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PurposeColour Doppler ultrasound (CDUS) is the main radiologic tool to evaluate scrotal masses and intratesticular-vascularised solid lesions are mostly considered malign lesions. Objective of this trial is determine ratio of benign lesions in patients with hypervascularised solid intratesticular lesions.Material and methodPatients who underwent radical orchiectomy due to hypervascularised intratesticular solid lesions detected in CDUS are evaluated retrospectively. Those with previous testicular cancer history and inguinal/scrotal surgeries were excluded from the study. All patients are evaluated for age, preoperative testicular atrophy, multicentricity, echotexture and size of solid lesions, preoperative tumor markers (AFP, bHCG and LDH), and postoperative pathology results. Two tailed p value test was used to evaluate numeric parameters and Fisher’s exact test was used to evaluate non-numeric parameters.ResultsA total of 117 patients with a mean age of 35.9 (5–86) were included to the study. Mean size of solid lesions was 4.39 cm. Seven patients had subcentimeter (subcm) lesions. 101 patients had hypoechoic, ten patients had isoechoic and six patients hyperechoic solid lesions. Preoperatively 60 patients (51.2%) had at least one tumor marker elevated. Postoperative pathology examination resulted to; 21 patients (17.9%) had benign lesions. Elevation of tumor markers, palpability, hypoechoic texture and larger size of the solid lesion were found to be parameters that predict malignancy.ConclusionBenign incidence of vascular testicular solid lesions detected with scrotal ultrasound with colour Doppler is greater than expected. In patients with smaller, non-palpable lesions without elevated tumor markers, treatment options other than radical orchiectomy such as testicular sparing surgery should be considered.

Objectives To describe the imaging findings in a series of patients with mesothelioma of the tunica vaginalis testis. Methods We reviewed clinical data, imaging findings and follow-up information in a series of 10 pathology-proven cases of mesothelioma (all had US; 2 had MR) of the tunica vaginalis. Results A variety of patterns could be observed, the most common (5/10) being a hydrocele with parietal, solid and hypervascular vegetations; one patient had a septated hydrocele with hypervascular walls; one had multiple, solid nodules surrounded by a small, physiological quantity of fluid; one a cystic lesion with thick walls and vegetations compressing the testis; two had a solid paratesticular mass. MR showed multiple small nodules on the surface of the tunica vaginalis in one case and diffuse thickening and vegetations in the other one; lesions had low signal intensity on T2-w images and were hypervascular after contrast injection. Conclusions A preoperative diagnosis of mesotheliomas presenting as solid paratesticular masses seems very difficult with imaging. On the contrary, the diagnosis must be considered in patients in whom a hydrocele with parietal vegetations is detected, especially if these show high vascularity. Key Points • Mesotheliomas of the tunica vaginalis are rare, often challenging to diagnose preoperatively . • Most common finding is a complex hydrocele with hypervascular parietal vegetations . • Septated hydrocele, nodules without hydrocele, a thick-walled paratesticular cyst are less common . • Preoperative diagnosis may allow aggressive surgical approach and, possibly, a better prognosis .

Although syndecan-4 is implicated in cancer progression, there is no information for its role in testicular germ cell tumours (TGCTs). Thus, we examined the expression of syndecan-4 in patients with TGCTs and its correlation with the clinicopathological findings. Immunohistochemical staining in 71 tissue specimens and mRNA analysis revealed significant overexpression of syndecan-4 in TGCTs. In seminomas, high percentage of tumour cells exhibited membranous and/or cytoplasmic staining for syndecan-4 in all cases. Stromal staining for syndecan-4 was found in seminomas and it was associated with nodal metastasis (P=0.04), vascular/lymphatic invasion (P=0.01), and disease stage (P=0.04). Reduced tumour cell associated staining for syndecan-4 was observed in nonseminomatous germ cell tumours (NSGCTs) compared to seminomas. This loss of syndecan-4 was associated with nodal metastasis (P=0.01), vascular/lymphatic invasion (P=0.01), and disease stage (P=0.01). Stromal staining for syndecan-4 in NSGCTs did not correlate with any of the clinicopathological variables. The stromal expression of syndecan-4 in TGCTs was correlated with microvessel density (P=0.03). Our results indicate that syndecan-4 is differentially expressed in seminomas and NSGCTs and might be a useful marker. Stromal staining in seminomas and reduced levels of syndecan-4 in tumour cells in NSGCTs are related to metastatic potential, whereas stromal staining in TGCTs is associated with neovascularization.

Background Human seminoma is classified as classical seminoma (SE) and spermatocytic seminoma (SS). Human SE is known to be more malignant and metastasizing more frequently than SS. Tumor angiogenesis is highly related with tumor progression and metastasis, with microvessel density (MVD) being an important parameter of metastatic potential. Canine seminoma is not yet well-established as SE or SS type including correlation with angiogenesis. We classified canine SE and SS, and then compared them to tumor associated vessels. Methods Twenty-three cases of canine seminomas (2 intratubular, 9 diffuse, and 12 intratubular/diffuse seminomas showing both intratubular and diffuse patterns) were classified as SE or SS by immunohistochemistry (IHC) using monoclonal antibody against PLAP and by PAS stain. The histopathological data were then compared to see if there was a correlation with SE or SS. Angiogenesis of seminomas were evaluated by immunohistochemical assay using polyclonal antibody against Von Willebrand factor (vWF) and by calculating the means of MVD, vessels area and perimeters using computerized image analysis. Statistical Package for Social Sciences (SPSS) program was used for various statistical analyses. Results The numbers of PLAP+/PAS+ canine SEs were 8/23 (34.8%) and PLAP-/PAS- SSs were 15/23 (61.2%). All SE cases (8/8, 100%) were intratubular/diffuse types. SS types included 2 intratubular (2/15, 13.3%), 9 diffuse (9/15, 60%), and 4 intratubular/diffuse (4/15, 26.7%) types. MVD and vascular parameters in SEs were significantly higher than in SSs, showing the highest value in the intratubular/diffuse type. Seminomas observed with neoplastic cells invasion of vessels presented higher perimeter and area values than seminomas without conformed neoplastic cells invasion. Conclusion In this study, we demonstrated a positive relationship between canine SE and tumor angiogenesis. Furthermore, we also showed that a tumor cells invasion of vessels were a correlated vascular parameter. Although metastasis of canine seminomas has rarely been reported, our results support that canine SE could have high metastatic potential similar to the human counterpart. Further studies are required to clarify the relationship between canine SE and clinical data with metastatic factors.

Background Germ cell testicular tumors have survival rate that diminishes with high tumor marker levels, such as human chorionic gonadotropin (hCG). hCG may regulate vascular neoformation through vascular endothelial growth factor (VEGF). Our purpose was to determine the relationship between hCG serum levels, angiogenesis, and VEGF expression in germ cell testicular tumors. Methods We conducted a retrospective study of 101 patients. Serum levels of hCG, alpha-fetoprotein (AFP), and lactate dehydrogenase were measured prior to surgery. Vascular density (VD) and VEGF tissue expression were determined by immunohistochemistry and underwent double-blind analysis. Results Histologically, 46% were seminomas and 54%, non-seminomas. Median follow-up was 43 ± 27 months. Relapse was present in 7.5% and mortality in 11.5%. Factors associated with high VD included non-seminoma type ( p = 0.016), AFP ≥ 14.7 ng/mL ( p = 0.0001), and hCG ≥ 25 mIU/mL ( p = 0.0001). In multivariate analysis, the only significant VD-associated factor was hCG level ( p = 0.04). When hCG levels were stratified, concentrations ≥ 25 mIU/mL were related with increased neovascularization ( p < 0.0001). VEGF expression was not associated with VD or hCG serum levels. Conclusion This is the first study that relates increased serum hCG levels with vascularization in testicular germ cell tumors. Hence, its expression might play a role in tumor angiogenesis, independent of VEGF expression, and may explain its association with poor prognosis. hCG might represent a molecular target for therapy.

Background: Carcinoma in situ (CIS) of the testis is considered to be a precancerous germinal cell lesion, but the precise cellular and molecular mechanisms underlying transformation of CIS into invasive pluripotent cancer cells remain to be elucidated. Moreover, a satisfactory animal model for the experimental study of germinal tumours has not been developed to date. METHODS: We have developed a tumour model that involves the microinjection of green fluorescent protein-labelled embryonic stem (ES) cells (which are functionally equivalent to CIS cells) into syngenic mouse seminiferous tubules, a unique cell microenvironment in which germinal cells mature and CIS arise. To characterise the vascularisation of teratocarcinomas, which arise after cell transplant, we used immunohistochemistry, together with a qualitative and quantitative analysis of scanning electron microscopy images of corrosion casting samples. Results: Embryonic stem cells transplanted into seminiferous tubules did not differentiate into germinal cells, but rather they behaved as invasive embryonal carcinoma (EC) stem cells. The vascular pattern of the experimental teratocarcinomas showed a highly disorganised architecture, and some of the neoplastic capillaries were derived, at least in part, from the original transplanted ES cells. Conclusion: The transplantation of pluripotent ES cells into seminiferous tubules efficiently recapitulates the early stages of development of teratocarcinomas. Consequently, this method constitutes a novel in vivo model to study the mechanisms of invasion and progression of experimental germinal tumours.

As granulosa cell tumors of the adult type are extremely uncommon testicular neoplasms, relatively few case reports and case series have been published. Treatment for localized, small-volume, or oligometastatic disease is generally surgical resection alone. Visceral or widely metastatic disease is relatively rare, so there is no consensus approach to treatment. We report the case of an advanced granulosa cell tumor of the testis with a confirmed partial response to an angiogenesis inhibitor after initial resistance to cytotoxic chemotherapy.

The potential role of angiogenesis stimulators in the pathogenesis of different tumor entities has been confirmed in several studies. We measured the serum levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) in 51 patients with testicular germ cell tumors and in 39 healthy volunteers. Serum concentrations of bFGF, VEGF and PDGF-AB were determined by enzyme-linked immunosorbent assay. The median serum bFGF level for tumor patients was 3.46 pg/ml (range 0-61.6) compared to 0.7 pg/ml (0-11) in the control group (P<0.01). In patients with metastatic disease, the median serum bFGF level was 10.3 pg/ml (0-61.6) in contrast to 2.8 pg/ml (0-50) in patients with localized disease (P<0.01). The median serum VEGF and PDGF levels were 270 pg/ml (0-1,903) and 37,837 pg/ml (9,075-108,800), respectively, for tumor patients and 200 pg/ml (44-585) and 23,000 pg/ml (4,250-70,650) in the control group ( P<0.05). Our data suggest that angiogenesis, as reflected by serum concentrations of bFGF, VEGF and PDGF, plays a functional role in the growth and progression of testicular germ cell tumors.

Use of contrast enhancement in conjunction with magnetic resonance (MR) imaging provides a means to evaluate tissue function, as well as morphology. Moreover, physiologic properties derived from kinetic analysis of dynamic contrast-enhanced data can improve the specificity of MR examinations. In this study, quantitative analysis of microvascular characteristics based on dynamic MR imaging were performed both for malignant and benign lesions using two types of contrast agents (CAs). A new MR macromolecular contrast medium (MMCM), 24 gadolinium-tetraazacyclododecanetetraacetic acid (DOTA)-dendrimer, was found to have a greater ability to distinguish benign from malignant lesions. When a blood pool agent was used, permeability differences in the two types of lesions were the most significant findings among all parameters considered.