Fungating Mass of the Glans Penis: A Case Report and Discussion on Penile Squamous Cell Carcinoma

Abstract

Penile squamous cell carcinoma (PSCC) is a rare presentation in the United States and Europe, accounting for only 1% of male malignancies. Most commonly due to human papilloma virus (HPV), PSCC has an insidious onset, often ignored by patients until functional impairments are present. This report outlines an interesting presentation of penile squamous cell carcinoma while focusing on current developments in the prognosis and treatment of PSCC. We present the case of a 68-year-old male who presented with a 5 cm fungating mass of the glans penis after emergent care following a stroke. Visual inspection revealed a large mass of the glans penis which had completely obliterated the urethral meatus. A partial penectomy and urethrostomy were performed. Surgical excision revealed a unifocal moderately differentiated (G2) squamous cell carcinoma, with immunohistochemical staining demonstrating p16 positivity, consistent with HPV-associated etiology. This case highlights the importance of individualized treatment regimens and prognostic determination for optimal patient outcomes.

Introduction

Squamous cell carcinomas are malignant transformations of epithelial cells that can occur in any region of the body where squamous epithelial or metaplastic cells are present, most notable the skin, cervix, and lungs. In the genitourinary system, squamous cell carcinomas are a rare presentation—particularly of the glans penis. ¹ In the United States, penile squamous cell carcinoma only accounts for 1% of malignances in men, with ~2000 new cases being diagnosed each year. ² A vast majority of cases of PSCC are due to infection with high-risk subtypes of human papilloma virus (HPV).^3,4

Given the rarity of PSCC in the United States, the information surrounding proper treatment regimens and adequate prognosis indicators are lacking. Currently, no definitive standards of care have been established to help facilitate optimal treatment of PSCC—particularly once the malignancy has surpassed the efficacy of localized excision. ⁵ We present a case of PSCC while highlighting the importance of individualized treatment regimens and prognostic indicators for optimal patient outcomes.

Clinical Case

A 68-year-old male patient is sedated and intubated in the intensive care with complete urinary obstruction. Past medical history is notable for new onset right-sided weakness and aphasia secondary to MCA stroke diagnosed after arrival at the emergency department. The patient underwent same-day mechanical thrombectomy and was transferred to the ICU following the procedure for continuing care. Eighteen hours after arriving at the facility, the patient remained anuric and urology was consulted for evaluation. Physical examination revealed a large fungating penile mass at the glans penis obstructing visualization of the urethral meatus.

Bedside ultrasonographic imaging revealed >1000 ml of fluid within the urinary bladder. Attempted placement of a foley catheter was unsuccessful. Emergent bedside suprapubic cystostomy with pelvic guided ultrasound was performed with placement of a Malecot drain resulted in the efflux of clear urine—the drain was left in place following the procedure until definitive correction could be performed. Overnight, urinary output halted, and the urinary bladder was full on repeat examination. After discussion with the patient’s healthcare surrogate, the patient underwent partial penectomy with urethrostomy.

Originating from the balanopreputial sulcus, the lesion is 5.0 × 5.0 × 3.5 cm tan-white, irregular, and exophytic with areas of surface ulceration and necrosis. On cut section, the mass is firm and infiltrative, extending into and completely obliterating the distal one-third of the penile urethra (Figure 1). The surrounding tissue shows focal hemorrhage and induration. Surgical pathological analysis revealed a unifocal moderately differentiated (G2), squamous cell carcinoma with invasion of the corpus cavernosum (Figure 2). Immunohistochemical studies revealed a diffuse block-type p16 positivity (Figure 3) which is a surrogate marker for HPV-associated malignant processes. Pathological TNM classification was established as pT3 with negative surgical resection margins for dysplasia and malignancy.

Figure 1.

Anatomical sites and levels. Compartments: G, glans; F, foreskin; COS, coronal sulcus; S, shaft; U, urethra; levels: E, epithelium; LP, lamina propria; CS, corpus spongiosum; TA, tunica albuginea; CC, corpus cavernosum; Dt, dartos; d, dermis; ep, epidermis; PF, penile fascia. Note the mucosal epithelium inner surface of the foreskin (in purple) in contrast with the epidermis (in brown).

Figure 2.

20× H&E staining showing invasion of corpus cavernosum. (A) Urethra, (B) corpus cavernosa, (C) malignant invasion.

Figure 3.

200× P16 (+) showing diffuse nuclear and cytoplasmic staining (arrow).

Discussion

Penile squamous cell carcinoma is a rare oncologic presentation in the United States, accounting for only 1% of male cancers. ² As of the writing of thisarticle, no large-scale clinical trials have been completed to establish definitive guidelines for treatment of PSCC. Most clinical practice is guided by case reports, physician knowledge, and evidence from treatments of squamous cell carcinoma in other regions of the body. While simple localized lesions are treatable by resection without need for lymph node biopsy, advanced disease states require more complex intervention. There exists a need to further expand the clinical knowledge of physicians to determine standards are care for these patients, with shortcomings in both prognostic indicators and treatment of advanced disease.

Given the rarity of PSCC in the United States, proper prognostic indicators are still under active investigation. In this report, the nidus for malignant transformation was infection with HPV. It is believed that high-risk HPV (HR-HPV) subtypes, such as HPV-16 and HPV-18 account for 30% to 50% of penile cancers. ⁴ These subtypes are involved in the carcinogenesis of penile cancer by mediating the activity of E6/E7 viral oncoproteins—allowing for inactivation of p53 and retinoblastoma-1 tumor suppression proteins. ⁶ E7’s inhibitory effect is specifically associated with an increased expression of p16^INK4a (p16) in PSCC. Given the overwhelming predominance of HR-HPV as a mediator of PSCC, the prognostic value of p16 positivity is a crucial component in understanding a patient’s treatment outcomes. A retrospective study of 143 patients determined that individuals with p16+ tumors had a significantly better 5-year cancer-specific survival compared to individuals with p16– tumors at 88% and 58%, respectively. ⁷ Although the utilization of p16 IHC staining proves to be a valuable tool in determining the prognosis of patients, its specificity leaves room for more definitive prediction in advanced or atypical disease presentation.

The treatment of advanced PSCC requires more aggressive therapeutic interventions and monitoring to track disease progression or recurrence. In other solid organ malignancies, the utilization of neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation, has been shown to be an independent predictor of oncologic outcomes. ⁸ Prior to receiving treatment, NLR was determined from patients’ blood samples. Individuals found to have a NLR >3 had a shorter median overall survival when compared to patients with a NLR <3. Additionally, NLR >3 was found to be an independent predictor of worse overall survival, although NLR <3 was not found to be an independent predictor for better overall survival. The authors of this study suggest that pretreatment analysis of inflammatory biomarkers could prove useful in more accurately determining the prognosis of advanced diseases state. ⁸

The use of radiation therapy for penile malignancies provides the opportunity for organ preservation and improvement in patient well-being. ⁹ Currently 2 primary strategies exist for the treatment of PSCC with radiation therapy: external beam radiotherapy and brachytherapy. Traditional external beam radiation therapy employed in T1 to T2 stage cancers has a 62% 5-year sustained local control, with 40% of patients at 5 years maintaining preservation of function. ¹⁰ In more advanced disease states, such as T3 to T4 staged malignancies, local control falls to 40% with preservation of function dropping to 38%.^11,12 Brachytherapy has proven to be a more efficacious treatment modality that can be used in place of standard penectomy if the malignancy is staged a T1 to T2. A 2015 meta-analysis by Hasan et al demonstrated that penile preservation with brachytherapy was 74%, with an overall survival rate of 79% at 5 years posttreatment. ⁸

There are currently 2 clinical trials seeking to provide essential clinical information for the treatment of advanced SCC of the penis—The PERICLES and InPACT trials. The PERCILES trial was a phase 2 clinical study that focused on the use of Atezolizumab, and anti-PD-L1 monoclonal antibody, in addition to conventional radiotherapy for the treatment of metastatic disease. The primary endpoint of 1-year progression free survival was not met in this study, but additional biomarkers were identified that may allow for determination of individuals who have a more profound response to treatment. The biomarkers for high-risk HPV and intratumoral CD3+CD8+ T-cell infiltration were highlighted as avenues for future investigation. ¹³ The InPACT trial is an ongoing phase III clinical trial aiming to establish more definitive treatment protocols for advanced PSCC through the combination of surgical, chemotherapeutic, and radiotherapeutic treatment modalities.

Ultimately, the most effective medical intervention regarding PSCC is the prevention of malignancy itself. Given that HPV is the causative agent in the development of PSCC, it is reasonable to focus attention on the current progress being made in the United States for prevention of infection. As of 2024, 61% of all adolescents have completed the full series of vaccinations for HPV; 64% were female and 59% were male, with 77% of all adolescents having received at least 1 dose of the vaccine. ¹⁴ While progress is being made in the prevention of HPV among the adolescent population, few adults are fully vaccinated against the pathogen. Since the approval of HPV vaccinations for individuals aged 27 to 45, on 16% of adults in the United States have received 1 dose of the vaccine. ¹⁵ As it stands, there is a large portion of the population, that is, not protected against HPV—this could allow for future cases of PSCC to manifest if action is not taken to prevent disease transmission.

Conclusion

This interesting presentation of penile squamous cell carcinoma provides an opportunity to analyze the existing literature and knowledge surrounding this uncommon oncologic disease. Given the rarity of PSCC in the United States, a lack of standardized guidelines for care places a burden upon physicians to determine an efficacious treatment plan while attempting to optimize positive outcomes for their patients. While official guidelines are not established at the time of writing, the positive outcome of this report hopes to provide additional insight into how to effectively manage PSCC and review current developments in the field for advancing care in this domain of Urology. Given the multidisciplinary nature of urologic care, cases such as this one will help aid physicians and academics across various fields in their pursuit of knowledge; potentially leading to the establishment of definitive standards of care.