Mitotic frequency in different early stages of testicular seminoma

Summary. The proliferation behaviour of early seminoma was studied by analysis of the mitotic frequency in defined stages of tumour development: Carcinoma in-situ , intratubular seminoma, intratubular seminoma with interstitial seminoma cells and solid seminoma.
It was shown that the mitotic frequency increased during the process of tumour development and that tumour cells in different tissue compartments show a different proliferation behaviour. The first stage example (CIS) showed a mitotic frequency of 0.65% while the second stage example (intratubular seminoma) showed a mitotic frequency of 0.84%. The separated analysis of the third stage example (intratubular seminoma with interstitial seminoma cells) showed a mitotic frequency of 1.45% for the intratubular compartment and 0.72% for the interstitial compartment. The fourth stage example (solid seminoma) showed a mitotic frequency of 3.59%.
The finding that mitotic frequencies differ in the examined stage examples are interpreted as an adaptation process of the tumour cells to a changed tissue micro-environment. Considering that little experimental data exists on the biological behaviour of early seminoma cells this study adds information to the present knowledge of their proliferation kinetics.     

Anaplastic seminoma

Fourteen patients with anaplastic seminoma were analyzed retrospectively. At the time of presentation anaplastic seminoma has similar prognosis stage for stage as the classic seminoma. However, the distinctive histologic findings and the high rates of local invasion and of elevations of serum beta-subunit human chorionic gonadotropin serve to distinguish anaplastic seminoma from the classic seminoma. These features, suggesting a possibly greater metastatic potential for anaplastic seminoma, warrant its continued identification as a distinct pathologic subtype.     

Das spermatozytäre Seminom Bericht über 2 eigene Fälle und eine Literaturübersicht

The spermatocytic seminoma is a distinct testicular neoplasm with a low tendency to metastasize. Two own cases with the diagnosis of a spermatocytic seminoma are presented. A third patient is described, where the initial diagnosis of a spermatocytic seminoma was retrospectively changed to classical seminoma after developing retroperitoneal relapse during surveillance. A literature review revealed distinct histopathological characteristics and a remarkably good prognosis for spermatocytic seminoma. With only one case of relapse confirmed in the literature, in these patients postoperative treatment can safely be omitted in favor of surveillance. In case of spermatocytic seminoma diagnosis should be confirmed by a second pathologist.     

Importance of alpha-fetoprotein in patients with seminoma

Since one third of the patients who die of seminoma have unsuspected nonseminomatous metastases, testicular histology alone does not establish the diagnosis of “pure seminoma.” The serum protein markers alpha fetoprotein and the beta subunit of human chorionic gonadotropin are rarely, if ever, elevated in pure seminoma. An illustrative case is reported in which an elevated alpha fetoprotein led to the diagnosis of unsuspected yolk sac tumor in a patient with seminoma. Persistent elevation of alpha fetoprotein in a patient with seminoma is an indication of nonseminomatous disease and should be managed accordingly.     

Late recurrent seminoma: 18 years after bilateral orchidectomy in patient with bilateral stage one testicular seminoma

Late recurrence of stage I seminoma is an uncommon event. We reported a patient with seminoma recurred 18 years after the initial bilateral orchidectomy for bilateral stage I seminoma. He was on surveillance after the initial treatment and remained disease free for 18 years. He then presented with liver mass and diagnosed as recurrent seminoma. Systemic chemotherapy and subsequent hepatectomy for residual hepatic tumour mass were performed and the disease was cleared. The incidence and management of the late recurrence of seminoma would be discussed.     

Occult primary seminoma: eighteen-year delay in presentation

Primary retroperitoneal seminoma is well documented. A case is reported in which a patient presented with a seminoma of testis eighteen years after removal of a retroperitoneal seminoma. Histologic appearance of the testis was identified to the original pathology, and it is proposed that this represents recurrence of an occult testicular seminoma.     

Management of testicular seminoma at Westmead Hospital from 1980 to 87

Testicular seminoma comprises fewer than 1% of male cancers but is a relatively common malignancy in young men. The management and outcome of 73 consecutive patients with testicular seminoma were reviewed. Median follow-up was 51 months (range: 15-109 months). Their median age was 37 years (range: 21-67 years). There was a history of testicular maldescent in 5.5% of patients. Beta-human chorionic gonadotropin was elevated in 22% of patients prior to orchidectomy and in 5% post-surgery. The majority of patients had stage I (78%) or stage II (19%) seminoma after clinical staging. One patient (2%) with stage I seminoma relapsed, while two patients (14%) with stage II seminoma relapsed. The latter two were salvaged with further therapy. One of two patients treated for stage III seminoma died. A residual mass after radiotherapy was commonly observed in patients with stage II seminoma, but did not represent viable tumour. These results reflect the high cure rates that are achievable in seminoma with radiotherapy for early stage and non-bulky abdominal disease and, more recently, with cisplatin-based chemotherapy for bulky abdominal or disseminated disease.     

Fas配体mRNA在正常睾丸组织及精原细胞瘤中的表达

为明确Fas配体mRNA在正常睾丸组织及精原细胞瘤中的表达情况，采用原位杂交，反转录PCR（RT－PCR）法检测正常睾丸组织8例Fas配体mRNA的表达，采用原位杂交法检测33例精原细胞瘤组织中的Fas配体mRNA的表达。结果RT－PCR方法证明正常人睾丸组织中有Fas配体mRNA的表达；原位杂交法证明8例正常睾丸组织中均有Fas配体mRNA的表达，且表达局限于睾丸Sertoli细胞，正常生殖细胞中无Fas配体mRNA的表达；原位杂交方法在33例精原细胞瘤组织中检测到Fas配体mRNA表达阳性11例，阳性率为33．33％，多呈现小片状或点状表达。提示Fas配体mRNA仅表达于人类睾丸的Sertoli细胞中，Fas配体mRNA在精原细胞瘤组织中的出现可能是精原细胞瘤形成及进展的原因。     

Can radiotherapy be a viable salvage treatment option for the relapsed seminoma confined to the infra-diaphragm region recurring after primary chemotherapy for bulky stage II seminoma?

There has been a paucity of research describing a potential role of radiotherapy as salvage treatment for recurrent seminoma following primary chemotherapy for bulky stage IIC seminoma. We report a case of a bulky stage IIC seminoma relapsed in the pelvis after primary chemotherapy and surgery for post-chemotherapy residual mass, which was subsequently salvaged with radiotherapy. The patient has remained free of relapse at 3.7 years post-salvage radiotherapy. This case demonstrates that radiotherapy can be a salvage therapeutic option for recurrent seminoma following primary chemotherapy for bulky stage IIC seminoma, provided that the recurrent tumour is confined to a limited area of the infradiaphragmatic region. There is a need for further study to examine the potential role of radiotherapy as a salvage therapeutic tool for post-chemotherapy recurrent seminoma.     

Primary paratesticular seminoma - A case report

INTRODUCTIONParatesticular tumours are rare. Rhabdomyosarcomas are the commonest malignant paratesticular tumours although tumours can arise from any paratesticular structure. Here we report a case of a primary paratesticular seminoma and a review of the literature.PRESENTATION OF CASEA 42 year old man presented with a right scrotal mass. Histology revealed a paratesticular seminoma. Following a radical orchidectomy, there was no evidence of testicular seminoma.DISCUSSIONPrimary paratesticular seminoma in the absence of testicular seminoma is extremely rare.CONCLUSIONAfter a thorough review of the literature, this is, to our knowledge only the second reported case of a primary paratesticular seminoma.     

Bone scintigraphy in testicular tumours

The role of bone scintigraphy was assessed by follow-up and review of 61 patients with testicular tumours. Skeletal metastases were present in all five patients who died with seminoma and in two of the eight whose deaths were due to teratoma. The only patient with skeletal metastases to have a prolonged survival had a mixed teratoma/seminoma. Bone scintigraphy is indicated in patients with recurrence after radical treatment for seminoma and may be indicated in patients presenting with stage IV seminoma, to identify a sub-group with the worst prognosis. In other patients it is indicated only if there is a specific clinical suspicion of bone metastases.     

Chemotherapy of advanced seminoma

Seminoma is one of the most radiosensitive of the solid tumors. Radiotherapy provides a high cure rate for patients with stage I and II seminoma, but the survival rate of the patients with clinically advanced stage III seminoma is only about 30% in the literature. Our case of advanced metastatic seminoma was treated with cisplatinum, vinblastine and bleomycin. Metastatic tumors in the lung disappeared after chemotherapy but recurred shortly. Then regional radiation was given and the tumors disappeared completely. Subsequent prophylactic chemotherapy was given. In view of the observed chemosensitivity of seminoma, it appears that all patients who present initially with metastatic or bulky retroperitoneal disease should be treated with multiple drug chemotherapy including cis-platinum. Residual tumors can be treated by radiation and surgical resection, which will improve the cure rate of advanced metastatic seminoma.     

A case of cranial and intracranial metastasis from testicular seminoma]

The case presented is of a 44-year-old man with skull and intracranial metastasis of seminoma. He was operated on for a testicular tumor at 41 years of age. Pathologically, it was pure seminoma. Coronal CT scan showed tumor invasion of the subcutaneous vault, and of the epidural and intraparenchymal region of the right parietal region. We treated him with a combination of surgical excision, radiation and PVB chemotherapy. He was neurologically disease-free for ten months after being discharged. However, he then succumbed to liver metastasis of seminoma. Seminoma mainly metastasizes via the lymph stream. CNS metastasis of seminoma is only 0.7% in Japan. We would like to stress that prophylactic chemotherapy would be essential even after patients get remission from CNS metastasis of seminoma.     

Two cases of spermatocytic seminoma]

Two cases of spermatocytic seminoma are reported. The first case was a 58-year-old man who visited our hospital with a complaint of painless swollen left scrotal content. Left orchiectomy was performed under the diagnosis of testicular tumor. Since the pathological diagnosis first made was anaplastic seminoma, he was treated with combined chemotherapy (PVB, 1 course). However, since the pathological diagnosis after re-examination of the specimen, was spermatocytic seminoma, he underwent prophylactic radiation therapy. The second case was a 64-year-old man who visited our hospital with a complaint of painless swelling of right scrotal content. Right orchiectomy was performed under the diagnosis of testicular tumor. The pathological diagnosis was spermatocytic seminoma. He underwent prophylactic radiation therapy. Postoperatively these two patients have been well with no evidence of recurrence. These are the 14th and 15th cases of spermatocytic seminoma reported in Japan.     

Correlation between expression of metastasis-related genes and lymph node metastasis in testicular cancer

To investigate the factors related to lymph node metastasis of testicular germ cell tumors, we first established a seminoma orthotopic model with lymph node metastasis in SCID mice by inoculating small fragments from subcutaneous xenografts. Second, we compared the expression patterns of metastasis-related genes of the seminoma xenografts and of the TCam-2 cells which were established as a seminoma cell line from a primary testicular seminoma. Third, we immunohistochemically analyzed human germ cell tumors (25 seminomas, 17 nonseminomas) using monoclonal antibodies to CD34, VEGF, VEGF-C, Flt-4, MMP-2 and E-cadherin. Testicular seminoma xenografts grew in 32/32 (100%) of the inoculated mice, of which 15 (47%) developed macroscopic metastasis to the renal hilar lymph node. Circulating tumor cells were detectable by using a PCR assay for the human beta-globin gene in 25/32 (78%) mice, although metastatic foci were not histologically evident in the visceral organs, including lungs, liver, kidneys and spleen. This may reflect the lymphophilic characteristics of the seminoma cells used. Regarding mRNA expression of metastasis-related genes, an increased expression of MMP-2 and VEGF compared with that in the s.c. xenografts was demonstrated by RT-PCR assay in the testicular seminoma xenografts. In addition, uPAR, MMP-1, MMP-2, MT1-MMP and MT3-MMP showed a a stronger expression and PAI-2 a weaker expression in the seminoma xenografts than did TCam-2 cells. These results suggest a higher metastatic potential of the seminoma xenografts, especially testicular xenografts, as compared with TCam-2 cells. In the immunohistochemical study, a significant correlation was found between MMP-2 expression and lymph node metastasis, which is compatible with the results for the metastasis-related gene expression from the seminoma xenografts.     

Serum and tissue levels of placental alkaline phosphatase in patients with testicular tumor

Placental alkaline phosphatase (PLAP) levels in sera and tissues from 40 patients with testicular tumor were measured using a monoclonal immuno-catalytic assay. The mean value of the PLAP levels of seminoma tissues was found to be 92-fold higher than that of normal testes, being significantly high compared with that of non-seminoma tissues. The mean value of the serum PLAP levels from patient's with seminoma was also significantly higher than that from patients with non-seminoma. In 2 groups of seminoma and mixed type tumor containing seminoma and non-seminoma components, the PLAP levels of tissues from patients who had high levels of the serum PLAP (greater than or equal to 100 mKAU) were significantly higher than those from patients who had normal serum PLAP levels (less than 100 mKAU). In the seminoma or mixed type tumor groups, the serum PLAP levels of all patients who had high levels before treatment decreased to within a normal range after orchiectomy with or without chemotherapy or radiation therapy. We conclude that PLAP seems to be an useful tumor marker for the diagnosis and the monitoring of response to treatment in patients with seminoma.     

Serum lactate dehydrogenase and human choriogonadotrophin in seminoma

The clinical significance of serum lactate dehydrogenase (LDH) and serum human choriogonadotrophin (HCG) as tumour markers was assessed in 105 patients with pure seminoma from whom 981 blood samples were analysed. The specificity of elevated HCG and LDH was 100 and 93% respectively. The comparable sensitivity was 32 and 47%. Serum LDH could not discriminate between patients with clinical stage I seminoma, prior to orchiectomy, and those with benign testicular lesions. In patients with advanced metastatic seminoma subjected to orchiectomy, serum LDH was increased in 82%, but elevated HCG was found in only 40%. After cisplatin-based chemotherapy, falsely elevated LDH was observed in 7 of 37 tumour-free patients, but HCG was normal in all patients with no evidence of disease. Six patients with residual tumour after chemotherapy had normal LDH and 4 of them had elevated HCG; 70% of the relapses in seminoma patients were associated with increased LDH (64%) and/or HCG (48%). In seminoma patients with comparable disease extension, elevated HCG seemed to be correlated with a high risk of relapse. Patients with normal pre-treatment LDH had a lower relapse-free survival rate than patients with elevated LDH. HCG is a highly specific tumour marker in seminoma with a rather low sensitivity. HCG is particularly useful for the primary diagnosis in patients with testicular lesions and during monitoring of chemotherapy in seminoma patients. LDH is less specific than HCG. Both markers should be analysed during follow-up of seminoma patients, since 70% of relapses are associated with an increase in one or both markers. Elevated pre-treatment HCG, but not elevated LDH, seems to indicate an increased risk of relapse in patients with seminoma.     

Globotriaosyl ceramide glycolipid in seminoma: its clinicopathological importance in differentiation from testicular malignant lymphoma.

Glycolipids were biochemically extracted from 14 specimens of seminoma, 2 of testicular malignant lymphoma (both of which were difficult to differentiate from seminoma with a high mitotic index) and 4 of normal testicle. The pattern of their expression was compared. Marked accumulation of globotriaosyl ceramide was observed in seminoma but it was present in a small amount in testicular malignant lymphoma. Differentiation between seminoma and malignant lymphoma is sometimes difficult by histopathological findings but it is considered to be greatly facilitated by examination of the pattern of glycolipid expression.     

HLA-antigen distribution in seminoma,HCG-positive seminoma and non-seminomatous tumours of the testis

Summary Histocompatibility antigens play a certain role in the development of testicular tumours. 151 patients with testicular cancer (86 non-seminomatous germ cell tumours—NSGCT-and 65 pure seminoma) were typed for the HLA-antigens of the A, B, C and DR locus. 24 patients of the pure seminoma group and 50 patients of the NSGCT group had an elevated serum HCG level preoperatively. The antigen DR-5 was elevated in the seminoma group whereas the incidence of B-13 was increased in the NSGCT group. In terms of antigen distribution HCG-positive seminoma resembles seminomatous tumours rather than NSGCT.     

Spermatocytic seminoma

A case is reported of a forty-four-year-old man with spermatocytic seminoma with nc evidence of metastasis for twelve years. This patient is the second to have undergone retroperitoneai lymph node dissection and the third to have histopathologic examination of these lymph nodes. Revieu of 52 cases of spermatocytic seminoma disclosed 70 per cent of patients were over fifty years of age; none developed in a cryptorchid testis, none occurred in association with teratoma, and there was no histopathologic evidence of metastasis. Whether or not radiation therapy is necessary is questionable. Prognosis appears to be good if not better than in classic seminoma. Available data indicate that spermatocytic and classic seminoma are two distinct neoplasms with different histogenesis and pathologic, clinical, and biologic features.