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An Unusual Presentation of Chronic Myeloid Leukemia Case Report J Med Cases. 2020;11(7):196-200 Eosinophilia With Hepatic Mass and Abnormal Liver Function Tests: An Unusual Presentation of Chronic Myeloid Leukemia Neeraja Yerrapotua, Susmitha Edappallatha, Mohammad Jarrarb, Caroline Hammb, Pat Allevatob, Ali Gabalia, Indryas Woldieb, c Abstract chromosome. EoCML typically presents with the involvement of the heart, lungs, and central nervous system. Here, we report Chronic myeloid leukemia (CML) is a chronic myeloproliferative a rare and unusual case of eoCML presenting as a liver mass neoplasm characterized by excess granulocytes at different stages of with abnormal liver function tests, which has not been reported maturation and the presence of BCR-ABL1 fusion gene or Philadel- in the literature so far. phia chromosome. Absolute eosinophilia, basophilia, and monocyto- sis are not uncommon in CML. However, a rare entity called eosino- Case Report philic variant of CML (eoCML) can present with eosinophilia without excess neutrophils or basophils. Here, we report a rare and unusual case of eoCML presenting as a liver mass with abnormal liver func- A 26-year-old male with a past medical history of depression tion tests, which has not been reported in the literature so far. and marijuana use presented to the emergency room (ER) with abdominal pain and dyspepsia for 6 weeks. He had no history Keywords: Chronic myeloid leukemia; BCR-ABL; Hypereosinophil- of liver disease, alcohol abuse, recent travel, itching, changes ic syndrome; Chronic myelomonocytic leukemia in bowel habits, weight loss, fever, or chills. Vital signs in the ER were within normal limits. Physical exam was significant for icteric sclera. There was no mass or tenderness on abdomi- nal exam. Complete blood count was significant for leukocy- tosis of 25.4 × 109/L (reference range (RR): 3.6 - 11 × 109/L) Introduction with an absolute eosinophil count of 18.7 × 109/L (RR: 0 - 0.5 × 109/L). His absolute neutrophil count was within normal lim- 9 9 Chronic myeloid leukemia (CML) is a chronic myeloprolifera- its at 3 × 10 /L (RR: 2 - 7.5 × 10 /L), hemoglobin and platelet tive neoplasm characterized by excess granulocytes at differ- count were within normal limits as well. Liver function tests ent stages of maturation and the presence of BCR-ABL1 fusion were elevated with aspartate transaminase (AST) of 944 U/L gene or Philadelphia chromosome. The natural course of CML (RR: < 37), alanine transaminase (ALT) of 613 U/L (RR: 11 - consists of chronic phase (CP), accelerated phase (AP), and 61), alkaline phosphatase (ALP) of 956 U/L (RR: < 126), total bilirubin of 199 µmol/L (RR: 0 - 18), conjugated bilirubin of blast phase. Absolute eosinophilia, basophilia, and monocy- 122 µmol/L (RR: 0 - 10), and LDH of 1,437 U/L (RR: < 234). tosis are not uncommon in CML [1]. However, a rare entity Other blood tests, including prothrombin time (PT)/interna- called eosinophilic variant of CML (eoCML) can present with tional normalized ratio (INR), activated partial thromboplastin eosinophilia without excess neutrophils or basophils. Hypere- time (aPTT), lipase, renal function panel were within normal osinophilic syndrome (HES), characterized by high eosinophil limits. count, differs from eoCML by the absence of the Philadelphia Extensive testing was performed to identify the etiology of liver injury, which revealed negative viral hepatitis panel, Manuscript submitted May 29, 2020, accepted June 6, 2020 normal ceruloplasmin, alpha-fetoprotein (AFP), anti-mito- Published online June 29, 2020 chondrial antibody (AMA), carcinoembryonic antigen (CEA) and immunoglobulin G (IgG) levels. The IgE level was elevat- aDepartment of Pathology, Detroit Medical Center, Wayne State University, ed at 1,706 kU/L (RR: < 100 kU/L). Imaging with computed Detroit, MI 48201, USA b tomography (CT) of the abdomen revealed a hypodense mass Windsor Regional Cancer Center, Windsor, ON N8W 1L9, Canada in the liver involving the porta hepatis and left lobe measuring cCorresponding Author: Indryas Woldie, Windsor Regional Cancer Center, 1995 Lens Ave.,Windsor, ON N8W 1L9, Canada. at 11.5 × 5.8 × 7.5 cm. The spleen was unremarkable and had Email: [email protected] normal size measuring at 10 × 4.9 cm. Peripheral blood smear examination revealed marked leu- doi: https://doi.org/10.14740/jmc3513 kocytosis (due to eosinophilia) without overt dysplasia. There Articles © The authors | Journal compilation © J Med Cases and Elmer Press Inc™ | www.journalmc.org 196 This article is distributed under the terms of the Creative Commons Attribution Non-Commercial 4.0 International License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited Yerrapotu et al J Med Cases. 2020;11(7):196-200 Figure 1. The bone marrow biopsy shows a markedly hypercellular marrow with prominent eosinophilic hyperplasia. No reticulin or collagenous marrow fibrosis is present. was no increase in blasts or basophils. A concurrent bone mar- men demonstrated three-way variant translocation t (2;9;22) row examination revealed an increased myeloid/erythroid ra- (q13;q34;q11.2) in five of 16 metaphases examined. Next- tio with marked eosinophilia. There was no morphologic or generation sequencing performed on the bone marrow aspirate immunohistochemical evidence of dysplasia, an increase in identified the presence of a p210 BCR-ABL1 fusion transcript. blasts, nor the presence of B- and T-cell lymphoproliferative However, mutations for PCM1-JAK2, PDGFRA/PDGFRB as neoplasms. Special stains for amyloid deposition and infec- well as FGFR1 were negative. tious organisms (mycobacteria and fungus) were negative. Due to a longer turnaround time for cytogenetic studies, The hematoxylin and eosin stain of the bone marrow biopsy the patient was initially placed on steroids for eosinophilia was shown in Figure 1. Concurrent flow cytometry of the bone and organ damage, which resulted in severe steroid psycho- marrow aspirate did not reveal any increase in blasts or mono- sis. However, once molecular and cytogenetics results were cytes or any evidence of aberrant T cells, monoclonal B cells, available, the patient was diagnosed with eoCML and started and plasma cells. on tyrosine kinase inhibitor (TKI), imatinib at 400 mg daily. A core needle biopsy of liver mass was performed, and The patient achieved hematologic remission within 6 weeks of histopathological examination revealed extensive infiltration TKI initiation (except an intermittent and very mild increase in with eosinophils associated with a portion of residual hepatic eosinophil count). Within 10 weeks of TKI initiation, his liver parenchyma (Fig. 2). There was no morphologic or immuno- enzymes (AST, ALT, and ALP), as well as bilirubin, normal- histochemical evidence of an increase in blasts or involvement ized and he achieved 1.92 log reduction on his quantitative by B- or T-lymphoproliferative disorders. Additional findings polymerase chain reaction (PCR) for BCR-ABL (1.2% BCR- include cholestatic changes, patchy portal, and peri-portal fi- ABL/ABL1) and IS-score of 0.73 which is within the expected brosis. response milestone per National Comprehensive Cancer Net- Cytogenetics performed on the bone marrow speci- work (NCCN) guidelines (NCCN guidelines version 1.2019, Figure 2. The core biopsy of the liver mass shows an extensive eosinophilic inflammatory cell infiltrate with the destruction of the hepatic parenchyma. Other areas displayed liver lobules and portal tracts infiltrated by numerous eosinophils with degeneration of hepatocytes and cholestasis. Articles © The authors | Journal compilation © J Med Cases and Elmer Press Inc™ | www.journalmc.org 197 An Unusual Presentation of CML J Med Cases. 2020;11(7):196-200 CML). FRB or FGFR1 or PCM1-JAK-2, ETV6-JAK2, or BCR-JAK2 Repeat ultrasound imaging performed at 14 weeks follow- fusion , and other acute and chronic myeloid neoplasms that ing initiation of TKI showed mild hepatomegaly at 18.1 cm could present with eosinophilia, like acute myeloid leukemia with reduced penetration (possibly mild fatty liver infiltration) (AML) with inv(16)(p13.1q22); t(1;16)(p13.1;q22), t(8;21) but no discrete hepatic mass. (q22;q22.1), polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, CMML and BCR-ABL1-negative atypical CML [12]. Discussion Secondary HES is a reactive, polyclonal proliferation of eo- sinophils in response to eosinophilic cytokines seen in parasitic According to the World Health Organization (WHO) clas- infections, certain solid tumors, hematologic neoplasms like sification of tumors of hematopoietic and lymphoid tissue, T-cell lymphoma, Hodgkin lymphoma, systemic mastocytosis, chronic myelogenous leukemia, BCR-ABL1-positive leuke- and lymphoblastic leukemia. Systemic mastocytosis may be as- mia is defined as myeloproliferative neoplasm presenting sociated with the clonal proliferation of eosinophils [8, 9, 12]. with marked granulocytosis in different stages of maturation A rare entity called a lymphocytic variant of HES (L-HES) with a predominance of myelocytes. Usual clinical findings at presents as persistent eosinophilia due to cytokine release by presentation include fatigue, malaise, weight loss, and spleno- aberrant T cells. It is defined as a clonal proliferation of abnor- megaly. Absolute basophilia and absolute eosinophilia are the mal memory T cells. Symptoms mimic Sezary syndrome with most common supplementary peripheral blood findings in the predominant dermatological
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