A guide to the investigation and treatment of patients with AIDS and AIDS-related disorders.

In 1977 the rate of death from testicular cancer in Ontario began to decline following a long period of relative stability. This coincided with the addition of cisplatin to the chemotherapeutic regimens used in the treatment of disseminated germ-cell testicular cancer. A study was carried out to determine whether the decline has been similar for the two major histologic subgroups, seminoma and nonseminoma. By means of Ontario Cancer Registry data, histologic type was determined for all testicular cancers causing death in Ontario residents between 1964 and 1982, and death rates were calculated for seminoma and nonseminoma germ-cell testicular cancer. The rates of death from nonseminoma exceeded those from seminoma for the entire study period. Although the death rates for both subgroups declined by about 50% after 1976, the reduction in the overall rate of death from testicular cancer is primarily attributable to the decline in the rate for nonseminoma germ-cell testicular cancer. The increased overall rate of death from testicular cancer (all types) between 1980 and 1984 is cause for concern and indicates the need for continued monitoring of the trends in rates of death from this disease.     

Tumeur testiculaire et cryptorchidie bilatérale. Piège diagnostic

Undescended testis is a major risk factor for testicular seminoma. Correction of undescended testis during childhood improves the prognosis. The surgical technique has been improved over the last thirty years, based on a knowledge of older techniques and the contribution of the laparoscopy now allows a more precise operative technique during surgical treatment of testicular tumour.     

Bilateral germ cell testicular tumors

PURPOSE: To study the clinical characteristics of bilateral testicular tumors in the cisplatin era. PATIENTS AND METHODS: Between November 1988 and November 1998 2386 testicular cancer patients were treated in our Department and 72 bilateral germ cell testicular cancer patients were retrospectively explored (3%). The incidence, the clinical and histological characteristics and, in the case of asynchronous tumor, the interval between the two tumors were analyzed. RESULTS: During the 10 years 19 synchronous (26.4%) and 53 asynchronous bilateral germ cell testicular cancers (73.6%) were treated. The incidence of bilateral synchronous seminoma was 68.4%. Among the asynchronous tumors 9 concordant seminomas and 9 concordant nonseminomas were detected. In the first, second and third 5-year follow-up period 39.6, 30.2, and 28.2% of asynchronous tumors were diagnosed. The incidence of seminoma after the first castration in the 5, 10 and 15 years was 19, 37.5, and 60%, respectively. The overall survival rates of synchronous and asynchronous testicular cancer were 84 and 93%. In cases of asynchronous tumor the prevalence of stage I cancer was significantly greater in a regularly controlled population (p=0.014) than in the not regularly followed population, but the survival rate was good in both groups. Nonseminoma showed up earlier as first and second tumor than seminoma (p=0.05, p=0.045). The interval between the two asynchronous tumors was shorter in the case of nonseminoma than in the case of seminoma (p=0.002). CONCLUSION: The prognosis of bilateral germ cell testicular cancer is good because of the high incidence rate of seminoma and the effective treatment. With regular follow-up the early diagnosis of second testicular tumors is probable. The interval between the tumors depends on the patients' age and the histology of the second tumor, in the case of seminoma it is longer. The effect of the previous treatment on the incidence of seminoma and the interval between the two asynchronous tumors requires further investigations.     

Évolution du cancer du testicule en France

As in many countries, the mortality rate of testicular cancer in France has decreased from 0.75 in 1978 to 0.25 per 100,000 in 2000 (standardized on world population). Over the same period, the incidence rate increased from 3.17 in 1978 to 4.82 per 100,000 in 2000 (standardized on world population). However, although the incidence of seminoma has increased continually with all birth cohorts, the incidence of non-seminomas first decreased for the men born between the first and second world wars and then increased at the same rate as the seminoma rate. No explanation for this pattern has yet been provided, but it does not appear to be simply an artefact. A North/South and East/West gradient has been observed, as the incidence varies from 4.0 in the South West to 8.0 in the North East. There is an estimated 1,500 new cases of testicular cancer each year in France, including 960 new cases for men between the ages of 15 and 40.     

Prolactin secretion in testicular cancer patients

The role of prolactin (PRL) in testicular function and in its disorders is still obscure. To draw some preliminary conclusions on the relation between the PRL and testis cancer, we assessed the PRL response to thyrotropin-releasing hormone (THR) in 15 patients with testicular cancer (8 seminoma; 6 nonseminoma; 1 leydigioma), and in 11 healthy male subjects as controls. The results showed that 5/15 cancer patients gave no PRL response to TRH; 4 of them had a nonseminoma and the fifth a seminomatous testis carcinoma. Patients with nonseminoma had significantly lower mean peak values of PRL after TRH than controls or patients with seminoma. The biological significance of the altered PRL response to TRH in testicular carcinoma has still to be established.     

Chronic myelogenous leukemia following radiation therapy for testicular seminoma

A 43-year-old man was treated with orchiectomy and radiotherapy for testicular seminoma. Four years later, he developed a typical Philadelphia chromosome positive chronic granulocytic leukemia. Since the patient was not eligible for bone marrow transplantation, he was treated with busulfan. Long term follow-up of patients who received radiotherapy for testicular seminoma is warranted in order to detect possible secondary tumors.     

Expression of Connexin 43 in normal canine testes and canine testicular tumors

In human testis, gap junctions containing connexin(Cx)43 are located within the seminiferous epithelium between Sertoli cells and between Sertoli and germ cells. Cx43 is known to play a role in the differentiation and proliferation of these cell types. It can further be associated with human seminoma development. The dog has been proposed as a model for studies of the male reproductive system, because of the frequent occurrence of testicular neoplasms. Thus, we investigated Cx43-mRNA and -protein expression in testes of normal prepubertal dogs, adult dogs, and in canine testicular tumors. Sertoli cells in prepubertal cords express Cx43 mRNA, but do synthesize only less Cx43 protein. Within the seminiferous tubules, Cx43 mRNA was detected in Sertoli cells, spermatogonia, and spermatocytes. Cx43 protein was mainly present in the basal compartment. In canine testicular tumors Cx43 mRNA was detectable in both seminoma and neoplastic Sertoli cells, whereas Cx43 protein was only found in neoplastic Sertoli cells. Our data indicate that Cx43 is regulated differentially in testicular tumors and that alterations of Cx43 expression may be involved in the pathogenesis of canine testicular malignancies. This study represents the first morphological work on the spatiotemporal expression pattern of Cx43 in normal and neoplastic canine testis.     

Trends in the incidence of testicular germ cell cancer in Ontario by histologic subgroup, 1964-1996

BACKGROUND: Testicular cancer is rare but is notable because it affects mainly young men. The incidence of this disease has been increasing in developed countries throughout the world for several decades. The authors examined trends in the incidence of testicular germ cell cancer in Ontario for the period 1964-1996 according to the 2 main histologic groups, seminoma and non-seminoma. METHODS: Data on incident cases of testicular germ cell cancer diagnosed in Ontario residents aged 15-59 years between 1964 and 1996 were extracted from the population-based Ontario Cancer Registry. Annual rates of testicular cancer for the 2 histologic groups were analysed by means of log-linear regression to estimate average annual percent change. RESULTS: Between 1964 and 1996 the incidence of testicular germ cell cancer increased by 59.4%, from 4.01 to 6.39 per 100,000. This corresponded to an average annual increase of about 2% for both nonseminoma and seminoma. The relative increase in incidence was greatest in the lowest age group (15-29 years) for both histologic groups, although the data suggest that the incidence of nonseminoma cancer in this age group began to decline in the early 1990s. The increase in incidence appears to be due to a birth cohort effect, with more recent cohorts of men at increased risk. INTERPRETATION: The rise in the incidence of testicular germ cell cancer, not only in Ontario but also in many developed countries, requires investigation. The search for explanatory factors should focus on exposures whose prevalence may have increased over the past few decades and that are common enough to affect population incidence. The similarity of trends for seminoma and nonseminoma cancer suggests that the underlying risk factors are likely the same.     

Cytochrome P450 aromatase expression in human seminoma

Background  

The enzyme cytochrome P450 aromatase, catalysing the conversion of androgens into estrogens, has been detected in normal human testicular cells suggesting a physiological role of local estrogen biosynthesis on spermatogenesis control. Estrogens, regulating cell growth and apoptosis, can also be involved in tumorigenesis process, but the possible link between estrogens and testicular neoplastic process is, up to now, scarcely known. This study examined aromatase expression in human seminoma, which is the most common germ cell tumour of the testis.     

Annulate lamellae in human tumor cells.

Annulate lamellae have been found in a primitive neuroectodermal tumor, a metastatic cerebellar tumor, a testicular seminoma, a retinoblastoma and three melanomas. These annulate lamellae are arranged in stacked parallel arrays in the cytoplasm of tumor cells. The number of annulate lamellae observed to comprise a single stack varies from 2--4 in the seminoma tumor to 5--18 in the cerebellar tumor. Although the functional significance of annulate lamallae is still unknown, in many instances they have been found to be continuous with rough-surfaced cisternae of the endoplasmic reticulum and ribosomes have been demonstrated on the surface of annulate lamellae. This may suggest that annulate lamellae participate in protein synthesis.     

Risk of testicular cancer in subfertile men: case-control study

ObjectiveTo evaluate the association between subfertility in men and the subsequent risk of testicular cancer.DesignPopulation based case-control study.SettingThe Danish population.ParticipantsCases were identified in the Danish Cancer Registry; controls were randomly selected from the Danish population with the computerised Danish Central Population Register. Men were interviewed by telephone; 514 men with cancer and 720 controls participated.ResultsA reduced risk of testicular cancer was associated with paternity (relative risk 0.63; 95% confidence interval 0.47 to 0.85). In men who before the diagnosis of testicular cancer had a lower number of children than expected on the basis of their age, the relative risk was 1.98 (1.43 to 2.75). There was no corresponding protective effect associated with a higher number of children than expected. The associations were similar for seminoma and non-seminoma and were not influenced by adjustment for potential confounding factors.ConclusionThese data are consistent with the hypothesis that male subfertility and testicular cancer share important aetiological factors.

Key messages

• The incidence of testicular cancer has increased in the past 50 years, and there is some evidence to suggest that sperm quality has decreased in the same period
• It has been hypothesised that common aetiological factors may exist for testicular cancer and for male subfertility
• The association between male subfertility and subsequent risk of testicular cancer is strong and consistent with the hypothesis of a common aetiology
• The association is similar for seminoma and non-seminoma, and it persists when several potentially confounding factors are taken into account

     

Abus et danger du traitement au citrate de clomiphène dans l’infertilité masculine

Obiective

To describe a case of seminoma occurring in a patient with a past history of cryptorchidism, infertility and clomiphene citrate (CC) treatment. To review the literature of seminoma in association with these risk factors.

Case report

A 33 year old man developed typical seminoma in the right testis. A bilateral cryptorchidism was lately diagnosed and treated by orchidopexy at the age of 17. Primary infertility due to oligoasthenospermia was diagnosed at the age of 29. Treatment was initiated with CC at the dose of 25 mG/day. Semen quality improved gradually. After failure of various assisted reproductive techniques, a spontaneous pregnancy was achieved and a healthy baby delivered. Shortly after delivery the seminoma was diagnosed, after a totla of three years of treatment. Six cases of testicular tumors have been reported in the literature in which patients had been pretreated with fertility drugs for various priods of time before tumors was diagnosed. Cryptorchidism is a well-known risk factor for testicular malignancy, as is the infertil state. Clomiphene citrate may promote malignant transformation by activation of estrogen receptors, by raising gonadotropin and/or testosterone concentrations, or by other mechanisms.

Conclusion

Clomiphene citrate may have a previously unappreciated malignancy-promoting effect in infertile men, especially those with other risk factors. Clinicians treating similar patients should take this into account and the literature monitored for other associated cases.     

Survival after a diagnosis of testicular germ cell cancers in Germany and the United States, 2002–2006: A high resolution study by histology and age

Introduction: The aim of this study was to provide detailed age-specific (5-year age groups) and histology-specific (histologic subtypes of seminoma and nonseminoma) relative survival estimates of testicular germ cell cancer patients in Germany and the United States (U.S.) for the years 2002–2006 and to compare these estimates between countries. Methods: We pooled data from 11 cancer registries of Germany and used data from the U.S. (SEER-13 database) including 11,508 and 10,774 newly diagnosed cases (1997–2006) in Germany and the U.S., respectively. We estimated 5-year relative survival (5-year-RS) by histology and age based on period analysis. Results: 5-year-RS for testicular germ cell tumors was 96.7% and 96.3% in Germany and the U.S., respectively. 5-Year-RS for spermatocytic seminoma was close to 100% in both countries. 5-Year-RS for nonseminoma was lower than for classical seminoma in Germany (93.3% versus 97.6%) and the U.S. (91.0% versus 98.2%). Among nonseminomas, choriocarcinomas provided the lowest 5-year-RS in both countries (Germany 80.1%, U.S. 79.6%). Age-specific 5-year-RS for seminoma showed only little variation by age. 5-Year-RS for nonseminomas tended to be lower at higher ages, especially for malignant teratoma. Discussion: This is the first study that provides up-to-date survival estimates for testicular cancer by histology and age in Germany and the U.S. Survival after a diagnosis of testicular cancer is very comparable between Germany and the U.S. 5-Year-RS for spermatocytic seminoma was close to 100% and the lowest 5-year-RS occurred among choriocarcinoma. Higher age at diagnosis is associated with a poorer prognosis among nonseminoma patients.     

Heterogeneity of intermediate filament expression in human testicular seminomas

Testicular seminoma has in the past been considered to represent a germ cell tumor incapable of further differentiation. In recent years this view has been challenged on the basis of morphologic and chromosomal studies. Moreover, studies of intermediate filaments (IF) of seminoma cells have provided evidence of the capability of seminoma cells to differentiate in different directions. In the present study of the IF protein profile of 26 human testicular seminomas, using frozen as well as formalin-fixed, paraffin-embedded tissues, we report evidence of a heterogeneous differentiation potential inherent in these neoplasms. Thus, in 4 of the seminomas neither cytokeratins nor vimentin were detected; 3 showed vimentin positive cells but no cytokeratins; in 4 seminomas only cytokeratins were detected. In the remaining 15 cases both cytokeratins and vimentin were present, with occasional cells demonstrating coexpression of cytokeratin and vimentin. While the cytokeratins present were mostly of the "simple epithelial type", in 2 instances seminoma cells also contained cytokeratins 4 and 17, normally found in stratified and/or complex glandular epithelia. Furthermore, in 3 cases scattered tumor cells stained for desmin and in 2 other seminomas neurofilaments were identified. All of the cases showed variable positive staining for desmoplakins and desmoglein, indicative of the presence of desmosomes. It can therefore be concluded that, while some seminomas seem to be devoid of IFs, most of them show varied differentiation patterns usually with epithelial features but occasionally also with components commonly regarded as characteristic of myogenic or neurogenic differentiation. These observations may help to elucidate the relationship of seminomas to other germ cell tumors, and also contribute to our understanding of the histogenesis of these neoplasms.     

Onco-testicular sperm extraction (Onco-TESE) from a single testis with metachronous bilateral testicular cancer: a case report

Background

Although oncologic testicular sperm extraction (onco-TESE) has been increasingly practiced, the evidence of onco-TESE performed in patients with testicular cancer is insufficient. Furthermore, in bilateral testicular cancer, accounting for 0.5%–1% of testicular cancers, onco-TESE is more challenging and has been insufficiently reported.

Case presentation

Here we report the case of a 25-year-old man who underwent onco-TESE from his residual single testis with a nonseminomatous germ cell tumor that occurred 5 years after orchiectomy of the contralateral testis. A second orchiectomy and simultaneous TESE from the noncancerous testicular tissue were performed. The pathological diagnosis was germ cell tumors, tumors of more than one histological type (embryonal carcinoma, immature teratoma, yolk sac tumor, seminoma, and choriocarcinoma; pT1N0M0). The patient subsequently married and hoped for fatherhood 3 years later. Whereas histological diagnosis of the normal testicular tissue was Johnsen score 6 (maturation arrest), morphologically normal and motile sperms were successfully retrieved from thawed TESE samples and used for multiple cycles of intracytoplasmic sperm injection. Although the conception has not been succeeded to date, ICSI attempts have been continuing.

Conclusion

This case demonstrates the effectiveness of onco-TESE for challenging cases such as bilateral and nonseminmatous testicular cancer.

     

Evidence of testicular dysgenesis syndrome in the dog

Human male reproductive disorders comprising testicular dysgenesis syndrome (TDS) have become more prevalent during the last 50 years. These disorders include cryptorchidism, hypospadias, decreased semen quality, and the development of seminomas. Based on experimental evidence, it has been suggested that environmental pollutants with oestrogen-like or anti-androgenic activities play a role in the pathogenesis of TDS. In humans, histological lesions associated with TDS have been well characterized; this includes seminomas as well as their precursors, carcinoma in situ (CIS) lesions. CIS are seminiferous tubules lined by gonocytes and are a sign of testicular maldevelopment. Such CIS have recently been described in canine species, and an increased frequency of testicular tumours in dogs has also been reported. In this study, we investigated the presence of TDS lesions in canine testes submitted to routine histological examination. Histological features considered typical of human TDS were observed in 8/38 dogs examined; as in humans, individual dogs presented with various TDS features with a range of severity. In all eight dogs, CIS and at least one of the histological feature of TDS was observed in combination with seminoma. These findings suggest that as in humans, TDS may predispose canines to develop testicular cancer. A larger study is needed to better evaluate the actual incidence of TDS in canines, its clinical consequences, and the possible underlying pathogenic factors.     

DNMT1 and HDAC1 gene expression in impaired spermatogenesis and testicular cancer

DNA methylation catalyzed by DNA methyltransferases (DNMTs) and histone deacetylation catalyzed by histone deacetylases (HDACs) play an important role for the regulation of gene expression during carcinogenesis and spermatogenesis. We therefore studied the cell-specific expression of DNMT1 and HDAC1 for the first time in human testicular cancer and impaired human spermatogenesis. During normal spermatogenesis, DNMT1 and HDAC1 were colocalized in nuclei of spermatogonia. While HDAC1 was additionally present in nuclei of Sertoli cells, DNMT1 was restricted to germ cells exhibiting a different expression pattern of mRNA (in pachytene spermatocytes and round spermatids) and protein (in round spermatids). Interestingly, in infertile patients revealing round spermatid maturation arrest, round spermatids lack DNMT1 protein, while pachytene spermatocytes became immunopositive for DNMT1. In contrast, no changes in the expression pattern could be observed for HDAC1. This holds true also in testicular tumors, where HDAC1 has been demonstrated in embryonal carcinoma, seminoma and teratoma. Interestingly, DNMT1 was not expressed in seminoma, but upregulated in embryonal carcinoma. Olufunmilade A. Omisanjo is a scholarship holder of the German Academic Exchange Service (DAAD). Sonja Hartmann is a member of the German Research Foundation (DFG) Research Training Group 533 Cell–cell-Interaction in Reproduction.     

W43X SDHD mutation in sporadic head and neck paraganglioma

OBJECTIVE: To analyze the presence of SDHD gene mutations in patients with sporadic head and neck paraganglioma. STUDY DESIGN: The presence of somatic and germline SDHD mutations was investigated in 10 patients by polymerase chain reaction and direct sequencing. RESULTS: Two patients displayed mutations: 259C>T (P87S) in 1 case and 129G>A (W43X) in the other. The first was considered a neutral polymorphism. The second was present in the germline of 1 of her sons, who had an apparently unrelated testicular seminoma and loss of heterozygosity (LOH) in the tumor cells. CONCLUSION: This is the first reported case of an SDHD mutation carrier showing LOH in a testicular seminoma.     

Lésion « pleurale » chez un patient avec antécédent de séminome

We report on the case of a man with a previous history of testicular seminoma and a pathological paravertebral mass definitely taking-up FDG on PET/CT. This mass was finally a benign schwannoma.