Morpho Pathology Review

1

Morpho-‐pathology Final Summary (Based on 1,2,3,4,5,6,7 chapters from Mr.Paiusan’s material and personal extras)

Alessandro Motta, Medicine Class in English, 3rd Year, UVVG

Chapter 1: Cellular reactions to aggression On this chapter we can jump a lot of notional material and focus on some keywords and few categories’ lists. Hypoxia: reduction of tissue oxygenation Anoxia: missing of tissue ox. Noxious Agents affecting tissue’s health status:

• Chemicals such as: strong acids/bases, poisons, “everyday” chemicals, substances found in workplaces, social chemicals (alcohol, cigarettes…)

• Physical agents: mechanical traumas, extreme temperatures, ionizing radiation, electricity etc.

• Infective/biological: bacteria, viruses, fungi… Adaptive cellular changes are performed by tissues to fight these aggressions, usually follows a recover but they could trigger also pre-‐cancerous stages, these is a quick revise:

• Hypertrophy: increase of volume/weight, either physiological (muscle) or pathological (cardiac)

• Hyperplasia: similar to the abovementioned but with an increase in numbers of tissue’s components, physiological in pregnancies, pathological for hormonal causes

• Atrophy: or involution is defined as the reduction in volume of a tissue or organ, previously normally developed. Either physiological (thymus, senility) or path. (Severe chronic diseases or prolonged immobilization)

• Metaplasia: means the transformation of a specialized tissue in other specialized tissue, but more resistant to the action of harmful agents.

• Dysplasia: It is more common in the epitheliums, due to action of extremely harmful agents. It is often associated with metaplasia or hyperplasia, and is being called atypical hyperplasia. It is considered more degenerative than an adaptive reaction.

If these stages are not enough to the survival of our damaged tissues it can develop two types of death: NECROSIS: uncontrolled cellular death, derived by traumas, noxious agents and anoxia. APOPTOSIS: process characteristic for programmed cell death during organogenesis and hormone-‐dependent involution occurs in adults (e.g. endometrium during menstruation). It is seen also in certain diseases, such as certain viral infections (viral hepatitis)

2

Types of cell necrosis:

1. Coagulation: triggered by brutal loss of oxygen supply (infarct), necrotic tissues are visually opaque, dry, and gray-‐whitish, with slightly higher consistency. Considered a structured necrosis.

2. Liquefaction: found in cerebral infarctions (ramollissement) and in the areas of necrosis in case of suppurative bacterial infections. Unstructured.

3. Caseous: Represent a variety of coagulation necrosis, characteristic of tuberculosis infection. Macroscopic, the cazeum looks like fresh cheese or casein. Unstructured.

4. Fat: called also steatonecrosis, fat necrosis is common seen in acute pancreatitis. In this disease occurs autodigestion of the organ due to local activation of enzymes from pancreatic juice composition. Lipase will decompose peripancreatic fat, with the release of free fatty acids that will combine with calcium, triggering a local saponification process. Unstructured.

5. Gangrenous: superimposed a process of putrefaction. It is caused by bacteria that trigger degradation of local structures, with gas release that gives a fetid smell and emphysematous consistency of affected tissues. Primary gangrene (gas gangrene) is produced by a group of anaerobic bacteria, and often occurs as a complication of traumatic wounds. The tissues are very dilated through the gas bubbles (crepe on palpation) and extremely painful. Secondary gangrene may be dry or wet. Dry form is more common in diabetes.

This is a nice interactive video with great explanations of necrosis’s steps: http://www.susanahalpine.com/anim/KubyHTML/Celdeath.htm Chapter 2: Degenerative processes Dystrophies This chapter provides only a list of types and subtypes of accumulation in intracellular or intercellular accumulation of substances, related to metabolic or enzymatic processes. Here I have to copy the same first division in categories:

- Dystrophy with predominant intracellular accumulation: o protein dystrophy: hydroproteique, nucleoproteique and

chromoproteique; o fat dystrophy; o carbohydrate dystrophies o mineral dystrophy.

- Dystrophy with predominant intercellular accumulation: o hyaline dystrophy; o amyloid dystrophy; o fibrinous dystrophy; o mucinous and mucoid dystrophy;

3

Dystrophies types one by one super-‐summary (revise them one by one from the word file before the exam, I do not want to loose time with details): Hydro-‐proteic: cells are no longer able to maintain fluid and electrolyte homeostasis, this leads to swelling (intumescent) cells. Increase in cell volume is due to the swelling of mitochondria. Are early lesions that occur after many cell aggressions, and are often reversible. Nucleo-‐proteic: depositing in tissues of uric acid and urate, of endo, or exogenous origin. The most important complication of hyperuricemia is the gout. Acute attack of gout is manifested as arthritis, with all signs of acute joint inflammation. In chronic gout, uric acid crystals are deposited in peri-‐articular tissues, forming so-‐called gout tophi. Chromo-‐proteic: pigments are colored substances, accumulated in some diseases. Two main subtypes:

1. Melanin: brown-‐blackish endogenous pigment, physiological accumulation occurs in pregnancies and pathological one in Addison’s disease

2. Bilirubin: yellow-‐green, produced by spleen, liver or bone marrow from hemoglobin, first stage in unconjugated, then in the liver becomes associated with glucuronic acid (conjugated). The consequence of accumulation is the Jaundice, which can be:

• Pre-‐hepatic ( unconjugated in bloodstream) • Hepatic ( unconjugated and conjugated in b.s.) • Post-‐hepatic (conjugated in b.s.)

Fat: by triglycerides triggers steatosis, with fomations of vacuoles and fatty cysts, a typical one is the Hepatic steatosis. By cholesterols triggers atherosclerosis, xanthomatosis or cholesterolosis. Carbohydrate: Diabetes mellitus is a metabolic disturbance, characterized mainly by hyperglycemia, resulted from a relative or absolute deficiency of metabolically active insulin. The etiology of this condition is not completely elucidated. There are two types of diabetes: insulin-‐dependent (juvenile) and non-‐insulin-‐dependent. This disease affects kidneys, pancreas, SNS, and gives also retinopathies, vascular diseases. Mineral: related to calcium metabolism disorders. Abnormal deposit of calcium in tissues is called pathological calcification, classification name them as dystrophic and metastatic. Hyaline: is a substance with a variable structure, incompletely studied, but essentially consists of proteins or glycoproteins. deposits can occur in both physiological and pathological conditions. Normally, hyaline occurs in the ovarian corpus luteum involution, in uterine arteries after menopause, and old scars. Pathological hyaline deposits are found in the serous membranes after chronic inflammations or in the benign or malignant tumors mass. Amyloid: pathological protein substance stored in various interstitial tissues and organs, in association with various clinical manifestations. Pathogenesis of

4

amyloidosis is not sufficiently elucidated so far, but immunological mechanisms appear to be particularly important. It can be divided in primary and secondary. Fibrinoid: eosinophilic substance, homogeneous or finely granular, showing similar tinctorial affinity with fibrin. The chemical composition is complex, including proteins and mucopolysaccharides and sometimes fibrin and gamma globulin. Are part of collagenosis disease. Mucinous and mucoid:

• Mucin: occurs in catarrhal mucosal inflammations, and in some neoplasm (mucinous carcinoma). These tumors are characterized by an intracellular accumulation of mucin, which pushes the nucleus to the periphery

• Mucoid: accumulations occur in certain connective tissue pathological conditions such as myxedema, or in certain mesenchymal tumors such as myxomas.

Chapter 3: Hemodynamic dysfunctions The terms hyperemia and congestion both indicate a local increased volume of blood in a particular tissue. Hyperemia is an active process resulting from augmented blood flow due to arteriolar dilation (e.g., at sites of inflammation or in skeletal muscle during exercise). The affected tissue is redder than normal because of engorgement with oxygenated blood. Congestion is a passive process resulting from impaired venous return out of a tissue. It may occur systemically, as in cardiac failure, or it may be local, resulting from an isolated venous obstruction. The tissue has a blue-‐red color (cyanosis), especially as worsening congestion leads to accumulation of deoxygenated hemoglobin in the affected tissues. Once again: Active Hyperemia: increased arterial blood supply to a tissue’s limited area, in terms of normal venous drainage. The result is local accumulation of increased blood volume, especially in the arterioles and capillaries. Passive Hyperemia: or congestion implies increased accumulation of blood in the capillaries and venules, as a result of insufficient venous drainage when there are normal intake pressure. It could be localized or systemic. Some featured cases:

5

Acute lung stasis occurs in the left heart failure, sudden, and has the major consequence pulmonary edema. Chronic lung stasis occurs due to left heart failure slowly installed, allowing pulmonary circulation to adapt to congestion. Lung weight and volume are increased, low elasticity and crepitation, rusty red color. Stasis liver occurs most commonly as a result of right heart failure, with increased pressure in the inferior vena cava. Mostly blood is stagnating in the veins and capillaries of centrilobular sinusoids.

1. Hemorrhages: loss of blood from circulatory system It could comes from the vessel’s interruption or by erythrodiapedesys (extravasation of blood trough healthy vessel, common of inflammation process) We can have several clinical forms of hemorrhages, external and internal are rough divisions. Then further ones: Interstitial Petechiae: punctiform hemorrhages, capillary origin, produced in the skin, mucous or serous Ecchymosis: larger hemorrhagic spots, diffuse, without tissue swelling. Purpura: spontaneous tegumentary hemorrhage, with diameters ranging between petechia and ecchymosis Hematoma: establishment of a collection of blood that deforms interstitial tissue. Apoplexy: large area of hemorrhagic tissue infiltration, to which are added and alteration of affected tissue. The term is used especially for cerebral and utero-‐placental hemorrhages Hemorrhages of serous cavities: Hemothorax, hemoperitoneum, hemopericardium, hemarthrosis and hematocele(testicular). From internal organs to the outside: Hematemesis: vomiting of blood coming from the digestive tract hemorrhages (gastric ulcer, cirrhosis with rupture of esophageal varices) Hemoptysis: expectoration of blood from broncho-‐pulmonary hemorrhages (lung tuberculosis, broncho-‐pulmonary cancers) Melena: digested blood through stool (duodenal ulcers) Proctorrhagia: removing fresh blood through stool (hemorrhoids) Hematuria: blood elimination in the urine (urinary stones) Menorrhagia: abundant and prolonged menstruation Metrorrhagia: inter-‐menstrual hemorrhages Epistaxis: hemorrhage from nasal fosses. The seriousness of the hemorrhage may depends of course by the quantity of blood loss but also by the place of installation (check out how dangerous are small cerebral hemorrhages), even 20% of blood loss from circulation have clinical relevance, even less for chronic bleedings in debilitated patients.

6

2. Thrombosis: formation process on the cv system of semi-‐solid masses called thrombi.

It is a pathological process, which is an extension of abnormal hemostasis. Basically, there are three thrombogenic factors:

• Endothelial/endocardial lesions • Alterations in blood flow • Blood hypercoagulability

By the morphological point of view a thrombus can be:

• White, of conglutination, fibrin smaller amount, in arteries, hard, slow-‐grow • Red, coagulation, in veins, fibrin and blood cells components, soft, • Mixed, levels of intercalated white and red components There are four clinical anatomical forms of thrombosis: • Cardiac Mural: by formation either in atrium, ventricles or valves • Arterial:less common due to speed of bloodstream • Venous: most common, called phlebothrombosis, predominantly in the

lower limbs due to stagnant blood. • Capillary: can occur during acute inflammation in a particular syndrome

which is called disseminated intravascular coagulation. If patient survives the first occlusion the thrombus can undergo other pathways such as extension, disaggregation, mobilization (thromboembolism) or reorganization of the vessels and reabsorption.

3. Embolism: transport in bloodstream of insoluble masses named embolus, that could stop in a vessel far away from its origin, and could create an infarction of that area.

Categories of emboli by nature: solid, liquid, and gaseous. These are the most common and their consequences may vary upon their nature: • Thromboembolism, 99% of all of them, they could evolve in pulmonary

(most silent -‐> dyspnea or giving right heart failure) or systemic (depends where the embolus stops).

• Fat: consequence of long bones fractures, released by adipose panicle. • Gas: because of difficult pregnancy, pneumothorax or in case of deep diving

with a sudden decompression. • Amniotic fluid: due to difficult births, may cause mother’s exitus (death).

4. Infarction: area of ischemic necrosis tissue produced as a result of brutal and complete interruption of arterial irrigation which serves that territory

An infarct differs from an ischemia only because the interruption of oxygen supply is more rapid and involves an entire vascular portion. Thrombosis and embolisms usually cause it. Consequences may vary according to the oxygen sensitivity, the vascular architecture and the functional status of the organ/area. They are classified as follows:

7

• Regular: have triangular shape per section, pointing to the hilum and the periphery toward the organ. Of course, seen spatially, these infarcts have a conical shape

• Irregular: in circulation anastomotic organs. This is seen in the myocardium, which are normally small anastomoses between three major coronary trunks: anterior descending left, left circumflex and right coronary. Others will at least for a while, complement occlusion of one of them.

• White: (anemic) occur in the organs with compact terminal circulation: kidney, spleen, myocardium

• Red: (hemorrhagic) are found in soft organs, with double circulation (lung) or anastomotic (gut). Venous obstruction, regardless of their location, is hemorrhagic infarcts.

5. Edema: abnormal accumulation of fluid in the interstitial space and /

or in body cavities. • These are key steps of its mechanism of formation: • Increased hydrostatic pressure; • Reduced oncotic pressure within blood vessels; • Increased tissue oncotic pressure; • Increased blood vessel wall permeability e.g. inflammation; • Obstruction of fluid clearance via the lymphatic system; • Changes in the water retaining properties of the tissues themselves.

Raised hydrostatic pressure often reflects retention of water and sodium by the kidney.

It may be also localized (as ascites for peritoneum or hydrothorax for lungs) or generalized and called anasarca (as a consequence of hearth, renal failure or nutritional causes)

• The Shock: circulatory collapse, resulting in tissue hypoperfusion and hypooxygenation. It is an acute imbalance between content (blood mass) and container (blood vessels), generated mainly by three mechanisms:

• decreased cardiac output; • generalized peripheral vasodilatation; • reduction of circulating blood volume.

It can be defined and divided also in terms of how it generates:

• Cardiogenic • Hypovolemic • Septic • Anaphylactic

I’ll not describe them one by one because I think each of us knows them from physiopathology, don’t’ ya ?!

8

Chapter 4: Inflammation (the easier to summarize, the most important to understand)

Inflammations are vascular, cellular and humoral reactions against harmful agents. This tries to destroy, dilute or neutralize noxious and protect body against aggression, may excess protective mechanisms and become harmful itself. Inf. involves all elements present in vascularized connective tissue. There are two kinds of inflammatory events: ACUTE: called also exudative, it lasts minutes to few days, usually ends with full resolution/no damages, is characterized by exudate production and leukocytes migration. Typical and classical morph pathological signs: • CALOR, increased temperature due to hyperemia • RUBOR, erythema formation triggered by vasodilatation • TUMOR, swelling, tissue distension, edema • DOLOR, local pain, due to compression of nerves terminations and release of

chemical mediators • FUNCTIO LAESA, reduction of functional properties

Mechanism:

Transitory short vasoconstriction (histamine/serotonine) Vasodilation of afferent arterioles accumulation of blood Active

Hyperemia Increased extravasation of fluid with high protein content more colloid-‐

osmotic pressure more fluid migration Exudate formation Decreased blood velocity accumulation of leukocytes Leukocytes will adhere through adhesive molecules to endothelial cells and

will leave vessels with a process named diapedesis

9

Leukocytes of inflammation process

Polymorphonuclear: most common, first activity Monocytes – Macrophages: replacing abovementioned after 1-‐2 days, longer life, proliferates in the in the inflammatory outbreak, phagocytes larger particles Lymphocytes: usually for chronic inflammation but present in acute inflammations of viral etiology Polymorphonuclear/eosinophils: characteristics for allergic reactions or parasitical ones.

How does leukocytes are involved in inflammatory process? 1st step Chemotaxis: is a migration process of leukocytes to aggression foci through chemical gradient • Phagocytosis: ingestion of material particles, acts in several stages: • Opsonization: overlaying material to immobilize foreign particles • Formation of the phagosome, a vesicle formed by Pseudopodia from the macrophage/monocytes

• Phagosome and lysosome cytoplasm form the phagolysosome, triggering leukocyte degranulation

• Intracellular bacterial destruction What are the possible evolutions of an Acute Inflammation? Complete Resolution Incomplete resolution Conversion into chronic inflammation

Which are the categories of acute inf.? • Catarrhal: viral/pollution etiology rhinitis 1° watery exudate, 2°

viscous, 3° mucopurulent • Pseudomembranous: usually of mucosae diphtheria

pseudomembranous exudations low invasive rate but rapid multiplication of bacterias

• Serous: of serosas accumulation in cavities parenchymal organs/teguments often at 1° stage of inflammation

• Fibrinous: serous membranes/lungs fibrin-‐rich exudate healing with sequels

• Suppurative (purulent): due to pyogenic germs toxins produce local necrosis as abscesses (circumscribed) or Phlegmon (diffused)

• Hemorragic: exudate + RBCs, encountered in TB, cancer or anthrax.

10

CHRONIC: or proliferative, has long-‐acting effect, with proliferations of granulation tissues (with macrophages) These inflammatory manifestations interpenetrate with destruction phenomena and attempts of regenerations; hence it could start as a “de novo” process, not only after an acute phase. Three key differences from the Acute to the Chronic: • Monocytes inf. infiltrate with macrophages • Tissue alteration • Granular tissue proliferation Macrophages are characteristics forming granulomas Lymphocytes lead antibody-‐mediated immunity and cell-‐mediated one. The leucocytic positive feedback:

• Plasmocytes: local source of antibodies • Plomorphonuclear: can be found in chronic inf. • Tissue Necrosis: due to chemical mediators released by macrophages action • Granulation: formation of new tissue Here we can find several different types of Chronic Inf.: Non-‐specific Proliferative are exudative reactions and proliferation of

granulation tissue (E.g.: chronic hepatitis, nonspecific nephritis/myocarditis)

Granulomatous inf. with partial specificity, can just suggest the etiology, are not taken in account for a sure diagnosis: 1. Granulomas from infectious diseases (typhoid fever, viral inf., chlamidia) 2. Foreign body granulomas, induced by exo/endogenous bodies 3. Granulomas with relatively uncommon diseases (collagen disorders,

sarcoidosis, legionnaire’s, etc.) Specific granulomatous inf. (microbial/parasitic nature, easy to identify) In this last type we have to pay attention about TB, Syphilis and parasitic inf. TB: tuberculosis generates a series of uncommon morphological reactions: Exudative: most early stage, like pulmonary macrophages alveolitis, serous/fibrinous exudate, resolution usually after 10 days, gives caseous necrosis / TB follicle / carnification Proliferative: single lesion complex Koster’s tubercular follicle (conglomerate of macrophages) (composed by Langhan’s giant cells + epitheloid cells + lymphocytic infiltrate) Alterative: coagulation necrosis called “cazeification” (most common pathway)

Lymphocytes Lymphokines

Macrophages Monokines

11

Nodular: circumscribed military (1mm) / simple (1mm to 3cm) / acinous (larger, alveolar-‐like shape) / tuberculoma (pseudotumoral, 10 cm) Ulcerative: resulting from caseous masses gives either ulcers or caverns and are source of hemoptysis Diffuse: from caseous bronchopneumonia It has a primary and a secondary form: Primary: first contact with Koch bacillus, primo infections is called Ranke primary complex, with various compliances and evolutions Secondary: re-‐infection, reactivation of dormant bacilli. Syphilis: an infectious disease with chronic evolution, caused by treponema pallidum spirochete, considered as a venereal disease. It could be either gained or congenital, for gained it could be: Primary: starts three weeks after infection, manifestation located on external genital organs, the specific lesion is called syphilitic chancre, gives ulcerations. It disappears after 5 weeks of evolution. Secondary: multiple and superficial rash, it has several ways of evolutions, and once again disappears for a third apparent healing period. Tertiary: an evolution of previous stages, can lasts from few months up to 30 years, characterized by nodular lesions or diffused ones. Congenital type: result of trans-‐placental infection from mother to child, it could be fetal, infantile or late congenital. Parasitic inflammation: chronic granulomatous inflammatory processes, specific of different forms of parasites. Vegetal: candidosis, actinomycosis. Animal: toxoplasmosis, trichinellosis Chapter 5: Healing Processes Means replacement of necrotic tissue by a viable one, with full or partial restoration of structure/functions. Regeneration is the replacement of destroyed cells from a tissue organ through proliferation of cells by the same type. The success depends on cells affected: Labile cells have high rate of destruction and replacement (squamous and glandular

epithelium) and high capacity of reg; Stable cells have low rate of proliferations, but can be stimulated to regenerate after

injuries (hepatocytes) Permanent cells after full development cannot multiply themselves and cannot

regenerate (mature neurons) Another success factor is the affected organ architecture: Simple structure will be easier to rebuild than a complex one Quantity of destroyed tissue: essential is remaining of a sufficient number of

specialized cells

12

Complete resolution is a healing mechanism in conditions of minimal tissue damage with focal or unicellular limited necrosis. Destroyed cells are replaced through proliferation of specialized cells in the vicinity. Reparation is characterized by organization (replacement of damaged cells by an unspecialized connective tissue, resulting in a fibrous scars), and these are the stages of this process: • Phagocytosis by macrophages • Proliferation endothelial cells and fibroblasts from the edge of affected area • Endothelial cells penetrate in the area, building a capillary network, that will

restore the blood flow • Fibroblast migrate along new network, making a conjunctive skeleton • Proliferation of collagen fibers with formation of a scar Cutaneous Wound Healing is a mixed process, consisting of a combination of specific mechanisms of regeneration and repair. Depending on the amount of destroyed tissue, the persistence of inflammatory reactions, surgical approach, to wound healing is of two types: • First intention: uninfected wounds, with minimal lack of substance, such as

surgical incisions. It takes place as follow a blood clot emerge on the edges to prevent dehydration or infections, then will act normal inf. response associated with the formation of unstratified epithelial layer, follows the granulation (small amount), removing the clot and what remain is just a linear scar.

• Second Intention: in unsutured wounds or more extensive ones, it has some stages as the 1° type but with: more granulation tissue, uncomplete epidermic restoration, smaller scar but with stronger contractions (deformations of affected segment)

Chapter 6: Immunopathy, consists of: Immunodeficiency: make the organism vulnerable to the action of inf. agents and development of neoplasies Exaggerated response: as anaphylactic shock and hypersensitivity Autoimmune diseases: immune system loses its ability to distinguish between self and non-‐self components. Here we summarize 4 types of hypersensitivity reactions: 1. Type I: anaphylactic type, manifestation appears after few minutes of

exposure to the antigen by antibody synthesis of IgE; they determine the activation of mast cells and basophils polymorphonuclear, which release mediators of anaphylactic reactions (E.g. histamine). Mediators action cause: vasodilation, increased vascular permeability, smooth muscle contraction, protein substances lysis. Clinical manifestation: allergic rhinitis, asthma, and circulatory collapse.

2. Type II: antibody mediated cytotoxicity, IgM and IgG initiates complement activation, with membrane alteration or activation on NK (natural killer)

13

which in turn will destroy the target cells. Clinical Manifestations: haemolitic anemia, basedow disease.

3. Type III: IgM, IgG and IgA form antigen-‐antibody complex, that can be deposited in various tissues; lesions may occur by attraction and activation of neutrophils and thrombocytes. Is involved in collagenosis.

4. Type IV: mediated by lymphocytes type T, involved in rejection of grafts and transplants.

In Immune reactions of transplant rejection are involved cell-‐mediated and antibodies immunity. It has three subcategories: (E.g. is Kidney’s transplant) • Super-‐Acute: is mediated by antigen-‐antibody reaction in vascular

endothelium and manifestation is immediate after surgery. Kidney appears cyanotic and secret few drops of hematic urine.

• Acute: from days to years, involves cellular and immune mechanisms. Cellular one is manifested by a rich interstitial monocyte inf. infiltrate while humoral by necrotizing vasculitis and thrombosis / neutrophilic infiltration

• Chronic: months or years, announced by a progressive increase of serum creatinine, vascular lesions, cellular inf. infiltrate are mainly plasma cells and eosinophils.

Autoimmune diseases to focus on in this chapter are lupus, scleroderma and AIDS. Systemic Lupus Erythematosus: affects skin, joints, kidneys and serous membranes. It causes necrotizing vasculitis, glomerulonephritis, tegumentary (butterfly shaped facial erythema, hives, rashes and ulcerations); joint level (non-‐erosive synovitis) Scleroderma: excessive fibrosis of the skin and internal organs. Morphologically: formation of collagen tissue deposits. Can be diffuse or localized; the skin is initially edematiate and after atrophyzed. Microscopically gives deposits of collagen in the dermis and hyaline thickening. The digestive tract is affected at esophagus level; mucosa and interlobular arterioles in kidney are thick because of collagen as abovementioned. At heart level it can cause pericarditis and myocardial fibrosis, it can cause also thickening of alveolar and vascular walls in lungs. AIDS: given by the HIV retrovirus, contracted by sexual contact, parenteral use of needles or congenital. It spreads in the collapse of the immune system, cell mediated immunity initially and lately humoral immunity. There are 2 phases, an asymptomatic period of variable duration and period of clinically manifest disease (AIDS-‐related complex = ARC) And now starts the interesting part… !

14

Chapter 7: Tumors This is the harder one, though to summarize and to study, but probably the most critical at the exam. A neoplasm (Tumor) is an abnormal mass of tissue, as a result of an uncontrolled and excessive irreversible proliferation. Cancer could develop in almost all kinds of tissues. The term is related to Tumor as swelling in classic inflammations. Nowadays tumors are defined for their microscopic characteristics and divided in benign and malignant (cancer). It could starts either by epithelium or conjunctive. It is made up of two aspects: the parenchyma (neoplastic cells mass) and the stroma (sustaining/nutritive role). Incidence of tumors depends on several aspects: geographic factors, age, sex, race, inherited predisposition and acquiring of pre-‐neoplastic lesions or conditions. Carcinogenesis: means the process of formation from normal to malignant cells, and there are a series of factors that are involved, such as: • Chemicals (aromatic hydrocarbons = cigarettes smoke triggers lung

carcinoma) • Viruses (IMPORTANT): Papilloma virus (cervical cancer), Epstein-‐Barr

Virus (for Burkitt Lymphoma) • Radiant Energy (ultraviolet for malignant melanoma, or ionizing radiation

specially for leukemias) They can alter the genetic unit of cells in 2 ways: inactivation of tumor suppressor genes or activation of some tumor stimulating genes (oncogenes). Bio morphological Characters of Tumors in comparsion:

Types: Benignant Malignant

Evolutional feat. 1. Slow grow, period of

stagnation or regression 2. No local invasion, no

relapse after surgery 3. No metastasis

4. No cachexia or death

1. Generally rapid evolutions 2. Local invasion and post-‐

operative recurrence 3. Gives metastasis 4. Cachexia and death

Clinical effects Do not destroy surrounding tissues, only compression of

adjacent structures Systemic effects generally

absent

Infiltrates invades and destroys surrounding tissues. Systemic effects are noisy, generates metastases and abnormal substances

(paraneoplastic syndromes)

15

Macroscopic feat. High consistency and color similar to original tissue.

Usually encapsulated, oval and well defined formations in parenchymal organs.

In teguments/mucosae grow vegetant polyps (sessile or

pedicle)

Decreased consistency and soft tumor tissue. White-‐gray for carcinomas and reddish-‐hemorrhagic for sarcomas. In parenchymal organs are

irregular, not well delimited and without envelopes. On teguments have 3 kinds of

grows: vegetant-‐fungal, diffuse on surface, infiltrative.

Microscopic feat.

Mature differentiated numerical increased cells,

morpho/functionally similar to original cells. Architecture generally is not disturbed,

nuclei are uniform in shape and configurations, rare mitosis and

seems typical.

Immature cells, no original cells morphology (anaplasia), malignant cells may stop in various evolution stages, with irregular shape, volume,

dimension (polymorphism). Increase usually in volume with irregular membranes, bizarre/monstrous giant cells. Architecture is deeply altered. Nuclei have important changes. Check below…

Cytologically speaking malignant tumors have some key features: • Nucleal features:

Different shape and size (nuclear polymorphism) High volume leading to a compartment ratio in favor of the nucleus Nucleolema has many irregularities with thickening and invagination Nucleoly are hyperplastic, hypertrophic, prominent with dense nuclear

material Mitosis is frequent and atypical unequal bipolar or multipolar DNA highly variable, giving polyploidy and/or aneploid

• Cytoplasmic features:

Reduced cytoplasm and content Increased basophilia (increased RNA) Great capability of phagocytosis (cannibalism) Simpler organization as anaplasia increase

Invasion and metastasis form of malignant tumors: most important characteristic, which explains post-‐operative recurrences. Favorited by abnormal mobility, decrease adhesion between malignant cells, and secretions of proteolytic enzymes. Metastasis: process of tumor mobilization, giving birth to new tumor at distance from its origin. It could follows different pathways, such as: 1. Lymphatic: early, specific for carcinomas. Could colonize a lymph node on

his road, replace it and attack a new one

16

2. Hematogenous: specific and early in sarcomas, lately in carcinomas, more severe than the first case. Even if more tumoral cells are destroyed in circulation a very few quantities could attack: liver, lungs, bone, adrenal cortex, CNS. Sometimes they tend to be similar to the first place of invasion, hence metastatic tumors tends to be less dangerous than firsts.

3. Along serous cavities: organs neighboring (Krukenberg tumor, ovarian metastasis through peritoneum)

4. Along perineural spaces: cause nerve compression, really painful, nerves atrophies and loss of functionality

5. Trough cerebro-‐spinal fluid: the only one possible for CNS tumors, cells migration is made through sub-‐arachnoid space

6. Along tubular organs: such as bronchi, ureters; e.g. pelvis renalis carnicoma metastazing in bladder

7. By direct contact: can occur in post-‐operative scars after excisions of malignant tumors, a cancer may be inoculated from one lip to the other

Prognosis criteria: In clinical practice is used a system with 3 degrees of differentiations: G1 – high differentiation (favorable) G2 – medium G3 – low differentiation (severe evolution) Hence the tumor staging is the assessment used for describing macroscopically and microscopically (after biopsy) the status of a tumoral invasion, it is called TNM international system, and uses imaging techniques associated with histological analysis: T – refers to the primitive tumor, the number means its size N – refers to the lymphnodal status, follows a number that describes how many are involved and their distribution M – presence and extension of metastases E.g. TxN0M1 = tumor not evaluable, no lymph nodes involved, 1 metastasis far from the origin

17

Methods of diagnosis (nonsense subchapter, isn’t a little premature to make them??? :D ) Are used several types of methods, usually cytological studies or even better histopathological, by biopsies taken during surgery or post-‐operative. Are widely used for therapeutic orientation. THAT’s IT! Now my little padawan and me will try to make a small table to summarize every kind on tumor we could face during the exam! B= Benign / M = Malignant

NAME

TYPE

TISSUE Features

Papilloma B Epithelial

multilayered squamous

Can develop anywhere in the body, has viral etiology (HPV) and can develop malignancy. Appear as a pedicle (narrow) or sessile (broad base of imp.).

Microscopically has several typical layers arising from a central axis: stratum spinosum, granulosum and

cornosum; all of them are thickened

Carcinoma M Epithelial

multilayered squamous

Can develop anywhere, appears as poorly defined masses, non-‐encapsulated with infiltrations in

surrounding tissues, low consistency and whitish color, with necrosis/hemorrhagic areas. Types of growth: vegetative, diffusive, and infiltrative. May

triggers ulceration.

Adenoma B Epithelial glandular

Can arise from exocrine or endocrine glands, can develop in internal organs (single or multiple nodular masses) or on membrane surfaces (GI tract, polyps)

attached by a pedicle.

Adeno-‐carcinoma M Epithelial

glandular

Occurs more frequent in GI tract, breast, pancreas, endometrium. May be sessile or polypoid, with

infiltrations and ulcerations, poorly defined masses, non-‐encapsulated containing cystic cavities.

Intraepithelial

Carcinoma M Epithelial

Particular proliferation by either benign or malignant charters. Known as pre-‐invasive carcinoma, or

carcinoma “stage 0” or “in situ”. Doesn’t present big changes in the mucosa and tegument.

Epidermoid Carcinoma M Squamous cells

Derived from epithelial cells of spinous layer, common located o skin/mucosal surface of squamous in metaplasia (tongue, vagina, anus). Divided in

keratinized or non-‐keratinized.

Basal membrane Carcinoma

M Epidermis

Develops from basal cell layer of the epidermis, is composed of cords of small dark cells with little

cytoplasm, nuclear polymorphism. Palisade layout at periphery of tumor island.

18

NAME

TYPE

TISSUE Features

Fibroma B Connective common

Can develop anywhere, appears as nodular formation, circumscribed, encapsulated, pearly white color. Rich of connective fibers (collagen-‐reticulin) and cells (fibroblasts, fibrocytes) More cells = softer, more fibers = harder.

Mixoma B Connective common

Soft tumor, poorly demarcated, gelatinous, can reach large size. Local infiltrative growth, star-‐shaped cells floating in mocoid mass. Difficult

surgical excision may re-‐occur.

Sarcoma M Connective common

Can develop anywhere, lower incidence than carcinoma, but could spreads at young age.

Generally large, low consistencies, reddish-‐pink like fish-‐fresh meat. With necrosis and hemorrhage.

Fibro – sarcoma M Connective

common Less aggressive growth in sarcoma’s family, rare

metastasis, usually relapses after surgery.

Fuzo cellular -‐ sarcoma

M Connective common

More aggressive evolution, fast growing, infiltrative. With early hematogenous metastasis.

Polymorphic sarcoma M Connective

common

Highest degree of malignancy, no more reminiscent of connective tissue from origin, undifferentiated cells with highly polymorphism and atypical

mitosis. Evolution is fulminating.

19

NAME

TYPE

TISSUE Features

Lipoma B Adipose

Occurs mainly in subcutaneous adipose tissue, with a symmetrical distribution. Consists of

hyperplasied unequal adult type of fat cells. Small peripheral nuclei, poor blood supply.

Lipo -‐ sarcoma M Adipose

Generally appears like a single nodular tumor, apparently well demarcated, can reach giant sizes. Looks gelatinous and with cystic areas. There is a well differentiated and a poor-‐differentiated

subtype.

Condroma B Cartilagenous

Most frequently in extremities (phalanges), can develop towards bony surface (Ecchondroma) or into the depth of bone (Enchondroma). Consists of islands of hyaline cartilage separated by vascularized fibrous

septa.

Condro -‐ sarcoma M Cartilagenous

Rare one, occur often “de novo” as malignant. Usually large tumors, poorly defined, smooth or

lobulated.

Osteoma B Bone

Most common location in skull and paranasal cavities, it is small, round and hard. Growing towards the bone surface into the depth. There are 3 types of osteoma:

osteoid, compact, spongeous.

Osteo -‐ clastoma B Bone

Has a benign evolution, in 10% act as malignant. Localized in long bone diaphysis, looks soft, reddish-‐brow, with hemorrhagic necrosis and

cystic formations. 2 types of cells: multinucleated giant osteoclasts and small connective cells (fibrous

type)

Osteo -‐ Sarcoma M Bone

Usually located in metaphysis, of long bones, large proliferations showing bony white hard areas alternated with soft fleshy masses, and area of necrosis and hemorrhage. 3 kinds: osteogenic (osteoids), osteoblastic (osteoblasts), osteolytic

(few bony element lysis)

20

NAME

TYPE

TISSUE Features

Leyomioma B Muscolar smooth

Anywhere in a smooth muscle, usually in the uterus. Has a characteristic fasciculated aspect, Damascus cloth. Slow growth, with possible

stagnation or involution.

Leyomyosarcoma M Muscolar

smooth

Well-‐differentiated form are difficult to distinguish from the benign one, just a large number of atypical mitosis helps diagnosis. Frequent vascular lacunae.

Rhabdomyoma B Striated

Muscolar

Mainly developed in skeletal muscle, appear as small nodular formation with hypertrophic muscle

fibers, incompletely differentiated.

Rhabdomyosarcoma M Striated

Muscolar

Similar location of abovementioned, can also arise in organs that normally have no striated muscles fibers (embryonic remnants). Several types, the most common is pleomorphic one, occurs in

advanced ages. The embryonic type (Botrioid) may appear in youg girl’s genitalia.

Hemangioma B Blood Vessels

It Is a conglomeration of blood vessels with irregular caliber and disordered arrangements. 3 types:

capillary, cavernous and sclerosing.

Hemangio -‐ sarcoma M Blood Vessels

Low consistency tumor, spongy, haemorrhagic, consisting of capillary lumens bonded by atypical endothelial cells. We can remember the hemangio-‐

pericytoma and kaposi’s sarcoma.

21

NAME

TYPE

TISSUE Features

Nevi B Melanic Pigmentary

Proliferations of melanocytes, found in the basal layer of epidermis. Frequently colored in brown,

rarely uncolored. Most of them are acquired during life, but can be found congenital. 3 types: junctional,

intradermal and compounds. Some of them have potential of malignancy, specially those in palms, plants

or mucous membranes.

Melanoma M Melanic Pigmentary

May develop as “de novo” or due to malignization of a nevus, for chronic exposure to irritants. Is one of the most aggressive giving early lymphatic and hematogenous metastasis.They appears as flat formations or polypoid masses with tendency to

ulcerations. Melanoma acroma is without pigmentation.

Hodgkin’s Lymphoma M Blood

Vessels

Both of them have high malignancy and are very aggressive. Is the most common tumor of this kind, affects usually men,

with two peaks of incidence (20/60 years old). Etiopathogenesis unknown. Starts in a single lymph node located in cervical region, then affects adjacent ones.

Simultaneously affects spleen, liver and bone marrow. Rubber like elasticity and whitish color. Partial or total removal of lymphnode’s structure by polymorphic cellular infiltrates.

Pathognomonic element is the Sternberg-‐Reed Cell.

Non -‐ Hodgkin’s Lymphoma

M Blood Vessels

Highly heterogeneous group of malignancy due to possibility of neoplastic proliferation of B and T-‐lymph cells. Begins in lymph nodes, spleen, liver and bone

marrow. From here tumor can infiltrate any tissue, also in peripheral blood (leukemia lymphoma). They are

sometimes they increase in fibrosis process, soft, whit or yellowish with necrosis. Very controversial classification.

It has been a though work, trust me, I was impressed by how synthetic this chart can be… 20 pages from all the morphopathology material is really a great effort…! Hope you all will find them useful as we guess, have a nice rehearsing time with this summary. Sincerely my team wishes you the best for this exam! Darth Vader: Ale Motta (the Boss) (in Yoda version for his patience) My padawan: Luke (Anakin) Serenas My Lord Sith: Luca “Darth” Silvestrus Your beloved colleagues specially wish for each of us….

“…May the force be with you…”

Morpho Pathology Review

Documents

Transcript of Morpho Pathology Review