Approach to Thyroid Nodule

1. APPROACH TO THYROID
NODULE
D R L AVA N YA B O N N Y
S R , D E P T O F E N D O C R I N O L O G Y
S T J O H N S M E D I C A L C O L L E G E
B A N G A L O R E

2. DEFINITION
• A thyroid nodule is a discrete lesion within the thyroid gland that is radiologically
distinct from the surrounding thyroid parenchyma.
• palpable lesions not corresponding to distinct radiologic abnormalities - do not meet
the strict definition for thyroid nodules.
• incidentally discovered nodules or ‘‘incidentalomas” - Nonpalpable nodules detected
on US or other imaging

3. EPIDEMIOLOGY
• Linear increase in the prevalence of thyroid nodules from near zero at the age of 15
years, to 50% by about age 60 to 65 years
• higher prevalence of thyroid nodules in countries affected by moderate or severe
iodine deficiency

5. CLINICAL EVALUATION
• A thyroid nodule is more likely to be a thyroid carcinoma in patients <20 years or >65
years of age than in those in between
• But overall most patients with thyroid carcinoma are in this middle age group
• Benign thyroid nodules - four to five times more common in women than men
• thyroid carcinomas - two to three times more common in women

6. CLINICAL EVALUATION
• FAMILY HISTORY
• Family history is relevant
• 5%–10% of DTCs have a familial occurrence.
• In most of the pedigrees only two members are affected
• There is controversy on whether two family members are sufficient to define a real
familial disease rather than a fortuitous association

7. CLINICAL EVALUATION
• FAMILY HISTORY
• probability estimates by Charkes - when only two first-degree family members are
affected, the probability that the disease is sporadic is 62%.
• This probability decreases when the number of affected family members is three or
more.
• In contrast, Capezzone et al demonstrated that even when only two family members
are affected, the disease displays ‘‘genetic anticipation’’

9. CLINICAL EVALUATION
• CAUSES OF PAIN
• Sudden growth of a nodule with pain, usually indicates hemorrhage into a cystic
nodule - occurs in both benign and malignant nodules.
• Subacute thyroiditis may present with unilateral thyroid enlargement and pain,
mimicking a thyroid nodule

10. CLINICAL EVALUATION
• Large thyroid nodules distort structures in the neck or upper mediastinum
• causes shortness of breath or cough from tracheal compression
• difficulty swallowing from esophageal compression.
• The presence of these symptoms increase likelihood of malignancy, but most
carcinomas are asymptomatic

11. CLINICAL EVALUATION
• non-tender cervical adenopathy – concern of malignancy
• patient's risk of malignancy is independent of the number of nodules, as well as
whether the nodule is palpable

12. CLINICAL EVALUATION
• Radiation therapy to the head, neck, and upper chest increases the risk of both benign
thyroid nodules and thyroid carcinoma
• Predominantly papillary cancers occur a median of 13 to 15 years after initial therapy
• can be diagnosed up to three decades after radiation exposure

13. LAB EVALUATION
• Serum thyrotropin measurement
• With the discovery of a thyroid nodule >1 cm in any diameter, TSH should be obtained
• If the serum TSH is subnormal, a radionuclide thyroid scan should be obtained

14. LAB EVALUATION
• Serum thyroglobulin measurement
• Routine measurement of serum thyroglobulin (Tg) for initial evaluation of thyroid
nodules is not recommended.
• can be elevated in most thyroid diseases
• insensitive and nonspecific test for thyroid cancer

15. LAB EVALUATION
• Serum Calcitonin
• may be considered in patients in whom an elevated calcitonin may change the
diagnostic or surgical approach
• Eg : Patients considered for less than total thyroidectomy, patients with suspicious
cytology not consistent with PTC
• If the unstimulated serum calcitonin is > 50–100 pg/mL, a diagnosis of MTC is common

16. IMAGING
• Radionuclide thyroid scan
• Nodules may be hyperfunctioning (‘‘hot,’’ i.e., tracer uptake is greater than the
surrounding normal thyroid)
• isofunctioning (‘‘warm,’’ i.e., tracer uptake is equal to the surrounding thyroid), or
• nonfunctioning (‘‘cold,’’ i.e., has uptake less than the surrounding thyroid tissue)

17. IMAGING
• Radionuclide thyroid scan
• hyperfunctioning nodules rarely harbor malignancy - if one is found that corresponds
to the nodule in question, no cytologic evaluation is necessary
• Higher TSH levels, even within the upper part of the reference range - increased risk of
malignancy in a thyroid nodule, as well as more advanced stage thyroid cancer

18. IMAGING
• Radionuclide thyroid scan
• Only about 5% to 10% of nodules are autonomously functioning, nearly all of which
are adenomas
• Since more than 90% of nodules do not produce thyroid hormone ("non-functioning"),
it is not cost-effective to perform radionuclide imaging as a screening test for all
patients with thyroid nodules.

19. IMAGING
• Radionuclide thyroid scan
• scintigraphy, with either 1231 or Tc 99 pertechnetate, is limited to those patients who
have subnormal TSH where the diagnostic possibilities include:
• Functioning nodule(s), a combination of functioning and non-functioning nodules,
• or Graves' disease with non-functioning nodules.

20. IMAGING
• Radionuclide thyroid scan
• functioning nodules may be composed of both solid and cystic areas.
• ultrasound imaging is required to confirm that scintigraphically non-functioning areas
of an otherwise hyperfunctioning nodule correspond to cystic areas
• If not, FNA is required to target a solid non-functioning area

21. IMAGING
• Radionuclide thyroid scan
• Both functioning and non-functioning nodules may be present within a gland
• sonographic correlation may be necessary to identify non-functioning nodules within
suppressed extranodular parenchyma, for which FNA is indicated on the basis of
sonographic features

22. IMAGING
• Fluorodeoxyglucose positron emission tomography scan
• Incidental 18FDG-PET uptake in the thyroid gland - either focal or diffuse.
• Focal uptake incidentally detected in 1%–2% of patients
• additional 2% of patients demonstrate diffuse thyroid uptake

23. IMAGING
• Fluorodeoxyglucose positron emission tomography scan
• Focal 18FDG-PET uptake within a sonographically confirmed thyroid nodule conveys
an increased risk of thyroid cancer, and FNA is recommended for those nodules >1 cm
• positive nodules <1 cm that do not meet FNA criteria can be monitored similarly to
thyroid nodules with high-risk sonographic patterns that do not meet FNA criteria

24. IMAGING
• Fluorodeoxyglucose positron emission tomography scan
• recent meta-analysis - one in three (35%) positive thyroid nodules were cancerous with
higher mean maximum standardized uptake value in malignant compared to benign
nodules
• Diffuse thyroid uptake - often represents benign disease corresponding to
inflammatory uptake in Hashimoto’s or other diffuse thyroidal illness.

25. IMAGING
• Ultrasound elastography (USE)
• Elastography is a measurement of tissue stiffness
• USE can only be effectively applied to solid nodules, thus excluding its utility for cystic
or partially cystic nodules
• index nodule must not overlap with other nodules in the anterioposterior plane.

26. IMAGING
• Ultrasound elastography (USE)
• Cannot be done in
• Obese patients
• multinodular goiters and coalescent nodules
• patients in whom the nodule is posterior or inferior

27. THYROID SONOGRAPHY
• should be performed in all patients with a suspected thyroid nodule, nodular goiter, or
radiographic abnormality suggesting a thyroid nodule incidentally detected on another
another imaging study

28. THYROID SONOGRAPHY
Ultrasound should evaluate the following:
• thyroid parenchyma (homogeneous or heterogeneous) and gland size
• size, location, and sonographic characteristics of any nodule(s)
• presence or absence of any suspicious cervical lymph nodes in the central or lateral
compartments.
• nodule size (in three dimensions) and location (e.g., right upper lobe)
• description of sonographic features- composition (solid, cystic proportion, or
spongiform), echogenicity, margins, presence and type of calcifications, and shape if
taller than wide, and vascularity.

29. THYROID SONOGRAPHY
• Ultrasound imaging also demonstrates the anatomic location of the nodule in the
thyroid (anterior/posterior)
• If US confirms the presence of a predominantly solid nodule corresponding to what is
palpated, the FNA may be performed using palpation or US guidance

30. THYROID SONOGRAPHY
• In the subset of patients with low TSH who have undergone radionuclide thyroid
scintigraphy suggesting nodularity, US should also be performed
• evaluate both the presence of nodules concordant with the hyperfunctioning areas on
the scan, which do not require FNA
• as well as other nonfunctioning nodules that meet sonographic criteria for FNA

31. THYROID SONOGRAPHY
• US features that are associated with thyroid cancer, the majority of which are PTC.
• Microcalcifications
• nodule hypoechogenicity compared with the surrounding thyroid or strap muscles
• irregular margins (defined as either infiltrative, microlobulated, or spiculated)
• shape taller than wide measured on a transverse view

32. THYROID SONOGRAPHY
• Features with the highest specificities (median >90%) for thyroid cancer are
• Microcalcifications
• irregular margins
• tall shape
• Up to 55% of benign nodules are hypoechoic compared to thyroid parenchyma,
making nodule hypoechogenicity less specific

33. THYROID SONOGRAPHY
• Echogenicity
• hypoechogenicity – d/t increased cellularity and cellular compaction that is present in
the classic papillary and MTCs
• A follicular adenoma or carcinoma, as well as a follicular variant of papillary cancer -
composed of microfollicles with colloid that provide reflecting surfaces - iso- or
hyperechoic appearance
• Probability of cancer is higher for nodules with either microlobulated margins or
microcalcifications than for hypoechoic solid nodules lacking these features

34. THYROID SONOGRAPHY
• Follicular carcinoma
• FTC - more likely to be iso- to hyperechoic, non calcified, round (width greater than
anteroposterior dimension) nodules with regular smooth margins
• Distant metastases are rarely observed arising from follicular cancers <2 cm in
diameter

35. THYROID SONOGRAPHY
• Cystic component
• vast majority (82%–91%) of thyroid cancers are solid.
• Of 360 consecutively surgically removed thyroid cancers at the Mayo clinic, 88% were
solid or minimally cystic (<5%), 9% were <50% cystic, and only 3% were more than
50% cystic
• a spongiform appearance of mixed cystic solid nodules is strongly correlated with
benignity
• defined as the aggregation of multiple microcystic components in more than 50% of

36. THYROID SONOGRAPHY
• Cystic component
• pure cysts, although rare (<2% of thyroid lesions), are highly likely to be benign

37. THYROID SONOGRAPHY
• Cystic component
• Higher risk of malignancy in
• An eccentric rather than concentric position of the solid component along the cyst
wall,
• an acute rather than obtuse angle interface of the solid component and cyst,
• and the presence of microcalcifications

38. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Size
• So far, nodules >1 cm in diameter were considered to have malignant potential and
should be referred to US-FNAC
• PTC is often found as microcarcinoma
• whereas PTC is largely predetermined at its inception and does not transform with
growth, the FTC develops from FTA only if expands to certain size

39. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Size
• nodule growth increases risk of secondary genomic mutations that transform FTA to
FTC.
• histological hallmarks of FTC (angioinvasion and/or capsular invasion) may occur only
when FTA reaches certain cellular number
• size of thyroid nodule may predict thyroid malignancy in follicular lesions, whereas the
risk of PTC is probably equal in small and large lesions

40. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Vascularization
• increased intra-nodular vascularity is a risk factor for thyroid carcinoma especially for
PTC
• Increased neovascularization in PTC d/t imbalance between pro-angiogenic and
antiangiogenic factors
• Presence of Doppler signal in the central part of the nodule increases the risk of

41. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Calcifications
• The presence of calcifications in thyroid nodules, regardless of their appearance, may be
associated with higher risk of malignancy
• Macrocalcifications are large (>2 mm) hyperechoic spots that cause acoustic shadow and
may be present both in benign and malign nodules.
• They originate in areas of tiny hemorrhages and destructions in thyroid nodules as a result
of reparative changes with precipitations of calcium salts (dystrophic calcifications).

42. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Calcifications
• Microcalcifications - small (≤2 mm) hyperechoic points without acoustic shadow
• associated with the papillary histomorphology and occur very common in malignant
nodules with frequency 26-70 %
• Histopathologically microcalcifications are psammoma bodies

43. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Calcifications
• Microcalcifications can be confused with dense colloid aggregations (in benign
“colloid” nodules) or with the fibrosis of the tissue (in Hashimoto`s thyroiditis).
• dense colloid aggregations vibrate due to ultrasonic wave and cause an artifact called
“comet tail”
• But the microcalcifications stay motionless

44. THYROID SONOGRAPHY
• Pathophysiological background of ultrasound markers of thyroid cancer
• Calcifications
• Macrocalcifications along with microcalcifications, in a nodule, confer the same
malignancy risk as microcalcifications alone
• However intranodular macrocalcification alone is not consistently a/w thyroid cancer
• a nodule that has interrupted peripheral calcifications, in association with a soft tissue
rim outside the calcification, is highly likely to be malignant

49. THYROID IMAGING REPORTING
& DATA SYSTEM (TI-RADS™)
• 5 point classification to determine the risk of cancer in thyroid nodules based on
ultrasound characteristics.
• This system has been mainly used for thyroid nodules that are ≥1 cm

72. APPROACH TO THYROID
NODULE-2
FNAC

73. FNAC
• FNA is the procedure of choice in the evaluation of thyroid nodules, when clinically
indicated
• most accurate and cost-effective method
• Ultrasound guidance : lower rates of both nondiagnostic and false-negative cytology

74. FNAC
• Conservative approach of active surveillance management may be appropriate as an
alternative to FNA in selected patients.
• patients with very low-risk tumors (e.g., no clinical or radiographic evidence of
invasion or metastases),
• patients at high surgical risk
• or those with a relatively short life span expectancy

75. FNAC
Nodules with a higher likelihood of either
• a nondiagnostic cytology (>25%–50% cystic component) or
• sampling error (difficult to palpate or posteriorly located nodules), US-guided FNA is
preferred.

76. FNAC
• US – advantages
• Real-time US permits visualization of the needle within the lesion, thereby facilitating
accurate biopsy of small nonpalpable nodules
• Even in palpable thyroid nodules, US guidance is superior to palpation for obtaining
adequate material for an accurate cytologic evaluation

77. FNAC - INDICATIONS

78. FNAC - INDICATIONS

79. FNAC - INDICATIONS

80. FNAC - PROCEDURE
• A screening test for coagulation is not routinely needed
• The patient is placed in a supine position with the neck slightly extended.
• After the lesion is localized, the overlying skin is cleansed with a 10% povidone-iodine
solution and the area is draped

81. FNAC - PROCEDURE
• A local anesthetic may be used during the procedure.
• Approximately 1–2 mL of 1% lidocaine hydrochloride solution may be injected into the
skin and superficial subcutaneous tissue at the predetermined site.
• Advantage - it allows repeated aspiration attempts without causing the patient any
discomfort

82. FNAC - PROCEDURE
• REQUIREMENTS
• A 22- to 27-gauge needle is used with an attached 2–20-mL syringe
• A high-resolution (7.5–15- MHz) linear-array transducer, with a sterile cover

83. FNAC - PROCEDURE
• The transducer is placed directly over the lesion.
• Before aspiration, scanning is performed in the transverse plane for lesion localization,
followed by color Doppler mapping to depict any large blood vessels
• Instructed not to swallow or speak during the insertion of the needle

84. FNAC - PROCEDURE
• INTRODUCTION OF NEEDLE
• The needle may be introduced parallel or perpendicular to the transducer
• The needle tip should be carefully monitored during the procedure.
• All needle movements should be continuously visualized in real time.
• Aspiration should be performed at least twice.

85. FNAC - PROCEDURE
• Aspiration method
• Non aspiration method

86. FNAC - PROCEDURE
• ASPIRATION METHOD
• In aspiration, the needle tip is advanced into various positions in the nodule and
moved to and fro while suction is performed.
• Suction is halted before the needle is removed from the lesion.
• Repeated at least five times before the needle is withdrawn

87. FNAC - PROCEDURE
• NON ASPIRATION METHOD
• Due to capillary action
• The needle is advanced into the nodule and vigorously moved to and fro
• Rotated on its axis until a small amount of cellular material collects inside the needle
hub.
• No suction.

88. FNAC - PROCEDURE
• NON ASPIRATION METHOD
• ADVANTAGES
• Useful in very hypervascular nodules - high probability of obtaining a bloodstained
specimen on aspiration that is inadequate for accurate cytologic analysis
• less traumatic

89. FNAC - PROCEDURE
• thinner the needle used for FNA, the higher the rate of sufficiency of cytologic material
• the sufficiency rate 56.6% with the use of a 20-gauge needle
• 82.5% with the use of a 24-gauge needle
• Bloodstained material more frequently seen in aspiration was performed with thicker
needles

90. FNAC - STAINS
• Papanicolaou staining is most commonly used for cytologic analysis of thyroid
specimens
• provides the clearest depiction of nuclear chromatin, ground-glass nuclei, and nuclear
groove characteristics in papillary carcinoma
• Giemsa stain helps visualize the characteristics of cytoplasm and colloid

91. FNAC - ADEQUACY
• US-guided FNA yields an inadequate specimen in 10%–20% of procedures
• Criteria for adequacy
• at least six groups of well-visualized follicular cells, each group containing at least 10
well-preserved epithelial cells, preferably on a single slide

93. NON DIAGNOSTIC CYTOLOGY
A. FNA should be repeated with US guidance and, if available, on-site cytologic
evaluation
B. Repeatedly nondiagnostic nodules without a high suspicion sonographic pattern
require close observation or surgical excision for histopathologic examination
C. Surgery should be considered for histopathologic diagnosis if the cytologically
nondiagnostic nodule has a high suspicion sonographic pattern, growth of the
nodule (>20% in two dimensions) during US surveillance, or clinical risk factors for
malignancy are present

94. NON DIAGNOSTIC CYTOLOGY
• Repeat FNA with US guidance will yield a diagnostic cytology specimen in 60%–80% of
nodules, particularly when the cystic component is < 50%

95. BENIGN CYTOLOGY
• If the nodule is benign on cytology, further immediate diagnostic studies or treatment
are not required

96. BENIGN CYTOLOGY – BETHESDA 2
• Thyroid follicular cells are evenly
spaced and have a small and uniform
nuclear size.

97. AUS/FLUS CYTOLOGY
• For cases with suspicious sonographic features, an indeterminate FNA, or relevant
adverse clinical history or physical examination findings,
• perform repeat imaging earlier, in 6 to 12 months
• If there is nodule growth (>50% change in volume or ≥20% increase in at least two
nodule dimensions with an increase of ≥2 mm), a repeat FNA is recommended

98. AUS/FLUS CYTOLOGY
• investigations such as repeat FNA or molecular testing may be used to supplement
malignancy risk assessment
• If repeat FNA cytology, molecular testing, or both are not performed or inconclusive,
either surveillance or diagnostic surgical excision may be performed for an AUS/ FLUS
thyroid nodule,
• depending on clinical risk factors, sonographic pattern, and patient preference.

99. AUS/FLUS CYTOLOGY
• If the cytologic findings are indeterminate, a second review by an experienced
cytologist may be useful
• Another option is mutational analysis or molecular profiling to better estimate the risk
of cancer

100. BETHESDA III
• atypia of undetermined significance
• In an otherwise benign aspirate, rare
groups of follicular cells show nuclear
enlargement

101. FN/SUSP FOR FN CYTOLOGY
• This diagnostic category is used for cellular aspirates
• (i) comprised of follicular cells arranged in an altered architectural pattern
characterized by cell crowding and/or microfollicle formation and lacking nuclear
features of papillary carcinoma or
• (ii) comprised almost exclusively of oncocytic (Hurthle) cells

102. FN/SUSP FOR FN CYTOLOGY
• molecular testing may be used to supplement malignancy risk assessment data in lieu
of proceeding directly with surgery
• If molecular testing is either not performed or inconclusive, surgical excision may be
considered for removal and definitive diagnosis of an FN/SFN thyroid nodule.

103. FN/SUSP FOR FN CYTOLOGY
• One molecular approach is to analyze the specimen by means of a gene-expression
classifier to rule out cancer.
• In a report that assessed messenger RNA expression of 167 genes from FNA samples from
indeterminate cytology nodules 1 cm or larger,
• negative predictive value - 95% for AUS/FLUS and 94% for FN/SFN
• positive predictive value - 38% for AUS/FLUS and 37% for FN/SFN.

104. FN/SUSP FOR FN CYTOLOGY
• These results suggest that, patients with AUS/FLUS or FN/SFN whose results are
negative can be monitored without immediate thyroidectomy.

105. BETHESDA IV
• follicular neoplasm.
• Smears contain a cellular aspirate
with only scant colloid.
• The follicular cells are of normal
size but form microfollicles
(abnormal architecture).

106. SUSP FOR MALIGNANCY CYTOLOGY
• If the cytology is reported as suspicious for papillary carcinoma (SUSP), surgical
management should be similar to that of malignant cytology
• mutational testing for BRAF or mutation marker panel (BRAF, RAS, RET/PTC, PAX8/
PPARc) may be considered in nodules with SUSP cytology if such data would be
expected to alter surgical decision making.

107. SUSP FOR MALIGNANCY CYTOLOGY
• When surgery is considered for patients with a solitary, cytologically indeterminate
nodule, thyroid lobectomy is the recommended initial surgical approach

108. SUSP FOR MALIGNANCY CYTOLOGY
• A total thyroidectomy recommended in the following situations:
• the nodule has a specific oncogene abnormality with a high positive predictive value
for cancer (e.g., BRAF mutation)
• FNA -malignant or “suspicious for malignancy”
• bilateral nodular disease with an indication for surgery in at least one nodule

109. SUSP FOR MALIGNANCY CYTOLOGY
• A total thyroidectomy recommended in the following situations:
• history of radiation to the head or neck during childhood or adolescence or a family
history of thyroid cancer
• nodule is larger than 4 cm in diameter.
• clinically significant cardiorespiratory disease or other coexisting conditions, in order to
to avoid the possible need for a second procedure (completion thyroidectomy).

110. BETHESDA V
• “suspicious for malignancy”
(papillary carcinoma).
• Aspirate shows some features of
papillary carcinoma, such as
hypercellularity, nuclear
enlargement, hyperchromasia, and
an increased nuclear-to-cytoplasmic
ratio.
• However, no definitive nuclear
pseudoinclusions

111. MALIGNANT CYTOLOGY
• If a cytology result is diagnostic for primary thyroid malignancy, surgery is generally
recommended

112. MALIGNANT CYTOLOGY
• surveillance management approach
• (A) patients with very low risk tumors (e.g., papillary microcarcinomas without clinically
evident metastases or local invasion, and no convincing cytologic evidence of
aggressive disease)
• (B) patients at high surgical risk because of comorbid conditions

113. MALIGNANT CYTOLOGY
• surveillance management approach
• (C) patients expected to have a relatively short remaining life span (e.g., serious
cardiopulmonary disease, other malignancies, very advanced age), or
• (D) patients with concurrent medical or surgical issues that need to be addressed prior
to thyroid surgery.

114. MALIGNANT CYTOLOGY
• PTMC - defined as a tumor 1 cm or less in size
• Very indolent
• Following thyroid surgery for papillary thyroid microcarcinoma -disease-specific
mortality rates have been reported to be < 1%
• loco-regional recurrence rates are 2%–6%
• distant recurrence rates are 1%–2%

115. MALIGNANT CYTOLOGY
• The prevalence of BRAFV600E mutations in PTMC with lymph node metastases and
tumor recurrence is higher than PTMC without LN metastases or recurrence
• BRAF status taken in isolation has a low PPV for detecting PTMC with extrathyroidal
spread and therefore has a limited role for guiding patient management.

116. BETHESDA VI
• Papillary carcinoma.
• cellular aspirate with numerous
abnormal follicular cells containing
enlarged hyperchromatic nuclei.
• Nuclear pseudoinclusions are present

117. MULTINODULAR
• How should multinodular thyroid glands (i.e., two or more clinically relevant nodules)
be evaluated for malignancy?
• Patients with multiple thyroid nodules >/=1 cm should be evaluated in the same
fashion as patients with a solitary nodule >/=1 cm
• each nodule that is >1 cm carries an independent risk of malignancy and therefore
multiple nodules may require FNA.
• When multiple nodules >/=1 cm are present, FNA should be performed preferentially
based upon nodule sonographic pattern and respective size cutoff

118. MULTINODULAR
• How should multinodular thyroid glands (i.e., two or more clinically relevant nodules)
be evaluated for malignancy?
• A low or low-normal TSH - suggest that some nodule(s) may be autonomous.
• In such cases, a radionuclide (preferably 123I) thyroid scan should be considered and
directly compared to the US images to determine functionality of each nodule </=1
cm.
• FNA considered only for those isofunctioning or nonfunctioning nodules, among
which those with high suspicion sonographic pattern

119. LONG TERM FOLLOW UP – INITALLY
BENIGN
• Nodules with high suspicion US pattern: repeat US and US-guided FNA within 12
months.
• Nodules with low to intermediate suspicion US pattern: repeat US at 12–24 months.
• If sonographic evidence of growth or development of new suspicious sonographic
features, the FNA could be repeated or observation continued with repeat US, with
repeat FNA in case of continued growth.

120. LONG TERM FOLLOW UP – INITALLY
BENIGN
• Nodules with very low suspicion US pattern - If US is repeated, it should be done at
>/=24 months.
• If a nodule has undergone repeat US-guided FNA with a second benign cytology
result, US surveillance for this nodule for continued risk of malignancy is no longer
indicated

121. FOLLOW-UP FOR NODULES THAT DO
NOT MEET FNA CRITERIA
• (A) Nodules with high suspicion US pattern: repeat US in 6–12 months
• (B) Nodules with low to intermediate suspicion US pattern: consider repeat US at 12–24
months
• (C) Nodules >1 cm with very low suspicion US pattern (including spongiform nodules) and
pure cyst: If US is repeated, it should be at >/=24 months.
• (D) Nodules </=1 cm with very low suspicion US pattern (including spongiform nodules)
and pure cysts do not require routine sonographic follow-up.

122. ROLE OF MEDICAL OR SURGICAL THERAPY
FOR BENIGN THYROID NODULES
• Routine TSH suppression therapy for benign thyroid nodules in iodine sufficient
populations is not recommended
• If inadequate dietary iodine intake is found or suspected, a daily supplement
(containing 150 mcg iodine) is recommended
• Surgery may be considered for growing nodules that are benign after repeat FNA if
they are large (>4 cm), causing compressive or structural symptoms, or based upon
clinical concern

123. ROLE OF MEDICAL OR SURGICAL THERAPY
FOR BENIGN THYROID NODULES
• Recurrent cystic thyroid nodules with benign cytology - surgical removal or
percutaneous ethanol injection (PEI) based on compressive symptoms and cosmetic
concerns

124. MOLECULAR GENETICS
• BRAFV600E single mutation testing - specificity of approximately 99%
• RAS mutations had an 84% risk of cancer and a 16% chance of benign follicular
adenoma.
• NRAS, HRAS, and KRAS point mutations, RET/PTC1 and RET/PTC3 with or without
PAX8/PPARc rearrangements
• the sensitivity of the seven gene mutational panel testing is variable - 44% to 100%

125. MOLECULAR GENETICS
• In AUS/FLUS or FN/SFN , mutational analysis indicates cancer in approximately 20 to
40% of FNA samples
• positive predictive value - 87 to 88%
• negative predictive value - 86 to 94%
• BRAF mutation positive - chance of cancer is almost 100%
• RAS mutation positive - chance of cancer is 80 to 90%

127. THANK YOU