Chapter 7 Neoplasia

PRE LECTURE QUIZ (True/false) Cancer is a disorder of altered cell differentiation and growth. Surgery, radiation, and chemotherapy are the only identified treatment modalities for cancer. The Papanicolaou test is a cytologic method used to detect cancer cells. Cell differentiation is the process whereby proliferating cells are transformed into different and more specialized cell types. Benign neoplasms are less differentiated tumors that grow in a crablike manner to invade surrounding tissues, have cells that break loose and travel to distant sites to form metastases, and inevitably cause suffering and death unless their growth can be controlled through treatment.

PRE LECTURE QUIZ The process of ______________ a tumor involves the microscopic examination of cancer cells to determine their level of differentiation and the number of mitoses. In general, benign tumors usually are named by adding the suffix __________ to the parenchymal tissue type from which the growth originated. The term ________________ is used to describe the development of a secondary tumor in a location distant from the primary tumor. ________________ spread would involve metastasis that occurs by way of the blood vessels. ________________ syndromes are defined as the production of signs and symptoms at sites that are not directly affected by the disease or cancer. grading Hematogenic Metastasis -oma Paraneoplastic

Neoplasia Neoplasms proliferate to form new tissue They do not wait for signals from the body that the new tissue is needed They ignore signals to stop dividing They often do not mature normally (differentiate) to do the “job” the tissue is supposed to do They do not die off (apoptosis) to keep the number of total cells constant

Cancer Incidence and Mortality

The Cell Cycle Normally, the number of cells produced = the number of cells that die The total number of cells in the body remains constant

Growth Factors Cells divide only when they are told to do so by growth factors These cause stable cells to enter the cell cycle and divide

Growth Factors (cont.) Attach to receptor proteins  Which often work by affecting G proteins  Which turn on enzymes (proteins)  Which make second messengers  Which go down inside the cell and make it divide

Growth Factor Receptors Now this cell is ready to respond to growth factors from another cell They bind to the receptors and stimulate cell division

The normal genes that code for normal proteins used in cell division Proto-oncogenes The normal genes that code for normal proteins used in cell division Growth factors Growth factor receptors G proteins Enzymes that produce second messengers Genes that turn the production of these proteins on and off

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Oncogenes Oncogenes are mutated proto-oncogenes They still code for the proteins needed for cell division But they might produce Too much of the protein An abnormal protein Protein that turns on all by itself Protein that is made when it is not needed Protein that cannot turn cell division off Protein that should be made by a different cell

Question True or False: Oncogenes code for normal proteins used in cell division.

Answer False The statement describes proto-oncogenes. Oncogenes are mutated proto-oncogenes that code for abnormal proteins.

Checkpoints in Cell Division Permanent cell Cyclin proteins measure whether the cell has grown large enough to divide Cyclins make sure the cell has made the proteins needed to separate the chromosomes G0 M G2 Mitosis Inter-phase G1 Cyclins check that the DNA has been correctly duplicated S R

Tumor-Suppressor Proteins The checkpoints usually stop the division of mutated cells They keep most mutations from developing into cancer So the proteins that control the checkpoints are called tumor-suppressor proteins Cyclins Cyclin-dependent kinases Cyclin inhibitors (p53) If the genes for these proteins were mutated, you might get many more cancers

Cell Division Requires Duplicating the DNA Telomeres: DNA sequences at the ends of the chromosomes The enzymes that duplicate DNA attach here The end of the telomere does not get duplicated What will happen to the telomere as the cell continues dividing? A man has a mutation that causes some of his cells to rebuild their telomeres after every division. Is this a good thing or a bad thing? Why?

Oncogenesis Initiation: Initial mutation occurs Promotion: Mutated cells are stimulated to divide Progression: Tumor cells compete with one another and develop more mutations which make them more aggressive

Labile = Apt or likely to change Normal Cells Labile = Apt or likely to change Normally, after a cell has divided, it becomes either a permanent cell or a stable cell These cells stop reproducing and continue working for the body M Permanent cell G2 G1 G0 S Stable cell

Differentiation “Grown-up” cells are called differentiated because they look different from one another You can tell a spleen cell from a skin cell

Cell Mutation When differentiated, “working” cells mutate, they form differentiated “working” tumors— benign tumors When undifferentiated, rapidly dividing cells mutate, they form rapidly dividing tumors—malignant tumors

Question When a well-differentiated cell mutates, is it more or less likely to become a malignant tumor? More Less Degree of differentiation has no bearing on whether a tumor is malignant or benign.

Answer Less The more differentiated a cell is when it mutates, the more likely it is to become a benign tumor. If poorly differentiated cells mutate, the tumor is more likely to become malignant.

Naming Tumors Benign tumors: tissue name + “-oma” Glioma - tumor of the brain composed of neuroglia. Malignant tumors (cancers) Epithelial tissue: tissue name + “carcinoma” Basal cell carcinoma Mesenchymal tissue: tissue name + “sarcoma” Osteo sarcoma

Contain cells that look like normal tissue cells Benign Tumors Contain cells that look like normal tissue cells May perform the normal function of the tissue (like secreting hormones) This may lead to oversecretion Usually have a capsule around them Usually do not invade neighboring tissues But they can damage nearby organs by compressing them

Malignant Tumors Contain cells that do not look like normal adult cells These cells divide rapidly, so: Tumors grow quickly Cells mutate faster and can change type The tumor does not have clear boundaries and sends “legs” out into surrounding tissue (the word cancer means “crab” and is based on these crablike legs) Do not perform the normal functions of the organ May secrete hormones associated with other tissues Can compress and/or destroy the surrounding tissues

Metastatic Carcinoma in Periaortic Lymph Nodes

Lung Cancer

Question What gross anatomic feature of the lung tumor you just saw makes it likely to be malignant? The tumor is growing quickly. The tumor has a poorly defined border. Cells do not look like normal cells. All of the above b and c

Answer b and c Gross anatomy can be viewed with the naked eye. Although rapid growth is a characteristic feature of malignant tumors, this cannot be determined from the slide. However, the lack of a clear border, and the different appearance of the group of cancer cells can be clearly seen.

Metastasis Cells in a primary tumor develop the ability to escape and travel in the blood Imagine you were a cancer cell. What abilities would you need to survive in the tumor? What abilities would you need to metastasize?

Scenario Mrs. T Has Liver Cancer Her doctor did an initial molecular diagnosis and put her on targeted therapy; the tumor shrank by almost 75% Two years later the tumor was growing again, and this time it did not respond to the drug Last year she was diagnosed with metastases in her femur that has not responded to the drug either Mrs. T wants to know why the cancer cells stopped responding. Are they not all the same cells?

Manifestations of Cancer Changes in organ function (organ damage, inflammation, and failure) Local effects of tumors (e.g., compression of nerves or veins, gastrointestinal obstruction) Ectopic hormones secreted by tumor cells (paraneoplastic disorders) Nonspecific signs of tissue breakdown (e.g., protein wasting, bone breakdown)

Changes in Organ Function Organ failure Benign tumors may cause overproduction of normal organ secretions Malignant tumors may occasionally cause overproduction (as in thyroid cancer), but more commonly decrease production of normal organ secretions

Question Why do malignant tumors usually cause a reduction in the amount of hormones the affected organ produces? Organ damage Inflammation of the organ Organ failure All of the above a and c

Answer All of the above Effects of malignant tumors on the organ system include inflammation and damage, which ultimately lead to organ failure. In all cases the organ cannot function optimally, and is unable to secrete the normal/typical amount of hormones.

Local Effects of Tumor Growth Bleeding Compression of blood vessels Superior vena cava syndrome Portal hypertension Compression of lymph vessels Edema, ascites, effusion Compression of hollow organs Compression of nerves Pain, paralysis

Paraneoplastic Syndromes Cancer cells produce hormones or hormone-like proteins ADH ACTH PTH-related protein Cancer cells produce proteins that affect clotting Paraneoplastic neurologic disorders

Clinical Manifestations of Cancer Cancer cachexia syndrome Weight loss Muscle wasting Weakness Anorexia Anemia Cachexia -Greek meaning Bad Condition

Tumor Markers

Cancer Treatment Surgery Radiation Therapy Chemotherapy Hormone and Antihormone Therapy Biotherapy

Incidence and Types of Childhood Cancer The incidence of childhood cancers is greatest during the first years of life