[The multitasking Sertoli cell]. / Die Multitasking-Sertoli-Zelle.

Sertoli cells (SCs) play a central role in the development of the male genital organs and are absolutely necessary in the adult testis for the maintenance of a normal spermatogenesis. They form the blood-testis barrier, which is a physical barrier between the blood vessels and the seminiferous tubules. Tight junctions between the cell membranes of adjacent SCs divide the seminiferous tubule in a basal compartment (in contact with blood and lymph) and an adluminal compartment (isolated from blood and lymph).The SCs produce more than 60 proteins, of which the most important are hormones. The anti-Müllerian hormone inhibits the development of the female Müllerian ducts in the male embryo. Inhibin inhibits the production of follicle-stimulating hormone (FSH). Activin is an antagonist of inhibin and follistatin inhibits the effect of activin. Furthermore, diverse growth factors are produced, which have auto- and paracrine effects. Androgen-binding protein makes the androgen less lipophilic and becomes more concentrated within the luminal fluid of the seminiferous tubules thus enabling spermatogenesis. Ferritin is necessary for the transport of iron to the rapidly growing germ cells.SCs selectively and rapidly eliminate apoptotic residua of spermatids through phagocytosis. Moreover, as shown in animal experiments, these cells are also able to phagocytize and kill bacteria.Sertoli cell tumors are characterized by a broad spectrum of diversity ranging from highly differentiated adenocarcinoma-like types to completely undifferentiated spindled cell variants.

Ectopias of the kidney, urinary tract organs, and male genitalia.

The most frequent anomaly of the urogenital tract is a simple renal ectopia with one organ lying in the pelvis. Crossed renal ectopia is a less common condition in which the ectopic kidney is located on the opposite side of the midline from the ureteral insertion in the urinary bladder. The cause of both types of renal ectopia is the arrest or failure of the kidney ascent from the pelvic to the lumbar position. Whereas an accelerated ascent leads to a subdiaphragmal or intrathoracic ectopic position, an ectopic ureter can be defined as one that does not drain into the trigonum vesicae. The ectopic orificium can be located situated in the bladder neck and urethra as well as somewhere in the genital area.Exstrophy of the urinary bladder is not a complete ectopia. Because the abdominal wall and the anterior part of the bladder wall are lacking, the bladder mucosa grows directly into the skin. The complex exstrophy of the bladder and intestine corresponds to a cloacal exstrophy, in which the bladder is split in two halves on either side of the gut portion. Testicular ectopia refers to the location of the testis in a position outside of its normal course of descent.Prostatic ectopia does not refer to the wrong location of the entire organ, but to a scattered group of prostate glands, which are mostly found in the submucosal part of the urinary bladder or proximal urethra. Other described locations are the intestinal wall, anus, pericolic fat tissue, spleen, seminal vesicle, testis, and cervix uteri.The associated ectopic penis, scrotum, and penoscrotal transposition are the least common and probably the absolutely most unknown malformations of the male genitalia. The ectopic penis and scrotum are located in the perineum, whereas in the transposition the penis lies above the scrotum.

[Ectopias of the kidney, urinary tract organs, and male genitalia. German version.] / Ektopien der Niere, Harnwege und männlichen Geschlechtsorgane.

The most frequent anomaly of the urogenital tract is a simple renal ectopia with one organ lying in the pelvis. Crossed renal ectopia is a less common condition in which the ectopic kidney is located on the opposite side of the midline from the ureteral insertion in the urinary bladder. The cause of both types of renal ectopia is the arrest or failure of the kidney ascent from the pelvic to the lumbar position. Whereas an accelerated ascent leads to a subdiaphragmal or intrathoracic ectopic position, an ectopic ureter can be defined as one that does not drain into the trigonum vesicae. The ectopic orificium can be located situated in the bladder neck and urethra as well as somewhere in the genital area.Exstrophy of the urinary bladder is not a complete ectopia. Because the abdominal wall and the anterior part of the bladder wall are lacking, the bladder mucosa grows directly into the skin. The complex exstrophy of the bladder and intestine corresponds to a cloacal exstrophy, in which the bladder is split in two halves on either side of the gut portion. Testicular ectopia refers to the location of the testis in a position outside of its normal course of descent.Prostatic ectopia does not refer to the wrong location of the entire organ, but to a scattered group of prostate glands, which are mostly found in the submucosal part of the urinary bladder or proximal urethra. Other described locations are the intestinal wall, anus, pericolic fat tissue, spleen, seminal vesicle, testis, and cervix uteri.The associated ectopic penis, scrotum, and penoscrotal transposition are the least common and probably the absolutely most unknown malformations of the male genitalia. The ectopic penis and scrotum are located in the perineum, whereas in the transposition the penis lies above the scrotum.

[Germ cell and sex cord-stromal tumors of the testis : WHO classification 2016]. / Keimzell- und Gonadenstromatumoren des Hodens : WHO-Klassifikation 2016.

Earlier revisions of the WHO classification of testicular tumors, which was originally published in 1977, contained only minor additions. In the WHO 2016 classification, in contrast, germ cell tumors are split into two major groups based on their distinct pathohistogenesis, i. e., those which derive from an in situ forerunner lesion and those which do not. The latter category includes prepubertal yolk sac tumors and teratomas, as well as spermatocytic seminoma. The classification of yolk sac tumors and teratomas as arising before or after puberty is also of prognostic value. The group of trophoblastic tumors has also been divided into choriocarcinoma and "nonchoriocarcinomatous trophoblastic tumors," which are rare but may also be clinically significant. The changes in the classification of the sex cord-stromal tumors are not particularly important; rare variants without clinical importance of the single well-known tumors have been omitted. A new entity, a kind of "in situ" large cell Sertoli cell neoplasia, has been introduced.

[Testicular cancer - a matter of geography? Epidemiology and etiopathogenesis of germ cell tumors]. / Hodenkrebs - eine Frage der Geographie? Epidemiologie und Ätiopathogenese der Keimzelltumoren.

More than 90 % of testicular tumors are germ cell tumors. There is no doubt that ethnicity is one of the single overriding etiological factors in the development of these tumors. White males living in western industrialized countries, particularly in northern Europe show the highest incidence rates, whereas black males in Africa show the lowest. These differences are the result of interaction of genetic factors and exogenous noxious agents. Some of these agents are chemical substances with an estrogen-like effect. Many exogenous substances have been blamed for causing testicular cancer, but clear epidemiological evidence is lacking for most cases. Some well-established risk factors prevail, such as cryptorchidism, familial association, gonadal dysgenesis (intersex) and germ cell tumor in the contralateral testis. In terms of importance, overalimentation appears to outweigh occupation. The development of germ cell tumors is assumed to have an intrauterine origin through defect gonocytes which evolve into atypical germ cells of unclassified intratubular germ cell neoplasms. The trigger event is, however, the appearance of isochromosome 12p, which makes these cells aggressive and results in overt invasive testicular cancer.

[Spermatocytic seminoma. A tumor with many faces]. / Spermatozytäres Seminom. Ein Tumor mit vielen Gesichtern.

Spermatocytic seminomas affect 0.3-0.8 per one million men. This tumor is not, as the name might suggest, a variant of classical seminoma but a distinct nosological entity, which differs markedly from all other germ cell tumors in its epidemiology, peculiar morphology, oncogenesis and clinical outcome. There are no racial differences in the incidence and risk factors are completely unknown. Patients are significantly older than is the case for other germ cell tumors with an average of 53.5 years; nevertheless, more than 25 % are younger than 40 years. Spermatocytic seminoma arises from differentiated spermatogonia, not from intratubular germ cell neoplasms. The tumor-specific gain of chromosome 9 seems to be the most important event in the oncogenesis. Conventional spermatocytic seminoma consists of three different cell types which give the tumor a highly aggressive appearance, although in actual fact, the tumor has a very favorable outcome, with few reported cases of general metastatic spread. Anaplastic spermatocytic seminoma, a recently described variant, also takes mostly a benign course; however, spermatocytic seminomas combined with sarcomas are extremely malignant.

Waterjet hydrodissection: first experiences and short-term outcomes of a novel approach to bladder tumor resection.

INTRODUCTION: TURB is the standard approach to bladder tumors but suffers from several disadvantages. Waterjet hydrodissection is a new technology for removing superficial tumors in the GI tract promising to preserve the histological structures of biopsy specimens with favorable long-term results as recent studies have shown. The aim of this study was to show the feasibility and applicability of waterjet hydrodissection for removing papillary superficial bladder tumors. MATERIALS AND METHODS: In five patients diagnosed with superficial papillary bladder tumor, transurethral submucosal dissection was conducted using the T-type I-Jet HybridKnife (Erbe, Tuebingen). The resection edges were labeled by means of electrical coagulation with the HybridKnife. Subsequently, a submucosal fluid cushion specific to the tissue layer was formed by the waterjet implementation function of the HybridKnife, thereby elevating the tumorous tissue. The tumor was endoscopically extracted with a retrieval bag. Biopsy specimens of the tumor edges and base were subsequently collected. RESULTS: All tumors could be resected en bloc, and the lamina propria was intact in all specimens, allowing the pathologist to distinguish between superficial and invasive tumors. Pathological analysis confirmed R0 resection in all samples. CONCLUSION: These initial results prove the feasibility of waterjet hydrodissection for removing bladder tumors. In contrast to conventional TURB, this new technique allows the pathologist to assess the entire lamina propria and the resection edges due to the en-bloc resection and to determine invasiveness as well as R0 versus R1 resection. These first results are promising, long-term oncological follow-up, and prospective randomized surveys investigating the recurrence rate have to be evaluated.

Pathology without microscope: From a projection screen to a virtual slide.

We have witnessed successive stages since the Seventies in the advancements towards digital pathology. We agree with Dr Pallua et al on the tremendous changes that are taking place in pathology, all leading toward greater role of digitalization in the field of pathology, both in terms of consultation and teaching. In particular, distance teaching using digital pathology will grow into a mainstream mode of pathology teaching, something that has been reinforced by COVID-19.

Handling and reporting of radical prostatectomy specimens in Europe: a web-based survey by the European Network of Uropathology (ENUP).

AIMS: To survey current European practices in handling and reporting of radical prostatectomy (RP) specimens. METHODS AND RESULTS: A European Network of Uropathology (ENUP) was organized for the dissemination of information, survey studies and research collaborations. Contact data of uropathologists were collected from 321 pathology laboratories in 15 West European countries. In the first ENUP survey, 67.6% (217/321) of the members replied to a web-based questionnaire. Some practices were adopted by a large majority, e.g. inking of the specimen (96.6%), Gleason grading (99.5%), stratifying extraprostatic extension (EPE) according to extent (88.2%), reporting TNM stage (88.6%) and reporting location of positive margins (98%). As many as 71.6% of respondents always embedded the entire prostate and only 10.8% always practised partial embedding. Whole mounts were routinely used by 37.5% and standard blocks by 55.5%. Among areas with variable routines were methods to define focal versus extensive EPE and methods to quantify margin positivity, probably reflecting that the optimal method has yet to be determined. CONCLUSIONS: Some practices are almost universally adopted in Europe, whereas others still need to be standardized. The results of the study may be helpful when judging what recommendations are reasonable to issue.

Malignant mixed mullerian tumor of the urinary bladder in a 73 year old woman.

A giant tumor of the urinary bladder in a 73 year old female patient consisting of mesenchymal and epithelial parts turned out to be the first case of a Malignant Mixed Muellerian tumor of the urinary bladder.

[Testicular tumors. Predictive factors]. / Hodentumoren. Prognostische Faktoren.

Patients with germ cell tumors of the testis can be given adjuvant treatment immediately after orchidectomy or put under surveillance with definitive treatment deferred until relapse. Both therapies are equally successful (success rate 98-99%), with surveillance alone, however, only approximately 50% of cases need toxic chemotherapy. The surveillance strategy is especially successful in patients with tumors which do not have morphological predictors of metastases. In seminomas the strongest predictor of metastases is tumor invasion of the rete testis followed by the size (Ø > or =4 cm) of the tumor. Vascular invasion, the most important predictor in non-seminomatous germ cell tumors, is less important in seminomas. The second most important predictor in mixed tumors is the presence or absence and the amount of embryonal carcinoma. The presence of teratomas and yolk sac tumors are considered to be predictors of a favorable course of the disease. The statistical impact of these markers is, however, not very strong. The only reliable predictor of malignancy of the gonadal stromal tumors is the size and tumors with a diameter > or =5 cm are always malignant.

[Malignant mixed Müllerian tumor of the urinary bladder]. / Maligner Müller-Mischtumor der Harnblase.

True mixed epithelial-mesenchymal tumors of the urinary bladder are exceedingly rare, and only two vesical adenosarcomas have been reported to date. These tumors originated from bladder endometriosis, and malignant transformation of endometriosis has been described, with endometrioid and clear-cell carcinomas being the most common malignancies. We report an unusual case of a malignant mixed Müllerian tumor with heterologous rhabdomyoblastic differentiation, which originated in the urinary bladder of a postmenopausal woman. To the best of our knowledge, such a neoplasm has not yet been reported in the literature.

Sertoli-Leydig cell tumours of the ovary and testis: a CGH and FISH study.

We present two malignant cases of Sertoli-Leydig cell tumours (SLCT) of the testis and one ovarian SLCT with benign behaviour. The DNA copy number changes affected chromosome 1, 8, 9p, 10, 11, 12, 16, 19, 22 and X. The present study is the first molecular-cytogenetic analysis of Sertoli-Leydig cell tumours of the testis.

Expression and prognostic significance of Tetranectin in invasive and non-invasive bladder cancer.

Tetranectin (TN) is a plasminogen kringle-4 binding protein that can be detected in the plasma and the extracellular matrix. In malignancies, TN is thought to enhance proteolytic processes enabling tumor cells to invade and metastasize. So far, TN expression has not been described in transitional cell bladder cancer (TCC), and there is no information on the prognostic significance of its in situ expression. TN expression was studied in 99 TCC patients diagnosed between 1994 and 1997. Immunohistochemistry was performed on a tissue microarray using a monoclonal antibody against TN (clone 11F1). Within the mean follow-up period of 60 months, pTa and pT2-4 TCC patients with stainable TN in the tumor stroma had a significant shorter recurrence-free survival and higher risk of recurrence compared to those without stainable TN (p = 0.0002 for both). TN expression in the tumor cells did not influence recurrence-free survival. In conclusion, TN is expressed in a subgroup of bladder cancer patients with a higher risk of recurrence who may take benefit from a closer follow-up.

Molecular-cytogenetic characterisation of sex cord-stromal tumours: CGH analysis in sertoli cell tumours of the testis.

Sertoli cell tumours (SCT) are rare and poorly explored neoplasias, and the genetic features of these uncommon tumours are largely unknown. Data about chromosomal aberrations in human SCT of the testis are very rare. We present in this paper the first molecular-cytogenetic study of SCT of the testis. DNA was isolated from paraffin-embedded tumour material from 11 patients with unilateral SCT. We used comparative genomic hybridisation to investigate changes in DNA copy number. The detected DNA imbalances showed variation from case to case, indicating a high genetic heterogeneity. Chromosomal aberrations were detected in 9 of the 11 tumours evaluated, with 13 losses versus 14 gains. The most frequent aberrations detected were gain of chromosome X (5 of 11 cases) followed by losses of entire or part of chromosomes 2 and 19 in three cases. This study suggests a high variability in histomorphological and genetic patterns. Only gain of the entire chromosome X seems to be a frequent aberration in these tumours. Further studies of these tumour types are necessary to clarify the significance of chromosomal alterations in carcinogenesis of SCT.

Pseudoneoplastic lesions of the testis and paratesticular structures.

Pseudotumors or tumor-like proliferations (non-neoplastic masses) and benign mimickers (non-neoplastic cellular proliferations) are rare in the testis and paratesticular structures. Clinically, these lesions (cysts, ectopic tissues, and vascular, inflammatory, or hyperplastic lesions) are of great interest for the reason that, because of the topography, they may be relevant as differential diagnoses. The purpose of this paper is to present an overview of the pseudoneoplasic entities arising in the testis and paratesticular structures; emphasis is placed on how the practicing pathologist may distinguish benign mimickers and pseudotumors from true neoplasia. These lesions can be classified as macroscopic or microscopic mimickers of neoplasia.

Leydig cell tumors of the testis: a molecular-cytogenetic study based on a large series of patients.

The genetic features of the uncommon Leydig cell tumors (LCT) are largely unknown. Consequently, it is of great importance to elucidate the pathogenesis of testicular germ cell tumors by cytogenetic and molecular biological investigations. The purpose of the present study was the examination of cytogenetic features of these tumors in a large series of LCT. It comprised formalin-fixed, paraffin-embedded tissue samples from 25 LCT to analyze the chromosomal constitution using comparative genomic hybridization (CGH). In most of the studied cases, the aberrant cell population was additionally defined by interphase fluorescence in situ hybridization (I-FISH). Our molecular-cytogenetic study indicates chromosomal imbalances in the majority of our cases (21/25, 84%). The most frequent findings were gain of chromosome X, 19 or 19p and loss on chromosome 8 and 16.

Conjoined epigastric heteropagus twins: excision of a parasitic twin from the anterior abdominal wall of her sibling.

Epigastric heteropagus twins (EHT) are an exceedingly rare form of asymmetric conjoined twins in whom the dependent twin (parasite) is attached to the right or left upper abdomen of the dominant part (autosite). Such a case observed at our institution with 34 month follow-up is presented here and the surgical technique described. A magnetic resonance imaging (MRI)-supported surgical separation of the parasite with successful closure of the abdominal wall defect of the autosite was performed. Follow-up studies showed an autosite which was alive and in optimal health. A comprehensive review including data from English and non-English literature is presented.