Presentation 2

NEOPLASIA Definition literally it means new growth and technically it is defined as 

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 ceasation of the stimuli, which is autonomous.

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Mechanism of Growth Disorders

Polyclonal

Monoclonal

Neoplasias differ from hyperplasia in that the latter does have a coordinator growth

that persists until the stimulus is there and it is not autonomous growth.

Tumour means any swelling including

neoplasme.

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Nomenclature: Neoplasms are named based on two factors Depending on the histologic types in to:

mesenchymal and epithelial Depending on behavioral patterns in to: benign

and malignant neoplasms

Benign and malignant neoplasms The suffix -oma denotes a benign neoplasm.

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Benign mesenchymal neoplasms originating from

named as

muscle bone fat blood vessel

Rhabdomyom osteoma lipoma heamangioma

nerve fibrous tissue cartilages

neuroma fibroma chondroma 5

Benign epithelial neoplasms are classified on the basis of cell of origin  for

example adenoma is the term for benign epithelial

neoplasm that form glandular pattern or on basis of microscopic or macroscopic patterns  for

example visible finger like or warty projection from

epithelial surface are referred to as papillomas.

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This nomenclature has however some

exceptions Nonneoplastic misnomers : hematoma,

granuloma, hamartoma Malignant misnomers : melanoma,

lymphoma, seminoma, glioma, hepatoma.

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Malignant neoplasm nomenclature essentially follows the same scheme used for

benign neoplasm with certain additions. Malignant neoplasms arising from

mesnchymal tissues  are

called sarcomas.

 These

neoplasms are named as fibrosarcoma,

liposarcoma, osteosarcoma, angiosarcoma etc.

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Malignant neoplasms of epithelial cell origin derived

from any of the three germ layers  are

called carcinomas.

 Eg.

Ectodermal origin: epidermis = squamous cell carcinoma,

basal cell carcinoma  Mesodermal

origin: renal tubles = renal cell carcinoma.

 Endodermal

origin: linings of the gastrointestinal tract

colonic carcinoma.

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Carcinomas can be further classified as  those

producing glandular microscopic pictures

are called adenocarcinomas and  those

producing recognizable squamous cells

are designated as squamous cell carcinoma etc. Furthermore, when possible the

carcinoma can be specified by naming the origin of the tumour such as renal cell adnocarcinoma etc. 10

Teratomas contain

representative of parenchyma

cells of more than one germ layer, usually all three layers. They

arise from totipotential cells and

so are principally encountered in ovary and testis.

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CLASSIFICATION TUMOURS

Benign Malignant Usually Harmless

Aggressive Kills if not

treated

All tumors, benign and malignant, have

two basic components:  (1) proliferating neoplastic cells that

constitute their parenchyma  (2) supportive stroma made up of

connective tissue and blood vessels. Sometimes the parenchymal cells

stimulate the formation of an abundant collagenous stroma, referred to as desmoplasia.

Characteristics of benign and malignant neoplasms  The difference in characteristics of these neoplasms can

conveniently be discussed under the following headings.

I. Differentiation and anaplasia  Differentiation refers to the extent to which parenchymal

cells resemble comparable normal cells both morphologically and function.  Thus well-differentiated tumorous cells resemble mature

normal cells of tissue of origin.

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Poorly differentiated or undifferentiated tumors

have primitive appearing, unspecialized cells. In general, benign neoplasms are well

differentiated. Malignant neoplasms, in contrast, range from well differentiated, moderately differentiated to poorly differentiated.  Malignant neoplasms composed of undifferentiated

cells are said to be anaplastic.

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Morphology of anaplastic cell includes 

large cells



Pleomorphism (variation in size & shape of nucleus),



hyperchromasia (dark staining of nucleus due to DNA and nuclear cytoplasmic ratio of 1:1(normally 1:4 to 1:6) usually large nuclei seen.



High and often abnormal mitoses,



tumor giant cells,



frequently lack of normal polar arrangement (loss of architectural orientation) denoting dysplasia and carcinoma-in-situ. 16

On functional differentiation The well differentiated the neoplasm, the more

completely it retains the functional capabilities found in its normal counterparts Thus, endocrine tumors produce hormone (ex.

Thyroid, adrenal) , well differentiated squamous cell carcinoma and

well differentiated hepatocellular carcinomas produce keratin and bile respectively.

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II. Rate of growth Most benign tumors grow slowly where as most

malignant tumors grow rapidly sometimes, at erratic pace. Some benign tumors for example uterine

leiomyoma increase in size during pregnancy probably due to steroidal effects (estrogen) and regress in menopause.

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In general, the growth rate of neoplasms

correlate with their level of differentiation and thus, most malignant neoplasms grow more rapidly than do benign neoplasms. On occasions, cancers have been observed to

decrease in size and even spontaneously disappear. Examples include renal cell carcinoma,

malignant melanoma, and choriocarcinoma 19

III. Local invasion Nearly all benign neoplasms grow as

cohesive expansile masses that remain localized to their site of origin and do not have the capacity to infiltrate, invade or metastasize to distant sites as do malignant neoplasms.

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Most benign neoplasms  are encapsulated by interims of fibrous capsules.  Thus, such encapsulations tend to contain the benign

neoplasms as a discrete, rapidly palpable and easily movable mass that can easily be surgically enucleated.

The growth of malignant neoplasms  is accompanied by progressive infiltration, invasion and

destruction of the surrounding tissue.  Generally, they are poorly demarcated from the surrounding

normal tissue (and a well defined cleavage plane is lacking).

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Next to the development of metastasis, invasiveness is

the most reliable feature that differentiates malignant from benign neoplasms. Steps in mechanisms of tumor invasion Carcinoma in-situ Malignant cell surface receptors bind to basement

membrane components (e.g. laminin). Malignant cell disrupt and invade basement membrane by

releasing type IV collagenases and other proteases

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Most carcinomas begin as localized growth confined to

the epithelium in which they arise. As long as this early cancers do not penetrate the

basement membrane on which the epithelium rests, such tumors are termed carcinoma in-situ. In those situations in which cancers arise from cell

that are not confined by a basement membrane, such as connective tissue cells, lymphoid elements and hepatocytes, an in-situ stage is not defined.

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IV. Metastasis It is defined as tumor implants discontinuous with

the primary tumor. Metastasis is the most reliable sign of malignancy. The invasiveness of cancers permits them to

penetrate in to the blood vessel, lymphatic and body cavities providing the opportunity for spread.

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Most malignant neoplasms metastasize except few

such as Gliomas in the central nervous system, Basal cell carcinoma (Rodent ulcer) in the skin and  dermatofibrosarcoma in soft tissues.

Since the pattern of metastasis is unpredictable, no

judgment can be made about the possibility of metastasis from pathologic examination of the primary tumor.

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Pathways of spread Dissemination of malignant neoplasm may occur

through one of the following pathways. 1. Seeding of body cavities and surfaces (transcoelomic spread)

This seeding may occur wherever a malignant neoplasm penetrates into a natural "open field".

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Most often involved is the peritoneal cavity, but

any other cavity-pleural, pericardial subarachnoids, and joint space-may be affected. Particular examples are krukenberg tumor 

which is a classical example of mucin producing signet ring adenocarcinomas arising from gastrointestinal tract (pancreas, breast, gall bladder) spreading to one or both ovaries and the peritoneal cavities.

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Pseudomyxoma peritoneale 

which is mucus secreting adenocarcinoma of ovarian and apperdicular origins.



These carcinomas fill the peritoneal cavity with a gelatinous soft, translucent Neoplastic mass.

2. Lymphatic spread  Most common for carcinomas,

follows the natural routes of

drainage. Sentinel lymph node is the first node in a regional

lymphatic basin that receives lymph from primary tumour. (breast-axillary- sentinel lymph node).

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3) Hematogenous spread  Typical for sarcomas but also seen with

carcinomas.  Liver and lungs are most frequently involved.

Arteries are rarely invaded Veins are the route of hematogenous spread

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CARCINOGENESIS  Carcinogenesis is a multistep process  Development of all human cancers requires the accumulation

of multiple genetic changes  i. Inherited germ line mutations  ii. Acquired mutations

 A tumor is derived from a monoclonal expansion of a mutated

cell  Most important mutations involve  i. Growth promoting genes (protooncogenes)

 ii. Growth inhibiting tumor suppressor genes  iii. The genes regulating apoptosis

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Acquired DNAdamaging agents •Chemicals •Viruses •radiation

Normal cell Successful DNA repair DNA damage Failure of DNA repair Mutation in the genome Of somatic cells

Activation of growth Promoting oncogenes

Inactivation of tumor Suppressor genes

Unregulated cell proliferation

Inherited mutations in •Genes affecting DNA Repair •Genes affecting cell Growth or apoptosis

Alterations in genes That regulate apoptosis Decreased apoptosis

TRANSFORMED CELL

Predisposition to cancer Cancer epidemiology In USA l in 5 deaths is due to cancer over the year’s cancer incidence increased in males

while it slightly decreased in females (due to largely screening procedures). The most common cancer in males is bronco–genie

carcinoma while breast carcinoma in females.

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Geographic and environmental factors Specific differences in incidence and death

rates of cancers are seen worldwide. 

Stomach carcinoma

- Japan



Lung cancer

- USA



Skin cancer

- Newzearland &

Australia 

Liver cancer

- Ethiopia

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 There are also occupational hazards including  asbestos= lung, mesothelioma;  Alcohol abuse-liver ca;  Cigarette smoking –lung ca,  Venereal infection (cervix) - cervical cancer etc.

Age  Most cancers occur >= 55 years of age but it declines

in death after age 75 years  Children under 15 years of age are susceptible to acute

leukemia, central nervous system tumors, neuroblastoma, wilm’s tumor, retinoblastoma, rhabdomyosarcoma and etc 34

Heredity  Familial retinoblastoma  Multiple endocrine neoplasia  Familial polyposis coli

Acquired pre- Neoplastic disorders  Cervical dysplasia  Endometrial hyperplasia  Cirrhosis  Ulcerative colitis  Chronic atrophic gastritis

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Carcinogenic Agents 1.Chemical carcinogens  Carcinogenesis is a multistep process involving a sequence of

initiation (mutation) followed by promotion (proliferation)

Initiators  Direct-acting chemical carcinogens. 

These are mutagens that cause cancer directly by modifying DNA.

 Indirect-acting chemical carcinogens (procarcinogens). 

These require metabolic conversion to form active carcinogens

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 Promotors  Cause cellular proliferation of mutated (initiated) cells  Proliferation of a mutated cell may lead to accumulation of

additional mutations

 Clinically important chemical carcinogens  Cigarette smoke: multiple malignancies  Asbestos:bronchogenic carcinoma, mesothelioma  Chromium and nickel: bronchogenic carcinoma  Arsenic: squamous cell carcinomas of skin and lung, angiosarcoma

of liver  Aromatic amines and azo dyes: hepatocellular carcinoma  Alkalating agents: leukemia, lymphoma, other cancer  Benezene:leukemia

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2.Radiation Ultraviolet radiation  UVB sunlight is the most carcinogenic.  Produces pyrimidine dimers in DNA leading to

transcriptional errors and mutations of onogenes and tumor suppressor genes  Increased risk of skin cancer  Xeroderma pimentosum: autosomal recessive

inherited defect in DNA repair 38

Ionizing radiation X-rays and gamma rays, alpha and beta particles, protons,

neutrons Cells in mitosis or G2 of the cell cycle are most sensitive Causes cross-linking and chain breaks in nucleic acids Atomic bomb: leukemias, thyroid cancer, other Uranium miners: lung cancer

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3.Oncogenic viruses RNA oncogenic viruses. The human T-cell leukemia virus (HTLV-l) causes

adult T-cellleukemia/lymphoma.

DNA oncogenic viruses Hepatitis B virus causes hepatocellular

carcinoma Epstein-Barr virus (EBV) 

Burkitt lymphoma



B-cell lymphomas in immunsuppressed patients



Nasopharyngeal carcinoma

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Clinical features of tumors  Neoplasms are essentially Parasites. Some cause only trivial mischief, but others are

catastrophic. All tumors, even benign ones, may cause

morbidity & mortality. With few exceptions, all masses require

anatomic evaluation.

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Tumour effects on Host  Tumours can effect the host in the following ways:  Local Effects  Cancer Cachexia  Paraneoplastic Syndromes –

Endocrinopathies

–

Neuromyopathies

–

Osteochondral Disorders

–

Vascular Phenomena

–

Fever

–

Nephrotic Syndrome 42

Local Effects • Tumor Impingement on nearby structures –

Pituitary adenoma on normal gland, Pancreatic carcinoma on bile duct, Esophageal carcinoma on lumen

• Ulceration/bleeding –

Colon, Gastric, and Renal cell carcinomas.

–

Patient presents with anaemia.

• Infection (often due to obstruction) –

Pulmonary infections due to blocked bronchi (lung carcinoma), Urinary infections due to blocked ureters (cervical carcinoma)

• Rupture or Infarction –

Ovarian, Hepatocellular, and Adrenal cortical carcinomas; Melanocarcinoma metastases 43

Systemic Effects of Neoplasms Hormonal effects Well differentiated tumor cells of endocrine glands can produce

hormones in an uncontrolled manner.  ACTH secreting pituitary adenoma,  Corticosteroid secreting tumors of the adrenal cortex,  Thyroid adenoma secreting thyroxine,  Feminization syndrome associated with testicular tumors (eg

estrogen from sertoli cells),  Pancreatic islet tumors (eg insulinoma, glucagonoma)

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Cachexia Cachexia is seen in advanced ca and includes body

wasting, weakness, anorexia, and anemia. It is *not* caused by the tumor's nutritional needs,

although the larger the tumor, the worse it is. Both fat and protein are consumed equally. Cause unknown, but some relation to Tumour

necrosis factor alpha (TNF-alpha) and perhaps to a newly isolated protein-mobilizing factor, which, when injected into healthy mice causes rapid weight loss despite maintenance of caloric intake. 45

Paraneoplastic Syndromes Are defined as "symptom complexes in cancer-

bearing patients that cannot readily be explained, either by the local or distant spread of the tumor or by the elaboration of hormones indigenous to the tissue from which the tumor arose“ These syndromes occur in about 15% of human

patients with advanced malignant disease; however, they can occasionally appear as a manifestation of an occult, small neoplasm.

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The pathophysiology of paraneoplastic

syndromes remains unclear, but some proposed mechanisms are:  1.- Hormone & hormone “like” synthesis  2.- Synthesis of identifiable chemical mediators  3.- Production of auto-inmune responses  4.- Activation of factors of the coagulation system

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