Acute leukaemia types and MPAL: Difference between pages
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'''Important Note''' | |||
Flow cytometry is an important element that may alert clinicians to a diagnosis of MPAL and has an advantage of rapidity. However conclusions may subsequently be modified (e.g. by results of immunohistochemistry, cytogenetics, or genetics). In some cases, findings will re-assign with significant treatment implications. It is important that this is acknowledged when assigning an initial diagnosis of MPAL. | |||
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---- | Frequency of MPAL types | ||
*MPAL with features of Myeloid and B-lineage | |||
*MPAL with features of Myeloid and T-lineage | |||
*MPAL with features of T- and B-lineage | |||
*acute Undifferentiated leukaemia | |||
Following further analysis cases may be assigned additionally as: | |||
MPAL with t(9;22) (q34.1;q11.2); BCR-ABL1) | |||
MPAL with t(v;11q23.3); with KMT2A re-arrangement | |||
<div style="width: | <span id="anchor_0"></span>. | ||
{| class=" | <div style="width: 100%; border: 1px solid black; font-size:100%"> | ||
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!colspan="2" <span style="font-size:90%; font-color:navy; style="text-align: left; border: 1px solid black; background:pale gray">|'''Requirements to assign myeloid lineage in MPAL'''</br></span> | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:80%; text-align:left;"></br>The assignment of myeloid lineage recognises MPO expression to be a defining marker of myeloid lineage. However MPO is expressed only by around 80% of AML cases. The assignment of myeloid lineage can therefore also be made if monocytic lineage can be established, requiring at least 2 of 5 possible lineage markers to be detected (although only 3 of these can be established by flow cytometry).</br> | |||
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|colspan=" | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker option 1''' | ||
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|colspan="1" style = "font-size:90%; color:black;" |''' | |colspan="1" style = "font-size:90%; color:black;" |'''Demonstrate expression of Myeloperoxidase (MPO)''' | ||
|colspan="1" style = "font-size:90%;"| | |colspan="1" style = "font-size:90%;"|[[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). | ||
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|colspan="2" style = "font-size:90%; color:black; background: | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker option 2''' | ||
|- | |||
|colspan="1" style = "font-size:90%; color:black;" |'''Demonstrate clear evidence of monocytic lineage''' | |||
|colspan="1" style = "font-size:90%;|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) | |||
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!colspan="2" <span style="font-size:90%; font-color:black; style="text-align: left; border: 1px solid black; background-color:white">|'''NOTE''' Interpretation of MPO positivity in MPAL</span> | |||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for details" data-collapsetext="Hide details"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:90%; text-align:left;"></br>The WHO classification advises that MPO expression is assessed by its intensity of expression. The is based on two considerations: | |||
<span style="font-size: | <span style="font-size:90%; font-color:navy;>'''1. 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.</br> | ||
'''2. MPO is not entirely specific for myeloid lineage:''' 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></br> | |||
Some suggestions have been made that may aid interpretation (weak evidence base): | |||
*<span style="font-size:90%;>Applying a threshold of >10% cells being positive for MPO may improve specificity. | |||
'' | *<span style="font-size:90%;>*Variability of expression level by blast cells may suggest partial maturation and support myeloid lineage origin. | ||
*<span style="font-size:90%;>*The expression of other myeloid markers may allow greater confidence that MPO is lineage specific. | |||
</br> | |||
<span style="font-size:90%;>Be aware of common patterns of aberrancy that are associated with specific alternative diagnoses: | |||
< | *<span style="font-size:90%;>*Dim (weak) expression of MPO may be a feature of otherwise typical B-LL/LBL | ||
*<span style="font-size:90%;>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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!colspan="2" <span style="font-size:90%; font-color:navy; style="text-align: left; border: 1px solid black; background:pale gray">|'''Requirements to assign B-lymphoid lineage in MPAL'''</br></span> | |||
| | <div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | ||
<div class="mw-collapsible-content"> | |||
<span style="font-size:80%; text-align:left;"></br>For B-lymphoid lineage assignment the key lineage-marker is CD19. However, this marker has recognised aberrant expression in AML cases so additional criteria of expression intensity it is required that other markers must be expressed in addition to allow B-lineage assignment.</br> | |||
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</ | |||
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</br> | |||
|- | |- | ||
| | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker option 1''' | ||
|- | |- | ||
|colspan=" | |colspan="1" style = "font-size:90%; color:black;"|'''Required''' [[CD19|Strong expression of CD19]] | ||
|colspan="1" style = "font-size:90%;"|To meet the definition of "strong" the expression intensity '''must exceed''' that of 50% of normal B lymphocytes | |||
|- | |- | ||
|colspan="1" style = "font-size:90%;"|'''In addition''' 1 of: [[CD10]], [[CD22]], or [[CD79a]] (surface or cytoplasmic) | |||
|colspan="1" style = "font-size:90%;"|If CD19 is strong then B-lineage can be assigned if there is '''at least ONE''' of these additional markers | |||
|- | |- | ||
|colspan=" | |colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker option 2''' | ||
|- | |- | ||
|colspan="1" style = "font-size:90%; color:black;"|'''Required''' [[CD19|Weak expression of CD19]] | |||
|colspan="1" style = "font-size:90%;"|To meet the definition of "weak" the expression intensity must be '''less than''' that of 50% of normal B lymphocytes | |||
|- | |- | ||
|colspan="1" style = "font-size:90% | |colspan="1" style = "font-size:90%;"|'''In addition''' 2 of: [[CD10]], [[CD22]], or [[CD79a]] (surface or cytoplasmic) | ||
|colspan="1" style = "font-size: | |colspan="1" style = "font-size:90%;"|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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<span id="anchor_0"></span>. | |||
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<span | !colspan="2" <span style="font-size:90%; font-color:navy; style="text-align: left; border: 1px solid black; background:pale gray">|'''Requirements to assign T-lymphoid lineage in MPAL'''</br></span> | ||
<div class="mw-collapsible mw-collapsed" data-expandtext="Click for explanation" data-collapsetext="Hide explanation"> | |||
<div class="mw-collapsible-content"> | |||
<span style="font-size:80%; text-align:left;"></br>For T-lymphoid lineage assignment the key lineage-marker is CD3. Provided that this marker meets the intensity criteria then it is T-lineage defining in MPAL. This expression can be determined either by CD3 detection by flow cytometry OR by immunocytochemistry on trephine.</br> | |||
</span> | |||
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{| class="wikitable" | |||
!colspan="2" style = " | |||
|- | |- | ||
|colspan="2" style = "font-size:90%; color:black; background:#ddeee1" |'''Marker requirement''' | |||
|- | |- | ||
|colspan="1" style = "font-size:90%; color:black;"|'''Either''' [[CD3|CD3 surface or cytoplasm (strong)]] | |||
|colspan="1" style = "font-size:90%;"|To meet the definition of "strong" the expression intensity '''must exceed''' that of 50% of normal T lymphocytes | |||
|- | |- | ||
|colspan="1" style = "font-size:90%;"|'''Or''' [[CD3|CD3 by immunocytochemistry (strong)]] | |||
|colspan="1" style = "font-size:90%;"|For immunohistochemistry it is important a '''non-zeta chain reagent''' is used | |||
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Revision as of 11:51, 16 November 2023
Important Note Flow cytometry is an important element that may alert clinicians to a diagnosis of MPAL and has an advantage of rapidity. However conclusions may subsequently be modified (e.g. by results of immunohistochemistry, cytogenetics, or genetics). In some cases, findings will re-assign with significant treatment implications. It is important that this is acknowledged when assigning an initial diagnosis of MPAL.
Frequency of MPAL types
- MPAL with features of Myeloid and B-lineage
- MPAL with features of Myeloid and T-lineage
- MPAL with features of T- and B-lineage
- acute Undifferentiated leukaemia
Following further analysis cases may be assigned additionally as: MPAL with t(9;22) (q34.1;q11.2); BCR-ABL1) MPAL with t(v;11q23.3); with KMT2A re-arrangement
.
Requirements to assign myeloid lineage in MPAL
| |
---|---|
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) |
.
NOTE Interpretation of MPO positivity in MPAL
1. 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.
|
---|
.
Requirements to assign B-lymphoid lineage in MPAL
| |
---|---|
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 |
.
Requirements to assign T-lymphoid lineage in MPAL
| |
---|---|
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 |