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Carcinoma of the rete testis is a rare malignant tumor which frequently occurs in middle-aged to older patients and has an aggressive biological behavior. We present the case of a 57-year-old man who presented with an ill-defined mass in the right testicle. The patient underwent a radical orchidectomy. Microscopic evaluation showed a neoplasm displaying a complex papillary-cystic architecture, infiltrating the testicular parenchyma. An in situ proliferation of neoplastic cells, with nuclear stratification and scanty cytoplasm was seen at the periphery, within the channels of the rete testis. The tumor infiltrated the tunica albuginea focally without disrupting it completely. Immunohistochemistry was positive for AE1/AE3, CK7, CK34βE12, D2-40, and PAX8. Imaging studies presented no evidence of metastatic disease. These findings are those of a primary rete testis carcinoma. The transition between benign and neoplastic rete testis epithelium served as a helpful diagnostic clue. Metastatic carcinomas from other sites were considered in the differential diagnosis., (Copyright © 2020 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Adenocarcinoma of the rete testis is rare and its etiological and pathologic characteristics are not well studied. We therefore investigated the clinical, morphologic, and immunohistochemical features of 6 cases diagnosed at our institution and conducted a detailed review of the literature. The mean age was 64 years. All patients presented with testicular masses; 4 were right-sided. On gross examination, all tumors were centered in the hilum and had solid and cystic cut surfaces. Microscopically, all had intrarete and invasive growth and showed multiple patterns, with a variable proportion of papillary, solid and glandular morphology, the latter varying from slit-like lumens to well-formed glands and tubules. Less common patterns included corded/trabecular (n=3), cribriform (n=3), glomeruloid (n=3), nested (n=2), and micropapillary (n=2). Discrete nests of eosinophilic and clear cells were a distinctive feature in 3 cases. Geographic necrosis occurred in 3 cases. All showed at least moderate nuclear pleomorphism with ovoid nuclei. Transition from benign to malignant rete epithelium was seen in all cases. The stroma was hyalinized to partially fibrotic. On immunohistochemical study, the tumor cells were positive for CK7 (5/5), AE1/AE3 cytokeratin (5/5), EMA (5/5), vimentin (5/5), EpCAM (detected by BerEP4 anitbody) (4/5), CK5/6 (4/5), nuclear Wilms Tumor-1 (4/5), epithelial specific antigen (detected by MOC31 antibody) (3/4), PAX8 (3/5), and calretinin (2/5). OCT3/4, SALL4, CD30, NKX3.1, PSA, α-inhibin, CK20, and S100 protein were negative. Ki-67 proliferative index ranged from 5% to 60% (mean: 40, median: 43). At presentation, 5 patients had retroperitoneal lymph node metastasis and one of these also had pulmonary metastases. The sixth patient developed pulmonary metastasis within 15 months of diagnosis. Three died within 4 years of diagnosis. In summary, adenocarcinoma of the rete testis is a rare malignant tumor with poor survival and a high propensity for retroperitoneal lymph node metastasis that must be distinguished from other testicular neoplasms and metastasis to the testis. Hilar localization, transition from benign to malignant rete epithelium, and supportive immunostains aid its accurate diagnosis.

Sertoliform cystadenoma of the rete testis (SCRT) is rare with only 9 cases reported to date in the literature, none with follow-up. Four large genitourinary pathology consult services were searched. We identified 15 cases of SCRT. Men were 21 to 84 years old (mean, 46 y) and had testicular discomfort or mass. Other findings were seminoma (n=1), spermatocele (n=2), hydrocele (n=1), varicocele (n=1), and scrotal hematoma (n=1). Eight had preoperative serum tumor markers, which were normal. Tumors ranged from 0.3 to 4 cm (mean, 1.5 cm). All of them were well circumscribed with solid and cystic features and occupied on average, 73% of the rete (20% to 100%). The tumors were mostly confined within dilated channels of the rete testis and showed classic features consisting of: (1) tubules with well-formed lumina in 87% of cases; (2) well-formed tubules with no lumina in 87% of cases; and (3) cords/nests in hyalinized or myxoid stroma in 73% of cases. Other patterns included: (1) solid/sheet growth in 26% of cases; (2) individual cells in 13% of cases; (3) festoons in 13% of cases; (4) branching tubules in 7% of cases; and (5) papillary in 7% of cases. Cells were cuboidal with round to oval nuclei with small nucleoli, except at the periphery where projections into rete tubules had a more columnar appearance. In the festooning pattern, nuclei were pseudostratified and columnar with prominent nucleoli and nuclear grooves. In 4 cases, tumor extended into adjacent seminiferous tubules surrounded by dense peritubular fibrosis, with in some cases small cysts lined by flattened epithelium containing pale lightly granular material. All cases lacked necrosis and significant atypia. Mitoses ranged from 0 to 2 per 10 high-power field. Follow-up ranged from 4 to 170 months with mean of 97 months. For the 13 cases with information, all patients were alive, except for 3 who died of either unrelated causes (9.2 and 10 y) or of unknown cause (4.8 y at age 89 y). We performed immunohistochemistry for steroidogenic factor 1 and inhibin in 4 of our cases, where 3 (75%) were positive for both markers. We also describe 2 additional cases which morphologically resembled SCRT but had more atypical features. This study highlights that SCRT has variable morphology. We also verify the benign nature of the lesion and its lack of association with any syndromes.

Sertoliform cystadenoma of the rete testis represents an uncommon benign tumour. They appear in patients from 26 to 62 years of age. We describe a case of a 66-year-old man with a tumour in the area of the epididymal head. The tumour markers were not increased. Under the assumption of a malignant testicular tumour an inguinal orchiectomy was performed. The cut surface of this tumour was of grey/white color and showed small cysts. The tumour consisted of two compartments. The epithelial like tumour cells showed a sertoliform growth pattern and cystic dilatations. In between the tumour cells repeatedly actin expressing sclerotic areas could be recognized as the second tumour component. Proliferative activity was not increased. Immunohistochemically the tumour cells were positiv for inhibin, S-100, and CD 99. Alpha feto protein (AFP), human chorionic gonadotropin (ß-HCG) and placental alkaline phosphatase (PLAP) as well as synaptophysin, epithelial membrane antigene (EMA), and BCL-2 were not expressed. As far as we know this is the sixth reported case of this tumour. Because of the benign nature of this tumour the correct diagnosis is important for the intra- and postoperative management. Here we present a case of this rare tumour and discuss potential differential diagnosis., Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1956026143857335.

An immunohistochemical and lectin histochemical study of the efferent ducts was performed in the alpaca. Two types of epithelium, consisting of principal and ciliated cells, were detected on the basis of the different cytokeratins expression and lectin binding pattern. AE1/AE3 and 13 cytokeratin antibodies intensely immunostained the entire cytoplasm of type I PCs, whereas AE1/AE3, but not anti cytokeratin 13, immunoreacted in type II principal cells along the apical, lateral and basal plasma-membrane. The histochemical characterization of the epithelial cells was carried out using a battery of different lectins: Con-A, UEA-I, LTA, WGA, GSA-II, GSA-IB4, SBA, PNA, ECA, DBA, MAL-II and SNA. Sialidase digestion and deglycosilation pre-treatments were also employed. In type I principal cells, the staining of the Golgi zone was interpreted giving evidence for the synthesis and secretion of O- and N-linked oligosaccharides. In particular, alpha-Man/alpha-Glc, GlcNAc, beta-Gal-(1-4)-GlcNAc, Neu5Acalpha2,3Gal and Neu5Acalpha2,6Gal/GalNAc residues were included in both O- and N-linked glycans, whereas alpha-Fuc, beta-GalNAc and alpha-Gal were only found in O-linked oligosaccharides; alpha-GalNac and beta-Gal-(1-3)-D-GalNAc were found subterminal to sialic acid moieties and they were included in O- and N-glycans. In type II principal cells, the lectin staining was observed in the apical cytoplasmic granules and in vacuoles that were interpreted as components of an elaborate endocytotic apparatus specialized for the uptake of particulate material and fluid from the lumen. These results suggest the existence of two structurally different epithelial segments along the ductuli efferentes of the alpaca, with a high degree of compartmentalization of the secretory and absorptive activities.

The transepithelial movement of water into the male reproductive tract is an essential process for normal male fertility. Protein water channels, referred to as aquaporins (AQPs), are involved in increasing the osmotic permeability of membranes. This study has examined the expression of AQP1, AQP2, and AQP7 in epithelial cells in adult dog efferent ducts, epididymis, and vas deferens. Samples of dog male reproductive tract comprising fragments of the testis, initial segment, caput, corpus and cauda epididymidis, and vas deferens were investigated by immunohistochemistry and Western blotting procedures to show the localization and distribution of the AQPs. AQP1 was noted in rete testis, in efferent ducts, and in vessels in the intertubular space, suggesting that AQP1 participated in the absorption of the large amount of testicular fluid occurring characteristically in the efferent ducts. AQP2 expression was found in the rete testis, efferent ducts and epididymis, whereas AQP7 was expressed in the epithelium of the proximal regions of the epididymis and in the vas deferens. This is the first time that AQP2 and AQP7 have been observed in these regions of mammalian excurrent ducts, but their functional role in the dog male reproductive tract remains unknown. Investigations of AQP biology could be relevant for clinical studies of the male reproductive tract and to technologies for assisted procreation.

The present study aims to establish the nature and frequency of testicular lesions in the parenchyma adjacent to testicular germ cell tumors (TGCT) to improve understanding of the factors involved in the development of testicular cancer. Fifty-three cases of TGCT that were fixed in both neutral-buffered formalin and Bouin solution, allowing for the nuclear characterization of Sertoli cells (SCs), were included in this study. In each case, at least 3 sections of different areas of preserved parenchyma surrounding the TGCT were studied. We found Leydig cell hyperplasia, microlithiasis, angiopathy, adenomatous hyperplasia of the rete testis, SC nodules, SC dysgenesis and involution, SC-only tubules, tubular atrophy, adluminal compartment lesions, hypospermatogenesis associated with spermatocyte sloughing, spermatogonial maturation arrest, and hypertrophic and multinucleated spermatogonia. These lesions were found in regions both adjacent and far away from the tumoral mass, and abnormal seminiferous tubules were found intermingled with those showing complete spermatogenesis, suggesting that these lesions are primary and existed before the development of the tumor. Our study suggests that SCs might play a more important role in the development of testicular tumors than previously thought. Our data supports the hypothesis that there is an abnormal differentiation of SCs, caused either by genetic anomalies or by environmental agents during fetal life. This abnormal SC differentiation may cause not only primary spermatogenesis failure and spermatogenesis arrest at different levels, but may also contribute to the poor differentiation of gonocytes into spermatogonia. The abnormal gonocyte differentiation might favor the development of dysplastic germ cells that may later transform into intratubular germ cell neoplasia, unclassified type.

The proximity and, in some instances, communication between several structures in the testis and paratestis (rete testis, epididymis, mesothelium, vestigial epithelium and paratesticular soft tissue) result in a plethora of interesting tumors and tumor-like lesions that together pose a formidable diagnostic challenge both because of their morphologic overlap and rarity. The occasional spread of tumors primarily at other sites to this region adds to the potential problem encountered. This review provides an overview of the pathology of nonmesenchymal paratesticular neoplasms and pseudotumors with a focus on the approach to tubulopapillary neoplasms for which diagnostic considerations may include carcinoma of the rete testis, malignant mesothelioma, ovarian-type epithelial tumors, epididymal carcinoma and metastatic carcinomas. The cornerstone of accurate characterization of these lesions is still a comprehensive, traditional clinicopathologic approach, clinical history (of another primary), gross examination (location) and routine light microscopy, but judicious incorporation of contemporary immunohistochemical markers may aid or in some instances be crucial in resolving the problems encountered.

Problem: Previous studies demonstrated that F4/80 antigen (murine macrophage-specific antigen)-positive cells in testes of normal adult mice accumulate particularly in the interstitium adjacent to the tubuli recti and rete testis (i.e., the central region). However, it remains unknown whether this accumulation is a congenital or acquired phenomenon., Method of Study: The distribution of F4/80-positive cells on frozen sections of testes obtained from various aged mice was immunohistochemically examined to determine when the positive cells specifically accumulate in the central region., Results: F4/80-positive cells were homogeneously distributed throughout the testicular interstitium with no specific accumulation until 2 weeks of age. However, at 3 weeks of age, the density of positive cells in the central region became slightly, but significantly, higher than that in the interstitium between the seminiferous tubules. Between 3 and 4 weeks of age, the cell density in the central region increased rapidly, the density at 4 weeks of age reaching the level of the mature testes of 8-week-old mice., Conclusion: These results demonstrate that the specific accumulation of F4/80-positive cells in the central region is an acquired phenomenon, which starts and ends before puberty.

This study was undertaken to determine the lectin affinity of the extratesticular rete testis and ductuli efferentes epithelial cells in adult and prepubertal horses, using ten different lectin horseradish peroxidase conjugates: Con-A, LCA, WGA, GSA-II, SBA, PNA, RCA-I, DBA, UEA-I, and LTA. In some cases, treatments with sialidase and KOH preceded the lectin staining. In sexually mature and immature horses the results showed the presence of different kinds of sialoglycoconjugates with the terminal sialic acid linked to D-GalNAc and beta-D-Gal residues in the rete testis. In the apical surface and cytoplasm of epithelial cells lining the ductuli efferentes of the adult horse, glycoconjugates with alpha-D-Man and/or alpha-D-Glc, GlcNAc, D-GalNac and beta-D-Gal residues were evidenced, whereas in the prepubertal horse only the apical surface of the ductuli efferentes epithelial cells resulted reactive toward some lectins. The differences observed in the presence of glycoconjugates between adult and prepubertal horse ductuli efferentes, suggest a hormonal control of the function of these tracts of the post-testicular ducts.

Objective: To evaluate the status of the intratesticular spermatic duct system (rete testis, RT) in patients with cryptorchidism., Materials and Methods: We examined 40 surgical orchiectomy specimens from postpubertal patients with undescended testis from pathology files at La Paz Hospital, Madrid, Spain. Special attention was given to the intratesticular spermatic duct system, mainly the RT., Results: In all cases, the RT was underdeveloped and was lined by columnar or large cuboidal cells (dysgenetic RT). According to the configuration of the mediastinal RT, the lesions were classified as diffuse hypoplastic RT (37.5%), hypoplastic-cystic RT (50%), or adenomatous pseudohyperplastic RT (12.5%)., Conclusion: Although these changes could have resulted from incomplete pubertal maturation, many other data suggest that a primary abnormality of the RT is present. Important clinical considerations are derived from the fact that a functional obstruction of the sperm-conducting mechanism is determined by these abnormalities of the RT. The presence of intraluminal spermatozoa in epididymis and RT suggest that at least some of these patients are potentially fertile.

The sites of action and the physiological role of oestrogens in the male reproductive tract are poorly understood. We have undertaken a systematic study of the immunoexpression of oestrogen receptor-alpha (ER alpha) in the male rat from late fetal life through to adulthood and compared the findings with results obtained in the marmoset monkey (Callithrix jacchus) from neonatal to adult life. The testes, rete testis, efferent ducts and epididymis were examined from normal male rats (aged 4, 8, 10, 15, 20, 25, 38, 48 and 90 days) and from male rat fetuses on days 17.5 and 18.5 of gestation; comparable tissues were examined from neonatal, infantile, peripubertal and adult marmosets aged 8, 18-24, 54-62 and 92-112 weeks respectively. Immunolocalisation of ER alpha used antigen retrieval and a monoclonal antibody directed to the N-terminus, which had proved superior to six other antisera tested. ER alpha was immunoexpressed in interstitial cells, including the fetal/ neonatal generation of Leydig cells, in both the rat and marmoset. In the rat, the adult generation of Leydig cells were also immunopositive for ER alpha whereas the comparable cells in the marmoset were only weakly immunopositive. ER alpha was not expressed in Sertoli cells, peritubular myoid cells, blood vessels or germ cells at any time in either species. In late fetal life in the rat, ER alpha was immunoexpressed in cells surrounding the mesonephric tubules, whereas postnatally it was expressed in the epithelium of the rete testis and efferent ducts at all ages from 4 to 90 days; this immunoexpression was most pronounced in the efferent ducts. In the marmoset, the efferent ducts, but not the rete testis, also showed intense immunoexpression of ER alpha. Apart from sporadic immunostaining for ER alpha in the epididymal duct of the rat in the neonatal period, the caput, corpus and cauda epididymis were negative for immunoexpression of ER alpha at all ages in both species. These findings suggest that the main actions of oestrogens in the male reproductive tract, mediated by ER alpha, are related to the development and function of the efferent ducts and the Leydig cells. In consideration of data from this and previous studies of oestrogen binding, we predict possible sites of expression of other oestrogen receptors (e.g. ER beta) in Sertoli cells and the epididymis. Interactive effects, related to the relative levels of androgens and oestrogens, could be physiologically important in the excurrent ducts of the adult testis.

The expression patterns of low and high molecular weight cytokeratins (LCK and HCK) vimentin and desmin were investigated by immunocytochemistry in the rete testis and epididymis in the dog. The epithelium of the rete testis displayed coexpression of LCK, vimentin and desmin. The epithelium of the efferent ductules was composed of ciliated and nonciliated cells; the ciliated cells expressed LCK strongly. The epithelium of the epididymal duct was composed of principal, apical and basal cells. Principal cells in the duct of the head of the epididymis displayed LCK and vimentin, with a predominance of LCK in the apical cytoplasmic regions and vimentin in the basal portions of the cells. Expression of vimentin in the principal cells decreased towards the body of the epididymis and disappeared in the tail region, where LCK remained unchanged. Apical cells of the epididymal duct expressed LCK. Basal cells in the duct of the head and body of the epididymis showed LCK and those of the duct of the body of the epididymis also HCK expression.

The localization of sulfated glycoprotein-1 (SGP-1) in the extratesticular duct system was analyzed using an affinity purified antibody raised against the protein in conjunction with light (LM) and electron (EM) microscope immunocytochemistry. In the LM an intense immunoperoxidase reaction product was observed over the cytoplasm of Sertoli cells as well as over the tails of late spermatids. The rete epithelial cells and nonciliated cells of the efferent ducts also showed an intense uniform reaction over their entire cytoplasm. In the EM, immunogold labeling was noted over the entire endocytic apparatus of these cells including coated pits, endosomes, multivesicular bodies, and secondary lysosomes. Since there was no labeling of the luminal contents including sperm along the epididymis, it was concluded that the Sertoli-derived SGP-1 must dissociate from the sperm and be taken up by epithelial cells at the level of the rete testis and efferent ducts. In all regions of the epididymis, except the cauda, the principal cells showed, in the LM, an intense reaction over bodies of various shapes and sizes in their supranuclear region; this corresponded in the EM to a strong immunogold labeling of secondary lysosomes. No labeling was noted, however, over coated pits, endosomes, or pale multivesicular bodies, suggesting that SGP-1 was not being endocytosed from the lumen. Similar observations were noted for the epithelial clear cells along the entire epididymis. In the cauda epididymidis, principal cells presented a weak immunolabeling of their secondary lysosomes. Northern blot analysis revealed a strong 2.6 Kb band corresponding to the mRNA of SGP-1 in the efferent ducts and all regions of the epididymis with the exception of the cauda. Coincident with the mRNA expression of SGP-1 it was found that small clusters of gold particles representing anti SGP-1, presumably membrane bound, were associated with the Golgi apparatus as well as in close proximity to secondary lysosomes. There was, however, no evidence for the secretion of SGP-1 into the lumen. These results suggest that SGP-1 is synthesized by the epithelial cells of the male duct system and ferried by small vesicles derived from the Golgi apparatus to secondary lysosomes. Because SGP-1 has recently been shown to have substantial sequence similarity to prosaposin, it may be speculated that SGP-1 is instrumental in the degradation of membrane glycolipids present within secondary lysosomes of epithelial cells of the extratesticular duct system.