Penile and Vulvar Intraepithelial Neoplasia

 Elongated and anastomosing rete ridges

image Atypical basal cells with hyperchromatic-staining nuclei

image Subtle abnormal maturation (large, eosinophilic keratinocytes)

image Whorling and keratin pearl formation

image Usually associated with LS&A

image Preferential association with HPV-unrelated variants of invasive SCC (i.e., keratinizing SCC)

• Basaloid, warty, and mixed (warty/basaloid) PeIN and VIN (a.k.a. usual VIN, HPV-related)
image Basaloid VIN/PeIN: Basaloid cells replace most to full thickness of epithelium

image Warty VIN/PeIN: Pleomorphic cells with koilocytic changes replace most to full thickness of epithelium

image Warty-basaloid VIN/PeIN: Pleomorphic cells with koilocytic changes seen on upper epithelium and basaloid cells replace lower epithelium

image Basaloid, warty, and mixed (warty/basaloid) PeIN and VIN is usually seen adjacent to HPV-related variants of invasive SCC (basaloid and warty types)

Ancillary Tests

• p16 diffuse (block) positivity is seen in HPV-related PeIN and VIN

• Differentiated PeIN and VIN are negative (or show non-block patchy positivity) with p16

Top Differential Diagnoses

• Squamous hyperplasia/lichen simplex chronicus

• Condyloma acuminatum

• Bowenoid papulosis

Differentiated (Simplex) PeIN
Acanthotic epithelium with subtle abnormal maturation and hyperchromatic-staining atypical basilar cells are features of differentiated penile intraepithelial neoplasia/vulvar intraepithelial neoplasia (PeIN/VIN). Prominent parakeratosis is seen on the surface image.

Keratin Pearls in Differentiated VIN and PeIN
Enlarged keratinocytes with abundant eosinophilic cytoplasm throughout most of the epithelium are seen in differentiated PeIN/VIN. Characteristic keratin pearl formation is present image.

Warty PeIN and VIN (HSIL, Warty Type)
Warty PeIN and VIN show pleomorphic and hyperchromatic-staining nuclei image, bi- and multinucleation, and multiple mitoses image throughout the epithelium.

HSIL (Basaloid Type)
The epithelium is completely replaced by atypical cells with basaloid features. Numerous mitoses image and apoptotic bodies image are seen. The diagnosis of carcinoma in situ is easily achieved in high-grade basaloid PeIN and VIN.



• Penile intraepithelial neoplasia (PeIN)
• Vulvar intraepithelial neoplasia (VIN)

• Lower anogenital squamous terminology (LAST)

image Low-grade squamous intraepithelial lesion (LSIL), vulvar and penile

image High-grade squamous intraepithelial lesion (HSIL), vulvar and penile


• Erythroplasia of Queyrat, Bowen disease, squamous cell carcinoma in situ (SCCIS)


• VIN and PeIN are considered intraepithelial (in situ) precursor lesions of invasive SCC
• LAST (2012) recommends 2-tiered nomenclature system for HPV-related precursor lesions (applicable to entire anogenital region)

image LSIL (includes some flat and atypical condyloma, VIN 1 and PeIN 1, low-grade dysplasia)

image HSIL (includes VIN 2-3, PeIN 2-3, moderate and severe dysplasia, SCCIS)

image Recommended terminology for HPV-associated squamous lesions of anogenital tract is LSIL and HSIL, which may be further classified by applicable -IN sub-categorization

– e.g., HSIL, PeIN 3, warty-basaloid

– e.g., HSIL, VIN 3, usual type

• HPV-unrelated precursor lesions
image Differentiated/simplex VIN

image Differentiated/simplex PeIN



• Bimodal pathway of tumor progression in vulvar and penile SCC (HPV-related and HPV-unrelated)
image Basaloid, warty, and mixed (warty/basaloid) VIN and PeIN, a.k.a. “usual type” VIN/PeIN are HPV-related (especially HPV-16)

– Warty PeIN has been recently shown to demonstrate heterogeneous pattern of HPV genotypes

image Differentiated (simplex) VIN and PeIN are not HPV-related

– May be related to lichen sclerosus et atrophicus (LS&A)

– May be associated with P53 mutations



• Incidence
image Real incidence is unknown

image 2/3 associated with invasive SCC

• Age
image 5th and 6th decades
– About 1/2 of patients with VIN are < 40 years old


• Differentiated PeIN and VIN
image Older patients

image Usually arises in setting of chronic scarring, inflammatory dermatosis, especially lichen sclerosus et atrophicus (LS&A)

• Warty, basaloid, and mixed PeIN and VIN (a.k.a. VIN of “usual type” in vulvar pathology)
image Younger patients

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Apr 24, 2017 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Penile and Vulvar Intraepithelial Neoplasia

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