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Neoplasia by Mind Map: Neoplasia
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Neoplasia

Epidemiology

MCC Cancer Deaths

Lung

Breast

Prostate

Colo-recal

MCC Cancer in Men

lung

prostate

colo-rectal

hematopoietic

urinary tract

pancreas

MCC Cancer in women

lung

breast

colo-rectal

hematpoietic

ovary

pancreas

MCC Cancer in Children

Leukemia

Lymphoma

Brain

Colo-rectal

Bone & Soft Tissue

Endocrine

Change in Incidence/Death

decline for GI, better food preservation, change in dietary habits

decline for breast, uterine, cervical, improved screening, early detection

lung cancer, reduce smoking prevalence, reduce environmental smoke exposure

inc incidence among ethinic groups, multifactorial, socioeconomic, environmental, genetic

Factors for Cancer incidence

hereditary/genetic predisposition, 5-10% of all cencer, autosomal dominant, single mutant gene, point mutation in single allele, tumor suppressor gene, mutation in second allele, somatic cells, tumors arise in specific sites, specific marker phenotype, RB, Retinoblastoma, P16INK4a, Melanoma, APC, Familial adenomatous polyposis, colon ca, brca1/2, breast, ovary, VHL, renal cell carcinoma, MEN1, endocrine tumor, RET, endocrine tumor, autosomal recessive, defective DNA repair, very rare, xeroderma pigmentosum, risk for skin cancer, RF exposed to UV light, defect in nucleotide exceision repair, ataxia-telangiectasia, bloom syndrome, fanconi anemia, familial cancer, occur at higher frequency in famlies, colon, breast, ovary, pattern not clearly defined, siblings - 2-3x great risk, no marker phenotpe, early onset < 40, multiple/bilateral tumors, fam hx of cx in 2 or more 1/2 degree

age

social habits

environmental/occupational

pre-existing disease states

chemo-radiation therapy

Definitions

Hyperplasia

inc in cell @

Hypertrophy

cell enlargement without division

metaplasia

irreversible change of one mature type to another

Neoplasia

new abnormal growth (tumor), proliferative, uncoordinated, autonomous, genetically unstable, composed of, proliferating neoplastic parenchyma, fibro-vascular supporting stroma

polyp

abnormal growth

from mucosal surface

attached by stalk

desmoplasia

dense fibrous stroma

seen w malignant tumors

invasion into ECM

altered stroma, activated fibroblasts, cytokines, growth factors

inc collagen deposition

histology, dense, pink, fibrotic, desmoplasia

Benign tumors

Examples, -oma, epithelial, cell of origin, microscopic pattern, macroscopic architecture, Papilloma, B9 epi neoplasm, finger-life projections, exophytic, slow growth outward, gross & micro, Hamartoma, benign aberrant proliferation of mature tissue, particular to site of origin, example, Adenoma, benign epithelial tumors with glandular differentiation, example

slow growing

well differentiated

localized (encapsulated margins)

Tx: surgical excision

may have lethal complications, meningioma - hydrocephalus, gastric leioma - hemorrhage, insulin-producing pancreatic tumor, insulinoma - hypoglycemia, atrial myxoma - cardiac obstruction

exceptions, capillary hemangiomas, invasive margins, pituitary adenomas, visual disturbances

Malignant tumors

Nomenclature, cells of origin, Carcinoma, Epithelial tumor from any of the three germ layers, Adenocarcinoma, epithelial cancer which forms glands, Example, Squamous cell carcinoma, can be epidermoid carcinoma, resemble squamous cells with variable differentiation, Example, Sarcoma, malignant mesenchymal tumor, can arise from adipose tissue, skeletal muscle, etc, Example, Melanoma, melanocyes

capable of invasion

capable of metastasis

rapid growing

moderate/poorly differentiated

desmoplastic stroma, example

Microscopic Characteristics, cellular & architectural pleomorphis, loss of organized growth, mitotic/apoptotic activity, abnormal mitotic activity, tumor necrosis, example, stromal & lympho-vascular invasion

Pathology of Neplasia

Differentiation

morphologic/physiologic characteristics

structure & function concordant

benign tumors, well differntiatied

malignant tumors, range of differntiation, increased proliferative act, variable loss of functional properties, anaplasia, little to no evidence of differentiation

Dysplasia

disordered growth

epithelium or mucosa

genetic changes

precursor to cancer

result in loss of, maturation, polarity, architectural orientation

pleomorphism, abnormalities in shape and size, example

increased mitotic activity

carcinoma in situ, premalignant/non-invasive state, full epithelial thickness of dysplasia, no invasion of the basement membrane

invasive carcinoma, dysplastic cells breach basement membrane

example

example

Tumor Grade

level of morphologic differntation, Example: Colon, well, moderately, poorly

categories of evaluation, size & shape, nuclear:cytoplasmic ratio, large nucleoli, nuclear and nucleolar characteristics, hyperchromasia, abundant dark & coarse chromatin, example, cytoplasmic differentation, mitotic activity, tissue organization, necrosis, lymphovascular invasion

Tumor Stage

distribution and extent of cancer @ time of diagnosis

tumor characteristics, tumor size, location, depth & extent of local invasion

nodal involvement

Metastases

aids in selection of therapy

Carcinogenesis

requires initiation & promotion for tumor growth

Agents, chemical carcinogens, examples, nitrosamines, related to gastric CA, food preservative, aromatic amines, bladder cancer, benzoapyrene, cigarettes, broiled animal fat, smoked meats, aspergilus, liver cancer, ingest grains & nuts, radiant energy, inc cutaneous cancer, UVB (280-320 nm), form pyrimidine dimers in DNA, excessive exposure & dimer, xeroderma pigmentosum, genetically susceptible, UVC (200-280 nm), filtered by ozone, ionizing radiation, affect different tissues, MC tumors, hematopoietic tumors, acute leukemia, chronic leukemia, thyroid, young people, solid, breast, lungs, long latency period, least common, Resistant, skin, bone, GI, oncogenic viruses & microbes, Human Papilloma Virus, 70+ types, HPV 6, 11, low risk, genital warts, non-integrated episomal, HPV 16, 18, 33, 35, 51, high risk, 85% of invasive squamous cell carcinoma, cervis/anogenital region, also in precursors, oncogenic role, nonkeratinizing squamous cell carcioma, oropharynx, younger non-smokes, integration of HPV genome, genomic instability, necessary for malignancy, Viral proteins (E6/E7), remove restraints to cell proliferation, inactivate tumor suppressors, inhibit apoptosis, Epstein Barr Virus, African Burkitt Lymphoma, B-cell lymphoma, immunosuppressed, Nasopharyngeal Carcinoma, Hep B, Hepatocellular carcinoma, Human T-Cell Leukemia (RNA) virus type 1, T-cell leukemia, T-cell lymphoma, H. pylori, curvilinear gram neg bact, chronic/atrophic gastritis, duodenal/gastric ulcers, genesis of gastric lymphoma/adenocarcinoma, 2-6 fold inc risk, gastric cancer, MALT lymphoma, Cag A gene, initiation of cascade, stimulate polyclona B-Cell proliferation, via reactive T cells, acquire add'l mutations, eradication @ this stage, regression of tumor, antibiotic treatment, in vivo, mutagens in virtro

initiation, irreversible, injures DNA, cellular mutation, 90-100 mutant genes, oncogenes, promote autonomous proliferation, suppressor genes, prevent uncontrolled growth, cellular function, cell cycle activity, signal transduction, DNA repair mechanisms, apoptosis, procarcinogens, indirectly damage DNA following metabolic activation

promotion, promoters, stimulate division of initiated cell, exogenous, cigarette smoke, drugs, alcohol, endogenous, hormones, bile acids, reversible, non-tumorgenic, proliferative, induces tumor formation, time dependent

progression, autonomous growth, genomic instability, tumor heterogeneity

cancer, invasion, metastasis

summary, carcinogenesis

Pathology of Tumor Growth

Rate

morphologic grade

mitotic activity

nature of neoplasm

supportive stroma & neovascularization

GF & hormone depenence

interventional treatment

Phases

Monoclonal proliferations, growth & genetic instability, Progression, subpopulations, inc rate of growth, invasiveness, metastatic potential, hormone or GF responsiveness, chemotherapeutic resistance

clonal growth and malignant change

local growth and angiogensis

regional invasion

metastatic spread, marks a tumor as malignant, 20-30% new dx have mestasis

growth fraction, proliferating component, minority of tumor cells, most susceptible to cell-cycle based chemotherapy, < 20% of tumor

Infiltrative Growth Margin

local destructive invasion

direct seeding, body cavities, peritoneal, pericardial, pleural, example

lymphatic spread, MC for carcinoma, example

hematogenous spread, MC for sarcoma, example

clinical presentation, most @ Site of origin, 20% metastatic distant site

Development

Growth factors, TGFbeta, bFGF, PDGF, VEGF

Host factors, angiogenesis

Proteinases, digest basement membrane, enable cell infiltration, digest stromal matrix

Invasion

Invasion of Extracellular Matrix, Loss of Adhesion molecules, down regulation of cadherins, attachment to matrix via integrins, degradation of ECM, detachment from solid mass, move into circulation

Vascular Dissemination/Horning of Tumor Cells, Intravasation, intrxn w host immune system, Dissemination, bind to blood cells, pass basement membrane, Extravasation, Micrometastasis, Proliferative, Dormant, Colonization, Macrometastases

Metastatic sites

determined by, anatomic, vascular, host-tumor paracrine effects, tropism certain organs, adhesion molecules for vascular bed

Brain, lung, breast, kidney, GI, melanoma

Liver, GI, pancreato-biliary, breast, lung

bone, prostate, breast, lung, kidney, thyroid, testes

Host-Tumor Interactions

Tumor Antigens

Tumor specific (tumor cells only)

Tumor associated (tumor/normal cells)

classification, molecular structure, source

characteristics, normal cellular proteins expressed abnormally, mutated genes, oncogenic viruses, high levels on cancer cells, altered glycolipids/glycoproteins, present on cells of origin

Immunity

Cell mediated immunity, dominant antitumor mechanism, CD8+ cytotoxic T cell, recognized MHCI, NK cells, Macrophages, Antibodies

Immune Surveillance, inc in immunocompromised host, can escape immune surveillance, Ag-neg variants, red MHC, lack co-stim, immunoosuppression, TGF-beta, Ag masking, glycocalyx molecules, sialic acid, mucopolysaccharides, CD8+ apoptosis

Clinical Features

clinical presentation

asymptomatic mass

pain/tenderness

non-healing lesino

persistent cough

abnormal bleeding

peforation/obstruction

non-specific weakness

fatigue

mechanisms

effect of compression/obstruction

secretory/physiological effects, pituitary adenoma, compress optic nerve, visual disturbances, hormone overexpression, i.e. galactorrhea (prolactin)

bleeding due to ulceration

vascular injury

secondary infection

cachexia, weakness, anorexia, weight loss, anemia, cause of 30% mortalitiy, result of TNF from macrophages

endocrine/neuroendocrine tumors

absence of function of hormone

overproduction of hormone

suppression of hormonal activity

overstimulation of hormonal activity

Tumor markers

detection, tumor cells, serum, effusions

indicators of specific cancer

confirm diagnosis

assess tumor staging

monitor for response to therapy

ID recurrent disease

examples, PSA, prostatic cancer, beta-HCG, gestational trophoblastic disease, choriocarcinoma, gonadal cancer, alpha fetoprotein, testicullar cancer, hepatocellular cancer, CEA, GI, Pancreato-biliary, CA-125, oavarian

Paraneoplastic Syndroms

seconary to tumor progression

hormones or factors

earliest manifestation of occule malignancy

10% of patients

presentation, endocrinopathy, hypercalcemia, neuromuscular deficiency, dermatologic conditions, bone changes, hematologic abnormalities

Tx: address primary deficiency

examples, Cushing syndrome, ACTH, muscle wasting, obesity, moon facies, diabetes, small cell carcinoma of lung, pancreatic carcinoma, neural tumors, Syndrome of Inappropriate Antidiuretic Hormone Secretion, ADH/atrial natriuretic hormone, free H2O resorption, hyponatremia, cerebral edema, small carcinoma of lung, intracranial neoplasms, Hypercalcemia, Parathyroid hormone related protein, Ca release from bone, inc intestinal absorption, TGF alpha, TNF, IL-1, Squamous cell carcinoma of lung, breast, renal, adutl T-cell leukemia/lymphoma, ovarian carcinoma, carcinoid syndrome, Serotonin, Bradykinin, carcinoid tumor, gastric carcinoma, pancreatic carcinoma

Lab Diagnosis

Clinical history

physical examination

radiologic imaging

lab tests

pathologic exam

surgical methods, Biopsy, excision, resection, rapid frozen section, at time of surgery

cytologic methods, Pap smears, Fine Needle Aspiration

ultrastructural methods, electron microscopy

molecular methods, immunohistochemistry, technique, light microscopy, visualized via enzymes, chromogenic substance to ID, special stains for Ab-Ag binding, function, classify undifferntiated tumors, classify leukemia/lymphoma, determine site of origin for metastatic tumor, detect molecules of prognostic/therapuetic significance, breast cancer, er, pr, her-2, flow cytometry, FISH, PCR, based on genetic makeup/expression, can alter treatment, more accurate testing/prognosis