慢性嗜酸性粒细胞白血病/高嗜酸性粒细胞综合征的诊断与鉴别诊断

 本文对高嗜酸性粒细胞综合征／慢性嗜酸性粒细胞白血病的定义,病因,临床表现,病理学特点,诊断标准,及鉴别诊断做了介绍。外周血嗜酸性粒细胞增多至少有5种情况：①非肿瘤反应性嗜酸性粒细胞增多;②淋巴细胞肿瘤伴反应性嗜酸性粒细胞增多;③慢性嗜酸性粒细胞白血病）;④骨髓增生疾病所具有的肿瘤（克隆）性嗜酸性粒细胞增多的其他肿瘤;⑤表型异常并产生异常细胞因子的T细胞群体所致的嗜酸性粒细胞增多。     

嗜酸粒细胞增多症二例并文献复习

 目的　结合文献分析嗜酸粒细胞增多症的诊断及治疗方法,进一步提高对嗜酸粒细胞增多症的发病机制及治疗的认识。方法　分析病因特殊或临床特点典型的嗜酸粒细胞增多症2例患者资料,结合文献分析其临床特点及治疗转归。结果　2例分别为继发性嗜酸粒细胞增多症和异常T 淋巴细胞克隆性嗜酸粒细胞增多症。二者疾病性质不同,治疗方法及转归亦不相同。结论　嗜酸粒细胞增多症是一类临床表现和发病机制多样性的疾病, 其诊断需通过详细的骨髓检查、核型分析及分子细胞遗传学方法鉴别继发性、克隆性或特发性,从而选择相应的治疗方法。     

骨髓增生异常综合征T淋巴细胞异常与克隆造血

 目的　了解T淋巴细胞异常在骨髓增生异常综合征（MDS）克隆造血中的作用。方法　对76例MDS患者的染色体核型、T淋巴细胞亚群及激活状态进行分析。结果　正常核型36例,异常核型40例,异常发生率52.6 %。40例异常核型中,三体8（+8）24例,占异常核型的60.0 %。与健康对照组比较,MDS患者CD+3 CD-19、CD+3 CD-4 CD+8以及CD+3 HLA-DR+细胞百分率显著升高,CD-3（CD16 CD56）+细胞的百分率明显降低。将MDS患者进行核型分组,异常核型组CD+3（CD16 CD56）+细胞的百分率显著高于正常对照组。将+8核型从MDS异常核型中独立出来进行分析,CD+3 CD+4 CD-8细胞的百分率明显低于正常核型以及其他异常组,CD4／CD8的比值明显低于健康对照组。结论　MDS存在T淋巴细胞异常,异常核型MDS可能恶性克隆增殖更为优势,预后更差。+8 核型MDS存在更为严重的免疫监视功能下降,导致恶性克隆过度增殖与残存造血过度受抑。     

甲状腺嗜酸细胞肿瘤16例临床分析

 目的 观察甲状腺嗜酸细胞肿瘤的临床病理学特点。方法 对16例甲状腺嗜酸细胞肿瘤进行临床病理学分析和免疫组化研究并结合文献进行分析。结果 本组13例嗜酸细胞腺瘤，3例嗜酸细胞腺癌，肿瘤以细胞质嗜酸性，粗颗粒为特点，细胞形态多样，排列成滤泡型、小梁型和实体型。良性和恶性嗜酸细胞肿瘤表达TG、S-100、Vim无差异。结论 甲状腺嗜酸细胞肿瘤是有独特病理形态特点且具有潜在恶性的肿瘤,对其生物学行为应长期跟踪随访，免疫组织化学和电镜不能区别良恶性，主要依靠传统的包膜、血管浸润或远处转移。     

是慢性嗜酸粒细胞白血病还是髓系／淋系肿瘤伴嗜酸粒细胞增多？

 2008年WHO将有PDGFRA、PDGFRB或PGFR1重排的慢性嗜酸粒细胞白血病（CEL）分类为髓系／淋系肿瘤伴嗜酸粒细胞增多,而将无这些异常但有其他克隆性异常的CEL分类为CEL不另分类（CEL-NOS）。文章阐述了作者的意见。     

低浓度苯,甲苯和二甲苯接触工人淋巴细胞微核和白细胞的检测

本组74例接触低浓度三苯工人的白细胞发生了程度不同的病理学改变,这表现在①虽然多数受检者白细胞总数在正常值范围内,但随工龄延长呈下降趋势,3例低于正常值下限,2例早期接触者可有白细胞总数的轻微上升;②白细胞分类异常主要是低工龄组的嗜酸粒细胞比例明显升高,其次是淋巴细胞比例上升,中性粒细胞比例下降;③接触三苯后淋巴细胞空泡变性山现早,在受检者中发现率高,它可能是三苯早期中毒的指标;④淋巴细胞微核率与对照组无明显的差异。     

2008年版"世界卫生组织造血及淋巴组织肿瘤分类"指要

 2008年第4版"世界卫生组织造血及淋巴组织肿瘤分类"把该类肿瘤分列为12个项目,对分子生物学进展结合较多,基因、染色体改变均加入分类中。慢性骨髓增生性疾病改为骨髓增生性肿瘤,并将肥大细胞增多症（mastocytosis）归于此栏中。新增了伴有嗜酸细胞增多的髓系及淋巴细胞系恶性肿瘤及异常的PDDFRA、PDDFRB或FGFR1基因一栏。在骨髓增生异常综合征／骨髓增生性肿瘤（MDS／MPN）一栏中增加了伴环形铁粒幼细胞再生障碍性贫血并显著的血小板增多（RARS-T）（可能为一单独性疾病）。在骨髓增生异常综合征（MDS）一栏中分为一系或多系增生异常伴有一系或多系血细胞减少,并增添了儿童MDS。在急性髓系白血病及其有关前体细胞恶性肿瘤中,把髓系肉瘤（myeloid sarcoma）单独分类;新增加了唐氏综合征（Down syndrome）伴有的髓系增生疾病;新增加了母细胞性浆细胞样树突细胞肿瘤（blastic plasmacytoid dendretic cell neoplasm）。把系列不明的白血病（acute leukemia of ambiguous lineage）单列为一个项目,含6种白血病。在前体淋巴系肿瘤中分为B系及T系,淋巴母细胞性白血病／淋巴母细胞性淋巴瘤,其区别点在于骨髓中淋巴母细胞＞25 %,则诊断为淋巴细胞白血病[和急性髓系白血病（AML）不同,不设下限为20 %]。成熟B淋巴细胞系肿瘤分为39种,包括慢性淋巴细胞白血病、骨髓瘤、重链病、Burkitt淋巴瘤等,但不包括移植后淋巴细胞增生性疾病（PTLD）。成熟T淋巴细胞系和NK细胞系肿瘤栏目下列举了22种成熟T淋巴细胞系和NK细胞系恶性肿瘤。霍奇金淋巴瘤栏目下列举了6种霍奇金淋巴瘤。组织细胞和树突状细胞恶性肿瘤包括7种恶性肿瘤及播散性幼年型黄肉芽肿。移植后淋巴细胞增生性疾病（PTLD）被单独分类在一个栏目中,又分为５种类型。     

急性嗜酸粒细胞白血病的临床和超微结构观察

急性嗜酸粒细胞白血病的临床和超微结构观察贺建霞，候淑玲，王列样，张俊萍，刘阳，王军急性嗜酸粒细胞白血病分原始细胞型、幼稚细胞型和成熟细胞型。有时骨髓中多量原粒细胞，但血象以嗜酸分叶核为多￣［１，２］。本文报告１例，和以上所见恰为相反。与国内报告的病例...     

急性嗜酸粒细胞自血病的临床和超微结构观察

急性嗜酸粒细胞白血病分原始细咆型、幼稚细胞型和成熟细胞型。有时骨髓中多量原粒细胞．但血象以嗜酸分叶核为多。本文报告1例．和以上所见恰为相反。与国内报告的病例不同。     

肾嗜酸细胞瘤螺旋CT特征及鉴别要点分析

目的：观察肾嗜酸细胞瘤的平扫及动态增强扫描特征,并与肾嫌色细胞癌进行比较。方法选择20例肾嗜酸细胞瘤患者为研究对象,另选择30例肾嫌色细胞癌患者为对照组,观察肾嗜酸细胞瘤CT表现,比较肾嗜酸细胞瘤与肾嫌色细胞癌病变形态学特征,病灶强化百分比及肿瘤-肾皮质强化指数。结果肾嗜酸细胞瘤密度于皮髓质期、实质期及排泄期均低于肾脏皮质,差异均有统计学意义（P﹤0.05）;肾嗜酸细胞瘤密度于皮髓质期、肾实质期及排泄期高于肾脏髓质,差异具有统计学意义（P﹤0.05）;肾嗜酸细胞瘤较肾嫌色细胞癌体积小,密度均匀的比例高,存在星芒状瘢痕的比例高,差异均具有统计学意义（P﹤0.05）。动态增强扫描,肾嗜酸细胞瘤与肾嫌色细胞癌强化程度间比较显示,肾嗜酸细胞瘤在皮髓质期、实质期的病灶强化百分比和肿瘤-肾皮质强化指数,均高于肾嫌色细胞癌,差异均具有统计学意义（P﹤0.05）。结论肾嗜酸细胞瘤的CT表现具有一定的特征,形态学特征及动态增强表现有助于鉴别诊断。     

Hypereosinophilic syndrome in children

Recently, according to the Hypereosinophilic Diseases Working Group of the International Eosinophil Society, six variants of hypereosinophilic syndrome have been proposed, i.e. (1) myeloproliferative, (2) lymphoproliferative, (3) idiopathic/undefined, (4) overlapping, (5) associated and (6) familial variant. Hypereosinophilic syndrome is a rare disorder in children and can occur at any age during childhood. Corticosteroids are the treatment of choice, whereas other treatment options are hydroxyurea, IFNα, imatinib, vincristine, mepolizumab. We present a fulminant fatal case of hypereosinophilic syndrome in a teenager with an initial presentation of an idiopathic thrombocytopenia (ITP) and present a narrative review of literature.     

Imatinib-responsive hypereosinophilia in a patient with B cell ALL

Hypereosinophilia is a rare presenting sign of acute lymphocytic leukemia. A 29-year-old male was diagnosed with idiopathic hypereosinophilic syndrome with respiratory symptoms. Although his peripheral blood eosinophilia decreased in response to treatment with imatinib mesylate, a follow-up bone marrow showed a diffuse infiltrate of myeloperoxidase-negative blasts. He was subsequently diagnosed with CD10 positive precursor B lymphoblastic leukemia. This case underscores the importance of follow-up bone marrow examination in patients who demonstrate imatinib mesylate-responsive eosinophilia.     

The hypereosinophilic syndrome in acute lymphocytic leukemia

A 21-year-old white man presented with marked peripheral blood eosinophilia that later evolved into acute lymphocytic leukemia (FAB2 ALL). He died precipitously from refractory congestive heart failure immediately after antileukemic therapy was started. Autopsy revealed multiorgan infiltration with eosinophils and the typical cardiac findings of L?fflers endocarditis. Clinical and pathologic features of this and the 14 other cases of ALL and the hypereosinophilic syndrome (HES) reported in the English-language literature are described. The eosinophilia in these cases is reactive and resolves with successful leukemia remission induction. Hydroxyurea is effective in rapidly lowering eosinophil counts. Early use of hydroxyurea in this disease may improve patient survival and decrease the risk of sudden cardiac death.     

Successful long-term control of idiopathic hypereosinophilic syndrome with etoposide.

A 38-year-old man with idiopathic hypereosinophilic syndrome had an inadequate response to steroids and severe side effects from hydroxyurea treatment, which necessitated withdrawal of the treatment. Successful control of clinical symptoms and eosinophil counts was obtained with etoposide (VP16-213) for 18 months. VP16-213 may be valuable in idiopathic hypereosinophilic syndrome treatment.     

Molecular characterization of the idiopathic hypereosinophilic syndrome (HES) in 35 French patients with normal conventional cytogenetics.

Idiopathic hypereosinophilic syndrome (HES) characterized by unexplained and persistent hypereosinophilia is heterogeneous and comprises several entities: a myeloproliferative form where myeloid lineages are involved with the interstitial chromosome 4q12 deletion leading to fusion between FIP1L1 and PDGFRA genes, the latter acquiring increased tyrosine kinase activity. And a lymphocytic variant, where hypereosinophilia is secondary to a primitive T lymphoid disorder demonstrated by the presence of a circulating T-cell clone. We performed molecular characterization of HES in 35 patients with normal karyotype by conventional cytogenetic analysis. TCRgamma gene rearrangements suggesting T clonality were seen in 11 (31%) patients, and FIP1L1-PDGFRA by RT-PCR in six (17%) of 35 patients, who showed no evidence of T-cell clonality. An elevated serum tryptase level was observed in FIP1L1-PDGFRA-positive patients responding to imatinib, whereas serum IL-5 levels were not elevated in T-cell associated hypereosinophilia. Sequencing FIP1L1-PDGFRA revealed scattered breakpoints in FIP1L1-exons (10-13), whereas breakpoints were restricted to exon 12 of PDGFRA. In the 29 patients without FIP1L1-PDGFRA, no activating mutation of PDGFRA/PDGFRB was detected; however; one patient responded to imatinib. FISH analysis of the 4q12 deletion was concordant with FIP1L1-PDGFRA RT-PCR data. Further investigation of the nature of FIP1L1-PDGFRA affected cells will improve the classification of HES.     

Lymphomatoid papulosis associated with both severe hypereosinophilic syndrome and CD30 positive large T-cell lymphoma

BACKGROUND: Previous reports have found an association between lymphomatoid papulosis and hypereosinophilic syndrome, as well as lymphomatoid papulosis and lymphoma. In the current study the authors report what to their knowledge is the first reported case of these three diseases occurring simultaneously in the same patient. METHODS: The authors followed the clinical course of a 64-year-old man with lymphomatoid papulosis associated with severe hypereosinophilic syndrome complicated by involvement of the lungs and heart. RESULTS: After 6 years of follow-up, the patient developped a large T-cell, CD30 positive lymphoma. The bone marrow biopsy was typical of hypereosinophilic syndrome associated with fibrosis, with focal lymphomatous infiltrates comprised of large cells resembling the type A cells of lymphomatoid papulosis. Complete remission of the lymphoma was obtained with chemotherapy. CONCLUSIONS: This exceptional case report suggests a link between the three diseases. Lymphomatoid papulosis belongs to the spectrum of CD30 positive lymphoproliferative disorders and CD30 positive lymphocytes of lymphomatoid papulosis are known to have a Th2 profile with possible secretion of eosinopoietic cytokines.     

Eosinophilia, chloromas and a chromosome abnormality in a patient with a myeloproliferative syndrome.

The existence of eosinophilic leukemia remains controversial since many authors challenge the existence of this entity. We present a patient with a hypereosinophilic syndrome whose findings were consistent with a leukemic process. The patient's course was marked my signs and symptoms of myeloblastoma formation and his illness terminated in an acute blastic crisis. chromosome studies on peripheral blood leucocytes demonstrated aneuploidy and an abnormal number four chromosome with additional material on its long arm. This case appears to be an unusual example of a hypereosinophilic syndrome with both myeloblastoma formation and an abnormal leucocyte karyotype.     

Emerging safety issues with imatinib and other Abl tyrosine kinase inhibitors

Imatinib and other Abl tyrosine kinase inhibitors (TKIs), such as dasatinib and nilotinib, have significantly improved the outcome of patients with chronic myeloid leukemia. Imatinib and dasatinib are currently Food and Drug Administration (FDA) approved, and nilotinib is expected to gain FDA approval soon. In addition, several other Abl TKIs are being evaluated in various clinical trials. Imatinib has also shown efficacy in the therapy of gastrointestinal stromal tumors, Philadelphia chromosome-positive acute lymphocytic leukemia and hypereosinophilic syndrome. Because of their efficacy, more patients will receive Abl TKIs for a longer period of time. Imatinib was FDA approved after a short follow-up because of its exceptional efficacy and safety profile. The most common adverse events reported included fluid retention, fatigue, diarrhea, and muscle cramps. With longer follow-up, issues related to the long-term use of imatinib have been discussed. Our aim is to review the emerging safety issues of Abl TKIs after a longer follow-up.     

Eosinophilic variant of chronic myeloid leukemia with vascular complications

Eosinophilic variant of CML (eoCML) is a unique disease with a poor prognosis. Like the hypereosinophilic syndrome (HES), eoCML has no clinically identifiable reason for an increased eosinophil count in the peripheral blood. In contrast to HES, eoCML patients carry a distinct chromosomal abnormality. The bcr/abl fusion gene (Philadelphia chromosome) is the genetic basis of this clonal disease. Recently, eoCML has been separated from HES. Patients with eoCML frequently suffer organ damage including the heart and lungs. This damage is related to the release of eosinophilic granules in the blood, which results in fibrosis of the endothelial lining. We report a case of a peripheral vasculitis complicated by gangrene of the fingers in a patient with eoCML. Despite an almost complete response to CML treatment with Gleevac, combined with prednisone, aspirin and coumadin the patient sustained irreversible damage to the vascular lining of the distal arteries of the upper extremities.     

Maintenance therapy with imatinib appears necessary despite molecular remission in FIP1L1-PDGFRA fusion gene positive hypereosinophilic disorder

Patients with primary hypereosinophilic disorders who are positive for the FIP1L1-PDGFRA fusion gene mutation are highly responsive to therapy with imatinib mesylate. A 35-year-old man with FIP1L1-PDGFRA positive hypereosinophilic syndrome and cardiac involvement, was treated with imatinib 100 mg daily. Hematologic and molecular remission and reversal of end-organ damage was achieved. He was then lost to follow up for 19 months. Imatinib successfully reinduced hematologic and molecular remission but worsening cardiac involvement was not reversed. Our experience and a review of limited literature suggest that imatinib maintenance therapy is necessary despite molecular remission of the FIP1L1-PDGFRA mutation.