Neoplasia Lecture Notes PDF

Dr. Naseer M. Mohammed  Introduction Neoplasia is a very important topic in pathology because neoplasms are both common and serious diseases. A neoplasm means a new growth of cells which is characterized by uncontrolled tissue proliferation. Neoplasia (Neo= new; pla...

Dr. Naseer M. Mohammed  Introduction Neoplasia is a very important topic in pathology because neoplasms are both common and serious diseases. A neoplasm means a new growth of cells which is characterized by uncontrolled tissue proliferation. Neoplasia (Neo= new; plasia= growth) means new growth. A neoplasm is a type of abnormal and excessive growth of tissue. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists in growing abnormally, even if the original trigger is removed. Oncology (oncos=tumor, logy=study) is the branch of science dealing with the study of neoplasms or tumors. Proto-oncogenes: normal cellular genes whose products promote cell proliferation. Oncoprotein: a protein encoded by an oncogene that drives increased cell proliferation through one of several mechanisms. Oncogenes: A mutated (changed) form of a gene called a proto- oncogene, which is involved in normal cell growth and division. When a proto-oncogene is changed so that too many copies are made or it becomes more active than normal, it is called an oncogene.  Nomenclature All tumors, benign or malignant, have two basic components Neoplastic cells constitute the tumor parenchyma. Supportive stroma is composed of fibrous connective tissue and blood vessels; it provides the framework on which the parenchymal tumor cells grow.  Classifications of neoplasms based on their parenchymal components. Benign when they are slow-growing and localized without causing much difficulty to the host. Malignant when they proliferate rapidly, spread throughout the body and may eventually cause death of the host. The common term used for all malignant tumors is cancer. The suffix ‘-oma’ is added to denote benign tumors. Malignant tumors of epithelial origin are called carcinomas, while malignant mesenchymal (tissues that connect, support and surround other body structure) tumors are named sarcomas.  Classification of neoplasms Epithelial tumors Benign forms – e. g adenoma , papilloma Malignant forms – carcinoma, e. g adenocarcinoma , squamous cell carcinoma. Masenchymal tumors Benign forms – e. g fibroma, leiomyoma. Malignant forms – sarcoma, e. g fibrosarcoma, leiomyosarcoma  Except Melanoma: Carcinoma of the melanocytes Hepatoma: Carcinoma of the hepatocytes Lymphoma: Malignant tumor of the lymphoid tissue Seminoma: Malignant tumor of the testis. Leukaemia: Cancer of blood forming cells.  Characteristics of tumors Majority of neoplasms can be categorized clinically and morphologically into benign and malignant on the basis of certain characteristics listed below: 1. Rate of growth 2. Cancer phenotype and stem cells 3. Clinical and gross features 4. Microscopic features 5. Local invasion (Direct spread) 6. Metastasis (Distant spread). Differentiation Rate of growth Benign Vs Malignant Local invasion Metastasis It is defined by the spread of a tumor to sites that are physically discontinuous with the primary tumor, and clearly marks a tumor as malignant. The invasiveness of cancers permits them to penetrate into blood vessels, lymphatics, and body cavities, providing the opportunity for spread.  Routes of tumor spread and metastasis Cancers may spread to distant sites by following pathways: Local spread this occurs by invasion into the adjacent tissues. Lymphatic spread: This is followed by spread of the tumor to regional lymph nodes and ultimately to other sites in the body. It is common in the initial spread of carcinomas.  Haematogenous spread : Because of their thinner walls, veins are more frequently invaded than are arteries, and metastasis tends to follow the pattern of venous flow. That is, hematogenous spread often follows distinct patterns depending on the location of the primary tumor. This is typical of all sarcomas, but is also the favored route for certain carcinomas (e.g., renal cell carcinoma). Spread along body cavities and natural passages (Transcoelomic spread, along epithelium-lined surfaces, spread via cerebrospinal fluid, implantation). This occurs by seedlings of surfaces of peritoneal, pleural, pericardial and subarachnoid spaces. Carcinoma of the ovary spreads transperitoneally to the surface of the liver or other abdominal viscera (transcoelomic spread).  Malignant tumor differs from benign four Cellular andfeatures: nuclear pleomorphism; refers to variation in size and shape of cells and their nuclei. Hyperchromatism; refers to dark staining of nuclei due to abnormally increased chromatin (nucleic acids contents), a reflection of aneuploidy (abnormality in the number of chromosomes in a cell due to loss or duplication). Increased nuclear-cytoplasmic ratio (N/C) reaching nearly 1:1 (instead of the normal 1:4 or 1:6), Abundant mitoses reflecting increased proliferative activity Abnormal mitoses, e.g., tripolar spindles (normally mitosis is bipolar). Tumor giant cells containing a single giant polypoid nucleus or multiple nuclei. Prominent nucleoli are one of the criteria that indicates the diagnosis of prostate adenocarcinoma. Cytoplasmic basophilia reflecting active protein synthesis.  loss of polarity; Loss of orientation and organization of tissue architecture (abnormal development of cells within tissues). Local invasion: benign tumor grows as cohesive(sold) mass and remaining confined to the site of origin without having the ability to invade locally or metastasize to distant sites. Benign tumors usually develop a rim of compressed connective tissue called fibrous capsule separating them from normal host tissue. Malignant tumor usually discohesive and penetrating the surrounding normal host tissue. Growth rate of the transformed cells: affect the tumor size and response to therapy. Cancers with high growth fraction more sensitive to cancer therapy but with faster metastases than cancers with low growth fraction. Tumors with high growth fraction include leukemia, lymphoma and small cell carcinoma of the lung. Tumors with low growth fraction include breast cancer and colonic cancer. At the beginning of cell transformation in malignant tumor it has high growth fraction so most of cancers treated well if they discovered early  Feature Benign Malignant Growth rate Slow Fast Invasive non Invasive and infiltrate Metastasis No (stay localized) Yes Capsulated Yes NO Pain Painful Pain less Differentiated Well differentiated Poorly differentiated Prognosis Good Bad Size Often small Large Pattern Similar to tissue of origin. Many differ from tissue of origin. Basal polarity Retained Often lost Pleomorphism Usually not present Often present Microscopic Nucleo-cytoplasmic ratio Normal Increased features Hyperchromatism Absent Present Mitoses May be present but are always Mitotic figures increased and are typical mitoses generally atypical and abnormal Function Usually well maintained May be retained, lost or become abnormal  Differentiation and anaplasia Differentiation is defined as the extent of morphological and functional resemblance of parenchymal tumour cells to corresponding normal cells. Well- differentiated means the cells are very similar in appearance and architectural arrangement to normal tissue of that organ. Poorly differentiated refers to tumors that show only minimal resemblance to the normal parent tissue they are derived from. Anaplasia ; is lack of differentiation and is a characteristic feature of most malignant tumors. Depending upon the degree of differentiation, the extent of anaplasia is also variable (poorly differentiated malignant tumors have high degree of anaplasia). Figure 1. (a) Normal colon tissue, detailed structure of a normal colon tissue; (b) malignant colon tissue, (c) moderately differentiated, (d) moderately-to-poorly differentiated, and (e) poorly differentiated.  Grading and staging of cancer ‘Grading’ and ‘staging’ are the two systems to predict tumour behavior and guide therapy after a malignant tumour is detected. Grading is defined as the gross and microscopic degree of differentiation of the tumour. Staging means extent of spread of the tumour within the patient.  Grading Cancers may be graded grossly and microscopically. Gross features like exophytic (describing growth out from an epithelial surface) or fungating (describes what the cancer might look like) appearance are indicative of less malignant growth than diffusely infiltrating tumors. However, grading is largely based on 2 important histologic features: the degree of anaplasia, and the rate of growth. Based on these features, cancers are categorized from grade I as the most differentiated, to grade III or IV as the most undifferentiated or anaplastic.  Grade I: Well-differentiated (less than 25% anaplastic cells). Grade II: Moderately-differentiated (25-50% anaplastic cells). Grade III: Moderately-differentiated (50-75% anaplastic cells). Grade IV: Poorly-differentiated or anaplastic (more than 75% anaplastic cells). Breast cancer (a) A well-differentiated tumor (grade 1) (b) A moderately differentiated tumor (grade 2). (c) A poorly differentiated (grade 3)  Staging The extent of spread of cancers can be assessed by 3 ways— by clinical examination, by investigations, and by pathologic examination of the tissue removed. Two important staging systems currently followed are: Tumor, lymph node metastasis (TNM) staging American Joint Committee(AJC) staging.  TNM staging T : primary tumor size N: regional nodal involvement M: distant metastases  AJC staging Divides all cancers into stage 0 to IV, and takes into account all the 3 components of the preceding system (primary tumour, nodal involvement and distant metastases) in each stage.  Generally, tumor of high grade present at high stage and vice versa  Tumor Angiogenesis Solid tumors cannot enlarge beyond 1 to 2 mm in diameter unless they are vascularized. Like normal tissues, tumors require delivery of oxygen and nutrients and removal of waste products. Angiogenesis is a physiological process of providing nourishment to growing tumour, new blood vessels are formed from pre-existing vessels. Angiogenesis is a necessary for: Continued tumor growth through supplying nutrient & oxygen. Metastasis of tumor.  Mechanism of invasion & metastasis: Invasion and metastasis are biologic hallmarks of malignant tumors. They are the major cause of cancer-related morbidity and mortality. It can be divided into the following steps: 1) Loss of adherence: detachment of tumor cells from each other. In some cancer expression of E-cadherin molecule is reduced resulting in loss of adhesion.  2) Invasion of the extracellular matrix (ECM): Tumor cells gain motility and invade through the matrix. This is achieved by attachment of tumor cells to the ECM components through obtain receptors for these components. Degradation of the ECM by release of digestive enzymes by tumor cells as metalloproteinase, cathepsin D and collagenase. 3) Migration of tumor cells through the ECM, promoted by cytokines. 4) Vascular dissemination and homing (intravasation). Within the circulation, tumor cells tend to aggregate in clumps. This is favored by adhesions of tumor cells to each other and to blood cells particularly platelets. THANK YOU