PENILE SQUAMOUS CELL

CARCINOMA
 Introduction
 Penile tumors present a difficult diagnostic
and therapeutic issue, mainly because of
their psychological implications.
 Introduction
 The diagnosis may be delayed because
many patients tend to disregard early
asymptomatic lesions, and they often seek
medical attention at an advanced stage
when a conservative surgical approach is
no longer feasible.
 Penile Squamous Cell Carcinoma

 The cause is unclear

 Risk Factors :
1. preexisting dermatoses
2. lack of circumcision
3. environmental exposures
4. human papillomavirus (HPV) - play a
major role
Incidence:
 The overall incidence of primary malignant penile
cancers has been constantly decreasing from 1973 to
2002.

 Mean: 0.69 case per 100,000 population

 Incidence varies in different geographic areas

- accounts for 1% of all malignancies in male
patients in the Western countries
- 10-20% in some parts of Asia, Africa, and South
America
 Incidence
 Higher incidences are reported in tropical areas,
such as Puerto Rico, Mexico, Paraguay, Venezuela,
Vietnam, Ceylon, Thailand, China, Uganda, and
parts of India

 An incidence of 0.6 case per 100,000 population

 

per year was recorded in the United Kingdom in

2007
 Incidence
 United States
- SCC accounts for at least 95% of all
penile malignancies. 
- represents approximately 2% of all
cancers of the male genitalia
- found in 0.3-0.5% of the cancer-
bearing male population. 
 Age
 The age at onset of penile SCC is 20-90
years, with a peak around the sixth and
seventh decades

 A few cases have been reported in

children.
Risk factors
 HPV infections
 A role of HPV infections is established but
not fully understood.

 Genital HPV infections mostly affect

middle-aged, sexually active individuals.
 LACK OF CIRCUMCISION

 Epidemiologic data have demonstrated

that penile SCC is exceedingly rare in men
who are circumcised at birth

 One study also demonstrated an increased

risk of HPV infection in uncircumcised men
(19.6%) compared with circumcised men
(5.5%).
 LACK OF CIRCUMCISION
 The prophylactic effect of circumcision on
penile carcinoma is likely related to the
lack of retained smegma that has been
proven to be carcinogenic in animals.

 Smegma retention may cause irritation

 

and recurrent infections, leading to

phimosis.
 Phimosis
 also a risk factor for penile SCC
 

development

 has been experimentally shown to induce

histologic changes in the epithelium of the
preputial sac.
 Hygiene
 Poor genital hygiene in uncircumcised males,
even in the absence of phimosis, may also play a
role, leading to the retention of smegma.

 This finding is confirmed by the lower incidence

of penile SCC in countries with good hygienic
standards.
 However, a 2001 study failed to detect
any correlation between personal hygiene
habits (frequency and method of bathing
and/or cleaning of the anogenital area)
and risk of penile cancer development.

Annals of Surgical Oncology 14(12):3614–3619

 Environmental Exposure
 Prolonged exposure to different chemical
compounds such as:
1. insecticides
2. Fertilizers
3. Styrene
4. acrylonitrile
= together with poor hygiene practice,
traumas, or chronic irritation, can be factors
contributing to penile SCC.
 Ritual circumsicion
 Late ritual circumcision followed by herbal
treatments to control bleeding performed
in the Southwestern Saudi region is
associated with extensive scarring and
may result in the development of invasive
tumors proximally and dorsally located on
the shaft
 Cigarette smoking
 has been found to show a clear-cut association
with penile SCC

 this association is related to the nicotine intake

and is independent of phimosis or balanitis.

 Whether tobacco products concentrate in

smegma has not been proven in humans.
 Immune suppression

 Whether due to either transplantation or

HIV infection, is associated with a greater
risk of SCC development on the penis and
on other skin sites.
 Reconstructive surgery for sex
reversal
 can be factor

 although whether the heterotopic penile

skin within the neovagina may be at an
increased risk of cancer development is
unclear
 Differential Diagnoses
 Bowen disease
 Erythroplasia of Queyrat
 Bowenoid papulosis
 Penile verrucous carcinoma
 Condyloma acuminata
 Bowen disease

 rare
 most common occurrence in elderly white
men.
 Usually occurs on the shaft
 appears as a solitary, dull-red plaque with
areas of crusting and oozing.
 Erythroplasia of Queyrat
 most common in elderly, uncircumcised
white men

 Ulceration and/or papillary outgrowths are

clinical signs of the disease.
 Erythroplasia of Queyrat
- appears as a solitary,
sharply defined,
bright-red, glistening,
velvety, nontender,
often-eroded plaque
on the glans, the
inner surface of the
prepuce, or the
coronal sulcus.
 Bowenoid papulosis
 mainly occurs on the shaft in young circumcised
men.

 Bowenoid papulosis is a HPV infection with a

characteristic bowenoid histology

 Extragenital involvement is exceedingly rare.

 Bowenoid papulosis
 It appears as
multiple, small,
slightly elevated, red-
to-violet, slightly scaly
or warty papules,
which sometimes
coalesce into large
plaques
 Bowenoid papulosis
- Lesions may remain static, spontaneously
regress, or progress to Bowen disease.

- Local recurrences after conservative

excision and the onset of Bowen disease
or SCC are reported in elderly and in
immunocompromised patients
 Penile verrucous carcinoma
 frequently appears as
an exophytic
cauliflowerlike mass
that may be foul
smelling and
sometimes ulcerated,
 in rare cases, it may
resemble a penile
horn.
Verrucous carcinoma.
 Penile verrucous carcinoma
 Swelling of the regional lymph nodes as a
result of secondary infection is frequent,
whereas local metastases are infrequently
reported.
 Verrucous carcinoma
 Verrucous carcinoma represents 5-16% of all
SCCs

 prevalence varies from 5-24% among all penile

malignancies

 may occur at any age (18-88 y), but two thirds

of all cases occur before age 50 years.
Condylomata acuminata
 The lesions clinically
appear as exophytic,
fleshy, fibroepithelial
proliferations involving
the mucosal and
cutaneous surfaces of the
anogenital area
(anogenital warts)
PENILE SQUAMOUS CELL
CARCINOMA
 Two growth patterns have been
described:
1. Papillary

2. Flat
Papillary squamous cell carcinoma
on the penis

 Papillary tumors usually originate as single or

multiple coalescing, elevated, and warty lesions
that may subsequently undergo necrosis and
ulceration

 usually involves the glans and the prepuce and

rarely the shaft
 Flat Tumors of the Penis
 extend on the surface
and infiltrate deeper
tissues.
 appear as small,
superficial, round
ulcers on a slightly
elevated and
indurated base
Diagnosis
 History
 Primary SCC may occur at any anatomic site on
the penis.

 In most cases, the earliest symptoms are:

1. itching or a burning sensation under the
foreskin
2. ulceration of the glans or the prepuce, which, if
untreated, may progress to a mass or a nodule.
 History
 With time, the tumor destroys the glans
and the prepuce and infiltrates the
corpora cavernosa.

 When the urethra is invaded, obstruction

and fistulae may develop.
 History
 Lymphatic metastases first occur in the
superficial or deep inguinal lymph nodes, then in
the regional lymphatics of the pelvis.

 Distant metastases resulting from vascular

dissemination (most commonly to the lungs and
the liver, followed by the bone, the brain, and
the skin) are rare and usually late.
 History
 With regard to penile verrucous
carcinoma, its apparent clinical benignity
may lead to lengthy periods of
misdiagnosis during which it is not likely to
spread to distant lymph nodes, but rather,
to the penis as it slowly but relentlessly
extends into underlying tissue
 Physical Examination
 Frequency of occurrence of Penile SCC :
1. glans (48%)
2. prepuce (21%)
3. both the glans and the prepuce (9%)
4. coronal sulcus (6%)
5. shaft (<2%).

 Invasion of the shaft by a tumor originating from

more distant sites may also be observed (14%).
 Physical Examination
 The clinical presentation varies from
slightly elevated areas of induration,
erythema, or warty growth to an extensive
tumor with sloughing and autoamputation
of the phallus
 Physical Examination
 Palpable inguinal lymphadenopathy is present at
diagnosis in 58% of patients.
- 45% have cancer in the nodes
- 13% have inflammatory lymphadenopathy
secondary to infection of the primary tumor

 Of nonpalpable lymph nodes, approximately

20% contain metastases.
 The extent of penile shaft
involvement, tumor grading,
and the growth pattern are
correlated with the frequency of
regional lymph node
metastases.
 Workup
 Laboratory Studies
- Hypercalcemia may rarely complicate a penile
carcinoma
 Imaging Studies
- recommended for a more accurate staging of
neoplastic disease and for periodic follow-up of treated
patients
1. ultrasonography
2. CT scanning
3. MRI
 Histologic Findings
 Histopathologic examination
- essential to establish the diagnosis
- provide information about the
extension of the tumor in deeper tissues
 Staging
 The staging systems currently used are:
- the Jackson classification and

- the tumor, nodes, metastases (TNM)

system
 Assessment of histologic grade and
infiltration or invasion of the adjacent
deep or lateral tissues aids in planning
treatment
 Treatment
 The treatment of penile SCC varies according to the
clinical stage.
 Treatment includes:
1. radiation therapy
2. medical therapy
3. surgery
- alone or in combination.
 However, because of the generally limited experience
with SCC of the penis, considerable controversy exists
as to the best form of treatment, specifically treatment
for regional lymph nodes
 Radiation therapy
 Radiation therapy with external beams or
mould techniques (cesium Cs 137, iridium Ir
192)
- small, superficial, exophytic lesions in
young individuals
- allows the preservation of sexual function
- high cure rate.

 Circumcision before therapy is recommended

 Medical treatment

 Local chemotherapy
- Early premalignant and in situ changes
can be treated with topical chemotherapy
- 5-fluorouracil or imiquimod

 Systemic chemotherapy
 Systemic chemotherapy
1. Palliative chemotherapy
- for local recurrences and for metastases when
other treatments fail
2. Adjuvant combined chemotherapy (VBM or CBM
therapy)
- reduce the incidence of metastases in patients
with involved nodes after surgical resection of the
lymph nodes
3. Neoadjuvant combined chemotherapy
- for locally invasive tumors (stages T3-T4)
- for fixed regional node enlargement
- to reduce the neoplastic mass before surgical
excision
Other medical treatments include the
following:
 Chemotherapy (bleomycin) and radiation
therapy
 Photodynamic therapy for Tis
 Regional intra-arterial chemotherapy
(methotrexate and mitomycin C)
 Systemic or intralesional interferon alfa
either alone or combined with surgical
shaving (for relapsing verrucous carcinoma)
 Surgical treatment
1. local excision
2. Circumcision
3. Glansectomy
4. partial penectomy
5. total penectomy, and
6. demasculinization

- The last 3 procedures may be performed in

conjunction with lymph node dissection
 Follow-up

 If patients do not undergo prophylactic

dissection of lymph nodes, careful follow-
up of the inguinal regions is required for 3
years.
 Follow-up
 monthly during the first year of follow-up

 bimonthly during the subsequent 2 years

 quarterly pelvic and abdominal CT scans

 Follow-up
 A different schedule for physical
examination has also been suggested:
1. monthly for the first year
2. every 6 months for the second year
3. yearly for the third and fourth years
4. every 5 years
 Prevention
 Circumcision in infancy and a good standard of
sexual hygiene are recognized as good
prophylactic measures.

 Future directions in the prevention of penile SCC

(as for cervical and vulvar carcinoma) should
include further elucidation of the role of
preexisting conditions, including HPV infections
and genital lichen sclerosus, in the pathogenesis
of the disease
 Prognosis
 In the absence of inguinal metastases,
patients with invasive SCC of the penis
involving the glans or the distal part of the
shaft who undergo adequate partial
amputation have a long-term survival rate
of 70-80%.
 Prognosis
 Of patients with involved lymph nodes,
40-50% can be cured with lymph node
dissection, whereas untreated patients
usually die within 2-3 years.
 Prognosis
 HPV infection does not seem to negatively
influence the prognosis of patients with
invasive SCC
 Mortality/Morbidity
 SCC is the cause of less than 1-2% of all
deaths from cancer in men in the United
States.
 Statistically significant decreased survival
has been found in African American men,
who tend to present with a high stage of
disease.
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