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Human Pathology Feb 2020Our objective was to evaluate the pathologic features and clinical outcomes in cases of invasive penile squamous cell carcinoma (SCC) and the association with p16...
Our objective was to evaluate the pathologic features and clinical outcomes in cases of invasive penile squamous cell carcinoma (SCC) and the association with p16 immunohistochemistry (IHC) and human papilloma virus (HPV) in situ hybridization (ISH). A retrospective multi-institutional database search was conducted for invasive SCC of the penis diagnosed between 2007 and 2018 that had undergone surgical resection. Pathologic features, p16 IHC, and HPV ISH were investigated with clinical outcomes. A total of 102 patients were included in the study. The average age was 63 ± 13.3 years. Based on histology, 46% of tumors displayed an HPV-related subtype, whereas p16 was positive in 52% of all cases. Tumor histology correlated well with p16 positivity (P < .001), and p16 IHC accurately predicted the presence of HPV in 25/26 (96%) cases. On multivariate analysis, perineural invasion was associated with local disease recurrence (P = .02), whereas lymphovascular invasion was associated with progression to metastatic disease (P = .002) and increased overall mortality (P = .02). Urethral involvement was also associated with increased overall mortality (P = .02). In addition, HPV-related tumors based on histologic features correlated with lower rates of metastatic disease (P = .007). HPV is a common cause of penile SCC and can be diagnosed by tumor histology and confirmed by overexpression of p16 on IHC. The presence of lymphovascular invasion, perineural invasion, and urethral involvement are poor prognostic indicators, whereas HPV-related tumors based on histology may have lower risk for metastatic disease.
Topics: Aged; Biomarkers, Tumor; Biopsy; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Databases, Factual; Disease Progression; Host-Pathogen Interactions; Human Papillomavirus DNA Tests; Humans; Immunohistochemistry; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Papillomaviridae; Papillomavirus Infections; Penile Neoplasms; Retrospective Studies; Risk Assessment; Risk Factors; Treatment Outcome; United States
PubMed: 31698006
DOI: 10.1016/j.humpath.2019.09.013 -
Journal of Robotic Surgery Dec 2021Open inguinal lymph node dissection (O-ILND) is the gold standard in the management of lymph nodes in carcinoma penis; however, video endoscopic inguinal lymphadenectomy...
Comparative study of perioperative and survival outcomes after video endoscopic inguinal lymphadenectomy (VEIL) and open inguinal lymph node dissection (O-ILND) in the management of inguinal lymph nodes in carcinoma of the penis.
Open inguinal lymph node dissection (O-ILND) is the gold standard in the management of lymph nodes in carcinoma penis; however, video endoscopic inguinal lymphadenectomy (VEIL) is performed in some centers. Our primary objective is to compare perioperative and survival outcomes in patients undergoing VEIL with O-ILND, as very few studies have reported long-term survival outcomes till date. We analyzed patients who underwent O-ILND and VEIL (laparoscopic or robot-assisted) from January 2009 to January 2020 in our institute for carcinoma of the penis. Patient details, perioperative complications, and survival outcomes were analyzed. Perioperative outcomes were analyzed by logistic regression and survival outcomes by log-rank and Cox regression methods. We analyzed 79 patients (32 O-ILND, 47 VEIL) with a median follow-up of 51 (IQR 25.5-75.5) and 42 months (IQR 21-62). Wound complications were common in O-ILND group (65.6%) compared to VEIL group (27.7%) (p = 0.001), predominantly skin flap necrosis in 14 groins (23.73%) after O-ILND and none after VEIL. Median overall survival was 80 and 88 months (p = 0.840) with five-year survival of 65% and 66.8% (p = 0.636) and five-year DSS of 76.6% and 73.9% (p = 0.96) in O-ILND and VEIL, respectively. Multivariate analysis showed that grade and pathological node status were significant (HR-2.650, p = 0.040; HR-3.218, p = 0.024) factors for survival. The retrospective nature of the study design is the limitation. Management of inguinal lymph nodes in carcinoma penis by VEIL is safe, associated with lesser wound-related complications, and equivalent survival outcomes compared to O-ILND. It should be considered as an alternative option for inguinal lymph node dissection.
Topics: Carcinoma; Groin; Humans; Lymph Node Excision; Lymph Nodes; Male; Penis; Retrospective Studies; Robotic Surgical Procedures
PubMed: 33484414
DOI: 10.1007/s11701-020-01189-x -
Human Pathology Dec 2023There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers...
OBJECTIVES
There is an unmet need for therapeutically relevant biomarkers for advanced penile squamous cell carcinoma (pSCC). Proposed immunohistochemistry (IHC)-based biomarkers include programmed death-ligand 1 (PD-L1), trophoblast cell-surface antigen 2 (TROP2), and nectin-4; however, there is a paucity of data pertaining to these biomarkers. Herein, we investigated the expression of PD-L1, TROP2, and nectin-4 in a well-annotated cohort of pSCCs.
METHODS
A single-institution pathology archive was queried for patients who had a partial or total penectomy for pSCC between January 2000 and December 2022. Whole-slide sections were stained with antibodies against PD-L1 (22C3), TROP2, and nectin-4. Expression in tumor cells was quantified using H-scores (0-300). Associations between IHC expression, human papilloma virus (HPV) status, clinicopathologic findings, and outcome parameters were evaluated.
RESULTS
This study included 121 patients. For PD-L1, the median combined positive and H-scores were 1 and 0, respectively; 32.7 % of the cases had an H-score>0. Compared to PD-L1-negative tumors, PD-L1-positive tumors had higher pT stage and grade. The median TROP2 and nectin-4 H-scores were 230 and 140, respectively, with high TROP2 and nectin-4, defined by an H-score>200, noted in 80.7 % and 10.9 % of cases, respectively. High-risk HPV-positive cases had higher TROP2 and nectin-4 scores compared to HPV-negative cases. Patients with high TROP2 expression had significantly more disease progression, and patients with high nectin-4 expression had significantly fewer deaths due to disease.
CONCLUSIONS
High expression of TROP2 and nectin-4 in pSCC support evaluation of these markers as therapeutic targets pending validation of our findings.
Topics: Male; Humans; B7-H1 Antigen; Nectins; Papillomavirus Infections; Carcinoma, Squamous Cell; Biomarkers; Penile Neoplasms; Biomarkers, Tumor
PubMed: 37977513
DOI: 10.1016/j.humpath.2023.10.003 -
International Braz J Urol : Official... 2021Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic... (Review)
Review
PURPOSE
Squamous cell carcinoma (SCC) of the penis is a rare disease in developed countries but is associated with significant morbidity and mortality. A crucial prognostic factor is the presence of inguinal lymph node metastases (ILNM) at the time of diagnosis. At least 25% of cases have micrometastases at the time of diagnosis. Therefore, we performed a literature review of studies evaluating factors, both clinical and pathological, predictive of lymph node metastases in penile SCC.
MATERIALS AND METHODS
Studies were identified using PubMed and search terms included the following: penile cancer, penile tumor, penile neoplasm, penile squamous cell carcinoma, inguinal lymph node metastasis, lymph node metastases, nodal metastasis, inguinal node metastasis, inguinal lymph node involvement, predictors, and predictive factor. The number of patients and predictive factors were identified for each study based on OR, HR, or RR in multivariate analyses, as well as their respective significance values. These were compiled to generate a single body of evidence supportive of factors predictive of ILNM in penile SCC.
RESULTS
We identified 31 studies, both original articles and meta-analyses, which identified factors predictive of metastases in penile SCC. The following clinical factors were predictive of ILNM in penile SCC: lymphovascular invasion (LVI), increased grade, increased stage (both clinical and pathological), infiltrative and reticular invasion, increased depth of invasion, perineural invasion, and younger patient age at diagnosis. Biochemically, overexpression of p53, SOD2, Ki-67, and ID1 were associated with spread of SCC to inguinal lymph nodes. Diffuse PD-L1 expression, increased SCC-Ag expression, increased NLR, and CRP >20 were also associated with increased ILNM.
CONCLUSIONS
A multitude of factors are associated with metastasis of SCC of the penis to inguinal lymph nodes, which is associated with poor clinical outcomes. The above factors, most strongly LVI, grade, and node positivity, may be considered when constructing a nomogram to risk-stratify patients and determine eligibility for prophylactic inguinal lymphadenectomy.
Topics: Humans; Lymph Node Excision; Lymph Nodes; Lymphatic Metastasis; Male; Penile Neoplasms; Prognosis
PubMed: 33650835
DOI: 10.1590/S1677-5538.IBJU.2020.0959 -
Clinical Genitourinary Cancer Jun 2024Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes. (Observational Study)
Observational Study
BACKGROUND
Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes.
METHODS
Retrospective observational study of patients with a histological diagnosis of carcinoma penis treated with systemic therapy at the Tata Memorial Centre (Mumbai, India) between August 2010 and February 2018. Primary objective was overall survival (OS); secondary objectives included assessment of clinical characteristics, treatment approaches, and toxicity profiles.
RESULTS
We included 91 patients with penile carcinoma who received systemic therapy at our center. Intent of therapy was curative in 71 patients (78%), and palliative in 20 (22%). Median age was 57 years (interquartile range [IQR], 50-65.5) for curatively treated patients and 58.5 years (IQR, 44-65.2) for those with advanced disease. Common presenting symptoms were lumps (70%), and pain (57%). Neoadjuvant chemotherapy (NACT) with paclitaxel + platinum was administered to 19 patients (20.9%), of which 7 (37%) attained complete or partial response. Six patients (31.5%) underwent R0 surgery post-NACT. All 71 patients underwent primary surgery; 47 (66.2%) undergoing partial penectomy. Of the 20 patients treated with palliative first-line chemotherapy, 4(20%) attained a partial response. Median OS of patients treated in curative and palliative settings was 33.8 months (95% CI, 17.2-not recorded) and 11.4 months (95% CI, 9.53-23.3), respectively.
CONCLUSIONS
Patients with penile cancer treated with systemic therapy have poor outcomes. Little over a third of the patients respond to neoadjuvant chemotherapy and those with advanced disease have poor survival despite systemic therapy, emphasizing the need for early detection and optimum management of primary and nodal disease.
Topics: Humans; Male; Penile Neoplasms; Middle Aged; Retrospective Studies; Aged; India; Tertiary Care Centers; Adult; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols; Treatment Outcome; Paclitaxel; Palliative Care
PubMed: 38442451
DOI: 10.1016/j.clgc.2024.02.004 -
Cancer Treatment Reviews Nov 2020Penile cancer (PeCa) is a rare disease worldwide, accounting for less than one percent of all malignancies in men. It usually presents as a painless ulcer or lump on the... (Review)
Review
Penile cancer (PeCa) is a rare disease worldwide, accounting for less than one percent of all malignancies in men. It usually presents as a painless ulcer or lump on the head of the penis. Squamous cell carcinoma represents the most common histological subtype of PeCa, with pathogenesis intimately linked to chronic Human Papilloma Virus (HPV) infection. Surgery is the cornerstone for the treatment of primary PeCa with potential mutilating outcome depending on the nodal extension of the disease. However, in case of extensive lymph node involvement, multidisciplinary treatment including perioperative chemotherapy and inclusion in clinical trial should be considered. To date, advanced or metastatic disease still have poor prognosis and are a therapeutic challenge with limited options, highlighting the need of new treatments and further investigations. Growing efforts to identify molecular alterations, understand the role of HPV and characterize immune contexture have expanded over the past years, providing further perspectives in prognostication, predictive biomarkers and therapeutic intervention. In this review, we provide an updated overview of current management of PeCa focusing on perioperative strategy. We discuss about new insights of the biology of PeCa and comment future directions in the field.
Topics: Carcinoma, Squamous Cell; Clinical Trials, Phase II as Topic; Combined Modality Therapy; Humans; Male; Neoplasm Staging; Papillomavirus Infections; Penile Neoplasms; Perioperative Care; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 32799062
DOI: 10.1016/j.ctrv.2020.102087 -
Urology Annals 2021The association between inflammation and malignancies is being recognized. In this study, we assessed the use of preoperative neutrophil-lymphocyte ratio (NLR) and...
The use of preoperative neutrophil-lymphocyte ratio and lymphocyte-monocyte ratio in predicting survival and groin node involvement of patients with squamous cell carcinoma of penis.
INTRODUCTION
The association between inflammation and malignancies is being recognized. In this study, we assessed the use of preoperative neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) in predicting cancer-specific survival (CSS) and inguinal node involvement in patients with carcinoma penis.
METHODS
Sixty-nine patients operated for squamous cell carcinoma penis with inguinal node dissection between 2012 and 2020 were identified. We recorded the type of surgery (partial/total penectomy), T stage, grade, lymphovascular invasion (LVI), perineural invasion (PNI), pathological status of inguinal nodes and nodal stage (pN1-3), extranodal extension (ENE), and CSS. The hemogram performed within 2 weeks of surgery was used for calculating NLR and LMR.
RESULTS
Partial penectomy was the most common surgery (65.22%) and pT2 was the most common stage (53.62%). Grade 2 was seen in 66.67%, LVI in 34.78%, PNI in 37.68%, 52.17% had inguinal node involvement with pN3 being the most common (36.23%), and 36.23% had ENE. Kaplan-Meier analysis revealed that NLR of >3 and the LMR ≤3 indicated an inferior CSS ( = 0.05 and 0.04, respectively). T stage, inguinal node involvement, LVI, pN stage, and ENE were also associated with inferior CSS ( < 0.05). On multivariate analysis, T stage was significantly associated with CSS ( = 0.02). The NLR >3 and LMR ≤3 were also significantly associated with the presence of pathological inguinal node involvement ( = 0.001 and 0.026).
CONCLUSION
NLR and LMR may help in predicting CSS and inguinal node involvement in patients of carcinoma penis.
PubMed: 34759652
DOI: 10.4103/UA.UA_112_20 -
Advances in Anatomic Pathology May 2023Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis,... (Review)
Review
Genitourinary malignancies include a broad spectrum of distinct tumor entities occurring in the kidney, the urinary tract, the prostate, the adrenal glands, the penis, and testicles. Each tumor entity presents with unique biological characteristics, especially in terms of immunobiology. The immune landscape of genitourinary malignancies differs between immunoreactive tumors like urothelial carcinoma or carcinomas of the kidney, for which several immunotherapeutic treatment options have been approved in the past years. In contrast, prostate cancer presents with low immunogenicity and previous trials exploring immune checkpoint inhibitors and other immunotherapeutic agents did not proof substantial survival benefits. In this review, we are presenting a streamlined overview on the role of surgical pathologists within the contemporary practice of immune oncology. It includes current indications for pathologic programmed death-ligand 1 (PD-L1) assessment and important pathologic considerations on PD-L1 testing harmonization including interassay and algorithm variabilities. In addition, we will discuss emerging biomarkers beyond PD-L1 and their potential to predict immunotherapy responses including tumor mutational burden, microsatellite instability, gene expression signatures, and histologic factors.
Topics: Male; Humans; Urinary Bladder Neoplasms; B7-H1 Antigen; Carcinoma, Transitional Cell; Pathologists; Programmed Cell Death 1 Receptor; Biomarkers, Tumor; Immunotherapy
PubMed: 36730368
DOI: 10.1097/PAP.0000000000000383 -
Handchirurgie, Mikrochirurgie,... Aug 2020The goals of penile reconstruction and phalloplasty include aesthetics as natural as possible and the ability of patients to void while standing and to have sexual...
BACKGROUND
The goals of penile reconstruction and phalloplasty include aesthetics as natural as possible and the ability of patients to void while standing and to have sexual intercourse. This article presents two more rare indications and techniques, the phalloplasty using free radial forearm flapin case of intersexuality and after penectomy due to penis carcinoma.
PATIENTS AND METHODS
In transsexual individuals numerous phalloplasties in Gottlieb and Levine`s technique, by means phalloplasty of free radial forearm-flap of the non-dominant forearm, were performed in our department over the last few years. However, this technique also has its significance for phalloplasty in non-transgender persons.Two patients are considered in detail with regard to indication and surgical technique and were followed up in a multimodal setting.Patient 1 is genetically male, thirty-five years old with a micropenis in the case of pseudohermaphroditism masculine and androgen resistance.Patient 2 is a fifty-one-year old genetically male and as a result of a penis carcinoma his penis had to be amputated at the level of penis root. After absence of recurrence for 1,5 years, the penile reconstruction took place after complete resection of the remaining residual penile stump and corpora cavernosa. Both patients underwent multimodal follow-up 15 months postoperatively with regard to phalloplasty sensors and donor-site restrictions.
RESULTS
An aesthetic and functional acceptable result could be obtained for both patients. Both patients are able to void while standing. The multimodal follow-up 15 months postoperatively revealed relevant differences in the sensory findings of both patients, which are due to the different anatomy of reinnervation.
CONCLUSION
In microsurgical experienced departments, the technique of A. radialis phalloplasty can also be used successfully in more rare indications, as shown here, a satisfying result can be achieved in terms of function and aesthetics. The complications shown here do not differ from those using phalloplasty in transgender persons.
Topics: Adult; Disorders of Sex Development; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Penis; Plastic Surgery Procedures; Surgical Flaps
PubMed: 32428939
DOI: 10.1055/a-1017-3629 -
Virchows Archiv : An International... Dec 2023The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of... (Review)
Review
The classification of the epithelial tumors of the male and female urethra includes benign and malignant neoplasms. Primary urethral carcinomas and adenocarcinomas of the accessory glands are the most relevant tumors, both from the morphologic and clinical point of view. An accurate diagnosis, grading and staging are essential for determining adequate treatment strategies and outcome. Information on anatomy and histology of the urethra is of fundamental importance in understanding the morphology of the tumors, including the clinical importance of their location and origin.
Topics: Humans; Male; Female; Urethra; Adenocarcinoma; Biomarkers, Tumor; Urethral Neoplasms
PubMed: 37233807
DOI: 10.1007/s00428-023-03565-y