Work Up & Evaluation of Thyroid Nodules In 2013: State of ... Work Up & Evaluation of Thyroid Nodules

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  • Work Up & Evaluation of Thyroid Nodules In 2013: State of The Art

    Todd McMullen MD PhD FRCSC FACS Endocrine Surgeon

    Divisions of General Surgery and Oncology Director, Division of Surgical Oncology

    BC Surgical Oncology Network, Fall Update

  • Learning Objectives

    • Defining the incidence of thyroid nodules

    • Risk factors for malignancy

    • The role of U/S in predicting malignancy

    • The role of FNA and cytology in predicting malignancy

    • Molecular testing in thyroid disease

    • No disclosures

  • Overall Prevalence of Thyroid Cancer

    SEER Database

  • Subtypes of Thyroid Cancer

    SEER Database

  • A Sea of Nodules

    Nieuwenhuis et al., 2013; Guth et al., 2009; Sosa et al., 2013

    • 8806 patients with 11618 thyroid ultrasounds - 56% had thyroid nodules (2013)

    • German Papillon study - 90 000 people using 7.5 MHz scanners revealed thyroid nodules in 33% of the population (2005)

    • Using a 13 MHz scanner – 650 patients, 68% had nodules (2009)

    • 1968 Vander et al., incidence of thyroid nodules about 5% of population

    In the US Surgical Community (2006-2011)

    • Use of thyroid FNA more than doubled (16% annual growth)

    • Number of thyroid operations increased by 31%.

    • Total thyroidectomies increased by 12%/year

  • 6 Schonfeld et al., 2012; Nieuwenhuis et al., 2013; Carpi et al., 2012; Septer S, et al., 2013

    • Patients with PTEN mutations and hamartoma tumour syndrome have a 30+% risk of thyroid cancer - females>males

    • Family history is also an important factor predicting risk and severity

    • Radiation is a clear risk: Bhatia et al. estimated the cumulative incidence of thyroid cancer to be 4.4% at 30 years after childhood treatment for Hodgkin lymphoma.

    Special Patients

    • Thyroid cancer is 4X more likely in patients with familial adenopolyposis (FAP) compared to general population

  • What is/is not Linked to Malignancy

    Smoking (HR= 0.5)

    Obesity (HR = 1.7)

    Benign disease (F, HR = 2.5; M, HR = 4.5)

    Age

    Reproductive status

    Diet

    Thyroiditis

    Meinhold et al. 2010; Agate et al. 2012; Kabat et al. 2012; Janovic et al. 2013

  • Radiation-Induced Risk of Thyroid Cancer

    Risk is strongest for infants Dental X-rays - the link is weak for normal exposure (1/year)

  • Familial Risk of Thyroid Cancer

    • 15 families with 2 or more thyroid cancers followed prospectively; 70 yo 90% had nodules, at 20 yo 20% had nodules.

    • In FNMTC, first-degree relatives 10 years or older, including the generation anterior to the index case, should have thyroid screening

    • Compared to sporadic cancers, familial non-medullary thryoid cancer (FNMTC): - tends to present at a younger age - multicentricity (48% vs. 22%, p=0.01) - lymph nodes (22% vs. 11%, p=0.02) - local invasion (5.4% vs. 0.6%, p=0.007) - higher recurrence rate (24% vs. 12%, p=0.03)

    Meinhold et al., 2010; Mazeh et al., 2013; Kabat et al., 2012; Janovic et al., 2013;Sadowski 2013

  • From: Establishing a Familial Basis for Papillary Thyroid Carcinoma Using the Utah Population Database

    JAMA Otolaryngol Head Neck Surg. 2013;():-. doi:10.1001/jamaoto.2013.4987

    Risk of Papillary Thyroid Carcinoma in Relatives of Probands

    Figure Legend:

  • Other triggers for investigation

    • FDG-avid lesions on PET scans present 2-5X risk compared to non-avid lesions (meta-analysis 34 studies >200 000 patients) – Pooled risk of malignancy was 36% – Depends also on intensity – increasing SUV more likely – Much more likely if focal uptake

    • Uptake on MIBG and octreotide scans also indicate increased risk

    • Voice change is sensitive for invasive malignancy (Present in 70% of invasive cases). Approximately 3-6% of all cancer represent disease with nerve/tracheal involvement

    Treglia et al., 2013; Randolph et al., 2006;

  • Ultrasound – Do it Yourself

    Bastin et al., J Med Imag and Rad Onc (2009)

    Can ultrasound identify a patient at risk of thyroid cancer?

  • Ultrasound – The Details

    Smith-Bindman R, et al., JAMA Intern Med. 2013

    9000 patients over 5 years

    Size: 2+cm nodule 3X more likely to be malignant than nodule

  • Ultrasound – The Reality

    Number of Reported Features

    Number of Cases N=336

    Percentage of all cases

    0 141 1 103 2 66 3 19 4 2 5 2 6 3

  • Ultrasound Feature Frequency of Reporting (%)

    Confirmed Cases of Cancer (%)

    P value

    Microcalcifications 24 77 0.002 Solid 40 48 0.008

    Irregular margin 14 37 0.002 Hypoechoic 36 24 0.18

    Intranodular vascularity 11 33 0.97 Absent halo sign 5 20 0.59

    Ultrasound – The Reality

  • Fine Needle Aspirate (FNA)

    U/S guided biopsy – 5X less likely to miss than by palpation – May consider thyroid scan first if TSH suppressed – Do not biopsy more than 2 nodules – Nodules over 4 cm may need surgery due to FN rate*

    U/S guided biopsy – the role of the pathologist – 2% of patients evaluated by a pathologist had a non-diagnostic result – 16% of patients had non-diagnostic result if lacking on-site evaluation – 40%+ non-diagnostic rate if cystic lesion – Cytopathologic evaluation of FNA specimens is cost-effective

    Simsek et al. 2013; Nasuti et al., 2002

  • Biopsy Technique: To Aspirate or Not?

    • A combination of capillary and aspiration samplings achieves better diagnostic yields.

    • For cystic nodules - second, after aspiration of the cystic contents of the nodule and exchange of the fluid- filled syringe, US-FNA of the small solid portion of the nodule was performed.

    • Non-diagnostic readings for the core needle biopsies were lower than repeat FNAs (1.6% v 28.1%, p

  • Who Gets a Biopsy?

    • Biopsy 0 to 1.5 cm.

    • May or may not use thyroid scanning.

    • Increasing nodule size impacts cancer risk – increasing risk up to 2.0 cm but larger nodules have increased risk of follicular carcinomas

    • The false negative rate of “ benign”nodules >4 cm is 10% (no suspicious U/S features).

    Kamran SC et al., 2013; Wharry LI et al., 2013

  • Bethesda Criteria

    Ali, S. Acta cytologica (2010)

    Currently in Edmonton – 75% of reports

  • • The new AUS/FLUS category was used more often than recommended (14%) with a higher than expected rate of malignancy (20%). (Broome JT et al. 2011)

    • The BSRTC resulted in more frequent repeat FNAB, fewer thyroidectomies. (Chen JC et al. 2012 )

    • The fraction of cases suspicious for follicular neoplasm increased from 6.1 to 7.4% (p = 0.0002); surgical follow-up rate increased from 55 to 61% (p < 0.00001), and the histological malignancy rate increased from 22 to 28% (p = 0.03) (Boonaarunnate et al. 2013)

    • Recommendations for repeat FNA (AUS/FLUS) results are cost-effective. (Heller M et al. 2012)

    Bethesda Criteria: Since 2008

  • A Second Biopsy or a Second Pathologist?

    Olson MT, JCEM 2013

    • The BSRTC classification changed 32% of the time

    • Indeterminate rate went down 38% to 28% (P < .000001)

    • Specimens with low cellularity and Hashimoto’s thyroiditis most likely to change.

    3885 thyroid cytological samples reviewed over 4 years

  • Molecular Testing in Thyroid Investigations

    Nikiforov YE et al. 2012; Alexander et al., 2012

    • Molecular and IHC markers of malignancy are actively pursued for cytologic testing

    • >3000 articles examining cancer “signatures”

    • > 25 randomized trials examining mRNA and IHC markers of cancer

    • FNA is suitable for IHC and mRNA analysis (all you need is ng of tissue)

    •Best studied / accepted - IHC marker for galectin 3 may predict PTC (Bartolazzi., 2008) - BRAF, RAS and RET/PTC mutations - Veracyte mRNA analysis - used to define low risk nodules

    Presenter Presentation Notes Proposed clinical algorithm for management of patients with cytologically indeterminate thyroid FNA applying the results of mutational analysis.

  • Molecular Testing in Thyroid Investigations.

    Nikiforov YE et al. 2011

    N=1056

    Presenter Presentation Notes Proposed clinical algorithm for management of patients with cytologically indeterminate thyroid FNA applying the results of mutational analysis.

  • ©2011 by Endocrine Society

    Technology Makes Life Better?

    Presenter Presentation Notes Proposed clinical algorithm for management of patients with cytologically indeterminate thyroid FNA applying the results of mutational analysis.

  • Technology Makes Life Better?

    John Hopkins School of Public Health

    Veracyte

    Testing benign nodules

    Presenter Presentation Notes Proposed clinical algorithm for management of patients with cytologically indeterminate thyroid FNA applying the results of mutational analysis.

  • If it is benign

    Oertel YC et al., 2007; Gharib et al. 2010

    • No strong evidence for any follow-up regime

    • Latest guidelines and cohort studies: - If see