Specialty Guide · Path-iQ Global Pathology Review
Haematopathology is the subspecialty concerned with diseases of blood, bone marrow, and lymphoid tissues. It is among the most intellectually demanding pathology subspecialties — integrating morphology, immunophenotyping, cytogenetics, molecular genetics, and clinical presentation to classify and prognosticate a heterogeneous set of neoplastic and non-neoplastic disorders.
The WHO Classification of Haematolymphoid Tumours (5th edition, 2022) introduced the most substantial reorganisation since 2008. The classification now comprises two separate volumes: Lymphoid Neoplasms (blue book) and Myeloid and Histiocytic/Dendritic Neoplasms (blue book vol. 2). Key changes include:
| Technique | Application | Turnaround | Key Targets |
|---|---|---|---|
| Bone marrow trephine H&E | Hypocellularity, fibrosis, infiltration pattern | 2–5 days | Cellularity, blast%, megakaryocyte morphology, reticulin grade |
| Flow cytometry (peripheral blood/BM) | Immunophenotyping of leukaemia, lymphoma, MRD | Same day – 2 days | CD19, CD20, CD5, CD10, CD23, κ/λ, TdT, CD34, CD117 |
| Immunohistochemistry (lymph node) | B vs T lineage, germinal centre vs non-GC | 2–4 days | CD20, PAX5, CD3, CD5, CD10, BCL2, BCL6, MUM1, Ki-67 |
| Conventional cytogenetics (karyotype) | AML, CML, MDS, ALL prognostic stratification | 10–14 days | t(9;22), t(15;17), t(8;21), inv(16), del(5q), -7, complex karyotype |
| FISH | Lymphoma translocations, AML, MDS | 3–7 days | MYC, BCL2, BCL6, CCND1, MYB, PDGFRB, TP53 del |
| RT-PCR / real-time PCR | Fusion transcript detection, MRD quantification | 3–7 days | BCR-ABL1, PML-RARA, RUNX1-RUNX1T1, NPM1 mutation |
| NGS myeloid/lymphoid panel | Somatic mutation profiling for diagnosis & prognosis | 7–21 days | FLT3-ITD, IDH1/2, NPM1, DNMT3A, TP53, SF3B1, ASXL1, JAK2 |
| Digital PCR | Ultra-sensitive MRD at depth of 10⁻⁵–10⁻⁶ | 5–10 days | NPM1, BCR-ABL1, FLT3-ITD (post-SCT monitoring) |
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma worldwide (~30–35% of NHL). Cell-of-origin (COO) classification into germinal centre B-cell (GCB) and activated B-cell (ABC)/non-GCB subtypes by IHC algorithm (Hans, Choi, or Visco-Young) or gene expression profiling (NanoString Lymph2Cx) carries prognostic significance and is increasingly used to select targeted therapies. High-grade B-cell lymphoma with MYC and BCL2 rearrangements ("double-hit") requires FISH confirmation and confers poor prognosis with standard R-CHOP, guiding intensified therapy (DA-R-EPOCH).
Follicular lymphoma (FL) grade 1–3A is characterised by CD10+/BCL6+/BCL2+ immunophenotype and t(14;18)(q32;q21)/IGH-BCL2 in 85% of cases. Grade 3B FL behaves aggressively and is treated as DLBCL. Mantle cell lymphoma (MCL) demonstrates cyclin D1 overexpression from t(11;14)(q13;q32)/CCND1-IGH and carries the worst 5-year OS among common B-cell lymphomas, though biologically indolent MCL with SOX11 negativity is now recognised.
Peripheral T-cell lymphomas (PTCL) are heterogeneous and generally carry a worse prognosis than their B-cell counterparts. Angioimmunoblastic T-cell lymphoma (AITL) and PTCL-TFH (T follicular helper phenotype) demonstrate RHOA G17V, IDH2 R172, and TET2 mutations and are now grouped together as T-follicular helper cell lymphomas. ALK-positive ALCL carries the best prognosis in PTCL; ALK-negative ALCL is prognostically intermediate. Extranodal NK/T-cell lymphoma, nasal type, is EBV-driven and more common in East Asia and South America.
AML is now molecularly classified per WHO 2022 into entities defined by specific genetic alterations (e.g., AML with NPM1 mutation, AML with RUNX1-RUNX1T1, AML with biallelic CEBPA mutation) and AML defined by differentiation (AML-MRC, where MRC = myelodysplasia-related cytogenetic changes or mutations). The ELN 2022 risk classification stratifies AML into favourable, intermediate, and adverse risk to guide treatment intensity and transplant decisions. FLT3 inhibitors (midostaurin, gilteritinib) and IDH1/2 inhibitors (enasidenib, ivosidenib) are targeted therapies now standard in AML.
Myelodysplastic neoplasms (MDS) are clonal stem cell disorders characterised by cytopenia, dysplasia, and risk of transformation to AML. The revised IPSS-M (molecular IPSS) incorporates 31 gene mutations alongside cytogenetics and clinical variables to improve prognostication. MPN (myeloproliferative neoplasms) — PV, ET, PMF — are driven by JAK2 V617F (detected in 95% of PV, 55% of ET and PMF), CALR exon 9, or MPL mutations.
Bone marrow assessment requires both aspirate smears (for blast morphology and differential) and trephine biopsy (for architecture, cellularity, fibrosis). The trephine core should be at least 20 mm in length for adequate assessment. Reticulin grading (MF-0 to MF-3) is mandatory in MPN and essential in MDS.
| Feature | Normal Adult | AML | MDS | MPN (PMF Fibrotic) |
|---|---|---|---|---|
| Cellularity | 40–70% | ↑↑ (blasts) | Variable; often hypercellular | Hypercellular early; fibrotic late |
| Blast% | <5% | ≥20% (WHO) | 2–19% | <20% (blastic transformation if ≥20%) |
| Dysplasia | Absent | May be present if AML-MRC | ≥10% in ≥1 lineage | Megakaryocyte atypia (cloud-like nuclei) |
| Reticulin fibrosis | MF-0 to MF-1 | Variable | MF-0 to MF-2 | MF-2 to MF-3 |
| Megakaryocytes | Normal clustering | Variable | Hypolobated, micro forms | Dense clusters, bizarre nuclei |
Principal architect of multiple WHO lymphoma editions. World authority on mantle cell lymphoma biology, BCL2/MYC double-hit lymphoma, and the molecular classification of aggressive B-cell lymphomas.
Founding editor of the WHO Classification of Haematolymphoid Tumours and architect of modern lymphoma nosology. Distinguished Professor Emerita at Harvard Medical School.
World authority on NK/T-cell lymphoma, extranodal lymphomas, and EBV-associated lymphoproliferative disorders. Contributor to all WHO haematolymphoid classifications since 1994.
Lead editor of the WHO Classification of Myeloid Neoplasms 5th edition (2022). Expert in AML molecular classification, MDS grading, and the integration of next-generation sequencing into haematopathology diagnosis.
WHO 2022 myeloid tumours working group member. Expert in MDS classification, bone marrow fibrosis grading, and clonal haematopoiesis of indeterminate potential (CHIP).
Discoverer of the diagnostic and prognostic significance of NPM1 mutations in AML. Also internationally recognised for ALK protein discovery in ALCL and the role of MYD88 L265P in Waldenström's macroglobulinaemia.