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Year 3 TCDs > Hematological Diseases > Flashcards

Hematological Diseases Flashcards

1
Q

What tests would you advise for someone with suspected cancer?

A
  1. Full blood count

2. Chest x-ray

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2
Q

What is clinically relevant lymphadenopathy?

A
  1. Adult > 1cm or 1.5cm at level 2 (ear to hyoid bone)
  2. Pediatric > 2cm
  3. Any node with associated head/neck symptoms that is persistent
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3
Q

What are the causes of lymphadenopathy?

A
  1. Inflammatory
    - Bacterial/viral - tonsils, teeth, ear, scalp (Strep, staph aureus, strep pneumonia, anaerobes/fusobacterium, bartonella/cat scratch disease, toxoplasmosis)
    - TB (consider if high risk population group)
    - HIV
    - Viral causes: adenovirus, rhinovirus, coxsackie virus A + B, EBV
  2. Malignancy
    - Metastatic (vast majority from head/neck primarily)
    - Lymphoma (multiple, often smooth and firm rather than hard)
    - Supraclavicular fossa can be 2º to lung/GI tract cancer
  3. Autoimmune
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4
Q

What are the metastatic node cancers?

A
  1. Mucosal squamous carcinoma
  2. Thyroid cancer
  3. Salivary gland cancer
  4. Skin cancer (squamous, melanoma)
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5
Q

What investigations would you do for a head/neck lump?

A
  • Fibreoptic endoscopy in ENT neck lump clinic
  • Imaging (US, CT, MRI, PET)
  • Biopsy FNA core
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6
Q

Which imaging is best for which disease?

A

US -> thyroid + benign nodes

CT -> primary disease below the hyoid

MRI -> primary above hyoid

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7
Q

What questions would you ask in the history of someone with a neck lump?

A
  1. Pain (odynophagia): unilateral, associated with otalgia (ear pain)
  2. Hoarseness: progressive, persistent, fluctuating
  3. Dysphagia: liquids, solids, intermittent, true or globus-like
  4. Neck lump: site, duration, fluctuation
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8
Q

What are the risk factors for head/neck cancer?

A
  1. Smoking
  2. Alcohol
  3. HPV
  4. Cannabis
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9
Q

How is tonsil cancer treated?

A
  • Chemo

- Neck dissection

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10
Q

What questions should be asked regarding salivary gland lumps?

A
  1. Recurrent tenderness with meals? -> stones
  2. Persistent slow growing? -> tumour (i.e. pleomorphic adenoma)
  3. Rapid growth pain? -> malignant
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11
Q

What does bilateral lymphadenopathy look like on X-ray?

A

The well defined margins suggest that the peri-hilar shadows are most probably lymph nodes.

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12
Q

What differentials would you consider in someone with bilateral lymphadenopathy?

A
  1. Sarcoid
  2. TB
  3. Disseminated malignancies
  4. Glandular fever
  5. Lymphoma
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13
Q

What are the clinical features of tuberculous lymphadenopathy?

A

Tuberculous lymphadenopathy is usually a result of infection of the lymph nodes by the TB bacillus. In the Western world it is most commonly observed in immunocompromised patients (about 50% of cervical tuberculous lymphadenopathy). The majority of infections in adults are due to Mycobacterium tuberculosis and the rest are caused by atypical mycobacterium (e.g. Mycobacterium scrofulaceum - and there are several other strains) or nontuberculous mycobacterium (NTM). This pattern may be different in different age groups.

A chronic, painless mass in the neck is the most frequent presentation. It is referred to as a “cold abscess”, as typical features of inflammation (redness, warmth and pain) may be absent. With time the mass gets adherent to the overlying skin and may even rupture through the skin to form a chronic discharging sinus.
The lymph nodes feel quite different to the discrete, firm and rubbery nodes seen in patients with lymphoma.

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14
Q

What is the arrangement of malignant lymph nodes?

A

The above node clearly shows a metastatic deposit which has a papillary architecture (seen under low power). The nuclear structure within these papillary cells is abnormal (Best seen under higher magnification: nuclear inclusions, nuclear grooves, nuclear clearing, overlap of nuclear membranes/crowding) and these features suggest that this may be a secondary deposit from a papillary carcinoma - possibly from the thyroid gland. The lymph node has several germinal centers (left, top/right of image) and adipose tissue (fat) is seen at the edge of the image (bottom and left).

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15
Q

What are malignant lymphomas?

A

When the normal lymphoid structure is replaced by a collection of malignant cells. They can be divided into 2 groups:

  1. Hodgkins Lymphoma – characterised by the presence of Reid Sternberg cells (RS)
  2. Non Hodgkins Lymphoma -Characterised by diffuse or nodular abnormal lymphocytes.
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16
Q

How are Non-Hodgkin’s lymphomas graded?

A
  1. Indolent: slow growing and may not require treatment for a long time. They are likely to respond well to chemotherapy but are rarely cured.
    - i.e. Follicular lymphomas
  2. High-grade: these tumours grow quickly and are frequently symptomatic. They are more likely to be completely cured than low-grade lymphomas with chemotherapy.
    - I.e. diffuse large B-cell lymphomas + Burkitt lymphomas
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17
Q

What is characteristic of TB infecting lymph nodes?

A

Central caseation

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18
Q

What other organs are commonly involved in lymphomas?

A
  • Spleen
  • Liver
  • Bone marrow

Thus exam of the abdomen for hepato-splenomegaly is an integral part of the examination

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19
Q

How are lymphomas staged clinically?

A

Ann Arbour Staging = stages lymph node malignancy

Stage I: only 1 LN area
Stage II: 2+ LN ares same side of diaphragm
Stage III: LN both sides of diaphragm
Stage IV: multifocal involvement of an extranodal site
B = > 10% weight loss over 6mo, night sweats, unexplained fever
E = extra nodal disease at a single site with or without adjacent adenopathy

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20
Q

What do you understand by the term lymphomas?

How do lymphomas differ from lymphocytic leukaemias in their origins?

A

Lymphomas are malignancies that involve the lymphocytes.

Lymphocytes are present in the circulation, bone marrow, lymph nodes and other organs that form the reticulo-endothelial system such as the liver and spleen. Characteristically, lymphomas are solid tumours involving the lymph nodes and when there is involvement of other organs it is referred to as extra-nodal involvement. Extra-nodal involvement may even include remote sites such as the skin, brain, bowels and bone.

Lymphomas are closely related to lymphoid leukaemias, which originate in the marrow and therefore typically involves circulating lymphocytes. Lymphomas are a part of the broad spectrum of haematological malignancies.

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21
Q

How are lymphomas classified?

A
  1. Lymphomas may be broadly classified into Hodgkin’s lymphoma (after Thomas Hodgkin, a British Pathologist who published the first description of lymphoma in 1832), and non-Hodgkins lymphoma.
  2. “Non-Hodgkins lymphoma” is an umbrella term used to describe a range of lymphomas described since the time of Thomas Hodgkin. These “non-Hodgkins lymphomas” have little in common with each other and hence the term is gradually being abandoned in the scientific literature.
  3. In 1996 an attempt was made to classify Non-Hodgkin’s lymphomas into four grades : Low grade, Intermediate grade, High grade, and Miscellaneous based on their prognosis. This has now been superceded by newer classifications based on cell morphology and surface markers.
  4. Nevertheless, you will still hear haematologists refer to lymphomas as Hodgkin’s lymphomas and non-Hodgkins lymphomas, hence it is useful to understand these terms
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22
Q

What are Reed-Sternberg cells?

A

Reed–Sternberg cells are large cells that are either multinucleated cells or have bilobed nuclei. They are found under light microscopy in lymph node biopsies from patients with Hodgkin’s lymphoma. The cells typically have an “owls eye” appearance.

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23
Q

What do you understand by the term leukaemia?

A
  1. The term “leukaemia” refers to a malignant neoplastic process involving one of the white blood cell lines (neutrophils, lymphocytes, monocytes etc). Depending on the cell line that is affected it could be classified into Myeloid (neutrophils) or Lymphocytic (lymphocytes) leukaemias.
  2. In the acute forms of the leukaemias the peripheral blood film is dominated by the immature cells or blast cells and they will be referred to as acute “myeloblastic” or “lymphoblastic” leukaemias. Crowding of the bone marrow by such immature cells renders the marrow unable to produce healthy blood cells. The patient may therefore become anaemic and/or thrombocytopenic.
  3. In the more chronic forms of the illness more mature cells (neutrophils or lymphocytes) will be seen in excess numbers in the peripheral blood films and then the terms “chronic myeloid leukaemia” and “chronic lymphocytic leukaemias” will be used. These malignant cells - in spite of their large numbers, are still very abnormal cells.

Acute leukaemias (AML or ALL) are the most common forms of leukemia in children and young adults.

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24
Q

How are lymphomas graded?

A

In addition to staging, the histological sub-type of lymphoma is very important. The subtype determines the behaviour, treatment and prognosis of the lymphoma. There are a number of different subtypes of non hodgkins lymphoma but put simply they may be graded into high grade or indolent lymphomas based on the histology:

Indolent: These tumours grow slowly and may not require treatment for long periods. When they do need treatment they are likely to respond well to chemotherapy but they are very rarely cured. Follicular lymphomas are low-grade Non-Hodgkins Lymphomas.

High-grade: These tumours grow quickly and are frequently symptomatic. However, they are more likely to be completely cured than low-grade lymphomas with chemotherapy. Diffuse large B-cell lymphomas and Burkitt lymphomas are examples of high-grade Non Hodgkins lymphoma.

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25
Q

What other organs can be involved in lymphoma?

A
  • Spleen
  • Liver
  • Bone marrow

Thus examine for hepatosplenomegaly

26
Q

How are lymphomas staged clinically?

A

Ann Arbour Staging:

Stage 1 : One group of lymph nodes is affected.

Stage 2: Two or more groups of nodes are affected, but the lymphoma is restricted to one side of the diaphragm only

Stage 3: Lymphadenopathy is evident on both sides (above and below) of the diaphragm.

Stage 4: The lymphoma has spread beyond the lymph nodes to other organs such as the spleen, bone marrow, liver or lungs.

A = No systemic symptoms

B = Systemic symptoms (such as weight loss greater than 10% of body weight, fevers or night sweats).

27
Q
  1. What do you understand by the term lymphomas?

2. How do lymphomas differ from lymphocytic leukaemias in their origins?

A

Lymphomas are malignancies that involve the lymphocytes. Lymphocytes are present in the circulation, bone marrow, lymph nodes and other organs that form the reticulo-endothelial system such as the liver and spleen. Characteristically, lymphomas are solid tumours involving the lymph nodes and when there is involvement of other organs it is referred to as extra-nodal involvement. Extra-nodal involvement may even include remote sites such as the skin, brain, bowels and bone.

Lymphomas are closely related to lymphoid leukaemias, which originate in the marrow and therefore typically involves circulating lymphocytes. Lymphomas are a part of the broad spectrum of haematological malignancies.

28
Q

How are lymphomas classified?

A
  1. Lymphomas may be broadly classified into Hodgkin’s lymphoma (after Thomas Hodgkin, a British Pathologist who published the first description of lymphoma in 1832), and non-Hodgkins lymphoma.
  2. “Non-Hodgkins lymphoma” is an umbrella term used to describe a range of lymphomas described since the time of Thomas Hodgkin. These “non-Hodgkins lymphomas” have little in common with each other and hence the term is gradually being abandoned in the scientific literature.
  3. In 1996 an attempt was made to classify Non-Hodgkin’s lymphomas into four grades: Low grade, Intermediate grade, High grade, and Miscellaneous based on their prognosis. This has now been superceded by newer classifications based on cell morphology and surface markers.
  4. Nevertheless, you will still hear haematologists refer to lymphomas as Hodgkin’s lymphomas and non-Hodgkins lymphomas, hence it is useful to understand these terms
29
Q

What are Reed-Sternberg cells?

A

Reed–Sternberg cells are large cells that are either multinucleated cells or have bilobed nuclei. They are found under light microscopy in lymph node biopsies from patients with Hodgkin’s lymphoma. The cells typically have an “owls eye” appearance.

30
Q

What do you understand by the term leukaemia?

A
  1. The term “leukaemia” refers to a malignant neoplastic process involving one of the white blood cell lines (neutrophils, lymphocytes, monocytes etc). Depending on the cell line that is affected it could be classified into Myeloid (neutrophils) or Lymphocytic (lymphocytes) leukaemias.
  2. In the acute forms of the leukaemias the peripheral blood film is dominated by the immature cells or blast cells and they will be referred to as acute “myeloblastic” or “lymphoblastic” leukaemias. Crowding of the bone marrow by such immature cells renders the marrow unable to produce healthy blood cells. The patient may therefore become anaemic and/or thrombocytopenic.
  3. In the more chronic forms of the illness more mature cells (neutrophils or lymphocytes) will be seen in excess numbers in the peripheral blood films and then the terms “chronic myeloid leukaemia” and “chronic lymphocytic leukaemias” will be used. These malignant cells - in spite of their large numbers, are still very abnormal cells.

Acute leukaemias (AML or ALL) are the most common forms of leukemia in children and young adults.

31
Q

What options can be offered to deal with Amanda’s anxiety vis-a-vis her long term fertility issues?

A

A 25-year-old who receives standard ABVD chemotherapy for Hodgkin’s Lymphoma should recover her fertility however she should be counselled about preventing pregnancy during chemotherapy and for at least 6 months afterwards. The highest risk of relapse from Hodgkin’s Lymphoma is in the first 2 years and it often recommended to delay pregnancy until after this point to ensure no further treatment is required. In older patients or women who require more gonadotoxic chemotherapy they can be referred urgently to St Mary’s Fertility Hospital for counselling and egg or embryo storage if appropriate.

32
Q

What scan is used to determine the stage of lymphoma?

A

PET CT scan

33
Q

How does a PETCT scan help in diagnosis in malignancies (Select all that apply)?

A
  1. The radioactive sugar is taken up by metabolically active cells and so shows how widespread a cancer or lymphoma is
  2. The PETCT helps shows the difference between a reactive node and a malignant node
34
Q

What are the risk factors of lymphoma?

A
  1. Family history of Hodgkin’s lymphoma
  2. Immunosuppression (HIV, transplant)
  3. Infection (EBV)
35
Q

What are the side effects of lymphoma treatment?

A
  1. Increased risk of infection (decreased WBC - leukopenia)
  2. Period disturbance, fertility should return to normal
  3. Hair loss
36
Q

What is the survival rate of Hodgkin’s lymphoma?

A

80% are cured

After 5y the chance of recurrence is low

37
Q

What does the finding of purpura signify? What is the nature of these lesions?

A

Purpura is the appearance of non-blanching red spots on the skin. They are caused by small areas of bleeding under the skin. Usually purpura are < 1cm. Larger bleeds are referred to as echymoses.

38
Q

What differential diagnosis would you consider at this stage?

A

Many patients - particularly older people - presenting with purpuric/echymotic rashes may not have a demonstarble underlying pathology. In such patients these are generally manifestations of increasing skin fragility with age and blood vessels that bleed with relatively minor trauma. However in a younger subject sudden onset of gum bleeding/purpurae, echymoses etc. should raise the possibility of:

  1. TTP - thrombotic thrombocytopenic purpura
  2. HUS - haemolytic uraemic syndrome
  3. Infections: such as meningococcal sepsis
  4. Haematological malignancies: such as leukaemias

TTP (thrombotic thrombocytopenic purpura) and HUS (haemolytic uraemic syndrome) are two related conditions, of autoimmune origin, that should be considered in patients who present with purpura and urinary manifestations such as haematuria or oliguria. Always consider sepsis, particularly meningococcal sepsis, whenever you see a patient who presents with fever and a purpuric rash

39
Q

What are the acute and chronic long term complications associated with chemotherapy? How would you deal with them?

A
  1. Paraesthesia in the limbs (nerve problems)
  2. Fatigue/tiredness
  3. Decreased WBC count (leukopenia)
  4. Decreased platelet count (thrombocytopenia)
  5. Increased risk of infection
  6. Hearing problems
  7. Breathlessness/pallor (anemia)
  8. Nausea/change in appetite
  9. Increased risk of DVT, heart/kidney/liver problems
  10. Decreased fertility during treatment
  11. Hair loss
  12. Cognitive impairment

Ask your doctor or specialist nurse about the drugs you are having if you are worried about long term effects from your treatment.

40
Q

What is the pathophysiology of non-Hodgkin’s Lymphoma?

A

Malignancy of B lymphocytes (diffuse large B cell lymphoma -> most common type of NHL)

Affects young patients (15-40y)

41
Q

What are the symptoms of Non-Hodgkin’s lymphoma?

A

B symptoms:

  • Drenching night sweats every night for weeks
  • Weight loss
42
Q

What is an important prognostic factor for Non-Hodgkin’s Lymphoma?

A

LDH (lactate dehydrogenase)

43
Q

What are the investigations ordered for someone with suspected NHL?

A
  1. Bloods (LDH)
  2. PET CT scan
  3. Bone marrow biopsy
44
Q

What is neutropenic sepsis?

A

Neutropenic sepsis is when a patient with a low level of neutrophils gets an infection which they can’t fight off and become septic. If they don’t receive urgent medical treatment, they will die from overwhelming infection.

It is common 10 days following chemotherapy from lymphoma in someone who has new pyrexia

45
Q

How are lymphomas treated?

A

Chemotherapy (CHOP chemo) + immunotherapy (rituximab targets CD20)

CHOP:

  • cyclophosphamide
  • doxorubicin
  • vincristine
  • prednisone
46
Q

What is the prognosis of someone with NHL?

A

50% survival

47
Q

What are the features of follicular NHL?

A
  • Indolent
  • Responds well to treatment
  • Recurrent relapses (“incurable”)
  • Median survival = 10y (50% will be arrive 10y after diagnosis)
48
Q

How is follicular NHL treated?

A

Radiotherapy to shrink lymph nodes

49
Q

Most NHL are B cell lymphomas, but what is the pathophysiology of T cell lymphomas?

A
  • Initial benign condition (psoriasis, eczema)

- Cutaneous T cell lymphoma of the skin

50
Q

What is multiple myeloma?

A

Multiple myeloma is a malignancy arising from plasma cells. Plasma cells are a type of white blood cells that are normally responsible for antibody production in response to an infection.

Proliferating nests of plasma cells may form deposits in bones, where they typically cause osteolytic lesions on x-ray. In the bone marrow proliferation of plasma cells result in reduced erythropoesis and reduced production of platelets (thereby causing anaemia and thrombocytopaenia).

Myeloma cells produce various paraproteins that may be detected in plasma (by plasma electrophoresis) or even in the urine.

Hypercalcaemia and bone pain are frequent additional features of myelomas.

Persistent back pain in an older subject - particularly when associated with anaemia and hypercalcaemia, should raise the suspicion of multiple myeloma

51
Q

What are Bence-Jones proteins?

A

Bence Jones proteins are monoclonal globulins that may be detected in urine in patients with multiple myeloma.

Presence of Bence Jones proteins in the urine is suggestive of multiple myeloma in the context of other significant clinical features such as lytic bony lesions on x-ray, anaemia or the presence of increased numbers of plasma cells in the bone marrow aspirate.

Bence Jones proteins are present in approximately 60% of patients with multiple myeloma.

52
Q

What are the findings on xray in a person with multiple myeloma?

A

Punched out osteolytic lesions

53
Q

Why do multiple myeloma patients develop anaemia, thrombocytopenia and leukopenia?

A

The entire marrow is packed with the malignant myeloma cells. This leaves very little room for other cell types to proliferate and mature

54
Q

What is radiotherapy?

A

Radiotherapy is the use of ionising radiation to treat malignant disease.

It preferentially treats dividing cells and can be targeted to include the tumour and avoid normal tissue.

55
Q

Patients with Hodgkins Lymphoma are highly likely to be cured so what other issues may be important for Amanda in the future?

A

Late side-effects of treatment. These can involve the risk of second cancers and cardiac or hormonal problems depending on what treatments patients had.

In addition, psychological problems (worry of cancer returning)

56
Q

What advice should a patient be given after being treated for lymphoma?

A

Smoking cessation

  • Lung cancer is increased in patients with Hodgkins lymphoma who were treated with chemotherapy and radiotherapy.
  • This risk is increased by 20x in smokers
  • Smoking will also increase her risk of future cardiac problems.
  • Her oncologist will also advise her if she requires any other screening tests dependant on her previous treatment.
57
Q

What is the most common haematological malignancy in the UK?

A

Non-Hodgkin’s Lymphoma

58
Q

What factors are important in the choice of chemotherapy in a 30 year old man with lymphoma?

A
  1. Patient’s wishes
  2. Past medical history
  3. Histology
59
Q

What factors have been shown to be strongly associated with development of haematological malignancies?

A
  1. Reduced immunity
  2. Unknown
  3. Previous treatment of cancer
    (Specifically alkylating chemotherapy is known to increase the risk of leukaemia from 2 years post treatment with the highest risk at 5-10 years.)
  4. Infection
60
Q

Which of the following may occur as a side-effect of treatment for a haematological malignancy?

A
  1. Alopecia (hair loss)
  2. Neutropenic sepsis (typically occurs 7-14d post chemo)
  3. Heart problems (anthracyclines -> arrhythmias + HF)
  4. Secondary malignancies (lung + breast cancer)
  5. Infertility (sperm banking + oocyte cyro-preservation offered)
61
Q

Which 3 leukemias/lymphomas can be cured?

A
  1. Acute myeloid leukemia
  2. Classical Hodgkin’s lymphoma
  3. Diffuse large B cell lymphoma

Year 3 TCDs (24 decks)

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