Neoplasia Flashcards by Samuel Dienel

What are the two most important angiogenic factors (that are frequently produced by tumor cells)?

VEGF (vascular endothelial growth factor) and FGF (fibroblast growth factor)

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What are the three defining features of neoplasia?

Monoclonal (genetically identical): come from a single parent cell.
Uncontrolled: growing outside the influence of normal growth factors
Irreversible

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What is the name of a benign neoplasm derived from epithelium? What is the name of a malignant neoplasm derived from epithelium?

Adenoma is epithelium derived benign tumor. Carcinoma is epithelium derived malignant tumor.

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What is the name of the cellular layer that lines pleura, pericardium, and peritoneum, and what is a malignant neoplasm that derives from it?

Mesothelium is the cell layer; mesothelioma is the malignant neoplasm

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What is the name of a benign neoplasm derived from mesenchyme? What is the name of a malignant neoplasm derived from mesenchyme?

Lipoma is the benign mesenchymal derived tumor. Sarcoma is the name give to mesenchymal derived malignant tumors (named based on tissue that it is derived from, e.g. osteosarcoma)

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What are the two main tests for determining monoclonality vs polyclonality?

G6PD enzyme isoform and androgen receptor isoform test (both are present on the X chromosome and X-inactivation can determine clonality)

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What are the two components of neoplasms that make up its structure?

Parenchyma (the actual proliferating neoplastic cells) and stroma (the intervening connective tissue that is not neoplastic)

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What intermediate filament used in an antibody test to distinguish epithelial tumors?

Keratin (or epithelial membrane antigen, EMA, or carcinoembryonic antigen, CEA, but lower yield)

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What intermediate filament is used in an antibody test to distinguish mesenchymal tumors?

Vimentin

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What intermediate filament is used in an antibody test to distinguish muscle tumors?

Desmin

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What intermediate filament is used in an antibody test to test neuroglia? And for neurons?

GFAP for neuroglia and neurofilament for neurons

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What immunostain is used to distinguish a lymphoid derived tumor (lymphoma)?

leuocyte common antigen (LCA or CD45)

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What immunostain is used to distinguish a melanoma (tumor from melanocytic cells)?

S-100

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What is the term for a tumor that resembles the normal counterpart (ie the tissue in which it grows)? What is the term for a tumor that does not resemble the normal counterpart?

A well-differentiated tumor resembles the normal counterpart. A poorly-differentiated tumor does not resemble the parent tissue; poorest prognosis

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What are 5 general traits of benign tumors?

Slow growing
Well-circumscribed (easily to distinguish)
Distinct (localized to one area)
Mobile
Well-differentiated

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What are 5 general traits of malignant tumors?

Rapidly growing
Poorly circumscribed
Infiltrative (into the underlying and surrounding tissue)
Non-mobile and fixed to surrounding tissues
Poorly-differentiated

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What are histological features of benign tumors?

Overall they are well-differentiated 
(think ORGANIZED) 
-organized growth
-uniform nuclei
-low nuclear to cytoplasmic ratio
-minimal mitotic activity
-lack of invasion

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What are histological features of malignant tumors?

Overall poorly differentiated
(think DISORGANIZED and dividing a lot)
-disorganized growth; loss of polarity
-nuclear pleomorphism (some large some small)
-hyperchromasia (nuclei stain very dark)
-High nuclear to cytoplasmic ratio
-high mitotic activity
-invasion into nearby tissue or basement membrane

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What immunological staining would be used for neuroendocrine cells?

Chromogranin (e.g. small cell carcinoma of the lung and carcinoid tumors)

What are the 5 most common ways for a neoplasm to metastasize?

Contiguous growth through adjacent structures
Hematogenous spread (via blood vessels)
Lymphatic spread (into regional draining lymph nodes)
Seeding of body cavities
Iatrogenic (tumor cells spilled during surgery or along a needle)

What is the common way that carcinomas spread?

Lymphatic spread (e.g. breast cancer to axillary ndoes)

What is the common way that sarcomas spread? What are 4 exceptions?

Via hematogenous spread. 4 carcinomas spread via hematogenous spread:

Renal cell carcinoma (invades renal vein)
Hepatocellular carcinoma (invades hepatic vein)
Follicular carcinoma of the thyroid
Choriocarcinoma (cancer of trophoblast in placenta)

What is the most common “-plasia” that indicates an early neoplastic process?

Dysplasia

What are hallmarks of dysplasia growth?

nuclear hyperchromasia (dark staining nuclei)
nuclear enlargement
irregular chromatin pattern
cellular pleomorphism
increased mitotic activity
loss of polarity

What is anaplasia, and what tumors typically show anaplasia?

"backwards" growth - resembles earlier undifferentiated versions of the cell; characteristic of malignant neoplasms

What is a desmoplasia? When is a desmoplastic reaction most commonly seen?

Is a term for the reactive stroma (fibrous tissue, new collagen) that surrounds the invading edge of a tumor; mostly seen in response to pre-invasive tumors (e.g. ductal carcinoma in-situ of the breast), very early invasive, or invasive carcinomas.

What is a polyp?

Any visible projection of a collection of tissue above the mucosa of an organ (projects into the lumen)

What is a teratoma?

Tumor composed of several tissue types from different embryonic germ layers (may have tissues, teeth etc)

What is a hamartoma?

benign collection of disorganized cells/tissues that are normal part of the location where the tumor arises (so you expect to find those cells/tissues there, but they are disorganized and form a tumro)

What is a choristoma?

This is a tumor that is a congenital abnormality that does not develop over time (NOT a neoplasm; is not a new growth)

What is carcinoma in situ?

Epithelial neoplasm with the features of malignancy but which has yet to invade surrounding tissues

Where is cancer on the "cause of death" list in the US?

second leading cause of death in US (cardiovascular disease is the first)

What is malignant transformation?

Term for the molecular events occurring in a cell that allows a cell to become neoplastic.

In malignant transformation, what is autonomy? Why does it result?

Autonomy is the ability to grow without external growth signals. Usually due to oncogene activation

What metabolic pathway do tumor cells usually under?

Aerobic glycolysis thus allowing for rapid synthesis of macromolecules for division and growth

In malignant transformation, how do tumor cells evade apoptosis?

Primarily by disabling the intrinsic pathway of apoptosis; one example is overexpression of Bcl2 in follicular lymphoma due to translocation(14;18) with Ig heavy chain (located on chromosome 14).

How do cancer cells replicate without end?

Tumor cells can avoid becoming senescent via upregulation of telomerase (which preserves telomeres)

What 2 factors are produced by tumor cells in order to promote angiogenesis into the tumor?

FGF and VEGF

How do cancer cells accomplish invasion and spread of neoplastic cells?

1. Must detach from other epithelial cells (via downregulation of E-cadherin) 2. Has enzymes such as collagenase that digests tissue matrix (and destroy basement membrane and collagen IV)

How do tumor cells escape the immune system?

Because mutations involved production of abnormal proteins, tumor cells will downregulate expression of MHC class I where the proteins would be produced and thus the cell would be destroyed by CD8+ T cells

Why does immunodeficiency predispose people to cancer?

Immune cells will naturally try to eliminate neoplastic cells, thus without the immune cells, there is a greater likelihood that they will not be detected by surveilling immune cells.

How many copies of a tumor suppressor gene must be knocked out in order to lead to neoplasia?

Both copies must be lost

What are 2 main examples of tumor suppressing genes?

p53 and Rb1 (retinoblastoma); both must be lost in order to lead to neoplasia

Between what two stages of the cell cycle do most tumor suppressor genes regulate?

Between G1 and S phase

How does p53 act as a tumor suppressing gene?

Recognizes DNA damage and arrests cell in G1 to allow for DNA repair. If not able to be repaired then it activates apoptosis by upregulating BAX (a pro-apoptotic gene)

In what lymphoma is Bcl2 overexpressed? Why would this cause cancer?

Bcl2 is overexpressed in follicular lymphoma. Bcl2 guards the mitochondrial membrane integrity and thus prevents release of cytochrome C and subsequent apoptosis; leading to reduced cell control.

What is the role of cyclin D1 (CCND1)?

It is a cell cycle regulator that (via cyclin dependent kinase) phosphorylates the Rb protein, promoting the transition from G1 to S phase in the cell cycle