천식 알 르기 제30권 제3호 Case Report

Vol 30 No 3 Sep 2010

237

A Case of Patient with Chronic Myelomonocytic Leukemia Presenting as HypereosinophiliaJin Wook Park1 Yi Rang Kim1 Soo Young Na1 Tai Sun Park1 Yun-Jeong Bae2 You Sook Cho2 Hee-Bom Moon2 and Tae-Bum Kim2

2Division of Allergy and Clinical Immunology 1Department of Internal Medicine Asan Medical Center University of Ulsan College of Medicine Seoul Korea

호산구증가증의 원인으로는 약물 기생충 감염 알 르기 질환 액종양 등이 있다 만성골수단구성백 병(chronic myelomonocytic leukemia CMML)은 말 액 단핵구가 1000μL 이상이고 액이나 골수에서 모세포가 20 이하이며 1개 이상의 이형성이 찰되는 질환으로 호산구증

가증이 동반될 수 있다 자들은 호산구증가증의 드문 원인 질환으로 만성골수단구성백 병이 동반된 환자 1 를 경험하고 이를 문헌고찰과 함께 보고하는 바이다 (Korean J Asthma Allergy Clin Immunol 201030237-240)

985103985103985103985103985103985103985103985103985103985103985103985103985103985103985103985103985103985103985103985103Key words Chronic myelomonocytic leukemiaEosinophilia Trisomy 8

CorrespondenceTae-Bum Kim Division of Allergy and Clinical Immunology Department of Internal Medicine Asan Medical Center University of Ulsan College of Medicine 388-1 Pungnap 2-dong Songpa-gu Seoul 138-736 KoreaTel ＋82-2-3010-3287 Fax ＋82-2-3010-3287 E-mail allergymedimail cokr

Received October 8 2009 Revised October 16 2009 Accepted October 20 2009

INTRODUCTION

Peripheral eosinophilia can be found in many medical settings

including drug reaction infections allergic diseases collagen vas-

cular diseases and hematologic malignancies1) It can be divided into

categories of primary and secondary eosinophilia and primary

eosinophilia is classified into clonal and idiopathic origin1) Clonal

eosinophilia can be accompanied by hematologic malignancies

including acute myeloid leukemia (AML) acute lymphocytic leu-

kemia (ALL) chronic myeloid leukemia (CML) myelodysplastic

syndrome (MDS) chronic eosinophilic leukemia (CEL) systemic

mastocytosis (SM) and chronic myelomonocytic leukemia (CMML)1)

CMML is categorized as a MDS by the French- American-British

(FAB) classification and as myelodysplastic syndromemyelopro-

liferative neoplasm (MDSMPN) by World Health Organization

(WHO) classification2) The MDSMPN includes disorders where

both dysplastic and proliferative feature co-exist Due to the

heterogeneous clinical and morphological features in CMML its

diagnosis and the prediction of biological behavior is not straight-

forward CMML is characterized by persistent peripheral blood

monocytosis greater than 1000μL fewer than 20 blasts in the

blood or bone marrow (BM) and dysplasia in one or more myeloid

lineages3) It is known that t(512) creates a chimeric ETV6-

platelet-derived growth-factor beta receptor (PDGFRB) which is

associated with eosinophilia in CMML4-7) Other previously reported

gene abnormalities associated with eosinophilia in CMML are the

FIP1L1-PDGFRA fusion gene (4q12) and pericentric inversion of

chromosome 167-9) Although several cytogenetic abnormalities

associated with eosinophilia in CMML have been reported4-9)

trisomy 8 has been rarely reported Hematologic malignancies are

rare causes of eosinophilia and clonal bone marrow disorders

account for less than 1 of eosinophilia10)

We describe an unusual case of CMML with trisomy 8 presenting

as severe eosinophilia

CASE REPORT

A 71-year old man with a past medical history of diabetes

mellitus visited our hospital for evaluation of exertional chest pain

He was diagnosed as mild coronary artery disease by coronary

angiography and treated medically A complete blood count (CBC)

on admission revealed a WBC of 244times103mm3 hemoglobin 105

gdL and platelets 297times103mm3 The differential counts of WBC

were 38 neutrophils 10 lymphocytes 15 monocytes and

37 eosinophils and neither blasts nor dysplastic granulocytes were

noted on a peripheral blood smear The total serum Ig E level was

333 IUmL

The patient was referred to the Department of Allergy to

determine the cause of the eosinophilia He did not complain of

238 천식 알 르기 제 30권 제 3호

Fig 1 Bone marrow aspirate shows eosinophilic hyperplasia and

increased monocytic series

Fig 2 Giemsa-banded karyotype of bone marrow cells shows

47XY+8

any other symptoms and took no medication except for hypogly-

cemic agents Neither skin rash nor splenomegaly was observed

upon physical examination at that time We performed serologic

tests for parasites including cysticercus sparganum clonorchis and

paragonimus but found no abnormalities The patient was followed

up for further evaluation of eosinophilia because he was considered

to have idiopathic hypereosinophilia Another CBC conducted 2

months later showed a WBC of 968times103mm3 hemoglobin 114

gdL and platelets 161times103mm3 The differential counts of WBC

showed 1 myelocytes 2 band-form neutrophils 53 segmented

neutrophils 3 lymphocytes 25 monocytes and 15 eosino-

phils and 1 atypical lymphocytes were noted on the peripheral

blood smear

We carried out a bone marrow (BM) examination to rule out

hematologic malignancies BM aspirate smears (Fig 1) showed

eosinophilic hyperplasia and differential counts of 28 myeloblasts

22 promyelocytes 140 myelocytes 30 metamyelocytes

56 band forms 434 segemented forms 14 immature

lymphocytes 46 lymphocytes 40 promonocytes 20 mono-

cytes 64 normoblasts and 102 eosinophils The BM biopsy

showed 95 cellularity with increasing granulocytic and monohi-

stiocytic series The patient was diagnosed as CMML The karyo-

types (Fig 2) in metaphase analysis (Giemsa banding) of BM cells

revealed 47 XY +8[18]46 XY[2] Nested reverse transcriptase

polymerase chain reaction was performed on BM samples to study

major and minor BCRABL rearrangement but revealed no rear-

rangement The dual-color split fluorescent in situ hybridization

(FISH) assays using FIP1L1-Chic2-PDGFRA (4q12) DNA probe

(Kreatech Diagnostics Amsterdam Netherlands) and PDGFRB

(5q33) DNA probe (Kreatech Diagnostics Amsterdam Nether-

lands) were performed to study the PDGFRA and PDGFRB

rearrangement respectively Neither PDGFRA nor PDGFRB rear-

rangement was noted

The patient was treated with hydroxyurea and his eosinophilia

gradually improved in about one month

DISCUSSION

Eosinophilia can be accompanied by a variety of reactive

conditions and clonal disorders including infectious allergic colla-

gen vascular and neoplastic diseases and the severity of associated

diseases can range from self-limited conditions to life- threatening

disorders110) Recent advances permit a more logical approach to

diagnosis of patients with eosinophilia A thorough patient history

is the most important part of the evaluation for blood eosinophilia

and it should guide the extent and type of laboratory tests

performed Initial evaluation for eosinophilia includes a detailed

history including medications travel history and allergic symp-

toms thorough physical examination X-ray of chest complete

blood count with differential count complete serum chemistry Ig

E and stool tests11112) The specific studies required to rule out

other etiologies differ depending on findings from a thorough

history physical examination and these studies In most cases an

underlying cause is known after such studies11)

but if the eosino-

238 천식 알 르기 제 30권 제 3호

Fig 1 Bone marrow aspirate shows eosinophilic hyperplasia and

increased monocytic series

Fig 2 Giemsa-banded karyotype of bone marrow cells shows

47XY+8

any other symptoms and took no medication except for hypogly-

cemic agents Neither skin rash nor splenomegaly was observed

upon physical examination at that time We performed serologic

tests for parasites including cysticercus sparganum clonorchis and

paragonimus but found no abnormalities The patient was followed

up for further evaluation of eosinophilia because he was considered

to have idiopathic hypereosinophilia Another CBC conducted 2

months later showed a WBC of 968times103mm3 hemoglobin 114

gdL and platelets 161times103mm3 The differential counts of WBC

showed 1 myelocytes 2 band-form neutrophils 53 segmented

neutrophils 3 lymphocytes 25 monocytes and 15 eosino-

phils and 1 atypical lymphocytes were noted on the peripheral

blood smear

We carried out a bone marrow (BM) examination to rule out

hematologic malignancies BM aspirate smears (Fig 1) showed

eosinophilic hyperplasia and differential counts of 28 myeloblasts

22 promyelocytes 140 myelocytes 30 metamyelocytes

56 band forms 434 segemented forms 14 immature

lymphocytes 46 lymphocytes 40 promonocytes 20 mono-

cytes 64 normoblasts and 102 eosinophils The BM biopsy

showed 95 cellularity with increasing granulocytic and monohi-

stiocytic series The patient was diagnosed as CMML The karyo-

types (Fig 2) in metaphase analysis (Giemsa banding) of BM cells

revealed 47 XY +8[18]46 XY[2] Nested reverse transcriptase

polymerase chain reaction was performed on BM samples to study

major and minor BCRABL rearrangement but revealed no rear-

rangement The dual-color split fluorescent in situ hybridization

(FISH) assays using FIP1L1-Chic2-PDGFRA (4q12) DNA probe

(Kreatech Diagnostics Amsterdam Netherlands) and PDGFRB

(5q33) DNA probe (Kreatech Diagnostics Amsterdam Nether-

lands) were performed to study the PDGFRA and PDGFRB

rearrangement respectively Neither PDGFRA nor PDGFRB rear-

rangement was noted

The patient was treated with hydroxyurea and his eosinophilia

gradually improved in about one month

DISCUSSION

Eosinophilia can be accompanied by a variety of reactive

conditions and clonal disorders including infectious allergic colla-

gen vascular and neoplastic diseases and the severity of associated

diseases can range from self-limited conditions to life- threatening

disorders110) Recent advances permit a more logical approach to

diagnosis of patients with eosinophilia A thorough patient history

is the most important part of the evaluation for blood eosinophilia

and it should guide the extent and type of laboratory tests

performed Initial evaluation for eosinophilia includes a detailed

history including medications travel history and allergic symp-

toms thorough physical examination X-ray of chest complete

blood count with differential count complete serum chemistry Ig

E and stool tests11112) The specific studies required to rule out

other etiologies differ depending on findings from a thorough

history physical examination and these studies In most cases an

underlying cause is known after such studies11)

but if the eosino-