病理学课件：肿瘤2

1、Page 1一、上皮组织肿瘤（覆盖上皮/腺上皮）（一）上皮组织良性肿瘤 1. 乳头状瘤（papilloma):来源：被覆上皮，好发于皮肤和膀胱特点：外生性生长，形成乳头状突起肿块，有蒂与正常组织相连。轴心为肿瘤间质，外被增生上皮为肿瘤实质。其实质上皮细胞类型依据起源部位不同而异。第八节 常见肿瘤举例Page 2Page 32. 腺瘤（adenoma)来源：腺体、导管或分泌上皮，多发生于甲状腺、卵巢、乳腺、涎腺和胃肠道等部位。分类：根据组成成分和肉眼形态又分为：（1）管状腺瘤与绒毛状腺瘤：多见于结肠、直肠，常呈息肉状。结肠多发、易早期癌变。（2）囊腺瘤：常见于卵巢，有浆液性和黏液性，其中浆液性乳

2、头状易恶变。（3）纤维腺瘤：乳腺常见。增生的间质是肿瘤的实质。（4）多形性腺瘤：多见于腮腺，易复发，起源于闰管上皮和肌上皮细胞。Page 4Adenoma of Colon Page 5Serous cystadenomaSerous cystadenoma with focal proliferation and atypia.Serous cystadenofibromaPage 6Breast fibroadenomaBreast fibrocystic diseasePage 7腮腺多形性腺瘤（切面粘液和软骨样组织） Mixed tumor. An intimate mixture o

3、f epithelial and stromal elements is seen in this mixed tumor. The stroma exhibits cartilaginous differentiationPage 8（二）上皮组织恶性肿瘤统称为癌，常见，且多见老年人。起源：腺上皮和被覆上皮形态学特点： 肉眼特征外形与发生部位关系密切，质硬、灰白、干燥、切面呈颗粒状或生梨状。 组织学特点实质呈巢状、腺状和不规则条索状排列，与间质分界清楚，癌细胞之间无网状纤维（在癌巢之间可见网状纤维）；多经淋巴道转移。Page 91. 鳞状细胞癌(squamous cell carcinoma

4、) 部位：皮肤、口腔、食管、喉、子宫颈等，支气管、胆囊、肾盂等处，通过鳞状上皮化生引起。 肉眼：常呈菜花状，可坏死脱落形成溃疡。 镜下：分化好者可见细胞间桥和角化珠。 分化差者异型性明显，分裂相多见。Page 10Squamous cell carcinomaPage 112. 腺癌 (adenocarcinoma) 来源: 腺体、导管或分泌上皮 部位: 胃肠、胆囊、子宫体等。 肉眼: 乳头状、菜花状、结节状, 可见坏死或溃疡 镜下: 管状和乳突状腺癌； 实性癌； 粘液癌Page 12 Intestinal adenocarcinoma of the stomach. Note the wel

5、l-formed glands and lack of cytoplasmic mucin. Diffuse carcinoma, showing multiple signet ring cells.Page 13 Adenocarcinoma of the colon. A resected colon shows an ulcerated mass with enlarged, firm, rolled borders. Microscopically, this colon adenocarcinoma consists of moderately differentiated gla

6、nds with a prominent cribriform pattern and frequent central necrosisPage 14 Carcinoma of the breast. A. Mammogram. An irregularly shaped, dense mass (arrows) is seen in this otherwise fatty breast. B. Mastectomy specimen. The irregular white, firm mass in the center is surrounded by fatty tissue. C

7、. Photomicrograph showing irregular cords and nests of invasive ductal carcinoma cells invading stroma.Page 15Patterns of breast carcinoma.Colloid (mucinous) B. Medullary C.Micropapillary D. Metaplastic E. Tubular Page 16 实性癌 (单纯癌） 属低分化腺癌，现已少用部位：多见于乳腺，胃及甲状腺少见。镜下：实性癌巢，无腺腔样结构，细胞异型性高，核分裂像多见。 Page 173.

8、基底细胞癌(basal cell carcinoma)部位: 多见老年人面部,如眼睑、 颊及鼻翼 肉眼: 溃疡, 生长慢镜下: 基底细胞样癌巢特点: 转移少,放疗敏感。4. 尿路上皮癌或移行细胞癌 (transitional cell carcinoma) 部位：膀胱、肾盂、输尿管 肉眼：常呈乳头状，多发性。 镜下：癌细胞多层排列，异型性明显。Urothelial carcinoma of the urinary bladderA. Low-grade papillary urothelial carcinoma consists of exophytic papillae that have

9、 a central connective tissue core and are lined by slightly disorganized transitional epithelium. B. Low grade papillary urothelial carcinoma at higher magnification shows mild architectural and cytologic atypia.Page 20L. High-grade papillary urothelial carcinoma shows prominent architectural disorg

10、anization of the epithelium, which contains cells with pleomorphic hyperchromatic nuclei. R. Invasive high-grade papillary urothelial carcinoma consists of irregular nests of hyperchromatic cells invading into the muscularis.Page 21二、间叶组织肿瘤“软组织肿瘤”（一）间叶组织良性肿瘤 1. 脂肪瘤(lipoma)（较常见） 2. 纤维瘤(fibroma) 3. 血管

11、瘤(hemangioma)和淋巴管瘤(lymphangioma) 4. 平滑肌瘤(leiomyoma) 5. 骨瘤和骨软骨瘤（osteoma/osteochondroma)Page 22lipoma多形性脂肪瘤fibromaPage 24HemangiomaPage 25leiomyomaPage 26（二）间叶组织恶性肿瘤常见恶性间叶组织肿瘤1. 脂肪肉瘤（较常见）(liposarcoma)2. 纤维肉瘤(fibrosarcoma)3. 横纹肌肉瘤(rhabdomyosarcoma)4. 平滑肌肉瘤(leiomyosarcoma)5. 血管肉瘤(hemangiosarcoma)6. 骨肉瘤和

12、软骨肉瘤（osteosarcoma/chondrosrcoma)Page 27Liposarcoma. Pleomorphic cells are present, many containinglipid vacuoles that indent the nuclei or completely displace themto one side (lipoblasts).Page 28leiomysarcomaLeiomyomaPage 29Undifferentiated pleomorphic sarcoma (“malignant fibrous histiocytoma”).Fibr

13、osarcomaPage 30Embryonal rhabdomyosarcomaalveolar rhabdomyosarcomaPage 31 Osteosarcoma. A. The distal femur contains a dense osteoblastic malignant tumor that extends through the cortex into the soft tissue and the epiphysis. B. A photomicrograph reveals pleomorphic malignant cells, tumor giant cell

14、s and mitoses (arrow). The tumor produces woven bone that is focally calcified.肉瘤（sarcoma）与癌的区别：癌肉瘤组织来源 上皮组织间叶组织发病率常见，约为肉瘤的9倍，多见40岁以上成人较少见，大多见于青年大体特点质较硬、色灰白、较干燥质软、色灰红、湿润、鱼肉状组织学特点癌巢，实质与间质分界清楚，常有纤维组织增生。瘤细胞弥漫分布，实质与间质分界不清楚，间质内血管丰富，纤维组织少。网状纤维癌细胞间多无网状纤维癌细胞间多有网状纤维免疫组织化学上皮标记物表达间叶标记物表达转移多经淋巴道多经血道Page 33三、多种组

15、织构成的肿瘤畸胎瘤(teratoma) 是发生于性腺或胚胎剩件中全能细胞的良性肿瘤，瘤组织含有两个或以上胚层的多种组织构成。 最常见于卵巢、睾丸，纵隔、腹膜后少见。恶性畸胎瘤：是发生于性腺或胚胎剩件中全能细胞的恶性肿瘤。Page 34Mature cystic teratoma. The lining of the cyst is composed of skin with its appendagesPage 35Squamous cell carcinoma (left) arising in and overgrowing mature cystic teratoma Squamous

16、cell carcinoma arising in mature cystic teratoma.The tumor has an infiltrating pattern showing numerouskeratin pearlsPage 36肾母细胞瘤(Wilms瘤) 来源：肾内残留的胚基组织 年龄：5岁以下 病变：成份多样，巢状胚基细胞可见到横纹肌、骨等癌肉瘤(carcinosarcoma) 同一肿瘤既有癌成分,又有肉瘤成分 癌：鳞癌、移行细胞癌、腺癌 肉瘤：纤维肉瘤、平滑肌肉瘤 Page 37Wilms tumor. A cross-section of a pale tan neo

17、plasm attached to a residual portion of the kidney. This small round blue cell tumor classically has three components: (1)epithelium, in which the cells form primitive tubules; (2) stroma, the mesenchymal component; and (3)blastema, the most primitive and undifferentiated component. Ratios may vary

18、by tumorPage 38Malignant mesodermal mixed tumor (carcinosarcoma).Adenocarcinoma merges with rhabdomyosarcoma Malignant mesodermal mixed tumor (carcinosarcoma).Both carcinomatous and sarcomatous components have malignant cytologic features (nuclear pleomorphism and mitotic activity)Page 39癌前病变（precan

19、cerous lesions）： 是指某些具有癌变的潜在可能性的病变，如长期存在即可能转变为癌 。（癌前疾病）遗传性 多发性结肠、直肠的息肉状腺瘤获得性 粘膜白斑、慢性子宫颈炎和子宫颈糜烂、慢性萎缩性胃炎和胃溃疡、乳腺增生性纤维囊性变、慢性溃疡性结肠炎、肝硬变和皮肤慢性溃疡。第九节 癌前病变、非典型增生和原位癌Page 40Tubular adenoma from a resection specimen. The head of the polyp isdivided into lobules.Gross photograph of a large villous adenoma. The

20、lesion is spreading and sessile.Page 41结肠绒毛状腺瘤Page 42Tubular adenoma (L) Low power view. The neoplasitic glands form tubules. (R) Higher power view. The nuclei are elongted and dysplastic. Some nuclear palisading is noted. The nuclei do not reach the cell surface. The apical portion of the cell show

21、s mucin production. These adenomatous changes are considered low grade dysplasiaPage 43High-grade dysplasia in an adenoma. The diagnosis is largely based on architectural features,such as cribriform growth (arrow). low-grade dysplasia is seen in the surface glands (arrow), while the deeper glands ar

22、e uninvolved (arrowhead). Page 44Adenoma with high-grade dysplasia. (L) Low-power view showsarchitectural changes of glandular buckling. (R) Higher power view shows dysplastic nuclei extending to the cell surface. Mitosis is also present at the surface. The changes in this lesion are those of high-g

23、rade dysplasia.Page 45Adenomas with high-grade dysplasia. (L) Low-power view of a cribriform (gland-in-gland) pattern. (R) Higher power view. These changes represent high-grade dysplasia.Page 46Simple hyperplasia. The glands appear proliferative and are too crowded (the gland-to-stroma ratio is grea

24、ter than 1). Complex atypical hyperplasia. (A) The glands are very crowded, even back to back, and the gland lumens have become branching and irregular. (B Comparing the hyperplastic epithelium with normal residual glands, the hyperplastic cells have round nuclei, and pale, vesicular chromatin with

25、prominent nucleoli, diagnostic of atypia.Page 47非典型增生（atypical hyperplasia）概念：指增生上皮的形态呈现一定程度的异型性， 但不足以诊断为癌。特点：细胞大小不一，形状多样，染色深浓， 核浆比例大，核分裂多，无病理性核分裂细胞排列较乱，极向消失，层次增多。“异型增生（dysplasia）”Page 48常发生于鳞状上皮，可见于腺上皮。鳞状上皮：轻度 2/3、3/3.Page 49 原位癌（carcinoma in situ）一般指粘膜或皮肤鳞状上皮内的重度非典型性增生已累及上皮的全层，但尚未侵破基底膜而向下浸润者。 是一种早

26、期癌，早发现，早治疗Page 50Flat carcinoma in situ. The urothelium is partially denuded (stripped of cells), but the cells that remain show enlarged, round, hyperchromatic nuclei appearing to pop off the surface (arrow).High-grade papillary urothelial cancer. This papillary lesion shows large, dark, pleomorphi

27、c nuclei popping off the surface, similar to carcinoma in situ . A large mitotic figure is visible (arrow).Page 51Ductal carcinoma in situ (DCIS) with comedo necrosis.Intraductal carcinoma with a cribriform architecture and central comedo necrosis . Ductal carcinoma in situ noncomedo type. A cribrif

28、ormarrangement of tumor cells is evident.上皮内瘤变（intraepithelial neoplasia） 非典型增生原位癌 上皮内瘤变I级： 轻度非典型增生 上皮内瘤变II级： 中度非典型增生 上皮内瘤变III级：重度非典型增生和原位癌Page 53Interrelations of naming systems in premalignant cervical diseasePage 54第十节 肿瘤的流行病学、发病学 肺癌、女性乳腺癌、胃癌、肝癌、食管癌、结直肠癌、宫颈癌是我国常见的恶性肿瘤。肺癌、乳腺癌、结直肠癌、女性甲状腺癌呈上升趋势。肺癌、肝

29、癌、胃癌、食管癌、结直肠癌、女性乳腺癌、胰腺癌是主要的肿瘤死因。Page 55 要明确 肿瘤广泛存在于人类 。 不同地域 显著的肿瘤发病率差异提示环境致癌物。 肿瘤是可预防的 生物感染因素， 吸烟，酗酒，饮食，肥胖，生育史， 环境致癌物年龄 是影响肿瘤发生风险的最重要的因素Page 56获得性(后天)易感因素肿瘤获得性易感因素 可分为慢性炎症，癌前病变，免疫缺陷状态慢性炎症与肿瘤 1863年 Virchow提出， 包括感染性/非感染性， 癌前病变与肿瘤 与慢性炎症相关， 多表现为化生， Barrets 食管，支气管上皮鳞化（吸烟所致），胃的肠上皮化生 非炎性增生 子宫内膜增生， 皮肤黏膜白斑良

30、性肿瘤 结肠绒毛状腺瘤免疫缺陷状态与肿瘤 致瘤病毒 多为淋巴瘤，可有癌和肉瘤Page 57遗传易感性不超过5%-10%癌 通常由于抑癌基因的胚系突变 常染色体显性癌综合症 RB 视网膜母细胞瘤; APC 家族性结肠腺瘤性息肉病常染色体隐性DNA修复基因缺陷综合症DNA修复缺陷 色素沉着型燥皮病， Bloom综合症（染色体断裂综合征）易发生白血病遗传本质未确定的家族性癌遗传本质不明，但有家族聚集， 发病年龄，部位等散发性肿瘤占95%，没有家族背景但不能排除遗传成分 Page 58癌分子基础遗传学和表遗传学作用非致死性遗传损伤是肿瘤发生的关键四类正常调节基因是致瘤型突变的主靶 癌基因 / 抑癌基因

31、 / 凋亡 / DNA修复 除了DNA突变， 表遗传学变化也影响癌细胞恶性特征。肿瘤的克隆性扩增第十一节 肿瘤发生的分子基础 Page 59肿瘤发生的多步骤性 A possible five-hit scenario for colorectal cancer, showing the mutational events that correlate with each step in the adenomacarcinoma sequence.Page 60 Genetic events required to convert a normal human cell into a tumor

32、 cell. Weinberg and colleagues show that alterations in at least four pathways are needed. (rebuilding the road to cancer ,1999 nature)Page 61Page 62 癌细胞形成后，生长和进展中在达尔文选择压力下经历遗传学上的演进适者生存的癌细胞不仅可以解释癌的自然史， 也可解释治疗后肿瘤行为的改变。Page 63 环境致癌因素与致癌机制（一）化学致癌因素：约有1000多种。（1）各种化学致癌物在结构上是多种多样的。 直接作用的化学致癌物 间接作用的化学致癌物（2）在化学上都具有亲电子结构的基团，它们能与细胞大分子的亲核基团共价结合，导致DNA的突变。（3）某些化学致癌物的致癌性可由于其它本身无致癌性的物质协同作用而增