: NEOPLSAM

Tumor or neoplasm : is an abnormal mass of tissue , the growth of

which is autonomous and exceeds that of normal tissue .The growth
of the tumor persists after cessation of the stimuli that initiated the
changes . The tumors are classified into : I. Benign II . malignant .
: Nomenclature : all tumors have 2 basic component-
. transformed neolastic cells.1
supporting stroma composed of non-transformed elements like .2
.connective tissue and blood vessels
.Benign tumors : their name end with suffix "oma", e.g -
Benign mesenchymal tumors : lipoma , fibroma , angioma , ostema .1
. , liomyoma
:benign epithelial tumors.2
. a- adenoma : tumors arising in glands or forming glandular patterns
b-cystadenoma : adenoma producing large cystic masses seen in
. ovary
c-papilloma : epithelial tumors forming microscopic or macroscopic
. finger-like projections
d-polyp : tumor projecting from the surface or mucosa into the
. lumen of a hallow viscus e.g. stomach or colon

:Malignant tumors: are called cancer and are divided into -

a- carcinoma arising from epithelium : e.g squamous cell carcinoma ,
. adenocarcinoma , basal cell carcinoma
b- sarcoma : arising from mesenchymal tissue : e.g. osteosarcoma ,
.. liposarcoma , fibrosarcoma
: some tumors have more than one parenchymal cell types , include
Mixed tumors : derived from germ cell layer that differentiated into -
more than one parenchymal cell types e.g. mixed tumor of salivary
. gland contain epithelial cells , myxoid stroma and cartilage
: teratoma : more than germ cell layers , usually all three -
endoderm e.g gut epithelium
ectoderm : e.g skin
. mesnchymal : e.g. fat tissue
. such tumors seen in the testis and ovary

: Two non-neoplastic lesions simulating tumors include

a.Choristoma : ectopic , some time nodular , rests of non-
transformed tissue , e.g. pancreatic cells under the small bowel
. mucosa
b.Hamartoma : malformation , that present as a mass of organized
tissue , contain the same tissue component of the site , e.g.
. hamartoma of lung contain cartilage , bronchi , and blood vessels

: HEMATOPOITIC TUMORS
: a-leukemia : divided into acute and chronic
, Acute leukemia : 1.acute lymphoblastic leukemia -
. Acute myeloblastic leukemia .2
.Chronic leukemia : 1. Chronic lymphocytic leukemia -
. chronic myelocytic leukemia .2
:b. Lymphoma : primary tumor of lymphoid tissue , divided into
Hodgkin`s lymphoma : presence of Reed Sterinberg cell .1
( binucleated cell with owl-eye appearance .)
. non-Hodgkin`s lymphoma : no RS cell .2

:CHARACTERISTICS OF BENIGN AND MALIGANAT TUMORS -

The distinction between benign and malignant tumors is based on
appearance (morphology) and behavior ( clinical course ) , include
: four criteria
differentiation and anaplasia : differentiation is the extent to whch .1
the tumor cells resemble normal cells . Cell within most benign
tumors mimic corresponding normal cells , e.g. thyroid adenoma.
Malignant neoplasms display patterns ranging from well-
differentiated to poorly differentiated .Lack of differentiation called
anaplasia , The following cytological features characterize anaplastic
: or poorly differentiated tumors
cellular and nuclear pleomorphism : variation in shape and size of -1
. cells and nuclei
hyperchromatism :darkly stained nuclei , may contain prominent .2
. nucleoli
nuclear-cytoplasmic ratio (high N/C ): 1:1 instead of 1:4 or 1:6 (due .3
to enlarged nuclei)
abundant and abnormal mitosis: increased mitotic figure , may be .4
. abnormal , e.g. tripolar
tumor giant cells containing a single large polypod nucleus or .5
. multiple nuclei
. loss of polarity : not defined architecture .6

Well differentiated tumors ( benign or malignant ) retain in functional

characterize of their normal tissue , e.g. production of hormones in
.tumor of endocrine origin , or keratin in squamous epithelial tumors

Rate of growth : most of malignant tumors grow more rapidly than .2

benign tumors , some cancers grow slowly for years and grow
rapidly later on .Rapidly growing malignant tumors contain central
. area of ischemic necrosis

Local invasion : most of benign tumors are cohesive mass , .3

surrounded by a rim of connective tissue "capsule ", they don`t
penetrate the capsule or the surrounding normal tissue , presence of
. capsule facilitate surgical removal
Malignant tumors are invasive , infiltrating and destroying normal
tissue surrounding them , lacking of a well-defined capsule , making
surgical enucleation difficult or impossible , surgical removal of
malignant tumors require removal of healthy or uninvolved tissue
""safe margin

Metastatsis : "distant spread " , process of invasion of lymphatic , .4

blood vessels , and body cavities by the tumor , followed by
. transport and growth of secondary tumor cell masses
With the exception of brain tumors and basal cell carcinoma of the
. skin , almost all tumors have capacity to metastasize
: Distant spread of tumors occur by 3 routs
spread into body cavity : by seeding of surface in peritoneal , .1
pleural , pericardial and subarachnoid space , e,g. carcinoma of
. ovary spread transperitoneeally into the liver

invasion of lymphatics: transport of tumor cells to regional nodes .2

e.g. carcinoma of breast spread to axillary lymph nodes , which
. become large
hematogenous spread : all sarcomas certain carcinoma .Lung and .3
liver are common sites of hematogenous metastases because the
. receive the systemic and venous out flow

: Predisposing Factors
Geographic and environmental : in our country cancer of prostate , .1
colon and lung are the leading cause in male , while in female ,
cancer of breast , colon and lung are the most common cause of
. morbidity and mortality
Environmental factors influence the occurrence of specific tumors in
different part of world , e.g. in Japan carcinoma of stomach is 7
. times than U/S
Age : cancer is common in those > 45 yrs , but certain cancer are .2
common in children under 15 yrs e.g. lymphoma, leukemia , sarcoma
. , neuroblastoma, Wilm`s tumor , retinoblastoma
: Heredity : divided into.3
I. inherited cancer syndrome : inheritance of single mutant genes
that increase the risk of developing tumor , the predisposition is
autosomal dominant trait , e.g. familial retinoblastoma , familial
adenomatous polyposis .These syndromes associated with
inheritance of a single mutant allele of cancer suppressor
genes .This type of inheritance pattern associated with marker
phenotype , e.g. multiple benign tumors in familial polyposis of
. colon

II. Familial cancers are characterized by familial clustering of specific

forms of cancer , the transmission pattern isn`t clear , e.g. breast
cancer , colon , brain , and ovary .There is no marker phenotyping
. i.e. familial colon cancer don`t arise in pre-existing polyp
III . Autosomal recessive syndrome of defective DNA repair , are
characterized by chromosomal or DNA instability that increase the
predisposition to environmental carcinogens .e.g. pigmented
xeroderma which result in skin cancer, e.g. squamous cell
. carcinoma

Acquired Preneoplastic disorders :certain clinical conditions are -

: associated with an increased risk of developing cancer
. liver cirrhosis : hepatocellular carcinoma ,1
. atrophic gastritis in pernicious anemia : risk of gastric carcinoma .2
. ulcerative colitis : risk of colonic cancer .3
leukoplakia of the oral mucosa or genital mucosa : risk of .4
. squamous cells carcinoma
. villous adenoma : risk of colonic carcinoma .5

: MOLECULAR BASIS OF CANCER-

I.Oncogenes : are genes whose products are associated with
. neoplastic transformation ( growth promoting )

Proto-oncogens are normal cellular genes that affect growth and -

. differentiation
Activation of oncogenes : proto-oncogens may be converted to
: oncogenes by one of the following mechanism
point –mutation : about 15% of all human tumor carry mutated H- .1
. ras or K-ras oncogenes
: translucation : chromosomal translocation by .2
a. placement of gene e.g. Burkitt`s lymphoma , t(8:14), translocation
of places the c-myc –containing segment of chromosome 8 to Ig
. gene on 14
. b. fusion of the genes e.g. t(9:22) in CML
Gene amplification : reduplication of proto-oncogene lead to .3
increase expression or activity , e.g. N-myc amplification (3-300
times)in neuroblastoma , or c-erbB2 genes in 30-40 % in breast
. cancer
II-cancer suppressor genes : cancer may arise due to inactivation of
genes that normally suppress cell proliferation (cancer suppressor
.genes or anti-oncogene ) , e.g. Rhetinoblastoma , Rh gene
III. Genes that regulate apoptosis : bcl-2 prevent programmed cell
death or apoptosis .Over expression of bcl-2 extend cell survival and
if cells are genetically damaged , they continue to suffer additional
mutations in oncogenes , and cancer suppressor genes e.g. bcl-2
. over expression in B-cell lymphoma
: CAECINOGENIC AGENTS
Chemical carcinogenesis : neoplastic transformation caused by -1
: chemicals is multiple process, it can be divided into 2 steps
initiation : refer to induction of certain irreversible changes , in the .1
genome (DNA ) of the cells. The initiated cells has memory , they
may occur in the body but not transformed to malignancy unless
there is a suitable promoter , even after many years .Initiation should
be the first step before promotion in order to develop tumor , it dose
. independent
promotion : is the second step after initiation , memory isn`t .2
necessary , affect RNA and protein molecule inside the cells . the
changes occur during promotion are reversible e.g. female taken
estrogen cause reversible changes , these changes retain to normal
after with drawl of estrogen. It is dose dependent , take time , i.e. if
patient has been exposed to promoter once every year , may not
develop cancer . There should be proper time spacing and proper
: frequency of application
e.g. estrogen once 1 year : no tumor
. estrogen once 1 week : tumor
the frequency of application varies according to the carcinogen, very
little amount or small dose of any carcinogene may not produce
tumor . The promoter factor isn`t carcinogenic but it is important to
. have cell proliferation and cell division
: Carcinogenic chemicals
alkylating agents : include direct –acting agents , e.g. .1
"cyclophosphamide and busulfan " anti-cancer
. aromatic hydrocarbons : found in cigarette smock → ca. lung .2
Azo-dyes : B-naphthylamin used in rubber industries →ca. .3
. bladder

naturally occurring carcinogens : aflatoxin B1, produced by .4

.fungus Aspergillus flavus →hepatocellular carcinoma
nitrosamines and amides : these can be synthesized in the GIT .5
from ingested nitrites or derived from digested proteins, may cause
. carcinoma of stomach
miscellaneous agents : asbestos , vinyl chloride , metal e.g. nickel , .6
. hormone e.g. estrogen →ca. endometrium

Radiation carcinogenesis : ultraviolet (UV) rays and ionizing .2

. radiations can cause cancer
UV rays especially derived from the sun can cause skin cancer
( basal cell carcinoma , basal cell carcinoma and melanoma ), two
: mechanisms may be involved
. damage to DNA-
. Immunosuppression-
Ionizing radiation , electromagnetic and particulate radiation are all
: carcinogenic .These include
radioactive substance cause ca. lung .1
. leukemia can be caused atomic bombs in Jaban .2
Therapeutic radiation to the neck of children associated with late .3
.development of thyroid cancer
: Ionizing radiation can cause cancer through
. direct effect : mutation-
.indirect effect : generation of free radicals from water and O2 -
Particulate radiation : e.g. α - neurons , are more carcinogenic than
.megnatic radiation X-ray , gamma

DNA repair defects : four autosomal recessive syndrome or -

conditions : xeroderma pigmentosa , Bloom`s syndrome , Fanconi`s
. syndrome , ataxia telangiectasia
All these conditions characterized by defect in DNA repair and
resultant predisposition to cancer when exposed to DNA-damaging
agents including radiant energy , e.g. patient with xeroderma
.pigmentosa exposed to U/V light →skin ca

: Viral Carcinogenesis .3
DNA viruses : four associated with human tumors : HPV , EBV , -
. HBV , HCV
Human papiloma virus (HPV) : 65 genetically distinct types , some -
types (1, 2,4, 7) cause benign squamous papilloma (warts) , HPV in
human cancer include : 1.squamous cell carcinoma of uterian cervix
(type 16, 18)
. gental warts : HPV-6 , HPV-11.2
: Epstein Barr virus ( EBV): cause-
. Burkitt`s lymphoma-1
. Nasopharyngeal cancer-2
. Hepatitis B, C virus : cause hepatocellular carcinoma-
. RNA oncogenic virus : HT-LV-1 , Cause T-cell lymphoma -
: CLINICAL FEATURES OF TUMORS
Local and hormonal effects : related to location : intracranial tumors
e.g. pituitary adenoma can expand and destroy the remaining
pituitary gland , giving rise to an endocrine disorders .Tumor of GIT
. may cause obstruction of the bowel or ulceration and bleeding
Hormone production : tumor of endocrine gland may elaborate
. hormones , this is more common in benign than malignant
Cancer cashexia : loss of body fat , wasting and weakness are
: referred to as cancer cashexia , the causes include
. loss of appetite.1
metabolic changes that lead to reduce synthesis and storage of fat .2
. and increase mobilization of fatty acids from adipocytes
production of cachectin (TNF) by activated macrophages , that had .3
. metabolic effects

:Paraneoplastic syndromes
Can be defined as symptoms not directly related to the spread of the
tumor or elaboration of hormones indigenous to the tissue from
which the tumor arose .Paraneoplastic syndrome may be the earliest
clinical manifestation of the neoplasm and mimic distant spread .The
: most common syndrome are
endocrinopathy : some non-endocrine cancers produce hormones .1
or hormone-like factors , e.g. certain lung cancer ( small cell
. carcinoma ) produce Cushing syndrome by elaborating ACTH
hypercalcimia : which may occur owing to resorption of bone .2
resulting from elaboration of PTH-like peptide , or in some cases of
TGF-α by certain tumors e.g. squamous cell carcinoma of the lung ,
. T-cell leukemia/lymphoma

Acanthosis nigricans : acquired pigmented lesion of the skin is .3

. associated with visceral malignancy
clubbing of the fingers and hypertrophic osteoarthropathy are .4
. associated with lung cancer
Thrombotic diathesis : resulting from production of .5
thromoboplastic substances by tumor cells and may manifested as
. DIC

: GRADING AND STAGING OF MALIGNANCIE

Grading is based on the degree of differentiation and the number of -
: mitosis within the tumor , cancers are classified as
Grade I: well differentiated ( morphology and functional)
. Grade II : moderately differentiated
. Grade III : poorly or anaplastic
. Higher grade tumors are more aggressive than lower grade tumors
Staging : is based on anatomic extent of the tumor , two methods -
:used
. TNM : T =tumor size , N= number of lymph nodes involved
. M= metastasis
. AJC : American Joint Committee system

Laboratory Ddiagnosis of cancer : histological examination of the -

. tumor is the most important methods of diagnosis
: Others methods include

Fine Needle Aspiration Cytology: FNAS include aspiration of cells .1

or fluid from tumor or mass .It is a cheap , official , rapid method ,
with little or no complication , no need for hospitalization , give
psychological relief to the patient and planning for type of surgery or
treatment , with high sensitivity and specificity (70-99%) , can be
. used for superficial and deep tumors with radiological guidance
Cytological smears : examination of tumor cells that are readily .2
shed .Exfoliative cytology is used for diagnosis of dusplasia ,
. carcinoma in situ , invasive cancer of uterian cevix
Immunocytochemistry : detection of cells productions or surface .3
markers by monoclonal antibody , the binding then revealed by
. fluorescent labels or chremical reaction
. DNA probe analysis : used for diagnosis of lymphoma .4
. flowcytometry : measurement of DNA contents of tumor cells .5
tumor markers : can be detected in the blood or body fluid , they of .6
:.value in monitoring the response to therapy , ex
Carcinoembryonic antigen (CEA): normally produced by fetal gut , -
liver and pancreas , and cancer of colon , pancreas , stomach ,
breast –Alfa-feto-protein : (AFP) normally produced by fetal yolk sac
and liver , and in cancer of the liver , testicular germ cells , and liver
cirrhosis and hepatitis .It is of value indicating the presence of liver
or testicular cancer and monitoring the recurrence and response of
. therapy

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