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1、NEOPLASM （文字部分）,Zhu keqing 竺可青 Pathology Department Zhejiang University School of Medicine 2012-12,Neoplasia literally means the process of “new growth,“ and a new growth is called a neoplasm.The term tumor was originally applied to the swelling caused by inflammation. Neoplasms also may induce swel
2、lings, but by long precedent, the non-neoplastic usage of tumor has passed into limbo; thus, the term is now equated with neoplasm. Oncology (Greek oncos = tumor) is the study of tumors or neoplasms. Cancer is the common term for all malignant tumors. Although the ancient origins of this term are so
3、mewhat uncertain, it probably derives from the Latin for crab, cancer-presumably because a cancer “adheres to any part that it seizes upon in an obstinate manner like the crab.“Tumor/neoplasm/neoplasia/Mass Benign tumors Malignant tumors/cancer,我国常见恶性肿瘤依次为： 胃癌、肝癌、肺癌、食管癌、大肠癌、白血病及淋巴瘤、子宫颈癌、鼻咽癌、乳腺癌,肿瘤是机
4、体在各种致瘤因素作用下，局部组织的细胞在基因水平上失去对其生长的正常调控，导致克隆性异常增生而形成的新生物。这种新生物常形成局部肿块。Oncology Neoplastic proliferation/clonal/clonality Nonneoplastic proliferation/polyclonal Tumorigenic agent/carcinogen,定义 A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the nor
5、mal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.We know that the persistence of tumors, even after the inciting stimulus is gone, results from heritable genetic alterations that are passed down to the progeny of the tumor cells. These gene
6、tic changes allow excessive and unregulated proliferation that becomes autonomous (independent of physiologic growth stimuli), although tumors generally remain dependent on the host for their nutrition and blood supply. The entire population of cells within a tumor arises from a single cell that has
7、 incurred genetic change, and hence tumors are said to be clonal.,1. 肿瘤的一般形态和结构,数目 大小 形状 颜色 硬度,All tumors, benign and malignant, have two basic components: (1) proliferating neoplastic cells that constitute their parenchyma 实质 (2) supportive stroma间质 made up of connective tissue and blood vessels.,P
8、arenchyma 肿瘤细胞的总称，是肿瘤的主要成分 决定肿瘤的生物学行为，用于识别肿瘤的组织来源 肿瘤通常只有一种实质，但少数肿瘤可以含有多种实质Mesenchyma/stroma 主要是结缔组织和血管，有时有淋巴管和少量神经纤维 支持和营养肿瘤实质 与肿瘤转移有关,2. 肿瘤的异型性 atypia,肿瘤组织无论在细胞形态和组织结构上，都与其发源的正常组织有不同程度的差异。反映肿瘤组织的成熟程度（分化程度）诊断肿瘤，确定其良恶性的主要组织学依据,Degree of differentiation分化 Differentiation refers to the extent to which
9、neoplastic cells resemble comparable normal cells, both morphologically and functionally; lack of differentiation is called anaplasia 间变.,Well differentiated Poorly differentiated Undifferentiated,间变 anaplasia,指恶性肿瘤细胞缺乏分化，异型性明显。 分化不良 形态的多样性 生长的活跃性分化 幼稚 成熟间变,肿瘤组织结构的异型性,结构排列异常 失去正常的层次、极向 大小形状不一 浸润性生长,
10、Cellular atypia 异型性,Lack of differentiation分化, or anaplasia间变, is marked by a number of morphologic changes. Pleomorphism. Abnormal nuclear morphology. (hyperchromatic). Mitoses. Atypical, bizarre mitotic figures, sometimes producing tripolar, quadripolar, or multipolar spindles. Loss of polarity. O
11、ther changes. Another feature of anaplasia is the formation of tumor giant cells, some possessing only a single huge polymorphic nucleus and others having two or more nuclei.,正常细胞的特点,核：浆=1：4-6 有极性 同类细胞大小形态一致 染色正常均匀,恶性细胞的特点,1. 细胞的多形性：大小不一，形态不规则 2. 核的多形性： 核增大，核：浆比增加，甚至接近1：1 核大小、形状、染色不一，可见巨核、多核、奇异核 核染色
12、深，核膜厚 核仁肥大，数目增多，极性消失 病理性核分裂像3. 细胞浆呈嗜碱性或胞浆内异常产物或分泌物,3. 肿瘤的生长与扩散,肿瘤生长的动力学Growth kinetics肿瘤细胞倍增时间Doubling time=24-48小时 生长分数growth fraction：肿瘤细胞群体中处于增值阶段（S期+G2期）的细胞比例。 瘤细胞的生成与丢失化疗药针对处于增值期的细胞,肿瘤血管形成,恶性肿瘤诱导血管形成 肿瘤细胞和巨噬细胞产生血管生成因子VEGF,b-FGF 肿瘤细胞产生抗血管生成因子 肿瘤生长由血管生成因子和抗血管生成因子共同控制 抑制肿瘤血管生成是肿瘤治疗的一个途径,One can be
13、gin the consideration of tumor cell kinetics by asking the question: How long does it take to produce a clinically overt tumor mass?,It can be readily calculated that the original transformed cell (approximately 10 m in diameter) must undergo at least 30 population doublings to produce 109 cells (we
14、ighing approximately 1 gm), which is the smallest clinically detectable mass. In contrast, only 10 further doubling cycles are required to produce a tumor containing 1012 cells (weighing approximately 1 kg), which is usually the maximal size compatible with life. This calculation highlights an extre
15、mely important concept about tumor growth: By the time a solid tumor is clinically detected, it has already completed a major portion of its life cycle. This is a major impediment in the treatment of cancer, and underscores the need to develop diagnostic markers to detect early cancers.,肿瘤的演进和异质化,演进
16、 progression：恶性肿瘤在生长过程中越来越富有侵袭性.异质化 heterogeneity：由一个克隆来源的肿瘤细胞在生长过程中形成在侵袭能力、生长速度、对激素反应、对抗癌药的敏感性等方面有所不同的亚克隆的过程。抗原性较低的亚克隆可以逃避机体的免疫监视。,肿瘤的生长方式,Expansile growth Exophytic growth Invasive growth,肿瘤生长方式,膨胀性生长 大多数良性肿瘤的生长方式 生长缓慢，无侵袭性 周围有完整包膜，分界清 一般不破坏器官的结构和功能外生性生长 常见体表、体腔表面或管道器官表面 良恶性肿瘤均可发生 恶性肿瘤易形成恶性溃疡浸润性生长
17、 大多数恶性肿瘤的生长方式 浸润破坏周围组织 无包膜，无明显分界 手术切除时应扩大范围,肿瘤的扩散,直接蔓延：瘤细胞沿着组织间隙、淋巴管、血管或神经束衣浸润，破坏邻近正常器官或组织，并继续生长。转移 metastasis：瘤细胞从原发部位侵入淋巴管、血管或体腔，迁移到他处继续生长，形成与原发瘤同样类型的肿瘤。良性肿瘤不转移，只有恶性肿瘤才可能发生转移。Pathways of Spread Dissemination of cancers may occur through one of three pathways: (1) direct seeding of body cavities or surfaces, (2) lymphatic spread, and (3) hematogenous spread.,
