The Application Value of Contrast-Enhanced Ultrasound in Testicular Occupied Lesions.

OBJECTIVE: To discuss the clinical application value of contrast-enhanced ultrasound (CEUS) in testicular occupied lesions. METHODS: Nine conventional-ultrasound-found testicular occupied lesions which underwent CEUS meantime were analyzed retrospectively. The CEUS perfusion pattern was compared with the surgical pathological result or follow-up findings. RESULTS: Among all the 9 testicular occupied lesions, there were 5 testicular malignant tumors, 1 testicular benign tumor, 1 testicular tuberculosis, and 2 testicular hematomas. CEUS diagnosed 6 testicular malignant tumors, 1 testicular benign tumor, and 2 testicular hematomas, and its diagnostic accuracy was about 88.9%. CONCLUSION: CEUS has high clinical application value in the differential diagnoses of benign and malignant testicular occupied lesions.

Vascularity of Intra-testicular Lesions: Inter-observer Variation in the Assessment of Non-neoplastic Versus Neoplastic Abnormalities After Vascular Enhancement With Contrast-Enhanced Ultrasound.

The aim of this study is to assess the additional benefit of contrast-enhanced ultrasound (CEUS) over conventional ultrasonography (US) in identifying intra-testicular abnormalities among observers of different experiences. In this study, 91 focal testicular lesions (46 neoplastic, 45 non-neoplastic) imaged with gray-scale US/Doppler US and CEUS were classified using a 5-point scale. Three experienced and four inexperienced observers rated each lesion using gray-scale/color Doppler US alone and then with the addition of CEUS. Improved diagnostic specificity and accuracy with the addition of CEUS was observed for both experienced (specificity: 71.1% vs. 59.3%, p = 0.005; accuracy: 83.5% vs. 76.9%, p = 0.003) and inexperienced observers (specificity: 75.6% vs. 51.7%, p = 0.005; accuracy: 80.2% vs. 72.0%, p < 0.001). Significant inter-observer variability between the experienced and inexperienced observers when assessing conventional US alone was eliminated with the addition of CEUS. CEUS improves diagnostic accuracy of focal intra-testicular lesions for both experienced and inexperienced observers and reduces inter-observer variability in inexperienced operators.

[Ultrasound characteristics of testicular Leydig cell tumors , , , 1.]

OBJECTIVE: To explore the color Doppler ultrasonic characteristics of testicular Leydig cell tumors (LCT) and improve the clinical diagnosis of the disease. METHODS: We retrospectively analyzed 4 cases of testicular LCT diagnosed and treated in our hospital and summarized the experience in the ultrasonic diagnosis of LCT with a review of the relevant literature. RESULTS: All the 4 testicular LCTs were solitary and quasi-round, 1 in the left and 3 in the right. The smallest mass was 1.8 × 1.5 cm and the largest 3.1 × 2.5 cm, and 2 were complicated by hydrocele of tunica vaginalis. The margins of tumors were distinct in 2 cases and indistinct in 1, and changed from distinct to indistinct in another during the follow-up. Hypoechoes were revealed in all the 4 cases in ultrasonography, 2 with abundant internal blood flow, 1 with abundant peripheral blood flow, and the other with abundant internal blood flow changed from circular blood flow surrounding the mass. CONCLUSIONS: A typical sporadic LCT was ultrasonically manifested as an isolated hypoechoic infracentimetric mass with a clear demarcation from the adjacent pulp. It exhibited intrinsic hypervascularization associated with a typical peripheral rim pattern. Larger lesions more often presented a lobulated shape and intense hypervascularization. Although these ultrasonic characteristics do not reveal the nature of LCT with certainty, they can help the surgeon with the decision on testis-sparing surgery or perhaps even on the active monitoring for the smallest lesions in a population with impaired fertility.

Colour Doppler ultrasound imaging of blood flows variations in neoplastic and non-neoplastic testicular lesions in dogs.

Testicular tumours are the most common neoplasms in male dogs accounting for approximately 90% of all tumours affecting the genitourinary tract. Gray-scale ultrasonography in combination with colour and power Doppler imaging has been well accepted as an accurate technique for assessing scrotal lesions and vascularization of the testis. Colour Doppler sensitivity for low blood flows appears promising in the study of testicular disorders. The aim of this study was to assess if colour and power Doppler ultrasound is a good tool for the investigation of testicular lesions in dogs, to report the sonographic features of lesions and to measure colour and power Doppler parameters such as resistive index (RI), pulsatility index (PI), hypovascularization and hypervascularization (VI) determining if they can be used to distinguish testicular neoplasms from the wide spectrum of non-neoplastic pathological findings. In this study, 50 male dogs of various breeds, aged between 7 and 14 years, presented with testicular disorders were selected. RI and PI were calculated. Mean RI values for neoplastic, inflammatory and degenerative lesions were 0.54, 0.45 and 0.58, respectively. Mean PI values were 0.62, 0.55 and 0.63, respectively. Hypovascularization and hypervascularization of the lesion were evaluated throughout the vascularity index (VI). Vascular signals in neoplasms were significantly intensified around and inside the mass if compared with those measured during inflammatory and degenerative lesions. VI markedly increased in solid tumours. Pathological testes were removed; macroscopical, histological and immunoistochemical evaluations were carried out. Colour Doppler showed increased intralesional and peripheral flows in all neoplastic lesions analysed. No flows were detected around cysts.

Should we rely on Doppler ultrasound for evaluation of testicular solid lesions?

PURPOSE: Colour 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 METHOD: Patients 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. RESULTS: A 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. CONCLUSION: Benign 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.

Straight Vessel Pattern and Rapid Filling Time: Characteristic Findings on Contrast-Enhanced Sonography of Testicular Lymphoma.

Six patients with 7 lesions that were histologically confirmed as primary testicular lymphoma were preoperatively investigated with a standardized sonographic protocol including contrast-enhanced sonography. Duplex and contrast-enhanced sonography showed marked hypervascularization in all 7 lesions. On contrast-enhanced sonography, the filling time of lymphomatous lesions was significantly shorter than the filling time of a size-matched sample of 10 patients with seminomas (P < .0001). The sonographic hallmarks of testicular lymphoma in our case series were as follows: (1) sharply demarcated homogeneous hypoechoic testicular lesions with marked hypervascularization; (2) a rapid (<7 seconds) filling time of contrast bubbles; and (3) a straight and parallel course of intralesional vessels on contrast-enhanced sonography.

CEUS Time Intensity Curves in the Differentiation Between Leydig Cell Carcinoma and Seminoma: A Multicenter Study.

PURPOSE: Ultrasound (US) is the main imaging technique in the assessment of testicular masses, as it has proved to be highly accurate in the visualization of these pathologies. Identification of a Leydig cell tumor is essential since the lesion is benign in 90% of cases. The aim of this multicenter study is to assess the effectiveness of contrast-enhanced ultrasound (CEUS) in differentiating Leydig cell tumors from seminoma using qualitative and quantitative features. MATERIALS AND METHODS: From February 2011 to December 2013, 31 patients (mean age: 34 years; range: 25 - 52) were recruited for this prospective study. Three of them were monorchid. Therefore, a total of 59 testicles were assessed. All patients underwent grayscale US, color Doppler ultrasound (CDUS), CEUS and orchiectomy. The paired one-tailed Student's t-test was carried out to differentiate between Leydig cell tumors and seminomas. RESULTS: 31 lesions suspicious for malignancy were hypoechoic on grayscale US while they did not show a typical pattern on CDUS. CEUS qualitative analysis, based on contrast enhancement pattern, during the arterial and venous phases, did not allow discrimination of Leydig cell tumors from seminoma. Quantitative analysis of time-intensity curves (TICs) demonstrated that only three parameters presented statistical significance, i. e. wash-in rate (WiR) p = 0.014, peak enhancement (PE) p = 0.001 and time to peak (TTP) p = 0.003. CONCLUSION: The vascular bed of a Leydig cell tumor is wider and the blood flow velocity is higher than that of a seminoma due to more regular neovascularization. In contrast, a seminoma presents large areas of necrosis due to irregular neovascularization. This explains the different PE and WiR values. Further studies involving larger patient populations are mandatory to confirm these encouraging preliminary results.

Imaging of mesothelioma of tunica vaginalis testis.

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.

Diagnosis of Testicular Adrenal Rest Tumors on Ultrasound: A Retrospective Study of 15 Cases Report.

The aim of this study was to evaluate the imaging features of testicular adrenal rest tumors (TARTs) on baseline ultrasound (BUS).The imaging features of 30 TART lesions pathologically or clinically confirmed in 15 patients who had undergone BUS were evaluated, and the sonographic characteristics of the lesions were analyzed.All 15 cases were bilateral and located near the testicular mediastinum. Approximately 56.7% (17/30) of the TART lesions exhibited homogeneous hypoechogenicity, 36.7% (11/30) of the lesions exhibited heterogeneous hypoechogenicity, and 6.6% (2/30) of the lesions exhibited heterogeneous isoechogenicity. In addition, 76.7% (23/30) of the lesions exhibited a rich blood supply, whereas 23.3% (7/30) of the lesions exhibited a scarce blood supply.The sonographic characteristics of the TARTs were bilateral growth, location adjacent to the testicular mediastinum, hypoechogenicity, and rich blood supply, which may play important roles in early clinical diagnosis.

Contrast-enhanced ultrasound and real-time elastography for the diagnosis of benign Leydig cell tumors of the testis - a single center report on 13 cases.

PURPOSE: To describe sonomorphological features in testicular Leydig cell tumors (LCTs) with a special focus on contrast-enhanced ultrasonography (CEUS) and real-time elastography (RTE). PATIENTS AND METHODS: In a series of 186 patients with testicular surgery for neoplastic disease, 13 benign LCTs (in 12 patients) were histopathologically diagnosed. Preoperatively, all patients had been examined with a standardized protocol (high-resolution grayscale and color-coded ultrasonography, CEUS). 5 patients underwent RTE. In CEUS, the filling time of the lesion was compared to that of 14 size-matched germ cell tumors (GCT). RESULTS: 10/13 LCTs had a size of < 10 mm, and a sharply demarcated hypoechoic appearance was typical (10/13). Color-coded ultrasonography detected signals in 8 lesions, while CEUS showed clear hypervascularization in all. LCTs had a significantly shorter filling time than GCTs (p < 0.0005), with 9/13 LCTs being completely filled within 4 s. In RTE, all 5 examined lesions were clearly "harder" than the surrounding testicular tissue. CONCLUSION: Contrary to some earlier reports, we could demonstrate marked hypervascularization in LCTs. This feature clearly allows for the differentiation of a small LCT from focal scars. However, it may only be visible on CEUS. In CEUS, LCT is suggested by the findings of a short filling time or by a circumferential vessel with a rapid centripetal filling, combined with a "harder" appearance in RTE. These features along with the findings of a small and peripherally situated hypoechoic tumor would justify an operative strategy with frozen section examination and possibly organ sparing surgery instead of orchiectomy.

The antibody-based targeted delivery of interleukin-4 and 12 to the tumor neovasculature eradicates tumors in three mouse models of cancer.

Preclinical studies with recombinant murine interleukin 4 (IL4) in models of cancer have shown potent tumor growth inhibition. However, systemic administration of human IL4 to cancer patients exhibited modest antitumor activity and considerable toxicities. To improve the therapeutic index and reduce side effects of this cytokine, we developed of a novel "immunocytokine" based on sequential fusion of murine IL4 with the antibody fragment F8 (specific to the alternatively spliced extra-domain A of fibronectin, a marker for tumor-angiogenesis) in diabody format. The resulting fusion protein, termed F8-IL4, retained full antigen-binding activity and cytokine bioactivity and was able to selectively localize on solid tumors in vivo. When used as single agent, F8-IL4 inhibited tumor growth in three different immunocompetent murine cancer models (F9 teratocarcinoma, CT26 colon carcinoma and A20 lymphoma). Furthermore, F8-IL4 showed synergistic effects when coadministered with immunocytokines based on IL2 and IL12. Indeed, combination therapy with an IL12-based immunocytokine yielded complete tumor eradication, in spite of the fact that IL4 and IL12 display opposite immunological mechanisms of action in terms of their polarization of T-cell based responses. No weight loss or any signs of toxicity were observed in treated mice, both in monotherapy and in combination, indicating a good tolerability of the immunocytokine treatment. Interestingly, mice cured from CT26 tumors acquired a durable protective antitumor immunity. Depletion experiments indicated that the antitumor activity was mediated by CD8+ T cells and by NK cells.

Primo vessel as a novel cancer cell migration path from testis with nanoparticle-labeled and GFP expressing cancer cells.

BACKGROUND/AIM: Recently, a novel circulatory system, the primo vascular system (PVS), was found to be a potent metastatic route of cancer cells. The aim of the current work is to demonstrate that cancer cells injected into the testis migrate through the primo vessel (PV). MATERIALS AND METHODS: NCI-H460 cells labeled with fluorescent nanoparticles (FNP) or green fluorescent protein (GFP) gene transfection were injected into testicular parenchyma in 24 rats. After 24 hours of injection, the abdominal cavity was investigated via a stereomicroscope, to detect the PVS, and the samples were analyzed histologically with 4',6-diamidino-2-phenylindole (DAPI) and hematoxylin and eosin. RESULTS: Injected cancer cells were detected inside the PVS distributed on the abdominal organs. Some were detected inside intestinal parenchyma into which the attached primo vessels (PVs) entered. CONCLUSION: The results supported the fact that the PVS may be a novel migration path of cancer cells, in addition to the lymphatic and hematogenous routes.

Expression of syndecan-4 and correlation with metastatic potential in testicular germ cell tumours.

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.

Genomic gain and over expression of CCL2 correlate with vascular invasion in stage I non-seminomatous testicular germ-cell tumours.

Testicular germ-cell tumours (TGCT) are the most frequent solid tumour to affect young Caucasian adult males and have increased in incidence over recent decades. In clinical stage I non-seminomas, (NSGCT) histological vascular invasion (VI) is a prognostic factor for metastatic relapse. Using array comparative genomic hybridization, we have previously shown that the presence of VI is associated with gain of a region at 17q12, containing a cluster of genes encoding inflammatory cytokines. We here confirm this finding using fluorescence in situ hybridization (FISH) demonstrating gain in 12 out of 42 (29%) assessable samples. Interrogation of previously published expression microarray data suggests that of the genes contained within this region, CCL2 [monocyte chemoattractant protein 1 (MCP1)] is frequently overexpressed in TGCT. Immunohistochemistry confirms this finding in a collection of 67 clinical stage I NSGCT, demonstrating an association with the presence of VI (p=0.049) that was not seen with VEGF-A, MMP2 or MMP9, although all were frequently expressed. This work gives further insight into the mechanisms involved in invasion in this tumour type, which may ultimately have implications for the management of patients with stage I disease.

High expression of NPY receptors in the human testis.

NPY receptors represent novel molecular therapeutic targets in cancer and obesity. However, the extent of NPY receptor expression in normal human tissues is poorly investigated. Based on the role of NPY in reproductive functions, the NPY receptor expression was studied in 25 normal human testes and, additionally, 24 testicular tumors using NPY receptor autoradiography. In the normal testis, Leydig cells strongly expressed NPY receptor subtype Y2, and small arterial blood vessels Y1. Y2 receptors were found to be functional with agonist-stimulated [(35)S]GTPγS binding autoradiography. Full functional integrity of the NPY system was further suggested by the immunohistochemical detection of NPY peptide in nerve fibers directly adjacent to Leydig cells and arteries. Germ cell tumors expressed Y1 and Y2 on tumor cells in 33% and Y1 on intratumoral blood vessels in 50%. Based on its strong NPY receptor expression in Leydig cells and blood vessels, the normal human testis represents a potentially important physiological and pharmalogical NPY target.

Metronomic dosing enhances the anti-angiogenic effect of epothilone B.

BACKGROUND: High doses (10 nM) of epothilone B, a microtubule stabilizer, will inhibit the development of human tumor-derived angiogenesis following short (14 d) drug exposure times. Metronomic dosing regimes use lower drug doses and prolonged drug exposure times in an attempt to decrease toxicity compared with standard dosing schedules. We hypothesized that epothilone B would be an effective anti-angiogenic agent when administered at very low doses over an extended period of time. METHODS: Fragments of four fresh human tumors were cultured in a fibrin-thrombin matrix and maintained in nutrient media plus 20% fetal bovine serum (FBS) for 56 d. Tumor fragments (n=40-60 per group) were exposed to weekly doses of epothilone B at concentrations of 10, 5, 1, 0.5, or 0.1 nM. All of these concentrations are clinically achievable. Tumor angiogenesis was assessed weekly on d 14-56 using a validated visual grading system. This system rates neovessel growth, density, and length on a 0-16 scale [angiogenic index, (AI)]. The average change in AI between d 14 and 56 was calculated for all samples and used to evaluate the metronomic response. RESULTS: Epothilone B produced a dose-dependent anti-angiogenic response in all tumors. Two of the four tumors demonstrated a clear and significant metronomic anti-angiogenic effect over time. CONCLUSIONS: Epothilone B, when dosed by a metronomic schedule may have a significant anti-angiogenic effect on human solid tumors. This study provides evidence for the potential use of epothilone B on a metronomic dosing schedule.

4-(3-Halo/amino-4,5-dimethoxyphenyl)-5-aryloxazoles and -N-methylimidazoles that are cytotoxic against combretastatin A resistant tumor cells and vascular disrupting in a cisplatin resistant germ cell tumor model.

New combretastatin A analogues featuring oxazole or N-methylimidazole bridged Z-alkenes and halo- or amino-substituted A-rings were tested against various cancer cell lines and in testicular germ cell tumor xenografts in mice. Imidazoles with 3-halo-4,5-dimethoxy substituted A-rings and 3-amino-4-methoxy substituted B-rings (7b and 8b) were efficacious at nanomolar concentrations against cells of combretastatin A refractory HT-29 colon carcinoma, multidrug-resistant MCF-7/Topo breast carcinoma, and cisplatin-resistant 1411HP testicular germ cell tumor. They induced apoptosis and inhibited tubulin polymerization. While well tolerated by mice at high doses, these imidazoles initiated extensive intratumoral hemorrhage and regressions of highly vascularized 1411HP xenografts.

Epithelial versus endothelial CEACAM1 expression and angiogenesis in epididymal adenomatoid tumor.

BACKGROUND/AIM: To study the expression of the pro-angiogenic factor carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) in epididymal adeno-matoid tumor tissue, a very rare benign neoplasia, in relation to its vascularization. MATERIALS AND METHODS: Immunohistochemistry for CEACAM1 and for both endothelial markers CD31 and CD34 was performed in normal human epididymal and epididymal adenomatoid tumor tissue. The vessel density was calculated in four tumor regions with different degrees of vascularization in comparison to the vascularization of the normal epididymal tissue. RESULTS: CEACAM1 was found in normal epididymal epithelium, while the epithelium of tumor glands was mostly negative. Only few blood vessels and lymphatics in adenomatoid tumor tissue expressed CEACAM1. The assessment of vascularization revealed either equal or a significantly lower vessel density in some adenomatoid tumor regions in comparison to normal epididymal tissue. DISCUSSION: These data demonstrate that despite its epithelial down-regulation, CEACAM1 is not present in the majority of adenomatoid tumor blood vessels, which might be related to the lower angiogenic activity and benign behaviour of this tumor.

Canine classical seminoma: a specific malignant type with human classifications is highly correlated with tumor angiogenesis.

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.

Vascularization of testicular germ cell tumours: evidence from experimental teratocarcinomas.

Testicular germ cell tumours (TGCTs) represent about 2% of male malignancies, being the most common cancer among adolescents and young adults. As in most neoplasias, TGCTs show a chaotic vascular architecture, altered blood supply and over-expression of pro-angiogenic factors, aspects closely related to tumour overgrowth and metastasis. Following this trend, our laboratory has analysed the effect of the hypoxic tumour microenvironment on cancer stem cells, particularly the expression of factors related to vascularization, such as matrix metalloproteinases, adhesion molecules, vascular endothelial growth factors (VEGF) and VEGF receptors. This review also summarizes our present knowledge on vascularization in the normal and neoplastic testis, the potential role of the factors involved in TGCT neovascularization and their importance as possible therapeutic targets.