Anaplasla dlfferenLlaLlon

ur nlveen M uaoud
Ass rof cllnlcal paLhology
neoplasm
8enlgn MallgnanL
Carclnoma Sarcoma
nomenclaLure
neoplasm
8enlgn MallgnanL
Carclnoma Sarcoma
oJeoomo
ooqlomo
tbobJomyomo
nomenclaLure
neoplasm
8enlgn MallgnanL
Carclnoma Sarcoma
omonellnotnloomo
oJeoonotnloomo
nomenclaLure
neoplasm
8enlgn MallgnanL
Carclnoma Sarcoma
ooqlootnomo
tbobJomyootnomo
nomenclaLure
@lssue of orlgln 8enlgn MallgnanL
llbrous Llssue llbroma llbrosarcoma
laL Llpoma Llposarcoma
CarLllage Chondroma Chondrosarcoma
8one CsLeoma CsLeogenlc sarcoma
8lood vessels Pemangloma Anglosarcoma
MesoLhellum MesoLhelloma
PemaLopoleLlc cells Leukemla
Lymphold cells Lymphoma
Squamous eplLhellum Squamous cell papllloma Squamous cell carclnoma
Clandular eplLhellum Adenoma Adenocarclnoma
apllloma aplllary adenocarclnoma
CysLadenoma CysLadenocarclnoma
SmooLh muscle Lelomyoma Lelomyosarcoma
SkeleLal muscle 8habdomyoma 8habdomyosarcoma
MelanocyLes nevus Melanoma
know Lhese names!
Sample board quesLlon
Whlch of Lhe followlng descrlbes a benlgn Lumor
arlslng from skeleLal muscle?
A Lelomyoma
8 apllloma
C 8habdomyoma
u Lelomyosarcoma
L 8habdomyosarcoma
redlsposlng lacLors for Cancer
W Age
MosL cancers occur ln persons 33 years
Chlldhood cancers
W Leukemlas CnS neoplasms
W 8one Lumors
W CeneLlc predlsposLlon
lamlllal cancer syndromes
W Larly age aL onseL
W @wo or more prlmary relaLlves wlLh Lhe cancer
W MulLlple or bllaLeral Lumors
olymorphlsms LhaL meLabollze procarclnogens eg nlLrlLes
W nonheredlLary predlsposlng condlLlons
Chronlc lnflammaLlon?
recancerous condlLlons
W Chronlc ulceraLlve collLls
W ALrophlc gasLrlLls of pernlclous anemla
W Leukoplakla of mucous membranes
W lmmune collapse?
Molecular basls of cancer
W 8aslc underlylng cause of cancer
nonleLhal geneLlc damage
W lour klnds of normal genes are damaged
- Cenes LhaL promoLe growLh (proLo
oncogenes)
- Cenes LhaL lnhlblL growLh (Lumorsuppressor
genes)
- Cenes LhaL regulaLe apopLosls
- Cenes lnvolved ln unA repalr
W Cancers develop ln mulLlple sLeps
AuLonomous CrowLh
W roLooncogene a normal gene whose producL
promoLes cell growLh
W Cncogene muLaLed proLooncogene!
Causes cell Lo grow auLonomously!
W CncoproLeln Lhe producL of an oncogene
ueflnlLlons
lnsenslLlvlLy Lo CrowLhlnhlblLory Slgnals
W @umorsuppressor genes normal genes whose
producLs acL as brakes on Lhe cell cycle
W MuLaLe Lhese guys and you lose Lhe brakes!
W CoLLa lose boLh coples of Lhe gene Lo cause Lumors
Pow do all Lhese geneLlc muLaLlons arlse?
W We are consLanLly exposed Lo muLagenlc
agenLs (sunllghL radlaLlon chemlcals)!!
W We don'L geL very many cancers because
normal cells are able Lo 8LAl8 unA
damage!!
W Many sysLems for unA repalr exlsL
W lf you lnherlL a defecL ln any of Lhese
sysLems you'll be more llkely Lo geL
cancer
lallure of unA repalr
ulfferenLlaLlon and Anaplasla
W ulfferenLlaLlon how much Lhe Lumor cells resemble Lhelr
cells of orlgln
- welldlfferenLlaLed closely resembles
- moderaLelydlfferenLlaLed sorL of resembles
- poorlydlfferenLlaLed doesnL resemble
W 8enlgn Lumors are usually welldlfferenLlaLed
W MallgnanL Lumors can show any level of dlfferenLlaLlon
ulfferenLlaLlon
W Well dlfferenLlaLed neoplasm
8esembles maLure cells of Llssue of orlgln
W oorly dlffenLlaLed neoplasm
Composed of prlmlLlve cells wlLh llLLle
dlffrerenLlaLlon
W undlfferenLlaLed or anaplasLlc" Lumor
W CorrelaLlon wlLh blologlc behavlor
8enlgn Lumors are well dlfferenLlaLed
oorly dlfferenLlaLed mallgnanL Lumors usually
have worse prognosls
If ce||s LCCk 8AD they are probab|y go|ng to 8LnAVL 8AD
Looking bad means NO1 looking like the cells they supposedly
arose from!
If ce||s LCCk GCCD they are probab|y go|ng to 8LnAVL GCCD
Looklng good" means looklng llke Lhe cells Lhey supposedly arose from!
W 9|eomorph|sm
Slze
shape
W Abnormal nuclear morphology
nyperchromas|a
n|gh nuc|ear cytop|asm|c rat|o
Chromat|n c|ump|ng
9rom|nent nuc|eo||
W M|toses
MlLoLlc raLe
LocaLlon of mlLoses
W Loss of po|ar|ty
AnALASlA" CAnCL8
ulfferenLlaLlon and Anaplasla
- leomorphlsm
- PyperchromaLlc large nuclel
- 8lzarre nuclear shapes dlsLlncL nucleoll
- LoLs of mlLoses and aLyplcal mlLoses
- ArchlLecLural anarchy
AnaplasLlc cells show
uysplasla
W L|tera||y means abnorma| growth
W Ma||gnant transformat|on |s a mu|t|step process
W In dysp|as|a some but not a|| of the features of ma||gnancy
are present m|croscop|ca||y
W Dysp|as|a may deve|op |nto ma||gnancy
W Graded as |owgrade or h|ghgrade often prompt|ng
d|fferent c||n|ca| dec|s|ons
W Dysp|as|a may NC1 deve|op |nto ma||gnancy
W nIGn grade dysp|as|a often c|ass|f|ed w|th CIS
ulfferenLlaLlon and Anaplasla
W uysplasla ls used Lo descrlbe dlsorderly changes ln
nonneoplasLlc eplLhellal cells
- Craded as mlld moderaLe or severe
W MlldmoderaLe usually reverslble
W Severe usually progresses Lo carclnoma ln slLu (ClS)
- nexL sLep afLer ClS lnvaslve carclnoma
uysplasla dlsorderly (dys) growLh (plasla)
; WalL a mlnuLe dysplasla sounds susplclously
slmllar Lo dlfferenLlaLlon whaLs Lhe dlfference?
; WalL a mlnuLe dysplasla sounds susplclously
slmllar Lo dlfferenLlaLlon whaLs Lhe dlfference?
A 8oLh Lerms descrlbe wheLher cells look normal or noL!
8uL
W dlfferenLlaLlon ls only used wlLh neoplasLlc cells and
dysplasla ls only used wlLh nonneoplasLlc cells!
W dysplasla ls only used wlLh eplLhellal cells buL
dlfferenLlaLlon can apply Lo any cell Lype
mlld
dysplasla
moderaLe
dysplasla
severe
dysplasla
well
dlfferenLlaLed
moderaLely
dlfferenLlaLed
poorly
dlfferenLlaLed
anaplasLlc
carclnoma
ln slLu
nonneoplasLlc eplLhellal cells
neoplasLlc cells
uysplasla
normal glands
normal gland
Mlld dysplasla
ModeraLe dysplasla
Severe dysplasla
normal squamous
eplLhellum
ModeraLe
dysplasla
Severe dysplasla
normal eplLhellum uysplasLlc eplLhellum
lnvaslve squamous cell carclnoma
@umor CrowLh 8aLe
W uoubllng Llme of Lumor cells
LengLhens as Lumor grows
30 doubllngs (10
9
cells) 1 g %months to years)
10 more doubllngs (1 kg) leLhal burden %#)
clonal"
8aLe of CrowLh
W MallgnanL Lumors grow fasLer Lhan benlgn ones
W oorlydlfferenLlaLed Lumors grow fasLer Lhan well
dlfferenLlaLed ones
W CrowLh ls dependenL on
- 8lood supply
- Pormonal facLors
- Lmergence of aggresslve subclones
CenerallzaLlons
8aLe of CrowLh
W Age of Lumor
- Larly on (subcllnlcal) Cl hlgh
- LaLer (cllnlcally deLecLable) Cl low
W @ype of Lumor
- Leukemlas lymphomas smallcell lung cancer hlgh Cl
- 8reasL colon cancer low Cl
W lmporLanL for LreaLmenL
- Plgh Cl Lumor LreaL wlLh chemoLherapy/radlaLlon
- Low Cl Lumor LreaL by debulklng
CrowLh fracLlon cells LhaL are acLlvely dlvldlng
@hyrold adenoma (welldlfferenLlaLed)
Squamous cell carclnoma welldlfferenLlaLed
Squamous cell carclnoma moderaLelydlfferenLlaLed
Squamous cell carclnoma poorlydlfferenLlaLed
lnLercellular brldges
AnaplasLlc carclnoma
Abnormal mlLoses