Neoplasia PDF

Neoplasia Dr. Riyam Naji Qassim M.B.CH.B C.A.M.P (path.) Definitions: Neoplasia: is uncoordinated and uncontrolled cell growth and division...

Neoplasia Dr. Riyam Naji Qassim M.B.CH.B C.A.M.P (path.) Definitions: Neoplasia: is uncoordinated and uncontrolled cell growth and division resulting in new growth formation. Tumor: is a swelling or mass caused by neoplasia or other causes. Oncology (Greek oncos = tumor) is the study of tumors or neoplasms. All tumors have two basic components: (1)The parenchymal tissue: It is made up of neoplastic cells of a tumor. The parenchymal tissue determines the behavior and classification of tumors. (2) The stroma (supporting) tissue: It is made up of connective tissue and blood vessels. The stroma determines the growth and spread of tumors.  Paranchymal and stromal tissue Classification of neoplasms (tumors): Is based on: 1. The behavior: tumors can be benign, malignant and locally malignant. 2. The origin of tissue (histology): tumors mainly arise either from epithelial tissue or non-epithelial tissue. 3. Degree of differentiation: differentiation refers to the extent to which neoplastic cells resemble normal cells, both morphologically and functionally.  Benign tumors are well differentiated, e.g. the neoplastic cells of a lipoma, a proliferation of benign adipocytes, may so closely resemble normal adipocytes. Malignant tumors are characterized by wide changes of cell differentiation from well differentiated, poorly differentiated or undifferentiated (anaplasia) cells. Adipocytic tissue (normal) lipoma (benign) liposarcoma(malignant) Characteristic features of benign tumours 1. Benign tumors are composed of well-differentiated cells that resemble the cells of the tissues of origin. 2. They are generally characterized by a slow, progressive rate of growth that may come to a standstill or regress. 3. They remain localized to their site of origin and do not have the capacity to infiltrate, invade, or metastasis to distant sites. 4. Because the benign tumors grow slowly by expansion, they surrounded by connective tissue called a fibrous capsule. This capsule is responsible for a sharp line of demarcation between the benign tumor and the adjacent tissues, a factor that facilitates surgical removal.  Characteristic features of Malignant tumor: 1. Malignant tumors are composed of undifferentiated cells, with anaplasia and atypical structure. 2. They can grow rapidly, invade and destroy adjacent structures. 3. They can spread to distant sites (metastasis). Metastasis is the development of a secondary tumor in a location distant from the primary tumor. The cells detach from the original tumor mass, invade the surrounding tissue, and enter the blood and lymph system to spread to distant sites. 4. They lack a capsule and their margins are not clearly separated from the normal surrounding tissue. The lack of a sharp line of demarcation separating them from the surrounding tissue makes the complete surgical removal of malignant tumors more difficult than removal of benign tumors. 5. As malignant tumors grow, they may also compress and erode blood vessels, causing ulceration and necrosis along with hemorrhage Carcinoma (cancer) in situ: Carcinoma (cancer) in situ (Locally malignant tumors): is a group of malignant tumor that spread only locally ( invasive) with no distant spread (metastasis). Depending on its location, in situ lesions usually can be removed surgically or treated so that the chances of recurrence are small. For example: In breast ductal carcinoma in situ the cells have not crossed the basement membrane. Carcinoma in situ of the cervix is essentially 100% curable.  DCIS (ductal carcinoma in situ): Characteristics of Benign and Malignant Neoplasms: Clinical and gross features of benign and malignant tumors: Microscopic features of benign and malignant tumors:  The grading and staging of malignant tumors: The two basic methods for classifying tumor are: 1. Grading according to the histologic or cellular characteristics of the tumor. 2. Staging according to the clinical spread of the disease. It is useful in determining the choice of treatment for individual patients, estimating prognosis, and comparing the results of different treatment regimens. Both methods are used to determine the course of the disease and aid in selecting an appropriate treatment or management plan. Grading of tumors: The grading of tumors involves the microscopic examination of tumor cells to determine their level of differentiation. It is based on the degree of differentiation. Accordingly, on a scale ranging from grade I to III. Grade I neoplasms are well differentiated and Grade III are poorly differentiated and display marked anaplasia. Anaplasia is a change in the structure of cells and in their orientation to each other that is characterized by a loss of cell differentiation.  Well differentiated liposarcoma (grade I) Poorly differentiated liposarcoma (grade III) The staging of tumors: The staging of cancers uses radiographic examination (CT and MRI) and, in some cases, surgical exploration to determine the size of the primary tumor, its extent of local growth, lymph node involvement, and presence of distant metastasis. The TNM staging system was developed by the Union International Cancer Centre (UICC), and the American Joint Committee (AJC) system. In the TNM system: T1, T2, T3, and T4 describe the increasing size of the primary tumor. N0, N1, N2, and N3 advancing node involvement. M0 or M1, describe the absence or presence of distant metastasis.  Naming of benign tumors: Benign tumours usually are named by adding the suffix-oma to the parenchymal tissue type from which the growth is originated. Benign tumours originate from epithelial tissue: Papilloma is a benign tumour arising from an surface epithelial tissue. Adenoma is a benign tumour arising from glandular epithelial tissue. Benign tumours originate from non-epithelial tissue: Fibroma is a benign tumour arising in fibrous tissue. Lipoma is a benign tumour arising in adipose tissue. Chondroma is a benign tumour arising in cartilage. Osteoma is a benign tumour arising in bone. Leiomyoma is a benign tumour arising in muscle. Neuroma is a benign tumour arising in nerve cell. Naming of malignant tumors: Malignant tumors originate from epithelial tissue: Carcinoma is a malignant tumor arising from an surface epithelial tissue which cover the internal organs and outer surfaces of your body. Adenocarcinoma is a malignant tumor arising from an glandular epithelial tissue. Malignant tumors originate from non-epithelial tissue: Sarcomas is a malignant tumor arising from connective tissue. E.g. A malignant tumor of fibrous tissue is a fibrosarcoma and a malignant tumor composed of chondrocytes is a chondrosarcoma. There are some examples contrary to this concept such as melanoma for malignant tumor of the melanocytes, lymphoma for malignant tumor of the lymphoid tissue and Leukemia is the term used for cancer of blood forming cells. Hallmarks of cancer cells: Cell cycle:  How is the cell cycle regulated? The cell cycle is regulated by two groups proteins: 1. The positive regulators proteins such as cyclins and cyclin-dependent kinases (Cdks) these regulatory molecules promote the progress of the cell to the next phase. 2. The negative regulators proteins such as p53, and Rb inhibit the cell cycle. Cancer-associated genes: Most cancer-associated genes can be classified into two main categories: 1. The proto-oncogenes: are a class of normal genes that produce proteins to enhance cell division and prevent cell death. These genes become cancer-causing oncogenes if mutated. E.g. The most important example is RAS oncogene carried in many human tumors such as bladder and pancreatic cancers. 2. Tumor-suppressor genes: are a class of genes that produce proteins to inhibit cell division, repair DNA mistakes, and control the cell death. E.g. 1. P53: induces apoptosis of cells with damaged DNA. Mutation on this gene is responsible for 50% of all cancer. 2. BRCA-1 (breast carcinoma 1) and BRCA-2 (breast carcinoma 2) their mutations are associated with an increased risk for several cancer types including breast and ovarian cancers.  Role of telomere in cell division: A telomere is repetitive DNA sequences at the endof a chromosome. Functions of Telomeres: 1. Telomeres protect the ends of chromosomes from degradation. 2. Telomeres have a role in cell division: Each time a cell divides, the telomeres become slightly shorter. As most somatic cells age, their telomeres become shorter and they exit the cell cycle, resulting in an inability to generate new cells to replace damaged ones. Telomere length is maintained by nucleotide addition mediated by an enzyme called telomerase. In cancer cells, telomerase is usually reactivated and telomere length is stabilized, allowing the cells to proliferate indefinitely.  Cancer spreads by: Spread of cancer cells: 1. Direct invasion and extension: There is a reduced tendency of cancer cells to stick together due to a loss of cell surface adhesion molecules. Most cancers synthesize and secrete enzymes that break down proteins and contribute to the infiltration, invasion, and penetration of the surrounding tissues. 2. Seeding of cancer cells in body cavities: It occurs during the surgical removal of cancers, where it is possible to accidentally introduce free cancer cells into a body cavity such as the peritoneal cavity. 3. Metastatic spread: The term metastasis (meta=change, stasis= position) is used to describe the development of a secondary tumor in a location distant from the primary tumor. Malignant tumors are spread by one of two pathways: 1. lymph channels (lymphatic spread) which is more typical of carcinomas 2. Blood vessels (hematogenous spread) which is favored by sarcomas. Etiology of cancer: Cancer caused by gene alterations that may result from exposure to several factors such as: Age. Heredity. Obesity and Hormone. Viral and microbial Agents. Chemical carcinogens. Radiation.  Heredity: Breast cancer, for example, occurs more frequently in women whose grandmothers, mothers, aunts, and sisters also have experienced a breast malignancy. Two tumor suppressor genes, called BRCA-1 and BRCA-2 have been implicated in a genetic susceptibility to breast cancer. These genes have also been associated with an increased risk of ovarian, pancreatic, colon, and other cancers. Viral and Microbial Agents: 1. DNA viruses: only four DNA viruses have been implicated in human cancers: the human papilloma virus (HPV), Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human herpesvirus 8 (HHV-8). 2. RNA viruses(retrovirus): human T-cell leukemia virus-1 (HTLV-1) is the only known retrovirus to cause cancer in humans. 3. There is also an association between infection with the bacterium Helicobacter pylori and gastric adenocarcinoma and gastric lymphomas.