Validation of Digital Cytology for Primary Diagnosis Across a Range of Specimen Types

This study evaluated the diagnostic performance of high-resolution whole slide imaging (WSI) for primary cytological diagnosis across a broad range of specimen types and preparations.

In a single-centre, retrospective validation study, 88 archived cytology cases representative of routine clinical practice were scanned at 40× equivalent magnification (0.23 μm/pixel) using the Hamamatsu NanoZoomer S360MD Slide scanner system. Specimens included gynaecological and non-gynaecological exfoliative and fine needle aspirate samples, prepared as smears, ThinPreps, cytospins or cell blocks. WSI were each reviewed independently by two expert cytopathologists with minimal prior digital cytology reporting experience, blinded to original light microscopy (LM) diagnoses. Discordant cases underwent LM review. Diagnostic concordance and agreement were assessed using percentage concordance and Cohen's κ (unweighted and weighted, for non-gynaecological cases only). A post-study questionnaire captured qualitative feedback.

Of the 88 cases, 65 showed concordance between digital and LM diagnoses. Amongst the remaining 23 cases, 15 demonstrated diagnostic discrepancy by LM. Excluding these, the digital-LM concordance rate was 95.1%. When all cases were included, concordance ranged from 89.5% for within-observer analysis to 89.8% when compared with a majority LM diagnosis. Agreement analysis demonstrated substantial to near-perfect digital-LM agreement (unweighted κ = 0.86; weighted κ = 0.83-0.95), improving further following exclusion of diagnostically discrepant cases (κ = 0.89-0.97). Inter-observer agreement was lower than intra-observer agreement for both digital and LM comparisons. Feedback indicated that image quality was generally good. Challenges included visualising thick smear preparations, three-dimensional cell clusters, sparse atypical cells and screening gynaecological (cervical) cytology cases. All participants expressed openness to adopting digital cytology.

High-resolution WSI demonstrated strong diagnostic concordance with traditional LM across a wide range of cytological specimen types and preparations. Despite limited prior experience, digital cytology was considered acceptable and feasible, supporting its integration into routine clinical practice, with appropriate training and quality assurance.