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


Topic Completed: 1 May 2010

Revised: 13 February 2019

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

PubMed Search: Penile intraepithelial neoplasia[TIAB]

Alcides Chaux, M.D.
Antonio L. Cubilla, M.D.
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Cite this page: Chaux A, Cubilla AL. Penile intraepithelial neoplasia (PeIN). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/penscrotumPeIN.html. Accessed September 23rd, 2019.
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
Treatment
Clinical images

AFIP images

Erythroplasia of Queyrat: moist red lesion involving glans

Bowen disease



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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



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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
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