I.

II.

Introduction A. Abnormal growth disease of tissue stem cells that fail to differentiate normally 1. Control of growth a. Hormones b. Growth factors c. Receptors 2. Proto-oncogenes code for growth factors and their cellular receptors a. Include epidermal growth factor (EGF) b. Platelet derived growth factor (PDGF) 3. Tumor suppressor genes act as brakes on the cell cycle, oppose proto-oncogenes 4. Cell proliferation is balanced by apoptosis Abnormalities of growth A. Atrophy of n organ is decrease either in size or number of individual cells 1. Causes of atrophy (reversible) a. Disuse b. Denervation c. Loss of trophic hormones d. Loss of nutrients e. Pressure f. Senile atrophy B. Hypertrophy (increase size of cells) and hyperplasia (increased numbers) 1. Causes of hypertrophy and hyperplasia (both reversible) a. Physiological adaptation to increased demand i. Ex. Muscle working against load, hormonal effects on breast I pregnancy b. Pathological occurs in the absence of a n appropriate functional demand i. Ex: sustained endometrial hyperplasia, bilateral adrenal hyperplasia due to ACTH) C. Metaplasia abnormality of cellular differentiation 1. One mature cell is replaced a different type of mature cell 2. New metaplastic tissue appears structurally normal but is in wrong place 3. Occurs after an abnormal growth stimulus or chronic irritation 4. Reversible 5. Squamous metaplasia = most common D. Dysplasia abnormality of both differentiation and maturation 1. Characteristics of dysplasia (reversible) a. Nuclear abnormalities i. Increased nuclear/cytoplasmic ratio ii. Hyperchromatism iii. Nuclear membrane irregularities b. Cytoplasmic abnormalities i. Failure of normal differentiation c. Increased rate of cell multiplication d. Dysplasia graded as mild, moderate or severe 2. Significance of dysplasia a. Epithelial dysplasia is a premalignant lesion b. Carcinoma in situ = severe dysplasia (show all features of cancer except invasion) c. Risk of developing invasive cancer varies with i. Grade of dysplasia ii. Duration of dysplasia

III.

iii. Site (risk greater in bladder than cervix) 3. Difference s between dysplasia and cancer a. Lack of invasiveness = excision of dysplastic area is curative b. Reversibility (dysplasia is reversible, cancer is not) 4. Diagnosis of dysplasia a. Gross examination usually no gross abnormality b. Microscopic examination i. Cell smears cytology ii. Tissue obtained by biopsy histology c. Diagnosis important to prevent later development of cancer d. Must be distinguished from inflammatory, degenerative and regenerative changes which may show some cellular disorganization Neoplasia A. Definition of neoplasia (not reversible_ 1. New growth abnormality of cellular differentiation, maturation and control of growth 2. Commonly form masses of abnormal tissue 3. Cancer = general term for a malignant neoplasm B. Classification of neoplasms 1. Biological behavior: benign vs malignant 2. Cell or tissue of origin (histogenesis) 3. Other features, such as site, embryological derivation, gross features C. Biologic Behavior 1. Benign neoplasm grows slowly, encapsulated and does not spread 2. Malignant grow rapidly, infiltrate surrounding tissue and metastasize 3. Classification based on several factors a. Rate or growth malignant generally grow more rapidly i. Clinical observation ii. Microscopic examination b. Size not helpful c. Degree of differentiation denotes the degree to which the neoplasm resembles the normal tissue in questions i. Benign well differentiated ii. Malignant well, moderately, or poorly differentiated iii. Anaplastic no resemblance to normal tissue (very poorly differentiated) d. Histological cytologic features of malignancy i. More densely cellular, higher mitotic rate, abnormal mitoses ii. High nuclear/cytoplasmic ratio iii. Variable appearance from cell to cell, abnormal differentiation, necrosis frequent e. Changes in DNA i. Abnormalities increase with the degree of malignancy ii. Malignant cells = hyperchromatic iii. Cytogenetic studies show aneuploidy iv. Molecular methods reveal abnormalities of oncogenes/tumor suppressor genes in all cases f. Invasion and metastasis malignant only i. Invasion local spread ii. Metastasis distant spread iii. Benign have smooth capsule and not invasive

D.

E. F. G. H. I. J. K. L.

iv. Malignant have no capsule, irregular and are invasive g. Metastasis absolute evidence of malignancy Cell or Tissue of Origin (Histogenesis) Neoplasms classified according to their potential for cellular development 1. Neoplasms of totipotent cells develop from residual germ ells a. Germ cell neoplasm may show minimal differentiation, resemble trophoblast, yolk sac or somatic structures. b. Teratomas contain elements from all three germ layers i. Mature (well-differentiated, usually benign) ii. Immature (made up of fetal type tissues, malignant) 2. Neoplasms of pluripotent (usually embryonic) cells partially differentiated fetal type stem cells a. Blastomas resemble embryonic organs, occur in childhood, malignant i. Nephroblastoma, neuroblastoma, etc. 3. Neoplasm of Unipotent (differentiated) cells include most neoplasm of adults a. Epithelial versus mesenchymal i. Epithelial neoplasms Benign 1. Adenomas (from epithelium within a gland) 2. Papillomas (from surface of squamous, glandular or transitional epithelium) Malignant = carcinomas 1. Adenocarcinomas (glandular epithelium) 2. Squamous carcinomas 3. Transitional carcinomas ii. Mesenchymal neoplasms Benign: cell type plus suffix oma (fibroma) Malignant: cell type plus suffix sarcoma (fibrosarcoma) iii. Exceptions to rules Lymphoma, plasmacytoma, melanoma, glioma and astrocytoma are all malignant Leukemia rarely produce local tumors and classified by clinical course and cell of origin Certain mixed tumors appear to be composed of more than one neoplastic ell type Some neoplasms named after person who described them iv. Hamartomas and choristomas developmental anomalies, not true neoplasm Hamartoma composed of tissues that are normally present in the organ in which it arises Choristoma contains tissues not normally present in its site of origin Incidence and distribution of cancer in humans (pg. 10) Theories of Origin of Neoplasia (pg. 12) Agents Causing Neoplasms (pg. 16) Characteristics of Neoplasia (pg. 21) Effects of neoplasia on the host (pg. 24) Approach to Cancer Diagnosis Treatment of neoplasm Symptoms and signs of cancer

M. Causes of death in cancer