1. Mononuclear cell infiltration, which include macrophages, lymphocytes and plasma cells, eosinophils and mast cells.
2. Tissue destruction or necrosis is brought about by activated macrophages by release of a variety of biologically active substances.
3. Proliferative changes. As a result of necrosis, proliferation of small blood vessels and fibroblasts is stimulated resulting in formation of inflammatory granulation tissue. There are four components of this process:
formation of new blood vessels (angiogenesis),
migration and proliferation of fibroblasts,
deposition of extracellular matrix,
maturation and organization of the fibrous tissue, also known as remodeling.
Types of chronic inflammation:
I. Nonspecific, when the irritant substance produces a non-specific chronic inflammatory reaction with formation of granulation tissue and healing by fibrosis, e.g. chronic osteomyelitis, chronic ulcer.
II. Specific, when the injurious agent causes a characteristic histologic tissue response, e.g. tuberculosis, leprosy, syphilis, scleroma.
However, for a more descriptive classification, histological features are used for classifying chronic inflammation into 3 corresponding types:
1. Chronic nonspecific inflammation.
It is characterized by nonspecific inflammatory cell infiltration, e.g. chronic osteomyelitis, chronic lung abscess.
A variant of this type of chronic inflammatory response is chronic suppurative inflammation in which infiltration by polymorphs and abscess formation is additional features, e.g. actinomycosis.
The inflammatory cell infiltration consists of lymphocytes, monocytes, plasmocytes, eosinophils and other cells.
2. Chronic nonspecific interstitial inflammation with formation of polyps and pointed condyloma.
It occurs on the mucous membranes and in the areas borderline with squamous epithelium.
Polyps are the end-result of prolonged chronic irritation. Nasal, cervical, colorectal polyps are common. Macroscopically they are gelatinous masses with smooth and shining surface. Microscopically they are composed of loose edematous connective tissue containing some mucous glands and varying number of inflammatory cells (lymphocytes, plasmocytes, eosinophils).
Condyloma acuminatum is commonly located on the coronal sulcus on the penis or the perineal area. Condyloma is the growth of squamous cell epithelium and connective tissue of the skin with appearance of numerous small papillas on the surface. In stroma there are hyperemic vessels, infiltrates of lymphocytes and plasma cells with admixture of leukocytes.
3. Chronic granulomatous inflammation.
It is characterized by formation of granulomas, e.g. tuberculosis, leprosy, syphilis, actinomycosis, sarcoidosis etc.
Granulomatous inflammation is the distinctive pattern of chronic inflammatory reaction in which the predominant cell type is an activated macrophage with a modified epithelial-like (epithelioid) appearance.
Granuloma is defined as a circumscribed, tiny lesion, about 1 mm in diameter, composed predominantly of collection of modified macrophages called epithelioid cells, and rimmed at the periphery by lymphoid cells.
The word “granuloma” is composed of granule meaning circumscribed granule-like lesion, and -oma, which is a suffix commonly, used for true tumors but here indicates inflammatory mass or collection of macrophages.
Epithelioid cells, so called because of their epithelial cell-like appearance, are modified macrophages which are somewhat elongated, having pale-staining abundant cytoplasm, lightly-staining slipper-shaped nucleus and the cell membrane of adjacent epithelioid cells is closely apposed.
Besides the presence of epithelioid cells and lymphoid cells, granulomas may have giant cells, necrosis and fibrosis:
The giant cells are formed by fusion of adjacent epithelioid cells and may have 20 or more nuclei. These nuclei may be arranged at the periphery like horseshoe or ring or clustered at the two poles (Langhans’ giant cells), or they may be present centrally (foreign body giant cells).
Necrosis may be a feature of some granulomatous conditions, e.g. central caseation necrosis of tuberculosis.
Fibrosis is due to proliferation of fibroblasts at the periphery of granuloma. The following two factors favour the formation of granulomas:
1. Presence of poorly digestible irritant, which may be organisms like Mycobacterium tuberculosis, particles of talc etc.
2. Presence of cell-mediated immunity to the irritant, implying thereby the role of hypersensitivity in granulomatous inflammation.
Types of granulomas:
1. Infectious, and noninfectous.
2. Foreign body granulomas and immune granulomas.
Granulomatous inflammation is typical of reaction to poorly digestible agents elicited by tuberculosis, leprosy, fungal infections, schistosomiasis, foreign particles, etc.
Microscopical examination of the spesific granulomas
In tuberculosis, the granuloma is reffered to as a tubercle and is classically characterized by the presence of central caseous necrosis surraunded by epitelioid cells, limphocytes, plasma cells and giant Langhance’s cells. In contrast, caseous necrosis is rare in other granulomatous diseases.
The syphilis granuloma is called gumma. Gumma consists of a central area of fibrinoid or caseous necrosis surrounded by mononuclear inflammatory cells, mostly plasma cells, lymphocytes, epitelioid cells, and seldom-giant Langhance’s cells. Around gumma forms the granulations tissue and endovasculitis.
In tuberculoid leprosy, the epidermis contains confluent granulomas composed of macrophages, plasma cells, and leprous Virhov’s cells. Leprous Virhov’s cells (or leprosy cells) refer as large foamy macrophages within fatty vacuoles containing leprous mycobacteriums.
In rhinoscleroma of nose, the granuloma (scleroma) consists of the plasma cells, epithelioid cells, lymphocytes, and hyaline sphere. Large macrophages with light cytoplasm containing Klebsiella rhinoscleromatis (Mikulicz’s cells), sclerosis and hyalinosis take place.
Microscopical examination of the non- spesific granulomas
Proliferative inflammation around echinococcus of the liver. The area of the liver’s tissue with destructive pink color shined chitinous membrane and surrounded necrotic tissue are seen. In peripheral areas crowded lymphocytes, plasma cells, fibroblasts and single “giant cells of the foreign bodies”can be found. In the outside –fibrous capsule.
Sarcoidosis. The tissue contains granulomas composed of epithelioid macrofages and only a few lymphocytes and giant cells. There is no central necrosis.
The outcomes of chronic inflammation depend on the type of inflammation, morphofunctional characteristic of the definite organ or tissue, where inflammation develops. Frequently sclerosis and hyalinosis may develop.
IMMUNOPATHOLOGY
Immunopathological processes are pathological states, which are associated with disturbances of structure and function of lymphoid tissue. Before studying the morphology of immunogenesis disturbance it is necessary to know the normal immune morphology.
Central organs of immune system producing immune-competent cells are bone marrow and thymus. The bone marrow contains progenitor cells for the other lymphoid organs. The progenitor cells produced in the bone marrow circulate to the thymus or peripheral organs of immune system, where they develop into more mature lymphoid cells. Populations of bone marrow cells that may have recirculated back to the bone marrow can respond to antigens and are called B-lymphocytes.
The thymus produces and differentiates small lymphocytes (T-lymphocytes).
Main peripheral organs of immune system are spleen; lymphatic nodes and gastrointestinal associated lymphoid tissue (GALT) and bronchus associated lymphoid tissue (BALT). The main immunocompetent cells are T-lymphocytes, B-lymphocytes, and macrophages.
There are T and B-zones in the peripheral organs of the immune system. Thus, in the spleen, periarterial zone of the follicle is T-zone, marginal zone is inhibited by B-lymphocytes. There are T-, B- lymphocytes and macrophages in the red pulp of the spleen; In the lymphatic nodes, paracortical zone and peripheral zone of the follicle is T-zone, cortical layer, light centers of the follicles age’s-zone. There are T-, B- lymphocytes and macrophages in the medullar substance. Gastrointestinal associated lymphoid tissue (GALT) and bronchus associated lymphoid tissue (BALT) have different immunocompetent cells, i.e. T-lymphocytes, B-lymphocytes, macrophages without any zones.
The main T-cell function is to recognize “host” and “foreign” cells. Transmission of the information is the main function of B-cells. Information transmission is carried out through macrophage system. The function of B-cells is to produce antibodies. At this stage B-lymphocytes are transformed into plasmoblasts and plasmocytes.
For identification of immunocompetent cells we use monoclonal antibodies to different immune cells.
Cellular Components of the Immune Response:
T-cells are thymus-derived lymphocytes and produce (1) B cell growth factor; (2) B cell differentiation factor; (3) colony stimulating factor; (4) fibroblast activating factor; (5) Gamma-interferon; (6) interleukin-2; (7) interleukin-3; (8) leikocyte inhibition factor; (9) lymphotoxin; (10) migration inhibition factor.
B-cells are defined as lymphocytes that bear membrane immunoglobulin and under appropriate conditions differentiate into antibody-secreting cells.
Natural Killer Cells have capacity to recognize directly and kill various tumors and virus-infected in vitro.
Mononuclear Phagocyte is a general term applied to populations of phagocytic cells found in virtually all organs and connective tissues. Among these cells are macrophages, monocytes, Kupffer’s cells of the liver, and the so-called histiocytes. Macrophages are dominant participants in subacute and chronic inflammatory reactions.
Human Major Histocompatability Complex or human leukocyte antigens are the main target antigens during rejection of transplanted organs.
Pathology of Thymus
Thymus is the organ regulating the whole immune system. At immunogenesis disturbances we usually see the following processes and pathology.
1. Accidental thymus transformation (involution), that is reduction in the size and mass due to thymocyte migration to the peripheral immune organs and blood as well as due to their partial" decomposition and absorption by macrophages (this is called apoptoses).
According to T. Ivanovskaya (1976), accidental involution consists of 5 stages.
Stage 1 – “holey clearing” - accumulation of lymphocytes around the macrophages. It occurs in the cortex.
Stage 2 - transition of the lymphocytes from the cortex to the medullar substance. The boundary between the layers is either poorly seen or not seen at all.
Stage 3 – “layer inversion”, when the cortex layer looks light, and medullar layer looks dark as a result of transition of lymphocytes from the cortex to the medullar substance.
Stage 4 - Reduction in the lymphocyte amount in the both layers, reticular stroma growth.
Stage 5 - collapse of the lobe of the thymus and sclerosis and lobe atrophy.
Accidental transformation more often occurs in the newborn suffering from stress factors. The more powerful is the stimulus, the more pronounced is the degree of involution. Accidental involution occurs in infections, intoxications, in the children born from sick mothers. The process is reversible. Elimination of pathological agent results in thymus normalization.
2. Thymus hyperplasia (thymolymphatic state, thymomegaly). The weight and the size of thymus are considerably increased. Microscopic examination reveals a large number of immature lobules (zones are not distinct). The density of the thymocytes is high. If this condition is accompanied by hypoplasia of adrenal and sexual glands as well as narrow aorta and arteries, this pathological process is called “thymolymphatic state”.
Sudden death syndrome (crib death) may occur in thymomegaly, it results from insufficiency of T-lymphocytes of the cortex and medullar substance of the adrenal glands.
3. Thymus hypoplasia is characterized by absence of lobule division into cortical and medullar substance, poor development, of reticuloepithelial component, responsible for hormonal function, as well as lymphocyte component. As a rule thymus hypoplasia is typical for congenital immune deficiency.
Changes of lymphoid tissue at antigen stimulation
In the thymus, different stages of accidental transformation are observed.
In the bone marrow the first hyperplasia of B- lymphocytes are observed, when it becomes empty, as a result of increased transition of lymphocytes.
The reaction in peripheral lymphoid organs is similar. First, T-zones and B-zone hyperplasia occurs. Macrophages and plasmatic cells appear as well as their blasts producing immunoglobulins. Vascular endothelium is swollen; there are lymphocytes in the lumen. After that both T and B-zones become empty. T-zone is characterized by “holey” appearance. In B-zone density of the cells decreases. The lymphocytes either die or circulate in the blood.
Reticuloepithelium hyperplasia and lympho-plasmocyte infiltration occur in the interstitial tissue of the kidneys, pancreas, intestines, liver, and muscles.
Hypersensitivity reaction
A state of balance in the immune responses (humoral or cell-mediated) is essential for protection against endogenous and exogenous antigens. Hypersensitivity is defined as a state of exaggerated immune response to an antigen. The lesions of hypersensitivity (immunologic tissue injury) are produced due to interaction between antigen and product of the immune response.
Immunologically Mediated Tissue Injury. An immune response that results in tissue injury is broadly reffered to as “hypersensitivity” reaction and is associated with a group of diseases categorized as immune and immunologically mediated disorders.
1. Type I Hypersensitivity (Immediate Type or Anaphylaxis) is manifested by a localized or generalized reaction that occurs immediately (within minutes) after exposure to an antigen to which the individual has previously become sensitized and is characterized by a specific cytotropic antibody that binds to receptors on basophils and mast cells and reacts with specific antigen. This results in the activation of mast cells and basophils and the release of performed (granule) products as well as the synthesis of mediators.
2. Type II Hypersensitivity (Cytotoxic Type) reactions are caused by an antigen-antibody reaction but, as the name implies, the antibodies formed are often cytotoxic and are directed against antigens on cell surfaces or in connective tissues. Complement is required for many of cytotoxic events. Lysis is mediated directly by complement or indirectly by opsonization or the chemotactic attraction of phagocytic cells. Complement-independent reactions, such as antibody-dependent, cell-mediated cytotoxisity also fall into this category.
3. Type III Hypersensitivity reactions involve tissue injury mediated by immune complexes. They represent the classic example of immune complex-mediated injury in which antigen-antibody complexes, which are usually not organ-specifiic, are formed in the circulation and mainly directly in tissues. Once deposited in the tissues, these complexes induce an inflammatory response by activating the complement system, consequently attracting neutrophils and macrophages. Activation of these cells by the immune complexes,with the release of potent inflammatory mediators, is directly responsible for the injury. Many human diseases, including anti-immune diseases such as systemic lupus erythematosus, as well as most types of glomerulonephritis, appear to be mediated by type 111 hypersensitivity reactions.
4. Type IV Hypersensitivity or Cell-Mediated Immunity is defined as an antigen-elicited cellular immune reaction that results in tissue damage and does not require the participation of antibodies. It includes: (1) delayed type hypersensitivity; (2) T cell-mediated cytotoxisity, and (3) natural killer cell-mediated cytotoxisity.
Depending upon the rapidity and duration the immune response, two distinct forms of hypersensitivity reactions are recognized:
Hypersensitivity of Immediate reaction morphologically manifests itself by the picture of acute immune inflammation, which develops rapidly, alteration and exudation stages prevail, and proliferation increases slowly. The vessels and connective tissues are involved first. Alteration manifests by mucoid, fibrinoid swelling and fibrinoid necrosis. The exudate is either fibrinous or fibrino-hemorrhagic. Acute immune inflammations are observed in tuberculosis, syphilis. It is responsible for vascular reaction in lupus erythematosus, glomerulonephritis, nodular periarteritis.
Hypersensitivity of Delayed reaction
Two types of cells take part in this reaction. They are sensibilized lymphocytes and macrophages. Morphologically it manifests by chronic immune inflammation characterized by lymphocyte-macrophage infiltration. When we see lymphocyte-macrophage infiltration accompanied by vascular plasmorrhagic and degenerative processes we can conclude about immune inflammation. The condition occurs in autoimmune diseases, tuberculosis, brucellosis, dermatitis, and granulomatosis.
Reaction of transplant rejection resembles delayed hypersensitivity reaction. Transplant antigens induce the production of antibodies and sensibilized lymphocytes, which infiltrate the transplant. Microscopically, lymphohistiocyte infiltration is observed in the transplant. Cellular infiltration causes the disturbance of blood circulation and edema; as a result degenerations and necrosis of transplant develop. The neutrophils and macrophages appear in the transplant. Enzyme destruction of the transplant begins which is followed by its rejection.
Immunodeficiency Diseases
Immunodeficiency disorders are classified into antibody (B cell), cellular (T cell), and combined T and B cell deficiencies. In many cases functional defects are localized to particular points in the ontogeny of the immune system. The defects are congenital or acquired and their precise etiologies are often unclear.
1. Deficiencies of Antibody (B cell) immunity:
Congenital (Bruton’s) X-linked infantile hypogammaglobulinemia.
Transient hypogammaglobulinemia of infancy.
Common variable immunodeficiency.
Selective IgA deficiency.
2. Deficiencies of Cell-Mediated (T Cell) Immunity:
DiGeorge syndrome.
Chronic mucocutaneous candidosis.
3. Combined T and B Cell Deficiencies
4. Acquired Immunodeficiency.
Autoimmune diseases
Autoimmunity implies that an immune response has been generated against self-antigen (autoantigens).
Central to the concept of autoimmunity is the breakdown in the ability of the immune system to differentiate between self- and nonself-antigens.
An abnormal autoimmune response to self-antigens implies that there is a loss of immune tolerance.
Tolerance is best looked on as a diversion of the immune system to an active state of nonreactivity: that is, inhibitory products block the immune response.
The causes of autoimmune diseases are not clearly known.
Chronic viral infections, radiation and genetic factors may be responsible for them. Before studying the pathogenesis of autoimmune diseases it is necessary to know the major histocompatibility complex (MHC), which includes class 1, 2, 3 markers.
Class 2 MHC markers are also called HLA-Dr. There are a lot of autoimmune diseases, which are connected, with genetic disturbances of HLA-Dr system. That is why HLA genes are included into predisposing factors in the pathogenesis of autoimmune diseases.
In the pathogenesis of autoimmune diseases the following factors are distinguished:
Predisposing (HLA genes, hormonal background, genetically dependent features of the target cells).
Initiating (viral and bacterial infections, exposure of immune system and target organs to chemical and physical factors).
Contributing (dysfunction of immune system, T-lymphocyte suppressor activity).
In the pathogenesis, 2 mechanisms can be distinguished; therefore all the autoimmune diseases can be divided into 2 groups:
Group 1. Organospecific diseases. They are characterized by disturbance of physiological isolation of the organs and tissues due to absence of immune tolerance. Lymphohistiocyte infiltration occurs in the tissues (like at slow hypersensitivity reaction). The main organ specific diseases are:
Endocrine glands: Hashimoto’s (autoimmune) thyroiditis, Graves' disease, insulin-dependent diabetes mellitus, idiopathic Addison’s disease.
Alimentary tract: Autoimmune atrophic gastritis in pernicious anemia, ulcerative colitis, Crohn’s disease.
Blood cells: Autoimmune hemolytic anemia, autoimmune thrombocytopenia,
Others Myasthenia gravis: Autoimmune orchitis, autoimmune encephalomyelitis, Goodpasture’s syndrome, primary biliary cirrhosis, chronic active hepatitis, and membranous glomerulonephritis.
Autoimmune skin diseases.
Group 2. Organ non-specific diseases. Primary disturbances in the immune system causing the loss of ability to distinguish “own” and “foreign” antigens are:
Systemic lupus erythematous.
Rheumatoid arthritis.
Scleroderma (Progressive systemic sclerosis).
Polymyositis-Dermatomyositis.
Polyarteritis nodosa (PAN).
Sjogren’s syndrome.
Reiter’s syndrome.
Mixed connective tissue disease.
The diseases with autoimmune disturbances
In these diseases antigenic properties of the tissues change, which causes immune reaction development.
Autoimmunization is responsible not for the beginning but the progress of the disease as autoimmune antibodies appear during the disease.
It is observed in glomerulonephritis, hepatitis, chronic gastritis, burn disease, rheumatism, hepatic cirrhosis.
Immune deficiency syndromes
Immune deficiency syndromes result from immune system insufficiency.
All immune deficiencies are divided into 2 groups: primary or congenital immune deficiencies and secondary, acquired immune deficiencies.
Primary IDS may be understood as primary defects in development of the immune system. Secondary ones results from diseases or drugs that affect immune system.
Primary IDS may be classified into following 4 general groups depending on the stage in development at which the defect occurs:
- T-cell deficiencies.
- B-cell deficiencies.
- Combined (T-B-cell) deficiencies.
- Deficiency in inflammatory cells (agranulocytosis).
T-cell deficiencies manifests by agenesis, hypoplasia of the thymus and T-dependent zones of the immune system. They are inherited according to autosome dominant type, e.g. MacCusic syndrome. Except for the pathology of thymus and primary lymphatic tissue, defects of development occur.
B-cell deficiencies. The type of inheritance is connected with X chromosome, e.g. agammaglobulinemia – Bruton’s syndrome. The thymus is preserved. B-zones in the peripheral lymphatic organs are absent. Immunoglobulins synthesis is absent.
Combined syndromes - insufficiency of cellular and humoral immunity (T- B-cell). This is inherited according to autosome-recessive type, e.g. Gianzmann-Riniker syndrome (agammaglobulinemia of Swiss type). Hypoplasia of thymus and peripheral lymphatic tissue.
Secondary deficiencies occur after full development of the immune system. Some of these are secondary to immunosuppressive therapy, e.g. in tumors, autoimmune diseases, glomerulonephritis, ect. Chronic virus infections and HIV (human immunodeficiency virus) may cause secondary deficiencies. The aquired immunodeficiency syndrome (AIDS) has become recognized as fatal and increasingly prevalent disease. AIDS exhibits a spectrum of clinical manifestations, including an asymptomatic state with only laboratory evidence of immunodeficiency; a prodromal state manifested by fever, weight loss, and lymphadenopathy, and the classic picture of opportunistic infections and Kaposi’s sarcoma. The major laboratory features of AIDS are lymphopenia and the loss of circulating T4 (helper/amplifier) lymphocytes. The etiologic agent of AIDS is now known to be a retrovirus originally called HTLV-111 (human T cell leukemia/lymphoma virus).
NEOPLASIA
General pathomorphology of neoplasia
The term “neoplasia” means new growth; the new growth produced is called “neoplasm” or “tumor”.
However, all “new growth” is not neoplasms since examples of new growth of tissues and cells also exist in the processes of embriogenesis, regeneration on repair, hyperplasia and hormonal stimulation.
Neoplastic cells lose control and regulation of replication and form an abnormal mass of tissue.
Satisfactory definition of neoplasm or tumor is “a mass of tissue formed as a result of abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of cells”.
The tumors are classified according to histogenetic principles with the account of their morphological structure, localization, peculiarity of their structure in a definite organ, benign or malignant character.
The classification was suggested as an international one by the Committee on Tumor Nomenclature of the International Anticancer Union. According to this classification, there are 7 groups of tumors; their total number exceeds 200.
1. Epithelial tumors without specific localization (nonorganspecific).
2. Tumors of endocrine and exocrine, glands as well as epithelial integument (organspecific).
3. Mesenchymal tumors.
4. Tumors of melanin-forming tissue.
5. Tumors of nervous system and brain membranes.
6. Tumors of blood system.
7. Teratomas.
The suffix “-oma” is added to denote benign tumors. Malignant tumors of epithelial origin are called carcinomas, while malignant mesenchymal tumors are named sarcomas (sarcos = fleshy). Some examples contrary to this concept are: melanomafor carcinoma of the melanocytes, hepatomafor carcinoma of the hepatocytes, lymphomafor malignant tumor of the lymphoid tissue, and seminomafor malignant tumor of the testis.
Tumors composed of a single type of parenchymal cells that differentiate towards more than one cell line are called mixed tumors. Teratomas, on the other hand, are made up of a number of parenchymal cell types arising from totipotent cells derived from more than one germ cell layer. Choristomarefers to the ectopic rests of normal tissue. Hamartomais a mass of disorganised-but mature cells of tissues indigenous to the particular site. The currently used classification of tumors is based on the histogenesis (i.e. tissue of origin) and on the anticipated behavior.
Characteristics of tumors
The characteristics of tumors are described under:
I. Macroscopic features.
II. Microscopic features.
III. Growth rate.
IV. Local invasion (Direct spread).
V. Metastasis (Distant spread).
Based on these characteristics, contrasting features of benign and malignant tumors are summarized in Table 6.
I. Macroscopic features
Almost all tumors have a different color, texture and consistency as compared to the surrounding tissue of origin. Gross terms such as papillary, fungati, infiltrating, hemorrhagic, ulcerative and cystic are used to describe the macroscopic appearance of the tumors.
Benign tumors are generally spherical or ovoid in shape. They are encapsulated or well-circumscribed, freely movable, more often firm and uniform, unless secondary changes like hemorrhage or infarction supervene.
Malignant tumors are usually irregular in shape, poorly-circumscribed and extend into the adjacent tissues. Secondary changes like hemorrhage, infarction and ulceration are seen more often. Sarcomas typically have fish-flesh like consistency while carcinomas are generally firm.
II. Microscopic features:
These are: microscopic pattern, cytomorphology of neoplastic cell (differentiation and anaplasia), angiogenesis and tumor stroma, and inflammatory reaction.
1. Microscopic patten:
The tumor cells may be arranged in a variety of patterns in tumors, e.g.
The epithelial tumors generally consist of acini, sheets, columns or cords of epithelial tumor cells that may be arranged in solid or papillary pattern.
The mesenchymal tumors have mesenchymal tumor cells lying separated from each other usually by the intercellular substance such as cartilaginous matrix in chondroma, osteoid in osteosarcoma, reticulin network in soft tissue sarcomas etc.
Hematopoetic tumors such as leukemias and lymphomas often have none or little stromal support.
Generally, most benign tumors and low-grade malignant tumors reduplicate the normal structure of origin more closely.
Other cellular deviations from the normal cellular arrangement in malignant tumors are: loss of basal orientation (polarity), altered alignment of tumor cells to each other, and stromal invasion by tumor cells.
2. Tumor Cytomorphology (Differentiation and Anaplasia)
Differentiation is defined as the extent of morphological and functional resemblance of parenchymal tumor cells to corresponding normal cells. If the deviation of neoplastic cell in structure and function is minimal as compared to normal cell, the tumor is described as “well-differentiated” such as most benign and low-grade malignant tumors. “Poorly differentiated”, “undifferentiated” or “dedifferentiated” are synonymous terms for poor structural and functional resemblance to corresponding normal cell.
Anaplasia is lack of differentiation and is a characteristic feature of most malignant tumors.
As a result of anaplasia, following noticeable morphological and functional alterations in the neoplastic cells are observed:
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