Penis and scrotum - Penile intraepithelial neoplasia (PeIN)

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Penis and scrotum

Dysplasia / carcinoma in situ

Penile intraepithelial neoplasia (PeIN)

Editors: Antonio Cubilla, M.D. and Alcides Chaux, M.D. (see Author/Reviewers page)

Revised: 13 May 2010, last major update May 2010

Definition

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● Any level of intraepithelial squamous cell atypia and alteration in squamous cell maturation

● Variants are differentiated (simplex), warty, basaloid and warty-basaloid

Terminology

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● 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, and has an 80% HPV incidence, usually due to HPV 16 (Int J Exp Pathol 2009;90:182)

● Bowen’s 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

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● 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

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● 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

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● With HPV-33 (Hautarzt 2009;60:952)

● 51 year old man with metastases to pelvic and inguinal lymph nodes (Can Urol Assoc J 2007;1:404)

Treatment

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● Laser therapy is effective, but associated with a high recurrence rate (BJU Int 2010 Jan 19 [Epub ahead of print])

● 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

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Various images

Erythroplasia of Queyrat: moist Bowen’s disease: circumscribed, raised granular

red lesion involving glans red lesion involving distal shaft and extending to

coronal sulcus

Gross description (Macroscopy)

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● 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

Micro description (Histopathology)

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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 Mar 19 [Epub ahead of print])

● 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

Micro images

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Contributed by Dr. Alcides Chaux and Dr. Antonio Cubilla

PENILE INTRAEPITHELIAL NEOPLASIA, BASALOID TYPE: The epithelium is entirely replaced by a monotonous population of small to medium-sized cells with scant basophilic cytoplasm, indistinct cell borders and high mitotic/apoptotic rate. Note the flat surface with abrupt parakeratosis.

PENILE INTRAEPITHELIAL NEOPLASIA, DIFFERENTIATED TYPE: Characterized by atypical epithelial cells, more prominent at bottom layers, with retained squamous maturation, ample eosinophilic cytoplasm, well-defined cell borders, acanthosis, hyperkeratosis and irregular rete ridges.

PENILE INTRAEPITHELIAL NEOPLASIA, DIFFERENTIATED TYPE: Atypical epithelial cells are seen throughout the entire epithelium, cytoplasm is ample and eosinophilic, cell borders are distinct and there is prominent parakeratosis. Note the presence of parabasal acantholysis, dyskeratosis and underlying stromal reaction

PENILE INTRAEPITHELIAL NEOPLASIA, WARTY TYPE: Acanthosis, pleomorphic epithelial cells with retained squamous maturation and superficial koilocytotic atypia, and a spiky surface with prominent parakeratosis.

ATYPICAL LICHEN SCLEROSUS: Differentiated penile intraepithelial neoplasia associated with underlying lichen sclerosus (left bottom field).

Squamous cell carcinoma in situ Keratinizing lesion

with moderate dysplasia

High grade warty lesion exhibits hyperkeratosis, parakeratosis, papillomatosis, acanthosis and koilocytotic atypia

Mitotic figures are present near the surface and cytoplasmic clearing in the figure on the right.

p16+

Virtual slides

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Erythroplasia of Queyrat Carcinoma in situ

Positive / negative stains

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● 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

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● Condyloma acuminatum: warty PeIN can appear similar, but has nuclear atypia and atypical parakeratosis

● Paget’s disease: Bowen’s 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 Ki-67 negative

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

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