H.P. van de Nieuwenhof

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.

The etiologic role of HPV in vulvar squamous cell carcinoma fine tuned.

Purpose: High-risk human papilloma virus (HPV) plays a role in the development of a subset of vulvar squamous cell carcinomas. Uncertainty exists about the true impact of HPV in this tumor type because conflicting reports have been published with diverging prevalence rates. This study was done to fine tune the role of high-risk HPV infection in vulvar squamous cell carcinoma development in relation to clinical prognosis. Experimental Design: 130 vulvar squamous cell carcinomas of patients with known survival data were analyzed for histology of the adjacent lesion (differentiated or HPV-associated usual vulvar intraepithelial neoplasia), in relation to p16INK4A expression as marker of HPV activity, and presence and integration of high-risk HPV DNA. Results: Usual vulvar intraepithelial neoplasia was present adjacent to vulvar squamous cell carcinoma in 25 of 130 cases. Usual vulvar intraepithelial neoplasia–associated squamous cell carcinomas had high p16INK4A expression, and 24 of 25 squamous cell carcinomas contained integrated high-risk HPV DNA. Differentiated vulvar intraepithelial neoplasia was found adjacent to 105 of 130 vulvar squamous cell carcinomas. High-risk HPV was detected in 11 (10.5%) differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinoma but correlated with high p16INK4A expression in only one case. Integration of viral DNA was never observed in differentiated vulvar intraepithelial neoplasia–associated squamous cell carcinomas, which suggests that a causal relationship of high-risk HPV in differentiated vulvar intraepithelial neoplasia–associated tumors is highly unlikely. The disease-specific survival of the differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinoma patients was significantly worse compared with patients with a usual vulvar intraepithelial neoplasia–associated tumor. Conclusions: High-risk HPV is causally associated with the development of usual vulvar intraepithelial neoplasia associated squamous cell carcinomas, which comprise 19% of all vulvar squamous cell carcinomas, but not with differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinomas. Differentiated vulvar intraepithelial neoplasia–associated vulvar squamous cell carcinomas have a significantly worse prognosis. (Cancer Epidemiol Biomarkers Prev 2009;18(7):2061–7)

Quality of life and sexual health in patients with genital psoriasis

Background  Knowledge about quality of life and sexual health in patients with genital psoriasis is limited.

First case of vaginal radical trachelectomy in a pregnant patient.

Women who present with cervical carcinoma during pregnancy pose for us a clinical problem. In general, three treatment options exist: (i) radical hysterectomy with termination of pregnancy, (ii) a planned delay, or (iii) chemotherapy until lung maturation has occurred, both followed by a radical hysterectomy. Vaginal radical trachelectomy is an alternative approach to preserve the pregnancy. We report on a woman with a stage IBI cervical carcinoma, diagnosed at 16 weeks of gestation treated with vaginal radical trachelectomy. At a gestational age of 36 weeks, a cesarean section was performed, followed by radical hysterectomy. Follow-up of 9 months is uneventful for both the mother and the child. The vaginal radical trachelectomy is a new approach in the treatment of cervical carcinoma during pregnancy.

New FIGO staging system of vulvar cancer indeed provides a better reflection of prognosis.

OBJECTIVE To find out whether the new FIGO staging system (introduced 2009) indeed leads to a more specific prediction of the survival for patients with vulvar SCC. METHODS A retrospective study of 269 patients with vulvar SCC from 1988 to 2009. All patients were staged according the old and revised FIGO staging system by histopathological data. Overall survival (OS) and disease specific survival (DSS) were calculated. RESULTS Of all 269 patients, a total number of 113 patients (42.4%) was restaged according to the new FIGO staging, mainly downstaged. In patients with negative nodes, tumor size was not predictive for OS (p = 0.475) and DSS (p = 0.915). Patients of old FIGO stage III and negative node status showed no difference in survival with the group mentioned above (OS p = 0.105 and DSS p = 0.743, respectively). An increasing number of positive lymph nodes (range 1-9) led to a decrease in survival in OS and DSS (p = 0.022 and p = 0.004 respectively). When corrected for the number of positive nodes, there was no difference in survival between patients with unilateral or bilateral lymph nodes. In patients with positive nodes, extranodal growth showed a significant worse survival compared to patients without extranodal growth (OS p < 0.001 and DSS p = 0.004). CONCLUSION The new FIGO staging system provides indeed a better reflection of prognosis for patients with vulvar SCC. An accurate description of clinical and histopathological data combined with information about which FIGO classification has been used is necessary to interpret the literature correctly and to keep the possibility to compare data of different studies.

Differentiated-type vulval intraepithelial neoplasia has a high-risk association with vulval squamous cell carcinoma.

Objective: To assess the potential malignant risk of vulval premalignant conditions, in particular, to investigate whether there is a difference in the cancer risk between women with the 2 types of vulval intraepithelial neoplasia (VIN). Methods: All vulval biopsy specimens taken for any reason in a single center for a 5-year period were identified. The histologic reports of 1309 biopsy specimens from 802 women were reviewed, and all pathologic conditions present were recorded for each woman. Reports of patients with biopsy specimens containing usual-type VIN, differentiated-type VIN, lichen sclerosus, and squamous hyperplasia were selected and analyzed for the presence of metachronous or subsequent carcinoma to give a proportional risk for each condition. Results: Five hundred eighty women were identified with premalignant vulval conditions: 171 had usual-type VIN, 70 had differentiated-type VIN, 191 had lichen sclerosus, 145 had squamous hyperplasia, and 3 had other conditions not included in this analysis. Within these groups, the numbers of women with prior, synchronous, or subsequent vulval squamous cell carcinoma were 44 (25.7%), 60 (85.7%), 53 (27.7%), and 53 (31.7%), respectively (P = 0.000). Conclusions: Differentiated-type VIN is significantly more associated with vulval squamous cell carcinoma than usual-type VIN.

Patients with usual vulvar intraepithelial neoplasia-related vulvar cancer have an increased risk of cervical abnormalities.

Background:Vulvar squamous cell carcinoma (SCC) originates the following two pathways, related to differentiated (d) vulvar intraepithelial neoplasia (VIN) or to human papillomavirus (HPV)-related usual (u) VIN. Multicentric HPV infections (cervix, vagina and vulva) are common. We hypothesise that patients with a uVIN-related vulvar SCC more often have cervical high-grade squamous intraepithelial lesions (HSILs) compared with women with dVIN-related vulvar SCC.Methods:All vulvar SCCs (201) were classified to be dVIN- (n=164) or uVIN related (n=37). Data with regard to the smear history and cervical histology were retrieved from PALGA, the nationwide Netherlands database of histo- and cytopathology. For HSIL cervical smears of which histology was taken, HPV DNA analysis on both the vulvar and cervical specimens was performed.Results:At least one smear was available in 145 (72%) of the 201 patients. Patients with a uVIN-related vulvar SCC more often had an HSIL compared with patients with a dVIN-related SCC (35 vs 2%, P<0.001). A total of 10 of the 13 HSILs were histologically assessed and identical HPV types were found in the vulva and cervix.Conclusion:These data emphasise the necessity to differentiate between dVIN- and uVIN-related vulvar tumours and to examine the entire lower female ano-genital tract once an uVIN-related lesion is found.

Significant decrease of adenocarcinoma in situ not reflected in cervical adenocarcinoma incidence in the Netherlands 1989–2003

Over the period 1989–2003, the incidence of cervical adenocarcinoma (n=1615) was stable whereas that of cervical adenocarcinoma in situ (n=1884) significantly decreased (P=0.008), mainly caused by adenocarcinoma in situ lesions with a concurrent squamous dysplasia.

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.