Definitions and Classifications in Neoplasia Folder: DefClass(NoTP) Updated: February 11, 2015

Definitions in Oncology. (Part 1) Neoplasia: (“Plasia = Cells) Abnormal new cell proliferation of altered cells Heritably Altered Relative autonomous growth Can be benign or malignant (See later) Hyperplasia: Abnormal proliferation of otherwise normal cells Tumor: Solid mass, usually cellular (but not necessarily) Can be neoplastic, non-neoplastic, or even non-cellular "Tumor" usually means a neoplasm in common usage Some free cell neoplasms can be non-tumorous

Definitions in Oncology. (part 2) Metaplasia: Replacement of one type of normal adult differentiated cell type that is normally present, by another normal adult differentiated type that belongs somewhere else. Usually in response to injury or irritation Reversible upon removal of the stimulus See “Reversible squamous metaplasia”, next slide) Dysplasia Abnormal interaction of cells giving abnormal tissue development Can be pre-neoplastic

Reversible Squamous Metaplasia

Normal Secretory & Ciliated Epithelial Cells Illustrating functional effect of ciliated vs non-ciliated cells Figure 16-19, ECB, 1998, p. 528 RespCilia Ciliated Epithelium of Human Respiratory Tract

Progressive Steps in Neoplastic Cell Development: Hyperplasia and Dysplasia To Here Presentation 7, Feb. 3, 2015

Progressive Steps in Neoplastic Cell Development: Cancer In situ and Invasive Cancer

Figure 11.7 The Biology of Cancer (© Garland Science 2007) Progression in Neoplastic Development: Weinberg, Chapter 11 on Multistep Tumorigenesis. Figure 11.7 CIS = carcinoma in situ CIN = cervical intra-epithelial neoplasm DCIS = ductal carcinoma in situ PIN = prostatic intra-epithelial neoplasm

Classifications of Cancers

Benign and Malignant Neoplasia Benign Neoplasm Generally Encapsulated Non-invasive Highly Differentiated Few Mitotic Figures Slow Growth or No Net Growth Little Anaplasia Non-Metastatic (by definition) Malignant Neoplasm Non-encapsulated Invasive Poorly Differentatied Mitotic Figures Common Can have rapid growth Relatively Anaplastic Metastatic or Capable of becoming so

Definitions in Oncology. (part 3) Anaplasia: Irreversible loss of normal cell structure and function Positional Anaplasia: Size, shape, arrangement, and overall organization of cells in a tissue are altered Cytological Anaplasia: Intra-cellular structures (mitochondria, cytoskeletal elements, nuclear size and morphology) are altered Cancer: Mass of cells with potentially unlimited growth, serves no useful function for the host, deprives the host of nutrients necessary for survival, expands locally by invasion and systemically by lymphatic and hematogenous pathways, untreated progresses to lethal condition in the host

Sites of Origin for Primary Clinical Cancers Collection of 200 Different Clinical Diseases (See Diversity of Cancers in Folder Title:"Clinical" and Two Graphics Following) Different Symptoms Different Cell Type of Origin Different Histology Different Cell Products and Cell Markers Different Prognoses Different Therapy

Cancer Incidence 2002: 1,285,000. Cancer Deaths 555, % Death Rate Cancer Incidence 2009: 1,479,000. Cancer Deaths 562,000 38% Death Rate Cancer Incidence 2014: 1,665,540. Cancer Deaths 585,720 35% Death Rate

Why do we get cancers in these tissues & organs with these distributions? Why are cancers of some sites more deadly than cancers at other sites?

Normal Proliferative Human Cells & Tissues Hematopoietic Pluripotent Stem Cells and Progenitor Cells Form Blood Cells: Red Blood Cells, Leucocytes,Megacaryocytes/Platelets Epithelial Linings Respiratory epithelium Gastro-intestinal linings Genito-urinary tract Glandular Linings Mammary gland Skin Ovary and Testis Bone Marrow Myoblasts Fetal Tissues Organ Hypertrophy Wound Healing Neurogenesis Brain Astrocytes/Glial Cells

Classification by Tissue Type for Cell Type of Origin (Histogenetic Classification) Connective Tissue Hematopoietic Tissue Nervous tissue Germinal Tissue & Mixed Tissue Types Epithelial Tissue Sarcoma Leukemia & Lymphoma Neuroectodermal malignancies Carcinoma

Classification of Cancer by Histogenetic Site of Origin Part 1: Connective Tissue Neoplasms Tissue of Origin Fibrous tissue Cartilege Bone Fat Smooth Muscle Skeletal Muscle Blood Vessels Benign Neoplasm Fibroma Chondroma Osteoma Lipoma Leiomyoma Rhabdomyoma Hemangioma Malignant Neoplasm Fibrosarcoma Chondrosarcoma Osteogenic Sarcoma Liposarcoma Leiomyosarcoma Rhabdomyosarcoma Hemangiosarcoma Sarcomas (Sarcomata) are malignant neoplasms of connective tissue origin. About 5% of all cancers in humans

Carcinomas: Cancers of Epithelial Origin

Classification of Cancer by Histogenetic Site of Origin Part 2: Epithelial Neoplasms Tissue of Origin Epidermis Stomach Adrenal cortex Surface Epithelium (Non-glandular) Glandular Epithelium Colon Breast Lung Benign Neoplasm Epidermal papilloma Gastric polyp Adrenocortical adenoma Papilloma Adenoma Colon adenoma Mammary adenoma Lung adenoma Malignant Neoplasm Epidermal carcinoma Gastric carcinoma Adrenocortical carcinoma Squamous carcinoma Adenocarcinoma Colon carcinoma Mammary carcinoma Lung carcinoma Carcinomas are malignant neoplasms of epithelial origin. About 85% of all cancers in humans!

Table 2.1 The Biology of Cancer (© Garland Science 2007) p. 30

Figure 2.4b Te Biology of Cancer Figure 2.4c The Biology of Cancer (© Garland Science 2007) Bronchiole of Lung Columnar Epithelium (Gall Bladder )

Figure 2.6c The Biology of Cancer (© Garland Science 2007)Figure 2.6a The Biology of Cancer (© Garland Science 2007) Squamous epithelium Uterine cervix Skin Glandular Epithelium (stomach) Columnar Epithelium, Small Intestine Goblet Cell (Mucous-secreting)

Figure 2.6d The Biology of Cancer (© Garland Science 2007) Adenocarcinoma(Stomach) Adenocarcinoma (Colon) Glandular Epithelium Stomach

Neuroectodermal Malignancies Cancers of the nervous system

Classification of Cancer by Histogenetic Site of Origin Part 4: Neoplasms of the Nervous System Tissue of Origin Brain glial cells Meninges Neurons Adrenal medulla Retina Benign Neoplasm Astrocytoma Oligodendroglioma Meningioma Ganglioneuroma Pheochromocytoma --- Malignant Neoplasm Glioblastoma multiforme Meningeal sarcoma Neuroblastoma Pheochromocytoma Retinoblastoma Neoplasms of the nervous system are generalized as Neuroectodermal malignancies comparable to carcinoma, sarcoma, or leukemia groupings. Part of the remaining 5% of all cancers in humans

Table 2.4 The Biology of Cancer (© Garland Science 2007) p. 34

Figure 2.9a The Biology of Cancer (© Garland Science 2007) p. 35 Astrocytes (Glial Cells) Astrocytoma (Glioblastoma), Glioblastoma Multiforme Neuroectodermal Neoplasm of Non-Neuronal Supporting Cells of Brain

Cancers of Hematopoietic Origin Blood Cell Cancers; Leukemia, Lymphoma

Classification of Cancer by Histogenetic Site of Origin Part 3: Hematopoietic and immune system neoplasms Tissue of Origin Lymphoid tissue and Lymphocytes Thymus Granulocytes Plasma Cells 1 Erythrocytes Benign Neoplasm Infectious mononucleosis and other lymphoproliferative diseases Thymoma Granulocytosis Plasmacytoma (localized) Polycythemia vera Malignant Neoplasm Lymphoma (lymphosarcoma) Lymphocytic leukemia (B and T Cell Leukemias) Reticulum cell sarcoma Hodgkin's Disease Thymoma Myelogenous leukemia (Granulocytic leukemia) Multiple Myeloma (dispersed) Erythroleukemia 1 Antibody secreting B-cell. Neoplastic plasma cell secretes monoclonal antibodies or parts of monoclonal antibodies (Bence- Jones proteins) Leukemias and Lymphomas (Lymphosarcomas) About 5% of all cancers in humans

Table 2.3 The Biology of Cancer (© Garland Science 2007) p. 33

Different Forms of Leukemias Acute (A) and Chronic (C) 3.4% of all forms of human cancers Lymphocytic54% (32% CLL; 22% ALL) Also called "lymphoblastic" Myelocytic 37% (26% CML; 11% AML) Also called "granulocytic" or "myelocytic" Monocytic 9% (All acute) ErythroleukemiaRare

Morphology & Staining of Blood Cells Kuby, 3rd Ed. Figure 3-1

Hematopoiesis (formation of blood cells) Fig 2-1, Kuby 4th Ed. p. 28

Pluripotent Stem Cell and Lymphoid and Myeloid Lineages (Fig 2-1, Kuby 4th Ed. p. 28 Myeloid Stem Cell

Lymphoid Lineage Fig 2-1 Kuby 4th Ed p. 28

Myeloid Lineage (Kuby, Fig 2-1, 4th Ed., p. 28)

Figure 8.32 The Biology of Cancer (© Garland Science 2007) Disease Progression in Chronic Myelogenous Leukemia p. 293

Classification of Cancers based on Tissue Type or Cell Type Source of Origin (Histogenic Classification) Classification by Site of Origin Slides 20 to 48

Benign and Malignant Neoplasia Benign Neoplasm Generally Encapsulated Non-invasive Highly Differentiated Few Mitotic Figures Slow Growth or No Net Growth Little Anaplasia Non-Metastatic (by definition) Malignant Neoplasm Non-encapsulated Invasive Poorly Differentatied Mitotic Figures Common Can have rapid growth Relatively Anaplastic Metastatic or Capable of becoming so

Sites of Origin for Primary Clinical Cancers Collection of 200 Different Clinical Diseases (See Diversity of Cancers in Folder Title:"Clinical" and Two Graphics Following) Different Symptoms Different Cell Type of Origin Different Histology Different Cell Products and Cell Markers Different Prognoses Different Therapy

Classification by Tissue Type for Cell Type of Origin (Histogenetic Classification) Connective Tissue Hematopoietic Tissue Nervous tissue Germinal Tissue & Mixed Tissue Types Epithelial Tissue Sarcoma Leukemia & Lymphoma Neuroectodermal malignancies Carcinoma

See Slides 14, 16, 20 for Benign vs Malignant

Diagnostic Pathobiology of Hodgkins Disease vs Non-Hodgkins Lymphoma (Right Click. Click on Open Hyperlink) University of Virginia, School of Medicine;Pathology Trends Derived from Lymphocyte, usually a B cell, Characterized by being binuclear. Presents “owl-like” appearance Incidence Early onset; 2 nd age-related risk later in life

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stage-breast-cancer-care/story?id= abcnews.go.com/Health/BreastCancerCenter/early- stage-breast-cancer-care/story?id= Surgical Excision of Regional Lymph Nodes in Breast Cancer (ABC News: February 8, 2011 (Copy & paste to Mozilla Firefox)

Neuroblastoma in a Little Boy (Viewed in Class in 501Intro) William Bunn: 8-Year-old Police Officer July, minutes and 32 seconds 1 1/2 minutes - actual funeral Refers to Stem Cell Transplants and Chemotherapy for Neuroblastoma in final 5 seconds of clip Also viewed story of Kuyler Van Nocker and Neuroblastoma

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