Ch 6 - Terminology, Characteristics, and Biology of Neoplasms

Neoplasm

also known as a tumor

• cellular growth (and prolifertation) that no longer responses to normal genetic controls

• cells continue to reproduce with the need for reproduction (they lose their ability to control replication and controlled apoptosis)

• deprives other cells of nutrition

What type of cells are in neoplasms?

atypical or immature cells

Characteristics of each tumor depeonds on what?

• Type of cell the tumor arises from

• Unique structure and growth pattern

• Location

Tumor

a swelling that can be caused by a number of conditions

• it is used to define a mass of cells that arises because of overgrowth

• also referred to as a neoplasm: “new growth”

Cancer

also called a malignant tumor

• derived from Greek work for “crab” - “karkinoma”

characterized by uncontrolled cell proliferation

Benign and Malignant neoplasms are distinguished by what?

1. Cell characteristics: the appearance and behavior of cells (benign tumors are well-differentiated when malignant are not)

2. Rate of Growth: how fast the cells multiply and increase in size (benign is very slow and has an encapsulated border and malignant is very quickly and has no encapsulated border)

3. Manner of Growth: the pattern by which a tumor expands and develops

4. Capacity to invade and metastasize other parts of body: ability to spread into tissues and distant parts (only malignant tumors metastasize)

5. Potential for causing death

Benign

Cell characteristics: well differentiated (resemble tissue of origin)

Rate of Growth: usually progressive and slow; may come to a standstill to regress

Mode of growth: grows by expansion without invading the surrounding tissue (remains local); usually encapsulated

Metastasis: does NOT spread by metastasis

• benign tumors do not cause death UNLESS their location interrupts vital body functions

Malignant

Cell characteristics: not well differentiated (low or poor); with anaplasia and atpyical structure

Rate of growth: variable and depends on level of differentiation; more undifferentiated cells, the more rapid the growth

Mode of growth: grows by invasion, sending out processes that infiltrate the surrounding tissues

Metastasis: uses metastasis, gains access to body and lymph channels to metastasize to other areas of the body

• causes death unless growth can be controlled through treatment

• malignant tumors have lost the ability to control both cell proliferation and differentiation

Leiomyosarcoma

malignant tumor that grows from stroma muscle cells

• grows from the estrogen that forms the thickness of the cell wall if found in uterus

Leioyoma

benign tumor that develops from smooth muscle

• common in women during childbearing years (50%)

  • estrogen feeds tumor, non-invasive grows only by expansion

• grows from the estrogen that forms the thickness of the cell wall if found in uterus

Lipoma

benign tumor of fat tissue

Papilloma

benign tumor of epithelial tissue

Carcinomas

malignant epithelial tumors

• ex) adenocarcinoma —> arise in ducts or glands

Sarcomas

malignant CT tumors

Lymphomas

malignant cancers of lymphatic tissue

• lymphomas are always malignant

Benign tumors - medical terminology endings

-oma

whenever the name ends in oma, it is benign

Malignant tumors - medical terminology endings

• sarcoma

• leukemia (always malignant)

• carcinoma

• myeloma (benign tumors are uncommon in the brain)

Clonal proliferation and expanion

occurs when cancer cells progeny can accumulate faster than nonmutant neighbors

• cancer cells don’t go through apoptosis, cancer cells secrete growth factors

Angiogenesis

mutant cells secrete growth factors

• these GF stimulate the development of new capillaries in the tumor

this is a normal response by cancer cells, stimulates proliferation and synthesis of new BVs

• malignant tumors have larger BVs supplying them

Malignant transformation

is the process during which a normal cell becomes a cancer cell

• genetic mutations are required before cancer can develop

Mutation

alternation of DNA sequence affecting expression or function of a gene

• multiple mutations are required for malignant transformation

Gene amplification

repeated duplication of chromosome

• 10s or 100s of gene copies are made

Chromosome translocation

large changes in chromosome structure

• piece of one chromosome is translocated to another chromosome

Proto-oncogenes

normal nonmutant genes that ocde for normal cellular growth

• they become oncogenes when mutated

Oncogenes

mutated proto-oncogens that promote excessive cell growth

Tumor-suppressor genes

prevent uncontrolled cell growth and help maintain genomic stability

• as these cells mutate, they lose their ability to suppress cancer

• they are referred to as anti-oncogenes

Carcinogenesis

the multi step process by which normal cells turn into cancer cells

Three key genetic mechanisms of human carcinogenesis:

• 1: activation of oncogenes

• 2: inactivation of tumor suppressor genes

• 3: defects in DNA repair genes

Activation of oncogenes

mutations of proto-oncogenes can convert them into oncogenes, promoting uncontrolled cellular growth and proliferation

• cells lose ability for apoptosis

one major mechanism of human carcinogenesis

Inactivation of tumor suppressor genes

loss or alteration of tumor suppressor genes removes important controls on cell division (becomes uncontrolled), DNA repair, and apoptosis (loses ability)

• one major mechanism of human carcinogenesis

Defects in DNA repair genes

mutations in genes responsible for repairing DNA damage allow additional mutations to accumulate, increasing cancer risk

• one major mechanism of human carcinogenesis

Burkitt Lymphoma

the MYC proto-oncogene (which encodes for growth signal protein), is translocated from its normal position on chromosome 8 to chromosome 14

• associated with chromosomal translocation

CML (chronic myloid leukemia)

translocation involving chromosomes 9 and 22 resulting in formation of an abnormal fusion protein

• fusion protein (single hybrid molecule made by joining two or more separate genes or proteins) is a hybrid oncogenic protein (bcr-abl) that promotes cell proliferation (Philadelphia chromosome)

Philadelphia chromosome is an abnormal, shortened chromosome 22 linked to certain types of blood cancer

• chromosomal translocation

Three steps of carcinogenesis

1. Initiation → exposure of cells to a carcinogenic agent causes alterations in DNA, affecting genes that regulate cell growth, DNA repair, or apoptosis (some carcinogenic agents include chemicals, radiation, viruses)

2. Promotion → allows growth and proliferation of cells triggered by multiple growth factors and chemicals (this is reversible if the promoter substance is removed)

3. Progression → the process where tumor cells acquire malignant phenotypic changes (become malignant and aggressive)

carcinogenesis is a long-term process

Risk factors of cancer

cancers do not have one single specific cause, rather, they have multiple risk factors such as:

• Heredity

• Hormonal Factors (ex. hormonal birth control)

• Immunologic mechanisms

• Environmental agents (chemicals, radiation, cancer-causing viruses)

cancer occurs because of interactions among MULTIPLE risk factors or prolonged REPEATED exposure to a single carcinogenic agent

BRCA1 and BRCA2 genes

have been identified in genetic susceptibility to breast and ovarian cancer

• people carrying BRCA mutation have a lifetime risk of 80% of developing breast cancer

note: women carrying no other risk factors other than BRCA have only a 40% risk of developing breast cancer

Carcinogen

agent that is capable of causing cancer

• classified in two groups: direct-reacting agents and indirect reacting agents

Direct-reacting agents

do not require activation in the body to become carcinogenic

• they can bind directly to DNA and cause mutations

Indirect reacting agents

pro carcinogens or initiators

• become active only AFTER metabolic conversation

activated metabolite binds to DNA, causing mutations

Carcinogen vs promoter

carcinogens produce genetic mutations that can transform a normal cells into a initiated cell (ex. cigarette smoke)

promoters do not directly cause mutations but encourage the growth and division of previously mutated cells (ex. inflammation caused by H. pylori increases the risk of gastric cancer)

Oncovirus

virus that causes or leads to cancer

• oncogenic viruses insert their genetic material (DNA or RNA) into a host cell

Viruses that cause cancer in humans

1. HPV

2. Epstein-Barr Virus (EBV)

3. Kaposi Sarcoma Herpesvirus (KSHV or HHV8)

4. Hepatitis B

Local effects of cancer

happens when cancer disrupts tissue integrity

• results from infiltration and disruption of lumen, blood supply, and leads to inflammation

• when cancer compresses and erodes blood vessles, causing ulceration, necrosis, and bleeding

Systemic effects of cancer

commonly seen in advances stages of cancer

• ex. cancer cachexia —> a syndrome characterized by progressive weight loss, loss of skeletal muscle and fat, weakness, and anorexia

Pain

local effect of cancer

• may be absent until late stages (which is bad)

• it occurs when the tumor is well advances

• the severity of pain depends on the type of tumor

Obstruction

type of local manifestation of cancer

• when the tumor compresses a duct or passageway (digestive tract, bronchi)

• blood supply or lymphatic flow might be restricted

obstruction can cause pain

tumor blocking the bronchi can lead to a lung collapsing

tumor compressing the GI tract can cause inability to pass feces

Tissue necrosis and ulceration

type of local manifestation of cancer

• may lead to bleeding or infection around tumor

Weight loss

a systemic clinical manifestation of cancer

• due to increased demands for tumor cells on the body

• anorexia, fatigue, pain, or stress

Anemia

a systemic clinical manifestation of cancer

• due to blood loss at tumor site

• nutritional deficits may reduce hemoglobin synthesis (slow bleeding can lead to chronic anemia)

Severe Fatigue

a systemic clinical manifestation of cancer

• due to inflammatory changes, cachexia, and anemia

Effusions

a systemic clinical manifestation of cancer

• inflammation causes fluid buildup in body cavities

Paraneoplastic syndrome

not associated with invasion, rather, often caused by ectopic hormone production or immune mechanisms

• result of cancer cells secreting hormone like substances

ex) squamous cell carcinoma of the lung can secrete PTH, resulting in hypercalcemia that can lead to metastatic calcification

Metastasis

the spread of cancer cells from the site of original tumor to distant tissues and organs through the body (spread and develop into secondary tumors)

Invasion

the local spread of cancer that is a prerequisite for metastasis and the first step in the metastatic process

• requires that the cancer attach to specific receptors and survive in specific environments

Epithelial-mesenchymal transition (EMT)

process in which epithelial cells lose their normal characteristics and acquire mesenchymal (immature cells that develop into other types of cells) features

• they lose epithelial like characteristics like polarity and the ability to adhere to basement membrane

this increase migratory capacity (cancer cells secrete protease)

this process also increases resistance to apoptosis

this process also increases dedifferentiation (loss of differentiation) → cells can withstand the physiologic stresses of travel

Protease

digests the extracellular matrix and basement membranes of epithelial tissue and creates pathways through which cells can move

• are released during EMT

Lymphatic metastasis

one of the major routes by which cancer spread from primary site to distant location

• used by most cancers because epithelial tissue has no BVs

• this is the earliest detectable spread in epithelial cancers

cancers first go to regional lymph nodes

• sentinel lymph node biopsy is important in detecting the cancer spread

• ex) breast cancer spreads first to the axillary lymph nodes

Hematologic metastasis

one of the major routes by which cancer spread from primary site to distant location

• used by most cancers originating in CT

• cancer cells spread throughout the blood (more associated with advanced disease)

cancers first go to organs with rich blood flow

• ex) osteosarcoma (malignant bone tissue tumor) → commonly spreads to the lungs via the bloodstream

• ex) renal cell carcinoma often metastasizes hematologic to lungs and bones

Stage 0 cancer

when the cancer is still in its original site

• ex) cancer is still in the epithelium and hasn’t reached the cervix

Invasive Carcinoma of the cervix

1. Carcinoma in the situ is noninvasive (pap-smears can detect at this time)

2. The cancer cells break down the basement membrane and enters lymphatic vessels to spread

3. vagina becomes invaded

4. widespread invasion occurs

Metastatic breast cancer

1. Primary breast cancer

2. spreads to axillary lymph nose using lymphatic metastasis

3. follows lymphatic to vena cava

4. lung metastasis is a secondary cancer that occurs

5. aorta carries tumor cells from lungs to all organs (hematologic metastasis)

6. ovary metastasis

7. brain metastasis

TNM system → T

T → tumor: primary tumor; the number equals size of tumor and its local extent

• T0 - organ is free of cancer

• Tis - carcinoma in situ (pre-invasive cancer)

• T1 - lesion <2 cm in size

• T2 - lesion 2-5 cm

TNM System → N

N → nodes: lymph node involvement; a higher number means more nodes are involved

• N0 - none involved

• N1 - regional lymph nodes involved

• N2 - more lymph nodes involved

TMN - M

M → Metastasis: extent of distant metastases

• M0 → absence of metastasis

• M1 → distant metastasis present

Stages of cancer

Stage 1 → tumor is confined to its organ of origin

Stage 2 → tumor is locally invasive

Stage 3 → tumor has advanced to regional structures (advanced to regional lymph nodes)

Stage 4 → tumor has spread to distant sites

Carcinoma in situ (CIS)

pre-invasive cancer in which abnormal cells are present only in the epithelium (the layer of tissue where they originated)

• they haven’t crossed the basement membrane yet

• there is no invasion of underlying tissue

• considered stage 0

• if this goes untreated, CIS can progress to invasive carcinoma

Tumor grade

refers to how closely the tumor resembles the normal tissue from which they arose (degree of differentiation)

Low-grade tumors

well-differentiated

look similar to normal cells

grow and spread more slowly

• in this type, the cancer has a better prognosis

High-grade tumors

poorly differentiated or undifferentiated

markedly abnormal appearance

higher mitotic activity → faster to grow and more aggressive (can lead to secondary cancers)

tend to behave more aggressively

Tumor markers

substances produced by benign or malignant cells

• found in tumor cells and secreted into body fluids (blood, spinal fluid, urine) → these can predict a prognosis

examples are hormones, enzymes, antigens, and antibodies

tumor markers are used for to screen and identify individuals at higher risk for cancer, diagnose specific types of tumors, and to follow the clinical course of cancer

Liver and germ cell tumors

they secrete alpha feto protein into the blood

Prostate tumors

secrete prostate-specific antigens (PSA)

• a high PSA is associated with malignant tumors requiring a biopsy as a follow up (a negative Bx means no cancer is present)

• if PSA remains high after anti-inflammatory treatment, another Bx is needed

Ovarian epithelial tumors

they secrete cancer antigen - 125 (CA-125)

• CA-125 is not a good screening test cause CA-125 can be elevated in benign conditions

• this test is used for monitoring treatment response and detecting recurrence of ovarian cancer

Surgery

surgery is the #1 treatment option for cancer

adequate margins → when the tumor along with a sufficient amount of healthy tissue surrounding the tumor is removed (negative margins are found if no cancer is detected at the end of the removed tissue, means successful surgery)

Palliative

performed not to remove surgery but to reduce symptoms and improve the quality of life

• colostomy → creates an alternative pathway for stool to bypass an obstructing colorectal tumor to relieve bowl obstruction

not a cure but removes symptoms

Colectomy

removal of colon

• mutations of APC gene have close to a 100% lifetime risk of colon cancer

Prophylactic mastectomy

removal of breast which prevents breast cancer

Bilateral salpingo-oophorectomy

removal of ovaries and uterine tubes

Radiation

cancer treatment used to kill cancer cells why minimizing the damage to normal structures

• radiation does not selectively target cancer cells so you need to be very careful

uses high-energy radiation to damage DNA of cancer cells, preventing them from growing and dividing

External beam

radiation is delivered from machine outside the body

Brachytheraphy

radioactive source is placed inside or near the tumor

Chemotherapy

uses cytotoxic drugs to destroy cancer cells or inhibit their growth and division

Induction chemo

causes shrinkage or disappearance or tumors

Adjuvant chemo

administered after surgical excision with a goal of elimination micrometastases (used to treat microscopic tumors after surgery)

Neoadjuvant chemo

administered before localized (surgical or radiation) treatment to reduce the size of the tumor to make it able to be removed

Cancer Prognosis

predicted course and outcome of cancer, including likelihood of recovery, recurrence, progression, and survival

Factors influencing:

• Type of cancer affects Px

• Stage of cancer (later stages have less chance of recovery)

• grade of tumor (lower grade tumors grow slower)

• size and loco of tumor

• presence of metastasis (if it has metasized it has a less chance of recovery)

Cancer free state

5-year survival without recurrence of cancer

some childhood leukemias can be considered cured after 10-year cancer-free period