Transcript Thyroid Nodules & Cancer

THYROID NODULES & CANCER
Ronen Gurfinkel, PGY4
February 8, 2012
Objectives


To review the presentation, investigation and
treatment of thyroid nodules
To review most recent clinical practice guidelines for
thyroid nodules
 American
Thyroid Association (ATA) Guidelines 2009
Background

Thyroid nodule
 Discrete
lesion within the thyroid gland
 Radiologically distinct from surrounding thyroid
parenchyma

Incidentaloma
 Nonpalpable
nodules detected on ultrasound or other
imaging study
 Have same risk of malignancy as palpable nodules of
same size
Epidemiology

Thyroid nodules are very common
 Palpable
nodules
 5%
of women
 1% of men
 Ultrasound
series
 19-67%
 Autopsy
series
 37-57%


The prevalence of nodules increases with age
Prevalence in women 1.5-1.7 times higher than men
Epidemiology
Prevalence of thyroid nodule by age
Age (years)
Women (%)
Men (%)
18-25
7.6
4.5
26-30
10.5
6.9
31-35
12.6
8.4
36-40
16.7
9.6
41-45
19.0
11.9
45-50
21.2
13.5
51-55
24.5
15.2
56-65
26.9
17.5
Thyroid Nodules

Why do we care?
 Cosmetic
Thyroid Nodules
Thyroid Nodules

Why do we care?
 Cosmetic
 Obstruction
Thyroid Nodules
Thyroid Nodules

Why do we care?
 Cosmetic
 Obstruction
 Thyroid
cancer
Thyroid Cancer


Thyroid cancer occurs in 5-15% of thyroid nodules, and rate
depends on risk factors
Types of thyroid cancer

Differentiated





Medullary
Anaplastic
Incidence of thyroid cancer is increasing



Papillary
Follicular
1973: 3.6 per 100,000
2009: 8.7 per 100,000
Rise in incidence mostly attributed to papillary thyroid
cancer and tumours < 2cm in size
Thyroid Cancer

Risk factors

Age
Thyroid nodules in children are twice as likely to be malignant
 In adults, higher rate of malignancy if age > 60


Sex


Malignancy rate 2x higher in men as compared to women (8%
versus 4%)
History of thyroid irradiation
~25% have thyroid nodules
 ~33% have of nodules are malignant
 No evidence that radiation-associated thyroid cancers are more
aggressive than other thyroid cancers

Thyroid Cancer

Risk factors
 Size
> 4cm
 Family history of multiple endocrine neoplasia type 2
(MEN2) or medullary thyroid cancer (MTC)
 Growing nodule
 Firm or hard nodule consistency
 Fixed nodule
 Cervical lymphadenopathy
 Persistent hoarseness, dysphonia, dysphagia, dyspnea
Thyroid Nodules - Causes
BENIGN (95%)
MALIGNANT (5%)
Multinodular (sporadic) goitre
Papillary carcinoma
Hashimoto’s (chronic lymphocytic thyroiditis)
Follicular carcinoma
Cysts: colloid, simple, or hemorrhagic
Minimally or widely invasive
Follicular adenomas
Hurthle-cell (oxyphilic) type
Macrofollicular adenomas
Medullary carcinoma
Microfollicular or cellular adenomas
Anaplastic carcinoma
Hurthle-cell (oxyphil-cell) adenomas
Macro- or microfollicular patterns
Primary thyroid lymphoma
Metastatic carcinoma (breast, renal cell,
lung, others)
Thyroid Cancer
Frequency of Thyroid Cancers
5%
1%
Papillary thyroid carcinoma
10%
Follicular thyroid carcinoma
Hurthle cell carcinoma
Medullary thyroid carcinoma
Anaplastic thyroid carcinoma
Lymphoma
75-80%
Sarcoma
Thyroid Cancer

Prognosis
 Papillary
 30-year
 Follicular
 30-year
thyroid carcinoma
survival 95%
thyroid carcinoma
survival 85%
 Medullary
 10-year
survival 65%
 Anaplastic
 5-year
thyroid carcinoma
thyroid carcinoma
survival 5%
 Median survival is 8.1 months
Presentation

How do patients with thyroid nodules present?
 Nodule
noted by patient
 Nodule noted on routine physical
 Nodule discovered incidentally on imaging
 Carotid
doppler U/S
 Neck CT
 18FDG-PET scan
 Etc
 Obstructive
symptoms
Evaluation

Who should be evaluated?
 Nodules
> 1cm
 Occasionally,
 Diffuse
nodules < 1cm
or focal uptake on 18FDG-PET scan
Evaluation




History & Physical
TSH
Ultrasound
Fine-needle aspiration (FNA)
Evaluation

Complete history
 Symptoms
of hyperthyroidism
 Risk factors for malignancy
 Childhood
head and neck irradiation
 Exposure to ionizing radiation from fallout in childhood or
adolescence
 Family history of thyroid carcinoma or thyroid cancer
syndrome in first-degree relative
 Rapid growth
 Hoarseness, dysphagia, stridor
Evaluation

Physical examination
 Thyroid
 Size




gland
of gland, goitre
Does this Patient Have a Goiter? – JAMA 1995
“Goiter ruled out”: normal size on palpation, not visible with neck
extended
“Goiter ruled in”: large goiter on palpation or lateral
prominence > 2 mm
“Inconclusive”: all other findings
 Nodule
 Adjacent
number, size, consistency, mobility
cervical lymph nodes
 Pemberton’s sign
Lateral Thyroid Prominence
A, Enlarged left lobe of the thyroid.
Jukić T , Kusić Z JCEM 2010;95:4175-4175
©2010 by Endocrine Society
Investigations

Laboratory tests
 Serum
TSH
 Serum thyroglobulin (Tg)
 Serum calcitonin
Investigations

Laboratory tests
 Serum
 If
TSH
low  radionuclide thyroid scan

Either 123I or 99mTc pertechnetate
 Further evaluation for possible FNA
 TSH level correlates to risk of thyroid cancer
 Otherwise
 Serum
thyroglobulin (Tg)
 Serum calcitonin
Thyroid Cancer and TSH
TSH (mU/L)
Prevalence of thyroid cancer (%)
< 0.4
2.8%
0.4 – 0.9
3.7%
1.0 – 1.7
8.4%
1.8 – 5.5
12.3%
> 5.5
29.7%
Investigations

Laboratory tests
 Serum
TSH
 Serum thyroglobulin (Tg)
 Can
be elevated in most thyroid diseases
 Insensitive and nonspecific test for thyroid cancer
 Not recommended as part of the initial evaluation
 Serum
calcitonin
Investigations

Laboratory tests
 Serum
TSH
 Serum thyroglobulin (Tg)
 Serum calcitonin
 Evaluated
in prospective, nonrandomized studies
 Screening with calcitonin may detect MTC at an earlier
stage (likely present if level > 100 pg/mL)
 But also detects C-cell hyperplasia and micromedullary
carcinoma (clinical significance uncertain)
 Cannot recommend either for or against routine
measurement
Investigations

Ultrasound
 Should
be performed in all patients with:
 Suspected
thyroid nodule
 Nodular goitre
 Nodule found on other imaging modality
Thyroid Cancer and Ultrasound
High Risk Features







Hypoechoic
Increased central
vascularity
Incomplete halo
Microcalcifications
Irregular borders
Taller than wide
(transverse view)
Suspicious lymph nodes
Low Risk Features





Hyperechoic
Peripheral vascularity
Complete Halo
Comet-tail
Large, coarse
calcifications
Central Vascularity
Microcalcifications
Irregular Borders
Taller Than Wide
Comet-tail Artifact
Investigations

Radionuclide scan
TSH low, 123I or 99mTc pertechnetate should be
obtained
 Hyperfunctioning (hot) nodules are rarely malignant
 If
Investigations

Fine-needle aspiration (FNA)

Most accurate and cost effective method for evaluating
thyroid nodules

Sensitivity 76-98%, specificity 71-100%
Prior to FNA, only 15% of resected nodules were malignant
 With FNA, malignancy rate of resected nodules > 50%
 False positive and non-diagnostic cytology rates lowered
with US guidance

Non-palpable
 Posterior location
 Predominantly cystic

Figure 7a. Parallel positioning of the fine-gauge needle for thyroid nodule biopsy.
Kim M J et al. Radiographics 2008;28:1869-1886
©2008 by Radiological Society of North America
Figure 7b. Parallel positioning of the fine-gauge needle for thyroid nodule biopsy.
Kim M J et al. Radiographics 2008;28:1869-1886
©2008 by Radiological Society of North America
Figure 8a. Perpendicular positioning of the fine-gauge needle for thyroid nodule biopsy.
Kim M J et al. Radiographics 2008;28:1869-1886
©2008 by Radiological Society of North America
Figure 8b. Perpendicular positioning of the fine-gauge needle for thyroid nodule biopsy.
Kim M J et al. Radiographics 2008;28:1869-1886
©2008 by Radiological Society of North America
Figure 9a. Aspiration (a) and nonaspiration (b) techniques for needle biopsy of thyroid
nodules.
Kim M J et al. Radiographics 2008;28:1869-1886
©2008 by Radiological Society of North America
Figure 9b. Aspiration (a) and nonaspiration (b) techniques for needle biopsy of thyroid
nodules.
Kim M J et al. Radiographics 2008;28:1869-1886
©2008 by Radiological Society of North America
Investigations

Fine-needle aspiration
 Complications
 Local
pain
 Bleeding or hematoma
 Infection
 Vasovagal reaction
Fine-needle Aspiration
Fine-needle Aspiration


Purely cystic nodule
Any size  No FNA
Abnormal cervical lymph nodes
Any size  FNA
Fine-needle Aspiration


High-risk history
> 5mm  FNA
Microcalcifications
> 1cm  FNA
Fine-needle Aspiration

Solid nodule
 Hypoechoic
>1cm  FNA
 Isoechoic or hyperechoic
>1-1.5cm  FNA
Fine-needle Aspiration

Mixed cystic-solid
 Suspicious
ultrasound features
> 1.5-2cm  FNA
 No suspicious sonographic features
> 2cm  FNA

Spongiform nodule
> 2cm  FNA
Investigations
Pathology

FNA results
 Historically,
FNA cytopathology reports were quite
variable
 In 2007, Bethesda System for Reporting Thyroid
Cytopathology was created
 Recommended
the use of 6 general categories
 Each category associated with a risk of malignancy and
linked to a management recommendation
Pathology

Bethesda System Categories
 Nondiagnostic
or Unsatisfactory
 Benign
 Atypia
of Undetermined Significance (AUS) or Follicular
Lesion of Undetermined Significance (FLUS)
 Follicular Neoplasm or Suspicious for a Follicular
Neoplasm
 Suspicious for Malignancy
 Malignant
Pathology

Bethesda System Categories
 Sample
is adequate if:
 Not
obscured (blood, air drying, thick smears, etc)
 At least 6 groups of benign follicular cells
 Each group composed of at least 10 cells
 Above criteria present in at least 2 aspirates
 Exceptions:



Abundant colloid  benign
Any atypia
Specific diagnosis can be made (eg lymphocytic thyroiditis)
Pathology

Bethesda System Categories
 Nondiagnostic
 Cyst

or Unsatisfactory
fluid only
Sonographic correlation required to determine malignancy risk
 Virtually
acellular specimen
 Other


Obscurring blood
Cloting artifact
Pathology

Bethesda System Categories
 Benign
 Consistent


with a benign follicular nodule
Hyperplastic/Adenomatoid nodule
Colloid nodule
 Consistent
with lymphocytic (Hashimoto’s) thyroiditis in the
proper clinical context
 Consistent with granulomatous (subacute) thyroiditis
 Other
Pathology

Bethesda System Categories
 Atypia
of Undetermined Significance (AUS) or Follicular
Lesion of Undetermined Significance (FLUS)
 For
FNAs that do not easily fit into one of the other
categories
 e.g. prominent population of microfollicles, but not sufficient
for diagnosis of follicular neoplasm
Pathology

Bethesda System Categories
 Follicular
Neoplasm or Suspicious for a Follicular
Neoplasm
 Follicular
carcinomas and adenomas have similar
cytomorphologic features
 Specify if Hürthle neoplasm

Considered variant of follicular adenoma or carcinoma by WHO
Pathology

Bethesda System Categories
 Suspicious
for Malignancy
 Used
if a malignant diagnosis cannot be made with
certainty
 Suspicious



for papillary carcinoma
Only 1 or 2 characteristics of papillary carcinoma
Abnormalities are focal
Sample is sparsely cellular
 Suspicious
for medullary carcinoma
 Suspicious for metastatic carcinoma
 Suspicious for lymphoma
Pathology

Bethesda System Categories
 Malignant
 Papillary
thyroid carcinoma
 Poorly differentiated carcinoma
 Medullary thyroid carcinoma
 Undifferentiated (anaplastic) carcinoma
 Squamous cell carcinoma
 Carcinoma with mixed features (specify)
 Metastatic carcinoma
 Non-Hodgkin lymphoma
 Other
Pathology
Diagnostic Category
Nondiagnostic or Unsatisfactory
Benign
Atypia of Undetermined Significance
or Follicular Lesion of Undetermined
Significance
Follicular Neoplasm or Suspicious for a
Follicular Neoplasm
Suspicious for Malignancy
Malignant
% of FNAs
2-20
60-70
3-6
5-11
1-7
3-7
Pathology
Management
Management

Nondiagnostic or Unsatisfactory
 Repeat
FNA with ultrasound guidance
 Satisfactory
specimen in 75% of solid nodules
 Satisfactory specimen in 50% of cystic nodules
 On-site
cytologic evaluation may improve yield
 7% of nodules continue to be nondiagnostic (and may
still be malignant)
 Close
observation or surgery (particularly if nodule is solid)
is recommended
Management

Malignant or Suspicious for malignancy
 Surgery
 Malignant:
total thyroidectomy
 Suspicious for malignancy: total thyroidectomy or lobectomy
Management

Follicular Neoplasm (not Hürthle cell)
 Malignancy
risk 15-30%
 If TSH is in low-normal range, can consider 123I thyroid
scan
 If no autonomously functioning nodule seen, lobectomy
or total thyroidectomy should be considered

Hürthle cell Neoplasm
 No
need for 123I thyroid scan
 Lobectomy
factors)
or total thyroidectomy (depending on other risk
Management

Benign
 Immediate
diagnostic studies or treatment are not
routinely required
 Follow-up is required
 Low,
but not negligible false-negative rate (up to 5%),
especially with larger nodules (greater than 4cm)
 Repeat US recommended at 6-18 months after initial FNA


If nodule is stable in size (<50% increase in volume or <20%
increase in 2 dimensions), can increase interval of follow-up
If evidence of nodule growth present (>50% increase in volume
or >20% increase in 2 dimensions with minimal increase of 2mm)
then FNA should be repeated
Management

AUS or FLUS
 Malignancy
risk 5-15%
 Diagnostic accuracy may be improved by considering
clinical risk factors
 The use of 18FDG-PET is not recommended for or
against to improve diagnostic accuracy
 In
one study, sensitivity 57%, specificity 50%
 Can
consider molecular markers to help guide
management
 e.g.
BRAF, RAS, RET/PTC, Pax8-PPAR-gamma, or galectin-3
Management

Molecular markers

Haugen et al (International Thyroid Congress, 2010)
Developed a molecular classifier using approximately 200 genes
 Tested classifier to 66 initially indeterminate FNA samples that
have underwent surgery and pathology review
 Sensitivity 95%, specificity 63%, NPV 96%
 Conclude that this can be used to reduce number of unnecessary
surgeries


Li et al (JCEM 2011)
Created decision making model and used on a hypothetical group
of adult patients
 Showed that using molecular test avoided ¾ of surgeries in
indeterminate group and lowered cost of health care

Multiple Nodules




Solitary nodules have higher malignancy risk than
nonsolitary nodules
Patients with multiple nodules have same risk of
malignancy as those with solitary nodules
Should aspirate nodules > 1cm with suspicious
sonographic appearance
If TSH is low or low-normal, can use thyroid
scintigraphy to direct FNA to iso- or nonfunctioning
nodules
Questions?