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 January 20th, 2021.
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
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
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