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Medicine - 3rd year > Haem Malignancies > Flashcards

Haem Malignancies Flashcards

1
Q

What do myeloid precusor cells give rise to?

A
  1. Granulocytes:
    - basophils
    - neutrophils
    - eosinophils
    - mast cells
    - monocytes –> macrophages
  2. RBCs
  3. Megakaryocytes –> platelets bud off
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2
Q

What do common lymphoid precusors give rise to?

A

Lymphocytes:

  • B cells
  • T cells
  • NK cells

*dendritic cells can arise from either this pathway or as part of granulocytes (from myeloid precursor)

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3
Q

Bone marrow samples - types and preferred sites

A
  1. bone marrow aspirate: takes a little of the liquid found in the bone marrow space
  2. bone marrow biopsy (trephine): takes a small sample of harder bone marrow tissue.

Preferred sites:

  • iliac crest (anterior or posterior)
  • tibia
  • sternum
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4
Q

Acute leukaemia - definition

A

Neoplastic disease of immature blood cells (blasts) in the bone marrow. Can arise from myeloid or lymphoid lineage

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5
Q

Acute leukaemia - general features

A
  • Tiredness, infection, bruising/bleeding
  • High white cell count
  • Low haemoglobin (anaemia)
  • Low platelet count (thrombocytopenia)
  • Low neutrophil count (neutropenia)
  • High WCC due to infections
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6
Q

Acute leukaemia and infections

A
  • Low neutrophil count (neutropenia) –> increased risk of infection (febrile neutropenia)
  • chemotherapy –> mucositis (risk of mouth infections)
  • Indwelling central venous line –> line infection (staph aureus)
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7
Q

Acute myeloid leukaemia (AML) - features

A
  • mainly >65 years
  • RF: Radiation, previous chemotherapy, congenital syndromes, previous myelodysplastic syndrome
  • auer rods on blood smear
  • Tiredness, infection, bleeding, ecchymoses or petechiae
  • splenomegaly, bone pain
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8
Q

What are auer rods?

A

Auer rods are cytoplasmic inclusions which result from an abnormal fusion of the primary granules.

  • seen in acute myeloid leukaemia
  • found on blood smear

Au = gold; granules of gold –> ganulocytes (myeloid)

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9
Q

Acute lymphoblastic leukaemia (ALL) - features

A
  • 30% of childhood cancer
  • 20% of adult acute leukaemia
  • RF: Radiation, Downs syndrome, M>F
  • +ve philadelphia chr common in adults

Symptoms and signs

  • Tired, anaemic, bruising, bleeding and low platelets, weight loss
  • Abdominal pain, lymphadenopathy, splenomegaly, hepatomegaly, bone pain, +/- fever, testicular swelling
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10
Q

What is the relevance of the philadelphia chromosome?

A

Cytogenetic abnormality results from chromosomal translocation t(9;22)(q34;q11) on the Philadelphia chromosome, found on molecular studies in:

  1. Chronic myeloid leukaemia (95%) - pathognomonic
  2. most common cytogenic abnormality in adult ALL
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11
Q

AML - treatment

A
  • 3 to 4 cycles of combination chemotherapy
    e. g retinoic acid induces blast to mature to neutrophil
  • Haemopoietic stem-cell transplant (HSCT) for some or bone marrow transplant
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12
Q

ALL - treatment

A
  • Induction (includes prednisolone/dexamethasone and vincristine) and consolidation chemotherapy (high-dose)
  • HSCT or bone marrow transplant
  • CNS prophylaxis throughout as can progress to/relapse in brain and spinal cord so intrathecal chemo +/- radio
  • If Philadelphia positive ALL- also give Imatinib(Glivec)
  • consider fluids, Abx prophylaxis, RBC transfusion etc
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13
Q

Acute vs Chronic leukaemia

A

ACUTE: no mature cells therefore low neutrophils, lymphocytes etc.
CHRONIC: mature cells affected therefore high neutrophils, lymphocytes

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14
Q

Chronic leukaemia - def and types

A

Neoplastic disease of mature white blood cells in the bone marrow
Types:
- Chronic myeloid leukaemia (CML): overlaps with myeloproliferative disorders
- Chronic lymphocytic leukaemia (CLL): overlaps with lymphomas

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15
Q

Chronic lymphocytic leukaemia (CLL) - features

A
  • Majority of pts > 60 (most common type in adults)
  • Slow accumulation of CLL cells in blood, bone marrow, lymph nodes, liver, spleen
  • Hepatosplenomegaly and lymphadenopathy
  • B symptoms: night sweats, persistent fever, weight loss, itching
  • autoimmune haemolytic anaemia in 10-15%
  • Can transform to high grade lymphoma (5%) (Richter’s transformation)
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16
Q

CLL - Dx and treatment

A

Diagnosed by FBC with differential (absolute lymphocytosis, can have normal or low Hb and platelets), blood smear showing smudge cells (aka smear cells), and flow cytometry

Treatment

  • Observation (early stage) or Chemotherapy
  • If not working or relapse, then use biological agents (Antibody therapy eg. Alemtuzumab, Rituximab)
  • Last resort is allogeneic stem-cell transplantation
17
Q

CLL progressing to lymphoma - presentation

A

similarly to CLL the lymphocyte count is high but when progession to lymphoma occurs the Hb level goes really low and the patient is anaemic

  • sudden onset of B symptoms
  • progressive lymphadenopathy
  • high serum levels of lactate dehydrogenase
18
Q

Chronic Myeloid Leukaemia

A
  • Median age 50-60yrs old
  • Philadelphia chromosome: most commonly associated with CML ( 95%)
  • 20-50% asymptomatic (‘incidental’ finding on FBC)
  • Splenomegaly, Bony pain
  • Peripheral blood and BM demonstrates the presence of BCR-Abl fusion gene
  • an increase in granulocytes at different stages of maturation +/- thrombocytosis
  • can progress to acute leukaemia (‘blast crisis’)
  • Mx: Imatinib or other Tyrosine kinase inhibitors; interferon-alpha; allogenic bone marrow transplant
19
Q

Myeloproliferative disorders

A

Over-production of mature blood cells

↑ Neutrophils = chronic myeloid leukaemia (CML)
↑ Red cells = polycythaemia rubra vera (PRV)
↑ Platelets = essential thrombocytosis (ET)
↑ fibroblasts = Idiopathic myelofibrosis: results in replacement of bone marrow/other sites with collagen

20
Q

Myelodysplasia (myelodysplastic syndrome - MDS)

A

Pre-cancerous disease of bone marrow, where the dysplastic cells may cause abnormal blood cell production (bone marrow trying to compensate)

  • Consider this in patients with abnormal blood counts with no obvious explanation (e.g. macrocytic anaemia)
  • Dysplastic morphology
  • Almost exclusively patients over 60
  • Can also progress to acute leukaemia
21
Q

Myeloma - definition

A

Neoplastic disease of plasma cells (activated B cell - antibody producing)

Leads to increase production of antibodies (in case of myeloma known as paraprotein) - they can build up in kidney
Also there is less room for other blood cells to grow in bone marrow, so can get pancytopenia

22
Q

Myeoloma - features

A
  • Anaemia
  • Pancytopenia
  • Median age at diagnosis 66
  • Bone problems: lytic bone lesions, pathological fractures (paraplegia), hypercalcaemia
  • Monoclonal paraprotein (IgG or IgA or free light chain)
  • Hyperviscosity of blood can lead to clots
  • Cx: Renal Failure

Treatment
Induction with combination chemotherapy
Autologous stem-cell transplant in first remission
bone disease –> biphosphonates (Zoledronic acid), analgesia

CRABBI - calcium, renal, anaemia, bleeding, bone, infections

23
Q

MM - investigations

A
  • bloods: FBC, U+Es, calcium
  • Serum or urine protein electrophoresis: raised monoclonal IgA/IgG proteins will be present in the serum. In the urine, they are known as Bence Jones proteins
    (the proteins are immunoglobulin light chains (paraproteins) and produced by neoplastic plasma cells)
  • Bone marrow aspiration and trephine biopsy: confirms dx if the number of plasma cells is significantly raised
  • Whole body MRI (or CT) is used to survey the skeleton for bone lesions
  • A common X-ray finding is a ‘rain-drop’ skull - numerous randomly placed dark spots which occur due to bone lysis.
24
Q

Lymphoma - definition and types

A

Neoplastic disease of mature lymphocytes in lymphoid tissues (lymph nodes, gut, tonsils, skin etc)
- commonly a solid tumour all in one place

  1. Hodgkin Lymphoma
    - classical HL
    - nodular lymphocyte predominant (NLPHL)
  2. Non-Hodgkin Lymphoma
    - B cell (low or high grade)
    - T cell (systemic or cutaneous)
25
Q

Hodgkin Lymphoma

A
  • Most present with painless cervical and/or supraclavicular lymphadenopathy
  • 2 peaks of incidence (15-30, >65)
  • Pruritus and intermittent fevers are often a/w night sweats (B symptoms)
  • anaemia of chronic disease
  • alcohol pain - pain on drinking
  • sometimes link with EBV infection

Dx: made by excision of a complete lymph node that is then submitted for detailed histological evaluation.
+ve Reed-Sternberg cell

26
Q

Lymphoma - investigations (general)

A
  • FBC, LFTs, LDH (lactate), U+Es
  • blood smear
  • Biopsy of nodes (shows type and grade of lymphoma)
  • bone marrow biopsy (staging)
  • CT neck/chest/abdomen/pelvis
  • Serum Ig
  • HIV serology (HIV can be a/w lymphoma)
  • PET-CT (increased uptake at involved sites)
  • FISH – cytogenetics study (can show chromosomal translocations in follicular, mantle cell and burkitt lymphoma)
27
Q

B cell Lymphoma - low vs high grade

A

Low Grade

  • Most patients are >50
  • presentation in advanced-stage disease is with painless widespread low-volume lymphadenopathy
  • Splenomegaly is common in advanced-stage

High Grade

  • Affects all ages
  • Usually present with systemic symptoms (B symptoms) and large masses/features of organ infiltration
28
Q

Non-Hodgkin’s Lymphoma - general

A
  • Painless lymphadenopathy (non-tender, rubbery, asymmetrical)
  • Constitutional/B symptoms (fever, weight loss, night sweats, lethargy)
  • Extranodal Disease - gastric (dyspepsia, dysphagia, weight loss, abdominal pain), bone marrow (pancytopenia, bone pain), lungs, skin, central nervous system (nerve palsies)
29
Q

T Cell lymphoma -features

A
  • less common type and worse prognosis than B cell

Acute = fatigue, skin rash and enlarged lymph nodes in the neck, armpit and groin, +/- hypercalcaemia which can cause confusion, bone pain and constipation

Chronic = slow growing and frequently characterised by enlarged lymph nodes that can be found anywhere in the body. Skin rash and fatigue are also common

  • cutaneous type tends to be indolent
30
Q

Stem cell transplant types

A
  1. Autologous – from patient’s own stem cells
    Allows delivery of very high doses of chemotherapy
    Can be curative (e.g. relapsed Hodgkin lymphoma) or to extend remission (e.g. myeloma)
  2. Allogeneic
    From a donor (sibling or unrelated donor)
    Done always with curative intent (all types of haematological malignancy, but most commonly in acute leukaemia)
31
Q

ALL vs AML blood smear features

A

ALL

  • lymphoblasts - smaller cells
  • glycogen granules
  • coarse chromatin

AML

  • myeloblasts - larger cells
  • auer rods
  • fine chromatin
32
Q

Hodgkin’s vs Non-Hodgkin’s Lymphoma

A
  • Lymphadenopathy in Hodgkin’s lymphoma can experience alcohol-induced pain in the node
  • ‘B’ symptoms typically occur earlier in Hodgkin’s lymphoma and later in non-Hodgkin’s lymphoma
  • Extra-nodal disease is much more common in non-Hodgkin’s lymphoma than in Hodgkin’s lymphoma
33
Q

Burkitt’s Lymphoma

A

Burkitt’s lymphoma is a high-grade B-cell neoplasm. There are two major forms:

  1. endemic (African) form: typically involves maxilla or mandible
  2. sporadic form: abdominal e.g. ileo-caecal tumours are the most common. More common in pts with HIV
  • strong association with EBV - esp endemic type
  • Microscopy findings - ‘starry sky’ appearance of lymphocyte sheets
34
Q

Lymphoma - treatment (general)

A
  • HL and high grade NHL: Combination chemotherapy +/- radiotherapy
  • Low grade NHL: Radiotherapy to lymph nodes (regional radiotherapy)
  • Analgesia
  • Other option is to offer rituximab alone or combined with a chemo drug or prednisolone
  • consider antimicrobial prophylaxis if severely neutropenic and CNS prophylaxis if HIV-associated
35
Q

Leukaemia - Investigations

A

Most important:

  1. FBC
  2. (Peripheral) Blood smear
  3. Bone marrow aspirate (biopsy)

Other:

  • LP: to exclude CNS involvement
  • Cytogenetics (FISH, karyotyping): looks at chromosomes e.g. philadelphia

Medicine - 3rd year (8 decks)

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