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An immunohistochemical study of androgen, oestrogen and progesterone receptors in the vulva and vagina.

OBJECTIVE: To map potential sites of sex steroid action in the human vulva. METHODS: Monoclonal antibodies to androgen, oestrogen and progesterone receptors were used to stain frozen sections of vulval skin, vagina and suprapubic skin. A scoring system was devised to compare receptor distribution in the epidermis and dermis of skin with vaginal epithelium and stroma. RESULTS: Androgen receptors were seen in epidermal keratinocytes, sebaceous glands, sweat glands, hair follicles and dermal fibroblasts of skin, and epithelial cells and stromal fibroblasts of the vagina. Androgen receptor scores were significantly higher in the epidermis of labia majora and minora than in vaginal epithelium. Oestrogen receptors were seen in basal and suprabasal cells of vaginal epithelium and epidermis of labia minora but were restricted to basal keratinocytes in true skin. They were seen in stromal fibroblasts and vaginal smooth muscle, and dermal fibroblasts of the skin. Oestrogen receptors were highest in vaginal epithelium and stroma, and lowest in suprapubic skin. Progesterone receptors were seen in vaginal epithelium, fibroblasts and smooth muscle but not in the vulva. There was no evidence of significant differences in androgen or oestrogen receptor staining in the vulva of pre- or postmenopausal women. CONCLUSION: The transition from vagina to vulva is marked by an increase in androgen and a decrease in oestrogen and progesterone receptors. This distribution of receptors would indicate a limited role for oestrogen creams on the vulva.

Adult↗

Changes of induction and competence during the evolution of vulva development in nematodes.

In Caenorhabditis, the vulva is formed in the central body region from three of six equivalent cells and is induced by the gonad. In some nematodes, however, the vulva is located in the posterior body region. Vulval development has been analyzed in three such genera. The same precursor cells give rise to the vulva in Caenorhabditis and in the posterior vulva species, but in the latter the cells first migrate posteriorly. In two such species, the vulva is not induced by the gonad, but instead relies on intrinsic properties of precursor cells. Thus, evolution of organ position involves changes in induction and competence.

Animals↗

Formation of the vulva in Caenorhabditis elegans: a paradigm for organogenesis.

The genes involved in the inductive interactions that specify cell fates in the vulva of Caenorhabditis elegans are known in some detail. However, little is known about the morphogenesis of this organ. Using a combination of cell biological and anatomical approaches, we have determined a complete morphogenetic pathway of cellular events that lead to the formation of the vulva. These events include reproducible cell divisions, migrations, remodeling of adherens junctions, cell fusions and muscle attachments. In the course of these events, an epithelial channel comprising a stack of 7 toroidal cells is formed that connects the internal epithelium of the uterus with the external body epithelium, forming the vulva. Vulval muscles attach to the epithelial channel and the whole structure everts during the final molt. The mature vulva has rotational, two-fold symmetry. Using laser microsurgery, we found that the two halves of the vulva develop autonomously.

Animals↗

Novel cell-cell interactions during vulva development in Pristionchus pacificus.

Vulva development differs between Caenorhabditis elegans and Pristionchus pacificus in several ways. Seven of 12 ventral epidermal cells in P. pacificus die of apoptosis, whereas homologous cells in C. elegans fuse with the hypodermal syncytium. Vulva induction is a one-step process in C. elegans, but requires a continuous interaction between the gonad and the epidermis in P. pacificus. Here we describe several novel cell-cell interactions in P. pacificus, focusing on the vulva precursor cell P8.p and the mesoblast M. P8.p in P. pacificus, unlike its homologous cell in C. elegans, is incompetent to respond to gonadal signaling in the absence of other vulva precursor cells, but can respond to lateral signaling from a neighboring vulval precursor. P8.p provides an inhibitory signal that determines the developmental competence of P(5,7).p. This lateral inhibition acts via the mesoblast M and is regulated by the homeotic gene Ppa-mab-5. In Ppa-mab-5 mutants, M is misspecified and provides inductive signaling to the vulval precursor cells, including P8.p. Taken together, vulva development in P. pacificus displays novel cell-cell interactions involving the mesoblast M and P8.p. In particular, P8.p represents a new ventral epidermal cell type, which is characterized by novel interactions and a specific response to gonadal signaling.

Animals↗

Housing of pregnant sows in loose and confined systems--a field study 1. Vulva and body lesions, culling reasons and production results.

A field study was carried out in 18 herds with loose housing of pregnant sows (loose herds) and in 18 herds with tethered or stalled pregnant sows (confined herds). Three of the loose herds were excluded due to different kind of flooring from the rest of the herds. The remaining 15 herds had partly slatted concrete floors and electronic sow feeding. The frequencies of sows with vulva and body lesions, thin sows as well as the culling reasons and production results were used as animal welfare indicators for the herds. Vulva lesions were found only in the loose herds and the mean prevalence proportion of sows with lesions within these herds was 15.2%. All vulva lesions observed in this study seemed to be caused by biting. The relative risk of vulva lesions was 2.6 times higher in the loose herds with no roughage feeding as compared to loose herds with appetite feeding of roughage. The sows in the loose herds, that had a feeding station with a mechanical hind gate had 1.8 greater risk of vulva lesions than sows in the loose herds that used a feeding station with an electronic gate. The mean prevalence proportion of sows with body lesions was 13.1% in the loose herds and 4.0% in the confined herds. Aggression between sows seemed to be the main cause of body lesions in the loose herds, while decubitus ulcers on the shoulders were the main cause of body lesions in the confined herds. Sows in loose herds that were not fed additional roughage feeding had 1.7 times greater risk of body lesions than sows in herds that used additional roughage feeding. The main culling reasons and production results were similar in the loose and confined herds. This study showed that there were welfare problems both in confined and loose herds, however, with improved management, many of the welfare problems associated with loose housing can be reduced.

Animal Feed↗

Risk factors for vulva biting in breeding sows in south-west England.

A postal survey was conducted on 410 pig farms in south-west England to investigate the risk factors for vulva biting. The results of the bivariate analyses indicated that group housing, keeping a boar in the same pen and the number of sows per drinker were significantly associated (P < or = 0.05) with vulva biting in service sows. Group housing, group size, keeping a boar in the same pen, straw bedding, electronic sow feeders, feeding once daily, providing water automatically and the number of sows per drinker were significantly associated with vulva biting in dry sows. Vulva biting was also significantly associated with an increased percentage of culled sows and the occurrence of tail biting on the farm. A logistic regression analysis showed that group size and the number of sows per drinker were significant risk factors for vulva biting in service sows, and once a day feeding, group size, the number of sows per drinker and providing water automatically were significant risk factors for dry sows.

Animal Husbandry↗

Merkel's cell (neuroendocrine) carcinoma of the vulva.

BACKGROUND: Merkel's cell carcinoma rarely arises in the vulva. It is unclear whether those cases arising in the vulva behave differently from the usual Merkel's cell carcinomas. METHODS: A Merkel's cell carcinoma of the vulva was studied by light microscopy, immunohistochemistry, and electron microscopy. The clinical data of this case and of other reported cases are summarized and compared with those of Merkel's cell carcinoma in general. RESULTS: This tumor showed the characteristic trabecular pattern of Merkel's cell carcinoma. The tumor cells were immunoreactive to low-molecular-weight cytokeratin and neuron-specific enolase. This patient was treated initially with local excision. She died 17 months later with progressive metastatic disease unresponsive to chemotherapy. This case study and the review of six other cases indicate that Merkel's cell carcinoma of the vulva is universally metastatic, both to the regional lymph nodes and distant sites, and that it invariably follows a rapidly fatal course. CONCLUSION: Merkel's cell carcinoma of the vulva appears to have a biologic behavior more aggressive than that of Merkel's cell carcinoma in general. An initial modality combining chemotherapy, with or without irradiation, with aggressive surgery should be tried in future cases.

Adult↗

Early invasive and in situ warty carcinoma of the vulva: clinical, histologic, and electron microscopic study with particular reference to viral association.

Cases of carcinoma of the vulva with a warty appearance were reviewed. Altogether, 27 cases of warty carcinoma of the vulva were treated at the University of Minnesota Hospitals between 1976 and 1980, which accounted for 22.4% of all vulvar epithelial malignancies. As compared to the previous experience between 1951 and 1970, this relative frequency increased fourfold. Clinical history indicated that warty carcinoma of the vulva was not necessarily preceded by long lead periods of in situ lesions. The lesions seemed to occur in all ages after adolescence, were multifocal in one third of the cases, were frequently locally recurring, and were relatively benign despite their often large size. Many of them were originally diagnosed as condyloma acuminatum. Virus-like particles were seen in eight of the 12 cases (67%) examined with transmission electron microscopy, which included six cases of invasive lesions. These observations suggest that human papillomavirus (HPV) may be the important etiologic agent of this group of tumors. Warty carcinoma of the vulva must be clearly separated from conventional invasive squamous cell carcinoma of the vulva, as its clinical behavior and a possible etiology appear unique.

Adult↗

Some epidemiologic aspects of carcinoma of the vulva in Israel.

A nationwide study of squamous cell carcinoma of the vulva in Israeli Jewish women has been conducted for a comparison of the incidence, the age pattern and the ethnic distribution of squamous cell carcinoma of the vulva to those of squamous cell carcinoma of the cervix. The mean annual incidence rates by age in squamous cell carcinoma of the vulva rise continuously to age 70 + while in squamous cell carcinoma of the cervix a plateau is reached at age 40 to age 69. In contrast to the relatively low incidence of squamous cell carcinoma of the cervix in Israeli Jewish women, the age-specific incidence rates of squamous cell carcinoma of the vulva are similar to those of white women in the United States. On the other hand, there is a trend to a higher incidence of both squamous cell carcinoma of the cervix and squamous cell carcinoma of the vulva in the North African ethnic group of Israeli Jewish women.

Adult↗

Paget's disease of the vulva.

Thirty-six patients with Paget's disease of the vulva were reviewed. Median age of the patients at diagnosis was 64 years (range 41-84 years). Five patients (14%) had an associated invasive adenocarcinoma of the vulva at the time of diagnosis. Of 31 patients with superficial noninvasive Paget's disease, 28 were available for follow-up. Treatment of patients with superficial Paget's disease was surgical and based on the extent of disease. Procedures performed included total vulvectomy (25), wide local excision (4), and skinning vulvectomy with skin graft (1). The median follow-up was 108 months (range 6-266 months). Twenty-two of twenty-eight patients remained free of disease. Six patients have required multiple procedures for recurrent superficial Paget's disease. Treatment of Paget's disease of the vulva is surgical. Radical surgery is the preferred treatment of patients with an associated invasive adenocarcinoma; three of five patients with an invasive adenocarcinoma were long-term survivors. Patients with superficial Paget's disease of the vulva should be treated by local excision utilizing frozen-section margin evaluation as a guide to extent of excision. Only one patient with an initial diagnosis of superficial Paget's disease of the vulva developed invasive adenocarcinoma.

Adenocarcinoma↗

Endometrial carcinoma metastatic to the vulva: a case report and review of the literature.

In this paper, we report a new case of metastatic endometrial carcinoma to the vulva and describe the clinical and pathological features. We reviewed the literature to determine the frequency and to evaluate the prognostic significance of this rare disease. Moreover, we discuss the criteria for the differential diagnosis of endometrial carcinoma metastatic to the vulva, the primary vulvar adenocarcinomas, and other metastatic adenocarcinomas. The patient, previously diagnosed to have endometrial adenocarcinoma with squamous differentiation at III C stage (according to the FIGO system) and T2N1M0 stage (according to the TNM system), presented with a small plaque on the vulvar mucosa 8 months after endometrial primary carcinoma had been diagnosed. The histological evaluation of excisional vulvar biopsy revealed a neoplasm with pathological features of endometrial carcinoma. Thus, the final diagnosis was metastatic endometrial carcinoma to the vulva. A total body computed tomography scan (CT) and an echotomography with contrast medium revealed a second metastatic lesion at the 8th segment of the liver. No other metastatic lesions developed, nor was a reduction in the size of liver metastasis observed after 3 months of hormonic treatment with progesterone. Fourteen months after the diagnosis of primary endometrial carcinoma, the patient died of disseminated metastatic lesions. In conclusion, metastatic endometrial carcinoma to the vulva, although rare, might develop and could appear within a few months after the diagnosis of primary tumor. Moreover, in the presence of metastatic endometrial carcinoma to the vulva, it is necessary to verify if other visceral metastases are present.

Adenocarcinoma↗

HER-2/neu expression in Paget disease of the vulva and the female breast.

OBJECTIVES: Paget disease of the vulva is a rare lesion that accounts for <1% of vulva neoplasms. A 12% prevalence of invasive Paget carcinoma and a 4% prevalence of associated adenocarcinomas are described. Furthermore, a high recurrence rate of 30% after surgical therapy is observed. This study aims to search for therapeutic strategies for recurrent Paget disease, which are less mutilating and less aggressive than reexcision, x-ray therapy, or chemotherapy. Trastuzumab (Herceptin) is a recombinant monoclonal antibody against HER-2/neu, approved by the U.S. FDA for the treatment of patients with HER-2/neu-positive metastatic breast carcinomas. The results of recent studies indicate that HER-2/neu oncoprotein may play a role in the pathogenesis of extramammary Paget disease. METHODS: Using HercepTest, we analyzed HER-2/neu overexpression in seven noninvasive Paget lesions, two invasive lesions, and one Paget disease of the vulva with underlying adenocarcinoma. In addition, we investigated five mammary Paget diseases. RESULTS: Overexpression of HER-2/neu oncoprotein labeling exclusively the membranes of Paget cells was demonstrated in 8 out of 10 cases. One noninvasive and one with underlying adenocarcinoma stained negatively. Overexpression of HER-2/neu was demonstrated in all five cases of mammary Paget disease. CONCLUSION: Using HercepTest as a standardized detection system, overexpression of HER-2/neu can be demonstrated in a majority of both noninvasive and invasive Paget disease of the vulva. The use of Trastuzumab should be considered for the treatment of patients with recurrent Paget disease of the vulva with overexpression of HER-2/neu.

Adenocarcinoma↗

The treatment of lateral T1 and T2 squamous cell carcinomas of the vulva confined to the labium majus or minus.

OBJECTIVE: To determine the pattern of lymph node metastases, recurrence rate, and survival of patients with lateral T1 and T2 squamous cell cancer (SCC) of the vulva treated by radical vulvectomy or hemivulvectomy and inguinal lymphadenectomy. METHODS: An institutional review was performed to identify lateral T1 and T2 SCC of the vulva confined to the labium majus and minus. RESULTS: Sixty-one patients with lateral T1 and 61 patients with lateral T2 SCC of the vulva were treated from 1963 to 2003. Radical vulvectomy (RV) was performed in 60 patients, and radical hemivulvectomy (RHV) in 62 patients. Seven of 61 patients (11%) with T1 lesions had ipsilateral superficial inguinal lymph node (SIL) metastases, but none had deep inguinal lymph (DIL) node metastases. Nineteen of 61 patients (31%) with T2 lesions had ipsilateral SIL metastases, and 8 had ipsilateral DIL metastases. No patient had contralateral SIL or DIL metastases. Six patients (10%) with T1 lesions and seven patients (11%) with T2 lesions developed recurrence to the ipsilateral vulva and were treated by re-excision. All patients are alive with no evidence of disease 10-195 months after treatment. One patient with T1 and three patients with T2 SCC developed distant recurrence and died of disease (DOD) 10-15 months after surgery. Disease-free survival of patients with T1 lesions was 98% at 2 years and 98% at 5 years, and with T2 lesions was 95% at 2 years and 93% at 5 years. Local or distant recurrence was not more common in patients treated by RHV than in those treated by RV. CONCLUSION: Lateral T1 and T2 squamous cell cancers of the vulva spread to the ipsilateral inguinal lymph nodes and can be treated effectively with RHV and ipsilateral SIL dissection. Deep inguinal lymphadenectomy is indicated only when the SIL are positive.

Adult↗

[Malignant mesothelioma of the vulva. About one case].

Most malignant mesotheliomas are pleural; they rarely occur within the peritoneum and their location in the vulva is exceptional. A case of a malignant mesothelioma of the vulva is reported in a 47-year-old woman. The patient was operated for a tumour of the vulva. The preoperative diagnosis was that of a cyst of the Bartholin's gland or a fibroma. The microscopic and immunohistochemical exam confirmed the diagnosis of a biphasic malignant mesothelioma of the vulva. The computed tomography scan of the chest and the abdomen was normal. A local recurrence of the tumour occurred in spite of the postoperative radiotherapy. Our objective about this particular case is to discuss the clinical and pathologic aspects and the diagnostic problems of this exceptional tumour of the vulva.

Female↗

Ductal carcinoma in-situ arising in mammary-like glands of the vulva.

Recently a variant of cutaneous glands has been recognized in the anogenital region that combines the morphologic and immunohistochemical features of eccrine, apocrine, and mammary glands, so-called 'mammary-like glands of the vulva'. Carcinoma arising in mammary-like tissue of the vulva is a rare occurrence. So far, there have been 11 cases of primary, mammary-type invasive carcinoma and one case of in-situ carcinoma reported in the vulva. We describe an unusual case of ductal carcinoma in-situ without invasion arising in mammary-like glands of the vulva. A 57-year old woman presented with a 1-year history of a 1 cm nodule in the right labium majus. Excision showed ductal carcinoma in-situ with cribriform and papillary morphology in an adenosis-like lesion associated with mammary-like glands. No invasion into the stroma was identified. Immunostains were positive for gross cystic disease fluid protein 15 (GCDFP-15) and estrogen and progesterone receptors. An extensive survey including bilateral mammograms was negative. One year postoperatively, the patient shows no evidence of disease. To our knowledge, this represents the second case of DCIS associated with mammary-like glands of the vulva reported in the English literature.

Biomarkers↗

Malignant melanoma associated with lichen sclerosus in the vulva of a 10-year-old.

Malignant melanoma of the vulva in childhood is a rare neoplasm. Lichen sclerosus of the vulva in childhood is also a rare disease. The association of these two rare lesions in the vulva of young girls is extremely rare. We present a 10-year-old white girl with malignant melanoma associated with lichen sclerosus of the vulva. She had dark pigmentation of both the labia minora and posterior fourchette. The inner labia majora and fourchette showed whitish, glistening areas of skin. Histologic examination found mostly an in situ lentiginous/mucosal melanoma with focal invasion to a depth of 0.44 mm in the left upper labium majus. All specimens showed evidence of lichen sclerosus. Partial vulvectomy was performed, and no metastases were detected at the time of treatment. The patient has been disease free for the 12 months after treatment. It is critical for physicians to realize that melanoma can occur in children, and although rare, can occur in the vulva. We feel that lichen sclerosus in this instance may represent a pattern of host immune response to melanoma.

Child↗

Coexistence of verrucous and squamous carcinoma of the vulva.

AIM: To evaluate the coexistence of verrucous and squamous carcinoma of the vulva and to assess the clinical course, survival and rate of recurrent disease of these patients. METHODS: The records of 17 patients who were diagnosed with verrucous carcinoma of the vulva over a 12-year period were studied retrospectively. Presence of genuine verrucous carcinoma or coexistence of verrucous and squamous carcinoma of the vulva on vulvar biopsies, results of histopathological assessment of final vulva and inguino-femoral node specimens and histological evaluation of recurrent disease specimens were the main outcome measures. RESULTS: Five of the 17 patients (29.5%) initially underwent radical vulvectomy and inguino-femoral lymphadenectomy. Histology of the specimens verified the coexistence of verrucous and squamous carcinomas in four of the five cases. Twelve women (70.5%) underwent simple vulvectomy for genuine verrucous carcinoma; in the final histology, 10 of these women (58.8%) were confirmed as having genuine verrucous carcinomas while two (11.7%) were found to have both verrucous and squamous carcinomas and were further managed by lymphadenectomy. None of our patients died of the disease. Three women (17.5%) presented with local relapse of the tumour, and were managed by wide local excision of the tumour. CONCLUSIONS: In the present study, 35% of patients with verrucous carcinomas of the vulva had coexistent squamous carcinoma. Separation of the cases of genuine verrucous carcinoma from coexistent verrucous and squamous tumours is based on the establishment of correct diagnosis by a large and deep vulvar biopsy as well as the meticulous assessment of the specimen by the pathologist. This will result in the decrease of the rate of over- and under-treatment of these patients.

Aged↗

[A case of Paget's disease of the vulva with bladder metastasis].

A very rare case of bladder metastasis of the Paget's disease of the vulva is reported. A 83-year-old woman first experienced an eczematoid eruption on the vulva 12 years earlier. It was diagnosed as Paget's disease of the vulva and treated with radiation 8 years earlier. In March, 1985 a biopsy of the vulva revealed a recurrence of Paget's disease. In August, 1986 she had a sudden attack of left flank pain. The excretory urogram showed bilateral hydronephrosis and transurethral echogram of the bladder demonstrated large nodular tumors of the bladder. Transurethral biopsies of the bladder revealed Paget's disease. Total cystourethrectomy with bilateral ureterocutaneostomy and wide skin excision of the vulva with skin transplantation were performed. The pathological specimen showed several yellowish-white nodular tumors of the bladder, which obstructed both ureteral orifices. Microscopically typical Paget's cells were seen, some of which were stained with PAS before and after amylase and with alcian blue. Postoperatively she developed a severe complication of necrosis of the small intestine due to thrombosis of superior mesenteric artery and died of panperitonitis on the 55th postoperative day. Related reports were also reviewed.

Aged↗