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This study evaluates the reliability of frozen hematology foundation models (FMs) across varying clinical settings by auditing 15 encoders for accuracy robustness and calibration against four public single-cell acquisition domains. While in-domain performance is high (macro-F1 scores of 0.98-0.997), cross-dataset performance reveals a significant drop of 34-72%, with notable shifts in ranking among models, highlighting vulnerabilities in deployment. The introduction of Class-Balanced Re-standardization (CBR) shows promise in improving target-prior scenario means and calibration, underscoring the need for comprehensive benchmarking in hematology FMs.
Cross-domain performance of frozen hematology models can plummet by up to 72%, revealing critical vulnerabilities in clinical deployment.
Frozen hematology foundation-model (FM) embeddings reach near-saturated in-domain white-blood-cell (WBC) accuracy, but clinical deployment demands reliability across scanners, sites, stains and preparation pipelines. We audit 15 frozen encoders (hematology, pathology, and general vision) across four public single-cell acquisition domains along two axes: accuracy robustness and calibration. In-domain linear-probe macro-F1 is saturated (0.98-0.997), yet cross-dataset macro-F1 drops 34-72% and rankings re-order: DinoBloom-L, the in-domain best, falls to 10th of 15 on the most-shifted target (MLL23) at the benchmark's shared 224-px input, behind RedDino and several general and pathology encoders. Rank transfer is probe-dependent: 1-NN retrieval is more stable on average than a source-fitted linear head (median $\rho$ 0.65 vs 0.45), but neither probe universally predicts target robustness. Calibration also collapses: source-trained probes are nearly calibrated in-domain (expected calibration error, ECE, 0.004) but confidently wrong off-domain (ECE 0.35), and source-fitted temperature scaling transfers poorly. We further audit pretraining exposure and identify MLL23 as DinoBloom's internal cohort; because DinoBloom's only held-out dataset is also our source domain, this benchmark cannot isolate exposure from scanner-associated shift. Label-free adaptation and marginal-entropy-based model selection appear safe under balanced evaluation but fail under realistic WBC class-prior shift. Class-Balanced Re-standardization (CBR), a training-free pseudo-label-balanced feature normalization, improves all evaluated target-prior scenario means and partially improves calibration, although encoder-level exceptions and residual miscalibration remain. Hematology FM benchmarks must therefore jointly audit accuracy, calibration, exposure, and class-prior robustness.