NEOPLASIA Nadia Ismiil MD FRCPC n n n

NEOPLASIA Nadia Ismiil, MD, FRCPC

n n n Neoplasia: “New Growth” and a new growth is called “neoplasm” Oncology: The study of tumors or neoplasms Cancer: Malignant Tumor

Neoplasm n n 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 evoked the change The persistence of tumors, even after the inciting stimulus is gone, results from heritable genetic alterations that are passed down to the progeny of the tumor cells

n n These genetic changes allow excessive and unregulated proliferation that becomes autonomous, although tumors generally remain dependant on the host for their nutrition and blood supply The entire population of cells within a tumor arises from a single cell that has incurred genetic change, and hence tumors are said to be clonal

n All tumors benign and malignant have two basic components: 1. Proliferating neoplastic cells that constitute their parenchyma 2. Supportive stroma made up of connective tissue and blood vessels

n n Benign tumors are generally designated by attaching “oma” to the cell of origin, e. g. Tumor of Fibrous tissue is “fibroma. ” This is generally true to tumors of stromal origin

n n Nomenclature of Benign tumors of epithelial origin is more complex. The suffix “oma” may follow cell of origin, microscopic or macroscopic features. A benign cystic tumor is “cystadenoma”, a papillary tumor is “papilloma”

n n The nomenclature of malignant tumors follows the same schema. Malignant tumors of the connective tissue are called “sarcoma”. Examples include fibrosarcoma for malignancy of the fibrous tissue and liposarcoma for malignancy of the adipose tissue.

n n Malignant tumors of epithelial cell origin , derived from any of the three germ cell layers are called “carcinoma”, ectodermal, mesoderm or endoderm. Examples include squamous cell carcinoma and adenocarcinoma.

n n n The natural history of most malignant tumors can be divided into four phases: Transformation which is the malignant change happening in the target cell. Growth of the transformed cell. Local invasion Distant metastases. The differences between benign and malignant tumors correspond to these characteristics.

Colonic polyp, benign

Metastatic carcinoma of the liver

Differentiation n The extent to which the neoplastic cells resemble comparable normal cells, both morphologically and functionally. Benign and well differentiated malignant tumors are composed of cells resembling the cells of origin. Poorly differentiated tumors have primitive unspecialized cells.

differentiation n Leiomyoma is a benign tumor of the smooth muscle. Can be seen in uterine fibroids. The tumor cells closely resemble the cells of origin that it may be impossible to recognize it as a tumor microscopically. The only way to recognize it , is because it forms a mass.

Leiomyoma, gross and microscopy

Anaplasia n n Definition: Lack of differentiation. Malignant tumors may be well differentiated. Malignant tumors may be anaplastic, ie, undifferentiated. The cells are primitive. There is mounting evidence that in most cancers, the cells of origin is a stem cell (an undifferentiated cell).

Anaplasia n n In well differentiated cancers, the stem cells will undergo specialization and maturation first then undergo malignant transformation. In undifferentiated cancers, the stem cell will proliferate directly without undergoing the cycle of maturation first.

Anaplasia n n n It is marked by a number of morphologic changes: Pleomorphism, variation in size and shape. It applies to the cells and nuclei. Abnormal nuclear morphology: high nuclear cytoplasmic ratio, hyperchromatism (abundance of DNA), variability of the nuclear shape and prominence of the nucleoli.

Anaplasia (cont. ) n Mitoses: large number of mitoses reflecting the high proliferative index. Its presence by itself is not diagnostic of malignancy since mitoses can be seen in benign tumors. However, the presence of abnormal mitoses is indicative of malignancy.

Anaplasia (cont) n n Loss of polarity: The orientation of the malignant cells is markedly disturbed. Other changes, presence of giant cells is an example. These may al; so be present in inflammatory conditions.

Anaplasia

Dysplasia n n Definition: disordered growth. Encountered principally in epithelia such as cervix and esophagus. Characterized by constellation of changes that include loss of uniformity of the individual cells and loss in their architectural orientation. The dysplastic cells are pleomorphic, high N/C ratio and lots of mitoses.

Dysplasia (cont) n n When dysplastic changes involve the entire thickness of the epithelium, they are considered peri-invasive tumors with no invasion (yet). The process is called carcinoma in situ. Dysplasia may be found next to an invasive cancer. The detection of early dysplastic changes in cervix by pap smear is one of the greatest success stories in medicine. Dysplastic changes in esophagus can be seen in cigarette smokers.

Cervical dysplasia

Dysplasia in the intestinal epithelium

Genetic predisposition to cancer n n Evidence now indicates that for a large number of cancer types, there exists not only an environmental influences but also hereditary predisposition. Less than 10% of cancer patients have inherited mutations that predispose to cancer.

Continued n n Genetic predisposition to cancer can be divided into three categories: Autosomal dominant inherited cancer syndrome, in which the inheritance of a single mutant gene increases the risk of developing a tumor. Retinoblastoma, a malignant tumor of the eye is an example.

Continued n n Defective DNA repair syndrome. There will be a defect in the repair process leading to DNA instability. Example is hereditary non polypoid cancer syndrome (HNPCC). Familial cancers. Cancer may occur more frequently in some families, so far non clearly defined pattern. Example, breast, colon and ovarian cancer.

Molecular basis of cancer n n Non lethal genetic damage lies at the heart of carcinogenesis. Such genetic damage (mutation) may be environmental such as chemicals, radiation or viruses or may be inherited in the germ line. A tumor is formed by the clonal expansion of a single precursor cell that has incurred the genetic damage, tumors are monoclonal.

continued n Four classes of regulatory genes, the growth promoting protooncogenes, the growth inhibiting tumor suppressor genes, genes that regulate apoptosis and genes involved in DNA repair ARE THE PRINCIPLE TARGETS OF GENETIC DAMAGE.

Molecular basis of cancer n WHAT ARE THE ESSENTIAL ALTERATIONS FOR MALIGNANT TRNSFORMATION? ?

n n n 1. Self sufficiency in growth signals , tumors have the capacity to proliferate without external stimuli. 2. Insensitivity to growth inhibiting signals. 3. Evasion of apoptosis 4. Defects in DNA repair 5. limitless replicative potential

n n 6. Sustained angiogenesis, vascular supply. 7. ability to invade and metastasize

Examples of occupational associated cancers n n Asbestos: lung mesothelioma Nickel: nose and lung cancer Vinyl chloride: liver tumors Ethylene oxide: Leukemia

Lung cancer