PROŠIRENA BOLEST DIFERENTOVANOG TIREOIDNOG KARCINOMA ZBOG ODLAGANJA TOTALIZACIJE TIREOIDEKTOMIJE PRIKAZ SLUČAJA

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1 58 MEDICINSKI GLASNIK / str Nenad Laketić 1, Kata Kovačić, Aleksandar Simić PROŠIRENA BOLEST DIFERENTOVANOG TIREOIDNOG KARCINOMA ZBOG ODLAGANJA TOTALIZACIJE TIREOIDEKTOMIJE PRIKAZ SLUČAJA Apstrakt: Diferentovani tireoidni karcinomi predstavljaju najčešće karcinome u tireoidnoj patologiji. Najčešći DTC je papilarni karcinom koji pokazuje tendenciju širenja i davanja metastaza limfnim putem. Pored širenja osnovnog oboljenja iz primarnog fokusa u lokalne i regionalne limfne žlezde uočava se tendencija intraglandularne limfogene diseminacije bolesti, kao i multicentrični karakter karcinoma. Iz ovog razloga nakon postavljanja dijagnoze papilarnog karcinoma štitaste žlezde terapija izbora bi trebalo biti totalna tireoidektomija (sa eventualnom disekcijom vrata), uz dopunsko lečenje radioaktivnim jodom. Rad: Diferentovani tireoidni karcinomi su najčešći od svih karcinoma štitaste žlezde i čine oko 90 %, najlakše se dijagnostikuju i najbolje leče. Papilarni tireoidni karcinomi se javljaju u 75 % slučajeva, folikularni tireoidni karcinomi u 10 % i Hürthl cell karcinomi u oko 2 4 % slučaja. Pacijentkinja G. K. (1990) se javila prvi put kod lekara godine zbog uočene nodozne strume desnog lobusa. Urađena FNA ukazala je na benignu promenu štitaste žlezde. Pacijentkinja je adekvatno dijagnostički obrađena i septembra godine učinjena desna lobektomija. Definitivni PH nalaz je ukazao na papilarni karcinom (klasični tip) 40mm. Nakon operacije je uvedena supstituciona terapija. Kompletizacija tireoidektomije nije savetovana. Zbog limfadenopatije desne strane vrata pacijentkinja je operisana februara 2015, kada je učinjena leva hemitireoidektomija (kompletirana totalna tireoidektomija) i funkcionalna disekcija desne strane vrata. 1 Specijalna bolnica Čigota, Zlatibor, laketic.cigota@gmail.com

2 PROŠIRENA BOLEST DIFERENTOVANOG TIREOIDNOG KARCINOMA ZBOG ODLAGANJA Definitivni PH nalaz: Levi lobus štitaste žlezde u kome se nalazi nekoliko sitnih fokusa papilarnog karcinoma štitaste žlezde prečnika do 1mm, što predstavlja intraglandularnu limfogenu diseminaciju karcinoma. Jedan od fokusa se nalazi i u okolnom vezivno-vaskularnom periglandularnom tkivu. Limfni nodusi desne strane vrata: od ukupno izolovanih 12 LN u 5 LN se nalaze metastaze karcinoma. Limfni nodus iz račve karotide sadrži metastaze karcinoma. Juna godine u našoj ustanovi primila terapijsku dozu I-131 od 5,55 GBq. Na postterapijskom scintigramu uočeno više konfluentnih zona nakupljanja radioaktivnog joda od submentalnog regiona do jugularne jame. Pri aplikaciji Th-doze TSH=64.0 miu/l, Tg>300ng/ml, antitgat=20 U/ml. Slika 1. Ciljani postterapijski snimak glave i vrata (jun 2015) U okviru pripreme za drugu reoperaciju urađen MDCT (septembar 2015): Mediosagitalno ispod donjeg pola tireoidne hrskavice i uz prednju konturu traheje diferencira se kružna promena, hipodenozna, veličine 11 x 7mm. U loži desnog režnja štitaste žlezde i pozadi hiperdenozna formacija 22 x 14mm. Kaudalnije uz anteromedijalnu konturu traheje desno hiperdenozna nodusna zona 15 x 12mm. Druga reoperacija oktobra godine, kada je učinjena centralna disekcija sa desne strane, ekstirpacija LGL lateralno od desne VCI, ekstirpacija LGL prelaringealno.

3 60 MEDICINSKI GLASNIK / str Definitivni PH nalaz: LN desne strane vrata: Dva LN sa metastazom papilarnog karcinoma štitaste žlezde. Prelaringealni LN: Od 2 LN u 1 LN se nalaze metastaze papilarnog karcinoma. LN centralno: od 12 LN u 11 LN se nalaze metastaze papilarnog karcinoma. Druga doza I-131 od 5,55 GBq aplikovana je krajem januara Pri aplikaciji Th-doze TSH>75.0 miu/l, Tg=76.8 ng/ml, antitgat=20 U/ml. Na postterapijskom scintigramu uočavaju se dva fokusa nakupljanja radioaktivnog joda, jedan u jugularnoj jami, a druga iza manubrijuma grudne kosti. Slika 2. Ciljani postterapijski snimak glave i vrata (februar2016) Nakon prijema doze u terapiju ponovo uvedena supresivno-supstituciona terapija preparatima levotiroksina. Diskusija: Papilarni karcinom štitaste žlezde predstavlja najčešći karcinom štitaste žlezde sa odličnim prognostičkim pokazateljima. Naime, petogodišnje preživljavanje je između 97 % i 99 % pacijenata. Iz ovog razloga u literaturi se sve češće sreću dileme koliko je postoperativna terapija radioaktivnim jodom zaista neophodna. S druge strane, karakteristike papilarnog karcinoma koje govore u prilog radikalnog lečenja (totalna tireoidektomija i dopunska terapija radioaktivnim jodom) su čest multicentrični karakter neoplazme, tendencija intratireoidnog limfogenog širenja, kao i tendencija širenja u lokalne i regionalne limfne žlezde. Od manjeg značaja (ali ne i zanemarljivog) je i mogućnost dediferencijacije papilarnog karcinoma u naročito agresivan anaplastični karcinom.

4 PROŠIRENA BOLEST DIFERENTOVANOG TIREOIDNOG KARCINOMA ZBOG ODLAGANJA Rizične grupe prema protokolu za lečenje radioaktivnim jodom su osobe mlađe od 15 i starije od 45 godina. Iskustva naše ustanove govore da je populacija koja je pod najvećim rizikom da ima proširenu ili upornu bolest upravo ona između 15 i 30 godina starosti. U ovom radu prikazali smo slučaj mlade ženske osobe kojoj je urađena hemitireoidektomija i postavljena je dijagnoza papilarnog karcinoma. Šest godina nakon prve operacije urađena je nova operacija kada je odstranjen preostali režanj i patološke limfne žlezde kontralateralne strane vrata. Fokusi papilarnog karcinoma u režnju su promera do 1mm, dok su patološke limfne žlezde bile promera oko 20mm. Ne može se očekivati da su fokusi karcinoma od 1mm dali metastaze kontralateralno, koje su navedenih dimenzija. Pretpostavka je da patološke lgl, koje su na istoj strani kao primarni karcinom (operisan 2009), predstavljaju kasnu manifestaciju proširene bolesti iz ovog primarnog fokusa. Fokusi mikrokarcinoma u suprotnom režnju predstavljaju intraglandularno limfogeno širenje karcinoma, kako se patolog izjasnio. Kako se patohistološki ne može razlikovati intratireoidno proširena bolest od de novo multifokalne neoplazme bez posebnih bojenja, u obzir dolazi i multifokalnost karcinoma u levom lobusu. Zaključak je da je godine kompletirana tireoidektomija i da je primenjena terapija radioaktivnim jodom desilo bi se nekoliko pozitivnih situacija: 1. sprečilo bi se intratireoidno limfogeno širenje karcinoma / pojava novih fokusa u okviru multicentričnog karcinoma; 2. izvršila bi se ablacija tkivnih ostataka tireoidne lože i sprečila pojava novih fokusa karcinoma dalje tokom života; 3. izvršilo bi se terapijsko delovanje na (pretpostavka) mikrometastaze u limfnim čvorovima iste strane. Zaključak: Nakon postavljanja dijagnoze papilarnog karcinoma štitaste žlezde terapija izbora bi trebalo biti totalna tireoidektomija (sa eventualnom disekcijom vrata), uz dopunsko lečenje radioaktivnim jodom. Jedino na ovaj način možemo smanjiti verovatnoću da se bolest proširi i/ili postane inoperabilna. Takođe, praćenje pacijenata u smislu nivoa markera u krvi (Tg i antitgat) je značajno lakše. Literatura: 1. Robert E. Henkin, Nuclear Medicine, Mosby, Emilio Bombardieri et al, Advances in Nuclear Oncology, Informa Healthcare The Patophysiologic Baics of Nuclear medicine (Second Edition), Abdelhamid Elgazzar, Springer, Georg F. W. Scheumann et al., Prognostic significance and surgical management of locoregional lymph node metastases in papillary thyroid cancer, World Journal of Surgery, 1993.

5 62 MEDICINSKI GLASNIK / str Nenad Laketic 1, Kata Kovacic, Aleksandar Simic DISSEMINATION OF DIFFERENTIATED THYROID CARCINOMA DUE TO PROLONGED TOTALIZATION OF THYROIDECTOMY CASE REPORT Abstract: Differentiated thyroid carcinomas (DTC) are the most common carcinomas in thyroid patology. The most common DTC is papillary thyroid carcinoma (PTC) which tends to spread lymphogenously. Beside spreading of malignant disease from the primary focus toward local and regional lymph nodes, intrathyroid lymphogenous spreading is also seen, as well as multifocal character of PTC. From this reason, after the diagnosis of PTC is established, desired therapy should be total thyroidectomy (with/without neck dissection) along with additional radioiodine therapy. Work: Differentiated thyroid carcinomas (DTC) are the most common carcinomas in thyroid patology. They represent 90% of all thyroid carcinomas. They are relatively easy to diagnose and have good prognosis. PTC occurs in 75%, follicular in 10% and Hurthle cell carcinomas in 2-4%. Female patient G.K. (1990) was diagnosed with nodular goiter of the right thyroid lobe in Although FNAC was benign, right lobectomy was performed the same year. Histopathological exam showed classic type of PTC 40mm in diameter. After the surgery patient was prescribed L-thyroxin supstitution. Totalization of thyroidectomy has not been advised. In 2015 patient underwent surgery for the second time due to a number of pathological lymph nodes of the right side of neck. Left lobectomy was performed along with extraction of lymph nodes of the right side of the neck. Definitive histopathological findings: Left lobe of the thyroid gland with several focuses of papillary thyroid carcinoma (up to 1mm in diameter) which represent intrathyroid lymphogenic dissemination of the disease. One focus is in adjacent connective and vascular tissue located outside of the thyroid gland. 1 Special hospital for thyroid diseases and metabolic diseases, Zlatibor, laketic.cigota@gmail.com

6 DISSEMINATION OF DIFFERENTIATED THYROID CARCINOMA DUE TO PROLONGED TOTALIZATION Lymph nodes (right side of the neck) among 12 LN, 5 had PTC metastasis. Lymph node from the carotid bifurcation PTC metastasis. In June 2015 patient received therapeutic dose of I-131 (5,55 GBq) in our institution. WBS after the therapy showed multiple focuses of radioiodine accumulation along the mid-line of the neck: from submental region down to jugular notch. Blood parameters were: TSH=64.0 miu/l ( ), Tg>300ng/ml, antitgat=20 U/ml. Picture 1. Posttherapeutic targeted scan of the head and neck (June 2015) Second reoperation was performed in October with the neck dissection (right central, right lateral and laryngeal anterior). Definitive histopathological findings: 1. Right lateral LN: 2 LN with PTC metastasis. 2. Right central LN: 11 LN out of 12 LN had PTC metastasis 3. Laryngeal anterior LN: one out of 2 LN had PTC metastasis. The second dose of I-131 (5,55 GBq) was received at the end of January Blood parameters were: TSH>75.0 miu/l, Tg=76.8 ng/ml, antitgat=20 U/ml. WBS after the therapy showed two focuses of I-131 accumulation: one in jugular notch and the other one behind manubrium.

7 64 MEDICINSKI GLASNIK / str Picture 2. Posttherapeutic targeted scan of the head and neck (February 2016) Discussion: Papillary thyroid carcinomas (PTC) are the most common carcinomas in thyroid patology. They are relatively easy to diagnose and have good prognosis. Five-year survival is between 97% and 99% of patients. Because of that, we can find more and more papers where is discussed whether there is a need for radicality (total thyroidectomy and radioiodine therapy) in this carcinoma at all. On the other hand, PTC characteristics that are speaking in favor of radicality are: multifocal PTC which is not rare, intrathyroid lymphogenic dissemination and tendency of dissemination in local and regional lymph nodes. Minor importance has tendency of poorly differentiated papillary carcinoma to dedifferentiate into very agressive anplastic carcinoma. High-risk population according to DTC treatment protocols are patients younger than 15 and older than 45 years. Our institution experience shows that the population which has the highest rate of disseminated disease or prolonged disease is between 15 and 30 years of life. This work presented the case of a young female patient who underwent right hemithyroidectomy and was diagnosed with papillary thyroid carcinoma. Six years after the first surgery she had another one when the surgeon has completed thyroidectomy (left lobe) and has extracted pathological lymph nodes on the right side of the neck. PTC focuses in the left lobe were up to 1mm in diameter while the lymph nodes were around 2cm in diameter. It can not be expected that these focuses in the left lobe have given metastasis in contralateral side of the neck which are this big.

8 DISSEMINATION OF DIFFERENTIATED THYROID CARCINOMA DUE TO PROLONGED TOTALIZATION We assume that lymph nodes, which were on the same side of the neck as the first PTC from 2009, represent late manifestation of disseminated disease from the primary focus. Focuses of microcarcinoma in left lobe present intrathyroid lymphogenous dissemination, as histopathologic findings showed. But, we can not distinguish between lymphogenous dissemination and new multicentric focuses without certain histopathologic procedures (which are not commonly done). Because of this, microcarcinoma in the left lobe could be de nuovo formed muticentric neoplasm. Our conclusion is: if totalization of the thyroidectomy and additional radioiodine therapy has been done right after the first surgery in 2009., there would be several positive outcomes: intrathyroid dissemination of the disease/appearance of new focuses could be prevented with radioiodine ablation in thyroid bed appearance of new focuses during the life could be prevented radioiodine therapy could have had therapeutic effect on (as we suppose) micrometastasis in the lymph nodes on the same side of the neck Conclusion: After the PTC diagnoses has been established the desired therapy should be total thyroidectomy along with additional radioiodine therapy. Only this way we can prevent the disease to disseminate or to become inoperable. Follow up of the patient in terms of tumor markers (thyroglobuline, antitg antibodies) is facilitated, also. References 1. Nuclear Medicine, Robert E. Henkin, Mosby, Advances in Nuclear Oncology, Emilio Bombardieri et al, Informa Healthcare The Patophysiologic Baics of Nuclear medicine (Second Edition), Abdelhamid Elgazzar,Springer, Prognostic significance and surgical management of locoregional lymph node metastases in papillary thyroid cancer, Georg F. W. Scheumann et al., World Journal of Surgery, 1993.