Haematological Malignancy Flashcards
How common are haematological cancers?
10% of all human cancers
What gender do haematological cancers generally tend to affect most?
Men
What leukaemia is most common in young children?
ALL - peaks 2-4y
What leukaemia is most common in adults?
AML
What is Hodgkin lymphoma associated with?
EBV (especially in older patients)
Describe the incidence of Hodgkin lymphoma
Peak in 18-35yos and peak in 70s
Describe the pathogenesis of haematological malignancy
Multistep process:
Genetic mutation to long lived cell that conveys survival advantage –> produces malignant clones –> malignant clones dominate the tissue (e.g. bone marrow/lymph nodes)
If the malignant clones start dominating the tissue what can occur?
Bone marrow failure (anaemia, thrombocytopenic bleeding, infection due to neutropenia)
If a mutation occurs in the hemopoietic stem cell causing leukaemia what is the cell called?
Leukaemia stem cell
What are the two most important properties of the hemopoietic stem cell?
Multipotential - can go down myeloid/lymphoid lineage
Self-renewing - one daughter cell will differentiate another will replace the hemopoietic stem cell
What cells are granulocytes?
Eosinophils, neutrophils, basophils, mast cells
What cells are included in the myeloid lineage?
Granulocytes, monocytes, platelets, erythrocytes
What cells are included in the lymphoid lineage?
B cells
T cells
In ALL, where does the mutation occur and what cells will accumulate?
Occurs in hemopoietic stem cell or early lymphoid progenitor leading to accumulation of lymphoblasts
Lymphoblasts retain their ability to proliferate rapidly but do not differentiate
Rapidly accumulation of these cells –> bone marrow failure (acute presentation)
In AML, where does the mutation occur and what cells will accumulate?
Hemopoietic stem cells or early myeloid progenitor cells
Proliferation occurs, differentiation blocked –> accumulation of early myeloid cells in bone marrow –> bone marrow failure & acute presentation
Where do lymphomas most commonly occur?
Mutations of lymphocytes in the germinal centre of the lymph nodes (as this is where there is the most genetic pressure)
Differentiate between lymphoma and leukaemia
Leukaemia - mostly in blood and bone marrow
Lymphoma - in lymph tissue mostly
What is the most common leukaemia?
Chronic lymphocytic leukaemia
How is CLL different when it presents in the lymph nodes?
If presents with swollen lymph nodes, biopsy of lymph nodes will show exact same morphology as if it was in the bone marrow
BUT it is known as small cell lymphocytic lymphoma instead
What are the features of Burkitt lymphoma?
Rapidly growing, very aggressive and tends to present with a lump
What are the acute leukaemias?
Acute lymphoblastic leukaemia
Acute myeloid leukaemia
What are the chronic leukaemias?
Chronic myeloid leukaemia
Chronic lymphocytic leukaemia
What are the malignant lymphomas?
Non-Hodgkin lymphoma
Hodgkin lymphoma
What are the main differences between the acute and chronic leukaemias?
Acute: leukaemic cells do not differentiate; chronic: able to differentiate (not fully)
Acute: bone marrow failure, chronic: proliferation without bone marrow failure
Acute: acute presentation, rapidly fatal if untreated, chronic: survival for a few years
What is the triad of bone marrow failure?
Anaemia Thrombocytopenic bleeding (purpura/mucosal membrane bleeding) Infection (due to neutropenia, predominantly fungal and bacterial infections)
What is the appearance of the bone marrow in acute leukaemia?
Absolutely packed with blasts
What is key about the petechiae seen in bone marrow failure?
Non-blanching
Aside from petechiae what other abnormal bleeding may you see in bone marrow failure?
Mucosal bleeding
Subscleral bleeding
What infections might you see in bone marrow failure?
Staph aureus (e.g. tunnel infections, cellulitis), pseudomonas Aspergillosus
Describe the structure of a lymph node
Paracortex surrounding outside
Cortex is outer area, with inner medulla
In medulla there are B cell follicles composed of a marginal zone, mantle zone and germinal centre
Where are B cells found in the lymph nodes?
Follicles
Where are T cells found in the lymph nodes?
Paracortex
Where are plasma cells found in the lymph nodes?
Medulla
What occurs in the germinal centre?
B cells undergoing expansion and selection
Where do B cells mature?
In the germinal centre of lymph nodes where they are forced to rearrange their genetic material to change into a plasma cell against a specific antigen
Where do T cells mature?
Thymus
What is the name of the process of genetic rearrangement that occurs in the germinal centre of lymph nodes?
Somatic hypermutation
What are the different presentations of lymphomas?
Nodal disease (lymphadenopathy) occurs in HL 90% and NHL 60% of the time
Extranodal disease, e.g. in CNS
Systemic (B) symptoms
What are the systemic B symptoms?
Fever, drenching night sweats, >10% loss of body wt, pruritus, fatigue
Indicative of a poorer prognosis
What is important to remember when trying to palpate and check lymph nodes?
Not all lymph nodes can be felt, e.g. mediastinal lymph nodes
What is the reason for localised and painful lymph nodes?
Bacterial infection
What are reasons for localised and painless lymph nodes?
Rare infections (TB, scratch fever)
Metastatic cancer - HARD
Lymphoma - RUBBERY
Reactive
What are reasons for generalised and painful lymph nodes?
Viral infections (EBV, CMV, hep, HIV)
What are reasons for generalised and painless lymph nodes?
Lymphoma Leukaemia Connective tissue diseases Sarcoidosis Reactive Drugs, e.g. phenytoin
What are the clinical features of multiple myeloma?
Lytic lesions and bone pain (cytokines –> osteoclast induction)
Anaemia (of chronic dx)
Recurrent infections (neutropenia)
Renal failure (deposition of light chains)
Amyloidosis (light chain accumulation in tissues)
Bleeding tendency
Hyperviscosity syndrome
