Vulva, Vagina, and Anus
lesions. Low-grade lesions, however, may be clinically indistinct
and the cellular changes subtle.
Cytologic scraping of high-grade lesions reveals abnormal cells
occurring singly or in loose aggregates. The cells are polygonal
and have well-defined cytoplasmic borders. Variation in size and
shape of the cells is usually noted; however, lesions may mimic
either a basal cell carcinoma having small uniform cells or a large
cell squamous carcinoma having marked variability. The nuclei
are enlarged and hyperchromatic and have granular chromatin.
Anucleated squames and parakeratotic cells are usually observed.
The above cytologic features are best applicable to the clas-
sic VIN (warty and basaloid) as dysplastic cells are present in
the superficial layers. A scrape of the differentiated VIN is likely
to yield cells derived from surface reaction and differentiated
squamous cells that lack dysplastic changes.
Key features of classic VIN on vulvar scrape
• Abnormal cells in loose aggregates or as single cells;
• Round to oval cells;
• Enlarged hyperchromatic nuclei; and
• Anucleated squamous and parakeratotic cells (usually).
Still, some have advocated that vulvar cytological evalua-
tion does not correlate well with tissue diagnosis for all types
of VIN and they do not support the use of this method in the
clinical management of VIN.20 The biopsy remains the criterion
standard management for any suspicious vulvar lesion.20
Benign Neoplasms and Tumor-Like conditions
Papillary hidradenoma is a benign tumor composed of complex
branching papillae lined by an inner layer of secretory cells and
an outer layer of myoepithelial cells. The lesion is usually diag-
nosed by biopsy; however, occasionally an FNA may be obtained.
The aspirates reveal variable combinations of three cell types:
uniform columnar, myoepithelial, and metaplastic apocrine.2,21
The differential diagnosis includes rare cases of mammary-like
tumors, endometriosis involving the vulva, and tumors of skin
adnexal origin.22,23
Malignant neoplasms
Malignant tumors of the vulva make up approximately 5% of all
gynecologic malignancies.24 The frequency with which each type
occurs is as follows: 51% squamous carcinoma, 25% squamous
carcinoma in situ, 8% metastatic tumor, 8% Paget's disease, 5%
malignant melanoma, 2% adenocarcinoma, 2% basal cell carci-
noma, and 1% sarcoma.25 Most vulvar carcinomas occur in an
older population.
Squamous Cell Carcinoma
Invasive squamous cell carcinoma (SCC) of the vulva is gen-
erally divided into three main groups: keratinizing, warty, and
basaloid carcinoma.13,26,27 Keratinizing squamous cell carcinoma
comprises approximately 70% of the vulvar carcinomas and
occurs at a mean age group of 77 years (Fig. 11.9A). Differenti-
ated (simplex) type of VIN is believed to be the precursor lesion
and cervical risk factors are absent (HPV-unrelated cancer).17,28
The warty/basaloid carcinomas comprise 30% of vulvar carcino-
mas and occur at a mean age of 55 years. The warty and basaloid
VIN lesions serve as precursors of these carcinomas, respectively.
The recognized cervical cancer risk factors are present (HPV
related). Immunohistochemical staining for p16 is a reliable
marker for HPV-positive vulvar squamous cell carcinoma and
its associated precursor lesions.29
The cytologic characteristics resemble, for the most part, their
cervical counterparts.30 The abnormal cells may occur in aggre-
gates or singly, depending on the tumor type and method of
preparation. Owing to the presence of increased numbers of
desmosomal junctions, those tumors showing evidence of kerat-
inization are more frequently found in aggregates. The cells are
polygonal and have well-defined cell borders and eosinophilic
cytoplasm. Variation in the size and shape of cells may be noted;
occasional bizarre forms have cytoplasmic processes that create
elongated or tadpole forms. The finding of abnormally kerati-
nized cells (dyskeratotic cells) should always raise concern for
The nuclei are reactively uniform although usually
enlarged and hyperchromatic. Anucleated squames or parakera-
totic cells are also frequently noted (Fig. 11.9B).
Key features of squamous cell carcinoma on vulvar scrape
• Aggregates or single abnormal cells;
• Cellular and nuclear pleomorphism; polygonal, elon-
gate, and tadpole forms;
• Abnormally keratinized cells; and
• Enlarged hyperchromatic nuclei.
Verrucous Carcinomas
These are large, cauliflower-like tumors that have a well-
demarcated base. Histologically, the tumors are composed of
exophytic papillary fronds with hyperkeratosis or parakera-
tosis on the surface. The tumor is well demarcated from the
underlying stroma, and the rete pegs have blunt, pushing bor-
ders. Nuclear pleomorphism is mild. Keratin pearls are usually
present. In cytologic smears from verrucous carcinomas, the
cells usually occur in aggregates that retain their cytoplasmic
processes. Sheets of hyperkeratotic and parakeratotic cells are
usually found. Little cellular or nuclear pleomorphism is noted.
Owing to the marked histologic and cytologic similarity to pseu-
doepitheliomatous hyperplasia and condyloma acuminatum,
verrucous carcinomas are difficult to diagnose, and a biopsy that
includes the base of the lesion is necessary for diagnosis.31,32
Basal Cell Carcinoma
This is a disease predominately of postmenopausal women hav-
ing an average age of 65 years. It constitutes 2-3% of all vulvar
malignancies. It most frequently involves the labia majora.33,34
Grossly, the lesion can show marked variability in appearance
and size. Histologically, these basal cell carcinomas are simi-
lar in appearance to basal cell carcinomas at other sites. Basal
cell carcinoma is generally regarded as non-fatal.33 Metastases
to lymph nodes are rare. Care should be observed with perirec-
tal lesions to distinguish basal cell carcinomas of the skin from
basaloid cloacogenic carcinoma of the rectum and adenoid
cystic carcinoma.35 Cytologically, few cases of basal cell carci-
noma have been described. The cells are small and uniform and
have a scant amount of poorly defined cytoplasm. The nuclei are
enlarged and uniform and contain hyperchromatic chromatin.
Nucleoli may be observed.
Paget's Disease
This disease of the vulva affects predominately white postmeno-
pausal women of an average age of 67 years.36 Although Paget's
disease histologically is similar in all sites at which it occurs, the
natural history and morphogenesis differ. Clinically, the lesions
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