Digital Image DNA Cytometry: A Useful Tool for the Evaluation of Malignancy in Biliary Strictures

Background: A preceding exploratory study (J. Clin. Pathol. 57(2004), 1201–1207) had shown that a karyometric assessment of nuclei from papillary urothelial neoplasms of low malignant potential (PUNLMP) revealed subtle differences in phenotype which correlated with recurrence of disease. Aim of the Study: To validate the results from the exploratory study on a larger sample size. Materials: 93 karyometric features were analyzed on haematoxylin and eosin-stained sections from 85 cases of PUNLMP. 45 cases were from patients who had a solitary PUNLMP lesion and were disease-free during a follow-up period of at least 8 years. The other 40 were from patients with a unifocal PUNLMP, with one or more recurrences in the follow-up. A combination of the previously defined classification functions together with a new P-index derived classification method was used in an attempt to classify cases and identify a biomarker of recurrence in PUNLMP lesions. Results: Validation was pursued by a number of separate approaches. First, the exact procedure from the exploratory study was applied to the large validation set. Second, since the discriminant function 2 of the exploratory study had been based on a small sample size, a new discriminant function was derived. The case classification showed a correct classification of 61% for non-recurrent and 74% for recurrent cases, respectively. Greater success was obtained by applying unsupervised learning technologies to take advantage of phenotypical composition (correct classification of 92%). This approach was validated by dividing the data into training and test sets with 2/3 of the cases assigned to the training sets, and 1/3 to the test sets, on a rotating basis, and validation of the classification rate was thus tested on three separate data sets by a leave-k-out process. The average correct classification was 92.8% (training set) and 84.6% (test set). Conclusions: Our validation study detected subvisual differences in chromatin organization state between non-recurrent and recurrent PUNLMP, thus allowing a very stable method of predicting recurrence of papillary urothelial neoplasms of low malignant potential by karyometry.

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Whole slide image with image analysis of atypical bile duct brushing: Quantitative features predictive of malignancy

Collins

Weimholt

2015

Journal of Pathology Informatics

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Background:Whole slide images (WSIs) involve digitally capturing glass slides for microscopic computer-based viewing and these are amenable to quantitative image analysis. Bile duct (BD) brushing can show morphologic features that are categorized as indeterminate for malignancy. The study aims to evaluate quantitative morphologic features of atypical categories of BD brushing by WSI analysis for the identification of criteria predictive of malignancy.Materials and Methods:Over a 3-year period, BD brush specimens with indeterminate diagnostic categorization (atypical to suspicious) were subjected to WSI analysis. Ten well-visualized groups with morphologic atypical features were selected per case and had the quantitative analysis performed for group area, individual nuclear area, the number of nuclei per group, N: C ratio and nuclear size differential.Results:There were 28 cases identified with 17 atypical and 11 suspicious. The average nuclear area was 63.7 µm2 for atypical and 80.1 µm2 for suspicious (+difference 16.4 µm2; P = 0.002). The nuclear size differential was 69.7 µm2 for atypical and 88.4 µm2 for suspicious (+difference 18.8 µm2; P = 0.009). An average nuclear area >70 µm2 had a 3.2 risk ratio for suspicious categorization.Conclusion:The quantitative criteria findings as measured by image analysis on WSI showed that cases categorized as suspicious had more nuclear size pleomorphism (+18.8 µm2) and larger nuclei (+16.4 µm2) than those categorized as atypical. WSI with morphologic image analysis can demonstrate quantitative statistically significant differences between atypical and suspicious BD brushings and provide objective criteria that support the diagnosis of carcinoma.

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Digital Image DNA Cytometry: A Useful Tool for the Evaluation of Malignancy in Biliary Strictures

Cited by 4 publications

References 26 publications

Sensitivity of alternative testing for pancreaticobiliary cancer: a 10-y review of the literature

Sensitivity of alternative testing for pancreaticobiliary cancer: a 10-y review of the literature

Chromatin Phenotype Karyometry Can Predict Recurrence in Papillary Urothelial Neoplasms of Low Malignant Potential

Whole slide image with image analysis of atypical bile duct brushing: Quantitative features predictive of malignancy

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