The real reason behind cervical pain?

Preamble

Leukemia is a heterogeneous group of hematopoietic malignancies caused by differentiation block, apoptosis disorder, and malignant proliferation of hematopoietic stem/progenitor cells at different stages of the differentiation process [1].

The clinical manifestations are mainly fever, anemia, bleeding, joint pain, etc
.

Case history

The patient, a 54-year-old woman, was admitted to the hospital
with neck pain, shoulder discomfort and dizziness, numbness in both upper limbs for more than a year, aggravated for seven days, and felt significant weight loss.
On admission, there are occasional dizziness, headache, chest tightness, shortness of breath, no enlargement of the tonsils, and untouched swelling
of superficial lymph nodes.
There are no bleeding spots
on the skin throughout the body.

Routine blood data and graphs:

Biochemical tests:

Coagulation tests:

Abdominal ultrasound showed that the bottom of the gallbladder was smooth, the posterior wall of the body was burrily protruding (inflammatory changes possible), and there were no obvious abnormalities
.

Chest CT examination shows: anterior mediastinal nodule, which may enlarge lymph nodes; Small left interlobar fissure, lymph nodes in the lungs may be
.

Morphological examination:

A: Peripheral blood smear

b: Bone marrow smear:

c: myeloperoxidase staining smear:

Bone marrow cell morphology report:

Immunophenotyping:

AML prognosis 15 gene mutation test report:

Chromosome karyotyping report:

Case studies

AML with biallele CEBPA gene mutation is the official disease updated by WHO 2016 version, revised from the WHO 2008 version of AML with CEBPA mutation this temporary disease, biallele CEBPA gene mutation occurs in 4%-9% of children and young adult AML patients, the incidence of the elderly is low, usually meet the criteria of AML mature type and AML immature type, some cases can present granulo-monocytes or monocytes characteristics, Patients with the CEBPA double mutation have a good prognosis [2].

AML patients with positive CEBPA gene mutations often show increased hemoglobin levels, low platelet count and lactate dehydrogenase, high number of peripheral blood blasts, more than 70% of AML with biallel CEBPA gene mutations in patients with normal chromosomal karyotype, del(9q) common, about 26% of patients can see multilineage pathological hematopoiesis, so it needs to be differentiated from AML-MRC, WHO2016 added a temporary category of germline-susceptible myeloid tumors, These include AML with germline CEBPA mutations [3].

AML with biallele CEBPA: when the myeloid blasts in peripheral blood/bone marrow are ≥20%, there is no prior history of chemotherapy/radiotherapy, no other reproducible genetic abnormalities, no history of MDS or MDS/MPN, no MDS-related cytogenetic abnormalities, and those with CEBPA biallele mutations can be diagnosed as AML with CEBPA biallele mutations, and when the above conditions are met, even the morphological features of multilineage pathological hematopoiesis are no longer classified as AML-MRC, Instead, AML should be diagnosed with a biallele CEBPA gene mutation;

When myeloid blasts ≥ 20% in peripheral blood/bone marrow, AML-MRC should be diagnosed if there is a history of MDS, MDS/MPN or cytogenetic changes associated with myelodysplasia [eg, del(11q)], even if there is a biallele CEBPA gene mutation; To diagnose AML with biallele CEBPA gene mutations, especially in younger patients, to exclude AML with germline CEBPA mutations, germline specimens (skin biopsy is preferred) mutation analysis can be performed
.
[4]

The patient was treated in the acupuncture department of our hospital with cervical spine pain and obvious emaciation, and the blood routine was found to be reduced and the white blood cell scatter map was abnormal, and 18% of
the original blood cells were found on smear microscopy.
This type of cell can be seen to have a large cell body or a small cell body, round or nearly round, nucleus nearly round, fine chromatin, visible nucleoli, medium cell quality, blue tall, one or more vacuoles/halos can be seen in the cytoplasm, "worm bite-like", Auer bodies
can be seen.
Consider AML (non-APL), MDS, or MDS/MPN
.

Immediately communicate with the clinician to refer to the hematology department, and further improve the relevant tests
of MICM.
Bone marrow and peripheral blood morphology accounted for 47% and 30% of blasts, respectively.
Myeloperoxidase staining showed that the original blood cells were distributed in coarse granules and medium coarse granules, and the positive rate was 91%.
Cellular immunophenotyping expressed HLA-DR, CD7, CD13, CD33, CD34, CD38, CD117, MPO, and partially expressed CD19; Fifteen gene mutations in AML prognosis detected with double mutations in CEBPA gene: c.
205dup (N-terminus, mutation frequency 14.
36%) and c.
890G>C (p.
Arg297Pro) (bZIP region, mutation frequency 14.
24%), nonsense mutations in TET2 gene: c.
1471C>T (p.
Gln491Ter) (mutation frequency 41.
85%) and insertion mutations: c.
4317dup (p.
Arg1440ThrfsTer38) (mutation frequency 39.
23%); The karyotype is normal
.
The patient has no prior history of chemotherapy/radiation therapy, MDS or MDS/MPN
.
Therefore, consider AML with CEBPA double mutation
.

Summary

Blood routine retest method is simple, fast, economical and intuitive, set up reexamination rules suitable for their own hospitals and laboratories, attach importance to the observation of the scatter plot/histogram of the blood cell analyzer, it has a good prompt for the abnormality of cell number and morphology, can guide and assist the review and analysis of test results, which is of great help
to the inspection work.

At present, with the application of new technologies and methods, the cell morphological diagnosis has been improved and promoted, and the original cell morphological diagnosis is unclear, missed, or even misdiagnosed less and less
.
Cell morphology and immunophenotyping, cytogenetics and molecular biology and other diagnostic technologies, each has its own merits, complementarity is obvious, only mutual combination and reference will make the experimental diagnosis reach a relatively accurate stage, new technology is also inseparable from cell morphological diagnosis
.

Let us morphologists strive to be the vanguard, peel back the cocoons from the routine data to discover the real reasons behind the clinical manifestations, and achieve early detection, early diagnosis and early treatment of the disease!

Expert reviews

(Teacher Li Hongwen, Ordos Central Hospital)

The accurate diagnosis and treatment of blood diseases requires the integrated diagnosis of MICM, and morphology still has irreplaceable advantages and roles
as an important part of disease diagnosis.
As the "pioneer warrior" of disease diagnosis, morphological people have keen insight, reasonable inference and prediction, and provide the fastest and most effective help
for clinical practice.

Especially in the diagnosis of AML with gene reproducibility, such as abnormal progranules in the "butterfly-like" nucleus for APL with PML-RARA fusion, abnormal mesomyelocytes with RUNX1-RUNX1T1 fusion in the "sunrise red" cytoplasm, abnormal eosinophils for AML with CBFB-MYH11 fusion, and goblet nuclear blasts for AML with NPM1 mutation and other diseases have been well known.
In this case, obvious vacuolar degeneration can be seen in the cytoplasm of myeloid blasts, suggesting that AML with CEBPA double mutation is possible, and subsequent molecular biological examination confirmed that AML with CEBPA double mutation, this case from morphology to gene, from gene to morphology mutual verification, the disease can be accurately diagnosed, and then help clinical further accurate treatment and judgment of prognosis, worthy of careful study
.

References

[1] Shen Ti, Zhao Yongqiang.
Diagnostic and Curative Criteria for Hematological Diseases.
Beijing:Science Press,2018.
4

[2] GAO Haiyan,LIU Yabo,LV Chengfang,CHEN Xueyan.
Clinical Laboratory and Diagnosis of Hematology[M].
Beijing:China Medical Science and Technology Press,2021.
3

[3] Ye Xiangjun, Lu Xingguo.
Interpretation of the provisional category of germline-susceptible myeloid tumors in the 2016 update of WHO Hematopoietic and Lymphoid Tissue Tumor Classification[J].
Journal of Clinical Laboratory Laboratory,2016,34(11):854-857.
)

[4] Qin Youwen et al.
A case of reverie caused by CEBPA double mutation, Laboratory Medicine [Public Number], 2021.
11.
9