NEOPLASIA

Introduction

 Neoplasia literally means "new growth

 “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” – Willis.
 It’s often referred to as a tumor, and the study of tumors is called oncology.
 Neoplasms can be of two types i.e. benign and malignant

Basic Structure

 All tumors, benign and malignant, have two basic components:

 Parenchyma: made up of transformed or neoplastic cells, – Largely determines its
biologic behavior, – Tumor derives its name.
 Stroma: supporting, host-derived, non-neoplastic, made up of connective tissue, blood
vessels, and host-derived inflammatory cells – crucial to the growth of the neoplasm -
carries the blood supply – provides support for the growth of parenchymal cells

Benign Tumors

 A tumor is said to be benign when its microscopic and gross characteristics are
considered to be relatively innocent, remain localized, non-metastatic and can be
surgically removaed; the patient generally survives.
 Designated by attaching the suffix –oma – Fibrous tissue: fibroma; – Cartilaginous
tumor: chondroma
 Adenoma – benign epithelial neoplasms producing gland patterns – derived from glands
but not necessarily exhibiting gland patterns
 Papillomas – Benign epithelial neoplasms, growing on any surface, – Produce
microscopic or macroscopic finger-like fronds
 Polyp – a mass that projects above a mucosal surface, as in the gut, to form a
macroscopically visible structure
 Cystadenomas – hollow cystic masses; typically they are seen in the ovary

Malignant Tumors

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  the lesion that can invade and destroy adjacent structures and spread to distant sites
(metastasize) to cause death
 Malignant neoplasms arising in – Mesenchymal tissue or its derivatives: sarcomas –
Epithelial cell origin: carcinomas – Glandular pattern: adenocarcinomas

SPECIAL CATEGORIES OF TUMOURS

 Mixed tumours
- Two types of tumours are combined in the same tumour
- Adenosquamous carcinoma
- Pleomorphic adenoma: salivary benign tumour having combination of both
epithelial and mesenchymal tissue
 Teratomas
- mixture of various tissue types arising from totipotent cells derived from the three
germ cell layers
- ectoderm, mesoderm and endoderm.
- Common sites: ovaries and testis
 Blastomas (Embryomas)
- arise from embryonal or partially differentiated cells which would normally form
blastema of the organs and tissue during embryogenesis
- more frequently in infants and children (under 5 years of age)

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 - neuroblastoma, nephroblastoma (Wilms’ tumour), hepatoblastoma, retinoblastoma,
medulloblastoma, pulmonary blastoma
 Hamartoma
- benign tumor which is made of mature but disorganised cells of tissues indigenous
to the particular organ
- Pulmonary Hamartoma

TUMOR CLASSIFICATION

CHARACTERISTICS OF TUMOURS

The characteristics of tumours are described under the following headings

- Rate of growth
- Cancer stem cells
- Clinical and gross features
- Microscopic features
- Local invasion (Direct spread)
- Metastasis (Distant spread)

RATE OF GROWTH

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  Generally proliferate more rapidly than the normal cells.
 Benign tumours grow slowly and malignant tumours rapidly
 Many exceptions to this generalization are there.
 Rapidly growing tumors tend to be poorly differentiated

CANCER STEM CELLS

 Cancer cell – heterogeneous population of cell which may contain Cancer Stem Cells
 It has been hypothesized that these cells - capacity to initiate and sustain the tumor
 So killing of these cells may be the principle of certain therapies.
 Whether cancer stem cells exist in all tumors is not yet clear

CLINICAL FEATURES

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  Benign
- Generally slow growing,
- Depending upon the location, may remain
 Asymptomatic: subcutaneous lipoma
 Symptomatic: meningioma in the nervous system
 Malignant
- malignant tumours grow rapidly,
- may ulcerate on the surface,
- invade locally into deeper tissues,
- may spread to distant sites (metastasis),
- systemic features such as weight loss, anorexia and anemia
- cardinal clinical features : invasiveness and metastasis

GROSS APPEARANCE

 Benign
- spherical or ovoid in shape
- encapsulated or well-circumscribed,
- freely movable,
- more often firm and uniform, unless secondary changes like haemorrhage or
infarction supervene
 Malignant
- Irregular in shape,
- poorly-circumscribed and extend into the adjacent tissues
- Secondary changes like haemorrhage, infarction and ulceration are seen more
often.

MICROSCOPIC
FEATURES

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  Its of greatest importance for recognising and classifying the tumours.
 These should be considered under
- Microscopic pattern
- Differentiation and anaplasia
- Tumour angiogenesis and stroma
- Inflammatory reaction

Microscopic Pattern

 Tumors may be either – Epithelial tumours

 acini, sheets, columns or cords of epithelium
 arranged in solid or papillary pattern – Mesenchymal tumours
 Interlacing bundles, fasicles or whorls,
 Separated from each other usually by the intercellular matrix substance
 Ex: cartilaginous matrix in chondroma, osteoid in osteosarcoma, – Mixed patterns –
Haematopoietic tumours: leukaemias and lymphomas
 Benign tumours and low grade malignant tumours reduplicate the normal structure

Differentiation

 Extent of morphological and functional resemblance of parenchymal tumour cells to

corresponding normal cells.
 Well-differentiated: minimal deviation of neoplastic cell in structure and function as
compared to normal cell
 ‘Poorly differentiated’; ‘undifferentiated’ or ‘dedifferentiated’: poor structural and
functional resemblance to corresponding normal cell.

Anaplasia

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  Following changes are noted in anaplastic cells
 Loss of polarity – basal polarity: Normally, the nuclei of epithelial cells are oriented
along the basement membrane – nuclei tend to lie away from the basement membrane
 Pleomorphism – Variation in size and shape of the tumour cells – often bigger than
normal
 Nucleas:Cytoplasmic ratio – Nuclei are enlarged - disproportionate to the cell size –
increased from normal 1:5 to 1:1
 Anisonucleosis – variation in size and shape of nuclei
 Hyperchromatism – Nuclear chromatin of malignant cell is increased and coarsely
clumped. – Due to increase in the amount of nucleoprotein resulting in dark-staining
nuclei
 Nucleolar changes – prominent nucleolus or nucleoli in the nucleus reflecting
 Mitotic figures: mainly of 2 types – Normal mitotic figures: seen in some non-neoplastic
proliferating cells like haematopoietic cells, intestinal epithelium, hepatocytes and
Certain benign tumours and some low grade malignant tumours – Abnormal or atypical
mitotic figures: malignant tumours and are identified as tripolar, quadripolar and
multipolar spindles
 Tumour giant cells – Multinucleate giant cells containing a single large and bizarre
nucleus – Found mainly in anaplasia in malignant tumours
 Functional (Cytoplasmic) changes – functional anaplasia as appreciated from the
cytoplasmic constituents of the tumour cells – The functional abnormality in neoplasms
may be quantitative, qualitative, or both
 Chromosomal abnormalities – abnormal genetic composition – on division they transmit
the genetic abnormality to their progeny.

LOCAL INVASION (DIRECT SPREAD)

 BENIGN TUMOURS
- Form encapsulated or circumscribed masses
- Expand and push aside the surrounding normal tissues
- Without actually invading, infiltrating or metastasising
 MALIGNANT TUMOURS
- Initially enlarge by expansion and some well- differentiated tumours may be partially
encapsulated as well
- But later they can be distinguished by invasion, infiltration and destruction of the
surrounding tissue,

METASTASIS (DISTANT SPREAD)

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  defined as the development of secondary implants (metastases) discontinuous with the
primary tumor, in remote tissues
 Benign tumours do not metastasise, EXCEPTION: gliomas of CNS and BCC.
 Approximately 30% of newly diagnosed patients with solid tumors (excluding skin
cancers other than melanomas) present with clinically evident metastases
 An additional 20% have occult (hidden) metastases at the time of diagnosis

Routes of Metastasis

 Cancers may spread to distant sites by following pathways:

- Lymphatic spread
- Haematogenous spread
- Spread along body cavities and natural passages

Lymphatic spread

 Carcinomas metastasise by lymphatic route while sarcomas favour haematogenous

route.
 Lymphatic permeation: walls of lymphatics are readily invaded by cancer cells.
 Lymphatic emboli: tumor detach to form emboli so as to be carried along the lymph to
the next draining lymph node.

Haematogenous spread

 Common route for sarcomas but certain carcinomas also frequently metastasise by this
mode.
 Ex: liver, lungs, brain, bones, kidney and adrenals
 Few organs such as spleen, heart, and skeletal muscle - do not allow tumour metastasis
to grow due to anatomical consideration

CARCINOGENESIS: ETIOLOGY and PATHOGENESIS OF CANCER

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  pathogenesis of cancer undergoes in the following 4 mechanism
- Molecular pathogenesis of cancer (genes and cancer)
- Chemical carcinogens and chemical carcinogenesis
- Physical carcinogens and radiation carcinogenesis
- Biologic carcinogens and viral oncogenesis.

MOLECULAR PATHOGENESIS OF CANCER

 Also known as genetic mechanisms of cancer

 It may be either based on
 Monoclonality of tumours – single clone of cells by genetic transformation or mutation –
Ex: multiple myeloma
 Genetic theory of cancer: various gene regulate the normal mechanism of growth in
human body like
- Proto-oncogenes: growth-promoting genes
- Anti-oncogenes: growth-inhibiting or growth suppressor genes.
- Apoptosis regulatory genes control the programmed cell death.
- DNA repair genes
 In cancer cell these are replaced by
 Activation of growth-promoting oncogenes
 Inactivation of cancer-suppressor genes
 Abnormal apoptosis regulatory genes
 Failure of DNA repair genes

CHEMICAL CARCINOGENS
AND CHEMICAL CARCINOGENESIS

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  Chemical carcinogens can be classified into
 DIRECT-ACTING CARCINOGENS: do not require metabolic activation
- Alkylating agents: various anti-cancer drugs (e.g. cyclophosphamide, chlorambucil,
busulfan, melphalan, nitrosourea etc), β-propiolactone and epoxides.
- Acylating agents: acetyl imidazole and dimethyl carbamyl chloride
 INDIRECT-ACTING CARCINOGENS (PROCARCINOGENS): prior metabolic activation before
becoming potent carcinogens.
- Polycyclic aromatic hydrocarbons: Anthracenes, Benzapyrene, Methylcholanthrene
- Aromatic amines and azo-dyes: β-naphthylamine, Benzidine
- Naturally-occurring products: Aflatoxin Bl, Actinomycin D, Mitomycin C, Safrole,
Betel nut
- Miscellaneous: Nitrosamines and nitrosamides, Vinyl chloride monomer, Asbestos,
Saccharin and cyclamates

PHYSICAL CARCINOGENESIS

 Radiation
- ultraviolet light and ionising radiation like X-rays, α-, β- and γ-rays, radioactive
isotopes, protons and neutron
- Higher dose and with high LET (linear energy transfer) caused carcinogenic effect
 Non-radiation
- Continous mechanical injury to the tissues such as from intrinsic stone
- implants of inert materials such as plastic, glass etc in prostheses

BIOLOGIC CARCINOGENESIS

 Various studies have proved the direct role of MCO’s in causing cancer.
 Parasites: Schistosoma haematobium - squamous cell carcinoma of the urinary bladder,
- Clonorchis sinensis, the liver fluke - cholangiocarcinoma.
 Fungus: Aspergillus flavus (in certain grains) - hepatocellular carcinoma.
 Bacteria: Helicobacter pylori - chronic gastritis and peptic ulcer; its prolonged infection
may lead to gastric lymphoma and gastric carcinoma,
 Viral: most important organism
- Oncogenic RNA Viruses : human T-cell leukemia virus-1 (HTLV-1) , only retrovirus
that has been demonstrated to cause cancer in humans
- Oncogenic DNA Viruses : -human papillomavirus (HPV), Epstein-Barr virus (EBV),
Kaposi sarcoma herpesvirus (KSHV) also called human herpesvirus 8), and hepatitis B
virus (HBV)

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