MPAL: Difference between revisions
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Second: MPO is not fully specific for myeloid lineage in all cases: this is particularly the case when expression is dim, so an element of subjectivity is allowed when interpreting (particularly when detected by more sensitive techniques such as immunocytochemistry).</br> | Second: MPO is not fully specific for myeloid lineage in all cases: this is particularly the case when expression is dim, so an element of subjectivity is allowed when interpreting (particularly when detected by more sensitive techniques such as immunocytochemistry).</br> | ||
Suggestions have been made that may aid interpretation (weak evidence base): Applying a threshold of >10% cells being positive for MPO may improve specificity. Detecting variability of expression level of MPO by blast cells may suggest partial maturation and support myeloid lineage origin. Consider whether other myeloid markers to provide greater confidence that MPO is lineage specific. Similarly, 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. | Suggestions have been made that may aid interpretation (weak evidence base): Applying a threshold of >10% cells being positive for MPO may improve specificity. Detecting variability of expression level of MPO by blast cells may suggest partial maturation and support myeloid lineage origin. Consider whether other myeloid markers to provide greater confidence that MPO is lineage specific. Similarly, 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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Revision as of 19:50, 22 November 2023
Important Note
Flow cytometry provides initial evidence of MPAL. However conclusions may subsequently be modified (e.g. by results of immunohistochemistry, cytogenetics, or genetics). It is important that the provisional nature of flow cytometry assignment of MPAL is acknowledged when making a flow cytometric diagnosis of MPAL.
Frequency of MPAL types Not all forms of MPAL occur with the same frequency, the following types are regognised. | |
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MPAL with features of Myeloid and B-lineage | This is the most common MPAL (more than 50% of cases). |
MPAL with features of Myeloid and T-lineage | The second most frequent form (over one third of cases). I |
MPAL with combinations: T- and B- +/-myeloid-lineage | These forms are infrequent (around 10% of cases) |
MPAL with defining molecular features | Following further analysis cases may be assigned additionally as:
|
Lineage Assignment
Assignment to a lineage requires specific criteria are met, these are given below:
MYELOID LINEAGE ASSIGNMENT
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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: lysozyme or non-specific esterase in malignant cells (enzyme cytochemistry) |
Notes on interpretation of MPO positivity in MPAL
The WHO classification advises that MPO expression is assessed by its intensity of expression. The is based on two considerations:
First: The techniques used to detect MPO do not have the same sensitivity: immunohistochemistry > flow cytometry > 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.
Second: MPO is not fully specific for myeloid lineage in all cases: this is particularly the case when expression is dim, so an element of subjectivity is allowed when interpreting (particularly when detected by more sensitive techniques such as immunocytochemistry).
Suggestions have been made that may aid interpretation (weak evidence base): Applying a threshold of >10% cells being positive for MPO may improve specificity. Detecting variability of expression level of MPO by blast cells may suggest partial maturation and support myeloid lineage origin. Consider whether other myeloid markers to provide greater confidence that MPO is lineage specific. Similarly, 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.
.
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 |