Case B08. Pathological WBC counts. Neutrophilia. Diagnosis: Severe injuries due to a traffic accident. Histograms. Peripheral blood film

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1 Pathological counts Case B08 Neutrophilia Diagnosis: Severe injuries due to a traffic accident A 63-year-old man who was admitted to the emergency department following a motorbike accident with severe injuries. is CBC-report present a of 15,5 x 10 9 /. On this primarily cytogram it seemed to be an increase in mature neutrophils. istograms : eukocytosis with neutrophilia. : Neutrophils x 10 9 /l ymphocytes 2,57 x 10 9 /l Three neutrophils are shown. TE MEDONIC CASE BOOK

2 Pathological counts Case B11 Increased band population Diagnosis: Unknown cause A 32-year old woman delivered a child on the day before this blood sample was taken. Mother and baby were discharged from the hospital four days later. istograms : Neutrophilia. Anemia. : Bands 3.08 x 10 9 /l Neutrophils x 10 9 /l Basophils 0.18 x 10 9 /l ymphocytes 1.09 x 10 9 /l Monocytes 0.54 x 10 9 /l Anisocytosis. A band cell is shown. TE MEDONIC CASE BOOK

3 Pathological counts Case B12 Atypical monocytos Diagnosis: Infection haemophilus influenzae This 69-year old man was operated in 1955 for coarctatio aortae, and reoperated in Chronic hepatitis C probably due to transfusion. In 1998 operation with aortic valve prosthesis due to endocarditis. In 2011 ruptured aortic aneurysm and received an endovascular graft. From late 2012 leakage of the aortic prosthesis and symptoms of heart failure. Blood cultures showed haemophilus influenzae. A CT scan showed signs of infection in connection to the endovascular graft in aorta descendens. Now he has been treated with antibiotics and improved. istograms : BD-flagging. Normocytic anemia. : Neutrophils 4.16 x 10 9 /l Eosinophils 0.44 x 10 9 /l Basophils 0.06 x 10 9 /l ymphocytes 0.63 x 10 9 /l Monocytes* 1.01 x 10 9 /l *Atypical monocytes Anisocytosis, poikilocytes, target cells. Anisocytosis. An atypical monocyte is shown i the middle of the picture. TE MEDONIC CASE BOOK

4 Infections Case C05 ymphocytosis Diagnosis: Tonsillitis mononucleosis A 5-year old boy with tonsillitis due to a primary EBV infection (EBV serology positive for IgG and IgM). Admitted to hospital due to problems with food and fluid intake. The blood film shows 17 % variant lymphocytes. istograms : The histogram shows a wider lymphocyte peak than normal. No flagging. : Bands 1.12 x 10 9 /l Neutrophils 3.08 x 10 9 /l Basophils 0.07 x 10 9 /l ymphocytes 1.12 x 10 9 /l Monocytes 0.35 x 10 9 /l Var. lymphocytes 1.19 x 10 9 /l In the center of the picture, below the band, a variant lymphocyte, with its characteristic basophilic cytoplasma, is seen. TE MEDONIC CASE BOOK

5 Erythrocyte case studies /Anemia Anemia Diagnosis: Evans syndrome Case D12 A woman in her mid twenties, without earlier health problems, now pregnant (week 17). Admitted to hospital three days ago due to bleeding tendency and fatigue after returning from a vacation in Cyprus. Blood tests showed pronounced anemia and thrombocytopenia, whereas the leukocyte count was elevated. The blood film showed dominating neutrophils among the nucleated cells, but also erythroblasts and myelocytes. At admission, the following tests showed elevated results: lactate dehydrogenase (D) 12 µkat/ (ref <µkat/), bilirubin 47 µmol/ (ref < 25µmol/), reticulocytes 9.8% (ref %). aptoglobin was low, <0.1 g/ (ref g/). Direct antiglobulin test (DAT) showed IgG+++ and C3d+, with evidence for autoimmune hemolytic anemia of the warm type. A bone marrow aspirate showed increased erythroblasts and megakaryocytes. The diagnosis was Evans syndrome, a combination of autoimmune hemolysis and autoimmune thrombocytopenia. She was treated with prednisone, plasmapheresis, high-dose intravenous immunoglobulin, immunoadsorbtion, rituximab and splenectomy and eventually recovered and gave birth to a healthy child. istograms : Increased numbers with granulocytosis (DE-flagging). Anemia with normal results for RDW and MCV. : Few. Bands 2.35 x 10 9 /l Neutrophils x 10 9 /l ymphocytes 6.66 x 10 9 /l Monocytes 0.39 x 10 9 /l Myelocytes 1.18 x 10 9 /l Metamyelocytes 0.39 x 10 9 /l N/100 7 Anisocytosis, microcytosis, polychromasia, sperocytosis, owel-jolly bodies and basophil stippling observed. Only single platelets observed. Three neutrophils and one nucleated red cell are shown. Marked anisocytosis, microcytosis and spherocytosis is noted. Polychromasia is also observed. TE MEDONIC CASE BOOK

6 Erythrocyte case studies /Anemia Anemia Case D13 Diagnosis: Sickle cell anemia A 30-year old man who is a homozygote for sickle cell anemia. In 2003 he was treated for acute chest syndrome in the intensive care unit. A few days ago he again suddenly developed chest pain, fever and cough. A CT scan has shown unspecific pleuro-pulmonary infiltrates. e is treated with antibiotics (piperacillin / tazobactam) as a bacterial infection can not be excluded and due to his functional asplenia. Probable diagnosis is acute chest syndrome due to sickling problems, with sickle cells also seen in peripheral blood. is severe pain gradually resolved over the next days. istograms : Increased. DE-flagging. Anemia with increased RDW. MCV normal. : Bands 0.21 x 10 9 /l Neutrophils 9.43 x 10 9 /l Eosinophils 0.21 x 10 9 /l Basophils 0.21 x 10 9 /l ymphocytes 6.56 x 10 9 /l Monocytes 3.90 x 10 9 /l Anisocytosis, polychromasia, target cells, sickle cells 1 %, intermediate forms 1.5 %. Single giant platelets observed. Below the neutrophil two sickle cells can be seen. Target cells and polychromasia are also noted. TE MEDONIC CASE BOOK

7 Acute eukemias Blasts, with Auer rods Diagnosis: Acute myeloid leukemia (AM) with t(8;21) Case F03 This 42-year old woman was diagnosed with breast cancer in 2009, which was treated with surgery and adjuvant chemotherapy. In 2011 she had new problems with fatigue, and although the gb and numbers of and platelets were normal, a blood differential showed 6-10 % blasts. Also in the bone marrow an increased blast count was seen, not initially fulfilling criteria for acute leukemia. When reinvestigated in February 2012 she had 21 % blasts and 15 % promyelocytes in the bone marrow and a diagnosis of AM was made. Chromosomal analysis showed a translocation between chromosomes 8 and 21, usually implying favorable prognosis. owever, the AM was considered secondary to earlier chemotherapy for the breast cancer and thereby poor risk. She received induction chemotherapy with Amsacrine, Cytarabine and Etoposide without achieving complete remission. A second chemotherapy course now with Fludarabine and Cytarabine was successful and led to complete remission. After a consolidation course with the same drugs she was transplanted with peripheral hematopoietic stem cells from an unrelated donor after reduced intensity conditioning in June Now in April 2013 she has had an upper respiratory infection and experiences increasing fatigue. er blood counts have deteriorated and blasts with Auer rods can be seen - relapse of secondary AM. istograms : eukocytosis shown an increased distribution in all three curves presented with DE-alarm. Anemia. : Pronounced thrombocytopenia. Bands 1.51 x 10 9 /l Neutrophils x 10 9 /l Eosinophils 0.38 x 10 9 /l ymphocytes x 10 9 /l Monocytes 1.51 x 10 9 /l Blasts 1.13 x 10 9 /l Promyelocytes 0.72 x 10 9 /l Myelocytes 1.13 x 10 9 /l Metamyelocytes 0.38 x 10 9 /l Anisocytosis and microcytosis. Only few platelets was found. A blastcell with Auer rods can de seen to the right and down to the left a band. TE MEDONIC CASE BOOK

8 Acute eukemias Acute leukemia Diagnosis: Acute lymphoblastic leukemia of the T-cell type, T-A Case F04 A woman, 73 years of age, who lately was diagnosed with small vessel vasculitis. Symptoms were mainly muscular pain and the diagnosis was made after muscle biopsy. Steroid therapy was instituted, and at a visit to a rheumatologist for consultation, blood tests were taken showing blasts in the blood and thrombocytopenia. At the chosen blood sampling occasion, 21 % blasts were seen, and a parallel bone marrow sample showed 57 % blasts which were classified as T-lymphoblasts by flow cytometry due to expressions of CD2, CD4, CD5 and TdT. She later received chemotherapy adapted for elderly patients and achieved complete remission. istograms : The histogram shows a wider lymphocyte peak than normal. The presence of immature cells can be suspected because the wider Y-peak and should always be followed-up by a microscopic examination of a blood film : Reduced count. Bands 0.34 x 10 9 /l Neutrophils 2.44 x 10 9 /l Eosinophils 0.08 x 10 9 /l ymphocytes 3.11 x 10 9 /l Monocytes 0.42 x 10 9 /l Blasts 1.93 x 10 9 /l Promyelocytes 0.72 x 10 9 /l Myelocytes 0.08 x 10 9 /l N/100 4 Anisocytosis, teardrop cells, spherocytosis. Only few platelets was found. A neutrophil is seen to the left and to the right a blast cell. Two teardrop cells is seen just below and to the right of the blast. TE MEDONIC CASE BOOK

9 Acute eukemias Case F05 Acute leukemia Diagnosis: Acute myelomonocytic leukemia, AM M5 A 62-year old man who noted decreased physical capacity at the gym and experienced a sore throat during the last weeks. When seeking advice from the general practitioner blood tests showed slight anemia, moderate thrombocytopenia and slight leukocytosis with blasts enumerated to 27 % by light microscopy. Acute leukemia was confirmed by bone marrow investigations displaying 80 % immature monocytoid cells (promonocytes), thus the diagnosis became acute monocytic leukemia (AM M5). Cytogenetic and molecular genetic investigations showed no abnormalities. e achieved complete remission after the second chemotherapy course and after the third course he was accepted for allogeneic hematopoietic stem cell transplantation from an unrelated donor, with reduced intensity conditioning. istograms : The histograms shows a wider GRApopulation. : Reduced numbers. Bands 0.24 x 10 9 /l Neutrophils 2.81 x 10 9 /l Eosinophils 0.24 x 10 9 /l ymphocytes 2.20 x 10 9 /l Monocytes 2.93 x 10 9 /l Blasts 3.42 x 10 9 /l Myelocytes 0.12 x 10 9 /l Metamyelocytes 0.12 x 10 9 /l N/100 1 Only few platelets was found. At the top left a neutrophil can be seen and below it to the right a blast. Just below to the right a monocyte and to the right of the monocyte a large platelet is seen. TE MEDONIC CASE BOOK

10 Chronich myeloproliferative diseases eukocytosis Diagnosis: Polycytemia vera Case G03 This 93-year-old man has been followed for Polycythemia vera (JAK2 V617F positive) since Treated with radioactive phosphorus (P32) in 2004 and 2006, as well as repeated venesectio to keep EVF below 45 % and prophylactic aspirin. Although platelet counts were normal, he had a stroke in 2007, and thereafter severe problems with dysphasia. Venesectio was latest performed 2013 when CT was Although platelet counts have increased lately, cytoreductive therapy has been abstained due to poor quality of life and poor prognosis.? istograms : eukocytosis with an abnormal celldistribution in the mid-cell population and DE-flag. DE Microcytic distribution. : Thrombocytosis. Bands 2.31 x 10 9 /l Neutrophils 48,55 x 10 9 /l Eosinophils 1.16 x 10 9 /l ymphocytes 3.47 x 10 9 /l Monocytes 1.16 x 10 9 /l Blasts 0.58 x 10 9 /l Myelocytes 0.58 x 10 9 /l Pronounced leukocytosis with neutrophilia, hyposegmentation, some hypergranulated cells. Several abnormalties, pencil cells, helmet cells, acanthocytes. Thrombocytosis, several giant platelets. The picture shows three neutrophils, two of them are hyposegmented (pseudo Pelger forms). In the middle of the bottom a giant platelet is shown. Among the packed erythrocytes some pencil cells are shown. Platelet anisocytosis. TE MEDONIC CASE BOOK

11 Chronich myeloproliferative diseases Atypical monocytes Diagnosis: Chronic myelomonocytic leukemia, CMM Case G04 An 87-year old man who is a smoker with atrial fibrillation and heart failure and has been followed conservatively for a chronic myelomonocytic leukemia (CMM) for approximately 5 years. Usually he has displayed leukocyte counts x10 9 /. e has moderate splenomegaly. Now he has suffered from abdominal pain and weight loss during the last months and was admitted to hospital where a CT scan showed an abdominal aortic aneurysm 9 cm in width. Despite high risk an endovascular operation was planned for the next morning when he suddenly collapsed due to rupture with a large retroperitoneal hemorrhage. e was acutely operated but abdominal compartment syndrome due to the hemorrhage took his life. The higher leukocyte count now above 100 x10 9 / at the intensive care unit is a postoperative phenomenon. istograms : Pronounced leukocytosis. The majority of the cells are to be find in the GRApopulation and the histogram is obviously pathologic and gives also suspicions of immature cells. DE-flagging. After dilution 1+1 the was found to be x10 9 /. Decreased count. ### DE : Decreased count. Bands 5.34 x 10 9 /l Neutrophils* x 10 9 /l ymphocytes 6.67 x 10 9 /l Monocytes* x 10 9 /l Myelocytes 8.00 x 10 9 /l Metamyelocytes 1.33 x 10 9 /l *ypogranulation, **Atypical monocytes Pronounced leukocytosis with neutrophilia, hyposegmentation, some hypergranulated cells. Anisocytosis, microcytosis. acanthocytes. Single giant platelets observed. Three hypogranulated neutrophils are observed together with two atypical monocytes. In the upper part of the picture two large platelets are shown. TE MEDONIC CASE BOOK

12 ymphomas Case 02 ymphocytosis Diagnosis: Chronic lymphocytic leukemia A man, 79 years old, who has been followed for chronic lymphocytic leukemia since Received treatment with chlorambucil 2003 in the context of a clinical trial. In 2004 splenectomized in connection with surgery for colon cancer. In 2006 treated with two courses of fludarabine and cyclophosphamide, after which the platelet count never recovered, since then no further treatment although the count slowly increases.? istograms : This histogram shows, after dilution of the sample due to the severe leukocytosis, a ym-peak dominated distribution. DE-flag. DE : Thrombocytopenic. Neutrophils 9.15 x 10 9 /l ymphocytes x 10 9 /l Monocytes 3.05 x 10 9 /l Slight anisocytosis and microcytosis. Thrombocytopenia with microcytic platelets. The lymphocytes are of normal size and maturity although cells with divided nuclei occur occasionally. Gumprecht s nuclear shadows are frequent. TE MEDONIC CASE BOOK

13 ymphomas Case 03 eukocytosis Diagnosis: Chronic lymphocytic leukemia This man, 69 years old, has been followed for chronic lymphocytic leukemia since Favorable normal genotype and un-mutated IgV. itherto no treatment.? istograms : Severe leukocytosis with lymphocytosis. This histogram shows a typical C pattern. Most of the cells are to be found within the lymphocyte peak. DE : Neutrophils 3.33 x 10 9 /l ymphocytes x 10 9 /l Pronounced lymphocytosis and presence of Gumprecht s nuclear shadows Essentially normal. Almost normal. The blood dominates of lymphocytes, some presence a nucleol. Gumprecht s nuclear shadows are frequent. TE MEDONIC CASE BOOK

14 ymphomas Case 04 airy cells Diagnosis: airy cell leukemia This 92-year old man surgically treated for bladder cancer several times since Now when operated on again anemia and leukocytosis were noted, and the blood smear showed 54 % hairy cells. By flow cytometry of bone marrow these lymphoid cells expressed CD19, CD20 and partly CD23 but not CD25. Erythrocyte trapping was noted in the bone marrow biopsy. The spleen was somewhat voluminous measuring 13x11x6.5 cm. The patient received the diagnosis hairy cell leukemia and treatment with one course of cladribine. istograms : The histogram shows a leukocytosis with lymphocytic cells dominating. The MID-cell population is pronounced increased. Anemia. : Reduced counts. Neutrophils 1.82 x 10 9 /l Eosinophils 1.09 x 10 9 /l ymphocytes x 10 9 /l Monocytes 1.46 x 10 9 /l Others* x 10 9 /l *54 % judged to be hairy cells Anisocytosis Reduced numbers Three hairy cells with their characteristic hairy cytoplasmic projections.. TE MEDONIC CASE BOOK

15 ymphomas Case 05 Immature cells Diagnosis: Burkitt lymphoma/tuberculosis This is a 4-year old boy who was born in ibya (Africa). e receives treatment for IV-1 infection that was transmitted from a blood transfusion. e also has a complicated tuberculosis infection. Unfortunately he is also afflicted by IV-related Burkitt lymphoma engaging the bone marrow, lymph nodes and CNS. Repeated courses of chemotherapy have been given. After the last course he developed febrile neutropenia, for which broad spectrum antibiotics and antifungal treatment were given. To shorten the neutropenia he also received G-CSF (ratiogastrim). Now the count has recovered and there is a left-shifted increased granulopoiesis with hypergranulation, as a result of the G-CSF treatment. istograms : eukocytosis, with a mid-gran histogram showing suspicion of immature cells (-flag). No clearly cellpopulations are distinguishable. Anemia. : Thrombocytopenia. Bands 4.52 x 10 9 /l Neutrophils x 10 9 /l ymphocytes 0.75 x 10 9 /l Monocytes 1.76 x 10 9 /l Promyelocytes 0.25 x 10 9 /l Myelocytes 1.51 x 10 9 /l Metamyelocytes 2.76 x 10 9 /l Anisocytosis, microcytosis, macrocytosi, polychromasia, tear drop cells, owell-jolly bodies Few, single giant forms A myelocyte and a clover shaped monocyte shown to the left. Just above the monocyte a cigar-shaped platelet is seen. TE MEDONIC CASE BOOK

16 ymphomas Case 06 arge granular lymphocytes, G Diagnosis: T-cell large granular lymphocytic leukemia A 70-year old woman who was splenectomized 25 years ago due to suspected ITP. She had recurrent pneumonias. Investigated with new bone marrow samples 1994 and 2012 as she developed neutropenia, lymphocytosis and monocytosis in addition to persisting thrombocytopenia. At the latter time point flow cytometry showed 36 % lymphocytes that were positive for CD57, CD8 and CD3 and probably also for CD7 and the T-cell receptor alpha beta. In addition, investigation by PCR showed presence of T-cell receptor rearrangements, confirming the diagnosis arge Granular eukemia (G). Immunosuppressive treatments with Prednisone and Methotrexate as well as high-dose intravenous immunoglobulins and Ratiogastrim have been given, with variable success, so that remissions and relapses have shifted. istograms : A little wider YM-peak that normal. : Thrombocytopenia. Bands 0.02 x 10 9 /l Neutrophils 0.31 x 10 9 /l Eosinophils 0.02 x 10 9 /l ymphocytes 1.49 x 10 9 /l Monocytes 0.55 x 10 9 /l Anisocytosis, microcytosis, macrocytosi, polychromasia, tear drop cells, owell-jolly bodies Few, single giant forms A large granular lymphocyte is shown and just above it a owell-jolly body.. TE MEDONIC CASE BOOK

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