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• New growth • Tumor is for any swelling may b inflammatory or adaptive or neoplasm • Oncology;study of tumors n neoplasm • Cancer is for malignant tumors.latin;cancer=crab • Britist oncologist;a neoplasm is an abnormal mass of tissue the growth of which exceeds n is uncordinated with that of normal tissues and persists in the same manner after cessation of the stimuli which evoked the change. • Genetic changes , autonomous n clonal.
COMPONENTS OF TUMORS
• 2 BASIC COMP. • Proliferatig neoplastic cells ie parenchyma • Supportive stroma made upof connective tissues n blood vessels • Stroma; growth blood supply n framework
NOMENCLATURE OF TUMORS • • • • • Based on parenchymal comp.eg fibroblast = fibroma • Cartilaginous chondroma . Basically 2 types of tumors Benign tumors Malignant tumors Benign tumors. attach suffix -oma to cell of origin especially to mesedermal cells .
• If fingerlike projections then papillary adenoma • If cystic then cystadenoma .• Osteoblast=osteoma • For epithelial benign tumors use term adenoma. • Eg .renal adenoma.
fleshy) • Eg fibrosarcoma.leiomyosa rcoma. sarcoma (gk.liposarcoma.carcinomas with its name of origin • Eg renal cell adenocarcinoma • Squamous cell carcinoma . • Of epithelal origin .MALIGNANT TUMORS • Of mesodermal origin.
EXCEPTIONS TO NOMENCLATURE • Carcinomas of melanocytes .melanoma • Carcinomas of testis. hepatomas .seminomas • Hepatocellular carcinomas.
rest of adrenal cells under renal capsule • Hamartomas.MISNOMERS • Choristoma. anomalous development at some places eg in lungs .
lipoma • More than 1 cell type but of 1 germ cell layer eg pleomorphic adenoma of salivary glands • More than 1 neoplastic cells of more than 1 germ cell layers eg teratoma .COMPOSITION OF TUMORS • USUALLY OF ONE PARENCHYMAL CELL TYPE eg fibroma.
DIFF BETN BENIGN N MALIGNANT TUMORS • • • • Differentiation / anaplasia Rate of growth Local invasion Metastasis .
mitotic figures rare • usually surrounded by capsule no invasion n infiltration. .BENIGN TUMORS • Well differentiated typical of parent tissues • Grow slowly n progressively. • Metastasis absent.
MALIGNANT TUMORS • Some lack of differentn with anaplasia atypical struct • Growth is erratic usually rapid. infiltrating normal tissues • Metastasis present. Mitotic figures numerous • Locally invasive . .
eg breast cancer invade axillary lymphnodes • Hematogenous.common site are liver n lungs . most common in peritoneal cavities n also pleural.venous spread more than arterial..common in carcinomas than sarcomas.eg carcinomas of ovaries.less in carcinomas. • 2)lymphatic spread.typical of sarcomas. pericardial. joint spaces.natural route of lymphatic system.Pathways of spread ie METASTASIS • 3ways of spread • 1) seeding of body cavities n surfaces.
.Squamous cell carcinoma • Note the haphazard arrangement of cords of infiltrating cells. Keratin formation and lack of gland formation identify this as a squamous cell carcinoma.
similar to a serous cystadenoma. endocervical-like. upon bisection. Benign. the typical multilocular pattern of a mucinous cystadenoma can be seen. mucinous epithelium lines the locules .Ovary multilocular mucinous cystadenoma • The outside surface of this tumor is smooth. however.
Friable papillae are characteristically seen in serous cystadenocarcinomas or serous tumors of low malignant potential . as in this example. Note the lack of friable papillae. Occasional serous cystadenomas may have several locules.Ovary serous cyst adenoma • Ovarian serous cystadenomas are typically unilocular and have a smooth inner surface.
Thus. High-power examination shows that the tumor forms glands. An ulcer with surrounding nodularity is observed on the lesser curvature of a gastric resection specimen. this is an example of the intestinal type of gastric adenocarcinoma . histologically.Stomach early adenocancer ulcerative • This is an example of an early gastric carcinoma. it fits the definition of early gastric carcinoma. Lowpower histologic examination reveals that the tumor involves only the mucosa and submucosa. thus.
. In the wall of the cyst is a structure resembling a tooth. Germ cell tumors can form tissues representing all three germ cell layers.Dermoid cyst teratoma ovary • This teratoma has a cystic space from which hair and keratin debris (on the right) have been removed.
and white. and has a firm.Fibroadenoma breast • This common benign breast tumor is usually round. well circumscribed. rubbery texture .
and some have a broad base of attachment to the normal mucosa. Some polyps are mushroomshaped with a stalk. Features seen here favoring (benign) adenomatous polyps include size (<2 cm) and lack of evidence of invasion of the colonic wall. . Polyps can be benign or they may contain carcinoma.Colon adenomatous polyps • Polyp is the term for a protruding growth from a mucosal surface.
"Leiomyomata" is the plural of "leiomyoma . They are well circumscribed with a homogeneously white cut surface.Leiomyoma uterus • Two examples of this very common benign mesenchymal tumor are seen in the uterine wall. "Leiomyo" refers to smooth muscle.
Note the small.Leiomyoma uterus • The neoplastic smooth muscle tissue of the leiomyoma is almost identical to the normal smooth muscle of the uterine wall. cigarshaped nuclei .
o WILMS'S TUMOR: NEPHROBLASTOMA. It can be deadly because it can compress on the brain. • Germ-Cell Tumors: o TERATOMA: Tumor composed of tissues derived from all three germ layers. Also Seminoma. It usually occurs in gonads. . and cartilage components. • MENINGIOMA: A BENIGN meninges tumor. Mixed tumor of renal tissue. o LEIOMYOSARCOMA: Malignant • Melanocytes: o A NEVUS is a benign tumor o MELANOMA is malignant. bone. Malignant Mixed Tumor of Salivary Gland is the name for the malignant tumor. DERMOID: Benign teratoma of the ovary. • MIXED TUMORS: Derive from a cell that is multipotent. o DIAGNOSIS: High levels of hCG and AFP are diagnostic of teratoma.SPECIFIC TUMORS: • • • • • • • • • • • • • • • • • • • • • • • • • Striated Muscle Tumors: o RHABDOMYOMA: Benign o RHABDOMYOSARCOMA: Malignant (more common) • Smooth Muscle Tumors: o LEIOMYOMA: Benign Leiomyoma of Uterus: Benign tumor of uterus presents with abdominal pain and dysmenorrhea. It has epithelial. having all sorts of strange tissue in it. o TERATOCARCINOMA: Malignant tumor. o PLEOMORPHIC ADENOMA: BENIGN tumor of the salivary gland. Neoplastic germ cells secrete hCG Neoplastic yolks cells (found in Teratoma) secrete AFP. o SEMINOMA: A malignant tumor of germ cells.
o MITOTIC ACTIVITY: Mitotic figures and atypical mitoses. is diagnostic of malignancy. or star-shaped jutting borders.DIAGNOSIS of MALIGNANCY: • • • • • • • • • • • • HISTOLOGICAL DIAGNOSIS: o ANAPLASIA Pleomorphism: Variation in the size and shape of cell nuclei. . • GROSS-APPEARANCE: Malignant tumors have irregular edges. o Bizarre Cells and Giant Cells. blood vessels. • INVASION: Demonstration of the tumor invading basement membrane. Enlarged and hyperchromatic nuclei Prominent nucleoli o Increased Nuclear to Cytoplasmic Ratio. or lymphatics.
o GRADE 1: Well differentiated o GRADE 2: Medium differentiation. based on TNM system. • DUKE'S CLASSIFICATION: Method of staging colon cancer. o (T) TUMOR SIZE Graded 1-4. M1: Metastases are present. o GRADE 3: Poorly differentiated. o (N) NODAL: Has it spread to any lymph nodes? Graded 0-3 N0: It has no spread to lymph nodes. N3: Most severe spread to lymph nodes. o (M) METASTASIS M0: No metastases are present. • CANCER STAGING: Clinical assessment of the spread of the tumor.GRADING AND STAGING OF TUMORS: • • • • • • • • • • • • • • • CANCER GRADING: Histological assessment of malignancy. . 1 is the mildest.
Secrete extracellular proteases that break down Collagen IV. • PROGRESSION: The process by which a benign neoplasm is transformed into malignant cells. Movement through interstitial tissues: Autocrine motility factor induces movement by pseudopodia. PROCESS: Step by step invasion. Penetrate Basement Membrane: Collagenases and proteases. o Promotion is reversible. Binding to the extracellular matrix: integrins. • PROMOTION: Single initiated cell is selected for and promoted into a benign tumor.CARCINOGENESIS: • • • • • • • • • • • • • • • • • • INITIATION: Irreversible damage to DNA in a critical target gene. in order to maintain the promoted state. fibronectin. o Initiation is a permanent genetic alteration (mutation) of the cell and is thus irreversible. irritation. o METASTASIS (STAGE II): Spread of the tumor to a non-contiguous site. Proteoglycans. o INVASION (STAGE I): Contiguous growth of the tumor. or treatment. through blood or lymph. . Degradation of extracellular matrix. Carcinoma In Situ: A malignant epithelial tumor that has not yet penetrated the basement membrane. It requires continual (or repeated) stimulation.
. • • Keratins: Indicates the presence of epithelial cells: carcinoma or mesothelioma.IMMUNODIAGNOSIS of CANCERS • : The origin of cancers that are histologically unidentifiable can be diagnosed by • immunohistology. • • Vimentin: Indicates tumors of mesenchymal origin: sarcomas. • • Desmin: Indicates a tumor of muscle origin: myoma.
that is ironically also carcinogenic itself. They form nitrosamines by reacting with acids in stomach.8-Epoxide product is an epoxide. METABOLISM: Mixed-Function Oxidase with an Epoxide Intermediate. AZO DYES: Their metabolites are excreted in the urine. found in moldy grains in other countries. AFLATOXIN-B1: Product of Aspergillus mold. Benzyl Chloride Nitrosylmethylurea o INDIRECT-ACTING CARCINOGENS: CISPLATIN: Chemotherapy drug that is ironically carcinogenic itself. very much like PAH. METABOLISM: Cytochrome-P450 Mixed Oxidase in liver microsomes. . Aryl Hydrocarbon Hydroxylase: PAH ------> 7.ENVIRONMENTAL CAUSES OF CANCER: CHEMICAL AGENTS • • • • • • • • • • • • • • • • • • • • • • • • o DIRECT-ACTING CARCINOGENS: Do not need to be metabolized in liver. NITROGEN MUSTARD: A cancer (chemotherapy) drug. RISK: Far increased risk for Hepatocellular Carcinoma. leading to lung cancer. where they can cause bladder cancer. Anabolic Steroids can cause brain and liver cancer POLYCYCLIC AROMATIC HYDROCARBONS (PAH): Produced by incomplete combustion of organic material. NITROSAMINES: METABOLISM: They originate as Nitrites found in food-preservatives. Charred meat. They are generally Electrophilic and thus attracted to the negatively charged substituents in the nucleus. AROMATIC AMINES. for example. METALS: Occupational hazards.
UV-C: Absorbed by the ozone layer. RISK: Linked to Mesothelioma of the pleural and peritoneal cavities. o FOREIGN BODIES . It is longer wavelength and penetrates the skin to a greater depth than UV-B. This is only about 3% of UV light. comprising 97% of UV radiation. so we don't come into contact with it.PHYSICAL CARCINOGENS • • • • • • • • • • • • o UV-RADIATION UV-A: Lower energy UV-light. Wavelength below 400nm. It is not innocuous. o IONIZING RADIATION o ASBESTOS: Made of silicates and rigid fibers. MECH: Formation of Thymine-Thymine Dimers in DNA resulting in a deletion. UV-B: Implicated in skin cancer.
Associated with rare T-Cell Leukemias in Japan and Carribean. INFECTIOUS MONONUCLEOSIS is caused by an acute EBV infection. E6 is an HPV protein that can bind the retinoblastoma gene to inactivate it. due to its known relatedness to the SV40 virus. . 16. o EPSTEIN-BARR VIRUS (EBV): RISKS: NASOPHARYNGEAL CARCINOMA BURKITT'S LYMPHOMA: EBV infects B-Lymphocytes. It blocks activation of P53. and cancer of Penis. 11. RISK: Hepatocellular Carcinoma. 18: All lead to Genital Warts HPV 16. HPV 18: Associated with increased risk for Cervical Cancer. MECH: HPV is known to cause cancer by blocking tumor-suppressor genes.• VIRAL CARCINOGENS: • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • • o HUMAN PAPILLOMA VIRUS (HPV): STRUCTURE: Circular double-stranded DNA Virus SUBTYPES: HPV-1. partial single-stranded DNA virus. HPV 6. EBV is found in all Burkitt's Lymphoma's in Africa. Hepatitis-C Virus is also associated with increased hepatoma risk. It occurs in regions where Malaria is endemic. Also can be caused by a translocation (see below). The level of risk is synergistic with the carcinogenic effects of Aflatoxin-B1. Vulva. E7 is an HPV protein that can bind p53 to inactive it. o POLYOMA VIRUSES: STRUCTURE: Small circular double-stranded DNA virus. BK Virus is being studied for oncogenicity. Disease is common in childhood. JC Virus is also being studied. HPV-2: Lead to epithelial warts. MECH: Hepatitis Virus codes for proteins that block Tumor Suppressor proteins. o HUMAN T-CELL LEUKEMIA VIRUS I and II (HTLV-I and II): The only known oncogenic Retrovirus. Perianal condylomata are found with HPV. o HEPATITIS-B VIRUS (HBV) STRUCTURE: Partial double-stranded. Especially in Asia and Africa. and about 20% of them in USA. Also. HBVX is a protein encoded by HBV. HODGKIN'S DISEASE: EBV is found in about 50% of these cases.
that codes for proteins that regulate cell division and growth. If • these protein lose their regulation or are overexpressed. • • PROTO ONCOGENES: • o c-onc: A human (cellular) proto-oncogene. thus making it lose its • regulation and become oncogen . • o v-onc: A proto-oncogene that has been incorporated (via transduction) into a virus.ONCOGENES • : These genes show dominant transmission. The presence of only one aberrant copy is sufficient to produce • cancer. they become oncogenic.
because loss of heterozygosity leads to cancer. Both copies must be defective before cancer results. • o It is known to be a tumor-suppressor gene.TUMOR-SUPPRESSOR GENES • : These are recessive cancer genes. . then you will almost ine• • WILMS'S TUMOR GENE: Childhood form of renal cancer. • • RETINOBLASTOMA GENE • o TWO-HIT HYPOTHESIS: If you inherit one bad copy of the gene.
Renal cell carcinomas. • FEVER: Especially with Hodgkin's. o GONADOTROPIC SYNDROME o HYPOGLYCEMIA • NEUROLOGIC SYNDROMES o SPINAL CORD: o PERIPHERAL: • SKELETAL MUSCLE • HEMATOLOGIC SYNDROMES: o ERYTHROCYTOSIS o ANEMIA: Frequently cause is not understood. CUSHING'S SYNDROME can result from ectopic production of cortisol. such as pancreatic cancers. • ANOREXIA AND WEIGHT LOSS • ENDOCRINE SYNDROMES o INAPPROPRIATE ANTIDIURESIS o HYPERCALCEMIA: About ten percent of all patients. o THROMBOCYTOSIS occurs in about one third of patients. ECTOPIC HORMONE PRODUCTION is the inappropriate secretion of hormones from a tumor. Cause unknown. which can occur in any tumor regardless of its origin. Sometimes from tumor bleeding. DISSEMINATED INTRAVASCULAR COAGULATION (DIC) NONBACTERIAL THROMBOTIC ENDOCARDITIS • MALABSORPTION • RENAL SYNDROMES • CUTANEOUS SYNDROMES . o THE HYPERCOAGULABLE STATE VENOUS THROMBOSIS: Often found in mucin-secreting cancers.PARANEOPLASTIC SYNDROMES • • • • • • • • • • • • • • • • • • • • • • • • • • • PARANEOPLASTIC SYNDROMES: The systemic effects of cancers in the host that are not due primarily to tumor or its METASTASIS. osteogenic sarcomas. Usually attributed to secreted of a PTH-like peptide by an epithelial tumor.
• o Hepatoma and Esophageal cancer are far more common far east. • o Lung cancer is biggest killer in both males and now females in USA. • • CANCER PREVALENCE • o Stomach cancer has gone down.EPIDEMIOLOGY OF CANCER • • CAUSE of DEATH: • o Cancer is #2 next to CV disease. Lung cancer has gone up. . • o Colorectal and Breast cancer are more common in USA.
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