Abstract

Histopathological diagnosis of lymphomas represents a challenge requiring either expertise or centralised review, and greatly depends on the technical process of tissue sections. Hence, we developed an innovative deep-learning framework, empowered with a certainty estimation level, designed for haematoxylin and eosin-stained slides analysis, with special focus on follicular lymphoma (FL) diagnosis. Whole-slide images of lymph nodes affected by FL or follicular hyperplasia were used for training, validating, and finally testing Bayesian neural networks (BNN). These BNN provide a diagnostic prediction coupled with an effective certainty estimation, and generate accurate diagnosis with an area under the curve reaching 0.99. Through its uncertainty estimation, our network is also able to detect unfamiliar data such as other small B cell lymphomas or technically heterogeneous cases from external centres. We demonstrate that machine-learning techniques are sensitive to the pre-processing of histopathology slides and require appropriate training to build universal tools to aid diagnosis.

Highlights

  • The microscopic diagnosis of lymphoma remains challenging

  • The diagnosis of lymphoma is currently based on histopathological examination of tissue sections at different magnification levels by a pathologist whose suspicion is based upon morphological features observed on haematoxylin and eosin (H&E) staining

  • We used a total of 378 lymph nodes: 197 were infiltrated by follicular lymphoma (FL) and 181 lymph nodes with follicular hyperplasia (FH)

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Summary

Introduction

The microscopic diagnosis of lymphoma remains challenging. A diagnostic discrepancy is established when the referral pathologist sends the case for a second opinion with a proposal (with or without a signed report), which is unconfirmed by the expert[1]. Recent data from our group within the French (nationwide) Lymphopath network pointed out a 20% discrepancy between referral and expert pathologists directly impacting on patient care[1]. The diagnosis of lymphoma is currently based on histopathological examination of tissue sections at different magnification levels by a pathologist whose suspicion is based upon morphological features observed on haematoxylin and eosin (H&E) staining. Approximately 10% of cases remain difficult (in particular those without expression of CD10 and/or Bcl2) and require additional tests such as fluorescent in-situ hybridisation or polymerase chain reaction techniques that are routinely unavailable in some laboratories

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