Cytology of the vulva: feasibility and preliminary results of a new brush.

OBJECTIVE: Taking a biopsy is a standard procedure to make the correct diagnosis in patients with suspicious premalignant vulvar lesions. The use of a less invasive diagnostic tool as triage instrument to determine whether biopsy is necessary may improve patient comfort especially in patients with chronic vulvar disorders that may warrant consecutive biopsies. This study was conducted to investigate whether vulvar brush cytology is feasible and may be used to detect (pre)malignant vulvar lesions. METHODS: A pilot study was performed with patients having clinically normal vulvar skin, lichen sclerosus (LS), usual or differentiated vulvar intraepithelial neoplasia or squamous cell carcinoma. A total of 65 smears were taken with the use of a vulvar brush and biopsies were performed for histopathological analysis. RESULTS: Out of 65 smears, 17 (26%) were discarded because of poor cellularity. A total of 28 of 29 (97%) smears with a histological proven (pre)malignancy had a smear classified as 'suspicious' or 'uncertain'. Cytology classified 11 smears as 'non-suspicious', of which 10 (91%) were indeed normal skin or LS. The accuracy, based on the presence of a lesion, for (pre)malignant lesions with the use of the brush showed a sensitivity of 97% and a negative predictive value of 88%. CONCLUSION: Vulvar brush cytology is feasible and may be a first step in the development of a triage instrument to determine whether subsequent biopsy of a clinically (pre)malignant lesion is necessary.

Bullous lesions of the vulvar region revealing both AL amyloidosis and vulvar carcinoma.

We report a patient with a bullous disorder which revealed both AL amyloidosis and a vulvar squamous cell carcinoma. Bullous amyloidosis is the rarest clinical manifestation of the amyloidoses, and is usually accompanied by systemic amyloid deposition with multiorgan involvement. This case illustrates that a localized disorder can trigger the diagnosis of a systemic disease.

Review of squamous premalignant vulvar lesions.

Vulvar squamous cell carcinoma (SCC) develops following two different pathways, which have their own premalignant lesions. In the absence of human papilloma virus (HPV), vulvar SCC can develop in a background of lichen sclerosus (LS), differentiated vulvar intraepithelial neoplasia (VIN) or both. The other pathway leading to vulvar SCC is associated with HPV and the HPV-associated premalignancy is usual VIN. In this review we will discuss the history, epidemiology, aetiology, histology, clinical characteristics, treatment options, malignant potential and prevention strategies of the three squamous premalignant vulvar lesions.

[Lichen sclerosus]. / Lichen sclerosus.

Lichen sclerosus is a chronic disorder of skin and mucosa which affects patients of all age groups, particularly women, but also men. It is most commonly seen on the female genital skin, but it also occurs on extragenital areas. Most patients complain of itching and, less frequently, a burning sensation, dyspareunia, dysuria and painful defecation are reported. The cause of lichen sclerosus is largely unknown. However, it has been suggested that a genetic predisposition to inflammatory disorders, an immunological constitution, hormonal influences and local factors might play a role. Anogenital lichen sclerosus is associated with an increased incidence of malignancies, especially vulvular squamous-cell carcinomas. The life-time risk of developing this carcinoma is about 5%. Extragenital lichen sclerosus and lichen sclerosus in children do not seem to be correlated with malignancy. Potent local corticosteroids form the mainstay of treatment for lichen sclerosus. The condition is characterised by remissions and exacerbations. Long-term follow-up is required for the early diagnosis of malignant changes.

Management of vulvar cancers.

AIM: The radical surgical approach in the treatment of vulvar cancer patients has led to a favorable prognosis for the majority of the patients with early stage squamous cell cancer. However, the morbidity is impressive, leading to more individualized treatment. The aim of this review is to give an overview of the management of vulvar cancer. METHODS: We have reviewed the literature on the modifications in treatment of vulvar cancer with the emphasis on surgery and radiotherapy for primary disease. RESULTS: While surgery is the cornerstone of treatment for early stage squamous cell vulvar cancer (with wide local excision and uni- or bilateral inguinofemoral lymphadenectomy via separate incisions as standard treatment), until now there has been a limited role for primary radiotherapy although this may be an attractive alternative for the inguinofemoral lymphadenectomy in the future. The sentinel lymph node procedure with the combined technique (preoperative lymphoscintigraphy with (99m)technetium-labeled nanocolloid and Patente Blue) is a promising staging technique for patients with vulvar cancer. The clinical implementation of the sentinel lymph node procedure and the role of additional histopathological techniques of the sentinel lymph nodes have to be investigated. In advanced vulvar cancer, chemoradiation followed by surgery should be regarded as the treatment of first choice for these patients. CONCLUSIONS: Due to the rarity of vulvar cancer it is quite clear that further studies will have to be performed by international collaborative groups. The sentinel lymph node procedure and primary radiotherapy are promising methods to reduce morbidity of treatment, but their safety needs to be studied in clinical trials.

Vulvar squamous cell carcinoma is a multifactorial disease following two separate and independent pathways.

Two separate pathways leading to vulvar carcinoma have been suggested. First, a human papillomavirus (HPV)-dependent pathway, in which premalignant stages of vulvar cancer are the classic vulvar intraepithelial neoplasia (VIN) lesions. Second, an HPV-independent pathway, associated with differentiated VIN III lesions and/or lichen sclerosus. To obtain insight into the mechanisms underlying these pathways, we determined the relationship between HPV DNA and the expression of p14(ARF) and p16(INK4A) in non- and (pre)malignant vulvar lesions. Seventy-three archival samples of non- and (pre)neoplastic vulvar lesions were selected and tested for hr-HPV DNA using a broad-spectrum HPV detection/genotyping assay (SPF(10)-LiPA) and the expression of p14(ARF) and p16(INK4A). The prevalence of HPV increased with the severity of the classic VIN lesions; in VIN I no hr-HPV was detected, in VIN II 43%, and in VIN III 71% of the samples were hr-HPV-positive. Roughly the same was true for the expression of p14(ARF) and p16(INK4A). The simultaneous expression of p14(ARF) and p16(INK4A) was highly associated with the presence of hr-HPV DNA. Hr-HPV was detected in only a single case of the differentiated VIN III lesions, whereas no expression of p14(ARF) was found and 16(INK4A) was present in only two cases. All 16 samples of vulvar cancer were hr-HPV DNA- negative, although in respectively 63% and 25%, p14(ARF) and p16(INK4A) was expressed. No relation was found between hr-HPV and the expression of p14(ARF) and p16(INK4A) in the 20 nonneoplastic vulvar lesions. Our results provide further evidence that vulvar squamous cell carcinoma is a multifactorial disease that develops from two different pathways. First, an HPV-dependent pathway with a remarkable resemblance to CIN lesions and cervical carcinoma and second, an HPV-independent pathway in which differentiated VIN III lesions that are hr-HPV-negative may be precursors.

Down regulation of estrogen receptor expression is an early event in human papillomavirus infected cervical dysplasia.

PURPOSE: To study the alterations in hormonal sensitivity in relation to proliferative activity during the development of cervical dysplasia in women infected with high-risk human papillomavirus (hr-HPV). METHODS: Three to five biopsies of the cervix of eight patients were taken at colposcopy. Dysplasia was detected in 22 of the 32 biopsies, and 20 of these 22 biopsies contained hr-HPV. The labeling index (LI) as well as the intensity of staining of the MIB-1-, estrogen receptor (ER)-, and progesterone receptor (PR)-expression was assessed in each biopsy, including normal epithelium directly adjacent to the dysplastic lesions. RESULTS: Statistical analysis showed a significant increase in the MIB-1 LI with increasing severity of the dysplasia. The ER LI and ER intensity of staining in dysplastic lesions, as well as in morphologically normal epithelium directly adjacent to the dysplasia, showed a significant inverse relation with the severity of the dysplasia. The PR LI and intensity of staining did not differ between normal epithelium and dysplasia. The ER/MIB-1 ratio (including the ER LI and ER intensity of staining), and the PR/MIB-1 ratio (intensity of staining only) in dysplastic lesions showed a significant inverse relation with the severity of the dysplasia, while no alterations in these ratios were observed in morphologically normal epithelium adjacent to the dysplasia. CONCLUSION: Down regulation of ER expression may be the first alteration to take place in normal epithelium during the development of cervical dysplasia in women infected with hr-HPV. The significant decrease in the ER/MIB-1-, and PR/MIB-1-ratio in progressively dysplastic lesions indicates a loss of normal growth control by sex steroid hormones, which is not observed in normal epithelium.