MPAL: Difference between revisions
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<span style="font-size: | <span style="font-size:90%; text-align:left;"></br>TThe WHO classification advises that MPO expression is assessed by its intensity of expression. The is based on two considerations: | ||
1. The techniques used to detect MPO are not equivalent: (In terms of sensitivity immunohistochemistry > FC > enzyme-cytochemistry). This means diagnosis of MPAL may be method dependent – expressing MPO as intensity allows expression to be compared with that of normal cells detected using the same method. | <span style="font-size:90%>1. The techniques used to detect MPO are not equivalent: (In terms of sensitivity immunohistochemistry > FC > enzyme-cytochemistry). This means diagnosis of MPAL may be method dependent – expressing MPO as intensity allows expression to be compared with that of normal cells detected using the same method. | ||
2. MPO is not entirely specific for myeloid lineage, particularly when expressed at low level, so an element of subjectivity is allowed when interpreting (particularly when detected by sensitive techniques and when expression is dim). | 2. MPO is not entirely specific for myeloid lineage, particularly when expressed at low level, so an element of subjectivity is allowed when interpreting (particularly when detected by sensitive techniques and when expression is dim). | ||
Some suggestions have been made that may aid interpretation, though caution is required as the evidence base is weak: | Some suggestions have been made that may aid interpretation, though caution is required as the evidence base is weak: |
Revision as of 10:35, 10 November 2023
Assignment of category to ambiguous cases in acute leukaemia:
Final lineage requires integration of additional molecular features; assignments made by flow are therefore "provisional" pending full molecular assessment. Four categories may be assigned:
- My/B
- My/T**
- T/B
- Undiff
MPAL with t(9;22) (q34.1;q11.2); BCR-ABL1) MPAL with t(v;11q23.3); with KMT2A re-arrangement
Flow cytometry is only one element in assigning a diagnosis of MPAL but conclusions may subsequently be modified by results of immunohistochemistry, cytogenetics, or genetics. It is important therefore that an element of uncertainty is acknowledged in assigning a diagnosis of MPAL by flow cytometry, acknowledging that any may be subject to modification if other disease-defining characteristics emerge.
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Requirements to assign myeloid lineage in MPAL
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Marker option 1 | |
Demonstrate expression of Myeloperoxidase (MPO) | Myeloperoxidase expression alone may be sufficient to establish myeloid lineage, but be aware of the limitations: (1) intensity should be at least half of that of mature neutrophils in at least of proportion of cells measured by the same method; (2) there are circumstances where judgement is required (see notes). |
Marker option 2 | |
Demonstrate clear evidence of monocytic lineage | If MPO is not demonstrated then myeloid lineage may still be assigned through demonstration of monocytic features. This can be assigned by the detection of at least two of the following features: By flow cytometry: CD11c, CD14, CD64; by other approaches: raised lysozyme in serum or urine or non-specific esterase in malignant cells (enzyme cytochemistry) |
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NOTE Interpretation of MPO positivity in MPAL
1. The techniques used to detect MPO are not equivalent: (In terms of sensitivity immunohistochemistry > FC > enzyme-cytochemistry). This means diagnosis of MPAL may be method dependent – expressing MPO as intensity allows expression to be compared with that of normal cells detected using the same method. 2. MPO is not entirely specific for myeloid lineage, particularly when expressed at low level, so an element of subjectivity is allowed when interpreting (particularly when detected by sensitive techniques and when expression is dim). Some suggestions have been made that may aid interpretation, though caution is required as the evidence base is weak: • Applying a threshold of >10% cells being positive for MPO may improve specificity. • Variability of expression level by blast cells may suggest partial maturation and support myeloid lineage origin. • The expression of other myeloid markers may allow greater confidence that MPO is lineage specific. Be aware of common patterns of aberrancy that are associated with specific alternative diagnoses: • Dim (weak) expression of MPO may be a feature of otherwise typical B-LL/LBL
• Burkitt-like entities may have strong MPO staining however other investigations will confirm their nature and other myeloid markers will be absent.
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Requirements to assign B-lymphoid lineage in MPAL
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Marker option 1 | |
Required Strong expression of CD19 | To meet the definition of "strong" the expression intensity must exceed that of 50% of normal B lymphocytes |
In addition 1 of: CD10, CD22, or CD79a (surface or cytoplasmic) | If CD19 is strong then B-lineage can be assigned if there is at least ONE of these additional markers |
Marker option 2 | |
Required Weak expression of CD19 | To meet the definition of "weak" the expression intensity must be less than that of 50% of normal B lymphocytes |
In addition 2 of: CD10, CD22, or CD79a (surface or cytoplasmic) | If CD19 is weak then B-lineage can be assigned only if there are at least TWO of these additional markers |
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Requirements to assign T-lymphoid lineage in MPAL
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Marker requirement | |
Either CD3 surface or cytoplasm (strong) | To meet the definition of "strong" the expression intensity must exceed that of 50% of normal T lymphocytes |
Or CD3 by immunocytochemistry (strong) | For immunohistochemistry it is important a non-zeta chain reagent is used |