What are the causes of limb pain in children? Be alert to acute leukemia!

Preface

Primitive B-lymphocytic leukemia/lymphoma (B-ALL/LBL) with reproducible genetics is a group of disorders caused by reproducible genetic abnormalities, including translocations and/or abnormalities

Today I will introduce you to a rare B-ALL with reproducible genetic abnormalities

Case passed

Brief medical history: the child male, 7 years and 5 months, was admitted to the hospital

Laboratory tests:

Blood count: WBC 18.

Figure 1 Blood routine report

Coagulation: PT13.

Biochemical immunity: CRP28.

Consult the national health industry standard WS/T779, the reference interval for blood cell analysis in children aged 7 years is as follows:

WBC (4.

Neut (1.

Lym (1.

Mon (0.

Eos (0-0.

Bas (0-0.

RBC (4.

Hb 118-156g/L，

HCT 36-46%，

MCV 77-92fl，

MCH 25-34fl，

MCHC 310-355 g/L，

PLT (167-453)× 10^9/L

The child has elevated white blood cells, abnormal scatter map, accompanied by anemia, thrombocytopenia, and clinical claudication, and the author has a bad premonition

Figure 2 Peripheral blood sheet

Figure 3 Peripheral blood sheet

The author's premonition became a reality, and he quickly contacted the clinical explanation and suggested that the child improve the bone marrow examination

Bone marrow cytology: abnormal proto-young lymphocyte hyperplasia, cell body size, cytoplasm is rare, blue, nuclear round, some cells are visible with incisions, nuclear chromatin is coarse, nucleoli are visible in some cells, acute lymphoblastic leukemia is
considered.
(Figure 4-8)

Figure 4 Bone marrow smear

Figure 5 Bone marrow smear

Figure 6 Bone marrow smear

Figure 7 POX staining × 1000, blast cells negative

Figure 8 PAS staining × 1000, blast cells negative

Immunotyping: Primitive cells occupy 93.
40% of nuclear cells, express TdT, CD10 and CD19, and partially express HLA-DR, which is in line with the acute B lymphoblastic leukemia immune phenotype

The blasts are red populations of cells

Figure 9 Immunotyping report

Chromosomal karyotype: for the analysis of mid-stage cells, see der(19)t(1;19)(q23; p13)

Figure 10 Chromosome report

Molecular biology examination: E2A::P BX1 (TCF3::P BX1) fusion gene detected
.

Figure 11 Fusion gene report

Based on the above MCM examination, the child was clearly diagnosed with B-ALL with t(1;19)(q23; p13)； TCF3: :P BX1, is a B-ALL recognized by the
WHO as accompanied by reproducible genetic abnormalities.

Case studies

In the revised 4th edition (2017 edition) WHO classification of hematopoietic and lymphoid tissue tumors, acute B-lymphoblastic leukemia with reproducible genetic abnormalities has the following types:

The penultimate of these is B-ALL with t(1;19)(q23; p13.
3)； E2A-PBX1(TCF3-PBX1)

It is said that in the 5th edition of the WHO classification of hematopoietic and lymphoid tissue tumors, acute B lymphoblastic leukemia with reproducible genetic abnormalities has the following types:

The penultimate is B-ALL with TCF3::P BX1 (E2A::P BX1), which emphasizes the importance of fusion genes and uses double colons instead of horizontal lines
.

Primitive B-lymphocytic leukemia/lymphoma with T(1;19) (q23; p13.
3)； E2A-PBX1 (TCF3-PBX1) is relatively common in children, accounting for about 6% of acute B lymphoblastic leukemia in children; It is relatively rare in adults, and the clinical manifestations are anemia, hepatosplenic lymphadenopathy, and obvious bone and joint pain, in this case, a 7-year-old child, due to fever, spleen enlargement, knee pain and crippled hospitalization
.

The disease has no specific morphological/cytochemical features that distinguish it from
other types of acute lymphoblastic leukemia.
Blasts have a typical CD19+, CD10+, cytosolic μ (Cμ) heavy chain positive pre-B cell phenotype, and this type of leukemia has typical CD9 strong expression and CD34 low expression characteristics, or only a small number of leukemia cells express limited CD34
.

The TCF3-PBX1 translocation leads to the production of a fusion protein that, as a transcriptional activator, has carcinogenic effects and appears to interfere with the normal function
of transcription factors encoded by TCF3 and PBX1.
Functional fusion genes are present on chromosome 19 and in some cases there may be a loss of derived chromosome 1, resulting in an imbalance translocation
.
Gene expression profile studies have shown that the disease has unique characteristics
.
It has also been reported that there are even B-ALL cases in which BCR::ABL1 coexists with TCF3::P BX1; It is generally believed that the clinical features of these cases are determined by BCR::ABL1
.

In earlier studies, TCF3-PBX1 was associated with a poor prognosis, but this condition has been gradually overcome
by modern intensive treatments.
However, these patients may have a relatively high risk
of central nervous system recurrence.
The author went to check the clinical practice guidelines of ALL in children with NCCN, and TCF3-PBX1 was indeed not in the group with poor prognosis (Figure 14):

Favorable means favorable, unfavorable means unfavorable

Experience

There are many reference intervals for child testing indicators that are different from those for adults, and the LIS system often shows the adult reference intervals, as is the case in this case
.
Nowadays, the National Health Commission has issued a reference range for some child testing indicators, and we should refer to them
.

Acute leukemia in children is more common in acute leukemia, and is often clinically manifested by thrombocytopenia and/or anemia and/or neutropenia, indefinite white blood cell count, hepatosplenic lymphadenopathy, and osteoarthralgia
.
For children with fever, ineffective treatment and crippled, we should be alert to the possibility of malignant blood disease, if peripheral blood protoblasts are visible, it often suggests the possibility of acute lymphoblastic leukemia, so peripheral blood cell morphology observation should be paid attention to
.

References

Mao Fei,Xu Wenrong.
Clinical Blood Test[M].
Beijing:Science Press,2020.
2

[2] KennethKaushansky，MarshallA.
Lichtman，JosefT.
Prchal，etal.
Williams Hematology.
Ninth Edition.
USA：McGraw-HillEducation，2016

[3] SwerdlowSH， Campo E， Harris NL， et al.
(Eds) ： WHO Classification of TumoursofHaematopoietic and Lymphoid Tissues.
Revised 4th edition.
Lyon，France： IARC Press， 2017.

Lu Xingguo, Ye Xiangjun, Xu Genbo.
Diagnosis of bone marrow cells and histopathology[M].
Beijing: People's Medical Publishing House, 2020

[5] Wang Jianxiang, Xiao Zhijian, Shen Zhixiang, etc.
Deng Jiadong Clinical Hematology[M].
2nd ed.
.
Shanghai: Shanghai Science and Technology Press, 2020.
12

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

[7] AlaggioRita，Amador Catalina，Anagnostopoulos Ioannis et al.
The 5th editionof the World Health Organization Classification of HaematolymphoidTumours： Lymphoid Neoplasms.
[J] .
Leukemia， 2022， 36： 1720-1748.

[8] NCCNClinical Practice Guidelines in Oncology (NCCN Guidelines).
PediatricAcute Lymphoblastic Leukemia.
Version 1.
2022

Reference interval for paediatric blood cell analysis (published version):WS/T779-2021[S].
2021.