12 Tumori
Transcript of 12 Tumori
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TUMORI
DR. MARICA CONSTANTIN
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TUMORI CU MALIGNITATE
REDUSA
• EVOLUTIE LENTA
• RECIDIVE LOCALE
• FOARTE RAR METASTAZANTE
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• Carcinoidul bronsic (carcinoidele)
-1-2%din tumorile bronsice-sunt tumori secretoriiserotonina
Carcinoidul comun
-proximal:vizibil endoscopic
vegetant
-periferic:asimptomatic
radiologic=nodul izolat
Carcinoidul atipic – neuroendocrin diferentiat-metastaze osoase,hepatice
*Manifestari endocrine = metastaze
(tesutul pulmonar inactiveaza serotonina)
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-continuare-
Carcinoame ale glandelor bronsice
#carcinomul adenochistic (cilindrom)traheal
#carcinom mucoepidermoid
bronhii mari
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TUMORI MALIGNE
BRONSICE PRIMITIVE
• Tumori bronhopulmonare care iau nastere
la nivelul mucoasei bronsice
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Cancer Clinical Trials
Staging of Lung Cancer
1993 World Health Statistics
33.04, 562651.190,130Female
72.09, 693783.7105,438MaleCanada
39.450, 194812.01,035,046Female
75.191, 091918.41,113,417MaleUnited States
Death
Incidence/10
0.000
Lung Cancer
Total Death
Incidence
Lung Cancer
Death
Incidence/10
0.000
All Causes
Total Death
Incidence
All Causes
SexCountry
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Frecventa cancerului br.pn.la barbat si
femeie
fata de alte localizari neoplazice
0
510
15
20
25
30
35
C.B.P. Barbat
C.B. Femeie
Alte cancere
22
11
33
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CANCER BRONSIC PRIMITIV
Epidemiologie –cel mai frecvent la om
(Franta)
La femei
200/000
La barbati
1982 – 710/000
80/000170/0001970 – 450/000
180/000210/0001950 – 180/000
300/000130/0001930 – 50/000
C.StomacC.ColonC.Bronsic
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Cancer Clinical Trials
Staging of Lung Cancer
Risk Factors• Smoking
• Secondary smoke exposure
• Asbestos
• Radon
• Bis(chloromethil) ether• Polycyclic aromatic hydrocarbons
• Chromium
• Nickel
• Inorganic arsenic compounds
• Genetic predisposition
Source:(Devita VT,Hellman S and Rosemberg SA. Cancer:
principles and practice of oncology ,4th edition Philadelphia;
J.B.Lippincott,1993
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CANCERUL PULMONAR
• Din 10 bolnavi de cancer pulmonar 9 sunt
fumatori,iar dintre fumatori 11% fac cancer
pulmonar.
• O persoana care fumeaza 40 tigari/zi inhaleazape un an 140g de substante cancerigene.
• Marii fumatori au un risc de 15-25 ori mai
mare de a face cancer pulmonar decat
nefumatorii.
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• Fumul de tigarete ar actiona prin substantelecarcinogene pe care le contine , dar in acelasi timp siprin alterarea cleareanceului muco-ciliar.Secvential
s-ar produce o hiperplazie a celulelor bazale,o metaplaziemalpighiana,aparitia de atipii celulare si de carcinoame
in situ (fara invazia membranei bazale),urmate decarcinoame veritabile invazive.
• Aryl-hidrocarbon-hidroxilazei(AHH),se atribuie un rolprincipal in activarea hidrocarburilor policiclice,apte
de a induce transformari maligne.• AAH a fost gasita considerabil crescuta in macrofagele
alveolare si in limfocitele fumatorilor.
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• Fumatul si expunerea in mediul industrial poluantimpreuna multiplica riscul de a face cancerpulmonar.Fumatorul a 20 de tigarete/zi care nu esteexpus la poluarea industriala are un risc deaproximativ de 20 ori mai mare de a deceda prin
cancer pulmonar comparativ cu nefumatorul.Nefumatorul din mediul de azbest, neprotejat fata deaceasta noxa,are o probabilitate de 4 ori mai mare de amuri de azbestoza decat nefumatorul care isidesfasoara activitatea intr-un mediu inconjurator de
munca nepoluat.Daca muncitorul expus la azbest maifumeaza si 20 tigarete /zi , probabilitatea de a muri decancer pulmonar este de 80 de ori mai mare decat aaceluia care nu este expus la unul din cele doua riscuri.
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• A fost emisa si teoria patogenica in 2
trepte a cancerului fumatorilor (Two
Steps Process) dupa care, intr-o prima
etapa s-ar produce iritatia nespecifica a
epiteliului ciliat (datorita cianurei dehidrogen,acroleinei, formaldehidei,
acizilor de azot)
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CONSECINTELE FUMATULUI
ASUPRA PLAMANULUI • Inhibitia mobilitatii cililor bronsici si a
macrofagelor ,ceea ce provoaca staza secretiilor sisensibilitatea la infectii;
• Hiperplazia si hipertrofia glandelor mucoase cu
hipersecretie de mucus;• Stimularea receptorilor de iritatie vagala cu
bronhospasm;
• Eliberarea enzimelor proteoliticede catre PMN;
• Alterarea calitatii surfactului.
La originea acestei patologii stau substantele iritantedin fumul de tigara ,gudronul si gazul
cianid,responsabile de dezvoltarea bronsitei siemfizemului.
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• Un studiu recent din Elvetia demonstreaza rata decrestere a incidentei adenocarcinoamelor la inceputulanilor `90 atat la barbati cat si la femeile tinere,valorilefiind de 3 ori mai mari decat pentru carcinoamelescuamoase din aceleasi grupuri.
• Carcinoamele scuamoase si cu celule mici care sedezvolta in bronsiile mari sunt traditional asociate cufumatul , dar cresterile relative si absolute in incidentaadenocarcinomului plamanului au fost recunoscute dince in ce mai mult.
• Partile periferice ale plamanului sunt in felul acestamai expuse la cantitati mai mari de substantecarcinogene asociate cu consumul tutunului,aici fiindsediul in care se dezvolta de electie adenocarcinomul.
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BIOLOGIA SI CRESTEREA TUMORALA
ONCOGENE SI FACTORI DE CRESTERE
TULORALA
• Deletia bratului scurt al cromozomului 3
• Amplificarea oncogenelor Cmyc si Nmyc
• Nr.insemnat de receptori pentru E.G.F.NSCLC
• Secretie si utilizarea hormonilor peptidiciSCLC
ca factori de crestere
(bombesina;calcitonina;ACTH;lipotrofina)
• Receptori pentru hormoni steroidieni
***Depistarea cancerului Br.Pn.se realizeaza dupa aproximativ 30
T.dublari
=1 cm(10 9 celule)
C.anaplazic
Cu celulemici
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30 timpi de dublare 10 timpi de dublare
Faza infraclinicaFaza clinica
1 cm
10 9
celule
Debut
10 12
celule
PERIOADA DE METASTAZARE
CRESTERE RAPIDA
TENDINTA MARE DE METASTAZARET.de dublare
-C.epidermoid 60 zile
ADENOCARCINOM 80 ZILE
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CARCINOMUL EPIDERMOID
FRECVENTA 40-45 %
SEDIU PROXIMAL• Microscopic +/- diferentiat (cheratinizare)
elemente epidermice
zone de necroza
stroma bogata
• Macroscopic: formatiuni burjorante endobronsic
Timp de dublare 60 zileEvolutie local + metastaze
CANCERUL CU CELULE MICI
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CANCERUL CU CELULE MICI
FRECVENTA 15-20%
SEDIU PROXIMAL
• Microscopic :celule mici 5% “bob de ovaz”(oat cell)
celule intermediare 15%
absenta arhitecturii
stroma discreta
necroza abundenta
Secretie argirofila(cel.KULTCHISCKY)neurosecretie
Neurosecretie T.neuroendocrine (TNE)-C.cu celule mici
-Carcin.neuroendocrine (CNE) diferentiat (carcinoid)
CNE putin diferentiate (c.cu celule mici intermediare)
CANCERUL CU CELULE MARI
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CANCERUL CU CELULE MARI
FRECVENTA 15-20%
SEDIU PROXIMAL SI DISTAL
• Microscopic :celule mari nediferentiate
• Macroscopic:variabil
• Evolutie:local + metastaze
• Timp de dublare : scurt
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CLASIFICARE ANATOMICA
Struct.
papilara
Pneumocite
II
Celule Clara
distal3%c.bronhiolo-
alveolar
Chimio-radio-
chirurgie
Local +
meta
VariabilCelule mariProximal
si distal
15-20%c.cu celule mari
Chirurgie+ra
dio-
chimioterapie
Variabil
asem
c.secundare
VariabilCel.struct.
Glandulare
Proximal
si distal
15-20%Adenocarcinomul
Chimio+radio
terapie
Extensiv
Meta
bilateral
Infiltratie
peribronsic
a
Celule “bob
de ovaz”
Intermediar
Proximal15-20%c.cu celule mici
Chirurgie
Radioterapie
Local+metaBurjon
endobronsic
Elem.tesut
epiteliat;Necroza
Proximal
sau distal
40-45%c.epidermoid
TratamentEvolutieMacroMicroSediuFrecventa
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ADENOCARCINOMUL
FRECVENTA 15-20%
SEDIU FRECVENT PERIFERIC DAR SI CENTRAL (C.SECUNDAR?)
• Microscopic:30% dezvoltat pe cicatrice
aspect glandular –tubular -acinos
-papilar
• Macroscopic:cu sau fara manifestari endoscopice
• Evolutie :variabila
• Timp de dublare: 80 zile
CANCERUL BRONHIOLO ALVEOLAR
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CANCERUL BRONHIOLO-ALVEOLAR
FRECVENTA 3%
SEDIU PERIFERIC
• Microscopic:celule din bronsiolele terminale(Clara)
si invelisul alveolar (Pneumocite tip II)
-unifocal - difuz• Macroscopic:endoscopie adesea normala
secretie abundenta
• Evolutie: variabila
• 1.etapa trenanta
• 2.etapa cu evolutie mai rapida
C Cli i l T i l
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Cancer Clinical Trials
Staging of Lung CancerFrequency of Lung Cancer Symptoms in a Group
of 69 Patients with Inoperable Non-small Cell
Lung Cancer
25hemoptysis
48Pain
54Weight loss
57Decreased appetite
59Dyspneea
71Cough
81Decreased activity84Fatigue
PercentageSymptom
MANIFESTARI CLINICE
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MANIFESTARI CLINICE
• Perioada asimptomatica lunga
Simptome de “imprumut”dominante-iritatie
-obstructie
-infectie
Simptome “proprii”sarace
-hemoptizie
-modificari radiologice
• Debut
1.lent 70% 2.Acut 20% 3.Atipic 10%
MANIFESTARI CLINICE
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• LENT –tuse iritativa rebela – hemoptizii(x)-durere toracica – sd.de
obstr.bronsica partiala (xx) –astenie.anorexie – rar febra –pierdere
ponderala
x-mici ,matinale,repetate,rar “jeleu de coacaze”
xx –caracteristic parasternal in expir si inspir
• ACUT –pneumopatie acuta(1)
- sindrom supurativ retrosternotic
- sindrom pleuretic :infectios metastatic
• ATIPIC –sd.embolic –sd.neurologic(2) –sd.de vena cava superioara
-disfonie(paralizie recurentiala) –disfagie(invazie esofag)
-dispnee acuta (3) –adenopatie supraclaviculara
-dureri toracice intense (invazie pleurala;sd.Pancoast- Tobias)-sd.algic osos –sindroame paraneoplazice
(13) –prelungita ,subacuta,recidivanta “in situ”
(2)-metastaza de la c.pn.latent
(3) –atelectazie brusca, invazie frenic , c.traheal
MANIFESTARI CLINICE
ASPECTE RADIOLOGICE
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ASPECTE RADIOLOGICE• Condensare parenchimatoasa
Pneumonie
Atelectazie
Localizate preferential in :
segm.ventral superior varf la lob inferior
Piramida bazala culmen
• Hil tumoral
-arborescent –umbra nucleara –contur policiclic(adenopatie)
• Nodul pulmonar solitar
Rotund –ombilicat –cu/fara prelungiri• Cavitati
Frecvent in c.epidermoide, c.cu cel.mici
Rar la adenocarcinom
Marginale –pereti grosi neregulati (“in rama”)
ASPECTE RADIOLOGICE
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• Aspecte particulare
Liza costala pleurezii de insotire/ metastatice
Noduli multiplii + condensari intinse uni/bilat
Localizari
Preferential plaman drept si lobii superiori
C.epidermoid si microcelular=central si periferic
Adenocarcinom=periferic
ASPECTE RADIOLOGICE
BRONHOLOGIC
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BRONHOLOGIC
• Muguri neoplazici
Netezi neuniformi vegetanti
Hemoragici necrozanti
• Infiltratie
Neregulata stenozanta
Disparitie cartilagii rigiditate bronsica
Bronhografic
Obstructie bronsica distala-amputare partiala/totala
-stenoza progresiva
-stenoza limitata cu bronsectazii in aval
ALTE EXAMENE
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ALTE EXAMENE
PARACLINICE• Angiopneumografia
Amputari compresii
Deplasari abolire de perfuzie
• Scintigrafia pulmonara I31 Tc99 Indiu 113
Amputari vasculare perfuzie in mozaic
Zone reci egale cu opacitatile (metastaze)
• Tomografia computerizata
Metoda neinvaziva de evaluare a extinderii tumorale
Asociere cu B.A.F.
• Esofagografia
Invazia mediastinala
EXAMEN HISTOLOGIC SI CITOLOGIC
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EXAMEN HISTOLOGIC SI CITOLOGIC
CONFIRMAREA DIAGNOSTICULUI• VSH
Crescut peste 50mm/ora80% din cazuri
nespecific
• Anemie normo sau hipocroma
• Markeri biologici
Antigen carcino-embrionar (ACE)
30% +
Enolaza neuronal specifica (NSE)80% + SCLC
30% + NSLC
• Anticorpi monoclonali
SINDROAME PARANEOPLAZICE
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SINDROAME PARANEOPLAZICE
FRECVENTA 2-20%
PRECED SAU INSOTESC C.B.P.DOMINA TABLOUL
CLINIC
MANIFESTARI FARA IDENTITATE NEOPLAZICA
TIPURI:
• Neurologice: neuropatia Denny-Brown
polinevrite senzitive/motoriisindroame cerebeloase
encefalomielopatii
• Musculare si cutanate
dermato si polimiozite
sd.psudomiastenice
acanthosis nigricans
SINDROAME PARANEOPLAZICE
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• Osteoarticulare
sd.Pierre –Marie-Bamberger
sd.reumatoidehipocratism digital
• Endocrine
sd.Cushing
hiper-tiroidism /paratiroidismsd.Schwartz-Bartter
ginecomastie
SINDROAME PARANEOPLAZICE
FRECVENTA 2-20%
PRECED SAU INSOTESC C.B.P.DOMINA TABLOUL
CLINIC
MANIFESTARI FARA IDENTITATE NEOPLAZICA
SINDROAME PARANEOPLAZICE
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• Hematologice
anemii
poliglobulii
purpura
reactii leucemoide etc.
• Vasculare
flebite superficiale recidivante
SINDROAME PARANEOPLAZICE
FRECVENTA 2-20%
PRECED SAU INSOTESC C.B.P.DOMINA TABLOUL
CLINIC
MANIFESTARI FARA IDENTITATE NEOPLAZICA
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Clasificarea T N M UICC 1988
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N-N0 =fara invazie ganglionara
-N1 =invazie ggl.homolaterali (hilari,peribronsici)-N2 =invazia ggl.carinali (anter.poster.)
mediastinali homolateral (frecv.paratraheali)
-N3 =ggl.mediastinali sau/si hilari controlateralisau ggl.supraclaviculari
Clasificarea T.N.M. UICC 1988
-pentru cancerele non small cells ,deoarece pentru cele cu celule mici
evolutia foarte rapida nu lasa timp de clasificare;
-permite stadializarea si abordarea relativ omogena a neoplasmelor
pulmonare
Clasificarea T.N.M. UICC 1988
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M
-M0 =metastazare absenta
-M1 =metastazare la distanta
Stadializare
Std. 0 –T1sNoMo
Std. I –T1NoMo;T2NoMoStd. II –T1N1Mo;T2N2Mo;T3No,1,2Mo
Std. III –A-T1N2Mo;T2N2Mo;T3No,1,2Mo
Std. IV –toate T toate N M1
C N U CC
-pentru cancerele non small cells ,deoarece pentru cele cu celule mici
evolutia foarte rapida nu lasa timp de clasificare;
-permite stadializarea si abordarea relativ omogena a neoplasmelor
pulmonare
DIAGNOSTICUL DIFERENTIAL
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DIAGNOSTICUL DIFERENTIAL
AL NB
•Cancerul periferic rotund
-metastaza unica pulmonara
-tuberculom
-granuloame infectioase (histoplasmoza,coccidiodomicoza,aspergilom)
-granuloame neinfectioase
-hematom-leziuni diverse(chist hidatic,pneumonie lipoida,
chist bronhogenic,infarct pulmonar rotund etc.)
continuare
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-continuare-• Cancerul centrohilar
-tuberculoza primara a adultului
-boala Hodgkin
-limfom non-Hodgkin
-tumori mediastinale
-sarcoidoza-adenopatii silicotice
• Cancer cu opacitate segmentara lobara
-pneumopatie acuta (diverse etiologii)
-tuberculoza
-pneumonii cronice
-infarct pulmonar
-atelectazii de diverse cauze
-continuare-
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• Cancer cavitar -abces pulmonar
-tuberculoza cavitara
-chist hidatic pulmonar
• Cancer bronsic cu pleurezie importanta
-toate tipurile etiologice de pleurezii
serofibrinoase,hemoragice sau chiloase
-continuare-
CONTRAINDICATII CHIRURGICALE
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CONTRAINDICATII CHIRURGICALE
IN NB.
• Semne de cancer nerezecabil
-metastaze la distanta ,inclusiv in plamanul controlateral-revarsat pleural persistent cu celule maligne +(sau-)
-afectare mediastinala (extensie directa sau metastaza limfatica)
Obstructia unei cave
Paralizia corzilor vocale prin afectarea nervului recurentCompresie sau invazie esofagiana
Paralizia hemidiafragmului
Adenopatie mediastinala controlaterala(cu histologie +)sau
supraclaviculara –laterocervicalaInfiltrarea peretelui traheal sau prinderea unei bronsii principale la
<2cm de carina (dupa unii,lez.rezecabila)
-neoplasm cu celule mici (scc)cu exceptia bolnavilor cu T1NoMo(posibil leziune chirurgicala)
CONTRAINDICATII CHIRURGICALE
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• Stare cardiaca
-insuficienta cardiaca necontrolata
-aritmii necontrolate
-infarct miocardic recent (3-6 luni)• Rezerva pulmonara mica
-PaO2<50mmHg sau PaCO2>50mmHg
CV<40%din valoarea anticipata
FEV1< 1l
-Pap < 35mmHg in repaus
CONTRAINDICATII CHIRURGICALE
IN NB.
ETIOLOGIA NPS
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ETIOLOGIA NPS
• Nodul malign aprox.40%
-carcinom bronsic-adenom bronsic
-leziune metastatica unica
• Nodul benign aprox.60%
-granuloame infectioase (tuberculom histoplasmoza,
coccidiodomicoza etc)
-granuloame neinfectioase (granulom reumatoid,
granulomatoza ,Wegener etc.)
-tumori benigne (hamartom etc)
-diverse (infarct pulmonar,fistula arterio-venoasa , leziuni de
amiloid ,pneumonie lipida ,chist bronhogenic etc)
METASTAZE
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METASTAZE• Ganglioni mediastinali 30-90%
• Ficat 30-50%• Ganglioni supraclaviculari 30-60%
• Pleurezii 5-30%
•Pulmonare 10-30%
• Cardio-pericardice 5-20%
• Cerebrale 20-30%
• Osoase 25-30%
• Renale 15-20%
• Subcutanate 1-5%
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PROGNOSTIC
NETRATAT 80-90% DECES SUB 1 AN
• Factori determinanti:
-tip histologic
-timp de dublare
-stadiul TNM
-stare clinico-biologica
-varsta/sex
• Microcelular –supravietuire 1-6 luni
• Nemicrocelular –dependent de stadiul TNM
• Epidermoid S II- III 10 % la 5 ani
• Indicele KARNOFSKY (1948)-capacitatea de activitate
-simptome
-nevoia de asistenta