NEOPLASIA

DR A.O. OLUWASOLA
• Neoplasia literally means ‘’new growth”
and the new growth is a neoplasm.
• Oncology (Greek oncos = tumour) is the
study of tumours or neoplasms.
• Cancer is the common term for all
malignant tumours (derived from the
latin word for crab)
• “A neoplasm is an abnormal mass of tissue, the
growth of which exceeds and is uncoordinated
with that of the normal tissue and persists in
the same excessive manner after cessation of
the stimuli that evoked the change”.

• Tumour can be benign or malignant and are

made up of two basic components:
1. Parenchyma: the proliferating neoplastic
cells.
2. Supportive stroma: made up of connective
tissue and blood vessels.
 NOMENCLATURE
• Based on parenchymal component
– Cells of origin
• In general attach the suffix -oma to the cell of
origin.
– Microscopic architecture &
– Macroscopic patterns.
Epithelial tissue- -e.g. cysts, papillae & polyp.

• Malignant Mesenchymal tissue are usually called

sarcomas (Greek sar = fleshy) because they have
little connective tissue stroma
Papilloma
Colonic Polyp
Gross appearance of an opened
cystic teratoma of the ovary
 NOMENCLATURE CTD
• Degree of diferentiation : Well; Mod; Poorly
differentiated or undifferentiated malignant
tumor
• Non-classical designations:-
• Melanomas, seminomas, hepatomas.
• choristoma-as
• hamartoma -Aberrant
differentiation/anomalous development
• Specific designations have specific clinical
implications.
Tissue of Origin Benign Malignant
Nomenclature of Tumors
Composed of One Parenchymal Cell Type
Tumors of mesenchymal origin
Connective tissue and derivatives Fibroma Fibrosarcoma
Lipoma Liposarcoma
Chondroma Chondrosarcoma
Osteoma Osteogenic sarcoma
Endothelial and related tissues
Blood vessels Hemangioma Angiosarcoma
Lymph vessels Lymphangioma Lymphangiosarcoma
Synovium Synovial sarcoma
Mesothelium Mesothelioma
Brain coverings Meningioma Invasive meningioma
Blood cells and related cells
Hematopoietic cells Leukemias
Lymphoid tissue Lymphomas
Muscle
Smooth Leiomyoma Leiomyosarcoma
Striated Rhabdomyoma Rhabdomyosarcoma
Tumors of epithelial origin
Stratified squamous
Basal cells of skin or
adnexa
Epithelial lining of glands
or ducts
Respiratory passages
Renal epithelium
Liver cells
Urinary tract epithelium
(transitional)
Placental epithelium
Testicular epithelium
(germ cells)
Tumors of melanocytes
Squamous cell papilloma Squamous cell or
epidermoid carcinoma
Basal cell carcinoma
Adenoma Adenocarcinoma
Papilloma Papillary carcinomas
Cystadenoma Cystadenocarcinoma
Bronchial adenoma Bronchogenic carcinoma
Renal tubular adenoma Renal cell carcinoma
Liver cell adenoma Hepatocellular carcinoma
Transitional cell papilloma Transitional cell
carcinoma
Hydatidiform mole Choriocarcinoma
Seminoma
Nevus Malignant melanoma
More Than One Neoplastic Cell Type-Mixed Tumors, Usually Derived from
One Germ Cell Layer
Salivary glands Pleomorphic adenoma Malignant mixed tumor
(mixed tumor of of salivary gland origin
salivary origin)
Renal anlage Wilms tumor

More Than One Neoplastic Cell Type Derived from More Than One Germ
Cell Layer-Teratogenous
Totipotential cells in Mature teratoma, Immature teratoma,
gonads or in dermoid cyst teratocarcinoma
embryonic rests
 Comparisons Between Benign and Malignant Tumors
Characteristics Benign
Differentiation/ana Well differentiated; structure
plasia may be typical of tissue of
origin
Rate of growth Usually progressive and slow;
may come to a standstill or
regress; mitotic figures are
rare and normal
Local invasion Usually cohesive and
expansile well-demarcated
masses that do not invade or
infiltrate surrounding normal
tissues; Encapsulation
Metastasis Absent
Malignant
Some lack of differentiation
with anaplasia; structure is
often atypical
Erratic and may be slow to
rapid; mitotic figures may be
numerous and abnormal
Locally invasive, infiltrating
the surrounding normal
tissues; sometimes may be
seemingly cohesive and
expansile
Frequently present; the larger
and more undifferentiated the
primary, the more likely are
metastases
Leiomyoma of the uterus
Benign tumor (adenoma) of the
thyroid
Malignant tumor (adenocarcinoma)
of the colon
Anaplastic tumor showing cellular
and nuclear variation in size and
shape
Fibroadenoma of the Breast
Invasive carcinoma of the breast
 Biology of Tumor Growth
• The natural history of most malignant
tumors can be divided into four phases:
• (1) malignant change in the target cell,
referred to as transformation;
• (2) growth of the transformed cells;
• (3) local invasion; and
• (4) distant metastases
 DIFFERENTIATION AND
ANAPLASIA
• Differentiation –extent of functional &
morphologic resemblance to mature normal
cell.
• Anaplasia is lack of differentiation
• Hallmark of malignant transformation
• Xrized by: Pleomorphism; Hyperchromasia;
frequent/atypical mitosis; loss of polarity;
tumour giant cells; Necrosis
Anaplastic tumor of the skeletal
muscle (rhabdomyosarcoma)
Carcinoma in situ
 DYSPLASIA
• Loss in the uniformity of the individual cells
as well as a loss in their architectural
orientation
• Disorganized;Pleomorphism;
Hyperchromasia; Mitosis
• Carcinoma in situ;
• Invasion
 Factors influencing tumour
development
• Tumour development is influenced by
many factors that may be considered
under three headings:

1. Kinetics of tumour cell growth

2. Tumour angiogenesis and
3. Tumour progression and heterogeneity
Schematic representation of tumor
growth
 METASTASIS
• Unequivocal marker of malignancy
• Exceptions: Gliomas & BCC
• Pathways of spread:
1. Direct seeding of body cavities
2. Lymphatic spread
3. Haematogenous spread
Figure 7-42 The metastatic cascade. Schematic illustration of the sequential steps involved in the hematogenous spread of a tumor.

Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 3 August 2005 11:45 PM)
© 2005 Elsevier
A liver studded with metastatic
cancer.
 EPIDEMIOLOGY
• Can give insight to the cause of cancer
• Factors in patient & environment.
• US residents have 1/5 chances of dying
from cancer.
• In Nigeria 100,000 new cases occur each
year (T. F. Solanke, 2000)
• 500,000 in the 21st century
• Lung, Breast, prostate C/rectum-death/US
LEADING CAUSES OF CANCER
IN UNITED STATES
MEN WOMEN
• PROSTATE • BREAST
• LUNG • LUNG
• COLORECTAL • COLORECTAL
LEADING CAUSES OF CANCER
IN NIGERIA
MEN WOMEN
• PROSTATE • BREAST
• LIVER • CERVIX
• LYMPHOMA • LYMPHOMA
Geography and Environmental
Factors
 Factors Predisposing to Cancer
• Geog/Environ: Age, Sex, Diet, Lifestyle,
Occupation, ambient environ
• Genetic:
• Nonhereditary conditions:
Cx infla; UC, Crohn`s dx, viral hep. Cx pan.
Precancerous cond.- CAG/Pernicious
anaemia; Solar Keratosis; leukoplakia;
adenoma
 MECHANISM OF
CARCINOGENESIS/MOLECULAR
BASIS OF CANCER
• Cancer is essentially a genetic disease at the
cellular level.
• Carcinogenesis,
• The process of development of cancer in living
tissues, is a complex multistage process at both
the phenotypic and the genetic levels.
• A malignant neoplasm has several phenotypic
attributes,
• Such as excessive growth,
• Local invasiveness and the ability to form distant
metastases.
• These characteristics are acquired in a stepwise
fashion,
• A phenomenon called tumour progression.
• At the molecular level, progression results from
accumulation of genetic lesions.
• Such genetic damage [or mutation] may be
acquired by the action of environmental agents,
• Such as chemicals, Radiation or viruses or it
may be inherited in the germ line.
• The genetic hypothesis of cancer also
implies that a tumour mass results from
the clonal expansion of a single
progenitor cell that has incurred the
genetic damage –
• This is the basis of tumour
monoclonality.
Biology of tumor growth
The cell cycle and regulation of
cell growth:
 Normal cell division is closely regulated.
 Phases of cell cycle include:
• -Growth-G-phase-G1,G2;
• Synthetic-S-phase and mitotic-M-phase.
 After cell division daughter cells may re-
enter the cycle;
• Differentiate into its specialized forms or
undergo a programmed cell death (apoptosis).
CONTROL OF CELL CYCLE

© 2005 Elsevier
 During the cell cycle, the cell must
recognize, detect and repair any DNA
alteration or defect that might occur.
 Two important classes of genes control cell
growth:
• Proto-oncogenes;
• Tumour suppressor genes.
 Many of the cellular changes associated
with cancer affect this vital process.
 Multiple-hit concept of
carcinogenesis
• This involves primary and secondary genetic
abnormalities:-
• 1. Primary abnormalities:
 Consistent changes essential in establishing
the neoplasm,
 Strongly correlated with tumour type.
• Features that contribute to their development
include:
• Environmental factors and genetic factors
[hereditary].
 These primary abnormalities [or
mutations] effect phenotypic transformation in
tumour cells.
• Such as:
• – loss of capacity for growth arrest.
• –loss of contact inhibition of movement
• –change in cell morphology and growth habits
[anchorage independence] and
• - Capacity for indefinite replication
[immortality]
 Secondary abnormalities:
• These are additional mutations that confer an
evolutionary edge on the new clones of tumour
cells possessing them,
• Causing them to proliferate more vigorously;
• Have longer life span and eventually outgrow
their neighbours.
• These new subsets [tumour heterogeneity]
differ in their karyotype, invasiveness, growth
rate, hormonal responsiveness,
• Metastatic abilities and susceptibility to
antineoplastic drugs.
• These secondary genetic changes underlie the
phenomenom of tumour progression –
• Defined as “the acquisition of permanent
irreversible qualitative change in one or more
characteristics of a neoplasm”
• Environmental factors:
• Physical,
• Chemical &
• Biological.
 Genetic factors.
• Genetic alterations can occur sporadically or
may be inherited.
• The types of genetic changes seen in
tumouriogenes are:
• 1. Gene amplification
• 2. Gene re-arrangement [e.g. translocations]
• 3. Gene mutations and
• 4. Deletion of specific genes.
 Causes of mutation:
• Exposure to environmental genotoxic agents
and stresses,
• Gene classes
• 5 main classes of genes are involved in the
genetic changes underlying carcinogenesis.
• i. Oncogenes
• ii. Tumour suppressor genes
• iii. Metastasis genes
• iv. Apoptosis gene
. v. DNA repair genes
 ONCOGENES

• 1. ONCOGENES Cancer causing genes are

derived from proto-oncogenes.
• Proto-oncogenes can exert their functions
through production of:
5. Growth factors,
6. Growth factor receptors,
7. Signal tranducers and
8. Transcriptional factors.
 Mechanisms of activation of
Oncogenes
• a. Gene amplification – e.g.
• Small cell lung cancer [L-myc];
• b. Loss of control mechanism – e.g.
• Burkitt’s lymphoma [C-myc] t[8,14];
• c. Structural alteration – CML t[9,22] →
abl-bcr hybrid gene → a fusion protein.
• d. Point mutation in k-ras gene –
colorectal cancer
 (ii) TUMOUR SUPPRESSOR
GENES [TSG]
• Their gene products are involved in the
negative control of cell proliferation and
differentiation,
• And their loss or inactivation is associated with
carcinogenesis.
• E.g. P53, a TSG is the most common genetic
alteration found in cancers.-
• Li fraumeni syndrome, Rb, BRCA, APC genes.
 (iii) METASTASIS GENES:
• Ezrin- ERMS & Osteosarcoma
• Metastasis Suppressors: NM23 & KAI-1
genes.
• The loss or decreases expression of nm23
genes located on 17q 21.3 is associated
with high metastatic potential
• And poor survival in breast carcinoma.
 (iv) APOPTOSIS GENES:
• Bcl-2 oncogene may rescue cells from
apoptosis thus potentiating cellular
genetic alteration.
 (v) DNA REPAIR GENES
• Mutation in DNA repair genes are known to
lead to some cancers e.g.
• HNPCC[Hmsh2-(2p16) & Hmlh1-(3p21)] and
lymphoid malignancies.
• Failure of DNA repair is associated with a
group of autosomal recessive disorders
comprising:
• Bloom syndrome, Xeroderma pigmentosum,
Ataxia telangiectasia and Fanconi’s anaemia,
all of which are also associated with increased
predisposition to cancer.
 HEREDITY AND CANCER:
• A large number of types of cancer, [5-10% or
more] including the most common forms show
hereditary predisposition in addition to
environmental influences.
• These include:
• 1. Inherited cancer syndromes (Autosomal
Dominant):
• Retinoblastoma,
• Li fraumeni syndrome and FAP,
• All associated with TSG.
• 2. Familial cancers – evident familial
clustering of cancer, but role of inherited
predisposition may not be clear in each
case. e.g.
• BRCA 1 and 2.
• 3. Autosomal recessive syndromes of
defective DNA repair [as above]