[Establishment of a rat model of dimethylbenzanthracene-induced vulvar squamous intraepithelial lesions].

OBJECTIVE: To establish a SD rat model of vulvar squamous intraepithelial lesions. METHODS: Seventy female SD rats were randomized into 4 groups, namely the blank control group (n=10), mechanical irritation group (n=10), acetone solution group (n=10), and mechanical irritation with DMBA acetone solution group (n=40, model group), and the corresponding treatments were administered 3 times a week for 14 weeks. The changes of the vulvar skin of the rats were observed regularly until the 18th week. The expression of mutant p53 (mtp53) and vascular endothelial growth factor (VEGF) proteins were detected using immunohistochemistry and Western blotting, and the expressions of mtp53 and VEGF mRNA were detected with qRT- PCR in the blank control group and model group. RESULTS: No significant differences were found in the morphological or histopathological changes of the skin among the blank control group, mechanical irritation group and acetone solution group. In the model group, low-grade squamous intraepithelial lesions (LSIL) occurred in 28 rats (70%) and high-grade squamous intraepithelial lesions (HSIL) in 11 rats (27.5%) at 14 weeks, with a success rate of 97.5% in inducing vulvar squamous intraepithelial lesions. Compared with the blank control group, the rats in the model group showed significantly increased expressions of mtp53 and VEGF at both the protein level (P < 0.05) and the mRNA level (P < 0.05). CONCLUSIONS: DMBA in acetone solution combined with mechanical irritation can induce vulvar squamous intraepithelial lesions in female SD rats.

Focused ultrasound therapy for vulvar intraepithelial neoplasia in a mice model.

BACKGROUND: The purpose of this study was to determine the effectiveness and safety of focused ultrasound (FU) for the treatment of vulvar intraepithelial neoplasia (VIN) in a mice model. METHODS: Estradiol benzoate was subcutaneously injected into the abdomens of eighty 129/J mice. VIN was successfully induced in 56 mice and was divided into the FU group and the control group. Pathologic features and changes in vascular endothelial growth factor expression in the lesions were analyzed before and after treatment. RESULTS: Two months after treatment, lesions in 25 of the 56 mice showed restoration of normal skin. Nineteen of the 21 VINI and VINII lesions returned to normal and the other 2 VINII lesions were down graded to VINI, yielding a curative rate of 90.1%. In the control group, all 21 mice had persistent VIN (P < 0.0001). In the 14 mice with VINIII lesions, 6 returned to normal skin histology representing a curative rate of 42.9%, 5 were reclassified as VINI and 3 were reclassified as VINII. Thus, the total effectiveness rate was 100%. CONCLUSIONS: The present study suggests that FU therapy is effective, noninvasive and safe in treating VIN in a mice model.

Tattoo pigment lymphadenopathy mimicking metastasis in vulvar cancer.

BACKGROUND: Approximately 24% of American adults have tattoos. Studies of humans and mice demonstrate that tattoo pigment migrates to lymph nodes and can cause lymphadenopathy. CASE: A 32-year-old woman presented with a 6-cm vulvar mass and extensive bilateral inguinofemoral lymphadenopathy. Bilateral small tattoos were noted in the groins. Vulvar biopsy confirmed squamous cell carcinoma, and fine needle aspiration of the lymph nodes showed no evidence of malignancy. The patient underwent a radical hemivulvectomy and bilateral inguinofemoral lymphadenectomy. Both inguinal and femoral nodes were enlarged because of extracellular tattoo pigment and reactive follicular hyperplasia without any evidence of metastasis. CONCLUSION: This case emphasizes the need to consider tattoo pigment as a cause of lymphadenopathy in any patient with a regional tattoo.

Recurrent hypertrophy of the labia minora: a hormonally related lesion possibly related to fibroepithelial stromal polyps of the vulva.

The literature on hypertrophy of the labia minora has focused predominantly on surgical procedures, with little attention to etiology. We present a case of recurrent labial hypertrophy and postulate that this is a hormonally related lesion, similar to fibroepithelial stromal polyps.

Topical immunosuppressants, genital lichen sclerosus and the risk of squamous cell carcinoma: a case report.

BACKGROUND: Squamous cell carcinoma (SCC) has a recognized association with lichen sclerosus (LS) of the vulva. Several recent reports have indicated the usefulness of the new macrolide immunosuppressant agents pimecrolimus and tacrolimus in the treatment of LS, emphasizing the advantage over topical corticosteroids of lack of atophogenicity. Despite this there may be risks involved that could outweigh this benefit. The potential of these medications to potentiate the risk of SCC in LS in the short and long-term is unknown. Once lichen sclerosus is well controlled, there is often no need for ongoing use of superpotent corticosteroids, and there may be no reason to use immunosuppressants when moderate-strength corticosteroids provide adequate control. CASE: A 73-year-old woman with a 10-year history of hypertrophic LS and genital psoriasis presented with intractable superimposed inflammatory vulvitis. She was treated with topical pimecrolimus 1% cream on the assumption that she was either allergic to or intolerant of topical corticosteroids. One month after commencing therapy, she suddenly developed a rapidly growing vulvar tumor. This was excised and proved to be a well-differentiated squamous cell carcinoma. CONCLUSION: It may be safest to restrict the use of topical immunosuppressives to patients with LS who are unable to use topical corticosteroids because of the risk of potentiating SCC.

Effects of the dietary phytoestrogens daidzein and genistein on the incidence of vulvar carcinomas in 129/J mice.

The objective of this study was to determine the effect of dietary phytoestrogens on the incidence of spontaneous vulvar carcinomas in 129/J mice using three natural ingredient diets and two purified diets containing predetermined levels of daidzein and genistein. Eighty weanling female mice without clinical evidence of vulvar carcinomas were randomly assigned 16 per diet to each of 5 test diets. Mice were clinically examined for vulvar masses weekly for 3 months and at monthly intervals thereafter. Vulvar carcinomas in representative groups of mice were confirmed using routine histological procedures. The incidence of vulvar carcinomas increased sharply in mice on all test diets during the first 2 months with minor changes during the remainder of the study. Within one month, the incidence of vulvar carcinomas in mice fed the AIN-76A modified soy protein diet was significantly (P < .05) increased over those of mice fed the AIN-76A modified casein diet, the #5K96, or the # 5058 diet. At three months, the incidence of vulvar carcinomas in mice fed the soy protein diet was significantly (P < .05) increased over those of mice fed the NIH-31 diet or the PMI #5K96 diet. There was a marginally significant (P < .10) correlation between the total daidzein and genistein levels in the five test diets and the incidence of vulvar carcinomas in mice as determined by clinical examination. We concluded that dietary levels of daidzein and genistein were associated with an increase in the incidence of vulvar carcinomas in mice and that the 129/J mouse may provide an animal model for studying the development of vulvar carcinomas.

Postmenopausal estrogens and progestogens and the incidence of gynecologic cancer.

We reviewed the published medical literature to assess the impact of the use of estrogens, with and without progestogens, on the incidence of gynecologic cancer in postmenopausal women. Long-term use of an estrogen preparation that is not accompanied by a progestogen is associated with a large increase in the risk of endometrial cancer, an association that almost certainly is a causal one. The incidence of endometrial cancer in women who receive combined estrogen-progestogen therapy is not elevated to nearly the same degree. There are suggestions that, depending on the particular combined regimen, the incidence need not be elevated at all beyond that of a women who has never taken hormones. The occurrence of other forms of gynecologic cancer appear not to be associated with the use of unopposed estrogens, though relevant data on cervical cancer are sparse. The relation of ovarian, cervical and vulvar cancer to the prior use of combined estrogen-progestogen therapy has only begun to be evaluated.

Vulvar leiomyoma associated with estrogen/progestin therapy. A case report.

Leiomyomata of the vulva are reported rarely. A previously unrecognized leiomyoma in the area of Bartholin's gland grew rapidly during estrogen/progestin replacement therapy. Hormone receptors for both estrogen and progesterone were positive.

Hormonal factors in vulvar cancer. A case-control study.

As part of a case-control study of vulvar cancer, we examined the role of reproductive history, menstrual history, exogenous estrogen use and body mass in the etiology of this disease. A total of 330 women with vulvar squamous cell cancer (259 in situ, 81 invasive), aged 18-79 years, who were diagnosed with this tumor during 1980-1990 were interviewed. Their responses were compared to those of 1,010 women who were selected from the general population by means of random digit dialing. Cases and controls did not differ regarding age at menopause, parity, number of prior pregnancies or number of prior births, history of miscarriage or use of noncontraceptive estrogens. Women diagnosed with vulvar cancer were slightly more likely to have experienced menarche at < 12 years (odds ratio [OR] = 1.8, 95% confidence interval [CI] = 1.2-2.7, in situ cancer; OR = 1.6, 95% CI = 0.8-3.1, invasive cancer), to have excess weight (invasive cancer only, OR = 2.9, 95% CI = 1.5-5.8 for highest tertile of Quetelet's index) and, among gravid women, to have had their first pregnancy after age 24 (in situ cancer only, OR = 1.5, 95% CI = 0.9-2.5). These data, together with similar results from previous studies and quantitative studies of hormone receptors in vulvar tissue, suggest that in situ and invasive vulvar cancer are not strongly hormone dependent tumors.

Carcinogenic effects of a mixture of nitropyrenes in F344 rats following its repeated oral administrations.

The carcinogenic effects of a mixture of 1-nitropyrene and three dinitropyrenes (1,3-, 1,6- and 1,8-dinitropyrene) were investigated in rats. Female F344/Jcl rats were given one of three doses (5, 10 and 20 mg/kg body weight) of the mixture by repeated intragastric instillations twice a week for 55 weeks, and then autopsied 49 weeks later. Mammary adenocarcinomas were induced in rats of all the three experimental groups dose-dependently, while no adenocarcinoma was induced in the control rats which were given only vehicle. Clitoral gland tumors, most of which were diagnosed as squamous cell carcinomas, were also commonly observed in the NP-treated rats in a dose-dependent way. In addition, high incidences of mononuclear cell leukemias were noted in the NP-treated rats. Other tumors were frequently induced in the uterus and endocrine organs, such as the pituitary, adrenal, and thyroid glands. However, the incidences of these tumors were almost equal in both the control and NP-treated groups. The results of the present study indicated the potential carcinogenic activities of nitropyrene compounds in female rats when they were treated by oral route, and suggest that the oral intake of nitropyrene compounds might be related to the incidence of cancer in humans.

[Basal cell epithelioma of the vulva in chronic endemic regional arsenic poisoning]. / Epitelioma basocelular de vulva en HACRE.

A 65 years old patient with vulvar basal cell carcinoma and cutaneous manifestations of chronic arsenicism is reported; by its endemic origin is considered as hidroarsenicism ( ERCHA = endemic regional chronic hidroarsenicism ). The unusual presentation of this type of cancer is resalted , and it's attributed to its general disease . The principal characteristics of arsenical skin cancer are considered.

Tumorigenic action of N-n-butyl-N-formylhydrazine in mice.

Continuous administration of 0.04% N-n-butyl-N-formylhydrazine (BFH) in drinking water to 6-week-old randomly bred Swiss mice for life produced tumors of the lungs, preputial and clitoral glands. The tumor incidences in these three tissues of the treated animals were 87, 66, and 10%, whereas in the untreated controls they were 25, 0, and 0%, respectively. Histopathologically, the tumors were classified as adenomas and adenocarcinomas of the lungs, squamous cell papillomas and carcinomas, angio-, fibro-, and myxo- sarcomas of preputial glands and squamous cell papillomas and carcinomas of clitoral glands. N-n-Butyl-N-formylhydrazine is a structural homologue of the carcinogenic N-methyl-N-formylhydrazine and N-ethyl-N-formylhydrazine. These studies are integral parts of structure activity relationship inquiries.

[Does oral contraception cause cancer? (author's transl)]. / Begünstigt die "Pille" Krebs

A complete answer to the question of the relationship between malignant tumors in man and the administration of contraceptive steroids is at present not possible. Difficulties of the investigation are caused by the multiplicity of compounds used for contraception, the generally slow development of malignant tumors and the difficulty of the epidemiologic and statistical investigations on the multi-factorial etiology of cancer. Nevertheless, it can be stated with a high degree of certainty that "cancer due to the pill" does not exist in man and that a direct hormonal induction of malignant tumors in man cannot be proved. The question whether oral contraceptives may favor the development of cancer indirectly is explored in this paper regarding cancer of the female genital tract and the breast. No correlation between oral contraception and squamous cell carcinomas of the vulva and vagina and tumors of the ovary is known. As yet no statistics are available on the incidence of carcinoma of the endometrium in women who took oral contraceptives during their reproductive life span. Because of the direct hormonal suppression of the endometrial growth by oral contraception, a protective effect against endometrial hyperplasia and endometrial cancer must be expected. For cancer of the female breast no protective and no enhancing cancer risk due to progestational agents can be postulated. The known fragmentary data suggest a more protective value. Regarding dysplasia and carcinoma in situ of the uterine cervix large investigations in high numbers of patients are available. An increase of the risk to develop cancer of the cervix by using oral contraception cannot be shown with sufficient accuracy at our present state of knowledge by statistical means. Some observations suggest that oral contraception increases the relevant exogenous factors for carcinogenesis of the uterine cervix such as sexual behavior and hygiene.

PIP: The effect of oral contraceptives on the development of cancer indirectly is explored with regard to cancer of the female genital tract and the breast. No correlation between oral contraception and squamous cell carcinomas of the vulva and vagina and tumors of the ovary is known. As yet no statistics are available on the incidence of carcinoma of the endometrium in women who took oral contraceptives during their reproductive life span. Because of the direct hormonal suppression of the endometrial growth by oral contraception, a protective effect against endometrial hyperplasia and endometrial cancer must be expected. For cancer of the female breast no protective and no enhancing cancer risk due to progestational agents can be postulated. The known fragmentary data suggest rather a protective effect. Regarding dysplasia and carcinoma in situ of the uterine cervix, large investigations with great numbers of patients are available. An increase of the risk of developing cancer of the cervix by using oral contraception cannot be shown with sufficient accuracy at our present state of knowledge by statistical means. Some observations suggest that oral contraception increases the relevant exogenous factors for carcinogenesis of the uterine cervix such as sexual behavior and hygiene.

Oil and cancer.

A relatively high incidence of cancer of the skin, especially of the scrotum, due to occupational contact with mineral oil has been observed among shale oil workers and cotton mule spinners and, since the Second World War, among machine operators in the Birmingham region. A study has been made of the factors causing this high incidence and evidence is given that the respiratory and digestive tracts as well as the skin may be affected. The preventive measures are described and the suggestion made that they appear at the present time to be effective.