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ABSTRACT: : To analyze whether mixed compared with pure uterine papillary serous carcinoma histology affects clinical outcome, and to assess uterine papillary serous carcinoma for its association with the precursor lesion endometrial intraepithelial carcinoma.
: A multi-institution observational study of stage I-IV uterine papillary serous carcinoma patients was performed. Histopathologic slides were reviewed by four expert pathologists, with determination of the percentage serous histology within each tumor. The pre-existent endometrium was evaluated for the presence of endometrial intraepithelial carcinoma.
: We included 108 uterine papillary serous carcinoma patients. Fifty-eight patients had mixed and 50 patients had pure uterine papillary serous carcinoma histology. On multivariable analysis, advanced International Federation of Gynecology and Obstetrics (FIGO) stage (hazard ratio [HR] 3.15, 95% confidence interval [CI] 1.57-6.32), mixed uterine papillary serous carcinoma histology (HR 0.35, 95% CI 0.19-0.66), and lymphovascular space invasion (HR 2.10, 95% CI 1.07-4.16) were significantly associated with recurrence. International Federation of Gynecology and Obstetrics stage (HR 4.67, 95% CI 2.25-9.70) and mixed uterine papillary serous carcinoma histology (HR 0.39, 95% CI 0.20-0.76) were significantly and independently associated with survival. Endometrial intraepithelial carcinoma was identified in 83.9% of all cases, with no significant difference between mixed and pure uterine papillary serous carcinoma patients. Atrophic or weakly proliferative endometrium was found in 90.7% of pure uterine papillary serous carcinoma cases, whereas hyperplastic endometrium with atypia was more commonly found in 34.7% of mixed carcinoma patients with uterine papillary serous carcinoma (P=.004).
: Pure uterine papillary serous carcinoma histology and FIGO stage are the most important risk factors for recurrence and survival in patients with uterine papillary serous carcinoma. Adjusted for covariates, patients with pure uterine papillary serous carcinoma had a 2.9-times greater risk for recurrence and a 2.6-times higher risk of death compared with patients with mixed uterine papillary serous carcinoma. Furthermore, endometrial intraepithelial carcinoma was equally found among pure and mixed uterine papillary serous carcinoma cases, whereas the nonneoplastic endometrium was atrophic or weakly proliferative in pure uterine papillary serous carcinoma cases compared with more hyperplastic endometrium with atypia in mixed uterine papillary serous carcinoma cases.
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Obstetrics and Gynecology 12/2012; 120(6):1371-81. · 4.73 Impact Factor
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ABSTRACT: : Type I endometrial carcinomas are characterized by endometrioid histology, develop from hyper-plastic endometrium, and have a good prognosis. Type II, nonendometrioid carcinomas, arise in atrophic endometrium and have a poor prognosis. However, approximately 20% of cases do not fit within this dualistic model and include endometrioid carcinomas associated with recurrence and possibly with atrophy. We aimed to evaluate grade 1 endometrioid endometrial carcinomas with atrophic endometrium, a putative third type of endometrial carcinoma.
: Histologic slides of all grade 1 endometrioid endometrial cancers from the Radboud University Medical Centre and Canisius-Wilhelmina Hospital from 1999-2009 and from the Mayo Clinic from 2002-2008 were reviewed. Comparisons were made between patients with atrophic and hyperplastic endometrium.
: After review, 527 patients were identified. In 88 patients (16.8%), background endometrium was atrophic and 387 patients (73.3%) had hyperplastic endometrium. Fifty-two patients (9.9%) had proliferative endometrium or no background endometrium and were excluded. Atrophy correlated with older age, low body mass index, advanced International Federation of Gynecology and Obstetrics stage, malignant cells in peritoneal cytology, lymph node metastases, cervical involvement, lymphovascular space invasion, and deep myometrial invasion. Multivariable analysis showed that age (hazard ratio 1.06, 95% confidence interval [Cl] 1.01-1.12), International Federation of Gynecology and Obstetrics stage (hazard ratio 8.47, 95% Cl 1.73-41.57), and background endometrium (hazard ratio 3.11, 95% Cl 1.11-8.70) were predictors of progression-free survival.
: Atrophic endometrium is an independent prognostic factor for patients with grade 1 endometrioid endometrial carcinoma. Endometrioid carcinoma with atrophy may not follow the hypothesized progression model for type I tumors and may arise through unique carcinogenic pathways.
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Obstetrics and Gynecology 11/2012; 120(5):1124-31. · 4.73 Impact Factor
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ABSTRACT: Objective: We determined the clinical utility of preoperative serum CA-125 as predictor of extra-uterine disease and as prognosticator for survival in patients with uterine papillary serous carcinoma (UPSC).
Methods: Patients diagnosed with UPSC, identified between 1992 and 2009, and with preoperative CA-125 measurement were included. A receiver operator characteristic (ROC) curve was used to quantify marker performance. Overall and progression free survival were analyzed using the Kaplan-Meier method. Regression analyses were used to investigate the association of preoperative CA-125 levels and other clinicopathological variables with the presence of extra-uterine disease and the effects on survival.
Results: Sixty-six patients met the study criteria. Using ROC, the CA-125 concentration of 45 U/mL as cutoff level provided the best sensitivity (75%) and specificity (74%) for extra-uterine disease, with a positive predictive value of 86%. Survival was significantly longer in patients with preoperative CA-125 ≤45 U/mL (p<0.001). Only preoperative CA-125 >45 U/mL remained significantly associated with extra-uterine disease (OR=6.30, 95% CI 1.93-20.62). Furthermore, advanced FIGO stage (HR=4.53, 95% CI 1.50-13.62) and preoperative CA-125 >45 U/mL (HR=3.12, 95% CI 1.13-8.73) were associated with decreased survival.
Conclusion: Preoperative elevated serum CA-125 is an independent predictor for the presence of extra-uterine disease and an independent risk factor for survival in UPSC patients.
The International journal of biological markers 07/2012; 27(3):e263-71. · 1.48 Impact Factor
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ABSTRACT: Clinical decision making in ovarian cancer needs new (prognostic) biomarkers. Although the search for biomarkers has traditionally focused on tumor cells, their surrounding contains important information as well. Glycosaminoglycans, heterogeneous polysaccharides which are abundantly present in the stromal compartment, are indicated in several pathological processes including cancer. In this study we investigated a specific glycosaminoglycan motif (4,6-disulfated chondroitin sulfate) for its potential as a prognostic biomarker in ovarian cancer.
4,6-Disulfated chondroitin sulfate presence was studied immunohistochemically using the single chain antibody GD3G7 on 148 ovarian tumors including benign and malignant tumors, and tumors with low malignant potential. For comparative purposes p53 and Ki-67 were evaluated. X2 tests, univariate and multivariate Cox proportional hazards analyses were applied for statistical analysis.
The stroma of malignant tumors showed significantly increased expression of 4,6-disulfated chondroitin sulfate (GD3G7 epitope) compared with benign tumors and tumors with LMP (p-values<0.000 and 0.002, respectively). Expression of GD3G7 in malignant tumors was significantly correlated with serous subtype, high tumor grade, advanced FIGO-stage and high CA-125 levels. In patients with advanced FIGO stage GD3G7 expression was significantly correlated with incomplete debulking and good response to platinum-based chemotherapy. GD3G7 surpassed both p53 and Ki-67 in statistical analysis. Multivariate survival analysis revealed GD3G7 expression as an independent predictor for progression free survival.
Glycosaminoglycan motifs may form a new class of biomarkers for (ovarian) cancer, as indicated here for the GD3G7 epitope. Expression of GD3G7 may contribute in therapeutic decision making and constitutes a potential biomarker for poor prognosis.
Gynecologic Oncology 06/2012; 127(1):202-9. · 3.89 Impact Factor
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ABSTRACT: Cervical cancer screening with liquid-based cytology (LBC) has been developed as an alternative to the conventional Papanicolaou (CP) smear. Cost-effectiveness is one of the issues when evaluating LBC. Based on the results of a Dutch randomised controlled trial, we conducted cost-effectiveness threshold analyses to investigate under what circumstances manually screened ThinPrep LBC is cost-effective for screening.
The MISCAN-Cervix microsimulation model and data from the Dutch NETHCON trial (including 89,784 women) were used to estimate the costs and (quality-adjusted) life years ((QA)LYs) gained for EU screening schedules, varying cost-effectiveness threshold values. Screening strategies were primary cytological screening with LBC or CP, and triage with human papillomavirus (HPV) testing.
Threshold analyses showed that screening with LBC as a primary test can be cost-effective if LBC is less than 3.2 more costly per test than CP, if the sensitivity of LBC is at least 3-5 % points higher than CP, if the quality of life for women in triage follow-up is only 0.39, or if the rate of inadequate CP smears is at least 16.2 %.
Regarding test characteristics and costs of LBC and CP, only under certain conditions will a change from CP to manually screened ThinPrep LBC be cost-effective. If none of these conditions are met, implementation of manually screened ThinPrep LBC seems warranted only if there are advantages other than cost-effectiveness. Further research is needed to establish whether other LBC systems will be more favorable with regard to cost-effectiveness.
Cancer Causes and Control 06/2012; 23(8):1323-31. · 2.88 Impact Factor
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ABSTRACT: A precursor lesion for ovarian carcinoma, tubal intraepithelial carcinoma (TIC), has been identified in BRCA-mutation carriers undergoing prophylactic bilateral salpingo-oophorectomy (pBSO). Other lesions were also identified in fallopian tubes, but different terminology, interpretation, and lack of knowledge of normal epithelium, have hampered to unravel their possible role in carcinogenesis. The aim of this study is to classify tubal epithelial lesions in BRCA-mutation carriers and controls to enable comparison of prevalence, area of localization, and possible malignant potential.
Two hundred twenty-six BRCA1/2-mutation carriers were included; ovaries and fallopian tubes, embedded completely, were reviewed. Controls included 105 women who underwent BSO for non-malignant reasons. Tubal epithelial lesions included the following categories: hyperplasia, minor epithelial atypia, TIC, and invasive carcinoma.
Tubal neoplasia was identified in 7.1% (invasive carcinoma, 0.9%; TIC, 6.2%) of BRCA-mutation carriers compared to none in controls (p=0.004, Fisher's exact test). Hyperplasia and minor epithelial atypia were identified in 41.6% BRCA-mutation carriers and compared to 58.1% in controls (p=0.005, Pearson's chi square). Invasive carcinoma and TIC showed preference for the fimbrial ends (p=0.027, Pearson's chi square), while hyperplasia and minor epithelial atypia displayed more variation in localization.
Invasive tubal carcinoma and TIC were limited to BRCA-mutation carriers, whereas hyperplasia and minor epithelial atypia were commonly found in both BRCA-mutation carriers and controls. It is suggested that hyperplasia and minor atypia represent variations of normal tubal epithelium instead of premalignant lesions. Furthermore, total salpingectomy is strongly recommended as most but not all TIC occurred in the fimbriae.
Gynecologic Oncology 06/2012; 127(1):88-93. · 3.89 Impact Factor
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ABSTRACT: Patients with double primary cancer (DPC) of the ovary and endometrium are considered to have a better prognosis than patients with only epithelial ovarian cancer (EOC). The aim of this study was to clarify the difference in prognosis by comparing clinicopathologic characteristics and survival. From the population-based database of the nationwide Netherlands Cancer Registry, women diagnosed between 1996 and 2006 with EOC were identified. Within this database of all EOC patients in 11 hospitals, the DPC patients were identified. Differences in characteristics between EOC-only and DPC patients were tested using Pearson χ tests and t-tests. Differences in overall survival were analyzed by Kaplan-Meier survival analyses and log-rank tests. Multivariable Cox regression analyses were performed to study the factors that influence survival. Among 1105 EOC patients, 29 (2.6%) DPC patients were identified. DPC patients were more often premenopausal (P<0.01), in the early stage of disease (P<0.01), and more often had low-grade endometrioid tumors. Overall survival was better for DPC patients (P=0.004), but after stratification for stage the overall survival was similar. In multivariable analysis, DPC patients did not show a favorable prognosis after adjustment for age, disease stage, histology, tumor grade, and residual tumor after surgery. DPC patients seem to constitute a prognostically favorable group among EOC patients; however, after correction for age, stage, histology, tumor grade, and residue, survival is similar. This study shows how important it is for clinicians to distinguish DPC from metastatic diseases.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 05/2012; 31(4):344-51. · 2.07 Impact Factor
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ABSTRACT: The pathogenesis of serous ovarian carcinoma (SOC) is still unknown. Recently, endometrial intraepithelial carcinoma (EIC) was proposed to be the precursor lesion of SOC. This study examines the model of EIC as precursor for SOC.
Cases of SOC with a noninvasive or superficially invasive serous lesion, a hyperplastic lesion with/without atypia, or EIC in the endometrium were selected for inclusion in this study. Tissue sections from both ovaries, the fallopian tubes, and the uterus were extensively reviewed by an expert gynecopathologist. For both EIC and SOC, immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor; TP53 mutation analysis; and in situ ploidy analysis were performed.
Nine cases of SOC with concurrent EIC in the endometrium were identified. Immunostaining for p53, Ki-67, estrogen receptor, and progesterone receptor revealed almost identical expression patterns and similar intensities in each pair of EIC and coincident SOC. Identical TP53 mutations were found in SOC and coinciding EIC in 33% of the cases, suggesting a clonal origin. DNA ploidy analysis, as a marker for neoplastic progression, demonstrated an increased number of aneuploid nuclei in SOC compared to their corresponding EIC (P = 0.039). In addition, the mean amount of DNA per nucleus in SOC was higher (ie, more aneuploid) compared to EIC (P = 0.039).
This study provides a first indication of EIC as possible precursor lesion for SOC. This finding could have major clinical implications for future ovarian cancer management and underscores EIC as a possible target for early SOC detection and prevention.
International Journal of Gynecological Cancer 03/2012; 22(3):457-64. · 1.65 Impact Factor
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ABSTRACT: Recent randomized controlled trials have shown a significant decrease in unsatisfactory rates for liquid-based cytology (LBC) compared with conventional Papanicolaou test (CP). The underlying causes and relevance of unsatisfactory results for LBC and CP have never been compared within the setting of a randomized controlled trial.
To examine differences in causes and relevance of unsatisfactory and satisfactory but limited by (SBLB) results for LBC and CP.
Data from the Netherlands ThinPrep Versus Conventional Cytology (NETHCON) trial were used, involving 89 784 women. Causes and relevance of unsatisfactory and SBLB results were analyzed.
The primary cause for unsatisfactory results for CP and LBC was scant cellularity. Other causes for unsatisfactory CPs were virtually eliminated with LBC. The same was true for SBLB subcategories, with the exception of SBLB absence of transformation zone component and SBLB scant cellularity. The SBLB absence of transformation zone component showed a statistically significant 22% and SBLB scant cellularity a 12% nonsignificant increase with LBC. The detection rates of abnormalities found during 18 months of follow-up of unsatisfactory test results did not differ significantly between the 2 study arms, nor did they differ from the initial test positivity rates from the NETHCON trial.
Liquid-based cytology shows an almost complete elimination of most causes for unsatisfactory CP, with scant cellularity remaining as the sole cause for unsatisfactory LBC. On the other hand, with LBC a significant increase of smears without a transformation zone component was noted. Women with an unsatisfactory test result are not at increased risk for cervical abnormalities either with LBC or with CP.
Nederlands Trial Register, NTR1032, www.trialregister.nl .
Archives of pathology & laboratory medicine 01/2012; 136(1):76-83. · 2.58 Impact Factor
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ABSTRACT: The objective of the study was to assess the screening history of women with cervical cancer and review normal cervical smears 5 years preceding the diagnosis.
Cytological and histological results of 401 women treated for invasive cervical cancer between 1991 and 2008 at the Radboud University Nijmegen Medical Center were studied. Ninety-eight normal smears were reviewed.
Of the 401 women, 269 (67%) received at least 1 invitation for the national screening program for cervical cancer (NCSP). One- third fell outside the target age of the NCSP. Seventeen percent never responded to the invitation(s). Twenty-one percent had 1 or more normal smears within 5 years preceding the diagnosis. After review, only 39% of those smears were reviewed as a normal smear.
Half of the women with cervical cancer were never screened because of the limited target age range or nonattendance. Twenty-one percent had a normal smear within 5 years preceding the diagnosis, caused by interpretation and/or sampling errors.
American journal of obstetrics and gynecology 02/2011; 205(1):64.e1-7. · 3.28 Impact Factor
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ABSTRACT: The current paper presents Chapter 5 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening, which deals with the histopathological diagnosis of lesions of the uterine cervix. It completes a series of publications in journals containing the contents of other parts of the European Guidelines. Histopathology provides the final diagnosis on the basis of which treatment is planned, and serves as the gold standard for quality control of cytology and colposcopy. It is also the source of the diagnostic data stored at the cancer registry and used for evaluation of screening programmes. It is therefore important that histopathology standards are monitored and based on agreed diagnostic criteria. Histology is required to diagnose the degree of abnormality in women with persistent low-grade abnormalities including HPV-lesions, as well as high-grade lesions. Cytology may also suggest either glandular abnormalities or be suggestive of high-grade CIN, AIS or invasive cancer. Histopathologists should be aware of, and familiar with, the nature of cytological changes which may be relevant to their reports. The accuracy of the histopathological diagnosis of tissue specimens depends on adequate samples, obtained by colposcopically directed punch biopsies (with endocervical curettage if necessary) or excision of the transformation zone or conisation. An accurate histological diagnosis further depends on appropriate macroscopic description, technical processing, microscopic interpretation and quality management correlating cytological and histological diagnosis. This paper proposes guidelines for sampling and processing of cervical tissue specimens obtained by biopsy, excision and/or curettage.
Acta oncologica (Stockholm, Sweden) 02/2011; 50(5):611-20. · 2.27 Impact Factor
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ABSTRACT: Objective. Ovarian carcinomas are presumed to arise within ovarian inclusion cysts or from a coexisting epithelial lesion in the ovary. Insight may be gained by relating different subtypes of ovarian cancer with the presence of coexisting tumor-like conditions. Methods. The Dutch nation-wide pathology database PALGA (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief) identified the various histopathological subtypes of ovarian cancer in 824 patients diagnosed in 1996-2003, and recorded the presence of epithelial tumor conditions around the ovarian tumors. In addition, a PALGA database of all 153 consecutive patients referred to the Nijmegen University Medical Centre in 2007 for histopathological work-up was analyzed. Results. The prevalence of coexisting ovarian tumor conditions was 16.4% (135 out of 824 patients, (95% CI: 8.4%-24.4%)). The coexistence was highest for endometrioid, mucinous, clear cell, and borderline malignancies. The referral group revealed 35% (54 out of 153 patients, (95% CI: 28%-42%)) of coexisting epithelial ovarian tumor conditions. Conclusion. One in six patients with a malignant ovarian tumor has a coexisting epithelial tumor condition in the ovary, which is also rather frequently observed in the diagnostic work-up practice.
ISRN obstetrics and gynecology 01/2011; 2011:784919.
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ABSTRACT: The objective of this study is to determine the incidence and time trends of gestational trophoblastic disease (GTD) in The Netherlands using population-based data.
Data on patients with a pathologically confirmed diagnosis of GTD from 1995 to 2008 were obtained from PALGA, a national archive containing all histopathology reports in The Netherlands. Data on number of deliveries were obtained from the Database of Statistics Netherlands.
During the study period, 4249 GTD patients were registered. Overall incidence rates of hydatidiform mole (HM), choriocarcinoma and placental site trophoblastic tumor (PSTT) were 1.34 per 1000 deliveries, 3.1 per 100,000 deliveries, and 1.0 per 100,000 deliveries, respectively. Incidence rates of HM increased from 1.02 per 1000 deliveries in 1995 to 1.56 per 1000 in 2001, an increase of 0.091 per year (95% CI 0.081-0.101). After 2001 incidence rates remained constant (increase per year -0.010, 95% CI -0.045-0.024). Maternal age and ethnicity are known to influence the risk of HM. Highest incidences were observed in women under 20 and over 40years of age. The proportion of deliveries accounted for by women over 40years of age increased from 1.5% to 2.9%, whereas women under 20 accounted for 1.5% of deliveries. The proportion of live births of Asian descent increased from 2.6% to 3.7%.
The incidence of GTD in The Netherlands increased significantly from 1995 to 2008. This can partially be explained by increased maternal age and increased proportion of live births of Asian descent. Part of the increase might result from improved diagnostic techniques. However, these factors do not seem to account for the total observed increase and part of the increase therefore remains unexplained.
Gynecologic Oncology 01/2011; 121(2):334-8. · 3.89 Impact Factor
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ABSTRACT: Management of patients diagnosed on cervical smears with twice consecutively atypical squamous cells of undetermined significance (ASC-US) remains a clinical dilemma. We describe a follow-up of aggressive vs. less aggressive colposcopic treatment in order to determine which treatment is preferable.
Retrospective cohort study with a follow-up of 10 years.
Two hospitals in The Netherlands.
Women referred for primary colposcopy with two consecutive ASC-US smears (n=230) to either one of the two hospitals.
In one hospital, patients underwent direct loop excision of all colposcopically detected abnormalities, even if not suspected for cervical intraepithelial neoplasia (CIN; aggressive strategy; n=118). In the other hospital, a less aggressive policy was followed when low-grade CIN lesions were suspected at colposcopy (less aggressive strategy; n=112).
The number of loop excisions, detection of CIN lesions and cytological follow-up of both groups.
Less aggressive management resulted in less loop excisions (p<0.001). At initial colposcopy, the aggressive group showed a 10-fold incidence of histologically detected CIN lesions compared with the less aggressive group (1.8 vs. 19.5%). During 10 years of follow-up, both groups showed the same percentages of CIN lesions (8.1 vs. 8.4%). Aggressive management resulted in faster normalization of cervical smears (p<0.001). However, at final follow-up, there was no statistical difference in the percentage of normalization of cervical smears between both groups.
Aggressive and less aggressive colposcopic strategies are equally safe and show good clinical outcomes. Treatment decisions, however, must be adjusted to women's individual demands.
Acta Obstetricia Et Gynecologica Scandinavica 01/2011; 90(4):313-8. · 1.77 Impact Factor
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ABSTRACT: Background. Patients with epithelial ovarian cancer have a high risk of (non-)melanoma skin cancer. The association between histological variants of primary ovarian cancer and skin cancer is poorly documented. Objectives. To further evaluate the risk of skin cancer based on the histology of the epithelial ovarian cancer. Methods. A cross-sectional study within a large population-based dataset. Results. Skin cancer was found in 2.7% (95% CI: 2.3-3.1) of the 5366 individuals forming our dataset. The odds ratio (OR) for endometrioid cancer in the ovary to skin cancer in the under 50 age group was 8.9 (95% CI: 3.2-25.0). The OR decreased in older patients to 1.2. Conclusions. Patients with epithelial ovarian malignancies show an increased risk of skin cancer. A significantly increased risk (4.3%) for endometrioid ovarian cancer was found in the group aged under 50.
ISRN obstetrics and gynecology 01/2011; 2011:617082.
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ABSTRACT: Lichen sclerosus is considered to be the precursor lesion of vulvar squamous cell carcinoma, of which only 2-5% progress to squamous cell carcinoma. Differentiated vulvar intraepithelial neoplasia (VIN) has been proposed to be the direct precursor lesion, but this is a recently recognized, and a difficult to diagnose, entity, which may easily be mistaken for a benign dermatosis. The aim of this study was to test the hypothesis that of all lesions that have been diagnosed as lichen sclerosus in the past, a part might currently be diagnosed as differentiated VIN, and to identify histopathological differences between lichen sclerosus lesions with and without progression to vulvar squamous cell carcinoma. All lichen sclerosus slides were revised by two expert gynecopathologists and histopathological characteristics were documented. After revision of lichen sclerosus biopsies without progression (n = 61), 58 were reclassified as lichen sclerosus. Revision of lichen sclerosus biopsies with progression yielded concordant diagnoses in 18 of 60 cases (30%). Of 60 lesions, 25 (42%) were reclassified as differentiated VIN. The median time from differentiated VIN to vulvar squamous cell carcinoma was shorter (28 months) than that from lichen sclerosus to vulvar squamous cell carcinoma (84 months) (P < 0.001). Lichen sclerosus that progressed to squamous cell carcinoma, but did not meet the criteria for differentiated VIN, more often showed parakeratosis (P = 0.004), dyskeratosis (P < 0.001), hyperplasia (P = 0.048) and basal cellular atypia (P = 0.009) compared with lichen sclerosus without progression. In conclusion, differentiated VIN diagnosis has been frequently missed and is associated with rapid progression to squamous cell carcinoma. Patients with lichen sclerosus with dyskeratosis and parakeratosis, hyperplasia and/or basal cellular atypia should be kept under close surveillance as these lesions also tend to progress to squamous cell carcinoma.
Modern Pathology 11/2010; 24(2):297-305. · 4.79 Impact Factor
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ABSTRACT: Intratumoral hypoxia has been associated with poor prognosis in several solid tumors. The aim of this study was to determine whether the hypoxia-associated markers glucose transporter (GLUT)-1 and carbonic anhydrase (CA)-IX expression and preoperative hemoglobin (Hb) levels correlate with presence of inguinofemoral or distant metastases, and disease-free survival (DSS) in vulvar squamous cell carcinoma (SCC) patients. Vulvar SCC (n=103) were reviewed for histopathological characteristics by an expert gynecopathologist and stained for GLUT-1 and CA-IX. Clinical data and preoperative Hb levels were obtained from medical records. No significant correlations were observed between GLUT-1 or CA-IX expression patterns and preoperative Hb levels, presence of inguinofemoral or distant metastases and DSS. However, anemic patients (Hb<11.2 g/dL) had significantly more inguinofemoral metastases and lower Hb level was an independent prognostic factor for a worse DSS (p<0.001). The number of comorbidic conditions was inversely correlated with preoperative Hb level. Preoperative Hb levels are associated with poor DSS for vulvar SCC patients, whereas tumor hypoxia reflected by GLUT-1 and CA-IX expression does not have a predictive value. Because preoperative Hb levels inversely correlated with the number of comorbidic conditions and not with GLUT-1 or CA-IX expression, it is most likely that preoperative Hb levels represent overall physical condition.
Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 10/2010; 457(6):693-703. · 2.49 Impact Factor
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ABSTRACT: The molecular pathogenesis of human papilloma virus-unrelated vulvar squamous cell carcinoma is not well known. Whether malignant progression of lichen sclerosus and differentiated vulvar intraepithelial neoplasia to vulvar squamous cell carcinoma could be accompanied by altered DNA content has not been studied extensively. DNA content in isolated nuclei of microdissected normal vulvar epithelium (n = 2), lichen sclerosus (n = 9), differentiated vulvar intraepithelial neoplasia (n = 13), and squamous cell carcinoma (n = 17) from 22 patients was measured via DNA image cytometry. For additional analysis, 6 differentiated vulvar intraepithelial neoplasia lesions were selected, bringing the number of patients to 28. p53 expression was determined by immunohistochemistry on consecutive tissue sections. Thirty-eight percent (5/13) of differentiated vulvar intraepithelial neoplasia lesions and 65% (11/17) of squamous cell carcinomas were DNA aneuploid or tetraploid. In lesions that contained differentiated vulvar intraepithelial neoplasia and adjacent squamous cell carcinoma, the ploidy status of differentiated vulvar intraepithelial neoplasia did not exceed that of squamous cell carcinoma. We observed a strong correlation between high p53 expression and DNA aneuploidy. This relation was also present at the level of a single nucleus, measured by sequential image cytometry of p53 immunohistochemistry followed by DNA image cytometry on formalin-fixed tissue sections. Similarly, we found p53-positive nonproliferating cells with increased DNA content in the superficial compartment of 6 additional solitary differentiated vulvar intraepithelial neoplasia lesions that were not associated with squamous cell carcinoma, indicating ascending aneuploid cells from the basal compartment. DNA ploidy measurements suggest that differentiated vulvar intraepithelial neoplasia has a higher malignant potential than lichen sclerosus and thus is a more likely precursor of squamous cell carcinoma. Furthermore, high p53 expression correlates with increased DNA content and aneuploidy; but it requires further research to unveil a possible causal relation.
Human pathology 10/2010; 41(10):1475-85. · 3.03 Impact Factor
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ABSTRACT: The aetiology of vulvar squamous cell carcinomas (SCC) that are not causally associated with high-risk human papillomavirus remains largely elusive. The aim of this study was to analyse the inflammatory response in its presumed precursor lesions, lichen sclerosus (LS) and differentiated vulvar intraepithelial neoplasia (dVIN), and provide evidence that dVIN is a likely precursor of vulvar SCC.
Immunohistochemical analyses for CD4+, CD8+, CD20+, CD68+, S100+ and tryptase-positive immune cells were performed and quantified in LS (n = 7), dVIN (n = 19), SCC (n = 11), and normal vulvar tissue (n = 8). The subepithelial inflammatory response in dVIN and SCC was comparable, but absent in LS. Abundant intraepithelial mast cells were observed in dVIN only, and confirmed by electron microscopy, toluidine blue staining and cKIT expression. Adjacent keratinocytes displayed increased proliferation as determined by MIB-1 positivity. Electron microscopy revealed intraepithelial mast cell degranulation. Intraepithelial mast cells were not or infrequently observed in vulvar hyperplasia (n = 13), condylomata acuminata (n = 5), keratinocytic intraepidermal neoplasia of sun-exposed skin (n = 15), epidermal hyperplasia of head and neck (n = 12), and psoriasis (n = 3).
These data indicate that dVIN can be recognized by intraepithelial mast cells and that they might promote the progression of dVIN to SCC.
Histopathology 09/2010; 57(3):351-62. · 3.08 Impact Factor
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ABSTRACT: We report a patient with vulvar lichen sclerosus, Langerhans cell histiocytosis (LCH), and later vulvar cancer. In LCH, high amounts of non functional Langerhans cells are present in the affected tissue, making it possible that LCH may have contributed to vulvar cancer development in this patient.
American journal of obstetrics and gynecology 08/2010; 203(2):e7-10. · 3.28 Impact Factor
