| How is histology of bone marrow? | Bone marrow is the site of hematopoiesis.
Consists of - hematopoietic cells, vascular sinusoids, fibroblasts, fat cells, and
macrophages.
No lymphatic channels.
• The proportion of fat cells increases with advancing age with corresponding
decrease in hematopoietic tissue. Fats cells occupy -
children and adolescents -20-30%
adults - 50%
elderly - 70% |
| What are erythroid series? | RETICULOCYTE - juvenile red cells devoid of nuclei but contain ribosomal RNA so that they are still able to synthesise haemoglobin. Normal range :- Adults - 0.5-2.5% Infants - 2-6% Increased in - haemorrhage, haemolysis and haematopoietic response of anaemia to treatment
RED BLOOD CELLS - non-nucleated cells, biconcave disc, 7.2 μm in diameter, and has a thickness of 2.4 μm at the periphery and 1 μm in the centre. The lifespan of red cells is 120 +/- 30 days. |
| What are techniques of samping of BM? | . |
| What are indications for BM aspiration? | 1. Unexplained cytopenia.
2. Suspected acute leukemia : Comparison of baseline marrow smear with follow-up marrow aspiration smears during treatment, detection of remission.
3. Suspected myeloproliferative disorders : chronic myeloid
leukemia, polycythemia vera, essential thrombocythemia and myelofibrosis.
4. Suspected plasma cell dyscrasia: multiple myeloma.
5. Suspected chronic lymphoid leukemias like chronic lymphocytic leukemia, hairy cell leukemia.
6. Investigation of pyrexia of unknown origin.
7. Suspected storage disorder like Gaucher’s disease |
| What are indications for BM biopsy? | 1. Repeated failure of aspiration (dry tap) – myelofibrosis,
hairy cell leukemia.
2. Suspected aplastic anaemia.
3. Suspected focal lesions like granuloma, metastatic
deposit, or infiltrate of lymphoma.
4. Suspected bone disorder. |
| Table of indications of BM aspiration vs biopsy? | . |
| What is normal distribution of BM? | • The hematopoietic cells are present as cords between vascular sinusoids and are supported by a framework of branching processes of fibroblasts and reticulin fibers.
• Erythroid precursors are present as clusters (islands) and are closely associated with centrally placed sinusoids.
• Megakaryocytes, the largest of the hematopoietic cells, are closely apposed to the walls of the sinusoids.
• Lymphocytes and plasma cells are mostly present around capillaries and arterial vessels
• Early granulocyte precursors are located close to the
bony trabecule
• Mature granulocytes are located more centrally,
between adjacent trabeculae |
| What is silver impregnation technique? | Reticulin fibers are increased in :
Myelofibrosis
acute leukemias / lymphomas
chronic myeloid leukemia
polycythemia vera
hairy cell leukemia
metastatic carcinoma
Special stains -Giemsa stain, PAS, Perls |
| How is grading of BM fibrosis? | . |
| How is leukemia types figure? | . |
| Table of WHO classification of leukemia? | . |
| What are myeloproliferative neoplasms? | Group of clonal myeloid neoplasms in which a genetic alteration occurs in a hematopoieticprogenitor cell leading to its proliferation resulting in an increase in the peripheral blood white blood cells (WBCs),red blood cells (RBCs), platelets,or a combination of these cells
• Chronic myeloid leukemia (CML), BCR-ABL1 pos.
• Polycythemia vera (PV)
• Primary myelofibrosis (PMF)
• Essential thrombocythemia (ET)
• Chronic neutrophilic leukemia (CNL)
• Myeloproliferative neoplasm, unclassifiable (MPN-U)
• Chronic eosinophilic leukemia, NOS (CEL-NO) |
| What is CML? | • Median age at the time of diagnosis: 66 y.o.
• Clinical presentation: (Asymptomatic (~ 30%), Fatigue, weight loss, fever, Abdominal fullness, pain and/or early satiety due to splenomegaly (~ 50-90%), Easy bruising and purpura, Leukostasis, Pulmonary symptoms, Neurologic symptoms)
• 3 phases:
1.Chronic (proliferation of more mature cells; 90% in asymptomatic)
2.Accelerated (further cytogenetic alterations)
3.Blast crisis (totally immature blast cells)
• Therapy
1.Imatinib (TKI)
2.Allogenic stem cell transplantation |
| What are diagnostic considerations in CML? | Karyotyping in CML
1) Allows for the diagnosis of CML
2) Requires a bone marrow aspirate for optimal
metaphases
3) Allows for evaluation of clonal evolution as well as
additional chromosomal abnormalities in the nonPh+ clones
4) Occasional cryptic and complex karyotypes can result
in the missed identification of the t(9;22) |
| What are myelodysplastic syndromes? | • Clonal hematopoietic stem cell diseases
• Cytopenia and dysplasia in one or more major myeloid
lineages.
• Ineffective hematopoiesis
• Recurrent genetic abnormalities
• Variable increase in myeloblasts (<20%)
• Increased risk of developing AML
• Primary or de novo without a known history of
chemotherapy or radiation exposure |
| How is dysplasia assessment? | • Threshold of 10% of cells in any lineage
• Dysplasia is not always reproducible, even
among experienced hematopathologists
• Dysplasia is not specific for MDS
– Significant dysplasia in bone marrow of normal
volunteers
– Dysplastic changes are even more frequent in
patients with non-neoplastic cytopenias |
| What are info needed by pathologist for MDS dx? | • Clinical history
– Full CBC and WBC differential results
– Knowledge of duration of cytopenias and possible
other causes of cytopenia
• Morphology review
– Blood smear
– Bone marrow aspirate or touch prep
• Wright-Giemsa and iron stains
– Bone marrow biopsy
• Complete bone marrow karyotype |
| What is AML? | • AML with recurrent genetic abnormalities
• AML with myelodysplasia-related changes
• Therapy-related myeloid neoplasms
• AML, not otherwise specified
• Myeloid sarcoma
• Myeloid proliferations related to Down
syndrome
• Blastic plasmacytoid dendritic cell neoplasm |
| How is not specified otherwise AML lesions? | AML with minimal differentiation
AML without maturation
AML with maturation
Acute myelomonocytic leukemia
Acute monoblastic/monocytic leukemia
Pure erythroid leukemia
Acute megakaryoblastic leukemia
Acute basophilic leukemia
Acute panmyelosis with myelofibrosis |
| How is etiology of AML? | 1. Ionising radiation and X-rays
2. Drugs - alkylating agents, chemotherapy drugs
3. Chemicals – Benzene, tobacco, alcohol
4. Genetic disorders – Down’s syndrome, Fanconi’s syndrome,
ataxia telengiectasia, Patau’s syndrome, Klinefelter’s
syndrome
5. Acquired disorders – PNH, aplastic anemia (stem cell
disorders)
6. Myelodysplastic syndrome (MDS)
7. Infections (HTLV-I & ATLL) |
| How is pathogenesis of AML? | • Since hematopoietic cells have a rapid turnover, they are more vulnerable to chromosomal damages and cytogenetic changes.
•The single most prominent characteristic of the leukemic cells is a defect in maturation beyond the myeloblast / promyelocyte level in AML, and the lymphoblast level in ALL.
• AML develops due to inhibition of maturation of myeloid
stem cells due to mutations.
• Leukemic cells accumulate in the bone marrow suppression of normal hematopoietic stem cells
Stem cells remain in marrow capable of dividing after tx |
| How is BM of AML? | • M:E ratio increased
• Blasts > 20%
• Erythropoiesis: Erythropoietic cells are reduced.
Dyserythropoiesis, megaloblastic features and ring
sideroblasts are commonly present.
• Immunophenotyping:
CD34, CD117, MPO
Hypercellular; but sometimes a ‘blood tap’ or ‘dry tap’ occurs due to pancytopenia/ when the marrow is so much packed with leukaemic cells that they cannot be aspirated because the cells are adhesive and enmeshed in reticulin fibres. In such cases, trephine biopsy is indicated. |
| What are clinical features of AML due to bone marrow failure? | 1. Fatigue due to anemia - pallor, lethargy, dyspnea
2. Bleeding manifestations- due to thrombocytopenia
causing spontaneous bruises, petechiae, gum
bleeding, epistaxis
3. Infections - mouth, throat, skin, respiratory,
perianal
4. Fever - due to infections/leukemic process |
| What are clinical manifestations of AML due to organ infiltration? | 1. Pain and tenderness of bones (e.g. sternal tenderness) - bone infarcts or subperiosteal infiltrates by leukaemic cells
2. Splenomegaly – mild to moderate
3. Hepatomegaly – mild ; due to leukaemic infiltration but the infiltrates usually do not interfere with the function of the liver
4. Meningeal involvement - raised intracranial pressure,
headache, nausea and vomiting, blurring of vision and diplopia (more frequent in ALL during hematologic remission); sudden death from massive intracranial haemorrhage as a result of leucostasis
5. Gum hypertrophy – in M4, M5
6. Skin infiltration – violaceous rash
7. Chloroma/ Granulocytic sarcoma - localised tumour forming mass occurring in the skin or orbit due to local infiltration of the tissues by leukaemic cells. The tumour is greenish in appearance due to the presence of myeloperoxidase |
| What is myeloid sarcoma? | • Extramedullary tumor mass of neoplastic immature myeloid (granulocytic or monocytic) cells
• Also called extramedullary myeloid tumor, granulocytic sarcoma, chloroma
• Lymph nodes, subperiosteal bone, skin, orbit, spinal canal and mediastinum
• May or may not be associated with a myeloid neoplasm in the BM. It is considereddiagnostic of (AML) and should be classified and treated accordingly, regardless of the BM or PB status.
• May be the 1st manifestation of AML or may signal relapse in a previously treated patient. It may also signal transformation to acute leukemia in patients with MPN or MDS |
