A 6-year-old boy is brought to the pediatrician by his mother. He has not been himself for the past month. His teachers have become concerned about his ability to concentrate. He has reverted to napping after school rather than playing. He has complained of headaches for the past few weeks. The child has previously been healthy. His development has been normal and his immunizations are up to date. His lungs are clear. His heart has no murmur. His abdomen is soft. He has no edema. He has a few ecchymoses on his knees.
On Physical exam...
BP
100/56 mmHg
Pulse
98 /minute
Temp
98.4 F
Resp
25 /minute
CBC:
Patient
Normal Male
WBC
20.2x103
3.5 – 10.6 x103 /μL
RBC
2.07x106
4.27 – 5.69 x106 /μL
HGB
5.4
13.3 – 17.1 g/dL
HCT
17
38.9 – 48.0 %
MCV
82
81.0 – 98.0 fL
Platelets
32x103
150 - 450 x103 /μL
Question #1: What should you do next?
Wrong answer! Based on the history, physical exam and CBC, further investigation should be started. Increased WBC count can be seen in infections (bacterial or viral), however, there is also a significant anemia and thrombocytopenia.
Wrong answer! A bone marrow biopsy may be needed, but it is too early in the work-up to put the patient through this procedure.
Correct answer! Given the significant abnormalities present in the CBC, the peripheral smear should be reviewed and a differential count obtained.
VM System: Click here to view this patient's blood smear.
Wrong answer! Viral titers may be useful once the peripheral smear and WBC differential have been reviewed.
Question #2: Which WBC is increased?
Wrong answer! Neutrophils have multiple nuclear lobes (3-5), condensed nuclear chromatin and cytoplasmic granules.
Wrong answer! Monocytes are medium sized cells with irregular kidney bean shaped nucleus, and abundant light blue cytoplasm.
Wrong answer! Lymphocytes have small nuclei (the size of a RBC) with condensed nuclear chromatin and scant cytoplasm.
Correct answer! Blasts are medium to large in size with fine nuclear chromatin, prominent nucleoli and scant to moderate cytoplasm.
CBC:
Patient
Normal Male
WBC differential
% (absolute)
% (absolute)
Blasts
87% (17,400)
0.0 % (0 /μL)
Neutrophils
2% (400)
38 - 76 % (1,730 – 7,100 /μL)
Monocytes
1% (200)
1 - 12 % (70 – 870 /μL)
Lymphocytes
11% (2,200)
11 - 46 % (900 – 3,120 /μL)
Eosinophils
0
0 - 8 % (0 – 490 /μL)
Basophils
0
0 - 2 % (0 – 140 /μL)
Reticulocyte
0.4
0.5 - 2.0 %
Absolute count
8,280
25,000 - 100,000 /μL
Lactate Dehydrogenase
425
100 - 225 IU/L
Bilirubin
1.6
0.0 - 1.5 mg/dL
Partial thromboplastin time (PPT)
29.8
22 - 30 seconds
Prothrombin time (PT)
11.9
10 - 13 seconds
A bone marrow biopsy is performed. It showed 80% blasts cells with decrease in all normal hematopoeitic elements. The blast cells were mostly small size with open chromatin and a nucleolus. Cytoplasm was deep blue with scant amount.
Question #3: Based on your observations and available information so far, what is the most likely diagnosis?
Wrong answer! Unlikely with the leukocytosis. Also aplastic anemia is a decrease in all cells with no increase in blasts.
Correct answer! Acute leukemia is diagnosed by having ≥20% blasts in the peripheral blood or bone marrow. The peripheral blood has 87% blasts by differential count. Bone marrow is replaced by similar cells.
Wrong answer! MDS has <20% blasts in the peripheral blood and bone marrow.
Wrong answer! Unlikely due to the large number of blasts. One might see a small number of blasts in infiltrative disease, but never ≥20%.
Question #4: What is the likely mechanism of his anemia and thrombocytopenia?
Correct answer! The blasts are rapidly filling the bone marrow, crowding out the normal hematopoietic cells, such as erythroid precursors and megakaryocytes, which are trying to produce RBC's and platelets.
Wrong answer! In ineffective hematopoiesis, the bone marrow is producing hematopoietic cells, however, they are dying before they can get out of the bone marrow for various reasons.]
Wrong answer! If there was peripheral destruction (ie- hemolysis or removal of RBC's in the spleen), the bilirubin would be increased.
Wrong answer! In this case, the reticulocyte count will increase and there should be no blasts in the blood and bone marrow. Platelets will be normal or increased not decreased.
Question #5: Which test(s) do you perform next on the bone marrow to classify and prognosticate this disease further?
Wrong answer! Cytochemistry is used to help in the classification of acute leukemias, however, it is not the only test used today.
Wrong answer! Flow cytometry is used to help in the classification of acute leukemias, however, it is not the only test used today.
Wrong answer! Cytogenetics is used in the classification of acute leukemia, in determining prognosis and type/length of treatment. However, cytogenetic analysis is not the only test used today.
Correct answer! All three of the above tests are integral in the classification of acute leukemias. The blasts in this bone marrow are myeloperoxidase (MPO) and Sudan black (SBB) negative. By flow cytometric analysis, the blasts express CD19, CD10, and TdT and cytogenetics identified a t(9;22).
Question #6: Given the morphologic features and the provided information regarding the immunophenotype and cytogenetic translocation, what is your diagnosis?
Wrong answer! Blasts in AML express MPO and SBB (with the exception of AML,M0) and express CD13, CD33, CD34.
Wrong answer! This is leukemia of mature lymphocytes expressing CD19, CD20, CD25, CD103 and kappa or lambda restriction.
Correct answer! Blasts fail to express MPO and SBB. By flow cytometric analysis, the blasts express CD10, CD19, and TdT.
Fast facts about this disease:
Acute lymphoblastic leukemia and lymphoblastic lymphoma are the same disease presenting in different sites. Acute lymphoblastic leukemia presents in the blood and bone marrow predominantly, while Lymphoblastic lymphoma presents in the lymph nodes and other tissues.
Acute leukemias require ≥20% blasts in the peripheral blood or bone marrow for diagnosis.
B-ALL is typically a disease of children and most often occurs in children <6 years old.
T-ALL is typically a disease of adolescents and often presents with a mediastinal mass.
Wrong answer! Blasts fail to express MPO or SBB, however, express CD3 and TdT.