L.13 Malignancies Flashcards
What are Haematological Malignancies?
Cancer of the blood and blood forming tissue (bone marrow, lymph nodes, spleen)
Includes leukaemia, lymphoma, and plasma cell myeloma (multiple myeloma)
What can cause unbalanced haematopoiesis?
Damage or disease of the bone marrow caused by drugs, radiation, infiltrating cancer, or viruses
This leads to irregularities in the production of blood cells
What condition results from underproduction of blood cells?
Aplastic Anaemia
It is caused by damage to the bone marrow
What condition results from overproduction of blood cells?
Leukaemia
What are Haematological Neoplasma?
Myeloid and lymphatic tumours caused by disruption of normal hematopoietic function
They include leukaemia, multiple myeloma (MM), non-Hodgkin lymphoma (NHL), and Hodgkin lymphoma (HL)
Define Leukaemia.
A malignant disease of haematopoietic tissue characterised by the replacement of normal Bone Marrow cells with abnormal neoplastic blood cells
Abnormal cells are also seen in the Peripheral Blood
Define Lymphoma.
Abnormal proliferation of lymphoid cells within the lymphatic tissue or lymph nodes, resulting in a solid tumour
What are the characteristics of Lymphoma?
Solid Tumours of Lymphocytes that arise in many sites and present as tumourous masses in lymphoid organs
Includes lymph nodes, tonsils, spleen, thymus, lymphoid tissue of the GIT
How are lymphomas classified?
Hodgkins Lymphoma or Non-Hodgkins Lymphoma
What are the two grades of lymphomas?
Low-grade (progress slowly but are difficult to treat) and High-grade
What does the Lymphoid System consist of?
- Lymph
- Lymphatic vessels (e.g. thoracic duct)
- Lymphoid tissue
- Diffuse lymphoid tissue
- Lymphoid follicles
- Lymphoid organs (primary: BM, thymus; secondary: tonsils, spleen, lymph nodes, appendix, various mucosal-associated lymphoid tissues (MALT), cutaneous-associated lymphoid tissue)
What are clinical symptoms of lymphoma?
- Swollen lymph nodes (neck, armpits, groin)
- Systemic symptoms: fatigue, weight loss, loss of appetite, fever, night sweat
- Lung symptoms: shortness of breath, chest pain
What is Leukaemia a group of?
Malignant disorders affecting the blood and blood forming tissues/organs (Bone marrow, Lymph system, Spleen)
What is the onset of Acute Leukaemia?
Rapid
How aggressive is Acute Leukaemia?
Very aggressive
What type of cells are found in Acute Leukaemia?
Poorly differentiated with many blasts
What does AML stand for?
Acute Myeloid Leukaemia
What does ALL stand for?
Acute Lymphoid Leukaemia
What is the onset of Chronic Leukaemia?
Insidious
How aggressive is Chronic Leukaemia?
Less aggressive
What type of cells are involved in Chronic Leukaemia?
Usually mature cells
What does CML stand for?
Chronic Myeloid Leukaemia
What does CLL stand for?
Chronic Lymphoid Leukaemia
Where are the cells recognisable in the blood derived from?
Pluripotent stem cell in the marrow
What are the two lineage specific progenitor cells?
Common myeloid progenitor cell and Common lymphoid progenitor cell
What cells are derived from the Common myeloid progenitor cell?
- Erythrocytes
- Megakaryocytes (platelets)
- Granulocytes (neutrophils, eosinophils, basophils)
What cells are derived from the Common lymphoid progenitor cell?
- T lymphocytes
- B lymphocytes
- NK cells
What triggers leukaemia?
- Somatic mutation of a single haematopoietic stem or progenitor cell
- Unlimited self-renewal of the cancer-initiating cell
- Inhibition of normal haematopoiesis
- Defect in maturation of white blood cells
- Block in differentiation and/or apoptosis
- Acquired genetic changes
- Chromosomal abnormalities
What is the age range for Acute Lymphoid Leukaemia (ALL)?
2-5 years
What is the age range for Acute Myeloid Leukaemia (AML)?
40+ years
What is the typical clinical onset of Chronic Leukaemia?
Insidious
What is the typical course duration for Acute Leukaemia?
6 months or less
What is the typical course duration for Chronic Leukaemia?
2-6 years
What type of leukaemic cell is predominant in Acute Leukaemia?
Immature cells >20%
What type of leukaemic cell is predominant in Chronic Leukaemia?
More mature cells
How prominent is anaemia in Acute Leukaemia?
Prominent
How prominent is anaemia in Chronic Leukaemia?
Mild
How prominent is thrombocytopenia in Acute Leukaemia?
Prominent
How prominent is thrombocytopenia in Chronic Leukaemia?
Mild
What is the white cell count (WCC) in Acute Leukaemia?
Variable
What is the white cell count (WCC) in Chronic Leukaemia?
Increased
How is lymphadenopathy in Acute Leukaemia?
Mild
How is lymphadenopathy in Chronic Leukaemia?
Present, often prominent
How is splenomegaly in Acute Leukaemia?
Mild
How is splenomegaly in Chronic Leukaemia?
Present, often prominent
What samples are used for the lab investigation of leukaemia?
Peripheral blood, bone marrow aspirate
These samples are essential for accurate diagnosis and monitoring.
What are the key components of leukaemia laboratory investigations?
- FBC
- Morphology
- Flow cytometry – Immunophenotyping
- Cytogenetics
- Molecular = PCR, NGS
- Minimal Residual Disease (MRD) monitoring
Each component provides critical information for diagnosis and treatment.
What samples are used for the lab investigation of lymphoma?
Peripheral blood, bone marrow aspirate, bone marrow trephine biopsy, fluid, FNA, lymph node
These samples help in the comprehensive evaluation of lymphoma.
What are the key components of lymphoma laboratory investigations?
- FBC
- Morphology
- Flow cytometry – Immunophenotyping
- Cytogenetics
- Molecular = PCR, NGS
- Minimal Residual Disease (MRD) monitoring
Similar to leukaemia, these components are crucial for lymphoma assessment.
What is a common abnormality found in the Full Blood Count (FBC) for leukaemia?
Abnormal Full Blood Count
Results must be interpreted alongside clinical presentation.
What is a common finding regarding RBCs in leukaemia?
- RCC increased or decreased
- Normochromic, normocytic anaemia is common
- MCV can be raised in some conditions
These findings reflect the impact of leukaemia on red blood cell production.
What platelet abnormalities are associated with leukaemia?
- Thrombocytopenia is common
- A raised platelet count can indicate ET, PV
These findings can vary based on the type of leukaemia and other factors.
What white blood cell (WBC) findings are indicative of leukaemia?
- Raised count with abnormal morphology (immature cells)
- Reduced count due to myelosuppression
- Normal count with abnormal morphology
- Evidence of reversed ratio
These findings highlight the dysregulation of normal hematopoiesis in leukaemia.
What types of blasts are identified in leukaemia morphology?
- Myeloblast = a blast of the myeloid pathway
- Lymphoblast = a blast of the lymphocyte pathway
- Erythroblast = a blast of the red blood cell pathway
Each type of blast indicates a different lineage and potential leukaemic transformation.
What percentage of cells in normal bone marrow are myeloblasts?
Up to 4%
Myeloblasts should not be apparent in the peripheral blood.
What types of cells can a myeloblast produce?
Granulocyte lineage:
* Neutrophils
* Eosinophils
* Basophils
Myeloblasts have the potential to produce all three types of granulocytes.
What is the nucleocytoplasmic ratio of a myeloblast?
High
The nucleus occupies the majority of the cell.
Describe the chromatin pattern of a myeloblast.
Fine open lacy pattern with prominent nucleoli
This demonstrates the active nature of the DNA within the cell.
What color does the cytoplasm of a myeloblast stain?
Light shade of blue (basophilic)
This indicates a high RNA content.
What is the typical size of a myeloblast?
16 ± 4 μm
Size can vary within the given range.
What is a distinct feature that can indicate a Myeloid Malignancy?
Auer Rod
Auer Rods are indicative of certain types of blood cancers.
How do promyelocytes compare in size to myeloblasts?
Significantly larger, measuring 20 ± 5 μm
Promyelocytes are larger than myeloblasts.
What is the nuclear-cytoplasmic ratio of a promyelocyte?
Lower than that of myeloblasts
Promyelocytes show occasional nucleoli.
What color is the cytoplasm of a promyelocyte?
Deep blue
This is in comparison to the paler myeloblast and contains primary granules.
What do primary granules in promyelocytes represent?
They are retained in neutrophils, eosinophils, and basophils
Primary granules are characteristic of these cell types.
What is a characteristic feature of the nucleus in a promyelocyte?
Slightly indented
This is a distinguishing feature of promyelocytes.
Should promyelocytes be present in peripheral blood?
No
An increase in promyelocytes in peripheral blood can indicate a problem.
What subtype of AML is associated with an increase in promyelocytes?
Acute promyelocytic leukaemia
This is the specific subtype linked to promyelocyte increases.
What is the approximate diameter of myelocytes?
15 ± 5μm
Myelocytes are smaller than promyelocytes.
What evidence is shown in myelocytes regarding chromatin?
Chromatin clumping
Nucleoli are no longer visible in myelocytes.
What type of granules are present throughout the cytoplasm of myelocytes?
Secondary granules
Secondary granules have a cell-specific function.
Why are secondary granules called ‘secondary’?
They are produced after the primary granules
Secondary granules possess a cell-specific function.
Which stages of maturation are mitotic stages?
Myeloblast, promyelocyte, and myelocyte
Daughter cells are produced at each of these stages.
What is the size range of metamyelocytes?
10-18 μm
Metamyelocytes contain distinctive primary and secondary granules.
What is the shape of the nucleus in metamyelocytes?
Kidney-shaped
The nucleocytoplasmic ratio is much lower in metamyelocytes.
What happens to the nucleus of metamyelocytes as they mature?
It becomes increasingly curved
Eventually resembles a horseshoe.
What term is used for cells with a horseshoe-shaped nucleus?
Band forms
Once the nucleus represents a horseshoe, they are no longer considered metamyelocytes.
What happens to the nucleus after it becomes segmented?
Mature features of the effector cell become apparent
Effector cells include neutrophils, eosinophils, or basophils.
What is the structure of the nucleus in mature neutrophils?
The nucleus condenses to form 3 to 5 lobules connected by thin strands of heterochromatin.
What type of granules are found in the cytoplasm of mature neutrophils?
Azurophilic granules.
Where are granulocytes sequestered as they mature?
In the bone marrow storage compartment.
What happens to neutrophil levels during tissue injury or infection?
The demand for neutrophils can exceed their production, leading to a temporary reduction known as neutropenia.
What term describes a sharp rise in neutrophil count?
Neutrophilia.
What is a characteristic of neutrophils during neutrophilia?
They may appear as immature cells in peripheral blood.
What does ‘left-shifted’ refer to in neutrophils?
Neutrophils that appear immature in peripheral blood.
What is a band form in neutrophils?
A hyposegmented neutrophil with toxic granulation.
What type of cells are lymphocytes?
Mononuclear cells.
What is the appearance of small lymphocytes?
A round nucleus and a thin rim of cytoplasm with condensed chromatin.
What color is the cytoplasm of small lymphocytes?
Blue.
How does the cytoplasm of activated lymphocytes change?
It becomes more basophilic.
What terms describe activated lymphocytes?
Atypical or reactive.
What percentage of circulating lymphocytes are T-cells?
Approximately 75%.
Can T cells and B cells be reliably differentiated morphologically?
No.
What must be performed to differentiate between T cells and B cells?
Immunophenotyping.
