Case of gonadoblastoma in a 9-year-old boy without physical abnormalities

BACKGROUND: A 9-year-old boy was admitted to Jikei University Hospital complaining of gradual enlarging of the left scrotal contents. METHODS/RESULTS: Physical examination was significant for bilateral descended testicles. No abnormalities were detected in the testicles or along the spermatic cords. Scrotal ultrasound showed that hyperechoic shadows were recognized in the central area of the left testicle. Subsequent testicular biopsy and histopathological examination showed intratubular malignant germ cells in the testicular tubules. One week later, left orchiectomy was performed. CONCLUSIONS: Histopathological evaluation revealed gonadoblastoma. Gonadoblastoma, a rare gonadal neoplasm, is composed of germ cells and sex cord derivatives and usually occurs in phenotypically female patients with gonadal dysgenesis. To date, only three cases of gonadoblastoma have been reported in anatomically normal male patients with scrotal testicles. We report on a case of gonadoblastoma unaccompanied by a germ cell tumor in a physically normal male.     

Retroperitoneal germ cell tumor with testicular calcification indicating tiny testicular origin: consideration of the origin of retroperitoneal germ cell tumors: report of two cases

Two cases of germ cell neoplasm retrospectively considered to have been of testicular origin are reported. Case 1. A 19-year-old male with brain, liver and retroperitoneal tumors was diagnosed with yolk sac tumor by retroperitoneal tumor biopsy. After multidisciplinary treatment, a region of calcification was detected in the left testis on scrotal sonography and left high inguinal orchiectomy was performed. Case 2. A 57-year-old male with neck, lung and retroperitoneal tumors was diagnosed with yolk sac tumor by supraclavicular biopsy. From initial examination, scrotal sonography revealed a small calcified lesion in the right testis. After chemotherapy, high inguinal orchiectomy and retroperitoneal lymphadenectomy were simultaneously performed. Pathologic evaluation of these testicular specimens revealed calcification and a fibrous scar in correspondence with the clinical diagnosis. These changes were considered as scars of the primary testicular tumor due to burned-out tumor or the result of reaction to chemotherapy. Since a primary tumor of testicular origin may exist in the extragonadal germ cell tumor, it is important to examine the intrascrotal contents in detail in the case of so-called extragonadal germ cell tumors with palpably normal testes. In such cases, there are two possible conditions, an occult testicular tumor and a burned-out testicular tumor. We briefly reviewed 42 such cases in the Japanese literature. It appears that there are very few true extragonadal germ cell tumors, and that the possibility of primary testicular origin metastasizing from viable occult testicular tumor or burned-out testicular tumor with spontaneous regression is high in retroperitoneal germ cell tumors.     

The use of ultrasound for evaluating subacute unilateral scrotal swelling

In 15 patients with subacute (longer than 8 hours) unilateral scrotal swelling in whom the etiology was in doubt scrotal ultrasound was used to determine whether the pathological condition was intratesticular and/or extratesticular. Surgical exploration confirmed intratesticular or intratesticular and extratesticular findings in 9 patients: 8 had torsion of the spermatic cord (including a testis rupture in 1 and epididymal ruptures in 2) and 1 had a mixed germ cell carcinoma. Of the 6 patients with extratesticular findings 3 had clinical epididymitis that resolved on antibiotic therapy and 2 had what appeared to be paratesticular hematomas with normal testes presumed to be secondary to minor trauma. The condition resolved with conservative therapy in the latter 2 patients. The remaining patient required surgical drainage because of the size and an epididymal rupture suspected by the ultrasound examination. Scrotal ultrasound is a quick, noninvasive, easily applied, accurate method to diagnose scrotal pathological conditions and should be used whenever the etiology of scrotal swelling is in doubt.     

Leydig cell hyperplasia in cryptorchid patients: Quantitative evaluation of Leydig cells in undescended and contralateral scrotal testes

Summary Leydig cell number was evaluated quantitatively in testicular biopsies from post-pubertal cryptorchid patients and normal controls. For this quantitative evaluation we used the following method. This is based on the determination of the total number of Leydig cells, Leydig cell clusters and seminiferous tubules in the entire histologic sections of each biopsy and the determination of the following indices; mean Leydig cells per tubule, mean Leydig cell clusters per tubule and mean Leydig cells per cluster. In addition, the numbers of Sertoli cells were counted, and Leydig-Sertoli cell ratio was also determined. These indices were correlated with each other. All indices were significantly elevated not only in undescended but in contralateral scrotal testes of the cryptorchid patients in comparison to those in normal controls. Between undescended and descended scrotal testes of the same individual patients, those indices were significantly higher in the descended scrotal testes than in the undescended ones. Thus, Leydig cell hyperplasia was noted in the testes of post-pubertal cryptorchid patients, and was more prominent in the contralateral scrotal testes than in the undescended ones.     

Testicular ultrasonography after chemotherapy for germ cell neoplasm: significance of highly hyperechoic lesions.

The sonographic appearance of the testis after administration of chemotherapy for metastatic germ cell neoplasm is not well known. Fifty-six patients (60 testes) who were previously treated with chemotherapy for metastatic germ cell neoplasm (originally diagnosed by removal of the contralateral testis or by biopsy of metastatic disease) underwent sonography followed by orchiectomy. The sonographic characteristics found to predict viable intratesticular tumor were: lesion size larger than 5 mm, fewer echoes than adjacent parenchyma (hypoechoic), inhomogeneous echo texture, poor margin definition, cystic areas, or highly hyperechoic foci within a hypoechoic lesion. Fibrosis was predicted by finding single or multiple small, highly hyperechoic lesions. These results suggest the potential for predicting the pathologic diagnosis in some patients after receiving chemotherapy for germ cell neoplasm.     

Experimental production of testicular teratomas in the mouse

Testicular teratomas are congenital tumours that are extremely rare in mice except for the inbred strain 129 and strains derived from it. A third of the males of strain 129/Sv- ter has spontaneous teratomas. Teratomas may be easily produced experimentally in some inbred strains and hybrids by grafting genital ridges from male foetuses 12 days of gestation to scrotal adult testes. The grafted genital ridges develop into well formed testes and most of them have teratomas composed of many kinds of well differentiated tissues derived from all 3 germ layers. Experimentally induced teratomas may be recognized as early as six days after grafting when they are composed of small clusters of embryonal carcinoma cells. The low temperature of the scrotal testis is a critical factor in experimental teratocarcinogenesis. When genital ridges from genetically sterile (S1/S1) foetuses that lack germ cells are grafted, they develop into testes without teratomas whereas grafts from testes that develop from their normal littermates do have teratomas. This demonstrates that testicular teratomas are derived from primordial germ cells.     

Quantification of survivin mRNA in testes of infertile patients and in testicular germ cell tumours: high levels of expression associated with normal spermatogenesis

Deregulated apoptosis of germ cells may contribute to male infertility as well as malignant transformation. Survivin, an inhibitor of apoptosis (IAP), is overexpressed in all the most common human malignancies, but barely detectable in normal tissues. We used real-time polymerase chain reaction (PCR) to quantify survivin mRNA expression in normal testes (n = 22), testes with defective spermatogenesis (n = 26) and testicular germ cell tumours (TGCTs; n = 16). Survivin was expressed at high levels in normal testes. Testicular survivin levels in infertile patients were related inversely to the severity of spermatogenic failure (p < 0.001), with a lack of expression in most specimens with pre-meiotic spermatogenic arrest and in all those with germ cell aplasia. Lower levels of expression were observed in TGCTs than in normal testes. While survivin expression was detected in most TGCTs with undifferentiated components (12 of 13), it was absent in all mature teratomas (n = 3). These data show that survivin is expressed in normal and transformed germ cells. Its downregulation in spermatogenic disorders indicates that survivin may contribute to the normal balance between germ cell proliferation and apoptosis. In TGCTs, survivin expression appears to be lost with somatic differentiation.     

Postpubertal cryptorchism. Morphofunctional study with special reference to Leydig's cells

In a group of 17 patients of postpubertal age with unilateral (n = 15) or bilateral (n = 2) cryptorchism, a significant decrease in the tubular diameter was observed, in addition to Leydig cell hyperplasia (many with cytoplasm vacuolization and/or atrophy) in both the cryptorchid testes and in the contralateral scrotal testes. The number of testosterone-positive Leydig cells in testicular tissue sections, studied with peroxidase-antiperoxidase, was diminished in the cryptorchid testes, whereas in the contralateral scrotal testes it was similar to the control group. Together with normal testosterone levels and elevated luteinizing hormone and follicle-stimulating hormone levels in peripheral blood, this leads us to think of a compensated dysfunction of the Leydig cells. This possible lower testosterone production by the Leydig cells in the cryptorchid testis is not borne out morphologically, where the volume of the organelles is similar to the contralateral scrotal testes.     

Scrotal ultrasonography: should it be used in routine evaluation of infertile men?

Several studies have suggested that male infertility and testicular cancer may have common aetiological factors. Scrotal ultrasonography (US) has an important role in the diagnosis of testicular tumours when not palpable by physical examination. In this study, we present two infertile men referred to our clinic. Patients were evaluated by a detailed physical examination, semen analyses and hormonal assessment. Both patients underwent scrotal US examination. Semen analysis of the patients revealed oligoasthenospermia in both patients. Scrotal US revealed hypoechoic masses in the left and right testes of both patients, which were nonpalpable by physical examination. Scrotal exploration and subsequent orchidectomy were performed. Histopathological examination revealed mixed germ cell tumour and Sertoli-Leydig cell tumour in case 1 and case 2 respectively. With these cases, we discussed the role of scrotal US in the routine diagnostic evaluation of infertile men.     

Morphology and histochemistry of infant testes in the prune belly syndrome.

Testicular biopsy samples from 3 boys 5.5, 6 and 7 months old with the prune belly syndrome and intra-abdominal testes were examined morphologically and phenotypically for the presence of alkaline phosphatase. Findings were compared with those in age-matched autopsy controls. All patient specimens demonstrated atypical germ cells with large nuclei and prominent nucleoli, and intense alkaline phosphatase staining localized to the cytoplasmic membrane. The presence of these testicular abnormalities suggests that a developmental arrest is fundamental to the pathogenesis of the undescended testes associated with the prune belly syndrome. The similarity of the histological appearance of these testes to that of intratubular germ cell neoplasia suggests that long-term followup of these patients for the development of invasive germ cell tumors is important.     

Mixed germ cell tumor after bilateral orchidopexy in persistent Müllerian duct syndrome with transverse testicular ectopia

The persistent müllerian duct syndrome is characterized by the retention of müllerian derivatives (fallopian tubes, uterus) in patients otherwise normally virilized, usually with cryptorchidism or an inguinal hernia. Very rarely, this syndrome is associated with transverse testicular ectopia, which designates the condition when both testes descend through the same inguinal canal into the same scrotal sac. We report on a patient with both conditions, who had T1N2M0 scrotal mixed germ cell tumor of the testis (teratoma and embryonal carcinoma), 18 years after bilateral orchidopexy. The literature concerning this uncommon association is reviewed.     

Effect of unilateral cryptorchidism on the intertubular tissue of the adult rat testis: evidence for intracellular changes within the Leydig cells

Adult male rats were made unilaterally cryptorchid for 1, 2 or 4 weeks, and the morphological response of the Leydig cells was then studied using morphometric assessment of total Leydig cell volume and number per testis in abdominal and scrotal testes. Serum hormone levels were measured and the steroidogenic properties of isolated Leydig cells were evaluated by in-vitro stimulation with hCG and interstitial fluid (IF) obtained from normal rat testes. Total Leydig cell volume and number per testis were not altered in abdominal vs scrotal testes, although the volume of the abdominal testis was 46, 29 and 21%, respectively, of the volume of the contralateral scrotal testis after 1, 2 and 4 weeks. This reduction was accompanied by significant (P less than 0.05) elevation of the serum levels of FSH and LH, although serum testosterone levels were unchanged from the normal range. Despite the lack of quantitative alterations in Leydig cell morphology, hCG- and IF-stimulated testosterone production was significantly (P less than 0.01) greater by abdominal Leydig cells when compared with scrotal Leydig cells derived from the same animals. Ultrastructural examination of Leydig cells in situ suggested an increase in volumetric density of mitochondria in abdominal Leydig cells. Together with the enhanced steroidogenic responses of these cells, these findings suggest that disruption of spermatogenesis in the cryptorchid testis is accompanied by intracellular activation of Leydig cells. Since these effects were not exhibited by Leydig cells from the scrotal testis it is concluded that local factors within the cryptorchid testis are responsible, at least in part, for regulation of Leydig cell activity.     

端粒酶hTERT基因在男性不育症病人睾丸组织中的表达及其意义

目的 :研究端粒酶hTERT基因在男性不育症病人睾丸组织中的表达及其意义。　方法 :应用核酸原位杂交技术检测 4 7例男性不育症病人和 10例正常睾丸组织中端粒酶hTERT基因的表达和定位 ,并应用HPIAS 10 0 0高清晰度图像处理系统对hTERT阳性信号进行图像分析。　结果 :端粒酶hTERT基因阳性表达与生殖细胞 (精原细胞、精母细胞、精子细胞 )的分布定位一致 ,并且其表达强度与男性不育症病人睾丸组织中的生殖细胞的数量和密度显著相关 ,在唯Sertoli细胞综合征病人睾丸组织中无端粒酶hTERT基因的表达。　结论 :端粒酶活性的缺乏可能是生殖细胞发育停滞的原因之一     

Local regulation of Leydig cells by the seminiferous tubules. Effect of short-term cryptorchidism

Unilateral cryptorchism was induced in adult rats for 24 h, and its effect on testicular morphology and intratesticular testosterone concentration after hCG-stimulation were studied. In seminiferous, tubules from abdominal testes an increased number of degenerating germ cells was noted in stages XIV-III of the spermatogenic cycle and Sertoli cells contained an increased amount of lipid droplets in stages XIV-VIII. However, germ cells and Sertoli cells from tubules at other stages of the cycle appeared unaffected. In scrotal testes the size of peritubular Leydig cells varied in phase with the spermatogenic cycle. The largest cells were found adjacent to stage VII-VIII and the smallest adjacent to stage XI-XII. In abdominal testes no stage-dependent variation in the size of peritubular Leydig cells was seen. Perivascular Leydig cells were of equal size in abdominal and scrotal testes. The testicular testosterone concentration following stimulation with a low dose of hCG was significantly lower in abdominal testes. It is suggested that the seminiferous tubules locally modulate Leydig cell function and that the stage specific stimulatory influence from stage VII-VIII is rapidly lost during experimental cryptorchidism.     

Sonographic testicular microlithiasis as an indicator of premalignant conditions in normal and infertile men.

Sonographic detection of multiple, small hyperechogenic lesions in the testis (testicular microlithiasis; TM) can indicate germ cell tumors. However, it has not been well established whether this finding signifies a risk factor for development of testicular neoplasm in all cases or whether it indicates premalignant changes only in those men with additional risk factors for germ cell cancer, such as infertility, a history of testicular maldescent, or the presence of an atrophic testis. In a retrospective analysis of 1701 consecutively performed scrotal sonographies of patients with (n = 1399) and without (n = 219) infertility or with contralateral testicular tumors (n = 83), the prevalence of TM was compared with that in 198 healthy men who volunteered for different clinical trials. TM was equally frequent in all groups (2.3% [32/1399] of infertile patients, 2.3% [5/219] of other patients without infertility, and 1.5% [3/198] of healthy men). Results of testicular biopsies were available for a subgroup of infertile men. Carcinoma in situ (CIS) was present only in cases with TM (2/11). In addition, sonographic follow-up examinations were performed in another 14 men with TM. Testicular tumors had developed in 2 patients, one whom was infertile and one in the control group. None of these patients had a history of testicular maldescent but all testes affected either by CIS or tumors were reduced in volume. We conclude that diagnosis of TM, especially if it is present in an atrophic testis, demands a diagnostic biopsy or at least sonographic follow-up examinations.     

Expression of telomerase gene hTERT in testis of infertile male and its significance

Expression of telomerase gene hTERT in testis of infertile male and its significance     

Specific localization of the basigin protein in human testes from normal adults, normal juveniles, and patients with azoospermia

Basigin is a transmembrane protein belonging to the immunoglobulin superfamily. Specific localization of the protein in normal human testes, from those of a 2-year-old boy to those of a 50-year-old man, and in testes with Sertoli cell only syndrome and germ cell arrest, is reported. Basigin localization was determined using an immunohistochemical technique with an antibody against human basigin. In the normal adult testes, basigin was detected at the periphery of both spermatocytes older than zygotene and round spermatids. In the juvenile testes, it was expressed in accordance with the appearance of pachytene spermatocytes. In this study, pachytene spermatocytes were detected in an 11-year-old boy. Basigin was not expressed in immature testes with germ cells younger than pachytene spermatocytes, namely in testes from boys aged 2-9 years. In testes from adult patients with Sertoli cell only syndrome, basigin was expressed at the periphery of Sertoli cells, but localization was confined to the adluminal compartment of the seminiferous tubule. In testes with germ cell arrest, the protein was expressed on germ cells from pachytene spermatocytes to step 2 spermatids, where present. The results show that in the normal human testes basigin is expressed with the onset of spermatocyte differentiation. Because human basigin is expressed in adult testes with Sertoli cell only syndrome, the protein seems to be synthesized in Sertoli cells and expression continues after these cells dedifferentiate in the seminiferous epithelium.     

A rare diagnosis： testicular dysgenesis with carcinoma in situ detected in a patient with ultrasonic microlithiasis

A rare case is presented where a dysgenetic testis with microinvasive carcinoma in situ （CIS, also known as intratubular germ cell neoplasm of unclassified type [IGCNU] and testicular intraepithelial neoplasia [TIN]） with microinvasion to rete testis and the interstitial tissue was found in a 32-year-old man presenting with mild scrotal pain and ultrasonic testicular microlithiasis. Knowledge of the association of ultrasound and CIS is important to diagnose patients at the stage prior to development of an overt germ cell tumor. The patient had three of four disorders considered symptoms of the testicular dysgenesis syndrome （TDS）： a dysgenetic left testicle with CIS, a mild left-sided cryptorchidism （high positioned scrotal hypotrophic testis） and a slightly reduced semen quality. Therefore, it should be kept in mind that a patient with one TDS symptom may harbour the other, even CIS or testicular cancer. Accordingly, patients with one TDS symptom ought to be examined for the presence of the others, and if more that one is present, extra concern is warranted.     

Adult nonpalpable testis: is laparoscopy always required?

Laparoscopy is widely used in the diagnosis and treatment of nonpalpable testes. Some nonpalpable testes are vanishing testes. In such cases, unnecessary laparoscopic interventions can be avoided by a careful selection of cases. Between 1996 and 2001, laparoscopic intervention was applied to 107 patients with nonpalpable testes. Of the cases, 23 were bilateral and 84 were unilateral. Patients were between 19 and 27 years of age (average age, 23 years). Diagnostic ultrasonography was performed in 44 of the 84 patients with nonpalpable testes. Dimensions of the scrotal testis were determined by the Prader orchiometer method. The dimensions of the opposite scrotal testis (of the scrotal nubbin) and the abdominal testis were compared with the dimensions of 20 normal, healthy individuals' scrotal testis (control group). Results were evaluated by the Mann-Whitney U test. During laparoscopy, 24 (28.5%) of the patients were found to have a vanishing testis. The vas deferens and the testicular blood vessels ended bluntly at the anterior edge of the interior inguinal ring in one patient, inside the inguinal canal in five patients, and in the scrotum in 18 patients. Among the 84 patients with nonpalpable testes, no testis was found in any of the 18 patients with palpable scrotal nubbins. The opposite scrotal testes were hypertrophic in 17 (70.8%) of 24 patients who had vanishing testis (P < .05), and they were hypertrophic in 22 (36%) of the 60 patients (P > .05) who had laparoscopically identified intraabdominal testes. We conclude that clinical and radiologic diagnosis is sufficient for adult patients with nonpalpable testicles and palpable scrotal nubbins and hypertrophic contralateral scrotal testes. Laparoscopic intervention should be applied to patients who do not have palpable scrotal nubbins.     

Is the scrotal testis normal in unilateral cryptorchidism?

Bilateral testicular biopsies were performed on 66 children undergoing orchiopexy for unilateral cryptorchidism and the tubular fertility index (TFI) recorded. The results in both the descended and undescended testes at various ages were compared with previously reported control data. There were no significant differences between the germ cell activity of the scrotal testis in cases with unilateral cryptorchidism and that of controls. By contrast, the mean TFI of the undescended testis was significantly less than that of control patients of all ages. In neither group was there evidence of a progressive loss of germ cell activity during childhood. It is concluded that there is little to be gained from very early orchiopexy, performed before the third year of life.