Evaluation of Prognostic Parameters to Identify Aggressive Penile Carcinomas.

BACKGROUND: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. METHODS: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. RESULTS: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. CONCLUSION: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required.

[Importance of HPV status and p16 for the prognosis of penile carcinoma]. / Bedeutung von HPV-Status und p16 für die Prognose des Peniskarzinoms.

BACKGROUND: Penile cancer is a rare but often lethal tumour disease, especially in the metastatic stage. Most data on prognostic factors for penile cancer are based on small patient cohorts, and even meta-analyses are mostly limited in terms of patient numbers. There is a lack of sufficient parameters to predict the metastatic risk of these tumours. Furthermore, the role of the HPV status for the prognosis, and, in this regard, of p16INK4a is still unclear. MATERIAL AND METHODS: In this study, 236 patients from an international multicentre cohort were analysed with regard to histological subtypes, HPV and p16 status, and other clinical parameters. The HPV status was only graded as HPV-positive if HPV was detected by PCR and the p16 status defined by immunochemistry was positive. The statistical analysis was carried out using the Kaplan-Meier method as well as the log-rank test and a univariable and multivariable analysis using the Cox regression model. RESULTS: A positive HPV status was not a significant parameter for either metastasis-free (MFS), tumour-specific (CSS) or overall survival (OS). p16-positive tumours showed a significantly better MFS (p=0.026), which was also confirmed in the subgroup analysis of HPV-negative tumours (p=0.037) without differences in CSS or OS. In the usual type, there was also a trend towards an improved MFS, but without statistical significance (p=0.070). p16-positive tumours were associated with a highly significantly better MFS (hazard ratio 0.3; p=0.004) in the multivariable Cox regression, while patients with a pT1b tumour stage or advanced lymph node metastasis showed a significantly worse survival. In the multivariable analysis of HPV-negative tumours, p16 status was also confirmed as an independent predictor of MFS (Hazard ratio 0.2; p=0.007). CONCLUSION: HPV status alone seems to be lacking prognostic relevance. In contrast, p16 status was confirmed as an independent prognostic factor. Thus, the expression of p16INK4a is associated with a significantly better MFS. Especially in HPV-negative tumours, the p16 status should be evaluated with regard to the prognostic value and thus also with a view to the treatment decision.

Is the Standard Artificial Urinary Sphincter AMS 800 Still a Treatment Option for the Irradiated Male Patient Presenting with a Devastated Bladder Outlet?

BACKGROUND: Circular urethral compression with an artificial sphincter allows control of voiding, even in patients with severe stress urinary incontinence, but it heightens the risk of urethral atrophy and erosion. This study of one of the largest populations of patients treated with radiotherapy investigates the additive effect of the post-radiogenic stricture of the membranous urethra/bladder neck on AMS 800 artificial urinary sphincter outcomes. METHODS: In a retrospective multicenter cohort study, we analyzed patients fitted with an AMS 800, comparing those who had received radiotherapy with patients presenting a devastated bladder outlet (stricture of the membranous urethra/bladder neck). We determined the correlation between these groups of patients using both univariate and stepwise adjusted multivariate regression. The revision-free interval was estimated by a Kaplan-Meier plot and compared by applying the log-rank test. A p value below 0.05 was considered statistically significant. RESULTS: Of the 123 irradiated patients we identified, 62 (50.4%) had undergone at least one prior desobstruction for bladder-neck/urethra stenosis. After a mean follow-up of 21 months, the latter tended to achieve social continence less frequently (25.7% vs. 35%; p = 0.08). Revision was required significantly more often for this group (43.1% vs. 26.3%; p = 0.05) due to urethral erosion in 18 of 25 cases. A stenosis recurred in five cases; desobstruction was performed in two cases, leading to erosion in both. Multivariate analysis revealed a significantly higher risk of revision when recurrent stenosis necessitated at least two prior desobstructions (HR 2.8; p = 0.003). CONCLUSIONS: A devastated bladder outlet is associated with a lower proportion of men with social continence and a significantly higher need for revision compared with irradiated patients without a history of urethral stenosis. Alternative surgical procedures should be discussed beforehand, especially in cases of recurrent urethral stenosis.

The prominent role of the S100A8/S100A9-CD147 axis in the progression of penile cancer.

Currently, no established biomarkers are recommended for the routine diagnosis of penile carcinoma (PeCa). The rising incidence of this human papillomavirus (HPV)-related cancer entity highlights the need for promising candidates. The Calprotectin subunits S100A8 and S100A9 mark myeloid-derived suppressor cells in other HPV-related entities while their receptor CD147 was discussed to identify patients with PeCa at a higher risk for poor prognoses and treatment failure. We thus examined their expression using immunohistochemistry staining of PeCa specimens from 74 patients on tissue microarrays of the tumor center, the invasion front, and lymph node metastases. Notably, whereas the tumor center was significantly more intensively stained than the invasion front, lymph node metastases were thoroughly positive for both S100 subunits. An HPV-positive status combined with an S100A8+S100A9+ profile was related with an elevated risk for metastases. We observed several PeCa specimens with S100A8+S100A9+-infiltrating immune cells overlapping with CD15 marking neutrophils. The S100A8+S100A9+CD15+ profile was associated with dedifferentiated and metastasizing PeCa, predominantly of HPV-associated subtype. These data suggest a contribution of neutrophil-derived suppressor cells to the progression of HPV-driven penile carcinogenesis. CD147 was elevated, expressed in PeCa specimens, prominently at the tumor center and in HPV-positive PeCa cell lines. CD147+HPV+ PeCa specimens were with the higher-frequency metastasizing cancers. Moreover, an elevated expression of CD147 of HPV-positive PeCa cell lines correlated negatively with the susceptibility to IgA-based neutrophil-mediated tumor cell killing. Finally, stratifying patients regarding their HPV/S100A8/S100A9/CD15/CD147 profile may help identify patients with progressing cancer and tailor immunotherapeutic treatment strategies.

DKK1 inhibits canonical Wnt signaling in human papillomavirus-positive penile cancer cells.

Penile squamous cell cancer (PSCC) is the most frequent penile malignant disease. Infections with human papillomaviruses (HPV) are a major etiologic driver of PSCC. However, the molecular details of the underlying carcinogenesis are understudied because of rare clinical specimens and missing cell lines. Here, we investigated if the expression of high-risk HPV16 oncogenes causes an augmentation of the Wnt pathway using unique HPV-positive penile cancer (PeCa) cell lines in monolayer and organotypic 3D raft cultures as well as tissue micro arrays containing clinical tissue specimens. The HPV oncoproteins enhanced the expression of Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and the HPV-positive PeCa cells expressed a signature of Wnt target and stemness-associated genes. However, the notable lack of nuclear ß-catenin in vitro and in situ raised the question if the enhanced expression of Wnt pathway factors is tantamount to an active Wnt signaling. Subsequent TOP-flash reporter assays revealed Wnt signaling as absent and not inducible by respective Wnt ligands in PeCa cell lines. The HPV-positive PeCa cells and especially HPV-positive PeCa specimens of the tumor core expressed the Wnt antagonist and negative feedback-regulator Dickkopf1 (DKK1). Subsequent neutralization experiments using PeCa cell line-conditioned media demonstrated that DKK1 is capable to impair ligand-induced Wnt signaling. While gene expression analyses suggested an augmented and active canonical Wnt pathway, the respective signaling was inhibited due to the endogenous expression of the antagonist DKK1. Subsequent TMA stainings indicated Dkk1 as linked with HPV-positivity and metastatic disease progression in PeCa suggesting potential as a prognostic marker.

miRNA Expression Characterizes Histological Subtypes and Metastasis in Penile Squamous Cell Carcinoma.

Although microRNAs are described as promising biomarkers in many tumor types, little is known about their role in PSCC. Thus, we attempted to identify miRNAs involved in tumor development and metastasis in distinct histological subtypes considering the impact of HPV infection. In a first step, microarray analyses were performed on RNA from formalin-fixed, paraffin-embedded tumor (22), and normal (8) tissue samples. Microarray data were validated for selected miRNAs by qRT-PCR on an enlarged cohort, including 27 tumor and 18 normal tissues. We found 876 significantly differentially expressed miRNAs (p ≤ 0.01) between HPV-positive and HPV-negative tumor samples by microarray analysis. Although no significant differences were detected between normal and tumor tissue in the whole cohort, specific expression patterns occurred in distinct histological subtypes, such as HPV-negative usual PSCC (95 differentially expressed miRNAs, p ≤ 0.05) and HPV-positive basaloid/warty subtypes (247 differentially expressed miRNAs, p ≤ 0.05). Selected miRNAs were confirmed by qRT-PCR. Furthermore, microarray data revealed 118 miRNAs (p ≤ 0.01) that were significantly differentially expressed in metastatic versus non-metastatic usual PSCC. The lower expression levels for miR-137 and miR-328-3p in metastatic usual PSCC were validated by qRT-PCR. The results of this study confirmed that specific miRNAs could serve as potential diagnostic and prognostic markers in single PSCC subtypes and are associated with HPV-dependent pathways.

The HPV and p63 Status in Penile Cancer Are Linked with the Infiltration and Therapeutic Availability of Neutrophils.

Squamous penile cancer displays a rare human papillomavirus (HPV)-associated tumor entity. Investigations on the molecular pathogenesis of HPV-driven penile cancer are impaired by the rareness of clinical specimens and, in particular, are missing relevant cell culture models. Here, we identified in HPV-positive penile cancer cell lines that HPV16 oncoproteins control TP63 expression by modulating critical regulators, while integration into the TP63 open reading frame facilitates oncogene expression. The resulting feed-forward loop leads to elevated p63 levels that in turn enhance the release of the neutrophil-recruiting chemokine CXCL8. Remarkably, elevated CXCL8 amounts lead to the increased surface exposition of the Fc receptor of human IgA antibodies, FcαRI, on neutrophils and correlated with a higher susceptibility to antibody-dependent neutrophil-mediated cytotoxicity (ADCC) using an EGFR-specific IgA2 antibody. IHC staining of tissue microarrays proved that elevated expression of p63 together with neutrophil infiltration were significantly more frequent in HPV-positive penile cancer displaying a higher tumor grade. In summary, we identified a promising marker profile of patients with penile cancer at higher risk for worse prognosis. However, these patients may benefit from immunotherapeutic approaches efficiently engaging neutrophils for tumor cell killing.

High/low-volume center experience predicts outcome of AMS 800 in male stress incontinence: Results of a large middle European multicenter case series.

AIM: To analyze the influence of implantation volume of artificial sphincters (AMS 800) on outcome in a large central European multicenter cohort study. METHODS: As part of the DOMINO (Debates on Male Incontinence) project, the surgical procedures and outcomes were retrospectively analyzed in a total of 473 patients who received an artificial sphincter (AMS 800) between 2010 and 2012. Clinics that implanted at least 10 AMS 800 per year were defined as high-volume centers. RESULTS: Sixteen centers had a mean rate of 9.54 AMS 800/y of which five clinics were identified as high-volume centers. They implanted significantly more double cuffs (55% vs 12.1%; P < .001), used the perineal approach significantly more often (78% vs 67.7%; P = .003) and chose larger mean cuff sizes (4.63 cm vs 4.42 cm; P = .002). With a mean follow-up of 18 months, the revision rate was significantly higher at low-volume centers (38.5% vs 26.7%; P = .037), urethral erosion being the main reason for revision. Social continence (0-1 pads/24 h) was achieved significantly more often in high-volume centers (45.5% vs 24.2%; P = .002). CONCLUSIONS: Our study showed significantly better continence results and lower revision rates at high-volume centers, confirming earlier results that are still true in this decade. We, therefore, recommend surgery for male incontinence at qualified centers.

Secondary Sling Implantation after Failure of Primary Surgical Treatment for Male Stress Urinary Incontinence: A Retrospective Study.

OBJECTIVE: The artificial urinary sphincter (AUS) is the surgical gold standard after previously failed surgical treatment for male urinary stress incontinence. The evidence for a male sling as salvage treatment is poor, but there is a proportion of patients that refuse implantation of an AUS or have a relative contraindication. The goal of our retrospective study was an analysis of outcome and complications of patients with a secondary sling after previously failed surgery for stress urinary incontinence (SUI). MATERIALS AND METHODS: Data on 186 patients who had a prior incontinence surgery were extracted from the DOMINO database. 139 patients (74.7%) received an AUS and 41 patients (22.0%) who had received a secondary sling system between 2010 and 2012 after previously failed surgery for male urinary incontinence could be identified and were further analyzed. RESULTS: Eight patients (19.5%) received a secondary repositioning sling and 33 patients (80.5%) received a secondary adjustable sling system. A prior surgery for urethral stricture was performed in 4 patients (9.8%). No major intraoperative complications were reported. A simultaneous explantation was performed in 12 patients (29.3%). The mean number of pad reductions was 4.93 (p = 0.026). No intraoperative complications and no postoperative surgical revisions were reported. The mean follow-up of the patient cohort with a secondary sling was 16 months. CONCLUSION: We provide the largest cohort of male patients up to date with a secondary sling after primary failure of surgery for male SUI. Although the procedure is a rarely performed surgery and without a high level of evidence, a secondary adjustable male sling system might be a feasible option in selected patients with acceptable complication rates, whereas a valuable outcome regarding continence rates cannot be sufficiently supplied by our data.

Retropubic vs transobturator Argus adjustable male sling: Results from a multicenter study.

AIMS: To comparatively analyse outcomes after ARGUS classic and ArgusT adjustable male sling implantation in a real-world setting. METHODS: Inclusion criteria encompassed: non-neurogenic, moderate-to-severe stress urinary incontinence (≥2 pads), implantation of an ARGUS classic or ArgusT male sling between 2010 and 2012 in a high-volume center (>150 previous implantations). Functional outcomes were assessed using daily pad usage, 24-hour pad testing, and International Consultation on Incontinence (ICIQ-SF) questionnaires. Continence was defined as zero pads per 24 hours. Complications were graded using Clavien-Dindo scale. For multivariate analysis, binary logistic regression models were used (P < .05). RESULTS: A total of 106 patients (n = 74 [ARGUS classic], n = 32 [ArgusT]) from four centers were eligible. Median follow-up was 44.0 months (24-64). Patient cohorts were well-balanced. We observed a statistical trend in favor of ARGUS classic regarding postoperative urine loss based on standardized 24-hour pad test (71 ± 162 g [ARGUS classic] vs 160 ± 180 g [ArgusT]); P = .066]. Dry rates were 33.3% (ARGUS classic) and 11.8% (ArgusT, P = .114). In multivariable analysis, ArgusT male sling could not be confirmed as an independent predictor of decreased success (OR, 0.587; 95% CI; 0.166-2.076, P = .408). There were no Clavien IV and V complications. Inguinal pain was significantly higher after ArgusT implantation (P = .033). Explantation rates were higher for ArgusT compared to ARGUS classic (14.0 vs 23.3%; P = .371). Longer device survival for the ARGUS classic male sling was observed in Kaplan-Meier analysis (P = .198). CONCLUSIONS: In the largest comparative analysis of ARGUS classic and ArgusT male sling with the longest follow-up to date, we observed low continence rates with superior functional outcomes and decreased explantation rates after ARGUS classic implantation.

Artificial Urinary Sphincter Cuff Size Predicts Outcome in Male Patients Treated for Stress Incontinence: Results of a Large Central European Multicenter Cohort Study.

PURPOSE: The aim was to study the correlation between cuff size and outcome after implantation of an AMS 800 artificial urinary sphincter. METHODS: A total of 473 male patients with an AMS 800 sphincter implanted between 2012 and 2014 were analyzed in a retrospective multicenter cohort study performed as part of the Central European Debates on Male Incontinence (DOMINO) Project. RESULTS: Single cuffs were implanted in 54.5% and double cuffs in 45.5% of the patients. The cuffs used had a median circumference of 4.5 cm. Within a median follow of 18 months, urethral erosion occurred in 12.8% of the cases and was associated significantly more often with small cuff sizes (P<0.001). Multivariate analysis showed that, apart from cuff size (P=0.03), prior irradiation (P<0.001) and the penoscrotal approach (P=0.036) were associated with an increased erosion rate. Continence rate tended to be highest with median cuff sizes (4-5.5 cm). CONCLUSION: Apart from irradiation and the penoscrotal approach, small cuff size is a risk factor for urethral erosion. Results are best with cuff sizes of 4.5-5.5 cm.

Challenging the prognostic impact of the new WHO and TNM classifications with special emphasis on HPV status in penile carcinoma.

The evidence concerning prognostic parameters for clinical decision-making in penile cancer is either weak or missing. We therefore analysed the prognostic value of the revised TNM and WHO classification systems on relapse and survival with special emphasis on HPV status. We collected clinical data and tissue samples of 121 patients from centres in Germany and Russia. HPV genotyping and p16INK4a immunostaining were performed. The histological subtype and TNM were reclassified by two experienced uropathologists. Survival analyses were performed by Kaplan-Meier estimator and log-rank test. Uni- and multivariable analyses were performed by Cox proportional hazard model and Fisher's exact test for contingency analysis. HPV status was not found to be an independent prognostic factor. Histological subtypes differ in prognosis with the best outcome found in warty and the worst in basaloid carcinomas. Patients with pT1b defined by poor differentiation or lymphovascular invasion (LVI) had the shortest metastasis-free survival compared with pT1a (log-rank, p = 0.02). Lymph node metastasis and LVI were significantly associated with poor metastasis-free, cancer-specific and overall survival and could be identified as the only independent prognostic parameters. Prognostic value of TNM could not be improved using the 8th versus the 7th edition. In contrast to HPV status, histological subtypes are of prognostic value and should be an essential part of pathologic reports. The impact of the HPV status needs to be analysed in a subtype-specific manner. Parameters describing lymphatic dissemination have the highest impact on prognosis. Inclusion of tumour grade and LVI into a single T-category (pT1b) seems questionable.

The AdVance and AdVanceXP male sling in urinary incontinence: is there a difference?

PURPOSE: To compare the efficacy and perioperative complications of the AdVanceXP with the original AdVance male sling. METHODS: We retrospectively enrolled 109 patients with an AdVance and 185 patients with an AdVanceXP male sling. The baseline characteristics and complication rates were analyzed retrospectively. Functional outcome and quality of life were evaluated prospectively by standardized, validated questionnaires. The Chi2-test for categorical and Mann-Whitney U test for continuous variables were performed to identify heterogeneity between the groups. RESULTS: Regarding operation time, there was no significant difference between the slings (p = 0.146). The complication rates were comparable in both groups except for postoperative urinary retention. This occurred significantly more often in patients with the AdVanceXP (p = 0.042). During follow-up, no differences could be identified regarding ICIQ-SF, PGI or I-QoL or number of pad usage. CONCLUSIONS: The AdVance and AdVanceXP are safe and effective treatment options for male stress urinary incontinence. However, the innovations of the AdVanceXP sling did not demonstrate a superiority over the original AdVance sling regarding functional outcome.

Laser-supported partial laparoscopic nephrectomy for renal cell carcinoma without ischaemia time.

BACKGROUND: To date, elective nephron-sparing surgery is an established method for the exstirpation of renal tumors. While open partial nephrectomy remains the reference standard of the management of renal masses, laparoscopic partial nephrectomy (LPN) continues to evolve. Conventional techniques include clamping the renal vessels risking ischaemic damage of the clamped organ. Thus, new techniques are needed that combine a sufficient tissue incision for exstirpation of the tumor with an efficient coagulation to assure haemostasis and abandon renal vessel clamping in LPN. Laser-excision of renal tumors during laparoscopic surgery seems to be a logical solution. METHODS: We performed nephron-sparing surgery without clamping of the renal vessels in 11 patients with a renal tumor in exophytic position (mean size 32 mm, ranging 8-45 mm) by laser-supported LPN. RESULTS: Regular ultrasound monitoring and insertion of a temporary drainage showed no evidence of postoperative hemorrhage. All tumors were removed with a histopathologically confirmed surrounding margin of normal renal tissue (R0 resection). Serum creatinine, hemoglobin, and hematocrit were nearly unaltered before and after surgery. CONCLUSIONS: The experience won in these patients have confirmed that laser-assisted LPN without clamping of the renal vessels could be a safe and gentle alternative to classic partial nephrectomy in patients with exophytic position of renal tumors.

Synergistic effects of histone deacetylase inhibitor in combination with mTOR inhibitor in the treatment of prostate carcinoma.

The aim of this study was to elucidate whether the treatment of a prostate carcinoma cell line (LNCaP) and LNCaP-derived tumors with the histone deacetylase (HDAC) inhibitor valproate in combination with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus resulted in synergistic effects on cell proliferation and tumor growth. LNCaP cells were treated with valproate, temsirolimus or a combination of both. The proliferation rates and the expression of key markers of tumorigenesis were evaluated. In in vivo experiments, LNCaP cells were implanted into immune-suppressed male nude mice. Mice were treated with valproate (per os), temsirolimus (intravenously) or with a combination of both. Tumor volumes were calculated and mRNA expression was quantified. The incubation of LNCaP cells with the combination of valproate and temsirolimus resulted in a decrease of cell proliferation with an additive effect of both drugs in comparison to the single treatment. In particular, the combined application of valproate and temsirolimus led to a significant upregulation of insulin-like growth factor-binding protein-3 (IGFBP-3), which mediates apoptosis and inhibits tumor cell proliferation. In the mouse model, we found no significant differences in tumor growth between the different treatment arms but immunohistological analyses showed that tumors treated with a combination of valproate and temsirolimus, but not with the single drugs alone, exhibited a significant lower proliferation capacity.

Hereditary papillary renal cell carcinoma primarily diagnosed in a cervical lymph node: a case report of a 30-year-old woman with multiple metastases.

BACKGROUND: Papillary renal cell carcinoma is a rare cancer. Some cases can be attributed to individuals with hereditary renal cell carcinomas usually consisting of the clear cell subtype. In addition, two syndromes with hereditary papillary renal cell carcinoma have been described. One is the hereditary leiomyomatosis and renal cell carcinoma, which is characterized by cutaneous and uterine leiomyomas and renal cell carcinoma mostly consisting of the papillary renal cell carcinoma type II with a worse prognosis. CASE PRESENTATION: We describe a case of a 30-year-old woman with hereditary leiomyomatosis and renal cell carcinoma syndrome with extensively metastasized papillary renal cell carcinoma, primarily diagnosed in a cervical lymph node lacking leiomyomas at any site. CONCLUSION: Papillary renal cell carcinoma in young patients should be further investigated for a hereditary variant like the hereditary leiomyomatosis and renal cell carcinoma even if leiomyomas could not be detected. A detailed histological examination and search for mutations is essential for the survival of patients and relatives.

Occult gastric signet ring cell carcinoma presenting as spermatic cord and testicular metastases: "Krukenberg tumor" in a male patient.

Krukenberg tumor is a well-known ovarian metastasis, usually of gastric signet ring cell carcinoma in female patients. Although gastric carcinoma is more frequent in men, to our knowledge, only few cases of counterpart testicular metastases have been described as yet. We report a 64-year-old patient who complained of right testicular pain. Right-sided orchiectomy was performed, and metastatic signet ring cell carcinoma of spermatic cord and testis was diagnosed through histological examination and immunohistochemistry. The following stomach biopsy confirmed the primary signet ring cell carcinoma in the stomach. This extremely rare form of metastatic dissemination resembles the Krukenberg tumor of ovaries. Immunohistochemical staining plays an important role in the differential diagnosis of spermatic cord enlargement.