Sparse concept attribution for histomorphological hypothesis generation from whole-slide classifiers

Abstract: Histology images contain rich morphological information and can provide insights into pathological processes. However, deriving hypotheses relating morphological phenotypes to clinical attributes is bottlenecked by a manual image interpretation step. Here, we demonstrate that this process can be automated through interpretable deep learning. We present SCOPE, a method to interpret slide-level classifiers by combining pathology-specific vision--LLMs with sparse concept attribution onto a generalist histomorphological concept bank. To measure whether such explanations recover known morphology, we introduce MorphoRecoveryBench, a benchmark of seven tasks with pathologist-curated reference descriptions. On this benchmark, dense concept attribution is indistinguishable from a random baseline, whereas sparse attribution recovers substantial known morphology; decomposing the pooled slide embedding reaches similar explanation correctness at a fraction of the computational cost. Post-hoc interpretation of whole-slide classifiers can thus generate morphological hypotheses at scale, for expert validation.