One case of acute B-lymphoblastic leukemia with BCR-ABL1

preface

Acute lymphoblastic leukemia (ALL) is a type of acute leukemia that mainly originates from B or T line lymphoid progenitor cells, which abnormally proliferate and aggregate in the bone marrow, thereby inhibiting normal hematopoiesis, resulting in anemia, thrombocytopenia, and neutropenia
.
Leukemia cells can also invade extramedullary tissues, such as meninges, gonads, thymus, liver, spleen, lymph nodes and bone tissue, causing corresponding lesions
.

With the development of hematology diagnostic technology, the 2016 edition of WHO named ALL as a prodromal lymphocytic tumor (lymphoblastic leukemia/lymphoma) in hematopoietic and lymphoid tissue tumors, and emphasized the important role
of genetics and molecular biology in the diagnosis, treatment, prognosis and evaluation of diseases.
For our primary hospital, there is still a lot we need to learn in the diagnosis of MICM, a hematological disease, and a recent case encountered is learned and shared
with you.

Case history

Patient, female, 69 years old, 20 days ago, the patient had no obvious cause of physical discomfort, accompanied by fatigue, dizziness, nausea, no fever, chills, no hepatosplenic lymphadenopathy, came to our hospital for treatment, the doctor routinely checked the blood routine as follows:

Patients with markedly elevated white blood cells, increased lymphocyte ratio, severe anemia, platelet criticality, abnormal scatter plots, and violation of reexamination rules push-film microscopic examination:

PERIPHERAL BLOOD: 10X10 TIMES

Peripheral blood: 10X100 times

Description of abnormal lymphocyte morphology:

The proportion of abnormal lymphocytes reaches more than 90%, the cell body is small, round, round or irregular, tadpole-shaped, hand mirror-shaped, cytoplasmic less or none, the nucleus is round or round-like, chromatin structure is fuzzy, seemingly small blocks, seemingly loose, nucleoli are not clear, blue cells are easy to see, see two blood pieces, there are rare individuals in the tail larger than typical primitive naïve lymphocytes, a large number of abnormal lymphocytes with small cell bodies are primitive naïve? Or mature?

It is indeed a challenge for us who lack morphological experience, which will affect the direction of disease diagnosis and treatment, which we cannot ignore
.
At the urging of the doctor, we also analyze from other directions, from the patient's age of 69 years old for the elderly, the probability of suffering from chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL) is greater, ALL is mainly seen in children and young adults, is it CLL/SLL? Let's compare morphology
.

Chronic lymphoblastic leukemia/small lymphocytic lymphoma (CLL/SLL):

The pattern is as follows:

Chronic lymphoblastic leukemia is a clonal and multi-valued neoplastic disease of lymphocytes, mainly manifested as mature small lymphocytes invading peripheral blood, bone marrow, lymph nodes and spleen and other lymphoid tissues, small lymphocytic lymphoma (SLL) refers to this type of neoplastic lymphocytes mainly infiltrated in lymph nodes, spleen and other lymphoid tissues without significantly involving peripheral blood and bone marrow
.

CLL and SLL are considered to be different manifestations of the same biological entity, without essential difference, WHO classification clarifies that chronic lymphocytic leukemia and SLL specifically refer to chronic B lymphocytic leukemia, named mature B cell tumor CLL/SLL
.
The WHO classifies chronic T-lymphocytic leukemia, which was previously considered rare, as macrogranular T-lymphocytic leukemia, young T-lymphocytic leukemia and T-lymphocyte reactive hyperplasia
.

The pathological lymphocytes of CLL/SLL are mainly based on typical similar mature small lymphocyte hyperplasia as shown above, with small cell volume, chromatin concentration, no nucleocytes, less cell quality, high nucleoplasm ratio, and their morphology is often difficult to distinguish from
mature small lymphocytes.
Atypical cells include naïve lymphocytes, cells with notches in the nucleus, and mature lymphocytes with larger bodies and rich cytoplasm
.

The two contrasted different cell morphology, excluding CLL/SLL
.
Temporarily lean towards ALL
.
Proposed bone marrow aspiration combined with biopsy, flow cytometry, genetics, and molecular biology analysis
.
The report feedback is as follows:

Bone marrow test result report

Bone marrow reported results: blood film primitive naïve lymph accounted for 68%, bone marrow primitive naïve lymphocytes accounted for 95.
2%, POX (myeloperoxidase) staining was negative
.
Opinion: Consider ALL bone marrow image
.

Bone marrow biopsy result report:

Analysis conclusions and opinions: in line with B-acute lymphoblastic leukemia (B-ALL), remarks: the proportion of protojuvenile B lymphocytes accounts for about 90%, it is recommended to add BCR/ABL fusion gene and related gene screening to assist in diagnosis and prognosis assessment
.

Bone marrow flow cytometry immunofluorescence analysis results report:

Analysis conclusion: In line with the acute B lymphocyte leukemia (common-B-ALL) immunophenotype, BCR/ABL1 gene detection
is recommended.

Bone marrow cell karyotyping test form:

Due to the poor growth of coagulation cells in the specimen, multiple films, no analyzable division phase was seen, and the order was returned
.

Molecular pathology quantitative test report:

Molecular pathological qualitative results: BCR-ABL1 fusion genotyping (qualitative), positive
.
BCR::ABL1 fusion gene p190 positive, BCR::ABL1 fusion gene p210 negative, BCR::ABL1p230 negative
.

The case was eventually diagnosed as B-acute lymphoblastic leukemia BCR::ABL1
.

Case studies

This case is B-ALL/LBL with reproducible genetic abnormalities, which refers to B-cell lymphoblastoma with reproducible, specific cytogenetic, and molecular biological abnormalities
.
Tumor cells are widely present in the bone marrow and (or) peripheral blood, and the ratio of primitive and naïve lymphocytes is ≥ 20% of patients diagnosed with acute lymphoblastic leukemia
.

The disease can be seen with all ages, but mainly children and young adults, is more likely to occur in young adults and children malignant tumors, in adult leukemia, the incidence of ALL is significantly lower than AML, clinically to moderate to severe anemia, infection fever, mild to moderate hepatosplenomegaly for the manifestation, more than 50% of cases diagnosed with painless lymphadenopathy, joint pain and sternal tenderness, according to cytogenetics and molecular biology changes, with reproducible genetic abnormalities B-ALL is divided into 7 subtypes,

(1) with t(9;22)(q34; q11.
2)； B-ALL/LBL OF BCR-ABN, .
(2) with t(v; 11q23)； B-ALL/LLBL
for MLL rearrangement.
(3) with t(12;21)(q13; q22)； B-ALL/LBL
for TEL-AML (or EVT6-RUNX1).
(4) B-ALL/LLBL
WITH HYPERDIPLOID.
(5) B-ALL/LBL
WITH HYPODIPLOID.
(6) with t(5;14)(q31; q32)； IL3-IGH B-ALL/LBL
.
(7) with t(1;19)(q23; q13.
3)； B-ALL/LBL
of E2A-PBX1 (TCF3-PBX1).

where ALL in this example is accompanied by t(9;22)(q34; q11.
2)； BCR-ABL accounts for about 25% of adult ALL, but only 2%-4%
of childhood ALL.
The fusion protein produced by BCR/ABL1 has tyrosine kinase activity, which promotes cell value-added, and the clinical manifestations, cell morphology and cytochemical staining characteristics of this disease are the same as
other B-ALL.

The typical cellular immunological phenotype of lymphoblasts is CD19+/CD10+/TdT+; Myeloid antigens such as CD13 and CD33 are often expressed at the same time, but CD117 is generally negative; The expression of CD25 in adult patients is highly correlated with B-ALL with t(9;22), and in rare cases, the T cell phenotype, the BCR-ABL fusion gene in the vast majority of children is p190, while adult patients account for half of
p210 and p190.
In both adults and children, T(9;22) is the worst prognosis in
B-ALL.
The clinical features are that the white blood cell count is significantly increased, up to 300×109/L, the chemotherapy effect is poor, and the recurrence rate is high
.

Summary

The diagnosis of modern hematology diseases is based on the theory of hematology, and MICM is the diagnosis and treatment method
.
As early as 1976, the FAB classification program mainly divided acute leukemia into acute lymphoblastic leukemia and acute non-lymphoblastic leukemia and its subtypes according to the cell morphological characteristics, and this classification method played an important role in the diagnosis, treatment and prognosis of acute leukemia, but it also had certain subjectivity, limitations and uncertainty
.

In recent decades, on this basis, it has been continuously revised and improved, based on the characteristics of cell morphology, combined immunology, cytogenetics, molecular biology, a more comprehensive MICM classification has been proposed, which provides more powerful experimental data for clinical leukemia treatment and prognosis observation, after several years of practice and improvement, in 2008 many experts in 22 countries reformulated the new WHO classification standards.
The main difference is that the classification of acute leukemia and lymphoid tissue tumors is defined by biological homology and the essential characteristics of the disease, such as the classification of lymphocytic tumors is mainly classified according to the source of cells and the stage of cell development, therefore, lymphoblastic leukemia and lymphoma are classified
together.

The classification of WHO makes the diagnosis of hematopoietic and lymphoid tissue tumors rise from the cellular level to the subcellular level and molecular level, which is of great significance
for further studying the nature, pathogenesis, diagnosis and treatment of hematopoietic and lymphoid tissue tumors.

References

[1] Xia Wei, Chen Tingmei.
Clinical hematology testing techniques.
4th edition.
Beijing:People's Medical Publishing House,2015.
253--289,01-09.

[2] Xia Wei, Clinical Hematology Testing Technology.
Central China:Huazhong University of Science and Technology Press,2022.
2017-213,26-265,.

[3] HUANG Binlun,YANG Xiaobin.
Hematology tests.
5th edition.
Beijing:People's Medical Publishing House,2020.
176:200.