Penile Cancer

CHAPTER 49 Penile Cancer

Michael B. Williams, MD, MS
and John W. Davis, MD

True/False: Bowenoid papulosis of the penis is a premalignant condition with the natural history of progression to invasive disease.

False. Bowenoid papulosis has the histologic criteria of carcinoma in situ, but usually has a benign course. Malignant transformation occurs only in 2.6%.

What causes Bowenoid papulosis?

It is caused by human papilloma virus, most often type 16.

What is the best palliative treatment for a patient with acquired immunodeficiency syndrome (AIDS) and Kaposi sarcoma (KS) of the glans penis causing obstruction?

Radiation therapy.

Which forms of KS are associated with AIDS?

Classic KS, immunosuppressive treatment-related KS, African KS, and epidemic KS.

True/False: Verrucous carcinoma is a well-differentiated variant of squamous cell carcinoma (SCC) with similar metastatic potential.

False. Verrucous carcinoma of the penis invades locally and can cause local tissue destruction; metastasis does not occur unless invasive SCC coexists.

True/False: Both verrucous carcinoma and condyloma acuminatum typically remain superficial lesions.

False. Verrucous carcinoma can invade locally causing unrestrained local growth.

Which of the following local treatments is not recommended for verrucous carcinoma and which is the standard recommended therapy: partial or total penectomy, Mohs surgery, radiation therapy, topical podophyllin, 5-fluorouracil, or Nd:YAG laser?

Radiation therapy has been associated with malignant degeneration and is ineffective. Partial or total penectomy is standard therapy.

What differentiates condyloma acuminata from Buschke–Lowenstein tumors?

Condyloma never invades adjacent normal tissues and always remains superficial. Buschke–Lowenstein tumors displace and invade adjacent tissues destroying them. Additionally, despite the local invasion, Buschke–Lowenstein tumors do not metastasize.

What other terms are used for penile carcinoma in situ?

Penile carcinoma in situ is also known as erythroplasia of Queyrat when it involves the glans penis or prepuce, and Bowen disease if it involves the penile shaft.

A 55-year-old uncircumcised male presents with a 0.5-cm reddish, well-defined, barely raised plaque on the glans. The biopsy diagnosis is erythroplasia of Queyrat (CIS). What is the chance of progression to invasive disease and how is the lesion best managed?

The relative risks of progression to an invasive lesion and development of metastases is 10% and 2%, respectively. Superficial premalignant lesions may be treated with local excision, topical 5-fluorouracil, or laser therapy. Sexual partners should be counseled and examined for CIS.

For the lesion described in the previous question, what is the clinical differential diagnosis?

Chronic circumscribed balanitis, inflammatory process, drug eruption, psoriasis, and lichen planus, among others.

True/False: The diagnosis of erythroplasia of Queyrat requires a biopsy.

True.

What is the importance in differentiating Bowenoid papulosis from Bowen disease in the clinical setting?

Bowenoid papulosis is a dysplastic lesion of the epithelium involving the penile shaft in younger men. The histopathologic appearance may be similar to other forms of CIS. The lesions are light brown to gray papules that may coalesce to form plaques. These lesions generally have an indolent course, respond well to excision or podophyllin, may spontaneously regress, and do not usually progress to invasive cancer. Bowenoid papulosis is similar to multifocal vulvovaginal dysplasia in young women.

How does the incidence of SCC of the penis differ in the United States and Europe versus African and South American countries?

In the United States and Europe, SCC of the penis accounts for only 0.4% to 0.6% of all male malignancies. In some African and South American countries, SCC accounts for up to 10% of all diagnosed malignancies in men.

In the United States, what is the ethnic population with the highest age-adjusted incidence of penile cancer per million?

Hispanics are the highest at nearly 7 patients per million. This is followed by blacks, whites, American Indians, and Asian Pacific islanders.

What is the breakdown of likely tumor subtype between younger patients (∼50) and older patients (∼70)?

Younger patients have basaloid and warty carcinomas whereas older patients have verrucous and pseudohyperplastic carcinomas.

Which age range has the highest incidence of penile cancer?

If broken down by age, males older than 85 years of age have the highest incidence.

Over the past 3 decades, is the incidence of penile carcinoma in the United States increasing, decreasing, or remaining constant?

Based on SEER data, penile carcinoma rates are decreasing.

Describe the relationship between penile cancer and circumcision.

Chronic exposure to smegma in the prepubertal period is thought to contribute to the development of penile cancer. Phimosis may accentuate this effect, as it is a finding in up to 50% of cases of penile cancer. Neonatal circumcision virtually eliminates the risk of penile cancer, whereas adolescent or adult circumcision has no protective effect.

True/False: In populations that practice good hygiene but are uncircumcised, the incidence of penile carcinoma is similar to that of circumcised populations.

True.

Name the risk factors for penile carcinoma.

Sexually transmitted human papilloma virus (HPV), phimosis (smegma accumulation), lack of childhood circumcision, and smoking have been associated.

What is human papilloma virus (HPV)? Approximately how many HPV subtypes are known and which are well known to be benign versus malignant?

HPV is a double-stranded, supercoiled DNA virus with more than 65 subtypes identified. “Low risk” strands HPV-6 and HPV-11 are associated with benign condylomata of the anogenital area. “High-risk” types such as HPV-16, -18, -31, -33, -35, and -39 are associated with premalignant lesions of the cervix and penis.

HPV has been identified in what percentage of penile cancers?

HPV has been demonstrated in 50% of penile SCC cases.

True/False: Penile carcinoma secondary to HPV infection causes p53 and retinoblastoma (Rb) dysregulation.

True. Cells that are infected with high-risk HPV (ie, 16, 18, 31, 33, 35, and 39) continue to make viral genes known as E6 and E7. These genes have products that act to disrupt apoptotic pathways and proliferation pathways via Rb and p53 tumor suppressors.

How are penile cancer and cervical cancer related?

Both cancers have HPV as a potential etiology. In some studies, female sexual partners of men with SCC of the penis have a 3-fold increased risk of invasive cervical carcinoma. However, there are key differences as cervical carcinoma is much more common and affects younger women whereas penile cancer is rare and affects older men.

Describe the lymphatic spread of penile cancer.

Lymphatics from the glans and shaft drain to the superficial inguinal, deep inguinal, and pelvic lymph nodes. Drainage is bilateral, and crossover may occur.

What is the natural history of untreated penile cancer?

Untreated penile cancer progresses to death in the majority of patients within 2 years. Local and regional nodal enlargement and complications predominate over distant metastases to lung, liver, bone, or brain. Death may occur by erosion into the femoral vessels with subsequent hemorrhage. Spontaneous remission has not been reported.

List the sites of the primary tumor in penile cancer in order of frequency.

Glans (48%), prepuce (21%), glans and prepuce (9%), coronal sulcus (6%), and shaft (<2%).

What types of invasive penile carcinomas are associated with lichen sclerosus?

Verrucous, papillary, and pseudohyperplastic carcinomas.

What precautions should be taken to prevent dissemination of tumor during biopsy of a penile lesion?

None. Tumor dissemination due to a biopsy has not been reported.

True/False: The most important factors in determining prognosis in penile cancer are stage and presence of lymph node metastasis.

True. Of the 2, the presence or absence of nodal metastases is the strongest predictive factor for survival. Additionally, the histologic characteristics of the primary tumor provide further valuable prognostic information.

How does the appearance of well-differentiated (grade 1) SCC differ from poorly differentiated (grade 3)?

Grade 1 SCC shows downward finger-like projections of atypical squamous cells from the papillomatous epidermis. Keratin pearls are present, and there is limited cellular atypia and mitotic figures. Grade 3 SCC shows little to no keratin pearls and marked cellular nuclear pleomorphism, mitoses, necrosis, and deep invasion.

Compare the 5-year survival for the following groups of patients with SCC of the penis: all patients, negative nodes, positive inguinal nodes, and positive pelvic nodes.