OBJECTIVE:It was our aim to assess the usefulness of cytohistology in cervical thin layer brush samples with problems in the differential diagnosis of endometrial cells.STUDY DESIGN:This study reveals the cytological, cytohistological and immunohistochemistry findings of 8 cases suspicious of adenocarcinoma in situ (AIS)/adenocarcinoma (AC) in cervical liquid-based cytology (LBC) preparations that turned out to be normal endometrial cells.RESULTS:All 8 cervical LBCs featured endometrial and atypical endocervical-like columnar cells with frequent ragged 'feathered' edge appearance and rosette formations. Overlapping atypical glandular cell groups were present on 2 ThinPrep slides as well. In cytohistology of 7 cases, the recognition of endometrial stroma with endometrial glands easily allowed the diagnosis of normal endometrium. In 1 case with very small loose tissue fragments without glands, the diagnosis could be established by positivity for CD10 marker (endometrial stroma) and without proliferative activity in the Ki-67 immunostaining.CONCLUSION:In cervical LBC preparations, nuclear hyperchromasia, pleomorphism and nucleoli in normal endometrial cells are more obvious than in conventional smears, and their arrangement is sometimes suggestive of AIS or AC. In the 8 cases presented, we could avoid a false-positive diagnosis of AIS or AC through cytohistology/immunohistochemistry, and in consequence, unnecessary colposcopical/histological examination.

E. K. J. Risse, J. P. Holierhoek, E. M. Meijer‐Marres, E. Ouwerkerk‐Noordam and M. E. Boon

Background Tests for the DNA of high-risk types of human papillornavirus (HPV) have a higher sensitivity for cervical intraepithelial neoplasia grade 3 or worse (CIN3+) than does cytological testing, but the necessity of such testing in cervical screening has been debated. Our aim was to determine whether the effectiveness of cervical screening improves when HPV DNA testing is implemented.Methods Women aged 29-56 years who were participating in the regular cervical screening programme in the Netherlands were randomly assigned to combined cytological and HPV DNA testing or to conventional cytological testing only. After 5 years, combined cytological and HPV DNA testing were done in both groups. The primary outcome measure was the number of CIN3+ lesions detected. Analyses were done by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN20781131.Findings 8575 women in the intervention group and 8580 in the control group were recruited, followed up for sufficient time (>= 6.5 years), and met eligibility criteria for our analyses. More CIN3+ lesions were detected at baseline in the intervention group than in the control group (68/8575 vs 40/8580, 70% increase, 95% CI 15-151; p=0.007). The number of CIN3+ lesions detected in the subsequent round was lower in the intervention group than in the control group (24/8413 vs 54/8456, 55% decrease, 95% CI 28-72; p=0-001). The number of CIN3+ lesions over the two rounds did not differ between groups.Interpretation The implementation of HPV DNA testing in cervical screening leads to earlier detection of CIN3+ lesions. Earlier detection of such lesions could permit an extension of the screening interval.

Objectives: Quantitative cytology (Quanticyt (R)) is a valuable marker for the identification of high-risk superficial bladder cancer (SBC) patients and can be used to individualize surveillance of patients. A disadvantage is the necessity to perform an invasive procedure to obtain the required bladder wash sample. This study investigated whether quantitative cytology can be performed on voided urine with reliable results, consistent with the quantitative cytology performed on bladder wash samples.Methods: Between June 2003 and May 2005, 288 voided urine samples in combination with bladder wash samples were obtained from patients with SBC who visited our urologic outpatient department. Quantitative cytology was performed on all samples. Corresponding clinical pathologic features and washed cytopathology results were collected. Linear regression analyses were performed for comparison of results from both types of samples.Results: Ninety-one percent of the samples fell into the low or intermediate region on bladder wash. A clear deviation in the nuclear shape (MPASS) was seen in the voided urine samples, which led to more low-risk results. The clinical characteristics show that this shift is not the result of under-staging. The nuclear content (2c deviation index [DI]) did not change by performing the analysis on urine.Conclusion: When urine is correctly processed after voiding, quantitative cytology can be done on these samples. Voided urine-based quantitative cytology can be implemented in daily practice. (c) 2006 Elsevier B.V. All rights reserved.

The German Dr. Blum invented formalin as a fixative in 1893. This rapidly became popular for hardening and preserving gross human and animal specimens. As a result, microscopy for diagnostic pathology (combining paraffin embedding and formalin fixation) developed. Alcohol-based fixatives have as a main preservative effect coagulation of proteins. Because there is no cross-linking, immunostaining is not compromised, and DNA and RNA not damaged. Ethyl alcohol was used by Dutch scientists of the eighteenth century but was replaced by cheaper formalin with a much less pronounced hardening effect. Addition of low molecular weight polyethylene glycol (PEG) optimizes ethyl alcohol effects preventing excessive hardening and enhancing the speed of coagulation of proteins. DNA preservation is related to the concentration of ethyl alcohol, PEG, and acetic acid. Literature review and three decades experience with coagulant, formalin-free fixatives in pathology indicate that when health authorities realize formalin invalidates expensive tests, formalin might eventually be eliminated from diagnostic pathology legislatively.

BACKGROUND/AIMS:To improve the accuracy of conventional cytology in cervical cancer screening, high risk human papillomavirus (HPV) testing and neural network based screening have been developed. This study assessed the power of both techniques to detect women at risk of developing incident CIN III; that is, CIN III detected during the follow up of women with normal cytology and borderline nuclear changes.METHODS:A cohort of 2250 women, 34-54 years of age, who attended population based cervical cancer screening from 1988 to 1991 and had normal smears or borderline nuclear changes was followed. All smears were tested for high risk HPV and the smears were rescreened using neural network based screening. The value of neural network based screening for predicting incident CIN III during a mean follow up period of 6.4 years was compared with that of high risk HPV testing. In addition, morphological markers presumed to be related to HPV were correlated with HPV status.RESULTS:Thirteen (0.6%) women had incident CIN III. Both high risk HPV positivity and abnormal cytology were associated with an increased risk for incident CIN III (odds ratio, 240 and 22, respectively) and high risk HPV positivity was associated with abnormal cytology. The sensitivity of high risk HPV testing for predicting incident CIN III was much higher than that of neural network based screening (92% and 46%, respectively). None of the morphological markers assessed, including koilocytosis, was correlated with high risk HPV status.CONCLUSION:High risk HPV testing is superior to neural network based screening in identifying women at risk of developing CIN III. For women with normal cytology and borderline changes and a negative high risk HPV test, the screening interval can be considerably prolonged.