[P] Week 4: Neoplasia - Part 1 Flashcards by Geno Alinsub

means “new growth,” and the collection of cells and stroma composing new growths

Neoplasia

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Neoplasia means “new growth,” and the collection of cells and stroma composing new growths are referred to?

Neoplasms

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Benign or Malignant Neoplasia

Non-cancerous lesions
Cancerous lesions

Benign
Malignant

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Benign or Malignant Neoplasia

Naming of benign tumors of
mesenchymal cells is relatively simple; in general, the suffix “-oma” is attached to the name of the cell type
from which the tumor arises

Benign

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Benign or Malignant Neoplasia

Composed of single
parenchymal cell type

Malignant

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Enumerate the Benign tumors?

Adenoma
Cystadenoma
Papilloma
Lipoma
Leiomyoma

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Enumerate the Malignant Tumors

Carcinoma
Squamous Cell Carcinoma
Adenocarcinoma
Sarcoma
Liposarcoma
Leiomyosarcoma

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Benign Tumors

a gland-forming benign tumor. It is derived from glandular tissues even if the tumor cells fail to form glandular structures

Adenoma

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Benign Tumors

a gland-forming tumor but with large cystic masses/cavities

Cystadenoma

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Benign Tumors

a benign epithelial neoplasm producing fingerlike or warty projections from epithelial surfaces.

Papilloma

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Benign Tumor

Benign fatty tumors

Lipoma

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Benign Tumor

Composed of smooth muscle cells

Leiomyoma

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Malignant Tumors

malignant tumor arising in epithelial cells.

Carcinoma

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Malignant Tumors

a malignant tumor of the skin occurring in the epidermis.

Squamous Cell Carcinoma

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Malignant Tumors

occurs usually in the colon or large intestine when the neoplastic epithelial cells grow in a glandular pattern. (gland-forming)

Adenocarinoma

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Malignant Tumor

a malignant tumor arising in solid mesenchymal tissues/cells.

Sarcoma

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Malignant Tumor

Refers to malignant fatty tumors.

Liposarcoma

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Malignant Tumor

A malignant tumor found in smooth mucle cells./

Leiomyosarcoma

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RESEMBLES A MALIGNANT TUMOR BUT NON-NEOPLASTIC

Ectopic rests of non-transformed tissue. It is the term applied to a heterotopic (misplaced) rest of cells.
EXAMPLE: Pancreatic cells under the small bowel mucosa

Choristoma

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RESEMBLES A MALIGNANT TUMOR BUT NON-NEOPLASTIC

It is known as masses of disorganized tissue indigenous to a particular site or involved tissue.
○ The tissue is located in its normal location, only disorganized.
EXAMPLES: Cartilage, bronchi, and blood vessels in the lungs

Hamartoma

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TUMORS COMPOSED OF MORE THAN ONE PARENCHYMAL CELL TYPE

derived from one germ cell layer that
differentiates into more than one parenchymal type.

In embryology, there are three germ layers - ectoderm, endoderm, and mesoderm.
If the cells that make up the tumor are found in a single germ layer, it is classified as a?

Mixed tumors

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TUMORS COMPOSED OF MORE THAN ONE PARENCHYMAL CELL TYPE

derived from more than one germ cell layer producing various parenchymal cell types.
- if the cells that make up the tumor are found in two or three germ layers.

Teratoma / Teratogenous

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CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS

Refers to the extent to which neoplastic cells resemble the normal cells morphologically and functionally.

Differentiation

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CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS

In assessing the differentiation of a tumor, what are the steps?

Simillarity of the morphology
Similarity on the function

Example: In assessing the differentiation of a tumor affecting the squamous cells, (1) assess whether they still exhibit the squamoid shape–morphology, and (2) assess whether
they can produce keratin–function

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Cancer cells often exhibit other telltale morphologic changes, what are those?

- Pleomorphism - Abornmal nuclear morphology - Increased N:C ratio from 1:4-1:6 to 1:1 - Atypical, Bizarre mitotic figures - Loss of polarity - Tumor giant cells - Ischemic Necrosis

# CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS lack of differentiation, and is considered as the HALLMARK OF MALIGNANCY

Anaplasia

# CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS any disordered growth; the loss of uniformity of individual cells and in architectural orientation.

Dysplasia

# CHARACTERISTICS OF BENIGN AND MALIGNANT NEOPLASMS the replacement of one cell type with another, and is considered as a fertile soil for malignancy

Metaplasia

# Benign or Malignant Differentiation / Anaplasia 1. Exhibits anaplasia (lack of differentiation) 2. Well-differentiated

1. Malignant 2. Benign

# Benign or Malignant Mitosis 1. Mitotic figures are rare and just follow the normal proliferative rate 2. Mitotic figures may be numerous and abnormal (e.g. sunburst pattern, tripolar mitotic figures).

1. Benign 2. Malignant

# Benign or Malignant Local Invasion 1. Usually cohesive and expansile, well demarcated masses that do not invade or infiltrate the surrounding tissues 2. Invasive, infiltrating the surrounding tissues

1. Benign 2. Malignant

# Benign or Malignant Metastasis 1. Frequently metstasize or colonize distant organs 2. NO metastasis

1. Malignant 2. Benign

# CANCER CELLS OFTEN EXHIBIT OTHER TELLTALE MORPHOLOGIC CHANGES * Refers to the variations in size and shape of the cells in the tumor * Some tumor giant cells possess only a single huge polymorphic nucleus, while others may have two or more large, hyperchromatic nuclei

Pleomorphism

# CANCER CELLS OFTEN EXHIBIT OTHER TELLTALE MORPHOLOGIC CHANGES The nuclear shape is **variable and often irregular**, and the chromatin is often coarsely clumped and distributed along the nuclear membrane or more darkly stained than normal (hyperchromatic)

Abnormal nuclear morphology

# CANCER CELLS OFTEN EXHIBIT OTHER TELLTALE MORPHOLOGIC CHANGES * Characteristically, cancer cells have nuclei that are disproportionately large, with a **nuclear-to-cytoplasm ratio that may approach 1:1** instead of the normal 1:4 to 1:6. * Cytoplasm cannot longer be appreciated

Increased N:C ratio from 1:4-1:6 to 1:1

# CANCER CELLS OFTEN EXHIBIT OTHER TELLTALE MORPHOLOGIC CHANGES * **Morphologic feature of malignancy** * Unlike benign tumors and some well-differentiated malignant neoplasms, undifferentiated cancers often contain many cells in mitosis, reflecting their high rate of proliferation

Atypical, Bizarre mitotic figures

# CANCER CELLS OFTEN EXHIBIT OTHER TELLTALE MORPHOLOGIC CHANGES * In addition to cytologic abnormalities, the orientation of anaplastic cells with respect to each other or to supporting structures like basement membranes is markedly disturbed. * Sheets or large masses of tumor cells grow in a disorganized fashion

Loss of polarity

# CANCER CELLS OFTEN EXHIBIT OTHER TELLTALE MORPHOLOGIC CHANGES While growing tumor cells must have a blood supply, the vascular stroma is often insufficient; as a result, many rapidly growing cancers develop areas of ischemic necrosis.

Ischemic necrosis

defined as the spread of a tumor to sites that are physicallydiscontinuous with the primary tumor, an event that unequivocally marks a tumor as malignant

Metastasis | q

What are the pathways of spread/metastasis? enumerate

1. Seeding within body cavities and surfaces 2. Lymphatic spread 3. Hematogenous spread

# Pathways of spread/metastasis occurs when a malignant neoplasm penetrates into a natural **“open field”** lacking physical barriers

Seeding within Body Cavities and Surfaces ## Footnote For example: Masses such as gastric tumor or colonic mass had already invaded down to the serosa surface of the colon or the stomach

# Pathways of spread/metastasis * A characteristic of **ovarian cancer** * Sometimes, mucus-secreting appendiceal carcinomas or ovarian carcinomas fill the peritoneal cavity with a gelatinous neoplastic mass referred to as **pseudomyxoma peritonei**.

Seeding within Body Cavities and Surfaces

# Pathways of spread/metastasis Transport through lymphatic vessels is the most common pathway for the initial dissemination of carcinomas.

Lymphatic spread

# Pathways of spread/metastasis - typical of sarcomas but is also seen with carcinomas. - Sarcomas are the malignant tumors arising in solid mesenchymal (mesenchymal lesions) which initially spread by hematogenous route or through the bloodstream

Hematogenous spread

# MOLECULAR BASIS OF CANCER Cancer starts with a?

**Nonlethal genetic damage** This means that the cell has to survive, otherwise, there will be no cancer

# Molecular basis of cancer enumerate the steps of genetic and epigenetic alteration

1. Cancer starts with a nonlethal genetic damage 2. Clonal expansion 3. Tumor progression

# MOLECULAR BASIS OF CANCER Cancer starts with a nonlethal genetic damage, this can involve?

- Growth-promoting proto-oncogenes - Growth-inhibiting tumor suppressor genes - Genes that regulate apoptosis - Genes involved in DNA repair

# MOLECULAR BASIS OF CANCER Once the cell survives the genetic damage, it will undergo?

**Clonal expansion** - They multiply in number

# MOLECULAR BASIS OF CANCER this means that whatever is the genetic aberrations in that signeld cell (first cell) in carcinogenesis, all of the succeeding cells will also have the same genetic aberration?

Clonal (under clonal expansion)

# MOLECULAR BASIS OF CANCER - Accumulation of multiple mutations generating subclones - Example: There are 1 million cells after clonal expansion. In tumor progression, 100 thousand out of 1 million cells will have (aside from the original mutation) the mutation A, and then another 100,000 thousand will have on top of the original mutation, mutation B, and so on.

Tumor progression

Four classes of genes are the **principal targets of cancercausing mutations**, what are those? *As the cells proliferate and become clinically apparent in solid tumors that can be palpated, these lesions/tumors, when examined, will harbor many genetic mutations due to continuous tumor progression*

- Growth promoting proto-oncogenes (GOF) - Tumor suppressor genes (LOF) - Genes that regulate apoptosis (GOF/LOF) - Genes that involve DNA repair (LOF)

# 4 CLASSES OF NORMAL REGULATORY GENES They promote **entry into the cell cycle**. For these genes to participate in oncogenesis/carcinogenesis, they must suffer from **'gain of function'** mutation.

Growth promoting proto-oncogenes (GOF)

# 4 CLASSES OF NORMAL REGULATORY GENES These genes produce products and encode for proteins that serve to **apply brakes in the cell cycle.** For them to participate in carcinogenesis, they must suffer from **'loss of function'**

Tumor suppressor genes (LOF)

# 4 CLASSES OF NORMAL REGULATORY GENES These genes may suffer from **'gain of function' or 'loss of function' mutations**, depending on the specific role of the gene product in the regulation of apoptosis. ## Footnote Q

Genes that regulate apoptosis (GOF/LOF)

# 4 CLASSES OF NORMAL REGULATORY GENES For them to participate in carcinogenesis, they must suffer from **'loss of function' mutation**. And if the proteins of these genes are already absent, there will be no repair

Genes that involve DNA repair (LOF)

# 4 CLASSES OF NORMAL REGULATORY GENES Here, the mutation leads to the acquisition of mutations at an accelerated rate. The cell enters a **MUTATOR PHENOTYPE STATE,** leading to genomic instability.

Genes that involve DNA repair (LOF)

are mutated genes that cause excessive cell growth, even in the absence of growth factors and other growth-promoting external cues.

Oncogenese

These are genes that encode for proteins (oncoproteins) that when expressed, promote and can participate in autonomous cell growth in cancer cells

Oncogenes

A major discovery in cancer was that oncogenes are?

mutated or overexpressed versions of normal cellular genes, which are called proto-oncogenes

# STEPS IN CELL PROLIFERATION Physiologic growth factor–induced signaling can be resolved into the what steps?

1. Binding of a growth factor to its specific receptor 2. transient and limited activation of growth factor receptor 3. induction and activation of nuclear regulatory factors 4. Expression of genes and encoded factors that promote entry and progression of the cell into the cell cycle,

are products of oncogenes, and they dont depend on growth factos or external signal of them to act

Oncoproteins

The growth factor will act on the growth factor receptor through what receptor?

Paracrine Action

The growth factor will act on the growth factor receptor through PARACRINE ACTION, meaning the growth factors originate from?

Different cells in the surrounding tissue

Many cancer cells acquire the ability to synthesize the same growth factor to which they are responsive, creating an?

Autocrine loop

# Growth Receptors A large number of oncogenes encode growth factor receptors, of which receptor ____ ____ are arguably the most important in cancer.

tyrosine kinases

# Growth Factor Receptors Even if the growth factor will not act on the growth factor receptor, the growth factor of the cell can be constitutively activated due to?

- Mutation - Gene rearrangement - overexpression It will continuously deliver signals inside the cell for the cell to proliferate. ## Footnote This is the problem in certain lung and breast cancer

# Growth Factor Receptors FILL THE BLANKS Genetic Aberration: Point Mutation Gene: ERBB1 Protein: Disease:

Protein: EGFR Disease: Lung Cancer

# Growth Factor Receptors FILL THE BLANKS Genetic Aberration: Gene Amplification Gene: ERBB2 Protein: Disease:

Protein: HER2 Disease: Breast Cancer

# Growth Factor Receptors FILL THE BLANKS Genetic Aberration: Gene Rearrangement Gene: EML4-ALK Protein: Disease:

Protein: EML4-ALK Disease: Lung Cancer

If growth factors are activated you will have ____ ____ carried out by signal transducing proteins

Signal transduction

# Signal Transducing Proteins what signal transducing proteins is the Single most common abnormality of proto-oncogene

RAS oncogene

# Signal Transducing Proteins Mutated RAS is trapped in its activated ____ form and if it is activated it will continuously flood the nucleus with signals for proliferation causing continuous entry of cell into the cell cycle

GTP-bound

Transcription factors that can be included in carcinogenesis:

TF Oncogenes: MYC, MYB, JUN, FOS, REL | MYC is most commonly affected in cancer,

This orchestrates the orderly progression of cell through cell cycl by bindin to cyclins

Cyclin-Dependent Kinase (CDK)

Give the 2 examples of CDK

Cyclin D, CDK4

# Tumor Suppressor Genes * GOVERNOR OF PROLIFERATION * A gene that is located on **long arm of chromosome 13 region 1 band 4 (13q14)**

# Tumor Suppressor Genes This can be mutated in several tumors but it is highly associated with Retinoblastoma in the eye

# Tumor Suppressor Genes * GUARDIAN OF THE GENOME * Most common target for genetic alteration in human tumors

p53

# Tumor Suppressor Genes * Gene located on the **short arm of chromosome 17 region 1 band 3 sub band 1 (17p13.1)** * If this is active and not mutated, links cell damage with repair, promotes cell cycle arrest to be allowed for **repair** and if beyond repair, it will promote apoptosis to prevent neoplastic transformation

p53

# Tumor Suppressor Genes * GATEKEEPER OF COLONIC NEOPLASIA * This gene is located on long arm of chromosome 5 region 2 band 1 (5q21)

APC (Adenomatous polyposis coli) ## Footnote Associated with Adenomatous polyposis coli (many polyps in the colon) and colon cancer

# EVASION OF CELL DEATH/APOPTOSIS You will recall there are two pathways that lead to apoptosis, what are those?

1. **the extrinsic (death receptor) pathway** - triggered by death receptors of the tumor necrosis factor (TNF) receptor family, such as FAS, and their ligands 2. **the intrinsic (mitochondrial) pathway** - initiated by various stresses, such as the absence of growth factors and DNA damage.

# EVASION OF CELL DEATH/APOPTOSIS the most frequently disabled in the carcinogenesis

INTRINSIC PATHWAY

# EVASION OF CELL DEATH/APOPTOSIS In cancer formation, the goal of cancer cell is to avoid?

Apoptosis

# EVASION OF CELL DEATH/APOPTOSIS enumerate the 2 major mechanism by which apoptosis is avoided by cancer cells

- Loss of TP53 - Overexpression of BCL2

# EVASION OF CELL DEATH/APOPTOSIS Loss of p53 **function** prevents the upregulation of?

**PUMA** - a pro-apoptotic BH3-only protein, in response to DNA damage and other stresses, allowing cells to survive that otherwise would be killed

# EVASION OF CELL DEATH/APOPTOSIS If there is loss of p53, there will be no upregulation of?

BAX and PUMA

# EVASION OF CELL DEATH/APOPTOSIS Overexpression of ____ is a common event leading to the protection of tumor cells from apoptosis

BCL2 - anti-apoptotic gene

# THE STEM CELL–LIKE PROPERTIES OF CANCER CELLS Cells do not die and are able to continuously proliferate because they are capable of the following, enumerate

1. Evasion of senescence 2. Evasion of Mitotic Crisis 3. Self-renewal

# THE STEM CELL–LIKE PROPERTIES OF CANCER CELLS Cells do not age---forever young, due to **RB-dependent G1/S cell cycle checkpoin**t is disrupted

Evasion of Senescence

# THE STEM CELL–LIKE PROPERTIES OF CANCER CELLS - If the cells continuously proliferate, the telomerase shortens. Eventually the cell will age and die, this is called the mitotic crisis which can be evaded by cancer cells. They can do that by upregulation of telomerase (85-95% of cases) --- an enzyme that is almost absent in our somatic cells. - Alternative lengthening of telomeres

Evasion of mitotic crisis

# THE STEM CELL–LIKE PROPERTIES OF CANCER CELLS Long lived cancer stem cells possess another critical property, the capacity for?

Self-renewal

Even if a solid tumor possesses all the genetic aberrations that are required for malignant transformation, it cannot enlarge beyond 1 to 2 mm in diameter unless it has the capacity to induce?

Angiogenesis

# Sustained Angiogenesis Tumors that are more than 1-2 mm need blood supply, otherwise, there will be?

Ischemic Necrosis

# Sustained Angiogenesis occurs when there is change in phenotype that induces angiogenesis mostly controlled by hypoxia.

Angiogenic Switch

# Sustained Angiogenesis The molecular basis of the angiogenic switch involves what increased local production of angiogenic factors

- VEGf and bFGF - Loss of angiogenic inhibitors (thrombospondin-1)

# ABILITY TO INVADE AND METASTASIZE Steps in invasion 1. ____ or ____ of cancer cells from one another

Dissociation or detachment | Detachment is due to the downregulation of **Ecadherin**

# ABILITY TO INVADE AND METASTASIZE Steps in invasion (2) Degradation of the?

basement membrane and ECM/ interstitial connective tissue

# ABILITY TO INVADE AND METASTASIZE (From step 2) Tumor cells are able to move after detachment because they secrete? | `

proteolytic **enzymes** or induce stromal cells to secrete **enzymes**

# ABILITY TO INVADE AND METASTASIZE (3) Changes in attachment of tumor cells to?

ECM Protein | Tumor demonstrate complex changes in the expression of **integrins**

# ABILITY TO INVADE AND METASTASIZE what is the final step of evasion

Locomotion

# ABILITY TO INVADE AND METASTASIZE Such movement for locotiom is stimulated and directed by what factors?

▪ **Cytokines** from tumor cells themselves ▪ **Stromal cell motility factors** ▪ **Cleavage products** of matrix components (e.g., collagen, laminin)

[P] Week 4: Neoplasia - Part 1 Flashcards

(101 cards)