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Since 1982 we have been associating the study of hormonal receptors with the histological examination of the vulvar lesions in an attempt to interpret the action mechanism of steroids on the vulva, to find possible correlations between histological pictures and receptorial order and to find a possible predictive "marker" toward therapeutic and prognostic ends. In our Laboratory assays for androgen, estrogen and progesterone receptors were performed with the Dextran-Charcoal technique in 41 patients with vulvar dystrophy; 20 of whom had atrophic dystrophy and 21 with hypertrophic dystrophy. Another 24 patients with vulvar carcinoma were studied; 23 with epidermoid carcinoma of various differentiation grades and only one case of Paget's Disease. None of the three receptors assayed could be considered a predictive or prognostic marker in the approach to neoplastic forms. The levels of the progesterone receptor appears increased in the case of dystrophies. This justifies the hypothesis of a hormonal involvement in the pathogenesis of the lesion, as has already been documented by the beneficial effects of therapy with topical steroids.

The increased incidence of multiple primary tumors of genital-breast district has been evaluated, with the possibility of early diagnosis which consent greater survival in cancer patients. We found a particular high incidence of second neoplasia associated with vulval tumors (7.4%). With regard to pathogenetic factors, the oncogenic role of certain treatments is undoubtedly important, especially if they are protracted in time. It is necessary that these patients undergo complete gynecological screening for a time period that is much longer than that held sufficient to consider a patient cured.

On the basis of our clinical experience and a careful revision of the literature, we have attempted to identify the natural history of vulvar carcinoma by verifying the real evolutive possibility of these lesions, their possible genesis, the latent period between pre-invasive and invasive forms, and some events which seem to play a significant role in the onset of the invasive form in this period. These considerations indicate a new clinical and study approach to carcinoma in situ, which would thus become a pathology characterized by a more precise pathogenetic and evolutive individuality.

The Authors have studied the topical use of progesterone gel in the treatment of vulvar dystrophies. The results compared with those obtained previously with testosterone propionate pointed out the positive effects even of the progesterone, which has to be the first therapeutical approach for all the types of vulvar dystrophies, reserving to serious and resistants cases the treatment with testosterone propionate.

In the vulvar pathology surgery unit we have come across 3 patients with Sjögren's syndrome. Two of them also now show the presence of vulvar carcinoma, and one of them shows the presence of vulvar dystrophy with dysplasia. This has induced us to consider the possible connections between the 2 pathologies. All 3 of the patients, at different times and in different periods have been treated with steroids for the original disorder. The connections between the 2 affections are presumably to be found in the possible autoimmunitary genesis of the original disease and in the concomitant use of steroids.

In confronting the problem of prevention and early diagnosis of vulvar lesions at risk, the diagnostic methodology for their recognition and the therapeutic measures best taken are discussed. Through the use of routine, ambulatory screening tests, it is possible to detect and recognize those pathological situations which may evolve towards neoplasia. Among these, the vulvar dystrophies, some viral infections and sexually-transmitted diseases are particularly at risk. Patients with oncologic precedents are also at risk as well as patients receiving immunosuppressive therapy.

Hormone receptor assays for testosterone, estrogens and androgens were performed on 53 biopsy specimens of vulva from 40 patients, consisting of 6 with normal tissue, 14 with atrophic type dystrophy, 13 with hypertrophic type dystrophy, and 20 with malignancy. Atrophic and hypertrophic forms showed a different receptor pattern; hypertrophic forms were characterized by consistently higher levels of progesterone receptors not correlated with estrogen receptors. Neoplastic tissue showed no significant changes in values compared to normal or dystrophic forms, but range of variability was high. The bond between neoplastic forms and hormone activity seems without doubt less important than in the corresponding endometrial and mammary forms. The study of dystrophic forms, instead, should be further explored with a larger number of cases.

Assays have been developed for the quantitation of androgen, estrogen and progesterone receptors in the cytosol of 45 vulvar dystrophic tissues. In 27 patients we assayed only cytoplasmatic receptors, while in 18 patients both cytoplasmatic and nuclear receptors. The workers verified the possibility to assay these carriers, finding significant correlations neither with patient's age nor between atrophic and hypertrophic dystrophies. The research concerning the cytoplasmatic depletion and nuclear accumulation allowed us to understand the action mechanism of the androgen in vulvar tissues in patients in menopause.

Two cases of Paget's disease of the vulva are presented and the complex problem of diagnosis of this neoplasia is evaluated: all the diagnosis tests used in vulvar disease (vulvar citology, toluidine blue test) are insufficient in the presence of on eventual underlying carcinoma. In view of these considerations, the therapeutic approach is total vulvectomy.