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Neoplasia
LM 202
Dr. Hassan Kofahi
Nomenclature
• Neoplasia: means “new growth”
• An abnormal growth of a tissue.
• Neoplasm is often referred to as tumor.
• Neoplastic cells are also called “transformed cells”.
• Transformed (or neoplastic) cells continue to replicate without control
• The study of tumors is called oncology.
• Tumors are divided into two types:
• Benign tumors: remain localized. In most of the cases, can be removed by surgery
and affected patients generally survive.
• Malignant tumors: can invade and destroy adjacent structures and spread to distant
sites (metastasize) to cause death.
• Cancer is a general term that refers collectively to the malignant tumors.
Nomenclature: Benign tumors
• Most of benign tumors are named by attaching the suffix -oma to
the cell type from which the tumor arises.
• Fibroma: benign tumor of the fibrous tissue.
• Adenoma: benign epithelial tumors that form a gland-like structure or a
benign tumor that is derived from glands.
• Papillomas: are benign epithelial neoplasms, growing on any surface, that
produce a nipple-like or finger-like projections.
• Polyp is a mass that projects above a mucosal surface (such as the
intestines) to form a macroscopically visible structure.
Papilloma
Nomenclature: Malignant tumors
• Sarcomas: malignant tumors of connective tissue cells
• Examples
• Liposarcoma: a malignant neoplasm composed of fat-like cells.
• Osteosarcoma: a malignant neoplasm composed of osteocyte-like cells.
• Leukemia: malignant neoplasia of the hematopoietic cells in the bone marrow that
results in high number of abnormal white blood cells.
• Lymphoma: a malignant neoplasm that arises in the lymphoid tissues (e.g., lymph
nodes).

• Carcinomas: malignant tumors of epithelial cells

• Examples
• Adenocarcinoma: carcinoma that grow in a glandular pattern.
• Squamous cell carcinoma: carcinoma that produce squamous cells.
Characteristics of benign and malignant
neoplasms
• Benign and malignant neoplasms can be distinguished according to
four main characteristics:
1. Growth rate
2. Differentiation and anaplasia
3. Local invasion
4. Metastasis
1- Growth rate
• Usually, malignant tumors grow faster than benign tumors.
• Exceptions exist  Growth rate is not a reliable factor to differentiate
between benign and malignant tumors.
2- Differentiation and anaplasia
• Differentiation refers to the extent by which neoplasms resemble their cells
of origin, morphologically and functionally.
• Well-differentiated neoplastic cells are more likely to retain the morphology and
functions of their normal counterparts than the poorly-differentiated neoplastic
cells.
• e.g., well-differentiated cancer cells of endocrine origin can produce hormones.
• Benign tumors are always well-differentiated
• e.g., lipoma is made up of mature fat cells that resembles normal fat cells.
• Malignant tumors vary in their differentiation
• Can be well-differentiated, poorly differentiated or undifferentiated.
• Loss of differentiation is called Anaplasia.
• Anaplasia always indicates malignancy.
3- Local invasion
• Benign tumors:
• Grow as cohesive expansile masses that remain localized to their sites of origin
and do not invade surrounding tissues.
• Generally, benign tumors are well demarcated
• In most of the cases, benign tumors are encapsulated (i.e., surrounded by
capsules).
• Encapsulation makes the tumor separate, movable and excisable by surgery.
Not all benign tumors are encapsulated.
• Malignant tumors:
• Not encapsulated.
• Poorly demarcated.
• Infiltrate, invade and destroy surrounding tissues.
• Thus, surgical removal of a malignant tumor is accompanied with the removal of a wide
margin of surrounding normal tissues.
 Microscopic view of fibroadenoma of the breast. A fibrous
capsule (indicated by the arrow) separates the tumor from the Microscopic view of breast carcinoma. illustrates
surrounding tissue. the invasion of breast stroma and fat by nests and
cords of tumor cells. Note the absence of a well-
defined capsule.
4- Metastasis
• Metastasis is the spread of tumor cells to
distant locations that are physically
discontinuous with the primary tumor.
• Metastasis is a characteristic of malignant
tumors. Benign tumors do not metastasize.
• Approximately 50% of cancer patients have
metastasis at the time of diagnosis (30%
evident + 20% hidden).
• Generally, larger and less differentiated
tumors are more likely to metastasize.
• Exceptions exist.
• All malignant tumors can metastasize.
• However, some malignant tumors, such as basal
cell carcinomas of the skin, rarely metastasize but
are locally invasive.
Routes of metastasis
• Malignant tumors can spread by three routes:
1. Seeding within body cavities.
• Occurs when neoplasms invade a natural body cavity.
• e.g., ovarian cancer spread in the peritoneal cavity.
2. Lymphatic spread:
• Favored by carcinomas
• Neoplastic cells usually metastasize to the first lymph nodes to drain the site of
neoplasm.
• e.g., carcinoma of the breast usually spread to the axillary lymph nodes.
• In some cases, cancer cells pass through the proximate lymph node to be trapped in
the subsequent lymph nodes (called skip metastasis).
• Cancer cells may pass across all the lymph nodes and ultimately reach the blood.
Routes of metastasis
3. Hematogenous (blood) spread:
• Favored by sarcomas.
• Cancer cells spread through the veins and follow the venous flow draining the
site of neoplasm until they (usually) become trapped in the first capillary bed
they encounter.
• The liver and the lungs are the most affected sites of hematogenous spread.
Cancer: epidemiology, risk factors
genes and others.
Cancer incidence
• Cancer is the second leading cause of death worldwide after cardiovascular
diseases.
• In 2020, it is estimated that approximately 19.3 million new cases of cancer
were diagnosed causing 10 million deaths worldwide (Source: Sung et al.,
2021).

Good news!
• Cancer death rates are decreasing!
• 20% reduction in men and 10% reduction in women in the USA since 1995.
• What is causing this reduction?
• Improved detection
• Better treatment
• Reduction in cigarette smoking and in the exposure to other carcinogens.
Cancer risk factors
• Environmental factors:
• Smoking: increases the risk of many types of cancer, especially lung cancer.
• 90% of lung cancer deaths are related to smoking.
• Diet: obesity is associated with a modestly increased risk of many types of cancer.
• Alcohol consumption: increases the risk of liver cancer.
• Infectious agents: especially viruses, responsible for 15% of cancers.
• Age:
• Generally, cancer incidence increases with age.
• Why?  with age, somatic mutations accumulate and immune competence decline.
• Certain types of cancer affect mainly children (e.g., certain types of leukemia and
lymphoma).
Cancer risk factors (continued)
• Acquired predisposing factors
• Chronic inflammation:
• e.g., hepatitis  hepatocellular carcinoma
• e.g., peptic ulcer  stomach cancer
• Immunodeficiency:
• HIV (AIDS)  different types of cancer such as Kaposi sarcoma
• Precursor lesions
• Squamous metaplasia of bronchial mucosa seen in in habitual smokers—a risk factor for lung carcinoma.
• Endometrial hyperplasia associate with higher risk of endometrial carcinoma.
• Hereditary factors
• Inheritance of certain genes is known to increase the risk of cancer.
• e.g., BRCA1 and BRCA2 mutations
• It is estimated that approximately 70% of women who inherit a harmful BRCA1 or BRCA2 mutation will
develop breast cancer before the age of 80 (Source: Kuchenbaecker et. al. 2017).
Cancer genes
• Cancer is a disease caused by mutations that affect the function of
genes.
• Large number of genes can play roles in the development and
progression of cancer.
• Mutations in these genes may be inherited in the germline or, in most
of the cases, acquired during life.
• Acquired mutations are caused by:
• Chemical agents
• Physical agents
• Viruses
• In some cases, may occur spontaneously.
Cancer genes can be divided into four major groups:
1. Oncogenes:
• Oncogenes are mutated or overexpressed versions of normal cellular
genes called proto-oncogenes.
• Oncogenes promote the growth or survival of the transformed cells.
2. Tumor suppressor genes:
• Normal genes that prevent uncontrolled growth.
• Mutation or loss of tumor suppressor genes cause uncontrolled
growth of the transformed cells.
• Two groups of tumor suppressor genes:
1. Governors: inhibit cell proliferation.
2. Guardians: sense DNA damage.
3. Genes that regulate apoptosis:
• Induction of apoptosis is one of the major protective
mechanisms against malignant transformations.
• Cancer cells overcome apoptosis by:
• Overexpression of the anti-apoptotic genes (genes that prevent
apoptosis).
• Mutation, deletion or underexpression of the pro-apoptotic genes
(genes that induce apoptosis).
4. Genes that regulate interactions between tumor cells
and the immune system:
• e.g., mutations in certain genes may inhibit the recognition of
tumor cells by the host immune system.
Carcinogenesis: a multistep process
• Carcinogenesis is a multistep process in which, a normal cell acquire an initial mutation
followed by multiple other mutations to give rise to a transformed cell (the founding cell)
that acquire the hallmarks of cancer (see next).
• Cancers are almost always monoclonal (i.e., arise from a single cell, the founding cell).
• During the proliferation of the founding cell progeny, further random mutations
accumulate independently in different cells of the progeny.
• Some of these mutations increase the proliferation or survival of the cells. Other mutation
decrease or have no effect on the proliferation and survival.
• Natural selection occurs with time.
• The more adapted cells outgrow the others, leading to an overall evolution of cancer over time
cancer progression.
• As a result of the continuous accumulation of mutations and the natural selection,
subclones emerge and the tumor’s cell population become genetically heterogeneous
with time.
• Over time, cancer becomes more aggressive and less responsive to treatment.
The hallmarks of cancer
• All cancers display fundamental changes in cell physiology. These
changes are considered as the hallmarks of cancer.
Etiology of cancer: carcinogenic agents
• Carcinogenic agents: Agents that cause genetic damage and lead to
cancer.
• Three types:
1. Chemical agents
2. Physical agents (radiation)
3. Microbial agents: viruses and bacteria
Chemical carcinogens
• Direct-acting agents:
• Require no metabolic conversion to become carcinogenic.
• e.g., Alkylating agents used in chemotherapy causes leukemia.
• Indirect-acting agents:
• Require metabolic conversion to become carcinogenic.
• e.g., polycyclic hydrocarbons present in tobacco smoke cause lung cancer.
• e.g., aromatic amines and azo dyes, such as β-naphthylamine, increase the
risk of bladder cancers in heavily exposed workers in the rubber industries.
• e.g., Aflatoxin B1 is a naturally occurring agent produced by some strains of
Aspergillus, a mold that grows on improperly stored grains and nuts, increases
the risk of liver cancer.
Physical carcinogens (radiation)
• UV light
• Present in the sun light.
• Prolonged exposures without protection increases the risk of skin cancer.
• Ionizing radiation
• e.g., Survivors of atomic bombs in Hiroshima and Nagasaki had an increased
risk of different types of cancer.
• e.g., Therapeutic irradiation of the head and neck increases the risk of thyroid
cancers years later.
Viral and microbial oncogenes
• DNA viruses:
• Papilloma virus increases the risk of squamous cell carcinoma of the cervix.
• Epstein-Barr Virus increases the risk of burkitt lymphoma.
• Hepatitis B virus increases the risk of hepatocellular carcinoma.
• RNA viruses:
• Human T-cell leukemia virus type 1 (HTLV1) causes leukemia/lymphoma.
• Hepatitis C virus increases the risk of hepatocellular carcinoma.
• Bacteria:
• Helicobacter pylori infection increases the risk of stomach cancers.
Grading and staging of cancer
• Grading and staging are important for:
• Determining the appropriate therapeutic strategy (surgery,
radiation or chemotherapy) .
• Predicting the prognosis.
Prognosis is a forecast of the possible outcomes of a disease and the
chances of recovery and survival.
• Grading is based on the degree of differentiation of cancer
cells and, in some types of cancer, on other microscopic
characteristics.
• Grading systems vary between different types of cancer.
• Staging is based on the following criteria:
• The size of the primary tumor.
• The degree of spread to regional lymph nodes.
• The presence or absence of blood-borne metastases.
• The major staging system currently in use is the American Joint
Committee on Cancer Staging. (commonly known as TNM staging)
• T is for the size of the primary tumor, T0-T4.
• N is for lymph nodes involvement. N0: no lymph nodes involved. N1-N3:
indicate an increasing number and extent of lymph node involvement.
• M is for the degree of metastasis. M0: no metastasis, M1-M2: indicate the
presence and the degree of metastasis.