The utility of oral brush cytology in the early detection of oral cancer and oral potentially malignant disorders: A systematic review.

OBJECTIVES: This systematic review aimed to analyze the published evidence for the use of oral brush cytology for the early detection of oral cancer and oral potentially malignant disorders (OPMDs). METHODS: Literature was systematically searched through several databases: MEDLINE, EMBASE, PubMed, SCOPUS, Cochrane Library, and Web of Science. Additional review was performed through cross-checks on the bibliographies of selected articles. The inclusion criteria involved studies assessing the utility of oral brush cytology on human tissues and its applications in the diagnosis, screening, or surveillance of oral cancer or OPMDs. RESULTS: The search strategy resulted in 343 abstracts or full-text articles, of which 36 met the inclusion criteria. The year of publication ranged from 1994 to 2017, and a total of 4302 samples from OPMDs, oral squamous cell carcinoma, and healthy controls have been investigated. Baby toothbrush, cytobrush, OralCDx® , and Orcellex® are the brushes that were used to obtain transepithelial mucosal samples for conventional and liquid-based cytology evaluation. CONCLUSIONS: Findings from this study indicate that meaningful evidence-based recommendations for the implementation of a minimally invasive technique to be utilized as an adjunctive tool for screening and early detection of oral cancer and OPMDs are complicated from the reported studies in the literature. There is need for well-designed clinical studies to assess the accuracy of oral brush cytology utilizing validated cytological assessment criteria for the diagnosis and prediction of OPMDs.

Human papillomavirus (HPV) screening and cervical cancer burden. A Brazilian perspective.

This review tackles the issues related to disease burden caused by cervical cancer (CC) and its precursor (CIN) lesions in Brazil. A special focus is given to new technologies with potential to interfere with the development of CC by reducing the high-risk human papillomavirus (hr-HPV)-induced lesions that remain a major public health burden in all developing countries where organized screening programs do not exist. Globally, 85% of all incident CC and 50% of CC deaths occur in the developing countries. Unfortunately, most regions of Brazil still demonstrate high mortality rates, ranking CC as the second most common cancer among Brazilian women. Recently, CC screening programs have been tailored in the country to enable early detection of CC precursor lesions and thereby reduce cancer mortality. A combination of HPV testing with liquid-based cytology (LBC) seems to be a promising new approach in CC screening, with high expectation to offer an adequate control of CC burden in this country.

Posttreatment assessment of women at risk of developing high-grade cervical disease: proposal for new guidelines based on data from the Netherlands.

OBJECTIVE: Women treated for high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or grade 3 [CIN2/3]) face a significant risk of developing post-treatment disease. Therefore, in most European countries, they are monitored by cytologic testing at 6, 12, and 24 months after treatment. Although testing for high-risk types of the human papillomavirus (hrHPV) in the follow-up seems to be a valuable supplementary method, its use is not yet fully explored. METHODS: Besides reviewing the literature, we completed a long-term follow-up study describing the cumulative risk for CIN2/3 or cancer (CIN2+) of different hrHPV and cytology test results after treatment. CONCLUSIONS: High-risk HPV testing improves the sensitivity to detect posttreatment CIN2/3 (relative sensitivity=1.15, 95% confidence interval [CI]=1.06-1.25), but the highest sensitivity (95%, 95% CI=91%-98%) is reached by performing cotesting (both cytology and hrHPV). The CIN2+ risk after a single negative cotesting result taken 6 months after treatments was similar to the risk after 3 consecutive negative cytologic test results (5-y CIN2+ risk being 3.0% [95% CI=1.5%-6.1%] and 2.9% [95% CI=1.2%-7.1%], respectively). Women who test negative for cotesting at both 6 and 24 months after treatment have a minimal risk of developing CIN3+ in the next 5 years (0.0%, 95% CI=0.0%-3.0%). RECOMMENDATIONS: We propose a new posttreatment surveillance protocol, consisting of combined testing with both cytology and hrHPV at 6 and 24 months after treatment. After 2 negative cotesting results, women should be retested after 5 years.

Microscope use in clinical veterinary practice and potential implications for veterinary school curricula.

Microscopy (skill of using a microscope) and the concepts of cytology (study of cells) and histology (study of tissues) are most often taught in professional veterinary medicine programs through the traditional method of glass slides and light microscopes. Several limiting factors in veterinary training programs are encouraging educators to explore innovative options for teaching microscopy skills and the concepts of cytology and histology. An anonymous online survey was administered through the Colorado Veterinary Medical Association to Colorado veterinarians working in private practice. It was designed to assess their current usage of microscopes for cytological and histological evaluation of specimens and their perceptions of microscope use in their veterinary education. The first part of the survey was answered by 183 veterinarians, with 104 indicating they had an onsite diagnostic lab. Analysis pertaining to the use of the microscope in practice and in veterinary programs was conducted on this subset. Most respondents felt the amount of time spent in the curriculum using a microscope was just right for basic microscope use and using the microscope for viewing and learning about normal and abnormal histological sections and clinical cytology. Participants felt more emphasis could be placed on clinical and diagnostic cytology. Study results suggest that practicing veterinarians frequently use microscopes for a wide variety of cytological diagnostics. However, only two respondents indicated they prepared samples for histological evaluation. Veterinary schools should consider these results against the backdrop of pressure to implement innovative teaching techniques to meet the changing needs of the profession.

Expenditure and resource utilisation for cervical screening in Australia.

BACKGROUND: The National Cervical Screening Program in Australia currently recommends that women aged 18-69 years are screened with conventional cytology every 2 years. Publicly funded HPV vaccination was introduced in 2007, and partly as a consequence, a renewal of the screening program that includes a review of screening recommendations has recently been announced. This study aimed to provide a baseline for such a review by quantifying screening program resource utilisation and costs in 2010. METHODS: A detailed model of current cervical screening practice in Australia was constructed and we used data from the Victorian Cervical Cytology Registry to model age-specific compliance with screening and follow-up. We applied model-derived rate estimates to the 2010 Australian female population to calculate costs and numbers of colposcopies, biopsies, treatments for precancer and cervical cancers in that year, assuming that the numbers of these procedures were not yet substantially impacted by vaccination. RESULTS: The total cost of the screening program in 2010 (excluding administrative program overheads) was estimated to be A$194.8M. We estimated that a total of 1.7 million primary screening smears costing $96.7M were conducted, a further 188,900 smears costing $10.9M were conducted to follow-up low grade abnormalities, 70,900 colposcopy and 34,100 histological evaluations together costing $21.2M were conducted, and about 18,900 treatments for precancerous lesions were performed (including retreatments), associated with a cost of $45.5M for treatment and post-treatment follow-up. We also estimated that $20.5M was spent on work-up and treatment for approximately 761 women diagnosed with invasive cervical cancer. Overall, an estimated $23 was spent in 2010 for each adult woman in Australia on cervical screening program-related activities. CONCLUSIONS: Approximately half of the total cost of the screening program is spent on delivery of primary screening tests; but the introduction of HPV vaccination, new technologies, increasing the interval and changing the age range of screening is expected to have a substantial impact on this expenditure, as well as having some impact on follow-up and management costs. These estimates provide a benchmark for future assessment of the impact of changes to screening program recommendations to the costs of cervical screening in Australia.

Observer-independent cytoarchitectonic mapping of the human superior parietal cortex.

The human superior parietal cortex (SPC; Brodmann areas [BA] 5 and 7) comprises the superior parietal lobule and medial wall of the intraparietal sulcus (mIPS) laterally and the posterior paracentral lobule and precuneus medially. Receptor autoradiographic and functional studies indicate more complex segregations in the SPC than suggested by Brodmann (1909). Differences to other historical maps may be due to anatomical variability between brains and different definition criteria for areas. To provide a reliable anatomical reference of the SPC, we performed an observer-independent cytoarchitectonic mapping of this region in 10 human postmortem brains. Cytoarchitecture was analyzed in cell-body-stained brain sections using gray-level index profiles. Multivariate statistical analysis of profile shape allowed the exact localization of cytoarchitectonic borders and quantification of interareal differences. We identified 3 areas in BA 5 (5L, 5M, and 5Ci), 4 in BA 7 (7PC, 7A, 7P, and 7M), and 1 in the anterior mIPS (hIP3). Locations of their borders relative to macroanatomical landmarks varied considerably between brains and hemispheres. Cytoarchitectonic profiles of areas 5Ci and hIP3 differed most from those of the remaining areas, and differences between subareas were stronger in BA 5 than in BA 7. These areas are possible structural correlates of functional segregations within the SPC.

Utility of liquid-based cytology in endometrial pathology: diagnosis of endometrial carcinoma.

OBJECTIVE: The purpose of this study was to examine the utility of SurePath-liquid-based cytology (LBC) compared to conventional cytological preparations (CCP) in the identification of endometrial carcinoma. METHODS: During a 13-month period, direct endometrial samples were collected from 120 patients using the Uterobrush. The material comprised 30 cases each of endometrial carcinoma, proliferative endometrium, secretory endometrium and atrophic endometrium. The following points were investigated:(i) the frequency of cell clumps in endometrial carcinoma; (ii) the area of cell nuclei; (iii) overlapping nuclei. RESULTS: (i) Comparison of the frequency of cell clumps with irregular protrusion pattern and papillo-tubular pattern showed no statistically significant difference in either type of cell clump between CCP and LBC. (ii) Comparison of the nuclear area of cells showed a sequential decrease from endometrial carcinoma to secretory endometrium, to proliferative endometrium and to atrophic endometrium, which was significant in CCP and LBC. (iii) Nuclear area was significantly lower with LBC compared with CCP in endometrial carcinoma, secretory endometrium and proliferative endometrium but not atrophic endometrium. (iv) Comparison of the degree of overlapping nuclei showed a sequential decrease from endometrial carcinoma to proliferative endometrium, to secretory endometrium and to atrophic endometrium, which was significant in both CCP and LBC. (v) Comparison of the degree of overlapping nuclei between CCP and LBC showed no significant difference for normal types of endometrium, but LBC had significantly higher values (P < 0.0001) in endometrial carcinoma than in CCP. CONCLUSIONS: The results of this study revealed that applying diagnostic criteria used in CCP to LBC was easy to achieve, because LBC had excellent cytoarchitectural preservation and cells were well presented. Although we have not examined all cytological features of malignancy and have not considered atypical hyperplasia, we believe that this method may be a useful tool in the diagnosis of endometrial cytology.

The perceived and actual diagnostic utility of veterinary cytological samples.

OBJECTIVES: To establish the proportion of cytology samples sent to a commercial veterinary laboratory that yields diagnostically useful information in the context of current use and perceptions of cytology. METHODS: Nine hundred and forty-five cytology submissions were retrospectively collected and categorised according to diagnostic utility. A survey into the use and perceptions of cytology was distributed at the British Small Animal Veterinary Association Congress 2008. RESULTS: A specific diagnosis was reached in 23.1 per cent of samples and a cytological diagnosis in 35.3 per cent. 22.4 per cent of samples yielded some useful information, but 19.2 per cent were unacceptable. Seventy-four participants in the survey took an average of 3.9 cytological samples per week, of which they examined 27.0 per cent in-house only, 21.6 per cent in-house before sending to an external laboratory and 51.4 per cent were sent externally without prior examination. "To obtain a definitive diagnosis" was the principal reason cited for performing cytology. CLINICAL SIGNIFICANCE: Results suggest that cytology is underused and may be applied in an inappropriate context in the UK. It is hoped that illustrating the diagnostic outcome of samples received by a commercial laboratory will encourage increased, appropriate use of cytology.

Optimum web viewer application for DICOM whole slide image visualization in anatomical pathology.

BACKGROUND AND OBJECTIVE: Digital scanners are being increasingly adopt-ed in anatomical pathology, but there is still a lack of a standardized whole slide image (WSI) format. This translates into the need for interoperability and knowledge representation for shareable and computable clinical information. This work describes a robust solution, called Visilab Viewer, able to interact and work with any WSI based on the DICOM standard. METHODS: Visilab Viewer is a web platform developed and integrated alongside a proposed web architecture following the DICOM definition. To prepare the information of the pyramid structure proposed in DICOM, a specific module was defined. The same structure is used by a second module that aggregates on the cache browser the adjacent tiles or frames of the current user's viewport with the aim of achieving fast and fluid navigation over the tissue slide. This solution was tested and compared with three different web viewers, publicly available, with 10 WSIs. RESULTS: A quantitative assessment was performed based on the average load time per frame together with the number of fully loaded frames. Kruskal-Wallis and Dunn tests were used to compare each web viewer latency results and finally to rank them. Additionally, a qualitative evaluation was done by 6 pathologists based on speed and quality for zooming, panning and usability. The proposed viewer obtained the best performance in both assessments. The entire architecture proposed was tested in the 2nd worldwide DICOM Connectathon, obtaining successful results with all participant scanner vendors. CONCLUSIONS: The online tool allows users to navigate and obtain a correct visualization of the samples avoiding any restriction of format and localization. The two strategical modules allow to reduce time in displaying the slide and therefore, offer high fluidity and usability. The web platform manages not only the visualization with the developed web viewer but also includes the insertion, manipulation and generation of new DICOM elements. Visilab Viewer can successfully exchange DICOM data. Connectathons are the ultimate interoperability tests and are therefore required to guarantee that solutions as Visilab Viewer and its architecture can successfully exchange data following the DICOM standard. Accompanying demo video. (Link to Youtube video.).

Should pancreas cyst fluids be divided into two for cytological diagnosis and biochemical tests?

BACKGROUND/AIMS: The aim of the present study was to investigate whether pancreas cyst fluids should be divided into two for cytological diagnosis and biochemical tests. MATERIALS AND METHODS: The present study was conducted with fluids aspirated from 12 pancreas cysts. The fluids were divided into two and sent to the cytopathology (fluid 1) and biochemistry (fluid 2) laboratories. Fluid 1 was centrifuged at the cytopathology laboratory. Cytology slides were prepared from the deposit, and the supernatant was sent to the biochemistry laboratory. Fluid 2 was centrifuged at the biochemistry laboratory, and amylase, carcinoembryonic antigen, and cancer antigen 19.9 levels were determined in the supernatant. These procedures were repeated for fluid 1 from the cytopathology laboratory. The remaining fluid 2 was sent to the cytopathology laboratory. Fluid 1-like slides were prepared from fluid 2 in the cytopathology laboratory. Cytological diagnoses of fluid 1 and fluid 2 were compared, and the Pearson correlation coefficient for biochemical test results was identified. RESULTS: 92% of fluid 1 and 50% of fluid 2 were diagnostic. Biochemical test results of fluid 1 and fluid 2 were similar, and the Pearson correlation coefficient was high. CONCLUSION: Our results showed that pancreatic cyst fluids did not need to be divided into two for cytological diagnosis and biochemical tests. Following centrifugation of the whole fluid at the cytopathology laboratory, the deposit and the supernatant can be used for cytological diagnosis and for biochemical tests, respectively. With this protocol, the sensitivity of cytological diagnoses and biochemical tests of pancreatic cyst fluids may increase.

Utility of imprint cytology for early presumptive diagnosis in clinically suspicious cervical cancer.

OBJECTIVE: To determine the utility of imprint cytology (IC) in providing an early presumptive diagnosis of clinically suspected cervical carcinoma. STUDY DESIGN: A total of 219 clinically suspicious cervical cancer cases underwent Pap test, punch biopsy and IC at the same sitting. Correlations were performed between these diagnostic modalities to determine the sensitivity and specificity of IC in diagnosis of cervical cancer. RESULTS: The overall accuracy of IC in detecting cervical cancers was 96.2%. About 78% of squamous cell carcinomas (SCC), 60% of adenocarcinomas and 100% of small cell carcinoma could be accurately typed on imprints. Twelve malignant lesions were diagnosed on IC among 26 unsatisfactory biopsies. Although there was no false positive result, 3.5% false negative diagnoses were given on IC. The sensitivity and specificity of imprint smear cytology to detect malignancy was 96.2% and 100%. Agreement between imprint cytology and Pap smear diagnosis of malignancy was 95.3%. kappa Statistics revealed excellent agreement between imprints and biopsies and between imprints and Pap smears in diagnosis of malignant lesions. CONCLUSION: IC can be used as an adjunctive technique for an early and reliable preliminary presumptive diagnosis of cancer of the uterine cervix.

Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types.

Mass cytometry allows high-resolution dissection of the cellular composition of the immune system. However, the high-dimensionality, large size, and non-linear structure of the data poses considerable challenges for the data analysis. In particular, dimensionality reduction-based techniques like t-SNE offer single-cell resolution but are limited in the number of cells that can be analyzed. Here we introduce Hierarchical Stochastic Neighbor Embedding (HSNE) for the analysis of mass cytometry data sets. HSNE constructs a hierarchy of non-linear similarities that can be interactively explored with a stepwise increase in detail up to the single-cell level. We apply HSNE to a study on gastrointestinal disorders and three other available mass cytometry data sets. We find that HSNE efficiently replicates previous observations and identifies rare cell populations that were previously missed due to downsampling. Thus, HSNE removes the scalability limit of conventional t-SNE analysis, a feature that makes it highly suitable for the analysis of massive high-dimensional data sets.

Conventional Pap smear and liquid-based cytology as screening tools in low-resource settings in Latin America: experience of the Latin American screening study.

OBJECTIVE: To evaluate the performance of the conventional Pap test and liquid-based cytology (LBC) in an ongoing multicenter trial testing optional screening tools (cytology, screening colposcopy, visual inspection with acetic acid, visual inspection with Lugol's Iodine, cervicography and Hybrid Capture II [HCII] (Digene Brazil, São Paulo, Brazil) conventional and self-sampling), for cervical cancer in Brazil and Argentina. STUDY DESIGN: A cohort of 12,107 women attending four clinics (Campinas, São Paulo, Porto Alegre, Buenos Aires) were randomized into the 8 diagnostic arms. Women testing positive with any of the tests were referred for colposcopy, and cervical biopsies were used as the gold standard to assess performance characteristics of the diagnostic tests. Conventional Pap smears were sampled by all clinics (n = 10,240), and LBC (Autocyte PREP, [TriPath Imaging, Burlington, North Carolina, U.S.A.], n=320, and DNA-Citoliq [Digene Brazil], n =1,346) was performed by 1 of the clinics. RESULTS: Conventional Pap smears showed no squamous intraepithelial lesions (normal) in 8,946 (87.4%) and LBC in 1,373 (82.4%). Using high grade squamous intraepithelial lesions (HSIL) as the cutoff, Pap smears predicted high grade (cervical intraepithelial neoplasia [CIN] 3) with OR 63.0 (95% CI, 36.90-107.70), standard error (SE) 59%, SP 97.8%, positive predictive value (PPV) 68.1% and negative predictive value (NPV) 96.7%. The same figures for Autocyte PREP were: OR 9.0 (95% CI, 2.43-33.24), sensitivity (SE) 33.3%, specificity (SP) 100%, PPV 100% and negative PV (NPV) 88.8%. DNA-Citoliq detected CIN 3 as follows: OR 11.8 (95% CI 2.60-53.26), SE 40.0%, SP 94.6%, PPV 40.0% and NPV 94.6%. Lowering the cutoff to low grade squamous intraepithelial lesions increased SE and NPV but compromised SP and PPV. The detection rates for high grade lesions after an atypical squamous cells of undetermined significance diagnosis were similar with the 3 techniques. In our settings, the 3 methods of cervical cytology were slightly different in performance. The conventional Pap smear had the highest SE, while Autocyte PREP had 100% SP and PPV in detecting CIN3 with the HSIL cutoff. All 3 tests had lower SE but higher SP as compared to HCII.

Improved accuracy of sperm motility assessment using a modified Micro-Cell sperm counting chamber.

OBJECTIVE: To assess the effect of modifications made in the Micro-Cell sperm counting chamber on the motility of washed human spermatozoa. DESIGN: In a 2 x 2 experimental design, human sperm samples were washed with or without protein supplementation, loaded into modified or unmodified Micro-Cell chambers, and assessed by automated semen analysis for changes associated with sperm adhesion to the glass chamber surfaces. PARTICIPANTS: Twenty-one men who were undergoing semen analysis and presented with > or = 50% motile sperm, or normal donors. MAIN OUTCOME MEASURES: Reduced motility and elevated lateral head displacement associated with sperm adhesion to glass surfaces were compared using a doubly repeated measures analysis of variance. RESULTS: Addition of protein to the sperm washing solution partially reversed the adhesion of spermatozoa to the glass of unmodified Micro-Cell chambers. Chambers manufactured to reduce cell adhesion to glass surfaces yielded the highest motility and lowest lateral head displacement, whether the sperm were washed in a solution supplemented with or without protein. CONCLUSION: These findings indicate that, as in raw semen, kinematics of washed sperm can be measured reliably in the modified Micro-Cell chamber.

Pathological approach to breast conserving therapy.

There is no uniformly accepted definition of a positive margin in breast conserving surgery. In 1999, the Japanese Breast Cancer Society created the Guidelines for Breast-Conserving Treatment (GBCT). At that time, we did a questionnaire survey about the definition of margin status. Although 57.1% of hospitals/institutes used the definition of cancer cells present at the surface, the GBCT adopted the definition of cancer cells present within 5 mm of the surface. Moreover, the GBCT required that the distance between the edge of the cancer cells and the surface be recorded in millimeters when cancer cells were present within 5 mm of the surface. The risk factors for local recurrence after breast-conserving treatment were studied. From 1986 to 1995, 391 patients were treated with breast-conserving surgery at Osaka Medical Center for Cancer and Cardiovascular Diseases. Of these, 35 patients developed local recurrence. Multivariate analysis showed that positive margin (p=0.0002), high degree of ductal proliferative change around the tumor (p=0.0035) and high histological grade (p=0.0041) were significant independent risk factors for local recurrence, while radiation therapy (p=0.0327) significantly reduced local recurrence. There was no significant difference in the risk of local recurrence between the two different definitions of positive margin (tumor present at the surface and tumor present within 5 mm from the surface). It is hoped that more hospitals/institutes will adopt the definition of margin positivity presented by the GBCT and that a practical definition of margin positivity will be established.

Cellularity of liquid-based, thin-layer cervical cytology slides.

OBJECTIVE: To study the cellularity of liquid-based preparations (LBPs) for normal, abnormal and false negative cervical cytology cases. STUDY DESIGN: A series of 1,875 LBPs obtained by a split-sample protocol was examined. Slides had been examined by at least one cytotechnologist. All abnormals were reviewed by at least two cytopathologists. The cellular objects were counted using a fully automated microscope. Cellularity was evaluated for the entire population, normal (< LSIL) slides, abnormal (LSIL+) slides and "false negative" slides. False negatives were identified as those with an initial impression of < LSIL and (1) the reference pathologist's impression of the slide was LSIL+, (2) the simultaneous conventional smear was LSIL+, or (3) a cervical biopsy was LSIL+. Descriptive statistics and graphic comparisons were used. RESULTS: There were 192 confirmed abnormal cases and 1,683 normal cases, of which 53 were false negative. The frequency distributions of cellularity for the entire population and each category were skewed-right nonnormal. Median cell counts of the entire series, normals, abnormals and false negatives were 60,510, 59,822, 70,523 and 64,036 respectively. Cell counts at 2.5 percentiles were 8,677, 7,891, 11,864 and 6,009, respectively. The population of abnormal slides tended to have higher cellularity. The population of false negative slides could not be distinguished by their cellularity. CONCLUSION: Cellularity does not provide assurance of adequacy. Any cellularity criterion should be based on measurement of the prevalence of abnormal cells on abnormal slides.

Sputum cytology for the diagnosis of lung cancer. Comparison of smear and modified cell block methods.

OBJECTIVE: To compare the sputum smear cytology and cell block methods for specimen adequacy, cytology quality and diagnostic accuracy in the diagnosis of lung cancer. STUDY DESIGN: We assessed 2,524 sputum specimens from 768 patients. The specimens were prepared as smears and cell blocks for cytopathologic examination between March 1, 1992, and December 31, 1998. The smear and cell block slides were evaluated both separately and together, and the results were compared with radiologic and histopathologic diagnoses. RESULTS: The sensitivity of the smear method was 69.4% and specificity was 99.5%. The sensitivity of the cell block method was 84.4% and specificity, 100%. The sensitivity of the smear and cell block together was 87.6% and specificity, 99.5%. CONCLUSION: The cell block method increases the sensitivity and specificity of sputum cytology, and when smear and cell block slides are evaluated together, sensitivity reaches its highest value. Therefore, application of smear and cell block methods together seems most useful in the diagnosis of lung cancer.

Intraoperative cytologic diagnosis of sentinel node metastases in breast cancer.

OBJECTIVE: To clarify the usefulness of imprint cytology for intraoperative investigations of sentinel lymph nodes in breast cancer, comparing the results with those of examinations using frozen and permanent sections. STUDY DESIGN: The material consisted of 303 sentinel lymph nodes from 124 cases of clinically node negative breast cancer. Touch imprint cytologic slides and frozen sections were obtained from the same cut surface of the sentinel nodes. Correlations with the final histopathologic results in paraffin sections were evaluated. RESULTS: The sensitivity, specificity and accuracy of imprint cytology were 70.3%, 99.6% and 96.0%, and those of frozen sections were 83.8%, 100%, 98.0%, respectively. The values were improved when the 2 methods were combined (89.2%, 99.6%, 98.3%), though the concordance between imprint cytology and frozen section was 91.9%. CONCLUSION: Both imprint cytology and frozen section are useful for evaluating sentinel lymph node status in breast cancer. However, the 2 techniques should be combined to improve the diagnostic sensitivity.

Mapping dynamic epithelial cell proliferative activity within the oral cavity of man: a new insight into carcinogenesis?

Our aim was to characterize epithelial cell proliferative activity within the oral cavity and to find out if there were differences between sites with high and low incidence of cancer. A total of 105 samples of clinically normal mucosa were harvested from various intra-oral sites. Excised specimens were incubated in vitro with tritiated thymidine and bromodeoxyuridine to 'double label' cells undergoing DNA synthesis, and enable calculation of the duration of S phase and estimation of variables of cell flux to and from S. Mean labelling indices (percentage of cells within the S phase of the cell cycle) were highest in the floor of mouth (12.3%) and ventral tongue (10.1%), while activity was lowest in the dorsum of tongue (4.3%) and the palate (7.2%), P<0.001. In general, both cell influx and the duration of S increased proportionally to the labelling index. Sites with a high incidence of cancer were characterized by high labelling indices, increased cell influx and a prolonged S phase.

Characterization of epithelial cell activity in patients with oral cancer.

Accurate, predictive assessment of the clinical behaviour and progression of individual oral cancers and premalignant lesions requires reproducible and quantitative analyses of diseased tissue. In this paper we describe the use of in vitro double labelling (sequential tritiated thymidine and bromodeoxyuridine staining of proliferating epithelial cells) to calculate S phase labelling indices (LIs), estimation of S phase duration (tS), and measurement of variables of flux to and from S for excised specimens of oral squamous cell carcinoma, premalignant lesions, and clinically normal mucosa from patients with oral cancer. There was a significant increase in mean LIs in buccal mucosa leukoplakias (14.5%) compared with normal mucosa (10.3%); P = 0.03. LIs were also increased in patients with cancers of the floor of mouth and ventral tongue but neither these changes nor alterations in flux parameters or S Phase durations were significant. Twenty-one kinetic profiles of dysplastic and malignant tissue were compared with conventional histopathological results, however, and these showed a 2.2% increase in LIs with each increase in grade of dysplasia (P = 0.004) and a 12% increase in LIs with each reduction in tumour differentiation (P = 0.02).