By\King of pathology( Legand – Hazem

)
Tumor & Neoplasia .
Adaption and ifferentiatin
Cell adaption: cell adapts itself to a new function.
A) Congenital: B) Acquired:
-agenesis. – atrophy.
- aplasia. – hypertrophy.
- hypoplasia. – hyperplasia.
- Ectopic tissue. - metaplasia.
- Hamartoma. - ysplasia.
!rre"ersi#le$ %e"ersi#le$
A) Congenital:-


ef: congenital complete a!sence of an organ.
"ay !e in a single or paired organ.
# in case of a!sence of one of a paired organ $ the other organ undergo adapti%e changes.
E.g: Hypertrophy to compensate the a!sence of the other E.g:&idney.
# in case of a!sence of a single organ E.g: li%er incompati!le e' life.
Clinical note : the surgeon should !e sure of presence of the healthy (idney !efore remo%al of the
diseased one.
ef: the organ is rudimentary ) replaced !y fi!rous tissue E.g: aplastic (idney.
ef: failure of the organ to reach its mature site * the organ is fully formed !ut it is small in si+e).
E.g: Hypoplastic (idney. – Hypoplastic uterus *infantile).
ef: mature tissue is present in a!normal site.
E.g: - presence of pancreatic tissue in the wall of the stomach.
- presence of thyroid tissue on the !ase of the tongue.
ef: a mass of tissue formed as a result of de%elopmental error ch' !y:-
,- Composed of tissue of the same locality.
-- isorderly arranged ) %aries in quality.
.- Has no capsule.
/- 0tops its growth when the !ody stop growth *when reaching pu!erty).
&'amples: a)Cells: pigmented ne%us ةنسحلا
!)1issue: hemangioma or lymphangiomas .
c) group of tissues: 23ung hamartoma:mi4ed mass of cartilage $ epithelium $5..etc.
2 3i%er hamartoma: mass of !ile ducts ) li%er cells.
Agenesis
Aplasia
Hypoplasia
Ectopic tissue
Hamartoma
(auses of )ongenital )hanges* + $ لاؤس دنع اهتفاضا لضفيو ىويدبلا حاتفلا دبع د ا تارضاحم Hamartoma
,- 6nfection: E.g to4oplasma.
-- 7hysical agent: E.g ioni+ing radiation . the radiation affect the di%iding cells more then the
resulting cells.
.- Chemicals : some drugs as sedati%e drugs.
/- 0pontanous genetic a!normality: E.g awn syndrome.
B) Acquired:-
ef: decrease si+e and weight of an organ due to decrease si+e and8or num!er of its component
Cells.
1ypes: - 1ypes:-
,-.hysiologi)al atrophy*
- 3ocali+ed: - 9enerali+ed:
# :ew !orn: atrophy of foetal adrenal corte4. # 0enile atrophy due to aging process
# After pu!erty: atrophy of thymus glands.
# After menopause: atrophy of genitalia ; !reast.
/-.athologi)al atrophy*
- 3ocali+ed: - 9enerali+ed:
# <ascular atrophy coronary Ht dse. 3eads to # Hormonal atrophy: atrophy of
"yocardial infarction. pituitary hormone  atrophy of all
# :eurogenic atrophy poliomyelitis leads to endocrine glands.
"uscle atrophy. # 1o4ic atrophy: due to increase
# 1hermal atrophy  atrophy of undescended testis. 1issue cata!olism as 1.B.
# 6mmunological atrophy  autoimmune atrophic gastritis. # 0tar%ation atrophy: due to chronic
malnutririon result from:
2increase !ody demands.
2decrease food inta(e and a!sorption.
:8E of atrophy:
2All organs  atrophied.
2 0(in wrin(led due to atrophy of elastic fi!ers.
2 =at  e4hausted ) lost.
2 3i%er muscle atrophy.
2 3ung  atrophic emphysema.
2 Bone  osteoporosis.
2 Heart Bro0n atrophy of heart$ *cell in>ury chapter).
Atrophy

larene9
2 0i+e: small.
2 ?eight: light.
2 Capsule: wrin(led.
"8E of atrophy:
,- Cytoplasm: decrease amount of cytoplasm ) organelles * as mitochondria).
-- 0paces !etween the cells Either filled e' : # =i!rous tissue * Heart – &idney).
# =atty tissue * 3.:s – Bone marrow – 1hymus).
ةمداقلا ةحفلا ر!"ا
ef* transformation of mature *differentiated) type of tissue into another mature type of tissue of
the same category.
E.g: Epithelium into Epithelium . ) C.1 into C.1.
Types* A) &pithelial metaplasia*- * @e%ersi!le)
1 (auses: ,-chronic irritation. .-<it.A deficiency.
--6diopathic * on un(nown cause). /-genetic acti%ation.

1 .athogenesis: + $ لاؤس دنع اهتفاضا لضفيو ىويدبلا حاتفلا دبع د ا تارضاحم 2etalasia
all cellular functions are represented !y genes on their genetic map  0ome
genes are normally inhi!ited But Change of the en%ironment  @e-acti%ation of these
suppressed genes  metaplasia.
2&'amples: ,-squamous metaplasia :
- 1ransformation of columnar epithelium of gall !ladder into stratified squamous epithelium.
-1ransformation of transitional epithelium of urinary !ladder into stratified squamous epithelium.
--glandular metaplasia:
- 1ransformation of gastric mucosa to intestinal mucosa in atrophic gastritis.
B) 2esothelial metaplasia*-
# affect flattened cells that line serous sacs w' transformed to cu!ical $columnar$glandular or
0tratified cells.
# E.g: Enometrosis.
C)"esenchymal *C.1) metaplasia:- *6rre%ersi!le)
-transformation of one type of mesenchyme into another. E.g * fi!rous tissue8fatty tissue8!one8cartilage):-
6-cartilagenous metaplasia in healing of fracture.
66-Bone metaplasia is common and follows Ca deposition in: 21raumatic myositis ossificans.
23aryngeal cartilage in old age.
666-fi!rous tissue accumulate fat in o!ese people.
3-.rognosis: may !e 7recancerous especially in epithelial metaplasia.
3ocal
Hypertrophy ) Hyperplasia
"etaplasia
,-ef: failure of complete maturation and differentiation of primiti%e cells associated e'
3oss of polarity ) uniformity ) architecture of the cells.
--E.g: ,-0(in --urinary !ladder .-uterine cer%i4 /-!ronchial epithelium A-3i%er
.-"8E: cells are 2<aria!le in si+e ) shape *pleomorphism).
2increasing mitosis *normally mitosis is found in !asal layer only).
2 3arge hyperchromatic nucleus.
2 3oss of polarity.
/-=ate B prognosis:
a) mild and moderate dysplasia they are re%ersi!le when irritant is remo%ed.
!) se%ere dysplasia can turn to :
2 Carcinoma in situ *when in%ade entire thic(ness of epithelium). 4%
2 6n%asi%e carcinoma *when in%ade !asement mem!rane).
A- 9rades of dysplasia:
9rade 6  in%ol%e the lower third only of epithelium.
9rade 66 in%ol%e the lower two third only of epithelium.
9rade 666 affect the whole thic(ness * Carcinoma in situ) B *intra-epithelial carcinoma)
ifference !etween Hyperplasia ) :eoplasia:
ef: su!stances Cr factors produce cancer !y induction of non-lethal :A mutation or damage.
1ypes: 2internal as !ile. Cr 2E4ternal including *@adiation – chemical – <iral) .
,-%adiation
a)Non – ionizing radiation(5$6)* the D.< rays cause damage of :A if na en+ymes repair are
defecti%e E.g: Eerodermia pigmentosa 0(in cancers in faired s(in as :-
2 Basal cell carcinoma 8 0quamous cell carcinoma 8 "alignant melanoma.
#)!onizing radiation ( e$g* '-rays)*
,- 4-ray 3eu(aemia.
--@adioacti%e su!stances Cancer lung.
.- 1heraputic irradiation of the nec( of the children Cancer thyroid.
/- 0ur%i%ors of Hiroshima ) cherno!yl increase incidence of cancers.
Hyperplasia Neoplasia
,- may !e physiological Cr pathological
--Ha%e a useful function.
.-@e%ersi!le: initiated !y stimulus )
stop when remo%ed.
/- :ot dangerous.
A-Cells ha%e normal cytology)histology
,- Always pathological.
-- Has no useful function.
.-6rre%ersi!le : continue to grow after
stimulus remo%al.
/- <ery dangerous.
A- Cells ha%e a!normal characters.
ysplasia
فر#$%ل
ة
(ar)inogeni) agents .
A-@adiation is also associated e' leu(emia $ osteosarcoma.
# "echanism of action of radiation: ,- Chromosomal !rea(age.
--1ranslocation. .-7oint mutation.
/-Acti%ation of @as oncogen A-6nhi!ition of @! suppressor gene.
/-(hemi)al )ar)inogens ( /.,H,N 7 8A)
-7 7olycyclic hydrocar!ons !en+opyrine cause Cancer scrotum.
1o!acco products cause oral ca%ity8 laryn4 8oesophagus cancer
7esicide cause cancer s(in.
,H hea%y metals as chromium cause cancer lung.
,: :itrosamine cause cancer stomach.
Aromatic amines cancer urinary !ladder.
A+odyes li%er tumors.
AA Aflato4in hepatoma.
As!estos !ronchogenic carcinoma.
Anticancer agents as al(ylating agents leu(emia.
# "echanism of action: ,-"itogenic cause permanent change in :A.
--Affectinf @A0 suppressor gene. .-"ore effecti%e in case of a!sence of :A repair en+ymes
3-6iral )ar)inogens
a)@:A %iruses:
# mechanism of action: they produce en+yme called FF @e%erse transcriptaseFF w' transcri!e :A
=rom %iral @:A $ this new %iral :A share in *Host cell genoma)  1ransformation.
# E.g: H13< *human t-cell leu(emia %irus)  cause adult 1-cell leu(emia.
!):A %iruses: they form sta!le association e' host genome  1ransformation. =or e4amples:-

6-Human papilloma %irus *H7<):- 2 a!out AG genetically distinct type.
2types *,$-$/)H) cause !enign squamous papilloma *wart) in human.
2types *,I ) ,J) are in%ol%ed in cancer cer%i4.
21he proteins of these genes !ind to and neutrali+e the product of @! * loss of @!
gene ma(e child suscepti!le to tumor) ) 7A. * pA. stimulate apoptosis of a!normal cell ).
2the products of types *,I$,J).,) !ind to @! and 7A. e' high affinity.
2the products of types *I ) ,,) !ind to @! and 7A. e' lo0 affinity.
66-Epstein Barr %irus *EB<):
2 EB< cause Bur(ittFs lymphoma and nasopharngeal carcinoma.
2 EB< infect the B-cells and infect many cells causing them to proliferate.
666-Hepatitis B %irus:
6n%ol%ed in Hepatocellular carcinoma . %irus act on li%er !y:-
,-cause li%er cell in>ury e' su!sequent regeneration .the cells are predisposed to throm!us.
--"utation moti%ation to 7A. in li%er e4posed to HB< and Aflato4in.
.-HB %irus encode regulatory elements called E-proteins cause distur!ance to normal growth
control !y transcriptional acti%ation of se%eral proto-oncogen.
/- 1he %iral integration cause -ry re-arrangement of chromosome and inacti%ation of 7A..
Chemical carcinogens
com!ine to :A .
6<-H<J: cause &aposi sarcomas ةيومدلا ة&عو'ا (ا)رس
Tumor 9 Neoplasia 9 4n)ology 9 Ne0 gro0th
ef: Automonus – !rr"ersi#le – .urposeless – proliferation of )ells to form a#normal 2ass$
&')eptions:
(hara)ters*
,-:omenclature:- named !y attaching the suffi4 FFCmaFF to the cell type from w' the tumors arise
E.g: fi!roma $ chondroma.
--"onoclonal in origin: But it is more e' la!ile cells and sta!le cells and less e' permanent cells.
.-=ormed of - elements: *ا+ .aren)hyma & :troma
Beha%iour Consistency
Benign "alignant ) firm soft.
/-@ate of growth e4ceeds and is un-coordinated e' that of surrounding tissue .
A-6ts growth is progressi%e.
I-6t is un-controlled !y the normal growth control of the !ody.
H-6t compete e' normal cells for their meta!olic needs.
J-1umor arises as a result of mutation acquired either !y en%ironmental factors or inherited in
germ cell line.
K-1umors are lia!le to -ry pathological changes as infection $cell in>ury and He55..etc.
(lassifi)ation of tumors*- A))ording to *
,- Beha"iour*- /-Tissue of origin 9 Histogenous )lassifi)ation*-
1 Benign$
1 Lo)al malignant$
1 2alignant$ (is)ussed later)

2Benign $ malignant tumors ةمداقلا ةحفلا ر!"ا
1Lo)al 2alignant tumor
,-ef: 1umors capa!le of local infiltration But :o distant metastasis.
--Characters: 0lower than malignant tumors
2@ate of growth is
=aster than Benign tumors.
2 "ode of growth By infiltration ; non-capsulated. "alignant characters.
2 "icroscopicaly Cells show "g criteria ,ت-.
2 "ay turn malignant.
2 High incidence of recurrence.
2:o distant spread. Benign character.
.-1ypes: # Adamantinoma. # Craniopharyngiomas.
0ome tumors can
!e controlled !y
the !ody E.g:
cancer !reast .
E4amples :
2 carcinoma
لا /م *'ا *د 0ف ر1تني
pla)enta $ 23ارتي 45
2 "alignant
meanoma
1umor in supra-
renal gand can
destroy patient life .
- 3eu(emia not a mass .
- "alignant leu(ocytes
in !lood
فر#$%ل
ة
# Basal cell carcinoma. # =i!eromatosis.
# Csteoclastom. # 9liomas.
/- 7rognosis: a) 3ocal recurrence in case of incomplete remo%al.
B) 1urning into malignancy.
L "alignant criteria *atypia) are: *ا+ 6فح.
• pleomorphism * cellular and nuclear)
• ;; nucleocytoplasmic ratio *:8C ratio) &')ept in hypernephroma
• A!normal mitosis
• 9iant cell formation
• 3oss of polarity
• nuclei: large $ hyperchromatic $ with irregular nuclear chromatin and clumped chromatin
• nucleoli: large $ multiple $ eosinophilic.
.re-)an)erous lesions 9 .re-malignant lesions
ef: :on-malignant lesions w' ha%e high incidence of malignancy transformation.
E4amples:- ,- Chronic irritation.
a) 3eu(opla(ia: white patches of the s(in ) mucus mem!rane associated e' thic(ening )
e4cessi%e (eratini+ation.
!) Chronic s(in ulcer ) fistula: e.g peptic ulcers ) s(in ulcer ) fistula of chronic osteomylitis.
c) Chronic ulcerati%e colitis.

-- 0ome !enign tumors:- E.g:-
• 1ransitional cell papilloma *AGM turn into malignancy).
• "ultiple familial polyposis coli *,GGMturn into malignancy).
• ysplastic ne%us.
• Nunctional ne%us in adult.
• "ultiple neurofi!romatosis.
• <illus adenoma of the colon.

.- "etaplasia: ef:55,ت-ي
E.g:- urinary !ladder *in !ilhar+iasis).
6- 0quamous cell metaplasia Bronchi *cigratte smo(ing).
9all !ladder *!iliary stone).
66- 9landular metaplasia : cystitis glandularis.

/- ysplasia: ef:55,ت-ي
E.g:- *disscused !efore) ,ت-ي
A- Hyperplasia: ef:55,ت-ي
# Hyperplasia of urinaru !ladder epithelium.
# 3i%er cirrhosis may de%elop in case of Hepatocellular carcinoma.
I- Carcinoma in situ * +ero-stage ):
# ef: it is pre-in%asi%e carcinoma of epithelial surface.
# E.g: in uterine cer%i4.
H- Atrophy: ef:55,ت-ي
E.g: # non-descended testis*cryptochidism).
# atrophic gastritis.
J- Hereditary:
E.g: # Eerodermia pigmentosa.
(ar)inoma in situ
ef: pre-in%asi%e carcinoma of epithelial surface.
0ite: # Breast # 7rostata. # 0(in epidermis. # Cer%i4 uteri.
:8E: :ot in%isi!le 4% appear as minor thichening and iduration of the affected surface.
"8E: ,- 1he epithelial cells show all cytological and histological e%idence of malignancy ,ت-ي
-- 1hese changes in%ol%e whole epithelial thic(ness !ut the !asement mem!rane is intact.
7rognosis: 6t change to in%asi%e carcinoma e'in ,G – ,A years.
Tumor & 4n)ogenesis
9eneral points:- 4هفو 78ار9
• 1umor occur !y non-lethal mutation of genes.
• 9enes that regulate cell growth:-
a) structural genes. B) regulatory genes.
1he regulatory genes w' regulate cell growth are:-
# proto-oncogenes *stimulatory genes). # suppressor genes*Anti-oncogen).
# Apoptotic ) Anti-apoptotic genes. # :A repair genes * for :A repair en+ymes).
,- .roto-on)ogenes
ef: normally present gene responsi!le for stimulation of cell proliferation $ may affected !y
"utation ) change into oncogen w' cause :-
• a!normal cell proliferation.
• 1ransformation of normal cells into malignant.
How the cell proliferation is stimulated !y growth factors:- through the following steps
,- 9rowth factors * polypeptides w' stimulate cell growth ) !ind growth factor @s  acti%ation of
7rotein (inase en+yme.
--Acti%ation of series of proteins responsi!le for signal transduction to the nucleus.
.-0timulation of nuclear regulatory proteins *cycline)cycline dependant (inase) !y transcription.
/-1hese proteins stimulate cell proliferation.

1 4n)ogen1 *ا+
ef: gene responsi!le for a!normal cell proliferation ) transformation of normal cells into
"alignant $ it is present normally in the form of 7roto-oncogen w' change into oncogen !y
"utation
.roto-on)ogen #y mutation on)ogen$
Types: a) <iral oncogens * %-oncogenes) *e4ogenous).
!) Cellular oncogens * c-oncogens) *proto-oncogen).
78ار9
4هفو

1his classification is due to it was !elie%ed that the source of oncogenes was only the %irus !ut it
is now !elie%ed that oncogen comes from normally Cellular proto-oncogen !y mutation ) the
%irus may !e in%ol%ed in the mutation ) this genetic changes.
2e)hanism of a)ti"ation* # point mutation.
# 1ranslocation. # 6nsertional mutagenesis.
# Amplification num!er of co!ies of proto-oncogen.
2e)hanism of a)tion*
0timulate a!normal cell proliferation !y:-
,)A#normal gro0th fa)tors formation*
2By production of on)o-proteins proteins w' act li(e 9rowth factors.
2(-sis produce .;< *platelet deri%ed growth factors) continuous self-stimulation.
/)A#normal gro0th fa)tor %s formation* By
a)Change in the structure of @s: E.g
2C-Er!,*Erythro!lastosis %irus of chic(en) w' is now called HE@, *Human Epidermal growth
factors @s).
2"utation eficiency of e4ternal part of @s *truncated @s)  Continous signaling e%en in
a!sence of E9= * epidermal growth factor ).

!) 6ncreasing :o. of the growth factor @s:E.g
2C-Er!- *HE@-)
2"utation o%er-production of @s proteins increase :o. of @s Continous signaling.
# )lini)al important:- in diagnosis of cancer !reast as ;%e HE@- test means the need of
"astectomy.
3-!nterfering e= signal transdu)tion:E.g @as oncogen.
6t is responsi!le for production of onco-protein in%ol%ed in signal transduction.
/-6nterfering e' :uclear regulatory factors: By
7roduction of protein w' attach to :A ) stimulate transcription and thus cellular di%ision.
# 1he most common types:
- C-"ys  3ymphoma. - 3-"ys Cancer lung.
- :-"ys :euro!lastoma.
/- :uppressor ;enes (Anti-on)ogen)$
ef: 9enes w' inhi!it cell proliferation.
Types*
# @!,*@etino!lastoma):em!ryonal tumor of the eyes of children.
/GM are familial.
IGM are sporadic.
- the inherited form is usually !ilateral especially in children O -years )
Dnilateral in those O A years.
- loss of this gene may ma(e them suscepti!le to other tumors as Csteosarcoma.
# 7A.: inhi!it cell di%ision of a!normal cell * ;; apoptosis of a!normal cell).
# A7C *adenomatous polypoid coli):multiple polyposis of colon555cancer colon.
# CC *deletion cancer colon).
# :=, *:eurofi!roma).
#?.1,*wilmFs tumor): in (idney.
#Br-C *!reast cancer): A-,GM is familial.
2e)hanism of a)tion of suppressor genes*
,) 1ransmission of –%e signals to produce contact inhl!ition E.g:CC ) A7C.
-) Bloc(ing of signal transduction E.g::=, w' ;; 917ase.
.) Bloc(ing of transduction E.g:@!, $ 7A..
/) ecrease 9rowth factors production.
"echanism of inhi!ition of suppressor genes: # eletion.
# 7oint mutation. # Complete loss.
3-Apoptoti) & Anti-Apoptoti) genes$
(2ito)hondrial on)ogen)$
E.g: a) Bcl-- *B-cell lymphoma): follicular lymphoma $ -- apoptosis increase of population.
!) Ba4: help apoptosis.
c)7A.: ;; apoptosis of a!normal cell.
0o Apoptosis and thus :o.of cells  depend on !alance P O Apoptotic ) Antiapoptotic genes.
>- NA repair gene & enzyme$
6n Eerodermia pigmentosa due to deficiency of :a repair gene thus the en+yme 
high incidence of s(in cancers.
=or E.g : normally large :o. of mutations occur daily $ !ut :A repair en+yme repair mutations.
Biology of Tumor gro0th*
,)Kineti)s of tumor )ell gro0th*- /)Tumor angiogenesis*-
1he time ta(en !y single malignant cell to #1he tumor canFt grow more than - mm e'out
!e appear clinically as a mass depend on: !lood supply .
2 ou!ling time: the time for cell cycle is # =actors affecting tumor angiogenesis:-
normal Cr e%en longer than normal. ,) 0timulatory factors:
2 =i!ro!last growth factors*=9=): produced !y
29rowth fraction: the percentage of w' are tumor cells.
capa!le of proliferation in most tumors B -GM 2 19=-a $ E9= $ 1:=: from macrophages.

2Cell production ) Cell loss: rate of growth -) 6nhi!itory factors: e.g: angiostatic factors.
6ncreases when cell production e4ceeds 6f tumor is rich in %ascularity "alignant.
cell loss. 6f tumor is poor in %ascularity Benign.
2Cancer therapy: they are effecti%e only on
di%iding cells $ so the more the growth
fraction  the more suscepti!ility to
anti-cancer agents.
2ole)ular #asis of multistep )ar)inogenesis*-
2 Acpuired En%ionmental factors:-
- Chemical carcinogens.
- <iral carcinogens.
- @adiation.
29enetic factors
"ore "utations
"ore "utations
Normal )ell
NA 2utations
.ersistent 2utations
.romotion
NA )hange.
4n)ogen :uppressor gene 2utant
!nitiation
Tumor 2ass
!nfiltartion
2etastasis
NA %epair
!< su))essful
!< <ail
.rogression
:pread of 2alignant tumor
a)1he malignant cells in%ades tissue of origin  enlarge ) infiltrate normal structures prefering
line of least resistence *E.g: !one $ !lood %essels)  causing:-
2ysfunction of the organ: E.g in li%er li%er failure.
2C!struction of hollow organs: E.g in intestine.
2Erosion of an artery =atal Hge. 26nfiltration of ner%e se%ere pain.
#)2e)hanism: in%asion of E.C." *!asement "! – interstitium) !y / steps:-
,- deta)hment of tumor )ells from ea)h other
ue to loss of intercellular adhesion molecules.
/-atta)hment of tumor )ells #y %s to &$($2
"ainly to laminin *!asement "! component) anf fi!ronectin *interstitial tissue component).
3-degradation of &$($2*
1umor cells
By proteolytic en+yme secreted !y
0timulated host cells*fi!ro!last).
0e%eral en+ymes are released as *type 6< collagenase – cathepsin B ).
>-2igration of tumor )ells through degraded &$($2
Cccur !y tumor cyto(ines
-%e charges of tumor cells causing their repulsion.
ef: the a!ility of malignant tumor to form e'out direct continuity.
"ethods: 2 Blood spread B Haematogenous.
2 3ymphatic spread. 2 1ranscaelomic spread
2 6mplantation. 2 6noculation.
a) ef: spread of malignant tumor through !lood.
6t is the fa%ored pathway for sarcoma.
!)"echanism:-
,) !n"asion of e'tra)ellular matri' #y dire)t spread
:قف /يوان#لا ,ت-.
/-issemination
-=ormation of malignant throm!i *em!oli) formed of aggregation of malignant cells )fi!rin
) platelet w' resist destruction !y immune system of the host.
-etachment of em!oli carrying the malignant cells to !e impacted on ,
st
capillary networ( it
meet
3-Homing
6mpaction of malignant cells in capillaries  degeneration of the wall of the !lood %essels
6n%asion in E.C." -ry homing another malignant tumor.
>- N+&
-"etastatic deposits appear as scattered round nodules ch' !y:
0i+e: %aria!le.
2 -0
, ( Lo)al 9 ire)t spread 9 ire)t e'tension 9
!n"asion
/ ( istant spread 9 2etastasis
Blood
spread


0hape: rounded.
2 area of Hge $ necrosis are present.
Colour: grayish white.
2 -C
Consistency: hard.
8-2+&
2etastati) deposits resem#le ,ry tumor* لا ;<و 2+& of original tumor site ر=ا (ا-م ىا 0ف ,%) ول
)
?- Hematogenous spread
6t follow anatomical distri!ution of !lood %essels especially through %enous circulation !ecause
arteries resist penetration !ecause of their elastic muscular wall !ut may !e eroded causing fatal
Hge 0o "g. cells follow the %enous flow draining the site of neoplasm 0o:-
"g. cells metastasis Hematogenously as the following:-
# 3ower lim!s lung. # Colon ) appendi4 3i%er.
# systemic %eins lung. # 3ung systemic circulation.
@-2ost )ommon organs to #e affe)ted lung & li"er and %are in mus)les & spleen
N$B* 0ome tumors !ypass the lung * a!sence of lung metastasis):-
# 1umor cells are too small to !e impacted in the lung.
# @etrograde !lood spread. # 7ara%erte!ral system of %eins.
# <entricular septal defect *spatent foramen o%ale)


a) ef: spread of "g. cells through lymphatic %essels.
6t is the fa%ored pathway for carcinoma.
- 3ymph %essels ha%e :o !asement mem!rane 0o tumor cells in%ade easily and disseminate.
#) 2e)hanism: 0pread through one of the - ways:-
,)Lymphati) em#olism*
2 masses of tumor cells detach pass as tumor em!oli e'in lymphatic %essels reach afferent
lymphatics of the draining 3.:s arrested at su!capsular sinuses proliferate 0o gradually
estroy and replace su!stance of 3.:s.
2 tumor cells can in%ade capsular to perinodal tissue.
2 0pread of tumor cells from one 3.:s to another occur !y efferent lymphati)s.
2 0pread of tumor cells from one 3.:s to another in distant group dire)tly * 0(ip metastasis)
ef*The malignant )ells may es)ape from immediately pro'imal L$Ns to #e trapped in the su#seAuent L$Ns)
2 :8E: 0i+e: enlarged.
-0
0hape: separated or fused when perinodal tissue is in%aded.
C80: grayish white appearance ; area of Hge $ necrosis are present.
Colour: grayish white.
-C
Consistency: hard.
2"8E:
"etastatic deposits resem!le ,ry tumor.
/)Lymphati) permeation*
- "g. cells grow inside lumen of lymphatics as solid columns lymphatic o!struction.
Lymphati)
spread
3ymphatic edema.
- Common in !reast carcinoma.
ef* spread of "g. tumor through serous ca%ities from organs co%ered !y serous mem!ranes.
- 1he malignant cells infiltrate the serous layer detach drop mechanically @e-implant on
the surface of another organ w' is*rich in 7tn.– neoplastic cells ) fluid is important in diagnosis)
ef* -ry tumor occurring in the o%ary from ,ry in 961 through 1ranscaelomic spread .
N+&: !ilateral o%arian tu!e masses .
2+&: single ring carcinoma .
BB Kissing ul)er BB
ef* spontaneous transfer of "g. cells from one lip to the other lip in same person.
ef* direct artificial transplantation of tumor cells !y surgical instrument from one site to
another site in the same person. 6t is e4tremely rare.
(lassifi)ation of Tumors A))ording to Tissue of origin
9 Histogenous )lassifi)ation

- Benign
&pithelium - 2alignant (ar)inoma
- Benign
Tissue of origin 2esen)hymal - 2alignant :ar)omas
-
2i'ed - 2alignant
1ranscaelomic spread
&ru(en!urg tumor
6mplantation .
6noculation
Histogenous )lassifi)ation
Tissue of 4rigin Benign 2alignant

A) 4ne )ell type*-
,-Tumor &pithrlium*
C :tratified sAuamous
C Transitional
C ;landular
C 2elan#last
/-Tumor of ($T*
C <i#ro#last
C Lipo#last
C (hondro#last
C 4steo#last
3-Tumor of "essels*
C Blood "essels
C Lymph "essels$
>-Blood & Lymphoid*
C Haemopioti) )ells
C Lymphoid tissue
8- 2us)le*
C :mooth
C :triated
B) 2i'ed tumor 9
2ore than )ell type
from same germ layer
C :ali"ary gland$
C Breast$
( ) 2ore than one
)ell from more than
one germ layer*
:Auamous )ell papilloma
Transitional )ell papilloma
.aren)hymal )ell adenoma
Ne"us
<i#roma
Lipoma
(hondrome
4steoma
Hemangioma
Lymphangioma
DDDDDDDD$$
DDDDDDDD$$
Leiomyoma$
%ha#domyoma$
.leomorphi) adenoma$
<i#roadenoma$
2ature teratoma$
:Auamous )ell )ar)inoma
Transitional )ell )ar)inoma$
.aren)hyma )ell adeno)ar)inoma$
2alignant melanoma
<i#rosar)oma
Liposar)oma
(hondrosar)oma
4steogeni) sar)oma$
Angiosar)oma$
Lymphangiosar)omas$
LeuEemia$
Lymphoma
Leiomyosar)oma$
%ha#domyosar)oma$
2g$ mi'ed tumor of sali"ary gland origin$
2g$ )ystosar)oma phylodes
!mmature teratoma$
Benign &pithelial Tumors
.apilloma Adenoma
,) .apilloma* !enign epithelial tumor arise from protecti%e epithelium
Types* C :Auamous )ell papilloma$
C Transitional )ell papilloma$
C (olumnar )ell papilloma 9 Adenopapilloma C u)t papilloma
:Auamous )ell papilloma Transitional )ell papilloma (olumnar )ell papilloma9
Adenopapilloma 9 Adenomatous
polyp*-
:ite: 0(in $ laryn4.
(ause: may !e %iral in
Crigin *H7<) 6$66$6<$<66.
N+&: a) worty li(e.
!)may !e:-
2 :mall Cr large.
2 :ingle Cr multiple.
2 :essile Cr pedunculated
2 :imple Cr !ranched.
2+&*
&pithelium 7 ($T )ore:-
# Epithelium:
Hyperplastic stratified
squamous epithelium ;
Eeratin$
# C.1 core: - 1hic(.
- <ascular
- !ranching
.rognosis*
@arely transformed into
malignancy gi%ing
:Auamous )ell )ar)inom
Drinary tract.

5555..

Appear as %el%ety mass of
delicate papillary process.
&pithelium 7 ($T )ore:-
# Epithelium:
Dp to H layers of normal
transitional epithelium )
more than AG M of these cases
change to malignant tumor.
# C.1 core: - 1hin.
- <ascular
- !ranching
#7otentially malignant * AG M)
9i%ing transitional )ell
)ar)inoma$
# Hematuria.
Colon.

55555
Appear as sessile Cr
pedunculated Cr comple4
papillary pro>ection.
&pithelium 7 ($T )ore:-
# Epithelium:
0ingle layer of columnar
epithelium.
# C.1 core: - 1hin.
- <ascular
-:on - !ranching
# "ay turn malignant gi%ing
Adeno)arinoma$
# 961 !leeding.
>-u)t papilloma 9 Adenopapilloma 9 Adenomatous polyp:-
# 0ite: ma>or duct of the !reast.
# :8E: small comple4 papillary pro>ection inside duct lumen.
# "8E: delicate %ascular core co%ered !y regular ductal epithelial cells.
# Complication: - Bleeding per nipple.
- Hoarsness of %oice if arise on %ocal cords.
- "g. transformation uct carcinoma.
N$B: !reast may show papilloma $ adenoma.
uct papilloma squamous cell papilloma
ef: 9landular tumor arising from * glandular 8 secretory 8 columnar ) epithelium.
:ite: a) E4ocrine glans:E.g sweat glands$ sali%ary glands$ se!aceous glands$ simple tu!ular
glands of the stomach$ intestine.
!) Endocrine glands:E.g thyroid$ pituitary$ supra-renal$ pancreas.
c) Common in the o%ary.
Cause: may !e hormonal dependent. E.g increase 10H thyroid adenoma.
N+&*
0olid: - solitary encapsulated rounded Cr o%al mass.
- C80: greyish white homogenous appearance.
Cystic: # cystadenoma ,) "ucinous: cyst filled e' mucin.
-) 0erous: cyst filled e' serous watery fluid.
# papillary cystadenoma: 2*if contain papillary pro>ection from the cyst)
2 0i+e: %aria!le.
2 Colour: the same as its origin Cr may !e paler.
2+&: ,- 0olid adenoma:-
# simple adenoma: normally appearing acini ch' !y 2 uniform in si+e) shape.
2 3ined e' cu!iodal cells.
2 0canty mitosis.
2 0eparated !y normal ($T stroma ; encapsulated
#<i#roadenoma: normally appearing acini separated !y neoplasti) stroma; encapsulated
-- Cystadenoma:- cystically dilated acini distended e' mucin$ lined !y single layer of
epithelial cells.
- 1he rest of acini is present in the wall of the tumor.
- E.g: o%arian cystadenoma.

.- papillary cystadenoma: - 6f contain papillary pro>ection from the cyst.
- E.g: o%arian papillary cystadenoma
(lini)al effe)t of adenoma: 2 pressure on the surrounding causing hypofuncton of the gland from
w' it arises. 2 =unctioning adenoma may produce e4cess hormone: E.g pheochromocytoma.
.rognosis: may !e transformed into malignant : Adenocarcinoma.
Adenoma
Benign 2esen)hymal tumors
(,) Lipoma*
ef: !enign tumor of mature fat cells.
:ites* any where there is fatty tissue E.g su!cutaneous tissue peri-renal fat)retroperitoneal tissue
N+&*
2 ?ell defined – capsulated mass w' may !e lo!ulated if large.
2 ,0 0i+e: depends on duration.
Colour: yellow.
2 -C
Consistency: soft$ has slippery edge.
2 C8s: homogenous $ greasy.
2+& :
2 Capsulated tumor tissue surrounded !y fi!rous capsule sending C1 septa * con%eying
!l.< 1o tumor cells)  di%iding the tumor into lo!ules of mature fat cells B lipocytes.
2 =at cells are :
- uniform in si+e and shape $
-appear %acuolated due to dissolution of fat !y 4ylol and alcohol.
-nuclei are compressed against Q mem!rane gi%ing *0ignet ring appearance)
2 =atcan !e stained !y 24smi) a)id !lac(
2:udan !!!  Crange .
2 :)arlet red @ed.

/ry )hanges are: - "y4omatous changes "y4olipoma.
- ystrophic calcification.
- =ocal fi!rosis fi!ro-lipoma.
.rognosis* 6t is %ery rarely turn malignant.
(/) Angiomas
Hemangiomas 3ymphangiomas
Capillary Ca%ernous Capillary Ca%ernous
ةمداقلا ةحفلا ر!"ا
2alignant tumors
F- (ompare (ar)inoma & :ar)omas* ةمداقلا ةحفلا ر!"ا
- :Auamous )ell )ar)inoma 9 &pithelioma 9 &pidermoid )ar)inoma$
- Adeno)ar)inoma$ ةمداقلا ةحفلا ر!"ا
-Basal )ell )ar)inoma 9 %odent ul)er$
:Auamous )ell )ar)inoma* @-.rognosis*-
According to the location $ si+e $ depth of penetration 1here is BorderBs )lassifi)ation
(;rading system) 9 ifferentiation*-
2 @elated to the degree of differentiation Cr anaplasia of squamous cell carcinoma:-
-9rade 6: HAM - ,GGM of sheets ha%e cell nests.
-9rade 66: AGM - HAM of sheets ha%e cell nests.
-9rade 666: -AM -AGM of sheets ha%e cell nests.
-9rade <6: GM - -AM of sheets ha%e cell nests.
F- Dlcer on tongue e' raised $ e%erted edge e' enlarged su!mandi!ular 3.:s.
?hat is "8E of the 3.:s R please donBt forget that ( 2etastati) deposits resem#le ,ry tumor )
Adeno)ar)inoma*
/ - (ar)inoma )omple' 9 spheroidal )ell )ar)inoma *
2 formed of sheets of spheroidal "g. cells showing criteria of malignancy.. )arranged in solid
glandular structures $separated !y stroma .
2 found in !reast $ 961 ) prostate .
2 1ypes:- according to relati%e proportion !etween sheets *cellular elements))fi!rous stroma -:
a) 0chirrous carcinoma B Hard carcinoma:
-few sheets of malignant cells ) e4cessi%e fi!rous stroma.
-found in !reast ) stomach.
!) Encephaloid carcinoma B soft $ !rain li(e:
-large masses of malignant cells ) scanty fi!rous stroma.
-found in !reast.
c) "edullary carcinoma: * Encephaloid carcinoma ; lymphocytes in stroma ).
3-2u)oid adeno)ar)inoma*
# ef: adenocarcinoma in w' the mucus secretion is usually mar(ed.
# 1ypes: 2 mucoid degeneration in adenocarcinoma.
2 signet cell carcinoma.
# :8E: >elly – li(e mass.
# "8E: pools of mucin containing the remaining part of acini * mucoid degeneration) * tumor
cells floats in pools or la(es of mucus ) – :o acini – Cr signet ring cells * signet ring carcinoma)
# sites: colon *commonest) $ stomach $ !reast.
# prognosis: !ad.
Basal cell carcinoma *@odent ulcer)
F- 5l)er in the fa)e e= rolled in edge$ Ghat is 2+& H
Tumors of 2elano#lasts
Benign melanoma9 (ommon a)Auired ne"us9 2ole 2alignant melanoma
9 2elano)ar)inoma$
Benign melanoma
ef* Benign tumor of melanocytes *Hamartoma).
!n)iden)e* - <ery common lesion.
- 6nherited. - CccurP O ,G - /G years.
- A!sent at !irth $ they ,
st
appear in early childhood P O ,
st
and -
nd
year of life.
- Become frequent in middle adult life mostly on trun( region then progressi%ely disappear
-Cn the e4tremitis particularly those of palm and sole are less lia!le to disappear for un(nown cause.
Aetiology* due to proliferation of melanocytes w' start at !irth and passes into %arious stages till
matures at pu!erty.
N+&* 2 :ingle Cr multiple.
.0 2 :mall * ,-- mms )Cr large * rarly e4ceeds I mms).
2 :essile Cr pedunculated Cr flat.
-H 2 Hairy Cr non-hairy.
-B 2 Blac( Cr #rownish.
"8E: * 0tages of e%olution ):-
,- 3antigo: proliferation of melanocytes 0o replace the !asal layer of epidermis.

-- Nunctional ne%us: 2 increase proliferation of melanocytes w' are rounded or o%al in shape
1o form a mass at the >unction P O epidermis and dermis.
2 6t is precancerous.

.- Compound ne%us: the melanocyte are seen in !oth epidermis ) dermis.

/-ermal stage B mature stage *ne%us): 2 Cccur in adult.
2 Epidermal proliferation stops.
2 "igration of melanocytes stops.
2 :e%us cells in dermis !ecome more spindled and possi!ly dendretic 0o the drmis is occupied
By * # group of melanocytes and # some fi!rosis ).
7rognosis: Iun)tional ne"us in the adult may turn malignant at the sites of )hroni) irritation
as: * =ace – palm of the hand – sole of the foot – under the nail ).
4ther types of pigmented Ne"i*
Blue ne"us*
C ef* !lue spot commonly at the !uttoc(s in children.
C Aetiology: failure of melanocytes in em!ryological period to reach its final distenion in the
!asal layer of epidermis and remain in deep dermis.
C 2+&* groups of ne%us cells present in deep dermis w' are * immature – spindle in shape )
ysplasti) ne"us the most dangerous *-
# may arise de-no%o Cr in common acquired ne%us when fail to undergo orderly maturation.
1hey differ from acquired ne%i in:
7>و?@لا , ) although most donFt progress to mailgnancy $ the ris( is greater than e' common ne%i.
ة%Aا#لا - ) Cther mem!ers of family may ha%e similar lesions indicating that some mem!ers of
the family ha%e the familial ysplastic ne%us syndrome.
BCت='ا . ) 1hey differ grossely and microscopically from common ne%i and may !e difficult to
differentiate from "g. melanoma. ysplastic ne%i occur on sun e4posed as well as
un-e4posed 0(in surfaces.
C N+&* they tend to !e larger macules more than Imms and ha%e irregular !order and
ar( !rown to pin( colour.
C 2+&* 1hey appear to represent arrest of common ne%us at >unctional Cr compound stage !ut
the melanocytes ha%e degree of atypia and dysplasia.
2alignant melanoma 9 2elano)ar)inoma
ef: Highly malignant tumor arising from melano!last.
Age: Adult a!o%e /G years.
Aetiology: 2 7redisposing factors: - D.< ray.
- men e' fair e' !lue eyes s(in. 0o called s(in type 6 o!>ects.
2 7re-cancerous conditions: - Nunctional ne%us in adult.
- "ay arise de-no%o.
- Benign melanoma in sites of chronic irritation رDE.
6ncidence: --M of malignant tumors of s(in.
-"ay affect any age !ut pea( incidence /G – IG years.
:ite*mainly s(in !ut may appear in oral mucosa $ oesophagus $ %agina $ meninges $ con>uncti%a
Cr retina.
"ost common sites are : # in females is lower lim!.
# in male a!o%e the wrist.
# in Both is upper lim!s.
Classification: ,) @adial growth implies lateral spread confined to epidermis.
-) <ertical growth implies tumor progression leading to downward spread into the dermis.
N+&* a mass w' is Dlcerating ) fungating ) infiltarting ) %ariegated in colour
*red.!rown$white) )C8s show area of Hge$necrosis ) e' ill defined margin ) show
manifwstations of transformation ,ت-.
-The manfestations of transformation of #enign into malignant melanoma are*-
# @ecent increase in si+e. # Change in the colour * deeping of pigmentation )
# Dlceration # 0pontanous !leeding # 3oss of hair # Enlargment of draining 3.:s
2+&*
# 3entigo malignum *stage G ) B carcinoma in situ:-
- "alignant melano!lasts infiltrate !asal layer of the epidermis.
# 0uperficial spreading type * hori+ontal phase of spread ):-
- "alignant melano!lasts infiltrate !asement mem!rane ) spread hori+ontally.
# :odular melanoma * %ertical phase ):-
- 0pread %ertically ) infiltrate the dermis *the depth of infiltration is an important diagnostic
criteria ) ) may present in - pattrens:
2 0heets of malignant melano!lasts * melanocarcinoma ).
2 0pindle of shaped cells * melanosarcomas ).
- 1hese cells show chronic malignancy ; show 2 intra cytoplasmic melanin.
2 e4tra cytoplasmic melanin
:pread* - 3ocal spread.
- 3imited.
- 3ead to manifestations of transformation.
- Blood ) 3ymphatic spread * may e%en proceed the local spread ).
- 2etastasis in li"er may #e)ome dormant for years *ا+
.rognosis*
- 9ood e' melanoma e' radial growth pattren $ !ad e' melanoma e' %ertical growth pattren.
- 1he prognosis depend on the depth of in%asion $ determined !y measurement of the %ertical
e4tent of tumor !elow the stratum granulosum * Cler( Fs le%el).
F- 2an e= glass eye and enlarged li"er H
1 The ,
st
possi#ility is malignant melanoma$
onBt forget*-

(an)er sEin are* ,- :Auamous )ell )ar)inoma$
/- #asal )ell )ar)inoma$
3- 2g$ melanoma 9 melano)ar)inoma$
(omposite tumors
Teratoma
ef* composite tumors containing structures deri%ed from * ectoderm $ mesoderm $ endoderm)
Crigin: 1otipotent cells.
0ites:
,- o%ary and testis are the most common sites.
--Cther sites:anterior "ediastinum $retroperitonium $!ase of the s(ull and sacrococcygeal region
Types*
C 2ature teratoma ( #enign teratoma) Cystic teratoma and solid teratoma
C !mmature teratoma (2g$ teratoma)$
C 2onodermal teratomas ( spe)ialized teratoma)$
,- 2ature teratoma 9 #enign teratoma$
2 "icroscopically: it consists of mi4ture of mature ectoderm $ endoderm and mesodermal
structures E.g epidermis $ se!achous glands $ hairs $ muscles 55..etc.
2 9rossly: two types: cystic teratoma * dermoid cyst) and solid teratoma.
(ysti) teratoma 9 dermoid )yst :olid teratoma
,-:ites*
/-N+&*
3- 2+&*
>-
.rognosis*
C%ary
0i+e: less than ,A cm in diameter.
0hape: thic( walled rounded Cr o%al cyst
Consistency: tense and cystic.
C80: a cyst containing yellow se!achous
material. 1he wall show solid ele%ation
called dermoid ridge w' show different
tissue.
# 1he cyst is lined !y stratified squamous
epithelium w' s(in appendages.
#1he wall show mi4ture of mature tissues
deri%ed from . germ layer:-
2 "esoderm: muscle – !one – cartilage.
2 Ectoderm: -0(in *hair follicles$ sweat
glands and se!aceous glands - :er%ous
tissue.
2 Endoderm: -961 - 1hyroid tissue
- @s mucosa.
N$B* at least 3 tissues from ea)h layer$
6t is !enign tumor and ,J can turn to
malignant * carcinoma – sarcomas ).
1estis.
0i+e: less than ,A cm in diameter.
0hape: a solid$ rounded $ o%al or
irregular mass.
Consistency: %aries.
C80: solid$ may show multiple
cystic ca%ities filled e' thin
gelatinous fluid.
# "i4ture of mature tissues
deri%ed from . germ layer :- as
!efore ,ت-ي
6t is !enign tumor and can turn to
malignant *carcinoma – sarcomas)
/- !mmature teratoma 9 2g$ teratoma
2 :8E: Bul(y predominantly solid mass e' area of Hge and necrosis.
2"8E: ,- contain immature em!ryonic tissue Cr tissue w' show "g. criteria
-- 1he degree of malignancy and spread depend on the degree of immaturity.
3- 2onodermal teratomas 9 spe)ialized teratoma $
1hese are teratomas that differentiate along the line of a single a!normal tissue.
# :truma o"arri : a !enign o%arian teratoma composed of thyroid tissue.
# 4"arian 4r testi)ular )horio)ar)inoma.
&m#ryonal tumors 9 Blastomas
ef: Highly malignant tumors arising from em!ryonic rests.
Characters:
2 7resent during intra-uterine life ) early infancy.
2 Highly malignant.
2 @adio – sensiti%e.
1ypes: * from a!o%e to down )
a)Brain: "edullo – !lastoma.
B)Eye: @etio – !lastoma.
c)3i%er: Hepato – !lastoma.
d)0uprarenal gland: neuro – !lastomas.
e)&idney: nephro – !lastomas B ?ilmFs tumor.
f )Em!ryonal rha!domyosarcomas B sarcomas of striated muscle.

Host against 1umor * immunity ) 1umor against Host*complication)
* :eoplastic syndrome – paraneoplastic tumors )
,-Host againt tumors 9 Anti-tumor me)hanisms*-
How 6mmune system attac(s "g. cells R By:-
# :atural (iller cells *:&-cells) : ,
st
line of defense as they are a!le to destruct tumor cells e'out
0ensiti+ation.
# Cytoto4ic 1-effector lymphocytes: * cell immediated immune response )
# "acrophages: show some cyto-to4icity against tumor cells ) 1hey acti%ate 1-lymphocyte w'
re-acti%ate macrophage !y 6=: )
# Humoral mechanism : !y A! ) complement * type 66 cell mediated cyto-to4icity).
1he complement ;; opsoni+tion and phagocytosis of tumor cells
/- Tumor against Host
(ompli)ations*-
Tumor host intera)tion
A) Neoplasti) syndrome
,- 3ocal effects: occur at the site of origin
# "echanical: o!struction ) pressure. E.g:
6- 7ituitary adenoma: compress ) destroy normal gland hypofunction.
66- small cancers around !ile duct o!struction.
# Dlceration ) !leeding.
# 7erforation )rupture.
# -ry infection.
-- Hormonal production:
# cancer lung: - AC1H Cushing syndrome.
- AH.
# cancer oesophagus: - 71H hypercalcemia.
# E4cessi%e hormonal production if tumor occur in endocrine glands. E.g:
- B islets of pancreas insulin.
- Adrenal corte4 catecholamines.
1he acti%ity of the endocrine glands is more in !enign tumors than "g.
.- "alignant cache4ia:
a) ef: se%ere progressi%e wea(ness ) wasting ) loss of weight associated e' anemia ending in
death.
2 1he se%eritr of cache4ia is proportional to si+e of tumor ) e4tent of metastasis.
!) Etiology:-
# Etiology of wasting: # Etiology of anemia:
- Anore4ia. - "ala!sorption.
- ifficult mastication *e.g cancer tongue). - -ry infection.
- ysphagia *e.g cancer oesophagus). - Bleeding.
- <omiting *e.g cancer stomach). - Bone marrow depression due to:
- 2ala!sorption. 2 Auto – immune.
- 2eta!olic competition for nutrition P O 2 "g. cells: coming from metastasis Cr
normal cells ) tumor cells. produce to4ic su!stances.
- 1o4ic su!stances from tumor cells interfering
e' meta!olism.
- 6ncrease B.".@ due to circulation of 1:=-a
* tumor necrosis factor ) ) 63-, from acti%ated
"acrophage.
,- ef:- group of manifestations ) symptoms w' appear in a patient e' cancer and canFt !e
e4plained !y local infiltration Cr distant metastasis.
- Cccur in ,G – ,A M of patient.
- Dsually associated e' Bronchial carcinoma.
Cancer !reast.
Haematologic malignancy.
-- E4amples: * .C – .H – !lood – heart – C.:.0)
# Cushing syndrome: in tumors associated e' AC1H production.
# Clu!!ing of fingers ) osteoarthropathy : associated e' cancer lung.
# Cutanous syndrome: E.g Acanthosis nigricans ) E4ofoliati%e dermatitis.
B).ara - neoplasti) syndrome
# Hypercalcemia: in squamous cell carcinoma of lung * most common) ) oesophagus
6ncrease 71H ;; osteo!lasts ) ;; %it.
# Hypercoagula!ility ) deep %enos throm!osis.
# Haematological disorders: erythrocytosis ) associated e' renal cell carcinoma )
hepatocellular carcinoma ) anemia ) throm!ocytosis.
# -ry amyloidosis: associated e' lymphoma ) multiple myeloma ) renal cell carcinoma....etc
# :on-!acterial throm!otic endocarditis.
# :eurologic syndrome: peripheral neuritis ) dementia ) su!acute cere!ellar degeneration.
Tumor marEers ةمداقلا ةحفلا ر!"ا
.rognosti) fa)tors of malignant tumors
,- 1umor type: most sarcoma ha%e poor prognosis than carcinoma.
-- 1umor site: superficial tumors are diagnosed early and treated easier than deep tumors
.- 1umor grade: low grade tumors grow slowly than high grade tumors.
/- 1umor stage: low stage tumors ha%e much !etter prognosis than high stage tumors.
- 6t is the most important factors of diagnosis.
A- 7resence of immune response: of good prognosis.
I- 9rowth fraction: tumors e' high 9= are rapidly growing if untreated !ut respond well to
Anticancer therapy.
H-1umor hormone receptors: tumors of hormonally responsi%e tissues as !reast ratain hormone
receptors and respond well to hormonal therapy.
J-@adio-sensiti%ity of tumors: radio-sensiti%e tumors as lymphoma respond well to radio-therapy
and a%oiding surgical line of treatment.
;rading of )ar)inoma
,) ef: clinical estimation of aggressi%ness of tumor according to:-
2 degree of similarity of the tumor cells to the mother cell of origin.
2 :um!er of mitosis.
-) 9rading of carcinoma to:- 2 9rade 6 : well differentiated.
2 9rade66 : moderately differentiated.
2 9rade 666 : poor differentiated.
2 9rade 6< : undifferentiated * anaplastic)
:taging of )ar)inoma
,) ef: 6t is clinical estimate of the e4tent of spread of malignant tumor

-) 1wo methods of staging are in use:
A) Ameri)an Koint )ommittee system ( AI()*
# 0tage +ero * carcinoma in situ ):-
- se%ere dysplasia.
- "icro-in%asi%e carcinoma of the microscopic si+e.
- Cells acquire the properties of malignancy But ha%enFt changed into malignant cells yet.
- Cellular atepia: shorter of malignancy together e' loss of polarity.
- e' no manifestation 0o easily disco%ered.
# 0tage 6:-
- 1he tumor is confined to the organ of origin.
# 0tage 66:-
- 1umor spreads to near!y organ But still respecta!le.
# 0tage 666:-
- 1umor spread to near!y organ But it is irrespecta!le.
# 0tage6<:-
- istant metastasis.
B)TN2 system*
1umor * 1 ) @egional 3.:s * : ) "etastasis * " )
According to the si+e
of the tumor:-
G $ , $ - $ .
According to :o. of 3.:s that
are in%ol%ed:-
G $ , $ - $ . $ /.
According to presence Cr a!sence
G $ ,.
E4amples:-
1, $ :, $ "G 3east se%erity.
1. $ :G $ "G "oderate.
1G $ :, $ ", the most se%ere.
!mmune sur"eillan)e
- 6s the recognition and destruction of non-self tumor cells on ,
st
recognition.
1 &"iden)e of immune sur"eillan)e:
- increase incidence of cancer especially lymphoma in immunocompromi+ed patient.
1 Against this )on)ept*
- Lymphoma in immuno)ompromized patient is due to immuneproliferation due to /ry infe)tion
,- 1umor specific antigens *10A):-
2 7resent only on tumor cells.
2 E%o(e the immune response and used for tumor diagnosis.
Tumor immunity
Tumor Antigens
--1umor Associated antigens *1AA):-
2 7resent on tumor cells and also on some normal cells.
2 o not e%o(e the immune response $!ut are useful in tumor diagnosis.
a) ifferentiation specific Ags:
2 1hey are peculiar ةصصخم to the differentiation state at w' cancer cells are arrested E.g:
- 0-,GG: in neural creast deri%ed tumors.
- C ,G * B-lymphocyte).
- C . *1-lymphocyte).
- 70A in cancer prostate.
!) Cncofetal Ags:
2 :ormally e4pressed in em!ryonic tissue But not adult tissue.1heir e4pression in some tumor is
due to de-repression of genetic programs . 1he !est e4amples are:
- A=7: Hepatoma $ 1eratocarcinoma.
- CEA: cancer colon $ pancreas $ stomach $ lung and !reast.
Ho0 the tumor )ells e"ade the immune system*
,- =ormation of antigen –%e tumor cells during tumor progression.
--0hedding or modulation of tumor antigens.
.-6mmune suppressi%e agents secreted !y tumor cell E.g: 19= – alpha.
/-3oss Cr reduced e4pression of histocomata!ility antigens. 1hus !ecome less suscepti!le to
&illing !y cytoto4ic 1-cell lysis.

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