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Abnormalities of lymphocyte transformations in women with intraepithelial carcinoma of the vulva.

Cellular immunity of the delayed type in women with intraepithelial carcinoma (carcinoma is situ) of the vulva was investigated by an in vitro assay of mitogen-induced lymphocyte transformations. Test results from 9 patients were compared to those of 23 age-matched control subjects. Lymphocyte transformation responses in counts per minute were significantly lower for women with carcinoma in situ of the vulva than for control subjects for phytohemagglutinin-P (at 50 microgram/ml) 6238 and 28,102 (P less than 0.0001); for phytohemagglutinin-P (at 165 microgram/ml 7222 and 21,417 (P less than 0.001); for concanavallin A, 14,988 and 41,888 (P less than 0.0001); and pokeweed mitogen, 20,861 and 49,601 (P less than 0.001). No significant differences in lymphocyte transformations were noted between these two groups to the specific antigens, Candida or streptokinase-streptodornase. Four patients with carcinoma in situ of the vulva were also found to have intraepithelial carcinoma of the cervix and/or vegina. The occurrence and clinical course of carcinoma in situ of the vulva in some women may be related to an underlying defect in cellular immunity. Immunosuppression may also explain the frequent association noted between carcinoma of the vulva and the development of other malignant neoplasms.

Adolescent↗

Carcinoma of the vulva: HPV and p53 mutations.

Recent evidence suggests that squamous cell carcinoma of the vulva may have more than one etiology, with only some tumors associated with human papillomavirus (HPV). Cells infected with HPV produce a viral protein (E6) which binds to and causes rapid degradation of p53, possibly contributing to cellular transformation. In several human malignancies, point mutations of p53 alter activity of the p53 protein contributing to cellular transformation. We tested, for the first time, the possibility that HPV-negative tumors of the vulva may have a high incidence of inactivating mutations of p53; while HPV-containing vulvar tumors rarely would have p53 mutations. Twenty-one tumors of the vulva were evaluated for the presence of HPV sequences by amplication with the polymerase chain reaction (PCR) and Southern blotting. These were evaluated for p53 mutations by single strand conformation polymorphism and sequencing of PCR products. HPV DNA sequences were found in 12 of 21 (57%) cancers of the vulva; only one of these 12 (8%) HPV-positive samples had a missense mutation of p53. In contrast, four of nine (44%) HPV-negative vulvar tumors had point mutations of p53. The p53 mutations were found in only metastatic lesion and the only recurrent tumor samples suggesting that the acquisition of p53 mutations may be associated with neoplastic progression. In conclusion, alterations in p53 activity appear to be important in the development of carcinoma of the vulva.

Base Sequence↗

Efficacy of inosine pranobex oral therapy in subclinical human papillomavirus infection of the vulva: a randomized double-blinded placebo controlled study.

A randomized double-blind placebo controlled study was carried out to assess the efficacy of inosine pranobex (1 g orally 3 times a day for 6 weeks) in the treatment of symptomatic subclinical human papillomavirus infection of the vulva. In a series of 55 women, 22 patients in the inosine pranobex group and 24 patients in the placebo group were suitable for analysis. A total of 14 (63.5%) of the inosine pranobex treated patients and 4 (16.7%) of the placebo treated patients showed significant vulval epithelial morphological improvement (P = 0.005) at 2 months after initiation of treatment. Whereas 13 (59.1%) and 9 (37.5%) patients in the respective groups showed significant improvement in the severity of pruritus vulvae (P = 0.435). Twelve (66.7%) of 18 patients with morphological improvement compared to 10 (35.7%) of 28 patients with no morphological improvement experienced significant symptomatic alleviation of pruritus vulvae (P = 0.041). Similar results were seen at the second assessment 4 months after the initiation of treatment. Adverse drug reactions were reported by 2 patients in the treatment group and by 2 patients (skin rash) in the placebo group. These adverse reactions were mild and self limiting. It is concluded that inosine pranobex demonstrated a significant pharmacological activity in subclinical HPV infection of the vulva and should be considered an alternative treatment for the condition.

Administration, Oral↗

Isolation and characterization of mutations causing abnormal eversion of the vulva in Caenorhabditis elegans.

In Caenorhabditis elegans hermaphrodites, morphogenesis of the vulva culminates in a process called vulval eversion, whereby a passageway is made from the uterus through the vulva to the outside of the animal. We have screened for mutations causing abnormal eversion of the vulva (evl mutations) to identify new genes involved in vulval development, and found that evl mutants are relatively common after EMS mutagenesis. We also hoped to identify genes involved in lin-12-mediated cell fate decisions, since lin-12 null mutants have abnormally everted vulvae, but none of the 68 evl mutations recovered in our screen appeared to be good candidates for genes that function with lin-12. Initial genetic and phenotypic analysis of 30 evl mutations revealed that all affect the development of the uterus, but only some affect the vulval precursor cell lineages. We used laser ablation to show that the uterus and anchor cell are important for correct vulval eversion in wild type; the anchor cell is important early in the L3 stage, before the vulval cells have been generated, but not later, when vulval eversion occurs. We conclude that certain evl mutations may influence vulval eversion by primarily affecting the development of the somatic gonad, while others may affect processes required in the development of both structures.

Alleles↗

Use of a vacuum-assisted closure device in the treatment of recurrent Paget's disease of the vulva.

BACKGROUND: Paget's disease of the vulva is a rare malignancy for which common recurrence is related to inadequate surgical margins. Excision with adequate surgical margins might leave a large defect that does not readily heal. CASE: A 41-year-old woman with recurrent Paget's disease of the vulva underwent a skinning excision of the vulva and perineum. A vacuum-assisted closure device was placed on the wound until final pathologic analysis confirmed the adequacy of surgical margins. CONCLUSION: The vacuum-assisted closure device not only allowed us to safely temporize wound closure until the final histopathologic results, but also helped secure the skin graft to the large and irregular surface. Additional studies are needed to determine the effectiveness of vacuum-assisted closure device therapy in Paget's disease of the vulva.

Adult↗

Basal cell carcinoma of the vulva: clinical features and treatment results in 28 patients.

OBJECTIVE: To review our experience and that in the recent literature regarding basal cell carcinoma of the vulva to see whether current management guidelines are appropriate. METHODS: Twenty-eight women with basal cell carcinoma of the vulva were seen over 25 years at the BC Cancer Agency. The clinical-pathologic features were tabulated and the outcome was analyzed. RESULTS: The mean age was 74 years, and almost two-thirds were over the age of 70 at diagnosis. Patients typically presented with an irritation or soreness, with a symptom duration ranging from a few months to several years. Most lesions were confined to the anterior half of the vulva, and 23 of the 28 patients had T1 lesions. Wide local excision was the treatment method used most commonly. Only one patient was known to have died from disease metastasis. Ten women had other basal cell carcinomas, either before or after the diagnosis of their vulvar lesions, and in ten patients 11 other malignancies were diagnosed. CONCLUSION: Basal cell carcinoma of the vulva is an extremely uncommon tumor that rarely metastasizes or spreads. Primary treatment should consist of wide local excision and continued follow-up.

Aged↗

Germ-line induction of the Caenorhabditis elegans vulva.

Development of the Caenorhabditis elegans vulva serves as a paradigm for intercellular signaling during animal development. In wild-type animals, the somatic gonadal anchor cell generates the LIN-3/EGF ligand to induce vulval fates in the underlying hypodermis, whereas FBF, FOG-1, and FOG-3 control germ-line development. Here we report that FBF functions redundantly with FOG-1 and FOG-3 to control vulval induction: animals lacking FBF and either FOG-1 or FOG-3 have multiple vulvae, the Muv phenotype. The fog; fbf Muv phenotype is generated by aberrant induction of vulval precursor cells (VPCs): in wild-type animals, three VPCs are induced to form a single vulva, but, in fog; fbf mutants, four or five VPCs are typically induced, resulting in ectopic vulvae. Laser ablation experiments and mosaic analyses demonstrate that the germ line is critical for the fog; fbf Muv phenotype. Consistent with that site of action, we detect FBF and FOG-1 in the germ line but not in the VPCs. The simplest interpretation is that FOG-1, FOG-3, and FBF act in the germ line to influence vulval fates. The LIN-3/EGF ligand may be the germ-line signal to the VPCs: the fog; fbf Muv phenotype depends on LIN-3 activity, and the lin-3 3' UTR possesses an FBF binding element. Our findings reveal new insights into germ line-to-soma signals and the role of PUF proteins in animal development.

Animals↗

Quantitative microbiology of human vulva.

The microbial flora of the vulva is described and compared with the flora of the forearm by utilizing the detergent scrub method. Microbial counts were higher on the vulva (2.8 x 10(6)/cm2) than on the forearm (6.4 x 10(2)/cm2). Lipophilic diphtheroids, coagulase negative staphylococci, micrococci, non-lipophilic diphtheroids and lactobacilli formed the dominant flora of the vulva. Streptococci, Gram negative rods and yeasts were also noted. The highest incidence of S. aureus was noted on the vulva (67%) followed by perianal (30%), nose (30%), and the forearm (11%).

Adult↗

Vulvar intraepithelial neoplasia with superficially invasive carcinoma of the vulva.

OBJECTIVE: To investigate the long-term outcome of patients presenting with vulvar intraepithelial neoplasia (VIN) with superficially invasive carcinoma of the vulva (SICa). DESIGN: A retrospective study using information obtained from patient case notes. SAMPLE: Twenty-six women found at presentation to have VIN in association with superficially invasive carcinoma were identified during a 15-year period. RESULTS: Pruritus vulvae was the most frequent presenting symptom in 18 patients (69%). Sixteen women (61.5%) had multiple symptoms. Features noted at vulvar examination were variable and none were pathognomonic of either VIN or of superficial invasion. All patients had VIN 3 in association with a superficially invasive carcinoma. Histological changes associated with human papillomavirus were found in 19 (73%) women. Half had a co-existent or previous abnormality of the lower genital tract. Local excision was the most frequent initial treatment (n = 9 [35%]). Mean follow up time was 65 months (range 12-174). Disease persisted after primary treatment in five women (19%). Both histological recurrence (of either VIN or SICa) or symptomatic recurrence occurred in 10 patients (38%). All patients who experienced recurrence did so within 36 months of treatment. Overall, 12 patients (46%) relapsed (histological or symptomatic recurrence); the mean time was 18 months. Fourteen patients (54%) were managed satisfactorily by their initial treatment. One patient died of recurrent cervical cancer. Three progressed to frankly invasive disease: two (aged 31 and 39 years) with carcinoma of the vulva and one aged 34 years with carcinoma of the perianal margin. All are alive and well after treatment. One patient had recurrence of superficially invasive carcinoma treated by local excision with no further problems. No episode of metastasis via lymphatic or vascular channels has been seen. CONCLUSIONS: Patients with superficially invasive carcinoma of the vulva may be safely treated by local excisional methods without recourse to lymphadenectomy. Relapse after primary treatment is common, and there appears to be a significant risk of progression to frankly invasive carcinoma.

Adult↗

Shrinkage in the horizontal dimensions of the vulva (vulvar shrinkage) as an indicator of standing heat in the beagle.

During the proestrous and estrous periods in 12 beagles, the following parameters were measured daily: the horizontal dimensions of the vulva, vaginal cytology, and serum luteinizing hormone (LH) and progesterone concentrations. Measurements of serum LH concentrations allowed for the identification of the LH surge and the optimal time for artificial insemination (AI). Nine out of the 12 beagles became pregnant through AI and completed a gestation. Shrinkage in the horizontal dimensions of the vulva (i.e., vulvar shrinkage) was primarily observed prior and subsequent to the LH surge. In six of the nine (66.7%) beagles that became pregnant, vulvar shrinkage was observed on the days in which the LH surge was confirmed, and the rate of vulvar shrinkage tended to be greater at higher serum LH concentrations. Further vulvar shrinkage was identified in all nine beagles within two days of the LH surge. An increase in the serum progesterone concentration was observed after the LH surge in each of the beagles that became pregnant, together with clinical signs of estrous behavior (i.e., standing heat) as well as a change in vulva condition from swollen to soft. This demonstrates that vulvar shrinkage is induced in response to the onset of the LH surge and that the LH surge can be predicted through the measurement of the horizontal dimensions of the vulva, vaginal cytology, and the assessment of serum progesterone concentrations in beagles.

Animals↗

Adhesion of Corynebacterium renale and Corynebacterium pilosum to epithelial cells of bovine vulva.

Corynebacterium renale and C pilosum adhered effectively to the epithelial cells of the bovine vulva; the numbers of these organisms that adhered to the vulval epithelial cells were 50 and 30/cell, respectively, which were several times as many as those that adhered to the uroepithelial cells. Of the epithelial cells of the vulva, cornified cells lacking nuclei bound more bacteria than did those with indistinct nuclei, indicating that adhesion of bacteria was most effective to the most aged cells. The marked adhesion of C renale and C pilosum to the epithelial cells of the vulva may indicate that the vulva is an important portal of entry of these bacteria.

Adhesiveness↗

[Consequences of a surgical correction of an insufficient closure of the vulva on genital flora and conception rate in mares].

In this thesis the influence of pneumo-vagina on the microbiological colonization of the genital tract and their manifestation in cytological smears was examined. For mares with poor vulval conformation a comparison of the bacterial growth before and after plastic surgery of the vulva and vestibulum was carried out, as well as the registration of conception rates after operation and insemination. The biggest reduction of the bacterial content in the reproductive tract was found between vestibulum and cranial section of the vagina. The increased number of contaminant bacteria in the cranial section of the vagina during abnormal vulval conformation could be reduced significantly by the plastic surgery of the vulva and vestibulum (p < 0.05). Assuming that an 18-20 days pregnant uterus is free from a colonization with virulent bacteria, a high significant reduction of the increased number of contaminant bacteria in the uterus during vulval incompetence was found after surgical correction (p < 0.01). In mares with poor conformation of the vulva, which had not been operated, the contamination of the reproductive tract had increased at the time of checkup in comparison to the first swab specimens, taken 18-20 days before. The share of mares with a negative bacteriological and positive cytological result was in case of vulval incompetence twice as large as if they had a proper vulval conformation. A decrease of these latent infections was found after plastic surgery of the vulva and vestibulum. From the operated mares a total of 72.9% became pregnant.

Animals↗

Non-neoplastic epithelial alterations of the vulva: recognition assessment and comparisons of terminologies used among the various specialties.

To assess the recognition of non-neoplastic epithelial alterations of the vulva and to compare terminologies used for these lesions by various specialties, we performed a clinical and dermatopathologic review of all of the cases diagnosed as non-neoplastic epithelial alterations of the vulva that were followed by one gynecologist. Forty-five initial clinical and pathologic diagnoses made by a group of 14 general surgical pathologists during a 15-year period were compared to the diagnoses made by two dermatopathologists at the time of review. Comparison of diagnoses between the three specialties revealed two types of disparities. The first represented differences in nomenclature. Although all parties frequently agreed on a diagnosis of lichen sclerosus, which represented the most frequent histologic diagnosis, the dermatopathologists did not use the term squamous hyperplasia for any case. Of greater significance was the second type of disparity identified, i.e., failure of the gynecologist and general surgical pathologist to identify uncommon dermatoses in eight cases. Concordance in diagnosis among the dermatopathologists was found in 43 of the 45 cases. These findings are consistent with the view that non-neoplastic epithelial alterations of the vulva are the same as elsewhere in the skin and that terms such as vulvar dystrophy or squamous hyperplasia are not meaningful or helpful in identifying or treating vulvar dermatoses. Unfamiliarity with specific dermatoses and the modified appearance of a dermatosis when occurring on the vulva might cause recognition failure by the gynecologist and general surgical pathologist. Entity recognition might be greatly improved if non-neoplastic vulvar lesions are approached as specific dermatoses rather than being labeled as squamous hyperplasias or vulvar dystrophies. Careful histories and physical examinations aid in identifying less common vulvar dermatoses. Referral to a dermatologist/dermatopathologist is indicated when the diagnosis is in doubt or if the response to treatment is poor.

Adolescent↗

Adenosquamous carcinoma of skin appendages (adenoid squamous cell carcinoma, pseudoglandular squamous cell carcinoma, adenocanthoma of sweat gland of Lever) of the vulva: a clinical and ultrastructural study.

History and clinical findings of 18 cases of adenosquamous carcinoma of the skin appendages found among 135 cases of primary carcinoma of the vulva seen at the University of Minnesota Hospital between 1951 and 1970 were analyzed. In addition, two recent cases of this tumor were studied with conventional transmission electron microscopy. Adenosquamous carcinoma of the vulva showed poorer survival and a higher rate of lymph node metastases than squamous cell carcinoma of the corresponding stages (carcinoma in situ excluded). In four out of thirteen cases, the metastatic lesions in the lymph nodes retained glandular pattern. The ultrastructure showed mucin-producing columnar cells lining glandular lumina, and poorly differentiated squamous cells elsewhere; further, cells of the intermediate type between the two were present. This study indicates that adenosquamous carcinoma of the vulva is a distinctively separate entity from squamous cell carcinoma of the vulva, and possibly arises from mucin-producing cells of the skin appendages as suggested by Johnson and Helwig.

Adenocarcinoma↗

Mixed tumor of the vulva: a report of two cases probably arising in Bartholin's gland.

A case of benign mixed tumor of the vulva and a case of carcinoma arising in a similar benign mixed tumor of the vulva are reported. Both mixed tumors were of salivary gland type and probably arose in the Bartholin's gland. Only three previous cases of benign mixed tumor of the vulva have been documented in the literature. Two arose in the vestibular glands, and the third arose in cutaneous sweat glands. No case of carcinoma arising in a benign mixed tumor of the vulva has been previously documented.

Aged↗

Cancer of the vulva: a review.

Localized carcinoma of the vulva in situ can be treated by wide local excision and continued close observation. Skinning vulvectomy, with or without subsequent skin grafting, is now well accepted as a treatment of Multifocal preinvasive disease. Microinvasive carcinoma of the vulva, on the other hand, is not treated with vulvectomy alone since the regional lymph nodes must be accurately assessed. The currently accepted treatment of invasive carcinoma of the vulva is radical vulvectomy and bilateral groin lymph node dissection. No longer is pelvic lymph node dissection to be considered a routine part of this therapy but is included only under specific circumstances. On rare occasion a more radical procedure such as anterior or posterior pelvic exenteration is considered appropriate therapy when the geographic location of the tumor requires this approach. The treatment of recurrent disease is influenced by its extent and location and must be tailored for the individual patient. Palliative vulvectomy is still used as a treatment of the far advanced disease in an attempt to improve personal and social hygiene, as well as to control serious infection and to prevent localized hemorrhage. The role of x-ray therapy in the treatment of carcinoma of the vulva is discussed.

Carcinoma in Situ↗

Evolution of vulva development in the Cephalobina (Nematoda).

Ventral cord and vulva development are analyzed in a large sample of nematode species of the suborder Cephalobina. We find a specific range of evolutionary variations at distinct developmental steps. (1) Unlike Caenorhabditis elegans and relatives, the vulva is formed from the four precursor cells P(5-8).p or, exceptionally, from P(6, 7).p only. (2) The vulval competence group is restricted to these four cells or is larger. (3) The fates of more anterior and posterior Pn.p cells vary between closely related species (mostly cell death versus epidermal fate). (4) The mechanism of vulval cell fate patterning varies within a single genus, even between strains of the same species. (5) We describe the first example of a vulval cell lineage that is asymmetric between the anterior and the posterior sides of the vulva. For a selection of the investigated taxa, phylogenetic trees were constructed in order to map vulval characters and infer evolutionary polarities. We can conclude that in this group, death of the Pn.p cells probably constitutes a derived character state compared to a syncytial fate. Rhabditophanes sp. and Strongyloides ratti are placed as sister taxa, probably sharing an exclusive common ancestor in which the number of precursor cells forming the vulva was reduced from four to two.

Animals↗

Sebaceous carcinoma of the vulva: a case report and review of the literature.

Although sebaceous glands are prominent on the vulva, sebaceous carcinomas of the vulva rarely occur. In fact, there have been only two cases of sebaceous carcinomas of the vulva reported in the literature. Eighty percent of vulvar cancers are squamous in origin with human papillomavirus (HPV) DNA detected in approximately 60% of these cancers. We present a third patient with sebaceous carcinoma of the vulva and the first to our knowledge that has been analyzed for HPV DNA. The case report and a review of the literature are presented.

Adenocarcinoma, Sebaceous↗