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Why do we make mistakes in morphological diagnosis how can we improve? Michelle Brereton & John Burthem Manchester, UK UK NEQAS(H) DM scheme 1. Select up to 5 significant morphological features from a defined list 2. Place these in


  1. Why do we make mistakes in morphological diagnosis – how can we improve? Michelle Brereton & John Burthem Manchester, UK

  2. UK NEQAS(H) DM scheme 1. Select up to 5 significant morphological features from a defined list 2. Place these in priority order 1-5 3. Answer multiple choice question : “what would I do next?” 4. Offer free text opinion generally: “what is your preferred diagnosis?”

  3. But some people get the answers wrong! Are we really helping this group sufficiently? Do we really know why they get things wrong?

  4. Analysing morphology is more complex than we think 14/320 4000 20000

  5. To understand why this is we need to look at the process of diagnosis

  6. All parasite forms seen, diagnosis: P.vivax 2. 1.

  7. Can we analyse our data to see why we arrive at incorrect answers?

  8. The Heuristic Approach: “Fast and Frugal” A model to understand how people arrive at a morphological opinion 1. Familiarity/unfamiliarity 2. Recognition 3. Classification 4. Reinforcement 5. Priority assignment 6. Interpretation 7. Action

  9. We all use these approaches (1) ....... Reinforcement Priority assignment Interpretation Recognition Familiarity Action Classification A simple case

  10. We all use these approaches (2) ..... Reinforcement Prioritisation 2 Interpretation Action Recognition Reinforcement Familiarity Classification Prioritisation 1 A complex case

  11. We all use these approaches (2) ..... Reinforcement Prioritisation 2 Recognition Reinforcement Familiarity Classification Prioritisation 1 Made the evidence fit my view = Framing effect bias Persisted in original view = anchoring bias Simplification = multiple alternatives bias Stopped looking or thinking = Satisfaction of search (premature closure)

  12. Heuristic approaches can introduce major sources of bias!

  13. CASE 1 and 2 Simple cases

  14. Inherited Pelger Huet anomaly CASE 1 Overview of features A routine pre-operative blood sample reveals these features on the film. Preferred answer: 1. Pelger cells +/- other normal features 2. Pelger cells ranked most important 3. Action: low priority action 4. Diagnosis: Pelger Huet anomaly

  15. Inherited Pelger Huet anomaly CASE 1 Overview of selected features Participants completing all aspects of survey: 1029 Major distinct diagnostic groups Priority given to neutrophil features 700 100 583 600 80 % selection 500 p = n.s.* Number 400 60 300 40 200 142 20 100 44 0 0 1 2 3 4 5 Diagnosis Priority Pelger Huet anomaly Myelodysplasia Reactive changes *Chi Square test two tailed (Fisher’s exact)

  16. CASE 1 Selected features and final diagnosis 22% 25% 41% 33% 27% 35% 7% 10% Pelger Huet Myelodysplasia Pelger cells 7% 16% **** Band neutrophils Reactive features 33% Dysplastic features 44% *** Reactive Chi Square Test two- tailed (Fisher’s exact)

  17. Reactive lymphocytes in glandular fever CASE 2 Overview of features A young man presenting with enlarged neck lymph nodes. Preferred answer: 1. Reactive lymphocytes (one or more choices) 2. Reactive lymphocytes ranked most important 3. Action: low priority action 4. Diagnosis: Reactive viral (?EBV)

  18. Reactive lymphocytes (glandular fever) CASE 2 Overview of selected features Participants completing all aspects of survey: 713 Priority given to lymphocyte features Distinct diagnostic groups 500 80.00 460 70.00 400 60.00 % selection 50.00 Number 300 p = n.s.* 40.00 200 30.00 137 20.00 100 51 10.00 0.00 0 1 2 3 4 5 1 Features of viral infection Viral infection exclude neoplasia Neoplastic cells *Chi Square test two tailed (Fisher’s exact)

  19. CASE 2 Selected features and final diagnosis 2% 3% 15% 14% 11% 20% 3% 18% 53% 61% Consistent with viral infection Viral infection, exclude neoplasia 2% Lymphocytosis 15% 16% Reactive lymphocytes Neoplastic lymphocytes 30% 37% Supports neoplastic Supports reactive Neoplastic

  20. CASES 1 and 2 Why be interested? 80.0 80 70 70.0 **** 60 60.0 ** % selection % selection 50 50.0 Axis Title Viral Pelger 40 40.0 Unsure MDS 30 30.0 Neoplastic Reactive 20 20.0 10 10.0 0 0.0 1 2 3 4 5 1 2 3 4 5 LOW HIGH LOW HIGH Clinical priority of findings Clinical priority of findings CASE 1 CASE 2 (Pelger Huet anomaly) (Viral infection) ** p<0.001 **** p<0.00001 Mann Witney U test

  21. CASES 1 and 2 Principle sources of error In these cases interpretation depended predominantly on accurate assessment of a single abnormal cell Analysis Familiarity, recognition and prioritisation: well completed irrespective of diagnosis MAJOR ERROR SOURCE: Classification: recognising the abnormal cell Substantial contributions: Framing effect (overstating supportive features) Anchorage (ignoring lack of support) NOTE The highly significant effect on action/outcome

  22. CASE 3 Complex morphology unifying diagnosis

  23. Microangiopathic haemolysis (TTP) with acute viral CASE 3 infection (HIV) A patient attending an evening clinic is unwell Preferred answer: 1. Thrombocytopenia, Fragmentation features, general haemolyisis features 2. Thrombocytopenia and fragmentation ranked most important, reactive lymphocytes recorded 3. Action: High priority action 4. Diagnosis: Microangiopathic haemolysis +/- viral infection

  24. Thrombotic thrombocytopenic purpura with acute HIV CASE 3 Overview of selected features Participants completing all aspects of survey: 751 Feature choice Feature priority 6.00 19% 19% 5.00 Thrombocytopenia 4.00 Fragmentation 3.00 11% Other haemolytic features 19% 2.00 Reactive lymphocytes 1.00 0.00 Other selections 32% Low Fragments Haemolysis Reactive platelets lymphs Microangiopathic haemolysis (MAHA) 381 (51%) Preferred diagnosis: MAHA and viral illness 125 (16%) Haemolysis unspecified 155 (21%)

  25. CASE 3 Selected features and final diagnosis MAHA alone MAHA and viral illness 19% 19% 19% 18% 10% ** 15% 19% 19% 33% 29% * Haemolysis other Thrombocytopenia 20% ** 26% Fragmentation Other haemolytic features 17% * 9% Reactive lymphocytes 28% *p<0.01 ** p<0.001 Other selections Chi Square test

  26. CASE 3 Priority assigned to features according to preferred diagnosis 70.0 Thrombocytopenia Fragments 70.0 60.0 60.0 50.0 50.0 Axis Title Axis Title 40.0 40.0 30.0 30.0 20.0 20.0 *** 10.0 10.0 0.0 0.0 1 2 3 4 5 1 2 3 4 5 Priority Priority 70.0 70.0 Haemolytic features Reactive lymphocytes 60.0 60.0 50.0 50.0 Axis Title Axis Title *** 40.0 40.0 30.0 30.0 ** 20.0 20.0 10.0 10.0 0.0 0.0 1 2 3 4 5 1 2 3 4 5 Priority Priority ** p<0.001 *** p<0.0001 TTP & viral TTP only Haemolysis Mann Witney U test

  27. CASE 3 Elements governing diagnostic conclusion Interpretation Feature selection was remarkably similar BUT diagnosis differed MAJOR ERROR SOURCE: Prioritisation ( confirmation bias – emphasising features that fit ) Simplification ( multiple alternatives bias and elimination by aspects ) Possible contribution: Premature completion ( I have a diagnosis, I can finish looking)

  28. CASE 4 Complex case – dual pathology

  29. CASE 4 HbSC disease with acute myeloid leukaemia A patient under long-term follow up as an out patient clinic has changed blood count features. Preferred answer: 1. Blast cells and features of haemoglobinopathy (HbC or HbSC) 2. Blast cells ranked most important, red cell features recorded 3. Action: high priority action 4. Diagnosis: acute leukaemia with haemoglobinopathy

  30. CASE 4 HbSC disease with acute myeloid leukaemia Acute myeloid leukaemia selected (n= 162) Haemoglobinopathy features 2% 12% Other red cell features 42% 21% Blast cells Other white cell types 23% Other white cell features Reactive white cells selected (n= 90) 23% 41% 5% 4% 27%

  31. CASE 4 HbSC disease with acute myeloid leukaemia 160 140 Haemoglobinopathy features AML selected 120 Other red cell features 100 80 Blast cells 60 40 Other white cell types 20 Other white cell features 0 1.0 2.0 3.0 4.0 5.0 140 Blasts not seen 120 100 80 60 40 20 0 1.0 2.0 3.0 4.0 5.0

  32. CASE 4 HbSC disease with acute myeloid leukaemia How did the perception of 19% 26% red cell and white cell findings relate to the perception of white cells? 27% 28% Blast cells seen 6% 8% Haemoglobinopathy 20% Thalassaemia Liver disease 66% No additional diagnosis Blast cells not seen

  33. CASE 4 Elements governing diagnostic conclusion Interpretation This did not appear to be a classification error or prioritisation error, those making an incorrect diagnosis simply failed to see the blast cells! MAJOR ERROR SOURCE: Multiple alternatives bias (simplified to exclude other important features) Framing effect (substantial influence of other features) Premature closure (arriving at a single diagnosis and stopped)

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