Complex karyotype with novel translocation in pure erythroid leukemia patient

Hematology Reports 2015; volume 7:5674 Abstract Case Report Clinical history N on co m Pure erythroid leukemia (PEL) is rare hematopoietic neoplasm characterized by uncontrolled proliferation of immature erythroid precursors − mainly abnormal proerythroblasts − comprising at least 80% of bone marrow cells. In this paper, I present a case of 48 years old patient, who presented with pancytopenia and circulating erythroblast in peripheral blood after long history of alcohol abuse. Bone marrow examination revealed hypercellular marrow which is markedly infiltrated with immature erythroid precursors. An expanded panel of immunophenotyping markers has confirmed the diagnosis of PEL. Cytogenetics analysis detected a complex karyotype with multiple chromosomal abnormalities and a novel translocation, t(8;9) (p11.2;q12), which has not been reported in acute myeloid leukemia (AML) in the past. The patient was treated with standard AML chemotherapy but he did not show an optimal response and passed away. An updated and short review about various aspects of PEL has been made with special focus on immunophenotyping and genetic studies. A 48 years old Saudi male presented to the emergency department with shortness of breath, persistent low grade fever and easy bruising for 3 days. The patient also complained of progressive weakness, loss of appetite for 2 months duration and had lost 7 kg of weight over the last 2 months. His family or medical history was unremarkable and was not receiving any medical treatment for any chronic illness. Social history revealed that he was unemployed with low economic status. He was a heavy smoker consuming two packs of cigarettes daily for several years and had long history of heavy alcohol abuse. He denied any drug abuse or toxin exposure. On physical examination; he was pale, had multiple bruises particularly on the lower limbs and his body temperature was 38.2°C. There was mild hepatosplenomegaly with no lymphadenopathy. Correspondence: Mansour Semar Aljabry, Hematology Unit, Pathology Department, King Khalid University Hospital, King Saud University, P.O Box 2925, Riyadh 11461, Kingdom of Saudi Arabia. Tel.: +966.114.671812. E-mail: Key words: pure erythroid leukemia, acute erythroid leukemia, acute myeloid leukemia. Conflict of interest: the authors declare no potential conflict of interest. Funding: this paper has been funded by King Saud University, Deanship of Scientific Research, College of Medicine, Research Center. Received for publication: 14 October 2014. Revision received: 20 February 2015. Accepted for publication: 24 February 2015. on ly Department of Pathology, King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia Hematological investigation revealed hemoglobin of 51 g/L (120-160 g/L), red blood cells (RBC) 2.15×1012/L (4.2-5.5×1012/L), mean corpuscular volume 88 fl (78-97 fl) and mean corpuscular hemoglobin 28 pg (27-32 pg). Leukocytes were 2.01×109/L with 3% blasts, myelocytes 3%, neutrophils 19%, monocytes 8%, basophils 1% and 67% lymphocytes. Platelet count was 23×109/L (140-450×109/L). Biochemical markers revealed elevated serum levels of lactate dehydrogenase (LDH), uric acid and total bilirubin. Renal function and liver function tests were within normal limits. Peripheral smear showed marked anisopoikilocytosis with schistocytes, basophilic stippling, spherocytes, many nucleated RBC and rare circulating blasts. Erythroid precursors showed significant dysplastic changes with nuclear irregularities, budding and bi-nucleation while neutrophil morphology was essentially normal. The circulating blasts were medium to large blasts with round nuclei, fine chromatin, prominent nucleoli and deep blue a granular cytoplasm without Auer rods. The bone marrow aspirate yielded a markedly hypercellular bone marrow essentially replaced by erythroid precursors, representing approximately 87% of the marrow cells. Of this, the proerythroblasts comprised 58%. The erythroid precursors displayed dysplastic morphology, including multi-nucleation, nuclear budding and megaloblastoid changes. Myeloblasts were about 3% and megakaryocytes were reduced without obvious dysplasia. Periodic Acid Schiff (PAS) stain revealed globular and block-like positivity in many abnormal erythroblasts. Perls Perl’s stain showed a few sideroblasts; however no ringed sideroblasts were observed. Flow cytometry analysis of the bone marrow aspirate revealed many immature cells which were positive for CD71, glycophorin A and partially positive for CD36, consistent with erythroid precursors. Staining for CD13, CD33, CD34, CD41, CD61 and all other myeloid and lymphoid makers was negative. Myeloblasts were not detected. The bone marrow biopsy revealed a hypercellular packed marrow with monotonous leukemic infiltrate composed of primitive looking blasts. The infiltrating blasts had scant cytoplasm, high nuclear to cytoplasmic ratio, round nucleus with fine chromatin and 1-2 prominent nucleoli (Figure 1). Immunohistochemistry revealed strong positivity to E-cadherin (ECH-6; Ventana Medical Systems, Inc., Roche, Basel, Switzerland), weak positivity for glycophorin A (GA-R2; Ventana Medical Systems, Inc.) and negative for CD34, MPO, vWF, CD3 and CD79a. These morphological and immunophenotypic findings supported the diagnosis of pure erythroid leukemia (PEL) FAB subtype M6b. al us e Mansour Aljabry Methods and investigations m er ci Complex karyotype with novel translocation in pure erythroid leukemia patient [Hematology Reports 2015; 7:5674] This work is licensed under a Creative Commons Attribution NonCommercial 3.0 License (CC BYNC 3.0). ©Copyright M. Aljabry, 2015 Licensee PAGEPress, Italy Hematology Reports 2015; 7:5674 doi:10.4081/hr.2015.5674 Cytogenetics analysis was performed on 20 metaphases and detected a complex karyotype with multiple chromosomal aberrations (Figure 2): 46-48,XY,add(4)(q?) [11]del(4)(p?)[17],del(5)(q23)[8],add(6)(p 23)[16],del(7)(q22)[12], t(8;9)(p11.2;q12)[20],+del(9)(q22)[17],de l(18)(q21)[13] Hospital course The patient was treated with a standard induction (7+3) chemotherapy regimen consisting of daunorubicin 45 mg/m2 daily for 3 days and cytarabine 100 mg/m2 daily continuous infusion for 7 days. Blood and platelet transfusions were administered during induction period. On post-induction day 28, the bone marrow biopsy showed hypercellular marrow with 38% residual erythroblasts. Cytogenetics showed persistent multiple chromosomal abnormalities. He was re-inducted again with FLAG regimen (fludarabine + high-dose cytarabine + G-CSF). He failed to tolerate the treatment and died after 10 days due to severe pulmonary infection. Discussion Pure erythroid leukemia is exceedingly rare type of AML representing <1% of all AML cases and 13% of acute erythroid leukemia cases.1 It [page 21] al us e m er ci Figure 1. Morphological and Immunohistochemistry findings of bone marrow. A) Bone marrow aspirate with erythroid p (...truncated)