NEOPLASIA
DEFINITION: NEOPLASIA
Is an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change.
Fundamental to the origin of all neoplasm is loss of responsiveness to normal growth control. The neoplastic cells are referred as transformed because they continue to replicate against the regulatory influences that control normal cell growth.
Nomenclature:-
All tumors have 2 basic components:-
1-Parenchyma: made up of transformed neoplastic cells.
2- Supporting component which is host derived non neoplastic stroma made up of connective tissue and blood vessels.
The parenchyma determines the biologic behavior of the tumor and hence the name derives from it.
BENIGN TUMORS:
Benign tumors are designated by adding the suffix OMA to the cells type of origin of the tumor in mesenchimal tumors (fibroma, lipoma etc.)
Epithelial benign tumors- derived from glands or exhibit glandular pattern are designated adenoma. If they are finger-like fronds from surface –papillomas. Polyps are surface projections tumors in the gut. If there is cyst formation- cystadenoma.
Malignant tumors:
Those derived from mesenchimal tissue or its derivatives are designated as sarcomas (fibrosarcom, chondrosarcoma etc.)
Epithelial malignant tumors are designated as carcinomas. If they are from a glandular origin or exhibit glandular pattern- adenocarcinoma.
Sometimes the cells are unrecognizable and are merely called poorly or undifferentiated malignant tumor.
The parenchyma is derived from one cell line but undergo divergent differentiation. Such tumors are called mixed tumors or pleomorphic tumor whether they are benign or malignant e.g. the mixed tumor of the parotid gland.
Characteristics of benign and malignant tumors:
Ø The distinction between benign and malignant tumors is based on the differentiation and anaplasia, rate of growth, local invasion and metastasis
1. Differentiation and anaplasia:
· Differentiation is the extent to which parenchymal tumor cells resemble to comparable normal cells morphologically and functionally. Differentiated tumors resemble the cells of normal tissue of origin while poorly differentiated or undifferentiated tumors have primitive appearing cells
· Benign tumors: are well differentiated so their cells can not be distinguished from normal cells at HPF. Only the cells are massing into a nodule disclose their tumorous nature.
· Malignant tumors: in contrast range from well differentiated to undifferentiated. The latter one contains anaplastic cells. The anaplasia is considered the hall mark of the malignant tumors.
Anaplasia
Anaplasia (to form backward) implies loss of structural and functional differentiation of the normal cells. The anaplastic cells display marked variation in size and shape, with extremely hyper chromatic large nucleus, high nucleus/cyt, ratio, coarsely clumped chromatin and evident nucleoli. Sometimes there are giant bizarre tumor cells. There are many atypical mitotic figures (tri- quardri- multipolar spindles)
Other features of anaplasia are loss of polarity and disorientation.
When the stroma is scanty there is ischemic necrosis at the centre of the tumor
Dysplasia
Dysplasia (disorderly non neoplastic proliferation); is the loss of uniformity of the individual cell and loss in their architectural orientation. The dysplasia is encountered in the epithelium. The cells display all the characteristics of cancer cell previously stated.
If the dysplastic changes involve the whole thickness of the epithelium the lesion is preinvasive and is referred as in situ carcinoma.
If the dysplastic change involves the basal or medium layer it is referred as mild or moderate dysplasia respectively. Such dysplasia is reversible. If the inciting cause is removed the epithelium may revert to normal.
2-Rate of growth
The growth rate of a tumor correlates with their level of differentiation and thus most malignant tumors grow more rapidly than do benign ones.
Some malignant tumors may grow slowly for years, then suddenly, increase in size until they cause death of host within few months. This is due to emergence of an aggressive sub clone.
3-Local invasion
Nearly all benign tumors grow as cohesive expansive mass which have not the capacity to infiltrate, invade or form distance metastasis. It develops a capsule, CT rim formed as a result of compression of parenchyma cell atrophy under pressure. Hemangioma (uncapsulated) make un exception.
Cancers are accompanied by progressive infiltration, invasion, tissue destruction and distant metastasis.
4-Metastasis
Is tumor implants discontinuous with the primitive tumor and its presence marks a tumor as malignant.
The invasiveness of malignant tumors permit them to penetrate lymphatic, blood vessels and body cavities and spread to distance sites.
All malignant tumors metastasize except glioms and basal cell carcinoma of the skin but are high invasive.
30% of malignant tumors with initial diagnosis have already made metastasis and metastasis reduce the possibility of cure.
Pathway of spread
Dissemination of cancer occurs in:
Direct seeding of body cavities,
Lymphatic and surfaces and
Hematogenous spread
1-Seeding of the body cavities occurs when the cancer penetrates into natural open field e.g. ovarian cancers in the peritoneal cavity.
2-Lymphatic spread is common in cancer but also in sarcomas. Cancer cells follow the natural lymphatic drainage and lodge the nearest lymph nodes (e.g. breast cancer spread in axillary's nodes.) Sometimes the nearby nodes may be bypassed (skip metastasis) because of venous lymphatic anastomasi or obstruction due to inflammation or radiation.
Thus, regional nodes serve as effective barrier for further dissemination for sometime.
Cancer cells lodged in the nodes may be destroyed by tumor specific antigen response.
The enlarged nodes are due to the presence of cancer cells or reactive hyperplasia to the cancer
DEFINITION: NEOPLASIA
Is an abnormal mass of tissue the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after the cessation of the stimuli which evoked the change.
Fundamental to the origin of all neoplasm is loss of responsiveness to normal growth control. The neoplastic cells are referred as transformed because they continue to replicate against the regulatory influences that control normal cell growth.
Nomenclature:-
All tumors have 2 basic components:-
1-Parenchyma: made up of transformed neoplastic cells.
2- Supporting component which is host derived non neoplastic stroma made up of connective tissue and blood vessels.
The parenchyma determines the biologic behavior of the tumor and hence the name derives from it.
BENIGN TUMORS:
Benign tumors are designated by adding the suffix OMA to the cells type of origin of the tumor in mesenchimal tumors (fibroma, lipoma etc.)
Epithelial benign tumors- derived from glands or exhibit glandular pattern are designated adenoma. If they are finger-like fronds from surface –papillomas. Polyps are surface projections tumors in the gut. If there is cyst formation- cystadenoma.
Malignant tumors:
Those derived from mesenchimal tissue or its derivatives are designated as sarcomas (fibrosarcom, chondrosarcoma etc.)
Epithelial malignant tumors are designated as carcinomas. If they are from a glandular origin or exhibit glandular pattern- adenocarcinoma.
Sometimes the cells are unrecognizable and are merely called poorly or undifferentiated malignant tumor.
The parenchyma is derived from one cell line but undergo divergent differentiation. Such tumors are called mixed tumors or pleomorphic tumor whether they are benign or malignant e.g. the mixed tumor of the parotid gland.
Characteristics of benign and malignant tumors:
Ø The distinction between benign and malignant tumors is based on the differentiation and anaplasia, rate of growth, local invasion and metastasis
1. Differentiation and anaplasia:
· Differentiation is the extent to which parenchymal tumor cells resemble to comparable normal cells morphologically and functionally. Differentiated tumors resemble the cells of normal tissue of origin while poorly differentiated or undifferentiated tumors have primitive appearing cells
· Benign tumors: are well differentiated so their cells can not be distinguished from normal cells at HPF. Only the cells are massing into a nodule disclose their tumorous nature.
· Malignant tumors: in contrast range from well differentiated to undifferentiated. The latter one contains anaplastic cells. The anaplasia is considered the hall mark of the malignant tumors.
Anaplasia
Anaplasia (to form backward) implies loss of structural and functional differentiation of the normal cells. The anaplastic cells display marked variation in size and shape, with extremely hyper chromatic large nucleus, high nucleus/cyt, ratio, coarsely clumped chromatin and evident nucleoli. Sometimes there are giant bizarre tumor cells. There are many atypical mitotic figures (tri- quardri- multipolar spindles)
Other features of anaplasia are loss of polarity and disorientation.
When the stroma is scanty there is ischemic necrosis at the centre of the tumor
Dysplasia
Dysplasia (disorderly non neoplastic proliferation); is the loss of uniformity of the individual cell and loss in their architectural orientation. The dysplasia is encountered in the epithelium. The cells display all the characteristics of cancer cell previously stated.
If the dysplastic changes involve the whole thickness of the epithelium the lesion is preinvasive and is referred as in situ carcinoma.
If the dysplastic change involves the basal or medium layer it is referred as mild or moderate dysplasia respectively. Such dysplasia is reversible. If the inciting cause is removed the epithelium may revert to normal.
2-Rate of growth
The growth rate of a tumor correlates with their level of differentiation and thus most malignant tumors grow more rapidly than do benign ones.
Some malignant tumors may grow slowly for years, then suddenly, increase in size until they cause death of host within few months. This is due to emergence of an aggressive sub clone.
3-Local invasion
Nearly all benign tumors grow as cohesive expansive mass which have not the capacity to infiltrate, invade or form distance metastasis. It develops a capsule, CT rim formed as a result of compression of parenchyma cell atrophy under pressure. Hemangioma (uncapsulated) make un exception.
Cancers are accompanied by progressive infiltration, invasion, tissue destruction and distant metastasis.
4-Metastasis
Is tumor implants discontinuous with the primitive tumor and its presence marks a tumor as malignant.
The invasiveness of malignant tumors permit them to penetrate lymphatic, blood vessels and body cavities and spread to distance sites.
All malignant tumors metastasize except glioms and basal cell carcinoma of the skin but are high invasive.
30% of malignant tumors with initial diagnosis have already made metastasis and metastasis reduce the possibility of cure.
Pathway of spread
Dissemination of cancer occurs in:
Direct seeding of body cavities,
Lymphatic and surfaces and
Hematogenous spread
1-Seeding of the body cavities occurs when the cancer penetrates into natural open field e.g. ovarian cancers in the peritoneal cavity.
2-Lymphatic spread is common in cancer but also in sarcomas. Cancer cells follow the natural lymphatic drainage and lodge the nearest lymph nodes (e.g. breast cancer spread in axillary's nodes.) Sometimes the nearby nodes may be bypassed (skip metastasis) because of venous lymphatic anastomasi or obstruction due to inflammation or radiation.
Thus, regional nodes serve as effective barrier for further dissemination for sometime.
Cancer cells lodged in the nodes may be destroyed by tumor specific antigen response.
The enlarged nodes are due to the presence of cancer cells or reactive hyperplasia to the cancer
fragments.
-Hematogenous spread.
This is common in sarcomas but not rare in cancers. The most frequent site for lodging of malignant cells in this type of spread is the lung and the liver whether from arteries or veins (all portal area to the liver, all caval to the lung.)
Cancers arising near the vertebral column embolize through Para vertebral plexus to the vertebra (e.g. prostate and thyroid)
Some cancers have the propensity of invasion and growth in veins (renal carcinoma in renal veins then in cava inf. HCC in portal veins)
Epidemiology
· Some environmental factors can be risk factors for malignant tumors e.g. sun for skin cancers, smoking for cancer of the lungs, fats for cancers of the gut.
Heredity and cancer
· The most studied inherited cancers are retinoblastoma, familial adenomatose polyps and colorectal carcinoma, neurofibromatosis and multiple endocrine neoplasms. All of these neoplasms are inherited as autosomal dominant type of inheritance.
Acquired preneoplastic disorders
· Some disorders predispose to cancer and are called preneoplastic. (e.g. atrophic gastritis of pernicious anemia, solar keratosis, ulcerative colitis and leukoplakia of the oral mucosa and vulva.) This means that these individuals have higher risk to develop cancer.
· Other disorders are endometrial hyperplasia, cervical dysplasia, metaplasia of the bronchial mucosa of cigarette smokers.
Molecular basis of cancer.
There are 4 main things in the cancerogenesis:
Non lethal genetic damage acquired or inherited. The genetic hypothesis of cancer implies that a tumor mass results from the clone expansion of a single progenitor cell that incurred the genetic damage. This means that cancer are monoclonal.
There are 3 classes of regulatory genes:
a) Proto-oncogene- they promote growth and are dominant (mutant alleles suffice one to have malignant transformation)
b) Growth inhibitors or cancer suppressors (antioncogenes)- they are recessive (the 2 alleles must be mutant to have the cancer)
c) Genes regulating apoptosis- they can be either dominant or recessive
DNA repair genes:
They affect cell proliferation or survival indirectly by influencing the ability of the organism to repair non lethal damage in other genes including the upper cited 3 genes.
Disability in DNA repair genes can predispose mutation in the genome and hence neoplastic transformation.
CARCINOGENESIS
Cancerogenesis is a multiple step process at both the phenotypic and genotypic level. Malignant tumors have many attributes like excessive growth, invasiveness, metastasis potential, etc. These attributes are acquired in a stepwise fashion. The phenomenon is called tumor progression and results from accumulation of genetic lesions. These genetic changes fuel tumor progression and involves genes of growth regulation, angiogenesis, invasion and metastasis.
Oncogenes and cancer:
· They are derived from proto-oncogene (cellular genes that promote normal growth and differentiation.) They are discovered as passengers within the genome of the acute transforming retrovirus. This virus causes rapid induction of tumor in animals and vitro. In their genome there’s unique transforming sequence (viral oncogenes) not found in the genome non-transforming retrovirus.
· Surprisingly molecular hybridizing reveals v-ons sequence were identical to sequence found in normal DNA. From here appeared the concept that during evolution retrovirus oncogenes were transduced (captured) by the virus through recombination with host DNA of the infected cell. The genes are first discovered as virus genes.
Proto-oncogene are named after their virus homolog. Those of feline sarcoma virus are called v-fes. The correspondent proto-oncogene are called Fes.
Biology of the tumor growth:
Ø The natural history of malignant tumor are divided into 4 phase
v Malignant change in target cells (transformation)
v Growth of transformed cells.
v Local invasion.
v Distant metastasis
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