Implementing Guidelines For Thyroid Nodules Hirotoshi Nakamura Kuma Hospital, Kobe, Japan

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


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


cystic legion

solid legion


palpa-tion thyroid

nodules


ultrasono-graphy


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



palpa-tion thyroid

nodules


ultrasono-graphy


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


cystic legion

solid legion


palpa-tion thyroid

nodules


ultrasono-graphy


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


cystic legion

solid legion


palpa-tion thyroid

nodules


ultrasono-graphy


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


cystic legion

solid legion


palpa-tion thyroid

nodules


ultrasono-graphy


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


cystic legion

solid legion


palpa-tion thyroid

nodules


ultrasono-graphy


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% 　


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%


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.



It may be recommended to repeat FNA after a couple of years for

affirmation of “benignancy”.

Should levothyroxine suppressive therapy be performed?



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


(Suspicious of follicular tumor)

probability of


probability of


follicular adenoma ?follicular carcinoma ?

④ ‘Indeterminate B’by FNAC (1)


(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


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


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!

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Implementing Guidelines For Thyroid Nodules Hirotoshi Nakamura Kuma Hospital, Kobe, Japan