Bone Marrow Evaluation
Systematic approach for the reporting pathologist or haematologist
All Pathways
PathologyDiagnostic
Bone Marrow Biopsy Systematic Interpretation
Bone Marrow Biopsy Systematic Interpretation: Bone Marrow Evaluation → Suspected APL: phone the treating team now → Specimen Assessment → Cellularity As...
Pathway Overview
12 steps
Algorithm Steps
12 total
01Start 02Warning Suspected APL: phone the treating team now
Medical emergency. Act before you finish the report.
- Clues: abnormal promyelocytes (hypergranular or hypogranular), Auer rods or faggot cells, DIC
- ATRA and coagulopathy support start on suspicion; do not wait for genetics (ELN 2019)
- Request urgent PML::RARA confirmation (FISH or PCR)
03Action Specimen Assessment
Check adequacy before you interpret
- Core: at least 1.5 cm of evaluable marrow (ICSH 2008); note crush artefact or subcortical-only core
- Aspirate: spicules present; a haemodilute aspirate underestimates blasts and plasma cells
- Dry tap: use core touch imprints and CD34 IHC on the core
- Blood film and FBC from the same day
- Samples sent for flow cytometry, cytogenetics/FISH and molecular studies
- Infection suspected (e.g. TB, fungi, Leishmania): send fresh aspirate for culture; fixed tissue cannot be cultured
04Action Cellularity Assessment
Estimate on the core against age (rough guide: 100 minus age = expected %)
- Do not use subcortical spaces; they are normally hypocellular
- Hypocellular, normocellular or hypercellular; patchy or diffuse
- Very hypocellular: aplastic anaemia vs hypoplastic MDS (25% or less, age-adjusted; WHO 5th) vs hypocellular AML
- Hypocellular work-up: PNH clone by flow cytometry, cytogenetics and myeloid NGS (BSH 2024)
- Hypocellular with germline GATA2, DDX41, Fanconi or telomere gene variants: can evolve to MDS/AML; no response to immunosuppression (WHO 5th)
- Hypercellular: consider MPN, MDS, leukaemia or a reactive cause
05Action Trilineage Assessment
Erythroid, myeloid and megakaryocyte lineages
- M:E ratio (adult reference about 2:1 to 4:1; use the laboratory reference range)
- Erythroid maturation
- Myeloid maturation; left shift or maturation arrest
- Megakaryocyte number, distribution and morphology
06Action Dysplasia Assessment: exclude mimics first
Mimics: B12, folate or copper deficiency, alcohol, drugs, recent chemotherapy or G-CSF, HIV, germline predisposition
- Significant: 10% or more of cells in a lineage (WHO 5th)
- Erythroid: nuclear budding or irregularity, megaloblastoid change, multinuclearity; ring sideroblasts on iron stain
- Myeloid: hypogranulation, pseudo-Pelger-Huet nuclei
- Megakaryocytes: micromegakaryocytes, monolobated or separated nuclear lobes
- MDS-SF3B1 (low blasts): not with del(5q), monosomy 7 or complex karyotype. WHO 5th: 15% or more ring sideroblasts can replace the mutation. ICC: needs SF3B1 VAF 10% or more, no multi-hit TP53 or RUNX1
- TP53 overrides blast groups: WHO 5th MDS-biTP53 (2 hits, <20% blasts); ICC MDS with mutated TP53 (multi-hit, or VAF >10% with complex karyotype); ICC MDS/AML or AML with any TP53 mutation (VAF >10%)
- MDS needs cytopenia plus dysplasia, excess blasts or MDS-defining genetics
07Warning Before blast cut-offs: genetics, age and recent treatment
Blast percentage alone can misclassify AML as MDS
- AML-defining genetics (e.g. PML::RARA, RUNX1::RUNX1T1, CBFB::MYH11, NPM1, KMT2A) = AML below 20% blasts
- Under 18 years: childhood MDS criteria; the ICC MDS/AML category does not apply
- After chemotherapy, G-CSF or ATRA/ATO: regenerating or maturing cells can mimic excess blasts
08Action Blast Assessment
Myeloid blasts and blast equivalents in marrow and blood
- AML-defining genetics: WHO 5th no blast cut-off (except BCR::ABL1 and CEBPA: 20%); ICC 10% or more (BCR::ABL1: 20%)
- WHO 5th: MDS-LB <5% marrow and <2% blood; MDS-IB1 5-9% marrow or 2-4% blood; MDS-IB2 10-19% marrow, 5-19% blood or Auer rods
- ICC 2022 (adults): MDS-EB 5-9% marrow or 2-9% blood; MDS/AML 10-19% marrow or blood
- Myeloid blasts 20% or more in marrow or blood: AML. Lymphoblasts: classify by flow cytometry (ALL)
- 500-cell aspirate differential; also count blood blasts
- Blast equivalents: monoblasts, promonocytes; abnormal promyelocytes in APL
- CD34 IHC on core if the aspirate is poor; APL, NPM1-mutated and monocytic blasts are often CD34-negative
- Erythroid predominance (usually 80% or more) with 30% or more proerythroblasts: acute erythroid leukaemia (WHO 5th)
09Action Abnormal Populations
Identify infiltrates on core and aspirate
- Plasma cells: CD138 IHC to count; kappa and lambda for clonality
- Lymphoid aggregates: benign vs lymphoma pattern; IHC and flow cytometry for clonality
- Metastatic carcinoma: cytokeratin, then site-specific markers
- Children: small round blue cell tumours (neuroblastoma, rhabdomyosarcoma, Ewing sarcoma) are cytokeratin-negative and can mimic leukaemia; use a paediatric IHC panel
- Haemophagocytosis: supports but does not prove HLH; correlate with HLH-2004 criteria and phone if suspected
- Granulomas: stains and culture for mycobacteria and fungi; consider sarcoidosis, drugs, lymphoma
- Mast cells: tryptase, CD117, CD25, CD30 (WHO 5th systemic mastocytosis criteria)
10Action Fibrosis Grading
Reticulin stain (trichrome for collagen); grade in cellular areas only
- MF-0: scattered linear reticulin, no intersections (normal)
- MF-1: loose reticulin network with many intersections, mainly perivascular
- MF-2: diffuse, dense reticulin with extensive intersections; occasional focal collagen or focal osteosclerosis
- MF-3: as MF-2 with coarse collagen bundles, often with osteosclerosis
- Grade 2-3 with megakaryocyte proliferation and atypia supports overt PMF, with JAK2, CALR, MPL or another clonal marker (ICC 2022)
- Exclude reactive fibrosis: infection, autoimmune disease, hairy cell leukaemia or other lymphoma, metastatic cancer, toxic myelopathy
- MDS with 5-19% marrow or 2-19% blood blasts and MF-2 or MF-3 fibrosis: MDS-f (WHO 5th)
11Action Integrated Diagnosis
Correlate morphology with all other results
- Clinical history, FBC and blood film; prior chemotherapy, radiotherapy or G-CSF; family history
- Flow cytometry
- Cytogenetics and FISH
- Molecular studies (myeloid NGS panel)
- Classify by WHO 5th (2022) or ICC 2022, and state which
- Add qualifiers: therapy-related, progressed from MDS, germline predisposition
12Outcome Final Report
Phone urgent findings first (new acute leukaemia, Burkitt or other high-grade lymphoma, suspected HLH, disseminated infection). Synoptic report: adequacy, cellularity, differential, blasts, dysplasia, infiltrates, fibrosis grade, IHC and integrated diagnosis with classification used
Guideline Source
WHO Classification of Haematolymphoid Tumours, 5th edition: myeloid neoplasms (Khoury et al. 2022) and International Consensus Classification 2022 (Arber et al. 2022)
Clinical Safety Information
Clinical Decision Support — Not a Substitute for Clinical Judgment
Individual patient factors may require deviation from these recommendations.
Known Limitations
- Blast cut-offs differ between WHO 5th and ICC 2022; the report must state which classification it uses
- Morphology alone can miss AML-defining genetics; the final diagnosis needs flow cytometry, cytogenetics and molecular results
- Specimen adequacy limits interpretation
- Childhood MDS and germline predisposition need specialist criteria
- Lymphoma and myeloma staging need their own criteria and IHC panels
Applicable Regions
USAUUKEU
AU: Laboratories may report by WHO 5th or ICC 2022; state the classification. Phone suspected APL to the treating team under the laboratory critical-result policy.
Version 2Next review: 2027-09-30
Next steps
Finish the workflow by opening the most relevant calculator, then convert the session into a live account when you are ready.
Related Resources
Frequently Asked Questions
What is the Bone Marrow Biopsy Systematic Interpretation?
The Bone Marrow Biopsy Systematic Interpretation is a diagnostic clinical algorithm for Pathology. It provides a structured decision tree to guide clinical decision-making, based on WHO Classification of Haematolymphoid Tumours, 5th edition: myeloid neoplasms (Khoury et al. 2022) and International Consensus Classification 2022 (Arber et al. 2022).
What guideline is the Bone Marrow Biopsy Systematic Interpretation based on?
This algorithm is based on WHO Classification of Haematolymphoid Tumours, 5th edition: myeloid neoplasms (Khoury et al. 2022) and International Consensus Classification 2022 (Arber et al. 2022) (DOI: 10.1038/s41375-022-01613-1).
What are the limitations of the Bone Marrow Biopsy Systematic Interpretation?
Known limitations include: Blast cut-offs differ between WHO 5th and ICC 2022; the report must state which classification it uses; Morphology alone can miss AML-defining genetics; the final diagnosis needs flow cytometry, cytogenetics and molecular results; Specimen adequacy limits interpretation; Childhood MDS and germline predisposition need specialist criteria; Lymphoma and myeloma staging need their own criteria and IHC panels. Individual patient factors may require deviation from these recommendations.
Get AI-Powered Analysis Alongside This Algorithm
In AttendMe.ai, the Bone Marrow Biopsy Systematic Interpretation appears automatically when your clinical question matches — alongside evidence from 3M+ peer-reviewed articles.
Try AttendMe Free