title: Preleukemic phase of chronic myelogenous leukemia: morphologic and immunohistochemical characterization of 7 cases.
abstract: Patients with chronic myelogenous leukemia (CML) present typically with an elevated white blood cell count (WBC) and cytogenetic or molecular genetic evidence of t(9;22)/BCR-ABL1 fusion gene. Rarely, CML patients may present with a normal or mildly elevated WBC and are asymptomatic, and we describe 7 patients in this study. The WBC in these patients ranged from 3.6 to 14.3 K/mm(3) with 50% to 73% granulocytes and 0% blasts. In all patients, t(9;22)(q34;q11.2) was detected by conventional cytogenetics, and BCR-ABL1 fusion was shown, supporting the diagnosis of preleukemic CML (pre-CML). We compared these patients with a group of 5 cases of CML in chronic phase (CML-CP) and 5 bone marrow specimens with a leukemoid reaction (n=5). Reticulin, CD34, and CD61 immunostains were performed on all bone marrow biopsy specimens. Peripheral blood absolute basophilia (≥200/mm(3)) was noted in only 4 of 7 pre-CML cases, whereas it was present in all CML-CP cases and absent in leukemoid reaction cases. The mean ±SD of microvascular density of pre-CML cases (10.0 ± 4.3 vessels/200× field) was twice that of leukemoid reaction cases (5.0 ± 1.0) (P=.02; Student t test) but similar to that of CML-CP cases (12.5 ± 3.6). Microvessels in pre-CML, highlighted by CD34, were tortuous with abnormal branching, although to a lesser extent than those found in CML-CP. Microvessels in leukemoid reaction were generally straight. The percentage of small, hypolobated megakaryocytes, highlighted by CD61 in pre-CML, was 40%, 3 times that found in leukemoid reaction cases (13%) but less than that of CML-CP cases (86%). We conclude that pre-CML should be suspected in patients with a normal to mildly elevated WBC and absolute basophilia. Bone marrow examination can usually distinguish pre-CML from a leukemoid reaction based on the percentage of small, hypolobated megakaryocytes; microvascular density; and morphologic features.
authors.affiliation: Department of Pathology, University of Southern California Keck School of Medicine, 1200 N State St, Room GNH 3850, Los Angeles, CA 90033, United States. Electronic address: Le.Aye@med.usc.edu.
authors.forename: Le Le
authors.initials: le L
authors.lastname: Aye
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States. Electronic address: SLoghavi@mdanderson.org.
authors.forename: Sanam
authors.initials: S
authors.lastname: Loghavi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States. Electronic address: khyoung@mdanderson.org.
authors.forename: Ken H
authors.initials: KH
authors.lastname: Young
authors.affiliation: Department of Pathology, University of Southern California Keck School of Medicine, 1200 N State St, Room GNH 3850, Los Angeles, CA 90033, United States. Electronic address: Imran.Siddiqi@med.usc.edu.
authors.forename: Imran
authors.initials: I
authors.lastname: Siddiqi
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States. Electronic address: cyin@mdanderson.org.
authors.forename: C Cameron
authors.initials: CC
authors.lastname: Yin
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States. Electronic address: mark.routbort@mdanderson.org.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Routbort
authors.affiliation: Department of Pathology, Orlando Regional Medical Center, 52 W Underwood St, Orlando, FL 32806, United States. Electronic address: mliang100@gmail.com.
authors.forename: Mei
authors.initials: M
authors.lastname: Liang
authors.affiliation: Santa Rosa Medical Group, 3661 Las Posas Rd, Camarillo, CA 93010, United States. Electronic address: keith.eilerman@gmail.com.
authors.forename: Keith
authors.initials: K
authors.lastname: Eilerman
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States. Electronic address: ljmedeiros@mdanderson.org.
authors.forename: L Jeffrey
authors.initials: LJ
authors.lastname: Medeiros
authors.affiliation: Department of Pathology, University of Southern California Keck School of Medicine, 1200 N State St, Room GNH 3850, Los Angeles, CA 90033, United States. Electronic address: Russell.Brynes@med.usc.edu.
authors.forename: Russell K
authors.initials: RK
authors.lastname: Brynes
authors.affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, United States. Electronic address: cbuesora@mdanderson.org.
authors.forename: Carlos
authors.initials: C
authors.lastname: Bueso-Ramos
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001853:Bone Marrow / Q000473:pathology; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D007955:Leukemoid Reaction / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D008533:Megakaryocytes / Q000473:pathology; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D010677:Philadelphia Chromosome
chemical_list: C581634:BCR-ABL1 fusion protein, human; D014408:Biomarkers, Tumor; D016044:Fusion Proteins, bcr-abl
keywords: BCR-ABL1 fusion gene; Bone marrow; Chronic myelogenous leukemia; Megakaryocytes; Microvasculature; Philadelphia chromosome; Pre-leukemia