GENERAL

PATHOLOGY
NEOPLASMS
Lecture outline
1. Definition of terms 6. Molecular basis of cancer

(carcinogenesis)
2. Classifications of tumours
7. Predisposing factors to cancer
3. Nomenclature of tumours
8. Clinical aspects of neoplasms

4. Characteristics of neoplasms 9. Laboratory Diagnosis of Cancer

5. Cancer epidemiology
 Introduction

• Neoplasm means "new growth." also referred to as a tumour

• Oncology (Greek oncos - tumor) is the study of tumors or neoplasms.

• Tumours are quite common and the leading cause of death worldwide.
 Definition

• 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 the cessation of the stimuli which evoked the change. (Willis)
 Classifications

• Two (2) classifications - benign and malignant tumours.

• A tumour is benign when its microscopic and gross characteristics are

considered to be quite innocent.

• Implying that it will remain localized and will not spread to other sites.
 Classifications ………………..

• A tumour is malignant when the lesion can invade and destroy adjacent structures and spread to

other sites (metastasize) and can cause death.

• Malignant tumour is also referred to as cancer

• Cancer is one of the leading cause of death worldwide.

• More agonizing than the mortality rate is the emotional and physical suffering inflicted by the disease.
 Nomenclature
• All tumours have two basic components:

• The proliferating cells which is the parenchyma

• Stroma – composed of fibrous connective tissue and blood vessels which support the tumour growth.

• Tumours get their names from the parenchymal component.

• The stroma however is crucial to the growth of a tumour as it support the growth of cells.
 Nomenclature ………………

Benign Tumors
• Benign tumors are named by attaching the suffix - oma to the cell of origin e.g.

• Fibrous tissue (fibrocytes) is a fibroma

• Benign cartilaginous tumor (chondrocytes) is a chondroma.
• However, naming of benign epithelial tumors is more complex.
 Nomenclature ………………

• Papillomas are benign

epithelial neoplasms, growing

on any surface, that produce

microscopic finger-like

fronds.
 Nomenclature ………………

Some are classified on the basis of their microscopic pattern.

• For instance: Cystadenomas are cystic masses; typically

seen in the ovary.

• Adenoma is applied to benign epithelial neoplasms derived

from glands and those producing gland patterns.

 Nomenclature ………………
• Malignant Tumors – use embryonic origin of tissue (carcinoma or sarcoma)

• Carcinomas - (from ectoderm and Endoderm) epithelial and glandular tissues

• Carcinomas may be classified further.

• Those which forms glandular pattern are called adenocarcinomas, and those that
produce squamous cells are called squamous cell carcinomas.
 Nomenclature ………………

• Sarcomas - (arise from mesoderm) connective tissue, muscle, nerve and

endothelial tissues.

• Hence, cancer of the fibrous tissue is called fibrosarcoma

• And a malignant tumour composed of chondrocytes is a chondrosarcoma.

 Nomenclature ………………

• Although, there is a broad generalisation regarding nomenclature, there are some exceptions to this concept:

• Melanoma for carcinoma of the melanocytes

• Hepatoma for carcinoma of the hepatocytes

• Lymphoma for malignant tumour of the lymphoid tissue

• Seminoma for malignant tumour of the testis

• Leukaemia for cancer of blood forming cells

Special categories of tumours
• Some tumours defy the generalisation given above e.g.
Mixed tumours.

• This is when two types of tumours are combined in the same

tumour e.g. Adenosquamous cell carcinoma
(adenocarcinoma and squamous cell carcinoma mostly
affecting endometrium).
 Special categories of tumours ………………
Teratomas

• These tumours arise from totipotent cells and are made up of a mixture of various types of tissue

• In these tumours you can find skin (ectodermal), intestine - like and bronchial-like structures

(endodermal), and tissues such as bone or cartilage (mesodermal ) all intermixed in a haphazard

manner.

• Most common sites for teratomas are ovaries and testis

 Special categories of tumours ………………

• Teratomas may be benign or

mature (most of the ovarian
teratomas) or

• Malignant or immature (most of

the testicular teratomas).
 Special categories of tumours ………………

• Blastomas or embryomas are malignant tumours arising from embryonal cells which normally

form organs and tissue during embryogenesis

• Nephroblastoma (Wilms’ Tumour), Retinoblastoma, Medulloblastoma, Pulmonary Blastoma.

• Occurs in children less than 5 years

 Special categories of tumours ………………

Hamartoma

• Hamartoma are benign tumours made of mature but disorganised cells of tissues

indigenous to the particular organ

• Thus, all mature differentiated tissue elements are present but are jumbled up as a mass.
Characteristics of Neoplasms

• There are four fundamental features by which benign and malignant tumors can be distinguished.

• These are;

• Differentiation and anaplasia,

• Rate of growth,

• Local invasion and

• Metastasis.
1. Differentiation and Anaplasia
• This refer to the extent where tumour cells resemble the normal cells
morphologically and functionally.

1. Size - Anaplastic cells display marked pleomorphism

2. Nuclear - The nuclei are extremely hyperchromatic (darkly stained) and large

• Nuclear-to-cytoplasmic ratio - may approach 1 : 1 instead of the normal 1 : 4 or 1 : 6.

Differentiation and anaplasia ……………….

• Anaplastic nuclei chromatin is coarse and clumped, and nucleoli may be of big size.

4. Mitoses are often numerous and distinctly atypical; multiple spindles may be

seen and sometimes appear as tripolar or quadripolar forms.

5. Polarity - Anaplastic cells usually lose normal polarity.

 Differentiation and anaplasia ……………….

With regard to differentiation in tumours,

• Benign tumours are composed of well-differentiated cells that closely resemble their normal counterparts.

• Malignant tumours are characterized by a wide range of parenchymal cell differentiation, from well

differentiated to completely undifferentiated.

Well differentiated
Undifferentiated
2. Rate of Growth

• Benign tumors grow slowly, and malignant tumours grow much faster.

• There are some exceptions to this generalization.

• Under certain situations, Some benign tumors may grow faster than malignant tumours

• For example, leiomyomas (fibroids) are influenced by the circulating

levels of estrogens ( in during pregnancy menopause while CSCC is a
slow growing tumour.
• The rate of growth of malignant tumors correlates in general

with their level of differentiation.

• In other words, rapidly growing tumors tend to be poorly

differentiated.
3. Local Invasion

• A benign neoplasm remains localized at its site of origin.

• It is contained in the capsule.

• For example; leiomyomas slowly expand and develop an enclosing fibrous capsule that separates them from the host tissue.

• The capsule is derived from the stroma of the host tissue as the parenchymal cells atrophy under the pressure of the expanding

tumor.
• Cancers grow by progressive

infiltration, invasion and penetration

of the surrounding tissue.

• Hence, they do not develop well-

defined capsules.
Leiomyomas Metastatic cancer to the liver
4. Metastasis

• The term metastasis means development of secondary tumours in remote tissues.

• Malignant neoplasms disseminate by one of three pathways:

1. Natural pathways - transcoelomic and seeding within body cavities,

2. Lymphatic spread, or

3. Hematogenous spread.
Natural pathways – (Transcoelomic and seeding) Spread

• It occurs when neoplasms invade a natural body cavity.

• This mode of dissemination is particularly characteristic of cancers of the ovary, which often cover the peritoneal

surfaces widely.

• The implants may cover peritoneal surfaces and yet not invade the underlying parenchyma of the abdominal organs.
Natural pathways – (Transcoelomic and seeding) Spread
Lymphatic spread

• This is more typical of carcinomas e.g. melanoma.

Haematogenous spread

• It is the most feared consequence of cancer.

• It is the favoured pathway for sarcomas, but carcinomas

use it as well.
Molecular Basis of Cancer
• To understand how cancer develop, we need to understand the
characteristics of a normal cell.

1. Mortality
• Normal cells have a limited capacity to grow and divide even when
provided with optimal growth conditions

• Normally, after 50–60 population doublings, the cell ages and die.
2. Dependence on Growth Factors to Support Proliferation

• Cells require various growth factors to continue proliferating.

• In normal human tissues, growth factors are generally produced

extracellularly at distant sites and then are either carried through

the bloodstream or diffuse to their nearby target cells.

3. Anchorage-Dependent Growth and Cell Adhesion

• Normal mammalian cells do not proliferate, but instead undergo

cell death if they become detached from a solid substrate.
In cell cycle;

• There are four phases (G1, S, G2, and M) of a cell cycle

• Three of these phases are assigned to replicating cells and only the G1 phase

and G0 are non-replicative.

• Once a cell enters a replicative phase it is committed to completing a cell division.

• Hence, these phases are tightly regulated by genes.

There are 4 classes of normal regulatory genes:

i. Proto-oncogenes: these are normal genes concerned with the regulation of cell
proliferation.

Important proto-oncogenes:

• HER-2/neu stimulates cell division. This gene is amplified up to 30% in human

breast cancers.

• The RAS gene is involved in kinase signaling pathways that control transcription
of genes, regulating cell growth and differentiation.

• MYC protein is a transcription factor and controls expression of several genes.

ii. Tumour suppressor genes: these are normal cells which act

as braking signals during G1 phase of the cell cycle, to stop or

slow the cell cycle before S phase.

• A few important tumor-suppressor genes are:

• p53: a transcription factor that regulates cell division and cell death.

• Rb: alters the activity of transcription factors and therefore controls cell

division.

• APC: controls the availability of a transcription factor.

iii. DNA repair genes code for proteins which correct errors
that arise when cells duplicate their DNA prior to cell division.

• These genes are active throughout the cell cycle, particularly

during G2 after DNA replication and before the
chromosomes divide.

iv. Genes that regulate cell death (apoptosis) p53

Formation of cancer

• Cancer is a multistep process that requires the accumulation of multiple

mutations in a single cell.

• Mutation can be due to metabolic activities and environmental factors such

as exposure to UV light and radiation, chemicals or infective agents such

viruses.
• In cancer, 3 things in the cell cycle can go wrong in:

• These are oncogenes, tumor-suppressor genes and DNA repair genes.

i. An oncogene is a mutated proto-oncogene – this leads to uncontrolled cell growth.

• An oncogene does not allow cell stoppages at cell checkpoints to insure that it is normal.
ii. When a tumor-suppressor gene is mutated, the normal brake mechanism

will be disabled, resulting in uncontrolled growth, i.e. cancer.

iii. Mutations in DNA repair genes lead to a failure in repair.

• If the rate of DNA damage exceeds the capacity of the cell to repair it, the

accumulation of errors can overwhelm the cell and result in cancer.

Cancer cells therefore display the following characteristics

• Immortality.

• Non-dependence on growth factors to support proliferation.

• Non-anchorage-dependent for growth and cell adhesion –

basis of metastasis.
 Epidemiology of neoplasms
• Worldwide, it is estimated that about 20% of all deaths are cancer-related.

• There have been changing patterns in incidence of cancers in both sexes and geographic
locations

• In general, most common cancers in the developed and developing countries are as under:

• Developed world: lung, breast, prostate and colorectal.

• Developing world: liver, cervical and oesophageal.

 Epidemiology of neoplasms …….
• In Zambia, cancer cases are increasing.

• However the 2013 & 2014 patients have almost been the same in statistical terms.

• In a week CDH receives about 30-60 new patients

• In a month CDH receives about 130-200 new patients.

• However, the figures fluctuate.

• Below is an over view of new Cancer Cases from 2006- 2014

Top 10 cancers for Both Males & Females in Zambia - 2013

Cancers # of Pts % 35
Cervical 665 32 30
25
Breast 188 9
20
Kaposi's 15
sarcoma 151 7 10
Prostate 102 5 5
Lymphomas 100 5 0

esophagus 51 2.5
Colerectal 39 2
keloids 30 1.5
Hepatocellular 18 1
Eye 15 1

cervical cancer (32%) has always been on top of CDH disease chart, then breast(9%) , and
a fluctuation between Kaposi's sarcoma, prostate and lymphomas.
 Predisposing factors to neoplasia
• differences affecting the whole population such as climate, soil, water, diet, habits, customs
etc.

• E.g. Malignancies of the lung, breast, and colon are common in whites whileFamilial and
genetic factors; cancers run in families e.g. cancer of the ovary and breast.

• Racial and geographic factors. Due to partly genetic composition and largely due to
influence of the environment and geographic cancer of the penis and cervix common in

blacks.
 Predisposing factors to neoplasia ………..
• Age. Generally, cancers occur in older individuals above 65 years of age.

Environmental and cultural factors;

• Cigarette smoking causes cancer of the oral cavity, pharynx, larynx,

oesophagus, lungs, pancreas and urinary bladder.

• Alcohol abuse predisposes to the development of cancer of oropharynx,

larynx, oesophagus and liver.
 Predisposing factors to neoplasia ………..
• Infective agents e.g. HPV, HIV and Helicobacter pylori

• HPV causes cancer by binding tumour suppressor proteins in the host, thus
affecting the cellular cycle of the infected cells

• HPV has been linked to Cancer of the cervix.

• However, CA cervix has been associated to a number of factors such as age

at first coitus, multiple sexual partners, parity and HIV.
 Predisposing factors to neoplasia ………..

• Sexual partners of circumcised males have lower incidence of

cervical cancer than the partners of uncircumcised males.

• Helicobacter pylori is associated with cancer of the stomach.

Clinical Features of Neoplasms

• Cachexia defined by progressive loss of body fat and lean body mass, accompanied by

• Profound weakness
• Anorexia and
• Anaemia

• Is caused by release of cytokines by the tumor or host.

Laboratory Diagnosis of Cancer

1. Histological Methods

• These methods are based on microscopic examination of properly fixed tissue

(excised tumour mass or open/needle biopsy from the mass), supported with

complete clinical and investigative data.

2. Cytological Methods

• Cytological methods for diagnosis consist of study of cells shed off into body cavities

(exfoliative cytology) and study of cells by putting a fine needle introduced under

vacuum into the lesion (fine needle aspiration cytology, FNAC).

3. Histochemistry and Cytochemistry

• Histochemistry and cytochemistry are additional diagnostic tools which help the

pathologist in identifying the chemical composition of cells, their constituents and their

products by special staining methods.

4. Tumour Markers (Biochemical Assays)

• tumour markers are biochemical assays of products elaborated by the tumour cells in

blood or other body fluids e.g. CA 125 in Cancer of the ovary.

References
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Philadelphia, 8th edition, 1987
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London, 4th edition, 1974
5. Macfarlane, Reid, callander, Illustrated Pathology, Churchill Livingstone, 5th
edition, 2000.
6. Cotran RS, Kumar V, Collins T. Robins pathologic basis of diseases. Philadelphia,
J.B. Saunders Company. 6th edition 1999
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