B-ALL/LBL Molecular Classifier
Flowchart algorithm assigning the WHO molecular subtype from selected cytogenetic/molecular findings, or NOS by exclusion.
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This algorithm follows the essential/desirable diagnostic-feature structure of the WHO/CAP classification table for B-lymphoblastic leukemias/lymphomas. It is an educational and documentation-support aid only and does not replace professional pathologist judgment, institutional protocols, or the current edition of the applicable classification.
Reference
How the classifier works
Walks through the WHO/CAP diagnostic-feature table for B-lymphoblastic leukemias/lymphomas as a flowchart: confirm the lineage-defining diagnostic criteria, then select the single molecular/cytogenetic finding present — the app assigns the specific WHO category, or NOS once a more specific category has been genuinely excluded.
CD34 and TdT expression may be absent in rare cases and pose a diagnostic challenge — the source acknowledges this exception rather than requiring immaturity-marker positivity unconditionally.
Table 1 — Essential & desirable diagnostic features by category
| Category | Essential | Desirable |
|---|---|---|
| B-lymphoblastic leukemia/lymphoma, NOS | B-ALL: >20% B lymphoblasts by flow cytometry with B-cell lineage markers. B-LBL: effaced lymph node architecture or diffuse infiltration of an organ by a monomorphic population of blasts with B immunophenotype (CD19, CD22, cCD79a, and/or PAX5) and markers of immaturity (TdT, CD34, and/or CD99), surface immunoglobulin negative (CD34/TdT may rarely be absent). Exclusion of a more specific category using ancillary methods including karyotype, FISH, and molecular genetics. | — |
| B-lymphoblastic leukemia/lymphoma with high hyperdiploidy | Meets criteria for B-ALL/LBL. Karyotype 51–65 chromosomes, absence of other subtype-defining translocations by karyotyping and/or FISH. Flow cytometry DNA Index can indicate high hyperdiploidy but cannot confirm precise chromosomal gains. | SNP arrays to better exclude double near-haploid/low hypodiploidy. |
| B-lymphoblastic leukemia/lymphoma with hypodiploidy | Meets criteria for B-ALL/LBL. Karyotyping and/or FISH showing less than 44 chromosomes. Flow cytometry DNA Index can indicate hypodiploidy but cannot confirm precise chromosomal losses. | SNP arrays to better identify 'masked' hypodiploidy. |
| B-lymphoblastic leukemia/lymphoma with iAMP21 | Meets criteria for B-ALL/LBL. Demonstration of ≥5 copies of RUNX1 per cell, with ≥3 or more copies on a single abnormal chromosome 21. | — |
| B-lymphoblastic leukemia/lymphoma with BCR::ABL1 fusion | Meets criteria for B-ALL/LBL. Detection of the BCR::ABL1 fusion. Exclusion of cases of B-ALL that acquire BCR::ABL1 secondarily during therapy. | Exclusion of lymphoid blast crisis of chronic myeloid leukemia. |
| B-lymphoblastic leukemia/lymphoma with BCR::ABL1-like features | Meets criteria for B-ALL/LBL. BCR::ABL1-like gene signature and/or genomic alteration described for this type. | — |
| B-lymphoblastic leukemia/lymphoma with KMT2A rearrangement | Meets criteria for B-ALL/LBL. Demonstration of KMT2A rearrangement. | Identification of KMT2A rearrangement partner. |
| B-lymphoblastic leukemia/lymphoma with ETV6::RUNX1 fusion | Meets criteria for B-ALL/LBL. Demonstration of ETV6::RUNX1 rearrangement. | — |
| B-lymphoblastic leukemia/lymphoma with TCF3::PBX1 fusion | Meets criteria for B-ALL/LBL. Demonstration of TCF3::PBX1 rearrangement. | — |
| B-lymphoblastic leukemia/lymphoma with IGH::IL3 fusion | Meets criteria for B-ALL/LBL. Demonstration of IGH::IL3 rearrangement. | — |
| B-lymphoblastic leukemia/lymphoma with TCF3::HLF fusion | Meets criteria for B-ALL/LBL. Demonstration of TCF3::HLF rearrangement. | — |
| B-lymphoblastic leukemia/lymphoma with other defined genetic alterations | Meets general criteria for B-ALL/LBL. Demonstration of a specific genetic abnormality as defined (DUX4 rearrangement, MEF2D rearrangement, ZNF384 rearrangement, PAX5alt, PAX5 p.P80R, NUTM1 rearrangement, or MYC rearrangement). Absence of genetic mutations of other definitive and provisional B-ALL types. | Depends on particular subtype. |
Sources
Table 1 carries an in-text superscript citation ("1") in the supplied excerpt, whose bibliographic entry was not included in the excerpt — it is not reproduced here. Consult the complete published protocol for the exact reference.
Source document: CAP Cancer Protocol, Heme.Lymphoid.Bx.Res_1.0.0.2.REL_CAPCP.