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 1. Characteristics of chronic and accelerated phases of primary chronic basophilic leukemia patients [2,3,4,5].Characteristics Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Case 7(Acceleratedphase of Case 6)Age/Sex 30/Male 67/Male 52/Male 32/Male 81/Male 68/Female At the age of 73PresentingsymptomsPolyurea,Diabetesinsipidus,Polydisplasia,PituitarylesionProgressivefatigue,Severe motorneuropathyProgressivefatigue,Epigastric pain,Pruritisurticaria,Weight lossProgressive fatigueDecreasein appetite,Weight lossFebrile episodesoccuring with8-week intervalswith abdominalpain, Weight lossSplenomegaly Absent Marked Absent Marked 3-4 cm Absent 4 cmHemoglobin (g/dL) 11.1 12.6 13.2 9.1 10.5 11.2 5.7-7.1WBC (x10 9 /L) 9.9 9.3 52.0 47.5 50.0 59.1 59-315Platelet (x10 9 /L) 200 319 227 240 874 226 134-41BM blast (%) 7 2 8 5 NR <1 6BM basophil (%) 15 26 20 NR 40 75 51BM eosinophil (%) 3 3 6 6 15 8.5 13BM dysplasiaAtypicalmegakaryocytichyperplasiaAtypicalmegakaryocytichyperplasiaAtypicalmegakaryocytichyperplasiaDysmegakaryopoiesis See text See text See textPB basophil (%) NR NR NR NR 38 70 54-65PB dysplasia NR NR NR NR See text See text See textToluidine blue NP NP NP NP NP Positive PositiveAntigenexpression by flowcytometryCytogeneticfindingsMolecular geneticstudiesNP NP NP NP CD11a, CD11b,CD13, CD18,CD33, CD45,CD123+8, 11q- -7, -7/-4 46, XY 46, XY 46, XY, t(5;12)(q31;p13)- - - - Absence ofJAK2, (V617F)mutation,BCR/ABLrearrangementby PCRCD10 (dim),CD11c (dim),CD13, CD15,CD22 (dim), CD25,CD33, CD38,CD45, CD123,MPO, IgDR47, XX, der(6)t(6;?)(q25-27;?)+mar(16)IL-6 geneexpressionin neoplasticbasophils andabsence ofJAK2 mutationdetected by realtime PCRIL-6 (pg/mL) NP NP NP NP NP 15.8 38.5Febrile episodeswhen basophilcount >40x10 9 /Lwith abdominalpainCD10 (dim), CD11c(dim), CD13, CD15,CD22 (dim), CD25,CD33, CD38,CD45, CD123,MPO, IgDR, CD11747, XX, der(6)t(6;?)(q25-27;?)der(17) t(17;?)(p13;?) +mar(16)Heterozygotesubstitutionof C1650A>T(K550N) on exon11, wild typesequence on exons9, 13, 17. Absenceof PIF1L1-PDGFRArearrangementTryptase (μg/L) NP NP NP NP NP NP 42.9-51.2Treatments ALLO-SCT HydroxyureaprednisoneFollow-up(months)Imatinib ALLO-HSCT Hydroxyurea Hydroxyurea Hydroxyurea,Imatinib,Etoposide,Leukapheresis,Prednisone CTX,RBC transfusion35, alive 48, dead 2, alive 10, dead 9, dead >50, alive 5, deadCBL: Chronic basophilic leukemia, WBC: white blood cells, BM: bone marrow, PB: peripheral blood, NR: not recorded, NP: not performed, IL-6: interleukine-6, ALLO-SCT: allogeneichumanstem cell transplantation, RBC: red blood cells, PCR: polymerase chain reaction.284
Turk J Hematol 2018;35:283-289Cavit Çehreli, Diagnostic Problems in Chronic Basophilic Leukemia2 h. Physicians were misled in making a differential diagnosis offamilial Mediterranean fever because they relied on differentialcounts made by ABCCs [4]. However, manual differential countsmade on PB smears during a febrile episode revealed that the ABCCswrongly characterized 70% of basophils as neutrophils; this wasconfirmed by toluidine blue stain and antigen expression by flowcytometric analysis. Marked elevation in plasma interleukin-6 (IL-6) level of 15.8 pg/mL (normal: <5.8 pg/mL) was detected duringthe febrile episode. Real-time polymerase chain reaction showedIL-6 gene expression in neoplastic basophils, revealing that IL-6was released from neoplastic basophils infiltrating the BM [4](Table 1). IL-6 production and release by normal human basophilshas not been reported in the literature [10].Values of PB and BM Basophil Percentages in the Diagnosis of CBLAs shown in Tables 1 and 2, BM basophil percentages of 15%,26%, and 20% in 3 of 4 patients with primary CBL were reportedby Pardanani et al. [2]. These values are almost equal to theBM basophil percentage of ≥20% in 11% of 25 patients in theaccelerated phase of CML reported by Kantarjian et al. [11] andalso BM basophil percents greater than 1% (range 1 to 27%) in34 cases and median 19% (range 14 to 27%) in 6 patients (in 4of whom toluidine blue staining was positive) were reported byHoyle et al. [12] in their series of 750 patients with acute myeloidleukemia. However, the BM basophil percentages in patientsreported by Pardanani et al. [2] were markedly lower comparedto the BM basophil percentages (40%,75%) of two patients in thechronic phase [3,4] and the value recorded (51%) in a patient inthe accelerated phase of primary CBL [5] (Table 1). BM basophilpercentages of 55%, 51.4%, 63%, 72%, and 66% in six patients withsecondary CBL were also respectively recorded (Table 2) [6,7,8,9].Dysplastic Changes in Primary CBLIn Case #5, a patient with primary CBL, dysplasia in the PB smearincluded hypogranular basophils with small and fine granulationsand nuclear hyperlobation. In the BM smear, an increase incellularity and megakaryocytes and hypogranular, agranular,and hypersegmented forms of basophils and eosinophils withcoarse granulations and nuclear hyperlobation in addition tomegakaryocytes with many small and hypolobated forms werereported [3].In Case #6, a patient with primary CBL in the chronic phase,dysplasia appeared as basophils with coarse basophilic granules,occasionally hypersegmented or giant segmented, and band formsof basophils in PB smear [4].In the BM smear, an increase in cellularity, megakaryocytes,eosinophils, and prominent basophilic hyperplasia with thepresence of all stages of maturation that resulted in markedneutrophilic suppression and mild suppression in erythroidlineages were noted. Three-lineage dysplasia manifestedas hyposegmented basophils, giant segmented bands, andmetamyelocyte forms of basophils and hypogranular basophilicmetamyelocytes were noted. Dysplasia seen in eosinophilsincluded binuclear metamyelocyte and myelocyte forms ofeosinophils and large eosinophilic myelocytes. Occasionalbinuclear (Figure 1A) and multinuclear red cell precursorswere also noticed. In addition, binuclear agranular immaturemegakaryocytes, mononuclear giant forms of megakaryocytes,and megakaryocytes with nuclear hyperlobation were observed.Toluidine blue stain showed red (metachromatic) granularstaining in about 75% of non-erythroid granular cells in themarrow fields (Figure 1B).Dysplastic Changes in the Accelerated Phase of Primary CBLClinical and hematologic features of the accelerated phase ofprimary CBL were only observed by Cehreli et al. [5] in theirpatient in the chronic phase of primary CBL (Case #6) after53 months of hematologic remission; this is shown as Case #7in Table 1. She presented with symptoms of anemia and wasfound to have relapse of her CBL and development of systemicmastocytosis (SM) as a secondary neoplasia. Three monthslater, the patient showed a rapid downhill clinical course whentransformation of primary CBL to the accelerated phase withsimultaneous occurrence of mast cell leukemia (MCL) wasdetected [5]. She experienced febrile episodes with abdominalpain during the accelerated phase of primary CBL with MCL.Although mast cells and eosinophils were shown to produceIL-6 [10], no febrile episodes were observed despite increasesin mast cell (MC) counts to 3x10 9 /L and eosinophil counts to5.3x10 9 /L unless her basophil counts climbed to >40x10 9 /L whenprominent elevation in IL-6 level (38.5 pg/mL) was found. Ina Wright-stained BM smear, basophilic hyperplasia with thepresence of all stages of maturation that resulted in markedsuppression in neutrophilic and erythroid lineages in addition toaggregates of MCs with a new and undefined MC morphologywere demonstrated. MCs have round or oval nuclei, one or morenucleoli in immature forms, and mixed orange and dark purplishto black round cytoplasmic granules (Figure 2A). Tryptaseimmunohistochemical staining of the PB smear showed round,brown, granular cytoplasmic staining in the aggregates of thecells, confirming that these cells demonstrated tryptase activityand represented MCs (Figure 2B), because β-tryptase is a naturalserine protease and is the most abundant mediator stored in thegranules of MCs [13]. Three-lineage dysplasia manifested as gianthypersegmented basophils, giant binuclear metamyelocytes,binuclear hypogranular basophilic metamyelocytes, binuclearerythroblasts, and Pelger-Hüet anomalies were noted.Additionally, marked pyknosis, manifested as a decrease in bothcellular and nuclear sizes, resulted in dense chromatin clumping,inducing a nuclear appearance that resembled a chromatin mass.Pyknotic myelocytes, metamyelocytes, binuclear basophilicmetamyelocytes, and drum stick-like nuclear sticks in bothpyknotic eosinophils and basophils were observed (Figure 2A).Dysplastic changes in the megakaryocytic lineage were similarto those seen in the chronic phase of the patient [4].Marked pyknotic changes in the accelerated phase of primary CBL[5] have not been reported in patients with the chronic phase ofprimary CBL [3,4] as well as in patients with the accelerated [5,7,8]and chronic phase [9] of secondary CBL in the literature.285
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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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