Penis & scrotum
Dysplasia/carcinoma in situ
Penile intraepithelial neoplasia
Authors: Alcides Chaux, M.D., Antonio L. Cubilla, M.D.
Topic Completed: 1 May 2010
Minor changes: 1 July 2020
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Penile intraepithelial neoplasia[TIAB]
Table of Contents
Definition / general | Terminology | Epidemiology | Clinical features | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive / negative stains | Differential diagnosisCite this page: Chaux A, Cubilla AL. Penile intraepithelial neoplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/penscrotumPeIN.html. Accessed August 6th, 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:
Basaloid PeIN:
Warty PeIN:
Warty basaloid 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
