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Letter to the Editor
Diagnostic Hematology
A Case of Acute Myeloid Leukemia Concurrent With Untreated Chronic Lymphocytic Leukemia
Hye-Young Lee, M.D., Chan-Jeoung Park, M.D., Enkyung You, M.D., Young-Uk Cho, M.D., Seongsoo Jang, M.D., and Eul-Ju Seo, M.D.
Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, Seoul, Korea
Dear Editor,
The association of CLL with hematologic malignancies such as AML is relatively rare [1, 2], with mostly associated with prior cytotoxic chemotherapy [3]. Few reports of untreated CLL mani- festing with or followed by AML suggested that each tumor prob- ably evolved from simultaneous expansion of two independent clones, not a common clone [1]. Concomitant AML and CLL hav- ing a common clonal origin is exceptional, and to our knowledge, only two cases were reported previously [4, 5]. We present a case of de novo AML concurrent with untreated CLL, with two karyo- typic abnormalities in the same clone.
A 76-yr-old man was presented with fever and chills in August 2015, with a history of hypertension, but no cancer, chemother- apy, or irradiation. Physical examination indicated mild pallor and a skin lesion with redness and swelling on the left thigh, without lymphadenopathy or gingival lesions. Laboratory exami- nations showed moderate leukopenia (white blood cells [WBC], 2.8×109/L), comprising 1% myeloblasts and 60% mature lym- phocytes, macrocytic anemia (Hb, 92 g/L; mean corpuscular volume, 104.0 fL), and thrombocytopenia (platelets [PLT], 31×109/L). Bone marrow (BM) examination indicated a normo- cellular marrow for his age (cellularity, 20%), including 21.6%
myeloblasts and 16.6% mature lymphocytes (Fig. 1). The clot
section showed multiple irregularly shaped medium-to-large lym- phoid nodules, comprising small mature lymphocytes. Immuno- histochemicalstains of the BM clot section showed that the my- eloblasts were positive for CD34 and CD117, and the small lym- phoid cells in the lymphoid nodules were positive for CD5, CD19, and CD23.
Flow cytometric immunophenotyping of BM aspirate showed two populations: one positive for myeloblast markers (CD34, CD13, CD33, CD117, and HLA-DR) and another for B lymphoid mark- ers (CD5, CD19, CD20, and CD23) along with co-expression of CD19 and CD5 (Fig. 2A). Chromosome analysis showed an ab- normal karyotype (46,XY,del(13)(q14),add(14)(q32)[3]/46,XY[17]) (Fig. 2B). FISH analysis performed by using the probes D13S319/
13qter Dual Color Probe (Cytocell, Cambridge, UK) and LSI IGH Dual Color Probe (Vysis, Downers Grove, IL, USA) showed nu- cish (D13S319x2,13qterx1)[18/200] and nucish (IGHx1)[30/200], respectively (Fig. 2C). Skin biopsy of the left thigh suggested pyo- derma.
On the basis of the WHO 2008 criteria, the patient was diag- nosed as having AML, NOS (AML with maturation). However, he did not receive induction chemotherapy for AML because of his advanced age and comorbidities such as hypertension and worsening left thigh cellulitis. He was treated with a hypomethyl-
Received: September 13, 2016 Revision received: January 2, 2017 Accepted: March 8, 2017
Corresponding author: Chan-Jeoung Park
Department of Laboratory Medicine, University of Ulsan, College of Medicine and Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 05505, Korea
Tel: +82-2-3010-4508, Fax: +82-2-478-0884, E-mail: cjpark@amc.seoul.kr
© Korean Society for Laboratory Medicine.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Lee H-Y, et al.
A case of AML concurrent with CLL
https://doi.org/10.3343/alm.2017.37.4.336 www.annlabmed.org 337
Fig. 1. Coexistence of myeloblasts and neoplastic lymphoid cells on bone marrow aspirate smear (Wright stain, ×1,000).
Fig. 2. Flow cytometric immunophenotyping and chromosomal analysis with bone marrow aspirate. (A-a) Gating for the two populations of neoplastic cells (myeloblasts of AML and mature lymphoid cells of CLL); (A-b) Myeloblasts with co-expression of CD34 and CD117; (A-c) Mature B-lymphoid cells with co-expression of CD19 and CD5; (A-d) Mature B-lymphoid cells with co-expression of CD19 and CD23.(B) Abnormal karyotype with del(13q) and add(14q).(C) FISH findings with each probe. (C-a) Terminal deletion of 13q34 with the D13S319/13qter Dual Color Probe (Cytocell, Cambridge, UK); (C-b) IGH deletion on 14q32 with the LSI IGH Dual Color Probe (Vysis, Downers Grove, IL, USA).
Abbreviations: SSC, Side Scatter; CD, cluster of differentiation.
A B
C
(a) (b)
ating agent (2 cycles of decitabine, 35 mg/day), and transfused intermittently. He was subsequently presented to the hospital in March 2016 with worsening dyspnea and exhibited pancytope- nia (Hb, 73 g/L; PLT, 45×109/L; WBC, 1.5×109/L with 12% seg- mented neutrophils, 84% mature lymphocytes, and 4% mono-
cytes). BM aspirates showed 6% myeloblasts and 24% mature lymphocytes. The AML appeared to respond to chemotherapy.
He was treated with empirical antibiotic therapy for suspected pneumonia. After being discharged, he has been undergoing rou- tine follow-up, without a third cycle of decitabine treatment.
We describe a case of simultaneous development of AML and CLL. Regarding primary etiology, impaired immunity and old age have been discussed previously [6]; our patient had both these risk factors. Graf [7] suggested that, due to the plasticity of neo- plastic common progenitor cells, the neoplastic transformation of common progenitor cells could occur during hematopoietic differentiation, and they could develop into two separate lineages (myeloid and lymphoid). Although we detected two populations of myeloid and lymphoid lineages withflow cytometry, both chro- mosomal abnormalities, add(14q) and del(13), were observed in the same clones on karyotyping. Del(13q) could be found in my- eloid and lymphoid malignancies. While del(14q) and 14q32- related translocation are associated with B lineage malignancies, the significance of additional material on 14q32 such as add(14q) in tumor cytogenetics is unclear. Moreover, 14q32/IGH rearrange-
Lee H-Y, et al.
A case of AML concurrent with CLL
338 www.annlabmed.org https://doi.org/10.3343/alm.2017.37.4.336 ment of B-lymphoid malignancies was not detected, suggesting
that both myeloid and lymphoid cells originated from the same clone. Hou et al [8] reported a human B-cell/myeloid common progenitor, which matured into a lineage according to the cul- ture environment; thus, the pathways for myeloid and lymphoid development may not be very strict. In the current case, we be- lieve that a common progenitor clone expanded and differenti- ated into two separate lineages. The flow cytometric sorting of the two populations into myeloid or lymphoid cells, followed by karyotyping of each population, is required to confirm the clon- ality. Thus, we report a case of concomitant occurrence of AML and CLL. On the basis of the chromosomal abnormalities in this patient, we suspect that the myeloid and lymphoid lineages were evolved from common progenitor cells.
Authors’ Disclosures of Potential Conflicts of Interest
No potential conflicts of interest relevant to this article were re- ported.
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