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Penile (Penis) Cancer

Cancer can affect any part of the penis, but is most common on the foreskin and on the glans (the sensitive bulbous end of the penis). It is most commonly diagnosed in med aged over 50. The vast majority (about 95%) are squamous cell carcinoma (cancer developing in the flat skin cells). Less common types of penile cancer include verrucous carcinoma (Buschke-Lowenstein tumor), melanoma, basal cell carcinoma, adenocarcinoma (sweat glands) and penile sarcoma.

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    MeSH term: Penile Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Lützen U, Zuhayra M, Marx M, et al.
Value and efficiency of sentinel lymph node diagnostics in patients with penile carcinoma with palpable inguinal lymph nodes as a new multimodal, minimally invasive approach.
Eur J Nucl Med Mol Imaging. 2016; 43(13):2313-2323 [PubMed] Related Publications
PURPOSE: The international guidelines recommend sentinel lymph node biopsy (SLNB) for lymph node staging in penile cancer with non-palpable inguinal lymph nodes (LN) but it is not recommended with palpable inguinal LN. The aim of this study was to evaluate the reliability and morbidity of SLNB in combination with an ultrasound-guided resection of suspect inguinal LNs as a new multimodal, minimally invasive staging approach in these patients.
METHODS: We performed SLNB in 26 penile cancer patients with 42 palpable inguinal LNs. Prior to the combined staging procedures the patients underwent an ultrasound examination of the groins as well as planar lymphatic drainage scintigraphy and SPECT/CT scans. During the surgical procedure, the radioactive-labelled sentinel lymph nodes and, in addition, sonographically suspect LNs, were resected under ultrasound guidance. Follow-up screening was done by ultrasound examination of the groins according to the guidelines of the European Association of Urology.
RESULTS: Nineteen groins of 42 preoperatively palpable inguinal findings were histologically tumor-positive. SLNB alone showed lymphogenic metastases in 14 groins. Sonography revealed five further metastatic groins, which would not have been detected during SLNB due to a tumor-related blockage of lymphatic drainage or a so-called re-routing of the tracer. During follow-up, none of the 28 groins with tumor-negative LN status showed any LN recurrence in this combined investigation technique. The median follow-up period was 46 (24 to 92) months. Morbidity of this procedure was low at 4.76 % in relation to the number of groins resp. 7.69 % in relation to the number of patients.
CONCLUSIONS: The results show that this combined procedure is a reliable multimodal diagnostic approach for treatment of penile cancer patients with palpable inguinal LNs. It is associated with low morbidity rates. SLNB alone would lead to a significantly higher false-negative rate in these patients. The encouraging results of this work can extend the range of indications for nuclear medicine in the form of SLNB using radioactive tracers in this patient group.

Li ZS, Deng CZ, Yao K, et al.
Bilateral pelvic lymph node dissection for Chinese patients with penile cancer: a multicenter collaboration study.
J Cancer Res Clin Oncol. 2017; 143(2):329-335 [PubMed] Related Publications
BACKGROUND: Current guidelines recommend pelvic lymphadenectomy (PLND) for patients with pelvic lymph node metastasis and special state. However, these data and recommendations do not distinguish the role of PLND in different patient groups and confirm the final benefits. The aim of this study was to confirm the efficacy of pelvic lymphadenectomy (PLND) for the different groups of patients.
METHODS: Data obtained from 7 centers were retrospectively analyzed. Of the patients, 190 pN2-3 penile carcinoma patients confirmed by bilateral inguinal lymph node excision were included in this study. Sixty-nine and 121 of these patients did and did not undergo bilateral PLND, respectively. The baseline differences from the patients were matched by propensity score analysis.
RESULTS: In this study, the Kaplan-Meier estimated disease-specific survival (DSS) was not significantly different between the PLND and no-PLND groups (P = 0.796). According to the propensity score matching for T stage, N stage, grade, adjuvant therapies, and lymph node stage (number of inguinal lymph node metastasis and extranodal extension), 48 patients were selected for each group. Among the pN2 patients, the PLND group showed higher DSS rates than the no-surgery group (P = 0.030). However, even after matching, survival did not differ between the PLND and no-PLND patients among all patients (P = 0.609) and pN3 patients (P = 0.417) with comparable DSS.
CONCLUSION: Bilateral PLND may improve survival in pN2 patients. Men with pN3 may not benefit from bilateral PLND.

Gupta S, Sonpavde G
Emerging Systemic Therapies for the Management of Penile Cancer.
Urol Clin North Am. 2016; 43(4):481-491 [PubMed] Related Publications
Penile squamous cell carcinoma (PSCC) is a rare cancer, but is more common in developing countries. Locally advanced and metastatic PSCC is associated with significant morbidity and mortality, with the prognosis remaining extremely poor. The authors searched PubMed and published abstracts for metastatic PSCC studies to describe emerging therapies. Multimodality treatment using chemotherapy, radiation, and consolidative surgery are standard of care. Utilizing anti-EGFR therapies and novel immunotheraputic approaches may help improve outcomes in PSCC.

Ravi P, Pagliaro LC
Multimodal Therapy in the Management of Advanced Penile Cancer.
Urol Clin North Am. 2016; 43(4):469-479 [PubMed] Related Publications
A multimodal approach to therapy is increasingly used in treating men with advanced penile cancer. Adjuvant chemotherapy improves outcomes in chemotherapy-naïve men with node-positive positive disease, and neoadjuvant chemotherapy can downstage bulky nodal disease sufficiently to permit surgery and has the potential to offer durable long-term survival. However, there remain several unanswered questions in this field, and international collaboration in the form of clinical trials is required to optimize treatment and improve survival in men with advanced penile cancer.

Sharma P, Zargar H, Spiess PE
Surgical Advances in Inguinal Lymph Node Dissection: Optimizing Treatment Outcomes.
Urol Clin North Am. 2016; 43(4):457-468 [PubMed] Related Publications
Lymphadenectomy (LND) for locally advanced penile cancer is often necessary in patients with suspected disease within the inguinal or pelvic lymph nodes because the results of systemic therapy are somewhat marginal. It has utility in staging, disease prognosis, and treatment in certain men because early dissection of involved lymph nodes improves survival. Despite its mainstay in the management of this disease, inguinal and pelvic lymph node dissection can be associated with significant postoperative complications and patient morbidity. Recent refinements in surgical technique, however, and appropriate patient selection can minimize these risks and lead to better short-term and long-term outcomes.

Horenblas S, Minhas S
Minimal Invasive Management of Lymph Nodes.
Urol Clin North Am. 2016; 43(4):449-456 [PubMed] Related Publications
Penile cancer is a rare genitourinary malignancy. Lymph node involvement is the single most important factor determining survival in these patients, and those patients with occult disease are difficult to identify on conventional cross-sectional imaging. Until recently, lymph node sampling (eg, lymphadenectomy) has been the diagnostic modality of choice in the detection of micrometastasis. More recently, several novel molecular and minimally invasive diagnostic techniques have been developed, which have been demonstrated to decrease the false-negative and -positive results of conventional imaging and lymphadenectomy. This article focuses on the minimally invasive management of lymph nodes in men with penile cancer.

Crook J
Contemporary Role of Radiotherapy in the Management of Primary Penile Tumors and Metastatic Disease.
Urol Clin North Am. 2016; 43(4):435-448 [PubMed] Related Publications
Squamous cell cancer of the penis is a radiocurable malignancy all too often managed solely by partial or total penectomy. Effective management of the primary tumor while preserving penile morphology and function is a priority. External radiotherapy and brachytherapy have a role to play in the definitive management of the primary tumor. Surgical nodal staging remains a cornerstone of management because it is the strongest predictor of survival, and inguinal status determines pelvic management. Postoperative radiotherapy of the regional nodes for high-risk pathology is indicated. Chemoradiotherapy should be considered as neoadjuvant treatment for unresectable nodes or as definitive management.

Mahesan T, Hegarty PK, Watkin NA
Advances in Penile-Preserving Surgical Approaches in the Management of Penile Tumors.
Urol Clin North Am. 2016; 43(4):427-434 [PubMed] Related Publications
Penile-preserving surgery offers a revolutionary alternative to more traditional radical surgery. It offers better sexual, functional, and psychological results and evidence suggests it achieves this without sacrificing oncological outcomes. We examined the evolving nature of such surgeries, addressing controversies such as safe margins and survival outcomes and discussing more conventional techniques, including laser. At our UK center, we treat a high volume of penile cancer and here, based on such experience, we describe our glans resurfacing, glansectomy, and partial penectomy techniques; their application by disease stage; and the limitations of such surgeries.

Diorio GJ, Giuliano AR
The Role of Human Papilloma Virus in Penile Carcinogenesis and Preneoplastic Lesions: A Potential Target for Vaccination and Treatment Strategies.
Urol Clin North Am. 2016; 43(4):419-425 [PubMed] Related Publications
Penile cancer is a rare and devastating disease, especially at advanced stages. The etiology of penile cancer is multifactorial with multiple established risk factors including infection with the human papillomavirus (HPV). Approximately 40% of penile cancers are attributable to HPV, although the literature describing HPV as a prognostic factor is mixed. The pathogenesis of HPV infection as well as vaccination practices may provide valuable therapeutic agents to treat this rare and difficult disease.

Lützen U, Naumann CM, Marx M, et al.
A study on the value of computer-assisted assessment for SPECT/CT-scans in sentinel lymph node diagnostics of penile cancer as well as clinical reliability and morbidity of this procedure.
Cancer Imaging. 2016; 16(1):29 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Because of the increasing importance of computer-assisted post processing of image data in modern medical diagnostic we studied the value of an algorithm for assessment of single photon emission computed tomography/computed tomography (SPECT/CT)-data, which has been used for the first time for lymph node staging in penile cancer with non-palpable inguinal lymph nodes. In the guidelines of the relevant international expert societies, sentinel lymph node-biopsy (SLNB) is recommended as a diagnostic method of choice. The aim of this study is to evaluate the value of the afore-mentioned algorithm and in the clinical context the reliability and the associated morbidity of this procedure.
METHODS: Between 2008 and 2015, 25 patients with invasive penile cancer and inconspicuous inguinal lymph node status underwent SLNB after application of the radiotracer Tc-99m labelled nanocolloid. We recorded in a prospective approach the reliability and the complication rate of the procedure. In addition, we evaluated the results of an algorithm for SPECT/CT-data assessment of these patients.
RESULTS: SLNB was carried out in 44 groins of 25 patients. In three patients, inguinal lymph node metastases were detected via SLNB. In one patient, bilateral lymph node recurrence of the groins occurred after negative SLNB. There was a false-negative rate of 4 % in relation to the number of patients (1/25), resp. 4.5 % in relation to the number of groins (2/44). Morbidity was 4 % in relation to the number of patients (1/25), resp. 2.3 % in relation to the number of groins (1/44). The results of computer-assisted assessment of SPECT/CT data for sentinel lymph node (SLN)-diagnostics demonstrated high sensitivity of 88.8 % and specificity of 86.7 %.
CONCLUSIONS: SLNB is a very reliable method, associated with low morbidity. Computer-assisted assessment of SPECT/CT data of the SLN-diagnostics shows high sensitivity and specificity. While it cannot replace the assessment by medical experts, it can still provide substantial supplement and assistance.

Lützen U, Naumann CM, Dischinger J, et al.
10-Year experience regarding the reliability and morbidity of radio guided lymph node biopsy in penile cancer patients and the associated radiation exposure of medical staff in this procedure.
BMC Urol. 2016; 16(1):47 [PubMed] Free Access to Full Article Related Publications
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.

Cordoba A, Escande A, Lopez S, et al.
Low-dose brachytherapy for early stage penile cancer: a 20-year single-institution study (73 patients).
Radiat Oncol. 2016; 11:96 [PubMed] Free Access to Full Article Related Publications
PURPOSE/OBJECTIVES: The aim of this study is to analyze the results of exclusive interstitial brachytherapy (IBT) as a conservative approach in the treatment of penile cancer confined to the glans or the shaft with long-term follow-up in a single institution.
MATERIALS/METHODS: Between July 1992 and November 2013, 73 consecutive patients with non-metastatic invasive penile cancer were treated by Low dose rate (LDR) IBT in our institution. The localization of the primary lesion was glands in 67 patients (91.8 %) and shaft in 6 patients (8.2 %). All 73 patients presented with squamous cell carcinoma with grades of differentiation as follows: 34 patients with grade 1 (44.7 %), 9 patients with grade 2 (11.8 %), 9 patients with grade 3 (11.8 %) and 21 patients unknown (28.8 %). Six patients (7.8 %) presented with in situ carcinoma, 55 patients (75,3 %) presented with T1, 11 patients (15 %) presented with T2, and one patient (1.3 %) presented with Tx. Inguinal nodal dissection was performed in 29 patients (38.2 %); 13 patients (17.8 %) presented with histologically confirmed positive ganglion. After circumcision, IBT was performed using a hypodermic needle. The median dose delivered was 60 Gy (range, 40 to 70 Gy). The median activity of the iridium-192 wire was 1.12 mCi/cm, and the median reference isodose rate was 0.4 Gy/h (range, 0.2-1.2). Patients with histological inguinal metastases received external beam radiotherapy to the selected inguinal affected area with a median dose of 45 Gy (30-55 Gy).
RESULTS: The median follow-up time was 51.8 months (range 34.4 to 68.7). The 5-year overall survival was 82.0 %, with eight deaths from cancer and five non-cancer-related deaths. Disease-specific survival was 91.4 %, relapse-free survival was 64.4 %, and local relapse-free survival as 74 %. Total or partial penile preservation was 87.9 % at 5-years. Complications rates at 5 years were 6.6 % urethral stenosis (five patients), two patients (2.6 %) with pain related to sexual intercourse and four patients (5.3 %) with dysuria grade 2. Five patients (6.8 %) required penile amputation for necrosis.
CONCLUSIONS: IBT provides good local control with organ preservation, excellent tolerance and low complication rates in early-stage penile cancers.

Barnes KT, McDowell BD, Button A, et al.
Obesity is associated with increased risk of invasive penile cancer.
BMC Urol. 2016; 16(1):42 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: To validate the association between obesity and penile cancer at a population level, we conducted a matched case-control study linking the Iowa Department of Motor Vehicles Drivers' License Database (DLD) with cancer surveillance data collected by the State Health Registry of Iowa (SHRI).
METHODS: All men diagnosed with invasive penile squamous cell carcinoma from 1985 to 2010 were identified by SHRI. Two hundred sixty-six cancer cases and 816 cancer-free male controls, selected from the Iowa DLD, were matched within 5-year age and calendar year strata. Body mass index (BMI) was calculated using self-reported height and weight from the DLD.
RESULTS: Conditional logistic regression was used to evaluate the association between BMI and the risk of developing invasive penile cancer. Obesity was significantly associated with an increased risk of developing penile cancer. For every five-unit increase in BMI the risk of invasive penile cancer increased by 53 % (OR 1.53, 95 % CI 1.29-1.81, p < 0.0001).
CONCLUSION: We previously reported an association between obesity and higher risk of invasive penile cancer and advanced cancer stage at diagnosis in a hospital-based retrospective study. This population-based study confirms an association between obesity and invasive penile cancer.

De Luca F, Zacharakis E, Shabbir M, et al.
Malignant priapism due to penile metastases: Case series and literature review.
Arch Ital Urol Androl. 2016; 88(2):150-2 [PubMed] Related Publications
Malignant priapism secondary to penile metastases is a rare condition. This term was originally used by Peacock in 1938 to describe a condition of painful induration and erection of the penis due to metastatic infiltration by a neoplasm. In the current literature there are 512 case reports. The primary tumor sites are bladder, prostate and rectum. The treatment has only palliative intent and consists of local tumor excision, penectomy, radiotherapy and chemotherapy. We present one case of malignant priapism originated from prostate cancer, and two from urothelial carcinoma of the bladder. Different approaches in diagnosis and therapy were performed. The entire three patient reported a relief of the pain following the treatment, with an improvement of their quality of life, even though it was only temporary as a palliative. Malignant priapism is a rare medical emergency. Penile/pelvis magnetic resonance imaging (MRI) scan and corporal biopsies are considered an effective method of diagnosis of the primary organ site.

Maranda EL, Nguyen AH, Lim VM, et al.
Erythroplasia of Queyrat treated by laser and light modalities: a systematic review.
Lasers Med Sci. 2016; 31(9):1971-1976 [PubMed] Related Publications
Erythroplasia of Queyrat (EOQ) is a squamous cell carcinoma in situ most commonly located on the glans penis or prepuce. EOQ accounts for roughly 10 % of all penile malignancies and may lead to invasive squamous cell carcinoma. Standard therapy includes local excision, partial or total penectomy, cryotherapy, and topical cytotoxic agents. Treatment of EOQ has proven to be challenging due to low response rates and recurrence. In addition, radical procedures can significantly affect sexual function and quality of life. Alternative laser treatments and photodynamic therapy (PDT) offer promising results for treating EOQ. A systemic review of the literature was performed for articles discussing laser and light therapy for EOQ. Among the patients treated with the CO2 laser, 81.4 % of cases had complete remission after one session of treatment. Patients treated with PDT presented with more variable results, where 62.5 % of those treated with methyl aminolevulinate photodynamic therapy (MAL-PDT) achieved complete remission. Aminolevulinic acid (ALA-PDT) treatment showed a similar rate of remission at 58.3 %. One study utilized the Nd:YAG laser, which resulted in a recurrence of the lesion in four of the five patients treated. Of the methods reviewed, the CO2 laser offered the most promising results with a cosmetically excellent prognosis. Further studies with larger power and longer follow-up times are needed to determine the optimal treatment regimen for this penile malignancy.

James M, Amaranathan A, Nelamangala Ramakrishnaiah VP, Toi PC
Rectal adenocarcinoma infiltrating the bulbar urethra and metastasising to the penis.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
Secondary penile tumours from rectal carcinoma is a known clinical entity but can be missed unless carefully evaluated. We report a case of rectal adenocarcinoma with synchronous painless penile nodules. A patient presented with constipation and rectal bleeding. He had an anorectal growth as well as palpable nodules on his penis. Rectal biopsy yielded adenocarcinoma. Imaging revealed direct infiltration of tumour into the bulb of the penis as well as distal shaft lesions. Fine-needle aspiration cytology of the penile nodule showed metastatic adenocarcinoma. Diversion colostomy was performed and the patient referred for chemoradiation. Since he did not have any urinary symptoms, the penile lesions were left unaltered. Repeat imaging after concurrent chemoradiotherapy showed no response. The prognosis was explained and the patient was given palliative clinic care.

Lützen U, Zuhayra M, Marx M, et al.
Value and Efficacy of Sentinel Lymph Node Diagnostics in Patients With Penile Carcinoma With Nonpalpable Inguinal Lymph Nodes: Five-Year Follow-up.
Clin Nucl Med. 2016; 41(8):621-5 [PubMed] Related Publications
PURPOSE: Sentinel lymph node biopsy (SLNB) has been described as a minimally invasive method for lymph node staging in patients with a penile carcinoma and nonpalpable inguinal nodes in national and international guidelines of involved professional societies. However, this method is rarely used. The aim of this study was to validate reliability and morbidity of this method and to discuss radiation exposure of persons involved.
METHODS: Twenty-eight patients with histologically negative sentinel lymph nodes in 47 groins with nonpalpable inguinal lymph nodes were included in this study (17 T1(a/b)-, 8 T2- and 3 T3-stages). We recorded prospectively all cases of lymph node recurrence and complications in patients with initially nonpalpable inguinal lymph nodes and histologically negative sentinel lymph nodes. False-negative findings and morbidity were calculated as qualitative criteria. Inguinal regions with palpable lymph nodes and/or evidence of metastases were not considered in accordance with the guidelines.
RESULTS: During a median follow-up of 68 (4-131) months, we observed one case of bilateral lymph node recurrence and one case of prolonged inguinal lymphorrhea, which could be managed conservatively. Per inguinal region, false-negative rate was 4.25%, and morbidity rate was 2.12%; seen per patient, the rates were both 3.57%.
CONCLUSIONS: Sentinel lymph node biopsy under use of radioactive tracers is a reliable method of lymph node staging in patients with penile carcinoma and nonpalpable inguinal lymph nodes. The methodical complexity is justified by high reliability and low radiation exposure for both patient and medical staff and low morbidity rates.

Gao W, Song LB, Yang J, et al.
Risk factors and negative consequences of patient's delay for penile carcinoma.
World J Surg Oncol. 2016; 14:124 [PubMed] Free Access to Full Article Related Publications
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.

Michal M, Michal M, Miesbauerova M, et al.
Penile Analogue of Stratified Mucin-Producing Intraepithelial Lesion of the Cervix: The First Described Case. A Diagnostic Pitfall.
Am J Dermatopathol. 2016; 38(5):e64-7 [PubMed] Related Publications
The authors report a case where undifferentiated (classic) penile intraepithelial neoplasia was associated with the presence of goblet cells throughout the full epithelial thickness and which later progressed into an invasive carcinoma. The lesion evolved in three consecutive biopsies from only surface epithelium occupying numerous goblet cells in the first to variably sized solid nodules in the dermis composed of atypical squamous and/or basaloid cells intermixed with numerous goblet cells in the third biopsy. Both cellular components expressed CK7 and p16 protein. Human Papillomavirus (HPV) genotyping revealed high risk HPV type 16. To the best of our knowledge, this is the first description of such a lesion occurring on the penis, which can be considered the penile analogue of cervical stratified mucin-producing intraepithelial lesion (SMILE). The correct diagnosis was rendered retrospectively, after recognition of the existence of a vulvar lesion resembling cervical SMILE. The initial biopsy was misinterpreted as extramammary Paget disease, which also constitutes the main pitfall in the differential diagnosis. Another important differential diagnosis is penile/vulvar mucinous metaplasia. The finding of atypical squamous epithelial cells positive for p16 associated with mucinous cells present throughout the full epithelial thickness is a clue to the diagnosis of penile SMILE.

Mu Mu Shwe, Hlaing Myat Thu, Khin Saw Aye, et al.
Determination of Oncogenic Human Papillomavirus (HPV) Genotypes in Anogenital Cancers in Myanmar.
Acta Med Okayama. 2016; 70(2):103-10 [PubMed] Related Publications
Molecular and epidemiologic investigations suggest a causal role for human papillomavirus (HPV) in anogenital cancers. This study identified oncogenic HPV genotypes in anogenital cancers among men and women in a 2013 cross-sectional descriptive study in Myanmar. In total, 100 biopsy tissues of histologically confirmed anogenital cancers collected in 2008-2012 were studied, including 30 penile and 9 anal cancers from Yangon General Hospital and 61 vulvar cancers from Central Women's Hospital, Yangon. HPV-DNA testing and genotyping were performed by polymerase chain reaction-restriction fragment length polymorphism. Overall, 34% of anogenital cancers were HPV-positive. HPV was found in 44.4% of anal (4/9), 36.1% of vulvar (22/61), and 26.7% of penile (8/30) cancers. The most frequent genotypes in anal cancers were HPV 16 (75% ) and 18 (25% ). In vulvar cancers, HPV 33 was most common (40.9% ), followed by 16 (31.8% ), 31 (22.7% ), and 18 (4.6% ). In penile cancers, HPV 16 (62.5% ) was most common, followed by 33 (25% ) and 18 (12.5% ). This is the first report of evidencebased oncogenic HPV genotypes in anogenital cancers among men and women in Myanmar. This research provides valuable information for understanding the burden of HPV-associated cancers of the anus, penis, and vulva and considering the effectiveness of prophylactic HPV vaccination.

Stratton KL, Culkin DJ
A Contemporary Review of HPV and Penile Cancer.
Oncology (Williston Park). 2016; 30(3):245-9 [PubMed] Related Publications
Human papillomavirus (HPV) is a widespread sexually transmitted infection. In both men and women, HPV infection can result in a spectrum of genitourinary manifestations ranging from genital warts to cancer. Cervical cancer is nearly always associated with high-risk HPV infection. For men, penile cancer can develop following or independently of HPV infection. Basaloid and warty subtypes of penile squamous cell carcinoma are most frequently associated with HPV infection. Further research into the molecular alterations caused by HPV infection may provide prognostic markers and future treatment targets. Until an effective treatment for HPV infection is developed, prevention will remain the focus of disease control. For women, vaccination is increasingly utilized to prevent HPV infection and subsequent cervical cancer development. New recommendations for routine male vaccination may further reduce cancers for both men and women.

Franceschini G, Sanchez AM, Di Leone A, et al.
Penile cancer metastasizing to the breast: a case report.
J Med Case Rep. 2016; 10:53 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Penile cancer is a relatively uncommon cancer in developed nations. Metastatic disease is rare, but lymphatic or vascular spreading has been previously reported to the liver, lungs, bones, brain, heart and skin.
CASE PRESENTATION: We report a case of a 49-year-old white man with a penile squamous cell carcinoma previously treated with partial penectomy and bilateral inguinal lymph node dissection, followed by adjuvant therapy. Three years after treatment, the primitive neoplasm metastasized to the breast, presenting as a painful lump. Differentials of a secondary versus a malignant primary tumor were considered and in view of a diagnostic dilemma the lesion was excised.
CONCLUSIONS: This case is unusual in its site of metastatic progression as well as in its pattern of clinical presentation. Awareness of such a condition by physicians is mandatory in order to make an early diagnosis and start prompt and correct therapeutic planning.

Muñoz JJ, Drigo SA, Kuasne H, et al.
A comprehensive characterization of cell cultures and xenografts derived from a human verrucous penile carcinoma.
Tumour Biol. 2016; 37(8):11375-84 [PubMed] Related Publications
This study aimed to establish and characterize primary cell cultures and xenografts derived from penile carcinoma (PeCa) in order to provide experimental models for cellular processes and efficacy of new treatments. A verrucous squamous cell carcinoma (VSCC) was macrodissected, dissociated, and cultivated in KSFM/DF12 medium. Cell cultures were evaluated at passage 5 (P5) using migration and invasion assays and were serially propagated, in vivo, in BALB/c nude mice until passage 3 (X1-X3). Immunophenotypic characterization of cultures and xenografts was performed. Genomic (CytoScan HD, Affymetrix) and transcriptomic profiles (HTA 2.0 platform, Affymetrix) for VSCC, cell cultures, and xenografts were assessed. P5 cells were able to migrate, invade the Matrigel, and produce tumors in immunodeficient mice, demonstrating their malignant potential. The xenografts unexpectedly presented a sarcomatoid-like carcinoma phenotype. Genomic analysis revealed a high similarity between the VSCC and tumor-derived xenograft, confirming its xenograft origin. Interestingly, a subpopulation of P5 cells presented stem cell-related markers (CD44(+)CD24(-) and ALDH1(high)) and sphere-forming capacity, suggesting their potential xenograft origin. Cell cultures and xenografts retained the genomic alterations present in the parental tumor. Compared to VSCC, differentially expressed transcripts detected in all experimental conditions were associated with cellular morphology, movement, and metabolism and organization pathways. Malignant cell cultures and xenografts derived from a verrucous penile carcinoma were established and fully characterized. Nevertheless, xenograft PeCa models must be used with caution, taking into consideration the selection of specific cell populations and anatomical sites for cell/tumor implantation.

Yu C, Hequn C, Longfei L, et al.
Sexual Function after Partial Penectomy: A Prospectively Study From China.
Sci Rep. 2016; 6:21862 [PubMed] Free Access to Full Article Related Publications
The Purpose of this study was to evaluate the sexual function after partial penectomy for penile carcinoma patients. Between January 2010 and May 2013, patients treated with partial penectomy at our institution were prospectively enrolled in this study. Sexual function (IIEF-15), age, body mass index, penile length in the flaccid state after partial penectomy (PL), treatment, having a partner and psychological factors (SAS scores and SDS scores) were assessed. Univariate and multivariate linear regression analyses were performed. 43 patients were included in our study. The median age was 56 years, and the median PL was 4 cm. The preoperative IIEF-15, SAS, SDS scores were significantly different from the postoperative scores. There was no statistically significant difference between the patients treated with partial penectomy and partial penectomy+ lymphadenectomy on IIEF-15 scores. Age was negatively associated with erectile function, sexual desire, and overall satisfaction; PL was positively associated with intercourse satisfaction; SAS score was negatively associated with erectile function, orgasmic function, sexual desire, and intercourse satisfaction. Our preliminary findings suggest that the sexual function after partial penectomy was significantly reduced. The sexual function was negatively affected by age and anxiety but positively affected by PL.

La-Touche S, Lemetre C, Lambros M, et al.
DNA Copy Number Aberrations, and Human Papillomavirus Status in Penile Carcinoma. Clinico-Pathological Correlations and Potential Driver Genes.
PLoS One. 2016; 11(2):e0146740 [PubMed] Free Access to Full Article Related Publications
Penile squamous cell carcinoma is a rare disease, in which somatic genetic aberrations have yet to be characterized. We hypothesized that gene copy aberrations might correlate with human papillomavirus status and clinico-pathological features. We sought to determine the spectrum of gene copy number aberrations in a large series of PSCCs and to define their correlations with human papillomavirus, histopathological subtype, and tumor grade, stage and lymph node status. Seventy formalin-fixed, paraffin embedded penile squamous cell carcinomas were centrally reviewed by expert uropathologists. DNA was extracted from micro-dissected samples, subjected to PCR-based human papillomavirus assessment and genotyping (INNO-LiPA human papillomavirus Genotyping Extra Assay) and microarray-based comparative genomic hybridization using a 32K Bacterial Artificial Chromosome array platform. Sixty-four samples yielded interpretable results. Recurrent gains were observed in chromosomes 1p13.3-q44 (88%), 3p12.3-q29 (86%), 5p15.33-p11 (67%) and 8p12-q24.3 (84%). Amplifications of 5p15.33-p11 and 11p14.1-p12 were found in seven (11%) and four (6%) cases, respectively. Losses were observed in chromosomes 2q33-q37.3 (86%), 3p26.3-q11.1 (83%) and 11q12.2-q25 (81%). Although many losses and gains were similar throughout the cohort, there were small significant differences observed at specific loci, between human papillomavirus positive and negative tumors, between tumor types, and tumor grade and nodal status. These results demonstrate that despite the diversity of genetic aberrations in penile squamous cell carcinomas, there are significant correlations between the clinico-pathological data and the genetic changes that may play a role in disease natural history and progression and highlight potential driver genes, which may feature in molecular pathways for existing therapeutic agents.

Tan AW, Koh MJ, Ng SK
Benign Eccrine Tumors Presenting on the Penis: Common Tumors at an Uncommon Site.
Skinmed. 2015 Jul-Aug; 13(4):331-3 [PubMed] Related Publications
Case 1 A 60-year-old Chinese man presented to the dermatology clinic with an asymptomatic, 0.5 × 0.5-cm erythematous papule on the penile shaft for a 2-year duration (Figure 1a). His medical problems consisted only of well-controlled hypothyroidism and hypertension. The initial clinical diagnoses considered were pyogenic granuloma or condyloma accuminatum. The excisional biopsy revealed a polypoidal lesion entirely covered by epidermis, with a proliferation of cuboidal, basaloid cells, consistent with an eccrine poroma (Figure 1b). Case 2 A 28-year-old Chinese man presented with an asymptomatic fusiform, 1.4 × 0.4-cm nodule over the ventral aspect of the prepuce, for a 10-year duration (Figure 2a). His medical history was otherwise unremarkable. Lymphangioma was the initial clinical diagnosis but biopsy results revealed large collapsed cystic spaces within the superficial dermis lined by a double layer of epithelial cells with eosinophilic cytoplasm, without evidence of decapitation secretion, consistent with an eccrine hidrocystoma (Figure 2b).

Matulewicz RS, Flum AS, Helenowski I, et al.
Centralization of Penile Cancer Management in the United States: A Combined Analysis of the American Board of Urology and National Cancer Data Base.
Urology. 2016; 90:82-8 [PubMed] Related Publications
OBJECTIVE: To assess the potential benefit of centralization of care in penile cancer. Centralization of care in other disease processes standardizes treatment and improves outcomes. Because penile cancer is a rare malignancy with unchanged mortality rates over the last two decades, we hypothesize that there may be a benefit to centralization.
METHODS: We identified surgeon, patient, and hospital characteristics captured by the National Cancer Data Base (1998-2012) and American Board of Urology case logs (2003-2013) for all penile cancer cases and procedures. Differences in patient demographics, stage of disease, referral patterns, and surgical quality indicators were assessed between academic and community hospitals.
RESULTS: Using case logs to evaluate the distribution of penile cancer care, we found that only 4.1% of urologists performed a penile surgery and 1.5% performed a lymph node dissection (LND). Academic centers treated higher-stage cancers and saw more cases/year than community centers, suggesting informal centralization. Two guideline-based quality indicators demonstrated no difference in use of penile-sparing surgery but a higher likelihood of having an LND performed at an academic center (48.4% vs 26.6%). The total lymph node yield was significantly greater at academic centers (18.5 vs 12.5). Regression modeling demonstrated a 2.29 increased odds of having an LND at an academic center.
CONCLUSION: Our data provide the first evidence for centralization of penile cancer in the US. At the time of diagnosis, equal number of patients is treated with penile-sparing surgery but there is greater use of LND and higher lymph node yield at academic centers. Ultimately, longer follow-up is necessary to determine if this improves survival of patients with penile cancer.

Galot R, Christian N, Bitar M, Seront E
Unusual presentation of bladder cancer resurgence and efficacy of radiotherapy.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A 68-year-old man with a history of bladder cancer presented with perineal pain and penile priapism. The work up showed multiple lesions strictly located in the penis; biopsy confirmed metastases of bladder cancer. Surgery was judged unfeasible and chemotherapy failed to improve symptoms. Radiotherapy was therefore delivered on the whole penis and resulted in a rapid clinical benefit and persistent control of the disease. Penile metastases are very rare and no consensus exists concerning their management; radiotherapy appears as a promising therapeutic option not only to palliate pain but also to control the disease.

Bozzini G, Provenzano M, Romero Otero J, et al.
Role of Penile Doppler US in the Preoperative Assessment of Penile Squamous Cell Carcinoma Patients: Results From a Large Prospective Multicenter European Study.
Urology. 2016; 90:131-5 [PubMed] Related Publications
OBJECTIVE: To determine the role of penile Doppler ultrasound (PDU) compared with magnetic resonance imaging (MRI) in preoperative diagnostic evaluation of patients with penile squamous cell carcinoma.
MATERIALS AND METHODS: A prospective analysis on patients presenting with clinical diagnosis of penile squamous cell carcinoma from 6 different European hospitals between 2012 and 2014 was carried out. Each patient who had planned an organ sparing approach underwent an MRI and PDU both with an artificial erection with prostaglandin E 1. Age, evidence of MRI or PDU corpora cavernosa infiltration, frozen section examination report, definitive pathological report, and surgical approach used per patient were recorded. Accuracy, precision, negative predictive value, sensitivity, and specificity were calculated. Outcomes were statistically evaluated.
RESULTS: Two hundred patients were enrolled in the study. The mean age of the patients was 67.35 ± 15.45 (range 51-82). All of the patients were treated surgically. Of the 200 patients, 135 (67.5%) underwent a corpora sparing approach, whereas 65 had a partial penectomy because of the frozen section outcome. About corpora cavernosa infiltration, the definitive outcome confirmed the frozen section examination. PDU vs MRI accuracy was 96.5% vs 90.5%; precision was 92.6% vs 96%; sensitivity was 96.9% vs 73.8%, specificity was 96.2% vs 98.5%. Despite sensitivity (P <.05) no statistical evidence was found between ultrasound and MRI.
CONCLUSION: PDU has a statistical similar outcome on detecting infiltration of corpora cavernosa and could be used as a less expensive tool to drive surgical strategy in patient with a diagnosis of penile squamous cell carcinoma.

Antonini G, Vicini P, De Berardinis E, et al.
Three-component hydraulic penile prosthesis malfunction due to penile fibrolipoma secondary to augmentative phalloplasty: A case report.
Arch Ital Urol Androl. 2016; 87(4):339-41 [PubMed] Related Publications
Fibrolipomas are an infrequent type of lipomas. We describe a case of a man suffering from subcutaneous penile fibrolipoma, who twelve months earlier has been submitted to augmentative phalloplasty due to aesthetic dysmorphophobia. The same patient three years earlier has been submitted to three-component hydraulic penile prostheses implantation due to erectile dysfunction. After six months from removing of the mass, the penile elongation and penile enlargement were stable, the prostheses were correctly functioning and the patient was satisfied with his sexual intercourse and life. The diagnostics and surgical characteristics of this case are reported.

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