|
|
| Line 1: |
Line 1: |
|
| |
| ---- | | ---- |
| <div style="width: 200px"> | | <div style="width: 200px"> |
| Line 9: |
Line 8: |
| -------- | | -------- |
|
| |
|
| <div style="width: 100%">
| | The ETP-ALL/LBL |
| {| class="wikitable" style="border-style: solid; border-width: 5px; color:black"
| |
| |colspan="1" style = "font-size:90%; color:black; background: #bcd4e6"|'''1. The immunophenotype of the blast cells should be consistent with their "primitive" nature'''
| |
| |}
| |
| </div>
| |
| | |
| [[Image:AML M1.png|110px]]
| |
| </br></br><span style="font-size:90%;">Assigning primitive nature in most cases is straightforward, but some sun-types of AML may present difficulties.</span>
| |
| | |
| <div style="width: 95%; font-size:90%;">
| |
| {| class="wikitable" style="border-style: solid; border-width: 4px; color:black"
| |
| !colspan="1" style = "background:#ddeee1; border:solid; border-width: 3px;"|<span style="font-size:90%;">'''Demonstrating primitive phenotype in AML'''</span></br>
| |
| |-
| |
| !colspan="1" style = "background:white; font-size:90%; border:solid; border-width: 1px; color:black"|'''Primitive phenotype:''' In most cases, cells of AML will demonstrate typical features of immature cells with: '''weak expression of CD45''', and expression of '''CD34''' and/or '''CD117'''</br>However, patterns are not always typical and difficult cases other markers of early differentiation may also help</br></br>[[Markers used to demonstrate primitive nature in AML|''Click for a more detailed table of markers associated with primitive phenotype'']]
| |
| |-
| |
| !colspan="1" style = "background:#ddeee1;border:solid"|<span style="font-size:90%;">'''Difficulties may occur where blast cells have significant maturation so their primitive nature may be less easy to demonstrate.'''</span></br>
| |
| |-
| |
| !colspan="1" style = "background:white; font-size:90%; border:solid; border-width: 1px;"|'''Difficulties:''' These are most frequently encountered in monocytic cases of AML, or in acute promyelocytic leukaemia (APL) (although occasionally in other types).</br></br>[[Atypical patterns of primitive marker expression in acute myeloid leukaemia|Click to see common patterns that may cause difficulty in assigning primitive phenotype]]
| |
| |-
| |
| |}
| |
| </div>
| |
| | |
|
| |
|
| ---- | | The immunophenotype of ETP-ALL requires careful consideration – this reflects that the condition was identified using gene expression profiling rather than by immunophenotype. Using immunophenotype to establish the diagnosis is therefore challenging and may underestimate the number of true cases.* and may not be easily separated from ALAL T/my |
| | Or T-ALL |
|
| |
|
| <div style="width: 100%">
| | The approach presently advocated by WHO requires: |
| {| class="wikitable" style="border-style: solid; border-width: 5px; color:black"
| | 1. Required expression: Cytoplasmic CD3 (may be heterogenous but should be expressed by ≥25% of blasts) |
| |colspan="1" style = "font-size:90%; color:black; background:#bcd4e6"|'''2. The immunophenotype of the blast cells should allow myeloid lineage to be assigned'''
| | 2. Required expression: One or more myeloid antigen (CD11b, CD13, CD33, CD65, CD117) and/or stem cell antigens (CD34, HLA-DR) |
| |}
| | 3. Required absence: CD3, CD1a and CD8 (<5% of blasts) |
| | 4. Required absent/dim CD5 expression (<75% positive blasts) |
|
| |
|
| [[Image:AML M2.png|130px]]
| | Note that CD7 is consistently positive in ETP-ALL and does not count as a stem cell antigen in this context |
| | *CD4 may have the same pattern |
|
| |
|
|
| |
|
| <span style="font-size:90%;">The criteria to assign myeloid lineage in AML have been established, two alternative sets of criteria may be used (although most cases will meet both):
| | The ETP-ALL immunophenotype may also be established by immunohistochemistry. |
| | |
| | |
|
| |
|
| <div style="width: 95%; font-size:90%;">
| | *T-ALL cases that have an immunophenotype similar to ETP-ALL but where CD5 is expressed (≥75% of blasts) may be designated as “near-ETP-ALL”, but the clinical implications of such a designation remain unclear. |
| {| class="wikitable" style="border-style: solid; border-width: 4px; color:black"
| |
| !colspan="1" style = "background:#ddeee1; border:solid; border-width: 3px;"|<span style="font-size:90%;">'''Pattern A: AML diagnosis based on lineage-defining markers'''</span></br>
| |
| |-
| |
| !colspan="1" style = "background:white; border:solid; border-width: 1px; color:black"|A myeloid lineage-defining marker pattern is present '''and''' no lineage-defining markers of T or B cells are present</br>
| |
| <span style="font-size:90%;">[[Flow cytometry: Myeloid-defining markers|Click to view table of criteria]]</span>
| |
| |-
| |
| !colspan="1" style = "background:#ddeee1;border:solid"|<span style="font-size:90%;">'''Pattern B: AML diagnosis based on lineage-associated marker patterns'''</span></br>
| |
| |-
| |
| !colspan="1" style = "background:white; border:solid; border-width: 1px;"|At least two myeloid lineage-associated markers are present '''and''' there are no lineage defining markers of T or B cells '''and''' no more than one T-cell or B-cell lineage-associated marker is present</br>
| |
| <span style="font-size:90%;">[[Myeloid lineage-associated markers|Click to view table of criteria]]</span>
| |
| |}
| |
| </div>
| |
|
| |
|
|
| |
|
| ---- | | Distinction from mixed-phenotype acute leukaemia (MPAL) requires that MPO is not expressed - in this context of ETP-ALL the WHO advocate a threshold of <3% to define negative myeloperoxidase expression (by cytochemistry or flow cytometry). This threshold is different from that of T/myeloid MPAL so may not be optimal but is retained at present. |
| | |
| <div style="width: 100%">
| |
| {| class="wikitable" style="border-style: solid; border-width: 5px; color:black"
| |
| |colspan="1" style = "font-size:90%; color:black; background:#bcd4e6"|'''3. Alternative diagnoses should be considered and excluded'''
| |
| |}
| |
| [[Image:Lymphoblast.png|110px]]
| |
| </div>
| |
| <span style="font-size:90%;"></br>In some cases lineage may be unclear - in such cases it is important to consider possible alternative diagnoses</span></br>
| |
| | |
| | |
| <span style="font-size:90%;">Alternative potential diagnoses in difficult cases:</span>
| |
| | |
| <div style="width: 95%; font-size:95%;">
| |
| {| class="wikitable" style="border-style: solid; border-width: 4px; color:black"
| |
| !colspan="2" style = "background:#ddeee1;border:solid"|<span style="font-size:90%;">'''Mixed Phenotype Acute Leukaemia''' (MPAL)</span>
| |
| |-
| |
| !colspan="2" style = "background:white;border:solid; font-size:90%;;"|'''Consider MPAL:''' Where myeloid lineage can be assigned based on '''lineage-specific''' patterns '''but''' the cells also have marker patterns that meet the criteria to assign T or B cell lineage.</br></br>[[Flow cytometry:MPAL|''Click for diagnostic criteria of MPAL'']]
| |
| |-
| |
| !colspan="2" style = "background:#ddeee1;border:solid"|'''Acute Undifferentiated Leukaemia''' (AUL)
| |
| |-
| |
| !colspan="2" style = "background:white; border:solid; font-size:90%;"|'''Consider AUL:''' In cases where the evidence is insufficient to assign myeloid lineage '''and''' there is insufficient evidence to assign to T-cell or B-cell lineage </br></br>[[Flow cytometry:AUL|''Click for diagnostic criteria of AUL'']]
| |
| |-
| |
| !colspan="2" style = "background:#ddeee1;border:solid"|'''Acute Leukaemia of ambiguous lineage not otherwise sepcified''' (ALAL-NOS)
| |
| |-
| |
| !colspan="2" style = "background:white; border:solid; font-size:90%;"|'''Consider ALAL-NOS:''' if classification to specific lineage is not possible '''but''' blast cells cannot be classed as AUL or MPAL.</br></br>[[Flow cytometry:ALAL-NOS|''This is most often a useful provisional diagnosis - click here for details'']]</br>
| |
| |-
| |
| !colspan="2" style = "background:#ddeee1;border:solid"|''' Early T-cell precursor acute lymphoblastic leukaemia''' (ETP-ALL)
| |
| |-
| |
| !colspan="2" style = "background:white; border:solid; font-size:90%;"| This disorder has diagnostic criteria sufficient to assign T cell lineage (cCD3 is expressed) but may express myeloid-associated antigens cases may share features with T/myeloid MPAL</br>[[Flow cytometry:ETP-ALL|''Click for diagnostic criteria of ETP-ALL'']]
| |
| |-
| |
| !colspan="2" style = "background:#ddeee1;border:solid"|'''Blastic plasmacytoid dendritic cell neoplasm''' (BPDCN)
| |
| |-
| |
| !colspan="2" style = "background:white; border:solid; font-size:90%;"|'''Consider BPDCN:''' Generally in cases that resemble AUL (rarely AML), most often with skin rash. A specific marker profile should be sought: expression of bright CD4 and/or CD56 is expected. CD33 is frequently expressed but other myeloid markers are less frequent and MPO and CD34 should be absent. Look for specific additional markers as described in the diagnostic criteria.</br></br>[[Flow cytometry:BPDCN|''Click for diagnostic criteria of BPDCN'']]
| |
| |}
| |
| </br>
| |
| | |
| </br>
| |
| <span style="font-size:90%;">*'''NOTE''' Some "non-lineage" markers are frequently expressed in AML and may be associated with specific AML subtypes, these do not necessarily indicate mixed phenotype ([[Table of frequent aberrant markers in AML|Click here for further detail]]). Other features should give concern for alternative diagnosis (see the table below more detailed guidance).
| |
| | |
| ----
| |
The ETP-ALL/LBL
The immunophenotype of ETP-ALL requires careful consideration – this reflects that the condition was identified using gene expression profiling rather than by immunophenotype. Using immunophenotype to establish the diagnosis is therefore challenging and may underestimate the number of true cases.* and may not be easily separated from ALAL T/my
Or T-ALL
The approach presently advocated by WHO requires:
1. Required expression: Cytoplasmic CD3 (may be heterogenous but should be expressed by ≥25% of blasts)
2. Required expression: One or more myeloid antigen (CD11b, CD13, CD33, CD65, CD117) and/or stem cell antigens (CD34, HLA-DR)
3. Required absence: CD3, CD1a and CD8 (<5% of blasts)
4. Required absent/dim CD5 expression (<75% positive blasts)
Note that CD7 is consistently positive in ETP-ALL and does not count as a stem cell antigen in this context
- CD4 may have the same pattern
The ETP-ALL immunophenotype may also be established by immunohistochemistry.
- T-ALL cases that have an immunophenotype similar to ETP-ALL but where CD5 is expressed (≥75% of blasts) may be designated as “near-ETP-ALL”, but the clinical implications of such a designation remain unclear.
Distinction from mixed-phenotype acute leukaemia (MPAL) requires that MPO is not expressed - in this context of ETP-ALL the WHO advocate a threshold of <3% to define negative myeloperoxidase expression (by cytochemistry or flow cytometry). This threshold is different from that of T/myeloid MPAL so may not be optimal but is retained at present.