haem onc 2 Flashcards

Question

What are the symptoms of hereditary angioedema?

Answer 1

attacks may be proceeded by painful macular rash painless, non-pruritic swelling of subcutaneous/submucosal tissues may affect upper airways, skin or abdominal organs (can occasionally present as abdominal pain due to visceral oedema) urticaria is not usually a feature

Answer 2

high grade B cell neoplasm

Answer 3

endemic (African) form: typically involves maxilla or mandible sporadic form: abdominal (e.g. ileo-caecal) tumours are the most common form. More common in patients with HIV

Answer 4

Burkitt's lymphoma is associated with the c-myc gene translocation, usually t(8:14).

Answer 5

Starry sky appearance

Answer 6

Rasburicase (a recombinant version of urate oxidase, an enzyme which catalyses the conversion of uric acid to allantoin*) is often given before the chemotherapy to reduce the risk of this occurring

Answer 7

hyperkalaemia hyperphosphataemia hypocalcaemia hyperuricaemia acute renal failure

Answer 8

pernicious anaemia: most common cause post gastrectomy vegan diet or a poor diet disorders/surgery of terminal ileum (site of absorption) Crohn's: either diease activity or following ileocaecal resection metformin (rare)

Answer 9

if no neurological involvement 1 mg of IM hydroxocobalamin 3 times each week for 2 weeks, then once every 3 months if a patient is also deficient in folic acid then it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

Answer 10

it is important to treat the B12 deficiency first to avoid precipitating subacute combined degeneration of the cord

Answer 11

Gain of function polymorphisms * factor V Leiden (activated protein C resistance): most common cause of thrombophilia * prothrombin gene mutation: second most common cause Deficiencies of naturally occurring anticoagulants * antithrombin III deficiency * protein C deficiency * protein S deficiency

Answer 12

Antiphospholipid syndrome Drugs the combined oral contraceptive pill

Answer 13

A monoclonal proliferation of well-differentiated lymphocytes, almost always B-cells (99%)

Answer 14

Chronic lymphocytic leukaemia (CLL)

Answer 15

* Often none * Anorexia * Weight loss * Bleeding * Infections * Lymphadenopathy more marked than chronic myeloid leukaemia

Answer 16

Lymphocytosis anaemia: may occur either due to bone marrow replacement or autoimmune hemolytic anaemia (AIHA) thrombocytopenia: may occur either due to bone marrow replacement or immune thrombocytopenia (ITP)

Answer 17

Smudge cells (smear cells)

Answer 18

Immunophenotyping

Answer 19

* CD5 * CD19 * CD20 * CD23

Answer 20

exact cause not known genetics - most common genetic change is the deletion in chromosome 13, but other chromosomes such as 11 and 17 can also be affected. Fam History - 6- to 9-fold increased risk for first degree relatives of CLL patients. Imuunology. - People with low immunity due to HIV or AIDS are three times more likely than the general population to develop leukaemia.

Answer 21

Chronic lymphocytic leukaemia (CLL) is a neoplastic disorder characterised by the progressive accumulation of functionally incompetent lymphocytes, which are monoclonal in origin. The pathogenesis of CLL involves a stepwise progression that begins with the development of a monoclonal B-cell lymphocytosis, followed by clonal expansion and eventual evolution into clinically apparent disease. The initial event in the pathogenesis of CLL is thought to be a genetic mutation in a single B-lymphocyte progenitor cell. This mutation confers a survival advantage on the cell, leading to the development of monoclonal B-cell lymphocytosis (MBL), a pre-leukaemic condition characterised by low levels of circulating monoclonal B cells. MBL can exist for many years without progressing to CLL.

Answer 22

* The most common genetic abnormalities associated with CLL include deletion 13q (del[13q]), trisomy 12, deletion 11q (del[11q]) and deletion 17p (del[17p]). These genetic changes are often detected at diagnosis and can provide prognostic information. * Another key event in the pathogenesis of CLL is the dysregulation of apoptosis, or programmed cell death. In normal lymphocytes, apoptosis serves as a mechanism to remove aged or damaged cells. However, in CLL, apoptotic pathways are disrupted resulting in an overaccumulation of these abnormal cells. * A further contributor to disease progression is microenvironment interaction. The tumour microenvironment plays an important role in promoting survival and proliferation of malignant B cells. Signals from stromal cells within lymphoid tissues can protect CLL cells from spontaneous and drug-induced apoptosis.

Answer 23

It's important to note that not all patients with MBL will progress to CLL, and the rate at which this occurs can vary widely. Some patients may remain in a stable MBL phase for many years, while others may rapidly progress to symptomatic disease. This variability is likely due to differences in underlying genetic abnormalities and microenvironment interactions.

Answer 24

B Symptoms Fatugue Lymphadenopathy - painless, usually symmetrical Hepatosplenomegaly Bone marrow failure: As CLL progresses, bone marrow infiltration can lead to cytopenias including anaemia, thrombocytopenia and neutropenia resulting in fatigue, increased bleeding tendency and susceptibility to infections respectively.

Answer 25

Autoimmune haemolytic anaemia (AIHA): This is characterised by destruction of red blood cells by autoantibodies. Patients may present with symptoms of anaemia such as fatigue, pallor and jaundice. Immune thrombocytopenia (ITP): Here, autoantibodies destroy platelets leading to thrombocytopenia. This may result in easy bruising, petechiae or more serious bleeding complications.

Answer 26

due to hypogammaglobulinaemia and neutropenia associated with CLL. Infections commonly involve the respiratory tract but can also include herpes zoster reactivation.

Answer 27

Richter's transformation, although rare, is a serious complication where CLL transforms into an aggressive lymphoma. Patients may present with rapidly enlarging lymph nodes, splenomegaly and B symptoms.

Answer 28

* Mantle cell lymphoma It is a type of non-Hodgkin's lymphoma which is very similar to CLL, but more aggressive. Mantle cell lymphoma expresses CD5 but not CD23 antigen, which is expressed in CLL. * Marginal zone lymphoma It has a similar presentation and immunophenotype as CLL, but typically has a bright surface immunoglobulin and CD20, and bone marrow examination often reveals lymphocytes with notched nuclei. * B-cell pro-lymphocytic leukemia It is a very rare and typically aggressive malignancy and has similar clinical features as CLL. Circulating cells are greater than 55% pro-lymphocytes that are often CD5 negative. * Lymphoplasmacytic lymphoma CLL and lymphoplasmacytic lymphoma are lymphoproliferative disorders with similar presentation. However, the later can also manifest as hyperviscosity syndrome associated with macroglobulinemia, where the clinical picture varies. | *

Answer 29

The Binet staging system is commonly used in the UK for CLL staging and it has 3 stages. Stage A: Hb at least 10 g/dL, platelets at least 100 x 109/L, and fewer than three lymph node areas involved. Stage B: Hb and platelet levels as in stage A and three or more lymph node areas involved. Stage C: Hb <10 g/dL, platelets <100 x 109/L, or both.

Answer 30

watch and wait in early disease with no symptoms Chemotherapy should only be given to patients with active, symptomatic disease

Answer 31

Evidence of progressive marrow failure Massive or progressive or symptomatic splenomegaly Massive or progressive or symptomatic lymphadenopathy Progressive lymphocytosis with an increase of more than 50% over a 2-month period Lymphocyte doubling time of less than 6 months Autoimmune anaemia or thrombocytopenia not responding to prednisolone One or more of the following CLL-related symptoms or signs such as Night sweats High fever Extreme fatigue Unintentional weight loss >10%

Answer 32

Tamoxifen is a SERM which acts as an oestrogen receptor antagonist and partial agonist. It is used in the management of oestrogen receptor-positive breast cancer.

Answer 33

menstrual disturbance: vaginal bleeding, amenorrhoea hot flushes - 3% of patients stop taking tamoxifen due to climacteric side-effects venous thromboembolism endometrial cancer

Answer 34

Anastrozole and letrozole are aromatase inhibitors that reduces peripheral oestrogen synthesis. This is important as aromatisation accounts for the majority of oestrogen production in postmenopausal women and therefore anastrozole is used for ER +ve breast cancer in this group.

Answer 35

osteoporosis NICE recommends a DEXA scan when initiating a patient on aromatase inhibitors for breast cancer hot flushes arthralgia, myalgia insomnia

Answer 36

BRAC2 ## Footnote This mutation is more common in those with Ashkenazi Jewish heritage.

Answer 37

Autosomal dominant Consists of germline mutations to p53 tumour suppressor gene High incidence of malignancies particularly sarcomas and leukaemias Diagnosed when: *Individual develops sarcoma under 45 years *First degree relative diagnosed with any cancer below age 45 years and another family member develops malignancy under 45 years or sarcoma at any age

Answer 38

Carried on chromosome 17 (BRCA 1) and Chromosome 13 (BRCA 2)

Answer 39

Associated risk of developing ovarian cancer (55% with BRCA 1 and 25% with BRCA 2).

Answer 40

Autosomal dominant Develop colonic cancer and endometrial cancer at young age 80% of affected individuals will get colonic and/ or endometrial cancer High risk individuals may be identified using the Amsterdam criteria

Answer 41

Autosomal dominant familial colorectal polyposis Multiple colonic polyps Extra colonic diseases include: skull osteoma, thyroid cancer and epidermoid cysts Desmoid tumours are seen in 15% Mutation of APC gene located on chromosome 5 Due to colonic polyps most patients will undergo colectomy to reduce risk of colorectal cancer Now considered a variant of familial adenomatous polyposis coli

Answer 42

Subtypes 16,18 & 33 are particularly carcinogenic.

Answer 43

HPV viruses 16 and 18 produces oncoproteins which causes inhibition of tumour suppressor genes causes cervila carcinoma?

Answer 44

Infected endocervical cells may undergo changes resulting in the development of koilocytes. These have the following characteristics: enlarged nucleus irregular nuclear membrane contour the nucleus stains darker than normal (hyperchromasia) a perinuclear halo may be seen

Answer 45

sepsis trauma obstetric complications e.g. aminiotic fluid embolism or hemolysis, elevated liver function tests, and low platelets (HELLP syndrome) malignancy

Answer 46

A typical blood picture includes: ↓ platelets ↓ fibrinogen ↑ PT & APTT ↑ fibrinogen degradation products schistocytes due to microangiopathic haemolytic anaemia

Answer 47

a malignant disease of the bone marrow that arises from myeloid cell lines The immature cells, arrested in early stages of development, are released into the blood and impair normal haematopoiesis causing anaemia, bleeding, and infections.

Answer 48

AML median age of onset in 65 years

Answer 49

* Genetic Factors: Chromosomal abnormalities such as translocations (e.g., t(8;21), t(15;17), and t(9;11)) Gene mutations impacting cell proliferation and apoptosis, including FLT3, NPM1, and CEBPA * Environmental Exposures: Previous chemotherapy or radiation therapy, termed therapy-related AML Exposure to benzene and other petrochemicals Radiation exposure, notably ionising radiation * Haematological Disorders: Antecedent haematologic disorders like myelodysplastic syndromes and myeloproliferative neoplasms predisposing to secondary AML * Genetic Syndromes: Conditions such as Down syndrome, Fanconi anaemia, and Li-Fraumeni syndrome associated with increased AML risk

Answer 50

AML arises due to the acquisition of genetic mutations in haematopoietic progenitor cells that disrupt normal cell proliferation and differentiation. This disruption results in the accumulation of immature cells, known as blasts, in the bone marrow and peripheral blood, leading to bone marrow failure.

Answer 51

First hit: The pathogenesis of AML often begins with a 'first hit' mutation that confers a proliferative advantage to a haematopoietic stem cell. This leads to clonal expansion of this cell and its progeny. Common 'first hit' mutations occur in genes such as FLT3, NPM1, or DNMT3A. Second hit: A 'second hit' mutation subsequently occurs in one of the clonally expanded cells, affecting a gene involved in haematopoietic differentiation, such as RUNX1 or CEBPA. This 'second hit' mutation further promotes proliferation and blocks differentiation, leading to the accumulation of immature blasts. Blast accumulation: The accumulation of immature blasts in the bone marrow leads to bone marrow failure due to the suppression of normal haematopoiesis. This can present clinically as anaemia, thrombocytopenia, or neutropenia. Invasion of other organs: As the disease progresses, the leukaemic blasts can invade other organs, such as the spleen, liver, and central nervous system, leading to organomegaly and other clinical manifestations.

Answer 52

AML with recurrent genetic abnormalities AML with myelodysplasia-related features Therapy-related AML and MDS AML, not otherwise specified Myeloid sarcoma Myeloid proliferations related to Down syndrome

Answer 53

French-American-British (FAB) M0: Acute myeloblastic leukaemia without maturation M1: Acute myeloblastic leukaemia with minimal granulocyte maturation M2: Acute myeloblastic leukaemia with granulocyte maturation M3: Acute promyelocytic leukaemia (APL) M4: Acute myelomonocytic leukaemia M5: Acute monocytic leukaemia M6: Acute erythroid leukaemia M7: Acute megakaryoblastic leukaemia

Answer 54

anaemia: pallor, lethargy, weakness neutropenia: whilst white cell counts may be very high, functioning neutrophil levels may be low leading to frequent infections etc thrombocytopenia: bleeding splenomegaly bone pain

Answer 55

mmature leucocytes predisposes to frequent infections.

Answer 56

Normocytic, normochromic anaemia Thrombocytopenia Leucocyte count: maybe low, normal, or raised.

Answer 57

Raised myeloblasts: myeloblasts are immature cells with large nuclei, usually with prominent nucleoli, and pale blue cytoplasm with Wright Giemsa stain. Auer rods: Pink/red, rod-shaped cytoplasmic granular inclusions. Myeloperoxidase positive. Pathognomonic of myeloblasts. Mostly seen with acute promyelocytic leukaemia.

Answer 58

≥ 20% myeloblasts in the bone marrow confirm the diagnosis

Answer 59

AML must be distinguished from other haematologic malignancies with shared clinical features. Acute lymphocytic leukaemia: Similarities: clinical features are mostly similar (fever, anaemia, thrombocytopenia, infections). Differences: no Auer rods, lymphoblasts, myeloperoxidase negative, terminal deoxynucleotidyl transferase (TdT) positive. Myelodysplastic syndrome Similarities: anaemia, thrombocytopenia, infections Differences: blasts (< 20%), pseudo-Pelger-Huet abnormality (neutrophils with bilobed nuclei) Myeloproliferative neoplasms: Similarities: infections, abnormalities in different cell lines Differences: JAK2 mutation, thrombocytosis. Chronic myeloid leukaemia in blast crisis Similarities; anaemia, thrombocytopenia, infections Differences: Philadelphia chromosome or t (9:22), raised matured cells (myelocytes)

Answer 60

A distinct form of AML that represents a medical emergency APML, the M3 subtype of AML The importance of identifying APML lies in both the presentation (classically disseminated intravascular coagulation) and management.

Answer 61

APML is associated with the t(15;17) translocation which causes fusion of the PML and RAR-alpha genes.

Answer 62

Features presents younger than other types of AML (average = 25 years old) DIC or thrombocytopenia often at presentation good prognosis

Answer 63

APML is treated with all-trans retinoic acid (ATRA) to force immature granulocytes into maturation to resolve a blast crisis prior to more definitive chemotherapy.

Answer 64

The ECOG score is a 'performance status' scale, or a score that measures the functional status a patient. It is used to decide if a patient is a good or poor candidate for future oncological therapies. Those with a poor functional status is a poor candidate for further chemotherapy.

Answer 65

an IgE-mediated hypersensitivity reaction to specific raw, plant-based foods including fruits, vegetables, nuts and certain spices. ## Footnote This hypersensitivity reaction is initiated by cross-reaction with a non-food allergen, most commonly birch pollen whereby the protein in the food is similar but not identical in structure to the original allergen. This explains why OAS is strongly linked with pollen allergies and presents with seasonal variation. It also explains why cooking culprit food, and thereby denaturing the proteins, prevents symptoms occurring.

Answer 66

It typically presents with mild tingling or pruritus of the lips, tongue and mouth

Answer 67

A food allergy is caused by direct sensitivity to a protein present in food. OAS is caused by cross-sensitisation to a structurally similar allergen present in pollen. Non plant foods do not cause OAS because there are no cross reactive allergens in pollen which would be structually similar to meat. Food allergies are more likely to cause systemic symptoms (vomiting and diarrhoea) and are more likely to lead to anaphylaxis because the allergens are not readily broken down. The symptoms of OAS are normally limited to the oropharynx because the proteins that cause the symptoms are denatured by stomach enzymes.

Answer 68

OAS should be suspected in patients with a history of seasonal allergy symptoms (rhinitis, conjunctivitis and asthma) who present with symptoms minutes after eating a specific raw food. Itching and tingling of the lips, tongue and mouth are the most common symptoms Mild swelling and redness of the lips, tongue and throat may occur. In severe cases, patients develop nausea and vomiting. Symptoms fully resolve within one hour of contact. Anaphylaxis is a very rare complication.

Answer 69

Markedly elevated white cell count with almost all being lymphocytes, which is more characteristic of CLL Smudge cells seen on blood film Invesitgaiton of Choice Immunophenotyping with flow cytometry

Answer 70

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the commonest red blood cell enzyme defect

Answer 71

x-linked recessive

Answer 72

G6PD is the first step in the pentose phosphate pathway, which converts glucose-6-phosphate→ 6-phosphogluconolactone this reaction also results in nicotinamide adenine dinucleotide phosphate (NADP) → NADPH i.e. glucose-6-phosphate + NADP → 6-phosphogluconolactone + NADPH NADPH is important for converting oxidizied glutathine back to it's reduced form reduced glutathine protects red blood cells from oxidative damage by oxidants such as superoxide anion (O2-) and hydrogen peroxide ↓ G6PD → ↓ reduced NADPH → ↓ reduced glutathione → increased red cell susceptibility to oxidative stress

Answer 73

neonatal jaundice is often seen intravascular haemolysis gallstones are common splenomegaly may be present Heinz bodies on blood films. Bite and blister cells may also be seen

Answer 74

Diagnosis is made by using a G6PD enzyme assay levels should be checked around 3 months after an acute episode of hemolysis, RBCs with the most severely reduced G6PD activity will have hemolysed → reduced G6PD activity → not be measured in the assay → false negative results

Answer 75

anti-malarials: primaquine ciprofloxacin sulph- group drugs: sulphonamides, sulphasalazine, sulfonylureas

Answer 76

thrombotic, 'vaso-occlusive', 'painful crises' acute chest syndrome anaemic aplastic sequestration infection

Answer 77

also known as painful crises or vaso-occlusive crises precipitated by infection, dehydration, deoxygenation (e.g. high altitude) painful vaso-occlusive crises should be diagnosed clinically - there isn't one test that can confirm them although tests may be done to exclude other complications infarcts occur in various organs including the bones (e.g. avascular necrosis of hip, hand-foot syndrome in children, lungs, spleen and brain

Answer 78

vaso-occlusion within the pulmonary microvasculature → infarction in the lung parenchyma dyspnoea, chest pain, pulmonary infiltrates on chest x-ray, low pO2 management pain relief respiratory support e.g. oxygen therapy antibiotics: infection may precipitate acute chest syndrome and the clinical findings (respiratory symptoms with pulmonary infiltrates) can be difficult to distinguish from pneumonia transfusion: improves oxygenation the most common cause of death after childhood

Answer 79

caused by infection with parvovirus sudden fall in haemoglobin bone marrow suppression causes a reduced reticulocyte count

Answer 80

sickling within organs such as the spleen or lungs causes pooling of blood with worsening of the anaemia associated with an increased reticulocyte count

Answer 81

Sideroblastic anaemia is a condition where red cells fail to completely form haem, whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus called a ring sideroblast. It may be congenital or acquired.

Answer 82

Congenital cause: delta-aminolevulinate synthase-2 deficiency Acquired causes myelodysplasia alcohol lead anti-TB medications

Answer 83

supportive treat any underlying cause pyridoxine may help

Answer 84

full blood count hypochromic microcytic anaemia (more so in congenital) iron studies high ferritin high iron high transferrin saturation blood film basophilic stippling of red blood cells bone marrow Prussian blue staining will show ringed sideroblasts

Answer 85

Management no antibiotics - may worsen outcome plasma exchange is the treatment of choice steroids, immunosuppressants vincristine

Answer 86

Lead poisoning results in defective ferrochelatase and ALA dehydratase function.

Answer 87

the blood lead level is usually used for diagnosis. Levels greater than 10 mcg/dl are considered significant FBC - microcytic anaemia. Blood film shows red cell abnormalities including basophilic stippling and clover-leaf morphology raised serum and urine levels of delta aminolaevulinic acid may be seen making it sometimes difficult to differentiate from acute intermittent porphyria urinary coproporphyrin is also increased (urinary porphobilinogen and uroporphyrin levels are normal to slightly increased) in children, lead can accumulate in the metaphysis of the bones although x-rays are not part of the standard work-up

Answer 88

Low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Recurrent chest infections. May also predispose to autoimmune disorders and lymphona

Answer 89

Methaemoglobinaemia describes haemoglobin which has been oxidised from Fe2+ to Fe3+. This is normally regulated by NADH methaemoglobin reductase, which transfers electrons from NADH to methaemoglobin resulting in the reduction of methaemoglobin to haemoglobin. There is tissue hypoxia as Fe3+ cannot bind oxygen, and hence the oxidation dissociation curve is moved to the left

Answer 90

Fe3+ cannot bind oxygen, leading to tissue hypoxia.

Answer 91

The oxidation dissociation curve is moved to the left.

Answer 92

* haemoglobin chain variants: HbM, HbH * NADH methaemoglobin reductase deficiency.

Answer 93

* drugs: sulphonamides, nitrates (e.g. amyl nitrite), dapsone, sodium nitroprusside, primaquine * chemicals: aniline dyes.

Answer 94

* 'chocolate' cyanosis * dyspnoea * anxiety * headache * severe: acidosis, arrhythmias, seizures, coma * normal pO2 but decreased oxygen saturation.

Answer 95

Ascorbic acid.

Answer 96

IV methylthioninium chloride (methylene blue).

Answer 97

Thymomas are the most common tumour of the anterior mediastinum and is usually detected between the sixth and seventh decades of life.

Answer 98

myasthenia gravis (30-40% of patients with thymoma) red cell aplasia dermatomyositis also : SLE, SIADH

Answer 99

compression of airway cardiac tamponade

Answer 100

Polycythaemia vera (previously called polycythaemia rubra vera) is a myeloproliferative disorder caused by clonal proliferation of a marrow stem cell leading to an increase in red cell volume, often accompanied by overproduction of neutrophils and platelets.

Answer 101

t has recently been established that a mutation in JAK2 is present in approximately 95% of patients with polycythaemia vera

Answer 102

pruritus, typically after a hot bath splenomegaly hypertension hyperviscosity arterial thrombosis venous thrombosis haemorrhage (secondary to abnormal platelet function) low ESR

Answer 103

full blood count/film (raised haematocrit; neutrophils, basophils, platelets raised in half of patients) JAK2 mutation serum ferritin renal and liver function tests

Answer 104

It has a peak incidence in the sixth decade, with typical features including hyperviscosity, pruritus and splenomegaly.

Answer 105

aspirin reduces the risk of thrombotic events venesection first-line treatment to keep the haemoglobin in the normal range chemotherapy hydroxyurea - slight increased risk of secondary leukaemia phosphorus-32 therapy

Answer 106

thrombotic events are a significant cause of morbidity and mortality 5-15% of patients progress to myelofibrosis 5-15% of patients progress to acute leukaemia (risk increased with chemotherapy treatment)

Answer 107

Combined B- and T-cell disorders: SCID WAS ataxic (SCID, Wiskott-Aldrich syndrome, ataxic telangiectasia)

Answer 108

Desmopressiin -raises levels of vWF by inducing release of vWF from Weibel-Palade bodies in endothelial cells

Answer 109

penicillins cephalosporins macrolides tetracyclines trimethoprim

Answer 110

Platelets are stored at room temperature, which increases the risk of bacterial proliferation. Common contaminants include Staphylococcus epidermidis and Bacillus cereus. Clinical impact: Bacterial contamination of platelets is more likely to lead to rapid onset of sepsis and septic shock, given the optimal growth conditions during storage.

Answer 111

Factor V Leiden is the commonest inherited thrombophilia