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.     

Experience of screening for carcinoma-in-situ of the testis among young men with surgically corrected maldescended testes

One hundred and twelve young men with maldescended testes which had been surgically corrected were examined for premalignant/malignant changes in the testes. Bilateral testicular biopsies were made in ninety-four patients. Three had carcinoma-in-situ of the testis in the biopsy. Invasive tumour of seminomatous type was found in two of these testes after orchidectomy had been performed. No correlation was found with testicular localization pre- or postoperatively, with testicular volume or with tumour markers.     

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.     

Expression of the c-kit protein product in carcinoma-in-situ and invasive testicular germ cell tumours

Carcinoma-in-situ of the testis (CIS) is the precursor of invasive germ cell tumours. It is believed that CIS cells may originate from early fetal gonocytes. Recently, the proto-oncogene c-kit has been implicated as crucial for the development and migration of primordial germ cells. In this study, CIS and overtly invasive human male germ cell tumours were analysed immunohistochemically for expression of the c-kit proto-oncogene protein product. Testicular tissue samples from 36 patients with various types of testicular germ cell neoplasia and 19 control specimens were stained using an indirect immunoperoxidase method. High expression of c-kit was found in almost all cases of CIS, both when the lesion was the only pathology, and when CIS was adjacent to invasive tumours. The Kit staining was retained in seminomas with variable intensity; the majority of cells in tumour mass exhibited c-kit expression in 61% of the samples while focal expression was observed in 39% of the samples studied. No expression of c-kit was detected in non-seminomas or in normal testicular germ cells. High expression of the proto-oncogene in CIS cells supports the hypothesis of their origin from primordial germ cells. In addition, we propose that the c-kit protein product is a new marker for carcinoma-in-situ of the testis.     

Clinical evaluation of DNA flow cytometry of fine needle aspirates from testes of infertile men

DNA flow cytometry was performed on fine needle aspirates from the testes of 40 oligozoospermic or azoospermic men under investigation for infertility. The DNA distributions from men with increased FSH serum levels were all abnormal. The values were below the level of detection (or very low) with respect to both haploid (1c) and tetraploid (4c) cells, indicating reduced proportions of spermatids and primary spermatocytes. This confirms that increased FSH serum levels are indicative of severely damaged spermatogone-sis. The findings of both normal and abnormal testicular DNA distributions in the large group of oligozoospermic men indicate that the presented method may be of importance for evaluating prognosis, and for selection of men for further investigation and therapy. Many azoospermic men showed normal testicular DNA distribution patterns, suggesting the value of DNA flow cytometry for selection of such cases for surgical treatment (epididymovasos-tomia).     

Management of carcinoma-in-situ of the testis

Carcinoma-in-situ (CIS) of the testis progresses to invasive cancer within 5 years in 50% of cases, and therefore requires therapeutic intervention. CIS is probably eradicated by intensive cancer chemotherapy but this is too toxic for the management of non-invasive disease. Eight patients with unilateral testicular cancer and contralateral CIS received localized irradiation (20 Gy in ten fractions of 2 Gy) to the remaining testis: after 3 months the CIS cells had disappeared and 'Sertoli-cell-only' tubules were found. LH and FSH levels were elevated but testosterone levels remained fairly constant. Localized irradiation should be considered as the treatment of CIS in the contralateral testis of testicular tumour patients unless chemotherapy is indicated for the primary tumour. Unilateral orchidectomy is recommended for unilateral CIS associated with infertility or testicular maldescent. Localized testicular irradiation should now be considered for bilateral disease. Patients with the androgen insensitivity syndrome should normally be treated with bilateral orchidectomy, but irradiation may be useful in selected cases.     

Immunohistochemical demonstration of tumour associated antigens in carcinoma-in-situ of the testis

Atypical germ cells or so-called carcinoma-in-situ of the testis are often found in the tissue adjacent to germ cell tumours. The present study was performed to investigate if tumour associated antigens demonstrated immunohistochemically in the tumours could also be demonstrated in the carcinoma-in-situ. Using indirect immunoperoxidase technique 39 orchidectomy specimens were examined for the presence of a series of antigens: alpha-foetoprotein (AFP), alpha₁-antitrypsin (A₁AT), human chorionic gonadotrophin (hCG). specific pregnancy β-glycoprotein (SP₁), human placental lactogen (hPL), carcino-embryonic antigen (CEA) and ferritin (FER).
FER was demonstrated in the atypical cells in 24/29 cases of carcinoma-in-situ of the testis. HCG was demonstrated in intratubular syncytiotrophoblast-like cells in one case and in atypical germ cells in another specimen. No staining reaction was found for the other antigens investigated Normal germinal epithelium and germinal epithelium in non-malignant pathological changes of the testis were never stained.
These findings which indicate that FER may be a possible marker of carcinoma-in-situ of the testis is of utmost interest, however investigation of a larger series is mandatory.     

Testicular carcinoma in situ in subfertile Danish men

Carcinoma in situ (CIS) testis is the precursor stage for the majority of testicular germ cell tumours (TGCT). Infertility is one of the conditions known to predispose to TGCT, but based on scarce existing data, the prevalence of CIS in this risk group was estimated at only approximately 1%. To establish more objective data, we investigated retrospectively the prevalence of CIS based on testicular biopsies performed in a well-defined group of subfertile males. We included 453 patients who had testicular biopsies performed for infertility reasons during 1995-2005 at the Copenhagen University Hospital (Rigshospitalet). Biopsies were evaluated by two experienced observers independently. CIS was detected in 10 individuals, of whom three had bilateral CIS, corresponding to a prevalence of 2.2% (95% CI 1.1-4.0%). This is greater than the estimated risk of 0.45% for the age- and birth cohort-matched general Danish population. All patients with CIS testis had severe oligozoospermia (相似文献   

Microspectrophotometric DNA measurements of carcinoma-in-situ germ cells in the testis

Early detection of premalignant changes of the testis in at-risk groups seems to be of considerable significance. Hitherto the diagnosis of carcinoma-in-situ testis has been based upon conventional histological techniques. A microspec-trophotometric study of the DNA content in Feulgen stained carcinoma-in-situ germ cells of eight infertile men revealed an aneuploid DNA distribution pattern. The results support the assumption that these cells are of malignant nature, and furthermore, the findings indicate that DNA measurements may be of value in discriminating between malignant and non-malignant intra-tubular germ cells in testicular biopsies.     

Testicular biopsy as an outpatient procedure in screening for carcinoma-in-situ: complications and the patient's acceptance

Testicular biopsy has been performed as a simple outpatient procedure to facilitate screening purposes. The target population was men aged 20–30 years with previous cryptorchidism, and the aim of the study was to discover carcinoma-in-situ. When results from the first 209 consecutive males were assessed, very few and minor complications were encountered. Only three patients needed hospitalization for drainage of pus from the wound. The effects of the procedure as experienced by the patients were evaluated by a questionnaire. 72% of the patients found the method acceptable. The advantages were the patients' minimal absence from their jobs, and the low consumption of resources.     

Histological and hormonal testicular function in oligo/azoospermic infertile men

We characterised and correlated the histological and hormonal aspects of a cohort of 261 azo/oligozoospermic men, applying a quantitative/qualitative evaluation of testicular tissue and serum and intratesticular hormonal measurements. One hundred and 93 azo?oligozoospermic patients were diagnosed as: complete sertoli cell only syndrome (cSCOS), n = 76; focal SCOS, n = 31; maturation arrest, n = 34; hypospermatogenesis, n = 17; mixed atrophy, n = 25; and severe atrophy, n = 10. Normal spermatogenesis was observed in 68 infertile men (controls). Patients with cSCOS, focal SCOS, mixed and severe atrophy had larger LC/clusters (11.5; 11.0; 10.7; 18.9 LC/cluster) than controls (6 LC/cluster; P < 0.001). cSCOS, focal SCOS, mixed and severe atrophy patients had higher FSH, LH and lower T/LH ratio serum levels than the other groups. Intratesticular testosterone concentrations were higher in tissues with complete or focal SCOS (45.6 ng mg^?1 protein) and mixed atrophy (79.0 ng mg^?1 protein) than normal tissues (20.3 ng mg^?1 protein; P = 0.03 and P = 0.007). Considering all subjects, significant correlations were found between T/LH ratio and Leydig cells/cluster (r = 0.510, P < 0.001), FSH levels (r = ?0.692, P < 0.001) and with intratesticular testosterone (r = ?0.354, P = 0.001); these correlations follow the pattern of severity of spermatogenic damage. By a thorough histological evaluation, we validate the concept that the severity of spermatogenic impairment is associated with major morphological and functional disturbance of the Leydig cell compartment.     

Bilateral testicular germ cell tumours: a systematic review

What's known on the subject? and What does the study add? Bilateral testicular germ cell tumours (BTGCTs) are rare neoplasms. Most previously published studies consist of case reports or small retrospective case series. Little is known about their epidemiological and clinicopathological characteristics. BTGCT corresponded to 1.82% of testicular tumours. Metachronous disease was about twice as frequent as synchronous disease. The primary tumour histology, chemotherapy use and the interval between metachronous tumours influenced the histology of the second tumour. Overall, synchronous tumours were associated with more advanced disease and presented less favourable survival rates than metachronous tumours. Testicular cancer is the most common tumour in young men. It is known that a second primary contralateral testis tumour may occur in up to 5% of men with a proior tumour. About 35% of these men present with synchronous tumours, and 65% present with metachronous tumours. However there is little data about bilateral testicular germ cell tumours (BTGCT) in the literature and the most published articles are case reports on a small series of men, which makes it difficult to draw conclusions about therapeutic strategies for the treatment of BTGCTs. In fact, current guidelines for the treatment of testicular cancer contain little information related to bilateral disease. Therefore, the aim of our study is to provide a broad overview of BTGCT and to update data focusing on incidence, pathological features, and clinical outcomes of men with BTGCTs. Thus, an extensive review containing 94 studies and more than 50,000 patients was conducted.     

Experimental testicular germ cell tumorogenesis in mouse strains with and without spontaneous tumours differs from development of germ cell tumours of the adult human testis

The aim of this study was to undertake a morphological analysis of the earliest stages of experimentally induced (by genital ridge grafting) germ cell tumours in mouse strains with (129/Sv-ter) and without (MA) spontaneous tumorogenesis. Genital ridges from fetuses aged 12 or 13 days from 129/Sv-ter and MA were transplanted into the testes of adult 129/Sv-ter . The results show clearly that experimentally induced carcinoma-in-situ in mouse testes differs considerably from its human counterpart, found in patients with and without testicular germ cell tumours, and considered to be the precursor for all kinds of germ cell tumours of the adult testis apart from spermatocytic seminoma. The results indicate that development of testicular germ cell tumours is different in man and the mouse.     

Androgen receptor-CAG repeats in infertile Egyptian men

This study aimed to assess the androgen receptor (AR) codon amino acids glutamine (CAG) repeats in 185 Egyptian men divided into fertile controls (n = 30), oligoasthenoteratozoospermic (OAT) men (n = 35), nonobstructive azoospermic (NOA) men (n = 120; 18 successful testicular sperm extraction (TESE) and 102 unsuccessful TESE cases). They were subjected to history taking, genital examination, semen analysis, testicular biopsies for NOA cases, serum hormones and CAG repeats by PCR. The mean AR-CAG repeats showed significant difference between NOA group compared with fertile controls or OAT groups. Nonsignificant difference was elicited between OAT group and fertile controls. In NOA cases, CAG repeats demonstrated nonsignificant difference between unsuccessful and successful TESE. AR-CAG repeats elicited significant negative correlation with sperm count, significant positive correlation with sperm normal forms percentage and nonsignificant correlations with sperm motility per cent, tested serum hormones or testicular volume. It is concluded that AR-CAG repeats in Egyptian infertile men are in the range of other international or regional studies. AR-CAG repeats have demonstrated nonsignificant difference regarding TESE outcome in NOA cases.     

Screening for carcinoma-in-situ of the testis

Germ cell neoplasia detected at the preinvasive stage of carcinoma-in-situ (CIS) can be cured by orchidectomy or by localized irradiation of the testis. Therefore, screening for carcinoma-in-situ of the testis has been applied to groups of individuals known to have an increased risk of testicular cancer. A high (5.5%) incidence of CIS was found in the contralateral testis of men with a unilateral cancer of the testis. An increased incidence of CIS was also found among men with a history of cryptorchidism. We recommend routine screening for CIS of the testis in both groups of men. The role of screening for CIS among subfertile men remains to be elucidated.     

不育男性双侧Ⅰ度精索静脉曲张对睾丸体积和生殖激素水平的影响

目的 评价不育男性双侧I度精索静脉曲张对睾丸体积和生殖激素水平的影响.方法 185例不育男性双侧I度精索静脉曲张(A组)和149例正常生育男性(B组),比较其睾丸体积、卵泡刺激素(FSH)、黄体生成素(LH)和睾酮(T)水平.结果 A组患者两侧睾丸体积均小于B组,但睾丸体积绝对差异和睾丸体积相对差异与B组比较,无统计学意义.A组患者血清FSH水平高于B组,而LH、T与B组相比,差异无统计学意义.结论 不育男性双侧I度精索静脉曲张可导致患者双侧睾丸体积减小,血清FSH水平升高.     

Mast cells in testicular biopsies of infertile men with 'mixed atrophy' of seminiferous tubules

Mast cells in the bilateral testicular biopsies of 30 patients with a 'mixed atrophy' of seminiferous tubules were analysed. Seven biopsies from vasectomized patients served as controls. With regard to their characteristic location within testicular tissue, two groups of mast cells could be distinguished, in both control and infertile patients: 'interstitial' mast cells (located between Leydig and other interstitial cells as well as in the vicinity of blood vessels) and 'peritubular' mast cells (located in the close proximity of the tubular lamina propria or incorporated in the lamina propria itself). Morphometric data indicated a significant increase in the number and volume of mast cells in infertile patients when compared with controls. In the biopsies of infertile patients that were analysed both 'interstitial' and 'peritubular' mast cells showed a significant increase in their number and volume, although it appeared that 'peritubular' mast cells increased at a higher rate than 'interstitial' mast cells. A significant negative correlation was found between the following variables: volume and number of mast cells, testis volume and the status of spermatogenesis evaluated by Johnsen's scoring. It was concluded that the increased presence of mast cells is closely associated with an impairment of spermatogenesis.     

Idiopathic hemochromatosis in a 45-year-old infertile man

The clinical manifestations of primary or idiopathic hemochromatosis include mainly hepatomegaly, diabetes mellitus, and hypogonadism. Most investigators postulated that the hypogonadism is caused by pituitary dysfunction and that the deposition of iron in the testes is of little importance. We found not only pituitary failure in a 45-year-old man with idiopathic hemochromatosis (low LH and FSH levels, no response to GnRH) but could also detect by light microscopy deposition of iron in capillary endothelial cells and in the perivascular space of the testicular tissue. Electron microscopic study of tissue from the testes showed intracytoplasmic hemosiderin deposits in capillary endothelial cells. Abundant lipofuscin granules were present in Sertoli cells and Leydig cells. The serum testosterone levels were also lowered. In our opinion, the androgenic deficiency in idiopathic hemochromatosis is not only caused by pituitary failure but also by testicular dysfunction due to deposits of hemosiderin and lipofuscin in the testes.     

Presence of IL-18 in testicular tissue of fertile and infertile men

Recently, IL-18 was identified in human testes. Moreover, an inverse correlation was found between the levels of IL-18 and the number and motility of spermatozoa. We examined the presence of IL-18 protein in normal and impaired spermatogenesis. Testicular tissue specimens were taken from 25 nonobstructive azoospermic patients undergoing testicular sperm extraction and from autopsies of three healthy controls. The presence of IL-18 in human testicular cells was examined by immunohistochemical staining of paraffin-embedded sections, using a specific antibody for human IL-18. In testicular tissue of healthy controls as well as in study cases, presence of IL-18 was identified in somatic, mitotic, meiotic and post-meiotic cells in correlation with their presence. In all patients, Leydig cells were less intensively stained. Mitotic cells were immunostained in the control group and less intensively in hypospermatogenesis and maturation arrest subgroups. Primary spermatocytes were in general most efficiently stained. The expression of IL-18 mRNA (as examined by real-time PCR analysis) showed significantly lower expression in testicular tissues with impaired spermatogenesis when compared to normal tissues. We report the first study demonstrating the presence of IL-18 in human testicular tissue at the protein level. The presence of this cytokine in somatic as well as in different types of germ cells may suggest its involvement in the regulation of the spermatogenic process and steroidogenesis under physiological and pathological conditions.