Infrared Spectroscopic Analysis in the Differentiation of Epithelial Misplacement From Adenocarcinoma in Sigmoid Colonic Adenomatous Polyps

Abstract

Purpose: The differential diagnosis of epithelial misplacement from invasive cancer in the colon is a challenging endeavour, augmented by the introduction of bowel cancer population screening. The main aim of the work is to test, as a proof-of concept study, the ability of the infrared spectroscopic imaging approach to differentiate epithelial misplacement from adenocarcinoma in sigmoid colonic adenomatous polyps. Methods: Ten samples from each of the four diagnostic groups, normal colonic mucosa, adenomatous polyps with low grade dysplasia, epithelial misplacement in adenomatous polyps and adenocarcinoma, were analysed using IR spectroscopic imaging and data processing methods. IR spectral images were subjected to data pre-processing and cluster analysis based segmentation to identify epithelial, connective tissue and stromal regions. Statistical analysis was carried out using principal component analysis and linear discriminant analysis based cross validation, to classify spectral features according to the pathology, and the diagnostic attributes were compared. Results: The combined 4-group classification model on an average showed a sensitivity of 64%, a specificity of 88% and an accuracy of 76% for prediction based on a ‘single spectrum’, whilst a ‘majority-vote’ prediction on an average showed a sensitivity of 73%, a specificity of 90% and an accuracy of 82%. The 2-group model, for the differential diagnosis of epithelial misplacement versus adenocarcinoma, showed an average sensitivity and specificity of 82.5% for prediction based on a ‘single spectrum’ whilst a ‘majority-vote’ classification showed an average sensitivity and specificity of 90%. A 92% area under the curve (AUC) value was obtained when evaluating the classifier using the Receiver Operating Characteristics (ROC) curves. Conclusions: IR spectroscopy shows promise in its ability to differentiate epithelial misplacement from adenocarcinoma in tissue sections, considered as one of the most challenging endeavours in population-wide diagnostic histopathology. Further studies with larger series, including cases with challenging diagnostic features are required to ascertain the capability of this modern digital pathology approach. In the long-term, IR spectroscopy based pathology which is relatively low-cost and rapid, could be a promising endeavour to consider for integration into the existing histopathology pathway, in particular for population based screening programmes where large number of samples are scrutinised.

Imaging of colorectal adenomas with pseudoinvasion and malignant polyps using two-photon excitation microscopy

“…Deeper-level sections through the paraffin block and seeking a second opinion from a pathologist with expertise in digestive pathology are recommended for equivocal cases ( 13 ). Various methods, including immunohistochemistry - both epithelial (p53, E-chaderin) and stromal markers (collagen IV, MMP-1) and three-dimensional reconstruction or infrared spectroscopic techniques ( 12 , 14 ), have been explored for the differential diagnosis of these entities. However, their utility in distinguishing challenging cases remains limited ( 15 ).…”

Imaging of colorectal adenomas with pseudoinvasion and malignant polyps using two-photon excitation microscopy

“…Immunohistochemistry may be helpful -both epithelial (p53, Echaderin) and stromal markers (collagen IV, MMP-1), but their usefulness in differentiating di cult cases is limited [26]. Three-dimensional reconstruction or infrared spectroscopic techniques were used in the attempt to differentiate malignant polyps from adenomas with epithelial misplacement [12], [27].…”