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.     

PVB therapy for advanced testicular cancer

Twelve cases of advanced testicular cancer, including 5 cases of seminoma, 3 cases of teratocarcinoma, 1 case of yolk sac tumor, 1 case of embryonal carcinoma and 2 cases of mixed cell type, were treated with cisplatin-vinblastine-bleomycin (PVB) therapy. Among them, 10 cases had measurable metastatic lesions and the objective response rate was 80%. Three cases showed complete response. Ten cases showed nonexistent disease after PVB therapy and salvage operation. Though PVB therapy was useful for the treatment of advanced testicular cancer, a few cases having poor prognostic factors showed no response to the therapy.     

Testicular seminoma occurring 8 years after treatment of a metastatic extragonadal germ cell tumor

A 30-year-old man was admitted with a chief complaint of left-sided scrotal enlargement, and was diagnosed as having testicular seminoma after orchiectomy. Eight years earlier, he had been treated with chemotherapy for an extragonadal germ cell tumor, without orchiectomy, leading to complete remission. His histological diagnosis at that time was a germ cell tumor, composed of choriocarcinoma and embryonal carcinoma. He was followed up without testicular biopsy. Routine pretreatment testicular biopsy in patients with extragonadal germ cell tumor is controversial, but regular long-term follow up and information on the risk of developing a metachronous testicular tumor are needed after treatment of extragonadal germ cell tumors, even when there seems to be a partial or complete clinical response.     

Development and characterization of a monoclonal antibody to human embryonal carcinoma

A monoclonal anti-testicular carcinoma antibody was obtained via the somatic cell fusion technique by immunization of BALB/c mice with freshly prepared single cell suspension from a patient with testicular embryonal carcinoma with choriocarcinoma components. The hybridoma supernates were screened against the testicular carcinoma cells used in the immunization as well as normal mononuclear white blood cells isolated from the same patient. An antibody (5F9) was selected which bound to fresh tumor cells from two patients with embryonal testicular carcinoma and failed to bind to fresh tumor cells from 24 patients (2 seminoma, 2 melanoma, 3 neck, 2 esophageal, 1 ovarian, 3 colon, 1 prostate, 2 breast, 1 liposarcoma, 3 endometrial, 1 kidney, 1 adrenal, 1 larynx and 1 bladder tumors) or cell suspensions prepared from normal liver, lung, spleen, ovary, testes, kidney, red blood cells or white blood cells. The antibody was tested for its binding to several well established cancer cell lines, and was found to bind to the BeWo human choriocarcinoma and two human embryonal carcinoma cell lines. The antibody did not react with 22 other cell lines or with hCG. The antibody was labeled with 131I and injected into nude mice bearing BeWo tumors and evaluated for tumor localization by performing whole body scans with a gamma camera 5 days later. Six mice injected with the antibody showed positive tumor localization without the need for background subtraction while six mice injected with MOPC-21, a murine myeloma immunoglobulin, demonstrated much less tumor localization. Tissue distribution studies performed after scanning showed specific tumor localization (8:1 tumor: muscle) for the monoclonal antibody and no specific localization for MOPC-21. This antibody thus has selective reactivity with the surface of tumor cells from embryonal carcinoma (testicle) and choriocarcinoma both in vitro and in vivo.     

Primary mediastinal nonseminomatous germ cell tumors. Results of a multimodality approach

Before cisplatin-based chemotherapy, long-term survival after resection of primary mediastinal nonseminomatous germ cell tumors was unusual. We reviewed the case histories of 48 patients who underwent multimodality treatment for mediastinal nonseminomatous germ cell tumor between 1976 and 1988. Twenty-eight patients received initial therapy at Indiana University and 20 were referred after having had unsuccessful initial therapy elsewhere. In 44 patients (92%) the levels of either one or both serum tumor markers were elevated at the time of diagnosis. Five patients had choriocarcinoma, three embryonal carcinoma, 12 yolk sac carcinoma, four teratocarcinoma, 22 mixed cell type, and two had an unclassified type. Twenty-two of the 28 patients in our initial therapy group had a complete response to treatment, as defined by normal serum tumor markers and absence of residual tumor. In this group, 16 patients had resection of residual disease after chemotherapy, four had total or near total resection before chemotherapy, and only two had chemotherapy alone. Seventeen patients are surviving after this treatment with a median survival of 64 months and a 57% 5-year Kaplan-Meier survival rate. Only two of the 20 patients who were referred for salvage chemotherapy had a complete response. Both required resection of residual disease after salvage chemotherapy. Only one patient survived after this treatment. There was no significant treatment morbidity or mortality. A multimodality approach to primary mediastinal nonseminomatous germ cell tumor with intensive cisplatin-based chemotherapy, emphasis on normalizing serum tumor markers, and aggressive resection of residual disease now offers survival to a significant number of patients.     

The synchronous appearance of multiple testicular epidermoid cysts and of a malignant mixed germinal tumor in the contralateral testis]

We describe the simultaneous appearance of multiple epidermoid cysts in the right and an adult teratoma containing embryonal carcinoma and choriocarcinoma in the left testis. No similar case has previously been described. Epidermoid cysts of the testis are rare, accounting for about 1% of all testicular tumors. Epidermoid cysts are now regarded as monoepidermally developed teratomas of germ cell origin. Testicular teratomas in adults, however, are always malignant. Because epidermoid cysts are rare tumors, primary therapy often consists in ablation of the testis. In the case described, excision of the epidermoid cyst protected the patient from complete castration. This case demonstrates the simultaneous appearance of a malignant and a benign testicular germ cell tumor.     

Intracranial germ-cell tumors. Immunohistochemical study of three autopsy cases

Histological and immunohistochemical findings in three cases with primary intracranial germ-cell tumors are reported. Based on histological examination, they were diagnosed, respectively, as an endodermal sinus tumor with immature teratoid differentiation, teratoma and embryonal carcinoma, and choriocarcinoma and germinoma. The first case was presumed to be a combination of endodermal sinus tumor and germinoma. An immunohistochemical examination showed positive reactions to alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) in the endodermal sinus tumor, and to human chorionic gonadotropin (HCG) in the choriocarcinoma, but showed no reaction in the embryonal carcinoma. Human chorionic gonadotropin was demonstrated in syncytiotrophoblastic cells and CEA in a gland-like structure. The value of measuring CEA in cases of germ-cell tumors, in addition to AFP and HCG assays, is stressed, and the characteristics of CEA-positive tissue are discussed.     

Embryonal carcinoma of abdominal testis

Two cases are reported of embryonal carcinoma of an abdominal testis, one a large tumor with a massive retroperitoneal metastasis. Several months after removal of the testicle and roentgen-ray therapy both patients are in good health and present no evidences of metastasis or recurrence.Roentgen therapy is of proved value in embryonal testicular tumors.Local operation plus radiation is contrasted with the radical operation.     

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.     

Prognostic factors in nonseminomatous testicular cancer

The clinical, pathological and laboratory data for 60 patients with pathological stage I, 50 with stage II and 55 with stage III nonseminomatous testicular cancer were reviewed to identify prognostic factors that may be used to guide therapeutic approaches. In patients with stage I disease the presence of embryonal carcinoma (p less than 0.001) and vascular invasion in primary tumors (p less than 0.01) are significant predictors of metastases and/or recurrence after retroperitoneal lymphadenectomy. In patients with clinical stage II disease, lymph nodes greater than 2 cm. in diameter or more than 5 in number, vascular and/or lymphatic invasion and the presence of embryonal carcinoma with or without choriocarcinoma indicated an increased risk for recurrent tumor after retroperitoneal lymphadenectomy. In patients with stage III disease the involvement of 3 or more organ systems was associated with decreased survival. Patients in this group with intrathoracic metastases smaller than 2 cm., retroperitoneal metastases less than 4 cm., normal kidneys and liver, and no evidence of yolk sac tumor or choriocarcinoma had improved survival. These observations can be used to guide the type and duration of therapy selectively in patients with nonseminomatous testicular cancer.     

Testicular choriocarcinoma presenting as cutaneous metastasis. A case report and review of the literature

Choriocarcinoma are germinal tumors from testicular cells in men or foetal trophoblast in women. Cutaneous metastasis are very rare. The authors report a case of angioma-like tumor in a 22-year-old man which was a cutaneous metastasis of a testicular carcinoma. Diagnosis was of course histologic. Testicular echography showed an intra testicular tumor, pulmonary and abdominal CT-scan showed multiple metastases. Orchidectomy and retroperitoneal lymphadenectomy were performed before a general chemotherapy. Patient died 14 months after diagnosis. Only 11 cases of cutaneous metastasis of choriocarcinoma were found in the world literature (7 men and 4 women). All cases showed diagnosis trap for plastic surgeon.     

A giant testicular tumor detected with dyspnea due to lung metastases: a case report

A 19-year-old male presented with dyspnea. Clinical examination revealed the left infant-head-sized testicular tumor, multiple lung metastases and retroperitoneal bulky lymph node metastasis with marked elevation of serum lactic dehydrogenase (LDH) and alpha-fetoprotein. Left radical orchiectomy followed by the chemotherapy with etoposide and cisplatin (EP) for 4 cycles was performed. The tumor weighed 1,700 g, and was pathologically diagnosed as mixed germ cell tumor consisting of embryonal carcinoma and yolk sac tumor. After the treatment, the tumor markers were normalized with partial response (PR) of lung metastases and complete response (CR) of retroperitoneal lymph node metastasis. Thereafter, biopsy of lung metastases through video-assisted thoracoscopic surgery (VATS) was performed, and pathologically no viable cells were detected. Five months after the treatment, he was seized with convulsion due to brain metastasis with hemorrhage. Therefore, a surgical resection of brain metastasis and 2nd line chemotherapy with etoposide, ifosfamide and cisplatin (VIP) chemotherapy for 3 cycles was performed. The patient has been free of recurrence for 21 months after the 2nd line chemotherapy.     

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 metastasis from hepatocellular carcinoma

We document a case of testicular metastasis from hepatocellular carcinoma. The patient suffered from bilateral testicular painful swelling for 6 months. Scrotal ultrasonography showed bilateral testicular tumors and the whole abdominal computed tomography revealed a huge tumor in the left lobe of the liver. Bilateral orchiectomy and postoperative ultrasound-guided liver biopsy were done. Pathological examination revealed metastatic hepatocellular carcinoma. Hepatocellular carcinoma with testicular metastases is a very rare disease.     

Intra-arterial infusion chemotherapy for liver metastases of testicular tumors: report of two cases

Two cases of testicular tumors with lymph node involvement and multiple lung and liver metastases were treated successfully with intra-arterial infusion chemotherapy. Case 1: A 30-year-old man presented with right scrotal swelling and an abdominal mass. He had a large retroperitoneal mass and multiple lung and liver metastases on computed tomographic (CT) scan and chest X-ray. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed embryonal cell carcinoma and choriocarcinoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was started and repeated for 2 courses. The retroperitoneal mass and lung tumors decreased in size, but liver tumors enlarged. Systemic and intrahepatic arterial infusion combined with chemotherapy was administered, and intra-arterial chemotherapy (cisplatin, VP-16) was added. The patient also received systemic chemotherapy (carboplatin, VP-16, ifosfamide). After chemotherapy, retroperitoneal lymph node dissection was performed. Microscopic examination revealed no viable cancer cells. On CT scan, no retroperitoneal, liver, or lung tumor was detected. Case 2: A 43-year-old man presented with right scrotal swelling and an abdominal mass. CT scan revealed a large retroperitoneal mass as well as lung and multiple liver metastases. Right inguinal orchiectomy was performed. Histopathological diagnosis revealed seminoma. Cisplatin, vinblastine, VP-16 and pepleomycin combination chemotherapy (PVeBV) was administered, but the liver tumors ware enlarged on CT scan. Intrahepatic arterial infusion chemotherapy (cisplatin, VP-16) was started and repeated for 4 courses. On CT scan, the lung metastasis seemed to have disappeared, and the retroperitoneal mass and liver metastases were decreased in size.     

Diffuse embryoma of the testis. A distinctive form of mixed germ cell tumor

Two testicular tumors characterized by a diffuse, orderly arrangement of embryonal, yolk sac, and trophoblastic elements are described as examples of a newly recognized form of mixed germ cell neoplasia. In one case, ribbons of embryonal carcinoma and yolk sac tumor wound around one another to create a distinctive necklace pattern. In the second case, differentiation of the yolk sac component was more advanced with the formation of numerous clusters of cells resembling hepatocytes. Tumors with these patterns are appropriately designated diffuse embryomas to distinguish them from polyembryomas and other forms of malignant mixed germ cell tumor.     

A case of bilateral testicular tumor

A case of bilateral germ cell tumor of the testis is reported. In 1988, a 36-year-old male presented with painless swelling of left scrotal contents. Right orchiectomy and retroperitoneal lymph node dissection for embryonal carcinoma had been performed 5 years earlier. Left orchiectomy was performed and its histological finding was seminoma and embryonal carcinoma. Evaluations including CT scan and Ga scintigraphy revealed no metastasis. Postoperatively, the patient was treated with PVB therapy. Previous reports of bilateral germ cell testicular tumor were reviewed, and the age distribution, interval, and histological classification of these cases are discussed.     

Biology of testicular tumors.

Testicular tumors arise from the germ cell line and therefore exhibit characteristics of both neoplastic and normal growth and differentiation. Experimental model systems of animal and human tumors have been reviewed with emphasis on the biologic characteristics of these tumors. The embryonal carcinoma cell is the totipotential stem cell that resembles normal germ cells in many ways and is capable of differentiating along the somatic pathways to form endoderm, mesoderm and ectoderm cell types (teratoma) or along extraembryonic pathways to form trophoblast (choriocarcinoma) or yolk sac (endodermal sinus tumor). Markers of the extraembryonic cell types have been defined, and the cell surface characteristics of embryonal carcinoma cells are being intensively studied. Clarification of the biology of testicular tumors will provide the basis for future rational therapy.