Failor-FRIDAY-NEW - FOR POSTING - American College of … · Treated with I131 therapy for a “toxic” nodule ... Bethesda I, Non‐diagnostic ... In a multinodular goiter, which

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Alan Failor, M.D.Clinical Professor of Medicine

Division of Metabolism, Endocrinology and NutritionUniversity of Washington

April 20, 2017

No disclosures to report

1. Appropriately evaluate thyroid nodules in adult patients

2. Interpret initial evaluation results to help guide further treatment or surveillance

3. Understand the options for molecular testing in thyroid nodules and the indications for testing.

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Ahn et al N Engl J Med 2014; 371

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Initiation of national screening program

Ahn et al N Engl J Med 2014; 371

US incidence 2011

~5% have palpable nodules in iodine replete areas

up to 2/3 have nodules by ultrasound screening

>50 % of people over age 50 have nodules by autopsy

6‐30 % rate of thyroid cancer in autopsy studies

~5‐8 % of thyroid nodules are malignant

41 yo man with thyroid nodule detected on CT

52 yo woman with cough and trouble swallowing

28 yo female nursing student with a thyroid nodule on exam

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• Suffered a neck injury while working as a security guard.

• CT scan detected a thyroid nodule

• No hoarseness, trouble swallowing, history of radiation exposure. No family history of thyroid disease.







• Healthy, mother of 3• 6‐9 month history of

chronic cough, sense of having to clear her throat, occasional trouble swallowing dry foods

• Barium swallow identified external compression from a mass at the level of the thyroid.







• Healthy, mother of 3• 6‐9 month history of

chronic cough, sense of having to clear her throat, occasional trouble swallowing dry foods

• Barium swallow identified external compression from a mass at the level of the thyroid.

• Otherwise healthy young woman with a history of hypothyroidism in her mother.

• Nodule was detected by a co‐student when learning to do thyroid exams.

• No hoarseness, trouble swallowing, history of radiation exposure.

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Check the thyroid stimulating hormone (TSH)

Kondo et al. 2006 Nat Rev Cancer




• TSH 1.4 IU/L (normal)• Free T4 1.0 ng/dL

(normal)

• TSH 0.02 IU/L (low)• Free T4 2.0 ng/dL (high)

• TSH 5.8 IU/L (high)• Free T4 0.4 ng/dL (low)

TSH reference range 0.4‐5.0 IU/LFree T4 reference range 0.6‐1.2 ng/dL


Ultrasound:• Right 4.2 cm solid and

cystic nodule with coarse calcifications.

• Left 2.4 cm solid, hyperechoic nodule without calcifications.


Muscle

Carotid

Trachea

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Ultrasound:• Right 4.2 cm solid and

cystic nodule with coarse calcifications.

• Left 2.4 cm solid, hyperechoic nodule without calcifications.

Muscle

Carotid

Trachea

Right 4.2 cm thyroid nodule

Left 2.4 cm thyroid nodule

Which nodule needs a fine needle aspiration?

Haugen et al. 2016 Thyroid; 26(1)

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History, PhysicalCheck TSH

Low TSH

Radio‐iodine Uptake and Scan

RAO

Right 4.2 cm thyroid nodule, low suspicionNo FNA indicated for a “hot” nodule

Left 2.4 cm thyroid nodule, low suspicionFNA indicated

Which nodule needs a fine needle aspiration?

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Left nodule FNA shows bland follicular cells, abundant colloid, consistent with a benign thyroid nodule

Diagnostic Category Description

I Nondiagnostic/Unsatisfactory

Must have a least 6 groups of follicle cells, at least 10 cells per group

II Benign Bland follicular cells in follicles, abundant colloid, macrophages ok

III Atypia of undeterminedsignificance (AUS)/ Follicular lesion of undetermined significance (FLUS)

AUS –not clearly benign, nor suspicious; may be poor fixationFLUS – highly cellular, overcrowding, nuclear overlap, scant colloid

IV Suspicious for follicular neoplasm

FNA cytology cannot distinguish adenoma from carcinoma –capsular or vascular invasion needed

V Suspicious for malignancy Nuclear features of carcinoma, but not enough cells for diagnosis

VI Malignant Enlarged and elongated nuclei, pseudoinclusions, nuclear grooves, powdery chromatin, psammomatous calcifications

Cibas and Ali 2009 Am J Clin Pathol;132

Diagnostic Category Risk of Malignancy

I Nondiagnostic/Unsatisfactory 1‐4%

II Benign 0‐3%

III Atypia of undetermined significance / Follicular lesion of undetermined significance (FLUS)

AUS 5‐15%FLUS 15‐30%

IV Suspicious for follicular neoplasm 15‐50%

V Suspicious for malignancy 60‐75%

VI Malignant 97‐99%


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Right thyroid nodule with benign FNA Treated with I131 therapy for a “toxic” nodule Cough and dysphagia resolved over 6 months Labs on follow‐up:

3 mo post‐I131: TSH 0.03 (low), free T4 1.2 (nl)6 mo post‐I131: TSH 3.4 (nl), free T4 0.8 (nl)9 mo post‐I131: TSH 2.5 (nl), free T4 0.9 (nl)

1 yr ultrasound – Rt thyroid nodule decreased in size, ltnodule unchangedRemains off thyroid hormone





(normal)





Low TSH


Hot nodule?

Treat for hyperthyroidism

If yesIf no

Neck ultrasound

Normal TSH

Nodule on US – Do

FNA if indicated

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Ultrasound: • Left 1.5 cm solid, ill‐

defined, hypoechoic thyroid nodule with calcifications and posterior shadowing.

• No other nodules• No abnormal lymph

nodes

Trachea

Muscle

Carotid

Normal thyroidtissue

Nodule

Acoustic shadowing

Does this nodule need an FNA?


FNA shows few follicular cells and blood Impression: Bethesda I, Non‐diagnostic

What should be done next for a non‐diagnostic, 1.5 cm, high suspicion thyroid nodule?

A. Repeat an ultrasound in 6‐12 months.B. Repeat FNA.C. Refer for diagnostic lobectomy?

Diagnostic Category Description

I Nondiagnostic/Unsatisfactory

Must have a least 6 groups of follicle cells, at least 10 cells per group

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Overall risk of malignancy low, 1‐4%

Guidelines recommend repeating an FNA

If repeat FNA non‐diagnostic, 6‐12 month surveillance by ultrasound• Repeat FNA if change in size or characteristics

• Consider diagnostic lobectomy in high suspicion nodules

Initial FNA non‐diagnosticRepeat FNA consistent with papillary thyroid cancer

Initial FNA non‐diagnosticRepeat FNA consistent with papillary thyroid cancer

Total thyroidectomy with ipsilateral central neck dissection• 1.6 cm papillary thyroid cancer, no extrathyoidal extension or vascular invasion

• 6/9 lymph nodes contained foci of thyroid cancer• Stage 1, T1bN1a

Treated with radioactive iodine (I131)Excellent response to treatment

• Undetectable tumor marker (thyroglobulin) and normal ultrasound at 1 year

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After surgery – levothyroxine 1.6‐1.8 mcg/kg Initial goal is TSH below normal rangeGoal will change based on response to therapy






(normal)




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Low TSH


Hot nodule?

Treat for hyperthyroidism

If yesIf no

Neck ultrasound

Normal TSH

Nodule on US – Do

FNA if indicated

High TSH

Evaluate and treat hypothyroidism


Ultrasound:• Left 1.8 cm complex

nodule, primarily cystic with central vascularity.

• No other nodules • Mildly prominent

cervical lymph nodes but symmetric bilaterally and without increased vascularity. No suspicious lymphadenopathy.

Muscle

Carotid

Trachea

Low suspicion nodule – FNA recommended if > 1.5 cm

Benign follicular cells Malignant follicular cells

Atypical follicular cells

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Diagnostic Category Risk of Malignancy

I Nondiagnostic/Unsatisfactory 1‐4%

II Benign 0‐3%

III Atypia of undetermined significance / Follicular lesion of undetermined significance (FLUS)

AUS 5‐15%FLUS 15‐30%

IV Suspicious for follicular neoplasm 15‐50%

V Suspicious for malignancy 60‐75%

VI Malignant 97‐99%


What should be done next for a low suspicion thyroid nodule with an indeterminate FNA result?

A. Repeat an ultrasound in 6‐12 months.B. Repeat FNA.C. Refer for diagnostic lobectomy?D. All of the above are reasonable options!

1. Repeat FNA – can yield benign results in up to 50% of cases

2. Diagnostic lobectomy for definitive diagnosis• High clinical suspicion

• Symptomatic nodule

• Patient preference

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DNA/RNA mutation analysis• ThyroSeq• ThyGenX

RNA gene expression• Afirma GEC

MicroRNA analysis• ThyraMir• Rosetta Reveal

Con: Low sensitivity (you can’t identify EVERY mutation)

Con: Cost effectiveness variable based on underlying risk of cancer and experience of cytology

Con: Accuracy of diagnosis still in early testing

Pro: High specificity (mutation present = cancer)

Pro: Pattern recognition to rule out cancer

Pro: Combination of pattern recognition and specific mutations identified

Nishino 2016 Cancer Cytopathology

FNA shows a follicular lesion of undetermined significance (FLUS) (risk of malignancy 15‐30%)

Repeat FNA 2 months later shows FLUS againAfirma Gene Expression Classifier (GEC) sent on repeat FNA – “suspicious”

Is this “likely” to be cancer?No – risk of cancer is still 15‐30%

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FNA shows a follicular lesion of undetermined significance (FLUS) (risk of malignancy 15‐30%)

Repeat FNA 2 months later shows FLUS againAfirma Gene Expression Classifier (GEC) sent on repeat FNA – “suspicious”

Patient underwent hemithyroidectomyPathology showed follicular adenoma1 month post‐operatively, TSH 12 (high)Levothyroxine initiated

What is the long‐term follow‐up for a thyroid nodule with a benign FNA result?

A. Begin levothyroxine therapy to suppress nodule growth.

B. Repeat a neck ultrasound in 12 months for surveillance.

C. Begin Thyroid Support Supplement

No role for thyroid suppression of nodules and increases risk of osteoporosis and atrial fibrillation

Adequate iodine intake (150 mcg/day) is important in deficient regions, but many supplements actually contain undocumented thyroid hormone

YES! Even benign nodules need to be followed at 1 year, then every 2‐5 years, for growth, symptoms or change in ultrasound characteristics

In a multinodular goiter, which nodule should undergo evaluation by fine‐needle aspiration?

A. Every nodule greater than 1 cm should have an FNA.

B. Only the largest nodule on each side should undergo FNA.

C. The highest risk nodules by ultrasound should undergo FNA, regardless of size.

FNA size criteria varies by ultrasound risk stratification, so not every nodule >1cm requires FNA

YES! FNA should be performed preferentially based on ultrasound risk pattern and respective size cut‐offs

This is correct only if all nodules have similar risk based on ultrasound characteristics

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Questions?

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Failor-FRIDAY-NEW - FOR POSTING - American College of … · Treated with I131 therapy for a “toxic” nodule ... Bethesda I, Non‐diagnostic ... In a multinodular goiter, which