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Nastaje iz parafolikularnih stanica atitnja e koje secerniraju kalcitonin, javlja se u 4-10 % svih malignih tumora atitnja e, veinom sporadi no, ali oko 25 % slu ajeva je nasljedno. Nasljedni oblik medularnog raka mo~e biti detektiran molekularnim screening-om za RET proto-onkogene mutacije. Prognoza bolesti ovisi o stadiju kad se dijagnosticira rak. Prognoza bolesti je loaa kad je tumor vei, ako je prisutno ekstratiroidno airenje tumora i kad su zahvaeni limfni vorovi, a pogotovo ako se pojave udaljene metastaze. Stopa 5 godianjeg pre~ivljavanja je 78-91 %, a 10-godianjeg 61-75%. Ultrazvukom mo~emo otkriti nepaplabilne i vrlo male vorove u atitnja i ali ne mo~emo prepoznati razli ite tipove tumora. Medularni rak se prikazuje hipoehogeno u odnosu na normalno tkivo atitnja e u 85 % slu ajeva jer tumorsko tkivo ima vei celularitet od normalne folikularne grae atitnja e, sli no kao i papilarni rak (u 86% slu ajeva). Folikularni rak prikazuje se hipoehogeno u manjem postotku (56%) jer eae od papilarnog i medularnog raka zadr~ava folikularnu grau sli nu adenomima i nodularnim strumama. Ultrazvukom mogu se prepoznati neke karakteristike raka kao ato su infiltrativni rast (neravne konture vora) i prisutnost sitnih kalcifikata, grupiranih ili rubno smjeatenih kalcifikata. Na temelju tih pokazatelja mo~e se prepoznati rak ato je naro ito va~no pri odabiru vorova za ciljanu citoloaku punkciju, pogotovo ako se radi o manjim vorovima jer vee vorove treba punktirati bez obzira na ehostrukturu. Na temelju navedenih ultrazvu nih kriterija za rak mo~e se prepoznati medularni rak u 44 % slu ajeva, papilarni u 54 % a folikularni u 28 % slu ajeva. Ciljana citoloaka punkcija pod kontrolom ultrazvuka je visoko specifi na metoda (97 %) i dosta senzitivna (oko 90 %) u dijagnostici medularnog i papilarnog raka atitnja e. Ultrazvukom mo~e se procijeniti veli ina vora, smjeataj u atitnja i i odnos prema kapsuli atitnja e. Subkapsularno smjeateni vorovi imaju veu vjerojatnost ekstratiroidnog airenja u okolne strukture. Zato treba obratiti pa~nju na subkapsularno smjeatene vorove i treba ih ciljano punktirati pa makar se radi i o manjim vorovima. Kolor Doppler omoguuje prikaz vaskularizacije vora. Patoloaka vaskularizacija raka ne mora biti uvijek vidljiva ali jaka intranodalna vaskularizacija, pogotovo bez zna ajnije periferne vaskularizacije scintigrafski ЋhladnogЛ vora je vrlo suspektan nalaz za rak. Ultrazvukom se dobro prikazuju limfni vorovi, prikazuju se hipoehogeno u odnosu na atitnja u, pravilnog su oblika, naj eae izdu~eni i prepoznaje se pravilan hilus. Metastatski limfni vorovi mogu se prepoznati zbog promijenjene ehostrukture, viae su ehogeni i pokazuju strukturu kao tkivo atitnja e, esto su nepravilne ehostrukture s cisti nim promjenama i kalcifikatima. Kolor Doppler znatno poma~e u prepoznavanju metastatskih vorova, pogotovo manjih kod kojih nije joa naruaena ehostruktura ali je prisutna patoloaka periferna vaskularizacija s ruba vora prema unutra koja nikad nije prisutna u normalnom limfnom voru kod kojeg se vidi samo diskretna vaskularizacija u hilusu. Ultrazvuk poma~e u ocjeni proairenosti raka i u planiranju opse~nosti operativnog zahvata. U bolesnika s medularnim rakom kad su u vrijeme postavljanja dijagnoze zahvaeni limfni vorovi, koji su operativno odstranjeni, esto se pojavljuju novi metastaski limfni vorovi, pogotovo ako su poviaene vrijednosti kalcitonina u serumu i nakon operativnog zahvata. Ultrazvu na dijagnostika je va~na i u ispitivanju nasljednog oblika medularnog raka. Iako je danas mogu molekularni screening za RET proto-onkogene mutacije na temelju kojih se mo~e preporu iti profilakti ka tireoidektomija ispitanici se ne odlu uju lako za taj zahvat. Pomnim pretra~ivanjem atitnja e ultrazvukom mo~emo otkriti vrlo sitne vorie, veli ine 2-3 mm, koji mogu biti punktirani pod kontrolom ultrazvuka. Kod nesigurnog citoloakog nalaza i urednih vrijednosti kalcitonina u serumu mo~e pomoi i odreivanje kalcitonina iz punktata, razrijeenog s 1 ml fizioloake otopine. Kalcitonin iz punktata mo~e biti znatno viai nego u serumu ako je punktiran vori medularnog raka. Papilarni i folikularni rak spadaju u dobro diferencirane maligne tumore. U svim statistikama analiziraju se prognosti ki imbenici i ishod bolesti za te dvije grupe pacijenata, ali danas znamo da to nisu jedinstvene bolesti. Danas se dijagnosticira minimalno invazivni i invazivni folikularni i Hќrthle cell rak, inzularni rak kao morfoloaka varijanta folikularnog raka, papilarni mikrokarcinom, inkapsulirana varijanta, folikularna varijanta, solidna trabekularna varijanta, sklerozna difuzna varijanta, tall cell i columnar cell varijanta papilarnog raka, clear cell rak, mucinozni i skvamozni oblici raka atitnja e. Da li su to posebne vrste raka s razli itim bioloakim ponaaanjem tumora i razli itim ishodom bolesti ili samo pojedine faze maligne bolesti to joa ne znamo, no poznato je da se slabije diferencirani i anplasti ni rak razvija veinom iz dobro diferenciranog raka. Anaplasti ni rak brzo raste, infiltrira okolne organe i ima vrlo loau prognozu, naj eae s letalnim ishodom bolesti. Ultrazvukom se prikazuje kao nepravilna velika tvorba, razli ite ehostrukture s kalcifikatima i nekroti nim sadr~ajem, mo~e se vidjeti infiltrativni rast u miaie i duanik, odnos s krvnim ~ilama i opse~nost metastaza ato je va~no u planiranju operativnog zahvata. Slabo diferencirani rak i anaplasti ni rak esto se ne mo~e u potpunosti odstraniti, esti su lokalni recidivi i udaljene metastaze. Slabo diferencirani tumori ne nakupljaju radioaktivni jod, slabo reagiraju na vanjsko zra enje i kemoterapiju. Slabije diferencirani tumori eai su u starijoj dobi ali mogu se javiti i u djece i mladih ljudi. Anapasti ni rak atitnja e javlja se u 1-5 % svih malignih tumora atitnja e, a prema novijim literaturnim podacima rjee nego ranije, na ato je vjerojatno utjecala jodna profilaksa i sve ranija dijagnostika raka atitnja e. Zaklju ak: Ultrazvu na dijagnostika atitnja e i ciljana citoloaka punkcija su neophodne u dijagnostici raka atitnja e. Ultrazvukom mo~emo otkriti medularni rak na sistematskom pregledu kad joa nema palpabilnog vora i meu lanovima obitelji bolesnika oboljelog od nasljednog oblika medularnog raka (mo~emo otkriti tumor veli ine 2-3 mm). Iako je prognoza bolesti dobra u bolesnika s rakom atitnja e, loaiji prognosti ki pokazatelji i dobro diferenciranih tumora kao ato su veli ina tumora, dob i ekstratiroidno airenje tumora pokazuju znatno loaiju prognozu, ote~ano i skuplje lije enje koje zahtjeva i nekoliko operacija i radiojdnih terapija a esto i s letalnim ishodom. Terapija medularnog raka je isklju ivo operativna, radioterapija ima slabi uspjeh. Terapija slabo diferenciranog i anaplasti nog raka veinom je bezuspjeana te jedino rana dijagnostika mo~e poboljaati prognozu bolesti i smanjiti mortalitet bolesnika oboljelih od medularnog i slabo diferenciranog raka i sprije iti razvoj slabo diferenciranog i anaplasti nog raka atitnja e. Role of ultrasonography in the diagnosis of medullary, poorly differentiated and anaplastic thyroid carcinomas Zdenka Bence-}igman Clinical Department for Nuclear Medicine and Radiation Protection, Clinical Hospital Center Zagreb Medullary thyroid carcinoma originates from the parafollicular cells of the thyroid, which secrete calcitonin. Medullary thyroid carcinoma represents 4-10 % of all malignant thyroid tumors. Approximately 25 % of medullary thyroid cancers are familial forms that can be detected by molecular screening for RET proto-oncogene mutations. The prognosis is usually poor since, at the time of diagnosis, lymph node involvement and distant metastases are frequently present. In general, the strongest prognostic variable is the extent of disease at presentation. Presentation with a thyroid mass strongly correlates with regional nodal disease. The 5-year survival rate is between 78% and 91%, and 10-year survival is between 61% and 75%. Early diagnosis and radical surgical treatment improve the morbidity and mortality associated with medullary thyroid carcinoma. Ultrasound examination of thyroid gland can detect nonpalpable and very small nodules, but we are not able to distinguish different types of cancers by ultrasound. Medullary carcinomas present hypoechogenic echo-pattern in relation to normal thyroid follicular structure in 85 % of cases, similar as papillary carcinomas (in 86 % of cases). Follicular carcinomas present hypoechogenic echostructure in 56 % of cases because follicular carcinoma more often preserve follicular structure than papillary and medullary carcinomas. If the contour of hypoechogenic nodule is irregular or blurred, or microcalcifications, grouped calcification, or edge calcifications are present the probability of carcinoma is high with specificity of 97 %. Characteristic findings of carcinoma present 44 % of medullary carcinomas, 54 % of papillary carcinomas and 28 % of follicular carcinomas. Ultrasonically guided cytology is highly specific method (97%) and quite sensitive (about 90%) in the diagnosis of medullary and papillary carcinoma. The precise description of echostructure, size and localization of the nodules in thyroid facilitates the choice of the nodules for biopsies. Subcapsular tumors have high probability for extrathyroidal spread, therefore it is important to perform ultrasonically guided biopsy of subcapsular nodules even if, when they are small. Color Doppler is an additional tool for understanding vascularity of nodules. Pathological vascularisation of cancers is not always visible, but the presence of intranodal vascularity by color Doppler is a sign of malignancy if the nodule is “cold” by scintigraphy. Small nonpalpable neck lymph nodes can easily be detected by ultrasound. They are presented as hypoechogenic nodules, sometimes with central echognic hilum. Experienced examiner can recognize metastatic lymph node due to its round shape, or more echogenic, irregular or cystic appearance, or small calcifications within the nodule, or abnormal peripheral vascularity using color Doppler. If lymph node metastases are diagnosed lymph node dissection is performed at the same time with total thyroidectomy. Ultrasound helps to evaluate the stage of disease and to plane the extent of surgery. In patients with lymph node involvement, at the time of diagnosis, new lymph node metastases are often occurred after initial surgery, especially if serum calcitonin levels remain increased. Ultrasonography is also an important method in investigation of familial form of medullary thyroid cancer among family members. Although they can be detected by molecular screening for RET proto-oncogene mutations, participants are reluctant to have total thyroidectomy which is recommended on the bases of this procedure. Precise ultrasound examination can detect small nodules 2-3 mm in diameter. Ultrasonically guided fine-needle biopsy can reveal medullary carcinoma. Measurement of calcitonin from fine-needle biopsy material, diluted with one milliliter of normal saline, can be helpful in cases with negative cytological findings. Calcitonin levels from such solution can be several times higher than serum calcitonin levels if medullary cancer is punctured. Prognostic indicators of differentiated thyroid carcinoma and outcome of disease are analyzed in many statistical date. But, nowadays we know that many histologic features of such cancer exist: minimally invasive follicular carcinoma, widely invasive follicular and Hќrthle cell carcinoma, insular carcinoma as a morphological variant of follicular carcinoma, papillary microcarcinoma, encapsulated variant, follicular variant, solid/trabecular variant, diffuse sclerosing variant, tall cell and columnar cell variants of papillary carcinoma, clear cell carcinoma, mucinosus and squamosus variant of thyroid carcinoma. We don’t know if there are different types of thyroid carcinoma with different biological behavior or stages of malignant thyroid disease. But, it is generally accepted that poorly differentiated carcinomas and anaplastic carcinomas arise from well-differentiated carcinomas. Poorly differentiated and anaplastic carcinoma present rapidly enlarging neck mass, produces compression signs such as dyspnea, dysphagia, and hoarseness. Extrathyroid extension, invasion of major vessels and nerves of the region, and spread into the larynx, trachea esophagus are common. Lymph node and distant metastases are frequent. Ultrasound examination shows large irregular inhomogeneous mass with calcifications and necrosis, infiltration of muscles and other neck structures, and tumor relation with major vessels. Radical surgical treatment, radiotherapy and chemotherapy are not efficient. Poorly differentiated carcinoma are more frequent in elderly patients however, children and young patients can also have advanced disease and poorly differentiate carcinoma at the time of diagnosis. Anaplastic carcinoma is rare, represents 1-5% of all malignant thyroid tumors but, it is one of the most lethal human malignant tumors. Conclusion: Ultrasonography and ultrasonically guided fine-needle biopsy are methods of choice in diagnosis of thyroid cancers. Ultrasound can detect small medullary cancer during general check-up in apparently healthy participants, also among family members of patients with familial form of medullary thyroid carcinoma, size of 2-3 mm in diameter. Although prognosis for patients with thyroid carcinoma is usually excellent, a subset of patients develops more aggressive disease. The strongest prognostic variable of medullary thyroid cancers is the extent of disease at presentation. Therapy of poorly differentiated and anaplastic carcinomas is mostly not effective. Early diagnosis and surgical treatment are the keys to improving the morbidity and mortality associated with medullary and differentiated thyroid carcinoma, preventing development of poorly differentiated and anaplastic carcinoma. В˜ Zlž"А"А=>†?Š?ˆL‹L=Z?Z§њѕѕюѕюѕѕ CJmH sH mH sH CJCJ ВДмоX˜šž ~В!'f5ž=Ђ=Є=І=Ј=Њ=Ќ=Ў=А=Ž>>И>К>B?„?†?§ћћћћћћћћћћћћћћћћћћћћћћћћћћћћ?Z§†?ˆ?Š?Œ?$CFoHzI‹L‰OВV9Z:Z=Z>Z?Z§§ї§§§§§ё§§§§§§„Ф`„Ф Ц“,1hА‚. 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