LETTER TO THE EDITOR

Korean J Intern Med 2018;33:642-644 https://doi.org/10.3904/kjim.2016.100

Loeffler endocarditis in chronic eosinophilic with FIP1L1/PDGFRA rear- rangement: full recovery with low dose Dae Sik Kim1, Sunki Lee2,*, and Chul Won Choi1

1Division of Oncology and To the Editor, parasites were negative and no other Hematology, Department of Internal Chronic eosinophilic leukemia (CEL) allergic symptoms were present. In the Medicine, 2Cardiovascular Center, Korea University Guro Hospital, with FIP1L1/PDGFRA (factor interact- bone marrow (BM) aspirate, marked Seoul, Korea ing with PAPOLA and CPSF1/plate- , often with bizarre nucle- let-derived growth factor α) ar lobulation, and dysgranulation were rearrangement is a rare cause of hyper- found (Fig. 2A). The biopsy specimen eosinophilia, with few reports in Korea showed hypercellular (90%) marrow [1]. One of the most critical types of or- for age (Fig. 2B). Fluorescence in situ gan damage caused by infiltration with hybridization (FISH) analysis was pos- is Loeffler endocarditis, itive (92%) for FIP1L1/PDGFRA fusion with fibrous thickening of the endo- (Fig. 3A). According to the 2008 World cardium leading to apical obliteration Health Organization classification, he and restrictive cardiomyopathy. There was diagnosed with myeloid and lym- are some reports of Loeffler endocardi- phoid neoplasm (CEL) associated with tis in patients with hypereosinophilic FIP1L1/PDGFRA. Low-dose imatinib syndrome [2,3]. This is the first report- (100 mg) and anticoagulation with ed case of CEL with FIP1L1/PDGFRA enoxaparin were started. The WBC, eo- rearrangement combined with Loeffler sinophil and platelet count normalized Received : March 15, 2016 endocarditis in Korea. within 10 days of imatinib treatment. Revised : July 21, 2016 A 28-year-old man presented to the After 2 months of treatment, FISH for Accepted : March 27, 2017 emergency department with a head- FIP1L1/PDGFRA fusion became neg- Correspondence to ache, dyspnea, and aphasia. Acute in- ative (Fig. 3B). Endocardial thicken- Chul Won Choi, M.D. farction in the left posterior middle ing and thrombus in both ventricles Division of Oncology and Hema- cerebral artery territory was found resolved on serial echocardiography tology, Department of Internal on brain magnetic resonance imag- during 3 months of treatment with Medicine, Korea University Guro Hospital, 148 Gurodong-ro, Guro- ing. A transthoracic echocardiogram imatinib (Fig. 1B and 1C). Follow-up gu, Seoul 08308, Korea revealed endocardial thickening and BM aspiration and biopsy slides after Tel: +82-2-2626-3058 thrombus in both ventricular apices, 3 months of treatment showed normo- Fax: +82-2-862-6453 E-mail: [email protected] typical finding of Loeffler endocardi- cellular marrow with 1.3% of eosino- tis (Fig. 1A). Initial laboratory findings phil count (Fig. 2C and 2D). The patient *Current affiliation: Division of were as follows: hemoglobin 12.5 g/dL, remains in complete cytogenetic re- Cardiology, Department of Inter- nal Medicine, Hallym University white blood cell (WBC) count 26,400/ mission and had no signs or symptoms Dongtan Sacred Heart Hospital, µL (eosinophils 12,302/μL), and platelet for over a year. Hwaseong, Korea count 44,000/μL. All antibody tests for CEL with FIP1L1/PDGFRA rear-

Copyright © 2018 The Korean Association of Internal Medicine pISSN 1226-3303 This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ eISSN 2005-6648 by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited. http://www.kjim.org Kim DS, et al. Loeffler endocarditis in CEL

A B C Figure 1. Serial transthoracic echocardiogram (TTE) in apical 4-chamber view. (A) Initial TTE images demonstrate large ech- odense masses attached to significantly thickened biventricular endocardial walls (white arrows). (B) After 15 days of treatment (warfarin and imatinib), TTE demonstrated complete regression of echogenic wall thickening in the left ventricular apex, but was still noted in the right ventricular apex (arrowheads). (C) Follow-up TTE was performed after 3 months of treatment, with no further evidence of wall thickening or thrombi in both ventricular apices.

A B C

Figure 2. Bone marrow (BM) aspirate and biopsy findings. (A) BM aspiration slide at baseline (×1,000). Myeloid:erythroid ratio was 13.7:1. Granulocytic precursors were increased. Eosinophils accounted for up to 28.0% of the marrow absolute count. Abnormal features of eosinophils were sparse granulation with clear areas of cytoplasm, cytoplasmic vacuolation, bizarre nuclear lobulation, and nuclear hyper- segmentation. (B) BM slide at baseline (H&E, ×400). The biopsy specimen showed hypercellular (90%) marrow for age. Megakaryocytes were increased and nucleated cells were mostly eosinophils and other hematopoietic cells. (C) BM aspiration slide after 3 months of treatment (×1,000). Eosinophils with normal morphology were counted up to 1.3% of marrow neutrophil. (D) BM slide after 3 months of treatment D showed normocellular (30% to 40%) marrow for his age (H&E, ×400). rangement is very rare, and only four cases have been these, patients with restrictive cardiomyopathy known reported in Korea [1]. Two had cardiac findings with as Loeffler endocarditis have a very poor prognosis [2,3]. valvular regurgitation. Cardiac involvement is frequent- The prognosis of Loeffler endocarditis depends on how ly reported in patients with hypereosinophilia. Among well the eosinophilia is controlled [4]. This is the first

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A B Figure 3. Fluorescence in situ hybridization (FISH) findings for FIP1L1/PDGFRA (factor interact­ing with PAPOLA and CPSF1/ plate­let-derived growth factor receptor α) fusion. (A) FISH result at diagnosis shows abnormal green-green fusion signal lacking an orange signal (white arrow). (B) FISH result after 2 months of treatment. All cells show normal tri-color signal with green, orange, and green (arrowhead). report of CEL with Loeffler endocarditis in Korea. CEL Conflict of interest with FIP1L1/PDGFRA showed dramatic response to ima- No potential conflict of interest relevant to this article tinib mesylate, unlike other causes of hypereosinophilia was reported. [5]. In the present case, hematologic and cytogenetic re- mission was achieved with imatinib 100 mg daily, and cardiac involvement also improved. Although neurologic REFERENCES deficits due to multiple cerebral infarctions and severe endocardial thickening and thrombi were observed on 1. Shin SY, Jung CW, Choi DC, Lee BJ, Kim HJ, Kim SH. admission, these abnormalities completely resolved with Chronic eosinophilic leukemia with a FIP1L1-PDGFRA low-dose imatinib and anticoagulation. Recurrence of rearrangement: two case reports and a review of Korean thrombus or infarction was not observed after discon- cases. Blood Res 2015;50:58-61. tinuation of anticoagulation when cytogenetic remission 2. Chao BH, Cline-Parhamovich K, Grizzard JD, Smith TJ. was confirmed. In conclusion, cardiac dysfunction in Fatal Loeffler’s endocarditis due to hypereosinophilic patients with hypereosinophilia can be fatal, but a tar- syndrome. Am J Hematol 2007;82:920-923. geted agent such as imatinib showed dramatic cardiac 3. Sato T, Matsuyama TA, Seguchi O, et al. Restrictive myo- improvement in a CEL patient with FIP1L1/PDGFRA cardium with an unusual pattern of apical hypertrophic rearrangement. Thus, early workup and active manage- cardiomyopathy. Cardiovasc Pathol 2015;24:254-257. ment for eosinophilia should be performed in cases of 4. Inoue T, Watanabe C, Ayukawa H, et al. Biopsy-proven cardiac dysfunction combined with hypereosinophilia. Loeffler endocarditis successfully treated with steroids. Circulation 2015;131:e353-e354. Keywords: Loeff ler endocarditis; Pdgfra-associated 5. Gotlib J. World Health Organization-defined eosino- chronic eosinophilic leukemia; Imatinib mesylate philic disorders: 2015 update on diagnosis, risk strati- fication, and management. Am J Hematol 2015;90:1077- 1089.

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