Basic of neoplasia

1. Neoplasia
Dr. Md. Nazmus Sakib
Resident Oncology
Phase- A
Dhaka Medical College
15-Nov-20
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2. What is Neoplasia ?
Neoplasia means “new growth,”
Neoplasms- the collection of cells and stroma composing
new growths
Tumor originally described swelling caused by
inflammation, but is now equated with neoplasm.
Oncology
(Greek oncos = tumor) is the study of tumors or neoplasms.
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3. “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.”
--British oncologist Willis
In the modern era, a neoplasm is defined as a genetic
disorder of cell growth that is triggered by acquired or less
commonly inherited mutations affecting a single cell and
its clonal progeny.
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4. Basic components:
All tumors are composed of two components:
(1) Parenchyma: neoplastic cells that constitute the tumor
parenchyma.
 classification of tumors and
their biologic behavior are based
primarily on the parenchymal component
(2) Stroma: the supporting, host-derived, non-neoplastic
reactive stroma made up of
connective tissue
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5. Basic components: continue…
blood vessels and
cells of the adaptive
and innate immune
system
Growth and spread are
critically dependent on
their stroma
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6. Benign Tumor
A tumor is said to be benign when its gross and microscopic
appearances are considered
relatively innocent,
remains localized at their site of origin
dose not spread to other sites, and
is amenable to local surgical removal
 designated by attaching the suffix –oma to the name of
the cell type from which the tumor originates
 Tumors of mesenchymal cells generally
follow this rule.
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7. Benign Tumor…..
Example
 Fibroma -arising in fibrous tissue
 Chondroma - cartilaginous tumor
The nomenclature of benign epithelial tumors is more
complex;
• Some are classified based on their cell of origin,
• others on their microscopic appearance, and
• still others on their macroscopic architecture.
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8. Benign Tumor…..
 Adenoma -benign epithelial neoplasms derived from
glandular tissues although they may or may not form
glandular structures.
 Papillomas - fingerlike or warty projections from epithelial
surfaces
 Cystadenomas- large cystic masses; typically they are seen
in the ovary
 Polyp- a mass that projects above a mucosal surface, as in
the gut, to form a macroscopically visible structure
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9. Exceptions
 Many “–omas” are malignant
Lymphoma
Hepatoma
Seminoma
Melanoma
Mesothelioma
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10. Malignant Tumors
 tumors that can invade and destroy adjacent structures and
spread to distant sites (metastasize).
 Malignant tumors are collectively referred to as cancers
 Sarcomas -Malignant tumors arising in solid mesenchymal
tissues
 Carcinomas: Malignant neoplasms of epithelial cell origin
 Adenocarcinoma the neoplastic epithelial cells grow in a
glandular pattern
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12.  Mixed tumor:
 (1) More than one neoplastic cells type derived from
one germ cell layer.
eg. Pleomorphic adenoma- having combination of both
epithelial and mesenchymal tissue
 (2) More than one neoplastic cells type derived from
more than one germ cell layer.
eg. Teratoma- mixture of various tissue types arising
from totipotent cells derived from the three germ
cell layers— ectoderm, mesoderm and endoderm
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13. CHARACTERISTICS OF NEOPLASMS
 Benign and malignant tumors can be distinguished from one
another based on
 the degree of differentiation,
 rate of growth
 local invasiveness, and
 distant spread.
 Differentiation and Anaplasia
 Differentiation -refers to the extent to which neoplastic
parenchymal cells resemble the corresponding normal
parenchymal cells, both morphologically and functionally
 Anaplasia -lack of differentiation
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14. CHARACTERISTICS…..
Benign tumors resemble the tissue of origin and
are well differentiated;
malignant tumors are less well differentiated or
completely undifferentiated (anaplastic)
Lack of differentiation, or anaplasia, is
considered a hallmark of malignancy.
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15. CHARACTERISTICS…..
 In addition to anaplasia, cancer cells often exhibit other
telltale morphologic changes:
 Pleomorphism - variation in cell size and shape
 Abnormal nuclear morphology: hyperchromatic,
nuclear-to-cytoplasm ratio 1:1. [Normal 1:4 or 1:6]
 Mitoses: atypical, bizarre mitotic figures
 Loss of polarity- orientation of anaplastic cells is
markedly disturbed
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16. CHARACTERISTICS…..
 Rate of growth:
 Generally proliferate more rapidly than the normal cells
 Benign tumors are slow growing, while malignant tumors
generally grow faster
 Local Invasion- progressive infiltration, invasion, and
destruction of the surrounding tissue
 Benign tumors -circumscribed and have a capsule,
lack of local invasiveness
 Malignant tumors are poorly circumscribed and invade
surrounding normal tissues
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17.  Metastasis (distant spread):
-spread of a tumor to sites that are physically
discontinuous with the primary tumor, an event that
unequivocally marks a tumor as malignant
 Benign tumors remain localized at the site of origin;
malignant tumors metastasize to distant sites
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18.  Pathways of Spread
Dissemination of cancers may occur through one of three
pathways:
(1) direct seeding of body cavities or surfaces,
(2) lymphatic spread, and
(3) hematogenous spread.
eg. Liver, lung, Brain, bone, kidney, adrenal
 Carcinomas tend to spread via lymphatics, whereas
sarcomas prefer the hematogenous route.
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20. Benign vs Malignant tumors
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21. EPIDEMIOLOGY
 Global impact:
In 2018 it was estimated that
 18.1 million new cases
 there were over 9.5 million deaths caused by cancer
worldwide, representing nearly 1 in 6 of all deaths
By the year 2030
-cancer cases projected to increase to 21.4
million
-cancer-related deaths projected to increase13.2
million
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22. EPIDEMIOLOGY...
 The incidence of cancer varies with
geography,
age,
race, and
genetic background.
 Cancers are most common in adults older
than 55 years of age, but occur in adults at all ages and
in children and infants.
 The geographic variation is thought to
mainly stem from different environmental exposures.
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23. EPIDEMIOLOGY...
 infectious agents,
 smoking,
 alcohol,
 diet,
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 obesity,
 reproductive history, and
 exposure to environmental
carcinogens.
Important environmental factors implicated in
carcinogenesis include -

24. ..
 The risk of cancer is increased by reparative
proliferations caused by
 chronic inflammation or tissue injury,
 certain forms of hyperplasia, and
 immunodeficiency
Interactions between environmental factors and
genetic factors may be important determinants of
cancer risk.
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25. Molecular pathogenesis ofcancer
 Various gene regulate the normal mechanism of growth in
human body like
 Proto-oncogenes: growth-promoting genes
 Tumor suppressor genes : growth-inhibiting or growth suppressor
genes.
 Apoptosis regulatory genes control the programmed cell
death.
 DNA repairgenes
 In cancer cell these are replaced by
 Activation of growth-promotingoncogenes
 Inactivation of tumor-suppressorgenes
 Abnormal apoptosis regulatorygenes
 Failureof DNA repairgenes
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26. • Self-suffciency in growth signals
• Insensitivity to growth-inhibitory
signals
• Altered cellular metabolism
• Evasion of apoptosis
• Limitless replicative potential
(immortality)
• Sustained angiogenesis
• Invasion and metastasis
• Evasion of immune surveillance
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All cancers display eight fundamental changes in cell
physiology, which are considered the hallmarks of cancer

27. CHEMICAL CARCINOGENESIS
 Chemical carcinogens have highly reactive electrophile
groups that directly damage DNA, leading to mutations and
eventually cancer
 Direct-acting agents do not require metabolic conversion to
become carcinogenic , Most are weak
 Indirect-acting agents are not active
until converted to an ultimate carcinogen by endogenous
metabolic pathways
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28. Direct-Acting Carcinogens Indirect-Acting Carcinogens
Alkylating Agents
β-Propiolactone
Dimethyl sulfate
Diepoxybutane
Anticancer drugs (cyclophosphamide,
chlorambucil, nitrosoureas, and
others)
Polycyclic and Heterocyclic Aromatic
Hydrocarbons
Benz[a]anthracene
Benzo[a]pyrene
Dibenz[a,h]anthracene
3-Methylcholanthrene
7,12-Dimethylbenz[a]anthracene
Acylating Agents
1-Acetyl-imidazole
Dimethylcarbamyl chloride
Aromatic Amines, Amides, Azo Dyes
2-Naphthylamine (β-naphthylamine)
Benzidine
2-Acetylaminofluorene
Dimethylaminoazobenzene (butter yellow)
Natural Plant and Microbial Products
Aflatoxin B1
Griseofulvin
Cycasin
Safrole
Betel nuts
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29. RADIATION CARCINOGENESIS
 Ionizing radiation causes chromosome breakage,
translocations and less frequently point mutations,
leading to genetic damage and carcinogenesis.
 UV rays induce the formation of pyrimidine dimers within
DNA, leading to mutations. Therefore UV rays can give
rise to skin cancers.
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30. Microbial Carcinogenesis
 Oncogenic RNA Viruses
 Human T-Cell Leukemia Virus - adult T-cell leukemia/lymphoma
 Oncogenic DNA Viruses
• Human Papillomavirus
-squamous cell carcinomas of the cervix, anogenital region
• Epstein-Barr Virus -Burkitt lymphoma, Nasopharyngeal
carcinoma
• Hepatitis B and C Viruses-hepatocellular carcinomas
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31.  Oncogenic Bacteria
 H. pylori: implicated in gastric adenocarcinoma and MALToma.
 OncogenicParasites:
 Schistosoma haematobium-squamous cell carcinoma of the
urinary bladder,
 Clonorchis sinensis, the liver fluke - cholangiocarcinoma.
 Fungus:
 Aspergillusflavus(in certain grains) - hepatocellular carcinoma.
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32. Grading & Staging
 Grading: determined by cytologic appearance;
Grading of a cancer is based on
the degree of differentiation of the tumor cells and
the number of mitoses or architectural features.
 Staging: determined by surgical exploration or imaging,
is based on
Size of the primary lesion
Local and regional lymph node spread and
Distant metastases;
 Has greater clinical value than grading
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33. Laboratory Diagnosis of Cancer
Several sampling approaches exist for the
diagnosis of tumors including
• excision,
• biopsy,
• fine-needle aspiration, and
• cytologic smears.
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34.  Immunohistochemistry and flow cytometry studies help
in the diagnosis and classification of tumors because
distinct protein expression patterns define different
entities.
 Molecular analyses are used
 to determine diagnosis and prognosis,
 to detect minimal residual disease, and
 to diagnose hereditary predisposition to cancer.
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35.  Tumor markers:
Proteins(enzymes, hormones) released by tumors into
the serum, such as PSA, can be used to monitor for
recurrence after treatment but are problematic as
screening tests because of low sensitivity and specifcity.
 Useful to monitor a tumor’s response to therapy and in
detecting tumor recurrence.
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36. Tumor marker
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Hormones Tumor type
Human chorionic gonadotropin
Trophoblastic tumors,
nonseminomatous testicular tumors
Calcitonin Medullary carcinoma of thyroid
Catecholamine and metabolites
Pheochromocytoma and related
tumors
Ectopic hormones Paraneoplastic syndrome
Oncofetal Antigens
α-Fetoprotein
Liver cell cancer, nonseminomatous germ cell tumors of
testis
Carcinoembryonic antigen
Carcinomas of the colon, pancreas, lung,
stomach, and heart

37. Lineage-Specifc Proteins Tumor type
Immunoglobulin Multiple myeloma and other
gammopathies
Prostate-specifc antigen (PSA) Prostate cancer
Mucins and Other Glycoproteins
CA-125 Ovarian cancer
CA-19-9 Colon cancer, pancreatic cancer
CA-15-3 Breast cancer
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38. Thank you all
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