the who classification of hematological malignancies pathology grand rounds april 11 2001
TRANSCRIPT
The WHO Classification of Hematological Malignancies
Pathology Grand Rounds
April 11 2001
No, it’s not that kind of Who
So what is it?
• Classification that includes myeloid, lymphoid, histiocytic and mast cell neoplasms
• applies the principles of the REAL classification to hematological neoplasms– morphology– immunophenotype– genetic features– clinical features
WHO classification of myeloid neoplasms
• Myeloproliferative disease (MPD)• Myelodysplastic/Myeloproliferative disease• Myelodysplastic disease (MDS)• Acute myeloid leukemia (AML)
– AML w/recurrent cytogenetic translocations– AML w/ myelodysplasia-related features– Therapy-related AML and MDS– AML not otherwise categorized
Myeloproliferative Disease
• clonal stem cell disorder with “effective” hematopoiesis resulting in elevated peripheral blood cells and hepatosplenomegaly– Ph1+ CML– polycythemia vera– idiopathic myelofibrosis– essential thrombocytopenia
Juvenile myelomonocytic leukemia (JMML)
• distinct from adult CML or CMML
• classified as a MDS/MPD
• lack Ph1 or BCR/ABL translocation
• usually <3 years old at diagnosis
• dysplasia present but not prominent
Chronic myelomonocytic leukemia (CMML)
• some patients with MDS features - normal PMN counts, multilineage dysplasia, no organomegaly, and BM morphology of RAEB with monocytosis
• some patients with MPD features - neutrophilia, monocytosis, and splenomegaly
• classified as MDS/MPD
Atypical CML (aCML)
• lack Ph1 or BCR/ABL translocation
• predominantly neutrophil series
• dysplastic as well as proliferative features
• often multilineage dysplasia
• worse prognosis than Ph1+ CML
• classified as MDS/MPD
Refractory cytopenia with multilineage dysplasia (RCMD)
• RA and RARS (FAB) - dysplasia is largely limited to erythroid lineage
• MDS with <5% blasts but multilineage dysplasia have worse prognosis and are more likely to die of marrow failure or progress to acute leukemia (like RAEB)
• Multilineage dysplasia is defined as dysplastic features in the cells of two or more cell lines
What blast count should define AML?
• Recent studies have shown that patients with 20-30% blasts (RAEB-T) have similar prognosis to those who have >30% blasts (AML)
• WHO - AML is defined as >20% blasts
• RAEB-T category dropped
Cytogenetic/molecular categories of AML
• specific cytogenetic abnormalities do not correlate precisely with FAB categories
• these should be recognized as distinct entities
• include low blast count cases previously categorized as MDS (<20% blasts)
• currently include four categories
Cytogenetic/molecular categories of AML
• AML with t(8;21)(q22;q22),AML1(CBF )/ETO
• Acute promyelocytic leukemia (AML with t(15;17)(q22;q11-12) and variants, PML/RAR )
• AML with abnormal bone marrow eosinophils (inv(16)(p13q22) or t(16;16)(p13;q11), CBF /MYH11X)
• AML with 11q23 (MLL) abnormalities
Dysplasia and AML
• multilineage dysplasia associated with poor outcomes– dysplasia in two or more cell lines
• history of prior MDS associated with poor outcomes
Prior therapy and AML-Alkylating agents
• different from de novo AML• associated with characteristic
cytogenetic alterations– 3q-, -5, 5q-, -7, 7q-, +8, +9, 11q-,
12p-, -18, -19, 20q-, +21, t(1;7), t(2;11), and complex karyotypes
• associated with a worse prognosis
Prior therapy and AML-Topoisomerase II inhibitors• epipodophyllotoxins and
adriamycin• associated with secondary
leukemias (may be lymphoid)• associated with cytogenetic
abnormalities of de novo AML– 11q23 (MLL), occ. t(8;21), inv(16) or
t(15;17)
Lymphoid neoplasms
• WHO adopted the REAL classification with minor modifications
• split some categories• adopted some “provisional”
categories as “real”
Lymphoblastic neoplasms
• dropped FAB L1, L2, L3 terminology• ALL and lymphoblastic lymphoma
single disease• group by cytogenetic abnormalities
– t(9;22)(q34;q11); BCR/ABL– t(v;11q23); MLL rearranged– t(1;19)(q23;p13) E2A/PBX1– t(12;21)(p12;q22) ETV/CBF
Follicular lymphoma
• changed nomenclature from “follicle center lymphoma” to “follicular lymphoma”
• in the rare case of a purely diffuse lymphoma of follicle center cell origin retain the term “follicle center lymphoma, diffuse”– BCL2– CD10
Grading follicular lymphoma
• grade 1 and 2 are similar - grade 3 has earlier relapses
• use Berard cell counting method for grade
• grade 1: 0-5 centroblasts/hpf• grade 2: 6-15 centroblasts/hpf• grade 3: >15 centroblasts/hpf
– 3a - centrocytes still present– 3b - no centrocytes
Reporting diffuse areas
• should be reported and quantified as per ILSG recommendations– predominantly follicular - >75% follicular– follicular and diffuse - 25-75% follicular– predominantly diffuse - <25% follicular
• areas of DLBCL should be reported separately– e.g. follicular lymphoma grade 3 (75%)
with DLBCL (25%)
Large cells in marginal zone/MALT lymphomas
• recent studies suggest increased transformed cells (5-10% with clusters >20 cells) conferred a slight but significantly worse prognosis
• if DLBCL coexists a separate diagnosis should be made
Mantle cell lymphoma
• mantle zone pattern is less aggressive
• blastic morphology has worse prognosis
• since no effective treatment morphologic subtyping is not required but encouraged for research purposes
Diffuse large B-cell lymphoma
• no biological or clinical data to support subtyping
Burkitt’s vs. Burkitt’s-like lymphoma
• Burkitt’s-like is a non-reproducible category
• DDx - Burkitt’s and DLBCL• reserve Dx of Burkitt’s-like for high
grade lymphomas– morphologically resembles Burkitt’s– has more pleomorphic or large cells than
classical Burkitt’s– Ki-67 proliferative fraction >99%
ALCL definition
• ALK+ and/or t(2;5) - relatively good prognosis
• not restricted to ALK + cases• ALK should be performed on all
cases to the extent possible
Cutaneous vs. systemic ALCL
• cutaneous ALCL– indolent course– lack t(2;5)(p23;q35)– ALK negative– form spectrum with lymphomatoid
papulosis