Haematology Flashcards
Haemopoiesis sites
3rd week of intrauterine life- yolk sac
3rd month of intrauterine life- liver
4th month of intrauterine life- bone marrow and liver
Just before birth- bone marrow
CD marker to identify hematopoietic stem cell
CD-34
Myeloid series
- Myeloblast
- Promyelocyte: largest cell
- Myelocyte
- Metamyelocyte
- Band form
- Neutrophil
Size 🔽 from promyelocyte to neutrophil
Leucopenia
Agranulocytosis
🔽 in WBC county Usually due to neutropenia Cause: 1. Aplastic anemia 2. Drug toxicity Agranulocytosis: clinically significant 🔽 in WBC count
Leucocytosis
🔼 WBC count
Reactive proliferation of WBC
Neutrophilia
🔼 neutrophil count Normal neutrophil count: 40-70% Cause: 1. Acute infections 2. Tissue injury like MI, burns 3. Bacterial infections 4. Myeloproliferative disorders
Eosinophilia
Normal count: 1-6% Causes: 1. Type 1 hypersensitivity like allergy 2. Parasitic/ helminthic infections 3. Tropical pulmonary eosinophilia
Basophilia
Normal: 1% Causes: 1. CML 2. Lymphocytosis • TB • viral infections • chronic infections 3. Lymphoproliferative disorders like CLL, ALL
Monocytosis
Normal: 2-8% Causes: 1. Malaria 2. Endocarditis 3. Rickettsiosis 4. Viral infections
Peripheral smear in sepsis or infection
- Toxic granule:
Course & dark granule - Dohle bodies:
Patches of dilated endoplasmic reticulum
Neutrophil classification based on lobes
1. Hypersegmented: >5 lobes seen In megaloblastic anemia due to vitamin B12 deficiency 2. Hyposegmented: <2 lobes seen Pseudo pelger huet cell In myelodysplastic syndrome
Morphological abnormalities in May Hegglin anomaly
- Giant platelets
- Low platelet count
- Inclusion within the cytoplasm
Abnormalities with granules in neutrophil
Chediak Higashi syndrome:
Dark purplish granule in giant granules in neutrophils
Alder Reilly abnormalities:
Most of the neutrophils have granules that obscure the nucleus
Classification of WBC neoplasms
1. Lymphoid: ALL Chronic lympho proliferative disorders 2. Myeloid: AML Myeloproliferative disorders Myelodysplastic syndrome MDS/MPN 3. Dendritic cells: Langerhan’s histiocytes
Acute lymphoblastic leukemia
WHO definition:
>20% blasts in bone marrow and peripheral blood
Based on markers
FAB definition:
>30% blasts in bone marrow and peripheral blood
Based on morphology of blasts
Lymphoblast (🆚 myeloblast)
Smaller Scanty cytoplasm (🆚 moderate) No granules Auer rods absent Course, clumped chromatin: most prominent Inconspicuous nucleoli Stain: PAS +ve
Myeloblast (🆚 lymphoblast)
Larger size Moderate cytoplasm Granules present Auer rods: hallmark Open up/homogenous chromatin: most prominent 2-5 prominent nucleoli Stain: MPO, Susan black B, NSE +ve
Acute lymphoblastic leukemia
ALL
M/C cancer in children Age: 2-9 years Clinically: 1. Anemia ➡️ pallor, fatigue 2. 🔽 no of WBC - infections 3. 🔽 platelets - bleeding tendency 4. Hepatosplenomegaly due to extramedullary hematopoiesis 5. Bone pain (eternal tenderness) 6. CNS involvement 7. Testicular involvement 8. Lymph node involvement
FAB classification of ALL
1. L1: Small homogenous blasts Scanty cytoplasm Inconspicuous nucleoli 2. L2: Large, heterogenous Moderate cytoplasm Prominent nucleoli 3. L3: Large Burkitt’s ‘lymphoma-like’ blasts Vacuoles in blue 🔵 cytoplasm
Differences b/w ALL types (FAB classification) based on their occurrence and prognosis
L1: M/C Best prognosis 🍀ly L3: Least common Worst prognosis
WHO classification of ALL
1. B-ALL: ☄️ M/C with better prognosis 🍀ly Usually children No mediastinal invasion Loss of function mutation In PAX-5, E2A or EBF 🧬 2. T-ALL: Adolescents Mediastinal invasion can be present Gain of function mutation in NOTCH I 🧬 Poor prognosis
ALL
Lab diagnosis
1. CBC Hb and PLC 🔽 TLC 🔽 or 🔼 2. Peripheral smear: >20% lymphoblasts 3. Bone marrow aspiration: >20% lymphoblasts In aleukemic leukemia: No blasts in peripheral smear but on bone marrow aspiration >20% blasts
Stains for ALL
- PAS +ve called DOT/BLOCK positivity
In AML-M6 shows diffuse PAS +ve - T-ALL are acid phosphatase positive
Markers of ALL
- Of both pre B and pre T lymphocytes: TdT+ Terminal deoxynucleotidyl transferase
- B-ALL: CD19, 10, PAX-5
- T-ALL: CD1, 2, 5, 7
- CD-10 called CALLA Common ALL Ag
ALL
treatment
- Stem cell transplantation
- Chemotherapy: VAPD
Vincristine
L Asparaginase
Prednisolone
Doxorubicin - Intrathecal methotrexate for CNS prophylaxis
ALL prognostic factors
Good prognostic factors (🆚 bad = everything else)
- Age: 2-9 years
- Females
- Whites
- L1 subtypes
- B-ALL
- CNS, testis, spleen not involved
- Hyperdiploidy (>50 chr) 🆚 hypodiploidy
- Trisomy 4,7,10, t(12:21) 🆚 t(9:22)
- TLC < 1,00,000/ml
AML
age and clinical presentation
Age: 15-45 years Clinically: 1. Non specific: • Pallor, fatigue, 🔼 infections, bleeding tendencies, hepatosplenomegaly • Usually no CNS, testes or lymph node involvement 2. Specific: • Gun hyperplasia/bleeding • DIC • Chloroma or granulocytic sarcoma
AML
risk factors
- Chemicals and radiation ☢️
- Genetic syndromes:
• Fanconi’s anemia
• Bloom’s syndrome
• Down’s syndrome
AML
FAB classification
AML M0 AML undifferentiated M1 AML w/o maturation M2 AML with maturation M3 acute promyelocytic leukemia M4 acute myelomonocytic leukemia M5 acute monocytic leukemia M6 acute erythro leukemia M7 acute megakaryoblastic leukemia
Special features of some types of AML
AML M0 is MPO -ve AML M2: • Pathogenesis t(8:21) • M/C FAB type of AML • Maximally associated with chloroma AML M3: Best prognosis
Myeloblastoma
Chloroma
Granulocytic sarcoma
Soft tissue involvement of AML Comprised of myeloblasts and granulocytes Green due to MPO +ve M/C site: 👁 ➡️ proptosis Arbiskov cells: Presence of monocytes in a chloroma
AML M3
Acute promyelocytic leukemia
Associated with t(15:17): PML gene and RARA-α gene ➡️ AML RARA fusion protein ➡️ 🔽 vitamin A level ➡️ 🔽 conversion of promyelocytes-myelocyte ➡️ 🔼 promyelocytes
Characteristics of cells of promyelocytes
- Have plenty of cytoplasmic granules and are usually hypergranular (azurophilic granules)
- A hypogranular variant also exists
- Few granules combine - Auer rods
- Criss cross pattern of Auer rods: Faggot cells
- Auer rods and faggot cells
AML M3
complication
treatment
Complications:
Granules contain thrombotic material ➡️ breakage of granules causes its release ➡️ DIC
Treatment:
All trans retinoic acid ATRA + arsenic trioxide
AML M4,5
Stains: • MPO +ve • NSE +ve, a stain for monoblasts Strongly associated with gum bleeding AML M5 is M/C AML in infants 👶 Associated with skin involvement: Leukemia cutis
AML M6
Also called Di Gugleimo disease
Diffuse PAS +ve
AML M7
Secrete PDFG ➡️ myelofibrosis ➡️ dry tap on bone marrow aspirate Associated with Down’s syndrome CD 41+, CD 61+ Budding cytoplasmic margins can be seen Least common type of AML
WHO classification of AML
1. AML with recurrent genetic abnormalities: • t(8:21), t(25:17) • inv 16 or t(16:16) • t(11q:V) • with normal cytogenetics and mutated NPM 2. AML therapy related: 🔽 prognosis 3. AML with MDS like features 4. AML not otherwise specified: all except AML M3
WHO classification of AML with recurrent genetic abnormalities
- With t(8:21) RUN XI / ETO fusion gene: AML M2
- With t(15:17) PML / RARA fusion gene: AML M3
- AML with inv 6 out t(16:16) CBFB / MYHII fusion gene:
AML M4 (eosinophilia) - AML with t(11q:V) MLL fusion gene
- AML with normal cytogenetics and mutated NPM
AML
lab diagnosis
- CBC:
🔽 Hb, TLC, platelets - Peripheral smear and bone marrow aspirate:
• >20% myeloblasts
• <20% with t(8:21), t(15:17) or inv. 16 - Stains
- Markers CD 13, 33, 117+, MPO +
AML
stains
- MPO+ myeloperoxidase
- SBB+ Sudan black B
- NSE+ monoblasts
AML M6 is diffuse PAS+
AML
treatment
- Definitive Rx: stem cell transplantation
2. For AML M3 ATRA +Arsenic trioxide
Biphenotypic leukemia
If blasts show both myeloid lineage markers as well as lymphoid markers, it is called biphenotypic
• Myeloid lineage markers: CD 13, 33, 117+, MPO+
• Lymphoid lineage markers: CD 19, 20, 10+, PAX 5+, CD 2, 3, 5, 7+
