The document discusses thyroid nodules and guidelines for performing fine needle aspiration (FNA). It notes that while thyroid nodules are common, detected in up to 67% of ultrasound exams, only 5-15% of nodules are malignant. Sonographic features that increase the likelihood of malignancy include microcalcifications, irregular margins, hypoechogenicity, and intranodular flow. The document recommends FNA for nodules over 1 cm in size or if sonographic features suggest cancer risk. Strategic FNA based on risk factors aims to identify the minority of nodules that are cancer while avoiding unnecessary biopsies of predominantly benign nodules.
The Epidemic of Thyroid Nodules: Which Should Undergo Fine Needle Aspiration?
1. The Epidemic of Thyroid
Nodules: Which Should
Undergo Fine Needle
Aspiration?
Jill E Langer, MD
Associate Professor of Radiology
And Endocrinology
Co-Director of the Thyroid Nodule Clinic
Hospital of the University of Pennsylvania
DC Metro Radiological Society
2. Overview
• Review the histologic and sonographic
appearance of thyroid nodules
• Assess the ability of sonography to predict
that a nodule is malignant or to predict that
it is benign
• Review the recommendations for FNA of
thyroid nodules as developed by The
Society of Radiologists in US
Thyroid Consensus Committee*
*Frates MC et al, Radiology, December 2005
3. The Clinician Perspective
• About 5 % of the adult US
population will have a
nodule that is palpable on
physical exam of the neck
– The vast majority of palpable
nodules are over 1 cm
• The ATA recommendation
is to measure a serum TSH
( to exclude a functioning
nodule) The risk of cancer
• Perform an FNA in palpable nodules is
5 to 10%
4. The Clinical Perspective:
Cancer risk is increased if
• The nodule is hard and • Has a hereditary
fixed syndrome
– +/- rapid growth – MEN 1
• The patient presents – MEN 2 A and B
with hoarseness and/or – Familial Adult Polyposis
lymphadenopathy syndrome
– Cowden’s syndrome
• The patient is under 15
years old or over 60 • Familial papillary and
medullary cancers
• Has a history of prior
radiation exposure
5. Sonographic Thyroid Nodule
• “Nodule”- one or more
areas of the thyroid with a
different echotexture than
surrounding parenchyma
• Most nodules are not true
tumors but hyperplastic
regions of the thyroid
• Most thyroid nodules are
detected “incidentally”
5 mm non palpable nodule
6. Focal Thyroid Lesions on
Ultrasound
• Benign hyperplastic nodules (at least 70 to
80%)
• Benign thyroid adenoma (10 %)
• Thyroid carcinoma ( 5 to 12 %)
– Papillary carcinoma (70-80%)-includes mixed
papillary and follicular carcinoma
– Pure Follicular Carcinoma (10 to 15%)
– Medullary Carcinoma (5 to 10%)
– Anaplastic carcinoma (<1%)
• Focal area of thyroiditis (1 to 5%)
• Unusual lesions: Intrathyroidal parathyroid, true
cyst, metastatic disease
7. How common are thyroid nodules in
the United States on Ultrasound?
Ultrasound/autopsy
Palpation
Mazzaferri, N Engl J Med 1993
8. What nodules can’t we feel?
Ultrasound vs. Palpation
35
# Nodules found by US
30
25
42%
20
Nodules MISSED by palpation
15 50% Nodules FOUND by palpation
10
5 94%
0
< 1cm 1-2cm >2cm
Nodule size by US
Brander, J Clin Ultrasound 1992
9. Thyroid sonography should be performed in all
patients with one or more suspected thyroid
nodules.
USPSTF Recommendation B
Management guidelines for patients with thyroid nodules and differentiated
thyroid cancer, ATA Task Force, David Cooper, Chair, Thyroid, 2006
Thyroid ultrasound . . . is mandatory when a
nodule is discovered at palpation
European consensus for the management of patients with differentiated
thyroid carcinoma of the follicular epithelium, Eur J Endocrinol 2006
In all patients with palpable thyroid nodules or
MNG, US should be performed
AACE/AME guidelines for clinical practice for the diagnosis and
management of thyroid nodules, Endocrine Pract 2006
10. The “epidemic” of thyroid nodules
• Commonly detected on US (also CT, MR)
– 10 to 67% of US exams in asymptomatic adult
patients
– Additional non-palpable nodules are noted in
over 50% of patients with palpable nodules
• Risk of malignancy is the same for non-
palpable nodules as for palpable nodules
*Ross DS, J Clin Endo Metab, 2002 Ezzat, S et al, Arch Intern Med, 1994;
Tan GH et al, Ann Intern Med, 1997;Marqusee E et al, Ann Intern Med, 2000
11. What not biopsy all nodules
detected by sonography?
• Direct effects:
– Health care resources; up to 67% of the
population has nodules
– The vast majority of nodules are benign;
thyroid cancer is relatively uncommon ( 25,000
cases/yr in US)
– Many benign nodules would undergo FNA to
detect the few malignancies
Cooper DS et al, Thyroid, 2006
12. What not biopsy all nodules
detected by sonography?
• Direct effects:
– Most of the newly diagnosed thyroid cancers
are the smaller cancers
– Most thyroid cancer does not act in an
aggressive manner such that the overall
mortality from thyroid cancer has not changed
despite the marked increase in rate of US-
guided FNA
Cooper DS et al, Thyroid, 2006; Davies JAMA 2006
13. How common is thyroid cancer in the
United States?
0-1.0cm
1.1-2.0cm
2.1-5.0cm
Davies, JAMA 2006
>5.0cm
295:2164
14. Nodule size threshold for FNA
• Papillary thyroid microcarcinomas
– Occult or incidentally detected papillary thyroid
cancers under 10-15mm (WHO)
– PTMCs noted in 0.45 to 13% on autopsy in
USA
• Size threshold for most labs of 8 or 10 mm
for FNA, in the absence of metastatic
disease (LNs) or local invasion
1Machens A et al, Cancer 2005; 2 Ross DS, J Clin Endo Metab, 2002
16. What not biopsy all nodules
detected by sonography?
• Indirect effects:
• Patients with non-diagnostic and
“indeterminate” or follicular neoplasm
FNA results (20 to 35% of all FNAs) are
typically referred for surgery; over 80%
are benign nodules (follicular adenomas
and hyperplastic nodules)
Cooper DS et al, Thyroid, 2006
17. What thyroid nodules
detected “incidentally”
should undergo FNA??
“incidentally” means a non-
palpable nodule in a patient
without risk factors for
thyroid cancer
18. PET positive thyroid nodules
• PET positive nodules are noted on 0.1 to
4.3% of all PET scans
• A PET positive nodule has a 14 to 40 %
chance of being malignant
– Higher rates if microcarcinomas are included
• False positives include diffuse or patchy,
focal uptake in thyroiditis
Kind DL et al, Oto-Head and Neck Surgery, 2007
20. What is the risk of malignancy
for nodules detected by
sonography?
Are there sonographic
features that help stratify the
risk that a nodule is a
malignancy?
21. Features associated with
malignancy
• Lymphadenopathy/local invasion
• Micro -calcifications
• Coarse calcifications in a solid nodule
• Markedly hypoechoic echotexture
• Hypoechoic echotexture with solid consistency
• Irregular, infiltrating margins
• Intranodular flow in association with
hypoechogenicity/irregular margins/Ca++
• Absence of a halo
22. Invasion of capsule and metastatic
lymphadenopathy
CA
Sagittal view of left lobe Trv view of left lateral neck
11 mm Papillary Thyroid Carcinoma
23. Papillary thyroid cancer:
Lymph node metastases
IJV
CCA
Entirely cystic
Solid with Ca++
IJV
Mixed cystic and solid
CA
25. Localization of nodal mets in 119 pts
having thyroidectomy and bilateral
cervical neck dissection (61% LN+)
100 85% Contralateral node
Lymph nodes location (%)
90
80
involvement in 18%
63% of patients with
70
60 unilateral tumors
50
40
30
22%
15%
20
10
0
Level VI Level VI + Level VI Lateral
Lateral alone alone
Mirallie et al, World J Surg 1999
26. Lateral cervical lymph nodes
• Important to evaluate prior to surgery
• If sonographically suspicious LNs are
noted, perform FN of the LN
• If positive lateral nodes, a modified radical
neck LN dissection is performed at the
time of thyroidectomy
• Most common place for “recurrence” in
patients following thyroidectomy
27. Microcalcifications
• Multiple bright punctate (under 1 mm) echoes
without shadowing
• Most specific sign of malignancy (85-95%)
• Pitfall: colloid in a hyperplastic nodule-
reverberation artifact
Papillary carcinoma Hyperplastic nodule
28. Mixed population of calcifications
Multifocal calcified papillary
cancer
Mixed coarse and
microcalcifications
30. Coarse calcifications
• Coarse calcifications are common in
multinodular goiters secondary to dystrophic
calcifications in long standing benign nodules
• When present in a solitary nodule have
malignancy rates approaching 75%
Khoo ML, Arch Oto Head Neck Surg 2002
31. Coarse calcification: Medullary
thyroid cancer
• Typically a hypoechoic,
unencapsulated lesion
• Mean size 20 mm
• Up to 90% are calcified
– 53% coarse calcifications
– 42% micro-calcifications
Gorman B et al, Radiology, 1987
34. Calcifications
Microcalcifications Coarse calcifications in
(psammomatous) in papillary follicular thyroid cancer
thyroid cancer
35. Hypoechoic nodules
Benign hyperplastic nodule Papillary carcinoma
• Most papillary cancers are hypoechoic
• However, since benign nodules are much more
common, most hypoechoic nodules are benign
• The likelihood of a cancer increases if
hypoechogenicity is combined with all solid
consistency, calcifications and/or intranodular flow
37. Evaluation of the margins
• Irregular or infiltrating border is associated with
malignancy, varying from 35 to 86%
• High inter-observer variability
40. Surrounding halo
• Hypoechogenic thin rim surrounding the nodule
(thought to represent the compressed
perinodular vessels)
– present
– absent-suggestive of an infiltrative malignancy but
often lacking in hyperplastic nodules
• A thick, irregular halo is more suggestive of a
neoplasm (CAPSULE --follicular or Hurthle cell
carcinoma or adenoma; encapsulated papillary
cancer)1
1Cerbone et al, Hormone Res 1999
41. Thin halo Thick or irregular halo
sagittal
sagittal
Thin halo is compressed
blood vessels Follicular cancer
44. Intra-nodular flow
• In general there is a tendency toward increased flow
increasing the risk of malignancy
• The risk increases to about 30 or 40% in solid,
hypervascular nodules
• However, still over 50% of hypervascular nodules
are benign
Adenoma Hyperplastic nodule
52. US Prediction of Malignancy
# nodules Cancers Cancers
aspirated found missed
Size criteria
>10mm1 286/365 10 (63%) 6 (37%)
>10mm2 325/402 19 (61%) 12 (39%)
US criteria
Hypoechoic AND 139/365
solid1
Hypoechoic AND 125/402
irregular margins, increased vascularity, OR microCa2+2
1Leenhardt, J Clin Endocrinol Metab, 1999; 2Papini, J Clin Endocrinol Metab, 2002
53. US Prediction of Malignancy
# nodules Cancers Cancers
aspirated found missed
Size criteria
>10mm1 286/365 10 (63%) 6 (37%)
>10mm2 325/402 19 (61%) 12 (39%)
US criteria
Hypoechoic AND 139/365 13 (81%) 3 (19%)
solid1
Hypoechoic AND 125/402 27 (87%) 4 (13%)
irregular margins, increased vascularity, OR microCa2+2
1Leenhardt, J Clin Endocrinol Metab, 1999; 2Papini, J Clin Endocrinol Metab, 2002
54. The Sonographic of Thyroid
Nodules
Hypoechoic
Irreg margins
No halo
BENIGN ↑Vascularity BENIGN
MicroCa2+
BENIGN BENIGN
BENIGN BENIGN
55. Nodules which are likely benign
• Entirely cystic nodule
• Nearly entirely cystic nodule with no flow or
calcification in the solid part (under 2 cm)
• Honeycomb or spongiform nodule without
calcifications (under 2 cm)
• “Pseudonodules” in autoimmune thyroid disease
(chronic lymphocytic thyroiditis)
• Mixed cystic and solid nodules with a functioning
solid component ( any size)
57. Mixed cystic and solid nodules
• 30% of nodules have
cystic change
• More common in
benign nodules Hyperplastic nodule
• Up to 6% of papillary
cancers are
predominantly cystic
• Usually have other
features such as Ca++
or vascular flow
Cystic papillary cancer
58. Predominantly Cystic Nodules:
50% or greater cystic component
• up to 50% non-
diagnostic rate on FNA
• Target vascular areas for
FNA
• Indications for surgery:
large cyst size (over 3 or
3.5 cm), bloody aspirate,
recurrence after
repeated aspirations, h/o
previous irradiation
61. Hyperplastic nodule
• Area of the thyroid that is stimulated to undergo
follicular hyperplasia and accumulation of colloid
• Composed of follicles of various sizes and age,
colloid, macrophages
Hyperplastic
nodule
Normal
thyroid
62. “Spongiform” left nodule
Transverse Sagittal
trachea
Distinction between small calcifications and comet tail artifact from
colloid is easier with a lower frequency probe 1
1Ahuja J Clin Ultrasound 1996
64. “Pseudo-nodule”:Graves’ Disease
• may have focal areas of increased echotexture
• represents islands of follicular hyperplasia
superimposed on a lymphocytic infiltrate
65. SRU Consensus for
Sonographically Detected Nodules
Solitary nodule biopsy recommendations:
• Bx if microcalcifications if 10 mm or larger
• Bx if solid and/or coarse calcifications if 15
mm or larger
• Consider bx if mixed cystic/solid or cystic
with a mural nodule and over 20 mm
• Consider bx if substantial growth
• Apply clinical judgment!!!!
*Frates MC et al, Radiology, December 2005
66. US-guided FNA Technique
• 25 gauge, 1 ½ inch BD
needle
• 10 cc syringe
• Aseptic technique
• Capillary action rather
than aspiration
67. Non-diagnostic Rates of
US FNA and Palpation FNA
US -FNA P- FNA
Takashima, 1994 4% 19%
Carmeci, 1998 7% 16%
Danese, 1998 4% 9%
Hatada, 1998 17% 30%
70. False Negative Rates of
US FNA and Palpation FNA
US FNA P-FNA
Carmeci, 1998 0% 0.5%
Danese, 1998 0.6% 2.3%
False negative specimens due to sampling error
(cystic lesions or nodule was not sampled)
71. Indications for US-guided FNA
• Difficult to palpate nodule
• Predominantly cystic nodule
• Nodule with previous non-diagnostic
biopsy
• Nodule with “significant” interval growth
72. FNA vs. Core Biopsy
• The use of core biopsy does not improve
the non-diagnostic rate of thyroid biopsies
• Core does not aid in discrimination of
follicular adenoma vs. carcinoma
• Lower complication rate with FNA
• Inability to check for cellular adequacy with
core bx
• Core is preferable in some less common
circumstances: fibrotic tumors
Nishiyama RH et al, Surgery 1986; Silverman JF et al Diagn Cytopath 1986;
Pisani T et al Anticancer Res 2000
73. Cancer Rates for Solitary and
Multiple Thyroid Nodules
Definition FNA Ca rate
of nodularity technique Sol MNG
McCall I-123/histo palpation 17% 13%
Belfiore I-123 palpation 5% 5%
Cochand I-123/US US 13% 14%
Sachamechi I-123 palpation 8% 10%
Marqusee US US 7% 9%
Franklyn palpation palpation 6% 1%
74. Sonographic evaluation of a
multinodular gland
• Incidence of cancer in patients undergoing
FNA is 9.2-13%
– Independent of the number of nodules
detected by imaging exam
• Cancer is present in the “non-dominant
nodule” at least one third of patients
*Frates MC et al, Radiology, December 2005
75. Multinodular Gland
1. If a patient has multiple thyroid nodules
that require FNA based upon size criteria,
those with the most suspicious features on
US should be aspirated first
2. Nodules with similar sonographic features
may be considered to be of similar
histology
3. Nodules that are not biopsied can be
followed and considered for FNA if they
grow
76. Multinodular thyroid with one
sonographically suspicious nodule
Microcalcifications, Hypoechoic, Solid
77. Multinodular goiter = Multiple
nodular gland
Enlarged thyroid with multiple
sonographically similar
nodules with little or no
normal parenchyma Normal parenchyma
with more than one nodule
78. SRU Consensus Statement
Multiple nodule biopsy recommendations:
• Bx of one or more nodules using solitary
nodule guidelines
• May not need to perform bx if gland is
diffusely enlarged and replaced by multiple
sonographically similar nodules without
suspicious features (true multinodular
goiter)
79. American Thyroid Association
Guidelines
Multiple nodule biopsy recommendations:
• Perform FNA of those with the most
suspicious features on US first
• Follow the patient by US at 6 to 18 month
intervals
Solitary nodule biopsy recommendations:
• Biopsy if over 10 to 15 mm
• Consider bx if smaller and suspicious
Cooper DS et al, Thyroid, 2006
80. Role of I-123 scan
• Useful if patient has low TSH to determine
if hyperthyroidism is secondary to one or
more functioning nodules
• Useful if have nodule with Follicular
Cytology on FNA; 5% will function and
obviate the need for surgery
86. Why is there a grey zone?
• Small nodules may be just as likely to be
thyroid cancers as larger ones
- some are latent
- some are clinically relevant
• Cancer risk is the same for patients with
multiple or solitary thyroid nodules
Leenhardt J Clin Endocrinol Metab 1999; Papini J Clin Endocrinol Metab 2002;
Nam-Goong Clin Endocrinol 2003; Ito World J Surg 2004; Cappelli Clin Endocrinol
2005; Marqusee Ann Intern Med 2000; Frates J Clin Endocrinol Metab 2006
87. Recommendations:
What do we do at HUP TNC?
• FNA all PET positive nodules
• Incidental nodules detected by other
imaging should have sonographic
assessment to determine if malignant
features are present
88. We recommend FNA if
• micro Ca2+ ≥ 8mm
• hypoechoic (solid) ≥ 10mm
• solid ≥ 10-15mm*
• complex ≥15- 20mm*
• Multiple nodules:
– prioritize based upon above
– if multiple sonographically similar,
coalescent nodules without suspicious
US features, FNA largest
89. The exact role of ultrasound is still to be
defined … the traditional use of ultrasound to
separate cystic from solid lesions is probably
outdated.
Simeone, Daniels, Maloof, et al, Radiology 1982
Thanks to
Susan Mandel, MD
The exact role of ultrasound is still to be
defined. The use of ultrasound to simply
document thyroid nodules is not sufficient, we
must try to identify those nodules for which
FNA is indicated and those for which it is not!
90. Future Directions
Society of Radiologists in Ultrasound Part II
Prospective study at 10 Institutions
6000 nodules undergoing US-guided FNA
• Standardization of nodule description
• Stratified risk of malignancy
• Reporting of nodules in a BioRads-like
fashion, analogous to mammography