neoplasia core concepts

8/12/2019 Neoplasia Core Concepts

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Neoplasia: core concepts

Hamartomasand choristomasare tumor-like growths thought to be the result of developmental

anomalies. They are NOT true neoplasms (ie, they do not show continuous excessive growth. Thetumors are abnormal, disorgani!ed, proliferating masses of several different adult cell types.

" hamartomais composed of tissues that are normally present in the organ in which the tumor arises# ahamartoma of the lung consists of a disorganized mass of bronchial epithelium and cartilagethatmay become so large that it presents as a lung mass. $ts growth is coordinated with that of the lung

itself.

" choristomaresembles a hamartoma but contains tissues that are NOT normally present in its site oforigin. " disorderly mass of smooth muscle and pancreatic acini and ducts in the wall of the stomach is

properly called a choristoma. " gastric choristoma such as this may present as an intramural mass that is

clinically indistinguishable from a benign neoplasm.


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" benignepithelialneoplasm is called an adenoma if it arises within a gland (eg, thyroid adenoma,

colonic adenoma or a papillomawhen arising from an epithelial surface. %apillomas may arise froms&uamous, glandular, or transitional epithelium (eg, s&uamous papilloma, intraductal papilloma of the

breast, and transitional cell papilloma, respectively.

-Malignantepithelialneoplasms are called carcinomas(adenocarcinomasif derived from glandularepithelia# s&uamous carcinomaand transitional cell carcinomaif originating in those kinds of

epithelia.

Benignmesenchymalneoplasms are named after the cell of origin (a 'reek or atin word is usedfollowed by the suffix -oma(Table )*-+. The names of these tumors may contain the organ of origin

and an adective, eg, cavernous hemangioma of the liver

Malignantmesenchymalneoplasms are named after the cell of origin, to which is added the suffix

-sarcoma."gain, adectives are commonly used# liposarcomas are classified as sclerosing, myxoid,round cell, or pleomorphic

Mixed Tumors:Neoplasms composed of more than one neoplastic cell type are called mixed tumors.

alignant mixed tumors may have two epithelial components, as in adenos&uamous carcinoma# twomesenchymal components, as in malignant fibrous histiocytoma# or an epithelial and a mesenchymal

component, as in carcinosarcoma of the lung and malignant mixed mllerian tumor of the uterus


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Mechanisms and Causes

Intro: Neoplasia is an abnormality of cell growth andmultiplication characterized by the following features: (1)

excessive cellular proliferation that typically produces anabnormal mass, or tumor; (2) uncoordinated growth

occurring without any apparent purpose; and (3)persistence of excessive cell proliferation and growth

even after the inciting stimulus that evoked the changehas been removedie, neoplasia is an irreversible

process.

Origin of tumor:Monoclonal: the initial neoplastic change affects a singlecell, which then multiplies and gives rise to the neoplasm.Example: neoplasms of B lymphocytes (B-cell lymphomasand plasma-cell myelomas) that produce immunoglobulin.

-REMEMBER: as a neoplasm progresses, furthersubclones may evolve from the initial clone as a result

of additional ongoing genetic changes (multiple hits)Field origin: A carcinogenic agent acting on a large

number of similar cells may produce a field of potentiallyneoplastic cells. Neoplasms may then arise from one ormore cells within this field. In many cases the result is

several discrete neoplasms, each of which derives from aseparate clonal precursor. The field change may be

regarded as the first of 2 or more sequential steps thatlead to overt cancer.

Multiple HitsTheory that carcinogenesis re&uires two hits. The first event is initiation, with the carcinogen causing it

called the initiator.The second event, which induces neoplastic growth, is promotion,and the agent is

the promoter.$t is now believed that in fact multiple hits occur (five or more, that multiple factors may


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cause these hits, and that each hit produces a change in the genome of the affected cell that is

transmitted to its progeny (ie, the neoplastic clone.

-another way to put it - 'enetic predisposition / )sthit, then a somatic mutation (due to, for

example, a carcinogen provides the 0ndhit

-another example1 Oncogenesis in 2urkitt3s lymphoma. The )st hit is infection of 2 lymphocytes

with 4pstein-2arr virus. 5hronic malaria induces proliferation of 2 lymphocytes, increasing thelikelihood of the 0nd hit, which is a chromosomal translocation that activates a cellular oncogene and

leads to malignant lymphoma.


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Oncogenes and tumor suppressor genes

There are two main categories of genes that regulate cell growth, and the abnormal action of either or

both may lead to neoplasia. roto!oncogenes "cellular oncogenes: c!onc#code for a variety of growth

factors, receptors, and signal-relay or transcription factors, which act in concert to control entry into the

cell cycle (eg, the growth promoter effect. The action of these genes is opposed by the action of tumor

suppressor genes,which serve to down-regulate the cell cycle. " net increase in the production ofstimulatory (promoter factors, a decrease in inhibitory (suppressor growth factors, or the production of

functionally abnormal factors may lead to uncontrolled cell growth.

The neoplastic cell is then the result of several such changes interacting in summative fashion (multiple

hits. 6its may result from inherited genetic abnormalities, spontaneous mutations, or the actions of

external agents that may affect the gene. These mutagens include chemical carcinogens, ioni!ingradiation, and viruses (which introduce new 7N". The effect of these agents is exacerbated by

incompetent 7N" repair mechanisms such as mutation of the genes that monitor 7N" duplication.

7efective repair is common in peeps with certain inherited conditions (such as xeroderma pigmentosum8sunlight# skin cancer9. $n dudes with these conditions, a first hit (eg, defective repair mechanisms is

inheritedand is already present in every cell in the body.

Mechanisms of gene acti$ation and inacti$ation

Neoplastic transformation occurs as a result of activation (or :derepression; of growth promoter genes

(proto!oncogenes or inactivation or loss of suppressor genes. %cti$ation is a functional concept where

the normal action of growth regulation is diverted into oncogenesis. The resultant activated proto-

oncogene is referred to as an acti$ated oncogene (or a mutant oncogene, if structurally changed."ctivation and inactivation may occur through several mechanisms1

() mutation,including single nucleotide loss (frameshift or substitution (nonsense or missense codon,

codon loss, gene deletion or more maor chromosomal loss

(0 translocationto a different part of the genome where regulatory influences may favor inappropriate

expression or repression

(


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Biological and clinical effects of neoplasias

roducts&mar'ers of neoplasias

). (nzymes: 4levated serum levels of prostate!specific acid phosphataseoccur in prostate cancer,

usually when invasion has occurred beyond the capsule of the gland. easurement of prostate-specific epithelial antigen (%?" is more sensitive and has found use as a screening test in older

men.

0. (xcessi$e Hormone )ecretion: Aell-differentiated neoplasms of endocrine cells are fre&uentlyassociated with excessive production of hormones. Overproduction is due not only to the increased

number of cells caused by the tumor but also to a failure of normal control mechanisms. The

resulting clinical symptoms are readily predictable because they represent the manifestations of

excess hormone levels.

0.). 4xample1 '6, prolactin, "5T6 in pituitary adenoma

%bnormal differentiation and anaplasiaAhen benign or slow-growing malignant neoplastic cells proliferate, they tend to differentiate normally

and resemble their normal counterparts (ie, they are well-differentiated. Bor example, the cells

constituting a lipoma resemble mature adipocytes on microscopic examination.

"s the degree of malignancy increases, the degree of differentiation decreases, and neoplastic cells do

not resemble the cell of origin so closely. Ahen the cell of origin cannot be recogni!ed on microscopic

examination, it is dubbed undifferentiatedor anaplastic.

-"naplastic cells display markedpleomorphism.The nucleiare characteristically extremely

hyperchromatic(darkly stained and large. The nuclear-cytoplasmic ratiomay approach )1)

instead of the normal )1+ or )1>. 'iant cells that are considerably larger than their neighbors may

be formed and possess either one enormous nucleusor several nuclei (syncytia. "naplasticnuclei are variable and bi!arre in si!e and shape. Thechromatinis coarse and clumped, and

nucleoli may be of astounding si!e. ore important,mitosesare often numerous and distinctlyatypical. "lso, anaplastic cells usually fail to develop recogni!able patterns of orientation to one

another (i.e. they lose normal polarity. They may grow in sheets, with total loss of communal

structures, such as glandformation or stratified s&uamousarchitecture. "naplasia is the most

extreme disturbance in cell growth encountered in the spectrum of cellular proliferations.

-Metaplasia:Neoplastic cells may occasionally differentiate in a manner that is abnormalfor

the cell of origin. Bor example, neoplastic endometrial glandular epithelium sometimes

differentiates to form both glandular and s&uamous epithelial cells (adenos&uamous carcinoma.

To put it another way, metaplasiais thereversible

replacement of one differentiatedcell typewith another mature differentiated cell type. This is often due to an abnormal stimulus, forcing

the cells to convert into a different type which is better suited for the situation.
http://en.wikipedia.org/wiki/Pleomorphismhttp://en.wikipedia.org/wiki/Pleomorphismhttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/w/index.php?title=Hyperchromatic&action=edit&redlink=1http://en.wikipedia.org/w/index.php?title=Hyperchromatic&action=edit&redlink=1http://en.wikipedia.org/wiki/NC_ratiohttp://en.wikipedia.org/wiki/NC_ratiohttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/wiki/Syncytiahttp://en.wikipedia.org/wiki/Chromatinhttp://en.wikipedia.org/wiki/Chromatinhttp://en.wikipedia.org/wiki/Nucleolihttp://en.wikipedia.org/wiki/Mitoseshttp://en.wikipedia.org/wiki/Mitoseshttp://en.wikipedia.org/wiki/Mitoseshttp://en.wikipedia.org/wiki/Glandhttp://en.wikipedia.org/wiki/Glandhttp://en.wikipedia.org/wiki/Squamoushttp://en.wikipedia.org/wiki/Squamoushttp://en.wikipedia.org/wiki/Cellular_differentiationhttp://en.wikipedia.org/wiki/Cell_typehttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/w/index.php?title=Hyperchromatic&action=edit&redlink=1http://en.wikipedia.org/wiki/NC_ratiohttp://en.wikipedia.org/wiki/Cell_nucleushttp://en.wikipedia.org/wiki/Syncytiahttp://en.wikipedia.org/wiki/Chromatinhttp://en.wikipedia.org/wiki/Nucleolihttp://en.wikipedia.org/wiki/Mitoseshttp://en.wikipedia.org/wiki/Glandhttp://en.wikipedia.org/wiki/Squamoushttp://en.wikipedia.org/wiki/Cellular_differentiationhttp://en.wikipedia.org/wiki/Cell_typehttp://en.wikipedia.org/wiki/Pleomorphism


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*n$asion&*nfiltration

5arcinomas and sarcomas demonstrate similar patterns of invasion despite their different tissues oforigin. $nvasion of the basement membrane by carcinoma distinguishes invasive cancer from

intraepithelial (i.e. carcinoma in situ cancer. 6aving penetrated (haha, penetrated the basement

membrane, malignant cells gain access to the lymphatics and blood vessels, the first step toward general

dissemination (Bigure )C-)D. $nfiltrating neoplastic cells tend to follow fascial planes along thepathway of least resistance# eventually, destruction of tissue occurs. The mechanisms whereby

neoplastic cells invade and destroy tissues are poorly understood, but protease production, loss of

contact inhibition of neoplastic cells, and decreased cell adhesiveness are believed to play a part.

?o, to sum up the se&uence of events1

E +ysplasiais the earliest form of pre-cancerous lesion recogni!able in a pap smear or biopsy.

7ysplasia can be low grade or high grade. The risk of low grade dysplasia transforming into highgrade dysplasia, and eventually cancer, is low. Treatment is usually straightforward. 6igh grade

dysplasia represents a more advanced progression towards malignant transformation.

E arcinoma in situ represents the transformation of a neoplastic lesion to one in which cells

undergo essentially no maturation, and thus may be considered :cancer-like;. $n this state,epithelial cells have lost their tissue identity and have reverted back to a primitive cell form that

grows rapidly and without regulation. 6owever, this form of cancer remains localized, and has-OT in$aded past the basement membrane.

E *n$asi$ecarcinomais the final step in this se&uence. $t is a cancer which has invaded beyond the

basement membrane and has potential to metastasi!e.

ymphatic Metastasis

etastasis via the lymphatics occurs early in carcinomas and melanomas but is an unusual occurrence inmost sarcomas, which tend to spread mainly via the bloodstream

Hematogenous Metastasis

4ntry of cancerous cells into the bloodstream tends to occur during the early clinical course. ost of

these malignant cells are thought to be destroyed by the immune system, but some become coated with

fibrin and entrapped in capillaries. etastasis can occur only if enough cancerous cells survive in thetissues to become established and proliferate at a second site. %roduction of tumor angiogenesis factor

(T%/ by the cancerous cells stimulates growth of new capillaries in the vicinity of tumor cells and

encourages vasculari!ation of the growing metastasis.

0rade $s. )tage

0rade1 the degree of cellular differentiation. " low grade is well differentiated, a high grade is

poorlyFundifferentiated.

)tage1 the extent of spread of a neoplasm# pathologic stage is determined by the extent of infiltrationand metastasis (eg, depth of invasion of the wall of a viscus# lymph node, bone marrow, or organ

involvement. 7escribed using T-Mclassification, which classifies neoplasms on the basis of size of

the primary tumor (T, lymph nodeinvolvement (N, and distant metastases(.
http://en.wikipedia.org/wiki/Carcinoma_in_situhttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Carcinomahttp://en.wikipedia.org/wiki/Carcinoma_in_situhttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Carcinoma

neoplasia core concepts

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