Turkish Journal of Hematology Volume: 35 - Issue: 4

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Cavit Çehreli, Diagnostic Problems in Chronic Basophilic LeukemiaTurk J Hematol 2018;35:283-289Table 2. Characteristics of secondary chronic basophilic leukemia patients reported in the literature [6,7,8,9].Characteristics Case 1 Case 2 Case 3 Case 4 Case 5Age/Sex 45/Male 57/Female 61/Male 49/Male 45/MalePhase of CBL Accelerated Accelerated Accelerated Accelerated ChronicPresenting symptomsFatigue,Gas,FullnessTiredness,Weight loss,Abdominal pain,Night sweatsFatigue,Productive coughWeakness,Myalgia,Intermittent feverFatigue,Weight lossSplenomegaly Massive Massive Massive NR 3-4 cmHemoglobin (g/dL) 7.7 7.7 6.7 9.1 5.1WBC (x10 9 /L) 223 190 175 42 173Platelet (x10 9 /L) 16 162 NR 12 NRBM blasts (%) 11 5.8 NR 7 9BM basophils (%) 55.2 51.4 63 72 66BM eosinophils (%) 2 5 NR NR 8BM dysplasia NR NR NR Large basophilic granules See textBM cellularity andfindingsHypercellular,BDSMHypercellular,BDSMIncreased,BDSM90-100%,BDSMPB basophils (%) 75 71 NR 90 40PB dysplasia NR NR NR NR NRToluidine blue NP NP Metachromatic staining Metachromatic staining NPAntigen expression byflow cytometryCytogenetic findingsInterval between CMLand CBL (months)TreatmentsHypercellularNP NP NP NP CD11b, CD13, CD33, CD34,CD117, CD123, HLA.DR,CD45, CD7 (aberrant)InsufficientanalysisInsufficientanalysis[46, XY, t(8;21), t(9;22)/48,XY, +8, t(8;21), t(9;22)+Ph’/49, XY, +8, t(8;21),t(9;22), 9q+, +Ph’]Diagnosis CML Ph’ t(9;22),Diagnosis of CBL, extrachromosomes (8, 10, 17, X)12 31 4.5 48 -Busulfan,SupportivecareBusulfan,Splenicirradiation,Supportive careHydroxyurea, +3 cyclesCHOPALLO-HSCTFollow-up (months) 3, dead 1, dead 4, dead Died after ALLO-HSCT NR46, XY, t(9;22)Resistant to Gleevec,aggressive treatmentCBL: Chronic basophilic leukemia, WBC: white blood cells, BM: bone marrow, PB: peripheral blood, NR: not recorded, NP: not performed, ALLO-HSCT: allogeneic-human stem celltransplantation, BDSM: basophils at different stages of maturation, CHOP: cyclophosphamide, doxorubicin, vincristine, and prednisone.Dysplastic Changes in the Chronic and Accelerated Phases ofSecondary CBLCase #5 in Table 2 was the only patient in the chronic phase ofsecondary CBL presenting with dysplasia. Diagnosis of CML maypossibly be made when transformation of CML to CBL occurs; inthis case, the patient had marked basophilia with the presence of40% and 66% basophils in PB and BM, respectively, and antigenexpressions by flow cytometric analysis revealed the nature ofcells as basophils. Dysplasia included cytoplasmic hypogranulationor agranulation and nuclear hypersegmentation, eosinophilswith abnormal granulation and nuclear hyperlobation, anddyserythropoiesis [9]. No dysplastic findings have been reported inpatients in the accelerated phase of secondary CBL [6,7,8] (Table 2).Confirmatory Laboratory StudiesBoth basophils and MCs have electron-dense cytoplasmic granulesand produce numerous mediators such as histamine common toboth cells. They also both show metachromatic staining withbasic dyes, toluidine blue, and Alcian blue [1]. Toluidine blue stainshowed a red (metachromatic) granular cytoplasmic staining inboth basophils and MCs (Figure 1B) [4,5,14,15]. Peroxidase stainshowed black granular cytoplasmic staining in basophils, but MCsdo not contain myeloperoxidase and showed negative activityby peroxidase stain (Figure 2C) [16]. Flow cytometric analysis ofmononuclear cells (MNCs) of the BM using monoclonal antibodiesagainst the following antigens in Cases #6 and #7 showed thatantigen expressions were positive for CD10 (dim), CD11c (dim),CD13, CD15, CD22 (dim), CD25, CD33, CD38, CD45, CD123,286
Turk J Hematol 2018;35:283-289Cavit Çehreli, Diagnostic Problems in Chronic Basophilic Leukemiaimmunoglobulin D (IgD) receptor, and myeloperoxidase andnegative for HLA-DR, CD7, CD34, CD71, and CD117 with aberrantexpression of CD10 [17,18], thus revealing that the neoplastic cellswere basophils.Expression of the IgD receptor on normal basophils wasdemonstrated by Chen and Cerutti [19] and was also shown onneoplastic basophils by Cehreli et al. [4,5].Importance of Confirmatory Laboratory Studies for the Diagnosisof CBLTang et al. [3] and Vaidya et al. [9] reported that automatedhematology analyzers did not characterize cells as basophils,but simply flagged them. Flow cytometric immunophenotypingbecame particularly important in confirming the nature of cellsas basophils [9]. Cehreli et al. [4,5] reported that ABCCs, evenwith advanced technology, wrongly characterized basophils asneutrophils, misleading physicians in making differential diagnosiswhen the physicians relied on differential counts made by ABCCs.These reported observations suggest that manual differentialcounts should be seen before making a decision for diagnosis andalso confirmed by metachromatic staining with toluidine blue stainin PB or BM smears and antigen expressions by flow cytometricanalysis in BM MNCs to make an accurate diagnosis of CBL. Theauthors also proposed that neoplastic basophils with coarse, darkpurple basophilic granules as demonstrated in Figure 1A maypossibly mimic neutrophils with toxic granules [5]. Neutrophilsusually contain light purplish-blue fine granules on Wright-stainedPB smears (Figure 1A). Interestingly, in 1932, Kugel and Rosenthal[20] found that during bacterial infections fine neutrophilicgranules are replaced by large, dark, irregular basophilic granules,which are called toxic granules, compared to the fine granules ofthe neutrophils.Oscillation in Leukocyte CountsSimilar to cyclic oscillations in leukocyte (neutrophil) countsreported in patients with CML [21,22], cyclic oscillations in basophilcounts with simultaneous elevations in CRP levels and associationwith febrile episodes were only demonstrated by Cehreli et al. [5]in patients with primary CBL [4], but not reported in patients withprimary [3] and secondary CBL [6,7,8,9].Literature findings reveal that the diagnosis of CBL is mainly basedon basophil morphology and increase in PB and BM basophilpercentages. The literature also suggests that higher BM andPB basophil percentages are required to establish a satisfactorymorphologic diagnosis of CBL. Based on the reported literaturefindings [2,3,4,5,6,7,8,9], diagnostic criteria for CBL as shown inTable 3 can be proposed.Differential DiagnosisThe presence of an increase in megakaryocytes with atypicalmegakaryocytic hyperplasia and BM basophil percentages ofless than 40% in 3 of four patients (Cases #1-3), the absenceof diagnostic confirmatory laboratory studies (Table 1), and anabnormal pattern of perivascular atypical MC infiltration detectedby tryptase immunohistochemical staining (Cases #2 and #4)suggesting concurrent MC disease were reported as primary CBL byPardanani et al. [2]. These findings created diagnostic problems inclassifying the cases as primary CBL as described by Pardanani et al.[2] because according to the proposed diagnostic criteria for CBL(Table 3) BM basophil percentages were less than ≥40%, increasedmegakaryocytes with dysplasia have been described in patients withessential thrombocythemia and chronic idiopathic myelofibrosis[23], and presence of abnormal pattern of perivascular atypical MCinfiltration detected by tryptase immunohistochemical staining inthe BM biopsy is one of the diagnostic criteria for SM [24].Figure 1. A) Showing hyposegmented basophils (1, 2, 6), binuclear erythroblast (3), giant forms of basophilic bands (4, 5), largeeosinophilic myelocyte (7), erythroblast with dysplastic nucleus (8), giant basophilic hypogranular metamyelocyte (9), giant binuclearbasophilic metamyelocyte (10), basophilic myelocyte (11), neutrophilic band (12), segmented neutrophil (13) in chronic phase of primarychronic basophilic leukemia (Wright’s stain, 100 x ); B) Demonstrating red color (metachromatic) granular cytoplasmic staining in 70%nucleated cells of the bone marrow (toluidine blue stain, 100 x ).287
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Page 114 and 115: AUTHOR INDEX 2018Olga Meltem Akay..
Page 116 and 117: SUBJECT INDEX 2018Basophilic stippl
Page 118 and 119: SUBJECT INDEX 2018Gluteal lymphoma
Page 120 and 121: SUBJECT INDEX 2018Diffuse large B-c
Page 122 and 123: SUBJECT INDEX 2018Thalassemia / Tal
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Turkish Journal of Hematology Volume: 35 - Issue: 4

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