daviT tvildianis samedicino universiteti

xelnaweris uflebiT

ekaterine barabaZe

BRAF mutaciis eqspresiis Taviseburebani farisebri

jirkvlis sxvadasxva tipis kvanZovani dazianebebis

dros

Mmedicinis akademiuri doqtoris xarisxis mosapoveblad warmodgenili

disertacia

samecniero xelmZRvaneli:

medicinis mecnierebaTa doqtori prof. giorgi burkaZe

Tbilisi 2018

1

sarCevi

disertaciis irgvliv gamoqveynebuli publikaciebis nusxa------------------------------------3

gamoyenebuli grafikebis sia---------------------------------------------------------------------------------------4

gamoyenebuli sqemebis sia--------------------------------------------------------------------------------------------5

gamoqveynebuli cxrilebis sia------------------------------------------------------------------------------------6

Sesavali-------------------------------------------------------------------------------------------------------------------------7

Tavi I. literaturis mimoxilva---------------------------------------------------------------------------------13

Tavi II. Kkvlevis masala da meTodebi----------------------------------------------------------------------- 50

Tavi III. sakuTari gamokvlevebis Sedegebi---------------------------------------------------------------- 56

Tavi IV. Ggamokvlevebis Sedegebis ganxilva------------------------------------------------------------- 84

daskvnebi --------------------------------------------------------------------------------------------------------------------- 92

praqtikuli rekomendciebi --------------------------------------------------------------------------------------- 94

gamoyenebuli literatura ---------------------------------------------------------------------------------------- 96

2

disertaciis irgvliv gamoqveynebuli publikaciebis nusxa

1. “farisebri jirkvlis paTologiebis ganawilebis Taviseburebani

saqarTveloSi sxvadasxva asakobriv jgufSi.Distribution of thyroid

pathologies in different age groups in Georgia“__Georgian Medical News, N-9(246),

seqtemberi 2015, gv 41-46.

2. “farisebri jirkvlis wvrilnemsiani aspiraciuli biofsiuri

masalebis diagnostikuri sirTuleebis da diagnostirebis daxvewili

principebis mimoxilva“,A „Accurate diagnosis of thyroid nodules:a review of

diagnostic dilemmas on thyroid fine-needle aspiration biopsies“__Georgian Medical News-

N-3(252), marti2016, gv 89-95.

3. “BRAF antisxeulis eqspresiis Taviseburebebi farisebri jirkvlis

sxvadasxxva tipis kvanZovani dazianebebisas“- „BRAF antibody expression in

the different types of thyroid nodular lesions”__Georgian Medical News_N10(271)

oqtomberi 2017, gv. 107-113. F

4. farisebri jirkvlis citopaTologiuri diagnostireba betesdas

sistemis mixedviT: saqarTveloSi warmoebuli hospitaluri kvleva-

studentebisa da axalgazrda mkvlevarebis mesame saerTaSoriso

konferencia, Tbilisi, saqarTvelo, 2015w.

5. farisebri jirkvlis paTologiebis morfomolekuluri diagnostika-

citologTa ormocdameerTe evropuli konferencia-madridi, espaneTi,

2018w.

3

gamoyenebuli grafikebis sia

grafiki 1. KurTierTkavSiri asakobriv jgufebsa da wvrilnemsiani

aspiraciuli biofsiiT miRebuli masalebis betesdas klasifikaciis

kategoriebs Soris----------------------------------------------------------------------------------------- 56

grafiki 2.urTierTkavSiri asakobriv jgufebsa da betesdas klasifikacia 1-

s Soris-------------------------------------------------------------------------------------------------------- 57

grafiki 3. keTilTvisebiani warmonaqmnebis Tanafardoba betesda 2

kategoriaSi-------------------------------------------------------------------------------------------------------59

grafiki 4. KurTierkavSirebi asakobriv jgufebsa da betesdas

klasifikaciiT meore klass(BN)-keTilTvisebian dazianebebs Soris---- 60

grafiki 5.Bbetesda 3 kategoriis histologiuri Sefasebis Semdgomi

monacemebi----------------------------------------------------------------------------------------------------------64

grafiki 6. KurTierkavSirebi asakobriv jgufebsa da betesdas

klasifikaciiT mesame klass-AUS ganusazRvreli atipiis mqone dazianebebs

Soris---------------------------------------------------------------------------------------------------------------- 65

grafiki 7. urTierkavSiri asakobriv jgufebsa da betesdas klasifikaciiT

meoTxe klass-folikulur neoplaziebs Soris------------------------------------------- 67

grafiki 8. KurTierkavSiri asakobriv jgufebsa da betesdas klasifikaciiT

mexuTe klass-saeWvo avTvisebianobaze dazianebebs Soris---------------------------70

grafiki 9. Bbetesda 6 kategoriis histologiuri Sefasebis Semdgomi

monacemebi----------------------------------------------------------------------------------------------------------72

grafiki 10. KurTierkavSiri asakobriv jgufebsa da betesdas klasifikaciiT

meeqvse klass-avTvisebian dazianebebs Soris----------------------------------------------- 73

grafiki 11. BRAF antisxeulis eqspresiasa da farisebri jirkvlis

histotipebs Soris arsebuli urTierkavSiri---------------------------------------------- 76

4

gamoyenebuli sqema

sqema 1.Mmsoflio jandacvis organizaciis mier aRiarebuli farisebri

jirkvlis aramedularuli kibos 2017 wlis modificirebuli versia-------- 25

5

gamoyenebuli cxrilebis sia

cxrili 1.antisxeulTa eqspresiasa da farisebri jirkvlis sxvadasxva

kvanZovan dazianebebs Soris arsebuli korelaciebi------------------------------------------

---------------- 74

cxrili 2.korelaciebi BRAF mutaciis eqspresiasa daHBME-1, CK-19, KI-67 CD-

56, TTF-1eqspresias Soris---------------------------------------------------------------------------75

6

Sesavali

farisebri jirkvlis kibo yvelaze xSiri endokrinuli simsivnea(1).

msoflios masStabiT aRiniSneba axali SemTxvevebis yovelwliuri zrda da

amave dros, matulobs axladdiagnostirebuli SemTxvevebis procentuli

maCvenebelic(2). daavadebaTa kontrolis erovnuli centris(NCDC)

monacemebze dayrdnobiT, saqarTveloSiKkibos populaciuri registris 2015

wlis monacemebis mixedviT farisebri jirkvlis kibom me-2 adgili daikava

qalebSi registrirebuli yvela lokalizaciis kibos axal SemTxvevebSi.

amave monacemebze dayrdobiT, farisebri jirkvlis kibos axali

SemTxvevebis raodenoba, mozard gogonebSi pirvel adgils, xolo mozard

biWebSi meore adgils ikavebs(3). msoflio statistikiT farisebri jirkvlis

kibos gansakuTrebuli zrda aRiniSna, xolo maTi ZiriTadi umetesoba

klasikur papilarul karcinomaze modis(1).Kkibos statistikisTvis Zalian

mniSvnlovania is faqtic, Tu romel asakobriv jgufSi xdeba misi

gamovlena, vinaidan calkeuli simsivnuri SemTxvevebisTvis Camoyalibda

modeli, romliTac ganisazRvreba kibos latenturoba (4). asaki, iseve

rogorc, simsivnis zoma, mniSvnelovani faqtoria riskis gansazRvrisTvis,

magaliTad, 1 sm zomis kvanZi axalgazrda asakSi atarebs ganxvavebul risks

amave zomis kvanZisagan 70 wlis asakSi, latenturi periodi mokleaa

axalgazrda asakSi, Sesabamisad zrdis sixSire maRalia, maRalia

metastazirebis koeficientic. sakmaod vrcelma kvlevam (5) gviCvena, rom

mikrokarcinomebis SemTxvevaSi, metastazirebis riski ufro maRalia

axalgazrda asakobriv jgufebSi, vidre xandazmul asakSi. A

miuxedavad imisa, rom wina wlebTan SedarebiT samedicino momsaxurebaze

xelmisawvdomoba gaizarda, gaumjobesda diagnostikis meTodebi,

SesaZlebeli gaxda maRalteqnologiuri aparaturiT kibos adreuli

7

gamovlena da amave dros, gaumjobesda mkurnalobis taqtika, SemuSavda

axleburi midgomebi, aRniSnuli daavadebiT sikvdilianobis maCvenebelma

mainc imata(0,8-1,5%)(6,7).

Tanamedrove Sexedulebebze dayrdnobiT, mcire zomis simsivneTa

umravlesoba saSiSroebas ar warmoadgens Semdgomi progresiis mxriv(8),

Tumca unda aRiniSnos isic, rom aseTi simsivneebis nawili mainc

progresirebs, da miuxedavad imisa, rom farisebri jirkvlis kibo, sxva

simsivneebTan mimarTebaSi, ufro keTilsaimedo prognoziT xasiaTdeba,

pacientebis 10-15% aReniSnebaT daavadebis agresiuli forma, rac

Sesabamisad sikvdilianobis ricxvis matebasTan asocirdeba(9).

genetikuri da garemo faqtorebi mniSvnelovan rols TamaSobs farisebri

jirkvlis kibos ganviTarebaSi, magram gansakuTrebiT didi mniSvneloba

eniWeba iodis deficits, rogorc daavadebis ZiriTad risk faqtors,

gansakuTrebiT ki iseT endemur zonebSi, rogoric saqarTveloa. zemoT

xsenebuli kibos ricxvis gansakuTrebuli mateba aRiniSna axalgazrda

asakSi, kerZod, axalgazrda gogonebSi. amasTan mimarTebaSi

gasaTvaliswinebeli xdeba maionizirebeli radiacia, rogorc farisebri

jirkvlis kibos gamomwvevi ZiriTadi risk faqtori, vinaidan axalgazrda

asakSi farisebri jirkvlis qsovili gansakuTrebiT mgrZnobiarea

maionizirebeli radiaciis mimarT. aRniSnul faqtze dayrdobiT,

mniSvnelovania ganisazRvros sxvadasxva asakobriv jgufSi kvanZovani

dazianebis arsebobis albaToba, SeZlebisdagvarad gaimijnos erTmaneTisgan

qirurgiuli da Terapiuli paTologiebi, agreTve, aRniSnul kvanZovan

dazianebebSi Sefasdes avTvisebianobis riski da Sesabamisad, sworad

ganisazRvros Semdgomi mkurnaloba.

farisebri jirkvlis kvanZovani dazianebebis arsebobisas wvrilnemsiani

aspiraciuli biofsiuri masalis citologiuri kvleva principulad

rekomendirebuli diagnostirebis meTodia(10) da aRniSnuli dazianebebis

swori marTvisTvis “ oqros standartadac” ki iwodeba(11). wvrilnemsiani

aspiraciuli biofsiuri masalis citologiuri kvleva SesaZlebelia

8

warvmarToT msoflio jandacvis organizaciis mier aRiarebul

klasifikacia - betesdas klasifikaciaze dayrdnobiT(The Bethesda System for

Reporting Thyroid Cytology(TBCRTC), romelic eqvsi ZiriTadi qvekategoriisagan

Sedgeba da erTgvar xids warmoadgens citopaTologs, klinicists,

radiologsa da qirurgs Soris urTierTobisTvis. aRniSnuli sistema

avTvisebianobis riskis gansazRvris idealur stratificirebis saSualebas

iZleva, magram, miuxedavad imisa, rom umetes SemTxvevebSi am sistemaze

dafuZvnebuli citopaTologiuri Sefaseba natifi da daxvewilia,

citopaTologiuri diagnozebis erTi mesamedi mainc xvdeba gaurkvevel,

rogorebicaa ganusazRvreli mniSvnelobis atipia(AUS-Atypia Undeterminated

Significance) an ganusazRvreli mniSvnelobis folikuluri dazianebebi(FLUS-

Follicular Lesions of Undeterminated Significance) kategoriaSi(12). aRniSnuli

kategoriebis menejmenti klinikur dilemas warmoadgens(13). Bbevri maTganis

mimarT midgoma qirurgiulia, iTvaliswinebs ra avTvisebianobis risks

aRniSnul kategoriebSi, romelic arc Tu ise dabalia Tanamedrove

kvlevebze dayrdnobiT (14,15). ganusazRvreli atipiis mqone

kategoriebSi(AUS/FLUS) molekuluri testebi mniSvnelovan diagnostikur

berkets warmoadgenen(16).

magram ismis mniSvnelovani kiTxva, Tu ra faqtori ganapirobebs swored

dabal asakobriv jgufSi kibos da kerZod, papiluri kibos ganviTarebas,

xom ar arsebobs gansakuTrebuli genetikuri mutaciebi, romlebic zrdis

swored am tipis kibos ganviTarebis albaTobas. calkeuli kvlevebi

Catarda Cernobilis cnobil afeTqebasTan dakavSirebiT, 4-10 wliani

intervalis Semdgom aRiniSna papiluri karcinomebis riskis mateba

axalgazrda asakobriv jgufSi (18). sporaduli papiluri karcinomis

SemTxvevebSi aRiniSna erTerTi ZiriTadi antigenis Ret an BRAF antigenis

mutacia. radiaciul karcinogenezTan ufro SeWidulad gvevlineba Ret geni

(19,20,21) Tumca kvlevebma cxadyo, rom Cernobilis afeTqebis Semdgom moxda

umeteswilad BRAF antigenis gaaqtiureba(17). swored am faqtze dayrdobiT,

Zalian mniSvnelovan safuZvlad gvevlineba am kuTxiT damatebiTi kvlevebis

9

warmoeba. vinaidan BRAF mutacia papiluri kibos tumorogenzSi

mniSvnelovan rols TamaSobs, misaRebi xdeba is azri, rom es mutacia

gansazRvravs am tipis kibos klinikur da paTologiur qcevas da Tamamad

SegviZlia miviCnioT novatorul prognozul markerad(23,24).

farisebri jirkvlis kvanZovani dazianebebisas molekuluri testebis

gamoyenebis mimarT mzardi interesi iTvaliswinebs BRAF mutacias, rogorc

papiluri karcinomis genetikuri profilis ZiriTad

maxasiaTebels(22,25).BBRAF antisxeulis pozitiurobis gamovlena

SesaZlebelia warmatebiT iqnes gamoyenebuli papiluri karcinomis ara

mxolod sadavo SemTxvevebis diagnostirebaSi, aramed, rogorc prognozuli

markeri, radganac swored am mutaciis arseboba papiluri karcinomebis

SemTxvevaSi Seesabameba arakeTilsaimedo prognozul maxasiaTeblebs,

rogorebicaa multicentruloba, eqstraTireoiduli gavrceleba da

limfur kvanZebSi metastazireba(26,27,28).

sxvadasxva riskis mqone papiluri kiboTi daavadebulTa riskis sworad

Sefasebam preoperaciulad SesaZlebelia srulad gansazRvros

Tireoideqtomiis farTobi da limfuri kvanZebis diseqciis masStabi(29).

papiluri mikrokarcinomebis SemTxvevaSi BRAF antigeni naklebad vlindeba,

Tumca gamovlenis SemTxvevaSi, aRniSnuli kibo agresiuli mimdinareobiT

xasiaTdeba. Sesabamisad im pacientebTan mimarTebaSi, romlebsac

mikrokarcinomebis SemTxvevaSi aReniSnaT BRAF antisxeulis eqspresia

aucilebeli xdeba aduvanturi mkurnalobis, radiaqtiuli iodiT ablaciis,

totaluri Tireoideqtomiis da limfodiseqciis Catareba (30). aRniSnuli

sakiTxi ki gansakuTrebiT aqtualuria dResdReobiT, vinaidan

mikrokarcinomebis menejmenti sayovelTao davis da azrTa sxvadasxvaobis

mizezs warmoadgens (31).

2016 wels ganxorcielebuli reklasificirebis safuZvelze papiluri

karcinomis folikuluri variantis invaziuri forma (IFVPTC-Inlarvasive

Follicular Variant of Papillary Thyroid Carcinoma) gaimijna arainvaziuri formisgan da

10

es ukanaskneli iwoda, rogorc arainvaziuri folikuluri neoplazia

papiluri karcinomis msgavsi birTvuli cvlilebebiT (NIFTP-noninvasive

follicular thyroid neoplasm with papillary-like nuclear features)(149). Sesabamisad BRAF

mutaciis statusis gansazRvra am tipis dazianebebis sadifereniaciod

gansakuTrebiT mniSvnelovani xdeba pacientis Semdgomi menejmentisTvis.

mniSvnelovania ganisazRvros BRAF antisxeulis gamovlena farisebri

jirkvlis kvanZovani dazianebebisTvlis damaxasiaTebel ukve kargad

adaptirebul antisxeulebTan mimarTebaSic. kerZod, HBME_1, CK-19, CD-56,

TTF-1 da KI-67-Tan mimarTebaSi. Aaucilebelia Sefasdes maTi Tanaeqspresiis

albaToba da sixSire, ganisazRvros Tu rogor SeiZleba icvlebodes maTi

Tanaeqspresia keTilTvisebian, mosazRvre da avTvisebian formebs Soris,

aseve Sefasdes, Tu rogor icvleba maTi Tanaeqspresia kibos agresiulobis

zrdasTan erTad.

zemoTxsenebuli miznis misaRwevad davsaxeT Semdegi amocanebi:

-wvrilnemsiani aspiraciiuli biofsiis diagnostireba betasdas

klasifikaciis mixedviT, betestas klasifikaciis TiToeuli kategoriis

gamovlenis albaToba sxvadasxva asakobriv jgufSi.

-farisebri jirkvlis kvanZovani dazianebebis citopaTologiuri da

histopaTologiuri korelaciebis gamovlena.

-farisebri jirkvlis paTologiebis fenotipuri maxasiaTeblebis gamovlena

-farisebri jirkvlis kvanZovani dazianebebis SemTxvevaSi betesdas

klasifikaciiT avTvisebianobis riskis gamovlena

-BRAF mutaciis eqspresiis gamovlena farisebri jirkvlis sxvadasxva

paTologiebis dros.

aRniSnuli kvleva saSualebas mogvcems farisebri jirkvlis kvanZovani

dazianeba Sefasdes mravalwaxnagovan WrilSi, ganisazRvros asakobrivi

Taviseburebebi da avTvisebianobis riski TiToeul asakobriv jgufSi,

gamovlindebs farisebri jirkvlis paTologiaTa fenotipuri

11

maxasiaTeblebi da BRAF mutaciis gadanawilebis Taviseburebebi sxvadasxva

paTologiebis dros. farisebri jirkvlis kvanZovani dazianebebis erTian

WrilSi gaanalizeba saSualebas mogvcems dResdReobiT metad aqtualuri

problemis klinikuri marTvisa da dagegmarebisTvis.

12

Tavi I. literaturuli mimoxilva

1.1. farisebri jirkvlis kibos gavrceleba da misi ganviTarebis risk-

faqtorebi

farisebri jirkvlis kibo yvelaze xSiri endokrinuli simsivnea(32).

aRsaniSnavia, farisebri jirkvlis kibos raodenobrivi zrda sxva organoTa

avTvisebian simsivneTa mimarTebaSic(33). daavadebaTa kontrolis erovnuli

centris(NCDC) monacemebze dayrdnobiT, saqarTveloSiKkibos populaciuri

registris 2015 wlis monacemebis mixedviT farisebri jirkvlis kibom me-20

adgilidan(200-wels) me-2 adgili daikava qalebSi registrirebuli yvela

lokalizaciis kibos axal SemTxvevebSi. 2015 wels qalebSi

registrirebulia farisebri jirkvlis kibos 591 axali SemTxveva,

incidentobis maCvenebeli 100000 qalze -30,5. qalebSi farisebri jirkvlis

kibo registrirebulia TiTqmis yvela asakobriv jgufSi. amave monacemebze

dayrdobiT, farisebri jirkvlis kibos axali SemTxvevebis raodenoba,

mozard gogonebSi pirvel adgils, xolo mozard biWebSi meore adgils

ikavebs.

amerikis kibos asociaciis 2013 wlis monacemebze dayrdnobiT(34), kibos

60220 axali SemTxveva dafiqsirda da aRniSnuli daavadebiT 1850 adamiani

gardaicvala. farisebri jirkvlis kibos axali SemTxvevebis zrda

gansakuTrebiT aRsaniSnavi gaxda qalebSi, magaliTad, Tu SevadarebT 1935

wlis monacemebs, romelic im droisTvis, yovel 100000 qalze 1,3%

Seadgenda, 2013 wlis monacemebiT es maCvenebeli 16,3%-mde gaizarda. Bbolo

monacemebze dayrdnobiT, farisebri jirkvlis kibo qalebSi sikvdilianobis

mixedviT mexuTe adgilzea msoflios maStabiT, xolo italiaSi ki 45

wlamde asakis qalebSi mesame adgils ikavebs(35).

genetikuri da garemo faqtorebis gavlena farisebri jirkvlis kibos

ganviTarebaze advilad xsnis axali SemTxvevebis arsebobis albaTobas

13

geografiuli mdebareobis da eTnikuri jgufebis mixedviT. Ggansvaveba ki

aTjer aRemateba garkveul geografiul areSi da eTnikur jgufSi (36).

genetikuri darRvevebi, magaliTad, rogoricaa ojaxuri adenomatozuri

polipozi, gardneris daavadeba, kaudenis daavadeba da kornei kompleqsi I

tipi papilaruli da folikuluri karcinomis ganviTarebis risk

faqtorebad gvevlinebian. Ggardneris sindromi PTEN genis mutaciiT

ganisazRvreba, xolo kornei kompleqsi I tipi ki UukavSirdeba PRKR1A genis

defeqts. Tu genetikuri kvlevebiT genetikuri darRvevis idenTificireba

ver xerxdeba, pirveli rigis naTesavebSi, rogorebicaa da-Zmebi da ded-mama

farisebri jirkvlis kibos arseboba riskis mniSvnelovan faqtorad

SeiZleba miviCnioT. Mmeduluri karcinoma ki RET genis Tandayolil

mutacias ukavSirdeba(37).

farisebri jirkvlis kibos ganviTarebis kargad cnobil risk faqtorad

maionizirebeli radiacia gvevlineba(38). aRniSnuli organo gansakuTrebiT

radiosensitiuria axalgazrda asakSi, Sesabamisad, es asakobrivi jgufi

daavadebis axali SemTxvevebis gamovlenis samizned iTvleba. Aam mxriv didi

mniSvneloba eniWeba bavSvTa asakSi Tav-kisris midamos dasxivebas, rogorc

wesi, riski izrdeba radiaciis maRali dozebis da dabali asakis mixedviT.

aRsaniSnavia isic, rom gasul wlebSi bavSvTa asakis zogierT daavadebas,

rogoricaa sokovani daavadeba, akne, gadidebul tonzilebs da adenoidebs

dasxivebiT mkurnalobdnen, ra Tqma unda riski am SemTxvevaSi izrdeboda.

riskis zrda aRiniSneba im bavSvebSic, romlebmac Caitares sxivuri Terapia

limfomebis, vilmsis simsivnis da neiroblastomis gamo. rendgenologiuri

da CT kvlevebic, garkveul risk-faqtorad SegviZlia miviCnioT.

radiaqtiuli afeTqebebi mniSvnelovnad zrdis risks, magaliTad, 1986 wels

Cernobilis atomuri sadguris afeTqebam gamoiwvia axali SemTxvevebis

mateba ara marto aRniSnul regionSi, aramed, mimdebare regionebSic(38).

iodis deficiti farisebri jirkvlis kibos ganviTarebis erTerTi yvelaze

mniSvnelovani faqtoria. is iwvevs sisxlSi momatebil Tireoid

mastimulirebeli hormonis(TSH)-is dones, romelic Tavis mxriv farisebri

14

jirkvlis folikuluri ujredebis zrdis ZiriTad faqtorad gvevlineba.

dResdReobiT kvebismieri ioddeficiti msoflio maStabiT 2 miliard

adamianze mets aReniSneba, rac sayovelTao jandacvis problemadac ki

gvevlineba. Tumca unda aRiniSnos is faqtic, rom mas Semdeg, rac

xelovnurad ganxorcielda iodis Canacvleba, imata hiperTireoziT

daavadebulTa raodenobamac, rac Semdgom iodinducirebuli

Tireotoqsikozis da autoimunuri mravalkvanZovani Ciyvis ganviTarebis

mizezi gaxda. Aam faqtze dayrdnobiT, mniSvnelovania moxdes iodis dabali

da maRali doneebis monitoringi. iodis efeqti dakavSirebulia

Tireoglobulinis Sinagan maxasiaTeblebTan, konkretulad ki, misi

modifikacia inducirdeba posttranslaciuri iodinaciiT. Ggenetikuri

mzaobis SemTxvevaSi ki iodi inducirebas ukeTebs autoimunur process,

radganac iwvevs Tireoglobulinis kriptuli epitopis anmaskirebas. Tavis

mxriv, autoimunuri procesi asocirdeba papilaruli karcinomis momatebul

riskTan, anu anTebiTi procesi safuZvels udebs malignantur

trasformacias, rac aRsaniSnavia sxva organoTa simsivneTa Camoyalibebis

drosac. Hhistologiur monacemebze dayrdnobiT, limfocituri

infiltraciis arsebobahaSimotos Tireoiditis ZiriTadi maxasiaTebelia,

Tumca papilarul karcinomas, autoimunuri procesis gareSec, SeiZleba Tan

axldes limfocituri infiltraciebis arseboba, rac Tavis mxriv simsivnur

procesze imunuri pasuxiT aris ganpirobebuli(39).

1.2. wvrilnemsiani aspiraciuli biofsia(FNA-biofsia)-wamyvani meTodi

farisebri jirkvlis kvanZovani dazianebebis citologiuri

kvlevisTvis

farisebri jirkvlis kvanZovani dazianebebis citologiuri Sefasebis

mizniT wvrilnemsiani aspiraciuli biofsiis(FNA-biofsiis) warmoeba

upirveles diagnostikur meTodad gvevlineba(40). Ppirvelad es meTodi

15

gamoyenebul iqna 1930 wels martin da elis mier niu iorkis memorialur

hospitalSi, Tumca momdevno wlebSi miiCnies, rom meTodi SezRuduli

diagnostikuri SesaZleblobebiT xasiaTdeboda, ris gamoc zemoT aRniSnul

hospitalSi misi warmoeba Sewyda. aRniSnuli faqtis gamo meTodma Sewvita

amerikaSi Semdgomi ganviTareba da momdevno 50 weli arc Catarebula.

Tumca 1980 wels, maSin roca skandinavielma mkvlevarebma kvlav aRiares

meTodis maRaldiagnostikuri Rirebulebebi, amerikaSi axal kvlevebs

Caeyara safuZveli, romlebic mileris da hamburgeris mier iqna

warmoebuli. dResdReobiT es meTodi farTod aris danergili msoflios

masStabiT da farisebri jirkvlis kvanZovani dazianebebis marTvis ZiriTad

diagnostikur saSualebad gvevlineba(41).

farisebri jirkvlis kvanZovani dazianebebis marTva, pirvel rigSi,

xorcieldeba saTanado klinikuri SefasebiT (bioqimiuri, imunologiuri,

radioizotopuri da ultrasonografiuli manacemebis mopovebiT)(42).

Semdgomi FNA-biofsiis warmoeba igegmeba swored am monacemebze

dayrdnobiT. farisebri jirkvlis kvanZovani dazianebebis citologiuri

kvleva xSir SemTxvevebSi avTvisebiani dazianebis gadaWriT diagnostirebis

saSualebas iZleva. Mmisi saSualebiT SesaZlebelia erTmaneTisagan

gavmijnoT Terapiuri da qirurgiuli paTologiebi, procedura amcirebs

keTilTvisebiani warmonaqmnebis SemTxvevaSi arasaTanado qirurgiuli

Carevebis ricxvs da dResdReobiT upirveles preoperaciul skrining

testad gvevlineba(43). wvrilnemsiani aspiraciuli biofsia xorcieldeba

ultrabgeriTi kontroliT, rac amcirebs araadeqvaturi masalebis

raodenobas da diagnostirebas ufro srulfasovans xdis(44).

wvrilnemsian aspiraciuli biofsiis warmoebas ultrasonografiuli

kontroliT dResdReobiT didi diagnostikuri Rirebuleba aqvs, raTa

SevarCioT pacientebi farisebri jirkvlis avTvisebiani

dazianebiT(sensitiuroba), gamovricxoT pacientebi, romlebsac ar

aReniSnebaT avTvisebiani dazianeba(specifiuroba), winaswar ganvsazRvroT

kibos arseboba/ ararseboba(dadebiTi da uaryofiTi savaraudo maCvenebeli).

16

aRniSnuli meTodis mgrZnobeloba 65-98% Seadgens, xolo specifiuroba 72-

100% -iT ganisazRvreba, kibos aRmoCenis cru dadebiTi SemTxvevebis ricxvi

0-7%-ia, cru uaryofiTi SemTxvevebis sixSire ki 1%- dan 11%-mdea(45,46).

FNA-biofsiis upiratesobebi:

1. meTodi martivi, swrafi, dabali Rirebulebisaa da moklebulia

mniSvnelovan proceduris Semdgom garTulebebs(40).

2. saSualebas iZleva ufro swrafad da srulfasovnad moxdes

kvanZovani dazianebebis diagnostireba, vidre es miiRweva romelime

sxva klinikuri da laboratoriuli testiT an maTi kombinaciiT(42).

unda aRiniSnos isic, rom wvrilnemsian aspiraciuli biofsiuri masalis

citologiur kvlevas gaaCnia SezRudvebic, kerZod, arasakmarisi/

araadeqvaturi masalis arseboba Semdgomi citologiuri kvlevisvis.

proceduris mTavar garTulebad ki SeiZleba CaiTvalos sisxlenis

ganviTareba calkeul SemTxvevebSi, romelic SemdgomSi didi hematomis

Camoyalibebas iwvevs, rac Tavis mxriv traqeis kompresias da

respiratorul distress ganapirobebs(44).

1.3. betesdas klasifikacia

dResdReobiT wvrilnemsiani aspiraciuli biofsiuri masalis

citologiuri kvleva srulad eqvemdebareba msoflio jandacvis

organizaciis mier aRiarebul klasifikaciis sam sistemas: amerikis

SeerTebul StatebSi aRiarebul betesdas klasifikacias(The Bethesda

System for Reporting Thyroid Cytology)-(TBCRTC), inglisur da italiur

klasifikaciebs(SIAPEC-AIT)(47). wvrilnemsiani aspiraciuli biofsiiT

miRebuli citologiuri masalebis Sesafaseblad, terminologiebisa da

kriteriumebis SesaTanxmeblad 2007 wels marilendSi kibos

nacionalurma institutma(NCI) umaspinZla Sexvedras, sadac betesdas

17

cnobili sistemis ZiriTadi monaxazi Camoyalibda. betesdas

klasifikaciam gansakuTrebiT didi aRiareba hpova, ris gamoc mravali

qveyana diagnostirebas am sistemis mixedviT awarmoebs. Bbetesdas

sistemis warmodgenis Semdgom SemuSavda citologiuri diagnostirebis

standartuli sqema. dResdReobiT betesda ara marto klasifikaciis

sistemaa, aramed gvaZlevs saSualebas SevimuSaoT mkveTri kriteriumebi

citologiur diagnostikaSi, TiToeul diagnostikur kategoriaSi

gansazRvravs avTvisebianobis risks, iZleva rekomendaciebs pacientis

Semdgomi menejmentisTvis. Bbetesdas sistema saukeTeso da advilad

gasagebia, ris gamoc is erTgvar xids warmoadgens citopaTologsa da

klinicists Soris urTierTobisTvis(48).

Bbetesdas sistema Sedgeba eqvsi ZiriTadi kategoriisagan:

1. araadeqvaturi/aradiagnostirebadi masalebi. es kategoria

gansazRvravs, rom biofsiiT miRebuli masala araadeqvaturia

citopaTologiuri SefasebisTvis, vinaidan Seicavs didi raodenobiT

eriTrocitebs, arasaTanadod aris fiqsirebuli,

gamomSralia(fiqsaciasTan dakavSirebuli problemebi), nacxi sqelia

an folikuluri ujredebis raodenoba ar Seesabameba

diagnostirebisTvis aucilebel raodenobas(TiTeuli pacietis masala

unda Seicavdes 5-10 ujredisgan Semdgar aranakleb 5-6 jgufs).

ultrabgeriTi kontroliT warmoebuli ganmeorebiTi biofsiuri

kvleva 50-80% SemTxvevaSi iZleva diagnostikuri Rirebulebis mqone

citologiur masalas(49).

es kategoria diagnostikur kategoriaTa 2-20%-s Seadgens,

malignantobis riski ki aseT masalebSi 1-8%-ia. damatebiT am

monacemebze, kvleva(50), romelic warmoebul iqna Akgül et al.-is mier

gvamcnobs, rom aranairi kavSiri avTvisebianobas, kvanZis diametrs da

klinikur monacemebs(asaki, sqesi, jirkvlis hormonalur statusi)

Soris ar arsebobs, xolo araadeqvatur masalebSi malignantobis

sixSire 12, 6% warmoadgens. Ali et.al.-ismierwarmoebuli kvleva (51)

18

gvauwyebs, rom wvrilnemsiani aspiraciuli biofsiiT miRebuli

masalaTa ricxvi, romlebic Sefasda araadeqvaturi diagnostikuri

kategoriis mixedviT, 10%-s ar unda aRematebodes. betesdas

klasifikacia ar iTvaliswinebs am kategoriaSi malignantobis riskis

gansazRvras, Tumca unda aRiniSnos, rom es kategoriac aris

garkveuli riskis mtarebeli, kvlevis mixedviT Payal Mahra et.al (52) is

daaxloebiT 8,9% Seadgens.

2. betesdas sistemis meore kategoria keTilTvisebian dazianebebs

aerTianebs. farisebri jirkvlis kvanZovani dazianebebisas

keTilTvisebiani procesebi 60-75%-Si fiqsirdeba. Ekategoria

aerTianebs: koloidur kvanZebs, autoimunur (haSimotos) da

granulomatozur (anu qvemwvave an de quarveinis Tireoiditebs),

kvanZovan Ciyvs kistozuri degeneraciebiT, ridelis Tireoidits.

aRniSnuli kategoria pacients icavs arasasurveli qirurgiuli

Carevisagan da mas Semdgomi dakvirvebisa da monitoringis jgufSi

aTavsebs. vinaidan am kategoriaSi moxvedril diagnozebs Soris cru

uaryofiTi SemTxvevebis riski dabalia (daaxloebiT 1-3%),

rekomendirebulia mxolod ultrabgriTi kontroli 6-8 Tviani

intervaliT(53). kvlevaSi (54), warmoebuli Mondal et.al.-is mier aRmoCnda,

rom kvanZovani dazianebebis 87,5% keTilTvisebiania, Sefasda ra

betesdas klasifikaciaze dayrdnobiT. Tumca kvlevebma (91)

warmoebuli Park et.al.-is mier aCvena, rom mxolod 40, 6%

warmonaqmnebisa SeiZleba Sefasdes keTilTvisebianad.

3. ganusazRvreli mniSvnelobis atipia an folikuluri dazianebebi

ganusazRvreli mniSvnelobis atipiiT. Eam kategoriaSi

citomorfologiuri diagnozebis arsebobis albaToba 3,2%-dan 29%-

mde meryeobs(91). betesdas kategorizaciiT, am kategoriaSi

ganTavsebul masalaTa raodenoba, sasurvelia ar scdebodes

SemTxvevaTa 7%-s, Tumca literaturaSi ar iZebneba aranairi

damadasturebeli informacia imis Sesaxeb, rom es kategoria 7%-s ar

19

unda aRematebodes(56). Shi et al (57) Tavis kvlevebiT asabuTebs, rom

diagnostikuri kategoria 3 (atipia ganusazRvreli) -is gamoricxva

betesdas klasifikaciidan, Seamcirebs wvrilnemsiani aspiraciuli

biofsiis, rogorc diagnostikuri testis mgrZnobelobas, gazrdis

cru uaryofiT da cru dadebiTi SemTxvevebis albaTobas.

masalebi, romlebic aRniSnul kategorias ganekuTvnebian Seicavs didi

raodenobiT ujredebs da mcire raodenobiT koloids, agreTve, atipiur

limfocitur infiltraciebs, ujredTa konturebi araTanabaria, aRiniSneba

msubuqi anizokariozi da hiperqromia, erTeul ujredebSi vlindeba

qromatinis araTanabari struqtura, Tumca Semdgomi histomorfologiuri

kvleviT, am jgufSi moxvedrili masalebis 80% keTilTvisebiania da

mxolod 20% SemTxvevebSi vlindeba avTvisebiani dazianeba, es jgufi

avTvisebianobis maRali riskis mtareblad gvevlineba. aRniSnul jgufSi

moxvedrili SemTxvevebis menejmenti efuZneba Semdgom xSir monitorings(3-6

Tviani intervalebiT) an qirurgiul Carevas lobeqtomiiT, klinikuri,

genetikuri,ultrasonografiuli monacemebis gaTvaliswinebiT(58).

Tanamedrove kvlevebi betesda 3 kategoriSi avTvisebianobis maRal

maCveneblebze migviTiTeben. kvlevaSi warmoebuli Kim et.al-is mier betesdas 3

kategoria (AUS) daajgufes qvekategoriebad: 1. AUS- birTvuli atipiiT 2.

AUS-arqiteqtonikuli atipiiT 3. AUS- gamokveTili onkocituri

cvlilebebiT. 4. AUS- birTvuli da arqitetonikuli atipiiT. aRniSnuli

kvlevis Sedegebze dayrdnobiT gamovlinda avTvisebianobis riskis sakmaod

maRali maCvenebeli(36%). Yqvekategoriebidan ki yvelaze maRali riski

aRiniSna AUS- birTvuli atipiiT qvekategoriaSi (65,8%).

vinaidan avTvisebianobis xarisxi zemoT aRniSnul kategoriaSi sakmaod

maRalia, es kategoria klinikuri dilemis winaSe gvayenebs, xSirad sakiTxi

dgeba qirurgiuli CarevisTvis, Tumca am kategoriaSi moxvedrili kvanZebis

didi nawili keTilTvisebian dazianebebs Seesabameba. Mmolekuluri

diagnostika, kerZod ki BRAF mutaciis gansazRvra, am SemTxvevaSi idealur

20

saSualebad gvevlineba. KTanamedrove kvlevaze dayrdobiT(59), romelic 227

iseT citologiur masalaze, romlebic AUS kategoriad iyo Sefasebuli,

aRmoCnda, rom genetikuri testirebis Semdgom citologiuri masalebi,

romlebSic mxolod arqiteqtonikuli atipia aRiniSneboda, avTisebianobis

arsebobis ufro dabali riski hqondaT(19%), vidre im citologiur

masalebs, romlebSidac citologiuri atipia(57%), an citologiuri da

arqiteqtonikuli atipia(45%) erTad aRiniSneboda. aRniSnul monacemebze

dayrdbiT AUS kategoriis arsebobisas gaTvaliswinebuli unda iqnes

citologiuri atipia, operaciuli dagegvmis dros swored aseT pacientebs

mieceT upiratesoba, citomorfologiur monacemebTan erTobliobaSi

sasurvelia Sefasdes genetikuri dazianebebis arseboba.

4. betesdas sistemiT meoTxeKkategoria folikuluri neoplazia an

saeWvo folikulur neoplaziaze. Tumca wvrilnemsiani aspiraciuli

biofsiuri masalis citologiuri kvleva umetes SemTxvevebSi

srulfasovnad gamijnavs avTvisebian da keTilTvisebian dazianebebs,

am meTods bolomde ar ZaluZs gaavlos mkveTri diagnostikuri

zRvari folikulur karcinomas, papilaruli karcinomis folikulur

variants, folikulur adenomasa da solidur

hiperplazias(adenomatozur) kvanZebs Soris(60,61). am faqtze

dayrdobiT, biofsiuri masalis citomorfologiuri interpretacia

umjobesia moxdes, rogorc saeWvo folikuluri neoplaziaze, xolo

am tipis dazianebebis marTva ganxorcieldes qirurgiulad,

diagnostikuri lobeqtomiiT. qirurgiuli Carevis Semdgom aseTi

kvanZebis histomorfologiuri diagnozi Seesabameba folikulur

adenomas an adenomatozur hiperplazias da mxolod 15-30%

SemTxvevebisa warmoadgens avTvisebian dazianebebs, romelTa

umetesoba histomorfologiurad Sefasdeba, rogorc, folikuluri

karcinoma, an papilaruli karcinomis folikuluri varianti(54,62).

kvleva (62) Catarebuli Bonzaninim et.al-is mier gviCvenebs malignantobis

21

dabal risks am kategoriaSi. avTvisebiani dazianebebi, romlebic

histologiuri kvlevis Semdgom aRmoCnda am diagnostikuri

kategoriiT Sefasebul wvrilnemsian aspiraciul biofsiur masalebSi,

ZiriTadad papilaruli karcinomis folikulur tips warmoadgendnen,

xolo namdvili folikuluri karcinoma an hurtlis ujreduli

karcinoma SedarebiT iSviaT nozologiad gvevlineba. Tanamedrove

kvleva(63), romlis Sedegebic adasturebs, rom citologiuri kvleva

warmoadgens preoperaciuli dagegmarebis ZiriTad berkets, saWiroebs

papilaruli karcinomis folikulur variantis SemTxvevaSi

citologiuri diagnostirebis gaumjobesebas da gvamcnobs, rom maT

kvlevaze dayrdobiT inkafsulirebuli dazianebebi citologiurad

ufro didi albaTobiT fasdeba, rogorc betesdas 4 kategoria, xolo

invaziuri an infiltrirebuli simsivneebi betesdas klasifikaciiT 5

an 6 kategoriebs miekuTvnebian (40,54% winaaRmdeg 8,33%-isa da

winaaRmdeg 22,73%).

betesdas sistemiT mexuTe kategoria aerTianebs avTvisebianobaze saeWvo

warmonaqmnebs. Tumca umetesi kvanZebisa srulfasovnad diagnostirdeba

citomorfologiurad, arasakmarisi ujreduli arqiteqtonikuli

cvlilebebi, ar iZleva srulfasovan informacias gadaWriT avTvisebiani

procesis arsebobis Sesaxeb. Yyvelaze did diagnostikur dilemad

gvevlineba papilaruli karcinomis folikuluri tipisa da

keTilTvisebiani folikuluri Senebis kvanZis diferenciacia.

aRsaniSnavia isic, rom didi sifrTxiliT unda ganxorcieldes

onkocituri cvlilebebis Sefaseba, sworad Sefasdes onkocituri

adenoma da is SecdomiT ar mivakuTvnoT papilarul karcinomas. Aam

kategoriaSi moxvedrili kvanZebi qirurgiul mkurnalobas

22

eqvemdebarebian da SemTxvevaTa 60-75%-Si Semdgom histomorfologiur

kvlevaze avTvisebian dazianebad interpretirdebian(64,65).

3. betesdas klasifikaciiT meeqvse kategoria-avTvisebiani dazianebebi. am

kategorias 97-99% SemTxvevebSi ganekuTvnebian iseTi dazianebebi,

romlebsac avTvisebianobis mkveTri citomorfologiuri

Taviseburebebi aReniSnebaT, kerZod, birTvebis gadideba, zeddeba,

dagrZeleba, araTanabari konturebi, birTvuli CanarTebi da Rarebi,

sqvamozuri citoplazma. vlindeba WeSmariti papilebi, fsasamomuri

sxeulakebi da avTvisebianobis sxva ZiriTadi maxasiaTeblebi. Aam

kategoriaSi moxvedril SemTxvevaTa umetesi nawili

histomorfologiuri diagnostirebisas Sefasdeba, rogorc

papilaruli karcinoma, Tumca betesdas klaifikacia iTvaliswinebs

imasac, rom am kategorias mivakuTvnoT farisebri jirkvlis

medularuli kibo, dabaldiferencirebuli, anaplaziuri karcinoma,

limfoma an metastazuri dazianebebi. Mmenejmenti mxolod

qirurgiulia da lobeqtomiiT an totaluri TireoideqtomiiT

Semoifargleba (51,53).

1.4. farisebri jirkvlis kvanZovani dazianebebis citomorfologiuri

maxasiaTeblebi

koloiduri kvanZi: aspirati Seicavs didi raodenobiT koloids da zomieri

raodenobiT folikulur ujredebs, romlebic SeiZleba dajgufdnen mcire

zomis folikulur struqturebad, erTSriani jgufebis saxiT. Uujredebi

mcire zomisaa, erTgvarovani qromatiniT da centralurad ganTavsebuli

birTviT, citoplazma mkrTalia da Seicavs perivakuolur granulebs. aseTi

kvanZi SeiZleba Seicavdes mcire raodenobiT hurtlis ujredebsac(66).

mwvave Tireoiditi: aRiniSneba didi raodenobiT neitrofiluri

leikocitebi da degeneraciuli cvlilebebi. Ffolikuluri ujredebi

reaqiulia, gamokveTili birTvakebiT (72).

23

greivsis daavadeba: nacxi hiperplaziuri kvanZis msgavsad uxvujredulia.

Seicavs folikuluri ujrdebis mcire an did jgufebs da mcire

raodenobiT koloids. SeiZleba aRiniSnebodes birTvuli atipia: gadideba,

zeddeba, gadidebuli birTvakebi. aRsaniSnavia, fseudopapilebis formirebac

da fsamomuri sxeulakebis arseboba(67).

granulomatozuri (qvemwvave Tireoiditi): adreul stadiaze aRsaniSnavia

neitrofiluri leikocitebis, reaqtiuli folikuluri ujredebis da

granulomebis formireba. Uufro mogvinebiT stadiaze ki gvevlineba

granulomebi, giganturi ujredebi, mcire raodenobiT neitrofilebi,

fibrozuli fragmentebi, qronikuli anTebisTvis damaxasiaTebeli suraTi.

giganturi ujredebi Seicavs fagocitur koloids, folikuluri epiTeli

mcire raodenobiT aris warmodgenili, biofsia aRiSnuli kvanZis arsebobis

SemTxvevaSi mtkivneulia, rac amosavalia diagnostirebisaTvis(48).

ridelis Tireoiditi: yovelTvis mciredujredulia, Seicavs fibrozuli

qsovilis fragmentebs da qronikuli anTebis suraTs. Ggranulomis

warmoqmna ar xdeba(68).

haSimotos Tireoiditi: axasiaTebs heterogenuli limfoiduri populacia

hiurtlis ujredebis TanxlebiT. Hhiurtlis ujredebi SeiZleba avlendnen

darRveul birTv-citoplzmur indeqss, gamoxatul birTvakebs da birTvul

anizokariozs. Kkoloidi mcirea. aRsaniSnavia brtyelujreduli metaplazia,

giganturi ujredebis, fibrozuli qsovilis da granulomebis arseboba(69).

dishormonogenul Ciyvs: axasiaTebs hiperplaziuri cvlilebebi papilaruli

struqturebis formirebiT, SeiZleba mogvevlinos mkveTri citologiuri

atipiiT da aseT SemTxvevebSi diagnostireba klinikur niSnebs

eqvemdebareba(70).

hiperplaziuri kvanZi: Seicavs sxvadasxva raodenobiT koloids,

folikuluri ujredebi ganlagebulia monoSreebis da qsovilovani

fragmentebis saxiT. “fiWiseburi” struqtura SenarCunebulia, Tumca

aRiniSneba zeddeba. SeiZleba Segvxdes fseudopapiluri struqturebi,

24

Tumca birTvuli maxasiaTeblebi erTgarovania. xSiria mikrofolikulebis

Tanaarsebobac, Tumca, Tu nacxi ZiriTadad mikrofolikuluri

struqturebisagan Sedgeba unda vivaraudod folikuluri neoplaziis

arseboba(66).

folikuluri neoplazia: masala mkveTrad uxvujredulia da koloidi

TiTqmis ar aRiniSneba. xSiria mikrofolikulebis arseboba, romlebis Tavis

mxriv Sedgeba 5-10 ujredisagan da kargad Camoyalibebul sanaTurs qmnian.

aRsaniSnavia rozetebis formirebac. Ffolikuluri ujredebi SesaZlebelia

ganlagebulni iyvnen qsovilur fragmentebad, warmoqmnidnen ra

samganzomilebian struqturebs. Ffolikuluri ujredebi Sejgufebulni da

dezorganizirebulni arian, Tumca monomorfuli da mkrTali citoplazmiT.

birTvi momrgvaloa da gluvi konturiT. Qqromatini granularulia.

birTvaki mcire da SeumCneveli. maxasiaTeblebi, romelic ufro

gvafiqrebineben avTvisebiani procesis arsebobaze aris: uxvujredovneba,

mouwesrigebeli jgufebis arseboba, uxvi izolirebuli ujredebis

arseboba, gadidebuli birTvebi, araTanabrad gadanawilebuli qromatini,

gamoxatuli birTvakebi(69).

hurtlis ujreduli neoplazia: msgavsia folikuri neoplaziisa, Tumca

folikuluri ujredebis nacvlad Seicavs didi raodenobiT hurtlis

ujredebs, mikrofolikulebisa da uxvi disocirebuli jgufebiT.koloidi

Zalian mcirea, warmogeba klasterebissaxiT. calkeul ujredebs

aReniSnebaT intranuklearuli CanaWdevebi da fseudoCanarTebi(67).

papilaruli karcinoma: nacxi uxvujredulia, koloidi ar aRiniSneba an

gvevlineba myari, momrgvalebuli burTebis saxiT, e. w. saReWi rezinis

msgavsi warmonaqmnis formirebiT. Uujredebi lagdebian papilaruli

struqturebis da disocirebuli jgufebis saxiT. xSiria samganzomilebiani

papilebis arseboba. Uujredebi poligonaluria, kargad gamokveTili

konturebiT da centraluri birTvebiT. citoplazma uxvi da myaria,

sqvamozuri. Uujredebi SeiZleba Seicavdes vakuolebs. BbirTvi ovaluria da

zomierad gadidebuli, qromatini granuluria, qviSiseburi, hiperqromuli,

25

SeiZleba gamoxatuli iyos birTvakic. damaxasiaTebelia optikurad sufTa

birTvevis arseboba, rac “oboli anas Tvalebis” fenomenadaa Sefasebuli.

birTvuli fseudoCanarTebi da Rarebi xSirad vlindeba, Tumca

fseudoCanarTebi ufro specifiuri diagnotikuri markeria, vidre Rarebis

arseboba. 50% SemTxvevebSi aRiniSneba mravalbirTviani giganturi ujredebi.

vlindeba fsamomuri sxeulakebic.

papilaruli karcinomis folikuluri tipis SemTxvevaSi vlindeba

sincitiumebis msgavsi fragmentebi, mikrofolikuluri struqturebi,

aRsaniSnavia papilebis ararseboba, damaxasiaTebelia tipiuri birTvuli

CanaWdevebi, qviSisebri, hiperqromuli qromatini, birTvSida

fseudoCanarTebi, sqeli koloidi ki fonad gvevlineba(68). O

onkocituri/ oqsifiluri varianti: folikuluri zrdiT xasiaTdeba, uxv,

granularul citoplazmasTan erTad birTvuli maxasiaTeblebi kvlav

saxezea.

solidur/ trabekuluri varianti: xasiaTdeba sincitiumebis warmomqneli

qsovilovani fragmentebiT da trabekulebiT, papilebis da folikulebis

gareSe(71).

makrofolikuluri varianti: maxasiaTeblebi Zalian hgavs hiperplaziuri

kvanZis maxasiaTeblebs, aucilebeli xdeba birTvuli maxasiaTeblebis

Sefaseba. Uuxvadaa qsovilovani fragmentebi da folikulebi. aRiniSneba

koloidis siWarbec(69). D

difuzur sklerozuli varianti: limfocituri infiltraciebi difuzurad

gvevlineba, aRiniSneba brtyelujreduli metaplaziuri ujredebis

monoSreebi, fsamomis sxeulakebi, fonad uxvi fibrozuli qsovili(68).

farTeujreduli varianti: maRali ujredebi, darRveuli birTv-

citoplazmuri indeqsiT, ujredebi, orjer imaze maRalia, vidre isini

siganeSi arian.

26

hialinur trabekuluri adenoma/karcinoma: arsebobs Sexedulebebi, rom is

papilaruli karcinomis arT-erTi tipia, radgan SeiZleba vlindebodes

fsamomuri sxeulakebi, birTvuli Rarebi da CanaWdevebi. papilaruli

struturebi da koloidi ar aRiniSneba. Uujredebi erTmaneTisagan

gamoyofilia metaqromatuli stromuli substanciiT, ujredebi SeiZleba

iyos calkeulad an folikulebis saxiT. vlindeba TiTistaras formis

ujredebic(66).

meduluri karcinoma: nacxi uxvujredulia, Seicavs didi raodenobiT

sustad koheziur ujredul sincitiumebs an rozetebs. Uujreduli

populacia erTi an ramodenime tipisaa, plazmocitoiduri, TiTistaras,

poligonuri, samkuTxa an mrgvalia. isini avlenen tipiur neiroendokrinul

maxasiaTeblebs: granulur qromatins, birTvakebi SeumCnevelia.

damaxasiaTebelia or- an mravalvirTvianoba, aRiniSneba birTvuli

fseudoCanarTebic. citoplazma uxvgranularulia da Seicavs wiTel

granulebs(vlindeba 30% SemTxevevbSi da mniSvnelovani diagnostikuri

Rirebulbisaa). Aamiloidi fonad ariswarmogenili(66).

insularuli karcinoma: warmoadgens gzajvaredins papilarul da

folikulur karcinomas Soris. aRiniSneba agregatebi, trabekulebi,

mikrofolikulebisoliduri sincitiumebis saxiT, koloidis gareSe.

ujredebi monotonuria, Tumca aRiniSneba arasworkideebiani birTvebi,

birTvuli CanaWdevebi, fseudoCanarTebi, zeddeba da citoplazmuri

vakuolizacia. Ppapilebi ar vlindeba, metaplazirebuli citoplazmac ar

aRiniSneba, xSiria nekrozebis arseboba(72).

anaplaziuri karcinoma: atipiuri ujredebi uxvadaa da jgufebs naklebad

qmnian, foni Zalian nekrozuli da sisxliania, anTebiTi komponenti ki,

ZiriTadad, neitrofilebiT aris warmodgenili. xSiria mravalbirTvani da

TiTistaras tipis ujrdebis Tanaarseboba. isini mkveTrad pleomorfulia,

aRiniSneba or- da mravalbirTvianoba, birTvebi aranormalurad didi

zomisaa, araswori kideebiT da hiperqromaziiT. gamoxatulia birTvakebic.

citoplazma uxvia, bazofiluri, vakuolizirebuli an granularuli.

27

calkeuli ujredebi brtyelujrduli an plazmocitoiduri tipisaa, xSiria

giganturi ujredebis arseboba(71).

limfoma: Sedgeba atipiuri limfoiduri ujredebis monotonuri

populaciiT, ujredebis sidide qvetipzea damokidebuli. foni

warmodgenilia limfogranuluri sxeulakebiT, hiurtlis da folikuluri

ujrdebi calkeuli mcire jgufebis saxiT SeiZleba gvevlinebodnen(69).

1.5.farisebri jirkvlis kvanZovani dazianebebis histomorfologiuri

maxasiaTeblebi:

farisebri jirkvlis simsivneebi iyofian keTilTvisebian da avTvisebian

warmonaqmnebad da maTi diferenciacia msoflio jandacvis organizaciis-

WHO(World Health Organization)-is mier mowodebul2017 wlisklasifikacais

efuZneba, romelic warmodgenilia sqematuri gamosaxulebis saxiT:

epiTeluri genezis simsivneebi

folikuluri ujredebida

ganviTarebuli

- folikuluri adenoma

-hialinuri trabekuluri simsivne

-hurtlis ujreduli adenoma

-mosazRvre folikulur

simsivne/inkafsulirebuli,kargad

SemosazRvruli foluluri zrdi

papilarul karcinomaze saeWvo birTvul

maxasiaTeblebiT

-FT-UMP(Follicular Tumor Uncertain Malignant Potential)

-WDT-UMP (Well Differentiated Tumor Uncertain Maligna

Potential)

-NIFTP

sxva epiTeluri simsivneebi

-sanerwyve jirkvlis msgavsi krcinom

-mukoepidermoiduli karcinoma

-sklerozuli mukoepidermoidul

karcinoma eozinofiliiT

-mucinuri karcinoma

-farisebrSida epiTeluri Timom

CASTLE(Carcinoma showing thymus-lik

differentiation of the thyroid)

-karcinoma romelic gviCveneb

Timusismagvar diferencirebas

-eqtopiuri Timoma

28

sqema 1. Mmsoflio jandacvis organizaciis mier aRiarebuli farisebri

jirkvlis aramedularuli kibos 2017 wlis modificirebuli versia

folikuluri ujredebidan ganviTarebuli simsivneebi.

folikuluri adenoma-folikuluri adenoma ganixileba, rogorc

keTilTvisebiani inkafsulirebuli simsivne folikulurujreduli

diferenciaciiT da Sesabamisad kvanZis erTgvarovani ujreduli SenebiT.

fibrozuli kafsulis zoma varirebs sisqeSi, magram is TiTqmis yovelTvis

Txeli da intaqturia, rogorc mikroskopulad aseve makroskopuladac.

folikuluri adenoma mravalkvanZovani zrdiT ar xasiaTdeba da yovelTvis

erTia, soliduria, ganakveTze homogenuria, magram xSirad gvxvdeba

hemoragiebi, kalcifikaciebi da cisturi degeneraciebi. sxvadasxva zomisaa

da misi zoma SeiZleba meryeobdes 1sm-dan 10sm-mde. Mmikroskopul

monacemebze dayrdobiT aRiniSneba folikuluri adenomis ramodenime

varianti, esenia: hiurtlis ujreduli adenoma anu onkocituri adenoma,

adenoma naTelujredovani cvliebebiT, atipiuri adenoma, hialinur-

trabekuluri adenoma, agreTve, iSviaTi tipis adenomebi, rogorebicaa

adenolipoma da adenoqondroma. Tanamedrove kvlevebiT,

-papilaruli karcinoma

-folikuluri karcinoma

-hurtlis ujreduli karcinoma

-dabaldiferencirebulikarcinoma

-anaplaziuri karcinoma

-brtyelujreduli karcinoma

29

hialinurtrabekuluri adenoma, xSirad moixsenieba, rogorc

hialinurtrabekuluri simsivne da molekulur safuZvlebze dayrdobiT

SegviZlia ganvixiloT, rogorc papilaruli karcinoma, Tumca zogierTi

mkvlevari miiCnevs pluriponturi primitiuli ujredbidan maT

multimimarTulebiT diferenciacias(73,150).

toqsiuri adenoma klinikuri nozologiaa da ara paTologiuri da

aRniSnavs hipermofunqcionire dazianebas da ara e.w. “cxel” adenomas,

mitozuri figurebi iSviaTia, arqiteqturuli da citologiuri

maxasiaTeblebi gansxvavdebian danarCeni qsovilisagan, romelic Tavis mxriv

kompresias ganicdis. zrdis mixedviT adenomebi iyofian mikrofolikulur,

makrofolikulur da trabekulur formebad(74).

folikuluri karcinoma- folikuluri simsivneebi, romlebsac aReniSnebaT

vaskuluri da kafsuluri invazia SegviZlia ganvixiloT folikulur

karcinomebad. Ddamokidebulia ra invaziis xarisxze folikuluri

simsivneebi SegviZlia davyoT or ZiriTad jgufad: minimalur invaziur anu

inkafsulirebul da farTod invaziurad. mikroskopulad xSirad Zalian

Znelia erTmaneTisagan ganvasxvaoT folikuluri adenoma folikuluri

karcinomisagan. Kkarcinomis SemTxvevaSi, is fibrozuli kafsula, rac

simsivnes gars akravs ufro sqeli da araTanabaria, vidre adenomebis

arsebobisas (75).

minimalurad invazirebuli folikuluri karcinoma kargad

inkafsulirebuli simsivnea, romelic mxolod mikroskopul doneze avlens

kafsulur da vaskulur invazias, maSin roca farTod invaziuri simsivneebi

xasiaTdebian sruli inkafsulaciis naklebobiT da sislZarRvovani

infiltraciiT. dResdReobiT malignantobis kriteriumebi sruli

kafsuluri da vaskuluri invaziis histomorfologiuri SefasebiT

ganisazRvreba. citologiurad, iseve rogorc gamyinavi mikrotomiT

momzadebul preparatebze, SeuZlebelia minimalurad inkafsulirebuli

karcinomis diagnostireba. avTvisebiani simsivneebi, romlebic upiratesad

onkocitebisagan Sedgeba(75%) da msgavsebas ganicdian folikulur

30

karcinomasTan, invaziuri xarisxis gaTvaliswinebiT SegviZlia miviCnioT

folikuluri karcinomis erTerT tipad(73).

papilaruli karcinoma- farisebri jirkvlis simsivneebs Soris yvelaze

xSiria da daaxloebiT 80% Seadgens. klasikuri papilaruli karcinoma

ganakveTze moruxo- moTeTro Seferilobisaa. misi zomebi meryeobs Zalian

mciredi, mikroskopulidan giganturamde. Kklinikurad axasiaTebs

SeumCneveli mimdinareoba, kargad SemosazRvrulia da farisebrSida zrdiT

xasiTdeba, Tumca mogvianebiT mosazRvre limfuri kvanZebic ziandeba.

Soreuli metatazebi mxolod Sorswasul SemTxvevebSi aRiniSneba,

cenraluri nawiburiTa da infiltrirebuli kideebiT, xSirad aRiniSneba

kalcifikaciebi da cisturi cvlilebebi, papilebis formireba zogjer

SeuiaraRebeli TvaliTac aris SesaZlebeli. Mmikroskopulad xasiaTdeba

papilaruli struqturebis formirebiT da kargad cnobili birTvuli

maxasiaTeblebiT (optikurad naTeli birTvebi, fseudoCanarTebi da

CanaWdevebi). Ppapilebi yovelTvis kompleqsuria, datotvili da Seicavs

fibrovaskularul RerZs. birTvuli maxasiaTeblebia: 1. Ooptikurad naTeli

birTvebi. 2. birTvuli fseudoCanarTebi 3. birTvuli CanaWdevebi 4.

birTvuli fseudofilamentebi. Mmitozuri figurebi iSviaTia. daaxloebiT

SemTxvevebis naxevarSi vlindeba fsamomuri sxeulakebi, isini

lokalizdebian papilarul RerZze, fibrozul stromaSi an simsivnur

ujredebs Soris. SemTxvevebis @20%-Si vlindeba solidur/trabekuluri

zrda da imave raodenobaSi aRiniSneba brtyelujrduli metaplazia.

zogierTi avtoris azriT es niSnebi simsivnis dabaldiferencirebulobaze

miuTiTebs. meoTxed SemTvevebSi aRiniSneba limfocituri infiltracia, rac

miuTiTebs simsivnis sawinaaRmdego sapasuxo reaqciaze an simsivniswinandel

Tireoiditze(76).

papilaruli karcinomis ramodenime qvetipi arsebobs, romlebic Semdgom

prognozs mizanmimarTulad ukavSirdebian:

1. Ppapilaruli mikrokarcinoma- mikrokarcinomad Sefasdebian is

papilaruli karcinomebi, romelTa diametric erT santimetramdea, maTi

31

nawili SeiZleba SevafasoT arainkafsulirebul sklerozul simsivned,

nawili ki avlens srul an subtotalur inkafsulacias. Ees forma

saukeTeso prognoziT xasiaTdeba, Tumca calkeul SemTxvevebSi aRiniSneba

regionalur limfur kvanZebSi metastazireba, Soreuli metastazebis

arseboba ar vlindeba(77).

2. Ppapilaruli karcinomis inkafsulirebuli tipi- am tips SeiZleba

ganvakuTvnoT is papilaruli karcinoma, romelic srulad

inkafsulirebulia. citoarqiteqtonikuli maxaiaTblebi msgavsia klasikuri

tipisa, Soreuli metastazebi ar axasiaTebs. mniSvnelovania sworad moxdes

diferencireba hiperplaziur kvanZTan, romelic papilebis an

fseudopapilebis formirebiT xasiaTdeba. Aam dros, ZiriTadad, birTvul

maxasiaTeblebs veyrdnobiT(78).

3. Ppapilaruli karcinomis folikuluri varianti-es aris papilaruli

karcinomis is tipi, romelic ZiriTadad Sedgeba folikulebisagan.

diagnostirebaSi gvexmareba klasikuri birTvuli maxasiaTeblebi, iseve

rogorc zrdis invaziuri tipis arseboba, fsamomuri sxeulakebi, mkveTrad

eozinofiluri koloidis arseboba da fibrozuli trabekulacia(79).

4. inkafsulirebuli folikuluri tipi- es tipi zemoT aRwerili qvetipis

niSanTvisebebs imeorebs, miuxedavad imisa, rom kapsuliT aris

SemosazRvruli, xasiaTdeba papilaruli karcinomis folikuluri variantis

citoarqiteqtonikuli maxasiaTeblebiT. aRiniSneba sisxlZarRvovani invazia.

Tumca is maRaldiferencirebul simsivneTa ricxvs ganekuTvneba.

5. Ddifuzur sklerozuli tipi- es qvetipi moicavs farisebri jirkvlis

orive wilis dazianebas, difuzur sklerozul cvlilebebis,

brtyelujredul metaplazias, fsamomuri sxeulakebis siuxves da mkveTrad

gamoxatul limfoplazmocitur infiltracias. xSiria Soreuli

metastazebis arseboba, ris gamoc cudi prognoziT xasiaTdeba(76).

6. oqsifiluri varianti- papilaruli karcinomaa, romelic upiratesad

hurtlis ujredebisagan Sedgeba. simsivne xandazmul asakobriv jgufSi

32

viTardeba da solidur/ trabekuluri zrdiT xasiaTdeba. aRsaniSnavia, rom

ujredebi karcinomis SemTxvevaSi ufro patara zomisaa vidre adenomis

arsebobisas. ZiriTad, diagnostikur kriteriumad ki vaskuluri an

kafsuluri invazia gvevlineba(79).

7. maRalujreduli varianti- papilaruli karcinomis qvetipia, romelic

Sedgeba papilebisgan, romlebic amofenilia maRali ujredebis erTi SriT

da didi zomis, acidofiluri, onkocitebis msgavsi citoplazmiT.

simsivnuri zrda ZiriTadad papilarulia. Aara keTilsaimedo prognoziT

xasiaTdeba(80).

hurtlis ujreduli karcinoma- anu oqsifiluri karcinoma SeiZleba

folikuluri karcinomis qvetipad ganvixiloT, mxolod ufro cudi

prognozuli maCveneblebiT, Tumca bevri mkvelavari am azrs ar iziarebs

da mas farisebris neoplaziebs Soris calke nozologiad moixseniebs.

oqsifiluri ujredebi xasiaTdebian maTi poligonuri kideebiT,

eozinofiluri granularuli citoplazmiT, hiperqromuli an vezikuluri

birTvebiT, didi birTvakebiT da uxvi mitoqondriebiT(81).

dabaldiferencirebuli karcinoma- folikuluri ujrdebisagan

ganviTarebuli dabaldiferencirebuli simsivnea, maSin roca folikuluri

da papilaruli karcinoma maRaldiferencirebuli kiboebia. mas insularul

karcinomasac uwodeben, radganac damaxasiaTebelia insularuli anu

budobrivi zrda, ris gamoc misi diferencireba medulur karcinomasTan

xSirad uWirT. citologiurad nacxi uxvujredulia, nekrozuli foniT,

atipiiT, trabekulebisa da mikrofolikulebis formirebiT, citoplazmuri

vakuolizaciiT. anaplaziuri karcinomisagan gansxvavebiT es simsivneebi

irTaven radioaqtiur iods. xasiaTdebian maRali agresiulobiT,

sisxlZarRvovani invaziiTa da Soreuli metastazirebiT(82).

anaplaziuri karcinoma- aseve iwodeba sarkomismagvar karcinomad,

xandazmul asakSi viTardeba, srafad mzardi simsivnea da disfagiiT da

dispneiT xasiaTdeba. ganakveTze farisebri jirkvlis didi nawili

33

Canacvlebulia sisxlCaqcevebiTa da nekrozuli qsoviliT. mikroskopulad

sami ZiriTadi qvetipi gamoirCeva, romlebic SeiZleba kombinaciaSic

Segvxvdnen. Ppirveli, sqvamozuri, roca ujredebi aradiferencirebulia,

magram inarCuneben epiTeloidur saxes. danarCeni ori tipi iwodeba

TiTistaraujredul da giganturujredul qvetipebad, xasiaTdebian

gamoxatuli neitrofiluri infiltraciiT, gamoxatuli vaskularizaciiT,

Zvlovan/ xrtilovani metaplaziiT. aseTma gamoxatulebam SesaZloa

gvafiqrebinos sarkomis arsebobaze, gansakuTrebiT ki safiqrebelia

avTvisebiani fibrozuli histiocitomis, angiosarkomis, fibrosarkomis an

avTvisebiani hemangiopericitomis arseboba. SeiZleba aRiniSnebodes

osteoklastebismagvari mravalbirviani ujredebi, romelic Zvlis

giganturujredul simsivneze eWvis gaCenis safuZvels iZleva, Tumca Tavis

mxriv, osteoklastebismagvari gigantur ujreduli simsivne ar warmoadgens

avTvisebian paTologias, aramed Sedgeba monocit/ histiocituri xazis

reatiuli ujrdebisagan, romlebic Tavis mxriv mononuklearuli ujredebis

SerwymiT warmoiqmneba. Pprognozulad Zalian swrafad mzardi simsivnea,

romelic zewolas axorcielebs traqeasa da saylapavze, amave dros,

swrafad viTardeba Soreuli metastazebic(82).

meduluri karcinoma-farisebri jirkvlis simsivneebis 5% SemTxvevebSi

viTardeba. Nneiroendokrinuli simsivneebis ricxvs ganekuTvneba da

nevraluri krestis ultimobraqialuri sxeulakidan aRmocendeba.

asekretirebs kalcitonins. 70% SemTxvevebisa sporadulia, 20-30% ki

ojaxur anamnezs atarebs. Oojaxuri anamnezis mqone simsivneebi autosomur

dominanturia da ret mutaciiT arian gamowveulni. Mmeduluri karcinoma sam

jgufad iyofa: mravlobiTi endokrinuli neoplazia 2a(MEN 2a), mravlobiTi

endokrinuli neoplazia 2b(MEN 2b) da ojaxuri meduluri karcinoma.

asakobrivi piki miiRweva 35 wlis asakSi, maSin roca sporaduli

SemTxvevebisas es 40-60 welia. Ddabal prognozul maCveneblebs

ganekuTvnebian: xandazmuli asaki, diagnostirebisas limfur kvanZebSi

arsebuli metastazebis arseboba, somaturi ret mutaciis gamovlena.

34

sporaduli SemTxvevebisas dazianeba yovelTvis erTeulia, maSin rodesac

ojaxuri SemTxvevebi yovelTvis multicentrulobas avlenen da dazianebas

bilateralurad iwveven.

meduluri karcinoma soliduri simsivnea, moruxo Seferilobisaa, ar

gaaCnia kargad SemosazRvruli kafsula. Uujredebi mrgvali an ovaluria,

TiTistaras, plazmocitoiduri an sqvamozuri formisaa, zogjer gigantur

zomebsac ki aRweven. farTo fibrovaskuluri RerZebi simsivnes kvanZebad

yofs. xasiaTdeba mkveTri neitrofiluri infiltaciiT. birTvebi momrgvalo

an ovaluria, qviSisebri qromatiniT. stroma infiltrirebulia

kalcitoninisgan miRebuli amiloidis depozitebiT. MZnelia diferencireba

folikuluri genezis onkocitur simsivneebTan, Tumca

diferencirebisTvTvis gvexmareba amfofiluri da ara mkveTrad

eozinofiluri ujredebis arseboba, amave dros, vlindeba simsivnis dayofa

budeebad da fibrozuli qsoviliT gamoyofa(83).

1.6. sirTuleebi papilaruli karcinomebis citomorfologiur

diagnostikaSi

ganusazRvreli mnivnelobis atipia/ ganusazRvreli mniSvnelobis

folikuluri dazianebebi(AUS/FLUS) betesdas sistemis yvelaze

heterogenuli jgufia(51). is moicavs im SemTxvevebs, romlebic

citologiuri kriteriumebiT, ujreduli Tu arqiteqtonikuli

maxasiaTeblebebiT ver mivakuTvnebT verc keTilTvisebin da verc

avTvisebian an saeWvo avTvisebianobaze procesebs. Ees kategoria moicavs

SemTxvevebs, romlebic upiratesad warmodgenilia mikrofolikulebiT,

onkocitebiT, calkeuli ujredebi avlenen papilaruli karcinomisTvis

damaxasiaTebel birTvul cvlilebebs, folikulur an limfoidur

infiltraciebSi fokalur birTvul atipias. vinaidan aRniSnuli

35

niSanTvisebebi damokidebulia mkvlevarebis calkeul Sexedulebebze, isini

did azrTasxvadasxvaobas iwveven. aseTi diagnozebis menejmenti

eqvemdebareba garkveuli intervalis Semdeg(3-6 Tve) ganmeorebiT biofsiur

kvlevas. AUS/FLUS SemTxvevebis ricxvi betesdas klasifikaciis

damkvidrebis Semdeg 5-15%-ia, calkeuli mkvlevarebis azriT ki 20-30%

aRwevs (84).

gamomSrali, arafiqsirebuli preparatebi iwvevs birTvebis gadidebs da

hiperqromazias, cvlilebebi qromatinis struqturaSi, romelic aseT

preparatebSi aRiniSneba emsgavseba papilaruli karcinomisaTvis

damaxasiaTebel ujredul cvlilebebs. Efiqsaciis deficiti Zalian xSirad

nacxSi didi raodenobiT eriTrocitebis Semcvelobas ukavSirdeba.

biofsiis warmoebisas ufro dabali gaudis Spricebis gamoyeneba Tavidan

agvacilebs am problemas(85).

kalcinatebis arseboba farisebr jirkvalSi Zalian xSiria. isini Tan

axlavs, rogorc keTilTvisebian aseve avTvisebian procesebs(26-

54%avTvisebian da 8-32% keTilTvisebian procesebs)(86). histologiurad

isini iyofian fsamomatozur da distrofiul kalcifikaciebad. zogjer,

roca es procesi mkveTrad aris gamoxatulidekalcifikacias mimarTaven,

rac SemdgomSi hiperqromaziis da birTvuli sicarieleebis gaCenis mizezi

xdeba.

Tanamedrove dakvirvebebiT Zalian naTlad SesamCnevi gaxda papilaruli

karcinomisa da autoimunuri Tireoiditis Tanaarseboba(87). es dResac

sayovelTao davis sagania, mecnierebis nawili am faqTs alternatiul

Tanaarsebobas miakuTvnebs, calkeuli mecnierebi ki maT erTian biologiur

WrilSi ganixilaven. Kkvevebma cxadyves rom calkeul SemTxvevebSi maT

msgavsi genetikuri darRvevebi axasiaTebT. aseTia, magaliTad cvlilebebi

RET genTan mimarTebaSi, Tumca papilaruli karcinomisTvis dResdReobiT

aqtualuri BRAF onkogeni ar vlindeba Tireoiditebis SemTxvevaSi.

36

yoveldRiur praqtikaSi autoimunuri TireoiditisTvis damaxasiaTebeli

reaqtiuli cvlilebebi da papilaruli karcinomis dros arsebuli

cvlilebebi sadavo sakiTxs warmoadgens, iseve rogorc

citomorfologiaSi, aseve histomorfologiaSi. Llimfoiduri agregatebis

miRma arsebuli folikuluri ujredebi avlenen papilaruli karcinomis

msgavs ujredul cvlilebebs, aseTebia, birTvuli membranis gasqeleba,

Rarebisa da CanaWdevebis arseboba da iSviaT SemTxvevaSi, birTvuli

fseudoCanarTebis gaCena (87).

aseT SemTxveveSi unda vixelmZRvneloT imiT, rom Tireoiditis dros

ujredebi mrgvalia, ar aRiniSneba zeddeba da gamokveTili

fseudoCanarTebi, uxvadaa warmodgenili limfocituri infiltraciebi(50).

papilaruli karcinomis is SemTxvevebi, romlebic qronikuli Tireoiditis

TanaarsebobiT xasiaTdebian avlenen simsivnuri ujrdebisagan Semdgari

fragmentebis arsebobas, romlebic limfocituri infiltraciebisagan

damoukideblad vlindebian da Seicaven papilaruli karcinomis yvela

birTvul maxasiaTebels(87).

calkeul SemTxvevebSi, magaliTad, Worthin’stumor-vorTinis simsivne, romelic

sanerwyve jirkvis simsivnes warmoadgens, iZleva ra didi raodenobiT

papilaruli struqturebis formirebas, papilarul karcinomasTan

sadiferenciacio nozologiad gvevlineba(88).

papilaruli karcinomis FfarTeujredulitipi da onkocituri karcinoma

SesaZloa keTilTvisebiani hurtlis ujreduli dazianebebisasSecdomis

wyaro gaxdes(81).

greivsis daavadebas, xagrZlivi mimdinareobisas axasiaTebs papilaruli

hiperplazia da sxvadasva simZimis sklerozuli cvlilebebi. aRsaniSnavia

zomieri birTvuli cvlilebebic, Tumca amosavali mainc papilaruli

karcinomis ZiriTadi birTvuli maxasiaTeblebia(86).

dishormonogenuli Ciyvis arsebobisas diddeba birTvebi, vlindeba

papilaruli an folikuluri zrda. Kkoloidis arseboba fonis saxiT,

37

arakvanZovani jirkvali, difuzuri hiperplaziis arseboba saSualebas

iZleva swori diagnozis gamosavlenad(89).

hialinur trabekulur adenoma farisebri jirkvlis simsivnea, romelsac

axasiaTebs wagrZelebuli simsivnuri ujredebi, romlebic trabekuluri

saxiT lagdebian, gaxveulni arian hialinur nivTierebaSi da kalcinatebSi,

riTac Zalian emsgavsebian fsamomur sxeulakebs. citologiurad sworedes

simsivne yvelaze xSirad SecdomiT diagnostirdeba papilarul karcinomad,

radganac ujreduli maxasiaTeblebiTac misgan Znelad ganirCeva(86).

1.7.ZiriTadi sirTuleebi farisebri jirkvlis kibos histomorfologiur

diagnostikaSi

papilaruli karcinomis folikuluri tipi aerTianebs im dazianebebs,

romelTac aReniSnebaT folikuluri struqturebis warmoqmna papilaruli

karcinomebisTvis damaxasiaTebeli ujreduli cvlilebebiT(60). Sesabamisad,

is saWiroebs diferencirebas folikulur dazianebebTan, rogoricaa

folikuluri adenoma da karcinoma. rodesac papilaruli karcinomis

folikuluri varianti inkafsulirebuli ar aris da farisebri jirkvlis

mimdebare qsovili infiltrirebulia simsivnuri ujredebiT, daignostireba

sirTuleebis gareSe aris SesaZlebeli.xolo inkafsulirebul SemTxvevebSi

diagnostireba srulad efuZvneba papilaruli karcinomis birTvul

maxasiaTeblebs, rac azrTasxvadasxvaobis da sirTuleebis gamomwvevad

gvevlineba, radgan gasaTvaliswinebeli xdeba folikuluri dazianebebis

arsebobac.xSirad diagnostikuri dilemis winaSe vdgebiT, radganac Tu

papilaruli karcinomis folikuluri varianti 1-1,5 santimetrs aRmateba

totaluri Tireoideqtomiis sakiTxi dgeba, rasac Semdgom radiaqtiuli

iodiT Terapia mosdevs. dResdReobiT, Tanamedrove kvlevebze dayrdnobiT

papilaruli karcinomis folikuluri tipi, romelic inkafsulirebulia,

miiCneva arainvaziurad da iwodeba, rogorc”arainvaziuri folikuluri

38

neoplazia, papilaruli karcinomisTvis damaxasiaTebeli ujreduli

cvlilebebiT” da fasdeba Zalian dabali riskis matareblad. Sesabamisad,

es faqti amcirebs im fsiqologiur stressa da klinikur mimdinareobas,

romelic Tavis mxriv kibos diagnozs ukavSirdeba.

farisebri jirkvlis folikuluri karcinoma, moicavs ra mis onkocitur

formasac, iyofa minimalur invaziurad da farTod invaziurad. Mminimalur

invaziuri simsivne sruladaa inkafsulirebuli kafsuliT, magram

axasiaTebs vaskuluri da kafsuluri invazia. ganakveTze invaziis SemCneva

SeuZlebelia. maSin, roca farTod invaziuri folikuluri karcinomebis

SemTxvevaSi invazia mikroskopulad da makroskopulad advilad SesamCnevia.

Mminimalur invaziur simsivneebs, amave dros, saukeTeso prognozuli

maCveneblebi gaaCniaT, Tumca calkeuli SemTxvevebi iZlevian metastazebsac.

Aminimalur invaziuri simsivnis sworad diagnostireba mniSvnelovania

qirurgiuli kuTxiT, radganac minimalur invaziuri simsivne, hiurtlis

ujreduli qvetipis CaTvliT, lobeqtomias eqvemdebareba. Tumca es midgoma

eWqveS dgeba maSin, roca minimalurinvaziuri karcinoma metastazirebis

potencialiT da cudi prognoziT xasiaTdeba.

mkvlevarTa didi ricxvi upiratesobas aniWebs uwodos mas

inkafsulirebuli folikuluri karcinoma intensiuri vaskuluri invaziiT.

termini “minimalur invaziuri” ar unda iqnes gamoyenebuli, aramed

daTvlili da Sefasebuli unda iqnes vaskuluri invaziis fokusebi da Tu

maTi ricxvi 4 aRemateba, aseTi SemTxvevebi unda CaiTvalos maRali riskis

mtareblad(90).

dResdReobiT kargad cnobili faqtia, rom is travma, romelic

wvrilnemsiani aspiraciuli biofsiisas adgeba qsovils, iwvevs sirTuleebs

Semdgom kvanZis histomorfologiuri Sefasebisas. termini “reaqtiuli

ujreduli an birTvuli atipia” gamoiyeneba im reparaciul/anTebiTi

procesis aRsawerad, romelic am dros mimdinareobs. Tumca calkeul

SemTxvevebSi am procesis garCeva neoplaziuri procesisgan garkveul

sirTuleebs ukavSirdeba, radganac vlindeba birTvebis gadideba,

39

gamoxatuli birTvakebi, qromatinis gaiSviaTeba. Livolsim da merinom post-

FNA cvlilebebi dayves mwvave da qronikulad. Mmwvave procesSi erTiandeba

hemoragia, granulaciuri qsovilis warmoqmna, birTvuli atipia, xolo

qronikul process ukavSirdeba kafsulis gajirjveba, fseudoinvaziebi

simsivnis kafsulasa da sisxlZarRvebSi, papilaruli endoTeluri

hiperplazia. reaqtiul/reparaciuli atipia da hialinuri stroma

SesaZlebelia calkeul SemTxvevebSi papilaruli karcinomis imitacias

iZleodes, Tumca gasaTvaliswinebelia isic, rom es birTvuli cvlilebebi

mxolod biofsiiuri aris mimdebared vlindeba. Aamave dros papilaruli

karcinomis diagnozi saWiroebs yvela birTvuli maxasiaTeblis

erTobliobis arsebobas(84).

mikrokarcinomad dignostirdeba 1 santimetrze dabali zomis

simsivneebi.farisebri jirkvlis karcinomis SemTxvevaTa 43%

mikrokarcinomebia, xolo maTgan 50%-ze meti papilaruli

mikrokarcinomebia. dResdReobiT diagnostirebaSi gaumjobesebulma

teqnologiebma, isini ufro advilad aRmosaCeni gaxada. calkeuli avtorebi,

maT keTilTvisebian mimdinareobaze saubroben, Tumca bevri avtori Tvlis,

rom isini namdvili avTvisebiani simsivneebia, Tavisi avTvisebiani

mimdinareobiT. calkeuli mkvlevarebi saubroben ra maT keTilTvisebian

mimdinareobaze, amtkiceben, rom maT minimaluri mkurnaloba esaWiroebaT,

maSin roca calkeuli avtorebi, agresiuli mkurnalobis Catarebas

emxrobian. amerikis farisebris kibos asociaciis Tanaxmad, is pacientebi,

romlebsac aRmoaCndaT mikrokarcinoma da dabali riskis mtarebelni arian,

Semoifarglebian mxolod lobeqtomiiT, xolo maRali riskis mqone

pirebi(iradiaciiT anamnezSi, ojaxuri anamneziT) totalur

Tireoideqtomias eqvemdebarebian(91).

4-16% pacientebisa aRiniSneba daavadebis Tavidan aRmoceneba da Soreuli

metastazebis ganviTareba. calkeul SemTxvevebSi ki papilaruli

mikrokarcinomebi multifokaluria(15,5-40% qirurgiuli Carevis Semdgom

40

gamovlenili da 80%-met SemTxvevebSi autofsiaze gamovlenili), es faqtori

ki simsivnis Tavidan ganviTarebis riskze miuTiTebs(81).

histomorfologiurad mikrokarcinomebis sworad idenTificireba da

Sefaseba Semdgomi Terapiuli marTvisTvisdidi mniSvnelobisaa(92). vinaidan

klasikuri papilaruli karcinomis mimarT Catarebuli mkurnaloba

totalur Tireoideqtomias da radiaqtiuli iodiT mkurnalobas moicavs,

maRali riskis mqone mikrokarcinomebi SeiZleba klasikuri mkurnalobiT

warimarTos, Tumca dResdReobiT ar aris kvlevebi imis Sesaxeb Tu

ramdenad efeqturia radiaqtiuli iodi mikrokarcinomebis Semdgomi

prognozis CamoyalibebisTvis(91).

1.8.Ppapilaruli karcinomis ZiriTadi imunofenotipuri maxasiaTeblebi:

1. HBME-1 monoklonuri antisxeulia, romelic Seicnobs normaluri

traqeis epiTeliumis, pankreasis, filtvis da ZuZus mezoTelur

ujredebs(93). cnobili kvlevebiT HBME-1 farisebri jirkvlis

avTvisebinobis mniSvnelovani markeria. Ffarisebr jirkvalSi HBME-1

eqspresirebs mxolod folikuluri epiTelidan ganviTarebul

simsivnur ujredebze, rogorc maRaldiferencirebul, aseve

dabaldiferencirebul variantebs, da sxvadasxva sensitiurobiT da

specifiurobiT xasiaTdeba. Mmisi eqspresia nols utoldeba normalur

farisebri jirkvlis qsovilSi. saintereso faqtia, isic, rom mas

axasiaTebs mxolod memranuli eqspresia. Ppapilaruli karcinomebis

umetesoba HBME-1-ze (55-100%, saSualod, 88%)difuzurad pozitiurad

iRebeba. mxolod folikuluri karcinomebismcirericxovani SemTxvebi

da papilaruli karcinomis onkocituri varianti avlens

pozitiurobas SemTxvevaTa 13%-66%-Si. aRsaniSnavia is faqtic, rom

hialinur trabekuluri simsivnis arsebobisas is ar vlindeba, rac

saukeTeso faqtad gvevlineba am simsivnis papilarul karcinomasTan

diferencirebaSi.Ddabaldiferencirebuli da anaplaziuri karcinoma

41

aseve avlens dadebiT eqspresias SemTxvevaTa 61%-91% da 0%-50%-Si.

calkeulma kvlevebma 29%-66%-Si aCvenes HBME-1-is dadebiTi eqspresia

iseT folikulur simsivneebSi, romelTac sadavo kafsuluri an

vaskuluri invazia aReniSnebodaT. mravlobiTma kvlevebma, romlebic

aRniSnuli markeris eqspresiis gamosavlenadCatarda normalur an

hiperplaziur kvanZebSi, gamoavlines aRniSnul SemTxvevebSi am

markeris araeqspresiuloba(93,94,95). Tumca HBME-1 mainc aRiniSna

adenomatozuri kvanZebi 3-12%-Si da folikuluri adenomebis 0%-27%-

Si. sensitiuroba, specifiuroba, dadebiTi prediqtoruli maCvenebeli

da diagnostikuri sizuste HBME-1-is, rogorc damoukidebeli

markeris keTilTvisebiani da avTvisebiani procesebis gasamijnad

Sefasebul iqna 80%, 96%, 96,7% da 86,4%. Bbevri avtori aRniSnavs am

markeris did diagnostikur Rirebulebas sxva markerebTan

kombinaciaSi(90,93).

2. TTF-1- pirvelad aRmoCenil iqna 1989 wels, rogorc birTv-specifiuri

membranuli antigeni, dnm-Tan SekavSirebis unariT, romelic TG genTan

urTierqmedebda virTxebSi(96). TTF-1 aregulirebs farisebri

jirkvlis, filtvebis da embrionaluri ganviTarebis dros

diencefalonis genebis eqspresias. mniSvnelovania, rom TTF-1 PAX8 –

Tan erTad normalur farisebr jirkvalSi akontrolebs TG, TPO,

Tireotropul receptors, kalcitoninis da ZiriTadi

histoSeTavsebulobis kompleqsis klasi-1 genebis eqspresias.

vinaidan,TTF-1 farisebri jirkvlisTvis metad specifiuri markeria, is

warmatebiT gamoiyeneba pirveladi simsivnisa da metastazuri simsivnis

sadiferenciaciod. Ffarisebr jirkvalSi TTF-1 -is birTvuli eqspresia

vlindeba folikuluri ujredebidan ganviTarebul keTilTvisebian da

avTvisebian simsivneebSi, agreTve,medularuli kibos dros.

Ddabaldiferencirebuli karcinoma avlens daqveiTebul an fokalur

eqspresias, xolo anaplaziuri simsivneebi ar avlenen mas. TTF-1-ze

42

imunoreaqtiuloba srulad gamoricxavs paraTireoiduli genezis,

paragangliomebis da metastazuri simsivneebis arsebobas(94).

3. CK 19 – farisebri jirkvali organoa, romelic gansakuTrebiT iqna

Seswavlili citokeratinebis mgrZnobelobaze(97). Sefasda

citokeratinebis eqspresia normaluri parenqimis, keTilTvisebiani

warmonaqmnebis da avTvisebini dazianebabis SemTxvevebSi. aRmoCnda,

rom papilaruli karcinomis arsebobisas SemTxvevaTa 80%-Si vlindeba

Zlieri imunoreaqtiuloba citokeratin-7-is, 18-is da 19-is. amave

citokeratinebis eqspresia SedarebiT dabalia dabaldiferencirebuli

kibos SemTxvevaSi (40-60%). Aanaplaziuri karconomis dros Zalian

iSviaTia citokeratin 19-is eqspresia. vinaidan, folikuluri

adenomebisa da folikuluri karcinomebis SemTxvevaSi misi eqspresia

dabalia da mxolod fokaluria, es citokeratini Zalian aqtiurad

gamoiyeneba farisebri jirkvlis simsivnuri procesebis

sadiferenciaciod. Bbevri avtori miiCnevs, rom farisebri jirkvlis

kvanZebis srulfasovani diagnostirebisTvis CK-19-is, rogorc

diagnostikuri markeris gamoyeneba Zalian mniSvnelovania,

gansakuTrebiT papilaruli karcinomebis sadiferenciaciod.

normaluri farisebri jirkvlis qsovili umetesad imunonegatiuria

CK-19-is mimarT, Tumca Tireoiditebis dros aRiniSneba misi

fokaluri eqspresia, magram es sruliad gansxvavdeba im

eqspresiisagan, rac papilaruli karcinomis SemTxvevaSi aRiniSneba.

Mmiuxedavad imisa, rom papilaruli karcinomis arebobisas SeRebva

difuzurad vrceldeba mTel dazianebul ubanze, CK-19-iTfokaluri

SeRebva yovelTvis ar gamoricxavs papilaruli karcinomis arsebobas.

Hhialinur-trabekuluri simsivneebisas CK19-is sxvadasxva

intensivobiT eqspresia (50%dan-100%mde) calkeul avtors imis

saSualebas aZlevs, rom es simsivne keTilTvisebian dazianebas an

piriqiT avTvisebian process miakuTvnos (98). Mmedularuli karcinoma

CK 19-ze mxolod fokalur SeRebvas avlens. Bbevri mkvlevaris mier

43

dadasturebulia, rom CK19 SesaZlebelia warmatebiT gamoviyenoT

citologiur masalazec, gansakuTrebiT sadavo SemTxvevebSi.

aRsaniSnavia, am markeris maRali sensitiuroba da specifiuroba,

rogorc damoukidebeli markerisa 92%-97%. misi mgrZnobeloba

maRalia papilaruli karcinomis citomorfologiuri Sefasebisas(99).

4. KI-67. ujredis proliferaciuli aqtivoba kibos biologiuri qcevis

ZiriTadi ganmsazRvrelia. dResdReobiT KI-67 iTvleva ujredis

proliferaciuli aqtivobis yvelaze aqtualur markerad, is

eqspresirdeba yvela ujredis mier, ujredis yvela fazaSi, garda G0

fazisa. KKI-67 mniSvnelovania keTilTvisebiani da avTvisebiani

procesebis diferencirebisas(100). Mmravali mkvlevari ikvlevda KI-67-

is aqtivobas farisebr jirkvalSi, Tumca maTi mosazrebebi metad

gansxvavebulia erTmaneTisgan (96). calkeuli mkvlevari miuTiTebs mis

mkveTr eqspresiaze farisebri jirkvlis avTvisebiani procesebis

dros, Tumca sxva mkvlevarebi amtkiceben, rom KI-67-is eqspresia ar

gansxvavdeba farisebri jirkvlis adenomebisa da karcinomebis

SemTxvevaSi(95).

5. CD56-warmoadgens imunoglobulinebis superojaxSi homofilur

damakavSirebel glikoproteins, romelic normaSi eqspresirdeba

bunebrivi kilerebis, aqtivirebuli T ujredebis, didi granularuli

limfocitebis, specifiuri endokrinuli da tvinis qsovilebis mier.

miiCneva, rom cila awesrigebs ujredul moZraobas, neironebs Soris

homofidur dakavSirebas. aRmoCenil iqna, rom is eqspresirdeba

farisebri jirkvlis folikuluri ujredebis mier(101,102,103).

erT-erTi ZiriTadi problema farisebri jirkvlis simsivnuri procesebis

diferenciaciaSi aris papilaruli karcinomis folikuluri tipisa da

folikuluri adenomebs Soris diferenciaruli diagnozis warmoeba(90).

diferencireba maT Soris klinikuri mniSvnelobisaa, rac moicavs pacientis

mkurnalobas da xangrZliv monitorings. ver Camoyalibda minimaluri

44

histologiuri maxasiaTeblebic ki, romelic srulad gadaWrida am

problemas.

CD-56-is daqveiTebuli eqspresia miuTiTebs simsivnuri procesis

progresiaze. Mmarkeris eqspresia daqveiTebulia da TiTqmis dakargulia

papilaruli karcinomebis, folikuluri karcinomebisas da anaplaziuri

karcinomebis arsebobisas(104).

aRniSnuli markeris eqspresiis deficiti gansakuTrebiT papilaruli

karcinomis dros SeimCneva, es faqti eTanxmeba adreul kvlevebs(93). Aaxali

kvlevebis Tanaxmad ki sagrZnobia CD-56-is eqspresiis Semcireba,Aara marto

papilaruli karcinomebis, aramed folikuluri karcinomebis drosac, rac

naCvenebi iqna monacemebis mkveTri sxvaobiT folikulur karcinomebsa da

adenomebs Soris(105).

sxvadasxva kvlevebi gansxvavebul mgrZnobelobas gviCvenebs am markeris

mimarT. sensitiuroba karcinomebTan mimarTebaSi 58%-dan 100%-mde

ganisazRvreba, xolo specifiuroba 46%-dan 100%-mde(105). AaRniSnuli

markeris umaRlesi sensitiuroba aRiniSneba papilaruli karcinomebis

SemTxvevaSi, xolo yvelaze dabali sensitiuroba folikuluri

karcinomebis SemTxvevaSi(106,107).

BRAF onkogeni- kvlevebiT kargad aRiarebuli faqtia is, rom papilaruli

karcinomis ganviTareba efuZvneba mitogen-aqtivirebuli protein kinazas

(mapk) aqtivacias, romelic SemdgomSi Suamdgomlobas uwevs ujredul

pasuxs da zrdis sxvadasxva signalebs(108). Aam rgolis darRveva iwvevs

arakontrolirebad ujredul proliferaciasa da mcdar apoptozs. BRAF

onkogeni am sasignalo gzas aaqtiurebs, rac SemdgomSi sxavdasxva kibos

gamomwvevi mizezi xdeba, esenia: avTvisebiani melanoma, koloreqtaluri

simsivne da sarkomebi. BRAF geni lokalizdeba qromosoma 7q24-ze da

kodirebas ukeTebs serin-Tironin kinazas. RAS-is aqtivaciis Semdeg, BRAF-is

fosporirireba ganapirobebs mapk kaskadis aqtivacias. BRAF mutacia

farisebri jirkvlis kibos arsebobisas yvelaze xSiri genetikuri

45

alteraciaa da kvlevebis Tanaxmad papilaruli karcinomebis 45%-80%

SemTxvevebSi aRiniSneba(108,109).

histologiur qvetipebs Soris BRAF mutacia yvelaze xSirad papilaruli

karcinomis klasikuri SemTxvevebis da farTeujreduli variantis

arsebobisas vlindeba(67%-da 68% mde da 80-83%)(110). aRniSnuli antigeni

TiTqmis ar vlindeba inkafsulirebuli papilaruli karcinomis

folikuluri variantis SemTxvevebSi. Tanamedrove kvleva(111) irwmuneba, rom

swored is faqti, rom BRAFmutacia ar aRiniSnebazemoTxsenebuli

daavadebis dros, SesaZlebels xdis ganvasxvaoT arainvaziuri folikuluri

neoplazia papilaruli karcinomis msgavsi birTvuli cvlilebebiT

(NIFTP),rogorc es axlaxans momxdari reklasificirebisas iwoda(149),

papilaruli karcinomis folikuluri variantis invaziuri formisgan

(IFVPTC). Sesabamisad am faqtisa, sworad daigegmos Semdgomi qirurgiuli

mkurnaloba.

BRAF mutacia SeiZleba gamovlindes limfomebis, anaplaziuri da

dabaldiferencirebuli kibos dros, Zalian iSviaTad ki hiperplaziur

kvanZebSi. BBRAF antisxeulis pozitiurobis deteqcia SesaZlebelia

warmatebiT iqnes gamoyenebuli papilaruli karcinomis sadavo SemTxvevebis

diagnosterebaSi. mniSvnelovania papilaruli karcinomis riskis gansazRvra,

vinaidan maTi Semdgomi marTvisTvis miRali riskis mqone pacientebma unda

imkurnalon aduvanturi, ufro agresiuli TerapiiT da Semdgomi Semowmeba

unda gaiaron ufro intensiurad, vidre dabali riskis mqone pacientebma.

preoperaciulad sxvadasxva riskis mqone papilaruli kiboTi daavadebul

riskis albaTobis sworad Sefasebam SesaZlebelia srulad gansazRvros

Tireoideqtomiis farTobi da limfuri kvanZebis diseqciis masStabi(112).

papilaruli mikrokarcinomebis SemTxvevaSi BRAF antigenis gamovlenis

SemTxvevaSi, aRniSnuli kibo agresiuli mimdinareobiT xasiaTdeba.

Sesabamisad im pacientebTan mimarTebaSi, romlebsac mikrokarcinomebis

SemTxvevaSi aReniSnaT BRAF antisxeulis eqspresia aucilebeli xdeba

46

aduvanturi mkurnalobis, radiaqtiuli iodiT ablaciis, totaluri

Tireoideqtomiis da limfodiseqciis Catareba(30). Ees sakiTxi ki

gansakuTrebiT aqtualuria dResdReobiT, vinaidan mikrokarcinomebis

menejmenti sayovelTao davis da azrTa sxvadasxvaobis mizezia(31). Matthias

Preusser at. Al (113) mier warmoebulma kvlevam cxadyo rom papilaruli

mikrokarcinomis SemTxvevebSi gansakuTrebuli yuradReba unda mieqces BRAF

onkogenis eqspresias, rac imunohistoqimiuri kvlevebis Sedegebze

dayrdnobiT, mis sarwmunoebas 95% mde zrdis, da amave dros did Terapiul

datvirTvas atarebs.M masStaburi kvlevis mixedviT(114), sadac gamokvleul

iqna 4000 papilaruli mikrokarcinomis SemTxveva, aRsniSnavia, rom 28%

SemTxvevebSi papilarul mikrokarcinomas axasiaTebs metastazireba, 0,6%-Si

Soreuli metastazebis arseboba da 3,3%_Si xelmeored ganviTarebis riski.

Park et.al-is(115) mixedviT, romelic 1500 SemTxvevaze iqna ganxiluli,

papilaruli mikrokarcinomebis SemTxvevebSi BRAF antisxeulis gamovlena

moxda 67%-Si, rac amave dros utoldeboda klasikuri papilaruli

karcinomebis SemTxvevebSi am antisxeulis gamovlenas da aseTi SemTxvevebi

67% warmoadgenda. damatebiT, maT awarmoes SedarebiTi prevalentobis

gansazRvra klasikur da mikropapilarul karcinomebs Soris

eqstraTireoiduli gavrcelebiT(72,4% sapirispirod 52,2%-isa) da limfur

kvanZebSi metastazirebis mixedviT(51,8% sapirispirod 34,9%-isa) 53 Tviani da

84 Tviani dakvirvebis mixedviT. mikrokarcinomebis menejmenti da Semdgomi

marTva azrTa sxvadasxvaobis sagans warmoadgens, magram savaraudod, im

pacientebSi, visac BRAF dadebiTi papilaruli mikrokarcinomebi

aRmoaCndebaT, unda dadges sakiTxi sruli Tireoideqtomiis,

limfadeneqtomiis da radioaqtiuri iodiT mkurnalobis Sesaxeb.

kvlevebma aCvenes, rom BRAF mutacia ufro meti sixSiriT aRiniSneba

klasikuri formis papilaruli kibos SemTxvevebSi, agreTve,

maRalujreduli qvetipis arsebobisas. Kkvlevis dros, Tu ar moxdeba

papilaruli kibos sxvadasxva histologiuri qvetipebis gamoyofa, da

TiToeul maTganSi BRAF mutaciis da Sesabamisad, maRali riskis

47

albaTobis gansazRvra, maSin Zneli warmosadgeni gaxdeba BRAF mutaciis

gavlena prognozul maCveneblebze. am Temaze dayrdobiT koreulma

kvlevam(116), sadac mxolod papilaruli kibos klasikuri SemTxvevebi

ganixileboda SesaZlebloba mogvca dagvenaxa uSualod klasikuri

papilaruli kibos dros BRAF mutaciis gavlena prognozul

maCveneblebze.(1117) iaponur kvlevaSi 126 papilaruli kibos SemTxvevaze

aCvena urTierTkavSiri BRAF mutaciis arsebobasa da kibos maRal stadias

Soris, agreTve, Soreuli metastazebis arsebobasTan [(7/38 (18%) BRAF mutacia

dadebiT winaaRmdeg BRAF mutacia uaryofiT SemTxvevebSi5/88 (6%), P=0.033)].

Kkoreuli kvleva (118) ki gviCvenebs BRAF mutaciis arsebobis maRal

albaTobas im SemTxvevebSi, romlebSic kisris limfuri kvanZebis dazianeba

vlindeboda[(39/58 (67%) BRAF mutaciiT winaaRmdeg SemTxvevebisa BRAF

mutaciis gareSe4/12 (33%), P=0.048](119). unda aRiniSnos isic, rom italieli

mkvlevarebis mier warmoebul or kvlevaze dayrdnobiT(120,121) BRAF

mutaciasa da maRali riskis mqone patologiur maxasiaTeblebs Soris

mniSvnelovani urTierTdamokidebuleba ar arsebobda. es faqti ki

mkvlevarebis azriT ZiriTadad ukavSirdeboda mcire raodenobiT sakvlevi

masalis arsebobas(50-60 SemTxveva). calkeulma kvlevebma ki aCvena rom

papilaruli karcinomis ganmeorebiT aRmoceneba uSualod BRAF mutaciis

arsebobas ukavSirdeboda(122,123,124). Kkvlevam M Xing et al.-is(125) mier

gamoavlina mniSvnelovani urTierTdamokidebuleba BRAF mutaciis

arsebobasa da papilaruli kibos eqstratireoidul gavrcelebs Soris,

limfur kvanZebSi metastazirebis meti albaToba, kibos xelaxali

aRmocenebis meti albaToba, kibos maRali stadiis arseboba. Aamave kvlevaze

dayrdnobiT, kibos xelmeored aRmocenebis riski 25% wamoadgens BRAF

dadebiT pacientebSi, xolo mxolod 9%BRAF uaryofiT pacientebSi(p=0,004).

kvlevis mixedviT, kisris limfuri kvanZebSi metastazebis arseboba

korelaciaSia preoperaciul klinikur parametrebTan: simivnis zomasTan,

asakTan da BRAF mutaciis statusTan(122). aRmoCnda, rom BRAF dadebiToba

kisris limfuri kvanZebis dazianebisas mniSnelovan prediqtorul markers

48

warmoadgenda, iseve rogorc univariabeluri analiziT(OR 8,4; p=0,01), aseve

multivariabeluri analiziT(OR=9,7; p=0,02).aRiniSna kavSiri sawyisi

qirurgiuli Carevisas pirveladi kibos arsebobisas mutaciasa da ufro

maRali dazianebis stadiasTan[(stadia III, 10/38 (26%) BRAF mutacia dadebiT

winaaRmdeg 2/66 (3%) BBBRAF - SemTxvevebisa, PP=0.006; stadia IV, 7/38 (18%)

BRAF mutacia dadebiTi winaaRmdeg 3/66 (4%) BRAFmutacia uaryofiT

SemTxvevebSi, PP=0.03)]. mutaciasa da klinikopaTologiur gamosavals Soris

urTierTdamokidebuleba gamokvleul iqna Semdeg kvlevebSi(126,127) .

dResdReobiT arsebulma arcerTma kvlevam ar aCvena BRAF mutaciis

arsebobis urTierTkavSiri pirveladi kibos did zomebTan, rac miuTiTebs

imaze, rom BRAF mutaciis arseboba ukavSirdeba ara pirveladi kibos

zrdas, aramed agresiulobiszrdas, rac gamoixateba, kibos Tavdapirvelad

ganviTarebaSi, limfuri kvanZebis dazianebasa da Soreuli metastazirebis

arsebobaSi(128).

BRAF antigenis eqspresia idealuri samiznea molekuluri TerapiisTvis(30).

cnobilia, rom pacientebi, romlebsac aRenebiSnebaT papilaruli karcinoma

BRAF dadebiTi mutaciiT cudi prognoziT xasiaTdebian, radganac TviT

mutacia ganapirobebs aduvanturi Terapiis mimarT mdgradobas.

radioaqtiuri iodiT ablaciiis efeqturoba papilaruli karcinomebisas

mTlianad damokidebulia Tireocitebis im unarze, rom natrium-iodis

simporteriT CairTos iodi. In vitro kvlevebma ki aCvenes, rom natrium-iodis

simporteris eqspresia Zalian dabalia BRAF mutacia dadebiT papilarul

karcinomebSi. Aaqedan gamomdinare, aseT pacientebSi BRAFinhibitoris

gamoyeneba mizanmimarTul da efeqtur Terapiul arCevans warmoadgens(129).

amave dros aRmoCnda, rom is pacientebi, romlebsac BBRAF mutacia

aReniSnebodaT radiaqtiuli iodis mimarT rezistentuli iyvnen, es faqti ki

sarwmunos xdis azrs imis Sesaxeb, rom BRAF mutaciis arseboba, aramarto

iwvevs kibos ganmeorebiT aRmocenebis riskis gazrdas, aramed iwvevs

49

radiaqtiuli iodiT mkurnalobis mimarT mkveTr rezistenobas, rac Tavis

mxriv ufro cud prognozTan asocirdeba(130).

50

Tavi II. kvlevis masala da meTodebi:

2.1. wvrilnemsiani aspiraciuli biofsiiT miRebuli maselebi(FNA-

biofsiuri masalebi):

erTi wlis ganmavlobaSi 2013-1014 Segrovili iqna 600 pacientidan miRebuli

wvrilnemsiani aspiraciuli biofsiuri masala. Mmasalis SegrovebaSi

CarTuli iyo sami klinikuri dawesebuleba (New Hospitals-niu hospitali,

Tbilisis onkologiuri centri da erovnuli skrining centri). Segrovda

aRniSnuli SemTxvevebis yvela klinikodiagnostikuri monacemi.

citopaTologiuri SemTxvevebis moZieba arqivis kompiuteruli moZiebis

Sedegad ganxorcielda.

yvela wvrilnemsiani aspiraciuli biofsia Catarda ultrabgeriTi

kontrolis qveS, aseptikis da antiseptikis ZiriTadi normebis

gaTvaliswinebiT. meTodisTvis gamoyenebuli iqna 23-25G gaudiani Spricebi.

proceduris SesrulebisTanave momzadda ramodenime nacxi da swrafadve

dafiqsirda 95%-iani eTilis spirtiT. Yyvela maTgani SeiReba papanikolaus

ukve kargad adaptirebuli meTodiT. im SemTxvevebSi, rodesac miviReT

siTxe, aRniSnuli siTxe davacentrifugeT da naleqi gavnacxeT ramodenime

sasagne minaze, romlebic aseve SeiReba rutinuli papanikolaus meTodiT.

masalis interpretacia ganxorcielda mikroskopis qveS gamocdili

citopaTologis mier, aseve,ganxorcielda sakvlev masalaTa umetesi

nawilis ganmeorebiTi Sefaseba sxva citopaTologis mier. Sefaseba

sruliad emyareboda citomorfologiaSi arsebul dRevandel standartebs

da interpretaciebs, Sesabamisad is ganxorcielda betesdas klasifikaciis

mixedviT. TiToeuli SemTxvevis klasifikaciis garkveul jgufSiganTavseba

moxdaMmasalis adeqvaturobasTan dakavSirebul gailainebze dayrdnobiT.

adeqvaturad da diagnostirebisTvis gamosadegad CaiTvala iseTi

citologiuri masala(91,3%), romelic Seicavda kargad Senaxul

folikuluri ujredebisagan SemdgarxuT-eqvs jgufs, romelTaganac

51

TiToeul jgufSi aRiniSneboda aranakleb aTi ujredi. SeirCa mxolod

iseTi masalebi, romlebic teqnikurad idealurad iyo momzadebuli,

Sesabamisad aspiratebis ganacxvac moxda swrafad, maTi swrafadve

dafiqsirebiT, raTa Tavidan agvecilebina, is ujreduli cvlilebebi,

romlebic sirTuleebs qmnis citomorfologiur diagnostikaSi da umetes

SemTxvevebSi fiqsaciis defeqtebs ukavSirdeba. diagnostikisas

gaTvaliswinebul iqna yvela klinikuri da radiologiuri monacemi, rac

ki TiToeul SemTxvevas ukavSirdeboda. Aaspiratebi, romlebic

araadeqvaturad Sefasdnen, daeqvemdebarnen ganmeorebiT aspiracias,

radganac mraval kvlevaze dayrdnobiT araadeqvatur masalebSi kibos

arsebobis riski daaxloebiT 5-15%-ia. ganmeorebiTi wvrilnemsiani

aspiraciuli kvleva Catarda 52 SemTxvevidan mxolod 24 SemTxvevaSi.

pacientTa nawilma uari ganacxada ganmeorebiT kvlevaze.

histomorfologiur bazaze dayrdnobiT SevarCieT iseTi pacientebi,

romlebsac ukve CautardaT qirurgiuli mkurnaloba. avTvisebianobis riski

betesdas sistemis TiToeul kategoriaSi ganisazRvra citopaTologiuri da

histopaTologiuri monacemebis gaTvaliswinebiT.

yvela pacienti, romelic CarTuli iyo am kvlevaSi daiyo asakis da sqesis

mixedviT, agreTve, klinikuri da radiologiuri monacemebis

gaTvaliswinebiT. pacientebis asaki meryeobda 20-dan 80 wlamde. Cven isini

pirobiTad davajgufeT oTx asakobriv jgufad: I- 20-dan 35 wlamde, II- 36-dan

50 wlamde, III- 51 wlidan 65 wlamde da IV- 66 wlidan 80 wlamde.

ganisazRvra, Tu betasdas klasifikaciis romeli klasi, ra upiratesobiT

vlindeboda TiToeul asakobriv jgufSi, Sefasda TiToeul jgufSi

betesdas kategoriaTa procentuli maCvenebelic. Semdeg Cven ganvsazRvreT

rogor TanxvedraSi iyo TiToeuli citomorfologiuri diagnozi moZiebul

histomorfologiur diagnozebTan, TiToeul aseT SemTxvevaSi

CamovayalibeT avTvisebianobis riski.

52

2.2. masalebi histomorfologiuri da imunohistoqimiuri kvlevisTvis:

erTi wlis ganmavlobaSi 2014 wlidan 2015 wlamde histologiuri

masalebis Segroveba ganxorcielda Sps paTologTa da citologTa

gaerTianeba- paTjeo -s (Tbilisi, saqarTvelo) da endokrinologia-

metabologia-dietologiis centr- enmedici-is (Tbilisi, saqarTvelo)

bazaze, histomorfologiur arqivebSi. kvlevaSi CarTulobis kriteriumebs

warmoadgenda: diferencirebuli farisebri jirkvlis simsivneebi, romlebic

folikuluri epiTelidan warmodgebodnen, moicavdnen ra adenomatozur

kvanZebs, papilaruli karcinomis formebs: papilaruli karcinomis

klasikur variants, papilarul mikrokarcinomebs, papilaruli karcinomis

folikulur variants(inkapsulirebuls), farTeujredulvariants,

papilarul karcinomas multicentruli zrdiT da eqstraTireoiduli

gavrcelebiT, folikulur adenomas, folikulur karcinomas, hurtlis

ujredul dazianebebTan erTad. kvlevaSi gamoyenebul iqna normaluri

farisebri jirkvlis qsovilisgan Semdgari masalebic. saerTo jamSi kvleva

ganxorcielda 54 SemTxvevaze, sadac 4 SemTxveva Seicavda mxolod

normaluri farisebri jirkvlis qsovils. parafinSi Cayalibebuli masala

kargad damuSavebuli da SenarCunebuli arqiteqtonikuli maxasiaTeblebiT

unda yofiliyo.

histomorfologiuri interpretacia ganxorcielda ganmeorebiT ori

damoukidebeli histopaTologis mier. Ddiagnostireba, greidingi mTlianad

daeyrdno msoflio jandacvis organizaciis (WHO) mier farisebri

jirkvlis simsivnuri procesebis diagnostikur kriteriumebs.

imunohistoqimiuri kvlevisTvis, formalinSi dafiqsirebuli da parafinSi

Cayalibebuli masalebisgan anaTlebis damzadeba ganxorcielda 3-4

mikronze mikrotomis saSualebiT. Mmasalebis ganTavseba moxda adheziviT

damuSavebul sasagne minebze. sasagne minebi moTavsda DAKO-ს PT Link-Si

kodi: PT10126). PT Link-Si, romelSic winaswar Casxmuli iyo buferi-Target

53

retrieval solution high ph 50X, romelic Tavis mxriv warmoadgens, rogorc

antigenis aRmdgens, aseve deparafinizaciis bufers. aRniSnul aparatSi

antigenis aRdgena ganxorcielda 20 wuTis ganmavlobaSi, 97 OC-ze.

aRdgenis procesis damTavrebisTanave sasagne minebi gadavida WASH BUFFER(

20X)-Si, amave firmis kodiT: K8000,DM831.

Semdegi etapi iyo Envision Flex Peroxidaze-blocking reagent -5wT.(kodiT: K8000,SM801)

kvlevaSi gamoyenebuli iqna Semdegi pirveladi monoklonuri antisxeulebi:

1.HBME-1 monoclonal mouse , kodiT :M3505, koncentirebuli antisxeuli

ganz:1:100.

2. TTF1 Monoclonal mouse , kodiT:M3575 koncentirebuli antisxeuli ganz: 1:100.

3. CD56 Monoclonal mouse , kodiT: M 7304. koncentirebuli antisxeuli ganz:

1:100.

4. CK19 Monoclonal mouse , kodiT: M 0888 , koncentirebuli antisxeuli ganz:

1:75.

5. Anti-BRAF antibody produced in rabbit , kodiT (SIGMA-HPA001328) ganz: 1:75

Semdeg etapi ganxorcielda meoradi antisxeuliT- Envision Flex/HRP, kodiT:K

8000,SM802

inkubaciis periodi warmoadgenda 20wuTs.

qromogenis etapi:Envision Flex substrate buffer , DAB + Chromogen (substrati da

koncentrati)ganzavebiT: 1:50.

inkubaciis dro: 5-25wT.

Semdeg preparatebi ramdenime wamiT SeiReba GILL 3 HEMATOXILIN -Si.

dehidratacia, gamWvirvaloba da safari minis dafareba Moutant synthetic .

54

imunohistoqimiuri Sefaseba ganxorcielda da Sejamda cxrilis saxiT.

mocemuli masalebi ganTavsda aRniSnuli cxrilis oTx grafaSi:

1. masalebi, romlebic ar avlenen mocemuli antisxeulebis eqspresias.

2. masalebi, romlebSic aRiniSneba susti eqspresia(naklebia 10%-ze)

3. masalebi, romlebic avlenen zomier eqspresias(11%-dan 50% mde)

4. masalebi, romlebic avlenen mkveTr eqspresias(metia 51%-ze)

Cvens mier warmoebuli kvlevis statistikuri analizi ganxorcielda

statistikuri analizis meTodis ANOVA,SPSS (Version 21) saSualebiT.

statistikurad sarwmunod da mniSvnelovnad CaiTvala kvlevis is Sedegebi,

romelTa P -value naklebi aRmoCnda 0,05(<5%)-ze.

histomorfologiuri kvlevis Semdgom, rogorc ukve aRiniSna, masalebi

dajgufda rva ZiriTad histologiur jgufad, romelTa gradacia

izrdeboda aRniSnuli histomorfologiuri jgufis agresiulobis xarisxis

mixedviT. TiToeul jgufSi ganisazRvra maTi sixSire da procentuli

maCvenebeli, agreTve, validuri da kumulaciuri procenti:

0---Nnormaluri farisebris qsovili- 4 (7,4%)

1---Aadenomatozuri hiperplazia - 6 (11,1%)

2---Ffolikuluri adenoma- 5 (9.3%).

3--- papilaruli karcinoma inkafsulirebuli- 3 (5,6%)

4--- papilaruli mikrokarcinoma- 9 (16.7%)

5--- papilaruli karcinoma-17 (31,5%)

6--- papilaruli karcinoma multicentuli – 4 (7,4%).

7--- papilaruli karcinoma eqstraTireoiduli gavrcelebiT – 3 (5,6%)

8--- folikuluri karcinoma – 3 (5,6%).

55

Catarda univariabeluri analizi, sadac damokidebul anu gamosavlis

cvladad (Dependent Variable) CaiTvala anti-BRAF antisxeulis eqspresia, xolo

mudmiv anu prediqtorul cvladad (Predicrors: Constant) danarCeni xuTi

antisxeulis eqspresia. Tu arastandartuli koepicenti Sefasda dadebiT

ricxvad, miCneul iqna, rom TiToeuli prediqtoruli cvladis eqspresia

ganapirobebs damokidebuli cvledis eqspresiasac, xolo statistikurad ki

es mniSvnelovania, rodesac P<0,05.

Cvens mier gamokvleul 54 SemTxvevaSi Sesrulda mravalcvladiani

statistikuri analizi. ganisazRvra SansTa Tanafardoba(OR).Nnormad

Sefasda gamokvleul antisxeulTa susti eqspresia an uaryofiTi eqspresia,

xolo 1_iT aRiniSna saSualo an mkveTri eqspresia.

56

Tavi III kvlevis Sedegebi

3.1. citologiuri da histologiuri kvlevis Sedegebi

wvrilnemsiani aspiraciuli biofsiuri masalis miReba ultrasonografiuli

kontrlolis qveS ganxorcielda 600 pacientSi, diagnostireba da FNA-

biofsiuri masalebis interpretacia moxda betesdas klasifikaciis

mixedviT. Qkacebsa da qalebs Soris Tanafardoba ganisazRvra da aRmoCnda,

rom is warmoadgenda 1:9, ramac gviCvena, rom farisebri jirkvlis kvanZovani

daavadeba Cvens mier gamoyenebul sakvlev masalSi dominirebs qalebSi.

ganisazRvra damokidebuleba asakobriv jgufebsa da betesdas sistemis

diagnostikuri kriteriumebiT Sefasebul sakvlev masalebs Soris. Ees

korelaciebi warmodgenilia Semdegi grafikuli gamosaxulebi saxiT:

grafiki 1. urTierTkavSiri asakobriv jgufebsa da wvrilnemsiani

aspiraciuli biofsiiT miRebuli masalebisbetesdas klasifikaciis

kategoriebs Soris (ND-diagnostirebisTvis arasakmarisi, BN-

keTilTvisebiani kvanZi, AUS-atipia ganusazRvreli mniSvnelobis, SFN-saeWvo

folikulur neoplaziaze, SM-saeWvo avTvisebiani procesis arsebobaze,

MGT-avTvisebiani.

20-35

50-650

50

100

150

200

I ND/UNS

II BN III AUS IV SFN V SMVI MGT

20-35

36-50

50-65

65-80

57

Cven kvlevaze dayrdnobiT, 600 Catarebuli biofsiidan 52 pacientis

SemTxvevaSi(8,7%) aspiraciuli biofsiuri masala Sefasda araadeqvaturad,

es faqti ki ukavSirdeboda cisturi warmonaqmnebis an makrokalcinatebis

arsebobas. Mmocemul pacientTagan 24 SemTxvevaSi ganxorcielda

ganmeorebiTi aspiraciuli biofsiis warmoeba,romlis Semdeg masalebis

gadanawileba ganxorcielda Sesabamis kategoriebSi, madgan 1 aRmoCnda

avTvisebiani procesi, xolo 6 SemTxveva Sefasda kvlav araadeqvaturad.

miRebuli Sedegebi warmodgeba Semdegi grafikuli gamosaxulebis saxiT:

grafiki 2. KurTierTkavSiri asakobriv jgufebsa da betesdas

klasifikacia 1-s (ND/ UNS-aradiagnostirebadi, araadeqvaturi

diagnostirebisTvis) Soris. I asakobrivi jgufi(n=7), II jgufi(n=13),

IIIjgufi(n=12), IV jgufi(n=20).

betesdas kategoria 2- anu keTilTvisebiani warmonaqmnebizogadad,

wvrilnemsiani aspiraciuli biofsiiT miRebul masalaTa 60-70%

warmoadgens. ACvens mier warmoebul kvlevaSi betesdas kategoria 2-ad anu

0

2

4

6

8

10

12

14

16

18

Group I(20-35) Group II(36-50) Group III(51-65) Group IV(66-80)

korelaciebi asakobriv jgufebsa da betesdas kategoria 1-s

Soris(ND/UNS)

58

keTilTviebian warmonaqmnebad Sefasda sakvlev SemTxvevaTa 63% da maTi

umravlesoba ganTavsda II(n=164), III(n=132) asakobriv jgufSi.

citopaTologiuri diagnostirebisas yvelaze xSirad aRiniSneboda

koloiduri kvanZebis arseboba(64%), moicavda ra koloidur kvanZebs

hemoragiebiT, cisturi degeneraciiT an adenomatoiduri zrdiT.

keTilTvisebian diagnozebs Soris aRiniSneboda haSimotos Tireoiditi(28%),

de querveinis Tireoiditi(5%) da far-inis cistebi(3%).keTilTviebian

warmonaqmnebSi folikuluri ujredebi ganlagebuli iyo erTSriani

plastebis saxiT, calkeul SemTxvevebSi ki qmnida Zalzed mowesrigebul

samganzomilebian struqturebs, romlebic sruliad intaqturi iyo, qmnida

ra ujredul sferoebs. TumcaAanizonukleozi aRiniSneboda calkeul

SemTxvevebSi, magram gamokveTili pleomorfizmi da birTvuli atipia ar

gamovlinda. aRiniSna erTeuli mikrofolikuluri struqturac.

Uuxvujredovneba ar aRiniSna, ZiriTadad, sakvlevi nacxebi avlendnen

mcireujredovnebas da es vlindeboda masalaTa 52,2%-Si, an

zomierujredovnebas da es aRiniSneboda 47,8% SemTxvevebSi. pleomorfizmi

aRiniSna mxolod SemTxvevaTa 2,9%-Si, erTeuli hurtlis ujredi

gamovlinda SemTxvevaTa 2,2%-Si, makrofagebi(Rrubliseburi ujredebi)

aRiniSna SemTxvevaTa 39%-Si. rac Seexeba fons, koloidTan narevi

eriTrocitebisagan Semdgari foni aRiniSna SemTxvevaTa 55,8%-Si, xolo

mxolod koloidi SemTxvevaTa 44,2%.

sakvlevi masalebis subkategiria haSimotos Tireoiditi warmoadgenda

keTilTvisebiani kategoriis SemTxvevaTa 28%. Yyvela nacxi zomierad

ujreduli iyo. Llimfoiduri populacia zomierad vlindeboda SemTxvevaTa

89%-Si. Llimfoiduri ujredebi polimorfizms avlendnen. SesaZlebeli iqna

intaqturi limfohistiocituri agregatebis aRmoCenac. umetes SemTxvevebSi

aRiniSneboda hurtlis ujredebis arseboba. mravalbirTviani ujredebi

aRiniSna SemTxvevaTa 27,8%-Si, xolo epiTeloiduri ujredebi 11,2%-Si.

keTilTvisebian warmonaqmTa Tanafardoba betesdas meore kategoriaSi

59

Segvilia grafikulad gamovsaxoT:

grafiki 3. keTilTvisebiani warmonaqmnebis Tanafardoba betesda

2kategoriaSi. cisferi-koloiduri kvanZebi, wiTeli-Tireoiditebi,

nacriferi-far/inis cistebi.

grafikulad Cveni kvlevis monacemebi SegviZlia Semdegnairad

warmovadginoT, sadac aRniSnulia Tanafardobebi diagnostikuri kategoria

2-s mixedviT sxvadasxva asakobriv jgufebSi:

64%

33%

3%

0

colloid nodule

thyroiditis

thyroglosal cysts

0

50

100

150

200

Group I(20-35) Group II(36-50) GroupIII(51-65) Group IV(66-80)

ko r el ac i ebi asako br i v j guf ebsa da bet esdas kat ego r i a 2-s So r i s(BN)

60

grafiki 4. KurTierTkavSiri asakobriv jgufebsa da betesdas

klasifikaciiT meore klass(BN)-keTilTvisebian dazianebebs Soris.I

asakobrivi jgufi(n=44), II jgufi(n=164), IIIjgufi(n=132), IV jgufi(n=38).

aseve warmovadgenT papanikolaus meTodiT SeRebil ramodenime SemTxvevis

fotosuraTs, sadac aRniSnulia farisebri jirkvlis keTilTvisebiani

warmonaqmnebi.

sur 1. koloiduri kvanZi. wvrilnemsiani aspiraciuli biofsiuri masala

36wlisqali.(papanikolaus SeRebva,40X)sur. 2 Kkoloiduri

kvanZi.wvrilnemsiani aspiraciuli biofsiuri masala 47 wlis qali.

papanikolaus SeRebva, 40X.

61

sur 3.limfoplazmocituri infiltracia haSimotos Tireoiditis

droswvrilnemsiani aspiraciuli biofsiuri masala 51w. qali(40X)

62

sur. 4 haSimotos Tireoiditi. wvrilnemsiani aspiraciuli biofsiuri

masala 57w. qali (papanikolaus SeRebva, 10X).

Cveni kvlevis farglebSi operciul masalaTa 76 SemTxvevidan, aRmoCnda,

rom 59(77,6%) SemTxveva ganekuTvneboda kvanZovan Ciyvs, 12(15,7%) SemTxeveva

dadiagnozda, rogorc folikuluri adenoma, xolo 5(6,5%) SemTxveva

rogorc papilaruli karcinoma, Tumca maTi zoma 1 sm-ze naklebi aRmoCnda

da maTi aspiracia arc ganxorcielebula, isini mxolod Tireoideqtomiis

Sedegad aRmoCenil SemTxveviTobad SegviZlia miviCnioT, radgan mravali

kvlevis Sedegad SemTxveviT aRmoCenili karcinomebi, mxolod autofsiis

Semdeg Tu gamovlindeba xolme(131).

63

betesdas kategoria 3- AUS/FLUS

betesdas kategoria 3-s, romelic yvelaze heterogenul diagnostikur

kategorias ganekuTvneba, Cvens mier gamokvleuli 600 pacientidan 88

pacientis wvrilnemsiani aspiraciuli biofsiuri masala(14.6%) miekuTvna da

maTi ZiriTadi umravlesoba II(n=32) da III(n=32) asakobriv jgufs

warmoadgenda. Cveni kvlevis farglebSi, am kategorias mivakuTvneT

SemTxvevebi, romlebic iyo uxvujreduli, calkeul ubnebze warmodgenili

iyo samganzomilebiani, mouwesrigebeli struqturebi, aRiniSneboda zomieri

pleomorfizmi(84%), calkeul SemxvevebSi vlindeboda birTvTa Rarebi da

CanaWdevebi(67%), birTvSida citoplazmuri fseudoCanarTebi(58%), romlebic

ver iqna Sefasebuli, rogorc srulyofili CanarTebi. 88 pacientidan 54

pacientma Caitara nawilobrivi an sruli Tireoideqtomia.

histopaTologiuri Sefasebis Semdgom 19(35.2%) SemTxveva Sefasda, rogorc

kvanZovani Ciyvi, 24(44.4%) SemTxveva Sefasda, rogorc folikuluri adenoma,

xolo 11(20.3%), rogorc avTvisebiani dazianeba. grafikulad es monacemebi

Semdegnairad gamovxateT:

35.20%

44.40%

20%

0

nodular goiter

follicular adenoma

Cancer

64

grafiki 5. Bbetesda 3 kategoriis histologiuri Sefasebis Semdgomi monacemebi.

wiTeli-kvanZovani Ciyvi, cisferi-folikuluri adenoma, nacrisferi-avTvisebiani

dazianeba.

avTvisebian SemTxvevaTa 9 SemTxveva(81,8%) aRmoCnda papilaruli 65ariant65a

da 2(18,2% ki folikuluri 65ariant65a). Ppapilaruli karcinomis 9

SemTxvevidan 6(66,6%) ganekuTvneboda papilaruli karcinomis folikulur

variants, xolo 3(33,4%) SemTxveva ki klasikur papilarul karcinomas

warmoadgenda.MganisazRvra avTvisebianobis riski, Cvens mier warmoebul

kvlevaze dayrdnobiT, betesdas kategoria 3-ad diagnostirebul

SemTxvevebSi is 20,4% Seadgenda.

Cveni kvlevis Sedegebi SegviZlia grafikulad warmovadginoT:

grafiki 6. KurTierTkavSiri asakobriv jgufebsa da betesdas

klasifikaciiT mesame klass-AUS/FLUS dazianebebs Soris.I asakobrivi

jgufi(n=11), II jgufi(n=32), IIIjgufi(n=32), IV jgufi(n=13).

0

5

10

15

20

25

30

35

Group I(20-35) Group II(36-50) Group III(51-65) Group IV(66-80)

65

betesdas klasifikaciiT meoTxe jgufi- folikuluri dazianebebi,

folikuluri neoplazia, romlis qveS igulisxmeba, rogorc folikuluri

adenoma, aseve folikuluri karcinoma da hurtlis ujreduli neoplazia.

aRniSnul jgufs mivakuTvneT is sakvlevi masalebi, romlebSic

aRiniSneboda uxvujredovneba, mikrofolikuluri da samganzomilebiani

struqturebis formireba, birTvTa araTanabari konturebis arseboba,

qromatinis araTanabrad gadanawileba.Cvens kvlevaSi gamoyenebuli

masalebis 6,3%(38 SemTxveva) Sefasda, rogorc folikuluri neoplazia. maTi

ZiriTadi umetesoba II(n=14) an III(n=12) asakobriv jgufSi ganTavsda. 26

pacientma Caitara Tireoideqtomia. Hhistologiuri kvlevis Semdgom 8(30,2%)

SemTxveva Sefasda, rogorc avTvisebiani dazianeba(ZiriTadad, papilaruli

karcinomis folikulur tipad an papilarul karcinomad), 18(69,8%)

SemTxveva ki Sefasda, rogorc folikuluri adenoma an adenomatozuri

hiperplazia. malignantobis riski aRniSnul kategoriaSi Cveni kvlevis

farglebSi 30,2% Seadgina.

0

5

10

15

Group I (20-35) Group II (36-50)

Group III(51-65)

Group IV(66-80)

korelaciebi asakobriv jgufebsa da betesdas kategoriiT 4-s Soris

66

grafiki 7. KurTierTkavSiri asakobriv jgufebsa da betesdas

klasifikaciiT meoTxe klass-folikulur neoplaziebs Soris.I

asakobrivi jgufi(n=8), II jgufi(n=14), IIIjgufi(n=12), IV jgufi(n=4).

sur.5 folikuluri neoplazia.Mmikrofolikuluri struqturebi.

araTanabari qromatini.wvrilnemsiani aspiraciuli biofsiuri masala 67w.

mamakaci. (papanikolaus SeRebva, 40X).

67

sur.6 folikuluri neoplazia.Mmikrofolikuluri struqturebi.

hiperqromia, koloidis ararseboba.wvrilnemsiani aspiraciuli biofsiuri

masala 71w. qali (papanikolaus SeRebva, 40X).

betesdas klasifikaciiT mexuTe diagnostikuri kategoria maRali

malignontobis riskis mtareblad gvevlineba da Tavis TavSi moisazrebs im

dazianebebs, romelic papilarul karcinomaze didi eWvis arsebobas

gansazRvravs. Aam kategoriaSi movisazreT SemTxvevebi, romlebic

xasiaTdebodnen papilaruli karcinomis ujreduli maxasiaTeblebis

arasrulfasovani arsebobiT(mag, birTvuli fseudoCanarTebis arseboba

mxolod erTeul ujredSi).Cveni kvlevis farglebSi masalaTa 2% (12

Semxveva) Sefasda saeWvo papilaruli karcinomis arsebobaze.Yvelaze

xSirad es diagnostikuri kategoria I (n=4) da III(n=4) asakobriv jgufSi

68

ganTavsda. Histologiuri kvlevis Semdgom TerTmeti SemTxveva(91,6%)

dadiagnozda papilarul karcinomad, maTgan eqvsi SemTxveva(54,5%) Sefasda,

rogorc papilaruli karcinomis folikuluri 69ariant,warmodgenili 12

SemTxvevidan mxolod erTi Sefasda, rogorc hurtlis ujreduli adenoma.E

es monacemebi SesaZlebelia gamovsaxoT Semdegi grafikis saxiT:

grafiki 8. KurtierTkavSiri asakobriv jgufebsa da betesdas

klasifikaciiT mexuTe klass-saeWvo avTvisebianobaze dazianebebs Soris.I

asakobrivi jgufi(n=4), II jgufi(n=2), IIIjgufi(n=4), IV jgufi(n=2).

0

1

2

3

4

Group I(20-35) Group II(36-50) Group III(51-65) Group IV(66-80)

korelaciebi asakobriv jgufebsa da betesdas kategoria 5-s Soris

69

sur.7 hurtlis ujreduli neoplazia saeWvo avTvisebianobaze.wvrilnemsiani

aspiraciuli biofsiuri masala 42w. qali. P(papanikolaus SeRebva, 10X)

betesdas meeqvse kategoria- avTvisebiani dazianebebi Tavis TavSi

moisazrebs ara mxolod uSualod farisebri jirkvlis simsivneebs, aramed,

farisebr jirkvalSi aRmocenebul metastazebsa da limfomebsac. birTvebis

gadideba, zeddeba, dagrZeleba, araTanabari konturebi, birTvuli CanarTebi

da Rarebi, sqvamozuri citoplazma, WeSmariti papilebis gamovlena,

fsamomuri sxeulakebi avTvisebianobis ZiriTad maxasiaTeblebs

warmoadgenda Cvens mier citologiurad Sefasebul aspiraciul biofsiur

masalebSi. Cveni kvlevis farglebSi CarTuli 30 avTvisebiani

SemTxvevidan(5%), romelTaganac yvela diagnozi dadasturebul iqna

histologiuradac, 14(46,6%) SemTxveva gamovlinda I asakobriv jgufSi.

pacientebi, romelTa wvrilnemsiani aspiraciuli biofsiuri masala

Sefasda, rogorc avTvisebiani anu betesdas kategoriiT meeqvse jgufi: 22

70

SemTxveva(73,3%) warmoadgenda papilaruli karcinomis klasikur variants,

3(10%) folikulur karcinomas(hurtlis ujredul variants), 1(3,3%)

medularul karcinomas, 3(10%) anaplaziur karcinomas da erTi(3,3%)

difuzur didujredul limfomas. Grafikulad es monacemebi Semdegnairad

SegviZlia gamovsaxoT:

Y

grafiki 9.Bbetesda 6 kategoriis histologiuri Sefasebis Semdgomi

monacemebi. cisferi–papilaruli karcinoma, wiTeli-folikuluri karcinoma,

nacrisferi-medularuli karcinoma, yviTeli-anaplaziuri karcinoma,

lurji- difuzuri didujreduli limfoma.

grafikulad asakobriv jgufebSi betesdas meeqvse kategoriad Sefasebuli

masalebis gadanawileba grafikulad Semdegnairad SegviZlia

warmovidginoT:

74%

10%

3%10% 3%

PTC

FC

Medullary Cancer

Anaplastic carcinoma

Diffuse large Cell Lymphoma

71

grafiki 10. KurTierTkavSiri asakobriv jgufebsa da betesdas

klasifikaciiT meeqvse klass-avTvisebian dazianebebs Soris.I asakobrivi

jgufi(n=14), II jgufi(n=10), IIIjgufi(n=4), IV jgufi(n=2).

0

2

4

6

8

10

12

14

Group 1(20-35) group II(36-50) Group III(51-65) Group IV(66-80)

72

sur.8.papilaruli karcinomis folikuluri

varianti.wvrilnemsianiaspiraciuli biofsiuri masala 22w.qali.papanikolaus

SeRebva, 40X

73

sur.9. papilaruli karcinoma. wvrilnemsiani aspiraciuli biofsiuri masala

29w.qali. papanikolaus SeRebva, 40X.

3.2. imunohistoqimiuri kvlevis Sedegebi

Cveni kvlevis farglebSi imunohistoqimiuri kvleva ganxorcielda 54

sakvlev histologiur masalaze Semdegi monoklonuri antisxeulebis

eqspresiis gamosvlenad: anti-BRAF, HBME-1, CD-56, CK-19, KI-67.normaluri

farisebri jirkvlis qsovili ar avlenda BRAF antisxeulis mimarT

dadebiT eqspresias. adenomatozuri hiperplaziis da folikuluri

adenomebis calkeuli SemTxvevebi (33% da 40%) mxolod sustad pozitiuri

aRmoCndnen am antisxeulis mimarT, Tumca sustad pozitiuroba Cveni

kvlevis farglebSi saerTo jamSi ar Sefasda dadebiT eqspresiad.

papilaruli karcinomebis inkafsulirebulma formebma gamoavlines susti

imunoreaqtiuloba aRniSnuli antisxeulis mimarT(68%) an sruliad

imunouaryofiTebi aRmoCndnen, Sesabamisad inkafsulirebuli formebis

arcerTi SemTxveva ar Sefasda dadebiT eqspresiad. papilaruli

mikrokarcinomebis SemTxvevebSi, imunoreaqtiuloba aRniSnuli antisxeulis

mimarT Semdegnairad gadanawilda: 22% mikrokarcinomebisa aRmoCnda

uaryofiTi BRAFantisxeulis mimarT, sustad imunoreaqtiuli aRmoCnda

SemTxvevaTa 22%, zomier eqspresias avlenda SemTxvevaTa 33,3%, xolo

mkveTri eqspresia gamovlinda 22,2%. zomieri da mkveTri eqspresia

Sefasebul iqna dadebiT eqspresiad.BRAF antisxeulis mimarT, papilaruli

karcinomebis klasikur SemTxvevebSi gamovlinda 47,1% mkveTri eqspresia da

11,8% zomieri eqspresia, saerTo jamSi dadebiT eqspresiad Sefasda

SemTxvevaTa 58,8%. xolo uaryofiTiTad CaiTvala 41,2%. papilaruli

karcinomis yvela SemTxvevam eqstraTireoiduli gavrcelebiT an

multicentruli zrdiT gviCvena BRAF antisxeulis zomieri(49%) an mkveTri

imunoreaqtiuloba(51%). folikuluri adenomebi, iseve rogorc,

74

folikuluri karcinomebi Cvens kvlevaSi ar avlendnen imunoreaqtiulobas

aRniSnuli antisxeulis mimarT.

Cven mier gamokvleul masalaSi aRiniSna, rom im simsivneebs, romelSic

aRiniSna BRAF mutaciis zomieri an mkveTri eqspresia, axasiaTebdaT

infiltraciuli kideebi da ar gaaCndaT intaqturi kafsula, agreTve,

aRiniSna isic, rom mutaciisSemcvel simsivneebs axasiaTebdaT simsivnesTan

asocirebuli stromuli cvlilebebi, desmoplazia, fibrozi da sklerozi.

urTierTdamokidebuleba BRAF antisxeulis eqspresisiisa da farisebri

jirkvlis kvanZovan dazianebebs Soris grafikulad Semdegnairad SegviZlia

gamovsaxoT:

grafiki 8: BRAF antisxeulis eqspresiasa da farisebri jirkvlis

histotipebs Soris arsebuli urTierTkavSiri. NT( normal tissue-farisebri

jirkvlis normaluri qsovili, AH(adenomatous hyperplasia-adenomatozuri

hiperplazia, FA(follicular adenoma- folikuluri adenoma, PTC(enc)(encapsulated

papillary carcinoma)- inkafsulirebuli papilaruli karcinoma,PTC(mic)(papillary

microcarcinoma)- papilaruli mikrokarcinoma, PTC(Papillary carcinoma)-

papilaruli karcinoma(klasikuri varianti), PTC(MN)(multifocal Papillary

0

2

4

6

8

10

12

NT AH FA PTC(inc) PTC(mic) PTC PTC(MN) PTC(EX) FC

neg.exp. pos.exp.

75

carcinoma)-multicentruli papilaruli karcinoma, PTC(ex)(papillary carcinoma

with extrathyroid extention)-papilaruli karcinoma eqstratireoiduli

gavrcelebiT, FC(follicular carcinoma)- folikuluri karcinoma.

sur. 10. Ppapilaruli karcinoma, BRAF-antisxeulis mkveTri eqspresia, 10X.

76

sur. 11 Ppapilaruli karcinoma, BRAF antisxeulis eqspresia, 40X

Cveni kvlevis mixedviT, aRmoCnda, rom HBME-1 antisxeuli avlenda mkveTr

membrnul eqspresias papilaruli kibos klasikuri formis dros, agreTve,

im SemTxvevebSi, romlebic xasiaTdebodnen eqstraTireoiduli

gavrcelebiTa da multicentruli zrdiT. inkafsulirebuli papilaruli

kobos SemTxvevebma ki gviCvenes susti an uaryofiTi eqspresia SemTxvevaTa

66,7%-Si da zomieri an Zlieri eqspresia 33,3%-Si. zemoTxsenebuli markeri

uaryofiTia an mxolod sustad vlindeba adenomatoiduri

hiperplaziis,folikuluri adenomebis da folikuluri karcinomebis

SemTxvevebSi. Ffarisebri jirkvlis papilaruli mikrokarcinomebi avlenden

uaryofiT eqspresias 11,1%-Si da mkveTr eqspresias 88,9% -Si.

77

sur. 12 Ppapilaruli mikrokarcinoma, HBME-1 mkveTri eqspresia, 40X

sur. 13Ppapilaruli karcinoma(Tall cell type), HBME_1-is eqspresia, 40X

78

Cveni kvlevis farglebSi aseve gamovikvlieT farisebri jirkvlis kvanZovani

dazianebebisas CK-19 antisxeulis eqspresiis Taviseburebani, Sesabamisad

gamovavlineT, rom am imunomarkeris eqspresia msgavsia HBME-1 antisxeulis

eqspresiisa papilaruli karcinomebis sxvadasxva qvetipebSi. CK-19 sustad

an sruliad ar vlindeba folikuluri dazianebebisa da adenomatoiduri

kvanZebis SemTxvevebSi.

gansvavebiT amisa, antisxeuliKI-67, romelic yvelasaTvis cnobilia, rogorc

simsivnuri zrdisa da proliferaciis markeri,zomierad eqspresirdeboda

folikuluri karcinomebis, papilaruli karcinomebis eqstraTireoiduli

gavrcelebiT da multicentrulizrdiT formebis dros, mkveTri eqspresia

ar gamovlinda arcerT SemTxvevaSi. aRniSnuli imunomarkeri sustad an

sruliad ar eqspresirda adenomatozuri hiperplaziebisa da papilaruli

karcinomis inkafsulirebuli formebis dros. papilaruli

mikrokarcinomebis SemTxvevebma gamoavlines zomieri pozitiuroba mxolod

66,7%-Si, xolo 33,3%-Si Zalzed susti eqspresia. Ppapilaruli karcinomis

klasikuri formebi mxolod 70,59% SemTxvevaSi avlendnen zomier da ara

mkveTr pozitiurobas, 29,41%-Si ki sustad pozitiurebi iyvnen.

79

sur. 14Ppapilaruli karcinoma KI-67 eqspresia, 10X.

sur. 15Ppapilaruli mikrokarcinoma, kvanZovani da papilaruli hiperplazia,

oqsifiluri metaplazia, KI-67-is eqspresia, 40X.

CD-56, rogorc folikuluri ujredebis markeri, mkveTrad dadebiTi

aRmoCnda folikuluri dazianebebis SemTxvevebSi, rogoricaa folikuluri

adenoma da karcinoma. EaRniSnuli antisxeuli ar gamovlinda papilaruli

karcinomebis arcerTi formis arsebobisas.

sur. 16. folikuluri adenoma CD-56 mkveTrad dadebiTi. 40X.

80

sur. 17 Ffolikuluri adenoma hurtlis ujreduli tipi, CD-56 mkveTrad

dadebiTi, 10X.

sur. 18 papilaruli karcinoma, TTF-1 mkveTri eqspresia, 10X.

folikuluri ujredebis markeri TTF-1 gamoyenebul iqna yvela sakvlev

masalaze, imis dasadastureblad, rom yvela masala folikuluri genezis

81

gaxldaT. Sesabamisad, es markeri mkveTrad eqspresirda, rogorc

keTilTvisebian dazianebebSi, aseve avTvisebian dazianebebSi.

antisxeulebis eqspresia Cveni kvlevis mixedviT cxrilis saxiT

Semdegnairad gamovxateT:

cxrili 1: antisxeulTa eqspresiasa da farisebri jirkvlis sxvadasxva

kvanZovan dazianebebs Soris arsebuli urTierTkavSiri.

Histotype/

anti.exp

NT

n=4

AH

n=6

FA

n=5

PTC(enc)

n=3

PTC(mic)

n=9

PTC

n=17

PTC(MN)

n=4

PTC(EX)

n=3

FC

n=3

BRAF Neg 4

100%

6

100%

5

100%

3

100%

4

44,4%

7

41,2%

1

25%

3

100%

Pos 5

55,5%

10

58,9%

3

75%

3

100%

HBME1 Neg 4

100%

6

100%

5

100%

2

66,7%

1

11,1%

1

5,9%

3

100%

pos 1

33,3%

8

88,9%

16

94,1%

4

100%

3

100%

CK-19 Neg 4

100%

6

100%

5

100%

1

33,3%

1

11,1%

1

5,9%

3

100%

Pos 2

66,6%

8

88,9%

16

94,1%

4

100%

3

100%

CD 56 Neg 3 9 17 4 3

82

100% 100% 100% 100% 100%

Pos 4

100%

6

100%

5

100%

3

100%

KI 67 Neg 4

100%

6

100%

5

100%

3

100%

3

33,3%

5

29,41%

1

25%

1 1

Pos 6

66,7%

12

70,59%

3

75%

2

100%

2

100%

Cvens mier gamokvleul 54 SemTxvevaSi Sesrulda mravalcvladiani

statistikuri analizi. ganisazRvra SansTa Tanafardoba(OR). Nnormad

Sefasda gamokvleul antisxeulTa susti eqspresia an uaryofiTi eqspresia,

xolo 1_iT aRiniSna saSualo an mkveTri eqspresia. SansTa Tanafardobis

gansazRvrisas gamovlinda, rom rac ufro izrdeba agresiulobis xarisxi

3,677-jer izrdeba anti-BRAF antisxeulis eqspresia, sxva antisxeulebTan

mimarTebaSi, xolo CD-56-is eqspresiisas Sansi mcirdeba 8,6-jer.

univariabelur analizze dayrdnobiT, sadac BRAF antisxeuli

damokidebuli cvladia, xolo danarCeni antisxeulebi ganmsazRvreli,

mudmivi cvladi, gamovlinda, rom umetes SemTxvevebSi HBME-1 antisxeulis

eqspresia asocirdeba BRAFantisxeulis eqspresiasTan(P=0,001). Aaseve CK-19

da KI-67 antisxeulebis eqspresia asocirdebaBRAF antisxeulis

eqspresiasTan (p<0,05). CD-56 antisxeulis eqspresia ar ukavSirdebaBRAF

antisxeulis eqspresias(p<0,05). Ees korelaciebi wrmodgenilia Semdegi

cxrilis saxiT:

Antibody Unstandardized P-value

83

Coefficients ant

BRAF

HBME-1 O,569 0,000

CK-19 0,735 0,000

KI-67 0,641 0,000

CD 56 -0,615 0,000

TTF-1 0,479 0,382

cxrili 2: urTierTkavSiriBRAF mutaciis eqspresiasa daHBME-1, CK-19, KI-67

CD-56, TTF-1eqspresias Soris. *Dependent Variable(damokidebuli cvladi): anti-

BRAF ,Predicrors: Constant(mudmivi cvladi) – HBME-1, CK-19, KI-67 CD-56, TTF-1

Tavi IV ganxilva/diskusia:

84

Cvens mier warmoebuli kvleva pirvelia saqarTveloSi, romelSic

citopaTologiuri diagnostireba ganxorcielda betesdas klasifikaciaze

dayrdnobiT.

Cvens kvlevaSi araadeqvaturi diagnozebis sixSire-betesdas kategoriiT

pirveli jgufi, aRiniSna SemTxvevaTa (8,7%)-Si. aspiraciuli biofsiuri

masalaTa Sefaseba, rogorc araadeqvaturi, ukavSirdeboda cisturi

warmonaqmnebis an makrokalcinatebis arsebobas, amave dros, unda aRiniSnos

isic, rom masalaTa araadeqvaturoba ar ukavSirdeboda gamomSral an

arasworad SeRebil an fiqsirebul preparatebs, rogorc es bevri mkvlevaris

mier aris mowodebuli(132,133).betesdas klasifikacia ar iTvaliswinebs am

kategoriaSi malignantobis riskis gansazRvras, Tumca unda aRiniSnos, rom

es kategoriac aris garkveuli riskis mtarebeli, radganac Cveni kvlevis

farglebSi 1 SemTxveva reaspiraciis Semdgom Sefasda avTvisebian dazianebad.

Cvens mier warmoebul kvlevaSi betesdas kategoria 2- anu keTilTviebian

warmonaqmnebad Sefasda sakvlev SemTxvevaTa 63% da maTi umravlesoba

ganTavsda II da III, an saSualo asakobriv jgufSi. zogadad, kvlevaTa

umravlesoba(136,138), irwmuneba, rom aspiraciuli biofsiiT miRebul sakvlev

masalaTa 34%-dan 87,5%-mde SesaZlebelia betesdas kategorizaciis mixedviT

mivakuTvnoT keTilTvisebian procesebs. Cvens kvlevaSi warmodgenili 378

keTilTvisebiani anu betesdas klasifikaciiT meore kategoriad Sefasebuli

SemTxvevidan (63%) SevecadeT, rom gangvesazRvra avTvisebianobis riski,

Tumca misi gansazRvra Cveni kvlevis mixedviT sakmaod sadao sakiTxad

SegviZlia miviCnioT, vinaidan kvlevaSi CarTuli pacientebis mxolod mcire

nawilis operaciuli masalebis moZieba gaxda SesaZlebeli, es faqti ki

SesaZlebelia ukavSirdeboda imas, rom umetesi nawili am

pacietebisa,betesdas klasifikaciis mixedviT warmodgenili rekomendaciebis

Sesabamisad, imyofeba klinikuri dakvirvebis qveS.

gamokvleuli 600 pacientidan betesdas mesame, yvelaze heterogenul

kategoriad, Sefasda 88 pacientis wvrilnemsiani aspiraciuli biofsiuri

masala(14,6%) mivakuTvneT ganusazRvreli mniSvnelos atipiis kategorias, da

85

amave kvlevaze dayrdobiT zemoT aRniSnul kvlevaSi gamoTqmul azrs

sruliad veTanxmebiT, radganac citologiuri diagnostireba ver iZleva

calkeul SemTxvevebSi zusti interpretaciis saSualebas, Tumca betesdas

kategorizaciiT interpretacia preoperciuli riskis gansazRvris mZlavr

berkets warmoadgens.

Cvens kvlevaSi CarTuli 88 SemTxvevidan 54(61.4%) pacientma Caitara

nawilobrivi an sruli Tireoideqtomia. histopaTologiuri da

citopaTologiuri diagnostirebis safucvelze ganisazRvra

avTvisebianobis riski da aRiniSna, rom is 20.3% Seadgenda.

kvlevis monacemebi(134) Catarebuli HO.Allen.S et. Al-is mier msgavsia Cveni

kvlevis Sedegebis. Mmis sakvlev amocanas warmoadgenda avTvisebianobis

riskis gansazRvra bioptatebSi, romlebic Sefasda rogorc atipia

ganusazRvreli, pacientebidan, romelTa diagnozebi ganekuTvna betesdas 3

kategorias, 64,7%-Si Caitara qirurgiuli mkurnaloba, 17,7% ganmeorebiTi

biofsia, xolo 17,6% darCa meTvalyureobis qveS. ganmeorebiTi biofsiebi

SemTxvevaTa 38,5% Sefasda isev atipia ganusazRvrelad, aqedan rezeqciis

Semdgom 26,3% miekuTvna avTvisebian process.

betesdas klasifikaciiT meoTxe jgufi- Cvens kvlevaSi CarTuli masalebis

38 SemTxveva(6,3%) Sefasda rogorc folikuluri neoplazia. mocemul

Sedegebze dayrdnobiT malignantobis riski betesdas sistemis meoTxe

kategoriaSi Cveni kvlevis farglebSi maRalia(30,2%). sxvadasxva kvlevebze

dayrdnobiT avTvisebianobis riski am jgufSi daaxloebiT 2,2%-dan 36,1%-mde

meryeobs(93,94). vinaidan Cven kvlevaSi ganisazRvra asakobrivi

damokidebuleba betesdas sistemiT asakobriv jgufebSi, unda aRiniSnos,

rom betesdas klasifikaciiT mesame da meoTxe jgufSi romelime asakobrivi

jgufi ar gamoikveTa, msubuqi mateba aRiniSna meore da mesame askobriv

jgufebSi,anu saSualo asakSi.

betesdas kategoriiT mexuTe klasi ganekuTvna 12 SemTxveva, anu sakvlev

masalaTa 2%. msgavsi Sedegebi iqna warmodgenili Semdeg kvlevebSi(136,137).

86

kvlevam(89,95), romelic warmoebuli iyo Theoharis et.al-is mier 2468 pacientis

aspiraciul biofsiur masalaze gamoavlina, rom mxolod 43 pacienti(1,3%)

miekuTvneba am diagnostikur kategorias, yvela maTgani ki saeWvo iyo

papilaruli karcinomis arsebobaze. histologiuri kvlevis Semdeg

SemTxvevaTa 87% Sefasda, rogorc papilaruli karcinoma. Cveni kvlevis

farglebSi avTvisebian dazianebad Sefasda 91,6%, rac TanxvedraSia

zemoTxsenebul kvlevebTan. Tumca gasaTvaliswinebelia is faqtic, rom am

dazianebaTagan mxolod nawili Sefasda rogorc klasikuri papilaruli

karcinoma, xolo 54,5% Sefasda rogorc papilaruli karcinomis

folikuluri inkafsulirebuli varianti, Cveni kvlevis es monacemi ki

TanxvedraSia Tanamedrove kvlevis monacemebTan, romelic gvidasturebs,

rom papilaruli karcinomis swored estipi ganTavsdeba betesda 4 an 5

kategoriaSi. rac Seexeba asakobriv jgufebSi am kategoriis gadanawilebas,

yvelaze metad is pirvel da mesame asakobriv jgufSia warmodgenili.

Y.Jo. et.al (138)kvlevis Sesabamisad 7% kvanZovani dazianebebisa avTvisebian

process ganekuTvneba, malignantobis sixSire ki am kategoriaSi 98%

warmoadgens. aRniSnuli kvlevis monacemebi TiTqmis TanxvedraSia Cveni

kvlevis monacemebTan, romelSidac kvanZovani dazianebebis 5% ganekuTvna

avTvisbian process. Ayvela SemTveva dadasturda histologiurad da

Sefasda rogorc kibo. Sedagebi, romelic Montal et.al (54)mier warmoebulma

kvlevam aCvena (4,7%) TiTqmis identuria Cvens mier warmoebuli kvlevis

Sedegebisa(5%). MavTvisebianobisriski Cvens kvlevaSi betesdas 6

kategoriaSi98% utoldeba. K

30(5%) avTvisebiani SemTxvevidan, romelic kvlevaSi iyo CarTuli 14

SemTxveva(46,6%) gamovlinda I asakobriv jgufSi. aRsaniSnavia is metad

sayuradRebo faqtic, rom I asakobriv jgufSi, yvela es 14 SemTxveva

warmoadgenda histopaTologiurad dadiagnozebul papilaruli karcinomis

klasikur variants. Ees Sedegi kidev ufro amyarebs Cvens hipoTezas imis

Sesaxeb, rom papilaruli karcinomis klasikuri varianti umetasad

axalgazrda asakSi gvevlineba.

87

Cvens kvlevaSi gamoyenebuli masalebi, histopaTologiuri kvlevis Semdgom

davajgufeT simsivnis agresiuli gamovlenis mixedviT, ganvsazRvreT ra

simsivneebi multicentruli, eqstraTireoiduli gavrcelebiT an limfur

kvanZebSi metastazirebiT. Cvens kvlevaSi moxvedrili masalebi,

rogorebicaa adenomatoiduri hiperplazia, agreTve, folikuluri adenomebi

da karcinomebi ar xasiaTdebodnen an sustad avlendnenBRAF antisxeulis

eqspresias. Aam azrs eTanxmeba yvela kvleva, rac am mimarTulebiT iqna

warmoebuli (139,140).

internacionaluri da multidisciplinaluri kvlevebis mixedviT axlaxans

gamovlinda, rom inkafsulirebuli papilaruli karcinomis folikuluri

varianti simsivnis gamorCeul tips ganekuTvneba da saukeTeso prognozuli

maCveneblebiT xasiaTdeba(90).(141) kvlevis mixedviT, simsivnis kapsulis

ararseboba erTaderTi histologiuri parametria, romelic mniSvnelovnad

asocirdeba BRAF mutaciis arsebobasTan. Cveni kvlevis mixedviTac

aRsaniSnavia is faqti, rom BRAF mutaciis mqone simsivneebs axasiaTebdaT

infiltraciuli kideebi da ar gaaCndaT intaqturi kafsula.Ddiagnostikuri

kriteriumebis mixedviT es simsivneebiunda Sefasdes, rogorc”farisebri

jirkvlis arainvaziuri folikuluri dazianebebi papilaruli kibos

msgavsi birTvuli maxasiaTeblebiT”. Aam mniSvnelovan reklasificirebasTan

mimarTebasa da TanxvedraSi inkafsulirebulma papilarulma karcinomebma,

romlebic Cvens kvlevaSi gamovikvlieT gamoavlines BRAF antisxeulis

uaryofiTi an Zalian susti eqspresia(68%), Sesabamisad, Cvenma kvlevam

gaamyara hipoTeza imis Sesaxeb, rom papilaruli karcinomebis

inkafsulirebuli formebi msubuqi mimdinareobiT xasiaTdebian da

genetikurad, savaraudod, gansxvavdebian infiltraciuli simsivneebisgan. A

mikrokarcinomebi, romlebic BRAF dadebiTia xasiaTdebodnen

estraTireoiduli gavrcelebiT, kibos infiltrirebuli kideebiT,

simsivnesTan asocirebuli fibroziTa da desmoplaziiT,klasikuri

papilaruli karcinomis birTvuli maxasiaTeblebiT (140). kvleviT aRmoCnda

rom papilaruli mikrokarcinomebis 70% aris BRAF dadebiTi(142), xolo

88

sxva mravalma kvlevam aCvena, rom es maCvenebeli naklebi iyo 50%-

ze(143,144,145). Cvens kvlevaSi ganxilul iqna papilaruli mikrokarcinomis

cxra SemTxveva,aqedan oTxi SemTxveva(44,4%) aRmoCnda sruliad uaryofiTi

BRAF antisxeulis mimarT, xolo xuTi SemTxveva(55,5%) aRmoCnda BRAF

dadebiTi. es maCveneblebi miuTiTebs imaze, rom Cveni kvleva Tavisi

monacemebis mixedviT msgavsia koreuli kvlevisa(144), romlis mixedviTac

mikrokarcinomaTa 65,5% dadebiTia BRAF mutaciis arsebobaze.A

kvleva(146)aRniSnavs, rom desmoplazia aRiniSneba maT mier gamokvleul

mikrokarcinomaTa 74%-Si, da es aucileblad asocirdeba limfur kvanZenSi

metastazirebasTan da simsivnis diametrTan. Cvens mier gamokvleul

SemTxvevaTa 55% aRiniSneba zemoTxsenebuli morfologiuri cvlilebebi,

rac udaod miuTitebs aRniSnul simsivneTa metastazur potencialze.

yvela am kvlevaze dayrdnobiT da Cveni kvlevis monacemebis gaTvalisinebiT

Tamamad SegviZlia virwmunoT, rom mikrokarcinomebi, iseve rogorc

klasikuri papilaruli karcinomebi, xasiaTdebian eqstraTireoiduli

gavrcelebis potenciiT da es sruliad damokidebulia BRAF onkogenis

eqspresiaze. Braf antisxeulis eqspresia mikrokarcinomebis arsebobis

SemTxvevaSi mniSvnelovan prognozul markers warmoadgens.B

Zalian mniSvnelovan morfologiur kriteriums warmoadgens birTvuli

cvlilebebis arseboba. Cven kvlevaSic, iseve rogorc msgavs kvlevebSi (144)

aRsaniSnavi gaxda is faqti rom papilaruli kibosTvis damaxasiaTebeli

birTvuli maxasiaTeblebi (birTvuli Rarebi da CanaWdevebi, citoplazmuri

fseudoCanarTebi) ufro gamokveTili da TvalsaCinoa BBRAF mutacia

dadebiT SemTxvevebSi. ACveni kvlevis farglebSi aseve

Sefasdacitoplazmuri maxasiaTeblebic, kerZod uxvi, sqvamozuri, mkvrivi,

eozinofiluri citoplazmis arseboba BRAF dadebiT SemTxvevaTa

umravlesobaSi (78%).Tanamedrove kvleva(147),romlis kvlevis amocanas

warmoadgenda urTirTdamokidebuleba citomorfologiur maxasiaTeblebsa

daBBRAF mutacia dadebiT SemTxvevebs Soris da gvauwyebs didi, uxv

89

citoplazmiani ujredebis Tanaarsebobas BRAF mutacia dadebiT SemTxvevaTa

ZiriTad nawilSi.

farTo kohortis mqone kvlevaSi aRmoCnda, rom BRAF mutacia aRiniSneboda

klasikuri papilaruli karcinomebis 48% SemTxvevaSi, rac Zalian axlos

dgas Cveni kvlevis monacemebTan. gansakuTrebiT didi maCvenebeli BRAF

mutaciis arsebobisa aRiniSna did braziliur kvlevaSi(148), rodesac

simsivnis dayofa ganxorcielda histologiuri qvetipebis mixedviT, kerZod,

klasikur SemTxvevebSi aRiniSna 66% SemTxvevebSi misi eqspresia, SedarebiT

papilaruli karcinomis folikulur tipTan 21%. Cven kvlevaSi papilaruli

karcinomis calkeuli inkafsulirebuli formebi mxolod sust eqspresias

avlebdnen. Ees monacemebi TanxvedraSia Semdeg kvlevebTan (108,109,110), sadac

aRniSnaven, rom klasikuri papilaruli karcinomebis SemTxvevaSi BRAF

eqspresia meryeobs38%-dan 69%-mde, xolo papilaruli kibos folikuluri

variantis SemTxvevaSi 0%-dan 32%-mde.

klinikopaTologiuri maxasiaTeblebs, romlebic arakeTilsaimedo

prognozze miuTiTeben, warmoadgens kibo eqstaTireoiduli gavrcelebiT,

multicentruloba, limfur kvanZebSi metastazireba da Soreuli

metastazebis arseboba. Lupi et.al(141) gamoikvlia 500 papilaruli karcinomis

SemTxveva, aqedan 43% aRmoCnda BRAF dadebiTi, kvlevaSi moxda braf dadebiTi

pacientebisSedareba pacientebTan BRAF antisxeulis uaryofiTi eqspresiiT,

aRmoCnda, rom BRAF dadebiT pacientebs ufro xSirad aReniSnebodaT

eqstraTireoiduli metastazireba, multicentruloba da daavadebis ufro

mkveTri da arasaimedo gamovlenis maxasiaTeblebi.

Cveni kvlevis monacemebze dayrdnobiT kvlevaSi arsebuli oTxi

SemTxvevidan erT SemTxvevaSi (25%) ar gamovlinda BRAF mutaciiis arseboba,

sami SemTxveva(75%) ki BRAF dadebiTi aRmoCnda. Ees monacemebi amyarebs sxva

ganxilul kvlevebSi miRebul monacemebis sarwmunoebas.

Cvens kvlevaSi simsivnis agresiulobis zrdasTan erTad BRAF antisxeulis

eqspresiis mkveTr momatebasTan gvqonda saqme. TiTqmis yvela SemTxveva,

90

romelic eqstaTireoiduli gavrcelebiT xasiaTdeboida BRAF antisxeulis

mimarT dadebiTi aRmoCnda an gamoavlina am antisxeulis zomieri eqspresia.

104 papilaruli kibos kvlevisas, romelic nikiforovas mier iqna

warmoebuli (127) amerikel pacientebzeaRmoCnda mkveTri asocireba BRAF

mutaciis arsebobasa da kibos eqstratireoidul gavrcelebas Soris[(16/38

(42%) BRAF+ winaaRmdeg BRAF-13/66 (20%), P=0.03)] .

Cveni kvlevis mixedviT, aseve unda aRiniSnos, rom kvlevaSi gamoyenebuli

sxva antisxeulebic BRAF dadebiTi SemTxvevebis arsebobisas mkveTr

korelaciaSi imyofebian mis eqspresiasTan. HBME-1 antisxeulis eqspresia

folikuluri adenomebisa da karcinomebis SemTxvevebSi ar gamovlinda, misi

zomieri eqspresia aRiniSna inkafsulirebuli papilaruli karcinomis

folikuluri tipis dros 33,3% SemTxvevebSi, aRsaniSnavia is faqtic, rom

Cvens mier warmodgenili inkafsulirebuli formis yvela SemTxveva

uaryofiTi aRmoCnda BRAF antisxeulis mimarT. KI-67-ma, romelic

sayovelTaod aRiarebulia rogorc proliferaciis markeri, gamoavlina

uaryofiTi eqspresia inkafsulirebul formebSi. aRniSnuli faqti kidev

ufro amyarebs azrs imis Sesaxeb, rom inkafsulirebuli papilaruli

karcinomis folikuluri simsivnis tipi avTvisebianobis da agresiulobis

dabali riskis mtarebelia.kvlevaSi gamoyenebuli papilaruli

mikrokarcinomebis SemTxvevebi, agreTve, papilaruli karcinomis sxva

formebi umetes wilad dadebiTi aRmoCndnenHHHBME_1 antisxeulis

mimarT.Uunivariabelur analizze dayrdnobiT HBME-1 antisxeulis eqspresia

Cveni kvlevis farglebSi asocirdeba BRAFantisxeulis eqspresiasTan

(P=0,001). Aaseve CK-19 da KI-67 antisxeulebis eqspresia asocirdebaBRAF

antisxeulis eqspresiasTan (p<0,05). CD-56 antisxeulis eqspresia ar

ukavSirdebaBRAF antisxeulis eqspresias (p<0,05).

91

daskvnebi

1. Cvens mier warmoebul kvlevaze dayrdnobiT, betesdas kategoria 3-ad

diagnostirebul SemTxvevebSi avTvisebianobis riski maRalia da 20.3%

Seadgens.

92

2. avTvisebiani SemTxvevidan, romelic kvlevaSi iyo CarTuli (46,6%)

SemTxvevebisa gamovlinda I asakobriv jgufSi (20-dan 35 wlamde). Ees faqti

amyarebs Cvens hipoTezas imis Sesaxeb, rom axalgazrda asakSi farisebri

jirkvlis kibos ganviTarebis riski maRalia. Cveni kvlevis mixedviT I

asakobriv jgufSi ganTavsebuli kibos yvela SemTxveva warmoadgenda

histopaTologiurad dadiagnozebul papilaruli karcinomis klasikur

variants. Ees Sedegi kidev ufro amyarebs Cvens hipoTezas imis Sesaxeb, rom

papilaruli karcinomis klasikuri varianti umetasad axalgazrda asakSi

gvevlineba.

3. Cvenma kvlevam gaamyara hipoTeza imis Sesaxeb, rom papilaruli

karcinomis inkafsulirebuli formebi, kerZod,”farisebri jirkvlis

arainvaziuri folikuluri dazianebebi papilaruli kibos msgavsi

birTvuli maxasiaTeblebiT”, rogorc es axlaxans ganxorcielebuli

reklasifikaciis Sedegad iwoda, msubuqi mimdinarebiT xasiaTdebian.

inkafsulirebulma papilaruli karcinomebma, romlebic Cvens kvlevaSi

gamovikvlieT gamoavlines BRAF antigenisuaryofiTi an Zalian susti

eqspresia (68%).

4. simsivnis kafsulis ararseboba erTaderTi histologiuri parametria,

romelic mniSvnelovnad asocirdeba BRAF mutaciis arsebobasTan. Cven mier

gamokvleul masalaSi SevniSneT, rom BRAF mutaciis mqone simsivneebs

axasiaTebdaT infiltraciuli kideebi da ar gaaCndaT intaqturi kafsula.

5. Cvens kvlevaze dayrdnobiT, mikrokarcinomebi, iseve rogorc klasikuri

papilaruli karcinomebi, xasiaTdebian eqstraTireoiduli gavrcelebis

potenciiT da aRiniSneba BRAFmutaciis maRali eqspresia. Braf antisxeulis

eqspresia mikrokarcinomebis arsebobis SemTxvevaSi mniSvnelovan

prognozul markers warmoadgens.

6. BRAF antisxeulis eqspresia izrdeba gamokvleul farisebri jirkvlis

kvanZovani dazianebebis agresiulobis xarisxis matebasTan erTad (p<0,005).

93

BRAF antisxeulis momatebuli eqspresia iwvevs farisebri jirkvlis

papilaruli karcinomebis agresiulobis zrdas 3,677-jer.

praqtikuli rekomendaciebi

94

Cveni kvlevis monacemebze dayrdnobiT, farisebri jirkvlis kibo, kerZod,

papilaruli karcinoma, gansakuTrebiT didi sixSiriT aRiniSna axalgazrda

asakSi, swored es faqti saSualebas gvaZlevs am asakobriv jgufSi

farisebri jirkvlis gansakuTrebiT maRal monitorings gavuwioT

rekomendacia.

mniSvnelovania, rom wvrilnemsini aspiraciuli biofsiuri masalebis

citopaTologiuri diagnostireba mTlianad daefuZvnos betesdas

klasifikacias, vinaidan es sistema SesaZleblobas gvaZlevs gavmijnoT

Terapiuli da qirurgiuli paTologiebi, vawarmooT swori monitoringi da

ganvsazRvroT amave sistemis TiToeul kategoriaSi avTvisebianobis riskis

albaToba.

betesdas klasifiaciiT mesame kategoriis arseboba betesdas sistemaSi,

saSualebs iZleva, sworad mivyveT betesdas rekomendaciebs, Catartes ufro

aqtiuri dakvirvebaan ganmeorebiTi aspiraciuli biofsiuri masalis

citologiuri kvleva, rac Tavis mxriv saboloo srulfasovan

interpretaciamde migviyvans. Bbetesdas mesame kategoriis arsebobisas,

citomorfologiur monacemebTan erTobliobaSi, sasurvelia Sefasdes

genetikuri dazianebebis arseboba.

BRAF mutacia TiTqmis ar vlindeba inkafsulirebuli papilaruli

karcinomis folikuluri variantis SemTxvevebSi. Ees faqti SesaZlebels

xdis ganvasxvaoT arainvaziuri folikuluri neoplazia papilaruli

karcinomis msgavsi birTvuli cvlilebebiT (NIFTP), papilaruli karcinomis

folikuluri variantis invaziuri formisgan (IFVPTC). Sesabamisad am

faqtisa, sworad daigegmos Semdgomi qirurgiuli mkurnaloba.

BRAF antisxeulis eqspresia mikrokarcinomebis arsebobis SemTxvevaSi

mniSvnelovan prognozul markers warmoadgens, Sesabamisad, BRAF dadebiTi

SemTxvevebis arsebobisas, unda dadges sakiTxi sruli Tireoideqtomiis,

limfadeneqtomiis da radioaqtiuri iodiT mkurnalobis Sesaxeb.

95

farisebri jirkvlis papilaruli karcinomebis Semdgomi marTvisTvis BRAF

mutaciisarsebobis gansazRvra mniSvnelovan faqtorad gvevlineba. BRAF

mutaciis arsebobaarakeTilsaimedo prognozTan asocirdeba da Cvens mier

warmoebuli kvlevis mixedviT, BRAF antisxeulis eqspresia izrdeba

farisebri jirkvlis kvanZovani dazianebebis agresiulobis xarisxis

matebasTan erTad.

gamoyenebuli literatura

96

1.Gharib H, Papini E et al. Thyroid nodules: Clinical importance, assessment, and

treatment. Endocrinol Metab Clin North Am. 2007;36:707–35.

2.L. S. Ward and H. Graf,et al. “Thyroid cancer: increased occurrence or simply its

detection?” Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 52, no. 9, pp. 1515–1516,

2008.

3.M. P. Curado, B. Edwards, H. R. Shin et al. Cancer analisys(preliminary)_Final_cc72355e-f239-

4f46-845c-cfb6e66b0996.pdf. Cancer Incidence in Five Continents, vol. 9 of IARC Scientific

Publications, No. 160, IARC, Lyon, France, 2007.

4. Beerenwinkel N, Antal T, Dingli D, et al: Genetic progression and the waiting time to cancer.

PLoS Comput Biol 2007; 3:e225.

5.Ito Y, Miyauchi A, Kihara M, et al: Patient age is significantly related to the progression of

papillary microcarcinoma of the thyroid under observation. Thyroid 2014; 24: 27–34.

6.Gabriella Pellegriti,1 et al.Worldwide Increasing Incidence of Thyroid Cancer: Update on

Epidemiology and Risk Factors Journal of Cancer Epidemiology. Volume 2013 (2013), Article

ID 965212, 10 pages

7. Santarpia L, Sherman SI, Marabotti A, Clayman GL, El-Naggar AK et al. Detection and

molecular characterization of a novel BRAF activated domain mutation in follicular variant of

papillary thyroid carcinoma. Hum. Pathol. 2009;40:827–833.

9.N. Howlader, N. N. A, M. Krapcho et al., Eds., SEER Cancer Statistics Review, 1975–2009

(Vintage 2009 Populations). 2012.Eur Thyroid J 2015;4:164---173

10. Haugen BR et.al. 2015 American Thyroid Association managment guidelines for adult

patients with thyroid nodules and differentiated thyroid cancer: The American Thyroid Association

Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016;

26:1-133.

11. J. Yang, V.et al, “Fine-needle aspiration of thyroid nodules: a study of 4703 patients with

histologic and clinical correlations,” Cancer, vol. 111, no. 5, pp. 306–315, 2007.

12. G. V. Teixeira, et al, “Incidence of malignancy in thyroid nodules determined to be follicular

lesions of undetermined significance on fine-needle aspiration,” World Journal of Surgery, vol. 36,

no. 1, pp. 69–74, 2012.

97

13. Alexander EK. et al.: Preoperative Diagnosis of Benign Thyroid Nodules with Indeterminate

Cytology.N Engl J Med 2012.

14. Leina Zhao et al. Cytological, molecular, and Clinical Features of Noninvasive Follicular

Thyroid neoplasm with Papillary-like Nuclear features Versus Invasive forms of follicular variant

of Papillary Thyroid Carcinoma. Cancer Cytopath. Volume 125/issue 5, 2017, pp 323

15. S.J. Kimet al. Risk of malignancy according to sub-classification of atipia of undetermined

significance or follicular lesion of undetermined significance (AUS/FLUS) category in Bethesda

system for reporting thyroid cytopathology. Cytopathology, volume 28, 2017,pp-65-73.

16. Nishino m. et al. Molecular CytopaThology for Thyroid nodules: areview of methodology and

test performance. Cancer Cytopathology 2016, 124:14-27.

17.Kazakov VS, et al:Thyroid cancer after Chernobyl. Nature 1992;

359: 21.

18. Baverstock K, et al: Thyroid cancer after Chernobyl.Nature 1992; 359: 21–22.

19.Cancer Genome Atlas Research Network: Integrated genomic characterization of papillary

thyroid carcinoma. Cell 2014; 159: 676–690.

20. Rabes HM, Demidchik EP, Siderov JD, et al:Pattern of radiation induced RET and NTRK1

rearrangements in 191 post-Chernobyl papillary thyroid carcinomas. Clin Cancer Res 2000; 6:

1093–1103.

21. Hamatani K, Eguchi H, Ito R, et al: RET/PTC rearrangements preferentially occurred in

papillary thyroid cancer among atomic bomb survivors exposed to high radiation dose.Cancer Res

2008; 68: 7176–7182.

22. Ciampi R, Knauf JA, Kerler R, et al: Oncogenic AKAP9-BRAF fusion is a novel mechanism of

MAPK pathway activation in thyroid cancer. J Clin Invest 2003; 115: 94–101.

23.Mingzhao Xinget.al BRAF Mutation Testing of Thyroid Fine-Needle Aspiration Biopsy

Specimens for Preoperative Risk Stratification in Papillary Thyroid CancerPublished online before

print May 4, 2009, doi:10.1200/JCO.2008.20.1426JCO June 20, 2009 vol. 27 no. 182977-298.

24.Adrienne L. Melck, et al. The Utility of BRAF Testing in the Management of Papillary Thyroid

Cancer First published online in THE ONCOLOGIST Express on December 8, 2010.

98

25.Mesa C, Mirza M, Mitsutake N, et al. Conditional activation of RET/PTC3 and BRAFV600E in

thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in

extracellular matrix remodeling. Cancer Res 2006;66:6521–6529 26. Ming Gao et.al. Progression of solitary and multifocal papillary thyroid carcinoma- a

retrospective study of 368 petient. Chinase medical journal vol.225.dec 20,2012

27.Hillary Kimbrell et.al. BRAF Testing in multifocal PTC. Hindawi Publishing Corporation. Vol

2015,ID 486391.

28.Seo ki kim, et al.BRAF mutation: Differential impact central lymph node metastasis by tumor

size in PTC-Doi 10 1002?hed.24192, 2015, viley online library.

29. Espinosa A, Porchia L, Ringel M.et al. Targeting BRAF in thyroid cancer. Br. J.

Cancer. 2007;96:16–20.

30. Sapio MR, et al. Combined analysis of galectin-3 and BRAFV600E improves the accuracy of

fine-needle aspiration biopsy with cytological findings suspicious for papillary thyroid

carcinoma. Endocr. Relat. Cancer. 2007;14:1089–1097.

31. Kumagai A, et al. Clinical implications of pre-operative rapid BRAF analysis for papillary

thyroid cancer. Endocr. J. 2007;54:399–405.

Bonzanini

32. A. Jemal, R. Siegel, J. Xu, and E. Ward,et al. “Cancer statistics, 2010,” CA: A Cancer Journal

for Clinicians, vol. 60, no. 5, pp. 277–300, 2010.

33. 8.Y. Ito, A. Miyauchi, H. Inoue et al., “An observational trial for papillary thyroid

microcarcinoma in Japanese patients,” World Journal of Surgery, vol. 34, no. 1, pp. 28–35, 2010.

34.L. Davies and H. G. Welch,et al. “Increasing incidence of thyroid cancer in the United States,

1973–2002,”Journal of the American Medical Association, vol. 295, no. 18, pp. 2164–2167, 2006.

35. Gabriella Pellegritiet al.Worldwide Increasing Incidence of Thyroid Cancer: Update on

Epidemiology and Risk Factors. Journal of Cancer Epidemiology.Volume 2013 (2013), Article

ID965212,10pages

36. E. Peterson, P. De, and R. Nuttall, et al. “BMI, diet and female reproductive factors as risks for

thyroid cancer: a systematic review,” PLoS One, vol. 7, no. 1, Article ID e29177, 2012.

99

37. Dillwyn Williams et.al.Thyroid Growth and Cancer Eur Thyroid J 2015;4:164–173DOI:

10.1159/000437263

38. Bridget Sinnott et al.Exposing the Thyroid to Radiation: A Review of Its Current Extent, Risks,

and Implications Endocrine Reviews, Volume 31, Issue 5, 1 October 2010, Pages 756–773 39.E. Fiore, T. Rago, M. A. Provenzale et al., “Lower levels of TSH are associated with a lower risk

of papillary thyroid cancer in patients with thyroid nodular disease: thyroid autonomy may play a

protective role,” Endocrine-Related Cancer, vol. 16, no. 4, pp. 1251–1260, 2009. 40. G. Nguyen et.al. Fine-needle aspiration of the thyroid: an overview Cytojournal. 2005; 2:

12.Published online 2005 Jun 29.

41.Frederico F. R. Maiaet al.Thyroid nodule management: clinical, ultrasound and cytopathological

parameters for predicting malignancy Clinics (Sao Paulo). 2012 Aug; 67(8): 945–

954.doi: 10.6061/clinics/2012(08)15

42.R. Bellantone et al. Management of cystic or predominantly cystic thyroid nodules: the role of

ultrasound-guided fine-needle aspiration biopsy. Thyroid, Vol. 14, 43–47, 2004.

43.Eng CY, Quraishi MS, Bradley PJ et al. Management of Thyroid nodules in adult patients. Head

& Neck Oncology. 2010;2(11):1–5.

44. L. Hegedus, S. J. Bonnema, F. N.et al. Bennedbaeket al. Management of simple nodular goiter:

current status and future perspectives. Endocrine Reviews, Vol. 24, 102–132, 2003.

45.Blair A Williamset al. Rates of thyroid malignancy by FNA diagnostic categoryJournal of

Otolaryngology - Head & Neck Surgery 2013, 42:61 doi:10.1186/1916-0216-42-61

46.Kihara M, Hirokawa M, Masuoka H, et al. Role of ultrasonography in patients with cytologically

follicular thyroid tumor. Auris Nasus Laynx. 2011;38(4):508–11.

47.G.Faddaet al. Cytological classification of thyroid nodules: Proposal of the SIAPEC-AIT Italian

Consensus Working Group. Pathologica 2010;102:00-00.

48. Jo VY, Stelow EB, Dustin SM, Hanley KZet al: Malignancy risk for fine-needle aspiration of

thyroid lesions according to the Bethesda system for reporting thyroid cytopathology.Am J Clin

Pathol 2010, 134:450-456.

49. Deepak Joshiet al. The Bethesda System for Reporting Thyroid Cytopathology. Pathology and

laboratory medicine.Print ISSN 0975-3109

100

50. Akgul O et al. Risk of malignancy in non-diagnostic thyroid fine-needle aspiration biopsy in

multinodular goitre patients. Endocr Regul. 2011;45(1):9–12.

51.Cibas ES, Ali SZet al; NCI Thyroid FNA State of the Science Conference. The Bethesda System

for Reporting Thyroid Cytopathology. Am J Clin Pathol 2009; 132:658–665

52.Payal Mehra et.al. Thyroid Cytopathology Reporting by the Bethesda System: A Two-Year

Prospective Study in an Academic Institution olume 2015 (2015), Article ID 240505, 11 pages

53.Theoharis CG, et al. The Bethesda thyroid fine-needle aspiration classification system: year 1 at

an academic institution. Thyroid. 2009;19(11):1215–23.

54. Mondalet al, The Bethesda system for reporting thyroid fine needle aspirates: A cytologic study

with histologic follow-up. Cytol. 2013 Apr-Jun; 30(2): 94–99.doi: 10.4103/0970-9371.112650

55.. P. G. Wasserman et al.“Fine-needle aspiration of thyroid nodules: a study of 4703 patients with

histologic and clinical correlations.,” Cancer, vol. 111, no. 5, pp. 306–315, 2007

56. L. J. Layfield et al. “Implications of the proposed thyroid fine-needle aspiration category of

follicular lesion of undetermined significance: a five-year multi-institutional analysis,” Diagnostic

Cytopathology, vol. 37, no. 10, pp. 710–714, 2009.

57.Y. Shi et al., “Thyroid fine-needle aspiration with atypia of undetermined significance: a

necessary or optional category?” Cancer Cytopathology, vol. 117, no. 5, pp. 298–304, 2009.

58.Ohori NP, Schoedel KEet al. Variability in the atypia of undetermined significance/follicular

lesion of undetermined significance diagnosis in the Bethesda System for Reporting Thyroid

Cytopathology: sources and recommendations. Acta Cytol 2011; 55:492–498

59.Sylvan C.Baca,et.al. Qualifiers of Atiopia in Cytologic Diagnosis Of Thyroid Nodules Are

Associated With Different Afirma Gene Expression Classifier Results and Clinical outcomes.

Cancer Cytopath. Volume125/Issue 5. May 2017.

60.Ji Hye Parket al. incidence and Malignancy Rates of Diagnoses in the Bethesda System for

Reporting Thyroid Aspiration Cytology: An Institutional ExperienceArialArialKorean J Pathol.

2014 Apr; 48(2): 133–139.Published online 2014 Apr doi: 10.4132/KoreanJPathol.2014.48.2.133

61. Colleen M. Kernan et al. The Bethesda System For Reporting Thyroid Cytopathology: A

Single-center experience over 5 years. Ann surg.oncol.(2014)21,3522-3527.

101

62.Bonzanini et al. Subclassification of the “Grey Zone” of Thyroid Cytology; A Retrospective

Descriptive Study with Clinical, Cytological, and Histological Correlation Journal of Thyroid

Research,Volume 2011 (2011), Article ID 251680, 8 pages

63.Ryan Glass et.al. Predicting histological subtypes of follicular variant of papillary thyroid

carcinoma based on cytomorphology. Can Cytomorphology optimize use of molecular testing?

Journal of the American Society of Cytopathology(2016) 5, 345-350.

64.Olson MT,et al'Suspicious for papillary thyroid carcinoma' before and after The Bethesda

System for Reporting Thyroid Cytopathology: impact of standardized terminology. [Journal Article,

Meta-Analysis]Acta Cytol 2014; 58(1):15-22.

65.S. Z. Ali and E. S. Cibas, et al. The Bethesda System for Reporting Thyroid Cytopathology.

Definitions, Criteria and Explanatory Notes, Springer, New York, NY, USA, 2010.

66.Bibbo M, Wilbur DC et al. Comprehensive Cytopathology Thyroid. 3 rd ed. 2013 Saunders:

Elsevier. p. 650.

67.Kumar S, Singh N, Siddaraju Net al. Cellular swirls and similar structures on fine needle

aspiration cytology as diagnostic clues to papillary thyroid carcinoma: A report of 4 cases. Acta

Cytol 2010;54:939-42.

68.Aspiration biopsy cytology in diagnosis of thyroid cancer, World Journal of SurgeryJanuary

1981, Volume 5, Issue 1, pp 61–70

69.Kini SR, Miller JM, Hamburger JI, Smith MJet al. Cytopathology of papillary carcinoma of the

thyroid by fine needle aspiration. Acta Cytol 1980;24:511-21.

70. Ho, Allen Set al. Malignancy Rate in Thyroid Nodules Classified as Bethesda Category III

(AUS/FLUS).Thyroid;May2014, Vol. 24 Issue 5, p832

71.Diana Set al. Fine needle aspiration biopsy of thyroid gland, apdated in 2015.

72.Duskova J, Tretinik P et al. Papillary thyroid carcinoma: An easy fine needle aspiration biopsy

diagnosis? Acta Cytol 2011;55:120-30.

73.Baloch ZW, LiVolsi VA et al (2007) Our approach to follicular-patterned lesions of the

thyroid. J Clin Pathol 60(3):244–250

102

74.Adeniran AJ, Zhu Z, Gandhi M et al (2006) Correlation between genetic alterations and

microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary

carcinomas. Am J Surg Pathol 30(2):216–222

75.Suster S et al (2006) Thyroid tumors with a follicular growth pattern: problems in differential

diagnosis. Arch Pathol Lab Med 130(7): 984–988

76.Escofet X, Khan AZ, Mazarani W, Woods WGet al (2007) Lessons to be learned: a case study

approach. Lateral aberrant thyroid tissue: is it always malignant? J R Soc Health 127(1):45–46

77. Baloch ZW, Livolsi V et al (2002) Pathology of thyroid gland. In: Livolsi V, Asa SL (eds) Endocrine

pathology. Churchill Livingstone, Philadelphia, pp 61–88

78.Classification and General Considerations of Thyroid Cancer, Hiroshi Katoh* et al. Annals of

Clinical Pathology,march 2015.

79.elfiore A, Russo D, Vigneri R, Filetti S (2001) Graves’disease, thyroid nodules and thyroid

cancer. Clin Endocrinol 55(6): 711–718

80.Deshpande AH, Bobhate SKet al (2005) Cytological features of dyshormonogenetic goiter:

case report and review of the literature. Diagn Cytopathol 33(4):252–254

81.Rago T, Di Coscio G, et al. Combined clinical, thyroid ultrasound and cytological features help

to predict thyroid malignancy in follicular and Hürthle cell thyroid lesions: results from a series of

505 consecutive patients. Clin Endocrinol (Oxf) 2007;66(1):13–20.

82. Update on Anaplastic Thyroid Carcinoma: Morphological, Molecular, and Genetic Features of

the Most Aggressive Thyroid Cancer International Journal of Endocrinology

Volume 2014 (2014), Article ID 790834, 13 pages

83. The pathology of preclinical medullary thyroid carcinoma September 2004, Volume

15, Issue 3, pp 227–231

84.Deveci MS, Deveci G, LiVolsi VA, Baloch ZW et al. Fine-needle aspiration of follicular lesions

of the thyroid: diagnosis and follow-up. Cytojournal 2006; 3:9

85.W. C. Faquin and Z. W. Baloch,et al. “Fine-Needle aspiration of follicular patterned lesions of

the thyroid: diagnosis, management, and follow-up according to National Cancer Institute (NCI)

recommendations,” Diagnostic Cytopathology, vol. 38, pp. 731–739, 2010.

103

86.Cibas, C. B. Benson et al., “Long-term assessment of a multidisciplinary approach to thyroid

nodule diagnostic evaluation,” Cancer, vol. 111, no. 6, pp. 508–516, 2007.

87.Emilio fiore et.al. Iodine,Thyroid Autoimmunity and Cancer. Europian Thyroid Journal,

2015:4:26-35.

88. Szporn AH, Yuan S, Wu M, Burstein DE et al. Cellular swirls in fine needle aspiarates of

papillary thyroid carcinoma: A new diagnostic criterion. Mod Pathol 2006;19:1470-3.

89.Harshan M, et al. Papillary thyroid carcinoma with atypical histiocytoid cells on fine-needle

aspiration. Diagn Cytopathol 2009;37:244-50.

90.Nikiforov et.al. Nomenclature Revision for encapsulated follicular variant of papillary thyroid

carcinoma. JAMA oncol.2016;2(8):1023-1029.

91.Chung-Yau Loet.al. Papillary Microcarcinoma: Is There Any Difference between Clinically

Overt and Occult Tumors?World Journal of Surgery,May 2006, Volume 30, Issue 5, pp 759–766

92.R. Gonzalez-Gonzalez, R. Bologna-Molina, R. G. Carreon-Burciaga, et al., “Papillary thyroid

carcinoma: differential diagnosis and prognostic values of its different variants: review of the

literature,” ISRN Oncology, vol. 2011, Article ID 915925, 2011.

93.Barroeta JE et.al: Diagnostic value of differential expression of CK19, Galectin-3, HBME-1,

ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an

immunohistochemical tissue microarray analysis.Endocr Pathol 2006, 17:225-234.

94. De Matos PS.et.al. Usefulness of HBME-1, cytokeratin 19 and galectin-3 immunostaining in the

diagnosis of thyroid malignancy. Histopathology. 2005;47(4):391–401.

95.Nasr MR.et.al. Immunohistochemical markers in diagnosis of papillary thyroid carcinoma:

utility of HBME1 combined with CK19 immunostaining. Mod Pathol. 2006;19(12):1631–163

96. Asa SLet al. The role of immunohistochemical markers in the diagnosis of follicular-patterned

lesions of the thyroid. Endocr Pathol.2005;16(4):295–309.

97. Baloch ZW.et.al. Differential expression of cytokeratins in follicular variant of papillary

carcinoma: an immunohistochemical study and its diagnostic utility. Hum

Pathol. 1999;30(10):1166–1171

98.Lenggenhager D, et al. HBME-1 expression in ¨ hyalinizing trabecular tumours of the thyroid

gland. Histopathology. 2013;62(7): 1092–1097.

104

99. Murphy KM, Chen F, Clark DPet al. Identification of immunohistochemical biomarkers for

papillary thyroid carcinoma using gene expression profiling. Hum Pathol. 2008;39(3):420–426.

100.Barroeta JE.et.al. Diagnostic value of differential expression of CK19, Galectin-3, HBME-1,

ERK, RET, and p16 in benign and malignant follicular-derived lesions of the thyroid: an

immunohistochemical tissue microarray analysis. Endocr Pathol. 2006;17(3):225–234.

101.Prag S. et.al: NCAM regulates cell motility.Journal of Cell Science 2002, 115:283-292.

102.Zeromski J.et.al: Expression of CD56/N-CAM antigen and some other adhesion molecules in

various human endocrine glands.Folia Histoc Cytobiol 1998, 36:119-125.

103.Scarpino S.et.al: Papillary carcinoma of the thyroid: low expression of NCAM (CD56) is

associated with down regulation of VEGF-D production by tumor cells.J Pathol 2007, 212(4):411-

419.

104.El Demellawy D et.al. Diagnostic utility of CD56 immunohistochemistry in papillary

carcinoma of the thyroid. Pathol Res Pract. 2009;205:303–9.

105.Ozolins A et.al. Diagnostic utility of immunohistochemical panel in various thyroid

pathologies. Langenbecks Arch Surg. 2010;395:885–91.

106.Park WY. et al. Diagnostic value of decreased expression of CD56 protein in papillary

carcinoma of the thyroid gland. Basic Appl Pathol. 2009;2:63–8

107.Abd El Atti RM, Shash LSet al. Potential diagnostic utility of CD56 and claudin-1 in papillary

thyroid carcinoma and solitary follicular thyroid nodules. J Egypt Natl Canc Inst. 2012;24:175–84.

108.Adrienne L. Melck.The Utility of BRAF Testing in the Management of Papillary Thyroid

Cancer.Oncologist.2010Dec;15(12):1285–1293.Published online 2010 Dec 8.

109.Chiosea S, et al . A novel complex BRAF mutation detected in a solid variant of papillary

thyroid carcinoma. Endocr. Pathol.2009;20:122–126.

110.Classification and General Considerations of Thyroid Cancer , Hiroshi Katoh* et al. Annals of

Clinical Pathology,march 2015.

111.Leina Zhao et al. Cytological, molecular, and Clinical Features of Noninvasive Follicular

Thyroid neoplasm with Papillary-like Nuclear features Versus Invasive forms of follicular variant

of Papillary Thyroid Carcinoma. Cancer Cytopath. Volume 125/issue 5, 2017, pp 3

112.elfiore A, Russo D, Vigneri R, Filetti S (2001) Graves’disease, thyroid nodules and thyroid

cancer. Clin Endocrinol 55(6): 711–718

105

113. Matthias Preusser et.al.Immunohistochemical detection of the BRAF V600E-mutated protein

in papillary thyroid carcinoma. American Journal of Surgical Pathology 2012, 844-850.

114. Lee X, Gao M, Ji Y, et al. Analysis of differential BRAF(V600E) mutational status in high

aggressive papillary thyroid microcarcinoma. Ann Surg Oncol2009;16:240–245.

115.Park YJ, Kim YA, Lee YJ, et al. Papillary mikmicrocarcinoma incomparison with larger

papillary thyroid carcinoma in BRAF(V600E) mutation, clinicopathological features, and

immunohistochemical findings. Head Neck2010;32:38–45.

116. Ziai J, Hui P. BRAF mutation testing in clinical practice. Expert Rev Mol Diagn2012;12:127–

138

117.Ying C et.al. High Rate of BRAF and RET/PTC Dual Mutations Associated with Recurrent Papillary

Thyroid Carcinoma.DOI: 10.1158/1078-0432.CCR-08-0933 Published January 2009

118.Jin Young Kwaket al,Association of BRAFV600E Mutation with Poor Clinical Prognostic

Factors and US Features in Korean Patients with Papillary Thyroid Microcarcinoma.December

2009Volume 253, Issue 3

119.Kim et al. The association of BRAF mutation with prognostic factors and poor clinical outcome

in papillary thyroid cancer. Cancer2012;118;1764-1773.

120.Zampi G, et.al. Papillary carcinoma of the thyroid: a clinicopathologic study of 241 cases

treated at the University of Florence, Italy. Cancer. 1985;55:805–828.

121.Mazzaferri EL et al. Management of low-risk differentiated thyroid cancer. Endocr

Pract 2007;13:498-512

122.Huang FJ1et.al ,BRAF mutation correlates with recurrent papillary thyroid carcinoma in

Chinese patients.Curr Oncol. 2014 Dec;21(6):e740-7. doi: 10.3747/co.21.2029.

123.Multicentric Papillary Thyroid Carcinoma: stratification for Treatment- Di-cano et.al J cytol

histol.2014; 5:4.

124.Gina M.Hoell, et.al.BRAF mutation independently predict central compartment lymph node

metastasis with PTC. Annals of Surgical oncology.January 2013, Volume 20, Issue 1, pp 47–52

106

125. M Xing, AS Alzahrani, KA Carson , etal: Association between BRAF V600E mutation and

mortality in patients with papillary thyroid cancer JAMA 309: 1493– 1501,2013

126.L. S. Ward and R. T. Kloos,et al. “Molecular markers in the diagnosis of thyroid

nodules,” Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 57, no. 2, pp. 89–97, 2013.

127.Nikiforova MN, Nikiforov YE et al. Molecular diagnostics and predictors in thyroid

cancer. Thyroid.2009;19:1351–1361.

128. Riesco-Eizaguirre G, et al. The oncogene BRAF V600E is associated with a high risk of

recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I-

targeting to the membrane. Endocr. Relat. Cancer. 2006;13:257–269.

129.Zatelli MC, et al. BRAF V600E mutation analysis increases diagnostic accuracy for papillary

thyroid carcinoma in fine needle aspiration biopsies. Eur. J. Endocrinol. 2009;161:467–473.

130.Basolo F, et al. Correlation between the BRAF V600E mutation and tumor invasiveness in

papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J. Clin.

Endocrinol. Metab. 2010;95:4197–205.

131.R. Harach et.al, “Occult papillary carcinoma of the thyroid. A ‘normal’ finding in Finland. A

systematic autopsy study,” Cancer, vol. 56, no. 3, pp. 531–538, 1985.

132.Castro-Gomez L, et al. Cytologic criteria of cystic papillary carcinoma of the thyroid. Acta

Cytol 2003;47:590-4.

133.M. D. Smith, et al. Fine needle aspiration in the management of benign thyroid cysts.

Australian and New Zealand Journal of Surgery. Vol. 73, 477–479, 2003.

134.Ho, Allen Set al. Malignancy Rate in Thyroid Nodules Classified as Bethesda Category III

(AUS/FLUS).Thyroid;May2014, Vol. 24 Issue 5, p832

135.Ryan Glass et.al. Predicting histological subtypes of follicular variant of papillary thyroid

carcinoma based on cytomorphology. Can Cytomorphology optimize use of molecular testing?

Journal of the American Society of Cytopathology(2016) 5, 345-350.

136.J. T. Broome et.al. “The impact of atypia/follicular lesion of undetermined significance on the

rate of malignancy in thyroid fine-needle aspiration: evaluation of the Bethesda system for reporting

thyroid cytopathology,” Surgery, vol. 150, no. 6, pp. 1234–1241, 2011.010.

107

137.M. M. Al-Shraim, O. M. Kaood, M. R. Hussein et al., “Assessment of malignancy rate in

thyroid nodules according to the Bethesda system of fine-needle aspiration: report from a tertiary

center in the Southwestern region of Saudi Arabia,” Saudi Medical Journal, vol. 33, no. 2, pp. 167–

171, 2012

138.Y. Joet al. Malignancy Risk for Fine-needle Aspiration of Thyroid Lesions according to the

Bethesda System for Reporting Thyroid Cytopathology

Am J Clin Pathol. 2010;134(3):450-456.

139. Kim KH, Kang DW, Kim SH, Seong IO & Kang DY 2004 Mutations of the BRAF gene in

papillary thyroid carcinoma in a Korean population. Yonsei Medical Journal45 818–821.

140.Rossi ED,et al. Braf mutation analysis on LBC-processed aspiration biopsies predict bilaterality

and nodal involvement in Papillary Thyroid microcarcinoma. Cancer Cyt. 2013;121;291-297

141.Lupi C. et.al. Association of BRAF V600E mutation with poor clinicopathological outcomes in

500 consecutive cases of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 2007;92:4085–

4090.

142.Finkelstein A, Levy GH, Hui P, et al. Papillary thyroid carcinomas with and without BRAF

V600E mutations are morphologically distinct. Histopathology2012;60:1052–1059.

143.Cohen Y, Xing M, Mambo E, et al. BRAF mutation in papillary thyroid carcinoma. J Natl

Cancer Inst 2003;95:625–627.

144.Kwak JY, Kim EK, Chung WY, et al. Association of BRAFV600E mutation with poor clinical

prognostic factors and US features in Korean patients with papillary thyroid

microcarcinoma. Radiology 2009;253:854–860.ArticlePubMedISI

145. Ugolini C, Giannini R, Lupi C, et al. Presence of BRAF V600E in very early stages of

papillary thyroid carcinoma. Thyroid 2007;17:381–388

146.Koperek O, Asari R, Niederle B, et al. Desmoplastic stromal reaction in papillary thyroid

microcarcinoma. Histopathology 2011;58:919–924.

147. G.Fadda et al. Morphological Features that can predict BRAF-mutated carcinoma in pediatric

thyroid cytology. Cytopathology. Volume 28, Issue1, February 2017.

108

148.Gisele Oler MSc,Janete M. Cerutti et al. High prevalence of BRAF mutation in a Brazilian

cohort of patients with sporadic papillary thyroid carcinomas†17 January

2009.DOI: 10.1002/cncr.24118

149.Nikiforov et.al. Nomenclature Revision for encapsulated follicular variant of papillary thyro

carcinoma. JAMA oncol.2016;2(8):1023-1029.

150.Lee S, Hong S, Koo JSet al. Immunohistochemical subclassification of thyroid tumors with

prominent hyalinizing trabecular pattern. APMIS. 2011;119:529–36.

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