Prognostic Factors for Inguinal Lymph Node Involvement and Tumor Recurrence in Squamous Cell Carcinoma of the Penis / Factores pronósticos de compromiso ganglionar inguinal y recaída tumoral en carcinoma escamocelular de pene

Zoom Image Abstract Introduction Penile carcinoma is an aggressive disease with catastrophic consequences that frequently lead to death. Therefore, further knowledge on the prognostic factors that can help identify patients in need of more aggressive treatments becomes essential. Objective To identify the prognostic factors for lymph node (LN) involvement and tumor recurrence in patients diagnosed with squamous cell carcinoma of the penis (SCCP). Methods A retrospective cohort study was conducted. Patients diagnosed and treated for SCCP at Instituto Nacional de Cancerología between 2008 and 2015 were included in the sample. Cases in which no information on recurrence was available for the follow-up were excluded, as well as patients with no initial pathology and those getting penile reconstructions after cancer. Relevant data was retrieved from the medical records of each patient, and a descriptive analysis was performed. Subsequently, this data was used to apply a logistic regression model to determine the potential clinical and histopathological prognostic factors. Results A total of 104 patients were included in the present study. The average age of the sample was 59 years, while the follow-up averaged 24 months per patient. Inguinal lymphadenectomy was performed on 61 patients (59%) during the follow-up. The logistic regression model showed that lymphovascular invasion (odds ratio [OR]: 6.7; 95% confidence interval [95%CI]: 1.2­35) and poor tumor differentiation (OR: 17; 95%CI: 3.2­92) were associated with tumor recurrence. Likewise, the lymphadenectomy procedures showed that lymphovascular invasion was associated with LN involvement (OR: 3.3; 95%CI: 1.1­10). Conclusion Lymphovascular invasion was the strongest prognostic factor observed in our sample, aiding in the prediction of inguinal LN involvement and tumor recurrence in SCCP patients

Introduccion El cáncer de pene es una enfermedad agresiva con consecuencias catastróficas que frecuentemente llevan a la muerte. Por lo tanto, es esencial un mayor conocimiento sobre los factores pronósticos que pueden ayudar a identificar a los pacientes que necesitan tratamientos más agresivos. Objetivo Identificar los factores pronósticos patológicos de compromiso ganglionar inguinal y recaída tumoral en pacientes con carcinoma escamocelular de pene. Métodos Se realizó un estudio de cohorte retrospectivo. Se incluyeron en la muestra pacientes diagnosticados y tratados por carcinoma escamocelular de pene (SCCP) en el Instituto Nacional de Cancerología entre 2008 y 2015. Los casos en los que no había información sobre la recurrencia en el seguimiento fueron excluidos, así como los pacientes sin patología inicial y aquellos que reciben reconstrucciones del pene después del cáncer. Se recuperaron los datos relevantes de los registros médicos de cada paciente, y una descripción fue realizada. Posteriormente, estos datos se utilizaron para aplicar un modelo de regresión logística para determinar los posibles factores pronósticos clínicos e histopatológicos. Resultados Un total de 104 pacientes fueron incluidos en el estudio. La edad promedio de la muestra fue de 59 años, mientras que el seguimiento promedió fue de 24 meses por paciente. La linfadenectomía inguinal se realizó en 61 pacientes (59%) durante el seguimiento. El modelo de regresión logística mostró que la invasión linfovascular (odds ratio [OR]: 6,7; intervalo de confianza del 95% [IC 95%]: 1,2­35) y la pobre diferenciación tumoral (OR: 17; IC 95%: 3,2­92) se asociaron con recurrencia tumoral. Así mismo, los procedimientos de linfadenectomía mostraron que la invasión linfovascular se asoció con afectación de LN. (OR: 3,3; IC 95%: 1,1-10). Conclusión La invasión linfovascular es el factor pronóstico independiente más importante que se asocia de manera independiente con compromiso ganglionar inguinal positivo y recaída tumoral.

The sentinel lymph node biopsy in penile carcinoma guided by multispectral separate-merge guided surgery device / 中华泌尿外科杂志

Objective To explore the method and clinical value of sentinel lymph node biopsy for penile carcinoma guided by multispectral separate-merge guided surgery device (MGS).Methods The clinical data of 7 patients with sentinel lymph node biopsy of penile cancer guided by MGS from April 2017 to April 2018 were analyzed retrospectively at First Hospital of Shanxi Medical University.They were 62-78 years old,with an average age of 65 years.All of carcinoma was located in the glans or coronal sulcus,which diameter was 1.0-3.5 cm,with an average of 2.5 cm.Three cases of inguinal lymph nodes could be non-palpable and the others palpable.All patients were injected 0.25 ml (2.5 mg/ml) of indocyanine greensolution with 1 ml syringe at 12,4,6 and 9 points in the proximal normal skin of penile tumors.Immediately,the imaging probe was aligned with the injection point to observe the dynamic changes of fluorescence image on MGS display.Results There were 14 sides of groin in 7 patients,except for 1 side without images,other 13 sides developed well.The images displayed by MGS include visible image,fluorescent image and merged image,and the merged image was green pseudo color.According to the dynamic changes of the image,it could be divided into five parts:injection point,penile body,pubic symphysis,inguinal region and sentinel lymph node.In 13 well-developed sides,fluorescence gradually disappeared in other parts about 15 minutes after injection,and the location of sentinel lymph nodes was determined in vitro by gradually consolidating and fixing the fluorescence images in the inguinal region.The lymph node-like tissue with strong fluorescence intensity was observed immediately after the skin incision.There was a clear boundary between the lymph node-like tissue and the surrounding tissue.Along this boundary,lymph nodes were separated,ligated,excised.No lymph nodes were found on the undetected side.Postoperative pathology confirmed that lymph nodes were located by fluorescence imaging in vitro and traced by fluorescence imaging in vivo,the coincidence rate was 100％.There were residual fluorescent tissues on three sides and lymphatic vessels were removed.Conclusions MGS-assisted intraoperative fluorescence imaging could improve the doctor's visual depth so that physicians can real-time,dynamic,accurate in vitro location and in vivo tracking of sentinel lymph nodes of penile cancer.

The variable morphological spectrum of penile basaloid carcinomas: differential diagnosis, prognostic factors and outcome report in 27 cases classified as classic and mixed variants

Background: Basaloid carcinomas of the penis, HPV-related tumors, are morphologically less homogenous than originally thought. The study objective was to evaluate the prognostic influence of the basaloid pattern in mixed tumors. Methods: We studied 154 Mexican patients from the Hospital de Oncología, CMN, Mexico City (2000­2013) and found 27 with basaloid features in at least 20% of the sections classified as classic basaloid (8 cases), warty-basaloid (7), papillary-basaloid (5) and usual-basaloid squamous cell carcinomas (7). We evaluated patients' age, site and size of tumor, histological classification, grade, thickness, anatomical level, vascular and perineural invasion, prognostic index score and node involvement. Penile intraepithelial neoplasia in adjacent epithelia was documented. Follow up ranged from 12­78 months. Statistical methods were Fisher's exact test and Kruskal-Wallis test. Kaplan-Meier method and log-rank test were used for survival analysis. The cutoff for statistical significance was p <0.05. Results: There were not clinical differences. Microscopically types were distinctive and easy to separate. Usual-basaloid squamous cell carcinomas were smaller, thinner and rarely invaded corpora cavernosa, with a low prognostic index score. Classic basaloid, warty-basaloid and papillary-basaloid carcinomas had higher rates of vascular and perineural invasion and higher prognostic index scores. These findings correlated with the rate of nodal metastasis. The majority of patients with classic and papillary-basaloid neoplasms died from systemic metastasis (87.5 and 80%) whereas only 1 patient with usual-basaloid carcinoma died of the disease (14%). Conclusions: Basaloid carcinomas are not a single entity but a spectrum of variable histological architectures mixed with those of classic basaloid tumors. Identification of mature squamous cells in a basaloid carcinoma may be important to recognize and report because patients with these tumors may carry a better prognosis (AU)

Progress in the research of CyclinD1 in urinary tumor / 实用肿瘤学杂志

Cyclin D is the most closely relationship with tumor ,and it is currently known one of the sub-types of cyclins.CyclinD1,as a positive regulatory factor ,has an important role in the process of cell cycle ,espe-cially in cell proliferation and division .CyclinD1 is unusually up-regulated in lots of human cancers .CyclinD1 is a recently discovered protein which is highly expressed in the urinary tumors ,and its expression in tumors is asso-ciated with a more aggressive phenotype ,prognosis and recurrence .Therefore,the research of the target point to CyclinD1 in the urinary tumors may provide a new method for the therapy to urinary tumors .

Oncogenic human papillomavirus detection in penile lichen sclerosus: An update.

Aims: Aim of this study was to better address a possible association of human papillomavirus (HPV) infection with penile lichen sclerosus (LS). Study Design: Paraffin-embedded penile biopsies obtained from adult patients with genital LS retrieved from institutional pathology files were evaluated. Place and Duration of Study: The study has been performed in the Dermatology Clinic of the University of Catania, Italy, spanning a 19-year period. Methodology: We previously demonstrated a high (17.4%) HPV detection rate in a study on 46 patients with genital LS. In this retrospective analysis we extended the analysis to a larger number of patients in order to strengthen these former data. HPV infection was assessed by polymerase chain reaction (PCR) in paraffin-embedded penile biopsies obtained from the glans or inner foreskin of 92 adult patients with penile LS and in brush cytology smears of penile healthy mucosa from an equal number of randomly selected control males matched for age. Statistical evaluation was performed using conditional logistic regression analysis. Results: PCR disclosed the presence of high risk HPV infection in 22.83% of LS patients (HPV 16:16 cases; HPV 18:1 case; HPV 31:1 case; HPV 45:2 cases; HPV 68:1 case) vs 15.21% of controls, (HPV 16:4 cases; HPV 31:1 case; HPV 53:1 case; HPV 56:1 case; HPV 68:1 case; HPV 70:1 case; HPV 81:5 cases). Statistical regression analysis confirmed that the rate of oncogenic HPV infection was higher among patients with genital LS than among healthy controls (χ2=8.26; P<.01; OR=3.59). Conclusion: These data suggest a possible pathogenetic interplay between LS and oncogenic HPV infection in the development of LS-associated penile cancer.

Relación entre los factores clínico patológicos y enfermedad ganglionar inguinal en cáncer de pene / Relation between clinical pathological factors and inguinal node disease in pennies cancer

Determinar la relación entre factores clínicopatológicos y enfermedad ganglionar inguinal en cáncer de pene, en los pacientes del Instituto de Oncología “Dr. Miguel Pérez Carreño”. Estudio retrospectivo, descriptivo, transversal, de 76 pacientes con cáncer de pene1995-2011. Un total de 76 pacientes, 20 (26,31%) entre los 51-60 años, siendo el grupo etario con mayor incidencia; el estadio más frecuentemente el IIIB con 23 casos (30,26%), histología predominante carcinoma epidermoide 62 casos (81,57%); la invasión angiolinfática positiva 37 pacientes y 19 casos (51,35%), presentaron metástasis ganglionar inguinal, y 31 casos (45,58%) sin invasión angiolinfática 0% de metástasis. Grado histológico: Los tumores GI 41 de 76 casos (54%), el 29,2% (12 casos) se presentó con metástasis inguinal, los tumores GII y GIII el 77% (17 casos), y 100% (5 casos) respectivamente; en relación al (T), grado histológico y metástasis inguinales, los T1G1 fueron los más frecuentes, con 22 casos, solo 1 de ellos con metástasis, de los T2, los T2G2 fue el de mayor frecuencia con 8 casos, 6 de ellos, con metástasis ganglionar inguinal, los T3G1, estuvo conformado por 10 pacientes, siendo el de mayor número de pacientes, 5 de ellos presentaron metástasis ganglionar inguinal; el resto de T3 y T4 presentaron MT. El grado histológico asociado a la profundidad de invasión y la invasión linfovascular son factores predictivos importantes de enfermedad ganglionar en cáncer de pene.

To determine the relationship between the clinics pathological factors and the presence of inguinal nodal disease in penile cancer in patients view in the Oncology Institute Dr. Miguel Pérez Carreño. Retrospective, descriptive and transversal investigation, with 76 patients with diagnostic of penile cancer view between the years 1995-2011. A total of 76 patients, 20 (26.31%) between 51-60 years old, and the age group with the highest incidence, stage IIIB more frequently with 23 cases (30.26%), squamous cell carcinoma predominant histology 62 cases (81.57%), positive angio lymphatic invasion in 37 patients and 19 (51.35%) had inguinal lymph node metastases, and 31 cases (45.58%) without groin metastases, as to histological grade, tumors GI 41 of 76 cases (54%), 29.2% (12 cases) presented with inguinal metastases, GII and GIII tumors 77% (17 cases), and 100% (5 cases) respectively, in terms of the (T), histological grade and metastatic inguinal T1G1 were the most frequent, with 22 cases, only 1 patient with metastasis, the T2, the T2G2 had the highest frequency of 8 cases 6 of them, with inguinal lymph node metastasis, the T3G1, consisted of 10 patients, with the largest number of patients, 5 of them presented inguinal lymph node metastasis, the rest of T3 and T4 showed metastases. The histological grade associated with the depth of invasion and lymph vascular invasion are important predictors of nodal disease in penile cancer.

A retrospective analysis of laparoscopic and open inguinal lymphadenectomy for the treatment of the patients with penis carcinoma / 中华泌尿外科杂志

Objective To compare the effects of laparoscopic surgery and open surgery of inguinal lymphadenectomy in patients with penis carcinoma.Methods A retrospective case-control study was carried out.The retrospective analysis of clinic data of 10 patients with penis carcinoma who had laparoscopic inguinal lymphadenectomy and 13 who had open inguinal lymphadeneetomy were collected from June 2007 to June 2011,with an average age of 57 (40-75 years),and the average follow-up of 18.6 months (7 days to 9 years).Preoperative clinical stage were T1 in 10 cases,T2 in 7 cases,T3 in 6 cases,with 10 patients detecting inguinal lymph nodes enlargement,while three of which have two enlarged lymph nodes.The age of patients,duration of disease,tumor stage and lymph node enlargement have no statistically significant difference between laparoscopic surgery (LS) group and open surgery (OS) group.The mean operation time,intraoperative blood loss,time of postoperative drainage,hospitalization duration,mean number of excised lymph nodes and postoperative complications were analyzed.Results The mean operative time,intraoperative blood loss,time of postoperative drainage,and hospitalization duration of LS group and OS group were (103.6 ± 15.2) min,(56.5 ±6.8) ml,(5.8±0.8) d,(8.5±1.1) d versus (156.8±18.3) min,(88.5±9.5) ml,(12.5±1.3) d,(15.7±1.9) d,respectively.There was significantly different between the two groups (P＜0.05).However,the mean number of lymph nodes and the mean number of positive lymph nodes excised were not statistically different between the two groups (P＞0.05).There was no transfusion,and no severe complications occurred in either group.With the follow-up of 12-48 months,only one case of lung metastasis detected in OS group.Conclusions Compared with the open inguinal lymphadenectomy,laparoscopic inguinal lymphadenectomy is more safe and effective.It leads to less intraoperative blood loss,less hospitalization duration,less postoperative complications and quick postoperative recovery.

Expresión de marcadores tumorales P16, ciclina D1, BCL2 y Ki67 en cáncer de pene / Expression of tumor markers P16, ciclin D1, BCL2 and Ki67 in penile cancer

El cáncer de pene es una enfermedad de baja incidencia. Su tratamiento se basa en la cirugía y no está establecido si el control tumoral local debe o no ser complementado con linfadenectomía inguinal y pélvica. La linfadenectomía en el cáncer de pene se asocia a elevadas tasas de complicaciones y no está establecido a qué pacientes se les debe realizar. Éste trabajo retrospectivo analiza la expresión de marcadores tumorales en cáncer de pene y su correlación con otros factores pronósticos. La expresión del marcador Ciclina D1 fue alta en todas las muestras, la de Ki-67 y P16 fue alta en los tumores de alto grado y la de BCL-2 fue negativa en todos los casos.

Penile carcinoma is a low incidence disease. Treatment is based in surgery and controversy persists regarding the need of inguinal and pelvic lymphadenectomy. To date, no specific inclusion criteria have been established to indicate surgery. This retrospective work analyses the expression of tumoral markers in penile cancer and correlation with other prognostic factors. The expression of the Cicline D1 marker was high in all the samples, Ki-67, P16 was high in high grade tumors and BCL-2 was negative in all cases.

CD34 immunoexpression in penile carcinoma

OBJECTIVE: To investigate microvessel density as a risk factor in squamous cell carcinoma of the penis. METHODS: Fifty patients with penile carcinoma were evaluated retrospectively. The mean age and standard deviation were 60.8±11.8 years. All of them were treated by penectomy and with positive nodes underwent groin lymphadenectomy. Tumor grading was 36 G1 and 24 G2/3. Primary lesion stage was 22 pT1 and 28 pT2-4. Positive inguinal nodes were observed in 18 patients. Selected paraffin embedded sections were submitted to CD34 immunohistochemical analysis by the avidin-biotin-immunoperoxidase method with antigen retrieval. All slides were examined using an automatic analyzer system and the number of micro-vessels in 10 high magnification power fields (400X) were counted in a blind analysis. RESULTS: Median number of microvessels was 631 in G1 versus 695 in G2/3 tumors (p=0.78), and 696 in pT1 versus 566 pT2-4 tumors (p=0.23). The respective data for pN0 patients was 525 and for pN+ was 696 (p=0.01), which is an unexpected result. CONCLUSION: CD34 immunoexpression or microvessel density determined by this method bear no association with tumor grade, stage or prognosis.

VEGF immunoexpression in penile carcinoma

OBJECTIVE: To investigate the vessel endothelial growth factor (VEGF) as a risk factor in squamous cell carcinoma of the penis (SCCP). METHODS: Forty-seven patients with penile carcinoma were evaluated retrospectively. The mean age and standard deviation were 61.1±11.7 years. All of them were treated by penectomy and those with positive nodes underwent groin lymphadenectomy. Tumor grading was 35 G1 and 12 G2/3. Primary lesion stage was 24 pT1 and 23 pT2-4. Positive inguinal nodes were observed in 15 patients. Selected paraffin embedded sections were submitted to VEGF immunohistochemical analysis by the avidin-biotin-immunoperoxidase method with antigen retrieval. All slides were examined using an automatic analyzer system and the proportion of labeled cells in 10 high magnification power fields (400X) were recorded in a blind analysis. RESULTS: Median (%) labeling index was 2.3 in G1 versus 2.2 in G2/3 tumors (p=0.60), and 4.0 in pT1 versus 1.8 pT2-4 tumors (p=0.10). The respective data for pN0 patients was 2.8 and for pN+ was 2.1 (p=0.20). Survival curves showed no association with patients survival. CONCLUSION: In squamous cell carcinoma of the penis the VEGF immunoexpression has no association with tumor grade or stage, as well as with patient survival.

Detection of Human Papillomavirus DNA in Invasive Squamous Cell Carcinoma of the Penis Using Polymerase Chain Reaction and in Situ Hybridization / 대한비뇨기과학회지

PURPOSE: Infection of the external urogenital system with human papillomavirus (HPV) has been implicated in the development of genital cancer. We evaluated the prevalence of HPV types 6/11, 16 and 18 deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) and the localization of HPV DNA by in situ hybridization. MATERIAL AND METHOD: A total of 22 formalin-fixed, paraffin-embedded specimens of invasive squamous cell carcinoma of the penis were analyzed. We used the PCR technique to evaluate type specific DNA sequences of unique E6 to E7 transforming regions of HPV. Also, we investigated the localization of HPV DNA by in situ hybridization in PCR positive cases. RESULTS: Overall, by PCR technique the detection rate for HPV DNA were 50% (11 of 22 cases). HPV DNA type 16 was detected in all positive specimen and type 6/11 in 5 cases, whereas type 18 could not be detected. All of HPV DNA type 6/11 positive specimens were also HPV DNA type 16 positive. Using in situ hybridization HPV DNA type 16 was detected in 2 (18.2%) from 11 specimens in which HPV DNA had already been detected by PCR, and HPV DNA type 16 was localized in the nuclei of scattered carcinoma cells. But, HPV DNA type 6/11 were not detected by in situ hybridization. CONCLUSIONS: These findings suggest that HPV DNA type 16 is the type most commonly associated with penile carcinoma. But the result of high detection rate for HPV DNA type 6/11 seems to require further investigations.

Clinical Experience with Penis Carcinoma / 대한비뇨기과학회지

A clinical experience was made on 14 patients of penis carcinoma admitted to the Department of Urology. Chosun University Hospital during the period from January, 1979 to December, 1987 and following results were obtained. 1. The incidence of penile carcinoma was 0.6% of total inpatients of the Urologic Department and 5.8% of genitourinary tract cancer. 2. Age distribution was between 42 and 78, showing highest incidence at 50-59 years old. 3. Clinical findings were ; mass 71.5%, ulcer 21.4% and inguinal lymphadenopathy 57%. 4. Clinical stages were distributed as follows : 2 cases in stage I, 6 cases in stage II, 5 cases in stage III, and 1 case in stage IV. 5. Surgical treatment were partial amputation only in 6 cases, partial amputation with lymph node dissection in 3 cases, total penectomy and lymph node dissection in 2 cases, total penectomy only in 1 case, circumcision only in 1 case. 6. Biopsy were performed in 7 cases whose lymph node were palpable and 4 cases were positive for metastasis (57.1 %).

Clinical Observation on the Penis Carcinoma / 대한비뇨기과학회지

Clinical observation was made on the 16 patients of penile carcinoma admitted to the Department of Urology, Seoul National University Hospital during the period from September, 1967 to August, 1976 and the following results were obtained. 1. The incidence of penile carcinoma was 0.5% of total inpatients of urologic department and 3.5% of male genitourinary tumors. 2. Age distribution was between 29 and 78, snowing highest incidence at 50-59 years. 3. Clinical findings were; mass 77%, discharge 28%, ulcer 25%, bleeding 13%, and inguinal lymphadenopathy 50%. 4. The average duration of the symptoms on admission to hospital was 10 months with the highest incidence in 1 to 6 months. 5. The locations of the tumors were; preputial cavity 87%, confined to glans 6%, penile shaft involved 6%. 6. Treatments were made with partial amputation in 50%, partial amputation with inguinal lymphadenectomy in 37%, and biopsy in 13%.

A Case of Penile Carcinoma Transformed from Giant Condyloma Acuminata / 대한비뇨기과학회지

Giant condyloma and carcinoma-like condyloma is relatively rare. Although it has histological similarities to condyloma acuminata, it is believed by most authorities to be a clearly defined variant of epidermoid carcinoma. Clinically it is easily mistaken for the more aggressive metastasing epidermoid carcinoma. The legion was first described by Buschke in the German literature in 1896. as a varient of condyloma acuminata. A case of malignancy of the penis which have apparently been transformed from giant condyloma acuminata of the penis are herein presented with review of literature.