Penile intraepithelial neoplasia (PeIN)

Penis and scrotum
Dysplasia / carcinoma in situ
Penile intraepithelial neoplasia (PeIN)

Authors: Alcides Chaux, M.D., Antonio L. Cubilla, M.D.

Topic Completed: 1 May 2010

Minor changes: 13 February 2019

Copyright: 2002-2019, PathologyOutlines.com, Inc.

PubMed Search: Penile intraepithelial neoplasia[TIAB]

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Table of Contents

Cite this page: Chaux A, Cubilla AL. Penile intraepithelial neoplasia (PeIN). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/penscrotumPeIN.html. Accessed May 24th, 2020.

Definition / general

Any level of intraepithelial squamous cell atypia and alteration in squamous cell maturation
Variants are differentiated (simplex), warty, basaloid and warty basaloid

Terminology

Penile dysplasia (low, moderate and severe) has been used in the past but is no longer recommended
Penile squamous intraepithelial lesion / SIL (low and high grade) has been used to establish similarities with cervical SIL but penile precancerous lesions are actually more similar to vulvar lesions than to cervical lesions
Carcinoma in situ: usually refers to basaloid or warty PeIN, has an 80% HPV incidence and is usually due to HPV 16 (Int J Exp Pathol 2009;90:182)
Bowen disease: clinical designation of carcinoma in situ located in the shaft
Erythroplasia of Queyrat: clinical designation of carcinoma in situ located in the glans, usually erythematous

Epidemiology

Isolated in situ lesions are more prevalent in geographical areas with a low incidence of penile cancer
PeIN associated with invasive carcinoma is more prevalent in regions with a high incidence of penile cancer
Common in HIV+ men with anal dysplasia (J Invest Dermatol 2008;128:2316)

Clinical features

Whitish areas in glans, coronal sulcus or inner foreskin
Erythema and ulceration may predominate in some cases
May be found as an exclusive in situ lesion or associated with an invasive component
May be difficult to distinguish from squamous hyperplasia

Case reports

51 year old man with metastases to pelvic and inguinal lymph nodes (Can Urol Assoc J 2007;1:404)
69 year old man with HPV 33 (Hautarzt 2009;60:952)

Treatment

Laser therapy is effective but associated with a high recurrence rate (BJU Int 2010;106:786)
Also local excision / Mohs surgery with reconstructive surgery (Urologe A 2010;49:392, J Urol 2007;178:1980), electrodessication and curettage, cryosurgery, topical 5-fluorouracil and topical imiquimod 5% cream (J Drugs Dermatol 2008;7:483)

Clinical images

AFIP images

Erythroplasia of Queyrat: moist red lesion involving glans

Bowen disease

Images hosted on other servers:

T1 G2 tumor of glans penis and foreskin

Erythroplasia of Queyrat: moist red lesion involving glans

Gross description

Flat to slightly raised areas with a pearly white aspect
Irregular and indistinct borders
May be found as isolated single or multiple lesions
May be found in continuity, near or distant from an invasive carcinoma
Cut surface has whitish epithelial thickening

Microscopic (histologic) description

Differentiated PeIN:

Most common pattern (72%)
Retained squamous maturation associated with epithelial atypia
Nuclear atypia more prominent at bottom layers
Distinct cellular borders with evident intercellular bridges
Flat surface with parakeratosis
Associated with concurrent lichen sclerosus ("atypical lichen," J Am Acad Dermatol 2010;62:284)
If penile carcinoma is present, is usually low grade keratinizing variant such as usual type, papillary, verrucous or pseudohyperplastic

Basaloid PeIN:

Epithelium is replaced by a monotonous population of small to intermediate sized cells
Cells have scant basophilic cytoplasm and indistinct cell borders
Flat or slightly irregular surface with parakeratosis
High mitotic / apoptotic rate
If penile carcinoma is present, is usually warty, basaloid or warty basaloid variant
Only rarely associated with concurrent lichen sclerosus ("atypical lichen")

Warty PeIN:

Retained epithelial maturation with spiky or papillary parakeratotic surface
Conspicuous koilocytosis, mainly in the upper third of the epithelium
Nuclear pleomorphism is commonly found
If penile carcinoma is present, is usually warty, basaloid or warty basaloid variant (Mod Pathol 2010;23:896)
Only rarely associated with concurrent lichen sclerosus ("atypical lichen")

Warty basaloid PeIN:

Warty features in the upper third of the epithelium (spiky parakeratotic surface with koilocytosis)
Basaloid cells present in the middle and lower third of the epithelium
If penile carcinoma is present, is usually warty, basaloid or warty basaloid variant

Microscopic (histologic) images

Contributed by Alcides Chaux, M.D. and Antonio Cubilla, M.D.

Squamous cell carcinoma in situ

High grade warty lesion

Keratinizing lesion with moderate dysplasia

Basaloid type

Differentiated type

Warty type

Atypical lichen sclerosus

Images hosted on other servers:

Squamous cell carcinoma in situ

Positive / negative stains

p53 positivity above the basal cell layer
p16 overexpression (full thickness positivity in all epithelial cells) in basaloid PeIN
p16 negative (including cases with patchy suprabasal positivity in epithelial cells) in differentiated PeIN (Am J Surg Pathol 2010;34:385)

Differential diagnosis

Condyloma acuminatum: warty PeIN can appear similar but has nuclear atypia and atypical parakeratosis
Paget disease: Bowen disease can appear clinically and pathologically similar, which may explain the reported association with internal visceral malignancies
Squamous hyperplasia: may resemble minimally atypical differentiated PeIN but lacks atypical changes and is p53 and Ki67 negative