Vulvar Dystrophy Research Articles

Human Papilloma Virus, Vulvar Dystrophy, and Vulvar Carcinoma: Differential Expression of Human Papillomavirus and Vulvar Dystrophy in the Presence and Absence of Squamous Cell Carcinoma of the Vulva

In situ hybridization (ISH) and polymerase chain reaction (PCR) for several common HPV types were performed on 41 cases of vulvar dystrophy, 19 of which were associated with previous or simultaneous invasive squamous cell carcinoma of the vulva. Three of the 19 cases (16%) of dystrophy associated with cancer were found to contain HPV-16/18 by PCR. In contrast, 12 of the 22 cases (55%) of dystrophy not associated with carcinoma contained HPV-16/18 by PCR (P < 0.01). A control group of 10 vulvar specimens without dystrophy or carcinoma was negative for all HPV types tested. ISH was negative for all HPV types in all 41 cases. The data confirm the association between vulvar carcinoma and hypertrophic/mixed dystrophy, and provide evidence for an association between HPV-16/18 and some cases of vulvar dystrophy. Cases of vulvar dystrophy not associated with HPV-16/18 may be at increased risk for the development of vulvar carcinoma.

Vulvar squamous cell carcinoma.

Squamous cell carcinoma of the vulva is a rare disease, mainly seen in elderly women. Risk factors are advanced age, an immunocompromised status, longstanding vulvar dystrophy, VIN, a history of vulvar human papillomavirus infection, and a history of cervical cancer. Vulvar cancer should be considered as a skin tumor and detection is possible in an early stage. However, because of patients' and doctors' delay, one in three vulvar cancers is not treated before an advanced stage. The tumor metastasizes mainly lymphatogenic. Spread starts in the inguinal lymph nodes. In the middle of this century, standard treatment, consisting of an en bloc dissection of the vulva and inguinal lymph nodes has been developed and applied. As a result, considerably improved survival rates were achieved: up to 90% 5-year survival rates for patients without lymph node metastases. However, complication rates were high. In recent years, a more individualized approach has replaced standard treatment. Surgical treatment now depends on the localization, size and extent of the tumor, and is followed or preceded by radiotherapy in selected cases. The role of chemotherapy in advanced disease is currently being studied in several referral centers. The most important success in the treatment of vulvar cancer in recent years is the maintenance of high survival rates despite considerably less extensive surgical treatment, resulting in lower complications rates. An important challenge for the near future will be the improvement of the management of advanced disease. However, an even more difficult issue may be the prevention of such large lesions. The reduction of treatment delays requires a considerable effort in education of both health care workers and the general public.

Gynäkologische Eingriffe in der zehnten Lebensdekade

We report on 28 surgical procedures performed between 1978 and 1992 performed on patients aged 90 years or older. 18 of them had a malignant tumour (11 mamma, 2 corpus, 3 vulva and 2 ovarian cancer), one had an ovarian cystoma. Three patients suffered from pelvic relaxation, four had postmenopausal bleeding, one vulvar dystrophy and one patient suffered from pyometra. Four laparotomies, three vaginal hysterectomies with colporrhaphy, four minor operations of the vulva, six curettages and eleven mammary operations were performed. During the surgical procedures, none of the patients died, whereas two patients died some time after the operation: so-called hospital mortality. The survival of the other patients was comparable to that of their age group. Two patients died of gynaecological diseases. After the surgical procedure, 21 patients reattained their preoperative level of health. 23 were satisfied with the result of the operation because of improvement of their complaints. If surgery in the aged allows the patients to lead a comfortable life, the operational risks can be justified.

Epidemiology and etiology of squamous cell carcinoma of the vulva

A literature review dealing with epidemiological and etiologic aspects of squamous cell carcinoma of the vulva is presented. It is a rare disease; the incidence is 1–2 per 100 000 women per year. Among women more than 75 years of age, the incidence is at least ten times higher. The cause of vulvar carcinoma is not known. In contrast to what has been stated for many years, in recent case-control studies no evidence was found that diabetes mellitus, obesity, vascular diseases, nulliparity, an early menopause and syphilis are risk factors for developing a vulvar carcinoma. The factors that play a role in the etiology of vulvar carcinoma are: vulvar dystrophy, a history of genital HPV-infection, a history of cervical neoplasia, advanced age, smoking and a compromised immunity. Usually, for the development of a vulvar carcinoma, more than one of the above mentioned factors have to be present.

Vulvar Dystrophy: A Clinical Follow‐Up

The vulvar dystrophy is an enigma and one of the most controversial topic as for the pathogenesis, clinical outcome and particularly the malignant potentiality. There has been very few systematic studies regarding vulvar dystrophy in Japan. Vulvar dystrophy with dysplasia is said to be a pre-malignant condition of the vulva. So in our institute a prospective follow-up of 5 months to 4 years was obtained in vulvar dystrophic patients after a conservative protocol of treatment. The initial histological diagnosis revealed 17 patients with squamous hyperplasia (9 patients with dysplasia and 8, without dysplasia), lichen sclerosus in 5 and other dermatoses in 1 patient. "Itching" was the most frequent complaint, encountered in 20 (69%) of the study patient. Amongst these patients 4/5 of lichen sclerosus and 16/18 of squamous hyperplasia and other dermatoses had complete symptomatic relief with testosterone and corticosteroid respectively. Morphologically 22/23 (96%) had more than 50% decrease of the total lesion. In squamous hyperplasia with dysplasia after treatment, the re-biopsy revealed improvement of the dysplasia in all the cases with total disappearance in the mild dysplasia group. So far, vulvar carcinoma did not develop in any of the patient followed in our study who received treatment for vulvar dystrophy. So, for vulvar dystrophy, a benign squamous epithelial disorder of the vulva, steroid hormone therapy is indeed a logical and a consistent one.

Vulvar dystrophies: ACOG technical bulletin number 139 — January 1990

The primary symptom of the vulvar dystrophies (non-neoplastic epithelial disorders of the vulvar skin and mucosa) is vulvar pruritus. The development of malignancy is relatively uncommon (1–5%) over a prolonged period. Medical therapy is effective in alleviating symptoms in most patients.

A Critique of Current Classifications of Vulvar Diseases

Several classifications of vulvar diseases have been proposed, but none of them is either consistent internally or applicable clinically and histopathologically. Ambiguous and even inexplicable terms such as "atypical epithelial hyperplasia (dysplasia)", "vulvar dystrophy," "vulvar atypia," "atrophic dystrophy," "mixed dystrophy," and "vulvar intra-epithelial neoplasia" prevent clinicians and histopathologists from communicating effectively with each other. In addition, these terms have different meanings to dermatologists, pathologists, and gynecologists--if indeed they have any meaning at all. If that maelstrom of confusion is to be avoided, diagnoses by histopathologists must be made in the language of clinical medicine. Only then will clinicians be able to understand those diagnoses and thereby manage patients rationally. For example, if findings by conventional microscopy are those of squamous-cell carcinoma in situ of the vulva, the diagnosis of pathologists should be Bowen's disease or bowenoid papulosis and not "vulvar intra-epithelial neoplasia"--a term that is just as applicable to seborrheic keratosis as it is to Bowen's disease and bowenoid papulosis.

Vulvar dystrophies: an evaluation.

Of 86 patients diagnosed as having vulvar dystrophy in a 10-year period 56 (65.1%) had hyperplastic dystrophy, 23 (26.7%) had lichen sclerosus and 7 (26.7%) had mixed vulvar dystrophy. The diagnoses were made by colposcopic or toluidine blue directed biopsies. Fluorinated corticosteroids were given to patients with hyperplastic dystrophy with a response rate of 90.1%. Patients with lichen sclerosus received topical testosterone propionate and the response rate was 87.7%. Topical fluorinated corticosteroids followed by testosterone propionate was given to patients with mixed dystrophy and 85.8% of the patients responded. Surgical therapy was reserved for patients with failed medical treatment.

Detection of human papillomavirus deoxyribonucleic acid from vulvar dystrophies and vulvar intraepithelial neoplastic lesions

Vulvar biopsy specimens from 16 patients with gross lesions of the vulva consistent with vulvar dystrophy were examined histologically and for the presence of human papillomavirus deoxyribonucleic acid by southern blot hybridization. None of the nonatypical dystrophies probed positive for human papillomavirus; however, three of five atypical hyperplastic dystrophies (vulvar intraepithelial neoplasia) contained human papillomavirus deoxyribonucleic acid type 16. We conclude that human papillomavirus does not seem to be a causal factor in nonatypical chronic epithelial changes of the vulva.

The measurement of plasma-free testosterone in normal menstrual females, pregnant females, post menopausal females and vulvar dystrophy

It is considered that plasma-free testosterone is a bioactive androgen in blood and is more reflective in androgenicity than plasma total testosterone. We measured plasma-free testosterone by dialyzable method in normal menstrual females, pregnant females, post menopausal females and vulvar dystrophy. The values of plasma total testosterone (T), fractional free testosterone (%FT) and plasma-free testosterone (free T) were 0.61 +/- 0.27 (mean +/- SD)ng/ml, 1.19 +/- 0.34% and 0.61 +/- 0.20 ng/kl in the follicular phase of normal menstrual females (n = 25), and 0.57 +/- 0.23 ng/ml, 1.29 +/- 0.46% and 0.56 +/- 0.35 ng/dl in the luteal phase of normal menstrual females (n = 24), respectively. The values in both phases showed no differences from each other. In post menopausal females (n = 18), the concentration of T (0.36 +/- 0.27 ng/ml) and free T (0.52 +/- 0.12 ng/dl) was significantly lower (T: P less than 0.01, free T: P less than 0.05) than that in normal menstrual females. However, %FT in post menopausal females (1.37 +/- 0.12%) was not different as compared with that in normal menstrual females. In pregnant females (n = 2) of second and third trimester, T (0.53 +/- 0.07 ng/ml) was not different as compared with that in normal menstrual females, but %FT (0.67 +/- 0.45%) and free T (0.33 +/- 0.23 ng/dl) were significantly lower (P less than 0.05) than in normal menstrual females. In vulvar dystrophy, lichen sclerosus (n = 19) and hyperplastic dystrophy without atypia (n = 12) were measured.(ABSTRACT TRUNCATED AT 250 WORDS)

Vulvar dystrophies.

Vulvar dystrophy is a relatively frequent gynecologic problem in postmenopausal women and may cause disabling discomfort. All patients with vulvar dystrophy should be carefully evaluated at the time of initial presentation and during therapy. Biopsies of vulvar lesions should be used liberally to define optimal therapy and to exclude atypia or malignancy, not only at the initial visit but also when lesions persist during therapy. In the absence of atypia, the patient can be reassured about the malignant potential of her disease. Most symptoms are relieved with conservative therapy alone.

Oral treatment of vulvar dystrophy with an aromatic retinoid, etretinate

Twenty patients with vulvar dystrophy (19 Lichen sclerosus, 1 Lichen ruber planus) were treated for 3 months with etretinate (Tigason) with an initial dose 0.54 mg/kg/day, maintenance dosage 0.26 mg/kg/day. All the patients had been unsuccessfully treated previously with topical oestrogen and corticosteroids. The therapeutic effect of etretinate on the subjective and objective symptoms of the disease was excellent. In most of the patients the pruritus and burning symptoms diminished within 2 weeks of treatment, and after 3 months the grade of symptoms was lower in 95% of cases. Clinically, a decrease in severity was achieved in 93% of cases among the group with severe vulvar dystrophy. The therapeutic effect of etretinate is strongly anti-inflammatory and it has a powerful effect on the epidermal tissues. According to the latest studies, etretinate also has a strong immuno-modifying effect on the epidermal cells. The secondary inflammatory changes, such as excoriatia, fissures and superinfections disappeared. In the histopathological follow-up hyperkeratosis in the stroma diminished and the inflamed cells and connective tissue normalised after 3 months of treatment. Side effects included cheilitis, dryness of mucous membranes and slight loss of hair. It must be taken into account that etretinate may cause liquid metabolism disturbances, particularly among risk factor patients (diabetes, obesity etc.). In our experience the best results to date in the treatment of vulvar dystrophy can be achieved with etretinate. Due to the teratogenic effect of etretinate, a reliable method of contraception must be used by fertile women of childbearing age.

The carbon dioxide laser in the treatment of vulvar disease.

Our review of the current use of the carbon dioxide laser in treating vulvar disease reveals that it holds significant promise in the treatment of vulvar intraepithelial carcinoma, condylomata acuminata, and focal vestibular adenitis. The long-range results of such treatment, however, are not yet known. Until sufficient data are accumulated to demonstrate the efficacy of the laser in treating the vulvar dystrophies and herpes genitalis, it should be used with caution, and the results should be carefully evaluated and reported.

Reactive and neoplastic epithelial alterations of the vulva: A classification of the vulvar dystrophies from the dermatopathologist's viewpoint

The clinical classification of the vulvar dystrophies has traditionally been difficult because most of these lesions present as a white hyperkeratotic patch. An international committee for the study of the vulva designed a histologic classification that consists of: I, hyperplastic type, with or without atypia; II, lichen sclerosus; and, III, mixed dystrophy, with or without atypia. A new classification and a fourth type are proposed by us to sort out a group of strictly benign dermatoses with distinctive histopathologic features which can present clinically as a white patch in the vulva; these are best designated as benign dermatoses. In addition to these, squamous cell carcinoma in situ and Paget's disease may also be manifested as a white patch. Hence, a classification of vulvar diseases with new nomenclature is presented from the dermatopathologist's perspective, based on histologic and clinical features.

Further observations on the effect of topical progesterone on vulvar disease

Follow-up studies have confirmed the beneficial effect of topical progesterone in the treatment of vulvar dystrophy, whether of the atrophic, hypertrophic, or mixed variety, in both postmenopausal and premenarchal women. If pruritus is a major symptom, topical corticosteroids should be alternated with the progesterone preparation in order to obtain maximum results. Topical progesterone was also found to be useful in the treatment of labial agglutination in children.

Topical progesterone in treatment of vulvar dystrophy: Preliminary report of five cases

Topical progesterone was used in five cases of chronic vulvar dystrophy which were confirmed by biopsy. Good results were obtained in three of the cases through the sole use of topical progesterone. In one case, topical testosterone was substituted for the progesterone, and it was not as effective. The concomitant use of estrogen vaginal cream was required in order to achieve maximum results in another case due to the presence of senile vaginitis. The apparent failure of the progesterone preparation to achieve satisfactory results in a diabetic patient could possibly be explained by the presence of neurodermatitis.

Vulvar dystrophies: An evaluation

The vulvar biopsy specimens from 128 patients were grouped according to a predetermined classification. When the charts on these 128 patients were reviewed, several facts relative to the vulvar dystrophies were noted. The presence of a vulvar dystrophy, when adequately treated, does not significantly predispose the patient to the developent of vulvar carcinoma. When first seen, the one patient who did develop carcinoma of the vulva had an initial vulvar carcinoma 3 years prior to the diagnosis of a second vulvar carcinoma and associated lichen sclerosus et atrophicus. The symptoms related to the vulvar dystrophies can be adequately controlled with medical treatment. Since the treatment will vary according to the type of dystrophy present, it is important that the diagnosis be accurately made. Vulvectomy is contraindicated as a means of treatment in the vast majority of patients with a vulvar dystrophy.

Treatment of vulvar dystrophies with topical testosterone propionate

Fifteen patients with vulvar dystrophy, classified histologically as lichen sclerosus et atrophicus or hyperplasia, were treated with a testosterone propionate ointment applied directly to the vulva. Evaluation of the data was based on pre- and post-treatment biopsies, observation of gross changes in the vulva, and a quantitative judgment of symptom relief by both observer and patient. All 15 of the patients had symptomatic relief and some improvement in the gross appearance of the vulva. Twelve of the 13 patients who had posttreatment biopsies showed histologic change toward a more normal epithelium. Plasma androgen and 17-ketosteroid excretion levels remained within normal limits during treatment in the 5 patients upon whom each of the determinations were made. Side effects were minimal and limited to mild to moderate clitoral hypertrophy in 2 patients and an increased libido in 4 patients.

PRECANCEROUS LESIONS OF THE VULVA.

The clinical classification of the vulvar dystrophies has been difficult because most of these lesions present as a white hyperkeratotic patch. A new classification was proposed by Sanchez & Mihm consisting of: I. Benign dermatoses; II. Vulvar epithelial hyperplasia; III. Lichen sclerosus; IV. Lichen sclerosus with foci of the epithelial hyperplasia. The vulvar white keratotic lesions which have been subjected to histological examination in Himeji National Hospital (1973-1987) included 13 cases in benign dermatoses, 4 cases in vulvar epithelial hyperplasia, 3 cases in lichen sclerosus, and 3 cases in lichen sclerosus with foci of epithelial hyperplasia.