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Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023
| Contributor Information
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Image courtesy of Gregory Diorio, DO.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Penile cancer is relatively rare in North America and Europe (an estimated 2,050 new cases will be diagnosed in the United States in 2023, contributing to about 470 deaths) but it remains a significant concern in many African, South American, and Asian countries.[1,2] Risk factors for developing penile cancer include having an uncircumcised penis, inflammatory conditions (eg, lichen sclerosus), tobacco use, obesity, infection with certain human papillomavirus (HPV) subtypes (particularly HPV 16 and 18), and ultraviolet A phototherapy.[2,3] If left untreated, these cancers can have devastating physical and psychological effects at advanced stages. This slideshow reviews the proper assessment, diagnostic criteria, and treatment for penile lesions.
Image courtesy of Medscape.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
A 35-year-old man presents with the above genital examination findings. Which of the following viral subtypes is most commonly associated with penile carcinoma?
Epstein-Barr virus (EBV)
HPV 6 and 11
HPV 16 and 18
Molluscum contagiosum
Herpes zoster
Image courtesy of Medscape.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Answer: C. HPV 16, 18
Condyloma acuminata (genital warts) (shown on this and the previous slide) are soft, papillomatous growths caused by HPV infection. These superficial, noninvasive lesions are typically considered benign and are most commonly found on the glans, penile shaft, and prepuce.[4] Risk factors for condyloma formation include numerous sexual partners, lack of condom use, and tobacco use.
HPV subtype 16 and 18 may target tumor suppressor gene products pRB and TP53, and they may cause a subset of penile cancers.[4] Multiple therapies are available to treat condyloma, including topical imiquimod 3.75% or 5% cream, podophyllotoxin 0.5% solution or gel, sinecatechins 15% ointment, trichloroacetic acid 80%-90% solution, carbon dioxide (CO2) laser therapy, cryotherapy with liquid nitrogen or cryoprobe, and surgical removal.[5] However, none of these therapies have been shown to eradicate transmission or prevent transformation to dysplasia or cancer.[5]
Adapted image from Nomikos M, Barmpoutis P, Papakonstantinou E, et al. Case Rep Med. 2014;2014:207026. [Open access.] PMID: 25477967, PMCID: PMC4244974.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Buschke-Löwenstein tumors (giant condyloma acuminata), shown above in a 63-year-old man,
are generally benign but can be locally invasive and destructive. Owing to their impressive growth patterns, these tumors displace and destroy adjacent structures from compression.[4] In addition the potential for malignant transformation to squamous cell carcinoma (SCC) exists in the long term, as does the rare risk for metastasis.[6-10] Buschke-Löwenstein tumors are frequently associated with HPV subtypes 6 and 11.[4]
Treatment involves surgical resection and possibly chemoradiotherapy.[4,6,7,9,10] Although penile sparing is the goal, total penectomy may be required. Buschke-Löwenstein tumors have high recurrence rates; therefore, close follow-up is crucial.[4]
Image courtesy of the National Cancer Institute (NCI).
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
A 24-year-old man with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS) presents to your clinic with the above painful violaceous lesions. Biopsy of the lesions would most likely reveal which pathology?
Haemophilus ducreyi
Kaposi sarcoma
Syphilis
JC (John Cunningham) virus
Coxsackievirus type 23
Adapted image from Nistico S, Campolmi P, Moretti S, et al. Biomed Res Int. 2016;2016:7981640. [Open access.] PMID: 27631010, PMCID: PMC5007316.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Answer: B. Kaposi sarcoma
Kaposi sarcoma is a tumor of the reticuloendothelial system associated with immunosuppressed states.[11] Human herpesvirus 8 (HHV-8) is strongly associated with these lesions, especially among HIV-AIDS patients.[12] Although initially seen in the lower extremities of older European and North American men, usually of Eastern European Jewish or Italian descent, Kaposi sarcoma is now associated with all age groups with HIV-AIDS and other immunocompromised conditions.[12] Although any skin region may be affected, penile (shown) or other genital involvement is uncommon.[13-15]
The focus of treatment in these patients is alleviation of symptoms. The glans and corpus spongiosum can become involved, causing obstruction. Depending on the size of the lesions, treatment options include laser therapy, radiation, proximal urethrostomy, or even partial or total penectomy.[4]
Image courtesy of Hon Pak, MD.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
An elderly man presents with the red, velvety, well-marginated lesion on the glans penis shown. The lesion has persisted despite over-the-counter skin creams and is beginning to ulcerate. A biopsy reveals carcinoma in situ
What is the most common site of penile cancer?
Frenulum
Scrotum
Glans
Shaft
Image courtesy of Medscape.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Answer: D. Shaft
SCC in situ of the glans penis or prepuce (shown) is called erythroplasia of Queyrat.[4] SCC involving the skin of the penile shaft, remainder of the genitalia, or perineal region is called Bowen disease.
Management involves histopathologic diagnosis and complete excision.[4] With lesions on the foreskin, circumcision, or excision with a 5-mm margin, is generally adequate for local control. If left untreated, in situ SCC may progress to invasive carcinoma in 5% to 33% of patients.[4] Treatment focuses on penile-sparing procedures, including wide local excision, glansectomy, Mohs surgery, topical therapy (imiquimod 5% or 5-fluorouracil [FU] cream 5%), or laser therapy (CO2, neodynium:yttrium-aluminum-garnet [Nd:YAG], potassium titanyl phosphate [KTP]).[16]
Squamous cell carcinoma of the penis. Image courtesy of Josh Palka, DO.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Invasive penile cancer occurs primarily in older men (peak incidence: sixth decade).[4] SCC is the most common type, demonstrating keratinization, epithelial pearl formation, and various degrees of mitotic activity. Although most lesions are confined to the penis on presentation, their location, size, mobility, and relationship to the corpora cavernosum should be assessed. Evaluation of the inguinal lymph nodes (ILNs), including nonpalpable nodes and primary staging, is also essential, as lymphatic metastatic spread to the ILNs is the most important prognostic factor for invasive penile SCC.[4,16]
Penile cancer is staged according to the American Joint Committee on Cancer (AJCC) tumor/node/metastasis (TNM) classification. Treatment is based on staging and may require lymphadenectomy, partial or total penectomy, and/or adjuvant chemoradiotherapy.[16]
Which of the following statements is true regarding the lymphatic metastatic spread of penile cancer?
Penile cancer initially spreads hematogenously to the lung and brain.
Lymphatic drainage is always ipsilateral to the primary site.
Metastasis initially involves the ILNs above the fascia lata.
Metastasis initially involves the ILNs below the fascia lata.
Perioperative photo of a patient with a palpable right ILN. Image courtesy of Gregory Diorio, DO.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Answer: C. Metastasis initially involves the ILNs above the fascia lata.[17]
Penile lymphatic drainage initially involves the ILNs; no side predilection exists, as crossover can occur.[16] ILN involvement is classified as either superficial or deep, according to its relation to the fascia lata; and as nonpalpable, palpable (nonbulky and nonfixed), or palpable and fixed.
In penile cancer, inguinal lymphadenectomy is diagnostic and therapeutic.[4] Patients with intermediate- to high-grade primary tumors (T1b and above) are at high risk for ILN metastasis; ILN dissection (ILND) is indicated.[16] ILND is technically demanding; complications include skin necrosis, wound infection/breakdown, significant lower extremity and penoscrotal lymphedema, as well as deep venous thrombosis (DVT).[18]
Image courtesy of Gregory Diorio, DO.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
A 72-year-old man presents with the penile findings shown above and a mobile right-sided ILN. An abdominopelvic CT scan confirms the presence of a 3-cm enlarged right ILN but shows no pelvic node involvement. He undergoes partial penectomy and is diagnosed with pT2 SCC (organ confined; corpus cavernosum involved).
Following the partial penectomy, which of the following is indicated next?
No other procedure is indicated.
Administer antibiotics for 6 weeks and reevaluate.
Inguinal lymph node dissection
Pelvic lymph node dissection
Adapted image courtesy of the NCI / Surveillance, Epidemiology, and End Results (SEER) training modules.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Answer: C. Inguinal lymph node dissection
The patient has high-risk disease (invasion into the corpora cavernosum), so assessment of the inguinal and pelvic lymph nodes is essential. Patients with palpable ILNs that are smaller than 4 cm and mobile should be risk stratified based on their original pathology, whereas those with high-risk primary lesions should proceed directly to ILND, with bilateral superficial ILND and deep ILND on the side of palpable nodes.[16] If the contralateral side is found to have disease on frozen section, a deep ILND should be carried out. Neoadjuvant chemotherapy can be considered prior to ILND, per National Comprehensive Cancer Network guidelines.[16]
The standard ILND border limits include the sartorius muscle laterally, the adductor longus muscle medially, the inguinal ligament at the base, and the apex of the femoral triangle as the peak. To reduce ILND morbidity, a modified template can be used, which excludes the space lateral to the femoral artery and caudal to the fossa ovalis, with preservation of the saphenous vein and no need to transect the sartorius muscle.
Methods to minimize complications include maintaining tissue vascularity with meticulous dissection, identification and ligation of lymphatic channels, saphenous vein preservation, and use of a sartorius muscle flap for femoral vessel coverage when performing deep ILND. Postoperative drains for prevention of lymphocele and/or seroma formation and pneumatic stockings and anticoagulation for DVT prophylaxis are recommended.[4]
Image courtesy of Gregory Diorio DO.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
A 72-year-old man presents with the above findings and no palpable nodes. He undergoes excisional biopsy, with the pathology results indicating SCC into the urethra. What is the best initial next step?
Observation
Mohs surgery
Penectomy
Circumcision
Partial penectomy specimen image courtesy of Josh Palka, DO.
Penile Cancer: Cases to Test Your Knowledge
Josh Palka, DO | January 25, 2023 | Contributor Information
Answer: C. Penectomy
In cases of high-grade penile cancer, the standard of care is partial penectomy with possible total penectomy and perineal urethrostomy.[19] The older belief that a 2-cm margin was required has been called into question; more recent studies have shown that margins of 10-20 mm provide adequate tumor control.[16] Intraoperative frozen sections should be obtained and sent for analysis; if a negative surgical margin cannot be attained, total penectomy and perineal urethrostomy should be considered.[20]
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Contributor Information
Authors
Josh Palka, DO
Urologist
Michigan Institute of Urology
West Bloomfield, MI
Disclosure: Josh Palka, DO, has disclosed no relevant financial relationships.
Editors
Olivia Wong, DO
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: Olivia Wong, DO, has disclosed no relevant financial relationships.
John Heinegg, RN
Section Editor
Medscape Drugs & Diseases
New York, New York
Disclosure: John Heinegg, RN, has disclosed no relevant financial relationships.
Pettaway CA, Crook JM, Pagliaro LC. Tumors of the penis. In: Wein AJ, Kavoussi LR, Partin AW, Peters CA, eds. Campbell-Walsh Urology. 11th ed. Philadelphia, PA: Elsevier; 2016: ch 37.
Centers for Disease Control and Prevention. Anogenital warts. Sexually Transmitted Infections Treatment Guidelines, 2021. Updated: July 22, 2021. https://www.cdc.gov/std/treatment-guidelines/anogenital-warts.htm. Accessed January 17, 2023.
Safi F, Bekdache O, Al-Salam S, Alashari M, Mazen T. Giant condyloma acuminatum of Buschke–Lowenstein tumour: disease development between 2000 and 2010. Surg Pract. 2014 Feb;2014:18(1):27-36. Available at: https://onlinelibrary.wiley.com/doi/full/10.1111/1744-1633.12047. Accessed January 17, 2023.
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Venter F, Heidari A, Viehweg M, Rivera M, Natarajan P, Cobos E. Giant condylomata acuminata of Buschke-Lowenstein associated with paraneoplastic hypercalcemia. J Investig Med High Impact Case Rep. 2018 Feb 15;6:2324709618758348. PMID: 29479542
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Marcos-Pinto A, Soares-de-Almeida L, Borges-Costa J. Nonvenereal penile dermatoses: a retrospective study. Indian Dermatol Online J. 2018 Mar-Apr;9(2):96-100. PMID: 29644193
Barakat LA, Malinis M. Nonbacterial microbiology of the head, neck, and orofacial region. In: Hupp JR, Ferneini EM, eds. Head, Neck, and Orofacial Infections: A Multidisciplinary Approach. St Louis, MO: Elsevier; 2016:38-59.
Hoffmann C, Sabranski M, Esser S. HIV-associated Kaposi's sarcoma. Oncol Res Treat. 2017;40(3):94-8. PMID: 28259888
National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology (NCCN guidelines): penile cancer. Version 1.2023 — December 1, 2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/penile.pdf. Accessed Janauary 17, 2023..
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Heyns CF, Fleshner N, Sangar V, Schlenker B, Yuvaraja TB, van Poppel H. Management of the lymph nodes in penile cancer. Urology. 2010 Aug;76(2 suppl 1):S43-57. PMID: 20691885
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