AN OVERVIEW OF PREMALIGNANT LESIONS OF penis.ppt

PENILE PREMALIGNANT LESIONS

1. PREMALIGNANT LESIONS of
penis

2. Introduction
•Some histologically benign penile lesions
have been recognized as having malignant
potential or close association with the
development of squamous carcinoma.

3. •42% of patients with squamous cell cancer
had a history of preexisting penile lesions.
•Although the incidence of progression of
these lesions to squamous cell carcinoma is
not known, all have been associated with the
disease

4. Cutaneous Horn
•The penile cutaneous horn is a rare lesion.
•It usually develops over a preexisting skin lesion (wart, nevus,
traumatic abrasion, or malignant neoplasm)
•and is characterized by overgrowth and cornification of the
epithelium, which forms a solid protuberance.
•On microscopic examination, extreme hyperkeratosis,
dyskeratosis, and acanthosis are noted.
•It is associated with human papillomavirus (HPV) type 16.

5. •Treatment consists of surgical excision with a margin of
normal tissue about the base of the horn.
•These lesions may recur and may demonstrate malignant
change on subsequent biopsy, even when initial histologic
appearance is benign.
•Because this tumor may evolve into a carcinoma or may
develop as a result of an underlying carcinoma, careful
histologic evaluation of the base and close follow-up of the
excision site are essential

8. Pseudoepitheliomatous Micaceous and
Keratotic Balanitis
•These unusual lesions present as
hyperkeratotic, micaceous growths on the
glans and may have some of the microscopic
features of verrucous carcinoma.
•They tend to recur and may represent an
early form of that tumor.

9. •Treatment includes excision, laser ablation,
and cryotherapy.
•These lesions require aggressive treatment
and close follow-up.
•Fibrosarcoma of the glans after treatment of
a pseudoepitheliomatous micaceous and
keratotic balanitis lesion with cryotherapy has
been reported.

10. Balanitis Xerotica Obliterans (Lichen
Sclerosus)
•This genital variation of lichen sclerosus et
atrophicus presents as a whitish patch on the
prepuce or glans, often involving the meatus
and sometimes extending into the fossa
navicularis.

11. •The lesions may be multiple and may assume a mosaic
appearance.
•The meatus may appear white, indurated, and edematous.
Glanular erosions, fissures, and meatal stenosis may occur.
•The disorder is most common in uncircumcised men and
occurs most commonly in middle-aged men, but it does occur
in boys.
•Symptoms include pain, local penile discomfort, pruritus,
painful erections, and urinary obstruction.

12. •On histologic examination, these lesions show
atrophic epidermis with loss of the rete pegs
and homogenization of collagen on the upper
third of the dermis combined with a zone of
lymphocytic and histiocytic infiltration.
•They resemble the lesions of lichen sclerosus
et atrophicus found elsewhere.

13. •There are reports documenting the association of
balanitis xerotica obliterans with squamous cell
carcinoma as well as with the development of
carcinoma long after a lesion of balanitis xerotica
obliterans has been treated.
•A well-differentiated nonverruciform variant of
squamous cell carcinoma associated with lichen
sclerosus et atrophicus that preferentially involves
the prepuce .

15. •Treatment consists of topical steroid cream,
injectable steroids, and surgical excision.
•Meatal stenosis is a common problem often
requiring repeated dilations, steroid injection, or
even formal meatoplasty.
•Close follow-up is essential, with biopsy if a change
in appearance or behavior occurs.

16. Leukoplakia
•These lesions present as solitary or multiple whitish
plaques that often involve the meatus.
•On histologic examination, there is hyperkeratosis,
parakeratosis, and hypertrophy of the rete pegs with
dermal edema and lymphocytic infiltration.
•Careful microscopic examination is necessary to
determine malignant change.

17. •Treatment involves elimination of chronic irritation, and
circumcision may be indicated.
•Surgical excision and radiation have been used in the
treatment of leukoplakia.
•This disorder has been associated with both in situ
squamous cell cancer and verrucous cancer of the penis.
•Because of this close relationship with carcinoma, meticulous
follow-up of the excision site with periodic biopsy of
incompletely excised lesions is necessary to detect early
malignant change.

18. Leukoplakia

19. Erythroplasia of Queyrat (Bowen Disease
of the Glans Penis)
•Erythroplasia of Queyrat (Bowen disease of the glans
penis) originally was described by Tarnovsky in 1891
and subsequently was appreciated as a penile
disease by Fournier and Darier in 1893.
•More intensive studies by Queyrat in 1911 allowed
erythroplasia of Queyrat to be accepted as a distinct
entity. Sulzberger and Satenstein in 1933 recognized
erythroplasia of Queyrat to be a form of carcinoma in
situ.

20. Pathophysiology
•Erythroplasia of Queyrat (Bowen disease of
the glans penis) arises from the
mucocutaneous epithelium of the penis.
•The glans and prepuce are most commonly
involved. Erythroplasia of Queyrat is seen
almost exclusively in uncircumcised men and
represents an in situ form of squamous cell
carcinoma.

21. •Progression to invasive carcinoma may occur
after a variable period in 10-33% of cases.
•Of note, progression to squamous cell
carcinoma is more common in erythroplasia of
Queyrat than in other forms of Bowen disease
of the penis.

22. Mortality/Morbidity
•Malignant transformation is possible within
erythroplasia of Queyrat lesions and could
affect prognosis if present.
•Special attention should be given to ulcerative
or verrucous changes within erythroplasia of
Queyrat lesions, and a histological evaluation
should be obtained, because these could
signify invasive malignancy.

23. Age
•The median age of onset is 51 years.
Erythroplasia of Queyrat (Bowen disease of
the glans penis) has been described in males
ranging from age 20-80 years.

24. Physical
•Solitary or multiple, minimally raised, erythematous papules
and plaques on the glans penis and/or adjacent mucosal
epithelium are seen in erythroplasia of Queyrat (Bowen
disease of the glans penis).
•The plaques may be smooth, velvety, scaly, crusty, or
verrucous.
•The classic lesion is described as a nontender, sharply
demarcated, bright-red, glistening plaque on the glans penis
of a middle-aged to elderly uncircumcised man
•Ulceration or distinct papillomatous papules within a plaque
may indicate progression to invasive squamous cell
carcinoma.

26. Causes
•Erythroplasia of Queyrat (Bowen disease of the glans
penis) most often occurs in uncircumcised men. The
precise etiology remains unclear. The following have
been proposed to contribute to the development
and progression of erythroplasia of Queyrat:
•Lack of circumcision
•Chronic irritation (urine, smegma, poor hygiene),
inflammation, and chronic infections (herpes simplex
virus, bacterial)
•Zoon balanitis: Several case reports describe
erythroplasia of Queyrat with coexistent Zoon
balanitis5

27. •Co-infection with human papillomavirus(HPV) type 8
and carcinogenic genital HPV types6
•Other physical factors (eg, heat, friction, trauma)
•Immunosuppression from organ transplantation,
systemic infections or disease (HIV), and medications
(prednisone, immunosuppressants): These factors
may contribute to an increased overall incidence and
to invasive disease in affected patients.
•UV light radiation/phototherapy
•Phimosis
•Multiple sexual partners (increase risk of HPV
infection)
•Smoking

29. Treatment
•5 fu
•Imiquimod
•Steroids
•excision

30. VIRUS-RELATED DERMATOLOGIC LESIONS
•There is increasing evidence to suggest that a
number of penile lesions share viral etiologies.
•Condyloma acuminatum and bowenoid papulosis
appear to be related to infection with human
papillomavirus.
•Human herpesvirus 8, also known as Kaposi's
sarcoma–associated herpesvirus, is strongly
suspected of being the etiologic agent of epidemic
(AIDS-related) Kaposi's sarcoma.

31. Human Papillomavirus in Malignant
Transformation
•Condylomata acuminata are soft, papillomatous growths
generally considered to be benign.
•Also known as genital warts or venereal warts, they have a
predilection for the moist, glabrous areas of the body and the
mucocutaneous surfaces of the perineal and genital areas.
•The lesions are soft and friable and may occur singly on a
pedicle or in a moruloid cluster on a broad base.
•These lesions are rare before puberty and when encountered
may suggest sexual abuse.

32. •In the male, condylomata occur most commonly on the glans,
the penile shaft, and the prepuce.
•The meatus should also be carefully inspected.
•Lesions recur frequently, both in new and in previously
treated sites.
•Approximately 5% of patients will demonstrate urethral
involvement, which may extend to the prostatic urethra.
•Rarely, extreme involvement of the urethra may require
urethroplasty.
•Bladder involvement, although rare, is extremely difficult to
treat effectively.

34. •On microscopic examination, condylomata
acuminata demonstrate an 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.

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36. •Treatment of these lesions with podophyllin
may induce histologic changes suggestive of
carcinoma.
•Consequently, preliminary biopsy of large
lesions that appear to be condylomata
acuminata should precede any treatment
with topical podophyllin.

37. HPV is recognized as the principal etiologic agent in
cervical dysplasia and cervical cancer.
•Significant numbers of male partners of women with
cervical condylomata will have lesions not identified
by simple inspection and may not be aware that they
are infected or have the potential to infect others.

38. •On histologic examination, the koilocyte—a
cell characterized by an empty cavity
surrounding an atypical nucleus—is
pathognomonic for HPV infection.
•DNA hybridization techniques have been used
to identify and classify HPV infections, and
some 40 subtypes of HPV virus have been
identified.

39. •Virus types 6, 11, and 42 to 44 are associated with gross
condylomata and low-grade dysplasia.
•Types 16, 18, 31, 33, 35, and 39 have a higher association
with malignant disease.
•More recently, reports have suggested that tumor virus
transforming proteins from HPV types 16 and 18, particularly
the E6 and E7 proteins, may target tumor suppressor gene
products pRB and p53 and may be the causative agents in a
subset of penile cancers.

40. •E6 appears to bind to cellular tumor suppressor
protein p53, leading to its rapid degradation,
resulting in chromosome instability, DNA mutations,
and aneuploidy.
•E7 binds to and phosphorylates the pRB
retinoblastoma protein, leading to the release of
transcription factor E2F that activates mitosis.

41. •Human immunodeficiency virus (HIV) infection may
predispose affected patients to rapid development of
squamous carcinoma from preexisting condyloma
infection.
•Whereas subtyping of HPV has been largely a
research tool, it is being developed as a means of
identifying potentially aggressive lesions to assist in
treatment planning.

42. •Subclinical disease may be detected by the application of 5%
acetic acid solution to the penis, followed by inspection with
a magnifying glass.
•Lesions will turn white, and flat lesions often invisible on
regular inspection may be detected.
•These “aceto-white” lesions are not always due to HPV, and
biopsy must be performed to confirm the diagnosis.
•Careful inspection of the base of the shaft, the scrotum, and
the inguinal folds is essential.
•The meatus should be examined, and if lesions are present,
urethroscopy should be performed.

43. •Topical podophyllin (Condylox 0.5%) or trichloroacetic acid has
been a well-established and often successful treatment for
small condyloma lesions.
•More recently, however, imiquimod cream (5%) has become
the topical treatment of choice for condyloma.
•Imiquimod is an immune modulator that enhances natural
killer cell activity and is the only topical treatment having
the potential to eliminate HPV.

44. •Circumcision will remove preputial lesions,
gain exposure for treatment, and allow post-
treatment monitoring.
•Fulguration and excision may be advisable to
avoid large areas of maceration, ulceration,
and secondary infection.

45. •Surgical laser therapy has been used extensively in
the management of condylomata.
•Surgical therapy with use of a pediatric resectoscope
may be helpful in debulking large intraurethral
lesions.
•The lowest power required to resect the lesions
should be used, and electrocautery should be
minimized to avoid the development of urethral
stricture.

46. •Intraurethral lesions may be extremely difficult to
treat. 5-Fluorouracil cream applied weekly for 3
weeks has been successful in eliminating urethral
lesions.
•Care must be taken to work the cream down the
urethra and to avoid exposure of the scrotal skin. Use
of a scrotal support or zinc oxide cream may be
helpful. The addition of 5-fluorouracil cream to laser
therapy did not improve the success rate.

47. •Various interferons have been used in
condyloma treatment .
•short-term intralesional interferon alfa-2b has
activity against condyloma.
Interferon therapy continues to be reserved
for extensive and recalcitrant lesions.

48. Bowenoid Papulosis
•Carcinoma in situ of the penis has been well
recognized.
•Kopf and Bart described bowenoid papulosis,
a condition having a histologic appearance
similar to that of carcinoma in situ but a
benign course.

49. •Bowenoid papulosis presents as multiple papules on
the penile skin or female vulva, usually during the
second or third decade of life.
•The lesions are usually pigmented and range from
0.2 to 3.0 cm in diameter, and smaller lesions may
coalesce into larger ones.
•Pigmented lesions present on the penile skin,
whereas glanular lesions tend to be flat papules.
•Diagnosis is confirmed by biopsy .

50. •These lesions meet all the histologic criteria of carcinoma in
situ but display differing growth patterns relative to flat,
endophytic, or exophytic clinical appearance.
•DNA sequences suggestive of HPV-16 have been found in
specimens of bowenoid papulosis, and a causative role for
HPV is suspected.
•Whereas histologically this condition is a carcinoma in situ,
the clinical course of bowenoid papulosis is invariably
benign.

51. •Treatment has included electrodesiccation,
cryotherapy, laser fulguration, topical 5-
fluorouracil cream, and excision with skin
grafting.

52. Thank you
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