5. Neoplasm Heritable genetic alterations Passed down from progeny of tumor cells Excessive and unregulated proliferation Becomes independent of physiologic growth stimuli (autonomous growth) PERSISTENCE OF TUMOR
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10. B Colonic polyp. A, This benign glandular tumor (adenoma) is projecting into the colonic lumen and is attached to the mucosa by a distinct stalk. B, Gross appearance of several colonic polyps.
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13. This mixed tumor of the parotid gland contains epithelial cells forming ducts and myxoid stroma that resembles cartilage. (Courtesy of Dr. Trace Worrell, University of Texas Southwestern Medical School, Dallas, TX.)
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15. A, Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. B, A microscopic view of a similar tumor shows skin, sebaceous glands, fat cells, and a tract of neural tissue (arrow).
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17. Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma). Note the marked cellular and nuclear pleomorphism, hyperchromatic nuclei, and tumor giant cells. (Courtesy of Dr. Trace Worrell, University of Texas Southwestern Medical School, Dallas, TX.) NORMAL
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19. Malignant tumor (adenocarcinoma) of the colon. Note that compared with the well-formed and normal-looking glands characteristic of a benign tumor, the cancerous glands are irregular in shape and size and do not resemble the normal colonic glands. BENIGN MALIGNANT
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23. Hamartoma of the spleen. The hamartoma is the dark circular object on the left that dominates the image. This is a cross-section, the growth being about 9cm in diameter, while the spleen is actually about 11cm.
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25. Complex choristoma (epibulbar). Complex choristomas, in addition to having the features of a dermoid or dermolipoma, include other tissues such as cartilage, bone, and lacrimal gland. In the image above there is cartilage (arrow 1), adipose tissue (arrow 2) and lacrimal gland tissue (arrow 3).
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29. (A) Normal smooth muscle. (B) Leiomyoma of the uterus. This benign, well-differentiated tumor contains interlacing bundles of neoplastic smooth muscle cells that are virtually identical in appearance to normal smooth muscle cells in the myometrium. P R O P E R T I E S A B
30. (a) Normal colonic epithelium. (b) Benign neoplasm of colon. The cells of a benign neoplasm (b) resemble those of the normal epithelium (a), in that they are columnar and have an orderly arrangement. Loss of some degree of differentiation is evident in that the neoplastic cells do not show mucin vacuolation. P R O P E R T I E S
31. (a) Normal colonic epithelium. (c) Well-differentiated malignant neoplasm of colon. Cells of the well differentiated malignant neoplasm (c) have a haphazard arrangement and, although gland lumina ( G ) are formed, they are architecturally abnormal and irregular. Nuclei vary in shape and size. P R O P E R T I E S
32. (a) Normal colonic epithelium. (d) Poorly differentiated malignant neoplasm of colon. Cells in the poorly differentiated malignant neoplasm (d) have an even more haphazard arrangement, with very poor formation of gland lumina ( G ). P R O P E R T I E S
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35. (a) Normal colonic epithelium. (e) Anaplastic malignant neoplasm of colon. Cells in anaplastic malignant neoplasm (e) bear no relation to the normal, with no attempt at gland formation. There is tremendous variation in the size of cells and of nuclei, with very intense staining (nuclear hyperchromatism) of the latter. Without knowing the site of origin it would be impossible to tell what sort of tumor this was by histology. P R O P E R T I E S
42. Progression of dysplasia to neoplasia. In the diagram, as in real life, the distinction between dysplasia and in situ neoplasia is difficult and emphasis is placed on loss of normal tissue architecture to signify the development of neoplasia. The altered cell turnover in dysplasia probably allows local environmental factors to cause genetic abnormalities leading to neoplasia.
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45. P R O P E R T I E S Rates of Growth Normal cell Single tumor cell 30 doublings 1 gm – 10 9 cells Smallest clinically detectable mass 10 doublings Microscopic metastases (?) 1 kg – 10 12 cells Maximum mass compatible with life Metastases
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49. Schematic representation of tumor growth. As the cell population expands, a progressively higher percentage of tumor cells leaves the replicative pool by reversion to G 0 , differentiation, and death.
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55. Benign neoplasm of thyroid gland. This low-power micrograph shows the features of a benign epithelial neoplasm. The tumor is very well circumscribed, and although it compresses adjacent tissue it does not grow into it.
56. Fibroadenoma of the breast . The tan-colored, encapsulated small tumor is sharply demarcated from the whiter breast tissue (A). Microscopic view of fibroadenoma of the breast (B). The fibrous capsule (right) delimits the tumor from the surrounding tissue. (Courtesy of Dr. Trace Worrell, University of Texas Southwestern Medical School, Dallas, TX.) A A B
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58. (A) Cut section of an invasive ductal carcinoma of the breast. The lesion is retracted, infiltrating the surrounding breast substance, and would be stony hard on palpation. (B) The microscopic view of the breast carcinoma seen in (A) illustrates the invasion of breast stroma and fat by nests and cords of tumor cells. The absence of a well-defined capsule should be noted. (Courtesy of Dr. Trace Worrell, University of Texas Southwestern Medical School, Dallas, TX.) A B
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65. Lymphatic invasion by tumor. (a) Histology of invasion of lymphatic vessel. (b) Tumor in para-aortic lymph nodes. Micrograph (a) shows malignant cells ( M ) in a small lymphatic vessel. Cells break off from the primary tumor, enter small lymphatics and are carried to lymph nodes, where they frequently grow as metastases. The macroscopic appearance of tumor in nodes is shown in (b); the nodes ( N ) are enlarged and replaced by tumor which, in this instance, originated from the testis.
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69. Main sites of blood-borne metastasis. (a) Sites of hematogenous metastasis. (b) Metastasis in bone. (c) Metastasis in brain. (d) Metastasis in liver. (e) Metastasis in adrenals. (f) Metastasis in lungs. P R O P E R T I E S
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74. Comparisons Between Benign & Malignant Tumors Characteristics Benign Malignant Differentiation/ anaplasia Well-differentiated; structure may be typical of tissue of origin Some lack of differentiation with anaplasia; structure is often atypical Rate of growth Usually progressive & slow; may come to a standstill or regress; mitotic figures rare and normal Erratic (may be slow to rapid); mitotic figures may be numerous and abnormal Local invasion Usually cohesive and expansile well-demarcated masses that do not invade or infiltrate surrounding normal tissues Locally invasive, infiltrating the surrounding normal tissues; sometimes may be seemingly cohesive and expansile Metastasis Absent Frequently present Telomerase activity Normal Increased
75. Comparisons Between Benign & Malignant Tumors Characteristics Benign Malignant Histology Resembles cell of origin Shows failure of cellular differentiation Few mitoses Many mitoses, some of which are abnormal forms Normal or slight increase in nuclear/cytoplasmic ratio High nuclear/cytoplasmic ratio Cells are uniform throughout the tumor Cellular and nuclear pleiomorphism
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82. E P I D E M I O L O G Y Cancer and Geography Most of the geographic differences are due to environmental and cultural factors rather than genetic predisposition.
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85. E P I D E M I O L O G Y Reported Deaths for the 5 Leading Cancer Types for Males by Age (US, 2000) All ages < 20 20 – 39 40 – 59 60 – 70 80+ Lung & bronchus Leukemia Brain and CNS Lung and bronchus Lung and bronchus Lung and bronchus Prostate Brain and CNS Leukemia Colon and rectum Colon and rectum Prostate Colon & rectum Bones & joints Lung and bronchus Pancreas Prostate Colon and rectum Pancreas Endocrine system NHL Esophagus Pancreas Urinary bladder NHL NHL Colon & rectum Liver NHL Leukemia
86. E P I D E M I O L O G Y Reported Deaths for the 5 Leading Cancer Types for Females by Age (US, 2000) All ages < 20 20 – 39 40 – 59 60 – 70 80+ Lung & bronchus Leukemia Breast Breast Lung and bronchus Lung and bronchus Breast Brain and CNS Uterine cervix Lung and bronchus Breast Colon and rectum Colon & rectum Endocrine system Leukemia Colon and rectum Colon and rectum Breast Pancreas Bones & joints Lung and bronchus Ovary Pancreas Pancreas Ovary Soft tissue Brain and CNS Pancreas Ovary NHL
87. Average 5-year survival rates for common neoplasms . The chances of surviving for 5 years after diagnosis vary greatly according to the type of neoplasm.
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91. G E N E T I C S Selected Autosomal Dominant Cancer Syndromes Syndrome Gene involved Features Retinoblastoma RB suppressor gene on chr. 13 Malignancy of eye in children; with predisposition for osteogenic sarcoma in adolescence Familial adenomatous polyposis APC suppressor gene Malignant transformation of polyps by age 50 Li-Fraumeni synd. TP53 suppressor gene Inc. risk for sarcomas, leukemia, carcinomas (e.g. Breast) before age 50
92. G E N E T I C S Inherited Predisposition to Cancer Inherited Cancer Syndromes (Autosomal Dominant) Gene Inherited Predisposition RB p53 p161NK4A APC NF1, NF2 BRCA1, BRCA2 MEN-1, RET MSH2, MLH1, MSH6 PATCH Retinoblastoma Li-Fraumeni Synd. (various tumors) Melanoma Familial adenomatous polyposis/colon cancer Neurofibromatosis 1 and 2 Breast and ovarian tumors MEN-1, MEN-2 Hereditary nonpolyposis colon cancer Nevoid basal cell carcinoma syndrome
99. G E N E T I C S Inherited Predisposition to Cancer Familial Cancers Familial clustering of cases, but role of inherited predisposition not clear for each individual Breast cancer Ovarian cancer Pancreatic cancer Inherited Autosomal Recessive Syndromes of Defective DNA Repair Xeroderma pigmentosa Ataxia-telangiectasia Bloom syndrome Fanconi anemia