Cancerul tiroidian derivat din

epiteliul folicular

Corin Badiu, 2020

Glanda Tiroidă

Corin Badiu, 2020

 Dezvoltare
Apare in sapt 4 (Foramen cecum)
Coboara pana in sapt 12-18
Reg cervicala anterioara
Duct tireoglos → Lob piramidal

Corin Badiu, 2020

Histologie MO

Corin Badiu, 2020

Foliculul tiroidian

Corin Badiu, 2020

Reglare

Corin Badiu, 2020

Actiunea TSH

Corin Badiu, 2020

 Teste diagnostice
Funcţionale Morfologice
• Reglajul axei tiroidiene • Ecografie
• Hormoni (totali/liberi) • Scintigrafie
• Transport şi efecte periferice • CT / IRM
• Metabolismul iodului • Anatomie patologică
• Autoimunitatea
• Genetica

ALGORITMI

Corin Badiu, 2020

 TSH / T4 / fT4

The relationship between serum TSH and free T4 concentration is shown for normal subjects (N) and in the
typical abnormalities of thyroid function: A, primary hypothyroidism ; B, central or pituitary-dependent
hypothyroidism; C, thyrotoxicosis due to autonomy or abnormal stimulation of the gland; D, TSH-dependent
thyrotoxicosis or thyroid hormone resistance. Note that linear changes in the concentration of T4
correspond to logarithmic changes in serum TSH.
Corin Badiu, 2020
 ECOGRAFIA TIROIDIANA
• Evidentiaza
– Gusa si caracterul difuz sau nodular al acesteia
– Nodulul < 1 cm / confirma nodulul > 1 cm
– Chistii tiroidieni
– Hipervascularizatie si calcificari
• Masoara
– Dimensiuni tiroida  calcul volum [=½*(d1+d2+d3)]
– Dimensiuni nodul (in dinamica)
• Diferentiaza
– Nodulii tiroidieni de cei extratiroidieni
– Nodulii de chisti
ECOGRAFIA TIROIDIANA

Corin Badiu, 2020

ECOGRAFIA TIROIDIANA

Corin Badiu, 2020

 Radio Iodo Captarea
Valori crescute Valori scăzute
• Sinteză crescută de HTir • Sinteză scazută de HTir
– Hipertiroidism – Hipotiroidism primar
(gusa polinodulara, Graves, Plummer) (Hashimoto, ATS, tiroidectomie, 131I)
– Depleţie hormonală – Hipotiroidism secundar
(diaree cronică, sdr. nefrotic) (leziuni hipotalamo-hipofizare)
• Sinteză normală de HTir – Aport exogen de HTir
– Carenţă iodată
• Fără scăderea sintezei HTir
– Aport iodat excesiv
(dieta, medicatie)

Corin Badiu, 2020

 SCINTIGRAFIA TIROIDIANA
• A nu se confunda cu radioiodocaptarea (RIC)
• Trasori : I123, I131 sau Tc 99m (pertechnetat)
 I123 (doze 200- 300 Ci) ,imagine la 8 - 24 ore;
 99mTcO4 (doze 1 - 10 mCi), imagine in 30-60 min;
 I131 (doze 300 Ci) imagine dupa 24 de ore;
– mai dezavantajos (ca timp / iradiere)
– mai avantajos in (penetranta mai mare emisii):
 gusi mari retrosternale
 metastaze de cancer tiroidian
• Imaginile se obtin cu :
– Scaner rectiliniar
– Gamma camera cu colimator “pinhole”
 Scintigrama Tiroidiana

Scintiscans of thyroid. The scan on the left is normal. A typical scan of a "cold" thyroid nodule failing to
accumulate iodide isotope is shown on the right.
 Noduli tiroidieni
Delimitare distincta a parenchimului tiroidian fata de ţesutul tiroidian
vecin, evidenţiata clinic vizual sau prin palpare şi/sau ecografic.

Tiroidieni Alte formatiuni

• Benigni (95%) • Adenopatii
• Maligni (5%) • Paratiroide
• Granulom

Corin Badiu, 2020

Nodulul tiroidian

Prezentare clinică:
 observat de pacient
 descoperit de medic
la examenul clinic
 identificat incidental:
o ecografie Doppler carotidiană
o examen CT/ IRM cervical/ PET-CT

4-6% cancer tiroidian !

Corin Badiu, 2020

 Noduli cervicali
Tiroidieni
Benigni
• Hiperplazie spontana
• Hiperplazie pe lob restant
• Tiroidita Hashimoto focala
• Tirodita subacuta
• Adenom folicular ± autonom/toxic
• Adenom cu celule Hurtle
Algoritmi
Maligni
• Carcinom T papilar
• Carcinom T folicular
• Carcinom T medular
• Cancer anaplazic
• Metastaza tirodiana
• Limfom tiroidian
Carenta iodata

*
 Gusa
Marirea de volum a glandei tiroide, fata de limita
corespunzatoare varstei si sexului.
OMS: 4 grade
Noduli tiroidieni
 CLASIFICAREA
A. Primar:
1. origine in celulele tireocitare foliculare
a. carcinom diferentiat
papilar (70-75%)
folicular (10-15%)
b. carcinom nediferentiat (anaplastic) – 5%
2. origine in celulele C (parafoliculare)= CMT– 5%
3. origine in alte celulele = foarte rar (lipom ,sarcom)

B. Secundar
1. Metastaze cancere solide (plaman, san, rinichi)
2. Limfom intratiroidian – 3%
 Premise

• Epidemiologie: dependenta de aportul de iod

• Imagistica performanta: intre 20 şi 76% in populaţia generala
• Impact psihologic
• http://www…..

Corin Badiu, 2020

Iodine deficiency
Thyroid
cancer
incidence

GLOBOCAN 2012
 Epidemiologie

CTD: al 2lea cancer la femei in 2018

Aschebrook-Kilfoy B, et al. Cancer Epidemiol Biomarkers Prev. 2013;22(7):1252-1259.

Incidenta cancerului tiroidian dependenta de varsta si rasa
Surveillance, Epidemiology and End Results (SEER) 13

Aschebrook-Kilfoy B.et.al.,Thyroid,2011.
Epidemiology
Epidemiology
 FRECVENTA
• - incidenta = 0.5 – 10 / 100,000 locuitori
• - prevalenta = 100 – 270 */ 100,000 locuitori
• - mortalitate = 0.8 / 100,000 locuitori / 1 an
• - sub 1 % din totalitatea cancerelor **
• - factori de risc:
  sex – F/B > 2
  varsta – la copii = sub 10% cazuri ***
  expunerea la iradiere
 * - necropsii
 ** - la copil al 3- lea cancer ca frecventa
 *** - de 10 ori mai mare dupa iradiere
 US SEER Cancer Registry 2009: Thyroid

Incidence

< 1,0 cm 1,0-2,9 cm 3,0-3,9 cm > 4,0 cm

Females

Males

Chen et al. Cancer 2009

31
 Epidemic of Thyroid Cancer in the US 2005-2009:
Role of Endocrinologists and Ultrasound

Age Stand.Incidence Rate by State

Density of Endocrinologists
r=0.44, P=0.0031

Counts of Neck Ultrasonography

r=0.40, P=0.0091

Udelsman & Zhang Thyroid 2013

Nodulul tiroidian
 Leziune radiologic distinctă de
parenchimul tiroidian înconjurător
 Unele formațiuni identificate palpator nu au
corespondent ecografic
 Incidentaloamele (noduli nepalpabili
depistați la evaluări imagistice efecutate în
alt scop) – au același risc de malignitate
ca un nodul palpabil !

! NB ! Captare focală 18FDG-PET - ↑ riscul de cancer

Noduli > 1 cm – potential cancere clinic semnificative

Majoritatea nodulilor tiroidieni sunt low risk!

Multe cancere reprezintă un risc minimal pentru sănătate și pot fi tratate
eficient!
Algoritm diagnostic

Almost never cancer !

Exc: metastatic FTC
malignant struma ovarii

Uptodate, accessed 23.08.2019

 Anamneza
Anamneza trebuie sa cuprindă următoarele informaţii
(Recomandare C):

• Istoric familial de boli tiroidiene

• Antecedente de afecţiuni sau iradiere la nivel cervical
• Creşterea unei formaţiuni cervicale
• Disfonia, disfagia sau dispneea
• Localizarea, consistenta şi dimensiunea nodulului
• Sensibilitatea sau durerea cervicala
• Adenopatia cervicala
• Simptome de hipo sau hipertiroidism
Istoric și examen clinic

Atenție la antecedente de:

 iradiere cap/ gât în copilărie
 iradiere pt transplant medular
 istoric familial de cancer tiroidian/ sd genetice:
- Sd neoplazie endocrină multiplă
- Polipoză adenomatoasă familială
- sd Cowden (AD- hamartoame, macrocefalie)

Clinic suspect:
 copil/ nodul solitar la ♂
 formațiune tumorală ↑ rapidă
 nodul dur la palpare
 adenopatii LC
 fenomene compresive
THYROID TUMORS
THYROID NODULES

Haugen et al,2015. Thyroid

THYROID NODULES

Haugen et al,2015. Thyroid

<2% <2% 5% 5 - 20 % > 20 %

Risk of malignancy

J Am Coll Radiol 2017;14:587-595

Fenomene compresive

 Dispnee
 Disfagie
 Disfonie
 Neurologice
(MTS osoase)
Tireoglobulina

R3. “Routine evaluation of serum thyroglobulin (Tg) for

initial evaluation of thyroid nodules is not recommended
- Tg levels can be elevated in most thyroid diseases and
are insensitive and nonspecific test for thyroid cancer1”

2015 ATA guidelines for adult patients with thyroid nodules and DTC
 Calcitonina și carcinomul medular tiroidian
 cancer agresiv, debut insidios, frecvent diagnostic tardiv
 curabil doar prin rezecție chirurgicală completă
 CT pentru diagn preop precoce al CMT/ hiperplaziei celule C →
îmbunătățirea supraviețuirii ! 1
 nivelul CT se corelează cu volumul tumoral

R4. “The panel cannot recommend either for or against routine

measurement of serum calcitonin in patients with thyroid nodules (No
recom, insuf evidence)”2
- Low rate of cure after MTC spreads outside thyroid gland
- MTC is present in only 0.3-1.4% of thyroid nodules – cost-effectiveness?
- Falsely ↑ Ct levels – confirmation by pentagastrin/ Ca stimulation tests

1. Elisei R, JCEM 2004

2. 2015 ATA guidelines for adult patients with thyroid nodules and differentiated thyroid cancer
 FNAB
(Recomandare A)
• Managementul clinic al nodulilor tiroidieni trebuie sa se facă în
concordanta cu rezultatele ecografiei şi ale puncţiei-aspiraţie cu ac fin
• Frotiurile trebuie evaluate de un anatomopatolog specializat in
leziunile tiroidiene

Indicaţii privind repetarea puncţiei unui nodul tiroidian

• Urmărirea unui nodul benign
• Creşterea nodulului
• Refacerea chistului
• Nodul tiroidian > 4 cm
• Puncţie-aspiraţie cu ac fin cu rezultat iniţial non-diagnostic
• Nodulul nu se micşorează după tratamentul de supresie cu levotiroxina
(Recomandare C)
Puncția tiroidiană cu ac fin
(Fine Needle Aspiration Biopsy)
Procedura diagnostică de elecție pentru
nodulii tiroidieni care întrunesc criteriile
ecografice de suspiciune
 Fine needle aspiration cytology specimens.

(A) Benign epithelial cells, colloid, and (B) Epithelial cells in a follicular arrangement
occasional macrophages, typical of a "colloid suggesting adenoma, but which could be from
nodule". a follicular carcinoma.
•Psammoma bodies: laminated calcified spheres, diagnostic of
papillary cancer
•Certain histological variants have higher risk of recurrence:
Tall cell, columnar cell, diffuse sclerosing cell
Bethesda Diagnostic Categories
(2017)
“A science of uncertainty and an art of probability”
Sir William Osler

FNA

Benign Indeterminate Malignant

0-3% 97-99%
AUS/FLUS FN
10-30% 25-40%

Unneeded surgery Diagnostic Suboptimal surgery

Benign histology surgery Malignant histology

70% 30%
Clinical Therapeutic
follow-up thyroidectomy

Modified from Nishino M. Cancer Cytopathology 2015

 Atypia of Undetermined Significance

• 10-15% of fine needle aspirations (FNAs)

• 5-15% risk of malignancy
• Often referred for diagnostic thyroidectomy
 Low but defined risk of complications
Evidente diagnostice

Modificarea prezentarii clinice:

► Masa palpabila
► Nodul tiroidian descoperit la imagistica cervicala
► Focare mici la anatomie patologica (tiroidectomie pentru alte indicatii)

Microcarcinoame - capatul “mic” al spectrului patologic:

► 30% din tiroide la autopsie
► “un singur focar de microcarcinom in piesa de tiroidectomie” –
“descoperire incidentala fara importanta clinica” 1
► chiar microcarcinomele pot metastaza regional !

Management: fara trialuri prospective → ghiduri bazate pe

analiza retrospectiva si opinia expertilor.
1 Tuttle et al, Overview of papillary thyroid cancer, UpToDate 2013
 Factori de risc pt KK Tir
• Expunerea la iradiere in copilarie (acnee, hiperplazie timica)
Intre 20-27% din copii iradiati fac noduli tiroidieni (30% din
acestia sunt KK tir)

• Varsta tanara (<30 ani) sau peste 60 ani.

• Sex masculin
• Adenopatie laterocervicala
• Nodul unic
• Mobilitate scazuta
• Disfonie
• Creşterea recentă şi rapidă (in luni de zile)
• Fenomene de compresie
• Consistenţa fermă/dură
Radiation exposure
Chernobyl – April 1986

Cesium 137

Korobova et al, Journal of Geochemical Exploration 142 (2014) 82–93

Iodine & Thyroid cancer

Cesium 137

Korobova et al, Journal of Geochemical Exploration 142 (2014) 82–93

Radiation exposure
Fukushima, March 2011
Regular thyroid US in children: 254 280 tests (81%
of the target population)

FNAB: 1490 children

Total: 33 confirmed, 42 suspected DTC since 2011

Mayor S., Lancet Oncol 2013; 14: 1042–43

 Management

NCCN Clinical Practice Guidelines in Oncology: Thyroid Carcinoma, vers I. 2013.

Durante C et al., J .Clin Endocrinol Metab, 2006.
 Limfom
CANCER TIROIDIAN
Inoperabil Papilar (?)

Radioterapie Tiroidectomie totala Lobectomie

Chemoterap

Radioablatie cu I 131

Adm T4 * (urmarire TSH)

TGL/ clinic /WBS cu I 131

RECIDIVA STATUS QUO

CHIRURGIE RADIOIODOTERAPIE *
* = cp/cf
Management

Pacini F, et al. Eur J Endocrinol. 154(6):787-803.

Management

Pacini F, et al. Eur J Endocrinol.;154(6):787-803.

Initial evaluation, treatment, and follow-up of
the patient with thyroid nodule.

Francis et al, Thyroid 25 (7) (2015) 716-759

 Clinically Management
insignificant
cancers
Stratificarea riscului

morbiditate tratament
risc de recurență
mortalitate prin boală

Invasive
aggressive
cancers Markeri de prognostic ?
2015 ATA guidelines for adult patients with thyroid nodules and DTC
Management of patient with known or suspected
residual/recurrent disease

Francis et al, Thyroid 25 (7) (2015) 716-759

Tireoglobulina

 sintetizată exclusiv în cel. folic.

 marker excelent pt CTD

→ info boală persistentă/recurentă

 Metode imunometrice (interacțiuni Ag – Ac)

 25% pacienți au Atg ↑ - interferă cu dozarea Follow-up dificil !
 Variabilitate mare inter-assay

ATENȚIE ! Monitorizarea seriată a Tg prin aceeași metodă

Tg, Atg mereu măsurați în pereche
Valoarea exactă este importantă în dinamică – diluție !
Management of patient with known or suspected
residual/recurrent disease

Francis et al, Thyroid 25 (7) (2015) 716-759

TSH targets

Haugen et al,2015. Thyroid

RadioIodine ablation

Haugen et al,2015. Thyroid

Scenariu 1

Examen HP: carcinom papilar 2.5 cm, forma clasică, invaziv marginal,
adenopatie LC drept, pT2 pN1

ATA Intermediate risk

Radioiod 50 mCi după pauză Euthyrox 3 săpt/ Thyrogen

TSH= 52 uUI/ml
Tg= 0.2 ng/ml
ATg= 20 UI/l
Scintigrafie WBS: pozitiv cervical, negativ în rest

Răspuns excelent la tratament

Monitorizare prin Tg seriată, ecografie regiune cervicală anterioară
TSH= 0.5 - 2 uUI/ml
Scenariu 2

Examen HP: carcinom papilar 2.5 cm, forma clasică, invaziv marginal,
adenopatie LC drept, pT2 pN1

ATA Intermediate risk

Radioiod 50 mCi după pauză Euthyrox 3 săpt/ Thyrogen

TSH= 52 uUI/ml
Tg= 12 ng/ml
ATg= 20 UI/l
Scintigrafie WBS: pozitiv cervical, negativ în rest

Răspuns biochimic incomplet

Monitorizare prin Tg seriată, eco regiune cervicală ant
TSH= 0.1 – 0.5 uUI/ml
Repetare I131, CT/ RMN pentru boală persistentă
Scenariu 3

Examen HP: carcinom papilar 2.5 cm, forma clasică, invaziv marginal,
adenopatie LC drept, pT2 pN1

ATA Intermediate risk

Radioiod 50 mCi după pauză Euthyrox 3 săpt/ Thyrogen

TSH= 52 uUI/ml
Tg= 0.2 ng/ml
ATg= 120 UI/l
Scintigrafie WBS: pozitiv cervical, negativ în rest

Răspuns nedeterminat
Monitorizare prin Tg, ATg seriat – trendul în timp ATg
ecografie regiune cervicală anterioară, imagistică CT, RMN
TSH= 0.1 – 0.5 uUI/ml
Boală recurentă/ persistentă

Ecografie cervicală și FNAB

Majoritatea recurențelor regiune cervicală

Caracteristici ecografice noduli suspecți

Tg în FNA înainte
de reinterv. chir. !

Leenhardt et al, Eur Thyroid J, 2013

 RadioIodine ablation
• Peri-ablation staging should evaluate:

 i. lymph nodes in the neck;

 ii. lung metastases, for which computed tomography (without contrast) is far
more sensitive than chest x-ray;

 iii. bone metastases, especially in the presence of musculoskeletal symptoms,

employing the bone scan and/or bone x-rays (each appear to be about 60–
70% sensitive). PET imaging with F- 18-FDG or F-18 sodium fluoride for this
purpose may prove valuable.

 iv. Cerebral metastases (MRI) in order to avoid cerebral radiation damage

SNM guidelines for thyroid 131I treatment v 2.0, Silberstein et al, 2006
 Limitations with Thyroid Hormone
Withdrawal
•Short-term hypothyroidism •THW may not lead to
results in: increase of TSH levels in:
• Cognitive & physical • Persistent thyroid hormone
impairment production by large thyroid
• Decreased quality of life in remnants or functional
young and middle-aged metastases
patients • Elderly patients

• Hypothalamic or pituitary
•THW can impair: disease
• Cardiac, cognitive and • Long-term steroid therapy
neurological function
• Consequent health risks
especially in the elderly
Biondi B, et al. Biologics. 2009;3:9-13.
 Inovative therapies

• rhTSH

• Tyrozine kinase inhibitors

Randomized, controlled, prospective trial
Study Objectives
•Determine the ablation rates of rhTSH prepared patients compared to
those who underwent THW
•Evaluate the safety profile of rhTSH when used for thyroid remnant
ablation
•Compare the uptake and retention of RAI in the remnant thyroid tissue
as well as radiation exposure to the blood with rhTSH versus THW
 Better Quality of Life with rhTSH
Treatment (Quality of Life SF-36 Scores)

THW
After Surgery-Before Remnant
Mean Score Changes from

rhTSH
Ablation

General Health
Mental Health*
Functioning*

Functioning*

Bodily Pain
Emotional
Physical*
Physical

Social
Role

Role
* In the remnant ablation study, following THW, statistically significant negative changes were noted in five of
the eight QOL domains (physical functioning, role physical, vitality, social functioning and mental health).
The difference between treatment groups was statistically significant (P<0.05) favoring rhTSH over THW

Pacini F, et al. J Clin Endocrinol Metab. 2006;91:926-932.

Multicentric randomized phase III trial
 Objectives

Primary clinical endpoint

TAblation rate at 8+/-2 months, assessed by:

• Neck-US + stimulated Tg determination
• Whole-body scan (WBS) in patients with Tg antibodies

I-131 activity
Secondary endpoints
TSH stimulation
1.1 GBq 3.7 GBq
method • Short-term side effects
• Hypothyroidism
1.1 GBq 3.7 GBq
rhTSH • Quality of life
+ rhTSH + rhTSH

Thyroid
Hormone 1.1 GBq 3.7 GBq
Withdrawal + THW + THW Schlumberger M et al. NEJM 2012; 366:1663-1673
(THW)
 Adverse Events during Ablation
Table: Adverse events reported during ablation and collected up to one week after administration of
radioiodine (recorded at the time of the 7-day WBS), in each of the four trial groups.

P-values for the comparison of 1.1 GBq & rhTSH with each of the other groups are:
P=0.001 (3.7 GBq & THW)
P=0.09 (1.1 GBq & THW)
P=0.01 (3.7 GBq & rhTSH)
Adapted from Mallick U et al. NEJM 2012; 366:1674-1685
RadioIodine refractory DTC

Haugen et al,2015. Thyroid

 Case report
Sept 2007

• 50 years old woman

• Iodine deficient area
• Right thyroid nodule, 4.4/3.8/3.9 cm
• Rapid growth
• Dysphagia and inspiratory dyspnoea
• Weight loss, fatigue
 Imaging
• Thyroid US:
 iso-/hypoechoic solid nodule of 4,4/3,8/3,9 cm occupying the
inferior 2/3 of the right lobe, with hyperechoic halo,
 internal calcifications,
 increased perinodular and internal blood flow on Doppler
imaging, exerting mass effect on the trachea;
 bilateral laterocervical lymphadenopathy was also revealed.
 Evolution

• 150 ug LT4 Dec 2007- Jan 2008;

 TSH < 0.05 mU/L, Tgl > 1700 ng/ml (Lung?)

• 3 weeks off LT4

 TSH=43 mU/L
 I131 thyroid scan (350 Ci) -two pulmonary foci of
tracer uptake: on the left basis and right apex;
without cervical tracer activity.

• Treatment with 100 mCi I131 , then WBS –

anterior cervical, lung and right parietal skull
 Evolution
• 150 ug LT4 Feb 2008- restarted;
• September 2008: a sincopal episode (no seizures)

CT scan: described a polycyclic, relatively well circumscribed

tumor located in the right parieto-occipital cortex, adherent to the
skull, measuring 3,2/2,5/3,6 cm, with inhomogeneous structure,
which maintained after contrast administration
 Evolution

75 75
3000 70.2 75 80
2569 70
2500
1700 1799 50 60
2000 43 45.5 50
1500 1000 1000 1000
40
1000 30
1000 731
462 20
500 10
0.05 0.08
0 0
Jan. Feb. Sept. Oct. May May Dec Jun Feb
2008 2008 2008 2008 2009 2010 2010 2011 2012
Time
Thyroglobulin (ng/ml) TSH (mU/L)
 Brain Metastasis Pathology
TG TTF1

HE

Pathology found cerebral metastasis of FTC whereas immunohistochemistry for

thyreoglobulin, thyroid transcription factor 1 showed intense immunostaining,
confirming the diagnosis of metastatic DTC.
 Evolution WBS
October 2008- June 2011

AntiTg RAI ablation

Date TSH (mUI/L) Tg (ng/ml)
(UI/mL) dose (mCi)
WBS
02.2008 43 462 36.2 100 persistent pulmonary foci
10.2008 75 >300 100 persistent pulmonary foci
05.2009 70.2 >300 150 persistent pulmonary foci
11.2009 130 persistent pulmonary foci
05.2010 >75 >300 80 persistent pulmonary foci
12.2010 45.5 2569 <20 100 persistent pulmonary foci
06.2011 >75 1799 100 persistent pulmonary foci
Total 760 mCi

She was on permanent suppressive LT4, keeping TSH <0.1 mUI/L. LT4
treatment was withdrawn usually 6 weeks before each radioiodine therapy,
replaced with T3, the latter being withdrawn 2 weeks before RAI ablation. She
underwent six subsequent 131I therapy sessions, totalizing 760 mCi.
 Brain, Lung & Liver imaging

February 2011

Postoperative porencephaly with surrounding gliosis in the right parieto-occipital lobes,

but no other mass lesions or contrast enhancement, certifying the absence of cranial or
cerebral metastases. Pulmonary CT describes multiple metastatic nodules of 8-9 mm
spread in both lungs. Abdominal CT - multiple liver lesions between 9-20 mm.
 Genetic alterations in thyroid cancer

Genetic alteration PTC FTC ATC MTC

RET rearrangement 13-43%   

30-50%
RET mutation   
(MEN2:100)

NTRK1
5-13%   
rearrangement
BRAF mutation 29-69%  10-35% 
RAS mutation 0-21% 40-53% 20-60% 
PPAR-γ
 25-63%  
rearrangement
P53 mutation   67-88% 

Kondo T, et al.Nat Rev Cancer. 2006

Modificări genetice în cancerul tiroidian

Inițierea/ progresia cancerului prin

acumularea de alterări genetice și
epigenetice

Activarea căilor de semnalizare MAPK și

PI3K–AKT !

Mecanisme mutaționale:
• Mutații punctiforme: BRAF, RAS
• Rearanjamente cromozomiale:
RET/PTC, PAX8/PPARγ

Nikiforova, Nature Rev Endocrinology, 2011

 Molecular Genetics of Thyroid Cancer

Nikiforov Y.E., Nikiforova M.N., Nat Rev Endocrinol 2011

 Clasificator de expresie genomică mRNA
Afirma GEC – panel 167 gene
-Test tip Microarray
-Diferențiază noduli benigni de maligni
pe baza patternului de expresie mRNA
-Rezultat: benign (test negativ)
suspect (test pozitiv)

Bethesda III-V:
(Alexander, NEJM, 2012)
Sen 92%

Spe 52%
NPV 93%
PPV 47% → test de excludere
rule-out test
 Markeri moleculari de prognostic

Co-existența mutațiilor BRAFV600E și TERT promoter puternic

corelate cu trăsături clinico-patologice de risc inalt

Fiecare mutație - efect independent modest !

Generația a 3-a

ThyroSeq v3
NGS targetat
Panel 112 gene
Mutații, inserții/ deleții, fuziuni,
Variații nr copii, expresie genică

Bethesda III-IV (Steward DL,

JAMA Oncology 2018)

Sen 94%
Spe 82%
NPV 97%
PPV 66%
 Evită intervenția chirurgicală la 61% pacienți cu citologii
nedeterminate
 Raportează probabilitatea de cancer și riscul de recurență –
management individualizat
Molecular Markers and Thyroid Nodule Evaluation, Springer, 2017
131I resistant DTC
 Radioactive Iodine-Refractory Differentiated Thyroid
Cancer: Molecular Pathways and Drug Targets

Adapted from Dadu R, Cabanillas ME. Minerva Endocrinol 2012;37(4):335-56.

 Selected Agents in Thyroid Cancer and Some of
Their Kinase Targets — Are These “Actionable”?

TIE
Agent FGFR VEGFR PDGFR BRAF CKIT FLT3 CMET 2 EGFR RET

Sorafenib X X X X X
Sunitinib X X X X X
Cabozantinib X X X X X X
Vandetanib X X X
Lenvatinib X X X X X
Lenalidomide X
Axitinib X X
Motesanib X X X X
Pazopanib X X X
Vemurafenib X

Colevas AD et al. Proc ASCO 2014;Discussant.

 SELECT: Kaplan-Meier Estimate of PFS

From The New England Journal of Medicine, Martin Schlumberger, Makoto Tahara, Lori J Wirth, et al, Lenvatinib versus Placebo in
Radioiodine-Refractory Thyroid Cancer, 372, 621-30. Copyright © 2015 Massachusetts Medical Society. Reprinted with permission
from Massachusetts Medical Society.
Concluzii
 Cancerul tiroidian diferentiat

• Majoritatea- evolutie blanda

• Chirurgia tiroidei in centre de excelenta
• I131 – tratament dupa chirurgie / NCG
• Evaluare dinamica a riscului
• Rezistenta la I131 alte optiuni:
radioterapie externa, TKI
 Personalised Decision Making
Accomplish best expectances in the circumstances of the individual
patient.
a. Discussion in the multi-disciplinary team (MDT) meeting,

b. Consideration of risk factors for tumour-specific mortality and

recurrence that apply to the intervention. Within this group of
patients there is a spectrum of risk defined by clinical and
histopathological parameters. Greater the number of risk factors the
stronger is the case in favour of the intervention.

c. Consideration of the patient’s personal circumstances and values

 Concluzii

Profilaxia IDD
FNAB Programe
de screening
Epidemiologie
Tratament
medical si Detaliere
chirurgical histologica
Echografie
sensibila
Prof. Corin Badiu

Email: badicrin@yahoo.co.uk