Germ cell tumours of the testis

The application of new techniques, particularly the identification of tumour markers, in the study of testicular germ cell tumours is presently leading to a reassessment of opinions regarding the origin and classification of these neoplasms. Some aspects of this controversy are examined.     

Germ cell tumour of testis

Germ cell tumour, though rare, represents most common malignancy among young men aged between 15 to 35 years. In 1990's dramatic improvement has taken place in survival rate of testicular tumours (from 10% in 1970's and 90% in 1990's). This has been possible because of effective diagnostic techniques, accurate monitoring with biological markers and use of effective platinum based combination chemotherapy in its management. The most significant improvement in survival rate has occurred in advanced stage germ-cell tumours. Seminomas are sensitive to radiation therapy and NSGCT (Non Seminomatous Germ Cell Tumours). are effectively treated by combination chemotherapy of 3 drugs of which Bleomycin is most expensive and many patient can not afford it and so compliance is poor. In the present series we have tried only 2 drug regimen consisting of Platinum and Etoposide (PE). Since January 1992 to December 1994, 40 cases of testicular tumours were treated. 16 cases received PEB regimen and 24 cases were treated by PE regimen of which only 6 cases in the former and 20 cases in the later group completed the scheduled course. Patients were given 6 cycles of PE regimen (inj. Platinum 20 mg/m2 D1-D5, VP-16 (ETOPOSIDE), 100 MG/M2 1.V. D1-D5) repeated every three weeks. Final evaluation was done in June 1996. 17/20 (85%) patients on PE regiment exhibited complete regression of the disease by the end of June 1996, I was lost to follow up, and 2 of them had the disease in progressive stage and were considered for another regimen. 18 months disease free survival was 85%. Table I. Royal Marsden Staging System Stage I: Disease econfined to testes Stage II: Intradiaphragmatic node involvement A: Less than 2 cm B: 2-5 cm C: Greater than 5 cm Stage III: Supradiaphragmatic node involvement Stage IV: Extralymphatic disease Lung, Liver, Bone etc.     

Germ cell neoplasms of the testis: Update for 2022

Germ cell neoplasia in situ (GCNIS) is the precursor of both seminomatous and non-seminomatous germ cell tumors. It consists of distended tubules that may have either intratubular seminoma or intratubular embryonal carcinoma cells. Many invasive non-seminomatous tumors contain a mixture of tumor types, which are reviewed here. Morphology, aided by a panel of immunostains, can determine the presence and percent of embryonal carcinoma, yolk sac tumor, choriocarcinoma, or teratoma in such tumors. Use of immunostains, required for diagnosis in perhaps 25% of testicular neoplasms, is reviewed. Changes of classification in the AJCC (8^th edition) in 2016 are discussed, including the partitioning of two tumor types: the central role of chromosome 12p amplification allows both teratoma and yolk sac tumor to be divided into prepubertal types (lacking amplification) and post-pubertal types. Occasionally, sex cord-stromal tumors, hematolymphoid tumors, or epididymal adenomatoid tumors enter the differential diagnosis of germ cell neoplasms.     

Germ cell tumors of testis, current concepts

Histological pleomorphism of testicular germ cell tumors complicates diagnosis. These tumors share highly specific differentiation properties ranging from intra-tubular neoplasia to classical infiltrating lesions. This general review presents the histopathological features and diagnostic criteria of typical forms and atypical variants. In current practice, distinction between seminoma and non-seminomatous germ cell tumors is fundamental for treatment. Histological typing of non-seminomatous tumors may be problematical, especially in "mixed" forms. Vitelline tumor variants and atypical embryonic carcinoma are described. Unlike scattered isolated syncytiotrophoblastic cells, true chorio-carcinoma is rare and must be carefully identified. Such cells are frequently associated with seminoma, embryonic carcinoma and vitelline tumors. Intra-tubular germ-cell neoplasia and gonadoblastoma, are pre-invasive lesions associated with cryptorchidism and gonadal dysgenesis. Teratomatous elements usually occur in mixed germ cell tumors. Rare pure teratoma are benign in children. On the contrary, post-pubertal forms have an unpredictable evolution.     

Orexin 1 receptor in the seminiferous tubules of boar testis: An immunohistochemical study

Orexin receptor 1 (OX₁R) and orexin receptor 2 (OX₂R) are two G-protein-coupled receptors that bind their ligands, orexin A (OXA) and B (OXB), with different affinities. The male genital system represents an important target for OXA, which appears to play a role in the control of steroidogenesis and germ cell development in the testis. It is known that among domestic breeding animals, in the boar the number of Leydig cells is very high and OXA appears to have stimulatory activity on testosterone production. In this study, we aimed to evaluate the presence of OX₁R in the boar testis in order to extend our knowledge concerning the distribution and a potential functional role of the orexinergic system in the male reproductive tract of farm animals. The presence of OX₁R immunopositive cells in seminiferous tubules of the boar testis enables us to hypothesize a possible role of OXA on male germ cells cycle in pig. Further investigations, involving functional and ultrastructural analysis, may contribute to our understanding of the role of orexins in the boar genital system.     

Electrophysiological characterization of rabbit distal convoluted tubule cell

The distal convoluted tubule (DCT) from rabbit kidney were perfused in vitro to study the conductive properties of the cell membranes by using electrophysiological methods. When the lumen and the bath were perfused with a biearbonate free solution buffered with HEPES, the transepithelial voltage (V _T) averaged –2.8±0.6 mV (n=20), lumen negative. The basolateral membrane voltage (V _B) averaged –77.8±1.1 mV (n=33) obtained by intracellular impalement of microelectrodes. Cable analysis performed by injecting a current from perfusion pipette revealed that the transepithelial resistance was 21.8±1.7 ·cm² and the fractional resistance of the luminal membrane was 0.78±0.03 (n=8), indicating the existence of ionic conductances in the luminal membrane. Addition of amiloride (10^–5 mol/l) to the luminal perfusate or Na⁺ removal from the lumen abolished the lumen negativeV _T and hyperpolarized the apical membrane. An increase in luminal K⁺ concentration from 5 to 50 mmol/l reduced the apical membrane potential (V _A) by 37.5±2.6 mV (n=7), whereas a reduction of Cl^– in the luminal perfusate did not changeV _A significantly (0.5±0.5 mV,n=4). Addition of Ba²⁺ to the lumen reducedV _A by 42.6±1.0 mV (n=4). When the bathing fluid was perfused with 50 mmol/l K⁺ solution, the basolateral membrane voltage (V _B) fell from –76.8±1.5 to –31.0±1.3 mV (n=18), and addition of Ba²⁺ to the bath reducedV _B by 18.3±4.8 mV (n=7). Although a reduction of Cl^– in the bathing fluid from 143 to 5 mmol/l did not cause any significant fast initial depolarization (1.8±1.7 mV,n=8), a spike like depolarization (14.0±2.5 mV,n=4) was observed, upon Cl^– reduction in the presence of Ba²⁺ in the bath. From these results, we conclude that the apical membrane of DCT has both K⁺ and Na⁺ conductances and the basolateral membrane has a K⁺ conductance and a small Cl^– conductance.     

Germ cell tumors of testis: histological classification of 552 cases according to the WHO-nomenclature

Using the WHO-nomenclature 552 germ cell tumors of testis were reclassified. The analysis revealed the following: germ cell tumors occur in early childhood at the age of 3 months to 3 years, in adult hood (26-35) the occurrence shows a peak, and in old aged men only some tumors are registered. No germ cell was found between 4 to 13 years. Our material comprised 245 seminomas (44.4%) and 307 non-seminomatous germ cell tumors (55.6%). In the group of tumors of one histologic type, 245 cases of seminomas represent the main part. The following subgroups were recognized: typical seminomas--229 cases (93.5%), spermatocytic seminomas--9 cases (3.7%), and anaplastic seminomas--7 cases (2.8%). In 10 seminomas (4.1%() we have found syncytiothrophoblastic giant cells. In comparison to other investigations, the number of anaplastic seminomas is very low, but on the other hand the diagnosis Of this tumor is problematic, especially, the differential diagnosis of solid variants of embryonal carcinomas. The most common non-seminomatous tumor in this group is the embryonal carcinoma (16.8%). No polyembryoma and choriocarcinoma were observed, and only 2 yolk-sac-tumors occurred in infants. The occurrence of teratomas was also low, i.e. 15 cases of mature teratoma and 13 cases of immature teratoma. In the group of tumors of more than one histologic type, cases showing embryonal carcinoma and teratoma prevail (83 tumors). In addition to this combination other common tumors of this group (contained structures of seminomas (25 cases), yolk-sac-tumors (22 cases), an choriocarcinomas (19 cases) and embryonal carcinomas and yolk-sac-tumors (13 cases). Altogether, this group comprised 72.8% of the non-seminomatous tumors. Furthermore, the peculiarities of germ cell tumors of childhood are described. In this group the mature teratomas prevail. No seminoma could be registered in infancy. The distribution of our cases among the various types and the subgroups agreed in the main classes with that reported in literature but in special differentiations there are some discrepancies. The problem of classification of germ cell tumors is discussed.     

Andrology: Germ cell and Sertoli cell interactions in human testis: evidence for stimulatory and inhibitory effects

In human Sertoli cell preparations obtained from healthy men(mean age 31.8± 6.8 years; n= 6), we have measured theproductions of lactate, 17-oestradiol, transferrin and inhibinbetween day 4 and day 5 after plating, either in the presenceor absence (hypotonic treatment of plated cells on day 2) ofgerm cells. The results, expressed per 10⁶ of cells plated/24h, showed that lacate, production was unchanged, whether ornot germ cells were present. However, if we calculated the lactateproduction per mg protein/24 h, the lactate output was decreased(30–60%) in the presence of germ cells. Whatever the modeof expression, Sertoli cell 17-oestradiol synthesis was diminished1.5-fold in the presence of germ cells. Conversely, the transferrinoutput was increased 3.2-fold in non-treated Sertoli cell preparationswhen compared to the hypotonic-treated plates. A similar observationwas recorded for the in-vitro production of inhibin by Sertolicells, which was enhanced 1.4-fold when germ cells were present.These results, together with a likely potentializing role ofgerm cells on follicle stimulating hormone control of Sertolicell function, strongly suggest that germ cells exert both stimulatoryand inhibitory effects in regulating human Sertoli cell functionthrough either direct contact and/or via secreted factors.     

Morphometric study of testis of Wistar rat after open-ended vasectomy

The effects on the testis of open-ended vasectomy in the Wistar rat have been assessed morphometrically and evaluated statistically at 1, 4, 12, and 24 weeks after operation, and compared to those in sham-operated controls. The open-ended technique, ie, without ligation of the epididymal end of the cut ductus deferens, allowed drainage of sperm into the spermatic cord. During the period of our study, it did not affect the structure of the testis; although the germinal epithelium, basement membrane, and the stroma and cells of the interstitial space all showed variations when compared to the control group, these were not statistically significant.     

The oligosaccharidic content of the glycoconjugates of the prepubertal descended and undescended testis: lectin histochemical study

The saccharidic content of the glycoconjugates has been studied in the descended the undescended testes of a 8 years old boy. For this purpose, a battery of seven HRP-conjugated lectins (SBA, DBA,PNA,WGA,UEAI, LTA and ConA) was used. D-galactose-N-acetyl-D-galactosamine and alpha-L-fucose sugar residues, which were present in the cytoplasm of the Sertoli cells of the normally positioned prepubertal testis, were not detected in the same cells of the undescended testis. The Leydig's cells of the descended testis appeared characterized by N-acetyl-D-glucosamine which was absent in the rare and atrophic Leydig's cells of the cryptorchid testis. Differences in sugar residues distribution between the descended and the undescended testis were also detected in the lamina propria of the seminiferous tubules. Peritubular myoid cells in the undescended testis only reacted with PNA, after neuraminidase digestion, thus revealing the presence of D-galactose (beta1-->3)-N-acetyl-D-galactosamine and sialic acid. In this study a complete distributional map of the sugar residues of the glycoconjugates in the descended and undescended prepubertal testis is reported.     

Elastic tissue in the limiting membrane of the human seminiferous tubule

The structure and distribution of elastic tissue were studied in the limiting membrane of the seminiferous tubule from normal human testis. The elastic and elastic-related fibers (oxytalan and elaunin) were recognized by their tinctorial and ultrastructural characteristics. The connective structures of the limiting membrane, including the fibrotubules and the amorphous material of the elastic system, were studied after tannic acid-glutaraldehyde fixation. Fibrotubules (oxytalan fibers) were observed in almost all intercellular spaces of the limiting membrane, closely related to the contractile cells; the elaunin fibers (patches of amorphous material surrounded by bundles of fibrotubules) were evident in the outermost layers. The function of this system of elastic tissue and myoid cells is discussed, considering the permeability of the limiting membrane and the role of the myoid cells in the elastogenesis and contractility of the seminiferous tubule.     

Degeneration of the seminiferous epithelium following epididymal obstruction in prepubertal rats

The development of the testes was studied in rats following prepubertal obstruction of the epididymis. Male rats received bilateral ligation of the corpus epididymidis or a sham operation at 10 days of age, and temporal changes in testicular morphology and weights of reproductive organs were determined at intervals spanning sexual maturation. Development of the testes was normal through 35 days of age. The initial histological changes in the testes of ligated animals, observed at 56 days, included an increased diameter of the seminiferous tubule lumen, depletion of spermatids, and the presence of multinucleate spermatids. Subsequently, germ cells were greatly depleted in the testes of 91‐ and 128‐day‐old rats with ligated epididymides. After puberty, testicular weight and volume declined relative to corresponding sham‐operated animals. On the other hand, the weights of the epididymides in ligated animals prior to puberty significantly exceeded those of sham‐operated rats but weighed significantly less than those of rats in the sham group after sexual maturation. Testicular alterations occurred after increases in the weights of the epididymides. Testicular changes may have contributed to rather than resulted from an autoimmune response to spermatozoa because testicular alterations preceded increases in antisperm autoantibodies. Anat Rec 254:76–86, 1999. © 1999 Wiley‐Liss, Inc.     

Germ cells influence cord formation and leydig cell gene expression during mouse testis development

Results: We now demonstrate that development of the mouse fetal testis is compromised in the absence of germ cells. Using two‐ and three‐dimensional imaging techniques, we reveal that W^e/W^e mutant testes devoid of germ cells have misshapen and poorly organized cords. We also found that mutant gonads have fewer Sertoli cells than normal and that the Leydig cells express key markers at higher than normal levels. 相似文献   

Distribution of actin in isolated seminiferous epithelia and denuded tubule walls of the rat

We have studied the distribution of actin, using NBD-phallacidin as a probe, in isolated sheets of seminiferous epithelia and denuded tubule walls of the rat. Sheets of intact seminiferous epithelia were separated from tubule walls using EDTA in PBS. The isolated epithelia and denuded tubule walls were fixed, mounted on slides, made permeable with cold acetone (-20 degrees C), and then treated with NBD-phallacidin. Actin was observed in myoid cells, in ectoplasmic specializations of Sertoli cells, and in Sertoli cell regions adjacent to tubulobulbar processes of late spermatids. In myoid cells, filament bundles course in circular and longitudinal directions relative to the tubule wall. In Sertoli cells viewed at an angle perpendicular to the epithelial base, actin filaments in ectoplasmic specializations adjacent to junctional complexes circumscribe the bases of the cells. Filament bundles in ectoplasmic specializations adjacent to germ cells closely follow the contour of and are arranged parallel to the long axis of the developing acrosome. Sertoli cell regions adjacent to tubulobulbar processes of late spermatids stain intensely with NBD-phallacidin. Isolated seminiferous epithelia, combined with NBD-phallacidin as a probe for actin, provide an ideal model system in which to study further the contractile properties of Sertoli cell ectoplasmic specializations and the possible involvement of these structures in events that occur during spermatogenesis.