Difficult topics Ben Ioanna Menti 4395 1413 Session

Difficult topics Ben & Ioanna Menti: 4395 1413

Session overview Haematological malignancies • Leukaemias • Lymphomas • Multiple Myeloma Myelofibrosis Polycythaemia Haemolytic anaemias HUS & TTP Brain haemorrhages

Disclaimer This section is mainly based on SBAs. Most of them are quite hard so do not panic if you do not get them right. It is intended to help you understand some difficult topics and challenge you.

SBA 1 A 4 -year-old boy is brought to see A&E after his mother noticed some bruises along his legs. The child does not recall injuring his legs. Chest X-ray shows a mediastinal mass. What is the most likely diagnosis? A) Non-accidental injury B) Immune thrombocytopaenic purpura C) Acute lymphoblastic leukaemia D) Acute myeloid leukaemia E) Haemophilia A Menti: 4395 1413

SBA 2 A 55 year old man presents to his GP with a 2 -week history of fatigue and easy bruising. Blood results show: • WCC 27 (4 -11) • Hb 90 (130 -180) • Platelets 30 (150 -450) • Neutrophils 0. 9 (1. 5 -6. 0) Blood film demonstrates cells with a big nucleocytoplamic ratio and cytoplasmic inclusions. What is the most likely diagnosis? A) Acute lymphoblastic leukaemia B) Acute myeloid leukaemia C) Chronic lymphoid leukaemia D) Chronic myeloid leukaemia E) Hodgkin’s lymphoma Menti: 4395 1413

SBA 3 A 54 year-old man presents to his primary care physician with a 2 -month history of fever, malaise, and weight loss. He also reports frequent epistaxis. Genetic studies show a t(9; 22) translocation. Given the most likely diagnosis, which of the following findings are consistent? A) B) C) D) E) Smear cells Auer rods Ring sideroblasts Left shift Teardrop cells Menti: 4395 1413

Acute Vs Chronic leukaemias Differentiation TWO Processes of Blood Cell Development Proliferation Abnormal differentiation ACUTE Leukaemia & Excessive proliferation Normal differentiation CHRONIC Leukaemia Excessive proliferation Clinical Features • Acute onset • Excessive blast cells • Unlikely to be asymptomatic • Bone marrow failure Clinical Features • Gradual onset • Mature cells • May be asymptomatic • BM failure later

Leukaemias cheat sheet table ALL Child (typically 2 -5 years old) BM failure: Bruising, anaemia, infections Signs of infiltration: hepatosplenomegaly, lymphadenopathy, bone pain, testicular swelling Bloods: ↓ Hb, ↓platelets, ↓ neutrs, ↑ WCCs (blasts) Blood film: blast lymphoid cells AML More common in adults BM failure: Bruising, anaemia, infections tissue infiltration; gums, mild splenomegaly) Bloods: ↓ Hb, ↓platelets, ↓ neutrs, ↑ WCCs (blasts) Blood film: myeloblasts & Auer rods CLL Elderly 50% asymptomatic, non-tender lymphadenopathy, as it progresses BM failure symptoms Bloods: ↑ WCCs with lymphocytosis, initially normal HB & platelets, BM failure: later Blood film: Smear cells CML 40 -60 years old, BCR-ABL 3 phases: chronic, accelerated, blast Initially asymptomatic → hypermetabolic symptoms, massive splenomegaly, hyperviscocity symptoms Bloods: ↑ WCCs (neutrophilia, basophilia), Hb usually normal, can have ↑ platelets BM failure later Blood film: left shift

SBA 1 A 4 -year-old boy is brought to see A&E after his mother noticed some bruises along his legs. The child does not recall injuring his legs. Chest X-ray shows a mediastinal mass. What is the most likely diagnosis? A) Non-accidental injury: does not explain the mass, legs common site of bruising B) Immune thrombocytopaenia purpura: can also present acutely in children but usually follows a viral infection; does not explain the mass C) Acute lymphoblastic leukaemia D) Acute myeloid leukaemia: Could be but less likely E) Haemophilia A: does not explain the mass; presents more with deep bleeding ALL is a childhood leukaemia Sign of thrombocytopaenia Sign of lymphocyte infiltration

SBA 2 A 55 year old man presents to his GP with a 2 -week history of fatigue and easy bruising. Blood results show: • WCC 27 (4 -11) Signs of BM failure • Hb 90 (130 -180) • Platelets 30 (150 -450) • Neutrophils 0. 9 (1. 5 -6. 0) Blood film demonstrates cells with a big nucleocytoplamic ratio and cytoplasmic inclusions. Acute onset Immature cells & Auer rods What is the most likely diagnosis? A) Acute lymphoblastic leukaemia B) Acute myeloid leukaemia C) Chronic lymphoid leukaemia History more in line with acute leukaemia D) Chronic myeloid leukaemia E) Hodgkin’s lymphoma: Disease mainly in LNs & extranodal tissue, pancytopaenia would occur in late disease (BM) involvement; would expect some lymphadenopathy

ALL or AML? ALL AML Pathophysiology Problem at lymphoblast stage Problem at myeloblast stage Epidemiology Most common childhood leukaemia Adults (incidence increases with age) Common BM FAILURE: anaemia, thrombocytopaenia (bleeding), neutropaenia (infections) Additional features Lymphadenopathy CNS involvement Testicular enlargement (specific) Thymic enlargement Can happen but less common Investigations: High WCC (lymphocyte blasts), low HB, low platelets, low neutrophils High WCC (granulocyte blasts), low HB, low platelets, low neutrophils – Auer rods on blood film

Auer rods = cytoplasmic Crystalline inclusions (specific to AML)

SBA 3 A 54 -year-old man presents to his primary care physician with a history of tiredness and frequent infections. Genetic studies show a t(9; 22) translocation. Given the most likely diagnosis, which of the following findings are consistent? A. B. C. D. E. Smear cells: CLL Auer rods: AML Ring sideroblasts: myelodysplasia, sideroblastic anaemia Left shift Teardrop cells: iron deficiency anaemia, myelofibrosis CML

CML: Left shift indicates the earlier release of immature neutrophil precursors. As the BM receives inflammatory stimuli to release more neutrophils, more immature forms of neutrophils are released

SBA 4 A 26 -year old man presents to his GP after a 3 - week history of intermittent fevers and drenching night sweats. Blood results show: • WCC: 7 (4 -11) • Hb: 125 (125 -155) • Platelets: 310 (150 -400) Examination reveals cervical lymphadenopathy which is biopsied. On biopsy there are multi-nucleated cells shown in the picture. Which is the most likely diagnosis? A) B) C) D) E) Tuberculosis CLL Hodgkin’s lymphoma Burkitt’s lymphoma CML

Leukaemia or lymphoma? Same disease different location Leukaemia Lymphoma Progression/as disease advances Blood & Bone Marrow Lymphoid or myeloid cells Lymph Nodes (& extranodal tissue) Only lymphoid cells (B or T cells)

Lymphoma Common features: • Painless lymphadenopathy • B symptoms = fever, night sweats, weight loss • Pruritus Hodgkin’s lymphoma Non-hodgkin’s lymphoma Bimodal incidence: 20 -30 & 50+ Increases with age Only B cell B or T cell Tends to affect a single group of nodes Tends to affect multiple nodes Pain after alcohol intake Reed Stenberg cells

SBA 4 A 26 -year old man presents to his GP after a 3 - week history of intermittent fevers and drenching night sweats. B symptoms Blood results show: • WCC: 7 (4 -11) Burden of disease not in BM & blood • Hb: 125 (125 -155) • Platelets: 310 (150 -400) Examination reveals cervical lymphadenopathy which is biopsied. On biopsy there are multinucleated cells shown in the picture. Which is the most likely diagnosis? A) B) C) D) E) Tuberculosis CLL Hodgkin’s lymphoma Burkitt’s lymphoma CML Reed Stenberg cells = Hodgkin’s lymphoma (also called owl’s eye appearance)

SBA 5 A 71 -year-old man has been suffering from hip pain and constipation for the past few months. He has also noticed that he is having to urinate more frequently than usual, and, consequently, he is always extremely thirsty. Blood results show: Hb = 10. 5 g/d. L (13 -18) Platelets = 120 x 109/L (150 -400 x 109) Neutrophils= 3. 0 (1. 5 -6. 0) Calcium: 3. 0 (2. 2 -2. 6) Creatinine = 125 umol/L (baseline: 72 umol/L, 3 months ago) Given the most likely diagnosis which is the most appropriate next investigation? A. Serum protein electrophoresis B. Bone marrow aspirate C. Skull X-Ray D. Lymph node biopsy E. CT-KUB Menti: 4395 1413

Pathogenesis of Haem malignancy: B cells Leukaemia Lymphoma Multiple Myeloma

Multiple myeloma A neoplastic monoclonal proliferation of bone marrow plasma cells resulting in excessive monoclonal immunoglobulin production Calcium ↑ Renal failure Anaemia Bone lesions Investigations: 1) Bloods: ↑ESR, CRP, urea, creatinine, normal ALP 2) Blood film: rouleaux formation 3) Serum/urine electrophoresis • Serum paraprotein (Ig. G or Ig. A) • Urinary Bence Jones proteins 4) Bone marrow plasma cells >10%

SBA 5 A 71 -year-old man has been suffering from hip pain and Due to bone lesions constipation for the past few months. He has also noticed that he is having to urinate more frequently than usual, and, ↑ calcium consequently, he is always extremely thirsty. Blood results show: Calcium: 3. 0 (2. 2 -2. 6) ↑ calcium anaemia Hb = 10. 5 g/d. L (13 -18) ↓ Can have Platelets in MM bc BM is affected Platelets = 120 x 109/L (150 -400 x 109) Neutrophils= 3. 0 (1. 5 -6. 0) Renal failure Creatinine = 125 umol/L ↑ (baseline: 72 umol/L, 3 months ago) Given the most likely diagnosis which is the most appropriate next investigation? • Serum protein electrophoresis • Bone marrow aspirate: part of MM diagnostic process but not NEXT • Skull X-Ray: could demonstrate lytic lesions but not NEXT • Lymph node biopsy: he does not have lymphadenopathy • CT-KUB: if you were suspected kidney stones

SBA 6 A 73 -year old man complains of feeling tired and of having discomfort after food and constipation. On Examination, he is pale and has a grossly enlarged spleen. FBC reveals pancytopaenia. Given the most likely diagnosis what would you expect to see on examination of the bone marrow? A. B. C. D. E. Hypocellularity Infiltration by mature lymphocytes Dry tap >20% of blasts Normal Menti: 4395 1413

SBA 7 A 65 -year old woman presents with headaches and visual disturbances. She has also noticed she gets an itchy rash when she gets out of a hot bath. On examination she has a palpable spleen. Her only previous medical history is gout. Initially blood tests reveal a raised packed red cell volume with a raised red cell mass and with a raised white cell count and thrombocytosis. What is the most likely diagnosis? A) Chronic myeloid leukaemia B) Lymphoma C) Migraine D) Polycythaemia rubra vera E) Soap allergy Menti: 4395 1413

Polycythaemia vera & myelofibrosis Polycythaemia Vera Bone marrow neoplasm characterised by excessive production of RBCs May also cause increased platelets Hyperviscosity symptoms (headache, visual disturbance) Aquagenic pruritus Myelofibrosis Clonal bone marrow disease characterised by excessive fibrosis and extramedullary haematopoiesis FBC: pancytopaenia Tear drop cells (blood film) Dry tap (bone marrow aspirate) MASSIVE splenomegaly

SBA 6 A 73 -year old man attends complains of feeling tired, having discomfort after food and constipation. anaemia Abdominal symptoms due to Massive splenomegaly On Examination he is pale and has a grossly enlarged spleen. FBC reveals pancytopaenia. Given the most likely diagnosis what would you expect to see on examination of the bone marrow? A. B. C. D. E. Hypocellularity: other causes of aplastic anaemia Infiltration by mature lymphocytes: CLL Dry tap >20% blasts: acute leukaemia, MM Normal In line with myelofibrosis

SBA 7 A 65 -year old woman presents with headache and visual Hyperviscocity Acquagenic pruritus disturbance. She has also noticed she gets an itchy rash when Increased cell she gets out of a hot bath. On examination she has a palpable turnover spleen. Her only previous medical history is gout. Initially blood tests reveal a raised packed red cell volume with a raised red cell mass and with a raised white cell count and thrombocytosis. What is the most likely diagnosis? A) Chronic myeloid leukaemia B) Lymphoma: C) Migraine D) Polycythaemia rubra vera E) Soap allergy

SBA 8 A 5 -year old boy develops bloody diarrhoea with crampy abdominal pain following a birthday BBQ. Blood tests, including a blood film show low Hb, low platelets and the presence of schistocytes. U&Es show high urea and creatinine. A stool culture has also been sent but results have not yet come back. What is the most likely diagnosis? A) B) C) D) E) Microagiopathic haemolytic aaemia Thrombotic thrombocytopaenia purpura Haemolytic uraemic syndrome Gastroenteritis Immune thrombocytopaenia purpura Menti: 4395 1413

Haemolytic anaemia Jaundice Anaemia: Pale Conjunctivae & Skin Splenomegaly Investigations: ↑ LDH, Haemoglobinuria, haemosiderinaemia, ↓ Haptoglobins

Causes of haemolytic anaemia Hereditary Membrane (hereditary spherocytosis) Acquired Autoimmune Haem (thalassaemias, sickle cell) Enzymes (G 6 PD deficiency) Drugs Fibrin strands Microangiopathic haemolytic anaemia (MAHA) Infection (malaria)

HUS & TTP HUS 1. MAHA 2. Renal failure 3. Thrombocytopaenia Children E. Coli Shigella TTP 1. 2. 3. 4. MAHA Renal failure Thrombocytopaenia Fluctuating CNS signs (confusion) 5. Fever

Splenomegaly • Extra medullary Haematopoiesis: • CML • Myelofibrosis • Lymphocyte infiltration: • Lymphoma (slow-growing) • CLL Other leukaemias: less prominent (because you don’t have enough time for it to develop) • Conditions that make the spleen work harder • Polycythaemia • Chronic haemolysis (extravascular)

SBA 8 A 5 -year old boy develops bloody diarrhoea with crampy abdominal pain following a birthday BBQ. Blood tests, including a blood film show low Hb, low platelets and the presence of schistocytes. U&Es show high urea and creatinine. A stool culture has also been sent but results have not yet come back. What is the most likely diagnosis? A) B) C) D) E) Microagiopathic haemolytic anaemia Thrombotic thrombocytopaenia purpura Haemolytic uremic syndrome Gastroenteritis Immune thrombocytopaenia purpura E. Coli MAHA, renal failure, thrombocytopaenia

SBA 9 A 45 -year-old man is brought to A&E by his wife. He mentions that he had an absolutely devastating headache that came out of the blue 3 hours ago. On examination, he has a stiff neck, and on palpation of the abdomen he has bilateral masses. His wife mentions that his father died 30 years ago from a kidney related disorder. CT is unremarkable? Which other investigation is most likely to give you results consistent with the most likely diagnosis? A) B) C) D) E) LP now LP in 9 hours Repeat CT in 6 hours Carotid Doppler ECG Menti: 4395 1413

Brain haemorrhages Epidural Subdural Headache Common features Symptoms of raised ICP Focal neurological signs Need urgent non-contrast CT Subarchnoid haemorrhage

Subarachnoid haemorrhage Investigations 1) Urgent Non-contrast CT head • Urgent Non-contrast CT scan of the head within 12 hours. • Sensitivity of CT decreases with time 2) Lumbar puncture: • If CT is normal • Xanthochromia & oxyhaemoglobin • From 12 hours after symptom onset Normal Xanthochromia

Types of brain haemorrhage summary Location CT appearance Epidural Subdural SAH Between the skull bone & the dura matter Between the dura & the arachnoid Between the arachnoid & the pia Rupture of the middle meningeal artery on the temporal bone of the skull Rupture of the bridging cranial veins Rupture of berry aneurysm History of trauma Lucid interval → decline in GCS History of trauma Older/alcoholic Slower onset Rupture of berry aneurysm Meningism Convex Concave Hyper-attenuation around the circle of Willis

SBA 8 A 45 -year-old man is brought to A&E by his wife. He had an absolutely devastating headache that came out of the blue 3 hours ago. On examination, he has a stiff neck, and on palpation of the abdomen he has bilateral masses. His wife mentions that his father died 30 years ago from a kidney related disorder. CT is unremarkable? Which other investigation is most likely to give you results consistent with the most likely diagnosis? What is the diagnosis here? Sudden onset very severe headache Polycystic kidney disease

SBA 9 A) LP now: xanthochromia take 12 hours to appear B) LP in 9 hours C) Repeat CT in 6 hours: sensitivity of CT in SAH ↓ over time so unlikely to show anything different D) Carotid Doppler: for stroke if suspect carotid artery stenosis (after CT and hyperacute management) E) ECG: Important to consider as might show arrhythmias but will not identify features of SAH

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