implementing guidelines for thyroid nodules hirotoshi nakamura kuma hospital, kobe, japan
TRANSCRIPT
Implementing Guidelines For Thyroid Nodules
Hirotoshi NakamuraKuma Hospital, Kobe,
Japan
1 . Purpose of this guidelines
2 . Classification and incidence of the nodules 2 - 1 Histological classification 2 - 2 Incidence of the nodules
3 .Algorithm for approaching thyroid nodules
4 . Diagnostic approach4 - 1 Clinical evaluation4 - 2 Ultrasonography (US)
B-mode two-dimensional image Doppler mode US Elastography4 - 3 Fine Needle Aspiration4 - 4 CT 、 MR 、 PET 、 Scintigraphy 4 - 5 Laboratory tests & Molecular markers
Guidelines of Japan Thyroid Association for the management of thyroid nodules
5 . Management and long-term follow-up5 - 1 Management based on FNA diagnosis5 - 2 TSH suppressive therapy5 - 3 Conditions for surgical treatment5 - 4 Treatment for papillary carcinoma
6 . Topics6 - 1 Adenomatous goiter 6 - 2 Cystic lesions6 - 3 Functioning nodules6 - 4 Nodules accompanied with Graves’
disease or Hashimoto thyroiditis6 - 5 Thyroid nodules during pregnancy6 - 6 Thyroid nodules in childhood
7 . Clinical data about thyroid nodules in major medical institutes in Japan
8 . Major guidelines outside Japan
(publish in 2013)
(Task Force : 29 doctors in endocrinology, endocrine surgery, radiology, nuclear medicine, pathology)
method region gender
nodules cancer rate of cancer
n rate n rate n of nodulescancer/ nodules
palpation
Japanmale 88858 0.64% 128664 0.08% 569 14.4%
female 289973 1.64% 469070 0.18% 4752 11.3%
outside Japanmale 9080 0.76%
female 9990 3.10%
ultrasonography
Japanmale 16811 16.6% 37459 0.26% 2795 1.9%
female 21907 28.1% 38524 0.66% 6164 3.2%
outside Japanmale 45500 20.1%
female 40658 26.7%
*
**
* **Maruchi et al. 1971Noguchi et al. 1985Yamashita et al. 1993Ishikawa et al. 1995Miki et al. 1998Suehiro et al. 2006
Ohara et al. 1986Saitoet al. 1991Yanohara et al. 1991Nakamutsu et al. 1993Sou et al. 1994Takebe et al. 1994
Karamatsu et al. 1996Shimuraet al. 2001Nishi et al. 2008Miyazaki et al. 2011
(summarized by Shimura)
Incidence of thyroid nodules discovered by palpation or ultrasonography in Japan
one of six males & one of 3.5 females
images
evaluation for thyroid nodules
cystic legion solid legion
123I- or99mTc- scintigraphy
palpationthyroid nodules
history, physical exam ultrasonography TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
Fine Needle Aspiration Biopsy observation
Nondiagnostic Normal/Benign Indeterminate Suspicious for malignancy
Malignant
Suspicious for nodular lesion other than follicular tumor
AB
repeated FNA observation / US monitoring
surgical resection
Suspicious for follicular tumor
image
evaluation for thyroid nodules
cystic legion
solid legion
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
rapid growth of a masschildhood head and neck or total body irradiationfamily history of thyroid cancer (MTC, PTC) or thyroid cancer syndromes (MEN 2, Cowden synd, Carney complex, familial polyposis )
size, location, movement, consistency of the thyroid nodulescervical lymphadenopathyassociated local symptoms (pain, hoarseness, dysphagia, dysphonia, dyspnea)signs of hyper- or hypo-thyroidism
image
evaluation for thyroid nodules
cystic legion
solid legion
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
Measurement of serum TSH is necessary in every patient, since TSH is an independent risk factor for predicting malignancy.
If TSH is low and suppressed, a nodule may be hyperfunctioning.A hyperfunctioning nodule is usually benign.
The risk of malignancy rises in parallel with TSH, even within the normal range.Higher TSH was found to be associated with advanced-stage thyroid cancer.
cystic legion
solid legion
image
evaluation for thyroid nodules
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
TgAb and TPOAb are useful to identify the existence of Hashimoto thyroiditis which is known to co-associate with thyroid nodules at high frequency.
image
evaluation for thyroid nodules
cystic legion
solid legion
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
Serum Tg is not sensitive nor specific for the detection of thyroid cancer and not recommended to be measured in the initial evaluation. However, Tg measurement may be helpful in some occasions, since very high level of serum Tg has been reported in some cases of FTC.
image
evaluation for thyroid nodules
cystic legion
solid legion
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
We do not recommend serum calcitonin measurement in the initial evaluation, except for suspicious familial MTC or MEN type2. The prevalence of MTC in Japan is low and pentagastrin stimulation test is not available.
image
evaluation for thyroid nodules
cystic legion
solid legion
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
Thyroid ultrasonography should be performed in every patient with suspected thyroid nodule(s).It provides considerable anatomic detail and its findings can be used to select nodules for FNA biopsy.
image
evaluation for thyroid nodules
cystic legion
solid legion
123I- or Tc- scintigraphy
palpa-tion thyroid
nodules
history,physical exam
ultrasono-graphy
TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
Fine Needle Aspiration Biopsy
observation
US diagnostic findings suspicious findings of malignancy
shape irregular, taller than wide
sharpness of border poorly defined, irregular
intensity of echoes hypoechoic
internal structure inhomogenous
calcification microcalcifications
Halo incomplete or absent
Doppler flow patterns central vascularity
Although none of these features alone is sufficient to differentiate a malignant nodule from majority of benign nodules, a combination of these can succeed in pointing out a lesion of high risk for malignancy.
US criteria for FNA biopsy of solid nodules
solid nodule
≦5mm> 5mm≦10mm
strongly suspicious
> 10mm≦20mm
suspicious finding(s)
FNAB
> 20mm
FNAB
FNAB++ --
observation
observation observation
Japan Association of Breast and Thyroid Sonology
FNAB is recommended for solid, hypoechoic nodule in diameter larger than 10mm.
cystic nodules
no solid legion
20mm≧
observation
presence of solid legion
size >10 mm
irregular, vascular, microcalcification
(+)(-)
20mm<
FNAC observationFNAB FNAB
US criteria for FNA biopsy of cystic nodules
Japan Association of Breast and Thyroid Sonology
or
Fine Needle Aspiration Cytology
Nondiagnostic
Normal ・ Benign
Indeterminate
Suspicious for
malignancy
Malignant
1
2
3
4
5
Diagnostic sample should contain a minimum of 6 groupings of well-preserved thyroid epithelial cells, consisting of at least 10 cells per group.
FTC is difficult to be diagnosed by FNAC, since its diagnostic criteria include capsular invasion, vascular invasion and/or metastasis.
follicular adenoma/follicular carcinoma follicular tumor any other lesions with atypia of undetermined significance
Diagnostic
( The Papanicolaou society of cytopathology. 1996)
The Bethesda System for Reporting Thyroid Cytopathology
IV.Follicular neoplasm
V.Suspicious for malignancy
5-10 %
20-30 %
(risk of malignancy)
II.Benign
I.Nondiagnostic
VI.Malignant
50-75 % 100 %
(Baloch et al.DiagnCytopathol, 2008)(Ali &Cibas(eds) 2009 The Bethesda System for Reporting Thyroid Cytopathology. Springer, NY)
< 3 %
III.Follicular lesion/Atypiaof undetermined significance
Fine Needle Aspiration Cytology
Indeterminate A
Indeterminate B
Suspicious of follicular tumor
Suspicious of nodular lesion other than follicular tumor
favor benign
(borderline)
favor malignant
3A
3B
(our new modified classification)
Nondiagnostic
Normal ・ Benign
Indeterminate
Suspicious for
malignancy
Malignant
1
2
3
4
5
Diagnostic
How to manage thyroid nodules based on the results of FNA
cytology ?
① Nondiagnostic specimen by FNAC
causes for nondiagnosticspecimen cystic nodules that yield few or no follicular cells, benign or malignant sclerotic lesions, nodules with a thick or calcified capsule,hypervascularor necrotic lesions, sampling errors or faulty biopsy techniques
How to manage thyroid nodules based on the results of FNA cytology ?
Diagnostic specimen should contain a minimum of 6 groupings of well-preserved thyroid epithelial cells, consisting of at least 10 cells per group.
① ‘Nondiagnostic’ specimen by FNAC
malignant rate: about 10%
How to manage thyroid nodules based on the results of FNA cytology ?
repeat FNA with US guidanceRe-FNA with US guidance can yield a diagnostic specimen in 50-80%.
75% of solid nodules & 50% of cystic nodules (Alexander et al. JCEM 2002)
repeated nondiagnostic
consulting US findings
solid nodule(s) cystic lesion
surgical resection for histological diagnosis
close observation with US surveillance
② ‘benign’nodules by FNAC (1)
reported false negative rate : 1 ~ 11%
How to manage thyroid nodules based on the results of FNA cytology ?
mostly adenomatous nodule/ adenomatous goiternodular goiter or colloid nodule
(about ~3%?)
clinically follow up with repeated US assessment at 1~2 year intervals for several years
If the nodule show significant growth (>50% in
volume) or suspicious US changes, to repeat FNAB is recommended.
Repeated FNA increased the benign probability from 90% to 98%. (Oertel et al. Thyroid 2007)
Repeated FNA detected cancer in 13.2% initially diagnosed as benign nodules. (Gabales et al. Eur J Endocrinol 2009)
Repeated FNA detected cancer in 15/16 nodules initially diagnosed as benign. (Kwak et al. Eur Radiol 2009)
It would be advisable to repeate FNA up to three times.(Orlandi et al. Thyroid 2005)
Repeated FNA can increase the “benign” probability.
② ‘benign’nodules by FNAC (2)
How to manage thyroid nodules based on the results of FNA cytology ?
It may be recommended to repeat FNA after a couple of years for
affirmation of “benignancy”.
Should levothyroxine suppressive therapy be performed?
② ‘benign’nodules by FNAC (3)
How to manage thyroid nodules based on the results of FNA cytology ?
Since Japanese consume sufficient amount of iodine, routine T4 treatment to suppress TSH is not recommended.
Routine suppression therapy of benign thyroid nodules in iodine sufficient populations is not recommended. (ATA-GLRecommendation F)
Routine T4 treatment in patients with nodular thyroid disease is not recommended. T4 therapy may be considered in young patients who live in iodine-deficient areas. (AACE-GLGrade BLevel 3)
favor benign
borderline favor malig.
A-1 A-2 A-3
probability of
malignancy 5〜 15%
careful follow-up withUS
monitoring every 6~18 months
surgical resection for histological diagnosis
③ ‘Indeterminate A’by FNAC
How to manage thyroid nodules based on the results of FNA cytology ?
(Suspicious of follicular tumor)
probability of
malignancy 15〜 30%
probability of
malignancy 40〜 60%
follicular adenoma ?follicular carcinoma ?
④ ‘Indeterminate B’by FNAC (1)
How to manage thyroid nodules based on the results of FNA cytology ?
(Suspicious of nodular lesion other than follicular tumor)
• nodules with focal features suggestive of PTC in an otherwise benign-appearing sample
• Hashimoto thyroiditis / malignant lymphoma?
Repeated FNA at an appropriate interval is
recommended
A repeat FNA can result in a definitive diagnosis.Only about 20 – 25% of nodules are repeated AUS (Atypia of Undetermined Significance) in Bathesda System
(Yassa et al.Cancer2007)
⑤Suspicious for malignancy by FNAC
How to manage thyroid nodules based on the results of FNA cytology ?
probability of malignancy (PTC) > 80%
⑥ Malignancy by FNAC probability of malignancy (PTC) > 99%
very high probability of PTC
Surgical resectiontotal / near total thyroidectomylobectomy
images
evaluation for thyroid nodules
cystic legion solid legion
123I- or99mTc- scintigraphy
palpationthyroid nodules
history, physical exam ultrasono-graphy TSH, (FT4) ( TgAb, TPOAb, Tg, Ct )
Fine Needle Aspiration Biopsy observation
Nondiagnostic Normal/Benign Indeterminate Suspicious for malignancy
Malignant
Suspicious for nodular lesion other than follicular tumor
AB
repeated FNA observation / US monitoring
surgical resection
Suspicious for follicular tumor
Thank you for your attention!