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Background: Penile squamous cell carcinoma (PSCC) is a rare malignancy. However, in developing countries the incidence rate is higher. The understanding of molecular alterations is essential for evaluating possible targets for more effective systemic therapies., Methods: We retrospectively collected clinical data of metastatic PSCC (mPSCC) patients who had received at least one prior systemic treatment from 3 Brazilian hospitals. Tumor samples were evaluated using the next-generation sequencing (NGS) Foundation One DX and immunohistochemistry (IHC). The objective was to identify and describe somatic genomic alterations known to be functional or pathogenic and their association with survival outcomes., Results: Twenty-three patients were identified, 22 and 18 patients had tumor samples analyzed by IHC and NGS, respectively. PD-L1 expression (CPS ≥ 1%) was positive in 14 patients (63.6%). Regarding the genomic alterations, 16 patients (88.9%) had some clinically relevant genomic alterations. TP53, TERT, CDKN2A, PIK3CA, NOTCH1, and CDKN2B loss were identified in 66.7%, 50%, 50%, 33.3%, 27.8%, and 22.2% of the patients, respectively. No MSI or TMB high (≥10 mutations/MB) cases were identified. NOTCH1 mutation was identified only in HPV-negative patients and it was associated with worse OS (yes: 5.5 vs no: 12.8 months, P = .049) and progression-free survival (yes: 5.5 vs no: 11.7 months, P = .032)., Conclusion: This study demonstrated that molecular alterations in mPSCC from developing countries are similar to those from developed countries. Predictive biomarkers for immunotherapy response such as TMB high or MSI were not identified. Specific gene mutations may identify patients with worse prognoses and open new avenues for therapeutic development., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors., Patients and Methods: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis. From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. About 48% of patients underwent first-line of therapy., Results: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs. 8.3 months; P < .001), and median age (≤77y 88.8 months vs. >77y 26 months; P = .013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death. Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs. PD 7.1 months; P < .001). Multivariate analysis showed that only age >77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil versus platinum plus taxane (4.9 vs. 3.4 months; P = .036) and regimens with 2 versus 3 drugs (3.4 vs. 8.6 months; P = .019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83)., Conclusion: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes., Competing Interests: Disclosure The other authors declare no conflict of interest. Francesco Pierantoni: Advisory board: Eli Lilly; Speaker and travel fees: Pfizer, BMS, MSD, AstraZeneca, Jannsen, Takeda, Merck, Astellas, Ipsen. Paola Ermacora: MSD, BMS, AAA, Astellas, Recordati, Eisai (advisory board), Jansenn (travel grant)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Research on penile cancer (PeCa) is predominantly conducted in countries with centralized treatment of PeCa-patients. In Germany and Austria (G + A), no state-regulated centralization is established, and no information is available on how PeCa-research is organized., Methods: Current research competence in PeCa was assessed by a 36-item questionnaire sent to all chairholders of urological academic centers in G + A. Based on PubMed records, all scientific PeCa-articles of 2012-2022 from G + A were identified. Current research trends were assessed by dividing the literature search into two periods (P1: 2012-2017, P2: 2018-2022). A bibliometric analysis was supplemented., Results: Response rate of the questionnaire was 75%, a median of 13 (IQR: 9-26) PeCa-patients/center was observed in 2021. Retrospective case series were conducted by 38.9% of participating clinics, while involvement in randomized-controlled trials was stated in 8.3% and in basic/fundamental research in 19.4%. 77.8% declared an interest in future multicenter projects. 205 PeCa-articles were identified [median impact factor: 2.77 (IQR: 0.90-4.37)]. Compared to P1, P2 showed a significant increase in the median annual publication count (29 (IQR: 13-17) vs. 15 (IQR: 19-29), p < 0.001), in multicenter studies (79.1% vs. 63.6%, p = 0.018), and in multinational studies (53% vs. 28.9%, p < 0.001); the proportion of basic/fundamental research articles significantly declined (16.5% vs. 28.9%, p = 0.041). Four of the top-5 institutions publishing PeCa-articles are academic centers. Bibliometric analyses revealed author networks, primary research areas in PeCa, and dominant journals for publications., Conclusions: Given the lack of centralization in G + A, this analysis highlights the need for research coordination within multicenter PeCa-projects. The decline in basic/fundamental research should be effectively addressed by the allocation of funded research projects., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Penile carcinoma is an uncommon cancer that develops in the penis tissue. The standard surgical method to manage regional lymph nodes after local excision is radical inguinal lymphadenectomy, but it has a high rate of complications. The objective of this retrospective study was to compare the long-term outcomes of endoscopic inguinal lymphadenectomy and open inguinal lymphadenectomy in patients with penile carcinoma., Methods: The study included patients diagnosed with penile carcinoma who underwent open inguinal lymphadenectomy (n = 23) or endoscopic inguinal lymphadenectomy (n = 27) at a single hospital between January 2013 and January 2021. Operation time, blood loss, drainage, hospital stay, postoperative complications, and survival rates were assessed and compared between the two groups., Results: The two groups were comparable in terms of age, tumor size and stage, inguinal lymph nodes, and follow-up. The endoscopic group had significantly lower blood loss (27.1 ± 1.5 ml vs 55.0 ± 2.7 ml, P < 0.05), shorter drainage time and hospital stay (4.7 ± 1.1 days vs 8.1 ± 2.2 days, and 13.4 ± 1.0 days vs 19 ± 2.0 days, respectively, P < 0.05), and longer operation time compared to the open group (82.2 ± 4.3 min in endoscopic group vs 53.1 ± 2.2 min in open group, P < 0.05). There were significant differences in the incidence of incisional infection, necrosis, and lymphorrhagia in both groups (4 vs 0, 4 vs 0, and 2 vs 0, respectively, P < 0.05). The inguinal lymph node harvested was comparable between the two groups. The mean follow-up time was similar for both groups (60.4 ± 7.7 m vs 59.8 ± 7.3 m), and the recurrence mortality rates were not significantly different., Conclusions: The study shows that both open and endoscopic methods work well for controlling penile carcinoma in the long term. But the endoscopic approach is better because it has fewer severe complications. So, the choice of surgery method might depend on factors like the surgeon's experience, what they like, and what resources are available., (© 2023. The Author(s).)

Introduction: Inguinal lymph node dissection (ILND) plays an important role for both staging and treatment purposes in patients diagnosed with penile carcinoma (PeCa). Video-endoscopic inguinal lymphadenectomy (VEIL) has been introduced to reduce complications, and in those patients elected for bilateral ILND, a simultaneous bilateral VEIL (sB-VEIL) has also been proposed. This study aimed to investigate the feasibility, safety, and preliminary oncological outcomes of sB-VEIL compared to consecutive bilateral VEIL (cB-VEIL)., Material and Methods: Clinical N0-2 patients diagnosed with PeCa and treated with cB-VEIL and sB-VEIL between 2015 and 2023 at our institution were included. Modified ILND was performed in cN0 patients, while cN+ patients underwent a radical approach. Intra- and postoperative complications, operative time, time of drainage maintenance, length of hospital stay and readmission within 90 days, as well as lymph node yield, were compared between the two groups., Results: Overall, 30 patients were submitted to B-VEIL. Of these, 20 and 10 patients underwent cB-VEIL and sB-VEIL, respectively. Overall, 16 (80%) and 7 (70%) patients were submitted to radical ILND due to cN1-2 disease in the cB-VEIL and sB-VEIL groups, respectively. No statistically significant difference emerged in terms of median nodal yield (13.5 vs. 14, p = 0.7) and median positive LNs ( p = 0.9). sD-VEIL was associated with a shorter operative time (170 vs. 240 min, p < 0.01). No statistically significant difference emerged in terms of intraoperative estimated blood loss, length of hospital stay, time to drainage tube removal, major complications, and hospital readmission in the cB-VEIL and sB-VEIL groups, respectively (all p > 0.05)., Conclusions: Simultaneous bilateral VEIL is a feasible and safe technique in patients with PeCA, showing similar oncological results and shorter operative time compared to a consecutive bilateral approach. Patients with higher preoperative comorbidity burden or anesthesiological risk are those who may benefit the most from this technique.

In the treatment of cancer, immune checkpoint inhibitors (ICIs) have demonstrated significantly greater effectiveness compared to conventional cytotoxic or platinum-based chemotherapies. To assess the efficacy of ICI's in penile squamous cell carcinoma (pSCC) we performed a retrospective observational study. We reviewed electronic medical records of patients with penile squamous cell carcinoma (SCC), diagnosed between January 2020 and February 2023. Nine patients were screened, of whom three were ineligible for chemotherapy and received immunotherapy, cemiplimab, in a first-line setting. Each of the three immunotherapy-treated patients achieved almost a complete response (CR) after only a few cycles of therapy. The first patient had cerebral arteritis during treatment and received a high-dose steroid treatment with resolution of the symptoms of arteritis. After tapering down the steroids dose, the patient continued cemiplimab without further toxicity. The other two patients did not have any toxic side effects of the treatment. To the best of our knowledge, this is the first real world report of near CR with cemiplimab as a first-line treatment in penile SCC.

Introduction: Penile cancer, while relatively rare in developed nations, presents substantial disparities in outcomes among different demographic groups. Previous research has shown race/ethnicity and socioeconomic status, often proxied by household median income, to be critical determinants of health outcomes across various diseases., Objective: This study examines the association of race/ethnicity and household median income with survival among penile cancer patients in the United States., Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) Registry to identify patients with a primary diagnosis of penile malignancies from 2000 to 2019. Our primary outcome of interest was the hazard of death following a diagnosis of penile cancer. We utilized the Cox regression model to explore the association between race/ethnicity and median household income and how this influences survival among these patients. We adjusted for patients' characteristics, disease stage at presentation, and treatment modalities., Result: Of the 6,520 penile cancer patients identified, 5,242 (80.4%) had primary malignancies. The distribution of patients was as follows: 64.1% non-Hispanic Whites, 8.9% non-Hispanic Blacks, 20.8% Hispanics, and 6.2% from other racial/ethnic groups. The median diagnosis age was 66 years (interquartile range: 56-74). Survival rates at 5, 10, and 15 years showed racial disparities: 76.4%, 72.5%, and 69.7% for non-Hispanic Whites; 70.6%, 64.1%, and 61.1% for non-Hispanic Blacks; and 70.5%, 67.4%, and 65.6% for Hispanics. Multivariate Cox regression revealed worst survival for Black (HR=1.40; 95% CI=1.08-1.81, p=0.01) and Hispanic patients (HR=1.24; 95% CI=1.01-1.52, p=0.04). No association was found between median household income and survival. Interaction analysis indicated that the poorest Black men had worse outcomes than the poorest Whites did (HR=2.08; 95% CI=1.27-3.41, p=0.003)., Conclusion: Survival rates for non-Hispanic Black and Hispanic patients are significantly lower than those for non-Hispanic Whites. Furthermore, survival is worse for low-income Black patients than their White counterparts in the same income bracket., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Akinyemi et al.)

Objective: Exploratory study of the effect and clinical value of carbon nanoparticle suspension injection (CNSI) as a tracer for inguinal sentinel lymph nodes in penile cancer., Method: We selected 29 patients with penile cancer in our department from January 2019 to October 2022. According to whether the CNSI tracer was injected during the pathological biopsy of the inguinal lymph nodes, the enrolled patients were assigned to the control group, the group in which CNSI was injected 12 h before the surgery (12HBS group) and the group in which CNSI was injected 0.5 h before the surgery (0.5HBS group). Evaluating the effectiveness of CNSI as a lymphatic tracer involves analyzing the following: its safety, the statistical analysis of the detection rate (DR) of different groups, the number of lymph nodes sent for each case (NOLNSFEC), the difference of positive rate of lymphatic metastasis (PROLM), and operation time (OT)., Results: The lymph nodes in the 12HBS group and 0.5HBS group had an obvious black staining appearance, and no adverse reactions or surgical complications were found. Most of the black-stained areas caused by CNSI injection were removed with penile excision, which did not affect the postoperative appearance. This did not affect the pathological analysis. The DR of lymph nodes in the 12HBS group was higher ( p < 0.05) than that in the control group. More lymph nodes were removed for examination ( p < 0.05), which improved the efficiency of surgery. Compared with the 12HBS group, the number of lymph nodes removed in the 0.5HBS group decreased ( p < 0.05). The OT was shortened ( p < 0.05), but there was no significant difference in the DR and PROLM., Conclusion: CNSI was applied to the naked-eye tracing of inguinal sentinel lymph nodes in penile cancer, which is safe and efficient. Injection of CNSI 0.5 h before surgery can help identify the "foremost position" of sentinel lymph nodes and reduce surgical trauma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Xu, Shao, Yang, Li, Li, Liu, Ding, Ma and Li.)

Background: Low-dose-rate brachytherapy is an effective organ-sparing treatment for patients with early-stage penile cancer. However, only limited data are available on the role of high-dose-rate brachytherapy (HDR-BT) in this clinical setting., Methods: Between 2002 and 2020, 31 patients with early penile cancer were treated at our center with interstitial HDR BT at a dose of 18 × 3 Gy twice daily. A breast brachytherapy template was used for the fixation of stainless hollow needles., Results: The median follow-up was 117.5 months (range, 5-210). Eight patients (25.8%) developed a recurrence; of these, seven were salvaged by partial amputation. Six patients died of internal comorbidities or a second cancer. The probability of local control at 5 and 10 years was 80.7% (95% CI: 63.7-97.7%) and 68.3% (95% CI: 44.0-92.6%), respectively. Cause-specific survival was 100%. Only one case of radiation-induced necrosis was observed. The probability of penile sparing at 5 and 10 years was 80.6% (95% CI: 63.45-97.7%) and 62.1% (95% CI: 34.8-89.4%), respectively., Conclusions: These results show that HDR-BT for penile cancer can achieve results comparable to LDR-BT with organ sparing. Despite the relatively large patient cohort-the second largest reported to date in this clinical setting-prospective data from larger samples are needed to confirm the role of HDR-BT in penile cancer.

Purpose: To investigate the local recurrence rates of men treated with Mohs microsurgery (MMS) for penile carcinoma. The secondary outcome was surgical complications from the MMS procedure or the subsequent reconstructive procedures., Materials and Methods: All patients from 2010 to 2020 with penile carcinoma at our institution were seen in a multidisciplinary setting. Patients with Ta, Tis, T1, and T2 disease were considered candidates for MMS. Clinical and pathologic data were collected for analysis. Local recurrence rates were stratified by stage and complications reported per the Clavien-Dindo Grade., Results: A total of 43 patients met inclusion criteria. The median age at diagnosis was 64 years. Stage distribution was Ta in 4.7%, Tis in 58.1%, T1a in 14.0%, T1b in 7.0%, and T2 in 16.3%. No patients had a positive surgical margin after MMS. The overall local recurrence rate was 2% (n = 1) at a median of 47 months. Local recurrence rates at 1, 3, and 5 years for Ta, Tis, and T1 patients were 0%. Local recurrence rates for T2 patients were 14% at 1 year. Complications occurred in 12% (n = 5), all of which were Clavien-Dindo ≤ III., Conclusions: MMS provides effective local control for Ta, Tis, and T1 penile cancer with an overall local recurrence rate of 2% and an acceptable complication rate. A multi-disciplinary team involving urologic oncology, reconstructive urology, and MMS is essential to patient management., Competing Interests: Conflicts of interest The other authors declare no conflict of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: In this article we review the quality of life and the psychosocial and functional outcomes experienced by patients and their partners following penile cancer diagnosis and treatment., Data Sources: A literature search for primary articles related to patient reported outcomes following penile cancer treatment was conducted using the electronic database PubMed., Conclusion: Penile cancer is a rare malignancy in the United States, and it carries an excellent prognosis if diagnosed early. However, increased survivorship carries devastating long-term consequences on the mental health of patients and their families. Factors impacting the quality of life of patients include sexual dysfunction, cosmetic changes, voiding dysfunction, depression, and anxiety. Treatment modalities vary depending on the extent of the cancer but include medical, interventional, and surgical options., Implications for Nursing Practice: The multidisciplinary team can support patients and their partners to develop, test and deliver posttreatment survivorship interventions to optimize psychosocial well-being and quality of life outcomes for this rare disease., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The presence of lymph node metastasis is the most important prognostic factor in penile cancer (PeCa). Due to limited sensitivity of currently available imaging modalities, invasive staging approaches remain indispensable for adequate nodal staging. As an alternative to radical inguinal lymphadenectomy and with the aim to reduce morbidity, staging strategies such as modified lymphadenectomy and dynamic sentinel node biopsy (DSNB) have been introduced. Over the years, DSNB evolved into a safe and reliable staging technique when performed in high volume centers. Recent enhancements of the procedure such as Single-photon emission computed tomography/computed tomography (SPECT/CT) and the introduction of hybrid tracers have improved pre- and intraoperative sentinel node (SN) visualization. Other technologies such as superparamagnetic iron oxide nanoparticles could have a potential future role to further refine DSNB. Future efforts should be aimed at optimizing diagnostic accuracy whilst minimizing perioperative morbidity., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Inguinal lymphadenectomy (iLAD) is effective for penile carcinoma treatment, but usually results in many complications. This study aims to clinically evaluate the feasibility and clinical significance of a laparoscopic radical iLAD approach partly preserving great saphenous vein branches for penile carcinoma patients., Methods: A total of 48 patients with penile cancer who underwent laparoscopic radical iLAD with retention of the great saphenous vein in Henan Cancer Hospital from 2012 Jan to 2020 Dec were included in this study. Sixteen penile carcinoma patients who underwent laparoscopic radical iLAD preserving parts of superficial branches of the great saphenous vein were identified as the sparing group, and the matched 32 patients who incised those branches were identified as control group. This new procedure was performed by laparoscopy, preserving parts of superficial branches of the great saphenous vein, superficial lateral and medial femoral veins. Clinicopathological features and perioperative variables were recorded. Postoperative complications, including skin flap necrosis, lymphorrhagia, and lower extremity edema were analyzed retrospectively., Results: We found that the operative time of the sparing group is significantly longer than the control group (p = 0.011). There was no statistical difference in intraoperative blood loss, the lymph node number per side, average time to remove the drainage tube and postoperative hospital stay between the two groups. Compared to the control group, the sparing group showed a significantly decreased incidence of lower extremity edema (p = 0.018). The preservation of parts of superficial branches of the great saphenous vein was mainly decreased the incidence of edema below ankle (p = 0.034)., Conclusions: This study demonstrated that the iLAD with preserving parts of superficial branches of the great saphenous vein, with a decreased incidence of postoperative complications, is a safe and feasible approach for penile cancer., (© 2022. The Author(s).)

Penile carcinogenesis can be superposed on vulvar carcinogenesis, with two pathways : with or without a link to HPV. Penile squamous cell carcinomas arise from precursor lesions: penile intraepithelial neoplasia (PeIN) defined by the presence of intraepithelial atypia, which can progress to invasive squamous cell carcinoma. Differentiated PeINs not linked to HPV, affect elderly men with inflammatory lesions, most often lichen sclerosus. PeINs linked to HPV, basaloid, condylomatous or condylomatous-basaloid growth affect younger men. Although clinically similar, their distinction is important, because the treatment differs with a greater risk of invasion for forms unrelated to HPV., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The high-risk human papillomavirus (HPV) infection represents one of the main etiologic pathways of penile carcinogenesis in approximately 30-50 % of cases. Several techniques for the detection of HPV are currently available including Polymerase chain reaction-based techniques, DNA and RNA in situ hybridization (ISH), p16 immunohistochemistry (IHC). The multiplex HPV RNA ISH/p16 IHC is a novel technique for the simultaneous detection of HPV E6/E7 transcripts and p16INK4a overexpression on the same slide in a single assay. The main aim of this study was to evaluate the discrepancy of p16 IHC expression relatively to HPV RNA ISH in penile cancer tissue., Methods: We collected a series of 60 PCs. HPV has been analysed through the RNA ISH, p16 IHC and the multiplex HPV RNA ISH/p16 IHC., Results: The multiplex HPV RNA ISH /p16 IHC results in the series were in complete agreement with the previous results obtained through the classic p16 IHC and HPV RNA scope carried out on two different slides. The multiplex HPV RNA ISH /p16 IHC showed that HPV positivity in our series is more frequently in usual squamous cell carcinoma than in special histotypes (19 out of 60 - 15 %- versus 6 out of 60 - 10 %-), in high-grade than in moderate/low grade carcinomas (6 out of 60 - 10 %- versus 4 out of 60 - 6.7 %-). In addition, our data revealed that in 5 out of 20 cases with p16 high intensity expression is not associated with HPV RNA ISH positivity., Conclusions: Our findings emphasize that the use of p16 as a surrogate of HPV positivity was unsuccessful in approximatively 8 % of cases analysed in our series. Indeed, p16 IHC showed a sensitivity of 100 % and a specificity of 71 %, with a positive predictive value (PPV) of 54 % and a negative predictive value of 100 %; when considering high intensity, p16 IHC showed a sensitivity of 100 %, a specificity of 89 %, with a PPV of 75 % and NPV of 100 %. Since HPV positivity could represent a relevant prognostic and predictive value, the correct characterization offered by this approach appears to be of paramount importance.

We aim to review the literature for studies investigating the oncological outcomes of patients with penile cancer (PC) undergoing bilateral pelvic lymph node dissection (PLND) in the presence of inguinal lymph node metastasis (LNM) who are at risk of harboring pelvic metastasis. A search of English language literature was performed using the PubMed-MEDLINE database up to 3 December 2020 to identify articles addressing bilateral PLND in PC patients. Eight articles investigating bilateral PLND met our inclusion criteria. Patients with pelvic LNM have a dismal prognosis and, therefore, PLND has an important role in both the staging and treatment of PC patients. Ipsilateral PLND is recommended in the presence of ≥2 positive inguinal nodes and/or extranodal extension (ENE). Significant survival improvements were observed with a higher pelvic lymph node yield, in patients with pN2 disease, and in men treated with bilateral PLND as opposed to ipsilateral PLND. Nevertheless, the role of bilateral PLND for unilateral inguinal LNM remains unclear. Although the EAU guidelines state that pelvic nodal disease does not occur without ipsilateral inguinal LNM, metastatic spread from one inguinal side to the contralateral pelvic side has been reported in a number of studies. Further studies are needed to clarify the disseminative pattern of LNM, in order to establish PLND templates according to patients' risk profiles and to investigate the benefit of performing bilateral PLND for unilateral inguinal disease.

Since the seminal study of Hart and Helwig in 1975, there are few detailed pathological studies of lichen sclerosus (LS). The aims of this study were to provide a detailed histopathological description of penile LS, as well as to explore its relationship with penile intraepithelial neoplasia (PeIN) or invasive carcinoma. We evaluated 200 patients and designed a topographical approach for the histological evaluation focusing in alterations of the following anatomical layers: squamous epithelium, lamina propria, dartos, and corpus spongiosum. We documented the quantity and topographical location of stromal lymphocytes. The prevalent lesions found were epithelial hyperplasia, atrophy, PeIN, basal cell vacuolization, lamina propria sclerosis, and variable patterns of lymphocytic infiltration. Various unique patterns of stromal sclerosis were described: perivascular, globular, linear, and solid fibrosis/hyalinization; any of them were found to be diagnostic for LS. The variation in the topography and density of lymphocytes was determinant for the identification of LS morphological variants: lichenoid, band-like, lymphocytic depleted, and mixed. A major finding was the identification of the variant designated as lymphocytic depleted LS, which we considered as the morphological prototype of LS associated with penile neoplasia. The detailed description of this complex lesion presented in this study may help pathologists in practice to identify and better define LS. The identification of the special variants suggests a role of the stromal lymphocytes in the process of carcinogenesis. Confirmation of the observations with more studies is necessary to determine the significance of these findings.

Penile carcinoma is a relatively frequent health issue in the developing countries such as Africa, Asia and South America, usually affecting men aged between 50 and 70 years. It is a highly treatable disease in its early stages, but has serious physical and psychological consequences. Usually, penile carcinoma is located in the penile glans, in approximately half the cases, with the most frequent histological type being squamous cell carcinoma with its microscopic subtypes. A large number of risk factors have been reported for this disease, having a multifactorial etiology, HPV infection being one of the most important factors involved in its appearance. Out of the HPV DNA positive genital cancers HPV-16 is the most frequently found type in men, followed by HPV-18. The evolution of penile cancer includes two independent carcinogenic pathways, related or unrelated to HPV infection. There is limited data available in literature regarding HPV-related neoplasia, as well as on the efficacy of vaccination in men, with studies still ongoing., (Copyright © 2020, Spandidos Publications.)

Treatment options for rare genitourinary malignancies, including adrenocortical carcinoma, bladder/upper tract cancers of variant histology, penile squamous cell carcinoma, and chemotherapy-refractory germ cell tumors, are limited, often with a poor response to systemic therapy. Given preclinical data and efficacy across multiple malignancies, immunotherapy has been and continues to be explored in this challenging setting. In this report, we explore the data for immunotherapy in these tumors and highlight ongoing clinical trials. International collaborations and innovative trials will be critical to advancing treatment for these rare tumors. PATIENT SUMMARY: In this report, we explore the data for immunotherapy in rare genitourinary malignancies and highlight ongoing clinical trials. International collaborations and innovative trials will be critical to advancing treatment for these rare tumors., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: Approximately 50% of cases of penile carcinoma (PeCa), a rare neoplasm worldwide, are associated with human papillomavirus (HPV). However, the detection of HPV-DNA is not sufficient to consider it the etiological factor in the development of this type of cancer. Currently, the overexpression of P16INK4A is used as a surrogate biomarker of HPV carcinogenesis. Information on PeCa in Mexico is scarce, particularly regarding cases related to HPV and genotype frequency., Objective: To evaluate the presence of HPV, its genotypes, and the presence of multiple genotypes, and the expression of P16INK4A, as well as its clinical and histopathological parameters., Methods: For HPV-DNA detection and P16INK4A expression, we used the INNO-LiPA® test and immunohistochemistry, respectively., Results: Sixty cases of PeCa were evaluated, of which 75% were HPV-non-related histological variants. We found that 58.9% (33/56) of PeCa cases were HPV-DNA positive, while 30.9% of the cases evaluated (17/55) were positive for P16INK4A. HPV16 was the main genotype in 42.9% of the cases, followed by HPV52 in 7.1% and HPV18 in 5.4%. Within the HPV-positive cases, 27.3% had multiple genotypes. All HPV-positive patients under the age of 45 years were positive only for HPV16., Conclusions: HPV16 was the most commonly detected genotype in PeCa. HPV 31, 35 and 39 were infrequent; however, they were related to a single infection and P16INK4A overexpression; thus, they seem to be relevant in PeCa carcinogenesis. Our results suggest that P16INK4A overexpression could be useful for the classification of HPV-related PeCa. The role of multiple HPV genotypes in the development and prognosis of PeCa is still not completely understood. Thus, it is necessary to define criteria to establish reliable ways to classify HPV-related PeCa that could lead to optimal therapeutic approaches.

Penile carcinoma is an uncommon but potentially mutilating disease with a heterogeneous etiology. We present a case in which a man died due to severe blood loss from an amputated penis. It was initially regarded as a violent death with an external cause. Autopsy found irregular defects with smooth edges in the external genital area and on both sides of the groin, with yellowish-gray callus-like structures and dried blood at the base of where the penis would have been located. Histological examination revealed the presence of squamous cell carcinoma with signs of keratinization. Subsequent investigation, along with information from the autopsy, revealed that the man suffered from penile carcinoma, thus death was attributed to exsanguination from an ulcerated femoral artery in a patient with penile carcinoma.

Purpose: Per American Brachytherapy Society guidelines, cT1-2N0 penile cancers <4 cm in diameter are excellent candidates for curative brachytherapy. Using that criterion, we evaluated national patterns of care and predictors of use of radiation techniques using the National Cancer Database., Methods and Materials: The National Cancer Database was queried for men with cT1-2N0 penile cancers <4 cm in size. Comparative statistics for treatment modality were generated using bivariate logistic regression analysis., Results: Among 1235 cases eligible for analysis, median age was 69 years. Median tumor size was 2.0 cm. 95.8% of men underwent surgery alone, with 91 (7.4%) undergoing radical penectomy, 673 (54.5%) partial penectomy, and 419 (33.9%) cosmesis-preserving surgical procedure. Only 4 (0.3%) men were treated with brachytherapy alone, 48 (3.9%) with external-beam radiation therapy (EBRT) alone, and 8 (0.6%) with EBRT after surgery. Surgical margins were positive in 118 (9.6%) patients, 14 of whom received adjuvant EBRT (11.9%) and two adjuvant brachytherapy (1.7%). There was no difference in demographic or clinical characteristics in groups treated with surgery vs. radiation (all p > 0.2). Age >70, lesions >2 cm, and T2 tumors were more likely to undergo non-organ-preserving therapy vs. radiation or a cosmesis-preserving procedure (all p < 0.05). The propensity-matched 5-year survival was not different between definitive radiation vs. surgery (61.6% vs. 62.2%, p = 0.70)., Conclusions: Men with penile-preserving eligible lesions in the United States are overwhelmingly treated with surgery. Penile-preserving radiation techniques including brachytherapy and EBRT are underutilized and should be offered as curative interventions., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Objective: To determine the incidence of penile intraepithelial neoplasia in the Netherlands using a nationwide histopathology registry and to discuss the nomenclature of premalignant penile lesions., Methods: Data from patients in the Netherlands diagnosed with a premalignant penile lesion between January 1998 and December 2007 were collected from the nationwide histopathology registry (PALGA); this database covers all pathology reports of inhabitants in the Netherlands. The premalignant lesions included were erythroplasia of Queyrat; Bowen's disease; bowenoid papulosis; mild, moderate and severe dysplasia; and carcinoma in situ of the penis. The terminology used in the pathological reports was translated to penile intraepithelial neoplasia. The grading was made analogous to that of vulvar premalignant lesions., Results: The PALGA database enrolled 380 patients with premalignant penile lesions. Severe premalignant lesions, penile intraepithelial neoplasia III, were found in 254 patients (67%), penile intraepithelial neoplasia II in 84 (22%) and penile intraepithelial neoplasia I in 42 patients (11%). Most lesions were located on the prepuce (45%), followed by glans (38%) and shaft (3%). The median age of patients with penile intraepithelial neoplasia was 58 years. Progression to malignant disease occurred (2% for penile intraepithelial neoplasia I vs 7% for penile intraepithelial neoplasia III) in 26 patients., Conclusions: Penile intraepithelial neoplasia is a rarely diagnosed condition. Because of the wide variation of terms used for premalignant intraepithelial neoplasia of the penis, we recommend restricting this nomenclature to penile intraepithelial neoplasia., (© 2018 The Japanese Urological Association.)

Androgen receptor (AR) is a member of the steroid and nuclear family receptor that acts as transcription factor. AR signaling plays pivotal role in the development and progression of prostate cancer. However, the role of AR in penile cancer (PeCa) is poorly explored. Our previous molecular studies unveiled frequent AR mRNA loss in PeCa, which was further predicted as a major driver alteration in this neoplasm. Herein, we assessed the AR protein expression in 59 usual PeCa tissues and 42 surrounding normal tissues (SNT) by immunohistochemistry using a tissue microarray. In a paired analysis, we found a total absence of nuclear AR expression in PeCa while 95.2% of SNT samples presented strong nuclear AR expression (P < 0.001). Interestingly, 17 of 42 PeCa presented weak or moderate cytoplasmic AR staining, contrasting with 5 of 42 SNT (P = 0.008). Increased levels of AR cytoplasmic expression were related with poor prognosis features including advanced clinical staging (P = 0.044), compromised surgical margins (P = 0.005), and pathological inguinal node status (P = 0.047). Furthermore, AR cytoplasmic expression was also related with shorter overall survival (P = 0.032). In conclusion, the frequent loss of nuclear AR protein levels suggests a potential function in PeCa development. Based on this result, the androgen deprivation therapy is not indicated for PeCa patients. In addition, the AR cytoplasmic expression found in a significant number of cases (40.5%) showed prognostic value and pathways activated by the non-genomic AR signaling may represent a promising therapeutic strategy.

Penile cancer is a rare neoplasm that seems to be linked to socio-economic differences. Mitochondrial genome alterations are common in many tumors types and are reported as regulating oxidative metabolism and impacting tumorigenesis. In this study, we evaluate for the first time the mitochondrial genome in penile carcinoma (PeCa), aiming to evaluate heteroplasmy, mitochondrial DNA (mtDNA) mutational load and mtDNA content in Penile tumors. Using next generation sequencing (NGS), we sequenced the mitochondrial genome of 13 penile tumors and 12 non-neoplastic tissue samples, which allowed us to identify mtDNA variants and heteroplasmy. We further evaluated variant's pathogenicity using Mutpred predictive software and calculated mtDNA content using quantitative PCR. Mitochondrial genome sequencing revealed an increase number of non-synonymous variants in the tumor tissue, along with higher frequency of heteroplasmy and mtDNA depletion in penile tumors, suggesting an increased mitochondrial instability in penile tumors. We also described a list of mitochondrial variants found in penile tumor and normal tissue, including five novel variants found in the tumoral tissue. Our results showed an increased mitochondrial genome instability in penile tumors. We also suggest that mitochondrial DNA copy number (mtDNAcn) and mtDNA variants may act together to imbalance mitochondrial function in PeCa. The better understanding of mitochondrial biology can bring new insights on mechanisms and open a new field for therapy in PeCa.

Background: No study has examined the possibility to perform an organ sparing strategy in older patients with penile carcinoma, and amputation is frequently proposed. We report our experience of interstitial brachytherapy for the conservative treatment of penile carcinoma confined to the glans in patients aged of 70years and more., Methods: A total of 55 patients candidates to conservative brachytherapy were identified. Median age was 73.8years (range: 70-95years). Patients underwent a circumcision then 3-4weeks later, an interstitial brachytherapy was delivered, median dose of 65Gy (range 55-74Gy). Salvage surgery was discussed in patients with histological confirmation of residual/relapsed tumor., Results: With median follow-up of 9.0years, eight patients (14.5%) experienced a relapse, including five patients with local relapse. Three patients with local relapse only underwent salvage penile surgery, including two partial glansectomies and one total penectomy, and were in second complete remission at last follow-up. Among 55 patients analyzed for late side effects, seven patients (13.0%) presented pain or ulceration, 12 (22.2%) experienced urethral or meatal stenosis requiring at least one dilatation, two patients (3.7%) experienced both ulcerations and urethral complication. Three patients (5.5%) needed partial glansectomy for focal necrosis. At five years, estimated overall survival rate was 74.5% (95%CI: 62.0-87.0%) and local relapse free rate was 91.0% (95%CI: 82.6-99.4%)., Conclusion: Brachytherapy is feasible in selected older patients with penile carcinoma, with efficacy and toxicity rates comparable to that of other series in younger patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: To assess the impact of primary surgery, partial and total penectomy, and of inguinal lymphadenectomy on health-related quality of life (HRQoL) and the sexual function of penile cancer patients., Materials and Methods: We invited 15 patients surgically treated for penile cancer in the Regional Hospital of Specialized Medicine of the Yucatan Peninsula between 2012 and 2016 to complete the SF-36 quality of life and International Index of Erectile Function (IIEF-5) sexual function questionnaires. We evaluated the impact of primary surgery type and inguinal lymphadenectomy on the outcome of HRQoL and sexual function., Results: A total of 10 patients (66%) completed the SF-36 questionnaire. Surgery type and extent of resection were overall not associated significantly with worse outcomes on the assessed domains of quality of life. However, men treated with partial penectomy reported significantly more pain (p = 0.0547) than men treated with total penectomy. Similarly, men who underwent lymphadenectomy reported significantly more pain (p = 0.0547) than those who were spared from the procedure due to the -primary tumor´s stage and grade. Sexual function was severely affected (IIEF mean = 6.5) in patients treated with partial penectomy., Conclusions: Although partial penectomy and lymphadenectomy were significantly associated with more postoperative pain, no differences were observed in other HRQoL domains. Sexual function was severely affected in patients treated with partial penectomy., (© 2018 S. Karger AG, Basel.)

Purpose: Brachytherapy (BT) is an effective organ-preserving treatment for selected localized penile carcinoma, providing high local control rates. Long-term functional results however, are still insufficiently evaluated., Methods and Materials: All consecutive patients treated with low-dose-rate or pulse-dose-rate BT in our institute for a localized penile cancer and who were in first complete remission and followed for at least 3 years were included. A self-reporting questionnaire was sent, to assess: 1/urinary function, 2/sexual function, 3/cosmetic aspect of the penis, and 4/quality of life., Results: Thirty-nine patients fulfilled inclusion criteria and were sent the questionnaire. Twenty-three patients (59%) answered. Median age was 63.4 years, (interquartile range [IR]: 49.7-67.0). Median followup was 5.9 years (IR: 5.2-6.7). The urinary scores showed moderate lower urinary tract symptoms. During the followup, a urethral dilation or self-catheterization had been necessary in 30% and 13%, respectively. Sixteen (70%) patients continued to maintain a sexual activity and the erectile dysfunction was mild. Finally, quality of life was good with a median score of 80/100 (IR = 65-90) and was only impacted by pain (p = 0.02). Overall, 57% and 39% declared having none or moderate pain/discomfort, respectively., Conclusions: Although this questionnaire needs to be validated in an independent cohort, our results show the moderate impact of BT on functional outcomes, confirming that it is an adequate first-intent organ-sparing strategy in patients with localized penile carcinoma., (Copyright © 2017 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Background: The presence of nodal metastases is the single most important prognostic factor in penile cancer. However, reliable assessment of nodal status in clinically node-negative (cN0) patients poses a challenge. Approximately 20% of these patients harbour occult nodal metastases. Currently available non-invasive radiological investigations are unreliable in excluding micrometastatic disease., Aim: Dynamic sentinel node biopsy (DSNB) is a minimally invasive procedure for assessing lymph node involvement. We report our initial experience with DSNB in assessing the status of regional lymph nodes in cN0 penile cancer patients., Methods: DSNB was performed in penile cancer patients with at least one cN0 groin. All patients undergoing DSNB at our institution were included. Lymphoscintigraphic images were obtained from all patients, after intradermal, peritumoral injection of a Technetium-99m nanocolloid. The sentinel nodes were defined as the nodes identified on lymphoscintigraphy, which were also radioactive intraoperatively using a gamma probe., Results: In total, 18 groins from 11 patients underwent DSNB. Of these, 11 patients underwent bilateral DSNB and 4 had unilateral DSNB. The mean (range) age of patients at the time of presentation of their primary tumour was 63 (39-78) years. A mean of 1.2 nodes per groin was retrieved. One lymph node was positive in one patient, who subsequently underwent a bilateral inguinal lymph node dissection. Overall, the median (range) follow-up was 12.8 (2.7-31.3) months with no local or regional recurrences., Conclusion: Further cases and longer follow-up will define the accuracy of this technique in the Irish population.

Penile carcinoma is a rare malignancy with a potential for local invasion and regional/distant extension. Penile cancer can be cured in over 80% of cases if diagnosed early. However, local treatment, although potentially lifesaving, can be mutilating and devastating for the patient's psychological well-being. In patients with long-term survival after penile cancer, sexual dysfunction, voiding problems and cosmetic penile appearance may adversely affect the patient's quality of life. Although there is little data in the literature about psychosocial impact of penile carcinoma, organ-preserving treatment seems to allow for better quality of life and sexual function and should be offered to all patients whenever feasible., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Insulin-like growth factor-1 receptor (IGF1R) plays a key role in cell growth and transformation. It is overexpressed in several solid tumors. This study evaluates IGF1R immunoexpression in penile squamous cell carcinoma (SCC). Four tissue microarrays were built from formalin-fixed, paraffin-embedded blocks of 112 penile SCC from Paraguay. Membranous IGF1R expression was evaluated by immunohistochemistry using two different approaches. An H-score was calculated in each spot (stain intensity by extent), and a median score per tumor was obtained. The second approach consisted of a score similar to the scoring system that was used for evaluating HER2 immunoexpression. For each case, the highest category obtained at any spot was used for statistical analyses. IGF1R expression was compared by histologic subtype, grade, and human papillomavirus (HPV) status. Median H-score was 22.5. The distribution of IGF1R expression by HER2 approach was as follows: 0 in 33.0% cases, 1+ in 46.4%, 2+ in 14.3%, and 3+ in 6.2%. IGF1R H-scores were associated with basaloid and warty/basaloid subtypes (p = 0.0026) and higher grade (p = 0.00052). Although weaker when using the HER2 approach, the association of IGF1R expression with subtype (p = 0.015) and grade (p = 0.015) remained significant. Furthermore, there was an association between IGF1R expression by HER2 approach and HPV status (p = 0.012). IGF1R was expressed in about two thirds of penile SCC cases, showing a strong positive association with histologic grade, subtype, and HPV status. Considering that grade is a predictor of outcome IGF1R expression may have prognostic relevance and could point to a potential role for IGF1R inhibitors in treating penile SCC.

Background: Different approaches have been described in published studies for carcinoma in situ (CIS) of the glans penis (erythroplasia of Queyrat), including topical chemotherapy or immunotherapy and laser or surgical excision. We evaluated the efficacy of topical imiquimod (IQ) followed by carbon dioxide laser ablation of the lesion., Patients and Methods: From 2010 to 2015, 10 patients affected by CIS of the glans were treated by IQ, followed by carbon dioxide laser ablation. For every patient, we performed histologic examination before and after IQ. Local toxicity and adverse effects were recorded., Results: After treatment, histologic examination showed no residual tumor in 6 patients (complete response [CR]), stable disease in 2 patients, and progressive disease in 2 patients. Those with a CR had human papillomavirus-related lesions, and they had no experienced relapses after a mean follow-up of 26 months. The 2 patients with progressive disease underwent total penectomy. All patients were alive at the last follow-up examination. All patients experienced a mild local toxicity (burning erythema) but no major adverse effects., Conclusion: Local treatment with IQ for glans CIS is effective mainly for human papillomavirus-related lesions. The present study is the first to record the histologic examination findings before and after IQ treatment. The small number of patients, owing to the rarity of this disease, was the main limitation of the present study. IQ must be used carefully, and a close follow-up protocol is mandatory because of the lack of long-term efficacy data., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Penile carcinoma (PeCa) is an important public health issue in poor and developing countries, and has only recently been explored in terms of genetic and epigenetic studies. Integrative data analysis is a powerful method for the identification of molecular drivers involved in cancer development and progression. miRNA and mRNA expression profiles followed by integrative analysis were investigated in 23 PeCa and 12 non-neoplastic penile tissues (NPT). Expression levels of eight miRNAs and 10 mRNAs were evaluated in the same set of samples used for microarray and in a validation set of cases (PeCa = 36; NPT = 27). Eighty-one miRNAs and 2,697 mRNAs were identified as differentially expressed in PeCa. Integrative data analysis revealed 255 mRNAs potentially regulated by 68 miRNAs. Using RT-qPCR, eight miRNAs and nine transcripts were confirmed as altered in PeCa. We identified that MMP1, MMP12 and PPARG and hsa-miR-31-5p, hsa-miR-224-5p, and hsa-miR-223-3p were able to distinguish tumors from NPT with high sensitivity and specificity. Higher MMP1 expression was detected as a better predictor of lymph node metastasis than the clinical-pathological data. In addition, PPARG and EGFR were highlighted as potential pathways for targeted therapy in PeCa. The analysis based on HPV positivity (7 of 23 cases) revealed five miRNA and 13 mRNA differentially expressed. Although in a limited number of cases, HPV positive PeCa presented less aggressive phenotype in comparison with negative cases. Overall, an integrative analysis using mRNA and miRNA profiles revealed markers related with tumor development and progression. Furthermore, MMP1 expression level was a predictive marker for lymph node metastasis in patients with PeCa.

Glandular and pseudoglandular tumors of the penile skin are extremely uncommon and can present diagnostic challenges. Primary adenosquamous carcinoma of the penis is an extremely rare tumor, composed of distinct areas of malignant squamous and glandular cells, making it a diagnostically challenging entity. The World Health Organization (WHO) recognizes several subtypes of squamous cell carcinoma (SCC), each with its own distinctive pathologic appearance, clinical associations and prognosis. Among these variants is the exceedingly uncommon adenosquamous carcinoma (ASC), representing 1%-2% of all SCC of the penis. Recent large studies have interrogated the presence of human papillomavirus (HPV) in malignant penile tumors and have shown specific morphologic patterns and clinical presentations to associate with HPV status. However, given the rarity of the adenosquamous variant of SCC, it has largely been excluded from these studies. The glandular components of these lesions can present a confusing appearance, particularly when a large tumor is represented on a small biopsy. Here we describe a difficult histologic presentation of this rare tumor, with the first published characterization of the HPV status of this subtype. This case represents a distinctly unusual case of metastatic HPV-positive primary cutaneous adenosquamous carcinoma of the penis., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: Our aims were to evaluate epithelial-mesenchymal transition (EMT) as a useful prognostic marker in penile carcinoma (PC), and establish an objective criterion to define EMT in PC specimens., Materials and Methods: A total of 149 consecutive cases surgically treated for PC were retrospectively selected. E-cadherin (E-CAD) and vimentin immunohistochemical expressions were evaluated. A combined analysis was performed using both markers to determine EMT status. To establish a normal control to E-CAD expression, we included 14 cases from circumcisions from patients without any neoplastic disease and 77 cases of tumor-free margins. The analyses of tumor samples were evaluated in 2 different areas of the tumor. The first one was in the tumor core. The second analyses were performed on the deepest infiltrative edge of the tumor, nominated invasion front. Cases were classified into EMT absent group, partial EMT group and complete EMT group. Overall survival (OS) and cancer-specific survival (CSS) were analyzed. Kaplan-Meier curves and the log-rank test were used. Cox proportional hazards model was used to determine which variables influenced survival., Results: Tumor specimens presented a significant loss of expression of E-CAD when compared with normal epithelium. Vimentin expression in more than 10% of tumor cells was observed in 50 cases. EMT status was associated with histologic grade, pattern of invasion, lymph node metastasis, and perineural and vascular invasion. Further, 10-year OS and CSS rates in patients with presence and absence of complete EMT status were 38.0% and 55.6%; and 48.0% and 91.9%, respectively. EMT status significantly affected CSS and OS rates even after patients were grouped based on lymph node involvement status. The presence of complete EMT status was associated with both CSS and OS rates. Patients in the complete EMT group had a higher risk of death from cancer (hazard ratio = 7.6, P<0.001) and overall death (hazard ratio = 3.0, P<0.001)., Conclusion: Our study represents an evidence of the prognostic effect of EMT in PC. We encourage the study of EMT markers in other centers to validate our findings and confirm its importance in such tumors., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The guidelines of the European Association of Urologists (EAU), of the German Society of Nuclear Medicine (DGN), and the European Society for Medical Oncology (ESMO) recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes as one diagnostic method. Despite this, the method is neither widely nor regularly applied in Germany - the same applies to many other countries, which may be due to insecurity in dealing with open radioactive tracers. This study aims to assess the reliability and morbidity of this method, as well as the associated radioactive burden for clinical staff., Methods: Between 2006 and 2016, 34 patients with an invasive penile carcinoma and inconspicuous inguinal lymph node status underwent SLNB in 57 groins after application of a radiotracer (Tc-99 m nanocolloid). We collected the results prospectively. The reliability of the method was assessed by determining the false-negative rate. In addition, we evaluated complication rates and determined the radioactive burden for the clinical staff both pre- and intraoperatively., Results: SLNB was performed in 34 patients with penile cancer with non-palpable inguinal lymph nodes in 57 groins. In two patients inguinal lymph node metastases were detected by means of SLNB. In one patient recurrent inguinal lymph node disease was found after negative SLNB in both groins. Thus, the false negative rate was 3.13 % per patient (1/32 patients) and 3.51 % per groin (2/57 groins). The morbidity rate was 2.94 % per patient (1/34 patients) and 1.75 % per groin (1/57 groins). Radiation exposure for the clinical staff during this procedure was low at a maximum of ca. four μSV per intervention., Conclusions: SLNB is a reliable method with low morbidity that is associated with a low radiation burden for clinical staff. Due to the enhanced methodological and logistic demands, this intervention should be performed in specialized centres and in an interdisciplinary approach.

Background: Delayed first medical consultation (patient's delay) is quite common in cases of penile carcinoma (PC), but its reasons and impacts remain unclear. We conducted this study to ascertain risk factors resulting in delayed treatment seeking and evaluate its influence on prognosis., Methods: From 2004 to 2010 at 4 centers, 254 patients were enrolled into this study from 262 consecutive PC cases. Patients' sexual performance was investigated using the International Index of Erectile Function (IIEF)-15 at the sixth-month end after treatment. Data for prognostic analyses was obtained via a 5-year follow-up., Results: A multivariate model ascertained 4 risk factors (single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms) and 1 protective factor (history of condyloma) significantly associated with patient's delay. Delay >3 months led to significant risks for adverse clinical characteristics, low penis-sparing rate, and poor sexual function restoration. Although patient's delay was not found to impact on postoperative relapses and 5-year overall survival (OS), patients with delay >6 months had significantly inferior 2-year OS., Conclusions: Single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms are significant risk factors of PC associated with patient's delay. Delay >3 months will lead to significantly inferior clinical consequences. Minimizing patient's delay is the key to avoid amputation and retain superior sexual potency. Improving patient education on initial symptoms of PC is necessary in men of >40 years old.

The number of studies reporting lymphoma as a secondary tumor has gradually increased. However, few studies have reported that occurrence of lymphoma as a secondary tumor following treatment for penile carcinoma, particularly cases in which the lymphoma was diagnosed by fine-needle aspiration cytology and flow cytometry. The present study reports the case of a 62-year-old male patient who was troubled with frequent urination and repeated chest tightness for 5 years. The diagnosis upon admission was penile carcinoma. Two months subsequent to the tumor removal surgery, enlarged lymph nodes were extracted from the patient using fine-needle biopsy, to be analyzed using light microscopy and flow cytometry. Smear results indicated a large number of abnormal cells scattered in the right axillary lymph node. Flow cytometry immunophenotyping of fine-needle aspiration samples indicated the increased expression of cluster of differentiation (CD)79a, CD19, CD20, CD38, κ chain and human leukocyte antigen-DR, which supported a diagnosis of B-cell lymphoma. Thus, the patient was diagnosed with B-cell lymphoma based on the results of the fine-needle aspiration biopsy and flow cytometry. The method of diagnosis and causes of therapy-related leukemia are discussed in the present report.

Objectives: To evaluate the effect of saphenous vein sparing during bilateral inguinal lymphadenectomy (BIL) for penile carcinoma patients., Methods: Between May 2011 and May 2013, 23 patients with penile carcinoma who underwent laparoscopic prophylactic BIL were included. All patients were randomized to receive the laparoscopic prophylactic inguinal lymphadenectomy with saphenous vein sparing on one limb and saphenous vein ligated on the other limb. Short-term and long-term complications were compared between the two groups., Results: There was no significant difference between the two groups in operation time, harvested number of nodes and incidence of positive nodes. Saphenous vein preservation technique significantly reduced the morbidity of acute lymphedema and lower limb lymphedema after BIL. There was no difference between the two groups in acute cellulitis, seroma, wound breakdown, deep venous thrombosis and cellulitis. One patient developed a local recurrence at the 9 months after lymphadenectomy., Conclusions: Our preliminary findings suggest that laparoscopic prophylactic BIL with saphenous vein sparing is beneficial in patients with penile carcinoma by reducing the incidence of short-term and long-term postoperative complications.

We report a case of penile carcinoma presenting as an inguinal bubo in a young man. The associated painful genital ulcer and history of high-risk sexual behaviour raised a strong suspicion of a sexually transmitted infection. We review the literature for similar cases, highlight the similarities with venereal disease and discuss the differential diagnosis of inguinal bubo., (© The Author(s) 2016.)