精准医学时代下的精准诊断

美国总统奥巴马于2015年1月20日发表国情咨文的演讲中宣布：“今晚，我将启动一个崭新的精准医学计划，这将使我们距离治愈癌症和糖尿病等疾病更进一步。并且，这将使我们所有人利用个性化信息让自己的家人更健康成为可能。”
　　精准医学（ precision medicine ）又称为精准医疗，是指基于每个个体的基因差异而制定的个性化治疗方案，正如量体裁衣才能制作出合身的衣服一样，这样的医疗才会比传统医疗更加有效。其实，早在4年前，美国几大科学机构联手，由Maynard V.Olsent博士起草撰写《走向精准医学》报告中就倡议加快人类基因组的临床转化，以推动个性化医疗的发展，实现人类疾病的精准治疗和预防。     

儿童指突状树突细胞肉瘤1例

1病例资料 患儿,男,23月龄,因＂双侧颈部淋巴结进行性肿大近1个月＂于2010年7月30日入复旦大学附属儿科医院（我院）。患儿于7月初发现颈部有2个小肿块,直径0.5～1.5cm,无红、肿、热、痛,未予特殊处理;     

非特指性外周T细胞淋巴瘤中EBER、 LMP1的表达及与预后的关系

目的 探讨非特指性外周T细胞淋巴瘤(peripheral T-cell lymphoma,not otherwise specified,PTCL-NOS)中EBER、LMP1的表达及与患者预后的关系.方法 采用原位分子杂交(in situ hybridization,ISH)技术和免疫组化法分别检测81例PTCL-NOS及59例对照组[48例血管免疫母细胞性T细胞淋巴瘤(angioimmunoblastic T-cell lymphoma,AITL)和11例结外NK/T细胞淋巴瘤(extranodal NK/T cell lymphoma,ENK/TCL)]中EBER和LMP1的表达,并分析EBER表达与PTCL-NOS患者临床病理特征及预后的关系.结果 (1)81例PTCL-NOS中,EBER阳性率为43.2％ (35/81);35例EBER阳性的PTCL-NOS病例中免疫组化得分1分+2分者共29例,占EBER阳性病例的82.9％(29/35),3分+4分者共6例,占17.1％ (6/35).EBER表达与PTCL-NOS患者年龄、性别、乳酸脱氢酶(lactate dehydrogenase,LDH)水平及临床分期均无明显相关性(P＞0.05).(2)81例PTCL-NOS组织中,LMP1蛋白阳性率为22.2％(18/81).LMP1蛋白表达与EBER表达具有一致性,但EBER阳性率明显高于LMP1 (P ＜0.05).(3)33例PTCL-NOS获得临床随访资料,随访时间1～63个月,中位生存期为23个月,总生存率为33.3％(11/33).Kaplan-Meier生存曲线分析显示,EBER阳性组的生存率明显低于EBER阴性组(P＜0.05).结论 EB病毒(EBV)感染可能是PTCL-NOS发生、发展中重要但非根本性的因素.EBER-ISH检测EBV感染具有较高的敏感性和特异性.EBV感染对PTCL-NOS患者的预后判断具有重要意义.     

恶性淋巴瘤病理学检查对治疗和预后的意义

恶性淋巴瘤的正确诊断和分型是临床治疗和预后判断的重要依据。传统的恶性淋巴瘤分类仅依据肿瘤的形态学特征进行组织学分型，但2001年新的WHO恶性淋巴瘤分类将每种类型淋巴瘤视为一个独立病种（disease entity），依据形态学、免疫表型、遗传学和临床特征四个方面来定义每一种类型淋巴瘤。     

肾混合性上皮间质肿瘤和成人囊性肾瘤的临床病理学观察

Objective To study the clinicopathologie features,immunophenotype and differential diagnosis of mixed epithelial and stromal tumor of kidney ( MEST) and adult cystic nephroma ( CN).Methods Five cases of MEST and 4 cases of CN were retrospectively analyzed.Immunohistochemical study was carried out and the literature was reviewed.Results All of the five patients with MEST were females.Their median age was 45 years.For CN,there were 3 males and 1 female and their median age was 41 years.All patients presented with loin pain and hematuria.On gross examination,MEST was well-circumscribed but non-encapsulated.There was no evidence of haemorrhage or necrosis.Three of the cases were solid in nature.One was composed of a mixture of solid and cystic elements,while the remaining case showed a multicystic cut surface bridged by thick fibrous septa.On the other hand,CN were well-circumscribed and encapsulated.They were multiloculated cystic in nature.The cystic spaces were separated by thin septa and there was no significant solid or necrotic component.Histologically,MEST consisted of proliferation of cystically dilated glands admixed with spindly stromal cells with various cellularity and growth patterns.Both the glandular and stromal elements were well-differentiated with no cytologic atypia identified.The glandular structures in 2 of the cases were partially lined by endometrial or tubal epithelium.In contrast,the thin-walled cystic spaces in CN were lined by a single layer of epithelium.Immunohistochemical　study showed that the epithelial cells were positive for pan-cytokeratin and epithelial membrane antigen.The spindle cells in MEST expressed vimentin (5/5 ) ,smooth muscle actin (3/5 ),desmin (4/5 ),CD10 (5/5),estrogen receptor (4/5) and progesterone receptor (4/5).They were negative for HMB45,CD34,CD117 and S-100 protein.On the other hand,the spindle cells in CN were variably positive for vimentin (4/4),smooth muscle actin (4/4),desmin (1/4),estrogen receptor (3/4) and progesterone receptor (1/4).They were negative for CD10,HMB45,CD34,CD117 and S-100 protein.Conclusions Both MEST and CN are uncommon renal neoplasm.Most of them run a benign clinical course.The stromal cells in MEST show smooth muscle or myofibroblastic differentiation.Areas demonstrating Miillerian features also existed in some cases.MEST and CN share overlapping histological and immunohistochemical features,and may represent spectrum of the same group of lesions.     

分子医学时代的外科病理学

20世纪70年代初,分子生物学、细胞和分子遗传学的发展,已将这些新知识、新理论和新技术应用到人类疾病的研究,从而诞生了病理学的一个新的分支--分子病理学.核酸分子杂交、比较基因组杂交(CGH)、荧光原位杂交(FISH)、聚合酶链反应(PCR)及其衍生技术(如RT-PCR、定量PCR等)和DNA测序等技术逐渐渗入到外科病理学,并已应用于肿瘤的诊断和分型、肿瘤治疗选择和预后评估、遗传性疾病的诊断、感染性疾病的病原体证实等方面.     

恶性淋巴瘤病理学进展评析

近年来,恶性淋巴瘤(以下称淋巴瘤)的发病呈上升趋势,对其研究逐步深入,建立于科学分类原则基础上的WHO淋巴瘤分类不但已被广大病理医师和临床医师所广泛接受和应用,而且还得到了及时的更新和修订,淋巴瘤病理研究中,临床因素以及遗传学特征的重要性也正日益凸显.     

介绍WHO的胸腺上皮肿瘤分类

胸腺肿瘤的分类一直是肿瘤病理学领域最有争议的难题之一 ,其焦点在于胸腺上皮肿瘤 (ｔｈｙｍｉｃｅｐｉｔｈｅｌｉａｌｔｕｍｏｕｒｓ ,ＴＥＴ)的分类上。传统上 ,主要根据淋巴细胞与上皮细胞的比例以及上皮细胞的形态将ＴＥＴ分为四个亚型 :梭形细胞型 ,淋巴细胞型 ,上皮细胞型和混合型〔1〕。由于与临床治疗和预后相关性不大 ,而被临床医生认为是聊胜于无 ,判断预后主要是根据临床分期。为了获得较好的临床和预后的相关性 ,Ｌｅｖｉｎｅ和Ｒｏｓａｉ等〔2〕根据肿瘤的侵袭性和肿瘤细胞的异型性将ＴＥＴ分为良性胸腺瘤 ,恶性胸腺瘤Ⅰ型和…     

肾混合性上皮间质肿瘤和成人囊性肾瘤的临床病理学观察

Objective To study the clinicopathologie features,immunophenotype and differential diagnosis of mixed epithelial and stromal tumor of kidney ( MEST) and adult cystic nephroma ( CN).Methods Five cases of MEST and 4 cases of CN were retrospectively analyzed.Immunohistochemical study was carried out and the literature was reviewed.Results All of the five patients with MEST were females.Their median age was 45 years.For CN,there were 3 males and 1 female and their median age was 41 years.All patients presented with loin pain and hematuria.On gross examination,MEST was well-circumscribed but non-encapsulated.There was no evidence of haemorrhage or necrosis.Three of the cases were solid in nature.One was composed of a mixture of solid and cystic elements,while the remaining case showed a multicystic cut surface bridged by thick fibrous septa.On the other hand,CN were well-circumscribed and encapsulated.They were multiloculated cystic in nature.The cystic spaces were separated by thin septa and there was no significant solid or necrotic component.Histologically,MEST consisted of proliferation of cystically dilated glands admixed with spindly stromal cells with various cellularity and growth patterns.Both the glandular and stromal elements were well-differentiated with no cytologic atypia identified.The glandular structures in 2 of the cases were partially lined by endometrial or tubal epithelium.In contrast,the thin-walled cystic spaces in CN were lined by a single layer of epithelium.Immunohistochemical　study showed that the epithelial cells were positive for pan-cytokeratin and epithelial membrane antigen.The spindle cells in MEST expressed vimentin (5/5 ) ,smooth muscle actin (3/5 ),desmin (4/5 ),CD10 (5/5),estrogen receptor (4/5) and progesterone receptor (4/5).They were negative for HMB45,CD34,CD117 and S-100 protein.On the other hand,the spindle cells in CN were variably positive for vimentin (4/4),smooth muscle actin (4/4),desmin (1/4),estrogen receptor (3/4) and progesterone receptor (1/4).They were negative for CD10,HMB45,CD34,CD117 and S-100 protein.Conclusions Both MEST and CN are uncommon renal neoplasm.Most of them run a benign clinical course.The stromal cells in MEST show smooth muscle or myofibroblastic differentiation.Areas demonstrating Miillerian features also existed in some cases.MEST and CN share overlapping histological and immunohistochemical features,and may represent spectrum of the same group of lesions.     

229例肾细胞肿瘤的临床病理学分析

目的研究肾细胞肿瘤的临床表现、组织学分型、形态学特征及预后。方法复习229例连续肾细胞肿瘤的临床资料、大体标本、HE切片、免疫组化染色结果,按2004年WHO肾细胞肿瘤分类标准重新分类,并随访。结果229例肾细胞肿瘤占同期肾实质肿瘤89.1%(229/257),其中223例(97.4%)为肾细胞癌,6例(2.6%)为肾嗜酸细胞腺瘤。肾细胞癌中,透明细胞癌180例(78.6%),乳头状肾细胞癌19例(8.3%),嫌色细胞癌13例(5.7%),1例嫌色细胞癌伴肉瘤变,多房性囊性肾细胞癌6例(2.6%),Xp11.2易位/TFE3基因融合相关肾细胞癌2例(0.9%),未能分类的肾细胞癌2例(0.9%),集合管癌1例(0.4%)。透明细胞癌5年生存率为75.5%;乳头状肾细胞癌5年生存率为80%;嫌色细胞癌随访6例,随访期8~57个月,1例于57个月后死于肿瘤转移;多房性囊性肾细胞癌随访2~40个月,无复发和转移。结论肾细胞肿瘤是一组形态学上各有特征的异质性肿瘤,以恶性为主,其中透明细胞癌、乳头状肾细胞癌、嫌色细胞癌最常见。不同类型肾细胞癌预后不同。WHO肾细胞癌的组织学分型有其实用性和先进性。