Diagnostic Cytology
Fig. 11.5 Classic type of VIN III. (H&E x LP)
Fig. 11.6 Simplex type of VIN. (H&E x LP)
Distinct pathogenic pathways exist for differentiated and clas-
sic VIN. The simplex type of VIN is the precursor lesion for the
most commonly seen vulvar keratinizing squamous cell carci-
noma and is not associated with HPV infection.16 Overexpres-
sion of p53 protein, probably due to p53 mutation, has been
observed in at least two-thirds of simplex VIN and in the majority
of keratinizing squamous cell carcinoma. The warty and basaloid
type of VIN serve as precursor lesions for the warty and basaloid
subtypes of squamous cell carcinomas. Classic VINs are associ-
ated with HPV infection. High-risk HPV types, such as HPV16,
have been identified in most of the VIN II/III cases. The distribu-
tion of low-risk HPV types in VIN I lesions generally supports
the notion that VIN I is synonymous with flat condyloma. The
low frequency of high-risk HPV types in VIN I compared to VIN
II/III suggests that they are distinct lesions or that HPV16 is criti-
cal in the progression to VIN III.19 The International Society for
the Study of Vulvovaginal Diseases (ISSVD) recently published
Fig. 11.7 Low-grade vulvar intraepithelial neoplasia (VIN I), classic
type. Superficial atypical squamous cells with enlarged nuclei and
paranuclear halos (koilocytosis) (Papanicolaou xHP),
Fig. 11.8 High-grade vulvar intraepithelial neoplasia (VIN III), classic
type. Dysplastic squamous cells with slightly enlarged nuclei and higher N/C
ratio (Papanicolaou xHP).
the 2004 modified terminology and classification on VIN. It has
recommended that the term VIN should be applied only to his-
topathologically high-grade squamous lesions (VIN II/III). Diag-
nosis of VIN I is no longer recommended as there is no evidence
that a VIN I/III morphologic spectrum reflects a biological con-
tinuum and VIN I has not been proven to be a true cancer precur-
sor. VIN I is an uncommon histologic finding and in most cases
constitutes HPV cytopathic effect as is seen in flat condyloma.
Cytologically, the abnormal cells in low-grade vulvar lesions
are usually polygonal (Fig. 11.7), whereas those from high-
grade lesions tend to be round or oval (Fig. 11.8). The nucleus-
to-cytoplasm ratio increases with the increasing severity of the
lesion. Koilocytotic change is frequently noted within and adja-
cent to the lesions. Hyperkeratosis, parakeratosis, and squamous
pearl-like formations may also be present. In most cases, the
number of abnormal cells and extent of cytologic abnormality
make it possible to separate low- from high-grade intraepithelial
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