1 STUDENT GUIDE TO HISTOLOGY AND PATHOLOGY IN FOUNDATIONS OF BIOMEDICAL SCIENCE (FBS) YEAR 1, MD PROGRAM, UNIVERSITY OF MELBOURNE Department of Pathology, University of Melbourne Angela Barbour, Chris Hopkins, Clare Hampson February, 2016 MEDICINE IS PATHOLOGY Introduction: what is pathology? Pathology is the study of the causes, nature and effects of disease. It is a core clinical science that builds on knowledge of normal biomedical sciences such as anatomy, histology, physiology, genetics, cell biology and biochemistry in order to understand the molecular, cellular, tissue and clinical aspects of disease. It involves understanding concepts as well as facts. It involves understanding the different patterns of reaction to injury, known as basic pathological processes, that occur at the molecular, cellular and tissue level and from which all diseases result, how these processes affect normal structure and function and how they result in the clinical features of disease. Disease is classified based on an understanding of pathological processes, and the terminology used in pathology forms the basis of medical terminology. Pathology also involves understanding the predisposing factors, causes, mechanisms of development, potential complications, natural history, morphological features (abnormal features that can be seen in the body) and investigation of specific diseases. Pathology test results are estimated to play a role in more than 70% of clinical decisions and it is important that you have an understanding of pathology such that you can choose appropriate tests and interpret the results in the context of your patients. Medical specialists need a detailed appreciation of the pathology (including macroscopic and often microscopic features) of their specialty. Accordingly pathology forms a component of many examinations in the medical specialties. It doesn’t matter what type of doctor you intend to be; pathology encompasses all aspects of the diseases that you will be treating. In medical school, pathology is a subject, just like anatomy and physiology that all students need to study. In clinical practice it is also a medical specialty, just like surgery, radiology and paediatrics, with various subdisciplines whose roles include the provision of laboratory services, advice on the selection of laboratory investigations and the interpretation of results. Pathologists are doctors trained and skilled in making diagnoses based on the analysis of human samples (e.g. fluids and secretions, DNA, cells or tissues). The different subspecialties of pathology include Haematologic Pathology, Immunopathology, Chemical Pathology, Anatomical Pathology, Forensic Pathology, Microbiology and Genetic Pathology. While some are primarily laboratory based, others are also clinical specialties where the pathologist has a greater degree of patient contact. Pathologists are part of multidisciplinary clinical teams that include surgeons, physicians, radiologists, oncologists and specialist nurses. The Royal College of Pathologists of Australasia (RCPA) is responsible for the training and professional development of pathologists. The term ‘pathologist’ is typically used to refer to Anatomical and Forensic Pathologists, who provide information based on the macroscopic and histological examination of tissue samples (biopsies, surgical specimens, autopsy). Histopathologic assessment is used as the gold standard in the diagnosis of many disease processes and is also used to guide individualised management and provide prognostic information. Pathology reports contain histological and pathological terminology which medical practitioners need to be able to understand. Learning anatomy provides an understanding of what organs and tissues look like normally, but learning pathology provides knowledge of what they look like in the disease processes in the patients you will meet every day, in their x-rays and scans and which cause their symptoms and signs. What better way to understand the diseases and their clinical and radiological features that you’ll be diagnosing and treating day-to-day as a doctor 2 than to see what they actually look like in the body. If you invest your time wisely, you will be able to connect what you learn here to day-to-day clinical practice. Pathology, and histology, the study of normal cell and tissue structure and function needed as a foundation for learning pathology, are challenging areas and the learning curve is steep so hit the ground running and be ready to make the most of it. This document contains valuable information that will help with your study and learning of these important disciplines. You are advised to read this document thoroughly and as soon as possible to optimise your study. • • • • • • • • • Introduction: what is pathology Pathology in the MD program Pathology in year 1, including aims, information on teaching sessions, assessment and studying Academic staff in pathology Resources (textbooks, websites etc) for learning histology and pathology Appendix 1: Background knowledge for learning pathology Appendix 2: Lecture topics in histology and pathology Appendix 3: Practical classes Appendix 4: Assessment of macroscopic pathology specimens p.2 p.3 p.3 p.7 p.7 p.12 p.15 p.17 p.22 Pathology in the MD program Pathology will be included in all 4 years of the MD program. In year 1 we will cover the basic pathological processes and the pathology of selected core diseases as examples of the basic pathological processes. The pathology content of year 2 will cover the pathology of organ systems and the role of pathology in clinical management in more breadth and depth. In year 3 you will cover pathology relevant to women’s health, child and adolescent health and general practice and in year 4 there will be opportunities for research and electives and we will revisit some core issues relevant to being a junior doctor. Pathology projects are likely to be available for the scholarly selective. If you are interested contact one of the scholarly selective subject coordinators. Opportunities for pathology electives are also likely to be available in year 4. Pathology in year 1 The foundation of your pathology learning occurs this year. Early in the year the focus is on understanding the principles of histology and the basic pathological processes. The principles of histology include understanding cell structure and function and the cell cycle and replication (assumed knowledge) and the features of the four basic tissue types i.e. connective tissues, epithelial tissues, muscle and nervous tissues. The key basic pathological processes that underlie disease are: • Cell injury and necrosis • Inflammation • Healing • Cellular adaptations • Disorders of blood flow and vessels • Immune-mediated injury • Neoplasia These principles of histology and pathology are understood best at the cell and tissue level, hence it is important to appreciate their appearances under the microscope. In relation to pathologic processes we will also examine macroscopic features and cover causes, clinical features and consequences. It is important to understand these basics as they are relevant to many different tissues and diseases and form the basis of how doctors classify, diagnose, treat and prevent disease. Later we will learn how these processes manifest in different tissues and organs by studying the pathology of selected diseases. Some of these will be from Case Supported Learning (CSL) cases, others are common and classic examples of disease that illustrate important basic pathological processes and the role of pathology in clinical practice. 3 In relation to specific diseases, in addition to an understanding of the basic processes involved, you also need to learn about their epidemiology, predisposing factors and causes (aetiology), the mechanisms by which these lead to disease (pathogenesis or pathophysiology), the structural (morphological), biochemical, haematological and other abnormalities that the disease causes in the body (needed for understanding the results of investigations), how these changes manifest as symptoms and signs, and the natural history or course of the disease, including duration, potential complications and outcomes. Thus to understand myocardial infarction, you first have to know about the normal structure and function of the heart and arteries (covered in anatomy, physiology, histology etc) and the basic pathological processes of vascular disease, thrombosis, necrosis, ischaemia and infarction, inflammation and healing. You will need to correlate this information with its clinical features, morphology, relevant biochemical abnormalities and complications. This understanding is necessary for diagnosing, treating and preventing the disease and its complications. Your learning of pathology in year 1 will be via lectures, pathology pot tutorials, histology and histopathology practical classes, CSL cases and self-directed learning. Pathology lectures will normally occur after relevant lectures in anatomy, histology, physiology, biochemistry, microbiology and immunology etc. It will be assumed that you have this background knowledge, in addition to knowledge from pre-requisite undergraduate courses. Appendix 1 is a list of background knowledge for learning pathology with references for some of the content if you need to catch up. Aims of pathology component of FBS Upon completion of the Foundations of Biomedical Science, in relation to histology and pathology students should be able to: • Explain the basic pathological processes and selected specific diseases including their aetiology, pathogenesis, morphology, natural history and complications, and how these features relate to clinical symptoms and signs, investigation and management, where relevant • Recognise morphological features in histology, histopathology and macroscopic pathology, describe them using appropriate terminology, and make appropriate differential diagnoses based on these features • Relate the scientific basis of disease to clinical diagnosis and management • Communicate using appropriate terminology • Integrate knowledge within and across disciplines and apply knowledge to solve problems • Take a logical and systematic approach to problem solving • Engage in self directed, active and lifelong learning Lectures The pathology lectures will be given by academic staff of the University and consultant pathologists from the hospitals. If you do not understand any part of a lecture, do not hesitate to seek clarification from the lecturer afterwards or by email. Histology is the study of normal structure and function and is also important as a basis for understanding pathology. Histology lectures will be given by Assoc. Prof. Barbour and members of the Dept of Anatomy and Neuroscience. Appendix 2 is a list of histology and pathology lectures for the year. A note about lectures Quite quickly in your first year of medical school you might become overwhelmed by the volume of information that you need to learn. It is true, there is a lot to learn in medicine. The good news is that you don’t have to learn it all in first year, or in medical school generally. It is impossible to learn it all, but developing those foundations covered in first year is important. The bad news is that even that foundation knowledge is vast, and it won’t necessarily all be covered in lectures. Lectures should be regarded as a guide to, but not a be-all and end-all of learning. Reading about the topic in appropriate resources is also important. This will remain true for the rest of the medical course, and for your career. Lectures and other teaching sessions are provided to highlight topics that are important at your level, provide an introduction and overview, and explain difficult concepts. The rest has to come from you. A large part of being a doctor (usually not included in the television shows as it lacks drama!) is time spent on self-directed learning by reading textbooks and journals. Graduation is not the end of exams and study groups so you are advised to get into good habits, become acquainted with appropriate resources and start the lifelong process of self-directed learning now. 4 What you get out of a lecture (and practical class and tutorial) is determined as much or more, by the work you put in before and/or afterwards. For some, this may include pre-reading (pre-reading relevant parts of the textbook is likely to be more effective than pre-reading PowerPoint slides). Review lecture content within a few days of each lecture to ensure you understand it. Reading relevant sections of a textbook (hardcopy or online), at least of topics you find more difficult and/or on things you didn’t understand from the lecture is also important to aid your understanding. Textbooks will help to give the lecture context, may explain concepts in a different way and they frequently also have additional diagrams and images to aid your understanding. Be careful not to spend too much time writing and editing notes at the expense of thinking about the content and relating it to your existing knowledge in that and other areas. Note also that information from some lectures will be needed as foundation for other lectures (and practical classes). If you don’t have that foundation knowledge you are likely to find it difficult to understand content that comes later. In relation to lecture recordings, be mindful of the following: • Knowledge of the existence of recordings may reduce your concentration during lectures as you know they will be available. • Take adequate notes during the lecture. You shouldn’t need to listen to lecture recordings again, or very little of them again. • Study time is likely to be better spent reading other resources rather than listening to recordings. • The words of the lecturer may take on an importance they were not meant to have – the lecturer is not a textbook. • Occasionally lectures aren’t recorded, so be cautious about relying on them. Practical classes (histology and histopathology) and tutorials (macroscopic pathology) In these sessions we will examine some histology and pathology relevant to each block. The classes will generally be divided into 2 sections: • An online histology and histopathology component where we will focus on examining the microscopic features, using virtual slides, of normal tissues, basic pathological processes and related disease processes in the major organ systems. These can be done in your own time, however, 2 hours will be allocated for questions and revision of slides in the Microscope and Computer Lab, W313, Level 3 West, Medical Building. • A 1 hour pathology ‘pot’ tutorial where preserved specimens (in ‘pots’) of macroscopic pathologies, some surgical specimens, some from autopsies, will be used as a basis for discussion. These will be held in the Harry Brookes Allen Museum of Anatomy and Pathology, Level 3 East, Medical Building. The practical classes and pot tutorials are primarily opportunities for you to develop and practise skills in observation, description, application of knowledge and use of the language of medicine, and to correlate clinical features with pathologic features (clinicopathologic correlation). The content will be based on, but not purely derived from, histology and pathology lecture content, during which relevant structure, visual features and terminology will usually already have been explained. They will thus provide an opportunity for you to apply and use the information you have gained from lectures and reading, to receive feedback on your progress and to ask questions if you don’t understand something. Appendix 3 contains further information on the practical classes and tutorials. Appendix 4 is a guide to assessing macroscopic pathology specimens, for use in pathology ‘pot’ tutorials. Assessment Our educational philosophy is • To promote the understanding of information, the communication of that information clearly and accurately, and the ability to integrate and apply that information to solve problems, rather than just the learning of facts • That learning should be active and student centred rather than passive and teacher centred • To promote skills in lifelong learning This is especially important for you as doctors as the practice of medicine involves the integration of knowledge across disciplines, use of that knowledge to solve problems, having skills in finding and critically analysing information and the ability to communicate your opinions clearly and accurately. We cannot emphasise this 5 enough – self-directed lifelong learning is an important skill for medical practitioners, and now is a good time to start becoming aware of and utilising various learning resources. Many of our multiple choice (MCQ) questions will be in a format regarded as best practice for the assessment of biomedical and clinical sciences and of the type that you will get in later years of the MD program and in exams for specialty training. They don’t just assess facts but the understanding, integration and application of knowledge from a variety of sources. While many will be answerable from the histology and pathology courses themselves (lectures, practical classes, tutorials, other resources), some may require integration of material from other disciplines, reading and CSL cases, and just as in the practice of medicine, the answer may not necessarily be black and white. There may be several correct answers - you will have to choose the single best answer. Note that the material covered in the practical classes, tutorials and lectures is not considered to be independent and the ‘practical’ or image based assessment will cover not only material from practical classes but also topics, including relevant images, covered in lectures. Images may be included in any test or exam. In relation to images in examinations, you may be asked (amongst other questions) about the: • diagnosis or differential diagnosis • morphological features • approximate duration or age of the disease process • predisposing factors and/or causes of the disease • pathogenesis of the disease • potential complications of the disease and how they arise • expected histological abnormalities in the abnormal areas • patient’s expected clinical symptoms or signs or investigation results • different ways the abnormality may be biopsied and other basic investigations that might be relevant • relevant anatomy, microbiology, immunology, histology, physiology, genetics etc Answering the questions correctly will frequently require knowledge and integration of several pieces of information. You may be asked to describe the expected macroscopic or microscopic features of various pathologies or even to describe the features in a photograph in the short answer question examination. Studying There is a lot of content in FBS, more than many of you will be used to. Nonetheless the content is important for understanding the scientific basis of medical practice and learning it will be worth the effort. While you are unlikely to be able to learn all of it, an effective study program and hard work will help you learn the large majority of it. Study Tips 1. Be organized and prepare a timetable for study, starting at the beginning of the year. If you get even a week behind it will be difficult to catch up, as the early weeks focus on basic concepts of the non-prerequisite disciplines, and you will need this information to build on later. 2. Take advantage of the integration and overlap in FBS generally, within and between disciplines. Try to recognize where this occurs and learn the material in an integrated fashion, rather than just learning individual lectures or disciplines. Ensure that you think about and understand what you are reading, viewing and hearing and relate it to your existing knowledge in that and other areas. 3. Do something active to help remember the material. To learn material effectively it generally needs to be reviewed many times over an extended period of time. “Memory devices” e.g. • Make summaries • Draw diagrams • Discuss and explain topics to others • Give the material purpose by understanding its relevance 6 • Test yourself: after you’ve read through and tried to remember the information, test your yourself on the information at intervals (days, weeks, months) afterwards and identify gaps in your knowledge. Re-read and learn and test yourself again on the aspects you’ve forgotten. 4. Set aside time for revision throughout the semester. Your approach should be sustained and thorough. To learn it well you will need to revisit information a number of times before exams. Serous final revision should begin many weeks before the test or exam. Committing that information to memory for the long term is important. You will not have time to look a lot up in day-to-day practice once you’ve graduated. You also need to have enough basic knowledge to be able to judge whether what you read is likely to be correct or not. 5. Our experience is that students find image-based questions more challenging than purely theory-based questions. To become confident at recognising histological and pathological (macroscopic and microscopic) features, we suggest that you practice by looking at a number of examples (not only the ones from lectures, practicals and tutorials) and test yourself on your ability to recognise the normal and abnormal features, make a diagnosis etc. You might also test yourself at the same time on relevant theory. Other examples can be found in various histology and pathology resources, information on which is provided later in this document. You need to put in many hours of study each week but be careful not to equate time spent studying with effectiveness. Some students can spend a lot of time studying but understand and retain little. If you believe you are putting in the time but not getting results consult one of the academic staff. The Academic Skills website (http://services.unimelb.edu.au/academicskills) also has a variety of additional documents giving more detail on approaches to learning and time management. Academic staff in Pathology • Dr Chris Hopkins. Practical class and tutorial coordinator. W602, level 6, west wing, Medical Building. Tel: 83441203. Email: [email protected] • Dr Clare Hampson. W602, level 6, west wing, Medical Building. Email: [email protected] • Assoc. Prof. Angela Barbour. Coordinator of pathology in FBS. Email: [email protected] Feel free to ask questions of academic staff, visiting lecturers and others involved in delivering pots tutorials. We are committed to constantly reviewing and improving the quality of teaching. We may provide questionnaires for feedback. However, students may give feedback and suggestions to the teaching staff at any time. We hope you will enjoy learning pathology as much as we do teaching it. Resources for learning histology and pathology Textbooks Your minimum library should consist of 3 books: • A histology text and atlas o Wheater's Functional Histology: A Text and Colour Atlas, 6th (or 5th) edition Young, O’Dowd and Woodford (Churchill Livingstone Elsevier) • A histopathology atlas o Wheater’s Basic Pathology, A Text, Atlas and Review of Histopathology, 5th edition Young, Stewart and O’Dowd (Churchill Livingstone Elsevier) • A pathology textbook (discussion of recommended texts below). One of o Robbins and Cotran Pathologic Basis of Disease o Robbins Basic Pathology o Rubin’s Pathology, Clinicopathologic Foundations of Medicine o Core Pathology 7 With the exception of Rubin’s Pathology, Clinicopathologic Foundations of Medicine, these books are all available online via the University Library catalogue individually or in ClinicalKey. Note that hard copies, however, often provide access to various additional online resources. We also highly recommend: • Pathophysiology of Heart Disease, A Collaborative Project of Medical Students and Faculty (5th or 6th edition), editor: L. S. Lilly (Lippincott Williams and Wilkins). This is an excellent integrated resource written by medical students and faculty of Harvard Medical School. Pathology textbooks Robbins and Cotran Pathologic Basis of Disease (9th edition) by Kumar, Abbas and Aster (Saunders) (‘big Robbins’) is pretty much the Bible of pathology and is used across the world in medical schools and for specialty training. It is often quite detailed and acts as a reference book as well as a general textbook. Some find the detail too much, and it can take a long time to read, but if you have a strong biomedical science background you may find it OK. You don't need to read it from front to back or to know every detail. It is the primary reference for the Basic Pathological Sciences (BPS) examination by the Royal College of Pathologists of Australasia (set at the level of a graduating medical student), and it will be your pathology reference later in the course. Robbins Basic Pathology (9th edition), by Kumar, Abbas, Fausto and Mitchell (Saunders), is a smaller version of Robbins. ‘Baby Robbins’ is good and is suitable for medical students (containing much of the detail of ‘big Robbins’) but is pitched mainly at students studying pathology in non-medical courses such dentistry, biomedical sciences or nursing. Rubin’s Pathology, Clinicopathologic Foundations of Medicine (7th edition) by Rubin and Strayer (Lippincott Williams and Wilkins) is an excellent pathology textbook, containing slightly less detail than Robbins and Cotran Pathologic Basis of Disease. In view of time constraints and for those without a strong background in the biomedical sciences, Core Pathology (3rd edition) by Stevens, Lowe and Scott (Mosby) also written for medical students is a great but less detailed alternative for first year. Core Pathology can be accessed electronically via the university library catalogue. It is no longer in print. Other textbooks For less detailed / more basic information: • Pathology Illustrated (6th edition, or an earlier edition) by Reid and Roberts (Elsevier Churchill Livingstone) • The Flesh and Bones of Pathology (1st edition) Bateman and Carr (Mosby) For macroscopic images • Robbins and Cotran Atlas of Pathology by E. Klatt (Saunders) is available electronically • Colour Atlas of Anatomical Pathology (3rd edition) by Cooke and Stewart (Churchill Livingstone) For more detailed histology: • Histology: a text and atlas with correlated cell and molecular biology (7th edition) by M. H. Ross and W. Pawlina (Lippincott Williams and Wilkins) With questions for self-assessment: • Lippincott’s Illustrated Q&A Review of Rubin’s Pathology (2nd edition) by Fenderson, Rubin et al (Lippincott Williams and Wilkins) • Robbins and Cotran Review of Pathology (4th edition) by Klatt and Kumar (Elsevier Saunders) • BRS (Board Review Series) Pathology (5th edition) by Schneider and Szanto (Lippincott Williams and Wilkins) • Wheater’s Review of Histology and Basic Pathology (1st edition) by Baldwin, Tadesse-Heath, Young, and Hakim (Churchill Livingstone). This is based on content in Wheater’s Functional Histology and Wheater’s Basic Pathology and is available via Clinical Key. 8 There are many textbooks out there. If you have another and would like to know if it is suitable, ask one of the academic staff. Note that old editions may not have up to date information on cell biology and genetics. The Patient Under the Microscope This computer-based resource is available on the computers in W313, where we will be holding the online practical classes, and via MD Connect (Year 1 resources section). It will run on Windows including Win 10, but may not run in different versions of Mac OS. It provides an introduction to histology, the role of cells and tissues in health and disease and integrates knowledge from cell biology, histology and pathology. The Harry Brookes Museum of Anatomy and Pathology This museum located on level 3 of the east wing of the Medical Building is a valuable resource. Specimens showing pathologies covered in the tutorials and others are on display. Photographs of many of the specimens are available to view via the online catalogue, however, many of the descriptions in the online catalogue are suboptimal. Descriptions of the specimens in the museum are gradually being updated system by system and can be found in folders at the end of each bay. 9 Websites There are many websites with information, images and practice questions and answers on pathology and histology information. Here is a selection. Site By BEST Network www.best.edu.au This includes the online library of virtual slides used in our practicals. There are also macroscopic images of disease and radiology (in SLICE) and various other online tutorials (COURSEWARE) Harry Brookes Allen Museum of Anatomy and Pathology http://harrybrookesallenmuseum.mdhs.unimelb.edu. au Login for the online catalogue of pots used in our tutorials The Internet Pathology Laboratory http://library.med.utah.edu/WebPath/webpath.html Pathology Education Instructional Resource http://peir.path.uab.edu/wiki/IPLab Histology Guide http://www.histologyguide.org/index.html Histopathology Atlas of Granulomatous Diseases http://granuloma.homestead.com/index.html Blue Histology http://www.lab.anhb.uwa.edu.au/mb140/ Museum of Pathology: photographs of pathology pot specimens with clinical histories and descriptions http://museum.med.monash.edu.au/ Pathology Podcasts: podcasts of pathology museum specimens http://www.e-pathpots.org.uk/ Neuropathology http://neuropathology-web.org The Histology Guide http://histology.leeds.ac.uk RCPA Manual http://www.rcpamanual.edu.au/ Macro Images Micro Images Network of various Australian and overseas universities Tutorials/ informati on University of Melbourne Mercer University School of Medicine University of Alabama at Birmingham T.C. Brelje and R.L. Sorenson. Yale Rosen University of Western Australia Monash University Quiz Royal College of Pathologists (UK) Dimitri Agamanolis University of Leeds Royal College A reference guide for interpreting of laboratory tests. You can search by the Pathologists name of the test or a clinical condition. Australasia In relation to websites generally, be cautious about using just any that might appear to be ‘medical’. Not all are reliable. Use ones that have been recommended, are hosted by universities or are authored by those with appropriate medical qualifications. In relation to resources for learning pathology, even good medical websites 10 (e.g. emedicine.medscape.com) do not necessarily have sufficient information in relation to pathology. It is preferable to use pathology websites written by medically qualified pathologists, or university pathology webpages. The Royal College of Pathologists of Australasia and the Basic Pathological Sciences Examination The Royal College of Pathologists of Australasia (RCPA) is responsible for the training and professional development of pathologists, the promotion of pathology and the quality use of pathology tests. Their website is at http://www.rcpa.edu.au. It contains a variety of information, including on pathology as a career, pathology testing, educational resources, the Basic Pathological Sciences examination and the Manual of Use and Interpretation of Pathology Tests. The Basic Pathological Sciences (BPS) examination is set at a level that the College recommends as appropriate for a graduating medical student such that they can demonstrate that they have adequate foundation knowledge of the important pathological processes and biological principles of disease. While primarily intended for students wishing to undertake specialty training in pathology, any final year medical students or prevocational doctors are encouraged to attempt the examination, as an understanding of basic pathological processes and principles of disease is important for the practice of all areas of medicine. The BPS curriculum is primarily based on the first 10 chapters of the recommended text, Robbins and Cotran Pathologic Basis of Disease, as well as basic principles of microbiology and immunology, the genetic basis of disease, biochemistry and basic haematology. You may wish to consider sitting this exam later on. 11 Appendix 1: Background knowledge for learning pathology The following is provided as an aid to your learning of pathology. It is not meant to be an exhaustive list, but a reasonably comprehensive guide as to the knowledge required as a foundation for learning pathology. Some of the topics below should have been covered in pre-requisite anatomy, physiology and biochemistry courses, and some will be covered this year. References for some of the content are provided. Information is also available in recommended anatomy, physiology, biochemistry etc textbooks and Medical Sciences, 2nd edition, edited by Naish and Syndercrombe. (Saunders Elsevier). Anatomy • Anatomical terminology • The principles of embryological development and the derivatives of the primary germ layers • Regional anatomy and the anatomy of the major organ systems, including blood and nerve supply and lymphatic drainage • The appearance of normal tissues and organs Physiology • The physiology of the major organ systems • Normal haemostasis Biochemistry, cell biology and molecular genetics • Cell structure and components including nucleus, heterochromatin and euchromatin, nucleolus, endoplasmic reticulum, mitochondria, Golgi apparatus, lysosomes, glycogen, lipid, secretory vesicles, cytoskeletal elements including actin and myosin, cilia, microvilli, lipofuscin, structure of cell membranes (Wheater’s Histology Chapters 1 and 2) • Autophagy • Movement of proteins within the cell and secretion of proteins • Cell signalling including patterns, receptors and signal transduction pathways • Cell movement • Intercellular junctions and cell adhesion • Stem cells • How nucleic acids replicate information and act as a template for the synthesis of RNA and proteins • Purine and pyrimidine nucleotide metabolism • DNA structure and conformation • DNA synthesis and recombination • RNA structure, transcription and processing • Amino acid metabolism, protein synthesis: translation and post-translational modifications • Recombinant DNA and biotechnology • Regulation of gene expression • DNA repair mechanisms • The cell cycle and the regulation of cell replication • Cell replication: mitosis and meiosis • Basic molecular and cell biology techniques e.g. polymerase chain reaction (PCR), sequencing, in situ hybridization, microarrays, southern blots, flow cytometry, immunohistochemistry and immunofluorescence • The structure and function of amino acids and proteins, including enzymes • The structure and role of lipids and lipid metabolism • Biological membranes: structure and membrane transport • Metabolic pathways including glycolysis, gluconeogenesis, oxidative phosphorylation and fat storage • Carbohydrate structure and metabolism • The biochemistry of hormones: polypeptide and steroid hormones • The cytochromes P450 12 • • • • Iron and heme metabolism Gas transport and pH regulation The principles of nutrition, digestion and absorption of nutrients Biochemistry relevant to the major organ systems Genetics and disease (Genetics textbooks and Robbins and Cotran Pathologic Basis of Disease, Chapter 5) • Understanding that there is significant variation amongst normal genes • The role of genetics in normal variation • Basic genetic terms and the language of genetics e.g. genetic variants, single nucleotide polymorphism, mutation, copy number variation • Patterns of inheritance: autosomal, sex linked, multifactorial, mitochondrial • The nature and types of mutation and implications of those mutations for human variation and disease i.e. understanding that disease/variation can be due to • Abnormalities of chromosomes: number, structure, deletions, translocations, inversion etc • Abnormalities of single genes: deletions, point mutations, amplification of trinucleotide repeats etc • Abnormalities within non-coding sequences • Abnormalities associated with genomic imprinting, mitochondrial genes, epigenetic alterations • Abnormality may be in all cells of the parent or abnormality may develop during meiosis or mitosis, mosaicism • Complex multigenic disorders: normal genetic variation predisposing to disease, variations in drug metabolism, adverse reactions to drugs Microbiology and Immunology (Microbiology and Immunology textbooks) • Basic immunology including phagocytosis, complement and its role, cell signalling molecules, subsets of helper T cells and relevant cytokines • Hypersensitivity types 1-4 and relevant cytokines • Basic microbiology • Important disease causing organisms Histology (Wheater’s Functional Histology, Chapters 3-7 and appendices, approximately 100 pages of easy reading – mostly pictures & tables) • Histological terminology • How tissue sections are prepared and the principles of H&E staining • Basic tissue types • The histological features and appearance of main cells, tissues and organs • The electron microscopic appearance of main cell and tissue components • The functional relevance of histological structure For understanding the pathology of specific diseases of the organ systems, one also needs knowledge of Basic pathological processes (Pathology textbooks and Wheater’s Basic Pathology, Chapters 1-10 - 100 pages, mostly pictures) • Cell injury and death and intracellular accumulations • Cell and tissue adaptations • Acute and chronic inflammation • Tissue regeneration and healing • Vascular and haemodynamic disorders, including atherosclerosis, thrombosis, embolism, ischaemia and infarction, shock • Neoplasia • Changes related to aging Other • The surgical/aetiological sieve • Understanding that diagnosis in anatomical pathology can involve o Macroscopic assessment 13 o Microscopic assessment o Routine histochemical stains o Immunohistochemistry o Electron microscopy o Molecular techniques o Cytopathology These pathology topics will largely be covered in the foundation, cardiovascular and respiratory blocks. 14 Appendix 2: Lecture Topics in Histology and Pathology Histology lectures cover the basic tissue types and the histology of organ systems. Pathology lectures cover basic pathological processes and selected common and classic diseases as examples of these pathological processes, some from CSL cases, in the different organ systems. Foundation (weeks 2 and 3) • Introduction to histology and blood • Histology: Connective tissues • Histology: Epithelia • Histology: Nerve and muscle • Cell injury and necrosis • Inflammation and healing (3 lectures) Cardiovascular (weeks 4-7) • Cardiovascular histology • Atherosclerosis and other vascular pathology: arteriosclerosis, arteriolosclerosis, dissection, aneurysms • Blood and anaemia • Haemostasis • Thrombosis, embolism, ischaemia and infarction • Ischaemic heart disease • Cellular adaptations, myocardial hypertrophy and introduction to valve disease Respiratory (week 8-11) • Respiratory histology • Obstructive and restrictive lung disease (intro to restrictive only) • Infection in the lung: pneumonia and tuberculosis • Deep venous thrombosis and pulmonary embolism • Neoplasia (3 lectures including carcinoma of lung as an example) Renal (weeks 12, 13) • Renal histology • Glomerular disease: overview and introduction to glomerulonephritis • Tubulointerstitial disease: overview with examples • Pathology of hypertension GIT and liver (weeks 14-17) • Gastrointestinal histology • Causes, mechanisms and consequences of acute and chronic gastritis • Coeliac disease • Dysplasia-carcinoma sequence: general with examples • Dysplasia-carcinoma sequence in the colon, colon carcinoma • Liver and pancreas histology • Liver pathology including patterns of liver injury, acute and chronic viral hepatitis, steatohepatitis, cirrhosis and portal hypertension (3 lectures) Neuroscience (weeks 19-24) • Histology of the nervous system • Head and spinal cord injury and raised intracranial pressure • Neural regeneration • Stroke • Pathogenesis of dementia Endocrine (weeks 24, 25) • Hormone measurement and interpretation • Thyroid histology and pathology (Graves, multinodular goitre and Hashimoto diseases) Metabolism (weeks 26, 27) • The pathology of diabetes Locomotor (weeks 28, 29) • Histology of bone and joint 15 • Bone pathology: fracture and fracture healing • Joint pathology: Osteoarthritis, rheumatoid arthritis and gout Exercise induced exhaustion (week 30) Reproduction (weeks 31, 32) • Histology of male and female reproductive tracts • Cervical HPV, dysplasia and carcinoma • Breast pathology: cancer and common benign pathologies Intersystems (weeks 33-35) • Skin histology and revision of healing • Leukaemia • Pathology of lymph nodes (with intro to lymphoma) 16 Appendix 3: Histology and Pathology Practical Classes The classes will generally be divided into 2 sections: • An online histology and histopathology component where we will examine the microscopic features, using virtual slides, of normal tissues, basic pathological processes and related disease processes in the major organ systems. These can be done in your own time, however, a 2 hour session for questions and review of slides will be held in the Microscope and Computer Lab, W313, Level 3 West, Medical Building. • A 1 hour pathology ‘pot’ tutorial where preserved specimens of macroscopic pathologies (in ‘pots’) will be used as a basis for discussion. These will be held in the Harry Brookes Allen Museum of Anatomy and Pathology, Level 3 East, Medical Building. The coordinator of these classes is Dr Chris Hopkins. The classes will be held 6 times: 3 times per week (Tuesday 9am - 12noon, Tuesday 2 - 5pm, Wednesday 2 - 5pm) over a designated two-week period. Class Weeks Topic Histology and Histopathology specimens examined 1 3,4 Introduction to Normal skin histology, basic tissue types and pathology pots 2 5,6 Inflammation and Blood (red and white blood cells), normal lung, lobar pneumonia healing (acute inflammation), lymph node (immune cells), rheumatoid synovitis (chronic inflammation), miliary tuberculosis (granulomatous inflammation), healing skin wounds x2 (granulation tissue and scar) 3 7,8 Vessels Normal aorta, normal muscular arteries and veins, normal small vessels (in pancreas), normal vena cava, including elastic tissue stains, aortic dissection, atherosclerosis (in aorta and coronary arteries), hyaline arteriolosclerosis (in benign nephrosclerosis) 4 9,10 Heart Normal LV wall, ultrastructure of cardiac muscle, recent (acute inflammation), healing (granulation tissue) and healed (scarred) infarcts, coronary artery atherosclerosis with thrombus 5 12,13 Respiratory Normal trachea, normal lung, lobar pneumonia, bronchopneumonia, TB bronchopneumonia, asthma 6 14,15 Renal Normal kidney, ultrastructure of glomerulus, light and electron micrographs of glomerulonephritis (principles of IgA and membraneous), acute pyelonephritis, acute tubular necrosis, renal infarct, benign nephrosclerosis, end stage kidney 7 16,17 GIT, pancreas and liver Normal histology of GIT, normal oesophagus, normal stomach, peptic ulcer of stomach, normal duodenum, coeliac disease, normal appendix, acute appendicitis, normal liver, cirrhosis and steatosis, normal pancreas 8 19,20 Neoplasia Normal colon, adenocarcinoma of colon, adenoma (dysplasia) of colon, cervical squamous dysplasia, squamous cell carcinoma (SCC) of lung, large cell undifferentiated carcinoma of lung 9 24,25 Nervous System 10 27,28 Endocrine 11 30,31 12 32,33 Musculoskeletal (histo and histopath), Revision/quiz (pots) Reproduction Normal brain, acute bacterial meningitis, images or slides of recent, healing and old cerebral infarcts, brain tumour, Alzheimer’s disease Normal thyroid, Hashimoto disease, Graves disease, multinodular goitre, diabetic kidney including ultrastructure of glomerulus, normal pancreas Normal bone, endochondral ossification of growing bone, healing fracture, examples of bone pathology, normal synovial joint, rheumatoid arthritis Normal cervix, CIN3, SCC cervix, cervical cytology, adenocarcinoma of cervix, normal uterus with proliferative 17 endometrium, normal uterus with secretory endometrium, leiomyoma, leiomyosarcoma, normal ovaries 13 34,35 Skin, breast, spleen and Normal lymph node, normal spleen, normal breast and ductal lymph node (histo and carcinoma in situ, Paget’s disease of nipple, invasive carcinoma of histopath only) breast, normal skin, two healing skin wounds, solar keratosis, SCC of skin, BCC of skin The histology and histopathology specimens listed are largely from 2015. There may be minor revisions for 2016. Note: These classes generally follow the relevant lectures in anatomy, physiology, histology and pathology, and as we have to run the same class 6 times over 2 weeks, the practical class of a specific block (e.g. cardiovascular) will tend to be in the subsequent block (e.g. respiratory). For this reason also, and due to reorganisation of the GIT and renal blocks, the class on neoplasia will be after the mid-year break. Histology and histopathology classes Objectives and notes will be provided online (via links in the timetable on MDConnect and via the “Pathology home page” on the Smart Sparrow website at https://aelp.smartsparrow.com/learn/open/eciak3ka) the week before the class. The main aim of these sessions is for students to learn to recognise and describe • cells and extracellular components of the basic tissue types • cells and extracellular components of the major organs and tissues • features of basic pathological processes and of selected core diseases of the organ systems These classes will be in the form of interactive online tutorials using an e-learning platform developed by Smart Sparrow (https://www.smartsparrow.com) that can be accessed outside of rostered class time. They generally commence with a series of ‘pre-practical’ questions that assess some basic facts from lectures and pre-reading. The tutorials focus on the examination of microscopic slides and images, however, there may also be images of electron microscopy, radiology and macroscopic pathology. Material is frequently presented in a clinical context. As you work through the tutorial you will have to answer questions (including MCQ and short answer) on the slides, and others relevant to the topic, including questions on histology, pathology and basic clinical features. There will also sometimes be a series of more complex post-practical questions that assess your understanding of the material. When examining a virtual slide: 1. Think first about what you would expect to see from knowledge gained from lectures and pre-reading of relevant textbooks. 2. Examine the section on low power (zoomed out) first, look for the features that you would expect to see and orientate yourself in relation to the overall layers or other low power features of the tissue. 3. Examine different areas on higher power (zoomed in), and attempt to identify features you would expect to see, and the specific features of various cells and tissues, so you can learn to recognise them again. After the first few classes and once you’ve learnt a few basics, we will recommend that you do the tutorial before the class. Class time can then be spent clarifying content with colleagues and demonstrators and watching the slide demonstrations (the latter will occur in the second hour of the class). Tips for histology and histopathology practicals • Come prepared. Pre-reading relevant lecture content and textbooks will allow you to get the most out of the sessions. We recommend (at least after the first few sessions) that you do the entire tutorial online beforehand • Bring copies of your histology and histopathology atlases to the classes (also available online) • Actively think about the content and integrate it with prior learning and lecture content • If you get a question wrong: • re-read the question to make sure that you have read it correctly • look up the relevant information, don’t just guess. Answers use standard terminology 18 • • from lectures and textbooks. Develop your visual skills by drawing your own labelled diagrams of the sections, annotating the slides online, or taking screen shots and labelling them Use the glossary provided (on the Pathology home page) A note about note taking in practical classes In the past, some students have made vast amounts of notes and taken many screen shots of slides in the practical classes. If you find yourself doing this, consider how efficient it is. You may just be repeating the notes you have already prepared (or should have prepared) of lecture content. You may also be wasting time by focussing on preparing notes rather than on thinking about, understanding and absorbing the content of the classes. Photographs of histology and histopathology are available in lecture notes and atlases. Note that satisfactory attendance of this part of the class will be based on completion of the online tutorial by the end of the fortnight in which the tutorial is run rather than attendance of the class itself. However, if you do attend, please attend the class to which you are rostered. Changing to an alternative class requires the approval of the coordinator. Access Instructions for the online practical class notes 1. For access to the tutorials you will need to have Flash installed (http://get.adobe.com/flashplayer/) and an up to date browser. 2. Login to MDConnect. 3. Click on the link to the relevant practical class from your timetable (or from the Pathology home page: https://aelp.smartsparrow.com/learn/open/eciak3ka. Login details will be the same as for the online practical classes). 4. Login using the username (email address) and password you receive from Smart Sparrow. The username (email address) you received from Smart Sparrow prior to practical class 1 is the email address used to enrol you, and which you should use for logging in, for all practical classes. Please note that it may differ slightly from your normal student address. Note that you can reset your password via the Smart Sparrow website but not your email address for logging in (if you wish to change the email address used for logging in, please contact Chris Hopkins). You can access notes for all classes from W313 or from other computers any time via MDConnect and the timetable. The notes will open at the screen that you last viewed. 5. If you are unsure of the email address that you are enrolled under, please contact Dr Chris Hopkins ([email protected]). If you are using the correct email address and not able to log in, try changing your password by clicking "Forgot your password" to reset your password. It may take a little while for a new password to register and you may not be able to login straight away. Instructions for annotating slides on BEST 1. Navigate to the slide you want to annotate (in most cases this will be from a link in the practical class, although there are hundreds of slides on BEST that you can search for yourself). 2. You will need to be logged in. The “LOG IN” button is in the top right-hand part of the screen, above the minimap. Use the same login details as for the practical classes in Smart Sparrow. 3. Annotations have to be saved in “Layers”. You can have multiple layers, e.g. you might like to annotate normal and abnormal features separately. Create a layer by clicking the blue underlined “Add Layer” link to the left of the slide. There are fields for you to create a name and description for the new layer, and two check-boxes which you can use to control how other people can view or copy your layer. 4. Now you can create an annotation. Click on the blue underlined “Annotate” link on the left. From here you have a number of tools: a) “Insert name” and “description” – these will appear in the sidebar for viewing. The name is restricted to perhaps 30 viewable characters, but the description can be larger and can contain hyperlinks. b) Insert a Shape – this can be a Pin, a Rectangle, a Circle or a Drawn shape. The options appear in the top left corner of the microscopic field. Click on one option, and then onto the slide to place the shape, then drag the shape around and/or change its size and dimensions. You can insert a number of pins, rectangles or other shapes for one annotation, e.g. if you identify many multinucleate giant cells you could annotate them all. c) “ICON” – you can make your new annotation a feature, region, notable point, or a query. 19 d) The program randomly selects a colour for each new annotation. However, you can change the colour of your annotation by clicking on the paint-pot button to the right of “Shapes”. All the shapes of a single annotation will have the same colour. e) “Associations” – you can link some annotations with others so you can click directly from one to the other while viewing your layer. f) The “DONE” button – click this when you’re finished and what you’ve done will be saved. To make a new annotation, press the Back button in the upper left and then click on the blue ”Annotate” link again. You can view your annotations at any time by clicking on their name. You can then edit them by selecting “EDIT” from the dropdown menu to the right of the annotation’s name. More information is available on the BEST website: https://www.best.edu.au/help-slice/ Pot tutorials Demonstration of macroscopic pathology is an important part of pathology education. Traditionally it has been done utilising pathology pot specimens, and both medical students and clinicians used to attend mortuary demonstrations where they would view an autopsy or the recently removed fresh organs. There are far fewer autopsies now and autopsy demonstrations are not practical for large numbers of students. Pathology pot specimens contain real examples of disease that have either been removed surgically from live patients or from autopsies. Their use enables one to get a 3 dimensional appreciation of anatomy and disease, something that photographs, x-rays and CT scans do not. Pathology pots are no longer utilised in some medical courses so consider yourselves lucky that they are a part of your education! The main aim of these sessions is to give you practice at seeking, recognising and describing macroscopic features of basic pathological processes and core diseases, at making differential diagnoses, at explaining the mechanisms of disease and at linking the clinical features of disease with the underlying pathology using appropriate terminology. You will be expected to examine all specimens allocated to your tutorial group before the tutorial. We may also ask you to match the specimen with a clinical history or a radiological image (relevant information will be provided beforehand in an email). In the tutorial individual students will be asked to describe and discuss at least one of the specimens. Subsequent discussion may include relevant anatomical features, what basic pathological process the disease is an example of, causes and risk factors, pathogenesis, natural history and complications. The investigation and management of disease has less focus at this stage, but it is appropriate to discuss basic principles. The pots will illustrate basic pathological processes and/or specific diseases. Most, but not all, will have been covered in lectures. Some will involve processes that you will be expected to be able to recognise based on an understanding of basic principles. We don’t provide the diagnoses, as the aim is for you to practise recognising features and work out the diagnosis or differential diagnosis yourself. The tutors are academic staff of the university and current or retired consultant pathologists and pathology registrars from the hospitals. You will be rotated amongst different tutors so that you experience a variety. The tutors will be given information in advance on the structure of FBS and the pathology content, the objectives of the tutorials, the lectures you have had and the pots to be discussed. Most will not be able to answer questions on assessment. Tips for Path Pots: • Come prepared with knowledge of the different pathologic processes and diseases covered in lectures. • Examine the pots prior to the tutorial, they will be made available at least a week beforehand. Compare the appearances of the pots in the different bays e.g. specimen A for each of the tutorial groups is an example of the same disease. This may help you decide what it is. • Read examples of macroscopic descriptions as a guide (provided in booklets at the ends of the shelves in the museum, for some systems). Pathology textbooks also have information on macroscopic features. You can find photographs of macroscopic pathology in recommended resources. • Don’t read from your notes in the tutorial – try and remember what you’ve read – it will be handy for later. 20 • It is expected that you can distinguish normal from abnormal, but if you’re struggling, take advantage of anatomy pots in the museum for comparison. Many pathology specimens also have normal areas. • You may wish to take notes and draw diagrams during tutorials (macroscopic pathology is assessed, and we don’t provide summaries or photographs). • Use the information from the lecture provided in the first practical class, the (ultimate) Guide to Assessment of Macroscopic Pathology Specimens (below) and the glossary provided (on the Pathology page). Please attend the tutorial to which you are rostered. Changing to an alternative class requires the approval of the coordinator. 21 Appendix 4: Assessment of macroscopic pathology specimens INTRODUCTION Developing powers of observation, a systematic approach to seeking relevant and important features for the diagnosis of disease, and accurate description and documentation are important in medicine generally. When a patient walks into a room you should be observing them (are they overweight, malnourished, pale, short of breath, is their posture stooped, do they walk with a limp, etc.). The diagnostic process subsequently involves gaining further information to formulate hypotheses and testing those hypotheses to arrive at a diagnosis or differential diagnosis. The approach to a pathology specimen is similar. There are also many other reasons for observing and understanding the macroscopic features of disease. • It helps us to understand clinical symptoms and signs • Understanding radiology requires an understanding of pathological processes and features • Macroscopic descriptions of pathologies removed surgically appear on pathology reports, which you need to be able to understand • Examining and documenting features of lumps and skin lesions is important for diagnosis clinically • Many specialties require a detailed understanding of pathology, including macroscopic (and sometimes microscopic) features, and demonstrating knowledge of morphology is a component of their examinations The aim of the pathology pot tutorials is to give you practice at developing skills in observation, description, integration, analysis, explanation and communication using appropriate terminology and to learn how to formulate a differential diagnosis i.e. to learn to think and talk like a doctor, and to correlate pathological features with clinical features of disease i.e. clinicopathologic correlation. Even if not asked for a description, you should develop an orderly systematic approach to examining a specimen in order to seek relevant features to make a diagnosis, just as you need an orderly systematic approach to clinical history taking and examination. Firstly, to appreciate the abnormal, you need to have a knowledge and understanding of the normal, in this case anatomy. You also need to have some background knowledge and understanding of basic pathological processes and their appearances and the diseases of different organ systems before you will be able to recognise a disease or process. This will help you to work out what the disease or process is if you don’t readily recognise it. Sometimes a definite diagnosis will not be able to be made, and in practice, diagnosis in Anatomical Pathology is largely made on histological examination, not just macroscopic appearances. However, in all cases you should be able to formulate a preferred diagnosis or reasonable list of differential diagnoses. Just as in clinical practice, you will not become proficient in diagnosing something if you have only seen one case. Exposure to a variety of cases to experience the variability in morphology will help your understanding and diagnostic ability greatly. Information on where you can find other examples is provided elsewhere in this document. Your observational, diagnostic and descriptive skills will improve with practice and as you learn more pathology. Some pathological abnormalities are easy to recognise, but make sure you understand why this is the diagnosis and be able to recognise and describe the features, such that you can defend your diagnosis if necessary. The topics covered in the pots tutorials will mostly have been covered in CSL cases and/or pathology lectures and you will learn much more from the session if you come having already read up on the area. Sometimes pathologies may be included that have not been covered in lectures but if you have knowledge and understanding of the principles you should still be able to recognise and interpret the features. OVERVIEW OF THE ASSESSMENT OF PATHOLOGY POT SPECIMENS In general: • Look at all sides of the specimen • Identify and orientate the organ/tissue • Consider whether the specimen is likely to have been removed surgically from a live patient or removed at autopsy 22 • Consider what you know about the diseases affecting this organ • Examine the specimen in a systematic way, including all anatomical features e.g. for the lung look at the pleural surfaces, parenchyma, bronchi, vessels, hilum, lymph nodes • Identify the abnormality/ies and from your knowledge of pathology look for features that may help to support or refute a particular diagnosis • Use any clinical information given to you – it may be relevant • If you can’t make a diagnosis, at least make a list of differential diagnoses • Be able to correlate pathological features with expected clinical features (clinicopathological correlation) i.e. explain how the pathological features might have caused relevant symptoms and signs. MACROSCOPIC ASSESSMENT AND DESCRIPTION The features that are important in determining what an abnormality is are also those used to describe and document it. 1) Examine the entire specimen, not just the front. Learn to recognise the organ or tissue (usually but not always possible) and orientate the specimen (i.e. left vs right, anterior vs posterior, left ventricle vs right ventricle, etc.) if necessary. How has it been sectioned (is it a coronal, sagittal or transverse section)? A good description starts by stating what the specimen is. 2) Is the organ/part of normal size, too small (is it atrophic or from a child?) or too large (hypertrophic, hyperplastic, other?). 3) Examine all parts of the specimen in an orderly sequence so that you don’t miss anything, including all anatomical features e.g. for the lung: Pleura Is it smooth, is it fibrotic, is there a fibrinous exudate? Parenchyma Is there normal fine spongy texture? Is there consolidation, enlarged alveolar spaces, thickened alveolar walls, tumour masses? Bronchi Are they dilated, narrowed, is there tumour arising focally? Vessels Is there thromboembolus in arteries? Hilar lymph nodes Are they enlarged, anthracotic, do they contain tumour? 4) Identify and describe the abnormality/ies. Is it: Focal: a single abnormality (or ‘lesion’) in one area. The features used to describe focal abnormalities generally include: Site Use appropriate anatomical terms Size Approximate dimensions can be given. Size can be of help in differential diagnosis and is also important clinically e.g. for prognosis, management, follow-up Shape Colour What colour is it? Is it all one colour or is it many colours (variegated)? Does it look homogenous (all the same the whole way through)? Does it look reddened or dark brown, suggesting vasocongestion/hyperaemia and/or haemorrhage? Does it look grey (altered blood) and/or friable (falling to bits), suggesting necrosis? Consistency This can be difficult to assess in a specimen that you can’t touch, but you can get some idea just by looking. Does it look solid or firm? Firm pale tissue may be tumour or fibrosis. Does it look friable (as if it’s falling to pieces) suggesting necrosis? Some lesions are cystic (well-circumscribed with a smooth lining, containing fluid or thick secretions or mucus) – there may be one or many (polycystic), or cavitated (there is a cavity with a ragged lining from loss of tissue following necrosis). Margins Are they well-defined or well-circumscribed, poorly defined or irregular? Is there a rim of fibrous tissue around the lesion (encapsulated)? Malignant neoplastic lesions typically have ill-defined/irregular/infiltrative margins (and may also demonstrate necrosis) whereas benign neoplastic lesions tend to have well-defined or well-circumscribed margins (however, there are many exceptions!). Surface For a lesion in an epithelium lined structure, assess and describe whether it is 23 protruding into the lumen from the surrounding epithelium (polypoid). Is the surface smooth and uniform or is it composed of many fine fronds (papillary or villous)? Is the lesion ulcerated (surface is replaced by necrotic friable slough rather than healthy epithelium)? Multifocal: this means that there is more than one distinct but similar lesions in the specimen. The features relevant to focal lesions apply here also. In addition, it may be important to note any variation between lesions. Diffuse: means involving the entire or majority of an organ/tissue or lobe. Some of the above features may also be of use for assessing and describing a diffuse process e.g. consistency, colour. Describe the site of an abnormality using appropriate anatomical terms e.g. “at the apex of the left upper lobe”, “in the anterior aspect of the left ventricular myocardium” (not, for example, “at the top of the pot”, or by pointing to it). As you identify and describe the features, consider what the diagnosis is. Try to avoid using the diagnosis in your description (what if your diagnosis is wrong?), keep your language broad at this point, using descriptive terms for the lesion, mass or other abnormality. 5) Now test your hypothesis as to the diagnosis. Think about and look for other related features, the presence or absence of which may help your diagnosis e.g. is there evidence of necrosis or are there enlarged local lymph nodes that may support a diagnosis of malignancy? Think about complications of the disease that may be present in the specimen e.g. transtentorial herniation with a space occupying lesion of the brain. If present, describe them. Likewise it is useful to state relevant negatives in your description. 6) Other pathologies. Have a look at the rest of the specimen to see if there are any other unrelated abnormalities. If present, describe them. A useful mnemonic for remembering the main features is these words beginning with ‘S’: • In relation to the specimen itself: Specimen (what is the organ/tissue) Section (plane of section and orientation) Size of the specimen (is it unusually large or small) • In relation to the abnormality: Site Size Shape Shade (colour) Solidity (firm or soft, cavitated, fluid filled etc) Symmetry (margins) Surface of any abnormality Supporting features (or absence thereof) for the preferred diagnosis. Descriptions should be succinct and objective, demonstrate appropriate use of terminology, include the important features that are used to make the diagnosis, and other features that may be important clinically. A good description will allow someone else to make the diagnosis without having seen the specimen. Specimens from some systems in the Harry Brooks Allen Museum have sample descriptions in folders at the end of the bays. 7) Synthesise the information and formulate a preferred diagnosis or differential diagnosis. Be as specific as possible (e.g. in general, a diagnosis of ‘tumour’ is insufficient - is it likely to be benign or malignant, primary or secondary, what type is it likely to be? Rather than just cholecystitis, is it acute or chronic? Is it an old, healed (months or years) or a recent (days) myocardial infarct?). Your diagnosis/differential diagnosis should include all the major clinically significant abnormalities in the specimen (that may or may not be related); sometimes there will be more than one. If you aren’t able to make a diagnosis or differential diagnosis, at least try and identify which of the broad groups of pathological processes the abnormality fits into using the 24 pathological/surgical/aetiological sieve. Or work through a list of the conditions that occur in the particular organ, excluding those that seem unlikely from the features, thus narrowing the list of possible diagnoses. The surgical (also known as a pathological/aetiological/diagnostic) sieve This is a tool for classifying and remembering in a systematic way the potential causes of disease, and for formulating differential diagnoses, especially when the diagnosis is not obvious, whether in clinical situations or for looking at pathology pots. The categories include congenital, genetic, traumatic, inflammatory (infection and immunological), vascular, degenerative, environmental, endocrine, metabolic, nutritional, neoplastic, psychiatric, psychological, thermal, toxic, iatrogenic and idiopathic. A number of mnemonics exist for helping to remember the categories. One is: TIN CAN BED PAN for: Trauma, Inflammatory, Neoplastic, Congenital, Arteriovenous, Neurological, Blood, Endocrine, Drugs, Psychogenic, Allergic, Not known. You can find others on the web. Notes on colour The specimens in the pots have been fixed or preserved. Fixation results in alterations of normal colour and tissues may fade. For example, when fresh, haemorrhage, areas of vasocongestion/hyperaemia and thrombi are generally dark red. In the pots they may look dark red, black or dark grey/brown. Dark red, black or dark grey/brown areas thus generally indicate excessive amounts of blood that may represent haemorrhage or dilated congested blood vessels (usually as a result of acute inflammation or venous obstruction) if in the tissues, or thrombus if in a vessel or chamber of the heart. Many students think that necrosis looks black/dark brown. This is only so in certain situations (where there has been haemorrhage or alteration of haemoglobin) and in many instances necrosis appears pale. Also remember that necrosis has a lot of causes, not just infarction. Haemorrhagic/red infarcts appear dark red/brown/grey/black because of haemorrhage. Pale or anaemic infarcts are mainly pale due to lack of blood but they may have associated red/grey, etc. areas due to small amounts of haemorrhage in and around the dead tissue, surrounding vasodilatation from the acute inflammatory response or vascular granulation tissue formation in healing, depending on their age. You should learn the situations and organs in which pale and haemorrhagic infarcts occur as they have relevance for clinical situations and radiological appearances. Necrosis in a malignant tumour typically looks pale but it may look greyish (and friable) due to small amounts of bleeding associated with the necrosis. Gangrene (e.g. of appendix or foot) looks black because of the presence of altered haemoglobin, following diffusion of red blood cells from dead vessels. Many organs have associated pale yellow or orange coloured tissue, often not seen in anatomy prosections as it has been dissected away. This is adipose tissue and is normal, and it can vary in amount. It is important to recognise as it is commonly mistaken as being pathological (e.g. in the hilum of the kidney). Off-white or pale grey tissue tends to represent connective tissue or tumour (though not all tumours are white). Connective tissue may be normal or abnormal (scar/fibrosis). Muscle tends to look a bit like cooked meat i.e. grey-brown. There are many other features and terms that you should learn to understand and use e.g. cyst, abscess, cavity, polyp/polypoid (polyps may be sessile or pedunculated), villous or papillary architecture, ulceration. In relation to images in examinations, you may be asked (amongst other questions) about the: • diagnosis or differential diagnosis • morphological features • approximate duration or age of the disease process • predisposing factors and/or causes of the disease • pathogenesis of the disease • potential complications of the disease and how they arise • expected histological abnormalities in the abnormal areas 25 • patient’s expected clinical symptoms or signs or investigation results • different ways the abnormality may be biopsied and other basic investigations that might be relevant • relevant anatomy, microbiology, immunology, histology, physiology, genetics etc Answering the questions correctly will frequently require you to integrate several of these pieces of information. When it comes to assessment, you may be asked to describe the expected macroscopic features of various pathologies or even to describe the features in a photograph in the short answer question examination. 26
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