Robbins Chapter 5

Do benign tumors have differentiated or anaplastic cells?

- benign tumors are made up of well-differentiated cells that closely resemble their normal counterparts -mitoses is usually rare and are of normal configuration

Autosomal Recessive Syndromes of Defective DNA repair

- characterized by chromosomal or DNA instability - associated with inherited defects in DNA repair

governor tumor suppressor genes

- classic tumor suppressor genes where mutation of the gene leads to transformation by removing an important brake on cellular proliferation -RB

dysplasia cells

- disorderly but non-neoplastic proliferation - encountered principally in epithelial cells - loss in the uniformity of individual cells and their architectural orientation - they exhibit considerable pleomorphism and often possess hyperchromatic nuclei that are abnoramlly large for the size of the cell

adenoma

- generally applied to benign epithelial neoplasms producing gland patterns and to neoplasms derived from glands but not necessarily exhibiting glandular patterns.

tumor suppressor genes

- genes that normally prevent uncontrolled growth and, when mutated or lost from a cell, allow the transformed phenotype to develop

describe the local invasion of malignant neoplasms

- grow by progressive infiltration, invasion, destruction and penetration of the surrounding tissue. - they do not develop well-defined capsules - their infiltrative mode of growth makes it necessary to remove a wide margin of surrounding normal tissue when surgical excision is attempted. they remove tissue until they have "clear margins" - next to development of metastases, local invasiveness is the most reliable feature that distinguishes malignant from benign tumors

autosomal dominant cancer syndromes

- inheritance of a single gene mutant gene greatly increases the risk of developing a tumor - childhood retinoblastoma is the most striking example of this category - linked to inheritance of a germ line mutation of cancer suppressor genes

carcinomas

- malignant neoplasms of epithelial cells - called this regardless of the tissue of origin.

Described the cells of malignant cancers

- neoplasms have a wide range of parenchymal cell differentiation, from well-differentiated to completely undifferentiated

spread by seeding

- occurs when neoplasms invade a natural body cavity

tumor progression

- over a period of time, many tumors become more aggressive and acquire greater malignant potential - not represented simply by an increase in tumor size

familial cancers of uncertain inheritance

- pattern of inheritance is unclear - ex: carcinomas of colon, breast, ovary and brain - features that characterize familial cancers include early age at onset, tumors arising in 2 or more close relatives of the index case, and sometimes multiple or bilateral tumors - not associated with specific marker phenotypes

preneoplastic lesions

- precancers; most do not progress to cancer - precursor lesions arise in the setting of chronic tissue injury or inflammation - these lesions increase the likelihood of malignancy by stimulating continuing regenerative proliferation or by exposing cells to byproducts of inflammation, both of which can lead to somatic mutations - if these are removed, it can prevent the development of cancer

malignant tumors

- referred to as "cancers" - implies that the lesion can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death

describe the local invasion of benign neoplasms

- remains localized at its site of origin - most develop an enclosing fibrous capsule that separates them from the host tissue. - they don't have the capacity to infiltrate, invade or metastasize to distant sites

Guardian tumor suppressor genes

- responsible for sensing genomic damage. - some of these genes initiate and choreograph a complex "damage control response" - this response leads to the cessation of proliferation or, if the dame is too great to be repaired, the induction of apoptosis - TP53 = "guardian of the genome"; prototype tumor suppressor gene of this type - loss of guardian genes permits and accelerates the acquisition of mutations in oncogenes and tumor suppressor genes that can lead to the development of cancer

what are metastases?

- secondary implants of a tumor that is discontinuous with the primary tumor and located in remote tissues. - this property identifies a neoplasm as malignant!

hematogenous spread

- spread by vascular system - arteries are penetrated less readily than are veins. - with venous invasion, the blood-borne cells follow the venous flow draining the sire of the neoplasm, with tumor cells often stopping in the first capillary bed they encounter

sentinel lymph node

- the first regional lymph node that receives lymph from a primary tumor

lymphatic spread

- the pattern of lymph node involvement depends primarily on the site of the primary neoplasm and the natural pathways of the local lymphatic drainage -in some cases, the cancer cells seem to traverse the lymphatic channels within the immediately proximate nodes to be trapped in subsequent lymph nodes, producing "skip metastases"

teratoma

- type of mixed tumor that has recognizable mature and immature cells or tissues representative of more than 1 germ cell layer and sometimes all 3. - they originate from totipotential embryonic cells

anaplastic cells

- undifferentiated cells of malignant neoplasms - hallmark of malignancy - literally means "backward formation" - dedifferentiation - loss of the structural or functional differentiation of normal cells - nuclei are highly hyperchromatic, variable and bizarre in size and shape - mitoses often are numerous and distinctly atypical - they fail to develop recognizable patterns of orientation to one another

pleomorphism

- variation in size and shape - anaplastic cells markedly display this

what 4 classes of normal regulatory genes are the principle targets of genetic damage?

1) growth-promoting proto-oncogenes 2) growth-inhibiting tumor suppressor genes 3) genes that regulate programmed cell death (apoptosis) 4) genes involved in DNA repair

what are the 3 pathways malignant neoplasma disseminate?

1) seeding within body cavities 2) lymphatic spread 3) hematogenous spread

Hallmarks of cancer

1) self-sufficiency in growth signals [growth of cancers become autonomous and is unregulated by physiologic cues] 2) lack of response to growth inhibitory signals that control non-neoplastic cellular proliferations [like hyperplasia] 3) evasion of cell death [cancer cells can survive conditions in which normal cells would die via apoptosis] 4)limitless replicative activity [cancer cells are immortal]. 5) development of angiogenesis to sustain cancer cell growth 6) ability to invade local tissues and spread to distant sites 7) reprogramming of metabolic pathways *** especially a switch to aerobic glycolysis even when there is abundant O2*** 8) ability to evade the immune system

2 basic components of all tumors (benign and malignant)

1) the parenchyma, made up of transformed or neoplastic cells 2) the supporting, host-derived, non-neoplastic stroma, made up of connective tissue, blood vessels and host-derived inflammatory cells.

Warburg Effect

AKA aerobic glycolysis - even in the presence of ample O2, cancer cells shift their glucose metabolism away from the O2-hungry but efficient mitochondria to glycolysis - this mode of metabolism is favored when rapid growth is required

True or False. Cancer is not one disease but many disorders that share a profound growth dysregulation

TRUE

genetic hypothesis of cancer

a tumor mass results from the clonal expansion of a single progenitor cell that has incurred genetic damage [tumors are monoclonal]

desmoplasia

abundant collagenous stroma

In general, the more _______and the _________ the primary neoplasm, the more likely is metastatic spread

anaplastic; larger [there are exceptions]

chondroma

benign cartilaginous tumor

fibroma

benign tumor arising in fibrous tissue

the term dysplasia is not synonymous with _______; mild to moderate dysplasias that do not involve the entire thickness of the epithelium sometimes regress completely, particularly if the inciting causes are removed

cancer

lymphatic spread is more typical of....

carcinomas

oncogenes

genes that induce a transformed phenotype when expressed in cells - most known oncogenes encode transcription factors, growth regulating proteins, or proteins involved in cell survival and cell-cell and cell-matrix interactions

in general, the frequency of cancer _______ with age.

increases - accumulation of somatic mutations associated with the emergence of malignant neoplasms - the decline in immune competence may also be a factor

the rate of growth of malignant tumors usually correlates ____________ with their level of differentiation.

inversely [poorly differentiated tumors tend to grow more rapidly than do well-differentiated tumors].

why do cancer cells engage in aerobic glycolysis?

it produces lots of lactate which suppresses cytotoxic T cell function

anaplasia

lack of differentiation; loss of the structural and functional differentiation of normal cells - hallmark of malignancy

the more rapidly growing and the more anaplastic a tumor, the ________ likely it is to have specialized functional activity

less

which 2 organs are the most frequently involved secondary sites in hematogenous dissemination?

liver & lungs

founder effect

loss of genetic variation

sarcomas

malignant neoplasma arising in "solid medenchymal (embryonic connective tissue) tissues or its derivatives - designated by the cell type of which they are composed which is presumably their cell of origin.

More than any other attribute, the property of ____________ identifies a neoplasm as malignant

metastasis

carcinogenesis is a ....

multistep process resulting from the accumulation of multiple genetic alterations that collectively give rise to the transformed phenotype

proto-oncogenes

mutated or over expressed versions of normal cellular genes

neoplasia

new growth

genetic drift

no new genes introduced into the genome - founder effect is related to this

what lies at the heart of carcinogenesis?

nonlethal genetic damage

hematogenous spread is favored by ....

sarcomas

typically benign tumors grow ___________, while cancers grow __________.

slowly; fast [there are exceptions]

Scirrhous tumors

the amount of stromal connective tissue does determine the consistency of a neoplasm - these types of tumors have dense, abundant fibrous stroma, making them hard

genetic evolution and selection can explain what 2 pernicious properties o cancers?

the tendency for cancers to become 1) more aggressive and 2) less responsive to therapy overtime.

when is a tumor said to be benign?

when its microscopic and gross characteristics are considered to be relatively innocent, implying that it will remain localized and is amenable to local surgical removal - patient generally survives [brain tumors can cause compression of neurons and dysfunction]