Evaluation of tumor budding and its correlation with histomorphological prognostic markers in oral squamous cell carcinoma and its association with the epithelial-mesenchymal transition process.

Objective: To evaluate the association of tumor budding (TB) with prognostic histomorphological parameters in oral squamous cell carcinoma (OSCC) and to investigate the correlation of TB intensity with epithelial to mesenchymal transition (EMT). Material and Method: A total of 200 cases diagnosed as OSCC were selected and their TB status was reviewed using Hematoxylin and eosin (H and E) and Immunohistochemistry (IHC). Correlation with histomorphological prognostic parameters was done. Also, IHC for Vimentin and E-cadherin was performed to look for EMT. Results: On H and E examination, TB was observed in 154/200 (77%). About 88/154 (57.14%) cases showed a high TB (>5 TB/10 hpf) which increased to 100/154 (64.9%) cases on IHC staining. The intensity of TB was significantly associated with tumor grade and depth of invasion. It was also significantly associated with reduced expression for E-Cadherin and upregulation of Vimentin establishing a pathogenetic correlation between the TB and EMT. Conclusion: Therefore, our results suggest that TB is associated with poor prognosis and histologically represents EMT in OSCC which further adds to the aggressiveness of the tumor.

Spectrum of histopathological changes and its quantification using a scoring system in patients with gastroesophageal reflux disease.

Aim: The aim of this study was to evaluate the role of histopathological and histomorphometric features in oesophageal biopsy of patients presenting with symptoms of Gastroesophageal Reflux Disease (GERD). Material and Methods: Present study included 42 patients and 12 controls. Complete clinical evaluation followed by endoscopic examination of the patients was done and multipleoesophageal biopsies were taken. Biopsies were processed routinely and stained with Hematoxylin and Eosin and examined for any changes related to GERD. Morphometric assessment was done by using Leitz optical micrometer. The histological scoring was done based on the parameters: basal cell hyperplasia, stromal papillae elongation, cells with irregular nuclear contour (CINC), eosinophilic infiltrate, gastric and intestinal metaplasia. A numerical score was assigned to each parameter and sum of these scores represented the total score. Statistics: The statistical analysis was done using graph pad prism, Medcalc software and Windows MS office. P value and mean standard deviation (SD) was calculated. Results: The endoscopic findings of all the controls and 83.33% of patients were normal. Only 16.67% of patients had reflux associated changes of varying grades on endoscopy. Oesophageal biopsy of all patients had changes related to GERD on histology. Immunohistochemistry confirmed that cells with irregular nuclear contour were T- lymphocytes. The mean (SD) histological scoring of control and patients were 1.75 (0.62) and 5.66 (1.31) respectively. The difference was considered to be statistically significant (P < 0.001). Thus, it was suggested that a cut-off of histological score > 3 can be used to indicate GERD. Conclusion: Patients with gastroesophageal reflux symptoms can have normal endoscopic findings but can be diagnosed on the basis of histological changes in the squamous epithelium. Scoring of the histopathological parameters along with the cut-off value can give a definitive diagnosis of GERD.

Evaluation and Quantification of Cytomorphometry in Conjunction with Visual Examination and Exfoliative Cytology in Early Diagnosis of Oral Premalignant and Malignant Lesions.

INTRODUCTION: Incidence of oral epithelial dysplasia and oral squamous cell carcinoma (SCC) is very high in south Asian countries as compared to western population owing to a greater use of tobacco in these regions. While visual examination and exfoliative cytology are the most common screening and diagnostic modalities at present, it is a subjective analysis. Quantitative analyses such as nuclear size, cell size, and nuclear-to-cytoplasmic ratio may provide an accurate diagnosis and improve reproducibility. The aim of the study was to evaluate the role of morphometry as a diagnostic adjunct to exfoliative cytology and to derive a significant cutoff to identify the population at risk for development of SCC among chronic tobacco users. MATERIAL AND METHODS: This was an outpatient-based prospective study done in a tertiary hospital over a period of 2 years. Hundred and fifty cases with a history of chronic tobacco use for a minimum period of 5 years were evaluated. Visual inspection using acetic acid was done. Oral scrapes were taken for cytological and morphometric analysis followed by incision biopsy for histopathological evaluation, wherever possible. RESULTS: On morphometrical analysis, mean nuclear area and nuclear:cytoplasmic (N:C) ratio increased, while the cytoplasmic area decreased from smears with normal cytology to oral dysplasia to SCC. Analysis of variance and post hoc Tukey's honest significant difference test showed a statistically significant difference among the 3 groups (p value <0.05). A cutoff value for a significant N:C ratio was calculated as ≥0.08 using Youden's index with a sensitivity and a specificity of 88% and 94%, respectively. CONCLUSION: In high-risk cases, morphometry can be a useful adjunct to exfoliative cytology and visual examination for an early and accurate diagnosis and timely intervention in oral potentially malignant and malignant lesions, thereby improving the prognosis.

Evaluation of Role of Visual Inspection Using Acetic Acid (VIA) and Exfoliative Cytology in Screening and Early Detection of Oral Premalignant Lesions and Oral Cancer.

OBJECTIVE: Oral cancer accounts for 50-70% of total cancer mortality. VIA screening has drastically changed the morbidity and mortality related to cervical cancer. In present study, we assessed the role of 5% Acetic Acid as a vital stain in oral mucosa of chronic tobacco chewers, to know if it can help in early diagnosis and improved prognosis of oral malignancies and to assess the sensitivity and specificity of VIA and exfoliative cytology for screening of Oral premalignant and malignant lesions in high risk population with limited health care infrastructure. METHODS: This was an outpatient department based prospective study done in a tertiary hospital over a period of two years. 150 cases with a history of chronic tobacco use were evaluated. Visual inspection (VI) followed by VIA using 5% Acetic acid was done. Oral scrapes were taken for cytological examination followed by biopsy for histopathological evaluation, wherever possible. RESULTS: Sensitivity, specificity, PPV, NPV and accuracy of VIA and Exfoliative cytology was 71%, 65%, 83%, 48%, 69% and 98%, 65%, 89%, 92%, 88% respectively keeping histology as gold standard. CONCLUSION: Acetic acid along with exfoliative cytology can be used as simple, cost effective and convenient methods for mass screening of OPMDs and OSCC in high risk population where biopsy is not possible.
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Role of Hematological Indices as a Screening Tool of Beta Thalassemia Trait in Eastern Uttar Pradesh: An Institutional Study.

A large majority of microcytic hypochromic anemia have defects in cellular hemoglobin synthesis due to either iron deficiency or thalassemia trait; both differing in management and prognosis. HPLC and serum iron profile as confirmatory tests are unavailable at health care centers. Blanket therapy of iron supplements is therefore given in all such cases which may cause iron overload in thalassemia cases. Easy to use and cost effective screening methods are desirable. The present study was undertaken to evaluate the diagnostic accuracy of twelve indices to effectively screen cases of thalassemia trait and differentiate them from iron deficiency anemia. Routine samples from the hematology lab with Hb < 13 gm/dl, MCV < 80 fl and MCH < 27 pg were screened. Taking HPLC and serum ferritin as gold standard, out of total 1353 cases, 98 cases of thalassemia trait (HbA2 > 3.5 on HPLC) and 1102 cases of iron deficiency anemia (serum ferritin < 12 g/ml) were evaluated using discrimination indices. Diagnostic accuracy for each index was calculated. While few indices showed a sensitivity of 100%, their specificity was low which meant more number of false positive cases. Based on Youden's Index, which measures the diagnostic tests ability to balance sensitivity and specificity, the best three indices in the decreasing order of their efficacy in our study were Ricerca Index (RI), Green and King Index (GKI) and Mentzer Index (MI). MI is considered a reliable index by many clinicians since a long time, however RI and GKI were found to have a better diagnostic accuracy based on our study.

Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.

BACKGROUND: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet. MATERIALS AND METHODS: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association. RESULTS: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns. CONCLUSION: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.