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 NEOPLASM What is Neoplasia or tumor …these refer to abnormal masses of tissue the growth of which are virtually autonomous and exceed that of normal tissue. “Cell division without control”  In modern molecular pathology: A neoplasm can be...

 NEOPLASM What is Neoplasia or tumor …these refer to abnormal masses of tissue the growth of which are virtually autonomous and exceed that of normal tissue. “Cell division without control”  In modern molecular pathology: A neoplasm can be defined as a disorder of cell growth that is triggered by a series of a cquired mutations affecting a single cell and its clonal progeny. How do tumor develop? Nonlethal genetic damage lies at the heart of carcinogenesis-Such genetic damage (or mutation) may be acquired(extrinsic) by the action of environmental agents, such as chemicals, radiation, or viruses, or it may be inherited(intrinsic) in the germ line. L Four classes of normal regulatory genes are the principal targets of genetic damage; 1.The growth-promoting proto-oncogenes 1 2.The growth-inhibiting tumor suppressor 2 genes 3.Genes that regulate apoptosis3 4.Genes involved in DNA repair  Irreversible DNA damage, resulting in autonomous growth of abnormal cells *  TUMORS ARE MONOCLONAL The entire population of cells within a tumor are one single cell that has undertake genetic change, and tumors are said to be “clonal” Clone= a group of cells arising from one single cell by division and having the same structure and function as that of the original cell DONEOPLASTICCELLS DIFFER FROM NORMALCELLS? Alterations in growth control proliferation cell death factors regulating growth and response Alterations in cellular interactions cell-cell cell-stroma e.g interaction with basement  GROWTHCONTROL -Normal cells, only divide a definit number of - times before they enter into a permanent state of growth arrest or simply die. - Cancer cells never stop to proliferate. -  Increased cell proliferation more cells enter cell cycle cell cycle “speeded up”  Cells have changed life span Alterations in cell death(decreased apoptosis)  Modification of cell metabolism Increased or decreased growth factor receptors or altered receptors Synthesis of growth factors – autocrine or paracrine effect Increase or modified growth control proteins e.g. oncoproteins  Angiogenesis formation of new blood vessels out of pre-existing WHY IT IS IMPORTANT? Supply of oxygen and nutrients Removal of waste products Cancer spread Metastasis  In low –oxygen regions of solid tumor mononuclear myeloid-derived suppressor cells (M-MDSC) quickly turn into tumor –associated macrophages. -Macrophages stimulate angiogenesis and facilitate tissue remodeling and angiogenesis by secreting number of protease and growth factors ex.VEGF ,FGFs ,PDGF…  CELLULAR INTERACTIONS Cell-cell interactions Cell-stromal interactions with basement membrane - Interaction of tumor cells with the extracellular - matrix ECM and mesenchymal stem cells MSC ,these interaction are mediated by direct cell – to – cell contact and the release the cytokines growth factors ,extracellular matrix proteins and matrix metalloproteases … - This interactions result in epithelial mesenchymal and stromal transition of tumor cells ,their migration , invasion and dissemination to distant organs.  Differentiation Differentiation: Differentiation refers to the extent to which neoplastic tumor cells resembles the corresponding normal parenchymal cells, both morphologically and functionally.  Characteristics of a malignant cells/ Features of Anaplasia Anaplasia is decease or loss of differentiation and it is a feature of malignant tumors Anaplasia associated with cellular feature like: Pleomorphism nuclear and cellular.1 Increased nuclear cytoplasmic ratio.2 Hyperchromasia.3 Increased mitosis and abnormal.4 mitosis Loss of polarity.5 Anaplastic tumor of the skeletal muscle (rhabdomyosarcoma). Note the marked cellular and nuclear pleomorphism, hyperchromatic nuclei, and tumor giant cells(Left).  Classification of tumors On the basis of biological behaviour and morphologic characteristics tumor is divided into: Benign tumor.i Malignant tumor.ii  All neoplasm have two basic component: Neoplastic cells: Cells that forms the (1 tumour parenchyma. Reactive Stroma : The connective tissue, (2 blood vessels and cells of the immune system.  Benign Tumor A tumor is benign when: Tumours gross and microscopic.i appearances are innocent remain localized will not spread to other.ii sites local surgical removal is possible..iii  The patient having benign tumour generally survives. Benign tumors are attaching the suffix -oma to the name of the cell type from which the tumor originates. Cell type+ OMA example: fibroma, chondroma, lipoma OMA” but Malignant HepatOMA, lymphOMA, gliOMA, melanOMA  Malignant Tumors : referred collectively as cancer When the tumor has: gross and microscopic appearances are aggressive.1 which invade and destroy adjacent structures..2 spread to distant sites (metastasis)..3  BENIGN MALIGNANT Nuclear variation in size and shape Nuclear variation in size and shape minimal minimal to marked, often variable (pleomorphism) dipoid Range of ploidy Retention of specialization Loss of specialization Structural differentiation retained Structural differentiation shows wide Functional range of changes differentiation usually Organized Not organized 29  DYSPLASIA ”. disordered growth“Dysplasia means Dysplasia is the loss of uniformity of the individual cells and loss of their.architectural orientation Dysplasia may be a precursor to malignant. transformation  Dysplasia Dysplastic cells may show pleomorphism and large hyperchromatic nuclei with a high nuclear-to- cytoplasmic ratio. Mitotic figures are more abundant than in the normal tissue and may be seen at all levels including surface epithelial cells. Dysplasia Can range from mild to severe (in-situ) Sites –cervix –bladder –breast –others Dysplasia does not always progress to cancer.  IN-SITU MALIGNANCY When dysplastic changes are marked and these atypical dysplastic cells involve the full thickness of the epithelium it is called carcinoma in situ. Carcinoma in situ is limited to the basement membrane and do not cross the basement membrane. -Once the tumor cells cross the basement membrane, it is called invasive carcinoma. -Early detection and screening programs increase detection of in situ carcinoma and increase survival rate.  A, Carcinoma in situ. Low-power view shows the entire thickness of the epithelium is replaced by atypical dysplastic cells. There is no orderly differentiation of squamous cells. The basement membrane is intact, and there is no tumor in the subepithelial stroma. B, High-power view of another region shows failure of normal differentiation, marked nuclear and cellular pleomorphism, and numerous mitotic figures extending toward the surface.  TYPES OF NEOPLASMS -Malignant Benign -Epithelial Connective tissue Lymphoid /haemopoietic Germ cell Nomenclature Colonic polyps (adenoma)  Fibroadenoma of the breast The tan-colored, encapsulated small tumor is sharply demarcated from the whiter breast tissue. Fibroadenoma  Cut section of an invasive ductal carcinoma of the breast The lesion is retracted, infiltrating the surrounding breast substance, and would be stony hard on palpation.  The microscopic view of the breast carcinoma shows the invasion of breast stroma and fat by nests and cords of tumor cells (compare with fibroadenoma The absence of a welldefined capsule should be noted. Lipoma Leiomyoma Germ cells Testis Teratoma 􀃆 malignant Seminoma Ovary Mature cystic teratoma (Dermoid cyst) 􀃆 benign Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. B, A microscopic view of a similar tumor shows skin, sebaceous glands, fat cells, and a tract of neural tissue (arrow). Hamartoma:: malformation that present as amass ⚫ of disorganized tissue ,or tumor like lesion composed of cells in ahubhazard arrangement e.g. gastric hammartomatous polyp..  Choristoma(Heterotopic tissue) Non-neoplastic tissue in a foreign location; ectopic rest of normal tissues Examples: pancreatic tissue in the stomach wall; gastric mucosa in Meckel diverticulum Thank You