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Questions and Answers
What is the morphology of a monoblast?
What is the morphology of a monoblast?
Which lymphocyte has a round nucleus that may be eccentrically placed?
Which lymphocyte has a round nucleus that may be eccentrically placed?
What characteristic distinguishes mast cells from basophils?
What characteristic distinguishes mast cells from basophils?
During the maturation process, what is the immediate precursor to monocytes?
During the maturation process, what is the immediate precursor to monocytes?
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What is the typical size range of mature lymphocytes?
What is the typical size range of mature lymphocytes?
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Which characteristic is associated with mature lymphocytes?
Which characteristic is associated with mature lymphocytes?
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What type of development pool do monocytes reside in?
What type of development pool do monocytes reside in?
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Which feature is common among mature granulocytes?
Which feature is common among mature granulocytes?
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What is characteristic of M3 Myelocytic acute myeloproliferative leukemia?
What is characteristic of M3 Myelocytic acute myeloproliferative leukemia?
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Which cytological feature is associated with M5a Monocytic acute myeloproliferative leukemia?
Which cytological feature is associated with M5a Monocytic acute myeloproliferative leukemia?
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Which chromosomal abnormality is associated with a poor prognosis in M1 Myelocytic leukemia?
Which chromosomal abnormality is associated with a poor prognosis in M1 Myelocytic leukemia?
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In relation to acute myeloproliferative leukemia, what does the term 'gigantism' refer to?
In relation to acute myeloproliferative leukemia, what does the term 'gigantism' refer to?
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Which M classification shows bundles of Auer rods?
Which M classification shows bundles of Auer rods?
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What is the N:C ratio of a myeloblast?
What is the N:C ratio of a myeloblast?
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Which granules are primarily found in promyelocytes?
Which granules are primarily found in promyelocytes?
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During which stage of granulocyte maturation does the nucleus start to assume a kidney bean shape?
During which stage of granulocyte maturation does the nucleus start to assume a kidney bean shape?
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What characterizes the cytoplasmic granulation of myelocytes?
What characterizes the cytoplasmic granulation of myelocytes?
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What is the diameter range of a promyelocyte?
What is the diameter range of a promyelocyte?
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Which of the following is a distinguishing feature of basophilic granules?
Which of the following is a distinguishing feature of basophilic granules?
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How long do segmented neutrophils typically remain in circulation?
How long do segmented neutrophils typically remain in circulation?
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What type of cell develops from the myeloid stem cell in granulopoiesis?
What type of cell develops from the myeloid stem cell in granulopoiesis?
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What is the most favorable prognosis for children with Acute Lymphoblastic Leukemia?
What is the most favorable prognosis for children with Acute Lymphoblastic Leukemia?
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Which type of lymphoblasts is primarily associated with adult Acute Lymphoblastic Leukemia?
Which type of lymphoblasts is primarily associated with adult Acute Lymphoblastic Leukemia?
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What are two common morphological findings in Myelodysplastic Syndromes (MDS)?
What are two common morphological findings in Myelodysplastic Syndromes (MDS)?
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What is the median age of diagnosis for Myelodysplastic Syndromes (MDS)?
What is the median age of diagnosis for Myelodysplastic Syndromes (MDS)?
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What is an important cause of Myelodysplastic Syndromes?
What is an important cause of Myelodysplastic Syndromes?
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In which type of Acute Lymphoblastic Leukemia are lymphoblasts large and homogeneous?
In which type of Acute Lymphoblastic Leukemia are lymphoblasts large and homogeneous?
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Which chromosomal abnormalities are associated with a poor prognosis in Acute Lymphoblastic Leukemia?
Which chromosomal abnormalities are associated with a poor prognosis in Acute Lymphoblastic Leukemia?
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What percentage of lymphoblasts in childhood ALL is classified as L1 morphology?
What percentage of lymphoblasts in childhood ALL is classified as L1 morphology?
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What is the primary characteristic of hematopoietic malignancies?
What is the primary characteristic of hematopoietic malignancies?
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Which of the following terms refers to the presence of abnormal cells in the bone marrow but not in peripheral circulation?
Which of the following terms refers to the presence of abnormal cells in the bone marrow but not in peripheral circulation?
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Acute leukemia is characterized by what percentage of blast cells in peripheral circulation?
Acute leukemia is characterized by what percentage of blast cells in peripheral circulation?
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What morphological evidence is NOT typically associated with hematopoietic malignancies?
What morphological evidence is NOT typically associated with hematopoietic malignancies?
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Which malignancy falls under the classification of chronic myeloproliferative disorders?
Which malignancy falls under the classification of chronic myeloproliferative disorders?
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Which type of leukemia involves primarily B and T lymphocytes?
Which type of leukemia involves primarily B and T lymphocytes?
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What is a common consequence of Acute Myeloid Leukemia?
What is a common consequence of Acute Myeloid Leukemia?
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What does ‘dys’ prefix signify in medical terminologies?
What does ‘dys’ prefix signify in medical terminologies?
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What is a distinguishing feature of chronic leukemia compared to acute leukemia?
What is a distinguishing feature of chronic leukemia compared to acute leukemia?
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Which type of leukemia is known for its rapid fatal course often associated with BMP?
Which type of leukemia is known for its rapid fatal course often associated with BMP?
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Which morphological finding is associated with dysmegakaryopoiesis?
Which morphological finding is associated with dysmegakaryopoiesis?
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Which condition is NOT considered sufficient evidence of Myelodysplastic Syndrome (MDS)?
Which condition is NOT considered sufficient evidence of Myelodysplastic Syndrome (MDS)?
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What is a consequence of abnormal maturation in MDS cells?
What is a consequence of abnormal maturation in MDS cells?
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Which classification system includes 'MDS With Excess Blasts'?
Which classification system includes 'MDS With Excess Blasts'?
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What is a common symptom related to cytopenia in MDS with single lineage dysplasia?
What is a common symptom related to cytopenia in MDS with single lineage dysplasia?
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Which type of Myelodysplastic Syndrome involves ring sideroblasts?
Which type of Myelodysplastic Syndrome involves ring sideroblasts?
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Which classification categorizes MDS based on the amount of dysplasia and number of blasts present?
Which classification categorizes MDS based on the amount of dysplasia and number of blasts present?
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Which of the following is a characteristic feature of platelets in MDS?
Which of the following is a characteristic feature of platelets in MDS?
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Study Notes
Granulopoiesis
- Granulopoiesis is the process of development, distribution, and destruction of Neutrophils (NEB) in the bone marrow (BM).
Granulocyte Maturation & Development
- Pluripotent stem cells differentiate into myeloid stem cells.
- CFU-GEMM (Colony-forming unit - granulocyte, erythrocyte, monocyte, megakaryocyte) is a precursor to more specific cell lines.
- CFU-GM (Colony-forming unit - granulocyte, macrophage) is a precursor to granulocytes.
- Myeloblasts, promyelocytes, myelocytes, metamyelocytes, band cells, and segmented neutrophils are the maturation stages of neutrophils.
Granulocytic Kinetics
- Progenitor cells: 0.1-0.2%
- Myeloblasts: 1%
- Promyelocytes: 3%
- Myelocytes: 12% (15 hrs - 4.3 days)
- Metamyelocytes: 45%
- Band neutrophils: 35%
- Segmented neutrophils: 20%
Peripheral Circulation (PC)
- Circulating pool
- Marginating pool (adhere to endothelium of blood vessels)
- Circulation pool to peripheral tissues
- Diapedesis (movement out of blood vessels into tissues)
- Neutrophils as phagocytes
- Segmented neutrophils: 7-10 hours
- Eosinophils: few hours
- Charcot-Leyden crystals
- Basophils: 8.5 hours
Hematopoiesis
- Pluripotent stem cell is the precursor to all blood cell types.
- Myeloid and lymphoid stem cells are further differentiated blood cell types.
Granulocyte Maturation & Development (specific cell types)
- Myeloblast: 10-18 µm, N:C ratio 4:1, finely reticular chromatin, 1-5 light-staining nucleoli, small rim of basophilic cytoplasm, lacks granules, Auer rods (aggregates of fused lysosomes, appear as red, needle-like inclusions).
- Promyelocyte: presence of prominent granulation, N:C ratio 3:1, primarily azurophilic granules, enzymes myeloperoxidase and chloroacetate esterase, 14-20 µm, nucleus more condensed, nucleoli are present, cytoplasm pale grayish blue.
- Myelocyte: appearance of secondary or specific cytoplasmic granulation, NEB (neutrophils) become visibly recognizable, N:C ratio 2:1 or 1:1, 12-18 µm, nucleus more oval in appearance, nucleoli are no longer visible, chromatin is more clumped, cytoplasm blue-pink, neutrophilic granules fine and stain blue-pink with Wright stain, eosinophilic granules larger, round or oval shaped, orange and glassy or semiopaque texture, basophilic granules dark blue-black and dense.
- Metamyelocyte: nucleus begins to assume an indented or kidney bean shape, chromatin is condensed, color of specific granulation becomes a major distinguishing feature, cytoplasm pink.
- Mature Granulocytes:
- Band form: elongated nucleus.
- Segmented form: not observed in healthy individuals, appearance is similar to blood basophils, round or oval nucleus, granules of mast cells do not overlap the nucleus as in basophils.
- Mast cells: not found in healthy blood, similar appearance to basophils, round or oval nucleus, granules do not overlap the nucleus as in basophils.
Monocytes & Macrophages
- CFU-GM
- CFU-M
- CFU-G
- Monoblast
- Promonocyte
- Monocyte
- 2-3 mitotic divisions in 2-2.5 days.
- No large reserve in maturation-storage pool
- Circulating and marginating pool in PC (ratio 1:3.5)
- 8.5 hours
- Largest mature cells in PC
- Irregular cytopalsmic outline
- Commonly observed vacuoles
- Blue-gray cytoplasm, with fine granulation resembling
Lymphocyte Maturation & Development
- Lymphoblast: 1st morphologically identifiable cell of the lymphocytic maturational series in BM, 15 to 20 µm, N:C ratio 4:1, round or oval nucleus, 1-2 nucleoli, chromatin pattern delicate, medium blue or darker blue border, no granules.
- Prolymphocyte: BM, thymus & 2° lymphoid organs, 15 to 20 µm, N:C ratio 4:1 or 3:1, round or slightly indented nucleus, 0-1 nucleoli, chromatin pattern slightly condensed, medium blue with thin darker-blue rim, few azurophilic granules.
- Mature Lymphocyte: BM, thymus & 2° lymphoid organs, 17-20 to 6-9 µm, N:C ratio 2:1 or 4:1 to 3:1, round or oval or indented nucleus, nucleoli not visible, chromatin pattern dense and appears clumped, light sky blue, few azurophilic granules.
- Mature B cell: 8 to 20 µm, round or oval nucleus, may be eccentrically placed, fine pattern chromatin, non-granular, mottled blue color.
Acute Myeloproliferative Leukemia
- Etiology: chemical (drugs/chemicals, cytotoxic agents, radiation), genetics (chromosomal aneuploidy, chromosomal breakage, Bloom syndrome), viruses.
- Classification (FAB): M0 to M7, based on morphological characteristics of Wright-stained cells in peripheral blood or bone marrow, cytochemical staining of blasts.
- Classification (WHO): based on morphology, cytochemistry, immunophenotype, genetics, and clinical features
- Clinical features: Anemia (S/S pallor, lethargy, dyspnea, fatigue, weakness, bm failure, dyserythropoiesis, decreased RBC survival, supportive therapy, RBC transfusion), Neutropenia (S/s fever, malaise, infection, bm failure, dysmyelopoiesis, supportive therapy, granulocyte transfusion, antibiotics, isolation techniques), Thrombocytopenia (S/s hemorrhage, bruising, purpura, epistaxis, bm failure, coagulation defects, supportive therapy, platelet transfusion), Organ infiltration (S/s bone tenderness, splenomegaly, hepatomegaly, lymphadenopathy, etc., pathophysiology extramedullary hematopoiesis, metastatic disease, supportive therapy, radiotherapy)
- French-American-British (FAB) System: proposed by 7 hematologists, based on morphological characteristics of Wright-stained cells in peripheral blood or bone marrow, cytochemical staining of blasts, divides acute leukemias into two major division (AML(M0-M7), ALL(L1-L3)).
- WHO Classification: Based on morphology, cytochemistry, immunophenotype, genetics, and clinical feature, recurrence chromosome translocation, inv 16(p13q22), complex karyotypes, partial deletions or loss of chromosome, unfavorable prognosis.
Acute Lymphoblastic Leukemia (ALL)
- FAB Type: L1, L2, L3 (Burkitt's type) based on morphology, size of blasts, nuclear shape, nucleoli, and cytoplasm.
- Prognosis: More than 90% children with ALL can be cured; favorable prognosis in children 2-10yo with early pre-B phenotype and range 51-60 chromosomes.
Myelodysplastic Syndromes (MDS)
- Acquired clonal hematopoietic disorders characterized by progressive cytopenias.
- Defects in erythroid, myeloid, and megakaryocyte maturation.
- Increased risk of transforming into acute myeloid leukemia (AML).
- Mutations in normal hematopoietic stem cells lead to clonal expansion, crowding normal cells.
- Morphologic findings include: dyserythropoiesis (abnormal RBC precursor morphology), dysmyelopoiesis (abnormal granulocyte maturation), and dysmegakaryopoiesis (abnormal platelet precursor morphology).
- Genetic mutations (de novo, therapy-related, secondary), inherited bone marrow failure syndromes. Exposure to heavy metals or chemicals and therapeutic radiation can increase risk.
- WHO classification includes: MDS with single lineage dysplasia (MDS-SLD), MDS with multilineage dysplasia (MDS-MLD), MDS with ring sideroblasts (MDS-RS), MDS with excess blasts (MDS-EB), MDS with isolated del(5q), MDS, unclassifiable (MDS-U), and childhood myelodysplastic syndromes.
- Subgroups based on peripheral blood (1-2 cytopenias and no or rare blasts) and bone marrow findings (unilineage or multilineage dysplasia and percentage of blasts).
Myelodysplastic/Myeloproliferative Neoplasms
- Myeloid neoplasms with clinical, laboratory, and morphological features characteristic of both MDS and MPN.
- Chronic myelomonocytic leukemia (CMML)
- Atypical Chronic Myeloid Leukemia (CML), BCR/ABL1 negative
- Juvenile Myelomonocytic Leukemia
- MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T)
- MDS/MPN, unclassifiable
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