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This study proposes and systematically evaluates four purpose-built lightweight convolutional neural network (CNN) variants (Lite-V0, Lite-V1, Lite-V2, and Lite-V4) for binary classification of colon histopathology images into\n                    <jats:italic>Colon_Adenocarcinoma<\/jats:italic>\n                    and\n                    <jats:italic>Colon_Benign_Tissue<\/jats:italic>\n                    . Experiments were conducted on a balanced dataset (24,000 images) with fixed train\/validation\/test splits and comprehensive evaluation using accuracy and macro-F1, supported by confusion matrices and ROC\/precision\u2013recall analyses. Among all variants, Lite-V2 achieved the best validation performance (macro-F1\n                    <jats:inline-formula>\n                      <jats:tex-math>$$\\approx$$<\/jats:tex-math>\n                    <\/jats:inline-formula>\n                    0.999), while remaining highly compact (1.53 MB; 127,682 parameters), indicating a favorable accuracy\u2013efficiency trade-off for deployment-oriented diagnostic support. On the independent test set, however, Lite-V2 exhibited a marked generalization drop, achieving approximately 50% accuracy and macro-F1 = 0.33, suggesting a domain-shift effect between validation and test samples. These findings demonstrate that lightweight CNNs can achieve near-perfect internal validation performance for colon histopathology classification, but robust cross-domain generalization remains essential; future work will focus on domain adaptation and stain-robust training strategies to improve reliability on unseen clinical data.\n                  <\/jats:p>","DOI":"10.1038\/s41598-026-35119-y","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T13:46:09Z","timestamp":1768830369000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Compact deep learning models for colon histopathology focusing performance and generalization challenges"],"prefix":"10.1038","volume":"16","author":[{"given":"Fareeha","family":"Hanif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Raza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heba Abdelgader","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,19]]},"reference":[{"key":"35119_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F. 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