肥大细胞白血病临床和实验室检查回顾分析

doi:10.3969/j.issn.1673-8640.2019.02.020

摘要/Abstract

摘要：

目的回顾分析1例肥大细胞白血病（MCL）患者的临床及实验室检查特点,以提高临床及实验室技术人员对该病的认知。方法对MCL患者行血细胞分析、细胞形态学分析、流式细胞术免疫表型分析、染色体核型分析及白血病突变基因检查,结合相关文献分析该病临床及实验室检查特点。结果患者以反复腹泻、乏力、皮疹、消瘦、脾大为主要临床表现,外周血及骨髓中肥大细胞（MC）分别占42%和79%。流式细胞术免疫表型为CD45+、CD117++、CD33++、CD13+、CD11b-、CD2++、CD9++、CD123-、CD25部分 +、CD34-、CD38-、HLADR-、CD64-、CD15-。细胞遗传学检查未见明显异常。分子生物学检查发现KIT基因 F522C突变,最终确诊为MCL。结论 MCL是一种罕见的血液系统恶性肿瘤,具有独特的临床和实验室表现,细胞形态上需注意与相似细胞的鉴别,同时应重点完善分子生物学检查以指导治疗。

关键词: 肥大细胞白血病, 细胞形态学, KIT基因突变

Abstract:

Objective To analyze the clinical and laboratory examinations' characteristics of a case of mast cell leukemia（MCL） retrospectively,and to understand the clinical and laboratory examinations' characteristics of MCL. Methods Through the clinical and pathologic findings,including complete blood count,bone marrow aspiration,flow cytometry,genetic analysis and DNA sequencing in a case of MCL,the clinical and laboratory examinations' characteristics were analyzed combined with literatures. Results Physical examination revealed recurrent diarrhea,asthenia,severe weight loss,urticaria and marked splenomegaly. In peripheral blood and bone marrow,mast cells（MC）accounted for 42% and 79%,respectively. The immunophenotypes of MC were CD45+,CD117++,CD33++,CD13+,CD11b-,CD2++,CD9++,CD123-,partial CD25+,CD34-,CD38-,HLADR-,CD64- and CD15-. No obvious abnormality was found in genetic analysis. F522C was detected by mutational analysis of KIT gene. Eventually,the case was diagnosed as MCL. Conclusions MCL is a rare hematological malignancy with unique clinical and laboratory examinations' characteristics. It should pay attention to the cell morphology to avoid the misidentification of similar cells,and the molecular biological examination should be emphasized to guide the treatment.

Key words: Mast cell leukemia, Morphology, KIT gene mutation

中图分类号:

R446.1

孙烨, 郭平, 熊树民, 吴蓉, 康向东. 肥大细胞白血病临床和实验室检查回顾分析[J]. 检验医学, 2019, 34(2): 180-184.

SUN Ye, GUO Ping, XIONG Shumin, WU Rong, KANG Xiangdong. Retrospective analysis of clinical and laboratory examinations' characteristics of mast cell leukemia[J]. Laboratory Medicine, 2019, 34(2): 180-184.

图/表 3

图1 全身大片风团样充血性皮疹注：（a）夜间;（b）白天

图2 外周血涂片瑞氏染色示原始细胞及MC注：（a）为原始细胞;（b）为MC

图3 骨髓染色注：（a）骨髓瑞氏染色,箭头示纺锤形MC;（b）骨髓POX染色,箭头（左）示MC阴性,（右）中性粒细胞阳性;（c）骨髓PAS染色,箭头示PAS阳性的MC;（d）骨髓CE染色,箭头示CE阳性的MC;（e）骨髓甲苯胺蓝染色,箭头示甲苯胺蓝阳性的纺锤形MC

参考文献 27

[1]	LIM K H,TEFFERI A,LASHO T L,et al.Systemic mastocytosis in 342 consecutive adults:survival studies and prognostic factors[J]. Blood,2009,113(23):5727-5736.
[2]	HARRIS N,JAFFEE E,DIEBOLD J,et al.The world health organization classification of neoplastic disease of the haematopoietic and lymphoid tissues[J]. Histopathology,2000,36(1):69-87.
[3]	EFRATI P,KLAJMAN A,SPITZ H.Mast cell leukemia? Malignant mastocytosis with leukemia-like manifestations[J]. Blood,1957,12(10):869-882.
[4]	ARBER D A,ORAZI A,HASSERJIAN R,et al.The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood,2016,127(20):2391-2405.
[5]	SWERDLOW S,CAMPO E,HARRIS N,et al.World Health Organization classification of tumours of haematopoietic and lymphoid tissues[M]. Lyon:IARC Press,2008:54-63.
[6]	VALENTINI C G,RONDONI M,POGLIANI E M,et al.Mast cell leukemia:a report of ten cases[J]. Ann Hematol,2008,87(6):505-508.
[7]	BUTTERFIELD J H,RAVI A,PONGDEE T,et al.Mast cell mediators of significance in clinical practice in mastocytosis[J]. Immunol Allergy Clin North Am,2018,38(3):397-410.
[8]	GEORGIN-LAVIALLE S,LHERMITTE L,DUBREUIL P,et al.Mast cell leukemia[J]. Blood,2013,121(8):1285-1295.
[9]	DAHLIN J S,HALLGREN J.Mast cell progenitors:origin,development and migration to tissues[J]. Mol Immunol,2015,63(1):9-17.
[10]	AGIS H,BEIL W J,BANKL H C,et al.Mast celll-ineage versus basophil lineage involvement in myeloproliferative and myelodysplastic syndromes:diagnostic role of cell-immunophenotyping[J]. Leuk Lymphoma,1996,22(3-4):187-204.
[11]	SHVIDEL L,SHAFT D,STARK B,et al.Acute basophilic leukaemia:eight unsuspected new cases diagnosed by electron microscopy[J]. Br J Haematol,2003,120(5):774-781.
[12]	CEHRELI C,ALACACIOGLU I,PISKIN O,et al.Mast cell leukemia associated with undefined morphology and chronic basophilic leukemia[J]. BMC Hematol,2014,14(1):17.
[13]	VALENT P,SOTLAR K,BLATT K,et al.Proposed diagnostic criteria and classification of basophilic leukemias and related disorders[J]. Leukemia,2017,31(4):788-797.
[14]	ARREDONDO A R,GOTLIB J,SHIER L,et al.Myelomastocytic leukemia versus mast cell leukemia versus systemic mastocytosis associated with acute myeloid leukemia:a diagnostic challenge[J]. Am J Hematol,2010,85(8):600-606.
[15]	HORNY H P,SOTLAR K,VALENT P.Mastocytosis:state of the art[J]. Pathobiology,2007,74(2):121-132.
[16]	VALENT P.Mast cell leukemia-a rare form of myeloid leukemia[J]. Wien Klin Wochenschr,2002,114(5-6):173-174.
[17]	YANAGIHORI H,OYAMA N,NAKAMURA K,et al.C-kit mutations in patients with childhood-onset mastocytosis and genotype-phenotype correlation[J]. J Mol Diagn,2005,7(2):252-257.
[18]	CHAN P M,ILANGUMARAN S,LA ROSE J,et al.Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region[J]. Mol Cell Biol,2003,23(9):3067-3078.
[19]	FURITSU T,TSUJIMURA T,TONO T,et al.Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product[J]. J Clin Invest,1993,92(4):1736-1744.
[20]	SOTLAR K,ESCRIBANO L,LANDT O,et al.One-step detection of c-kit point mutations using peptide nucleic acid-mediated polymerase chain reaction clamping and hybridization probes[J]. Am J Pathol,2003,162(3):737-746.
[21]	GARCIA-MONTERO A C,JARA-ACEVEDO M,TEODOSIO C,et al. KIT mutation in mast cells and other bone marrow hematopoietic cell lineages in systemic mast cell disorders:a prospective study of the Spanish Network on Mastocytosis(REMA) in a series of 113 patients[J]. Blood,2006,108(7):2366-2372.
[22]	BEGHINI A,CAIROLI R,MORRA E,et al.In vivo differentiation of mast cells from acute myeloid leukemia blasts carrying a novel activating ligand-independent C-kit mutation[J]. Blood Cells Mol Dis,1998,24(2):262-270.
[23]	LONGLEY B J Jr,METCALFE D D,THARP M,et al. Activating and dominant inactivating c-KIT catalytic domain mutations in distinct clinical forms of human mastocytosis[J]. Proc Natl Acad Sci U S A,1999,96(4):1609-1614.
[24]	PULLARKAT V A,PULLARKAT S T,CALVERLEY D C,et al.Mast cell disease associated with acute myeloid leukemia:detection of a new c-kit mutation Asp816His[J]. Am J Hematol,2000,65(4):307-309.
[25]	PIGNON J M,GIRAUDIER S,DUQUESNOY P,et al.A new c-kit mutation in a case of aggressive mast cell disease[J]. Br J Haematol,1997,96(2):374-376.
[26]	AKIN C,FUMO G,YAVUZ A S,et al.A novel form of mastocytosis associated with a transmembrane c-kit mutation and response to imatinib[J]. Blood,2004,103(8):3222-3225.
[27]	GOTLIB J,KLUIN-NELEMANS H C,GEORGE T I,et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis[J]. N Engl J Med,2016,374(26):2530-2541.