Moderator: Dr. Celeste N. Powers
Pemphigus Vulgaris presenting with genital ulceration, with cervical
Dr. Gladwyn Leiman
A 43-year-old female was seen with a one month
history of dyspareunia and an offensive vaginal discharge. The cervix appeared inflamed and hemorrhagic;
a Pap smear was taken.
The smear was markedly hypercellular, with a focally bloodstained
background. The parabasal-sized abnormal cells lay singly and in loosely cohesive sheets. Their
cytoplasm was dense and well defined, even within the sheets. Nucleo-cytoplasmic ratios were increased,
but nuclear outlines appeared extremely smooth. The chromatin was vesicular to mildly granular, with 1-3
very prominent nucleoli visible. Numerous normal mitotic figures were identifiable. The cytologic
features were similar to those seen in repair, except for the striking predominance of single cells. The
diagnosis rendered was that of at least atypical squamous cells of uncertain significance (ASCUS), with a
note appended indicating that the cytologic features were extremely unusual and that invasive carcinoma
could not entirely be excluded. Biopsy was suggested in view of the clinical presentation, as well as
the cytologic abnormality.
Biopsy and Clinical features:
The patient was referred to the Colposcopy Clinic, at which
time extensive erosions of the cervix were noted macroscopically. Colposcopy indicated a highly vascular
pattern, not characteristic of intraepithelial neoplasia or invasion. The erosions were geographically
extensive over the cervix and the upper vagina. A colposcopically-directed biopsy showed classical
acantholytic bullae of Pemphigus vulgaris. In areas, there was complete
denudation of the surface epithelium, with free lying acantholytic cells and conspicuous vilification in
relation to the blister floor. Areas of subtotal epithelial denudation were flanked by zones of
incipient suprabasal acantholysis. Direct immunofluorescence performed on the cervical biopsies revealed
3+ intercellular fluorescence for IgG and C3. Indirect immunofluorescence studies revealed 2-3+
epidermal intercellular fluorescence. These findings were diagnostic of Pemphigus vulgaris.
The patient was recalled for further re-evaluation; she was a member of the auxiliary staff of the
hospital, and returned quickly. Within days of the prior biopsy, it was found that the erosions and
blisters of the cervix were now so extensive and so painful that a general anesthetic was required to
visualize the cervix properly. Pressure on the cervix and vaginal wall elicited a positive Nikolsky
sign. In addition, the patient had by this time developed extensive ulceration of the oral mucosa, with
superimposed Candidiasis. There was no cutaneous involvement. Oral steroids were prescribed and within
one month the patient showed complete regression of oral and genital lesions.
Pemphigus Vulgaris presenting with genital ulceration, with cervical
Pemphigus vulgaris is an autoimmune disease characterized by vesiculo-bullous lesions of skin and
mucosal surfaces. The mucosal lesions have been described in esophagus, conjunctiva, larynx, urethra,
vulva and cervix. Individual case reports exist in the cytologic literature; most current texts mention
the entity and caution that the cytologic features may mimic malignancy. In almost all cases, however,
the diagnosis of generalized or oral pemphigus vulgaris is known prior to involvement of the cervix. The
case presented here is unusual in that the cervicovaginal changes preceded oral lesions, and also unusual
in that no dermal lesions appeared. At the time this case was initially encountered, it appeared to be
the first on record in which the diagnosis was made on cervicovaginal lesions prior to more usual
Pemphigus vulgaris is characterized by formation of suprabasal acantholytic vesicles and blisters
(bullae). Recent evidence regarding pathogenesis points to an autoantibody against a Cadherin-like cell
adhesion molecule on the surface of stratified squamous epithelial cells. The resulting flaccid blisters
break easily, forming erosions and ulcers. The mere scraping of a cervix by a spatula is sufficient to
break the overlying mucosal and obtain cellular samples from these lesions. The Nikolsky sign refers
either to pressure applied to a Pemphigus blister leading to its easy extension and enlargement, or to
pressure on adjacent normal mucosa or skin causing the epidermis to be dislodged. Cervical involvement
may be more common than apparent, because Pemphigus is usually treated by dermatologists, who rarely
examine the genitalia.
The cytology of cervicovaginal smears is similar to that of scrapings from oral vesicles. The
component cells have been termed "Tzanck cells"; they perfectly mirror the loose-lying intra-bullous
cells seen on histology. Smears are typically hypercellular, with extremely active nuclear chromatin
features including mitotic figures and large irregular nucleoli. Classically, the nucleoli are said to
be "bullet-shaped", but this was not an obvious feature in the current case. Despite the highly
"malignant" single cell exfoliation, and background blood, there is no true tumor diathesis.
Immunocytochemistry using E-cadherin permits specific diagnosis. If this is not available,
immunofluorescence for IgG and C3 is diagnostic.
Finally, it should be noted that there have been three reports of patients with Pemphigus of the
cervix in whom genital malignancy has been diagnosed. Two cases of micro-invasive squamous cell
carcinoma of the cervix have been seen, as has one case of endometrial carcinoma. Cautious examination
of the patient and screening of the smear are therefore required, even if the characteristic cytologic
features of Pemphigus vulgaris are overwhelming.
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