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Solving the Puzzle of Hans' Algorithm (HA) Methodological Shortcomings: Canadian Harmonization of Hans' Algorithm for
Emina Torlakovic1, Ariz Akhter2, Allam Shawwa3
1University of Saskatchewan and Saskatchewan Health Authority, Saskatoon.
Applied Immunohistochemistry & Molecular Morphology : AIMM
|April 20, 2026
Summary
Hans' algorithm (HA) for Diffuse Large B-cell Lymphoma (DLBCL) subtyping shows improved accuracy when immunohistochemistry (IHC) protocols are adjusted for analytical sensitivity, enhancing clinical practice. Harmonizing IHC assays and pathologist readouts ensures reliable cell-of-origin classification.
Area of Science:
- Hematology
- Oncology
- Pathology
Background:
- Diffuse Large B-cell Lymphoma (DLBCL) cell-of-origin (COO) subtyping is crucial for treatment decisions.
- Hans' algorithm (HA) is a common immunohistochemistry (IHC)-based surrogate for gene expression profiling (GEP) but faces reproducibility and accuracy challenges.
- The diagnostic accuracy of HA in routine clinical practice requires thorough evaluation.
Purpose of the Study:
- To assess the diagnostic accuracy of HA in clinical practice across Canadian laboratories.
- To harmonize the analytical phase of IHC assays used for HA.
- To optimize HA sensitivity and specificity against GEP-defined COO subtypes.
Main Methods:
- A DLBCL cohort (n=96) was subtyped by GEP (Lymph2CX, NanoString).
- Training (n=45) and validation (n=51) cohorts were established using tissue microarrays.
- Routine CD10, Bcl-6, and MUM1 IHC protocols from various labs were centrally reviewed and categorized by analytical sensitivity (weak, moderate, strong).
Main Results:
- Original HA showed good accuracy only with low-sensitivity IHC protocols.
- Adjusting HA readout criteria (cutoff >30% of >2+ intensity) significantly improved diagnostic accuracy against GEP for moderate and high sensitivity protocols.
- This modified approach enhanced accuracy without altering existing IHC protocols.
Conclusions:
- Hans' algorithm can achieve high accuracy and harmonization across laboratories for DLBCL subtyping.
- Standardized reference materials are essential for setting and monitoring IHC analytical sensitivity.
- Adjusting pathologist readout and cutoffs to match overall IHC protocol sensitivity is key for reliable clinical application.
