A Hierarchical Ensemble Inference Pipeline for Robust White Blood Cell Classification Under Domain Shifts

Leukemia cell image classification is challenged by real-world domain shifts from acquisition, staining, illumination, and site protocols, causing single-dataset models to generalize poorly in real clinical scenarios. This work presents a robust framework for leukemia classification across multiple heterogeneous datasets using a two-stage pipeline with a pretrained vision foundation model. Stage 1 performs binary classification (leukemia vs. non-leukemia) and is trained using 122,167 single-cell images. Stage 2 is conditionally applied to Stage 1 positives to perform subtype classification into Acute Lymphoblastic Leukemia (ALL) and Acute Myeloid Leukemia (AML), trained using 69,400 single-cell images. Labels are harmonized across five heterogeneous datasets to enable cross-dataset training, and performance is evaluated on a held-out dataset protocol to assess domain-shift generalization. Within this pipeline, three encoders are benchmarked (DinoBloom, pretrained on single-cell images; BiomedCLIP, pretrained on biomedical data; and CLIP as a general-purpose model) under linear probing, Low-Rank Adaptation (LoRA), and a Retrieval-Augmented Classification (RAC) module that retrieves the top-k most similar cell images to provide cytomorphological grounding. The objective is to quantify how much domain-specific pretraining contributes to performance under domain shift, and whether cost-effective adaptation and retrieval can be a viable alternative to expensive domain-specialized pretraining. The held-out protocol additionally serves as a diagnostic tool, revealing when classification performance is attributable to dataset-specific artifacts rather than to cytomorphological features.

The microscopic examination of white blood cells (WBCs) plays a fundamental role in pathology and is essential for diagnosing blood disorders such as leukemia and anemia. To support further research on WBC images, multiple datasets have been proposed. However, they mainly annotate cell categories, and lack detailed morphological characteristics that pathologists use to explain their interpretations of cells. To address this gap, we introduce WBCAtt+, a novel dataset of WBC images densely annotated with 11 morphological attributes and five pixel-level cell components. With 113k image-level labels and 10k segmentation maps, WBCAtt+ is the first to provide comprehensive annotations for WBC images. Leveraging this dataset, we provide baseline models for attribute recognition and semantic segmentation. We also design an attribute recognition model to incorporate compositional structure of cells, further improving the recognition performance. Lastly, we showcase various applications enabled by our dataset, such as explainable AI models, including counterfactual example generation. \revision{The dataset and code are publicly available\footnote{https://doi.org/10.57967/hf/8143}}.

Diagnosing and monitoring diseases frequently involves the analysis of human biological samples, with blood analysis being pivotal. Specifically, leukocytes, or white blood cells (WBCs), are essential markers for evaluating the body's defense mechanisms against infections. Traditional methods for WBC counting and classification are labor-intensive and prone to inaccuracies, primarily due to human error. The conventional processes for blood cell analysis, especially those concerning WBCs, are beset with difficulties. These include the laborious nature of manual counting and the susceptibility to errors, which can significantly impact the accuracy and reliability of disease diagnosis and monitoring. This study proposes an automated, machine learning-based solution aimed at mitigating the identified challenges. By employing a hybrid model that integrates Yolov5 for the detection of WBCs, coupled with a finely tuned, pre-trained MobileNetV2 model and a Logistic Regression classifier, the study innovates in the accurate identification, counting, and classification of WBCs into four distinct types. The methodology leverages the BCCD dataset for training and validation purposes. The application of the proposed hybrid machine learning model has yielded remarkable results, demonstrating a detection accuracy rate of 98% through the Yolov5 stage, and an unparalleled classification accuracy of 99.04% in subsequent stages utilizing MobileNetV2 and Logistic Regression. Additionally, Our proposed YOLOv5-based RBC detection module achieves an F1 score of 99.73%, which outperforms the baseline. These findings underscore the model's potential in transforming traditional laboratory practices for WBC analysis, offering a path towards more accurate, efficient, and reliable disease diagnostics and monitoring.