- Overall, penile malignancies are rare.
- Highest incidence: age group 50–70 years
- In the United States:
- Estimated annual incidence of approximately 2000 new cases
- Average incidence: 1 in 100,000 men per year
- In highly industrial countries (United States, Europe, Canada), annual incidence rates are lower.
- Prevalence rates are 5–10 times higher in nonindustrialized countries.
- Uncircumcised males:
- Greatest risk contributing to malignant penile lesions
- 22-fold increased risk versus circumcised males
- Maximal risk reduction of penile cancer with circumcision performed in the neonatal period
- History of HPV or HIV infection:
- 8-fold increase of penile lesions
- Up to 50% of penile cancers are associated with HPV serotypes 16 (most common), 6, and 18.
- Particularly increased risk of basaloid and warty penile carcinomas
- Lower socioeconomic status
- Poor genital hygiene (accumulation of smegma)
- Psoralens and ultraviolet A photochemotherapy
- Chronic inflammatory conditions:
- Most cancers of the penis arise from the squamous epithelium of the epidermis and dermis.
- Two distinct fascial layers arise beneath the penile shaft skin:
- Superficial dartos fascia
- Deep Bucks fascia
- Within Bucks fascia are the two cavernosal bodies dorsally and the solitary spongiosum ventrally.
- Lymphatic drainage of the penis is mainly via the inguinal lymph nodes in the groin:
- No pattern of laterality for drainage, with much crossover
- Superficial and deep lymphatics, either above or below the fascia lata
Pathogenesis and pathology
- Cancer growth:
- Small lesions initially, often noted on the glans or prepuce
- HPV-mediated penile carcinomas:
- Oncoproteins E6 and E7 produced by HPV infections can interfere with tumor suppressor gene function.
- Alterations of the RB1 and p53 genetic pathways and cell-cycle regulators p21 and p16 occur.
- Carcinoma in situ (CIS) or penile intraepithelial neoplasia:
- Bowen disease presents as lesions on the penile shaft.
- Erythroplasia of Queyrat presents with lesions on the glans.
- Squamous cell carcinoma (SCC):
- Common variant:
- Comprises up to ⅔ of SCC cases
- Typically invades the corpus spongiosum and grade II histology
- Inguinal node metastases are present in 25%–40% of cases.
- Papillary carcinoma: 2%–15% of cases
- Usually low grade or well differentiated but superficially invasive
- Microscopic evidence of hyperkeratosis and papillomatosis
- Not linked to HPV infection
- Not often associated with vascular or perineural invasion
- Warty (condylomatous): 7%–10% of cases
- Cauliflower-like lesions
- Prominent fibrovascular core with papillomatous formations
- Does not commonly reach vascular and neural structures
- Linked to HPV infection
- Inguinal node metastasis in 17%–25% of cases
- Basaloid carcinoma: 4%–10% of cases
- Ulcerated irregular masses related to HPV
- Histologically present as uniform and small hyperchromatic cells with central necrosis.
- Usually deeply invasive into the corpus cavernosum or spongiosum
- Verrucous carcinoma: 3%–7% of cases
- Usually low grade and exophytic
- Histologically straight papillae lined by extremely well-differentiated neoplastic cells
- Hyperkeratotic surface with interpapillary keratin
- Sarcomatoid (spindle cell) carcinoma: 1%–6% of cases
- Most aggressive variant
- Poorly differentiated, ulcerated, or rounded polypoid masses
- Usually with vascular and perineural invasion
- Common variant:
- Basal cell carcinoma: low risk of metastasis
- Sarcoma (including Kaposi’s sarcoma, which is associated with HHV-8
- Melanoma: most aggressive skin cancer
- Metastasis to the penis is rare.
Clinical Presentation and Diagnosis
- Initially presents as a skin abnormality or palpable lesion on the penis:
- Majority arise from the glans penis, at the coronal sulcus or on the prepuce.
- May be painful, but usually painless
- Lesions can vary in size and characteristics:
- Ulcerated lesions
- Infiltrative with progressive growth
- Inguinal adenopathy presents in about 30%–60% of cases.
- Distant metastasis:
- Usually means late disease presentation
- Affects adjacent genitourinary organs or distant organs
- Present in about 1%–10% of cases
- Generalized constitutional exam (assess for overall performance status)
- Focused genitourinary exam:
- Penile exam:
- Determine circumcision status.
- Characterize size, depth, location, and features of lesion.
- Assess for discharge, erythema, and swelling.
- Inguinal exam:
- Assess for inguinal lymphadenopathy.
- Number of palpable inguinal nodes
- Fixed or mobile nodes
- Penile exam:
- Tissue biopsy to confirm:
- Assesses primary tumor stage and surgical approach
- Identifies invasion into the corpora cavernosa or spongiosa
- Determines regional lymph node involvement
- Imaging of other sites in case of metastasis
- Staging of inguinal lymph nodes:
- Fine-needle aspiration:
- Performed under local anesthesia with 23-gauge needle
- Samples clinically palpable nodes
- Dynamic sentinel node biopsy:
- Involves injection of radioactive tracer dye
- Examines drainage of inguinal lymph nodes
- Allows for lymphatic mapping and sentinel node biopsy
- Superficial inguinal lymph node dissection:
- Provides direct information regarding suspicious nodes
- Performed by experienced pelvic surgeons
- Higher overall complication rates
- Fine-needle aspiration:
|Primary tumor (T)||Description|
|Tx||Primary tumor cannot be assessed.|
|T0||No evidence of tumor|
|Tis||Carcinoma in situ|
|T1a||Tumor without lymphovascular invasion or perineural invasion and not high grade|
|T1b||Tumor with lymphovascular invasion and/or perineural invasion or tumor is high grade|
|T2||Tumor invades corpus spongiosum with or without urethral invasion.|
|T3||Tumor invades corpora cavernosum with or without urethral invasion.|
|T4||Tumor invades adjacent structures.|
|Regional lymph nodes (N)||Description|
|cNx||Regional lymph nodes cannot be assessed.|
|cN0||No palpable or visibly enlarged inguinal lymph nodes|
|cN1||Palpable mobile unilateral inguinal lymph node|
|cN2||≥ 2 palpable mobile unilateral inguinal nodes or bilateral inguinal lymph nodes|
|cN3||Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral|
|Distant metastasis (M)||Description|
|M0||No distant metastasis|
|Treatment strategy for cancerous lesions||Explanation|
|Partial/total amputation||Partial excision decision has to be exercised with great caution in selected patients with locally invasive tumors.|
|Surveillance for lymph node metastasis||Low-risk patient with no vascular invasion|
|Early lymphadenectomy||For high-risk patients or with vascular invasion|
Carcinoma in situ or Tis–T1:
- Topical therapy:
- Fluorouracil cream indicated for CIS
- Imiquimod cream for CIS
- Laser ablation:
- CO2 laser commonly used
- For local ablation of superficial lesions
- Usually successful for CIS
- Total glans resurfacing:
- Removes the skin and lamina propria layers of the glans penis
- Followed by skin graft placement
- Effective method for CIS
- Mohs micrographic surgery:
- Layer-by-layer excision of penile lesion
- Requires multiple procedures and coordination
- Radiation therapy:
- Via external-beam or interstitial brachytherapy
- Requires multiple sessions and high doses of radiation
- Significant side effects: urethral mucositis, edema, secondary infection risks
Bulky T2–T4 tumors:
- Limited excisions for distal, smaller T2 tumors
- Penile amputation:
- Determined by extent and location of primary tumor
- Partial amputation for distal invasive tumors
- Total amputation for extensively invasive tumors
- Chemotherapy ± radiation therapy also used to shrink tumor or for large lymph nodes
- Low risk (up to T1): surveillance for lymph node metastasis
- High risk: confirm with node biopsy and if positive, proceed with lymphadenectomy
- Palpable lymph nodes: inguinal lymphadenectomy
- Angiokeratomas: uncommon benign, violaceous papules with an overlying scale: Angiokeratomas usually appear on the glans penis, but they can also be found on the scrotum. In most cases, the lesions are asymptomatic and do not require treatment.
- Lichen planus (penis): characterized by violaceous papules on the glans: Lichen planus is rarely symptomatic, although some patients may experience pruritus. Treatment will be for symptomatic control if needed.
- Condylomata acuminata: soft papillomatous growths that are highly associated with HPV infection: Most condylomata acuminata are benign and associated with low-risk HPV types 6 and 11. Treatment involves removal of lesions with laser treatment, topical agents, or surgical excision.
- Genital psoriasis: erythematous plaques with well-defined margins in genital area: These lesions are often asymptomatic but can be pruritic. The presence of other psoriatic plaques on other parts of the body distinguishes this condition from penile cancer.
- Chipollni, J. (2021). Penile neoplasms. AUA Urology Core Curriculum. Retrieved April 3, 2021, from https://auau.auanet.org/core
- Engelsgjerd J. S., LaGrange, C. A. (2020). Penile cancer. StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK499930/
- Pagliaro L. C. (2016). Penile cancer. Kantarjian H. M., Wolff R. A. (Eds.), MD Anderson Manual of Medical Oncology, 3rd ed. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=1772§ionid=121901369
- Pettaway, C. (2020). Carcinoma of the penis: Clinical presentation, diagnosis, and staging. UpToDate. Retrieved April 3, 2021, from https://www.uptodate.com/contents/carcinoma-of-the-penis-clinical-presentation-diagnosis-and-staging
- Pettaway, C. (2021). Carcinoma of the penis: epidemiology, risk factors, and pathology. UpToDate. Retrieved April 3, 2021, from https://www.uptodate.com/contents/carcinoma-of-the-penis-epidemiology-risk-factors-and-pathology
- Pettaway, C. (2021). Carcinoma of the penis: Surgical and medical treatment. UpToDate. Retrieved April 3, 2021, from https://www.uptodate.com/contents/carcinoma-of-the-penis-surgical-and-medical-treatment