Histological Image Classification Between Follicular Lymphoma and Reactive Lymphoid Tissue Using Deep Learning and...

Background/Objectives: The major question that confronts a pathologist when evaluating a lymph node biopsy is whether the process is benign or malignant, and the differential diagnosis between follicular lymphoma and reactive lymphoid tissue can be challenging. Methods: This study designed a convolutional neural network based on ResNet architecture to classify a large series of 221 cases, including 177 follicular lymphoma and 44 reactive lymphoid tissue/lymphoid hyperplasia, which were stained with hematoxylin and eosin (H&E). Explainable artificial intelligence (XAI) methods were used for interpretability. Results: The series included 1,004,509 follicular lymphoma and 490,506 reactive lymphoid tissue image-patches at 224 × 244 × 3, and was partitioned into training (70%), validation (10%), and testing (20%) sets. The performance of the training (training and validation sets) had an accuracy of 99.81%. In the testing set, the performance metrics achieved an accuracy of 99.80% at the image-patch level for follicular lymphoma. The other performance parameters were precision (99.8%), recall (99.8%), false positive rate (0.35%), specificity (99.7%), and F1 score (99.9%). Interpretability was analyzed using three methods: grad-CAM, image LIME, and occlusion sensitivity. Additionally, hybrid partitioning was performed to avoid information leakage using a patient-level independent validation set that confirmed high classification performance. Conclusions: Narrow artificial intelligence (AI) can perform differential diagnosis between follicular lymphoma and reactive lymphoma tissue, but it is task-specific and operates within limited constraints. The trained ResNet convolutional neural network (CNN) may be used as transfer learning for larger series of cases and lymphoma diagnoses in the future.