Discussion on premalignant lesions that are found on penis

1. PREMALIGNANT LESIONS
IN CARCINOMA PENIS
Dr. Saankhya Sekhar Mallick
Urology Resident
Madras Medical College

2.  Most common malignant tumor of penis –
squamous cell carcinoma (SCC)
 42% of patients with SCC had a history of
preexisting penile lesion
 All have been associated with SCC

3.  Two broad categories, according to etiology
1. Non-HPV related (inflammatory)
2. Virus related

4. Non-HPV related penile
premalignant lesions
 Cutaneous horn
 Pseudoepitheliomatous micaceous &
keratotic balanitis
 Male lichen sclerosus (balanitis xerotica
obliterans)

5. Cutaneous Horn

6.  Rare
 Develops over a preexisting skin lesion
 Overgrowth and cornification of the epithelium
 HPE : extreme hyperkeratosis,
dyskeratosis
acanthosis
 HPV 16 associated

7.  Lesions may recur
 Lesions may undergo malignant change
 Treatment consists of surgical excision with a
margin of normal tissue about the base of the
horn
 Close follow up is necessary

8. Pseudoepitheliomatous micaceous
and keratotic balanitis

9.  White keratotic plaque
 On glans penis
 Exclusively in older men
 Most cases appear following circumcision late
in life
 May progress to verrucous carcinoma or SCC

10.  Treatment – excision
laser ablation
cryosurgery
 Relapse not infrequent
 Close follow up needed
 Fibrosarcoma of the glans after treatment of a
pseudoepitheliomatous micaceous and
keratotic balanitis lesion with cryotherapy has
been reported

11. Male lichen sclerosus (balanitis
xerotica obliterans)

12.  Genital variation of lichen sclerosus et
atrophicus
 Middle aged men
 Uncircumcised / late-circumcised (after13 yrs of
age) men
 Can also occur in boys

13.  Exact etiology unknown
 Postulated: genetic factor,
hormonal factor,
autoimmune condition
koebner phenomenon
 Borrelia burgdorferi recently been identified in
early stage of the disease

14.  Early stage: pain,
dyspareunia,
pruritus,
painful erections,
urinary obstruction
 Late stage: phimosis
paraphimosis
 Whitish patch on prepuce or glans
 The meatus may appear white, indurated, and
edematous
 Glanular erosions, fissures, and meatal stenosis
may occur

15.  HPE: atrophic epidermis
loss of rete pegs
homogenization of collagen
in the upper third of dermis
zone of lymphocytic and histiocytic
infiltration

16.  Male lichen sclerosus (LS) is frequently (28-
50%) found in conjuction with SCC penis
 SCC is found subsequent to LS in 2.3-5.8%
cases
 SCC can develop long after a lesion is treated

17.  Medical care: for mild LS without scarring
topical clobetasol propionate
topical tacrolimus
topical acetretin
intralesional adalimumab
intralesional steroid (for stricture, stenosis)
 Surgical care:
circumcision
foreskin preputioplasty+intralesional
triamcinolone
meatotomy
BMG urethroplasty

18. Virus related penile premalignant
lesion
 Condyloma acuminata
 Bowenoid papulosis
 Kaposi sarcoma

19. Human papilloma virus (HPV)
infection
 HPV – principal causative agent in cervical
dysplasia and cervical cancer
 HPV – one of the prime cause of premalignant
penile lesions
 HPV – one of the causative agents of penile
cancers

20.  HPV 6, 11, 42, 43, 44 – gross condyloma and
low grade dysplasia
 HPV 16, 18, 31, 33, 35, 39 – malignancy
 E6 -> TP53 -> rapid degradation ->
chromosomal instability, DNA mutation,
aneuploidy.
 E7->pRB -> pRB phosphorylation ->
transcription factor E2F release -> mitosis
 HPE: koilocyte, a cell having empty cavity
surrounding an atypical nucleus,
pathognomonic of HPV

21.  Factors associated with high HPV infection –
presence of foreskin,
increased number of sexual partners,
lack of condom use,
smoking

22. Condyloma acuminata

23.  Soft, friable, papillomatous growths typically
considered benign
 Before puberty rare, may suggest sexual abuse
 Found on glans, penile shaft, prepuce
 Urethral involvement in 5%, may extend to
prostatic urethra. So inspect meatus
 Bladder involvement rare

24.  Also inspect base of shaft, scrotum, inguinal
fold.
 5% acetic acid solution followed by magnifying
glass use for subclinical disease detection,
lesions will turn white
 However, not all acetowhite lesions are HPV-
related, so biopsy must be done to confirm the
diagnosis

25.  HPE: outer layer of keratinized tissue covering
papillary fronds, which are supported by
connective tissue stroma. The epithelial layer
consists of well-ordered rows of squamous
cells. A dermal lymphocytic infiltrate is usually
present.
 Treatment of these lesions with podophyllin may
induce histologic changes suggestive of
carcinoma
 Hence, biopsy of large lesions that appear to be
condylomata acuminata should be done before
any treatment with topical podophyllin

26.  No proven treatment to reduce sexual
transmission or to prevent disease progression
 Medical treatment options:
5% podophyllotoxin solution or gel
35-85% trichloroacetic acid
cryotherapy with liquid N2
electrofulguration
CO2 laser therapy
5% imiquimod cream
1% cidofovir gel
intralesional IFN α2b injection
5FU cream for urethral lesion

27.  Circumcision
to remove prepucital lesion,
to gain exposure for treatment,
to allow post-treatment monitoring
 Pediatric resectoscope for large intraurethral
lesion, to use lowest power and minimal use of
electrocautery

28.  Prevention:
quadrivalent vaccine (Gardasil)
against HPV 6,11, 16 and 18,
approved for both males and females
in 9-26 years of age,
for prevention of both anal and genital lesions
65% efficacy in preventing genital lesion
consists of three injections over six months

29. Bowenoid papulosis

30.  Multiple papules on penile skin
 Usually pigmented on penile skin
 Glanular lesions tend to be flat papular
 0.2-0.3 cm in diameter, similar lesions coalesce
 In 2nd-3rd decade of life

31.  Diagnosis is confirmed by biopsy
 These lesions meet all the histologic criteria of
carcinoma in situ, but have a benign course,
display differing growth patterns relative to flat,
endomorphic, or exophytic clinical appearance
 Causative role of HPV 16 is suspected

32. Buschke-Lowenstein tumor

33.  AKA Verrucous carcinoma, Giant condyloma
acuminatum
 It differs from condyloma acuminata is that the
latter, regardless of size, always remain
superficial and never invade adjacent tissue,
while the former displaces, invades, and
destroys adjacent structures by compression
 However, it does not show any sign of
malignant change on HPE, neither does it
metastasize

34.  HPE: a luxuriant mass composed of broad
rounded rete pegs, often extending far into
underlying tissue. The pegs are composed of
well-differentiated squamous cells that show no
cellular anaplasia. These epithelial pegs are
characteristically surrounded by a dense band
of acute and chronic inflammatory cells
 Excisional biopsy or multiple deep biopsies
required
 HPV 6, 11 DNA found in tumors

35.  Treatment is local excision
 For larger lesions, total penectomy may be
needed
 Bleomycin may be used
 Systemic IFN therapy plus Nd:YAG laser
therapy
 Cryotherapy
 Recurrence is common, so close follow up

36. Kaposi sarcoma

37.  Tumor of reticuloendothelial system
 It appears as a cutaneous neovascular lesion, a
raised, painful, bleeding papule or ulcer with
bluish discoloration
 HPE: the tumor is vasoformative with
endothelial proliferation and spindle cell
formation
 Etiology: HHV8

38.  Four subtypes
1. Classic KS: in patients without known
immunodeficiency, indolent and rarely fatal
course
2. Immunosuppressive treatment-related KS: in
patients undergoing immunosuppressive
therapy, often reversed with dose modification
3. African KS: occurs in young men, have
indolent or aggressive course
4. Epidemic or HIV-related KS: occurs in patients

39.  Nonepidemic forms:
classic and immunosuppressive forms
limited organ involvement
should be treated aggressively
 Penile involvement more common in
homosexual men
 Urethral obstruction in glans or corpus
spongiosum involvement

40.  Treatment:
localized surgical excision
small-field external beam
electron beam radiation
partial penectomy
discontinuation of immunosuppressive
therapy
Nd:YAG laser
proximal urethrostomy
interferon
cytotoxic drugs

41. THANK YOU