Neoplasia References: Pathologic Basis of Disease by Robbins and Cotran, 8th Ed. (2010) - PowerPoint Presentation

Slide1

Neoplasia

References:

Pathologic Basis of Disease by Robbins and Cotran, 8th Ed. (2010)Slide2

Neoplasia

(TUMOR)

Definitions

-

“New growth” = Neoplasm

- Tumor

Oncology

-

Greek “oncos” = tumor

-

Study of tumors or neoplasms

-

Cancer

= Malignant tumorsSlide3

Neoplasia

(TUMOR)

Tumor

- An abnormal mass of tissue

- Growth

exceeds that of normal tissues

- Growth persists after cessation of the stimuli that initiated change

- Classified:

Benign vs. Malignant Slide4

What is the relationship of neoplasia

to

metaplasia

and dysplasia?Slide5

Metaplasia -replacement

of one type of cell with another type

.

found

in association with tissue damage, repair, and

regeneration.

the

replacing cell type is more suited to a change in environmentSlide6

Dysplasia

–means

disordered growth.

often

occurs in

metaplastic

epithelium, but not all

metaplastic

epithelium is also

dysplastic

- characterized

by

changes

that

include a loss in the uniformity of the individual cells as well as a loss in their architectural orientation

.Slide7

When dysplastic changes are marked and involve the entire thickness of the epithelium but the lesion remains confined by the basement membrane

, it is considered a

preinvasive neoplasm and is referred to as

carcinoma in situ

Once

the tumor cells

breach the basement membrane

, the tumor is said to be

invasive

.Slide8

However, dysplasia does not necessarily progress to cancer

. Mild to moderate changes that do not involve the entire thickness of epithelium

may be reversible

, and with removal of the inciting causes the epithelium may revert to normal.

Even

carcinoma in situ may take years to become invasive.Slide9

The growth of cancers is accompanied by progressive infiltration, invasion, and destruction of the surrounding tissue

.

Malignant tumors are poorly demarcated from the surrounding normal

tissue.Slide10

Metaplasia and dysplasia are still forms of cellular adaptation

in response to stress/injury.

Neoplasia

is not.

However,

metaplasia

and dysplasia

may lead to

neoplasia

.Slide11

Table on Nomenclature of Tumors

a. Origin

b. Cell type

c. Benign and Malignant types

NEOPLASIA

NomenclatureSlide12
Slide13
Slide14
Slide15
Slide16

2 Basic Components of Tumor

T

he

“transformed”

neoplastic

cells

Parenchyma

The

nontransformed

elements such as connective tissues & blood vessels

Supporting

stromaSlide17

Characteristics of Benign vs. Malignant Neoplasms

Differentiation and

Anaplasia

Rate of Growth

Local Invasion

MetastasisSlide18

Differentiation & Anaplasia

Parenchymal cells of

neoplasms

Differentiation

-

the extent to which

parenchymal

cells resemble comparable normal cells

- morphologically & functionallySlide19

Differentiation

Well-differentiated

- resemble mature normal cells of the tissue origin

Poorly

differentiated (

anaplastic

)

- Undifferentiated

- primitive, unspecialized cellsSlide20

Differentiation

All benign tumors

-

well-differentiated

Malignant

neoplasms

- range from

well-differentiated

to undifferentiatedSlide21

Anaplasia

Definition

- lack of differentiation

- hallmark of

malignant transformation

- “ to form backward”Slide22

Lack of differentiation, or anaplasia, is often associated with many other morphologic changes. Slide23

Pleomorphism

.

Both the cells and the nuclei characteristically display pleomorphism

—variation in size and shape. Cells within the same tumor are not uniform- some are large, some are small.Slide24

Abnormal nuclear morphology.

nuclei

contain abundant chromatin and are dark staining

(

hyperchromatic

)

nuclei

are disproportionately large for the cell, and the nuclear-to-cytoplasm ratio may approach 1 : 1 instead of the normal 1 : 4 or 1 : 6.

nuclear

shape

-variable

and

irregularSlide25

Mitoses

undifferentiated

tumors

possess

large numbers of mitoses, reflecting the higher proliferative activity of the

parenchymal

cells.

The

presence of mitoses, however, does not necessarily indicate that a tumor is malignant or that the tissue is

neoplastic

. Slide26

Loss of polarity

anaplastic

cells is markedly disturbed (i.e., they lose normal polarity)

. Sheets or large masses of tumor cells

grow in an anarchic, disorganized fashion.Slide27

Other

changes

formation

of

tumor giant cells

, some possessing only a single huge polymorphic nucleus and others having two or more large,

hyperchromatic

nuclei

vascular

stroma

is scant, and in many

anaplastic

tumors, large central areas undergo ischemic

necrosis

.Slide28

Rate of Growth

Most malignant tumors grow more rapidly than benign tumors

Cancers from hormone sensitive tissues affected by hormone levels

E.g. uterus

Hormone dependence & adequacy of blood supplySlide29

Local Invasion

Benign tumors

- cohesive expansile masses with capsule

- do not penetrate capsule & normal tissues

- Discrete, readily palpable and easily movable mass

- Surgically enucleatedSlide30

Local Invasion

Malignant tumors

- Invasive, infiltrating and destroying normal tissues

- Lack encapsulation

- Enucleation is difficult

- Surgery requires removal of some healthy, uninvolved tissuesSlide31

Local Invasion

Carcinoma in situ

-

Preinvasive

stage

-

Cytologic

features of malignancy without invasion of the basement membrane

- e.g. carcinoma of uterine cervixSlide32

Metastasis

Definition

- This process involves invasion of the lymphatics, blood veseels and body cavities by the tumor

- Tumor implants discontinuous with the primary tumor

- Single most important feature that differentiates from benign tumorsSlide33

Metastasis

All cancers can metastasize

Few and major exceptions:

- Gliomas

- Basal cell carcinomas of the skin

The more aggressive, the more rapidly growing, the larger the primary neoplasm, the greater likelihood of metastasisSlide34

Pathways of Spread

1. Spread into body cavities

2. Invasion of lymphatics

3. Hematogenous spreadSlide35

Seeding of body cavities and surfaces

Occurs by seeding of surfaces in peritoneal, pleural, pericardial, subarachnoid and joint spaces

Example: Carcinoma of the ovarySlide36

Lymphatic Spread

Most common pathway for the initial dissemination of carcinoma

Pattern of lymph node involvement follows the natural routed of drainage

Lymph nodes are frequently enlargedSlide37

Hematogenous spread

Typical of all sarcomas

Favored route for some carcinoma e.g. Kidney (renal cell carcinoma)

Veins are more frequently invaded than arteries

Lung and liver are common sites

Other sites: Brain and bonesSlide38

Comparisons between benign and malignant tumors

Differentiation/anaplasia

Benign

-well differentiated

-structure typical of tissue of origin

Malignant

-lack of differentiation with

anaplasia

- structure often atypical Slide39

Comparisons between benign and malignant tumors

Rate of growth

Benign

-usually progressive and slow

-mitotic figures are rare and normal

Malignant

-erratic and maybe slow to rapid

-mitotic figures maybe numerous and abnormalSlide40

Comparisons between benign and malignant tumors

Local Invasion

Benign

-cohesive and

espansile

well demarcated masses

-do not invade or infiltrate normal tissues

Malignant

-locally invasive, infiltrating surrounding normal tissuesSlide41

Comparisons between benign and malignant tumors

Metastasis

Benign

-absent

Malignant

-frequently present

More likely for larger and more undifferentiated massesSlide42

Grading and Staging of Cancer

Grading

- classified as grades I to IV with increasing

anaplasia

- higher grades tumors are more aggressive than lower grade tumorsSlide43

Grade refers to the

degree of differentiation

of a neoplasm.

Grade

I

(or well differentiated)

neoplasms

closely resemble the normal tissues from which they are derived.

Grade IV

(or

poorly differentiated) only slightly resemble the tissues they are derived from.

Patients

with Grade

IV

tumors have a poorer prognosis than those with Grade I tumors

.Slide44

Grading and Staging

of Cancer

Staging

-

(T)

based

on the size of the primary

tumor

-

(N)

extent

of spread to regional lymph nodes

-

(M)

presence

and absence of blood-borne metastases

-

TNM system

(

tumor,node,metastases

)

- Higher stages -larger, locally invasive, metastatic tumorsSlide45

Staging (TNM system)

- T1 to T4 (increasing size)

- N0 ( no nodal involvement)

N1 to N3 (involvement of increasing number and range of nodes)

- M0 (no distant metastases)

M1 to M2 (presence of metastases)Slide46

Stage

of a tumor

refers to the extent of spread. system

used is the

TNM (tumor, node, metastasis

)

There are different TNMs developed for various cancersSlide47

STAGING (TNM)

TNM for

breast cancer

(different for other cancers):

Tis

- Carcinoma-in-situ

T1

- Gross size of tumor is less than 2.0 cm diameter

T2

- Gross size of tumor is between 2-5 cm diameter

T3

- Gross size of tumor is above 5 cm diameter

T4

- Tumor of any size involving chest wall or

skinSlide48

N0 - No axillary node involved

N1

- Metastases to axillary nodes that are freely mobile

N2

- Metastases to fixed (immobile) axillary nodes

N3

- Metastases to internal mammary

nodesSlide49

M0 – No metastases outside of local nodes

M1

- Metastases present

Use of these

grading and staging can

predict prognosis for an individual patient and also allows comparison of treatment results from one centre to another.

 Slide50

Predisposition to cancer

Geographic and Racial factors

Environmental and cultural influences

Age and childhood cancer

Heredity

Acquired

preneoplastic

disordersSlide51

Race and Geographic locale

Leading cause of death in males

- cancers of the lung, colon & prostate

Leading cause of death in females

- cancers of the lung, breast & colon

Environmental factors influence occurrence of specific forms of cancer in different parts of the world Slide52

Environmental influences

examples of environmental factors

* increased risk with occupational exposure to asbestos, vinyl chloride and naphthylamine

* association of CA of the oropharynx, larynx and lung with cigarette smoking

* alcohol abuse – risk of CA in esophagus and liver carcinomaSlide53

Age

Most common = > 55 years of age

Common in children < 15 years

e.g. leukemias and lymphomas

neuroblastomas, Wilm’s tumor,

retinoblastomas and sarcomas of bone and skeletal muscleSlide54

Heredity

Close relatives of cancer patients have a higher than normal incidence of the same neoplasm

Approximately 40% of retinoblastomas are familial

Some defect in DNA repair

e.g. xeroderma pigmentosumSlide55

Acquired Preneoplastic Disorders

Clinical conditions associated with increased risk of cancers

Cirrhosis of liver – hepatocellular CA

Atrophic gastritis – stomach CA

Chronic ulcerative colitis – colon CA

Leukoplakia of the oral and genital mucosa – squamous cell CASlide56

Acquired Preneoplastic Disorders

Association between

- Endometrial hyperplasia and endometrial carcinoma

- Cervical dysplasia and cervical carcinoma

- Bronchial mucosal metaplasia and dysplasia and bronchogenic CASlide57

Clinical Manifestations

Varied and inconstant

Asymptomatic lesions or nonspecific symptoms

2 categories for advancing neoplasms:

Abnormalities from the tumor mass

Physiologic derangements produced indirectlySlide58

Cancer’s 7 Warning Signals

1. Change in bowel or bladder habits

2. A sore that does not heal

3. Unusual bleeding or discharge

4. Thickening or lump in breast

or elsewhere

5. Indigestion or difficulty in swallowing

6. Obvious change in wart or mole

7. Nagging cough or hoarsenessSlide59

Signs of expansile growth

Near or on the surface of the body

- visible or palpable mass

GIT,GUT, Respiratory

-obstruction, vomiting, jaundice, cough, urinary retention

CNS

- pain, paralysis or sensory loss

Slide60

Signs of infiltrative growth

Pain

Numbness

Paralysis

Signs of nerve invasion are also signs of incurabilitySlide61

Signs of tumor necrosis

Tumor

 necrosis, ulceration, bleeding

Fatigue and weakness (signs of anemia)

Edema, pain, tenderness and fever

Fever, leukocytosis, elevation of ESR, anorexia and malaiseSlide62

Cachexia

Loss of body fat , wasting, and profound weakness



Cancer cachexia

Multifactorial

1. Loss of appetite

2. Infections due to immunosuppression

3. Bleeding from ulcerative lesions

4. Production of cachectinSlide63

PAP SMEAR

A

cytologic screening (cells are collected and examined) which aims for cervical

cancer prevention and control

Short for

Papanicolaou

test

to

detect potentially pre-cancerous and cancerous

processes of the cervix

r

ecommended for females 21 yrs old and above to be done every 3 yearsSlide64

THE ENDSlide65