SydneyMTL: Interpretable Multi-Task Learning for Complete Sydney System Assessment in Gastric Biopsies

The Updated Sydney System (USS) provides a standardized framework for grading gastritis and stratifying gastric cancer risk. However, subjective observer variability and labor-intensive workflows impede its routine clinical use. To address these challenges, we developed SydneyMTL, a multi-task deep learning framework that uses Multiple Instance Learning (MIL) with task-specific attention pooling to predict severity grades across all five USS attributes simultaneously. Trained on an unprecedented cohort of 50,765 whole-slide images (WSIs), SydneyMTL generates interpretable histologic evidence for clinical practice. In retrospective evaluations against 24 board-certified pathologists, the model achieved an overall mean lenient accuracy of 89.1%, with 22 pathologists exhibiting >80% agreement with the model. When evaluated on an expert-adjudicated "Golden dataset," the models performance improved to 90.2%, demonstrating its capacity to align with multi-expert consensus and filter individual annotator noise. Latent space analysis confirmed that SydneyMTL captures the ordinal structure of the USS, by representing disease severity as a continuous biological spectrum rather than as disjoint categories. Finally, a randomized crossover reader study showed that AI-assisted review significantly reduced interpretation time and improved inter-observer agreement, establishing SydneyMTL as a scalable tool for supporting standardized gastric cancer risk stratification. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=154 HEIGHT=200 SRC="FIGDIR/small/26346304v1_ufig1.gif" ALT="Figure 1"> View larger version (66K): org.highwire.dtl.DTLVardef@bf83adorg.highwire.dtl.DTLVardef@15dff59org.highwire.dtl.DTLVardef@274874org.highwire.dtl.DTLVardef@105f759_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LISydneyMTL is the first unified framework to simultaneously predict the full 4-tier severity grades across all five Updated Sydney System attributes. C_LIO_LITrained on a massive cohort of 50,765 whole slide images, the model aligns with multi-expert consensus on a rigorous "Golden dataset". C_LIO_LIAI assistance significantly reduces pathologist reading time and harmonizes inter-observer variability in real-world clinical workflows. C_LIO_LILatent space analysis confirms that SydneyMTL preserves the biological ordinality of disease severity without explicit ordinal constraints. C_LI The bigger pictureGastritis is among the most frequent diagnoses in gastrointestinal pathology, and its histologic severity is central to gastric cancer prevention. In routine practice, pathologists convert subtle mucosal changes into semi-quantitative, ordinal grades using the Updated Sydney System, which evaluates five co-existing histologic dimensions. While this framework provides a shared language, grading is labor intensive and inherently dependent on reader-specific thresholds, creating variability that affects risk stratification and surveillance. A key concept motivating our study is that gastritis is not defined by a single finding but by multiple criteria that co-occur and interact. This suggests that computational models should learn these criteria jointly - capturing their biological correlations and the continuum of severity - rather than treating each grade as an isolated classification task. SydneyMTL implements this perspective through a unified multi-task, weakly supervised approach that learns directly from a massive cohort of 50,765 routine whole-slide images. Beyond diagnostic accuracy, our work reveals that the model preserves the ordinality of severity in its representation space, supporting the biological view that discrete clinical categories approximate an underlying continuous biological spectrum. Its attention-based explanations also connect model outputs to interpretable tissue evidence, enhancing clinical trust. Crucially, by harmonizing inter-observer variability, SydneyMTL provides a more reliable foundation for gastric cancer risk assessment, ensuring that premalignant changes are captured with greater consistency. More broadly, our findings reposition AI for gastritis from narrow detection toward scalable, evidence-based decision support that can standardize grading practices and reduce cognitive burden on the global pathology workforce.