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

2. 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

3. 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

4. Reversible Squamous Metaplasia

5. 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

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

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

8. 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

9. Classifications of Cancers

10. 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

11. 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

12. 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

13. Cancer Incidence 2002: 1,285,000. Cancer Deaths 555,000. 43% 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

14. 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?

15. 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

16. 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

17. 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

18. Carcinomas: Cancers of Epithelial Origin

19. 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!

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

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

22. 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)

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

24. Neuroectodermal Malignancies Cancers of the nervous system

25. 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

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

27. 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

29. Cancers of Hematopoietic Origin Blood Cell Cancers; Leukemia, Lymphoma

30. 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

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

32. 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

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

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

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

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

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

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

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

42. 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

43. 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

44. 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

45. See Slides 14, 16, 20 for Benign vs Malignant

46. Diagnostic Pathobiology of Hodgkins Disease vs Non-Hodgkins Lymphoma http://www.med-ed.virginia.edu/courses/path/innes/wcd/hodgkin.cfm (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

47. Cancer Breast Reconstruction Treatment for breast cancer can be overwhelming, both physically and emotionally. While... Mammography The recent controversy over when—and how often—women should begin having mammograms has left a... Cervical Cancer an HPV It is the second leading cause of cancer deaths in women worldwide. Would you be surprised to... Breast Cancer Breast cancer: two of the most frightening words in the English language. There's no shortage of... Prostate Cancer In America, prostate cancer is the most common form of cancer in men, and the second most common... Colon Cancer Colon cancer is the third most common type of cancer among American men and in women and is the... Skin Cancer Can that warm and fuzzy feeling of the sun bathing your body really come back to haunt... Lung Cancer With so much money going into cancer research and the success rate of cancer treatment... Life After Breast Cancer The diagnosis and treatment of breast cancer is a traumatic time for the patient and their loved... Leukemia Chronic Lymphocytic Leukemia (CLL) is a type of leukemia that mainly affects people over the age... Non-Hodgkin Lymphoma While other cancers continue to decline, lymphoma is on the rise. The good news is that with... Ovarian Cancer One of the deadliest forms of cancer, ovarian cancer is also one of the few cancers for which... Breast Cancer Recurrence While survival rates for breast cancer continue to improve, for some women, recurrence is a... HPV Vaccine/Cervical Cancer Cervical cancer is caused by several types of a virus called human papillomaviruses... Late Effects of Cancer Treatment Treatment of cancer involves the use of strong drugs that target the cancer with the goal of... Colon Cancer II Cancer of the colon or rectum is also called colorectal cancer... Geriatric Oncology More than 60% of cancers in the United States occur in people age 65 and older. Cancers of... Breast Cancer in Young Women Young women can and do get breast cancer. While breast cancer in young women accounts for a... The Future of Cancer Treatment Cancer is the second leading cause of death in the United States. About one-half of all men and... PBS Series: secondopinion-tv.org CML and Patient #9 in Gleevec Trial 1995 Highlight. Right Click. Open Hyperlink See episode 607

48. http://abcnews.go.com/Health/BreastCancerCenter/early- stage-breast-cancer-care/story?id=12870356abcnews.go.com/Health/BreastCancerCenter/early- stage-breast-cancer-care/story?id=12870356 http://abcnews.go.com/Health/BreastCancerCenter/early-stage-breast-cancer-care/story?id=12870356 Surgical Excision of Regional Lymph Nodes in Breast Cancer (ABC News: February 8, 2011 (Copy & paste to Mozilla Firefox)

49. Neuroblastoma in a Little Boy (Viewed in Class in 501Intro) William Bunn: 8-Year-old Police Officer July, 2010 http://abclocal.go.com/wtvd/story?section=news/local&id=7531763 - 2 minutes and 32 seconds http://www.msnbc.msn.com/id/26184891/vp/38084943#38084943 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

51. First-hand experiences with cancer incidence (This question is anonymous. You can respond with more than one number) 1.I myself have been treated for a cancer. 2.One (or more) of my parents or step parents has been or is a cancer patient. 3.One (or more) of my grandparents has been or is a cancer patient. 4.One (or more) of my brothers or sisters (or a step-brother or sister) has been or is a cancer patient. 5.I have a child or a niece or nephew who is or has been a cancer patient. 6.At least one of my close friends has been or is a cancer patient. 7.I have not experienced cancer first-hand. Response Counter

52. First-hand experiences with cancer Mortality (This question is anonymous. You can respond with more than one number) 1.One of my parents or step parents has died from cancer. 2.One (or more) of my grandparents has died from cancer. 3.One or more of my grandparents has passed away but not from Cancer. 4.One of my brothers or sisters (or a step-brother or sister) has died from cancer. 5.5. I have lost a child or a niece or nephew to cancer. 6.6. I have lost a close friend to cancer. 7.7. No one close to me has died of cancer. Response Counter

53. AgeEffct