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This Sqadia video is the demonstration of Neoplasia. Neoplasm refers to an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoke the change. Hyperplasia is an abnormal increase in number of normal cells in normal arrangement in an organ or tissue; proliferation of glandular epithelium of breast tissue at puberty, growth of residual tissue after loss/removal of a part, connective tissue response in healing etc. In Metaplasia, one adult cell type is replaced with another adult cell type; squamous changes in respiratory tract of smokes. Dysplasia is abnormal growth of a cell with some features of malignancy. Anaplasia is loss of differentiation of cells and their orientation to one another and their axial framework and blood vessels. In anaplasia, there is increased nuclear to cytoplasmic ratio, increased rate of mitosis and loss of polarity. Local invasion is the first stage in the process that leads to the development of secondary tumors or metastases. Metastasis, from the Greek methistanai, meaning to move to another place, describes the ability of cancer cells to penetrate into lymphatic and blood vessels, circulate through these systems and invade normal tissues elsewhere in the body. There is bony metastasis, Seeding, lymphatics spread and heamatogenic spread.
Classification and Properties
On basis of origin they are mesenchymal, epithelial, mixed-arising from one germ cell, and teratogenous-arising from more than one germ cell. On basis of spread they are classified into Benign whose characteristics are considered innocent, remain localized, and can be surgically removed, and Malignant that invade and destroy the surroundings and spread to distant sites causing death. Neoplasia proliferate and become insensitive to regulatory signals. They have the ability to synthesize the growth factors to which they are responsive and interact with stroma by activating normal cells. The RB gene normally controls the G1-to-S transition-in its active form. RB is hypo-phosphorylated and prevents expression of genes necessary for DNA replication, so cells are arrested in G1. Mutations or alterations anywhere in the RB pathway can release this brake. Cell death by apoptosis is exerted by the coordinated action of many different gene products. Mutations in some of them, acting at different levels in the apoptosis process, have been identified as cause or contributing factor for human diseases. Defects in the transmembrane tumor necrosis factor receptor 1 (TNF-R1) lead to the development of familial periodic fever syndromes. Mutations in the homologous receptor Fas (also named CD95; Apo-1) are observed in malignant lymphomas, solid tumors and the autoimmune lymphoproliferative syndrome type I (ALPS I).
Fundamental principles behind molecular basis of cancer is that non-lethal genetic damage lies at the heart of carcinogenesis that is caused by environmental (endogenous/exogenous) and hereditary agents. Normal regulatory genes are growth-promoting proto-oncogenes which transform normal cells regardless of presence of normal counterpart. In growth-inhibiting tumor suppressor genes, Both alleles of TSG must be damaged before transformation and genes regulating apoptosis may behave as proto-oncogenes or TSG. Genes involved in dna repair affect proliferation or survival by influencing ability of repair of damage. A multi-step process at both the phenotypic and the genetic levels, resulting for the accumulation of multistep mutation. Tumors become more aggressive and acquire greater malignant potential.
Etiology and Predisposing Factors
Chemical Carcinogens are of two types Direct-acting; requires nometabolic conversion and are anti-cancer drugs and indirect-acting; require conversion to a carcinogen. Radiation Carcinogens are UV rays, X-rays. Viral Carcinogens are Oncogenic RNA Viruses i.e Human T-Cell Lymphotrophic Virus-1 (HTLV-1): leukaemia and lymphoma. Oncogenic DNA Viruses such as HPV: warts. Predisposing factors non-hereditary are age, gender, occupation, and smoking. Acquired preneoplastic lesions include squamous metaplasia & dysplasia of bronchial mucosa: lung cancer, endometrial hyperplasia & dysplasia: endometrial ca, oral/vulvar or penile leucoplakia: scc, and villous adenomas or colon: colorectal ca. Some of the autosomal dominant cancer syndromes are retinoblastoma: RB, li-fraumeni syndrome: TP53, and familial adenomatous polyposis: apc. Autosomal recessive syndromes of defective DNA repair are xeroderma pigmentosum: nucleotide excision and repair (ner) enzyme mutations, and ataxia-telangiectasia: atm serine, atm threonine kinase and at-mutated gene. Familial cancer of uncertain inheritance are breast cancers: non-BRACA genes, ovarian cancers, and pancreatic cancers.
Grading and Staging
Grading is the estimate of the aggressiveness or the level of malignancy based on the cytologic differentiation of tumor cells and the number of mitosis within the tumor. Grade I-IV according to the level of anaplasia in a cell. Based on the size of the primary lesion, its extent of spread to regional lymph nodes, and the presence or absence of metastases is referred to as staging. It is determined by imaging or surgical exploration. There are 2 systems for grading and staging; TNM System and AJC System. Their importance lies effects on patients. Their functional activity is the secretion of hormones or hormone-like substances. Moreover, Adenomas of pancreas can cause hyperinsulinism leading to death. Progressive loss of body fat and lean body mass, accompanied by profound weakness, anorexia and anemia are not caused by nutritional deficiencies/demand of tumor. Symptoms complexes that occur in patients with cancer and that cannot be readily explained by local or distant spread of the tumor or by the elaboration of hormones, not indigenous to the tissue of origin of the tumor is Paraneoplastic Syndrome. Leiomyoma of the uterus contains interlacing bundles of neoplastic smooth muscle cells that are virtually identical in appearance to normal smooth muscle cells in the myometrium. Colonic Polyp; this benign glandular tumor is projecting into the colonic lumen and is attached to the mucosa by a distinct stalk.