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Recent advances in the pathology of the vulva.

This review addresses recent and important advances in our knowledge of several uncommon or rare disorders of the vulva including Paget's disease, vulva intraepithelial neoplasia, lichen sclerosus and squamous hyperplasia and their relationship to squamous carcinoma. Emphasis is placed on the two biologically different types of squamous carcinoma related and unrelated to human papillomavirus infection. Finally, the relatively recent concept of the sentinel node as applied to vulva carcinoma is discussed.

Adenocarcinoma↗

Microevolutionary analysis of the nematode genus Pristionchus suggests a recent evolution of redundant developmental mechanisms during vulva formation.

To identify the mechanisms by which molecular variation is introduced into developmental systems, microevolutionary approaches to evolutionary developmental biology have to be taken. Here, we describe the molecular and developmental characterization of laboratory strains of the nematode genus Pristionchus, which lays a foundation for a microevolutionary analysis of vulva development. We describe 13 laboratory strains of the Pristionchus genus that are derived from natural isolates from around the world. Mating experiments and ITS sequence analysis indicated that these 13 strains represent four different species: the gonochoristic species P. Iheritieriand three hermaphroditic species, P. pacificus, P. maupasi, and an as yet undescribed species Pristionchus sp., respectively. P. pacificus is represented by five different strains isolated from California, Washington, Hawaii, Ontario, and Poland. Developmental differences during vulva formation are observed between strains from different species but also between strains of P. pacificus, like the strains from California and Poland. In particular, redundant developmental mechanisms present during vulva formation in P. pacificus var. California are absent in other strains. Amplified restriction fragment length polymorphism (AFLP) analyses of the P. pacificus strains revealed that the American strains are highly polymorphic. In contrast, the developmentally distinct strain from Poland is identical to the Californian strain, suggesting that the developmental differences rely on a small number of changes in developmental control genes rather than the accumulation of changes at multiple loci.

Animals↗

[Cytologic diagnosis of Paget's disease of the vulva].

Unlike exfoliative cytology for detection of cervical neoplasia and its precursors, the cytologic detection of invasive and intraepithelial neoplasia of the vulva still presents some problems. In cases of Paget's disease of the vulva--a special form of intraepithelial neoplasia with typical histological features--primary cytologic diagnosis is possible. The cytologic criteria that led to preoperative detection are demonstrated on two cases of Paget's disease of the vulva. However, a Paget carcinoma has still to be excluded histologically.

Aged↗

[Dystrophy and precancerous changes in the vulva: symptoms, histology and therapy].

The article reports about the relatively rare diseases kraurosis vulvae (lichen sclerosus et atrophicus) and leucoplakia vulvae and the symptoms, aetiology, histology and therapy of these diseases. Both diseases are considered to be a "dystrophy" since 1976, by international convention. This publication is a report on 168 patients treated during the last 20 years (1964-1983). 34 patients suffered from diabetes mellitus (21%); 73.2% of the women were aged between the 61st and 90th year of life. 15 women already had an incipient vulvar carcinoma besides kraurosis (8.9%). Precancerous alterations, such as morbus Bowen (29 cases), morbus Paget of the vulva (6 cases), and erythroplasia of Queyrat are subsequently discussed.

Adult↗

The vulva skin microclimate: influence of panty liners on temperature, humidity and pH.

Many women use panty liners between menstrual periods. The aim of this study was to investigate whether the use of such products might influence the vulva skin. Twelve healthy women were studied on four occasions with three different product constructions and on one occasion without products. Temperature, surface wetness and surface pH were measured on vulva skin. Mean skin temperature when the women were wearing a conventional panty liner (with a non-breathable back sheet) was 35.9 degrees C, compared to 34.4 degrees C when wearing no panty liner at all (p < 0.01) and 34.5 degrees C when using a panty liner with a breathable (i.e. vapour permeable) back sheet (p < 0.01). Skin humidity was significantly higher when the conventional panty liner was used compared to no panty liner or to the breathable panty liner (both cases p < 0.01). The mean pH value at the exterior aspect of the labium majus was 5.8 with the conventional panty liner, 5.2 with no panty liner and 5.3 with the breathable panty liner (p < 0.001 and p < 0.01, respectively). The results indicate that the conventional panty liner changes the vulva skin microclimate, but that the breathable panty liner to a substantial degree keeps the microclimate at an undisturbed level. The actual effect of these differences on microbiological flora will be addressed in a subsequent study.

Adult↗

Mammary-like glands of the vulva and their disorders.

Supernumerary mammary glands derived from rudiments of the embryonic milk lines or mammary ridges in the vulva are considered a source of a series of unusual tumors resembling lesions of the breasts. This phenomenon was reevaluated in light of recent observations of mammary-like anogenital glands (MLG), which are a normal constituent of the vulva and appear to be closely related to eccrine glands. An analysis of the literature reveals that the concept of "milk lines" originated in a mixture of phylogenetic and ontogenetic theories at the beginning of this century and was not supported by observations in human embryos, which show that primordia of the mammary glands do not extend beyond the axillary-pectoral area. The breasts and the vulva are so widely separated by time and space that the vulvar MLG can not be derived from the mammary ridges or milk lines. The profile of the MLG, which can also reveal some eccrine or apocrine features, makes these glands the most likely source of a series of lesions occurring in the anogenital region and comprising lactating glands, lactating adenoma, fibroadenoma, hidrocystoma, hidradenoma papilliferum, and most cases of extramammary Paget's disease and invasive adenocarcinoma.

Adenoma, Sweat Gland↗

Paget's disease of the vulva: clinicopathologic study of type 1 cases treated at a single institution.

The aim of this study was to evaluate clinicopathologic characteristics of primary cutaneous Paget's disease of the vulva. Between 1986 and 2005, 22 patients with primary cutaneous Paget's disease of the vulva (type 1) were treated at Tohoku University Hospital. Medical records were reviewed for pathologic diagnosis, patient age, associated neoplasms, type(s) of eczema, symptom duration, treatment, surgical procedures, recurrence, and length of follow-up. Patient age ranged from 51 to 85 years (median 71.5 years). Median duration of symptoms was 24 months (range 2-60 months). Type 1a (intraepithelial) Paget's disease accounted for 18 patients, with 3 type 1b (invasive) cases and 1 type 1c (intraepithelial disease with underlying adenocarcinoma) case. Mean length of follow-up was 53.7 months, and median follow-up was 49 months (range 6-199 months). Only two patients had an associated internal malignancy: T-cell leukemia and breast cancer. Mapping biopsy was performed in 14 of the 18 type 1a cases. All patients were free of disease at the surgical margins and are alive without recurrence. The four patients with type 1b or 1c disease had lymph node metastases. Two has died of disease, and two are alive with no recurrence. The rate of secondary malignancy seems to be low in primary cutaneous Paget's disease of the vulva. Mapping biopsy with careful examination of characteristic skin surface may be useful for surgery of type 1a cases. Inguinal lymphadenectomy is recommended in cases with question of invasion or known underlying adenocarcinoma.

Adenocarcinoma↗

Determination of iron status in women attending genitourinary clinics with pruritus vulvae.

OBJECTIVE: To compare iron status in women with pruritus vulvae and in asymptomatic controls. METHODS: 42 women with pruritus vulvae and 42 asymptomatic broadly age-matched controls were enrolled in this prospective study. The outcome measures assessed were serum iron, serum ferritin, total iron-binding capacity, haemoglobin and transferrin saturation. RESULTS: 12 (29%) participants and 10 (24%) controls were iron deficient; 1 (2%) participant and 1 (2%) control had laboratory-defined iron deficiency anaemia. Participants generally had lower levels of iron markers than controls, with differences (95% confidence interval (CI)) of -3.5 microg/l (-9.89 to 6.99) for serum ferritin (p = 0.73), -4.9 mmol/l (-8.12 to 0.12) for serum iron (p = 0.06) and -5.5 mmol/l (-5.75 to 1.46) for total iron-binding capacity (p = 0.24). No significant difference in haemoglobin or mean cell volume was shown between the two groups (haemoglobin: p = 0.17, 95% CI -0.83 to 0.15; mean cell volume: p = 0.15, 95% CI -4.59 to 0.73). CONCLUSION: This study does not provide evidence to support the routine determination of iron status in patients presenting to genitourinary medicine clinics with pruritus vulvae from all causes.

Adult↗

Impact of inguinal dissection on prognosis of early-stage squamous cell carcinoma of the vulva--a retrospective analysis.

BACKGROUND: Inclusion of inguinal lymphadenectomy in the surgical procedure is a potential prognostic factor for squamous cell vulvar carcinoma. PATIENTS AND METHODS: A total of 33 women with early-stage squamous cell vulvar carcinoma were analyzed retrospectively. Before the establishment of FIGO criteria in 1983, 17 patients with stage I and 2 patients with stage II were evaluated clinically without inguinal lymphadenectomy. All patients underwent post-operative radiotherapy with a median dose of 45 Gy to the pelvis (vulva included) and boost dose to the vulva ranging from 10 to 20 Gy. Factors assessed for prognostic value included age, inguinal lymph node dissection, differentiation grade, and total irradiation dose to the vulva and pelvis. RESULTS: The log-rank test and the univariate regression analysis revealed that all above factors except irradiation dose decreased the overall survival. In the multivariate regression analysis, differentiation grade and the absence of inguinal dissection were independent predictors for decreased survival with a relative risk up to 2.6 (95% CI = 1.3, 5.6) and 2.7 (95% CI = 1.31, 5.44), respectively. CONCLUSION: Clinical evaluation of inguinal lymph node involvement is inadequate and node dissection is definitely the only appropriate surgical procedure for vulvar carcinoma.

Actuarial Analysis↗

The Pristionchus HOX gene Ppa-lin-39 inhibits programmed cell death to specify the vulva equivalence group and is not required during vulval induction.

In the two nematode species Caenorhabditis elegans and Pristionchus pacificus the vulva equivalence group in the central body region is specified by the Hox gene lin-39. C. elegans lin-39 mutants are vulvaless and the vulval precursor cells fuse with the surrounding hypodermis, whereas in P. pacificus lin-39 mutants the vulval precursor cells die by apoptosis. Mechanistically, LIN-39 might inhibit non-vulval fate (cell fusion in C. elegans, apoptosis in P. pacificus), promote vulval fate or do both. To study the mechanism of lin-39 function, we isolated P. pacificus cell death mutants and identified mutations in ced-3. Surprisingly, P. pacificus ced-3; lin-39 double mutants form a functional vulva in the absence of LIN-39 activity. Thus, in P. pacificus lin-39 specifies the vulva equivalence group by inhibiting programmed cell death. Furthermore, these data reveal an important difference in a later function of lin-39 between the two species. In C. elegans, LIN-39 specifies vulval cell fates in response to inductive RAS signaling, and in P. pacificus LIN-39 is not required for vulval induction. Thus, the comparative analysis indicates that lin-39 has distinct functions in both species although the gene is acting in a homologous developmental system.

Animals↗

Caenorhabditis elegans syndecan (SDN-1) is required for normal egg laying and associates with the nervous system and the vulva.

In Caenorhabditis elegans, the identification of many enzymes involved in the synthesis and modification of glycosaminoglycans (GAGs), essential components of proteoglycans, has attained special attention in recent years. Mutations in all the genes that encode for GAG biosynthetic enzymes show defects in the development of the vulva, specifically in the invagination of the vulval epithelium. Mutants for certain heparan sulfate modifying enzymes present axonal and cellular guidance defects in specific neuronal classes. Although most of the enzymes involved in the biosynthesis and modification of heparan sulfate have been characterized in C. elegans, little is known regarding the core proteins to which these GAGs covalently bind in proteoglycans. A single syndecan homologue (sdn-1) has been identified in the C. elegans genome through sequence analysis. In the present study, we show that C. elegans synthesizes sulfated proteoglycans, seen as three distinct species in western blot analysis. In the sdn-1 (ok449) deletion mutant allele we observed the lack of one species, which corresponds to a 50 kDa product after heparitinase treatment. The expression of sdn-1 mRNA and sequencing revealed that sdn-1 (ok449) deletion mutants lack two glycosylation sites. Hence, the missing protein in the western blot analysis probably corresponds to SDN-1. In addition, we show that SDN-1 localizes to the C. elegans nerve ring, nerve cords and to the vulva. SDN-1 is found specifically phosphorylated in nerve ring neurons and in the vulva, in both wild-type worms and sdn-1 (ok449) deletion mutants. These mutants show a defective egg-laying phenotype. Our results show for the first time, the identification, localization and some functional aspects of syndecan in the nematode C. elegans.

Alleles↗

Influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs: 38 cases (1990-1999).

OBJECTIVE: To determine influence of vestibulovaginal stenosis, pelvic bladder, and recessed vulva on response to treatment for clinical signs of lower urinary tract disease in dogs. DESIGN: Retrospective study. ANIMALS: 38 spayed female dogs. PROCEDURE: Medical records and client follow-up were reviewed for dogs evaluated via excretory urography because of clinical signs of lower urinary tract disease. Clinical signs, results of radiography, and response to surgical or medical treatment were analyzed. RESULTS: Clinical signs included urinary tract infection (n = 24), urinary incontinence (20), vaginitis (11), pollakiuria or stranguria (10), and perivulvar dermatitis (4). Vaginocystourethrographic findings included vestibulovaginal stenosis (n = 28), pelvic bladder (17), and ureteritis or pyelonephritis (4). Ten dogs had a vestibulovaginal ratio of < 0.20 (severe stenosis), 9 dogs had a ratio of 0.20 to 0.25 (moderate stenosis), 9 dogs had a ratio of 0.26 to 0.35 (mild stenosis), and 10 dogs had a ratio of > 0.35 (anatomically normal). Lower urinary tract infection, incontinence, and pelvic bladder were not associated with response to treatment for recessed vulva. Vestibulovaginal stenosis with a ratio < 0.20 was significantly associated negatively with response to treatment. Dogs without severe vestibulovaginal stenosis that received vulvoplasty for a recessed vulva responded well to treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Vestibulovaginal stenosis is likely an important factor in dogs with vestibulovaginal ratio < 0.20. Vaginectomy or resection and anastomosis should be considered in dogs with severe vestibulovaginal stenosis and signs of lower urinary tract disease.

Anastomosis, Surgical↗

[Cancer of the vulva and pregnancy: two cases and review of the literature].

The cancer of vulva is predominantly a disease of postmenopausal women. But some cases have been reported in young women during pregnancy. Surgical management during pregnancy depends on several factors: gestational age at the diagnosis, lesion size, depth and location, lymph node status. We have conducted a national survey and report here the only two cases of squamous cell carcinoma diagnosed and treated during pregnancy at 26 and 15 weeks gestation. All vulva symptoms without signs of infectious should be examined with attention in order to detect vulvar lesions. When in doubt, a biopsy must be obtained. Management of vulva carcinoma is not modified during pregnancy, but the age of pregnancy must be considered.

Adult↗

A case of vulvar metastasis from rectal cancer--regional resection of the right vulva labium and vulvar reconstruction with a rhomboid transposition flap: case report.

A 72-year-old woman visited our hospital to clarify the etiology of pain, swelling and ulceration of the right large vulva labium. Rectal cancer and pulmonary metastatic tumor were detected, and the rectal cancer was resected. Biopsy from the right vulva labium revealed that the vulvar tumor was a metastatic cancer originating from rectal cancer. Our patient underwent regional resection of the right vulva labium and the area lacking tissue was covered by a rhomboid transposition flap. Our patient experienced necrosis of the tip of the flap and the wound was healed by secondary intention.

Aged↗

Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group.

Although cure rates are high, the morbidity of radical operation for carcinoma of the vulva is substantial. Between 1983-1989, member institutions of the Gynecologic Oncology Group entered 155 patients in a prospective evaluation of modified radical hemivulvectomy and ipsilateral inguinal lymphadenecctomy for clinical stage I vulvar cancer. Only patients with neoplastic thickness of 5 mm or less, without vascular space invasion, and negative inguinal lymph nodes were eligible for this study. There have been 19 recurrences and seven deaths from disease among the 121 eligible and evaluable patients. Patients whose disease recurred on the vulva were frequently (eight of ten patients) salvaged by further operation. Five of the seven deaths due to cancer occurred among patients whose first recurrence was in the groin. Acute and long-term morbidity as well as hospital stay were each less than in the Group's previous experience in a comparable patient population treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. There was a significantly increased risk of recurrence but not death when compared with these same historic controls. Modified radical hemivulvectomy and ipsilateral inguinal lymphadenectomy is an alternative to traditional radical operation for these selected patients with stage I carcinoma of the vulva. The number of patients who experienced recurrence in the operated groin is of concern and may be attributable to the decision to leave the femoral nodes intact.

Adult↗

Microbiology of specialized skin: the vulva.

Human vulvar skin is an example of specialized skin. This is not only true for its gross and microscopic anatomy and physiology, but also for its microbiology. To the microbiologist, the vulva consists of several distinct ecotopes. These are defined by the physical factors, especially occlusion, nutrient factors, and by the close proximity to the vagina, the urethra, and the anus, which may result in contamination with the flora typical for those sites. Of the vulva ecotopes, only the labia majora have been seriously studied. The microbial flora of the labia majora is characterized by a high density of microorganisms, as is typical for occluded areas of the body, by the presence of organisms common for intertriginous skin such as gram-negative rods, and by the carriage of organisms unique for the vulva and probably related to urethral and vaginal flora such as the nonpathogenic neisseria, lactobacilli, and Gardnerella vaginalis. Finally, the labia majora skin is a preferred site of Staphylococcus aureus carriage that can be of clinical and epidemiological relevance.

Female↗

Adhesion of Corynebacterium pilosum by pili to epithelial cells of bovine vulva.

Piliated (P+) and nonpiliated (P-) clones of Corynebacterium pilosum were selected, and their adhesion to the epithelial cells of the bovine vulva and vaginal vestibule was examined. The number of P+ bacteria of C pilosum that adhered to vulval epithelial cells was greater than that of P- bacteria. The adhesion of P+ bacteria, but not P- bacteria, to the epithelial cells was inhibited by the antipilus antiserum; therefore, the adhesion of C pilosum to the epithelial cells of the vulva was primarily dependent on the pili. The number of C pilosum that adhered to the epithelial cells of the bovine vulva and of the vaginal vestibule increased by decreasing the pH.

Adhesiveness↗

Scanning electron microscopic study of the vulva of some trichurids (Nematoda).

The structure of vulva of four Trichocephalus species has been studied using scanning electron microscopy (SEM). The shape of vulva and cuticular elements on vulval appendages is described and documented. The cuticular structures on the vulva have a characteristic shape specific for each species. It is suppossed that SEM can be successfully employed in a detailed study of vulval structure, which is an important taxonomic character for the differentiation of females of Trichocephalus species.

Animals↗