Ch. 6 - Cancer/Neoplasia

Mechanism of actions of chemotherapy

Chemotherapy exposes the tumor cells to toxic doses of various chemicals, and targets the patient's DNA, inducing faulty division of cells (hopefully the tumor cells). Doesn't just affect malignant cells, and normal tissues are often damaged in the process, exposing the patient to side effects that are often severe.

Fibrous Stroma

Connective tissue framework, supports tumor cells. Tissue itself is nonneoplastic. The amount of fibrous stroma varies depending on the tumor. Tumors that produce little stroma: softer, fleshy consistencies, typical of sarcomas. Tumors that produce a lot of stroma: densly collagenous tumors, hard to the touch called a scirrhous tumor. Typical in adenocarcinoma (breast cancer).

Pain

Effect of tumor growth. Intermittent or constant and often severe is associate with tumor growth usually due to bone invasion leading to fractures, hollow organ obstruction that stretches and distorts their walls, direct invasion of nerves, tumors of the spinal cord or brain with compression

Hormonal Effects

Effect of tumor growth. Less anapestic tumors (AKA less malignant) functional hormones may be produced with hyper secretion and overestimation of target tissues. Increased anapestic tumors (AKA more malignant) will produce hormones that function only partially leading to hypo functioning of the target tissues.

Obstruction

Effect of tumor growth. Obstruction of a duct of passage to normal flow or movement. (pharyngeal or esophageal carcinomas, ureters, cerebral aqueduct)

Cachexia

Effect of tumor growth. Seen in advanced malignancies and is a syndrome involving generalize weakness, fever, wasting (weightless), anorexia (loss of appetite), and pallor (paleness) There are multiple possible causes for this.

Organ Compression

Effect of tumor growth. Tumor mass compresses organ causing harmful effects (Brain and spinal cord)

Ectopic secretion

Effect of tumor growth. Tumors of non endocrine origin develop the ability to secrete functional hormones.

Paraneoplastic Syndromes

Effect of tumor growth. refers to the wide variety of tumor-related effects who pathogenesis is poorly understood. (the link b/w the tumor and the paraneoplstic effects is unclear-Example: Leg vein thrombosis with pancreatic or lung tumors)

Oncogenesis

Formation of a tumor

Dysplasia

Is seen in an epithelium when irritation is more severe or prolonged. The tissue is replaced with tougher, stratified tissue as seen in metaplasia. However, the tissues architecture is disordered and its cells demonstrate pleomorphism.

Giant Cell Carcinoma

Malignant cancers with extreme anaplasia with cells that only resemble general embryonic tissue

Resistant tumors (to chemo)

Malignant melanoma Carcinomas generally Lung cancer Soft tissue sarcomas

Mucoid tumor (colon carcinomas)

Overproduction of mucus (tumor product) causes a loose gelatinous textured tumor

Antitumor intervention: Chemotherapy

Pros: Chemicals could kill the tumor cells off Cons: Normal tissue is susceptible to damage as well, Side effects often severe, Side effects often demoralize pt, Tumor cells may build up a resistance/tolerance (tumor reduction occurs first, but slows or stops completely after a few doses), If p53 protooncogene is damaged, apoptosis cannot occur and the tumor cells can survive and regenerate despite chemotherapy

Mechanism of actions of radiation therapy

Radiation therapy delivers a toxic dose of ionizing radiation to the tumor cells to destroy them. It targets fast-dividing cells (such as malignant tumors). Doesn't just affect malignant cells, and normal tissues are often damaged in the process, exposing the patient to side effects that are often severe.

Classification of tumors based on relative sensitivity to radiation therapy (Table 6.6)

Radiosensitive, Moderately RS, Non-RS *The more radiosensitive a tumor, the more likely it will respond well to radiation therapy*

Malignant Tumors

Rapid growth producing a large tumor mass, aggressively invasive, the tumor will send columns of cells into adjacent normal tissues disrupting structure and function, capsule occurrence is rare (nonexistent, incomplete, or irregular) ***lack of capsule leading to difficulty distinguishing between malignant and normal tissue makes surgical removal complicated

Highly susceptible tumors (to chemo)

Retinoblastoma Hodgkin's disease Wilm's tumor (renal tumor of childhood) Testicular tumors Acute lymphoblastic leukemia Choriocarcinoma

Moderately susceptible tumors (to chemo)

Small cell carcinoma of lung Lymphocyctic lymphoma Leukemia: acute & chronic myeloid Carcinoma of the breast and ovary

Moderately RS tumors

Squamous cell carcinoma Genital carcinoma Esophageal carcinoma Bronchogenic carcinoma

Effect/Consequences of Tumor Growth

Tissue Destruction, Organ Compression, Obstruction, Infection, Anemia, Pain, Hormonal Effects, Paraneoplastic Syndromes, Cachexia

How do metastasizing tumor cells migrate to secondary sites of occurrence?

Tumors can metastasize through blood vessels, lymphatic vessels, body cavities, natural passages, and Iatrogenic. In metastasis the original tumor mass (primary site) has invaded a vein or lymphatic vessel and will shed cells that travel in the blood as an emboli until they reach some part of the vascular system that prevents their passage, they become trapped and resume growth, as growth proceeds the tumor invades the vessel wall gaining access to the secondary site.

Lymphatic Vessel Metastasis

Tumors grow within the lymph nodes and easily spread from one lymph node to another causing multiple secondary sites. Blockage of the lymph by the tumor will lead to retrograde lymph flow and unusual and unexpected embolus dissemination. Also, lymph vessels close proximity to blood vessels increase metastasis.

Metastasis via Body Cavities

Tumors invade through the surface of the primary site organ and spread to other sites. Factors that assist with this type of metastasis: gravity, peristaltic motions, movement of the abdominal organs caused by movements of the diaphragm in normal breathing, repiratory pressure changes affecting CSF

Tumor Staging

a system of categorizing malignant tumors in terms of their potential or invasion and metastasis and is applied only to solid tumors (NOT leukemia). This is useful for assessing prognosis, selecting appropriate therapy and crying out epidemiological studies (relationship b/w tumors, their host populations, and relevant environmental factors)

Tumor

aka Neoplastic mass aka neoplasm. Will grow beyond the body's needs and can continue until the resulting disruption of function causes the victim's death

Secondary site

re: Malignant tumor. An established tumor at a distant location from the primary tumor site. (although there is no physical continuity. The secondary tumor is the same tissue as the primary tumor) ***The secondary site has NOT become neoplastic instead the tumor cells have been transported from the primary site and have resumed growth at the secondary site

Primary site

re: Malignant tumor. Original (first) growth site, original tumor mass.

Cancer

refers to a malignant tumor

Metastasis

spreading of a MALIGNANT tumor to a distant point in the body (single characteristic that differentiates a malignant tumor from a benign tumor)

Blood vessel Metastasis

thin walls of capillaries and veins are easy to penetrate by aggressively growing tumors. The tumor embolism then passes from the veins to the heart and into the lungs causing the lungs to be a common place for metastasis. *the major exception is the abdominal drainage (intestines and stomach) into the liver causing metastasis in the liver.

Iatrogenic Metastasis

very rare. seen in biopsies or surgical excision of a tumor.

Vascular Stroma

Blood vessels that are nonneoplastic, formed in response to increased demand from tumor. After a tumor reaches a diameter of 1 mm it begins angiogenesis (similar healing tissue) utilizing vascular endothelial growth factor (VEGF). it is thought that the > VEGF may overcome the effects of inhibiting growth factors. The vessel formation is less regular with loser endothelial junctions and may lack basement membranes then seen in regular healing tissue.

Characteristics of Benign v. Malignant tumors (table 6.2)

Cell structure: B=near normal, M = Abnormal shape, larger cell & nucleus. Tissue structure: B= Orderly, M = Disordered. Growth Rate: B= Above normal, M = Rapid. Invasive growth: B = Uncommon. M= Typical. Metastasis: B=Never, M = Typical. Capsule: B=Typical, M = Rare or incomplete if present. Anaplasia: B=Minimal, M=Poor. Prognosis: B=Good, M=Poor

Pleomorphism

Cells that are variable in their size and shape in contrast to regular cells structure seen in normal tissues. (seen as large, dark stained nuclei with increased mitosis rates). Pleomorphism is reversible but not as easily as metaplasia and is considered to proceed a tissue becoming neoplastic. Some forms are considered pre-cancerous.

Neoplastic Tissue

Degree of resemblance to its tissue of origin. Benign: slow, orderly tumor remaining localized, cells near normal size and shape, cell arrangement is close to normal tissue vs. Malignant: rapid, disorderly growth with aggressive invasion into adjacent normal tissues, cells are pleomorphic with enlarged, unusual shaped nuclei, abnormalities of chromosome structure and numbers, use of anaerobic glycolysis as an energy source (regardless of energy source), increased anaplasia

Tumor Products

Depends on the tumor's degree of anaplasia. The more anaplasia the less products the host tissue of the tumor will produce, or the product with be nonfunctional (ex: squamous cell carcinomas produce excessive keratin which lies below the surface of the skin) Tumors can overproduce enzymes that can lead to specific tumor diagnosis from blood work. Benign tumors: products more closely resemble normal products. Malignant: may somewhat resemble normal products or be completely nonfunctional

Anemia

Effect of tumor growth. Caused by chronic bleeding associated with many malignant tumors due to tumor disruption/growth into blood vessels and disruption of the bone red marrow (platelet production decline>decreased coagulation) chemo and radiation suppress marrow production as well. Renal Tumors the kidney's normal production of erythropoietin may decline (principle stimulus to RBC production) leading to anemia. Gastrointestinal tumors interfere with normal absorption and availability or iron and vitamin B12. Leukemia and some lymphomas can induce autoimmune responses directed against normal erythrocytes (hemolysis). Polycythemia (excessive production of RBC) is produced by benign renal tumor secretion of erythropoietin

Tissue Destruction

Effect of tumor growth. Compression of blood vessels by the tumor leading to reduced nutrients supply and waste removal. Tumors release of enzymes that disrupt the ECM necessary for normal function. Highly malignant tumors penetrate adjacent structures (cervical carcinoma causes renal failure)

Infection

Effect of tumor growth. Examples: Suppression of immune system in some malignancies, bone marrow suppression, tumor growth near the body surface disrupting the barrier to infection, disruption to normal patterns of motion that inhibit bacterial proliferation and infection

Non RS tumors

Fibrosarcoma Osteogenic carcinoma Various adrenocarcinomas

Tumor Grading

Following a biopsy the degree of differentiation, the extent of pleomorphism, and the frequency of mitosis are studied as a means of judging the degree of malignancy a tumor has achieved. Grades I-IV.

Tumor Grading (I-IV)

Grade I highly differentiated cells, well organized, few mitosis visible Grade II and III: intermediate degrees of malignancy Grade IV: poorly differentiated, pleomorphic, mitosis is increased *In general a low grade indicates a slow growing tumor with limited tendency to invade and metastasize.(usually good prognosis) Grade III and IV prognosis is less optimistic.

Benign Tumors

Grow more rapidly than normal tissue but not as fast as malignant, grow in an orderly pattern of expansion, ***slower growth and presence of a fibrous connective tissue capsule helps make surgical removal easier.

Classification of tumors based on relative sensitivity to chemotherapy (Table 6.6)

Highly susceptible, moderately susceptible, resistant

TNM staging system

Internationally recognized & widely used staging system. Has 3 tumor criteria assigned to modifying subscript number related to size or degree, with lower numbers indicating low degree and higher numbers referring to increasing degrees. T (size of the primary tumor)T0: no tumor can be found at the primary siteT1,T2,T3: tumors are increasing in sizeN (degree to which regional lymph nodes are involved)N0: No evidence of regional lymph node involvementN1, N2, N3: Increasing regional lymph node involvementM (tumor metastasis)M0: no metastasisM1, M2, M3: increasing metastasis

Oncology

Literal translation from greek word. Oncos = tumor.

What are the typical structural characteristics of a malignant versus a benign tumor?

Look at: Neoplastic tissue, Fibrous Stroma, Vascular Stroma, Tumor Products

Anaplasia

Loss of specialized functional capabilities of a specific tissue. Malignant tumor cell mitosis causes anaplasia within the host tissue. (>anaplosia → >malignancy).

Carcinoma

Name for malignant tumor arising from the ectoderm (outer lining of the body) or endoderm (internal lining of the body). Mainly skin & epithelial linings of the alimentary canal and respiratory passages. Ex. adenocarcinoma

Sarcoma

Name for malignant tumor in the mesoderm (in tissues): Ex. tumors in cartilage and fibrous connective tissues = chondrosarcoma, fibrosarcoma

Metastasis via Natural Passages

Natural Passages refers to lumens (small intestines etc.) this is very unlikely to occur due to the harsh environment of the lumen

Radiosensitive tumors

Neuroblastoma Chronic Leukemia Lymphomas Wilm's Tumor (Renal tumor of childhood)

Neoplasia

New tissue formation that involves the overgrowth of a tissue to form a neoplastic mass = neoplasm=tumor. Potentially grave growth abnormality, the more serious form = cancer. Irreversible alteration in cell's growth pattern. 2nd ranking cause of death in N. America.

Serous tumors

Overproduction of serous fluid (tumor product) may cause cysts

Antitumor intervention: Radiation therapy

Pros: Delivers destructive dose of ionizing radiation to tumor mass, Especially effective for radiosensitive tumors (the radiation does more harm to the tumor before it does to normal tissue) Cons: Normal tissue is susceptible to damage as well, Usually damage epithelia of skin, hair, and GI tract (rapidly dividing cells), Heat that develops in the skin as the radiation passes through it can cause burns

Antitumor intervention: Surgery

Pros: Simple and direct, Eliminates the problem by physically removing the tumor, Can cause minimal damage to normal tissue if the tumor is well-defined, encapsulated, or benign Cons: Malignant tumors often have poorly defined boundaries, and good tissue is lost or bad tissue remains after excision, Whole lymph channels need removal if tumor has spread via these channels, Manipulation of the tumor may cause tumor emboli, which can metastasize to produce secondary growths

Antitumor intervention: Immunotherapy

Pros: Using the immune system to combat tumor, Use of BCG antigen stimulates immune response at first, but now interleukin-2 is used to boost the immune system to combat tumor growth Cons: Not as successful at destroying tumors , Side effects: nausea, fever, liver damage, and inflammation/abscess formation at the site of antigen injection, Can provoke autoimmune response against normal tissues

General Staging Information (4 stages)

Stage I: Growth restricted to primary site. Stage II to III: Fall between the two extremes.... Stage IV: grown and invaded extensively and shows wide metastatic spread

Antitumor interventions

Surgery, Radiation therapy, Chemotherapy, Immunotherapy

Metaplasia

The conversion of one cell type to another. Chronic exposure to unfavorable condition produces this change. Examples: Respiratory epithelium undergoes metaplasia due to inhaled irritants (smoke, industrial pollutants). The normal ciliated pseudo stratifies epithelium is replaced by thicker, tougher linings that is well organized with a normal appearance. However the new lining loses its cilia and goblet cells leading to reduced ability to clear inhaled particles and microorganisms. Metaplasia in epithelia is usually reversible.

Be able to identify the benign or malignant tumor by its tissue of origin. Be able to identify if a specific tumor is benign or malignant. (Table 6.1, p. 135)

The table goes into more detail, but: General Info on naming tumors Benign vs Malignant. Suffix -oma: designates ANY tumor type. Benign Tumors: tissue type+oma (Example: Bone: osteoma). Some exceptions. Malignant Tumors: Based on Embryonic origin of the tissue (ectoderm, endoderm, mesoderm)

(Table 6.3) Primary tumor: Prostatic carcinoma

Typical sites of Metastasis: Bone (esp vertebral column)

(Table 6.3) Primary tumor: Carcinoma & breast adenocarcinoma

Typical sites of Metastasis: Bone (esp. vertebral column), brain, liver, adrenals, regional lymph nodes

(Table 6.3) Primary tumor: Nueroblastoma

Typical sites of Metastasis: Bone, regional lymph nodes

(Table 6.3) Primary tumor: Bronchogenic carcinoma

Typical sites of Metastasis: Brain, spinal cord, bone, regional lymph nodes

(Table 6.3) Primary tumor: Colon Carcinoma

Typical sites of Metastasis: Liver, brain, ovary, lung, regional lymph nodes

(Table 6.3) Primary tumor: Osteosarcoma

Typical sites of Metastasis: Lung, brain

(Table 6.3) Primary tumor:Renal carcinoma

Typical sites of Metastasis: Lung, liver, bone, brain

(Table 6.3) Primary tumor: Malignant melanoma

Typical sites of Metastasis: Lung, liver, spleen, regional lymph nodes