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1. Histopathology ECTs:5

2. Introduction By Hussein E. (BSc, MSc in Hematology and Immunohematology)

3. Learning Objectives Upon completion of this chapter, the student will be able to: Define pathology and Histolathology . Describe aspects of disease process Describe the Pathologic tissue changes Explain inflammation Describe neoplasia and neoplastic changes 3

4. Outline 1. Introduction 1.1 Pathology 1.2 Histopathology 1.3 Pathologic tissue changes 1.4 Inflammation 1.5 Introduction to Neoplasia 1.6 Purposes of histopathological examinations 4

5. 1. Introduction 1.1 pathology Pathology is the study of disease by scientific methods. The word Pathology originated from the Latin words “ Patho ” and “ logos ” . ‘Patho’ means disease and ‘ logos’ means study. Disease may be defined as an abnormal variation in structure or function of any parts of the body. 5

6. General pathology:- It is the reaction of cells and tissues to abnormal stimuli and to inherited defects . ►which are the main causes of disease . Systemic pathology:- It is the alterations in specialized organs and tissues . ►which are responsible for disorders that involve these organs.

7. Intro… Pathology gives explanations of a disease by studying the following four aspects of the disease namely: Etiology Pathogenesis Morphologic changes Functional derangements and clinical significance 7

8. Etiology Etiology of a disease means the cause of the disease. There are two major classes of etiologic factors: genetic environmental. Genetic factors includes : Chromosomal disorders (cytogenetic disorder); Mendelian disorders; Single gene diseases with non-classic patterns of inheritance; Multi factorial disorders: Multiple risk factors interacting to cause disease including molecular pathogenesis of diseases   8

9. Ethiolo… Environmental factors: Environmental causes of disease are many and are classified into: Physical agents; Chemicals; Nutritional deficiencies and excesses; Infections and infestations; Immunological factors. Physical agents Physical agents include trauma, radiation, extremes of temperature, and electric power etc…   9

10. Ethiol… Chemical agents These are chemical agents/ drugs used in industrial process and at home. Chemically induced injury has become very common. Their effects are vary and may include: Some act in general manner for example, cyanide is toxic to all cells; Others act locally at the site of application for instance, strong acids and alkalines Another group exhibit a predilection for certain organs involved in metabolic process, such as the effect of paracitamol and alcohol on liver cells. 10

11. Ethiolo… Nutritional deficiencies and excesses Nutritional deficiencies may arise as a result of poor supply, interference with absorption, inefficient transport with in the body, or defective utilization. On the other hand, dietary excesses play an important role in disease in western countries. Obesity has become increasingly common, with its attendant dangers of type 2 diabetes, high blood pressure and heart disease. 11

12. Ethiol… Infections and infestations Infection is invasion of the body by any pathogenic organism and the reaction of the host tissue to the presence of parasite or related toxins. Viruses, bacteria, fungi, protozoa, and metazoan can cause diseases May causes cell destruction directly as in viral infections (e.g., poliomyelitis) or protozoal infections (e.g.,malaria) Infestation is the establishment of arthropods up on or within a host. 12

13. Ethiol… Immunological factors The immune process is essential for protection against microorganisms and parasites. However, the immune system can be abnormal which can lead to disease. The abnormalities of the immune system include: Hypersensitivity reactions Immunodeficiency Autoimmunity Psychogenic disorders 13

14. Pathogenesis Pathogenesis is the mechanism through which the cause operates to produce the pathologic a l and clinical manifestations. The pathogenic mechanisms could take place in the latent or incubation period. The course of a disease in the absence of any intervention is called the natural history of the disease . 14

15. Pathoge.. The different stages in the natural history of disease include: Exposure to various risk factors B. Latency, that is the period between exposure and biological onset of disease; C. Biological onset of disease; this marks the initiation of the disease process, however, without any sign or symptom; D. Incubation (induction) period refers to variable period of time without any obvious sign or symptoms from the time of exposure; 15

16. Pathoge… E. Clinical onset of the disease, when the sign and symptoms of the disease become apparent.   F. The onset of permanent damage;recovery and /or death. 16

17. Morphologic changes The morphologic changes refer to the structural alterations in cells or tissues that occur following the pathogenic mechanisms. The structural changes in the organ can be seen with the naked eye or they may only be seen under the microscope. Those changes that can be seen with the naked eye are called gross morphologic changes and those that are seen under the microscope are known as microscopic changes . In addition, the morphologic changes will lead to functional alteration and to the clinical signs and symptoms of the disease. 17

18. Functional derangements and clinical significance The morphologic changes in the organ influence the normal function of the organ. By doing so, they determine the clinical feature (signs and symptoms), course, and prognosis of the disease. In general, understanding of the etiology, pathogenesis, morphologic changes, functional derangements and clinical significance of disease will help one to understand how the clinical features of different diseases occur and how their treatment works. 18

19. 1.2 Histopathology 19

20. 1.2 Histopathology Histology is the branch of anatomy which deals with the microscopic study of normal tissue structure. Normal Histology:- is the study of normal tissues. Histopathology is a branch of pathology that deals with tissue changes associated with disease or toxic effects. Emphasized in the histologic study of diseased tissue. 20

21. Clinical Significance of Histopathology To diagnose cancer To differentiate different types of tumor cells To identify the degree of malignancy (tumor grade) To confirm the complete removal of the cancerous cells after surgical removal 21

22. Tissues of the Body Histology: the study of tissues. Tissues: groups of cells which are similar in structure & perform common or related functions. Four Basic Kinds of Tissues: Epithelial Tissue Connective Tissue Muscle Tissue Nervous Tissue

23. 1. Epithelial Tissue O ccurs in sheets of tightly packed cells that: Covers the body Lines the cavities, tubes, ducts and blood vessels inside the body Covers the organs inside body cavities Epithelial Tissue Functions: Protection from physical & chemical injury, Protection against microbial invasion, Contains receptors which respond to stimuli, Filters, secretes & reabsorbs materials and Secretes serous fluids to lubricate structures.

24. Simple squamous epithelium ; - Squamous (meaning “scale”) - flat cells found on the surface of the skin (epidermis)

25. 2. Simple cuboidal epithelium - cells as tall as they are wide Kidney tubules, glands, lining of terminal bronchioles, etc.

26. 3. Simple columnar epithelium composed of single layered , tall, column shaped slender cells Glands, bronchioles, stomach, intestines, bile ducts, etc.

27. Mouth, throat, esophagus, urethra, skin (keratinized) Stratified - having multiple or stacked layers

28. Sweat gland ducts, salivary gland ducts, etc.

29. Mammary gland ducts, larynx, urethra (males)

30. Lines nasal cavity & sinuses, auditory tubes, trachea, bronchi

31. Bladder lining, ureters, and superior urethra Transitional - dome shaped surface cells

32. 2. Connective Tissue Connective tissue is made up of cells distributed through an extracellular matrix to bind and support other tissues. Loose connective tissue — the most widespread type of connective tissue in the body Attaches epithelial tissue to underlying tissues and holds organs in place.

33. Cont.… Connective tissue composed Matrix Cells Matrix - “non-living” component of connective tissue Ground substance Proteoglycan aggregates Fluid Minerals Fibers Collagen, Elastin, and Reticular Fibers

34. Cont.… Cells - “living” component of connective tissue Fibroblasts Macrophages Kupffer cells of the liver, alveolar macrophages of the lung, osteoclasts , Mast cells Plasma cells Leukocytes

35. 3. Muscle Tissue Muscle tissue , which accounts for about two-thirds of the bulk of a well-conditioned human , contains long, contractible cells designed - for movement and strength . Skeletal muscle , which is attached to bones by tendons , is responsible for most of the voluntary movements of the body. Cardiac muscle , which is striated and branched, forms the wall of the heart . Smooth muscle , which is found in the walls of most internal organs, contracts more slowly than other types of muscle but can remain contracted for a longer time.

36. 4. Nervous Tissue Are main components of the nervous system,ie ., brain, spinal cord & nerves . Nervous tissue is designed to sense stimuli and transmit signals from one part of the body to another. Nervous tissue consists of two groups of cell types: Nerve cells (Neurons ) Neuroglia - structural support for neurons E.g form BBB

37. 1.3 Pathologic tissue changes 37

38. Cellular Reactions to Injury Cell injury underlies all diseases. When a cell is exposed to an injurious agents the possible outcomes are:  The cell may adapt to the situation or  They cell may acquire a reversible injury or  The cell may obtain an irreversible injury & may die 38

39. Cont… The cell may die via one of two ways:  E ither by necrosis or by apoptosis 39

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41. 1.3 Pathologic tissue changes Cells are active participants in their environment, constantly adjusting structure and function to accommodate changing demands and extracellular stresses. As cells encounter physiologic stresses or pathologic stimuli, they can undergo adaptation, achieving a new steady state and preserving viability. The principal adaptive responses are : Atrophy Hypertrophy Hyperplasia Metaplasia 41

42. Atrophy Decrease in cell size and functional ability. It can be caused by decreased work load/disuse (immobilization), diminished blood supply, lack of hormonal or neural stimulation, malnutrition or aging. Physiologic: Ageing breast Uterus Ovary 42 -- Pathologic: Malnutrition Fracture

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44. Hyperplasia An increase in the number of cells in tissue or organ. Possible only in cells capable of cell division It can lead to an increase in the size of the organ. It is usually caused by hormonal stimulation. Physiological - breast in adolescent girl or during pregnancy Pathological - Nodular goiter 44

45. Metaplasia Metaplasia is the replacement of one differentiated tissue by another differentiated tissue. A reversible change of one cell type to another Usually in response to irritation. E.g. Bronchial epithelium - Protective against cigarette smoking irritation 45

46. Reversible and Irreversible cell There are clearly many ways to injure a cell, not all of them invariably fatal. The "point of no return," at which irreversible damage has occurred, is still largely undetermined; thus, we have no precise cutoff point to establish cause and effect. If the adaptive capability is exceeded, cell injury develops. Within certain limits, injury is reversible , and cells return to a stable baseline; however, with severe or persistent stress, irreversible injury results, and the affected cells die. 46

47. Morphology of reversible injury The ultrastructural changes of reversible cell injury include (1) plasma membrane alterations such as blebbing; blunting or distortion of microvilli; and loosening of intercellular attachments; (2) mitochondrial changes such as swelling and the appearance of phospholipid-rich amorphous densities; (3) dilation of the endoplasmic reticulum with detachment of ribosomes and dissociation of polysomes; (4) nuclear alterations, with disaggregation of granular and fibrillar elements. 47

48. Reverse… Two patterns of morphologic change correlating to reversible injury can be recognized under the light microscope: Cellular swelling Fatty change. Cellular swelling is the first manifestation of almost all forms of injury to cells When all cells in an organ are affected, there is pallor, increased turgor, and increased weight. Microscopically, small, clear vacuoles may be seen within the cytoplasm; these represent distended and pinched-off segments of the endoplasmic reticulum. 48

49. Reversi… This pattern of nonlethal, reversible injury is sometimes called hydropic change or vacuolar degeneration ; swelling of cells is reversible. Fatty change, occurring in hypoxic injury and various forms of toxic or metabolic injury, is manifested by the appearance of lipid vacuoles in the cytoplasm. It is a less universal reaction, principally encountered in cells participating in fat metabolism (e.g., hepatocytes and myocardial cells), and is also reversible. 49

50. Irreversible cell injury With continuing damage, the injury becomes irreversible, at which time the cell cannot recover. Irreversibly injured cells invariably undergo morphologic changes that are recognized as cell death. There are two types of cell death, necrosis and apoptosis, Two principal patterns of cell death are recognized; Necrosis Apoptosis which differ in their morphology, mechanisms, and roles in disease and physiology. 50

51. When damage to membranes is severe, lysosomal enzymes enter the cytoplasm and digest the cell, and cellular contents leak out, resulting in necrosis. Some noxious stimuli, especially those that damage DNA, induce another type of death, apoptosis, which is characterized by nuclear dissolution without complete loss of membrane integrity. Whereas necrosis is always a pathologic process, apoptosis serves many normal functions and is not necessarily associated with cell injury. 51

52. Necrosis Necrosis refers to a sequence of morphologic changes that follow cell death in living tissue (tissue placed in fixative is dead but not necrotic ). As commonly used, necrosis is the gross and histologic correlate of cell death occurring in the setting of irreversible exogenous injury. It’s most common manifestation is coagulative necrosis, characterized by cell swelling, denaturation of cytoplasmic proteins, and break down of cell organelles . 52

53. The morphologic appearance of necrosis is the result of two essentially concurrent processes : 1) Enzymatic digestion of the cell (autolysis). 2) Denaturation of proteins. The hydrolytic enzymes may derive from the dead cells themselves, in which case the digestion is referred to as autolysis . Enzymes leaked from damaged myocardium can be detected in the bloodstream as early as 2 hours after myocardial cell death. The classic histologic features of necrosis are not apparent until 4 to 12 hours after irreversible injury has occurred . 53

54. Morphology of Necrosis Dead cells show increased eosinophilia (i.e., pink staining from the eosin dye: the "E" in "H & E"). The cell may have a more glassy homogeneous appearance than viable cells, due mainly to the loss of glycogen particles. When enzymes have degraded the organelles, the cytoplasm becomes vacuolated and appears moth-eaten. Nuclear changes assume one of three patterns all due to non specific breakdown of DNA. pyknosis : characterized by nuclear shrinkage and increased basophilia; the DNA condenses into a solid shrunken mass. Karyorrhexis : Fragmentation of pyknotic nucleus. In 1 to 2 days, the nucleus in a dead cell completely disappears. karyolysis : Extensive hydrolysis (DNAse) of pyknotic nucleus with loss of staining (basophilia of the chromatin). 54

55. Types of necrosis The types of necrosis include: 1. Coagulative necrosis 2. Liquefactive necrosis 3. Fat necrosis 4. Caseous necrosis 5. Gangrenous necrosis 55

56. 1. Coagulative necrosis Cogulative necrosis most often results from sudden interruption of blood supply to an organ, especially to the heart ( Myocardial infarction). It is, in early stages, characterized by general preservation of tissue architecture. In an MI ( Myocardial infarction), in which acidophilic, coagulated, a nucleate cells may persist for weeks. Cogulative necrosis is marked by the following nuclear changes: Pyknosis (which is chromatin clumping & shrinking with increased basophilia), karyorrhexis (fragmentation of chromatin), & karyolysis (fading ofthe chromatin material). 56

57. In the instance of dominant enzymatic digestion, the result is liquefactive necrosis; in special circumstances, caseous necrosis or fat necrosis may develop. 2. Liquefactive necrosis Liquefactive necrosis is characterized by digestion of tissue. It shows softening & liquefaction of tissue . It characteristically results from ischemic injury to the CNS. 57

58. Cont.… The dead cell undergoes extensive autolysis, caused by the release of lysosomal hydrolases (proteinases, DNases, RNases, lipases, etc.) Liquefactive necrosis is also characteristic of focal bacterial or sometimes fungal infections, since these provide powerful stimuli for the accumulation of white cells. Seen classically in the spleen and brain following infarction. 58

59. 3. Caseous necrosis Caseous necrosis has a cheese-like (caseous, white) appearance to the naked eye. Microscopically, the necrotic focus is composed of structure less, amorphous granular debris enclosed within a distinctive ring of granulomatous inflammation . Unlike coagulative necrosis, the tissue architecture is completely destroyed. Caseous necrosis is typical of tuberculosis. 59

60. 4. Fat necrosis Fat necrosis can be caused by trauma to tissue with high fat content, such as the breast or it can also be caused by acute hemorrhagic pancreatitis in which pancreatic enzymes diffuse into the inflamed pancreatic tissue & digest it. Leakage of lipases from dead cells attack triglycerides in surrounding fat tissue and generate free fatty acids. The released fatty acids combine with calcium and produce grossly visible chalky white areas, which enable the pathologists to identify this disease on simple inspection. 60

61. 5. Gangrenous necrosis This is due to vascular occlusion & most often affects the lower extremities & the bowel. It is called wet gangrene if it is complicated by bacterial infection which leads to superimposed liquefactive necrosis. Whereas it is called dry gangrene if there is only coagulative necrosis without liquefactive necrosis. Necrosis can be followed by release of intracellular enzymes into the blood, inflammation or dystrophic calcification. 61

62. Irreverible… Apoptosis occurs as a result of an internally controlled "suicide" program, after which the dead cells are removed with minimal disruption of the surrounding tissue. This occurs in physiologic states when unwanted cells are to be eliminated (e.g., embryogenesis), as well as in a variety of pathologic states (e.g., irreparable mutational damage).   Apoptosis is a distinctive and important mode of cell death that should be differentiated from necrosis, although it does share some mechanistic features. 62

63. Irrevers.. Rather than the cellular "homicide" that occurs in necrotic cell death, apoptosis is a pathway of cellular "suicide." The programmed destruction of cells during embryogenesis, as occurs in implantation, organogenesis, and developmental involution. Deletion of autoreactive T cells in the thymus (>95% of thymocytes die in the thymus during maturation!), cell death of cytokine-starved lymphocytes, or cell death induced by cytotoxic T cells. A variety of mild injurious stimuli (heat, radiation, cytotoxic cancer drugs, etc.) that cause irreparable DNA damage that in turn triggers cell suicide pathways. 63

64. Irrevers… Morphology  Apoptosis usually involves single cells or clusters of cells that appear on H & E-stained sections as round or oval masses with intensely eosinophilic cytoplasm. The nuclear chromatin is condensed, and it aggregates peripherally, under the nuclear membrane, into well-delimited masses of various shapes and sizes. The cells rapidly shrink, form cytoplasmic buds, and fragment into apoptotic bodies composed of membrane-bound vesicles of cytosol and organelles. Moreover, apoptosis does not elicit an inflammatory response, further hindering microscopic recognition. 64

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68. 1.4. Inflammation 68

69. Inflammation The same exogenous and endogenous stimuli that cause cell injury also elicit a complex reaction in vascularized connective tissues called inflammation. Inflammation is a protective response intended to eliminate the initial cause of cell injury as well as the necrotic cells and tissues resulting from the original insult. Inflammation accomplishes its protective mission by diluting, destroying, or otherwise neutralizing harmful agents (e.g., microbes or toxins). 69

70. Inflamma… inflammation is also intimately interwoven with repair processes whereby damaged tissue is replaced by the regeneration of parenchymal cells, and/or by filling of any residual defect with fibrous scar tissue. Although inflammation helps clear infections and, along with repair, makes wound healing possible, both inflammation and repair have considerable potential to cause harm. Thus, inflammatory responses are the basis of life-threatening anaphylactic reactions to insect bites or drugs, as well as of certain chronic diseases such as rheumatoid arthritis and atherosclerosis. 70

71. Inflamma… The inflammatory response has many players. These include circulating cells and plasma proteins, vascular wall cells, and cells and extracellular matrix of the surrounding connective tissue. The circulating proteins include clotting factors, kininogens, and complement components, largely synthesized by the liver. The connective tissue cells include sentinels to invasion such as mast cells, macrophages, and lymphocytes , in addition to the fibroblasts that synthesize the extracellular matrix and can proliferate to fill in a wound. An initial inflammatory stimulus triggers the release of chemical mediators from plasma or connective tissue cells. 71

72. Inflam… Such soluble mediators, acting together or in sequence, amplify the initial inflammatory response and influence its evolution by regulating the subsequent vascular and cellular responses. The inflammatory response is terminated when the injurious stimulus is removed and the inflammatory mediators have been dissipated, catabolized, or inhibited. Inflammation is divided into two basic patterns. Acute inflammation Chronic inflammation 72

73. 1.Acute inflammation Acute inflammation is of relatively short duration, lasting from a few minutes up to a few days. Acute inflammation is characterized by fluid and plasma protein exudation and a predominantly neutrophilic leukocyte accumulation. Once there, leukocytes clear any invading microbes and begin the process of breaking down necrotic tissues. Cellular events: emigration of the leukocytes from the microcirculation and accumulation in the focus of injury (cellular recruitment and activation) 73

74. Inflamma… The major local manifestations of acute inflammation: (1) vascular dilation (causing erythema and warmth), (2) extravasation of plasma fluid and proteins (edema), (3) leukocyte emigration and accumulation in the site of injury. The cascade of events in acute inflammation is integrated by local release of chemical mediators. The vascular changes and cell recruitment account for three of the five classic local signs of acute inflammation: heat (calor), redness (rubor), swelling (tumor). 74

75. Inflamm… The two additional cardinal features of acute inflammation, pain (dolor) and loss of function (functio laesa. . Inflammation-Induced Tissue Injury limited tissue injury almost always accompanies the inflammatory response. release of lysosomal enzymes not only within the phagolysosome but also potentially into the extracellular space, where cell injury and matrix degradation result. In addition, activated leukocytes release reactive oxygen species, potent mediators capable of causing direct endothelial injury and tissue damage. 75

76. Inflam… leukocyte-dependent tissue injury from persistent and/or excessive leukocyte activation underlies many human diseases, including rheumatoid arthritis and certain forms of chronic lung disease. Outcomes of Acute Inflammation acute inflammation generally has one of three outcomes: Resolution. This involves neutralization or removal of the various chemical mediators, normalization of vascular permeability, and cessation of leukocyte emigration with subsequent death (by apoptosis) of extravasated neutrophils. 76

77. Inflamma.. Scarring or fibrosis results after substantial tissue destruction or when inflammation occurs in tissues that do not regenerate. Progression to chronic inflammation may follow acute inflammation, although signs of chronic inflammation may be present at the onset of injury (e.g., in viral infections or immune responses to self-antigens). 77

78. Chronic inflammation Chronic inflammation is of longer duration (days to years) chronic inflammation is characterized by the following: Infiltration with mononuclear ("chronic inflammatory") cells, including macrophages, lymphocytes, and plasma cells Tissue destruction , largely directed by the inflammatory cells Repair, involving new vessel proliferation (angiogenesis) and fibrosis 78

79. Chronic inflammation arises in the following settings: Viral infections: Intracellular infections of any kind typically require lymphocytes (and macrophages) to identify and eradicate infected cells. Persistent microbial infections: Most characteristically by a selected set of microorganisms including mycobacteria (tubercle bacilli), Treponema pallidum (causative organism of syphilis), and certain fungi. These organisms are of low direct pathogenicity, but typically they evoke an immune response called delayed hypersensitivity , which may culminate in a granulomatous reaction. Inflamma…

80. Inflamm… Prolonged exposure to potentially toxic agents Examples include non-degradable exogenous material such as inhaled particulate silica, which can induce a chronic inflammatory response in the lungs. Autoimmune diseases, in which an individual develops an immune response to self-antigens and tissues .(e.g., rheumatoid arthritis or multiple sclerosis ). Granulomatous Inflammation Granulomatous inflammation is a distinctive pattern of chronic inflammation characterized by aggregates of activated macrophages that assume a squamous cell-like (epithelioid) appearance. . 80

81. Inflam… Granulomas are encountered in relatively few pathologic states; Tuberculosis is the archetypal granulomatous disease due to infection and should always be excluded as a cause when granulomas are identified. Granulomas may also develop in response to relatively inert foreign bodies (e.g., suture, splinter, breast implant), forming so-called foreign body granulomas. The formation of a granuloma effectively "walls off" the offending agent and is therefore a useful defense mechanism 81

82. Definitions Neoplasia = new growth Tumor= swelling due to inflammation Oncology= oncos is tumor, logy is study Cancer= malignant tumors (crab)

83. 1.5 Introduction to Neoplasia 83

84. Neoplasm "A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change"

85. Fundamental to the origin of all neoplasms is loss of responsiveness to normal growth controls. Neoplastic cells are said to be transformed because they continue to replicate, apparently oblivious to the regulatory influences that control normal cell growth. neoplasms seem to behave as parasites and compete with normal cells and tissues for their metabolic needs. Tumors may flourish in patients who are otherwise wasting. 85 Neopl…

86. Neoplas… Neoplasms also enjoy a certain degree of autonomy and more or less steadily increase in size regardless of their local environment and the nutritional status of the host. All neoplasms depend on the host for their nutrition and blood supply. In common medical usage, a neoplasm is often referred to as a tumor, and the study of tumors is called oncology (from oncos , "tumor," and logos , "study of"). A tumor is said to be benign when its microscopic and gross characteristics are considered relatively innocent, implying that it will remain localized, it cannot spread to other sites, and it is generally amenable to local surgical removal; the patient generally survives. 86

87. Neoplas… Malignant tumors are collectively referred to as cancers, derived from the Latin word for crab -they adhere to any part that they grasp on in an persistent manner, similar to a crab. Malignant , as applied to a neoplasm, implies that the lesion can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death. Not all cancers pursue so deadly a course. Some are discovered early and are treated successfully, but the designation malignant constitutes a red flag. 87

88. Benign vs. Malignant Slow growing Encapsulated Expansile growth No Metastasis Well Differentiated Rapidly growing Non encapsulated Infiltrative growth Metastasis Well-Poorly differentiated

89. Malignant tumors Mesenchymal = sarcomas ( sar, fleshy). Fibro sarcoma , lipo sarcoma , leiomyo sarcoma Epithelial = carcinomas, glandular – adeno carcinoma , squamous – squamous cell carcinoma

90. Tissue of origin Benign Malignant Mesenchymal/ connective tissue Fibroma Lipoma Chondroma Osteoma Fibrosarcoma Liposarcoma Chondrosarcoma Osteogenic sarcoma Endothelial and related tissues Hemangioma Lymphangioma Meningioma Angiosarcoma Lymphangiosarcoma Synovial sarcoma Mesothelioma Invasive meningioma Hematopoietic Leukemias Lymphomas Muscle Leiomyoma Rhabdomyoma Leiomyosarcoma Rhabdomyosarcoma Epithelial Squamous papilloma Adenoma Papilloma Cystadenoma SCC or epidermoid CA Adenocarcinoma Papillary carcinoma Cystadenocarcinoma Melanocytes Nevus Malignant melanoma

91. 1. Anaplasia Lack of differentiation Hallmark of malignant transformation Numerous morphologic changes

92. Diagnosis clinical ( tumor markers, labs) gross cytology histology (ihc) molecular biology and cytogenetics most important, early detection.  screening

93. Treatment surgery radiotherapy chemotherapy immunotherapy hormonotherapy gene therapy

94. Death of Tissue Necrosis – premature pathological death. Gangrene – tissue necrosis due to insufficient blood supply. Infarction – sudden death of tissue due to obstruction of artery carrying its blood supply by a blood clot (thrombus) Apoptosis – programmed cell death. 94

95. Important terminologies Differentiation: The tissue type represented by the tumor. Well-differentiated tumors resemble the tissue of origin while poorly differentiated tumors may only be identifiable by the expression of cell markers. Anaplasia: Loss of differentiation

96. Dysplasia: An abnormal proliferation of cells characterized by changes in cell size, shape, nuclear enlargement and failure of maturation and differentiation . It is not cancer but may progress to cancer Invasion: Growth into the surrounding tissue by direct expansion. Metastasis: Spread of tumor to distant sites by lymphatic or hematogenous routes.

97. 1.6 Purposes of histopathological examinations Diagnostic techniques that can be used in pathology to diagnose the disease include: Histopathology Cytopathology Hematopathology Immunohistochemistry Cytogenetic, Microbiological examination Biochemical examination Molecular techniques and Autopsy. 97

98. Purpose… Histopathological Techniques Histopathology is the microscopic study of excised or removed tissues affected by certain diseases. It is usually the gold standard for pathologic diagnosis. The procedures adopted for the preparation of materials for such studies (Histopathology) are known as Histological or Histopathological techniques. It is with these techniques that the medical laboratory personnel in the Pathology Department are primarily concerned. 98

99. Purpose. . Cytopathology is the study of cells from various body sites to determine the cause or nature of disease. The main applications of cytopathology include:  Screening for the early detection of asymptomatic cancer;  Diagnosis of symptomatic cancer;  Follow up of patients treated for cancer. The different types of cytopathologic methods include:  Fine-needle aspiration cytology (FNAC);  Exfoliative cytology;  Abrasive Cytology. 99

100. Purpose… Hematopathology is the study of abnormalities of the cells of the blood and their precursor in the bone marrow to diagnose different kinds of anemias and leukemia’s. Immunohistochemistry is used to detect a specific antigen in a tissue in order to identify the type of disease. It is also useful to identify the type of disease and associated organ (s) involved (histogenesis). Microbiological examinations are methods by which body fluids, excised tissue and other samples are examined by microscopy, culture and serological techniques. 100

101. Purpose… Biochemical examinations are methods by which the metabolic disturbances of diseases are investigated by assay of various normal and abnormal compounds (proteins, lipids, enzymes, etc) in the blood, serum, urine and other clinical samples. Molecular techniques such as polymerase chain reaction (PCR), fluorescent insitu hybridization, southern blot and northern blot can be used to detect specific genetic diseases. Autopsy is examination of the dead body to identify the cause of death. This can be used for forensic or clinical purposes. 101

102. Samples for Hi s topathology lab Biopsy –specimen from patients taken by clinician, surgeons or gynacologist Necropsy –lesion representation from post mortem examination Scrapes sampling - easily from approachable body surface by spatula uterine cervix Aspirations - sampling from solid organ using needle Body fluids - body space eg. peritoneal, CSF

103. Review questions Explain the difference between histology and histopathology. Discuss the different diagnostic techniques used in pathology. Elaborate the categories of cause of disease. 103

104. References Cotran, Kumar and Callins. 1999. Pathologic Basis of Diseases. 6th edition. 2 . Paula A Rodriguez Urrego , Department Of Pathology & Laboratory Medicine RWJMS-UMDNJ January 17,2007 104