NEOPLASIA

NEOPLASIA

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Learning outcomes

Learning outcomes

After studying this section, you should be able to

Describe tumour nomenclature

Describe classification of tumours

Explain the characteristics of benign and malignant tumours

Explain the aetiology and associated factors for tumour

Describe carcinogenesis

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Introduction

Introduction

Neoplasia literally means new growth, and a new growth formed is known as a neoplasm (Greek, neo = new + plasma = thing formed).

The term “tumor” was originally used for the swelling caused by inflammation, but it is now used synonymously with neoplasm.

Oncology (Greek, oncos = tumor) is the study of tumors or neoplasms.

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Introduction cont…

Introduction cont…

Willis 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 cessation of the stimuli which evoked the change.”

In the present era, a neoplasm can be defined as a disorder of cell growth which is triggered by a series of acquired mutations involving a single cell and its clonal progeny.

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Neoplasia- The process that occurs to produce a neoplasm

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Neoplasm –Is a mass of tissue formed as a result of abnormal, excessive, uncoordinated, autonomous and purposeless proliferation of cells even after cessation of stimulus for growth which caused it.

Neoplasia- The process that occurs to produce a neoplasm

Tumor –Abnormal mass of tissue (can be benign or malignant)

Cancer- A malignant tumor(cells grow fast, uncontrollably and spread/invade other cells)

Benign tumors-(cells grow slow, uncontrollably BUT DO NOT spread/invade other cells)

Anaplasia- Backward differentiation where Cells(anaplastic cells) have loss of structural and functional differentiation

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Salient Features of Neoplasia

Salient Features of Neoplasia

Origin: Neoplasms arise from cells that normally maintain a proliferative capacity.

Genetic disorder: Cancer is due to permanent genetic changes in the cell, known as mutations. These mutations may occur in genes which regulate cell growth, apoptosis, or DNA repair.

Heritable: The genetic alterations are passed down to the daughter tumor cells.

Monoclonal: All the neoplastic cells within an individual tumor originate from a single cell/or clone of cells that has undergone genetic change. Thus, tumors are said to be monoclonal.

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Salient Features of Neoplasia cont…

Salient Features of Neoplasia cont…

Carcinogenic stimulus: The stimulus responsible for the uncontrolled cell proliferation may not be identified or is not known.

Autonomy: In neoplasia, there is excessive and unregulated proliferation of cells that do not obey the normal regulatory control.

But tumors are dependent on the host for their nutrition and blood supply.

Irreversible: Neoplasm is irreversible and persist even after the inciting stimulus is withdrawn or gone

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Salient Features of Neoplasia cont…

Salient Features of Neoplasia cont…

Differentiation: It refers to the extent to which the tumor cells resemble the cell of origin.

A tumor may shows varying degrees of differentiation ranging from relatively mature structures that mimic normal tissues (well-differentiated) to cells so primitive that the cell of origin cannot be identified (poorly differentiated).

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Six Ps of neoplasm:

Six Ps of neoplasm

Purposeless

Progressive

Proliferation unregulated

Preys on host

Persists even after withdrawal of stimulus (autonomous)

Permanent genetic change in the cell

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TYPES OF NEOPLASMS

TYPES OF NEOPLASMS

There are 2 groups of neoplasms, divided according to their behavioural characteristics namely;

BENIGN NEOPLASMS and

MALIGNANT NEOPLASMS

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BENIGN NEOPLASMS

Are the ones which remain localized

Do not invade the tissue in which they grow

Do not spread through the host body

Do not normally cause serious damage EXCEPT as a result of critical positioning or function

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MALIGNANT NEOPLASMS

MALIGNANT NEOPLASMS

Invade and destroys the host tissue

Spreads throughout the body of the host

It is invariably fatal if unchecked by removal or treatment

CANCER

Cancer and malignant are commonly used as synonymous of a malignant neoplasm, i. e cancer is a common term for all malignant tumours.

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NOMECLATURE AND CLASSIFICATION OF NEOPLASM

NOMECLATURE AND CLASSIFICATION OF NEOPLASM

It is usual to classify neoplasms according to:-

• The cell type from which they originate (HISTOGENESIS)

Epithelial or

Mesenchymal (connective) tissue

• Biological behaviour:-

benign or

malignant

• Names of individuals:-

Hodgkin’s disease – a malignant tumour of lymphnodes = Lymphoma, which has no malignant counterpart).

Burkitt’s lymphoma – a malignant neoplasm originating from B-cells

Grawitz tumour = Renal cell carcinoma (arising from renal tubular cells)

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NOMECLATURE AND CLASSIFICATION OF NEOPLASM

NOMECLATURE AND CLASSIFICATION OF NEOPLASM

• The cell type from which they originate (HISTOGENESIS)

Epithelial or

Mesenchymal (connective) tissue

• Biological behaviour:-

benign or

malignant

• Names of individuals:-

Hodgkin’s disease – a malignant tumour of lymphnodes = Lymphoma, which has no malignant counterpart).

Burkitt’s lymphoma – a malignant neoplasm originating from B-cells

Grawitz tumour = Renal cell carcinoma (arising from renal tubular cells)

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NOMECLATURE AND CLASSIFICATION OF NEOPLASM

NOMECLATURE AND CLASSIFICATION OF NEOPLASM

• Organs:-

Hepatoma – tumour of the liver parenchymal cells-is a malignant version of Hepatocellular carcinoma

Tumours derived from 3 germ layers (Endo-Meso-Ectoderm)

Teratoma – derived from totipotential cells in gonadal or embryonal rests (may be benign or malignant)

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NOT TRUE TUMOURS

NOT TRUE TUMOURS

HARMATOMA

Are congenital anomalies due to abberant differentiation of cells that results in a mass of disorganized but mature specialized cells or tissue indigenous to the particular site.

Examples; islands of cartilage or blood vessels within the lung.

CHORIOSTOMA

A normal ectopic piece of tissue in an organ that is not normally found at the site

Examples; – a piece of adrenal gland under the capsule of the kidney or – a nodule of pancreatic tissue in the submucosal of the small intestine or stomach

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COMPONENTS OF TUMOURS

COMPONENTS OF TUMOURS

All tumours benign or malignant have 2 basic components;

Parenchyma – proliferating neoplastic cells and

Supportive stroma – made up of connective tissue, blood and lymphatic vessels

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NOMECLATURE OF TUMOURS

Naming of tumours is based on parenchyma component.

The SUFFIX“OMA” denotes benign neoplasm

Note that there is no rule without exception. Example;

Granuloma and Harmatoma are not neoplasms

Hepatoma, lymphoma, melanoma are malignant tumors

The tissue origin appears as a “PRIFIX”

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BENIGN TUMORS

BENIGN TUMORS

They are generally named by attaching the suffix “oma” to the cell of origin

• Benign mesenchymal tumours:-

Are those arising in muscle, bones, cartilage, fat, blood/lymphatic vessels, fibrous tissue, etc

Are classified histogenetically according to cell type

• Epithelial Tumors:-

Their nomenclature is not uniform but more complex.

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BENIGN TUMORS cont…

BENIGN TUMORS cont…

• Epithelial Tumors:-

They are classified in different ways

• Cells of origin
• Microscopic pattern
• Macroscopic architecture; This includes;

Adenoma: Benign epithelial tumor arising from glands or forming glandular structures.

Papilloma: Benign tumor with visible finger-like projections.

Polyp: Tumor produces visible projection above mucosal surface and protrudes into the lumen.

NB: Polyp: May be benign or malignant.

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Table: Nomenclature of few benign mesenchymal tumors

Table: Nomenclature of few benign mesenchymal tumors

Cell of origin

Benign

Fibrous

Fibroma

Fatty

Lipoma

Cartilage

Chondroma

Smooth muscle

Leiomyoma

Striated muscle

Rhabdomyoma

Bone

Osteoma

Meninges

Meningioma

Blood vessels

Angioma

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Stratified squamous epithelium

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Stratified squamous epithelium

Basal cell

Transitional epithelium

Sweat gland

Liver cell

Sebaceous gland

Bile duct

Placenta epithelium (trophoblasts)

Squamous cell papilloma

Basal cell papilloma

Transitional cell papilloma

Sweat gland adenoma

Liver cell adenoma

Sebaceous gland adenoma

Bile duct adenoma

Hydatidform mole

Table: Nomenclature of few benign Epithelial Origin tumors

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MALIGNANT NEOPLASMS

MALIGNANT NEOPLASMS

Malignant tumour nomeclature are essentially follows the same scheme used for benign neoplasm with certain additions.

Cancers arising in MESENCHYMAL tissue are called SARCOMAS (Greek “sark”-fleshy) because they usually have very little connective tissue stroma and so are fleshy.

Malignant neoplasms of EPITHELIAL origin, are derived from 3 germ layers and are called CARCINOMAS.

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TISSUE OF ORIGIN

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TISSUE OF ORIGIN

Fibrous

Fatty

Cartilage

Bone

Smooth muscle

Streated muscle

Synovium

Blood vessels

TYPE OF TUMOUR

Fibrosarcoma

Liposarcoma

Chondrosarcoma

Osteosarcoma

Leiomyoma

Rhabdomyosarcoma

Synoviosarcoma

Angiosarcoma

TABLE: Nomenclature of few malignant mesenchymal tumors

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TISSUE OF ORIGIN

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TISSUE OF ORIGIN

Stratified squamous epithelium

Basal cell

Transitional epithelium

Glandular epithelium

Melanocyte

Placental epithelium

Liver cells (hepatocytes)

TYPE OF TUMOUR

Squamous cell carcinoma

Basal cell carcinoma

Transitional cell carcinoma

Adenocarcinoma

Melanoma

Choriocarcinoma

Hepatocellular carcinoma

TABLE: Nomenclature of few malignant tumors of Epithelial Origin

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BENIGN VS MALIGNANT TUMOURS

BENIGN VS MALIGNANT TUMOURS

In general, benign and malignant tumors can be distinguished on the basis of four fundamental features, namely:

Differentiation and anaplasia,

rate of growth,

local invasion , and

metastasis.

• Anaplasia refers to cancer cells that divide rapidly and have little or no resemblance to normal cells.

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1. Differentiation and Anaplasia

• Differentiation and Anaplasia

Degree of Differentiation

Defined as the extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells.

Differentiation determines the grade of the tumor.

Benign tumours are usually well differentiated

Malignant tumours may vary from well to poorly differentiated

Poorly differentiated tumours are usually “aggressive” (carry a poorer prognosis due to rapid growth, early metastasis and/or poor response to therapy)

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1. Differentiation and Anaplasia cont…

• Differentiation and Anaplasia cont…

Anaplasia

Anaplasia literally means “to form backward/backward formation”, i.e. reversal of differentiation of cell to a more primitive level.

Malignant neoplasms composed of undifferentiated cells are called as anaplastic tumors.

Lack of differentiation (both structural and functional) is called as anaplasia and is characteristic of malignancy.

The degree of anaplasia in a cancer cell correlates with the aggressiveness of the tumor.

Thus, more anaplastic the tumor, the more aggressive it becomes.

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2. Rates of Growth

• Rates of Growth

Most benign tumours grow slowly over a period of years

Most malignant tumours tend to grow rapidly over a period of months (from discovery) but also tend to grow erratically.

Hormones may influence the rate of growth of tumour e.g. leiomyoma of uterus (fibroid), may grow rapidly in pregnancy and disappear after menopause (oestrogen dependent)

Also depends on adequacy of blood supply.

Rarely both benign and malignant tumours may actually stop growing and reduce in size or disappear (the so-called “miracle” cure), e.g. very rarely malignant melanoma may regress and disappear

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3. Local Invasion

• Local Invasion

Generally benign tumours grow slowly by expansion and develop a fibrous capsule

Fibrous capsule usually allow easy surgical enucleation

Some benign tumours are not well encapsulated.

Malignant tumours are locally invasive,

They infiltrate the surrounding tissue and

Usually give irregular margins that are not encapsulated

Surgical removal requires a wide excision margin of “normal tissue to be resected (say, 2-3 cm) to ensure that all malignant cells are removed.

Malignant tumors may “erode” into normal blood vessels, increasing the like hood of metastasis

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METASTASIS

METASTASIS

Definition: Spread of malignant tumors to contiguous organs and distant sites.

Metastasis is the transfer of cancer cells from the primary site to a distant site

A metastasis at a distant site is also called secondary deposit.

Metastasis is the denominator for malignancy

Two types of spread

Direct inversion into surrounding tissue.

Dissemination of tumor cells to form secondary deposits at distant sites = metastasis.

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Methods of spread

Methods of spread

• Lymphatics:

This is the common mode of spread of carcinomas, whereby tumor cells are carried as emboli to distant organs

Secondary deposits are often also found within draining lymph nodes

Because the lymphatic system ultimately drains into the blood stream, carcinoma cells can reach the blood via the thoracic duct

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Methods of spread cont…

Methods of spread cont…

• Hematogenous spread

Early spread via blood stream is characteristic of sarcomas

Carcinomas may also invade blood vessels and form a tumor within the lumen, which can then break off and cells carried in a form of emboli to distant sites

Spread by blood stream is usually a late feature of carcinomas

However, tumor of the GIT may readily transmit cells via the portal vein to produce metastasis in the liver

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Methods of spread cont…

Methods of spread cont…

• Seeding through body cavities (Transcoelomic spread)

This is a mode of spread of colon carcinomas

After penetrating the intestinal wall, they release tumor cells in the peritoneal cavity

The tumor cells implant and grow widely within the peritoneal cavity

Lung tumors may also seed and grow within the pleural cavity

Special type

Carcinoma of the stomach invades through the wall into peritoneal cavity and produce secondary tumor growth in the ovaries.

This is known as KRUKENBERG’S tumor.

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Site of metastasis

Site of metastasis

Carcinomas

Common sites are;

lymph nodes,

liver,

lungs,

bone and

brain

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Methods of spread cont…

• Transplantation

Carriage of tumor cells by surgical instruments during operation

This is rare

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Significance of metastasis

Significance of metastasis

Is a disastrous complication of malignant tumors and bring about difficulty in management

This is the most important denominator of malignancy

Metastases clearly identify a tumor as malignant because benign neoplasms never metastasize.

Metastases strongly reduce the possibility of cure of cancer.

Metastatic spread is the most common cause of cancer death. Markedly worsens the prognosis.

Factors favouring metastasis

• Poorly differentiated tumor,
• more rapidly growing tumor, and
• large primary tumor.

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Aetiology and Associated Factors for Tumours

Aetiology and Associated Factors for Tumours

Three classes of carcinogenic agents can be include;

Chemicals

Radiant energy

Microbial agents

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Chemical Carcinogens

Chemical Carcinogens

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, while

Indirect-acting agents are not active until converted to an ultimate carcinogen by endogenous metabolic pathways Hence polymorphisms of endogenous enzymes like cytochrome P-450 may influence carcinogenesis

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Chemical Carcinogens cont…

Chemical Carcinogens cont…

Following exposure of a cell to a mutagen or an initiator, tumour-genesis can be enhanced by exposure to promoters, which stimulate proliferation of the mutated cells.

Examples of human carcinogens include.

Direct-acting (example alkylating agents used for chemotherapy).

Indirect-acting (example benzopyrene, azo dyes, and aflatoxin).

Promoters/agents that cause pathologic hyperplasia of liver and endometrium

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Radiation Carcinogenesis

Radiation Carcinogenesis

Ionizing radiation causes chromosome breakage, translocations, and less frequently, point mutations, leading to genetic damage and carcinogenesis.

UV rays (UVR-Ultra violet rays), induce the formation of pyrimidine dimers within DNA, leading to mutations.

Therefore, UV rays can give rise to squamous cell carcinomas and melanomas of the skin

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Oncogenic Viruses

Oncogenic Viruses

Human T-cell leukemia virus-1(HTLV-1) causes T-cell leukemia.

HPV has been associated with benign warts, as well as cervical cancer.

EBV has been implicated in the pathogenesis of Burkitt lymphomas,

Lymphomas in immunosuppressed individuals with HIV infection or organ transplantation,

Some forms of Hodgkin lymphoma, and nasopharyngeal carcinoma

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Oncogenic Viruses cont…

Oncogenic Viruses cont…

70% and 85% of hepatocellular ca are due to infection with HBV or HCV

The oncogenic effects of HBV and HCV are multifactorial, but the dominant effect seems to be immunologically mediated chronic inflammation, hepatocellular injury, stimulation of hepatocyte proliferation, and production of reactive oxygen species that can damage DNA.

Bacteria; Helicobacter pylori is strongly associated with development of gastric cancer

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SUMMARY

SUMMARY

Benign and malignant tumors can be distinguished from one another based on the degree of differentiation, rate of growth, local invasiveness, and distant spread.

Malignant neoplasms disseminate by the following pathways: seeding within body cavities, lymphatic or hematogenous spread and rarely transplantation

A carcinogen is an agent known or suspected to cause tumors and such agents are said to be carcinogenic (cancer causing).

Carcinogenic agents (1) chemicals, (2) microbial agents, and (3) radiation

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EVALUATION

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EVALUATION

Discuss the nomenclature and classification of tumors.

Briefly explain fundamental features that differentiate malignant from benign tumour.

Define metastasis.

Briefly explain modes of spread of malignant tumors

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References

References

Robbins Basic pathology 10th edition

Rapid Review Pathology 4th Edition Goljan Pathology

Ramdas Nayak (medicoideas.com) Exam preparatory Manual for Undergraduates Pathology-2nd Edition

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