Haematology — Short Cases

7 Haematology—Short Cases Fric Tse, Yok-Lam Kwong, and Luen-Bik To Overview * Patient categories: malignant and non-malignant haematologi- cal diseases. * Patients with malignant diseases: usual physical signs include lymphadenopathy and organomegaly. Patients with non-malignant diseases: examine for evidence of chronic haemolysis or a bleeding disorder. * Physical signs related to complications of treatment are also of importance. General * Nutritional status * Alopecia (take note of wigs) Anaemia * Jaundice Pigmentation Gums and tongue Evidence of a bleeding tendency (cutaneous: petechiae, purpura, and ecchymosis; central nervous system: fundoscopic examination) Superficial dilated veins

102 Problem-Based Medical Case Management Lymphadenopathy ¢ All lymph nodes should be examined. These include the pre- and post-auricular, occipital, submental, submandibular, upper, middle and lower cervical, supraclavicular, axillary, epitroch- lear, groin, and popliteal lymph nodes. * The tonsils are also part of the superficial lymphoid organs. Abdominal examination * The abdomen should be examined in the usual manner for palpable masses, enlargement of the liver, spleen, and kidneys. ¢ In selected patients, particularly those with a suspected lym- phoid malignancy, the testicles should also be examined. « A list of differential diagnoses for different degrees of spleno- megaly is needed, as different haematological diseases give rise to splenomegaly of different sizes. Small splenomegaly 1. Portal hypertension 2. Thalassaemia intermedia 3. Haematological malignancies Moderate splenomegaly 1. Haematological malignancies (chronic myeloid leukaemia, myelofibrosis, lymphomas) 2. Thalassaemia intermedia Massive splenomegaly 1. Chronic myeloid leukaemia 2. Myelofibrosis Treatment and its complications ¢ Presence of Hickman catheter for the administration of drugs and blood products * Reactivation of dormant viral infections (herpes simplex, herpes zoster) ) ¢ Opportunistic infections (oral candidiasis, lung complications)

Case 7.1 Haematology 103 « Peripheral neuropathy, as a result of chemotherapy + Central nervous system abnormalities, due to meningeal infil- tration or spinal cord compression 7.1 Chronic lymphocytic leukaemia Classical signs » Typically elderly patients older than 60 years * Anaemia * Generalized lymphadenopathy, with sometimes enlargement of the epitrochlear and popliteal lymph nodes + Tonsillar enlargement, however, is not usually found. * Hepatomegaly, usually not exceeding a few centimetres below the costal margin *+ Splenomegaly of mild to moderate degree, but enlargement to beyond the umbilicus is unusual Important differential diagnoses * Low-grade lymphomas Important investigations Examination of the peripheral blood to look for an increase in abnormal-looking lymphocytes and smudge cells Immunophenotypic analysis to look for a monoclonal CD5+ CD19+ CD23+ B cell population Detection of specific chromosomal aberrations by fluorescence in-situ hybridization (FISH) Pitfalls and tips * The more generalized the lymphadenopathy is, the more likely that the diagnosis is chronic lymphocytic leukaemia.

104 Problem-Based Medical Case Management Case 7.2 7.2 Chronic myeloid leukaemia Classical signs Typically presents in middle age Signs of anaemia and bleeding tendency are usually absent. Lymphadenopathy is not a typical feature. Hepatomegaly, usually not exceeding a few centimetres below the costal margin. Splenomegaly can be of any size, depending on when the leu- kaemia is diagnosed. Huge splenomegaly to the right iliac fossa is not uncommon. Auscultation over a massive spleen may reveal a splenic rub. Important differential diagnoses Myelofibrosis Chronic lymphoproliferative diseases (in which case, lymphad- enopathy should be expected) Important investigations Cytogenetic analysis to show the Philadelphia chromosome typical of t(9;22). Molecular analysis to show the fusion m-RNA BCR/ABL. Bone marrow examination, not necessarily for confirmation of diagnosis, but for determination of the phase of the illness (chronic, accelerated, blastic). Discussion Typical physical signs suggesting splenic enlargement as a diagnosis of a left upper quadrant mass, including inability to get above the mass, moves up and down with respiration, dull- ness on percussion and the presence of a notch Treatment options: tyrosine kinase inhibitor, bone marrow transplantation reserved for refractory and blastic transformed cases

Case 7.3 Haematology 105 Pitfalls and tips « Do not mistake hepatosplenomegaly as ballotable kidneys. « Do not mistake the enlarged spleen as an enlarged polycystic kidney, and the enlarged liver as one with cysts as in polycystic diseases. 7.3 Haemolytic anaemia Classical signs * Anaemia « Autoimmune haemolytic anaemia may be a complication of an underlying lymphoproliferative disorder, so that all Iymphoid tissues need to be examined + Abnormal facial features, with prominent forehead and cheek bones, in patients with long standing congenital haemolytic anaemias * Jaundice ¢ Hepatomegaly may occasionally be found, but usually not exceeding a few cm below the costal margin. * Splenomegaly may be found, and if so usually small in size. Important differential diagnoses * Other causes of anaemia * In patients with prosthetic heart valves, beware of mechanical haemolysis. Important investigations Complete blood count, and blood smear to look for polychro- masia, spherocytes, and fragmented red cells Reticulocyte count Direct and indirect anti-globulin test to look for autoantibodies Osmotic fragility test in hereditary spherocytosis Haemoglobin pattern and analysis in thalassaemia

106 Problem-Based Medical Case Management Case 7.4 Flow cytometric analysis, and testing urine for haemosiderin in paroxysmal nocturnal haemoglobinuria Discussion Different causes of haemolytic anaemia should be discussed. Patients with inherited haemolytic anaemias, including heredi- tary spherocytosis and thalassaemia, will have a positive family history. Autoimmune haemolytic anaemia may be associated with underlying systemic diseases, such as autoimmune diseases, or a lymphoproliferative disorder. Thalassaemic trait patients are asymptomatic. Instead, B-thalas- saemia intermedia patients may present with variable anaemia and splenomegaly. Adult B-thalassaemia major patients are not often encountered, and if so all of them would have undergone splenectomy. Haemoglobin H disease patients also present with anaemia and splenomegaly. Pitfalls and tips . Extravascular haemolysis is the commonest encountered form of haemolytic anaecmia. The anaemia is typically acholuric, meaning that there is no increase in bile in the urine. Intravascular haemolysis is rarely encountered. Glucose-6-phosphate dehydrogenase deficiency is not a form of chronic haemolytic anaemia. 7.4 Myelofibrosis Classical signs Anaemia Bleeding tendency is not present. Lymphadenopathy should be absent. Hepatomegaly of varying degree, from a few cm to more than 10 cm below the costal margin

Case 7.5 Haematology 107 + Splenomegaly of varying degree, from a few cm below the costal margin to extension to the right iliac fossa + In terminal cases, evidence of portal hypertension may be present, including caput medusae and ascites. + Auscultation over a massive spleen may reveal a splenic rub. Important differential diagnoses + Chronic myeloid leukaemia + Chronic lymphoproliferative diseases (in which case, lymphad- enopathy should be expected). Important investigations + Cytogenetic analysis to exclude the diagnosis of chronic myeloid leukaemia * Bone marrow examination to look for abnormal fibrosis and often abnormal megakaryocytes + Test for the presence of somatic mutations in JAK2, CALR, and MPL genes, which are importance prognostic markers. Pitfalls and tips * Do not mistake hepatosplenomegaly as ballotable kidneys. * Do not mistake the enlarged spleen as an enlarged polycystic kidney, and the enlarged liver as one with cysts as in polycystic diseases. Beware of exacerbation of gouty arthritis. 7.5 lymphoma Classical signs * Lymphomas can affect any age, but usually occur in middle age or elderly patients. * Anaemia may be present. * All the lymphoid tissues need to be examined.

108 Problem-Based Medical Case Management Case 7.5 » Lymphadenopathy is usually present at limited anatomical sites; generalized lymphadenopathy is unusual. » Enlargement of the tonsils may be found. » Hepatomegaly may be found, but usually not exceeding a few centimetres below the costal margin. « Splenomegaly may be found, and if so of small to moderate size. Important differential diagnoses « Chronic lymphocytic leukaemia Other chronic lymphoproliferative diseases * Non-haematological malignancies Important investigations » Lymph node biopsy, with histological and immunophenotypi- cal investigations « Imaging studies (preferably PET/CT scan in FDG-avid lym- phoma) and bone marrow biopsy for staging Discussion * Ann Arbor staging of lymphoma should be discussed. * Classification of lymphomas into Hodgkin’s lymphoma, B cell lymphoma, T cell lymphoma, and natural killer cell lymphoma should be discussed. Pitfalls and tips « Consider the possibility of lymphomas involving body cavities, giving rise to fluid accumulation (as in pleural effusion and ascites).