Pathology Lecture PDF

Pathologic Basis of Clinical Medicine (Introduction to Pathology) Deborah Fuchs MD Professor Department of Pathology  Deborah Fuchs MD Born & raised in New York BA, Ecology and Evolutionary Biology, 1992 MD, 1998 Post-Sophomore Patholo...

Pathologic Basis of Clinical Medicine (Introduction to Pathology) Deborah Fuchs MD Professor Department of Pathology  Deborah Fuchs MD Born & raised in New York BA, Ecology and Evolutionary Biology, 1992 MD, 1998 Post-Sophomore Pathology Fellowship, 1995-1996 Anatomic and Clinical Pathology Residency, 1998- 2002 Hematopathology Fellowship, 2002-2004 Faculty, University of Arizona, 2004-Present  Outline / Learning Objectives What is Pathology? LO#1: Understand the role of pathology in prevention, diagnosis, treatment, and management of disease. LO#2: Describe the basic mechanisms of disease LO#3: Describe the three basic competencies in pathology LO#4: Describe the approach used in the diagnosis of neoplasms and other pathologies, including the use of molecular/genetic testing and tumor markers. Sadofsky, M. Arch Pathol Lab Med, 2014 What is Pathology? Medical specialty that involves the study and diagnosis of disease Pathos: suffering; -logia: to study study suffering Bridge between basic science and clinical medicine; provides the scientific foundation for all medical practice. visible “Understanding the causes of disease and the changes in cells, tissues, and organs that are - - associated with disease and give rise to presenting signs and symptoms in patients.” (Kumar, Basic Pathology, 10th Ed) Built on understanding principles of chemistry, biochemistry, cell biology, anatomy/histology and physiology. Examination of a wide variety of specimens from LIVING patients Tissue biopsies, organs Blood, bone marrow Feces Sputum Other body fluids: urine, peritoneal fluid, pleural fluid, synovial fluid, cerebrospinal fluid Autopsy – post-mortem examination DIAGNOSIS, PREVENTION, TREATMENT AND MANAGEMENT OF DISEASE  “Training to become a physician requires acquisition of a foundation of knowledge, the understanding of how systems work normally and in pathologic states, and the ability to continue to improve in diagnosing and treating patients through ongoing experience." Sadofsky, M. Arch Pathol Lab Med, 2014 Two Main Branches of Pathology Clinical Pathology (Laboratory Medicine) Anatomic Pathology Laboratory tests performed during patient care for prevention, diagnosis or following a disease after Studies the effect of disease on the gross and treatment. microscopic structure of organs and tissues Tests are conducted by a team of medical laboratory technologists or technicians Surgical Pathology Pathologists or PhDs oversee the functioning of Many subspecialty areas the laboratory and are the key bridge between laboratory operations and clinical practice. This is the field most pathologists panas practice Schem Chemistry: Measurement of chemical constituents el in blood and other body fluids & Cytopathology Hematology: Analysis of blood cells, clotting Study of cells obtained from body secretions system and fluids; by scraping, washing the surface Microbiology: Identification of microorganisms of a lesion; or by aspiration of a lesion with a fine needle (FNA, fine needle aspirate) Transfusion Medicine/Blood Banking Ex: Cervical Pap smear Molecular Genetics Autopsy Pathology Pathology Residency: 4 years (combined AP / CP) Pathology – Subspecialty Areas --Fellowship training after Pathology Residency Surgical Pathology Chemistry Cytopathology Hematopathology Renal Pathology Microbiology Neuropathology Transfusion Medicine/Blood Banking Forensic Pathology Molecular Genetic Pathology GI Pathology GYN Pathology Pediatric Pathology Bone and Soft Tissue Pathology Heart/Lung Pathology Dermatopathology  Pathology Clinical Faculty - Subspecialty Areas of Pathology Erika Bracamonte, MD Lauren LeBeau, Rob Klein, MD Deborah Fuchs, MD Surgical Pathology MD Surgical Pathology Catherine Spier, Naomi Rance, MD, Laura Stephens, MD Clinical Pathology Bruce Parks, MD -Renal Pathology Surgical Pathology -ENT/Endocrine MD PhD Clinical Pathology -Hematopathology Autopsy Pathology -Immunopathology -Breast Pathology -GYN Clinical Pathology Surgical Pathology -BB/Transfusion (incl. Coagulation) -Informatics -Hematopathology -Neuropathology Medicine (CPR) (Foundations, CPR, I&I) (Life cycle) (Foundations, CPR, -HLA (Life Cycle, DMH) (Neuro) (I&I) I&I) Achyut Maria Proytcheva, Demaretta Rush, Ghassan Tranesh, William Richard Sobonya, MD Bhattacharyya, MD MD Ty Abel, MD, PhD MD MD Lainhart, PhD Surgical Pathology Belinda Sun, MD Chair Clinical Pathology Surgical Pathology Surgical Pathology Surgical Pathology Medical and -Heart/Lung /Muscle Surgical Pathology Surgical Pathology -Hematopathology -Neuropathology -GYN Pathology -Cytopathology Molecular Pathology -GI Pathology -GI Pathology -Transfusion Medicine Microbiology -Autopsy Pathology (Neuro) (CPR, Life Cycle) (MSK) (DMH) (Foundations, I&I) (CPR)  Basic Competencies in Pathology Foundations 2020 1) Understand core principles of disease mechanisms/processes (General Pathology) Cell injury, cell death and adaptations Inflammation and repair Hemodynamic disorders Diseases of the immune system Neoplasia Genetics and Pediatric disease Environmental and nutritional diseases  Which of the following disease mechanisms is / are S implicated in the leading cause of death worldwide? ALL IMPACT LEADING CAUSE OF DEATH ! 1) Cell injury, cell death and adaptations 2) Inflammation and repair 3) Hemodynamic disorders ↳ 4) Diseases of the immune system 5) Neoplasia 6) Genetics and Pediatric disease & elevated cholesterol 7) Environmental and nutritional diseases Cell injury, cell death and adaptations General Pathology --Cell injury, cell death and adaptations --Inflammation and repair Cells are constantly exposed to stresses due to changes in --Hemodynamic disorders --Diseases of the immune system their environment --Neoplasia --Genetics and Pediatric disease Cell adapts ---> It lives! --Environmental and nutritional diseases Cell unable to adapt ---> It dies! Irreversible injury and cell death (necrosis, apoptosis) Causes of cellular injury Hypoxia (reduced oxygen) Pulmonary disease, ischemia (insufficient blood flow), anemia (decreased O2 content of blood), etc. Pathogens (viruses, bacteria, parasites, fungi, prions) Immunologic dysfunction (hypersensitivity, autoimmune) Inherited mutations Chemical injury (drugs, poisons, occupational, alcohol, tobacco…) Physical injury (trauma, burns, frostbite) Nutritional or vitamin imbalance  Cellular responses to enlarge more cells injury Adaptation Atrophy Hyperplasia Hypertrophy Hypertrophy Normal Atrophy Hyperplasia Metaplasia Ciliated hypertrophy epithelial cell change cell 6 type a-, not or without Tobacco Metaplasia enlarged nuclei hyper-, over or excessive meta-, change in position, behind, after, beyond -trophy, nutrition or development -plasia, growth Squamous Myocardium cell Which type of adaptation do you see? * better adapted Hypertrophy Inflammation and Repair General Pathology --Cell injury, cell death and adaptations Protective response intended to: --Inflammation and repair --Hemodynamic disorders Eliminate initial cause of cell injury and resulting dead cells --Diseases of the immune system --Neoplasia --Genetics and Pediatric disease Tissue reaction to injury --Environmental and nutritional diseases Facilitates entry of inflammatory cells, plasma proteins and fluid to the site of injury. Components > dilate to become Vascular responses - leaky Migration and activation of leukocytes (WBCs) Systemic reaction Acute inflammation – immediate; vascular changes, chemical mediators and neutrophils Chronic inflammation – delayed response, inflammation of prolonged duration Involves: Lymphocytes, macrophages, plasma cells; tissue destruction; and repair [ Response to: Persistent infection Infections with certain organisms (viruses, mycobacteria, parasites, fungi) * Autoimmune disease Foreign material Some cancers Repair Initiated with inflammation MYOCARDIAL ANGIOGENESIS Involves ↓ new blood Hemostasis Vessels Inflammatory cells https://webpath.med.utah.edu/TUTORIAL/MYOCARD/MI025.html Regeneration of cells (if possible)# Angiogenesis MYOCARDIAL Fibrosis fibrosis FIBROSIS Remodeling M1 cheart attack M S. Park et al. Clinical Cardiology and Cardiovascular Medicine, 2019  General Pathology Hemodynamic Disorders, --Cell injury, cell death and Pitting --Inflammation and repair adaptations edema Webmd --Hemodynamic disorders Thromboembolism and Shock --Diseases of the immune system --Neoplasia --Genetics and Pediatric disease Edema – accumulation of fluid in the tissue &--Environmental and nutritional diseases heart failure or low albumin edema Hemorrhage – hemostasis inadequate, excessive bleeding may ensue If hemorrhage is rapid and massive, hypotension and shock may result Excessive clotting (pathologic thrombosis) +/- embolism (portion of clot migrates), may thromboembolism cause obstruction of a vessel and impair oxygen delivery to the tissue causing ischemia and/or infarction Embolism in the main pulmonary artery as it branches into R and L. Pathology Outlines  General Pathology --Cell injury, cell death and adaptations Diseases of the Immune System --Inflammation and repair --Hemodynamic disorders --Diseases of the immune system --Neoplasia --Genetics and Pediatric disease --Environmental and nutritional diseases Immunodeficiency diseases ---> increased susceptibility to infections Inherited or acquired (HIV, transplant immunosuppression, etc) Hypersensitivity reactions – immune reactions that cause tissue injury Autoimmune disorders – failure of tolerance to self-antigens and immune response is directed against self antigens  General Pathology Neoplasia and leading cause of death --Cell injury, cell death and adaptations --Inflammation and repair --Hemodynamic disorders Neo = new; plasia = growth --Diseases of the immune system --Neoplasia --Genetics and Pediatric disease --Environmental and nutritional diseases New tissue growth that is unregulated, irreversible and monoclonal Second leading cause of death in US (#1 is cardiovascular disease) Benign and malignant neoplasms  General Pathology --Cell injury, cell death and adaptations --Inflammation and repair Genetics and Pediatric Diseases --Hemodynamic disorders --Diseases of the immune system --Neoplasia --Genetics and Pediatric disease --Environmental and nutritional diseases Genetic abnormalities (mutations, amplifications, deletions, translocations, etc) ---> Alter structure and function of proteins, disrupt cellular homeostasis and cause disease Pediatric diseases May be genetic disorders Congenital anomalies, cystic fibrosis, etc Others are not genetic, but are unique to children or have distinctive features in this stage of life Congenital anomalies Perinatal infections Sudden infant death syndrome Respiratory distress of the newborn Certain neoplasms …  General Pathology Environmental and Nutritional Diseases --Cell injury, cell death and adaptations --Inflammation and repair --Hemodynamic disorders --Diseases of the immune system Exposures to chemical / physical agents in the environment --Neoplasia --Genetics and Pediatric disease --Environmental and nutritional diseases Climate change Tobacco Alcohol Drugs Therapeutic and drugs of abuse Physical agents Mechanical trauma, thermal injury, electrical injury, radiation Nutritional diseases Malnutrition, vitamin deficiencies/excess, obesity, anorexia, bulimia  Subsequent Basic Competencies in Pathology Blocks 2) Apply knowledge of disease mechanisms to organ systems and become familiar with the epidemiology, pathology (organ system pathology), clinical features, and diagnostic techniques of common disorders. Clinical presentation, natural history of disease if untreated, and likely outcome when treated. 3) Apply general and system pathology to diagnostic medicine Laboratory or imaging studies The rest of your career!  Pathology Methods for Diagnosis by eye Laboratory Medicine viewable Gross and Microscopic Examination Chemistry (incl. tumor markers) Hematology/Coagulation Microbiology Molecular Pathology Transfusion Medicine https://www.urmc.rochester.edu Molecular / genetic testing What % of data points in a health information system are derived from laboratory testing? 5-year analysis of Partners HealthCare, Boston (Arch Pathol Lab Med,. 2015; 139) * ↳ --60% of all the data points in the system were derived from the lab --500 million data points in the electronic heath record came from the laboratory versus 14 million from radiology. (USA: 7 billion lab tests / year = ~3-5% of medical costs) Many tissue sampling methods… Pap Endoscopic smear Biopsy Open, excisional biopsy Core Biopsy The one that provides sufficient diagnostic Which is best? tissue and minimizes harm to the patient.  Histologic Methods Pathologist evaluates H&E stained tissue sections to determine diagnosis DDx: Neoplasm, infection, inflammation, normal, etc Muscle biopsy with chronic If neoplasm: inflammation clean margins Subtype and tissue of origin Frequently requires ancillary techniques: I Immunohistochemistry Flow cytometry Molecular/Genetic studies Prognostic information Grade, stage, margins  Diagnostic Pap smear Cytopathology Examine cells from various body sites to determine the cause or nature of disease https://medicine.stonybrookmedicine.edu/pathology/cytopath  Frozen Section Diagnosis Intraoperative Consultation Indications Determine nature of a lesion Assessment of adequacy of STERIS Corporation tissue for diagnosis Evaluation of surgical margins ⇢ Guide the surgeon making immediate decisions, such as Lucy Han, MD UCSF Pathology Resident the extent or adequacy of Former Post-Sophomore https://newsnetwork.mayoclinic.org/ Fellow at UofA surgical procedure immediate X  Frozen Section Diagnosis Intraoperative Consultation Clinical History: 62-year-old man with a 50 pack year Hx of smoking and a Hx of melanoma. New cough Imaging ---> Lung nodule DDx: Malignancy (metastatic melanoma or lung adenocarcinoma), inflammation. CT guided biopsy of the nodule was inconclusive. The patient is taken to the OR for wedge resection of the nodule. Surgeon requests an intraoperative consultation from the pathologist, who will perform a frozen section and examine the tissue microscopically, while the patient is in the OR. Frozen Section Diagnosis - Intraoperative Consultation - Outcomes Source: Histopathology, 2015 Source: Webpath.med.utah.edu Source: Arch Pathol Lab Med. 2005 Diagnosis: Diagnosis: Diagnosis: Malignant neoplasm consistent Malignant neoplasm consistent Granulomatous inflammation with metastatic melanoma with adenocarcinoma (Infection?) Option #1: NO FURTHER PROCEED WITH LOBECTOMY, SURGICAL INTERVENTION +/- LYMPH NODE SAMPLING, NO FURTHER SURGICAL FROZEN SECTIONS FOR INTERVENTION; SEND FOR Option #2: REMOVE MASS BRONCHIAL MARGINS MICROBIOLOGY Laboratory Diagnosis of Disease Histologic and Cytologic methods Molecular/Genetic testing Tumor markers Genetic/Molecular Studies Evaluate for genetic changes (translocations, mutations, deletions, inversions, etc) associated with malignancy (or constitutional disease) FISH, karyotype, PCR, Next Generation Sequencing… Increasingly used for: Diagnosis Prognosis Treatment  Example of the use of Blood: Leukocytosis with neutrophilia, O genetic/molecular testing: eosinophilia, and basophilia Chronic Myelogenous Leukemia ↳ https://atlasofscience.org Normal Blood http://www.sysmex.nl FISH BCR/ABL as the first consistent chromosomal aberration linked to human cancer Babiker, HM and Proytcheva, MP. Blood 2014 124:2464 * Science. 1960;132:1497  Genetic Basis of Chronic Myelogenous Leukemia WBLS Identify tests required to make a diagnosis of cancer and guide therapy. & mosine kinase inhibitor imatiniy https://atlasofscience.org/chronic-myeloid-leukaemia-a-success-story-in-cancer-therapy/ blocks Laboratory Diagnosis of Disease Histologic and Cytologic methods Molecular/Genetic testing Tumor markers Tumor Markers - Uses Measured in blood, other body fluid or tissue Tumor screening PSA Support of tumor diagnosis Prognostic indicators Monitoring for relapse/disease status Tumor Markers don't need to memorize Table 7-12, Robbins Pathology  Case Study How tumor markers are used for diagnosis and disease monitoring 72M with severe back pain. MRI --> lesions in T4 and T5 vertebral bodies Biopsy→ Metastatic adenocarcinoma Primary site? / Case Study – cont. picking up PSA / Adenocarcinoma PSA Immunohistochemistry: positive Diagnosis: Metastatic prostate carcinoma Serum PSA elevated PSA as an aid in diagnosis and monitor of disease status https://biocare.net/product/prostate-specific-antigen-antibody/ Outline / Learning Objectives What is Pathology? LO#1: Understand the role of pathology in prevention, diagnosis, treatment, and management of disease. LO#2: Describe the basic mechanisms of disease LO#3: Describe the three basic competencies in pathology LO#4: Describe the approach used in the diagnosis of neoplasms and other pathologies, including the use of molecular/genetic testing and tumor markers. Questions? Deborah Fuchs MD Professor Department of Pathology [email protected] Interested in Pathology?! Opportunities for shadowing!! Email: [email protected] Post-Sophomore Pathology Fellowship Pathology Resident, PGY1, Mass General Hospital U of A, COM-T, Class of 2020 https://thepathologist.com/issues/0718/my-path-to-path/ Questions? Thrift Lab- UF Pathology (Thrift Shop Parody) (ORIGINAL) https://www.youtube.com/watch?v=ZL7a3_JRWQY