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PLoS One. 2018 Jun 13;13(6):e0197435. doi: 10.1371/journal.pone.0197435. eCollection 2018.

Histopathology of thymectomy specimens from the MGTX-trial: Entropy analysis as strategy to quantify spatial heterogeneity of lymphoid follicle and fat distribution.

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Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, United States of America.
Department of Neurology, George Washington University Medical Center, Washington, DC, United States of America.
Institute of Pathology, Charité, Berlin, Germany.
Department of Neurology, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, NY, United States of America.
Institute of Pathology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany.


The thymectomy specimens from the "thymectomy trial in non-thymomatous myasthenia gravis patients receiving prednisone therapy" (MGTX) underwent rigid and comprehensive work-up, which permits analysis of the spatial distribution of histological and immunohistological features. This analysis revealed strong intra- and inter-case variability. While many histological features (e.g. median percent fat content among different specimens) can easily be correlated with clinical parameters, intra-case spatial variability of histological features has yet defied quantification and statistical evaluation. To overcome this gap in digital pathology, we here propose intra-case entropy of measured histological features in all available slides of a given thymectomy specimen as a quantitative marker of spatial histological heterogeneity. Calculation of entropy led to one value per specimen and histological feature. Through these 'entropy values' the so far neglected degree of spatial histological heterogeneity could be fed into statistical analyses, extending the scope of clinico-pathological correlations.

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