NEOPLASIANEOPLASIA

Nadia Ismiil, MD, FRCPCNadia Ismiil, MD, FRCPC

NeoplasiaNeoplasia: “New Growth” and a new : “New Growth” and a new growth is called “neoplasm”growth is called “neoplasm”

OncologyOncology: The study of tumors or : The study of tumors or neoplasmsneoplasms

CancerCancer: Malignant Tumor: Malignant Tumor

NeoplasmNeoplasm An abnormal mass of tissue, the An abnormal mass of tissue, the

growth of which exceeds and is growth of which exceeds and is uncoordinated with that of the normal uncoordinated with that of the normal tissues and persists in the same tissues and persists in the same excessive manner after cessation of excessive manner after cessation of the stimuli which evoked the changethe stimuli which evoked the change

The persistence of tumors, even after The persistence of tumors, even after the inciting stimulus is gone, results the inciting stimulus is gone, results from heritable genetic alterations that from heritable genetic alterations that are passed down to the progeny of the are passed down to the progeny of the tumor cellstumor cells

These genetic changes allow excessive These genetic changes allow excessive and unregulated proliferation that and unregulated proliferation that becomes autonomous, although tumors becomes autonomous, although tumors generally remain dependant on the host generally remain dependant on the host for their nutrition and blood supplyfor their nutrition and blood supply

The entire population of cells within a The entire population of cells within a tumor arises from a single cell that has tumor arises from a single cell that has incurred genetic change, and hence incurred genetic change, and hence tumors are said to be clonaltumors are said to be clonal

All tumors benign and malignant All tumors benign and malignant have two basic components: have two basic components:

1. Proliferating neoplastic cells that 1. Proliferating neoplastic cells that constitute their parenchyma constitute their parenchyma

2. Supportive stroma made up of 2. Supportive stroma made up of connective tissue and blood vesselsconnective tissue and blood vessels

Benign tumors are generally Benign tumors are generally designated by attaching “oma” to designated by attaching “oma” to the cell of origin, e.g. Tumor of the cell of origin, e.g. Tumor of Fibrous tissue is “fibroma.” Fibrous tissue is “fibroma.”

This is generally true to tumors of This is generally true to tumors of stromal originstromal origin

Nomenclature of Benign tumors of Nomenclature of Benign tumors of epithelial origin is more complex. The epithelial origin is more complex. The suffix “oma” may follow cell of origin, suffix “oma” may follow cell of origin, microscopic or macroscopic features.microscopic or macroscopic features.

A benign cystic tumor is A benign cystic tumor is “cystadenoma”, a papillary tumor is “cystadenoma”, a papillary tumor is “papilloma”“papilloma”

The nomenclature of malignant The nomenclature of malignant tumors follows the same schema.tumors follows the same schema.

Malignant tumors of the connective Malignant tumors of the connective tissue are called “sarcoma”. tissue are called “sarcoma”. Examples include fibrosarcoma for Examples include fibrosarcoma for malignancy of the fibrous tissue and malignancy of the fibrous tissue and liposarcoma for malignancy of the liposarcoma for malignancy of the adipose tissue.adipose tissue.

Malignant tumors of epithelial cell Malignant tumors of epithelial cell origin , derived from any of the three origin , derived from any of the three germ cell layers are called germ cell layers are called “carcinoma”, ectodermal, mesoderm “carcinoma”, ectodermal, mesoderm or endoderm. or endoderm.

Examples include squamous cell Examples include squamous cell carcinoma and adenocarcinoma. carcinoma and adenocarcinoma.

The natural history of most malignant The natural history of most malignant tumors can be divided into four phases:tumors can be divided into four phases:

Transformation which is the malignant Transformation which is the malignant change happening in the target cell. change happening in the target cell.

Growth of the transformed cell.Growth of the transformed cell. Local invasionLocal invasion Distant metastases.Distant metastases. The differences between benign and The differences between benign and

malignant tumors correspond to these malignant tumors correspond to these characteristics. characteristics.

Colonic polyp, benign

Metastatic carcinoma of the liver

DifferentiationDifferentiation

The extent to which the neoplastic The extent to which the neoplastic cells resemble comparable normal cells resemble comparable normal cells, both morphologically and cells, both morphologically and functionally.functionally.

Benign and well differentiated Benign and well differentiated malignant tumors are composed of malignant tumors are composed of cells resembling the cells of origin.cells resembling the cells of origin.

Poorly differentiated tumors have Poorly differentiated tumors have primitive unspecialized cells. primitive unspecialized cells.

differentiationdifferentiation

Leiomyoma is a benign tumor of the Leiomyoma is a benign tumor of the smooth muscle. Can be seen in smooth muscle. Can be seen in uterine fibroids. uterine fibroids.

The tumor cells closely resemble the The tumor cells closely resemble the cells of origin that it may be cells of origin that it may be impossible to recognize it as a tumor impossible to recognize it as a tumor microscopically.microscopically.

The only way to recognize it , is The only way to recognize it , is because it forms a mass. because it forms a mass.

                                               

  

                                               

  

Leiomyoma, gross and microscopy

AnaplasiaAnaplasia

Definition: Lack of differentiation.Definition: Lack of differentiation. Malignant tumors may be well Malignant tumors may be well

differentiated.differentiated. Malignant tumors may be anaplastic, Malignant tumors may be anaplastic,

ie, undifferentiated. The cells are ie, undifferentiated. The cells are primitive.primitive.

There is mounting evidence that in There is mounting evidence that in most cancers, the cells of origin is a most cancers, the cells of origin is a stem cell (an undifferentiated cell). stem cell (an undifferentiated cell).

AnaplasiaAnaplasia

In well differentiated cancers, the In well differentiated cancers, the stem cells will undergo specialization stem cells will undergo specialization and maturation first then undergo and maturation first then undergo malignant transformation.malignant transformation.

In undifferentiated cancers, the stem In undifferentiated cancers, the stem cell stem cell will proliferate directly cell stem cell will proliferate directly without undergoing the cycle of without undergoing the cycle of maturation first.maturation first.

AnaplasiaAnaplasia

It is marked by a number of morphologic It is marked by a number of morphologic changes:changes:

PleomorphismPleomorphism, variation in size and shape. , variation in size and shape. It applies to the cells and nuclei.It applies to the cells and nuclei.

Abnormal nuclear morphology: Abnormal nuclear morphology: high high nuclear cytoplasmic ratio, nuclear cytoplasmic ratio, hyperchromatism (abundance of DNA), hyperchromatism (abundance of DNA), variability of the nuclear shape and variability of the nuclear shape and prominence of the nucleoli. prominence of the nucleoli.

Anaplasia (cont.)Anaplasia (cont.)

MitosesMitoses: large number of mitoses : large number of mitoses reflecting the high proliferative reflecting the high proliferative index. Its presence by itself is not index. Its presence by itself is not diagnostic of malignancy since diagnostic of malignancy since mitoses can be seen in benign mitoses can be seen in benign tumors. However, the presence of tumors. However, the presence of abnormalabnormal mitoses is indicative of mitoses is indicative of malignancy. malignancy.

Anaplasia (cont)Anaplasia (cont)

Loss of polarityLoss of polarity: The orientation of : The orientation of the malignant cells is markedly the malignant cells is markedly disturbed.disturbed.

Other changesOther changes, presence of giant , presence of giant cells is an example. These may al;so cells is an example. These may al;so be present in inflammatory be present in inflammatory conditions.conditions.

Anaplasia

DysplasiaDysplasia

Definition: disordered growth.Definition: disordered growth. Encountered principally in epithelia Encountered principally in epithelia

such as cervix and esophagus.such as cervix and esophagus. Characterized by constellation of Characterized by constellation of

changes that include changes that include loss of loss of uniformity of the individual cells and uniformity of the individual cells and loss in their architectural orientation.loss in their architectural orientation.

The dysplastic cells are pleomorphic, The dysplastic cells are pleomorphic, high N/C ratio and lots of mitoses.high N/C ratio and lots of mitoses.

Dysplasia (cont)Dysplasia (cont)

When dysplastic changes involve the entire When dysplastic changes involve the entire thickness of the epithelium, they are thickness of the epithelium, they are considered peri-invasive tumors with no considered peri-invasive tumors with no invasion (yet). The process is called invasion (yet). The process is called carcinoma in situ.carcinoma in situ.

Dysplasia may be found next to an invasive Dysplasia may be found next to an invasive cancer.cancer.

The detection of early dysplastic changes in The detection of early dysplastic changes in cervix by pap smear is one of the greatest cervix by pap smear is one of the greatest success stories in medicine.success stories in medicine.

Dysplastic changes in esophagus can be seen Dysplastic changes in esophagus can be seen in cigarette smokers. in cigarette smokers.

Cervical dysplasia

Dysplasia in the intestinal epithelium

Genetic predisposition to cancerGenetic predisposition to cancer

Evidence now indicates that for a Evidence now indicates that for a large number of cancer types, there large number of cancer types, there exists not only an environmental exists not only an environmental influences but also hereditary influences but also hereditary predisposition.predisposition.

Less than 10% of cancer patients Less than 10% of cancer patients have inherited mutations that have inherited mutations that predispose to cancer. predispose to cancer.

ContinuedContinued

Genetic predisposition to cancer can Genetic predisposition to cancer can be divided into three categories:be divided into three categories:

Autosomal dominant inherited cancer Autosomal dominant inherited cancer syndrome, in which the inheritance syndrome, in which the inheritance of a single mutant gene increases of a single mutant gene increases the risk of developing a tumor. the risk of developing a tumor. Retinoblastoma, a malignant tumor Retinoblastoma, a malignant tumor of the eye is an example. of the eye is an example.

ContinuedContinued

Defective DNA repair syndromeDefective DNA repair syndrome. There will . There will be a defect in the repair process leading to be a defect in the repair process leading to DNA instability. Example is hereditary non DNA instability. Example is hereditary non polypoid cancer syndrome (HNPCC).polypoid cancer syndrome (HNPCC).

Familial cancers. Familial cancers. Cancer may occur more Cancer may occur more frequently in some families, so far non frequently in some families, so far non clearly defined pattern. Example, breast, clearly defined pattern. Example, breast, colon and ovarian cancer. colon and ovarian cancer.

Molecular basis of cancerMolecular basis of cancer

Non lethal genetic damage lies at theNon lethal genetic damage lies at the heart of carcinogenesisheart of carcinogenesis.Such genetic .Such genetic damage (mutation) may be environmental damage (mutation) may be environmental such as chemicals, radiation or viruses or such as chemicals, radiation or viruses or may be inherited in the germ line. may be inherited in the germ line.

A tumor is formed by the clonal expansion A tumor is formed by the clonal expansion of a single precursor cell that has incurred of a single precursor cell that has incurred the genetic damage, tumors are the genetic damage, tumors are monoclonal.monoclonal.

continuedcontinued

Four classes of regulatory genes, the Four classes of regulatory genes, the growth promoting protooncogenes, growth promoting protooncogenes, the growth inhibiting tumor the growth inhibiting tumor suppressor genes, genes that suppressor genes, genes that regulate apoptosis and genes regulate apoptosis and genes involved in DNA repair ARE THE involved in DNA repair ARE THE PRINCIPLE TARGETS OF GENETIC PRINCIPLE TARGETS OF GENETIC DAMAGE. DAMAGE.

Molecular basis of cancer Molecular basis of cancer

WHAT ARE THE ESSENTIAL WHAT ARE THE ESSENTIAL ALTERATIONS FOR MALIGNANT ALTERATIONS FOR MALIGNANT TRNSFORMATION??TRNSFORMATION??

1.Self sufficiency in growth signals , 1.Self sufficiency in growth signals , tumors have the capacity to tumors have the capacity to proliferate without external stimuli.proliferate without external stimuli.

2.Insensitivity to growth inhibiting 2.Insensitivity to growth inhibiting signals.signals.

3.Evasion of apoptosis3.Evasion of apoptosis 4.Defects in DNA repair4.Defects in DNA repair 5.limitless replicative potential5.limitless replicative potential

6. Sustained angiogenesis, vascular 6. Sustained angiogenesis, vascular supply.supply.

7.ability to invade and metastasize7.ability to invade and metastasize

Examples of occupational Examples of occupational associated cancersassociated cancers

Asbestos: lung mesotheliomaAsbestos: lung mesothelioma Nickel: nose and lung cancerNickel: nose and lung cancer Vinyl chloride: liver tumorsVinyl chloride: liver tumors Ethylene oxide: Leukemia Ethylene oxide: Leukemia

Lung cancer