Revised 2016 WHO classification of eosinophilia-associated myeloid or lymphoid neoplasms and idiopathic hypereosinophilic syndrome
| Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 . |
|---|
| Diagnostic criteria of an MPN*with eosinophilia associated with FIP1L1-PDGFRA |
| A myeloid or lymphoid neoplasm, usually with prominent eosinophilia |
| and |
| Presence of a FIP1L1-PDGFRA fusion gene or a variant fusion gene with rearrangement of PDGFRA† |
| Diagnostic criteria for myeloid/lymphoid neoplasms associated with ETV6-PDGFRB fusion gene or other rearrangement of PDGFRB‡ |
| A myeloid or lymphoid neoplasm, often with prominent eosinophilia and sometimes with neutrophilia or monocytosis |
| and |
| Presence of t(5;12)(q31∼q33;p12) or a variant translocation¶ or demonstration of an ETV6-PDGFRB fusion gene or rearrangement of PDGFRB |
| Diagnostic criteria of MPN or acute leukemia associated with FGFR1 rearrangement |
| A myeloproliferative or myelodysplastic/myeloproliferative neoplasm with prominent eosinophilia, and sometimes with neutrophilia or monocytosis |
| or |
| Acute myeloid leukemia or precursor T-cell or precursor B-cell lymphoblastic leukemia/lymphoma or mixed phenotype acute leukemia (usually associated with peripheral blood or BM eosinophilia) |
| and |
| Presence of t(8;13)(p11;q12) or a variant translocation leading to FGFR1 rearrangement demonstrated in myeloid cells, lymphoblasts, or both |
| Diagnostic criteria for myeloid/lymphoid neoplasms with PCM1-JAK2 |
| A myeloid or lymphoid neoplasm, often with prominent eosinophilia |
| and |
| Presence of t(8;9)(p22;p24.1) or a variant translocation leading to JAK2 rearrangement§ |
| CEL, NOS |
| There is eosinophilia (eosinophil count >1.5 × 109/L) |
| Not meeting WHO criteria for BCR-ABL1-positive chronic myeloid leukemia, PV, ET, PMF, CNL, CMML, or atypical CML |
| No rearrangement of PDGFRA, PDGFRB, or FGFR1; no PCM1-JAK2, ETV6-JAK2, or BCR-JAK2 fusion gene |
| The blast cell count in the peripheral blood and BM is less than 20%, and inv(16)(p13.1q22), t(16;16)(p13;q22) and other diagnostic features of AML are absent |
| There is a clonal cytogenetic or molecular genetic abnormality, or blast cells are ≥2% in the peripheral blood or >5% in the BM |
| Idiopathic HES |
| Exclusion of the following: |
| Reactive eosinophilia |
| Lymphocyte-variant HE (cytokine-producing, immunophenotypically-aberrant T-cell population) |
| CEL, NOS |
| WHO-defined myeloid malignancies associated eosinophilia (eg, MDS, MPNs, MDS/MPNs, or AML) |
| Eosinophilia-associated MPNs or AML/ALL with rearrangements of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 |
| The absolute eosinophil count of >1.5×109/L must persist for at least 6 mo, and tissue damage must be present. If there is no tissue damage, idiopathic HES is the preferred diagnosis. |
| Myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1, or with PCM1-JAK2 . |
|---|
| Diagnostic criteria of an MPN*with eosinophilia associated with FIP1L1-PDGFRA |
| A myeloid or lymphoid neoplasm, usually with prominent eosinophilia |
| and |
| Presence of a FIP1L1-PDGFRA fusion gene or a variant fusion gene with rearrangement of PDGFRA† |
| Diagnostic criteria for myeloid/lymphoid neoplasms associated with ETV6-PDGFRB fusion gene or other rearrangement of PDGFRB‡ |
| A myeloid or lymphoid neoplasm, often with prominent eosinophilia and sometimes with neutrophilia or monocytosis |
| and |
| Presence of t(5;12)(q31∼q33;p12) or a variant translocation¶ or demonstration of an ETV6-PDGFRB fusion gene or rearrangement of PDGFRB |
| Diagnostic criteria of MPN or acute leukemia associated with FGFR1 rearrangement |
| A myeloproliferative or myelodysplastic/myeloproliferative neoplasm with prominent eosinophilia, and sometimes with neutrophilia or monocytosis |
| or |
| Acute myeloid leukemia or precursor T-cell or precursor B-cell lymphoblastic leukemia/lymphoma or mixed phenotype acute leukemia (usually associated with peripheral blood or BM eosinophilia) |
| and |
| Presence of t(8;13)(p11;q12) or a variant translocation leading to FGFR1 rearrangement demonstrated in myeloid cells, lymphoblasts, or both |
| Diagnostic criteria for myeloid/lymphoid neoplasms with PCM1-JAK2 |
| A myeloid or lymphoid neoplasm, often with prominent eosinophilia |
| and |
| Presence of t(8;9)(p22;p24.1) or a variant translocation leading to JAK2 rearrangement§ |
| CEL, NOS |
| There is eosinophilia (eosinophil count >1.5 × 109/L) |
| Not meeting WHO criteria for BCR-ABL1-positive chronic myeloid leukemia, PV, ET, PMF, CNL, CMML, or atypical CML |
| No rearrangement of PDGFRA, PDGFRB, or FGFR1; no PCM1-JAK2, ETV6-JAK2, or BCR-JAK2 fusion gene |
| The blast cell count in the peripheral blood and BM is less than 20%, and inv(16)(p13.1q22), t(16;16)(p13;q22) and other diagnostic features of AML are absent |
| There is a clonal cytogenetic or molecular genetic abnormality, or blast cells are ≥2% in the peripheral blood or >5% in the BM |
| Idiopathic HES |
| Exclusion of the following: |
| Reactive eosinophilia |
| Lymphocyte-variant HE (cytokine-producing, immunophenotypically-aberrant T-cell population) |
| CEL, NOS |
| WHO-defined myeloid malignancies associated eosinophilia (eg, MDS, MPNs, MDS/MPNs, or AML) |
| Eosinophilia-associated MPNs or AML/ALL with rearrangements of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2 |
| The absolute eosinophil count of >1.5×109/L must persist for at least 6 mo, and tissue damage must be present. If there is no tissue damage, idiopathic HES is the preferred diagnosis. |
Patients presenting with myeloproliferative neoplasm, AML, or lymphoblastic leukemia/lymphoma with eosinophilia and a FIP1L1-PDGFRA fusion gene are also assigned to this category.
If appropriate molecular analysis is not available, this diagnosis should be suspected if there is a Ph-chromosome–negative MPN with the hematologic features of chronic eosinophilic leukemia associated with splenomegaly, a marked elevation of serum vitamin B12, elevation of serum tryptase, and increased BM mast cells.
Cases with fusion genes typically associated only with BCR-ABL1-like B-lineage ALL are specifically excluded.
Because t(5;12)(q31∼q33;p12) does not always lead to an ETV6-PDGFRB fusion gene, molecular confirmation is highly desirable. If molecular analysis is not available, this diagnosis should be suspected if there is a Ph-chromosome–negative MPN associated with eosinophilia and with a translocation with a 5q31∼33 breakpoint.
Other variants giving rise to a fusion gene between JAK2 and an alternative partner include ETV6-JAK2 [t(9;12)(p24.1;p13.2)] or BCR-JAK2 [t(9;22)(p24.1;q11.2)].