Lecture 4 Neoplasia Jan 27, 2025 PDF

Neoplasia Week 4 – Neoplasia Robert Crozier, PhD Candidate Tuesday January 27, 2025  Outline and Learning Objectives Intro & definitions Define neoplasia and related terms tumor, cancer & oncology Classification and biology of tumors Differentiate between benign and malignant tumors an...

Neoplasia Week 4 – Neoplasia Robert Crozier, PhD Candidate Tuesday January 27, 2025  Outline and Learning Objectives Intro & definitions Define neoplasia and related terms tumor, cancer & oncology Classification and biology of tumors Differentiate between benign and malignant tumors and further classify tumors based on their clinical/histopathological features Causes of cancer Describe the general etiology and pathogenesis of cancer Immune responses to tumors Describe the host’s immune response to neoplasia Clinical Manifestations Describe local and systemic adverse effects of tumors on the host  Proliferation of Normal Cells Regulated by: 1. Genetic program of each cell 2. Signals from one cell to another through direct contact 3. Soluble substances that have growth promoting or inhibiting effects Differentiation: selective activation of genes and depression of other genes Proliferation of Neoplastic Cells Neoplasia (new growth): Unregulated growth of cells Proliferation: 1. Autonomous: independent of growth factors and stimuli that promote normal cells 2. Excessive: unceasing in response to normal regulators of cellular proliferation 3. Disorganized: do not follow rules governing formation of normal tissues  Terminology of Neoplasia Tumour: masses of neoplastic cells Benign – abnormal but noncancerous Malignant – cancerous Cancer: collective designation for all tumours Oncology (Cancer Research) Clinical oncology: clinical setting (diagnostics & therapeutics) Experimental oncology: lab setting (etiology, pathology, cell and molecular biology) Cancer epidemiology: human populations  Classification of Tumours Histological Classification Macroscopic features (gross, naked-eye examinations) Microscopic features (histological cell features) Chromosomal differences Biological features Clinical Classification Clinical presentation and outcomes Macroscopic Features Macroscopic Features (Benign vs. Malignant) FEATURE BENIGN MALIGNANT Growth Slow Expansion Fast Expansion Limited Uncontrollable Metastases No Yes External Surface Smooth Irregular Capsule Yes No Necrosis No Yes Hemorrhage No Yes  Microscopic Features (Benign vs. Malignant) FEATURE BENIGN MALIGNANT Architecture Resembles normal Does not resemble tissue of origin normal tissue of origin Cells Well differentiated Poorly differentiated Nuclei Normal size and shape; Pleomorphic, high uniform nuclear/cytoplasm ratio Mitoses Few cells Many irregular Anaplasia: cells exhibit new features not inherent to the tissue, does not resemble the original tissue Cellular Features – anaplasia  Cellular Features Malignant cells in a cervical Papanicolaou smear: Nuclear pleomorphism – variation in the size and shape of the tumour cells nuclei High nuclear/cytoplasmic ratio More prominent nuclei and may be multiple Hyperchromatic – increase in dark staining chromatin Cellular Features Acute myeloid leukemia: Bone marrow makes a large number of abnormal blood cells Cells exhibit exaggerated nuclear pleomorphism – non-distinguishable phenotype  Abnormal chromosomes Benign: usually normal chromosome number Diploid (46): 44 autosomes and 2 sex chromosomes (XX, or XY) Malignant: Aneuploid (abnormal number) Structurally abnormal Deletions Translocations Due to disorderly mitosis  Metastasis Tumour cells from one site to another Only malignant tumour cells 3 pathways: 1. Lymphatics 2. Blood (hematogenous spread) 3. Seeding of the surface of body cavities Metastasis  Biochemistry of Cancer Cells Less differentiated, more adapted to survive under unfavorable conditions; require less oxygen to survive Fewer mitochondria, RER, specialized enzymes, underdeveloped cytoplasm Simplified metabolism and function Anaplasia – atypical features, nuclear irregularities Can regress to assume some fetal features liver cells secrete alpha-fetoprotein  Histological Classification of Tumours Benign and malignant tumours retain some features of their tissue of original Benign – oma Malignant – sarcoma Fibroblast – firbroma Fibrosarcoma Cartilage – Chondrosarcoma chondroma Osteosarcoma Bone – osteoma Liposarcoma Fat – lipoma All of mesenchymal stem cell origin  Lipoma Benign tumour composed of adipocytes  Sarcoma Malignant tumour composed of elongated cells that resemble fibroblasts - fibrosarcoma  Histological Classification of Tumours Benign and malignant tumours retain some features of their tissue of original Benign – oma Malignant – carcinoma Squamous epithelium – Squamous cell epithelioma carcinoma Glandular/ductal – Adenocarcinoma adenoma Liver cell carcinoma Liver – liver cell adenoma Epithelial cell origin  Adenoma of the Colon Benign tumour composed of glands in the large intestine Also known as polyps  Histological Classification of Tumours Benign and malignant tumours retain some features of their tissue of original Malignant Leukemia (white blood cells) Lymphoma (lymphoid cells) Multiple myeloma (plasma cells) Blood cells and lymphocytes  Histological Classification of Tumours Benign and malignant tumours retain some features of their tissue of original Benign – oma Malignant – carcinoma Teratoma Teratocarcinoma Germ cells tumours (embryonic cells)  Teratoma “monster” Derived from germ cells Embryonic cells that differentiate into embryonic germ layers Contains tissues formed from all three germ layers: 1. Ectoderm (nervous system, epidermis) 2. Mesoderm (bone, muscle, connective) 3. Endoderm (GI, respiratory, urinary) Cystic ovarian tumour Exception to the Rules NOT all tumours ending in “oma” are benign NOT all malignant tumours are labelled as “carcinoma or sarcoma” Lymphoma: malignant tumour of lymphocytes Glioma: malignant brain tumour of glial cells Seminoma: malignant tumour of the testicular seminiferous epithelium Blastoma Malignant tumours composed of embryonic cells originating from embryonic primordia Retinoblastoma: eye Neuroblastoma: adrenal medulla or immature neural cells Hepatoblastoma: liver Nephroblastoma: kidney Eponymic Tumours Carry name of physicians who have described them first Hodgkin's Lymphoma (lymph nodes) Ewings Sarcoma (bones) Kaposi’s sarcoma (abnormal tissue growth under the skin, mouth, nose, throat – red or purple)  Tumour Staging and Grading 1. Staging (extent of tumour spread): based on clinical assessment during gross examination, surgery, x-ray examinations TNM system: size of tumor (T), presence of lymph node metastases (N), distant metastases (M) A tumour