Thyroid Nodules & Cancer
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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?