Path - Haematology Flashcards
Infection with which virus is associated specifically with adult T-cell leukaemia/lymphoma?
A. HPV B. HIV C. Epstein-Barr virus D. HTLV1 E. Human herpes virus 8
D. HTLV1
Particularly prevalent in the Caribbean and Japan
Hyper-lobated nuclei may be seen - flower cells
A 45 year-old male presents to his GP with a 3 week history of sore throat. He has recently had an episode of shingles. His EBV IgG serology is positive, and an FBC shows a lymphocytosis. The blood film shows normal mature lymphocytes. Flow cytometry is carried out and reveals 82% of the proliferated lymphocytes express kappa chains, and 0% express lambda chains.
What is the most likely diagnosis?
A. Viral pharyngitis B. Acute lymphoblastic lymphoma C. B-cell lymphoma D. Adult T-cell leukaemia/lymphoma E. Infectious mononucleosis
C. B-cell lymphoma
Though parts of this case sound as though they describe a normal response to infection, the flow cytometry shows light chain restriction - an indicator of monoclonal B-cell proliferation. This excludes infectious causes, as well as T-cell malignancy. The blood film features only mature cells, which excludes a lymphoblastic leukaemia.
The positive IgG result is significant because it implies past infection with Epstein-Barr virus, which increases the risk of many haematological malignancies, including B-cell lymphomas.
A 29 year-old woman presents with fatigue, weight loss, fever, and night sweats of one month duration. Lymphoma is diagnosed, and PET scanning reveals involvement of cervical, axillary and mesenteric lymph nodes, and of the spleen.
What would the staging of this cancer be?
A. Stage 2b B. Stage 3a C. Stage 3b D. Stage 4a E. Stage 4b
C. Stage 3b
Stage 1 - one group of lymph nodes affected
Stage 2 - >one group of lymph nodes affected, but above the diaphragm
Stage 3 - spread below the diaphragm
Stage 4 - spread outside the lymph nodes/ spleen
Either ‘a’ or ‘b’ is then added as a suffix: if there are one or more constitutional symptoms present (fever, weight loss, night sweats) then a ‘b’ is added, if not an ‘a’ is used
NB: for purposes of staging, the spleen is counted as a lymph node
A patient presents with epigastric pain which is particularly pronounced at mealtimes, as well as dark, offensive-smelling stools. An ODG reveals a peptic ulcer, and a stool antigen test reveals the presence of H. pylori.
Which cancer is this man at increased risk of due to chronic infection with H. pylori?
A. Enteropathy-associated T-cell Non-Hodgkin lymphoma
B. Marginal zone lyphoma of the parotid gland
C. Gastric MALT lymphoma
D. Gastric carcinoma
E. Adult T-cell leukaemia/lyphoma
C. Gastric MALT lymphoma
H. pylori is not only strongly associated with gastric ulcers, chronic infection can cause gastric MALT lymphoma. However this is a low grade lymphoma, and treatment usually centres on eradicating the H. pylori infection, as the lymphoma will often resolve once that stimulus is removed.
Which of the following stains would be useful in detecting hepatic siderosis?
A. Ziehl-Neelson B. Prussian blue C. Sudan black D. Congo red E. Rhodamine
B. Prussian blue
Also known as Perl’s stain, Prussian blue is commonly used to detect iron, e.g. in hepatic siderosis (iron acucmulation in the liver).
Which of the following is the most aggressive form of lymphoma?
A. Diffuse large B-cell lymphoma B. Follicular lymphoma C. Marginal zone lymphoma D. Burkitt's lymphoma E. Mantle cell lymphoma
D. Burkitt’s lymphoma
Burkitt’s lymphoma is the most aggressive of the lymphomas here. Burkitt’s lymphoma may produce a amass in the abdomen or jaw and is associated with younger patients. A ‘starry sky’ appearance on histopathology is pathognomic of Burkitt’s lymphoma.
Mantle-cell lymphomas and diffuse large B-cell lymphoma are also aggressive, Mantle-cell lymphoma typically over expresses cyclin D1. It presents in older patients, and is often widespread at the time of presentation, hence prognosis is poor.
Marginal zone lyphomas and follicular lymphomas are low-grade
Marginal zone lymphomas often arise at extra-nodal sites and are associated with specific diseases: gastric MALT lymphoma - H. pylori infection, thyroid marginal zone lymphoma - Hashimoto’s disease, parotid marginal zone lymphoma - Sjogren’s disease.
A blood film shows scattered tingible-body macrophages (macrophages filled with apoptotic remains) on a background of lymphoblasts.
What is the most likely cause of this histological appearance?
A. Acute lymphoblastic leukaemia B. Chronic lymphocytic leukaemia C. Sarcoidosis D. Burkitt's lymphoma E. Hodgkin's lymphoma
D. Burkitt’s lymphoma
This is a description of the classic ‘starry sky’ appearance of Burkitt’s lymphoma - a highly aggressive yet often very treatable cancer associated with Epstein-Barr virus infection which is more common in the developing world.
Burkitt’s lymphoma is an acute B-cell lymphoblastic lymphoma, and the lymphoblasts are tightly grouped together. These are stained blue which creates the appearance of the ‘sky’, whilst the presence of macrophages filled with debris from apoptosed tumour cells (tingible-body macrophages) creates the appearance of the ‘stars’, as upon fixation of the sample the cytoplasm of macrophages is lost leaving white gaps.
A patient presents with lympahdenopathy, fever, and fatigue. They have a previous history of EBV infection.
What would suggest a diagnosis of non-Hodgkin lymphoma rather than Hodgkin lymphoma?
A. Lymph nodes in both the groin and anterior cervical chain affected
B. Bence-Jones proteins in the urine
C. Lymph nodes in both the anterior cervical and sub-mandibular chains affected
D. Reed-Sternberg cells seen on histopathology
E. Previous history of infectious mononucleosis
A. Lymph nodes in both the groin and anterior cervical chain affected
Non-Hodgkin lymphoma more frequently features involvement of multiple groups of lymph nodes, and they are more likely to be in discontiguous groups.
Age is often a useful clue in differentiating between the two diseases, as Hodgkin’s lymphoma has a bimodal peak affecting both young and old patients, wheres Non-Hodgkin lymphoma favours older patients only.
What is the mechanism driving proliferation in CML?
A. Loss of chromosomes (hypodiploidy)
B. Inappropriate activation of retinoic acid receptors
C. Transcription factor mutation
D. Inappropriate activitation of tyrosine kinase
E. Addition of chromosomes (hyperdiploidy)
D. Inappropriate activation of tyrosine kinase
CML is caused by a 9, 22 translocation leading to formation of the Philadelphia chromosome. The Abl gene encodes a tyrosine kinase protein. When the 9-22 translocation occurs, the BCR-Abl fusion gene produces a constitutively active tyrosine kinase. The presence of the Philadelphia chromosome is 100% sensitive for CML but not totally specific as it may also be found in ALL.
Which of the following options accurately describes polycythaemia vera?
A. A malignant proliferation of RBCs driven by mutation of a kinase bound to the EPO receptor
B. Hyper-production of RBCs driven by an EPO-secreting tumour (e.g. renal cell carcinoma, uterine myoma)
C. A deceptive increase in haematocrit and haemoglobin due to loss of plasma volume rather than abnormal RBC production
D. A block in differentiation of lymphocytes which, in combination with increased proliferation, leads to large numbers of ineffective blasts in the peripheral blood which also crowd out the bone marrow
E. A physiological response to chronic hypoxia (e.g. cyanotic heart disease, living at high altitude, high affinity haemoglobin disorders)
A. A malignant proliferation of RBCs driven by mutation of a kinase bound to the EPO receptor
The kinase mentioned is JAK2, which is bound to the erythropoietin (EPO) receptor and is phosphorylated upon activation of the receptor. Polycythaemia is considered a myeloproliferative Philadelphia (Ph) negative neoplasm. The other myeloproliferative Ph negative neoplasms are essential thrombocytopenia and primary myelofibrosis, which are also associated with JAK2 mutations.
‘B’ describes inappropriate true secondary polycythaemia, and ‘E’ describes appropriate true secondary polycythaemia. In both cases the bone marrow is functioning normally, but is stimulated to produce more RBCs either as part of an appropriate physiological response to hypoxia, or in response to ectopic EPO production.
‘C’ describes a relative or pseudo polycythaemia: the actual red cell mass is unchanged, but loss of plasma volume concentrates red cells to give that impression.
‘D’ describes the pathology of ALL.
Which of the following options describes the aetiology of febrile non-haemolytic transfusion reaction?
A. IgG antibodies react against Rhesus D antigen
B. Endotoxin contamination causing systemic reaction
C. IgM antibodies react against A or B antigens
D. Cytokines released from WBCs cause an inflammatory reaction
E. Mast cell degranulation as IgE are crosslinked by an antigen in the donor plasma
D. Cytokines released from WBCs cause an inflammatory reaction
These reactions are generally mild and can be treated using paracetamol before restarting transfusion. They are rarer since the advent of leucodepeletion of blood.
During routine obs, a patient on the wards is noted to have a BP of 100/60, resp rate of 29, and an HR of 110. They are also noted to be febrile. Their notes reveal they received a blood transfusion 1 hour beforehand.
What is the most likely diagnosis?
A. ABO incompatibility
B. IgG haemolytic reaction
C. Febrile non-heamolytic transfusion reaction
D. Transfusion-associated circulatory overload
E. Anaphylaxis
A. ABO incompatibility
In the rare event that an error leads to blood being given to someone with an incompatible ABO status, a severe haemolytic reaction will ensue very quickly. This is mediated by IgM (in contrast to the IgG-mediated reaction against D antigens which is also a delayed haemolytic reaction) and causes circulatory shock (low BP, high HR) and fever along with chest/ loin pain, vomiting, collapse, flushing, and haemoglobinuria (later).
As it sounds, this is a medical emergency and it is the reason you should always LABEL AT THE BEDSIDE.
Bacterial contamination presents essentially identically, and so should be a differential in this patient.
This patient would need blood samples taking for FBC, coagulation, X-match, and direct anti-globulin test. You would then need to urgently consult a haematologist.
During routine obs, a patient on the ward is noted to have an increased resp rate, decreased O2 saturations, increased blood pressure, and dyspnoea. They received a transfusion 13 hours prior, and their past medical history includes diabetes and hypertension. A CXR shows increased opacity in a bilateral ‘bat-wing’ shape.
What is the most likely diagnosis?
A. Febrile non-haemolytic transfusion reaction
B. Transfusion-associated circulatory overload
C. Nephrotic syndrome
D. Allergic reaction
E. Delayed haemolytic transfusion reaciton
B. Transfusion-associated circulatory overload
This patient has renal impairment as a result of their diabetes and/or hypertension which has resulted in fluid overload from the transfusion (the ‘bat-wing’ appearance on CXR indicates pulmonary oedema). To avoid this, furosemide can be prescribed along with transfused blood. This is comfortably the most common cause of transfusion complications
During routine obs, a patient on the ward is noted to have an increased resp rate, fever, decreased O2 saturations, increased blood pressure, and dyspnoea. They received a blood transfusion 4 hours prior. A CXR shows bilateral infiltrates, but does not suggest oedema.
What is the most likely diagnosis?
A. Transfusion-related acute lung injury
B. ABO incompatibility
C. Anaphylaxis
D. Febrile non-haemolytic transfusion reaction
E. Transfusion-associated circulatory overload
A. Transfusion-related acute lung injury
TRALI is caused by aggregation of host WBCs by donor antibodies. The aggregated WBCs become stuck in pulmonary capillaries and release proteolytic enzymes and toxic O2 metabolites which damages the lung parenchyma. TRALI presents very acutely (usually within 4 hours) which helps to differentiate it from other transfusion reactions.
A patient presents with severe diarrhoea, jaundice, fatigue, and breathlessness. Furthermore their skin has begun to peel off, which has seriously scared them. Their notes show they received a transfusion two weeks ago, and a diagnosis of transfusion-associated graft-versus-host disease is made.
Which of the following is not a risk factor for TaGVHD?
A. The volume of blood transfused
B. The degree of HLA matching between donor and recipient
C. Sex difference between the donor and recipient
D. Reduced immune function
E. The age of the blood donor
C. Sex difference between the donor and recipient
TaGVHD is rare, but once firmly established it is invariably fatal. TaGVHD is caused by lymphocytes within the donor blood which destroy the recipient’s organs. In an immunocompetent individual this is not an issue, as the donor WBCs are destroyed, but in immunosuppressed patients disease can develop. This causes severe diarrhoea, liver failure, skin desquamation, bone marrow failure, and death weeks to months after transfusion. Death usually results from rampant infection due to pancytopenia from bone marrow destruction. TaGVHD can be minimised by irradiating blood components being given to heavily immunosuppressed patients.
This is a good BMJ article on TaGVHD if you would like more information:
https://heart.bmj.com/content/80/3/211
As part of routine G&S tests at 12 and 28 weeks, a pregnant woman is found to have anti-D antibodies. She has been pregnant once before, but her notes show she was not given RAADP.
What would be the next step in the management of this situation?
A. Give prophylactic anti-D immunoglobulin
B. Induce labour
C. Monitor using MCA doppler ultrasound scans
D. Give an intra-uterine transfusion through the umbilical vein
E. Check ffDNA sample
E. Check ffDNA sample
In this case, the patient has already been sensitised to D antigen by her previous pregnancy, so prophylactic immunoglobulin will not help. Checking the free fetal DNA will allow you to establish whether the fetus is Rh positive or negative: if negative, no further action is needed, if positive the fetus will need monitoring for anaemia with MCA doppler ultrasound. If the fetus becomes severely anaemic, transfusion or early delivery may be warranted.
Anti-D sensitisation in pregnancy is normally prevented through used of RAADP - routine anti-D antenatal prophylaxis, which involves giving anti-D immunoglobulin to the mother. The immunoglobulin binds to D antigen within the mother’s circulation leading to destruction of those red cells within the reticulo-endothelial system of the spleen before they can cause antibody production in the mother.
NICE recommend a single dose of 1500 units between 28-30 weeks of pregnancy. Additionally, RAADP is given whenever there is a potential sensitising event (e.g. at delivery if baby is RhD positive, amniocentesis, termination of pregnancy, abdominal trauma, intrauterine death etc.). Alternatively, patients may choose to have free fetal DNA analysed (must be done after 12 weeks to ensure accuracy) as, if the fetus if RhD negative, anti-D prophylaxis is not necessary
Which of the following is not a blood film feature of myelodysplasia?
A. Myeloblasts with azurophillic rod formations
B. Absence of granules within the neutrophil
C. Ringed sideroblasts
D. Dyserythropoiesis
E. Pelger-Huet anomaly
A. Myeloblasts with azurophillic rod formations
The azurophillic rod formations described here are Auer rods, which are pathognomic of acute myeloid leukaemia. While myelodysplasia has a risk of progressing to AML, they are separate diseases.
All these other features may appear on a blood film and can indicate myelodysplasia:
Neutrophils may show reduced granulation
Ringed sideroblasts are an abnormal type of red cell produced when the body has enough iron available, but the bone marrow is not functioning well enough to incorporate it into haemoglobin. These cells can be identified with a Perl stain.
Dyserythropoiesis refers to generic production of dysmorphic RBCs
A Pelger-Huet anomaly is a bi-lobed neutrophil. This can be seen as a result of an autosomal dominant genetic disorder, or may be the result of myelodysplasia
