'See and treat' approach for high-grade squamous intraepithelial cervical lesions.

PURPOSE OF INVESTIGATION: Evaluation of the over-treatment percentage when choosing a 'see and treat' approach in patients with de- viant cervical smear test results. MATERIALS AND METHODS: The authors performed a retrospective chart review among women who were treated for cytological low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL) from January 2009 until December 2010. All patients who were treated for deviant Pap-smears were analyzed. Patient characteristics were taken into account when performing the analysis. Data were analyzed using SPSS. Logistic regression was performed to determine the influence of age, smoking, and the reason to perform the Pap-smear. RESULTS: A total of 723 patients with deviant Pap-smear results were analysed. High-grade cervical intraepithelial neoplasia (CIN) was found in 70.3% of the patients with a Pap 3A average dysplasia (low-grade squamous intraepithelial lesion). This indicates that 29.7% of the patients would be over-treated with a 'see and treat' approach. For Pap 3B (high-grade intra-epithelial lesion) or higher the over-treatment percentage was 6.7% or less. CONCLUSION: Potential risks of a loop electrosurgical excision procedure (LEEP) on future pregnancies and fertility should be taken into account when treating fertile patients for potential CIN. This should be part of the counseling process of patients with a Pap 3A average dysplasia. A 'see and treat' approach can and probably should be proposed to patients with a Pap 3B or higher.

[Manifest carcinoma of the glandula vestibularis major (Bartholin's gland), detected one year after an inguinal lymph-node metastasis]. / Manifest carcinoom van de glandula vestibularis major (Bartholini), gedetecteerd één jaar na een lieskliermetastase.

A 68-year-old woman had had a TNM stage-III rectal carcinoma at the age of 54 for which she had undergone a low anterior resection followed by postoperative radiotherapy and adjuvant chemotherapy with fluorouracil and levamisol. More than 10 years later she presented with a swelling in the right groin, which turned out to be a metastasis; this was a poorly differentiated carcinoma with some of the characteristics of a transitional epithelial carcinoma, for which no primary tumour was found. The lymph node was excised. One year later, a swelling was detected on the labium majus, caused by a poorly differentiated transitional epithelial carcinoma of the glandula vestibularis major (Bartholin's gland). The patient was treated by means ofhemivulvectomy and postoperative radiotherapy.

Combining HPV and MIB-1 tests reduces the number of colposcopies in women with equivocal cytology.

BACKGROUND: In this study the MIB-1 immunostaining pattern as an index of cellular proliferation was analyzed in smears diagnosed as borderline dyskaryosis in order to establish whether the combination of human papillomavirus testing and MIB-1 staining could resolve equivocal cytology. METHODS: Conventional Pap smears of 108 women diagnosed as borderline dyskaryosis were stained with MIB-1 and the proliferation index was assessed. These women were evaluated by colposcopy, histological sampling, and human papillomavirus, semi-quantitative evaluated by hybrid Capture II test. RESULTS: All 64 human papillomavirus- and MIB-1-negative women had no underlying high-grade cervical intraepithelial neoplasia or cervical cancer. Forty of the 104 women with normal histology or cervical intraepithelial neoplasia I were positive for human papillomavirus, compared to only one positive MIB-1 test (i.e. proliferation index of more than 35%). CONCLUSIONS: Adding a MIB-1-test in human papillomavirus-positive women with equivocal cytology might reduce the number of colposcopies needed to predict > or = cervical intraepithelial neoplasia II. With this approach only four instead of 43 human papillomavirus-positive women would have been referred for colposcopy.

Can viral load, semi-quantitatively evaluated, of human papillomavirus predict cytological or histological outcome in women with atypical squamous or glandular cells of undetermined significance cytology?

OBJECTIVE: 1) To assess the regression to normal cytology in women with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) and absence or clearance of human papillomavirus (HPV) infection; 2) To evaluate the association between viral load, semi-quantitatively evaluated, and cytological or histological outcome. MATERIAL AND METHODS: In this cohort study HPV test and biopsy was taken in 148 women with ASCUS/AGUS cytology. After 12-18 months a HPV test and cervical smear were repeated in 121 women. RESULTS: Absence or clearance of HPV showed significantly more regression to normal cytology than persistent or newly acquired infected women, odds ratio 27 (95% confidence interval; 7-103). The viral load of the HPV test at enrollment was not correlated with the follow-up cytological outcome (Spearman correlation coefficient 0.2, p = 0.2). A marked association between viral load and histological outcome at enrollment was shown (Spearman correlation coefficient 0.43, p < 0.0001). CONCLUSION: Absence or clearance of HPV can predict regression to normal cytology. Viral load at enrollment cannot predict cytological regression. There was a marked association between viral load and the underlying CIN at enrollment. However, there was large overlapping of viral loads among the grades of CIN. Therefore, viral load is not a useful parameter to predict high-grade lesions in women with ASCUS/AGUS cytology.

Intraoperative detection of carcinoid tumor of the ovary by gamma probe.

PURPOSE: To demonstrate the detection of carcinoid tumor of the ovary by gamma probe during surgery in a patient in whom the exact location of a metastatic tumor was uncertain. METHODS: Twenty-four hours after injection of 350 MBq (9.5 mCi) I-123, an anterior image of the abdomen was acquired before surgery to demonstrate MIBG accumulation. Holding the ovary in the hand during the operation, a surgical gamma probe indicated the exact location of highest radioactivity. RESULTS/CONCLUSIONS: Intraoperative MIBG scanning is a useful noninvasive detection method to localize metastases of carcinoid in the ovary. This method should be used only when it is not clear where the area of increased activity is located in the body because there are certain costs involved.

[Female circumcision; histories of 3 patients]. / Vrouwenbesnijdenis; het verhaal van 3 patiënten.

Three Somali women presented with problems of the infibulation they had undergone when they were girls. The first one was 22 years old and had problems with coition, the second one was 21 years old and had problems with parturition, the third one was 28 years old and had an epidermal cyst near the ventral commissure of the vulva. Infibulation is a form of female circumcision, in which the clitoris, labia minora and labia majora are removed and the ostium vaginae is reduced to less than a centimeter. In the Netherlands the Ministry of Health, Wellbeing and Sport and the Association of Obstetricians and Gynaecologists have declared themselves opponents to female genital mutilation carried out by Dutch physicians. The association decided also to not carry out reinfibulation, e.g. after parturition.

[Sickle cell anemia during pregnancy]. / Sikkelcelanemie tijdens de zwangerschap.

A 31-year-old pregnant Creole woman with sickle-cell anaemia went through a crisis of acute cholecystitis at 29 weeks' amenorrhoea. The crisis subsided after cholecystectomy, at which relative reduction of the number of sickle-cells by blood transfusions, adequate oxygenation, fluid, and antibiotic prophylaxis were provided. After 35 weeks' amenorrhoea, a healthy son was delivered by caesarean section. After the delivery, she developed fever and abdominal aches with a wound infection, and 10 days later a generalized epileptic attack. She recovered without sequelae. Pregnancy in a woman with sickle-cell anaemia may induce a sickle-cell crisis. The maternal morbidity and mortality and perinatal mortality are high, in spite of a pronounced decrease due to improved care.

Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin.

OBJECTIVE: To investigate the prevalence of human papillomavirus (HPV) infection in various vulvar lesions. METHODS: HPV infection using consensus primer-PCR was studied in 66 patients with vulvar carcinoma and in the synchronous epithelial lesions. RESULTS: HPV infection was present in 13/66 carcinoma, in 1/33 VIN I, in 3/11 VIN II, in 8/16 VIN III, in 2/30 lichen sclerosus, in 1/37 squamous cell hyperplasia, and in 2/55 normal skin specimens. Normal skin from healthy controls showed HPV-negative specimens only. Patients with HPV-positive carcinomas were younger, presented in lower stages, and had high-grade VIN more often than those with HPV-negative carcinomas. CONCLUSIONS: In sum we found that all types of epithelial changes synchronous with carcinoma of the vulva showed HPV infection, indicating that they all might have malignant potential.

p53 protein overexpression is common and independent of human papillomavirus infection in squamous cell carcinoma of the vulva.

BACKGROUND: Human papillomavirus (HPV) infection and p53 abnormalities might both play a role in the carcinogenesis of subtypes of squamous cell carcinoma of the vulva. In this study, the authors investigated the prevalence of and the relationship between p53 overexpression and HPV infection in patients with vulvar carcinoma. METHODS: Immunohistochemical methods for the detection of p53 protein and consensus primer polymerase chain reaction (PCR) were used, followed by direct sequencing of the PCR product for the evaluation of HPV subtype infection. Sixty-six patients with squamous cell carcinoma of the vulva were available for this study. RESULTS: DO7, an anti-p53 monoclonal antibody, showed p53 overexpression in 35 carcinomas (53%). Consensus primer PCR showed HPV infection in 12 carcinomas (18%). No significant association was observed between p53 overexpression or HPV infection and tumor subtype. Approximately 57% of the HPV negative carcinomas and 33% of the HPV positive carcinomas had p53 overexpression. With regard to the patients with DO7 positivity in > or =50% of the nuclei only, significantly more HPV negative carcinomas were DO7 positive compared with HPV positive carcinomas (41% vs. 0%, respectively; P = 0.018). No relation was found between either HPV infection or p53 overexpression and disease free survival. CONCLUSIONS: p53 overexpression is common in both HPV positive and HPV negative carcinomas of the vulva. These findings indicate that these two both play a role in the pathogenesis of vulvar carcinoma, but do not influence disease free survival.

p53 protein overexpression, a frequent observation in squamous cell carcinoma of the vulva and in various synchronous vulvar epithelia, has no value as a prognostic parameter.

In this study we have investigated the prevalence of p53 overexpression in various vulvar lesions and its significance as a prognostic parameter in patients with vulvar carcinoma. Overexpression of p53 was studied in 66 patients with squamous cell carcinoma of the vulva and in the following synchronous epithelial lesions: intraepithelial neoplasia grade I (VIN I) (n = 33), VIN II (n = 11), VIN III (n = 16), lichen sclerosus (n = 30), squamous cell hyperplasia (n = 37), normal vulvar skin of patients with vulvar carcinoma (n = 55), and in 18 samples of normal skin from healthy controls. Survival curves of the p53-positive and p53-negative patients were compared using the log-rank test. The use of DO7, and anti-p53 monoclonal antibody, showed p53 overexpression in 35 (53%) specimens of carcinoma, in eight (27%) of lichen sclerosus, in five (14%) of squamous cell hyperplasia, in six (18%) of VIN I, in two (18%) of VIN II, in two (13%) of VIN III, and in seven (13%) specimens of normal vulvar skin. Staining of normal skin from healthy controls showed no p53 positive specimens. No relationship between expression of p53 and disease-free survival in patients with vulvar carcinoma was present. In malignant, synchronous premalignant and non-neoplastic epithelial disorders of the vulva, p53 overexpression is a frequent observation, indicating that the latter two groups have characteristics of premalignant lesions. In addition, p53 overexpression was not a useful prognostic parameter for patients with vulvar carcinoma.

The relevance of various vulvar epithelial changes in the early detection of squamous cell carcinoma of the vulva.

The objective of this study is to evaluate the possible relevance of vulvar epithelial changes as a risk factor for squamous cell carcinoma of the vulva. The data of 66 women surgically treated for squamous cell carcinoma of the vulva have been analyzed. More than 6500 slides from the resection specimens were revised with special emphasis on concurrent epithelial changes. Synchronous epithelial changes were seen in 63 patients. Thirty-nine patients had synchronous vulvar intra-epithelial neoplasia grade 1 (VIN I), 10 VIN II and 13 VIN III. Thirty-one patients had synchronous lichen sclerosus and 49 squamous cell hyperplasia. The difference between the percentage of patients with epithelial changes diagnosed preceding their carcinoma (30%) and the percentage of patients that had synchronous epithelial changes after reviewing the specimen (95%) was striking. It was concluded that more careful diagnosis, treatment and follow-up of these conditions might lead to an earlier recognition of squamous cell carcinoma of the vulva and therefore to a better prognosis.

Benign and malignant pathology of the vulva.

In this review, we focus on rare benign and malignant diseases. It is shown that benign vulvar conditions require thorough examination of other parts of the body, because a relationship with systemic diseases, like cicatricial pemphigoid, pemphigus vulgaris, toxic epidermal necrolysis, infections with parasites and Behçet's syndrome, may be present. Co-operation with medical specialists is warranted. One in every 10 malignancies of the vulva is not a squamous cell carcinoma. Apart from melanoma, several other tumors can occur on the vulva. A correct histological diagnosis is of paramount importance because treatment strategies depend on it.

beta-Glucuronidase deficiency as a cause of fetal hydrops.

Mucopolysaccharidosis type VII (MPS VII) was diagnosed in a case of severe fetal hydrops. beta-glucuronidase deficiency was demonstrated in the amniotic fluid, which was obtained at 25 weeks of gestation, and in the fibroblasts of the child, which were cultured after fetal death in the 26th week of gestation. In the amniotic fluid the two-dimensional electrophoresis pattern of glycosaminoglycans was in agreement with MPS VII. Based on these results, prenatal diagnosis could be offered to the couple for the next pregnancy.

The value of routine cervical cultures before transcervical chorionic villus sampling.

In 226 women requesting chorionic villus sampling (CVS), routine cervical cultures were obtained before the procedure. Transcervical CVS was performed irrespective of the test results. The prevalence of potential pathogens in cervical cultures at our institution is low. Beta haemolytic Streptococcus was cultured in 3 per cent of the women. No pathogenic microorganisms were isolated in 64 per cent of the women. There was no relationship between culture results and the outcome of pregnancy. These observations suggest that adequate antiseptic cleansing of the genital tract is a suitable approach and there is no need to routinely perform cultures before CVS.