Case Sharing | Aplastic Anemia or M5 Leukemia?

Author | Zhang Minqing Chen Yunzhi

Unit| Chengwu Hospital Affiliated to Shandong First Medical University

In blood analysis and clinical testing, we often encounter patients with three-line reduction. What comes to mind is aplastic anemia (aplastic anemia), especially for newly diagnosed patients with a lymphocyte ratio> 60%. Today I would like to share with you a case of a middle-aged male who was initially highly suspected of being aplastic anemia, and finally considered as M5 leukemia.

Case history

Patient, male, 51 years old, on the afternoon of April 9th, due to pale complexion, chest tightness, fatigue, headache, dizziness after exercise, etc., he went to the Chinese Medicine Clinic of our hospital. Routine blood test results: white blood cells 1.56×10 ⁹ /L, neutrophil ratio 15.1%, lymphocyte ratio 74.1%, monocyte ratio 10.0%. At the same time, there was a decrease in red blood cells (1.05×10 ¹² /L) and a decrease in platelets (30×10 ⁹ /L) (Figure 1).

Figure 1

Checking the results of the instrument found that the scatter plot and histogram indicate abnormalities, and the alarm message prompts "primordial cells/immature granulocytes?" (Figure 2). Follow the re-examination rules of the clinical examination room to the patient The blood smear stained microscopic examination of the specimen of the blood smear, with the help of the magnifying power of the microscope to carefully check the real situation of the microscopic cell world.

Figure 2

At the same time, the platelets were counted and rechecked under the optical method and manual microscope. Smear microscopy revealed that the number of white blood cells under the microscope of the patient was reduced, and the lymphocyte ratio was basically the same as that detected by the instrument. When browsing the whole film under low magnification and oil microscope, no primitive and naive cells; red blood cells were found. Obviously vary in size,Large red blood cells are more common; platelets in patients under the microscope are rare. Such microscopic examination results further strengthen the possibility of "re-barrier".

Then contact the clinician by phone promptly, suggesting that the patient be hospitalized as soon as possible for further examination. As a result, the patient was not hospitalized until the afternoon of May 8 for a whole month, and later learned that he refused to be hospitalized at that time, and took self-medicine treatment after returning home (specifically unknown). However, the symptoms of discomfort did not alleviate and fever occurred. The body temperature was as high as 39℃, chills, and muscle aches and other symptoms were admitted to our hospital's infection department. The results of blood routine on May 9th after admission are as follows: white blood cells 2.61×10 ⁹ /L, neutrophil ratio 8.7%, lymphocyte ratio 78.2%, monocyte ratio 12.9%, red blood cell 1.64×10 ¹² /L, platelets 14×10 ⁹ /L) (Figure 3). At this time, if you simply look at the results of blood routines, "aplastic anemia" still cannot be ruled out.

Figure 3

This time the instrument still shows abnormal scatter plots and histograms, the alarm message prompts "primordial cells?/abnormal/alien lymphocytes?", and the red blood cell histogram displays "uneven red blood cell size".

According to the re-examination rules of the clinical examination room, the push-film re-examination will be carried out immediately. Because the total number of white blood cells in the patient is small, the number of cells that can be counted under the microscope is very small, but in the end, the whole film is carefully scanned multiple times under the microscope. On the edge of the slice, the following few primitive naive cells were found (Figure 4).

Figure 4

Considering that the patient was injected with recombinant granulocyte stimulating factor and interleukin 11 at night on May 8, is G-CSF (granulocyte stimulating factor) acting on the neutrophil lineage? ), promote the proliferation, differentiation and activation of hematopoietic cells, stimulate hematopoietic progenitor cells, promote their proliferation and differentiation, a small amount of primitive naive cells released into peripheral blood caused this situation? Immediately recommended bone marrow aspiration .

On the afternoon of May 9th, the puncture of the anterior superior iliac spine of the bone marrow was successful at one time. Looking at a few pushed bone marrow slices, the bone marrow particles are abundant. Because the patient is more urgent, a diagnosis must be reached after working overtime. Under the microscope, the veil of "re-obstacle" was finally lifted, revealing the "true face of Lushan". Some bone marrow slices taken by mobile phones are shown in the picture below (Figure 5).

Figure 5

The primordial cells that can be seen in the bone marrow slice account for about 75%. The cell body of this type of cell is large, round, oval or irregular in shape; loose chromatin, large nucleolus, 1- 3; the cytoplasm is stained blue, small purple-red particles are visible, and there are obvious pseudopodia protrusions.

Bone marrow cytochemical staining is as follows (Figure 6):

Figure 6

Bone marrow cytochemical staining: POX(+)AS-DCE(-)a-NAE(+) sodium fluoride suppressed. The bone marrow report of

is shown in Figure 7:

Figure 7

excludes the transient blasts caused by and white medicine , does not exclude acute myeloid leukemia , please combine clinical and flow cytometry Learn to check. On the morning of May 19, another bone marrow was taken from posterior superior iliac spine , and the result was basically the same as the first time. Regrettably, apart from the bone marrow cytology examination, the patient did not undergo immunophenotyping, chromosome, and genetic examinations.

Case analysis

Based on the above results, on the basis of excluding the transient blast increase caused by the whitening drug, we basically determined that the patient should consider the possibility of acute myeloid leukemia. At this point, we should reflect that if granulocyte stimulating factor is not injected before bone marrow extraction,The problem was solved, and it was mainly caused by our usual inadequate communication with clinicians. Out of occupational habits, we are always concerned about the patient's follow-up treatment. Fortunately, one month later, when we followed up the case, we learned that the patient was diagnosed with M5 leukemia after going to the outside hospital for examination.

Summary

The veil of "re-obstacle" has been ruthlessly lifted by us. As an inspector, I will also talk about my views based on my experience and lessons in daily work for many years:

At present, In some grassroots hospitals, some clinicians see the reduction of the three-line system and regard it as "aplastic anemia." This diagnosis and treatment awareness really needs to be changed. At present, the three most common blood system diseases are reduced mainly in: aplastic anemia, acute leukemia, MDS, megaloblastic anemia, multiple myeloma, myelofibrosis , etc.; uncommon ones are mainly found in: infectious anemia, immune-related pancytopenia, PNH, solid tumor metastasis, systemic lupus erythematosus, hypoproliferative leukemia, hypersplenism, etc.

Clinicians try not to use granulocyte colony stimulating factor before extracting bone marrow from the patient. After the granulocyte colony stimulating factor is injected into the human body, within 1-2 days it stimulates the maturation of granules, monocyte macrophages, promotes the release of mature cells to peripheral blood, the number begins to rise, and can promote macrophages and tropism The multiple functions of acid cells; the number reaches a peak within 3-4 days. Due to individual differences between people, their sensitivity is different. If the bone marrow is taken for examination during the peak period, it is very easy to be misdiagnosed as leukemia.

Bone marrow cell morphology testers are best to go to the bedside to push the film personally when the clinician draws the bone marrow, so that we can judge the bone marrow sampling situation in the first time.At the same time, you can communicate face-to-face with the tube bed doctor to understand the patient's condition and preliminary diagnosis. At the same time, you can also ask the patient's medical history and current symptoms.

After mastering all the patient's information, combined with cell morphology (Morphology), it can greatly improve the correct rate of diagnosis results and reduce the rate of misdiagnosis. If you have conditions, you can start or send to other laboratories immunology (Immunology), cytogenetics (Cytogenetics) and molecular biology (Molecularbiology) typing, which is what we often call MICM typing, which is for leukemia patients The prerequisite for the correct selection of precise chemotherapy regimens.

Acute monocytic leukemia (M5) accounts for about 10% of AML. Divided into 2 subtypes: ①Undifferentiated (M5a) bone marrow non-erythroid nucleated cells of primitive monocytes ≥80%. ②Partially differentiated (M5b) bone marrow non-erythroid nucleated cells are primitive and naive monocytes >30%; promonocytic cells are <80%.>

clinical manifestations of bleeding, extramedullary (skin, gums and CNS) infiltration, or monocytic sarcoma ^[1] , the main manifestations (1) oral gum changes: gingival hyperplasia may occur due to leukemia infiltration In severe cases, the gums are swollen like spongy, and the surface is ulcerated and bleeding. (2) Skin changes: The appearance is maculopapular, nodular or lumps, and the color is purple-red. It can spread over the whole body or a few scattered on the body surface, and it is sensitive to radiotherapy. (3) Central nervous system manifestations: headache, dizziness, vomiting in severe cases, neck stiffness , even convulsions and coma. Papilledema, retinal hemorrhage, cranial nerve palsy may occur, often invading the pia mater, and brain parenchymal damage is rare ^[2] .

At present, the composition of the remission induction treatment plan for the treatment of AML (non-APL) is based on anthracycline combined with cytarabine. Commonly used are IDA or daunorubicin The IA/DA (3+7) program consisting of DNR combined with Cytarabine (Ara-C),The specific dosage needs to be determined according to the patient's condition. At the same time, with the development of new drugs, the treatment of AML (non-APL) can also be based on the 3+7 plan, with other drugs, such as midostauline and the immunotoxin GO monoclonal antibody targeting CD33 that have been marketed in the United States. Of course, if conditions are available, bone marrow transplantation can be performed after the first remission (CR1). This therapy can not only improve the survival rate, but also may cure the leukemia.

As a tester, we can find clues through test results in a timely and accurate manner, and provide clinicians with accurate laboratory evidence, which can help patients make a clear diagnosis as soon as possible, obtain early treatment opportunities, and prolong or save patients' lives.

References

[1] Zhang Zhinan, Shen Ti. "Diagnosis and Curative Effect Standards for Blood Diseases". Third Edition. Beijing: Science and Technology Press, 2007, ISBN978-7-1-03-019780-1.

[2] Standards for diagnosis and treatment of adult acute myeloid leukemia (2018 edition).

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