NEOPLASI

A
Prof. Dr. Hoda Abu-Seif Helmy

Pathology Department
Medical Research Institute
Alexandria University
 Definition
OUTLINE
 Classification of tumors

 Characteristics

 Predisposing factors

 Pathogenesis

 Effects on the host

 Lab Diagnosis of cancer

 Neoplasm/Tumour
Definition:
 Abnormal mass of tissue
 Growth is autonomous
 Exceeds that of normal tissues
 Entails not only cellular proliferation
 Altered differentiation of the tumour cells
 Some cases aberration of programmed
cell death
(Apoptosis)
 Classification
BENIGN MALIGNANT
 Ends with suffix “oma”  Carcinomas arising
 E.g. Mesenchymal : from epithelial cells
Lipoma, Fibroma,… e.g.:
 E.g. Epithelial : Adenocarcinoma
 Sarcomas arising
Adenomas, Papillomas,
… from mesenchymal
tissues
e.g.
Leiomyosarcomas
 Characteristics of Benign
& Malignant Neoplasm
Distinction between Benign & Malignant Tumours
is Based on:

 Differentiation & anaplasia

 Rate of growth
 Local invasion
 Metastases
 Differentiation &
anaplasia
 The extent to which tumour cells resemble
comparable normal cells

 Cells within most Benign Tumours mimic

corresponding normal cells

 Malignant Neoplasms display patterns

ranging from well differentiated to very
poorly differentiated
 Anaplasia
 =Lack of differentiation

 Characterized by:
 Nuclear & cellular pleomorphism
 Hyperchromatism
 ↑ nucleo-cytoplasmic Ratio
 Abundant mitoses
 Tumour Giant cells may be seen
 Local invasion
 Most Benign Tumours develop a rim of connective
tissue, or capsule, at periphery

 They don’t penetrate it

 The plane of cleavage facilitates surgical enucleation

 Malignant neoplasms are invasive & destroying

normal tissues

 Enucleation is impossible as capsule or plane of

cleavage are lacking
 Rate of growth
 Most malignant Tumours grow more rapidly than
Benign Tumours

 They often contain central areas of ischeamic

necrosis

 Growth of cancers such as uterine may be

affected by the variations in hormone levels in
pregnancy & menopause
 Carcinoma insitu
 This refers to preinvasive stage, confined to the epithelium,
although it displays all the cytologic features of malignancy

 However , because the basement membrane is not reached

 The tumour doesn’t invade the subepithilial tissue

 Such tumors eventually become invasive

ex. carcinoma insitu of uterine cervix
 Metastases
 This process involves invasion of
lymphatics, blood vessels, body
cavities by tumours, followed by
tranport & growth of 2ry tumour cell
masses that are discontinuous with
the 1ry tumour
 This is the single most important
feature distinguishing begnin from
malignant tumours
 Spread of tumours
Distant spread of tumours occur by
three routes:

 Spread into body cavities

 Invasion of lymphatics
 Haematogenous spread
 a) Spread into body
cavities

This occurs by seeding of sufaces in

peritoneal, pleural, pericardial and
subarachnoid spaces.

Eg. Carcinoma of the ovary

b) Invasion of lymphatics

 Is common in the initial spread of carcinomas

Eg. Carcinomas of the breast spread to either axillary

or internal mammary lympyh nodes depending on the
location (and therefore lymphatic drainage) of the
tumour

 Identification of the specific sentinel nodes that drain

the site of breast cancer is an important aid to assess
whether the tumour has metastasis via lymphatic
system.
 c) Haematogenous spread
 Typical to all sarcomas but also certain
carcinomas

 Lung & liver are common sites of

haematogenous metastases because they
receive systemic and venous outflow,
respectively

 Veins are more frequently invaded than

arteries, because of their thinner walls
 The grade and stage of
malignant neoplasms
 provide a semi-quantitative estimate of
the clinical gravity of the tumour
 Grading:
is based on the degree of differentiation
and the number of mitosis within the
tumour. Cancers are classified as grades I
to IV with increasing anaplasia

 Staging: is based on the anatomic

extent of the tumour.
 Staging (cont.)

The TNM (tumour, node, metastasis):

 Higher stages are for larger tumours,
locally invasive, and metastatic
 Both histologic grading and staging
are valuable for the prognosis and
planning of therapy of tumours
Predisposition to cancer
1) Environmental factors
2) Age
3) Heridity
4) Aquired preneoplastic disorders
5) Carcinogenic agents:
• Viral carcinogenesis
• Chemical carcinogenesis
• Physical carcinogenesis
 l) Environmental factors
Influence the occurrence of specific
forms of cancer in different parts of
the world

Eg. Increased risk of certain cancers

with occupational exposure to
asbestos, vinyl chloride …etc
 2) Age
 Cancer is most common in those
over 55 years of age.

 However certain cancers are

common in children under l5 years
eg.: leukaemia, neuroblasoma,
Wilm's tumour, retinoblastoma...
 3) Heredity
The role of heredity is illustrated by several
examples:

 Close relatives of cancer patients have a higher

than normal incidence of the same neoplasms

 Susceptibility to childhood retinblastomas is

inherited as an autosomal dominant trait.
(Approximately 40% of retinoblastoma are
familial)
 4) Aquired preneoplastic
disorders

Certain clinical conditions are associated with

an increased risk of developing cancer. Eg:

 Cirrhosis of the liver----- hepatocellular

carcinoma.
 Chronic ulcerative colitis------ carcinoma of
the colon
 5) Carcinogenic agents
Viral carcinogens:
Viral infections are responsible for
about l5% of all human cancers.

Human T cell leukaemia virus type I (HTLV-l)

(RNA retrovirus) and T cell leukaemia /
lymphoma.

Hepatitis B virus (HBV) (DNA virus) and HCV

(RNA) and primary hepatocellular carcinoma.
 5) Carcinogenic agents
Chemical carcinogens:
 They are mostly mutagens
 A mutagen is an agent that can permanently alter
the genetic constitution of a cell. Most mutagens
are carcinogenic.
 Eg. Polycyclic aromatic hydrocarbons found in
cigarette smoke------ lung cancer
 Aflatoxin ( a natural product of the fungus
Aspergillus flavus)------- potent liver carcinogens

Physical carcinogens:
( UV radiation----- skin cancer)
 Pathogenesis of cancer
 Cancer is a genetic disease. It arises when several
mutations accumulate within the genome.

 It occurs as a multi-step process in four stages:

 Initiation
 Promotion
 Progression
 Cancer
 Pathogenesis (2)
 Initiation:
Mutation in a single cell

 Promotion:
Clonal expansion of the initiated cell
"hyperplasia"
 Pathogenesis (3)
 Progression:
The growth becomes autonomous
(dysplasia and carcinoma insitu)

 Cancer:
The end result, the cells acquire the
capacity to invade and metastasise
Effects of tumour
on host
 l) Systemic effects of cancer
on the host
 The symptoms of cancer are referable to the local
effects of either the primary tumour or its
metastases.
However, a minority of patients may be related to
synthesis of bioactive compounds by the tumour.
Such effects are collectively termed
paraneoplastic syndromes

 Common systemic effects include: fever,

anorexia,and weight loss, endocrine syndromes and
amyloidosis.
 2) Organ specific effects of cancer
on the Host

 Effects resulting from mechanical

metastases.eg:

• Neurologic syndromes
• Skeletal muscle syndromes
• Haematologic syndromes
• Or affect gastrointestinal system,
kidney, skin...
 damages of the
Effects resulting from direct extension
involved organ or the adjacent tissue.

a) The growth may be extensive resulting in

replacement of the normal tissue--- functional
insufficiency of the organ eg. Hepatocellular
carcinoma

b) Life threatening because of its location eg.

Intestinal obstruction from cancer colon or even a
small tumour as a small lung cancer--- extensive
haemorrhages when eroding a blood vessel
c) Impair the function of adjacent organ
eg. Carcinoma of cervix-------obstruction
of ureters

d) Pain eg. Pancreatic carcinoma------

extension of the tumour to the coeliac
nerve plexus
Laboratory diagnosis of
cancer
 l) Histologic method
a) Paraffin embedded sections:

b) Frozen sections:
 Histologic examination is the most
important method of diagnosis.
 In addition to the usual paraffin
embedded sections, quick-frozen
sections are employed to obtain a rapid
diagnosis while the patient is still under
anaesthesia.
 2) Cytologic methods
a) Fine needle aspiration:
 This involves aspiration of cells and fluids from
tumours that occur in palpable sites eg.
Breast, thyroid. The aspirated cells are
smeared, stained and examined.

b) Cytologic smear:.
 These involves examination of cancer cells
that are shed. Exfoliative cytology is used
mainly in the diagnosis of dysplasia,
carcinoma in situ, and invasive cancer of the
uterine cervix and also tumours of the
stomach, bronchus, and urinary bladder.
 3) DNA Flow cytometry

 Measurement of the DNA content of

tumour cells by flow cytometry. With
several tumours there is a
relationship between abnormal DNA
content and prognosis.
 4) Tumour markers
 They are products of malignant neoplasms. They can
be detected in the cells themselves by
immunohistochemistry or in body fluids

 Immunohistochemistry involves the detection of cell

products or surface markers by monoclonal
antibodies: The binding of antibodies can be revealed
by fluorescent labels or chemical reactions that
result in the generation of a colored product.

 No marker exists to distinguish between benign and

malignant cells.
 They are used to identify the cell of origin of poorly
differentiated primary tumour whether of epithelial
or mesenchymal origin

 They may also be of value in determining the

therapeutic decisions. Eg. In treatment of
undifferentiated carcinomas and lymphomas

 Among these diagnostically useful markers are

immunoglobulins, fetal proteins, enzymes,
hormones nd cytoskeletal and junctional proteins.
 Carcinomas express intermediate filaments
cytokeratins

 Lineage associated markers are useful in

establishing the origin of a poorly
differentiated carcinoma.eg. prostatic
carcinomas express prostate specic
antigen, P.S. acid phosphate but colon
cancer are negative for these markers but
express CEA
 Lymphomas and leukaemias are grouped by so
called cluster designations (CDS) markers

 Lymphomas and leukaemias are generally

positive for (CD45) markers.

 Serum tumours markers allow monitoring of

tumour recurrence after surgery eg. High serum
level of alpha fetoproteins (AFP) suggest liver or
yolk sac tumour

 CEA in gastrointestinal tract and breast cancer.