Detailed information about Neoplasia in pathology.

1. Neoplasia

2. Neoplasia means “new growth,” and a newly grown
cell mass is called a neoplasm.
Definition of neoplasm by eminent British
oncologist Willis:
“A neoplasm 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 cessation of the
stimuli which evoked the change.”
Neoplasia

3. Cancer is not a single disease but many disorders
that share a profound growth dysregulation.
Some cancers, such as Hodgkin lymphoma, are
curable, whereas others, such as pancreatic
adenocarcinoma, have a high mortality.
Cancer cells are immortal and have limitless
proliferative capacity

4. A tumor is said to be benign when its
microscopic and gross characteristics are
considered relatively innocent, implying that it
cannot spread to other sites
Malignant neoplasm is a lesion that can invade
and destroy adjacent structures and spread to
distant sites (metastasize) to cause death. Not
all cancers pursue such deadly course.
Malignant tumors are collectively referred to
as cancers

5. Characteristics of Benign and Malignant Neoplasms
In general, benign and malignant tumors can be
distinguished on the basis of the following characteristics:
1. Differentiation and anaplasia
2. Rate of growth
3. Local invasion
4. Metastasis.

6. Characteristics Discussion on characteristics
Differentiation
and anaplasia
Differentiation refers to the extent to which neoplastic parenchymal cells
resemble the corresponding normal parenchymal cells, both
morphologically and functionally; lack of differentiation is called anaplasia.
In general, benign tumors are well differentiated.
Malignant neoplasms are characterized by a wide range of parenchymal cell
differentiation, from surprisingly well differentiated to completely
undifferentiated.
The morphologic diagnosis of malignancy in well-differentiated tumors may
sometimes be quite difficult.
Malignant neoplasms that are composed of poorly differentiated cells are
said to be anaplastic. Lack of differentiation, or anaplasia, is considered a
hallmark of malignancy.
Rate of growth The rate of growth of a tumor is determined by three main factors: the
doubling time of tumor cells, the fraction of tumor cells that are in the
replicative pool, and the rate at which cells die. Because cell cycle controls
are deranged in most tumors, tumor cells can be triggered to cycle without
the usual restraints. The dividing cells, however, do not necessarily
complete the cell cycle more rapidly than do normal cells.
The progressive growth of tumors and the rate at which they grow are
determined by an excess of cell production over cell loss. In some tumors
the imbalance is large. Example: Some leukemias

7. Characteristics Discussion on characteristics
Local invasion Nearly all benign tumors grow as cohesive masses that remain localized to
their site of origin and do not have the capacity to infiltrate, invade, or
metastasize to distant sites, as do malignant tumors. Because they grow and
expand slowly, they usually develop a rim of compressed connective tissue,
sometimes called a fibrous capsule, which separates them from the host
tissue. This capsule is derived largely from the extracellular matrix of the
native tissue due to atrophy of normal parenchymal cells under the pressure
of an expanding tumor. Such encapsulation does not prevent tumor growth.
The growth of cancers is accompanied by progressive infiltration, invasion,
and destruction of the surrounding tissue. In general, malignant tumors are
poorly demarcated from the surrounding normal tissue
metastasis Metastases are tumor implants discontinuous with the primary
tumor. Metastasis unequivocally marks a tumor as malignant because benign
neoplasms do not metastasize. The invasiveness of cancers permits them to
penetrate into blood vessels, lymphatics, and body cavities, providing the
opportunity for spread.
In general, the more aggressive, the more rapidly growing, and the larger the
primary neoplasm, the greater the likelihood that it will metastasize or
already has metastasized.
Approximately 30% of newly diagnosed individuals with solid tumors present
with metastases .Metastatic spread strongly reduces the possibility of cure

8. INVASION AND METASTASIS
Invasion and metastasis are biologic
hallmarks of malignant tumors. They
are the major cause of cancer-
related morbidity and mortality.
Studies in mice and humans reveal
that although millions of cells are
released into the circulation each
day from a primary tumor, only a few
metastases are produced.
Each step in the process is subject to
a multitude of controls; hence, at
any point in the sequence the
breakaway cell may not survive.

9. Carcinogenic Agents and Their Cellular Interactions
The following agents can cause carcinogenesis:
1. Chemical
2. Radiation
3. Microbial

10. Carcinogenic Agents and Their Cellular Interactions(contd.)
1. Carcinogenesis caused by chemical
agents:
Some chemical carcinogens are called
initiators and they cause initiation of
carcinogenesis in cells. Initiation causes
permanent DNA damage (mutations).
Initiation alone, is not sufficient for
tumor formation. A different type of
chemical carcinogens called Promoters,
can induce tumors in initiated cells, but
they are nontumorigenic by
themselves. promoters leads to
proliferation and clonal expansion of
initiated (mutated) cells. Driven to
proliferate, the initiated clone of cells
suffers additional mutations,
developing eventually into a malignant
tumor.
Figure: Carcinogenesis caused by chemical agents

11. 2. Carcinogenesis caused by radiation:
Different radiations can cause carcinogenesis. UV light is responsible for causing skin
cancers, and ionizing radiation exposure from medical or occupational exposure,
nuclear plant accidents, and atomic bomb detonations has produced a variety of
cancers.
The carcinogenicity of UVB light is attributed to its formation of pyrimidine dimers in
DNA. This type of DNA damage is repaired by the nucleotide excision repair
pathway. When UV radiation is excessesive, the repair mechanism fails and error-
prone alternative DNA-repair mechanisms become active that result in survival of
the cell at the cost of genomic mutations. These mutations may lead to cancer.
Carcinogenic Agents and Their Cellular Interactions(contd.)

12. 3. Carcinogenesis caused by viruses:
Virus/bacteria Cancer: mechanism of cancer generation
Oncogenic RNA Viruses (ex. Human T-Cell
Leukemia Virus Type 1)
T-cell leukemia: A component of viral genome
called Tax stimulates proliferation of T cells with
molecular and chromosomal abnormalities.
Oncogenic DNA Viruses (ex. Hepatitis C
Virus)
Liver cancer: Components of the HCV genome, such
as the HCV core protein, may have a direct effect on
tumorigenesis, possibly by activating a variety of
growth-promoting signal transduction pathways
Bacteria (Helicobacter pylori) gastric adenocarcinoma: increased epithelial cell
proliferation in a background of chronic
inflammation. There is an initial development of
chronic gastritis, followed by gastric atrophy,
intestinal metaplasia of the lining cells, dysplasia,
and cancer.
Carcinogenic Agents and Their Cellular Interactions(contd.)

13. Oncogenes and cancer
Four classes of normal regulatory genes—the growth-promoting proto-oncogenes, the
growth-inhibiting tumor suppressor genes, genes that regulate programmed cell
death (apoptosis), and genes involved in DNA repair—are the principal targets of
genetic damage.
Mutant alleles of proto-oncogenes are considered dominant, because they transform
cells despite the presence of a normal counterpart.
In contrast, typically, both normal alleles of the tumor suppressor genes must be
damaged before transformation can occur.
Genes that regulate apoptosis may behave as proto-oncogenes or tumor suppressor
genes.
Mutations of DNA repair genes do not directly transform cells by affecting proliferation
or apoptosis. Instead, DNA-repair genes affect cell proliferation or survival indirectly
by influencing the ability of the organism to repair nonlethal damage in other genes,
including proto-oncogenes, tumor suppressor genes, and genes that regulate
apoptosis. A disability in the DNA-repair genes can predispose cells to widespread
mutations in the genome and thus to neoplastic transformation. Cells with
mutations in DNA repair genes are said to have developed a mutator phenotype.
A new class of regulatory molecules, called microRNAs (miRNAs), has recently been
discovered. Even though they do not encode proteins, different families of miRNAs
have been shown to act as either oncogenes or tumor suppressors. They do so by
affecting the translation of other genes