric quantification of DNA in tumor cells was performed in histological sections of orchidectomy specimens from 36 men with testicular germ cell tumors (TGCT), 7 of them showing more than one tumor type. Among the variants of seminoma (classic and spermatocytic) the lowest DNA content were in spermatocytic seminoma. With respect to non-seminomatous tumors (yolk sac tumor, embryonal carcinoma, teratoma, and choriocarcinoma), choriocarcinomas showed the highest DNA content, and the lowest value was found in teratomas. No significant differences were found between the average DNA content of seminomas (all types) and non-seminomatous tumors (all types). Both embryonal carcinoma and yolk sac tumor showed similar DNA content when they were the sole tumor and when they were found associated with other tumors. In this study, except for the 4 cases of teratoma and the case of spermatocytic seminoma, all TGCT examined did not show modal values of DNA content in the diploid range. Such an elevated frequency of aneuploidism in these tumors may be helpful for their diagnosis.     

Cryptorchidism and testicular cancer

An analysis of 125 patients with a history or clinical evidence of cryptorchidism and testicular germinal tumor treated at our hospital from 1934 to 1975 is presented. Cryptorchidism was corrected ipsilaterally or contralaterally in 83 patients with intrascrotal testis cancer when they were from 4 to 42 years old, either spontaneously (21 patients), by orchiopexy (51 patients) or by hormonal therapy (11 patients). Forty-two cryptorchid patients (uncorrected cases) presented with either ipsilateral inguinal (24 patients), abdominal (14 patients) or contralateral intrascrotal tumors (4 patients). Tumor histologic types on orchiectomy were pure seminoma in 54 patients, embryonal carcinoma in 35, teratocarcinoma in 33 and pure choriocarcinoma in 3. The 5-year survival rates were 60 per cent for the corrected cases and 63 per cent for the uncorrected cases according to cryptorchid state, and they were 78 per cent in patients with pure seminoma and 48 per cent in patients with other germinomas according to histologic type. The majority (58 of 73) of 5-year survivors received regional lymphatic irradiation, in 39 patients with pure seminoma, and/or systemic chemotherapy, in 19 patients with germinal carcinomas, with or without regional lymphadenectomy.     

Chemotherapy of disseminated germ cell testicular tumors with cis-diamminedichloroplatinum and other drugs

The effect of single CDDP therapy and PVB therapy was examined in 7 cases of stage III germ cell testicular tumors with measurable metastases. The mean age of the patients was 30.6 years old, and their histological types of primary sites were seminoma in 3 cases, embryonal carcinoma in 2, immature teratoma in 1 case and embryonal carcinoma + teratoma in 1 case. In 1 case of seminoma, 375 mg of CDDP was administered. In 1 case of embryonal carcinoma + teratoma, 100 mg of CDDP and then 2 courses of PVB therapy were performed, and 3 courses of PVB therapy were given in all other cases. Three cases showed complete response, 2 cases partial response and 2 cases no change. Pulmonary metastatic nodules were extirpated after the PVB therapy in 1 of the cases showing no change, and the histological examination of these nodules was found to be mature teratoma. As a result, the effectiveness of the chemotherapy alone was 71.4%, and that of chemotherapy + surgical operation was 85.7%. Significance of intensive chemotherapy and necessity of extirpation of residual metastatic nodules after intensive chemotherapy in the management of advanced germ cell testicular tumors are stressed.     

Thoracotomy in re-staging germinal testis tumors

In 3 patients undergoing therapy for germinal testis tumors (teratoma with choriocarcinoma, seminoma and teratocarcinoma) solitary pulmonary lesions developed consistent with metastatic tumor. After non-diagnostic medical pulmonary evaluation thoracotomy established benign lesions in each (sarcoidosis, Cryptococcus and postoperative inflammatory cyst). Surgical pathologic restaging to obviate the institution of unnecessary chemotherapy and/or radiation with its attended morbidity in such instances is stressed.     

Cryptorchidism and non-seminomatous testis cancer

An analysis of 107 cases of cryptorchidism and non-seminomatous germ cell cancer treated between 1960 and 1976 is presented. The incidence of cryptorchidism in patients with testicular cancer is 9.8%.
Eighty patients presented with ipsilateral inguinal tumours, 12 with contralateral intrascrotal tumours and 15 with abdominal tumours. There were 52 embryonal, 36 teratocarcinoma, 9 teratoma, and 10 choriocarcinoma tumours. The 5 year survival for all patients was 52.3%. The age distribution, pathology and stage of the patients was similar to non-seminomatous tumours not associated with cryptorchidism.     

Histology in mixed germ cell tumors. Is there a favorite pairing?

PURPOSE: Mixed germ cell tumors account for approximately 30% to 50% of testicular tumors. To our knowledge a systematic review with statistical analysis of the associations of histological subtypes in mixed germ cell tumors has not been done previously. It was our impression that such associations exist. Delineating concordant histological types may provide insight into the ontogeny of testicular tumors and also have important clinical implications. MATERIALS AND METHODS: We retrospectively reviewed the testis cancer data base at our institution. The primary tumor of orchiectomy specimens was examined in 2589 patients. Of these patients mixed histology was noted in 1765 (68.2%). ORs were calculated for all possible combinations of teratoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma and seminoma. In addition, we evaluated the association of various histological types with teratoma at post-chemotherapy retroperitoneal lymph node dissection. RESULTS: Of 10 possible combinations of histological types in the primary tumor, positive correlations were noted in 4. The strongest correlation was found between teratoma and yolk sac tumor (OR 2.58, p <0.001). Teratoma or yolk sac tumor in the testis was associated with teratoma in the pathology specimen at post-chemotherapy retroperitoneal lymph node dissection. CONCLUSIONS: The strongest associations of histological subtypes in mixed germ cell tumors were seen between yolk sac tumor and teratoma. Similar associations are seen in late relapse and in some cases of prepubertal tumors. Further study of these associations may prove valuable in understanding the biology and clinical behavior of germ cell tumors.     

Treatment of nonseminomatous testicular tumor with liver metastases

Therapeutic course of 2 cases of nonseminomatous testicular tumor with liver metastasis is reported. One case had mixed tumors including embryonal carcinoma, choriocarcinoma and yolk sac carcinoma, and was positive pulmonary metastasis already at the initial examination. In the other case having mixed tumors of embryonal carcinoma and choriocarcinoma, metastasis to the supraclavicular lymph node was detected at the initial examination. In both cases liver metastasis occurred after complete response could be obtained by treatment chiefly consisting of PVB therapy. For liver metastasis four-drug combination treatment using cisplatin, vinblastine, adriamycin and actinomycin D was performed with partial response. However, this patient eventually died. The other case received VAB-6 therapy with complete response for liver metastasis. It is advisable to consider other modalities therapy in addition to conventional chemotherapy in cases of testicular tumor with liver metastasis since the prognosis is poor in these cases.     

Spontaneous maturation in the metastatic region of a bilateral testicular germ cell tumor

A case of bilateral testicular germ cell tumor of different cell types was found to have a mature teratoma in the metastatic region. Histology of the right testis revealed seminoma and embryonal carcinoma while the left testis revealed seminoma and mature teratoma. A mature teratoma, containing cartilage components, was also found in the right para-aortic lymph node. The findings of the case are described and the literature on cases with maturation in the metastatic region are reviewed.     

A case of bilateral testicular germ cell tumors of different cell types with maturation in the metastatic region

A case of bilateral testicular germ cell tumors of different cell types and maturation in the metastatic region is described. A 42-year-old man with bilateral testicular swelling visited our clinic. Bilateral high orchiectomy was performed. Subsequent histological examination revealed seminoma and embryonal carcinoma in the right testis and seminoma and mature teratoma in the left. Then bilateral retroperitoneal lymphadenectomy was performed and 7 metastatic regions were found in the para-aortic lymph nodes. One of these revealed histopathologically a mature teratoma containing cartilage constituents. After the operation, multiple drug treatment with Cis-DDP, vinblastine and pepleomycin was started. The patient has been in complete remission for about 1.5 year. In addition, we reviewed the literature about bilateral testicular germ cell tumors and maturation in the metastatic region.     

Association of intratubular seminoma and intratubular embryonal carcinoma with invasive testicular germ cell tumors

The classification of intratubular germ cell neoplasia of the testis includes an unclassified type (IGCNU), in addition to various other intratubular lesions that show specific forms of differentiation, such as intratubular seminoma and intratubular embryonal carcinoma. Although IGCNU is recognized as a precursor lesion for testicular germ cell tumors, the relationship between differentiated types of intratubular germ cell neoplasia and invasive germ cell tumors of the testis is not well established. The aim of the present study was to examine the association between invasive testicular germ cell tumors and intratubular neoplastic lesions, with particular emphasis on differentiated types of intratubular germ cell neoplasia. The seminiferous tubules adjacent to 42 testicular germ cell tumors were evaluated for the presence of various forms of intratubular germ cell neoplasia. IGCNU was observed in 37 (88%) of 42 cases, whereas intratubular seminoma and intratubular embryonal carcinoma were seen in 19% and 7% of the cases, respectively. Intratubular seminoma was associated primarily with seminomas or mixed germ cell tumors with a seminomatous component, but was also present in a case of a nonseminomatous germ cell tumor. Intratubular embryonal carcinoma was associated exclusively with nonseminomatous germ cell tumors. All cases of intratubular embryonal carcinoma were identified morphologically and exhibited histologic features corresponding to traditional definitions of this lesion. No examples of intratubular embryonal carcinoma as defined by CD30 expression alone in the absence of an intratubular proliferation were observed. The presence of intratubular seminoma in a nonseminomatous germ cell tumor suggests that it is a true preinvasive lesion rather than a manifestation of intratubular spread of an established invasive seminoma. The low incidence of intratubular embryonal carcinoma supports the theory that most nonseminomatous germ cell tumors evolve initially as seminomas, rather than directly from a differentiated intratubular neoplastic lesion.     

Testicular tumours in maldescended testes

Maldescent is known to increase the risk of cancer of the testis. However, the effect of orchiopexy on reducing tumour risk and altering tumour type or stage at diagnosis is not established. The authors review the records of patients with testicular tumours seen for seminoma (1958 to 1975) and nonseminoma (1958 to 1970). Of 646 patients, 53 (8.2%) had a history of testicular maldescent; in 42 (79%) the maldescent was unilateral and in 6 of these, the tumour developed in the normally descended testis. Twenty patients had successful orchiopexy at a median age of 14 years (range from 6 to 35 years). Tumours found in the 53 patients were seminoma (38 patients), teratoma (7 patients), embryonal carcinoma (6 patients), teratocarcinoma (1 patient) and choriocarcinoma (1 patient). Average age at the time of diagnosis of seminoma was 38 years and of nonseminoma 31 years. Average age was lower at the time of diagnosis of the tumour for those who had successful orchiopexy than for those who did not. Earlier stage nonseminomas were found in patients who had an orchiopexy. Twenty-five (66%) of the 38 seminomas occurred in testes located outside the scrotum, whereas only 6 (40%) of 15 nonseminomas occurred in a nonscotal position, suggesting that persistent maldescent favours seminoma over nonseminoma. In this retrospective review, no statement can be made about the effect of orchiopexy on tumour risk. However, this procedure appears to lead to an earlier diagnosis and may influence the type of tumour that subsequently develops.     

Expression of myc family oncogenes in primary human testicular cancer

In order to understand the role of myc family genes (c-myc, N-myc and L-myc) in the development and progression of human testicular cancer, we have analyzed the expression of myc family genes in three different types of primary human testicular cancer (seminoma, embryonal carcinoma and teratocarcinoma) and normal testis using Northern blot analysis. Expression of N-myc gene, which is usually limited in the neoplasms derived from neuroectoderm, was detected in seven out of ten cases of seminomas and two out of two cases of embryonal carcinomas. Gene amplification was not observed in these cases. Expression of N-myc gene was not detected in teratocarcinomas and normal testes. Expression of c-myc gene was observed in seminomas, embryonal carcinomas, teratocarcinomas and normal testes, but specific expression of c-myc gene was not seen in these cancers and normal testes. Expression of L-myc gene was not detected in all cases examined in our studies. Since N-myc gene expression was observed only in undifferentiated testicular neoplasm, such as seminoma and embryonal carcinoma, its expression may be positively related to the development and progression of special types of human testicular cancer.     

Malignant testicular tumors in three brothers

Three brothers out of four had malignant testicular tumors. The first of them had choriocarcinoma, the second seminoma, and the third teratocarcinoma of the testis.     

Localization of alpha-fetoprotein and human chorionic gonadotropin to specific histologic types of nonseminomatous testicular cancer

We used an indirect immunoperoxidase technique to localize alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) to specific histologic types of testicular germ cell cancers. Among 20 nonseminomatous tumors studied, yolk sac tumor reacted for AFP in 13 of 15 cases, teratoma in 3 of 11 cases, and embryonal carcinoma in 3 of 14 cases. Syncytiotrophoblasts alone reacted for HCG in 14 of 15 cases, and syncytiotrophoblasts associated with choriocarcinoma reacted for HCG in 2 of 2 cases. There was a close correlation between the tissue demonstration of AFP and HCG and elevated serum levels of AFP and HCG, respectively. We conclude that in nonseminomatous testicular cancer yolk sac tumor is the primary site of synthesis of AFP, and syncytiotrophoblasts are the only site of synthesis of HCG.     

A case report: simultaneous bilateral testicular tumors with different cell types--complete response after combination chemotherapy of cisplatin and irrinotecan hydrochloride--

A 38-year-old man was admitted to our hospital complaining of bilateral scrotal swelling. On examination, the patient was found to have bilateral testicular tumors with jugular chain lymph node and para-aortic lymph node metastasis. He underwent bilateral inguinal orchiectomy. Histopathological examination of the excised tumors revealed seminoma, embryonal carcinoma, yolk sac tumor and immature teratoma in the right testis and seminoma in the left testis. The patient was treated postoperatively with two courses of BEP (bleomycin, etoposide, cisplatin) therapy and two courses of EP (etoposide, cisplatinum) therapy. The patient had lung metastasis during the follow-up period and we treated him with salvage combination chemotherapy of cisplatin and irinotecan hydrochloride (CPT-11). After the third course of cisplatin and CPT-11 chemotherapy the lung metastasis disappeared and we performed retroperitoneal lymph node dissection. The patient has remained free of disease 11 months after discharge.     

A clinical study of 115 patients with testicular tumor]

One hundred and fifteen cases of testicular tumors treated at our Hospital between 1970 and 1989 were analyzed. The incidence of testicular tumors was 0.44% in the male outpatient department of our urological clinic. The age of these patients ranged from 6 months to 86 years (average: 31.7 years old) with two peaks in distribution; 0 to 5 and 21 to 45 years. Most of their chief complaints (77%) were painless swelling of scrotal contents. Location of the tumors included 56 in the right, 57 in the left and 2 on both sides. Histologically, there were 68 cases of seminoma, 10 cases each of embryonal carcinoma and teratoma, 22 cases of mixed type, 3 cases of malignant lymphoma and 2 cases of others. Stage of tumor was stage I in 69 cases, IIA in 25 cases, IIB in 8 cases and III in 13 cases. High orchiectomy was performed on all the patients. Radiotherapy, chemotherapy and retroperitoneal lymph node dissection were respectively done in 77, 42 and 16 cases. Seventeen patients died, and the 5-year survival rate calculated by the Kaplan-Meier method was 87.9% in seminoma and 68.9% in non-seminoma. The survival rate for the patients treated by chemotherapy including CDDP after 1983 was compared to those treated by other therapy before 1982. Between the two groups there was no significant difference.