etiology of ca penis

1. Carcinoma Penis
-DR Gaurav Pawarr
25/05/2021

2. Introduction
• Originates from the epithelium of the inner
prepuce or the glans.
• Incidence in India - from 0.7-2.3 cases per
100,000 men
• Sixth decade of life (mean- 58 years)
• More than 90% lesions are SCC.

3. • Most commonly on the glans (48%) and prepuce (21%)
• Lesions morphologically -- papillary and exophytic or
flat and ulcerative
• If it is untreated, penile autoamputation may occur as a
late result
• Lesions larger than 5 cm and those extending over 75%
of the shaft are associated with an increased incidence
of metastases and a decreased survival rate
• Penetration of Buck fascia and the tunica albuginea
permits invasion of the vascular corpora and
establishes the potential for vascular dissemination

4. Recognized aetiological and
epidemiological risk factors
Risk factors & Relevance
• Phimosis
– OR 11-16 versus no phimosis
• Chronic penile inflammation (balanoposthitis related to phimosis)
• Balanitis xerotica obliterans (lichen sclerosus)
• Sporalene and UV-A phototherapy for various dermatologic conditions such
as psoriasis
– Incidence rate ratio 9.51 with > 250 treatments
• Smoking
– 5-fold increased risk (95% CI: 2.0-10.1) versus nonsmokers
• HPV infection condylomata acuminata
– 22.4% in verrucous SCC
– 36-66.3% in basaloid-warty
• Rural areas, low socio-economic status, unmarried
• Multiple sexual partners, early age of first intercourse
– 3-5-fold increased risk of penile cancer

5. Premalignant penile lesions
Lesions sporadically associated with SCC of the penis
• Cutaneous horn of the penis
• Bowenoid papulosis of the penis
• Lichen sclerosus (balanitis xerotica obliterans)
Premalignant lesions (up to one-third transform to
invasive SCC)
• Intraepithelial neoplasia grade III
• Giant condylomata (Buschke-Löwenstein)
• Erythroplasia of Queyrat
• Bowen’s disease
• Paget’s disease (intradermal ADK)

6. Pre malignant - CIS
CIS
–Full thickness intraepidermal carcinoma, Mucosa replaced by
atypical hyperplastic cells with disorientation, vacuolation, multiple
hyperchromatic nuclei and mitotic figures. Epithelial rete ridges
extend into submucosa and appear elongated, broadened and
bulbous. Submucosa shows capillary proliferation and ectasia
– Originally described by Queyrat in 1911
– Histologically Queyrat and Bowen are similar
–Erythroplasia of Queyrat – velvety bright red patches on mucosal
surfaces of penis.
–Bowen disease - solitary well defined red plaques on penile shaft,
often with crusting ulceration

8. Giant condyloma
(Buscke -Lowenstein tumor)
•Locally aggressive, exophytic, low grade variant of SCC
that has little metastatic potential
• Warty appearance
• Slow growing and locally destructive
•Usually – uncircumcised on glans or prepuce (can be on
urethra, vulva, vagina, cervix, anus, oral/nasal cavities,
plantar surfaces of feet)
• Associated with HPV 6, 11 (NOT 16, 18)
• Treatment – local excision

10. Bowenoid papulosis
• Histologically resembles Bowen disease, except that the abnormal
keratinocytes are spread discontinuously throughout the epidermia
• Red-brown papules on glans or shaft (can occur in females as well)
• Multiple red velvety maculopapular areas. Similar to warts
• Age 20 – 30 (sexually active/promiscuous). Usually uncircumcised
male
• Clear association with HPV 16
• Sexually transmitted. Female partners have increased risk of cervical
neoplasia and should have close follow up.
• Spontaneous regression may occur
• Transition between genital wart and Bowen disease
• Management – conservative surveillance, 5-FU or ablation (laser,
cryotherapy, electric ablation)
• Often runs benign course unless immunosuppressed

12. Balanitis xerotica obliterans (Lichen
sclerosus at atrophicus)
• Arises from chronic infection, trauma, inflammation
• Most common pre malignant condition
• Unknown aetiology
• Presentation
– Flat, white patches on glans or prepuce
– Pathologic phimosis. May involve meatus or fossa navicularis
– Fibrotic
– Male and female (usually uncircumcised)
–Usually asymptomatic. May have pruritis, burning, painful erections,
dyspareunia in females
– Associated with meatus and urethral strictures
• Histology
• Hyperkeratosis, thinning of rete pegs, chronic inflammatory infiltrate
(lymphocytes, plasma cells)

13. Treatment
– Asymptomatic – no therapy
–Symptomatic – topical steroids to relieve itching and burning
(betamethasone BD or 0.1% triamcinolone BD)
– Avoid excision as recurrence high. Can do circumcision
– Biopsy if poor response to therapy
– Assess for urethral stricture if history suggests
• 2.3% of those diagnosed with BXO have SCC
•Synchronous BXO is found in 28-50% of those treated for
penile cancer
• 10 - 33% progress to invasive SCC
• Annual F/U because of malignancy risk (controversial)
• SCC latency time 15-17 years

14. Leukoplakia
• Rare
• White, verrucous plaques on
mucosal surfaces
• Usually glans or prepuce
• Clinically resemble BXO
• More common in patients with
diabetes
• Probably related to recurrent or
chronic infection
Cutaneous horn
• Rare. Usually develops over a pre
existing lesion (wart,
nevus, trauma, malignant neoplasm)
• Characterized by overgrowth and
cornification of the epithelium
• Microscopy – extreme
hyperkeratosis, dyskeratosis and
acanthosis (abnormal thickening of
the prickle-cell layer of
the skin)
• High risk of malignant
transformation
• Associated with HPV 16
• Treatment – surgical excision with a
margin
• Careful histologic assessment of
base and close follow up of
excision site

15. PEKMB
•Pseudoepitheliomatous, keratotic and micaceous (white,
scaly) balanitis
•Rare. Develops thick, hyperkeratotic, laminated plaque on
glans of penis
• Usually elderly, uncircumcised
• Can have concurrent verrucous carcinoma
• Controversial if pre malignant
•Histology – hyperplastic epidermia with ridges extending
deep into dermis
• Treat by surgical excision or ablation with close follow up

17. Histologic Subtype Frequency
(% of cases)
Prognosis
common SCC 48-65% depends on location, stage and grade
basaloid carcinoma 4-10 poor prognosis, frequently early
inguinal nodal metastasis
warty carcinoma 7-10 good prognosis, metastasis rare
verrucous carcinoma 3-8 good prognosis, no metastasis
papillary carcinoma 5 - 15 good prognosis, metastasis rare
sarcomatoid carcinoma 1 - 3 very poor prognosis, early vascular
metastasis
mixed carcinoma 9 - 10 heterogeneous group
pseudohyperplastic
carcinoma
<1 foreskin, related to lichen sclerosus,
good prognosis,

18. carcinoma cuniculatum <1 variant of verrucous carcinoma,
good prognosis
pseudoglandular carcinoma <1 high grade carcinoma, early
metastasis, poor Prognosis
warty-basaloid carcinoma 9 -14 poor prognosis, high metastatic
potential (higher than in warty,
lower than in basaloid SCC)
adenosquamous carcinoma <1 central and peri-meatal glans,
high grade carcinoma, high
metastatic potential but low
Mortality
mucoepidermoid carcinoma <1 highly aggressive, poor prognosis
clear cell variant of penile
carcinoma
1 -2 exceedingly rare, associated with
HPV,aggressive, early metastasis,
poor prognosis,outcome lesion
dependent, frequent lymphatic
Metastasis

19. NEOPLASIA

20. Condyloma Acuminata
• Sexually transmitted tumor caused by human
papilloma virus (HPV type 6 and 11)
• Gross: Thrives in any moist mucocutaneous
surface of the external genitalia

22. Condyloma Acuminatum

23. Koilocytosis

24. Condyloma Acuminata
• Micro: Koilocytosis or perinuclear
vacuolization is the pathognomonic lesion for
this disease.
• Presence of nuclear atypia

26. Bowen’s Disease
• Involves the skin of the shaft and scrotum
• Gross: solitary, thickened grey-white,
opaque plaque; can also be seen in the
glans and prepuce as single or multiple
shiny red, velvety plaques.
• Micro: surface cells are not much different
from the base cells, this is defined as a “loss
of maturation” pattern, and is quite typical
of squamous CIS everywhere

28. Invasive Squamous Cell Carcinoma
• Risk in developing penile carcinoma is related to
genital hygiene since exposure to carcinogens that
may be concentrated in the smegma increases the
likelihood of infection which may carry the
potential oncogenic type HPV 16 which is
detected in 50% of patients with penile
carcinoma.
• Cigarette smoking also elevates the risk of
developing penile cancer.

30. Infiltrating Squamous Cell
Carcinoma
Flat lesions appear as areas of epithelial
thickening accompanied by graying and
fissuring of the mucosal
surfacepapillary SCC

31. Histology SCC
 Most demonstrate
keratinisation, epithelial pearl
formation with various degrees
of mitotic activity
 Normal rete pegs are disrupted
 Broders classification (grade 1 –
4)
– Based on level of diffentiation,
keratinization, nuclear
pleomorphism, number of mitoses
– Low grades (1,2) 70 – 80% cases.
Well differentiated
– Shaft – more likely to be high grade
– Grade and stage often linked
Adverse prognostic features:
– Higher grade = more likely nodal
metastases
– Metastases present in 58% of
those with any grade 3 compared
to 14% without any grade 3
– Vascular invasion = more likely
nodal metastases
– Perineural invasion = more likely
nodal metastases

32. Natural History
• Begins as small lesion, papillary & exophytic or
flat & ulcerative.
• Flat & ulcerative lesions >5cm and extending
>75% of the shaft have higher incidence of
metastasis and poor survival.
• Pattern in lymphatic spread.
• Metastatic nodes cause erosion into vessels,
skin necrosis & chronic infection.
• Distant metastasis uncommon 1 – 10%
• Death within 2 years for most untreated cases.

33. Presentation
• Embarrassment, anxiety and
fear often results in delayed
presentation
• 5.8 months is average delay
• Lump 47%
• Ulcer 35%
• Erythematous lesion 17%
• Bleeding/discharge from
lesion concealed by prepuce
• Usually sharply demarcated
lesion
Location
• Glans 48%
• Prepuce 21%
• Glans and prepuce 9%
• Coronal sulcus 6%
• Shaft <2%
• Rare – nodal metastases,
hemorrhage, urinary
retention,urethral fistula

34. Examination
– Size, location, number, fixation,
involvement of corporal bodies
– Morphology – papillary, nodular,
ulcerous, flat
– Inspect base of penis, scrotum to
rule out extension
– Inspect corpus
spongiosum/cavernosum
– Inguinal lymphadenopathy
– Penile length
Laboratory
– Hypercalcemia is seen in
approximately 20%
(paraneoplastic)
– LFTs – metastases
Palpable lymph nodes
• Describe
– Node consistency
– Location
– Diameter
– Unilateral/bilateral
– Number of nodes in each area
– Mobile/fixed
– Relationship to other strictures (eg
skin)
– Edema of leg/scrotum
• Up to 50% palpable LNs at
diagnosis are reactive
• If persistent nearly 100% are
malignant

36. Recommendations for the diagnosis and
staging of penile cancer

37. TNM Staging

39. Prognosis
5yr survival of SCC penis:
• >85% -no inguinal metastases
• 75 – 88% :-1–2 inguinal metastases
• 25% :- >2 inguinal metastases
• <10% extranodal extension, nodes > 4cm or
pelvic metastases
• Without treatment, most die within 2 years
secondary to complications of uncontrollable
locoregional growth or distant metastases.

40. Recommendations for follow-up

41. QUALITY OF LIFE
• Consequences after penile cancer treatment
– sexual dysfunction, voiding problems and cosmetic penile
appearance.
• Sexual activity and quality of life :
– laser treatment
– glans resurfacing
– glansectomy
– partial penectomy – 33% sexual activity,GHQ-12, HAD scale
– no change
– full- or near-total penile amputation- consider phallic
reconstruction- cosmetic but not functional
– negative self esteem need psychological support.

42. Prevention
Education on risks of smoking, poor genital hygiene and
STIs
• Circumcision –AAP supports newborn circumcision
•Circumcision decreases HIV by 53-60% (and oncological
high risk HPV by 32-35%)
• HPV vaccination
• Cessation of smoking
• Shielding of genital area when using PUVA
• Condom use