How to diagnose lymphoblastic acute leukemia

foreword

Foreword Foreword

In the diagnosis of hematopoietic and lymphoid tissue tumors , morphologists are always on the front line

In the diagnosis of hematopoietic and lymphoid tissue tumors , morphologists are always on the front line

case after

Male, 92 years old, has fever without obvious incentives nearly 20 days ago, the highest body temperature is 39.

Male, 92 years old, has fever without obvious incentives nearly 20 days ago, the highest body temperature is 39.

Laboratory tests: white blood cells 2.

A type of unclassified cells can be seen.

The common morphological features of mature T lymphoma cells: often high nuclear to cytoplasmic ratio, irregular nuclear shape, mild to moderate basophilic cytoplasm and generally agranular, also generally referred to as abnormal T cells

Looking at the morphology of the patient's bone marrow cells, is it very similar to the morphology of tumorous T/NK cells? The patient also had multiple enlarged mediastinal lymph nodes that appeared to target lymphoma cell leukemia

 

No abnormality was found in each group of lymphocytes, but a group of abnormal cells were seen, which were considered as primitive cells

No abnormality was found in each group of lymphocytes, but a group of abnormal cells were seen, which were considered as primitive cells

Acute leukemia immunophenotyping was added, and the results were as follows:

 

 

Immunity typing prompt: consistent with acute myeloid leukemia phenotype

Immunity typing prompt: consistent with acute myeloid leukemia phenotype

Karyotype:

Karyotype:

 

 

Chromosomal results suggest that polyploid karyotypes are easy to see

Chromosomal results suggest that polyploid karyotypes are easy to see

 

According to the FAB classification, the patient can be diagnosed as M0; and according to the 2016 WHO classification, the patient can be diagnosed as: AML with RUNX1 mutation

According to the FAB classification, the patient can be diagnosed as M0; according to the 2016 WHO classification, the patient can be diagnosed as: AML with RUNX1 mutation Literature Review Literature Review

1.

1.

The FAB classification of acute leukemia was first published in 1976, when acute myeloid leukemia had 6 subtypes (M1~M6); it was first updated in 1985, adding acute megakaryocytic leukemia (M7); in 1991 For the second and final update, acute myeloid leukemia microdifferentiated (M0) was added

Bone marrow blasts ≥30% (NEC), with mostly clear or moderately basophilic cytoplasm, no azurophilic granules and Auer bodies, and obvious nucleoli, similar to ALL-L2 type

Cytochemistry: Peroxidase and Sudan Black B staining <3%; Cytochemistry:

Immunophenotype: positive for myeloid markers CD33 and/or CD13, negative for lymphoid antigens, but CD7+, TdT

Immunophenotype: Myeloid markers CD33 and/or CD13 may be positive, lymphoid antigen negative, but CD7+, TdT immunophenotypes may be present:

Electron microscope: myeloperoxidase (MPO) positive
.

Electron microscope: myeloperoxidase (MPO) positive
.
Electron microscopy:

WHO basically continued the classification of FAB and included it in acute myeloid leukemia unspecified (AML, NOS), but the proportion of blast cells was changed to ≥20% (ANC), and other types of AML need to be excluded:

WHO basically continued the classification of FAB and included it in acute myeloid leukemia unspecified (AML, NOS), but the proportion of blast cells was changed to ≥20% (ANC), and other types of AML need to be excluded:

This flowchart comes from the public account "Academic Exchange of Comprehensive Diagnosis of Hematology"

This flowchart comes from the public account "Academic Exchange of Comprehensive Diagnosis of Hematology"

2.
AML with RUNX1 mutation

2.
AML with RUNX1 mutation 2.
AML with RUNX1 mutation

It accounts for about 4-16% of AML.
It is more common in the elderly, and its morphology is mostly consistent with acute myeloid leukemia - not specified.
15-65% of cases resemble AML with microdifferentiation, and some cases show AML with mature, AML with mononuclear or Differentiation characteristics of mononuclear cells
.

It accounts for about 4-16% of AML.
It is more common in the elderly, and its morphology is mostly consistent with acute myeloid leukemia - not specified.
15-65% of cases resemble AML with microdifferentiation, and some cases show AML with mature, AML with mononuclear or Differentiation characteristics of mononuclear cells
.

Immunophenotype: blasts typically express CD13, CD34 and HLA-DR, with varying degrees of CD33, MPO and mononuclear antigens
.

Immunophenotype: blasts typically express CD13, CD34 and HLA-DR, with varying degrees of CD33, MPO and mononuclear antigens
.
Immunophenotype:

Cytogenetics: Most RUNX1 mutations are monoallelic and can be combined with abnormal karyotypes, the most common being +8 and +13
.
It can also be combined with other gene mutations such as ASXL1, FLT3-ITD, etc.
, suggesting a poor prognosis
.

Cytogenetics: Most RUNX1 mutations are monoallelic and can be combined with abnormal karyotypes, the most common being +8 and +13
.
It can also be combined with other gene mutations such as ASXL1, FLT3-ITD, etc.
, suggesting a poor prognosis
.
Cytogenetics:

The differential diagnosis is mainly acute myeloid leukemia-unspecified and AML with RUNX1 germline mutation
.
The former can be identified by molecular genetics, while the latter has a family history, manifested as platelet dysfunction since small, and the presence of inherited monoallelic mutations can be detected by molecular biology
.

The differential diagnosis is mainly acute myeloid leukemia-unspecified and AML with RUNX1 germline mutation
.
The former can be identified by molecular genetics, while the latter has a family history, manifested as platelet dysfunction since small, and the presence of inherited monoallelic mutations can be detected by molecular biology
.

case analysis

case analysis

1.
What is the FAB classification in this case?

1.
What is the FAB classification in this case? 1.
What is the FAB classification in this case?

Cytochemistry: According to the requirements of FAB typing, the POX of AML-M0 is negative or <1%, and the POX>3% of AML-M1 can be diagnosed
.

Cytochemistry: According to the requirements of FAB typing, the POX of AML-M0 is negative or <1%, and the POX>3% of AML-M1 can be diagnosed
.

Immunophenotype: as shown below

Immunophenotype: as shown below

Based on cytochemistry and immunophenotype, the FAB type in this case should be AML-M0
.

Based on cytochemistry and immunophenotype, the FAB type in this case should be AML-M0
.

2.
According to the 2016 WHO classification, the patient had RUNX1 mutation and no other recurrent genetic abnormalities, so the diagnosis was AML with RUNX1 mutation (and AML-M0 is indeed the most common type of the disease); in addition, the patient also Accompanied by mutations in ASXL1, IDH2, TET2, FLT3, etc.
, all suggest a poor prognosis
.

2.
According to the 2016 WHO classification, the patient had RUNX1 mutation and no other recurrent genetic abnormalities, so the diagnosis was AML with RUNX1 mutation (and AML-M0 is indeed the most common type of the disease); in addition, the patient also Accompanied by mutations in ASXL1, IDH2, TET2, FLT3, etc.
, all suggest a poor prognosis
.
experience, experience, experience

As Zhang Jianfu, director of Jiangsu Provincial People's Hospital, said, the cell shape is ever-changing, there are only things you can't think of/dare to think about, and you can't change without it
.
It is not uncommon for acute lymphoblastic leukemia (or even lymphoma bone marrow invasion/leukemia) diagnosed by cytomorphology to be finally diagnosed as AML by immunophenotyping
.
Morphologists must not "take it for granted" to make conclusions, especially in patients with negative MPO and PAS, comprehensive MICM typing is very important
.

As Zhang Jianfu, director of Jiangsu Provincial People's Hospital, said, the cell shape is ever-changing, there are only things you can't think of/dare to think about, and you can't change without it
.
It is not uncommon for acute lymphoblastic leukemia (or even lymphoma bone marrow invasion/leukemia) diagnosed by cytomorphology to be finally diagnosed as AML by immunophenotyping
.
Morphologists must not "take it for granted" to make conclusions, especially in patients with negative MPO and PAS, comprehensive MICM typing is very important
.

The ability to distinguish cells takes a long time to be tempered.
Just as Director Zhang Jianfu of Jiangsu Provincial People's Hospital said, when there is a difference between the cytomorphological diagnosis and the immunophenotyping report, we should re-examine the cell morphology to enhance the understanding of cell morphology.
control ability
.
Looking back at this patient, when looking at the cell morphology, it is found that the nuclear chromatin is more delicate, while the chromatin of lymphoma cells is relatively rough, and there is still a difference between the two
.

The ability to distinguish cells takes a long time to be tempered.
Just as Director Zhang Jianfu of Jiangsu Provincial People's Hospital said, when there is a difference between the cytomorphological diagnosis and the immunophenotyping report, we should re-examine the cell morphology to enhance the understanding of cell morphology.
control ability
.
Looking back at this patient, when looking at the cell morphology, it is found that the nuclear chromatin is more delicate, while the chromatin of lymphoma cells is relatively rough, and there is still a difference between the two
.

For acute leukemia with atypical morphology, the bone marrow can be reported as: acute leukemia, type to be determined, MICM classification is recommended, and timely communication with the clinic is required to complete the ICM examination as soon as possible
.

For acute leukemia with atypical morphology, the bone marrow can be reported as: acute leukemia, type to be determined, MICM classification is recommended, and timely communication with the clinic is required to complete the ICM examination as soon as possible
.

references

references

[1]Bennett JM, Catovsky D, Daniel MT, et al.
Proposals for the classification of the acuteleukemias (FAB Cooperative Group).
Br J Haematol 33:451–458

[1]Bennett JM, Catovsky D, Daniel MT, et al.
Proposals for the classification of the acuteleukemias (FAB Cooperative Group).
Br J Haematol 33:451–458

[2] Bennett JM, Catovsky D, Daniel MT, et al.
Proposed revised criteria for the classification of acute myeloid leukemia.
Ann Intern Med 103:620–629

[2] Bennett JM, Catovsky D, Daniel MT, et al.
Proposed revised criteria for the classification of acute myeloid leukemia.
Ann Intern Med 103:620–629

[3] Bennett JM, Catovsky D, Daniel MT et al.
Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7): Areport of the French-American-British Cooperative Group.
Ann.
Intern.
Med, 1985, 103: 460- 2.

[3] Bennett JM, Catovsky D, Daniel MT et al.
Criteria for the diagnosis of acute leukemia of megakaryocyte lineage (M7): Areport of the French-American-British Cooperative Group.
Ann.
Intern.
Med, 1985, 103: 460- 2.

[4] Bennett JM, Catovsky D, Daniel MT, et al.
Proposals for therecognition of minimally differentiated acute myeloid leukemia(AML-M0) .
Br J Haematol 78:325–329

[4] Bennett JM, Catovsky D, Daniel MT, et al.
Proposals for therecognition of minimally differentiated acute myeloid leukemia(AML-M0) .
Br J Haematol 78:325–329

[5]WHO classification of tumors of haematopoietic and lymphoid tissues/ edited by Steven H.
Swerdlow, Elias Campo, Nancy Lee Harris, ElaineS.
Jaffe, Stefano A.
Pileri, Harald Stein, Jurgen Thiele.
- Revised4th edition.
IARC: Lyon2017

[5]WHO classification of tumors of haematopoietic and lymphoid tissues/ edited by Steven H.
Swerdlow, Elias Campo, Nancy Lee Harris, ElaineS.
Jaffe, Stefano A.
Pileri, Harald Stein, Jurgen Thiele.
- Revised4th edition.
IARC: Lyon2017

[6] Lu Xingguo, Ye Xiangjun, Xu Genbo.
Bone marrow cells and histopathological diagnosis [M].
Beijing: People's Health Publishing House, 2020

[6] Lu Xingguo, Ye Xiangjun, Xu Genbo.
Bone marrow cells and histopathological diagnosis [M].
Beijing: People's Health Publishing House, 2020

[7] Gao Haiyan, Liu Yabo, Lv Chengfang, Chen Xueyan.
Clinical examination and diagnosis of blood diseases [M].
Beijing: China Medical Science and Technology Press, 2021.
3

[7] Gao Haiyan, Liu Yabo, Lv Chengfang, Chen Xueyan.
Clinical examination and diagnosis of blood diseases [M].
Beijing: China Medical Science and Technology Press, 2021.
3

 

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