Exfoliative Cytology Specimens Research Articles

Uncommon case of cytopathological features of sialadenoma papilliferum.

Sialadenoma papilliferum, a benign and rare salivary gland neoplasm, accounts for 0.4%-1.2% of all salivary gland tumors and occurs primarily in minor salivary glands of the oral cavity. Here, we report a case of sialadenoma papilliferum and its associated cytological findings. A papillary tumor was incidentally detected on the palate of an 86-year-old Japanese man. Conventional oral exfoliative cytology was performed; the cytology smear exhibited epithelial clusters composed of atypical epithelial cells with a high nuclear/cytoplasm ratio and arranged in sheet or small papillary-like projections. Cytoplasmic vacuoles were also observed in the papillae. It was difficult to make a definitive diagnosis due to the presence of uncommon cytological features. The excisional biopsy specimen revealed histological features characteristic of sialadenoma papilliferum. Mutational analysis detected BRAFV600E mutation, which confirmed the diagnosis of sialadenoma papilliferum. To the best of our knowledge, no prior cytomorphological evaluations of sialadenoma papilliferum have been reported in detail. Oral exfoliative cytology specimens from salivary gland tumors can demonstrate uncommon cytomorphological features. A differential diagnosis of sialadenoma papilliferum can be based on the observation of mildly atypical epithelial cells that form small papillary-like structures.

Biomarker testing of cytology specimens in personalized medicine for lung cancer patients.

Every patient with advanced non-small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.

Methylated DNA Markers of Esophageal Squamous Cancer and Dysplasia: An International Study.

Discovery of methylated DNA markers (MDM) of esophageal squamous cell carcinoma (ESCC) has sparked interest in assessing these markers in tissue. We evaluated MDMs in ESCC from three geographically and ethnically distinct populations, and explored the feasibility of assaying MDMs from DNA obtained by swallowed balloon devices. MDMs were assayed in ESCC and normal tissues obtained from the populations of United States, Iran, and China, and from exfoliative cytology specimens obtained by balloons in a Chinese population. Areas under the receiver operating curve (AUC) of MDMs discriminating ESCC from normal tissues were calculated. Random forest prediction models were built, trained on U.S. cases and controls, and calibrated to U.S.-only controls (model 1) and three-country controls (model 2). Statistical tests were used to assess the relationship between dysplasia and MDM levels in balloons. Extracted DNA from 333 ESCC and 322 normal tissues was analyzed, in addition to archival DNA from 98 balloons. For ESCC, model 1 validated in Iranian and Chinese tissues with AUCs of 0.90 and 0.87, and model 2 yielded AUCs of 0.99, 0.96, and 0.94 in tissues from the United States, Iran, and China, respectively. In Chinese balloons, MDMs showed a statistically significant trend of increasing levels with increasing grades of dysplasia (P < 0.004). MDMs accurately discriminate ESCC from normal esophagus in tissues obtained from high- and low-incidence countries. Preliminary data suggest that levels of MDMs assayed in DNA from swallowed balloon devices increase with dysplasia grade. Larger studies are needed to validate these results. MDMs coupled with minimally invasive collection methods have the potential for worldwide application in ESCC screening.

Argyrophilic nucleolar organizer regions in oral mucosa cells of crack and cocaine users: a cross-sectional study.

The objective of this study was to analyze and compare the presence of argyrophilic nucleolar organizer regions (AgNORs) in exfoliated cells obtained from the buccal mucosa among crack and cocaine users and non-users by the AgNOR staining technique. Seventy-three males ≥ 18years were categorized into two groups: 38 crack and/or cocaine users and 35 non-user volunteers. They were interviewed and responded a questionnaire regarding general health and drug addiction. Exfoliative cytology specimens were collected from the clinically intact buccal mucosa, and cytological preparations were fixed and stained by AgNOR technique. The mean number of AgNORs (p = 0.02) and the percentage of epithelial cells with more than 3 (p = 0.01) and 4 (p = 0.04) AgNORs/nucleus were significantly higher in the non-user group. In conclusion, the frequency and diversity of substances present in the drugs-cocaine, crack, and alcohol-consumed by the volunteers of this study may have influenced the number of AgNORs and the response to damage and consequent effect on protein synthesis.

Effects of Diabetes and Hypertension on Oral Mucosa and TGFβ1 Salivary Levels.

in this cross-sectional study, whole stimulated saliva and oral mucosa exfoliative cytology specimens were collected from 39 patients that were healthy (control, n=10) or presented history of arterial hypertension (HAS, n=9), diabetes mellitus (DM, n=10) or both (DM+HAS, n=10). Salivary flow rate (SFR), TGFβ1 level in saliva, AgNORs and the epithelial maturation were evaluated. Non-parametric Kruskal-Wallis test, followed by Dunn's multiple comparison post-test and the Spearman test correlation analysis were used. SFR showed a significant decreased in DM and DM+HAS (0.47±0.11 and 0.64±0.43 mL/min) when compared to control (1.4±0.38 mL/min). DM+HAS presented the highest value of TGFβ1 concentration (24.72±5.89 pg/mL). It was observed a positive correlation between TGFβ1 and glycaemia (R=0.6371; p<0.001) and a negative correlation between TGFβ1 and saliva (R=-0.6162; p<0.001) and glycaemia and SFR (R=-0.5654; P=0.001). AgNORs number and status of maturation of mucosa cells were similar for all conditions. DM and DM+HAS presented the lowest SFR, which correlated with increased TGFβ1 levels. Despite the higher TGFβ1 secretion it was not observed changes in the morphology or proliferation of epithelial cells when diabetes or hypertension was present.

Influence of factors in the oral mucosa maturation pattern: a cross-sectional study applying multivariate analyses

Aim: To evaluate the association between oral health status, socio-demographic and behavioral factors with the pattern of maturity of normal epithelial oral mucosa. Methods: Exfoliative cytology specimens were collected from 117 men from the border of the tongue and floor of the mouth on opposite sides. Cells were stained with the Papanicolaou method and classified into: anucleated, superficial cells with nuclei, intermediate and parabasal cells. Quantification was made by selecting the first 100 cells in each glass slide. Sociodemographic and behavioral variables were collected from a structured questionnaire. Oral health was analyzed by clinical examination, recording decayed, missing and filled teeth index (DMFT) and use of prostheses. Multivariable linear regression models were applied. Results: No significant differences for all studied variables influenced the pattern of maturation of the oral mucosa except for alcohol consumption. There was an increase of cell surface layers of the epithelium with the chronic use of alcohol. Conclusions: It is appropriate to use Papanicolaou cytopathological technique to analyze the maturation pattern of exposed subjects, with a strong recommendation for those who use alcohol - a risk factor for oral cancer, in which a change in the proportion of cell types is easily detected.

Biomarker Testing in Lung Carcinoma Cytology Specimens: A Perspective From Members of the Pulmonary Pathology Society.

The advent of targeted therapy in lung cancer has heralded a paradigm shift in the practice of cytopathology with the need for accurately subtyping lung carcinoma, as well as providing adequate material for molecular studies, to help guide clinical and therapeutic decisions. The variety and versatility of cytologic-specimen preparations offer significant advantages to molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is critical, not only from a lung cancer diagnosis standpoint but also for the myriad ancillary studies that are necessary to provide appropriate clinical management. A large fraction of lung cancers are diagnosed by aspiration or exfoliative cytology specimens, and thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. This review focuses on the opportunities and challenges of using cytologic specimens for molecular diagnosis of lung cancer and the role of cytopathology in the molecular era.

Role of Epstein‐Barr virus status and immunophenotypic studies in the evaluation of exfoliative cytology specimens from patients with post‐transplant lymphoproliferative disorders

Post-transplant lymphoproliferative disorders (PTLDs) are well characterized in tissue sections, but their evaluation in exfoliative cytology specimens is limited. This study reports a 25-year experience with PTLDs in exfoliative cytology specimens. All solid organ or allogeneic stem cell transplant recipients with PTLDs and exfoliative cytology specimens from 1987 to 2011 were identified. The cytomorphology, Epstein-Barr virus (EBV) status, flow cytometry, immunohistochemistry, and molecular studies were reviewed from all exfoliative cytology specimens previously diagnosed as atypical lymphoid proliferations or PTLDs. A total of 55 patients (age range, 1-72 years) with PTLDs had 434 exfoliative cytology specimens. Thirty-six of the 55 patients (65%) had 54 specimens with abnormal lymphoid proliferations (12% of the specimens), and 26 of these patients had 37 specimens available for review (15 cerebrospinal fluid specimens, 12 peritoneal fluid specimens, 9 pleural fluid specimens, and 1 bronchoalveolar lavage fluid specimen). Thirty percent of the reviewed cytology specimens were diagnostic of PTLDs, including 8 cases of monomorphic post-transplant lymphoproliferative disorder (M-PTLD) with abnormal B/T-cell populations identified with flow cytometry/immunohistochemistry and 3 EBV-positive specimens with a differential diagnosis of polymorphic PTLD versus M-PTLD. All cases diagnostic of a PTLD had 1 to 3 ancillary studies performed. Forty percent of the cytology specimens (15 of 37) were suspicious for a PTLD, but ancillary studies were performed for only a third of them, and they did not support a definitive diagnosis of a PTLD. Thirty percent of the cytology specimens (11 of 37) appeared reactive, but they lacked sufficient ancillary studies to exclude a PTLD. Atypical lymphoid proliferations are common in exfoliative cytology specimens from patients with PTLDs, and they require ancillary studies at least including immunophenotyping and EBV evaluations for a definitive diagnosis. Cancer Cytopathol 2016;124:425-35. © 2016 American Cancer Society.

Expression of ATP6V1C1 during oral carcinogenesis

We investigated the gene and protein expressions of V-type ATPase protein subunit C1 (ATP6V1C1) in cases of oral squamous cell carcinoma (OSCC) and contralateral normal mucosa in smokers, nonsmokers and former smokers. Subjects were separated into five groups of 15: group 1, smokers with OSCC; group 2, normal contralateral mucosa of OSCC patients; group 3, chronic smokers; group 4, former smokers who had stopped smoking 1 year earlier; group 5, individuals who had never smoked. Exfoliative cytology specimens from oral mucosa of smokers, former smokers and nonsmokers showed normal gene and protein expression. We found significantly greater gene expression in the OSCC group than in the nonsmoker groups. No difference in gene expression was observed between normal contralateral mucosa and nonsmoker groups, smoker and nonsmoker groups or former smoker and nonsmoker groups. We observed intense immunostaining for ATP6V1C1 protein in all cases of OSCC and weak or no staining in smoker, former smoker and nonsmoker groups. Significantly greater expression of ATP6V1C1 protein was observed in the OSCC group compared to the other groups, which supports the role of ATP6V1C1 in effecting changes associated with oral cancer. Analysis of the mucosae of chronic smokers, former smokers and the normal contralateral mucosa of patients with OSCC showed unaltered ATP6V1C1 gene and protein expression. Early stages of carcinogenesis, represented by altered epithelium of chronic smokers, had neither gene nor protein alterations as seen in OSCC. Therefore, we infer that the changes in ATP6V1C1 occur during later stages of carcinogenesis. Our preliminary study provides a basis for future studies of using ATP6V1C1 levels for detecting early stage OSCC.

Role of Cell Block in Diagnostics-A New Paradigm in Cancer Diagnosis

Major limitation of the conventional FNA smear is the limited material availability for adjuvant diagnostic investigations including Immunocytochemistry. The cell block technique may aid in overcoming this limitation. Cell-block preparations made from sedimented cells can be useful adjunct to the routine cytological methods used for pleural and peritoneal fluids. There are only few studies evaluating its diagnostic efficacy and additional benefits when used with routine cytology. This study was conducted to compare the diagnostic efficacy parameters of cell-blocks and routine cytological smears of fluids and fine needle aspirate in suspected cases of malignancy. Use of cell-blocks as an adjunct to routine cytology smears of body fluids can increase the sensitivity to a considerable extent. It is of further use in pin-pointing a diagnosis by pattern recognition or immunohistochemistry. Cell blocks should be considered in all fine-needle aspiration specimens whenever possible and in selective cases of exfoliative cytology specimens after review of the smears to increase the diagnostic yield.

Cytomorphological features of blastic plasmacytoid dendritic cell neoplasm on FNA and cerebrospinal fluid cytology: A review of 6 cases.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematopoietic tumor that was once believed to be derived from natural killer cells and is now recognized as originating from precursors of plasmacytoid dendritic cells. It generally involves the skin and has an aggressive clinical course. Due to its highly malignant behavior, a fast and accurate diagnosis of this condition is of the utmost importance. Six cytology specimens from 5 patients diagnosed with BPDCN were reviewed as well as their clinical records. Findings were compared with 3 previously published cases. Two exfoliative cytology specimens (cerebrospinal fluid) and 4 fine-needle aspiration specimens (3 lymph node specimens and 1 cutaneous specimen) were reviewed. The cytomorphological aspects were similar in all cases. The smears were hypercellular with a monotonous population of intermediate-sized cells, dispersed singly or arranged in loose aggregates. The cells had round to oval nuclei, with fine chromatin and prominent nucleoli; the cytoplasm was generally scant, without visible granules. Intracytoplasmic microvacuoles were found in the majority of cases. Four cases were also characterized by flow cytometry, which revealed expression of CD 123, CD56 and/or CD4. Fine-needle aspiration was used in 1 case for primary diagnosis. Histological confirmation was available in all cases. BPDCN is a highly malignant neoplasm with a poor outcome. Cytology, in association with flow cytometry immunophenotyping and clinical history, is a reliable method with which to establish the diagnosis.

Improved DNA Extraction Method for Molecular Diagnosis from Smaller numbers of Cells

Isolating total DNA from small samples using traditional methods is difficult and inefficient mainly due to loss of DNA during filtration and precipitation. With advances in molecular pathology, DNA extraction from micro-dissected cells has become essential in handling clinical samples. Genomic DNA extraction using small numbers of cells can be very important to successfully PCR amplify DNA from small biopsy specimens. We compared our experimental genomic DNA extraction method (A) with two other commercially available methods: using spin columns (B), and conventional resins (C), and determined the efficacy of DNA extraction from small numbers of cells smeared on a glass slide. Approximately 50, 100, 200, 500 and 1000 cells were isolated from fine needle aspiration biopsy (FNAB) slides aspirated from histologically proven papillary thyroid carcinoma masses. DNA was extracted using the three techniques. After measuring DNA quantity, PCR amplification was performed to detect the b-globin and BRAF V600E gene mutations. DNA extracted by method (A) showed better yield than the other methods in all cell groups. With our method, a suitable amount of genomic DNA to produce amplification was extracted from as few as 50 cells, while more than 100 to 200 cells were required when methods (B) or (C) were applied. Our genomic DNA extraction method provides high quality and improved yields for molecular analysis. It will be especially useful for paucicellular clinical samples which molecular pathologists often confront when handling fine needle aspiration cytology, exfoliative cytology and small biopsy specimens.

Cytopathology of lung cancer: moving from morphology to molecular

The recent discovery and availability of new targeted therapies for lung cancer has presented new challenges to pathologists. Since many lung cancers are diagnosed by aspiration or exfoliative cytology specimens in the primary or metastatic setting, these new therapies have had an impact on the practice of respiratory cytopathology. In particular, accurate subclassification of non-small cell carcinomas and acquisition of sufficient material for molecular studies is crucial. Balancing the need of adequate material for accurate diagnosis with the demands of clinicians to do more with less tissue has been a challenge and continues to impact the way lung cancers are approached in cytopathology. This review focuses on the changes and impact of the molecular era on the diagnosis of lung cancer in cytopathology.

Toxoplasmosis in a post-transplant bronchoalveolar lavage: A case report

Toxoplasma gondii usually causes an asymptomatic and then latent infection in human adults; however, a potentially fatal disseminated form can occur in immunocompromised patients. Given that the diagnosis of acute Toxoplasma infection, as opposed to latent disease, relies on finding direct evidence of T. gondii infection in tissue, pathologic examination is critical. There have only been a few reports describing the cytomorphology of Toxoplasma in exfoliative cytology, and no reports of the findings in Thin Prep. In this report, we describe a fatal case of toxoplasmosis in a cardiac transplant patient that was diagnosed by respiratory cytopathology. Although the extracellular organisms were well visualized on the Wright-Giemsa stained cytospin, they were only faintly seen on the Pap-stained cytospin trapped within mucin and were not easily appreciated on the ThinPrep slides nor the H&E stained cell block sections. An immunohistochemical stain for Toxoplasma performed on the cell block was strongly positive, and an autopsy performed on the patient confirmed disseminated infection. Our case illustrates that the diagnosis of Toxoplasma in exfoliative cytology specimens can be challenging since organisms are not well visualized on ThinPrep or Pap-stained material; therefore, Wright-Giemsa stained material can be particularly helpful.

The cytomorphologic spectrum of salivary gland type tumors in the lung and mediastinum: A report of 16 patients

In the lung and mediastinum, salivary gland type tumors (SGTTs) can occur as either primary tumors or metastases from tumors arising in the major or minor salivary glands. This study reviewed the cytology cases of SGTTs in the lung and mediastinum diagnosed over a six-year period at our institution. The specimens included a total of 22 exfoliative or aspiration cytology specimens identified in 16 patients. Two of the cases were primary tumors: adenoid cystic carcinoma (ACC) of the trachea and mucoepidermoid carcinoma (MEC) of the thymus. The remaining 20 tumors were metastases from the parotid, submandibular gland, tongue, nasal cavity, or soft palate. Eight of the 16 patients (50%) had a diagnosis of ACC, four (25%) had salivary duct carcinomas, two (12.5%) had MECs, one (6.25%) was a basaloid tumor, and one (6.25%) was polymorphous low grade adenocarcinoma. In our series, these SGTTs were more commonly metastatic in the lung or mediastinum (87.5% of the patients), and the most common histological subtype was ACC, followed by SDC. This study also illustrates the cytomorphologic features and diagnostic pitfalls of these unusual SGTTs.

Comparison of ThinPrep Preparations to Other Preparation Types in Gastrointestinal Cytology: Observations From the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology

Differences in participant responses for ThinPrep (TP) and non-ThinPrep (NTP) preparations for gastrointestinal cytology challenges, which circulated in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC), may help to identify performance variations between preparation types. To compare the performance of TP-prepared slides of gastrointestinal exfoliative cytology specimens to that of NTP preparations in the CAP NGC program. Participant responses between 2000 and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and biliary tract brush specimens with a reference diagnosis of adenocarcinoma, squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges were compared with NTP preparations (conventional smears, cytospins) for discordant responses. In all, 6023 pathologist responses and 3825 cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93% (n = 11 588) of the challenges, while 7% (n = 912) were TP material. A match for a "positive/suspicious" diagnosis was seen in 88.5% of NTP and 95.9% of TP preparations (P < .001). These results were statistically significant when the specific reference diagnosis was adenocarcinoma (P < .001). Overall performance of cytotechnologists was not different from that of pathologists (89.2% versus 89.0%; P = .75). Cytotechnologists had better performance for detecting squamous cell carcinoma (96.3% versus 92.6%; P < .001), while pathologists had better performance for detecting spindle cell neoplasm (79.7% versus 42.9%; P < .001). ThinPrep preparations performed significantly better than NTP preparations in gastrointestinal cytology specimens circulated in an interlaboratory comparison program. Performance varied by reference interpretation, with the best performance for the interpretation of adenocarcinoma. Cytotechnologists and pathologists performed at the same level overall, but with differences for the diagnosis of spindle cell neoplasm and squamous carcinoma.

Comparison of ThinPrep preparations to other preparation types in gastrointestinal cytology: observations from the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology.

Abstract Context.—Differences in participant responses for ThinPrep (TP) and non-ThinPrep (NTP) preparations for gastrointestinal cytology challenges, which circulated in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytology (CAP NGC), may help to identify performance variations between preparation types. Objective.—To compare the performance of TP-prepared slides of gastrointestinal exfoliative cytology specimens to that of NTP preparations in the CAP NGC program. Design.—Participant responses between 2000 and 2007 were evaluated for esophageal wash/brush, gastric wash/brush, and biliary tract brush specimens with a reference diagnosis of adenocarcinoma, squamous cell carcinoma, carcinoid, or spindle cell neoplasm. ThinPrep challenges were compared with NTP preparations (conventional smears, cytospins) for discordant responses. Results.—In all, 6023 pathologist responses and 3825 cytotechnologist responses were reviewed. Non-ThinPrep preparations comprised 93%...

Cytogenetic damage of oral mucosa by consumption of alcohol, tobacco and illicit drugs

The aim of the present study was to quantitatively evaluate micronuclei (MN) in the mucosa of users of alcohol, tobacco and illicit drugs in a Brazilian population. Patients were divided: (i) experimental group - 24 patients users of alcohol, tobacco and illicit drugs from the Center of Psychosocial Care for Alcohol and other Drugs (CAPSad), São José dos Campos city, and (ii) control group: 24 patients attending the clinics of the São José dos Campos Dental School FOSJC-UNESP. Criterion for inclusion in the two groups was no visible clinical alteration in the oral mucosa. Exfoliative cytology specimens were obtained from the left side of the border of the tongue. Feulgen staining was used and 600 cells per subject were evaluated by light microscopy. The frequency of MN and micronucleated cells was analysed statistically using the Kruskal-Wallis and Mann-Whitney tests. The incidence of MN was 3.08 +/- 3.20 in the CAPSad group and 2.08 +/- 1.93 in the control group. The frequency of micronucleated cells was 2.38 +/- 2.57 in the CAPSad group and 1.42 +/- 1.25 in the control group. The results showed a higher frequency of MN and micronucleated cells in the CAPSad group, but the difference compared with the control group was not significant.

Nano-Bio-Chip Sensor Platform for Examination of Oral Exfoliative Cytology

Oral cancer is a deadly and disfiguring disease that could greatly benefit from new diagnostic approaches enabling early detection. In this pilot study, we describe a nano-bio-chip (NBC) sensor technique for analysis of oral cancer biomarkers in exfoliative cytology specimens, targeting both biochemical and morphologic changes associated with early oral tumorigenesis. Here, oral lesions from 41 dental patients, along with normal epithelium from 11 healthy volunteers, were sampled using a noninvasive brush biopsy technique. Specimens were enriched, immunolabeled, and imaged in the NBC sensor according to previously established assays for the epidermal growth factor receptor (EGFR) biomarker and cytomorphometry. A total of 51 measurement parameters were extracted using custom image analysis macros, including EGFR labeling intensity, cell and nuclear size, and the nuclear-to-cytoplasmic ratio. Four key parameters were significantly elevated in both dysplastic and malignant lesions relative to healthy oral epithelium, including the nuclear area and diameter (P < 0.0001), the nuclear-to-cytoplasmic ratio (P < 0.0001), and EGFR biomarker expression (P < 0.03). Further examination using logistic regression and receiver operating characteristic curve analyses identified morphologic features as the best predictors of disease (area under the curve < or =0.93) individually, whereas a combination of all features further enhanced discrimination of oral cancer and precancerous conditions (area under the curve, 0.94) with high sensitivity and specificity. Further clinical trials are necessary to validate the regression model and evaluate other potential biomarkers, but this pilot study supports the NBC sensor technique as a promising new diagnostic tool for early detection of oral cancer, which could enhance patient care and survival.

Comparison of Exfoliative Pap Stain and AgNOR Counts of the Tongue in Smokers and Nonsmokers

To compare exfoliative cytology from the oral mucosa of smokers and nonsmokers, with emphasis on proliferative activity. Exfoliative cytology specimens were obtained from clinical normal mucosa from the lateral border of the tongue in 30 nonsmokers and 30 smokers ranging in age from 40 to 70 years of age, who were seen at the Heart Institute's Patient Center and the Smoking Cessation Program of the University Hospital, University of São Paulo Medical School (InCor-HCFMUSP). The cytologic specimens were evaluated by Papanicolaou staining and AgNOR quantification in order to evaluate the presence of cytological alterations suggestive of inflammation, dysplasia, keratinization, and proliferative activity of epithelial cells. Only Papanicolaou Class I and Class II smears were observed. Inflammatory alterations were found in 90% of smokers and in 87% of nonsmokers. The number of AgNORs/nucleus differed significantly between smokers and nonsmokers (3.372 +/- 0.375 versus 2.732 +/- 0.236). Within the limitations of this research, the results indicate higher proliferative activity in smoking patients compared to nonsmoking patients, even in the absence of clinical lesions.