Neoplasia PDF

NEOPLASIA Dr Anjorin Clinical lecturer/histopathologist Osun state University /Uniosun Teaching Hospital Neoplasia (Neo) literally means new and plasia means formation, scientifically defined as an abnormal growth of tissues exceeding and un-coor...

NEOPLASIA Dr Anjorin Clinical lecturer/histopathologist Osun state University /Uniosun Teaching Hospital Neoplasia (Neo) literally means new and plasia means formation, scientifically defined as an abnormal growth of tissues exceeding and un-coordinating with the evoking stimuli (loss of responsiveness to normal stimuli of growth). Neoplastic cells tend to be monoclonal, or similar in their genetic makeup, indicating the same origin from one transformed cell. Non-neoplastic proliferations (such as reactions to inflammation) have cells that are polyclonal in origin. Biological Behavior of Neoplasia: Neoplastic tissues behave as parasites, depending on the host nutrient, i.e., the tumour is flourishing in a wasting patient. Autonomy of growth, i.e., they increases in size regardless of the local environment. Additionally, some neoplasms behave as benign while others behave as malignant. Characteristics of Malignant Neoplasm: Malignant growth is not inhibited by contact with surrounding cells, they are discohesive and transplantable favouring invasion and metastasis. Tumour cells can bind to laminin and fibronectin in connective tissues, then secrete collagenases or proteases, and then invade the surrounding tissue. Neoplastic cells may attain “immortality” or the ability to keep dividing indefinitely. Nomenclature of Neoplasia: There are general rules for nomenclature with few exceptions and the rules depend on the following factors: - From where tumour arise?. Parenchymal or mesenchymal origin. What is the clinical behaviour of the tumours?. i.e., benign or malignant or borderline. Parenchymal Cells: The functioning cells, like gland, epithelial, and hepatic cells. Mesenchyemal Cells: The supporting stroma, fibrous, muscle, and bone tissue (connective tissue). Nomenclature of Benign Tumours: Benign tumours are named by adding the suffix (oma) to the end of the name of the tissue or cells from which they arise. For example, benign tumours of fibrous tissues are called fibroma, while of cartilages named chondroma, from glands are named adenoma, and from bone are named osteoma, papilloma – are given for tumors arising from surface epithelium like skin or gastrointestinal surfaces. Basis of Nomenclature of Malignant Tumours All malignant tumors are called cancer. Malignant tumors arising from epithelial tissues are named by adding suffix carcinoma to the name of tissue or cell of origin So it will be adenocarcinoma for glandular epithelium, squamous cell carcinoma for tumors arise from squamous epithelium…etc. While those arising from mesenchymal (connective) tissue are named by adding the sufix sarcoma at the end of the name of cell or tissue of origin, so it will be fibrosarcoma for tumor arises from fibrous tissues,…etc. Exceptions in Nomenclature of Malignant Tumors Some tumors are malignant even though ending with the suffix (-oma) e.g. Seminoma : Malignant tumor of spermatocyte Lymphoma: Malignant tumor of lymphoid tissue Melanoma: Malignant tumor of melanocyte Teratoma: Neoplasm that originates from germ cells, (sperm or ova), and is composed of mixed tissue are named teratoma, If it has benign features, it is called benign teratoma and if has malignant features it is named malignant teratoma. Papilloma: Benign epithelial neoplasms growing on any surface epithelium showing microscopic or macroscopic finger -like patterns. Polyp: A mass that projects above the epithelial surface to form a microscopically visible structure, e.g., colonic polyps and nasal polyps.  Hamartoma: This is not a neoplasm, it is a local malformed growth that resembles a tumour, and it grows at the same rate as the surrounding tissues do. It is composed of tissue elements normally found at that site, most often asymptomatic. Choristoma: A mass composed of normal cells in a wrong location, e.g., pancreatic choristoma in liver or stomach. Both hamartoma and choristoma are considered as malformations and not neoplasms, and they are distinguished from neoplasms by the fact that they do not exhibit continued growth. They are a group of tumor -like tissue masses which may be confused with neoplasms Cytological features of malignancy: There are abnormal cytological findings at the level of cytoplasm and the nucleus associated with malignancy, and used by the pathologist to diagnose malignancy which includes: Pleomorphism: Different shape and size of cells or nucleus Hyperchromatism: Darkened nucleus in H&E stain Coarse Chromatin: Normally the chromatin is finely stained Abnormal Mitotic Figure: Increased number with abnormal shape (Tri, quadri-polar ). Normally it is bipolar figure. Increase (Nuclear to Cytoplasmic) Ratio: High N/Cratio as result of big bizarre nucleus Presence of Nucleoli: Prominent and irregular nucleoli which normally should not be seen. Cellular Differentiation in Neoplasia Differentiation means the degree of resemblance of neoplastic tissue to the original one, and this criterion is used to predict the prognosis of the tumour , There are three degrees of differentiation: Well Differentiated Tumours: Means a high degree of resemblance to the normal tissue of origin (has good prognosis). Moderately Differentiated Tumour: Moderate degree of resemblance to the tissue of origin (moderate prognosis). Poorly Differentiated Tumour: Means no resemblance to the tissue of origin, sometimes are called anaplastic tumours. They have the worse prognosis Anaplasia It means failure of the tumour to resemble the original tissue, i.e., (Anaplasia = lack of differentiation). The cells will be large bizarre, pleomorphic and multinucleated. In general, benign tumours are well differentiated, while malignant tumours range from well differentiated to undifferentiated, Features of anaplasia include pleomorphism, abnormal cell morphology (atypia), abundant and/or atypical mitoses, and loss of polarity.  Tumour formation is a multifactorial and Etiology of multistep process, Neoplasm; The following factors plays major role in its formation. 1. Genetic Factors: Genetic damage lies at the core of the etiology of tumour, there are four main types of genes responsible for the formation of tumours. Proto-oncogene: A gene that normally produces growth factors when activated to oncogene they produce cancer Cancer Suppressor Gene: A Gene that prevents cancer formation. Its absence leads to tumor formation. Apoptotic Gene: A gene that is responsible for apoptosis. Its absence leads to tumor formation. DNA Repair Gene: Genes that is responsible for repairing errors in DNA synthesis. Their absence leads to tumor formation. Examples of Oncogene: RAS Oncogene: Found in 15-20% of all human cancers, normally RAS is activated by receptors to exchange GDP for GTP. Activated RAS returns to ground state by its intrinsic GTPase activity. Mutant forms of RAS. Tumour Suppressor Genes : Examples; Retinoblastoma Gene (RB) : First recognized in retinoblastoma a rare paediatric tumour of the eye. The RB tumour suppressor gene is a nuclear phosphoprotein that regulates the cell cycle, Activated hypophosphorylated state in non-dividing cells and inactive hyperphosphorylated state in cell cycle. Several cancers have mutations in the RB pathway 2-Oncogenic Viruses: These are viruses containing viral oncogenes i.e., (ABL,MYC, RAS…etc) which are transported to the human genome during viral infection, and later on causes neoplasms. Viral oncogene may be inserted in the human genome near a human oncogenes it amplify them and make them over expressed, example of oncogenic viruses: Human T-ce ll Leukaemia Lymphoma Virus Type 1 (HTLV-1 ) : Causing lymphoma and leukaemia in adults. Human Papillomavirus (HPV): Causing benign squamous cell papillomas of the skin, and carcinoma of the cervix. Epstein – Barr virus (EBV) : Causing Burkett’s lymphoma, Hodgkin disease and nasopharyngeal carcinoma. Hepatitis B Virus (HBV) : Infection is associated with liver cancer 3-Heredity Factors in Cancer Formation: Some cancers run in families due to specific Mendelian genes responsible for it. Cancer syndromes inherited as Mendelian patterns include familial retinoblastoma, familial adenomatous polyps of the colon, Neurofibromatosis types I and II 5-Chemical Carcinogens Alkylating Agents: They are anticancer drugs like Cyclo-phosphamide, chlorambucil, busulfan, and melphalan inspite of that, they may produce cancers. Aromatic Amines and Azo Dyes Nitrosamines and Amines: Related to gastric carcinoma. 7-Miscellaneous Agents: Asbestos which causes bronchogenic carcinomas, mesothelioma , Arsenic associated with skin cancer. 8-Radiation Carcinogens: UV light is a cause of skin cancers; ionizing radiations, X-rays, atomic radiation, and atomic bomb have produced a variety of malignancies, especially leukaemia, lymphoma, in Hiroshima, Nagasaki, and in Chernobyl village in Russia. 9-Premalignant Lesion: These are potentially malignant lesions found in tissues and after a period of time they may transform into malignancy e.g. gastric adenoma. Chronic Skin Ulcer: May be transformed into squamous cell carcinoma Liver Cirrhosis: May transform into hepatic carcinoma. Ulcerative Colitis: May transform into colonic carcinoma. Leukoplakia: Transforms into squamous cell carcinoma. Dysplasia (Disordered Growth) This is a premalignant change affecting a focal area of epithelial tissues without invading the basement membrane and represents a state between hyperplasia and carcinoma in situ (preinvasive neoplasia). Most of the cases are on top of metaplastic changes from continuous stimuli, e.g., prolonged cigarette smoking ends up with metaplasia, then dysplasia followed by broncogenic carcinoma. Dysplasia does not necessarily progress to cancer in all cases.  Mild Dysplasia: Affecting lower one-third layer of tissue. Grades of Dysplasia: Mode rate Dysplasia: More than lower one-third layer is affected. Severe Dysplasia: All layers are affected without breaching the basement membrane and also known as carcinoma in situ or preinvasive neoplasia. NB: If the basement membrane is breached, this is known as invasive carcinoma. Metastasis of Cancer: Secondary spread of cancer to other areas. for example, breast carcinoma metastasizes to the lung, liver , and bone marrow. Invasion: local spread when it breaches the basement membrane and invade the neighboring tissue. local invasion Occurs through a four-step process that includes: Detachment of Tumor Cells from Each Other: occur s due to loss of the intercellular glue substance (E. cadheren) and resulted in loosening up of tumour cells. Attachment of Tumor Cells to the Extracellular Matrix (E.C.M) : The E.C.M. Includes basement membrane which contains laminin and interstitial connective tissue, which contains fibronectin. Tumour cells develop laminin & fibronectin receptors, which let them adhere to the B.M. & interstitial C.T Degradation of the Extra Cellular Matrix: Tumour cells then secrete proteases which cause degradation of the E.C.M and type IV collagenase. Migration: Movements of malignant cell from its original site, this step occurs under the effect of certain chemotactic factors, e.g., tumour cell derived cytokines, products of matrix components and some growth factors. Distant Spread (Metastasis) It is the presence of a tumour cell away from its primary original site and without continuity with it. Distant spread can occur by- blood, lymphatics, transcoelomic route, through natural passages and by implantation and inoculation. The most important step in metastasis is angiogenesis (new vessel formation) in primary tumour site, then local invasion of the blood vessel with intravasation and transport through the circulation and arrested in micro-vessel in liver, lung or bones, followed by extravasations of cells from the vessels and forming of micro-metastasis, then proliferate to form macrometastasis (tumors). Routes of Spread of Cancer: Intracavitary spread through cavities, such as the peritoneum, pleura, etc. lymphatic spread (via the For example, gastric carcinoma lymphatic vessels), metastasize through the peritoneal cavity to ovaries called Krukenberg’s tumour, Direct invasion of the nearby haematogenous spread: via organs by extension of the arteries or veins, tumour from its origin. Stages of Cancer sub divided clinically into stage I-IV depending on the degree of metastasis and size of the tumor.  Stage I: Tumor confined to the site of origin Stage II: Cancer is locally invasive (in original organ) Stage III: Cancer has spread to regional structures (neighboring tissues) invasion of adjacent structures. Stage IV: Cancer has spread to distant sites. There is another system for staging called the TNM system: T= tumour size, N= node involvement, M= presence of distant metastasis,  Size of Tumour Includes, T0, T1, T2,and T3. Node Involvement: No involvement N0, involvement N1 Extent of Spread: No metastasis M0. Metastasis M1… The Stage may influence choice of management, i.e., stage I is treated differently from stage IV. Grading of Cancer: This is microscopic sub-categorization of tumours depends only on cytological and histological findings which affects prognosis and method of management of some tumours. There are three methods of grading depending on the degree of resemblance to the original tissue (differentiation).  Any question