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

Abstract

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.

Automatic evaluation of tumor budding in immunohistochemically stained colorectal carcinomas and correlation to clinical outcome

“…By applying methods of spatial statistics [ 50 – 53 ] to describe the spatial heterogeneity (as recently published for vessels in CRC [ 33 ], for lymphatic hyperplasia in the thymus [ 54 ] or for lymphatic infiltrates in the bone marrow [ 55 ]), we found significant accumulations of tumor budding foci independent of the overall frequency of tumor budding, which we called budding hotspots. The number of these budding hotspots and not their budding metrics (e.g., median budding score in the hotspots) did correlate with the nodal status.…”

Unraveling the role of ectopic thymic tissue in patients undergoing thymectomy for myasthenia gravis

“…In addition, it takes a lot of time, money and efforts to address the ectopic thymic tissue and active ectopic thymic tissue, thus a well-designed prospective observational study should be of great value to provide high level of evidence. A comprehensive work-up from the MGTX group has been reported in detail, describing a perfect way of addressing the histopathology of thymectomy specimens (48,49). The role of ectopic thymic tissue is currently being investigated and the results are eagerly awaited.…”