B Pathological counts
Pathological counts Basophilia Diagnosis: Chronic myelogenous leukemia Case B13 This 70-year old woman was earlier operated for melanoma and breast cancer in situ. In 2001 she was diagnosed with essential thrombocythemia (ET). The diagnosis was later changed to primary myelofibrosis (PMF), JAK2V617F mutation positive. Grade 3/3 reticulin fibrosis was seen in a recent bone marrow biopsy. Treatment with Hydroxyurea has been given, and in 2010 and 2012 splenic irradiation was performed achieving transient reduction of spleen size and better blood counts. Now in 2014, according to a recent CT scan, the spleen size is again increased to 26.5 12 15 cm. The spleen is palpable down to 10 cm below the umbilical plane on the left side, and onto the midsagittal plane. The patient is dependent on red blood cell transfusions in order to keep Hgb above 8,0 g/dl. A leukoerythroblastic blood smear is seen with increasing proportions of basophils and blasts, now reaching 18 % and 10 % respectively. A 3rd series of palliative splenic irradiation 2 Gy 5 is now started. : Slight leukocytosis. The delineation between the regions is poor, suggesting the presence of pathological distribution of the leukocytes. DE-flagging. : Anemia. : Thrombocytosis. Bands 2.22 x 10 9 /l Neutrophils 2.33 x 10 9 /l Eosinophils 0.78 x 10 9 /l Basophils 2.00 x 10 9 /l Lymphocytes 1.22 x 10 9 /l Monocytes 1.11 x 10 9 /l Blasts 0.33 x 10 9 /l Myelocytes 0.78 x 10 9 /l Metamyelocytes 0.33 x 10 9 /l Macrocytosis. Thrombocytosis, giant platelets. The picture shows a basophil granulocyte with characteristic course granules. Two giant platelets are seeing to the left and to the right of the basophils. The instrument gives a clear indication of an abnormal distribution.
C Infections
Infections Case C04 Variant lymphocytes Diagnosis: Mononucleosis This case is a baby boy (4-month old) weighing 7.4 kg who has been healthy from birth until now. Three days before hospital admission he got fever 38-39 C and symptoms of an upper respiratory infection. From the day before admission, spreading small non-raised hemorrhages (petechiae) appeared all over his skin. A small amount of blood was also seen in the diapers. Urticarial lesions with pruritus appeared after admission and he got antihistamine treatment. The platelet count at admission was 23 10 9 /l), with a nadir of 20 on the next day. Due to the bleeding tendency one dose of intravenous immunoglobulin (IVIG) was given during the first night in the hospital. The platelet count rose from day three onwards to 28, 72 and 174. The maximum rebound platelet count (662 10 9 /l) was reached a few days later. CRP was within the normal range. Transient moderate neutropenia and anemia were seen in the beginning. Variant lymphocytes were present in the blood, and serology for EBV and CMV were taken but inconclusive. No obvious lymphadenopathy or organomegaly could be noted. This acute episode of probable immunological thrombocytopenic purpura (ITP) as precipitated by a viral infection was entirely resolved and thrombocytopenia has not recurred thereafter. : A wider lymphocyte peak than normal indicates unnormal lymphocytes. : Normal. : Normal. Bands 0.09 x 10 9/ l Neutrophils 0.94 x 10 9 /l Eosinophils 0.17 x 10 9 /l Basophils 0.09 x 10 9 /l Lymphocytes 6.04 x 10 9 /l Monocytes 0.51 x 10 9 /l Plasmacells 0.26 x 10 9 /l Others* 0.43 x 10 9 /l *Variant lymphocytes Microcytosis Thrombocytopenia. A variant lymphocyte is shown in the picture. This celltype is somewhat larger than normal lymphocytes with a fine blast-like chromatin pattern and basophilic cytoplasm.
D Erythrocyte case studies/anemia
Erythrocyte case studies/ Anemia Sicklecells Diagnosis: Sicklecell anemia Case D13 The male teenager of African descent, living in Sweden with his parents, is followed for sicklecell anemia (homozygote HbSS) with concomitant alpha thalassemia minor (aa/-a3.7). A recent Hgb fractionation showed HbF 12 % and HbS 81 %. There have been recurrent episodes of back pain and/or fever. Hgb has otherwise usually fluctuated around 10,0 g/dl, with MCV 70-74 fl. Folic acid supplementation is given to compensate for the hemolysis. Although many sickle cells are detected in the microscope (together with other abnormalities of the erythrocytes), laboratory values including Hgb 10,1 g/dl, reticulocytes 10.2 %, LDH 6.7 µkat/l (reference < 6.0 µkat/l) and bilirubin 44 µmol/l are stable. : DE-flagging. : Anemia, reduced MCV, increased RDW. : Normal. Bands 0.11 x 10 9 /l Neutrophils 2.97 x 10 9 /l Eosinophils 0.17 x 10 9 /l Basophils 0.06 x 10 9 /l Lymphocytes 2.07 x 10 9 /l Monocytes 0.22 x 10 9 /l N/100 4 Anisocytosis, poikilocytosis, microcytosis, polychromasia, sickelcells, target cells Anisocytosis. The film shows some sicklecells.
Erythrocyte case studies/ Anemia Sicklecells Diagnosis: Sicklecell anemia Case D15 A 29-year old man of African descent has sickle cell anemia (homozygote HbSS), and a daughter is also affected. He experiences recurrent vaso-occlusive symptoms of pain in the extremities, sometimes treated in hospital with hydration and opioid analgesics. Obstructed microcirculation from sickled red blood cells, causing ischemic injury, is the cause of such symptoms. The patient also had an episode of acute chest syndrome and/or pneumonia in 2013 with nadir Hgb 8,3 g/dl and maximum CRP 218. Otherwise mostly stable Hgb 9,0-10,5 g/dl with slight reticulocytosis and elevations of LDH and bilirubin. So is also the case at this visit to the hematologist, when it is decided to start treatment with Hydroxyurea orally against the frequent pain episodes. A CT scan of his left femur shows signs of a distal infarction. : Presents a dubble lymphocyte peak due to the N. DE-flagging. : Anemia, increased RDW. : Normal. Neutrophils 3.92 x 10 9 /l Eosinophils 0.29 x 10 9 /l Basophils 0.20 x 10 9 /l Lymphocytes 4.21 x 10 9 /l Monocytes 1.18 x 10 9 /l N/100 4 : Anisocytosis, ovalocytosis, sicklecells. Anisocytosis, macrocytic. The picture shows a lymphocyte to the left and some sickling cells. Anisocytosis, ovalocytosis and target cells are also presented.
Erythrocyte case studies/ Anemia Elliptocytosis Diagnosis: Autoimmune hemolytic anemia Case D16 A 68-year old woman continuously treated with low-dose Prednisone for chronic immunologic thrombocytopenic purpura (ITP) with platelet counts lately in the range 50-100 10 9 /l). Recent laboratory investigation also showed IgG antibodies against cardiolipin 17 GPL-U/ml (reference < 10 GPL-U/ml) and beta-2-glycoprotein 79 U/ml (reference < 7 U/ml, lupus inhibitor positivity and ANA positivity (titer 400 with homogenous fluorescence). Now she is hospitalized because of pneumonia, heart failure and severe thrombocytopenia with nadir 2 10 9 /l one week before the presented results. She has been given antibiotics and a higher dose of oral Prednisone of 75 mg/d, and the platelet count has now begun to stabilize. There is also a suspicion of autoimmune hemolytic anemia because of Hgb below 10,0 g/dl and slightly elevated LDH and bilirubin, but no direct antiglobulin test (DAT) is available for review. : Leukocytosis, Granulocytosis. : Anemia. : Thrombocytopenia. Bands 0.19 x 10 9 /l Neutrophils* 15.33 x 10 9 /l Lymphocytes 1.87 x 10 9 /l Monocytes 0.75 x 10 9 /l Myelocytes 0.37 x 10 9 /l Metamyelocytes 0.19 x 10 9 /l * Hypersegmentation, hypergranulation Microcytosis, ovalocytosis, elliptocytosis, basophilic stippling. Thrombocytopenia. Some elliptocytes can be seen in the picture. The three white cells are neuthropils.
Erythrocyte case studies/ Anemia Teardrop cells Case D17 Diagnosis: Megaloblastanemi This 37-year old man with an earlier history of alcohol overconsumption had a normal Hgb of 14,4 g/dl in 1999. Increasing fatigue was experienced during the last year. Also weight loss and vomiting have been present. He has taken iron tablets intermittently without seeing a doctor for his pallor and weakness. When at last seeking his general practitioner, blood tests show severe anemia with Hgb 5,4 g/dl and he is sent to the hospital for investigations and transfusion. There is moderate pancytopenia, high MCV, highly elevated LDH 67 µkat/l (reference <4 µkat/l), and elevated bilirubin 35 µkat/l (reference <25 µkat/l). The reticulocyte count is low although the % is normal. Haptoglobin is low at <0.1 g/l (reference 0.22-1.9 g/l). Direct antiglobulin test (DAT) is however negative ruling out autoimmune hemolytic anemia. The explanation for the abnormalities turns out to be deficiency of vitamin B12 as the cobalamin value is < 62 pmol/l (reference 140-650 pmol/l), and there is also a very high homocysteine 124 µmol/l (reference < 15 µmol/l). The patient is given 2 units of erythrocytes and B12 substitution which subsequently normalizes all blood counts. A gastroscopy with biopsies shows no coeliac disease, but instead evidence for autoimmune atrophic gastritis, probably causing B12 malabsorption by intrinsic factor deficiency. Life-long B12 substitution is indicated and given. : Slight reduced numbers. DE-flagging. : Pronounced anemia with macrocytic distribution. : Slight increased. Bands 0.05 x 10 9 /l Neutrophils 1.22 x 10 9 /l Eosinophils 0.07 x 10 9 /l Lymphocytes 0.93 x 10 9 /l Monocytes* 0.10 x 10 9 /l Myelocytes 0.05 x 10 9 /l Metamyelocytes 0.02 x 10 9 /l *Atypical monocytes : Anisocytosis, macrocytosis, polychromasia, poikilocytosis, teardrop cells, ovalocytes, schistocytes Slight increased. The picture shows macrocytosis, anisocytosis and many teardrop cells. True teardrop cells have slightly rounded or blunted ends. Teardrop cells may be seen among others in megaloblastic anemia.
E Platelet case studies
Platelet case studies Platelet Satellitism Case E06 This is an 85-year old man with hypertension, heart failure and atrial fibrillation. He has bilateral glaucoma and cataract. He is now treated at the Department of Ophthalmology for endophthalmitis of his right eye. Hemolytical streptococci (group G) were found in cultures from the vitreous body. He receives intravitreal antibiotics, but probably the eye must eventually be removed. One of the causes of pseudothrombo- cytopenia is satellitism. This is an in vitro artifact found only in anticoagulated blood in which platelets adhere to the periphery of neutrophils and sometimes even to monocytes. This phenomenon is difficult to detect from the histogram and are often detected as a chance finding by microscopy. New sample taken in sodium citrate is necessarry for a correct platelet count. : The GRA-regions mode value is increased due to the attached platelets. : Normal. : Normal. Neutrophils 12.99 x 10 9 /l Lymphocytes 0.45 x 10 9 /l Monocytes 1.66 x 10 9 /l Normal, rouleaux formation. Some of the platelets are attached to neutrophils. The film shows platelets adhered to a neutrophil. There are still some free platelets to be seen in the illustration.
Platelet case studies Thrombocytemia Diagnosis: Polycythemia vera Case E07 This 70-year old man was diagnosed with polycythemia vera in 1999, with confirmed JAK2V617F mutation, and treated with Hydroxyurea and venesections, the latter to keep the HCT below 45 %. Development of secondary myelofibrosis was verified in 2014 with a bone marrow biopsy showing 90 % cellularity and reticulin fibrosis of grade 2/3. A moderate splenomegaly was one of the clinical features. Due to oral ulcers interpreted to be due to Hydroxyurea, a shift was made to Busulphan treatment after a one week washout period. Despite the initiated Busulphan treatment, the platelet count initially rose to the extremely high level >3000 10 9 /l, necessitating an acute thrombapheresis. Pruritus and oral problems continued despite addition of a pegylated interferon, but were later relieved after switch of therapy to ruxolitinib (Jakavi). : Pronounced leukocytosis. The majority of cells in the GRA-region. DE-flagging. : Normal. : Pronounced thrombocytosis over ranged. After dilution 2 890 x 10 9 /l. Bands 2.08 x 10 9 /l Neutrophils 16.90 x 10 9 /l Eosinophils 0.26 x 10 9 /l Basophils 1.30 x 10 9 /l Lymphocytes 1.82 x 10 9 /l Monocytes 3.12 x 10 9 /l Blasts 0.52 x 10 9 /l Anisocytosis, poikilocytosis, stomatocytes can be seen. Thrombocytemi, anisocytosis, giant platelets. The picture shows two neutrophil granulocytes surrounded by a great numbers of platelets with pronounced anisocytosis, some giant platelets can be seen.
G Chronic myeloproliferative diseases
Chronic myeloproliferative diseases Eosinophilia Case G04 A 35-year old male with ulcerative colitis, operated with colectomy in 2007. Also diagnosed with primary sclerosing cholangitis (PSC) leading to recurrent attacks of abdominal pain, and with asthma. Slight intermittent eosinophilia is documented since 2004. However, in 2014 an absolute eosinophil count of 6.91 10 9 /l was recorded at an episode of abdominal pain and fever three days after an endoscopic retrograde cholangiopancreaticography (ERCP), when the count was 24.0. No follow-up was planned, but in 2015 at a new episode of abdominal pain and fever a similar result was seen at hospital admission. After initiated antibiotic treatments with piperacillin / tazobactam intravenously followed by ciprofloxacin orally the patient experienced fatigue, headache, pain in muscles and joints, and swollenness around the eyes and in the groins, and ended ciprofloxacin by own decision. This is the time point when the extreme eosinophilia of the shown hematogram was recorded. Bone marrow investigation was unremarkable except for the dominance of eosinophils (65%), and no FIP1L1-PDGFRA rearrangement was found by fluorescent in situ hybridization (FISH). Stool ova and parasite tests were negative. The eosinophilia was treated with Prednisone, later changed to Hydroxyurea, with improvement of both blood counts and symptoms (fewer attacks of abdominal pain). : Pronounced leukocytosis. The delineation between the regions is poor, suggesting the precens of pathological distribution of the leukocytes. DE-flagging. : Normal. : Normal. Neutrophils 7.23 x 10 9 /l Eosinophils 54.23 x 10 9 /l Basophils 1.30 x 10 9 /l Lymphocytes 8.68 x 10 9 /l Monocytes 2.17 x 10 9 /l Normal. Normal. The picture shows nine eosinophilic granlocytes. The instrument gives a clear indication of an abnormal distribution of the.
H Lymphomas
Lymphomas Atypic Plasmacells Diagnosis: Plasmacell leukemia Case H10 This 74-year old man was diagnosed with multiple myeloma in 2011. Initial treatment with Melphalan, Prednisone and Thalidomide gave remission but also suspected neuropathy in the legs. In the spring 2013 there was laboratory progress with rising free light chains (FLC) kappa in serum, and Melphalan and Prednisone was restarted. The patient responded again regarding decreasing FLC-levels, but within less than a year there was laboratory progress again, now also with plasma cells in the blood. Only transient response to lenalidomide (Revlimid) and Dexamethasone was seen, and during the last months of his life there was overt plasma cell leukemia defined as more than 20 % of the nucleated blood cells being plasma cells. At the examination day there were 64 % plasma cells in the blood according to evaluation by light microscopy, mounting to an absolute plasma cell count of 7.0 10 9 /l. : Leukocytosis, lymphocytosis with a wider distribution than normal. No flagging. : Anemia, macrocytic distribution and an increased RDW. : Thrombocytopenia. Bands 0.14 x 10 9 /l Neutrophils 1.11 x 10 9 /l Eosinophils 0.28 x 10 9 /l Lymphocytes 4.59 x 10 9 /l Monocytes 0.56 x 10 9 /l Others* 7.23 x 10 9 /l * Mononuclear, dark blue-violet cells with immature appearance with irregular cytoplasm, some with an irregular nucleus. judge to be atypical plasma cells. Anisocytosis, poikilocytosis, macrocytosis. Thrombocytopenia. The picture shows three atypical plasmacells and down to the left a neutrophil granulocyte.