Computer generated transcript

Warning!
The following transcript was generated automatically from the content and has not been checked or corrected manually.

Hematological malignancies Ayah Shah 3rdyearclinicalteaching@gmail.comLeukemia vs lymphoma • Think of lymphoma as a solid tumor that consists of blood cells. It usually causes enlarged lymph nodes or masses. • Leukemia in contrast can be thought of as kind of a liquid cancer that travels through the blood as the cancer occurs due to your body making abnormal white blood cells that don’t work as they should. • So essentially, lymphomas involve cancerous white blood cells forming tumors in the lymphatic system. This can then interfere the ability of your lymphatic system to fight off pathogens. • Leukemia on the other hand has production of abnormal white blood cells by the body that then sort of overtake the bodies production of other, normal blood cells, again, reducing your bodies ability to fight pathogens.LymphomaThe lymphatic system • Consists of lymphoid organs and tissues which include: • Spleen • Thymus • Tonsils • Lymph nodes • Bone barrow • Peyer’spatches • The lymphatic system’srolesinclude: • Provides routes for fluid to travel between the blood and interstitial spaces. • Useful in nutrient absorptione.g. fats • component of this system and play a role in innate and acquired immunity. Lymphoid tissues also trap foreign particles found in circulating lymph.What are lymphomas? • Lymphomas are a group of cancers that develop from the lymphoid organs/tissues. • These can develop from lymphocytes e.g. B cells, T cells, natural killer cells and their precursors. • We cancategorizelymphomas into 2 categories: • Hodgkin’s lymphoma • Non-Hodgkin’s lymphoma • The key presenting symptoms is lymphadenopathy. • You may find enlarged lymph nodes in areas such as the neck, axilla, inguinal regions. • Lymphadenopathy is usually non tender and rubbery • When may a patient with lymphoma experience lymph node pain? • Patients with Hodgkin’s lymphoma may experience lymph node pain when drinking alcohol Presentation • Symptoms: • Fever of lymphoma • Weight loss B-symptoms • Night sweats • Fatigue • Itching • Cough • Shortness of breath • Abdominal pain • Recurrent infectionsHodgkin’ s lymphoma • Around 1 in 5 lymphomas are Hodgkin’s lymphomas. • Risk factors: • HIV • Epstein-Barr Virus (EBV) • Autoimmune conditions e.g. rheumatoid arthritis & sarcoidosis • Family history • Management: • The key treatments are chemotherapy and radiotherapy. The aim is to cure the condition.While this is usually and side effects of medications.elapse, other haem cancers • Chemotherapy - risk of leukaemia and infertility. • Radiotherapy - risk of cancer, damage to tissues and hypothyroidism.Hodgkin’s lymphoma classification Type Frequency Prognosis Notes Nodular sclerosing Most common (around Good prognosis More common in women. 70%) Associated with lacunar cells Mixed cellularity Around 20% Good prognosis Associated with a large number of Reed-Sternberg cells Lymphocyte Around 5% Best prognosis predominant Lymphocyte depleted Rare Worst prognosis • Poor prognostic factors: • B symptoms: • Weight loss > 10% in past 6m Hodgkin’s • Fever > 38 • Night sweats lymphoma • Age > 45 prognostic • Stage IV disease • Hb < 10.5 g/dl factors • Lymphocyte count < 600/µl or 8% • Male • Albumin < 40 g/l • White blood count > 15,000 /µl • Non-Hodgkin’s lymphomas refers to a group of lymphomas, these include: • Burkitt lymphoma - associated with EBV, malaria and HIV. • MALT lymphoma - affects themucosa-associated lymphoidtissue (MALT), usually around stomach.Associated with H. pylori infection. • painless mass in those > 65 years.ten presents as rapidlygrowing Non- • Risk factors: • HIV Hodgkin’ s • Epstein-Barr Virus • Hepatitis B or C infection • Exposure to pesticides and a chemical called trichloroethylene used in lymphoma several industrial processes • Family history • Hodgkin’s and non-Hodgkin’s present similarly, usually you can differentiate Wecan divided NHL: them when you’ve biopsied the lymph node. • Indolent: slow growing, respond • Management (depends on type and stage): well to treatment, but rarely • Watchful waiting cured e.g. follicularlymphoma • Chemotherapy • High-grade: fast growing, often • Monoclonal antibodies such asrituximab symptomatic, more commonly • Radiotherapy cured. E.g. Burkitt's, Diffuse • Stem cell transplantation large B cell.Lymphoma - investigations • Bedside: • Reticuloendothelial examination • Palpate liver and spleen– may find hepatosplenomegaly • Bloods: • FBC • U&E • LFTs • LDH (lactate dehydrogenase)- blood test, marker of high cell turnover, may be raised in Hodgkin’s lymphoma – be aware that this is not specific and may be raised due to other causes • Blood film • ESR – useful prognostic indicator • HIV, Hep B, Hep C screens - risk factors • Imaging/other: • Lymph node biopsy (excision biopsyReed-Sternberg cell (the key finding in Hodgkin’s lymphoma (abnormally large B cells with multiple nuclei with alveoli inside them. Appear like an owl face with large eyes) • CT, MRI, PET scans – for diagnosis & staging • CXR – hilar lymphadenopathyLymphoma - staging • Lugano classification: • Based on the older Ann Arbor system • Consists of 4 stages • The stages are described by Roman numerals I through IV (1-4). Limited stage (I or II) lymphomas that affect an organ outside the lymph system (an extranodal organ) have an E added (for example, stage IIE).Bilateral cervical lymphadenopathy • Most common causes: • sarcoidosis • tuberculosis • Other causes include: • Lymphoma/other malignancies • Pneumoconiosis • Fungi e.g. histoplasmosisCervical lymphadenopathy Acute infection: Chronic infection: Malignancy: Other causes: • Infective • Tuberculosis • Hodgkin's and non- • Rheumatoid arthritis mononucleosis • HIV Hodgkin's lymphoma • Sarcoidosis • Toxoplasmosis • Syphilis • Chronic lymphocytic • Phenytoin reaction • Infected eczema leukaemia • Acute lymphoblastic • Viral infection leukaemia • Kawasaki's syndrome • Secondary malignancies: Nasopharyngeal, thyroid, lung, breast, stomachLeukaemia • Leukemias are cancers of a particular stem cell lines in the bone marrow. • The cancer results in unregulated production of the What are cells of that line. • This results in suppression of the production of the leukemias? other cell lines, resulting in pancytopenia (anemia, leukopenia and thrombocytopenia) • We divide them into acute (quickly progressing) or chronic (slowly progressing) and myeloid or lymphoid • Symptoms are often non-specific, if you’re considering it as a differential, get an urgent FBC: • Signs & symptoms include: • Fatigue • Fever • Failure to thrive (children) Presentation of • Pallor due to anaemia leukemia • Petechiae and abnormal bruising due to thrombocytopenia • Abnormal bleeding • Lymphadenopathy • Hepatosplenomegaly • Bone pain On FBC you may see: Acute Lymphoblastic • Anemia: lethargy and pallor • Neutropenia: Leukemia frequent/severe infections • Thrombocytopenia: easy bruising, • The malignant change occurs in one of the lymphocyte petechiae precursor cells On blood film: • Blast cells • This results in acute proliferation of a single type of lymphocytes, usually this is B-lymphocytes • This results in these cells replacing other cells created in the bone marrow, leading to pancytopenia • This is the most common cancer in children and peaks around 2-4 years. It can also affect adults over 45. It is often associated with Downs syndrome. • Blood film shows blast cells.Chronic Lymphocytic On FBC you may see: Leukemia • Lymphocytosis On blood film: • Smudge/smear cells • Results in chronic proliferation of a single type of well differentiated lymphocytes, usually B lymphocytes • Often asymptomatic but can present, with infections, anaemia, bleeding and weight loss. • It can cause warm autoimmune haemolytic anaemia. • Can undergo Richter’s transformation into a high-grade lymphoma • Blood film shows smear or smudge cells. • Usually affects adults over 55 y/oAcute Myeloid On FBC you may Leukemia • Anemia • Neutropenia • Thrombocytop enia Blood film: • Most common acute leukemia in adults • Auer rods • Usually presents from middle age onwards • Can be the result of transformation from a myeloproliferative disorders .g. polycythemia rubra vera or myelofibrosis • Blood film shows high blast cells. These cells have rods in their cytoplasm called Auer rods On FBC you may Chronic Myeloid see: • Anemia • May be Leukaemia thrombocytosis Blood film: • You may also see an increase in granulocytes • Usually has 3 phases: at different • usually diagnosed incidentally with a high WCC.symptomatic, stages of • Accelerated phase: abnormalblast cells take up a high maturation proportion of the bone marrow cells and cells in the blood(10- 20%). Patients often becomore symptomatic, develop immunocompromised.ocytopenia and become • Blast phase: after theaccelerated phase the patient develops an even high proportion of blast cells and blood (>30%).Symptoms fatal.severe anad patients develop pancytopenia. It is often • a translocation of genes between chromosome 9 and 22: t(9:22)ch is translocation. • FBC – NICE recommend one within 48h if you suspect leukemia. In children or young adults with petechiae/hepatosplenomegaly you should immediately refer to hospital • Blood film – Can identify abnormal cells Leukemia • LDH – often raised in leukemia, but not specific • Bone marrow biopsy – this is main diagnosis for investigations definitive diagnosis • CXR – mediastinal lymphadenopathy or infection • Lymph node biopsy assess for lymph node involvement/assess for lymphoma • Lumbar puncture – may be CNS involvement • CT, MRI, PT for staging and assessing for lymphoma/other tumours • Treatmentoordinated by an oncology MDT • chemotherapy and steroids.ith Leukemia - • Other therapies include: management • Radiotherapy • Bone marrow transplant • SurgeryDifferentials for petechiae • Petechiae occur due to thrombocytopenia (low platelets) resulting in bleeding under the skin. • Differentials include: • Leukemia • Meningococcal septicemia • Vasculitis • Henoch-Schonlein Purpura (HSP) • Idiopathic Thrombocytopenia Purpura • Non-accidental injuryMultiple myeloma • produce antibodies).of the plasma cells (B lymphocytes that What is • Cancer in one type of plasma cell means large amounts of one type of antibody is produced. > 50% of the time it is IgG. myeloma?Myeloma - symptoms • Anemia: • The cancerous plasma cells will invade the bone marrow (bone marrow infiltration), this suppresses other blood cells lines neutropenia, and thrombocytopenia.e deuced causing anemia, • Myeloma bone disease: • The plasma cells release cytokines which result in increased osteoclast activity and suppressed osteoblast activity. This results in bones being metabolized. • Common areas to be affected are the skull, spine and long bones. These areas will have osteolytic lesions and the weak points in the bones can result in fractures. • The increased bone breakdown results in calcium being reabsorbed from the bone, causing hypercalcemia • Myeloma renal disease: • Can occur due to various factors e.g. hypercalcemia, immunoglobulin flowing through tubules, etc.Myeloma – investigations • In anyone over 60 with bone pain, especially back pain or unexplained fractures, you want to consider myeloma. Remember BLIP: • Initial investigations include: • Bence-Jones protein • FBC – low Hb, low WCC (urine electrophoresis) • Calcium – raised • L – serum free Light chain assay • ESR – raised • I Serum • Plasma viscosity raised (because more proteins are in Immunoglobulins the blood) • P – Serum Protein • If these are positive you can move on to do urgent serum electrophoresis electrophoreses and urine Bence-Jones protein test • Bone marrow biopsy is needed to confirm diagnosis X- ray findings include: • Imaging e.g. whole body MRI, CT, skeletal survey (x-ray) • Punched out lesions • Lytic lesions • Raindrop skull • MDT • Chemotherapy • Stem cell transplant – part of clinical trial • VTE prophylaxis with aspirin or LMWH when on Myeloma - chemo as there is increased risk • Management of bone disease: • Bisphosphonates management • Radiotherapy can hep bone pain •fracturesic surgery to stabilize bones and treat •stability and painon to improve spine • Infection • Pain • Renal failure Myeloma - • Anaemia • Hypercalcaemia complications • Peripheral neuropathy • Spinal cord compression • Hyperviscocity Myelodysplastic syndrome • Caused by myeloid bone marrow cells not maturing properly so don’t develop into healthy blood cells. • This results in low levels of blood components that originate from the myeloid line. This result in: • Anaemia – fatigue, pallor, SOB • Neutropenia - frequent or severe infections • Thrombocytopenia – purpura or bleeding • It is more common in those > 60, and those with a hx of chemotherapy and radiotherapy • These patients are at increased risk of acute myeloid leukemia (AML) • Diagnosis: Abnormal FBC, blasts on blood film, bone marrow aspiration and biopsy • Management: • Watchful waiting • Supportive treatment with transfusions • Chemotherapy • Stem cell transplantationMyeloproliferative disordersMyelofibrosis • Can be the result of primary myelofibrosis,polycythaemia veraor essential thrombocythemia. • It is where the proliferation of the cell line results in fibrosis of the bone marrow (replaced by scar tissue) due to cytokines being released by the proliferating cellse.g. fibroblast growth factor. • This can affect the production of blood cells resulting in anaemia and low WBCs (leukopenia) • When the bone marrow is replaced by the scar tissue, haemopoiesis will start to occur in other place like the liver and spleen (extramedullary haematopoiesis). This can cause hepatomegaly and splenomegaly, leading to portal hypertension. If it occurs around the spine, this can cause spinal cord compression. • Can start off asymptomatic • Systemic symptoms: • Fatigue • Weight loss • Night sweats • Fever • Signs and symptoms of complications: • Anemia (not in polycythemia) Myeloproliferative • Splenomegaly (abdo pain) disorders - • Postural HTN (varices, abdo pain, ascites) • Low platelets (bleeding, bruising) presentation • Thrombosis (common in polycythemia and thrombocythemia) • Raised RBCs (thrombosis, red face) • Low WBCs (infections) • Findings specific to polycythemia vera: • Conjunctival plethora (conjunctiva are excessively red – opposite of pallor you see in anemia) • Ruddy complexion • SplenomegalyMyeloproliferative disorders - findings • Polycythaemia Vera: • Increased haemoglobin (> 185g/l in men or > 165g/l in women) • Primary Thrombocythemia: • Increased platelet count (> 600 x 10 /l) • Myelofibrosis (either due to primary myelofibrosis, or secondary to polycythaemia veraor essential thrombocythemia) can give varied findings: • Anaemia • Leucocytosis or leukopenia (high or low white cell counts) • Thrombocytosis or thrombocytopenia (high or low platelet counts) • Blood film in myelofibrosis: teardrop-shaped RBCs, red blood cells of different sizes (poikilocytosis) and immature red and white cells (blasts). • Bone marrow biopsy is test of choice • Genetic testing can help guide management e.g. for JAK2, MPL and CALR genes • Management of primary myelofibrosis: • If mild – can be monitored with no active management • Allogeneic stem cell transplantation– can be curative Myeloproliferative • Chemotherapy – can help withdisorder control and improving symptoms but isn’t curative alone disorders - • Supportive management for compilationse.g. anemia, splenomegaly and portal HTN Diagnosis and • Management of polycythemia vera: management • Venesectionto keep Hb in normal range (1 line) • Aspirin – to reducerisk of clots • Chemotherapy – disease control • Management of essential thrombocythemia: • Aspirin – reduce risk of clots • Chemotherapy – disease controlProgress style questions • A 7-year-old boy has recently been diagnosed with acute lymphoblastic leukaemia (ALL). His mother would like to know his chance of survival is and how you determine it. You find thahte is on the 95th percentile for weight and the 60th for height. His white cell count at diagnosis was 12 * 10^9/l and there were no T or B cell markers on his blood film. Which of the aforementioned featuresfrom this case is a Question 1 poor prognostic factor? 1. Caucasian 2. Male sex 3. Presenting under the age of 5 4. WCC >11*10^9/l at diagnosis 5. ObesityQuestion 2 • A 37-year-old male presents to A&E with weakness, bone pain, and splenomegaly. He mentioned that for a few weeks he’s been feelinmore tired and weakday to day. On examination, he’s very pale and has petechiae on his legs. After his bone marrow sampling he is diagnosed with acute promyelocytic leukaemia (APML). Which of the following would most likely be seen on his blood film? 1. Tear dropoikilocytes 2. Auer rods 3. Smear cells 4. Spherocytes 5. Target cellsQuestion 3 • A 77-year-old male attends GP with episodes of fever forthe last 4 days. This is associated with weight loss. He has a productive cough which is long term which he attributes to his COPD. He also mentions having a sore throat about 1.5 weeks ago, which has now gone. PMH: COPD, CLL, HTN, and T2DM. On examination, he has a mild wheeze in his chest along with some non-tender, palpable cervical lymph nodes. His throat examination showed no abnormalities. What investigation is most likely to reveal the diagnosis? 1. Blood culture 2. Direct Coombs’ test 3. Lymph node biopsy New B symptoms in CLL -> 4. Sputum sample for MC&S Richter’s transformation 5. Throat swab CLL is associated with warm Question 4 autoimmune hemolytic anemia • A 6y-year-old man is investigated for anaemia which was detected on a routine FBC for his CLL which is currently going untreated. This discovery prompts the GP to send off further blood tests: • Direct Coombs test : positive • Reticulocytes: 3.1% (0.-2.5%) • Bilirubin 20 (3-17) • LDH : 350 (140-280) • What is the most likely diagnosis? 1. Aplastic crisis 2. Cold autoimmune haemolytic anaemia 3. Myelofibrosis 4. Paroxysmal nocturnalhaemoglobulinuria 5. Warm autoimmune anaemiaQuestion 5 • Which of the following types of Hodgkin's lymphoma carries the worst prognosis? 1. Nodular Sclerosing 2. Mixed cellularity 3. Lymphocyte predominant 4. Lymphocyte depleted 5. Hairy cellsQuestion 6 • A 78-year-old male presents to his GP due to persistent mid-back pain (7/10) forthe past few months that’s been affecting his sleep. PMH includes stable angina and hypertension. On examination there is bony tenderness particularly in the thoracic spine and reduced range of movement. Blood tests show a raised corrected calcium level as well as a leukopenia. Which of the following is the most appropriate action? 1. Measure serum PTH levels Patient > 60 presenting with 2. Urgent protein electrophoresis and Bence Jones protein testing bone pain, raised calcium, low 3. Refer to physiotherapy white cells 4. Refer for urgent MRI spine 5. Prescribe an appropriate analgesia regime THINK MYELOMAQuestion 7 • A 21 year oldmale attends his GP due to a in his neck. He has been feeling ‘off’ for the past couple of months. He mentions that he’s lost weight and experienced night sweats for the past month. • On examination the lump is non-tender and rubbery. • What is the single most likely diagnosis? 1. Reactive lymph nodes 2. Pleomorphic adenoma Non-tender rubbery lymph nodes + B symptoms in a young patient– think lymphoma 3. TB TB is possible but less likely due to demographics 4. Hodgkin’s lymphoma Reactive lymph nodes are possible but lack of recent illness + B symptoms makes this less likely 5. ALL ALL is possible but doesn’t classically present with lymphadenopathy and is more common in early childhoodQuestion 8 • A 67-year-old man with known polycythaemia rubra vera presents with tiredness over the past month. • A FBC is done with the following results: • Hb : 90 g/L (135-180) • Platelets : 95 * 10 ^ 9 / L (150-400) • WBC : 20 * 10 ^ 9 / L (4-11) • Which complication of polycythaemia rubra vera is the patient most likely to be experiencing? 1. Transformation to lymphoblastic leukaemia 2. Transformation to acute myeloid leukaemia AML can develop as a result of 3. Transformation to chronic lymphocytic leukaemia transformation from 4. Transformation to chronic myeloid leukaemia myeloproliferative disorders 5. Transformation to diffuse large B cell lymphoma • History taking e.g. lymphoma Possible • Rememberred flags, • Data interpretation e.g. leukemia, non-Hodgkin’s OSCE lymphoma, etc. stations • Reticuloendothelial examination • Explanation e.g. biopsy