Management of differentiated thyroid canncer

2. Dr Mohammed Rabei
Al-Azhar Faculty of Medicine
Cairo, Egypt.

3.  Differentiated Thyroid Cancers (DTCs) are primary
cancers arising from the thyroid follicular cells and
include papillary thyroid cancers (PTCs), Follicular
thyroid cancers (FTCs), and Hürthle cell cancers
(HCCs).
 DTCs are generally approached and managed
similarly.

5.  Thyroid nodules are very common and are present in approximately 50% of patients
on screening ultrasound or autopsy studies.
 Thyroid neoplasms are the most common endocrine tumours (annual incidence, 8–9
cases/100,000 people), and DTC accounts for more than 90% of cases.
 Thyroid cancer is the fastest increasing cancer in American men and women, with an
incidence that has risen approximately 270% over the last three decades.
 The rising DTC incidence in recent years may reflect a combination of increased
imaging ( 50-60 % of general population have nodules on US) and a concomitant true
rise in incidence (increased neck radiation).
 The number of deaths has remained largely stable ( 0.5 cases per 100000 ). Majority
of patients with DTC have indolent tumours.
 Incidental thyroid micro-carcinoma in autopsy( with no prior history of thyroid disease):
7%( British Study) – 37%( Korean study).

7. • The great majority of thyroid nodules are benign
while only 5-10 %( 15% in old age- 10-50% in
children) are malignant.
• The main clinical challenge is to avoid over-diagnosis
and over-treatment in patients with low-risk disease or
benign thyroid nodules while promptly identifying
those patients with more advanced or high-risk
tumours that require aggressive treatment
approaches.

11.  DTCs are primary cancers arising from the thyroid
follicular epithelial cells and include :
• PTCs 80%.
• FTCs 10%
• FVPTCs ( variant of PTC )
• HCCs ( variant of FTC )

12. PTC
 PTC is the most common type of thyroid cancer overall, comprising 84% of
all incident cases.
 Common in iodine sufficient areas.
 There is a female predominance with a 3:1 female-to-male ratio, mean age
at presentation is 30-40 yrs old.
 The predominant thyroid cancer in children and individuals exposed to
external radiation.
 PTC disseminates primarily via the lymphatic route and affects the cervical
LNs in the central and lateral compartments ; however, distant metastases
do occur in up to 3% to 5% of patients, typically to lung and bone.

13.  Orphan Annie eye .
 Intranuclear cytoplasmic
inclusions.
 Psammoma bodies.
PTC Pathology

14.  The term fvPTC ( follicular variant of PTC ) entered the
pathology nomenclature in the 1970s. It is used to
describe a tumour of neoplastic follicles without papillary
structures but with nuclear features of PTC.
 Two main subtypes of fvPTC were described:
encapsulated and invasive (unencapsulated).
 fvPTC has a similar prognosis to classical PTC .

15. The encapsulated subtype had been a subject of
contentious debate in the pathology community, because,
in the absence of capsular invasion, the diagnosis of cancer
was wholly dependent upon nuclear findings that are
highly subjective and variable. In addition, the clinical
behaviour and prognosis of encapsulated fvPTC were
extremely indolent and clearly distinct from those of its
invasive counterpart.

16.  In 2016 retrospective analysis of 109 patients with the
encapsulated variant and 101 patients with invasive
fvPTC.
 The authors found that none of the patients with
encapsulated fvPTC had died or had evidence of disease
after treatment , compared to a 12% rate of adverse
oncologic outcomes in the invasive fvPTC cohort.
 So, a change in terminology from encapsulated fvPTC to
“noninvasive follicular thyroid neoplasm with papillary-
like nuclear features,” or NIFTP.

18. NIFTPs may account for up to 10-20% of the tumours
previously classified as PTCs.
The word “cancer” has been eliminated from the definition
of NIFTP to underline its excellent prognosis: no adverse
outcomes (such as cancer-related death, distant or regional
metastases, and structural or biochemical recurrence) have
been recorded for these tumours.

19.  Other less common but more aggressive histologic
subtypes of PTC include: tall cell, hobnail, diffuse
sclerosing, and columnar variants, which together
comprise less than 1% of all PTCs.

20. FTC
 FTC is the second most common type of DTC. 3:1 female-to-male ratio.
 Mean age at presentation is 50 yrs old.
 Common in iodine deficient areas.
 Usually present as solitary thyroid nodule surrounded by a capsule.
 Follicles are present, but the lumen may be devoid of colloid.
 Malignancy is defined by the presence of capsular and vascular invasion
 May be hyperfunctioning in <1% of cases
 In contrast to that of PTC, the pattern of spread of FTC is
haematogenous, typically to the lungs and bone, tumour thrombus
within the middle thyroid or jugular veins.

21.  Cytologically, FTC can range from having virtually normal-appearing follicular
cells to those with various abnormal features, including nuclear atypia,
hypercellularity, and microfollicles.
 Thus, FNAB is unable to distinguish benign follicular lesions from follicular
carcinomas. So, preoperative clinical diagnosis of cancer is difficult unless distant
metastases are present.
 Large follicular tumors (>4 cm) in older men are more likely to be malignant.
 FTC can only be definitively diagnosed on histologic examination based on the
presence of capsular and vascular invasion.
 FVPTC has follicular architecture and cytologic features of papillary thyroid
cancer, sometimes permitting a diagnosis of malignancy based on cytology.

22. HCC
 Hürthle cell carcinomas account for approximately 3% of all
thyroid malignancies. Considered to be a subtype of FTC.
 Peak incidence in the sixth and seventh decades.
 Hürthle cell tumors differ from follicular carcinomas in that:
1) They are more often multifocal and bilateral (about 30%)
2) Usually do not take up RAI (about 5%)
3) More likely to metastasize to local nodes (25%) and distant sites.
Metastasis is present in up to 20% of patients at initial diagnosis.
4) Associated with a higher mortality rate (20% at 10 years).

23. HCC

25. INITIAL EVALUATION
1) HISTORY AND PHYSICAL EXAMINATION.
2) T.S.H
3) ULTRASOUND.

26. HISTORY AND PHYSICAL EXAMINATION
• Features that suggest an increased likelihood of malignancy:
1) Extremes of age ( < 18 years , > 55 years ).
2) History of neck irradiation (particularly in childhood and
adolescence), ( cumulative effect , Increased risk after 3
years ) >>> papillary and anaplastic thyroid cancers.
3) History of rapid growth of a neck mass.
4) Family History.

27.  We have to ask about :
1- Function.
2- Pressure symptoms.
3- Infiltrative symptoms.

28. Findings that suggest the possibility of cancer:
1) Hard fixed mass.
2) Cervical lymphadenopathy.
3) Infiltrative symptoms.

29. Work up
 Primary diagnostic assessments include neck ultrasound ,
TSH, FNA cytology.
 Preoperative ultrasound is the most sensitive test for the
characterization of thyroid nodules as well as
identification of pathologic lymphadenopathy.

30. SERUM T.S.H
If T.S.H is low:
1. Hyperthyroidism >> decreased risk of malignancy.
2. Thyroid Scan.
If T.S.H is normal or high:
• If suspicious criteria in US >>> FNA.
• If not >>> follow up.
When cancer is diagnosed a higher T.S.H is associated
with a more advanced stage of the disease.

31.  Cross-sectional imaging ( CT without contrast or MRI
of the neck and chest) and intraluminal imaging
(laryngoscopy, bronchoscopy, or esophagoscopy ) may
be required in patients with potentially more advanced
local and regional disease, obese short neck , degree of
extension of large retrosternal extension.
 It should be kept in mind that using iodine contrast media
during CT scan will delay RAI ttt for 8 weeks if the nodule
proves to be cancer and such ttt is needed.

32. Radionuclide Imaging
o Iodine-123 emits low dose radiation, has a half-life of 12 to 14 hours.
 Iodine-131 has a half-life of 8 to 10 days and leads to higher-dose
radiation exposure.
 Technetium Tc 99m pertechnetate (99mTc) also has the advantage of
having a shorter half-life and minimizes radiation exposure.
 The images obtained provide information about the size , shape of
the gland and the distribution of functional activity.
 Areas that trap less radioactivity than the surrounding gland are
termed cold , whereas areas that demonstrate increased activity are
termed hot.
 The risk of malignancy is higher in “cold” lesions (20%) compared to
hot ( 5 % ) or warm lesions (10 %).

33.  Routine isotope scanning has been abandoned.
 Thyroid scintigraphy (with Technetium Tc 99m or I123) is
recommended when TSH levels are reduced (<0.3–0.4
mIU/L) and toxicity is associated with nodularity, to
localize the area of hyperfunction.

34.  More recently, 18F-fluorodeoxyglucose (FDG) positron emission
tomography (PET) combined with computed tomography (CT) is
being increasingly used to screen for metastases in patients with
thyroid cancer with elevated Tg post thyroidectomy in whom other
imaging studies are negative.
 PET scans are not routinely used in the evaluation of thyroid
nodules; however, they may show clinically occult thyroid lesions.
 These incidental findings of focal thyroid uptake during PET scan
have a 14-33% risk of malignancy and they should be worked up by
ultrasound and fine needle aspiration biopsy (FNAB).

35.  Preoperative thyroglobulin level is not
recommended, used only for follow up of patients
after total thyroidectomy and RAI.
 The thyroid cancer genetic analysis for well-
differentiated thyroid cancer has identified BRAF,
RAS, RET, NTRK1, and PAX8-PPAR mutations as
potential driver mutations for thyroid cancer.

37. US suspicious criteria
 Solid
 Hypoechoic
 Taller than wider ( A-P diameter > Transverse diameter)
 Irregular contour.
 Incomplete halo (rim calcifications with extrusive component).
 Microcalcifications ( high +ve pred. value )
 Central hypervascularity
 Suspicious lymphadenopathy.
 Capsular invasion >> diagnostic.
 Size does not count but documented increase in size > 20%
of diameter or > 50% of volume in follow up US is suspicious.

38. Ultrasound characteristics of malignant
lymph nodes
 Round shape( instead of oval)
 Loss of architecture
 Cystic changes
Microcalcifications and hyper vascularity.

39. ATA nodule sonographic patterns
and risk of malignancy

42. ACR TI-RADS Classification
 The American College of Radiology (ACR) has
introduced an imaging staging system similar to
that used for breast imaging called TI-RAD score.
 Thyroid Imaging Reporting and Data System (TI-
RADS) is an ultrasound-based risk stratification
system (RSS) for thyroid nodules released in 2017
to reduce the number of unnecessary biopsies of
benign nodules.

45.  FNA can technically be performed without ultrasound
guidance for palpable nodules, but the accuracy overall with
ultrasound assistance is superior.
 FNA is performed with a small-gauge needle (typically 23–27
gauge ) with an attached 10 mL syringe.
 Adequate smear should have at least 6 clusters of cells each
containing about 10 cells

46.  The FNA is performed using an aspiration or nonaspiration technique.
 The non aspiration technique is preferred because it is less bloody. The needle is
moved back and forth within the nodule while rotating the needle on its axis
until material is noted within the needle hub.
 For the aspiration technique, the needle is placed into various areas of the
nodule and moved back and forth with suction applied; suction is released
before the needle leaves the nodule.
 For cystic lesions, the aspirated fluid is sent for cytology, and repeat ultrasound
is performed to evaluate for a solid component which, if present, should be
biopsied.
 After the biopsy is completed, pressure is placed on the puncture site for 5
minutes, and a dressing is applied.

47.  After the FNA is performed, the needle is detached from the syringe and
reattached after the syringe is filled with air so that the needle contents
can be expelled onto a glass microscope slide.
 A second slide is placed on top of the slide with the cellular contents,
and the slides are pulled in opposite directions, thus creating two slides
for evaluation. The slides can be placed in 95% ethyl alcohol or sprayed
with fixative for Papanicolaou staining or air-dried for Giemsa staining.
 The specimen should be evaluated for adequate cellularity if possible in
the ultrasound suite to avoid the need for 2nd setting.
 Molecular analysis ( e.g BRAF V600 mutation for PTC ).
 Complications from FNA are rare and primarily limited to bleeding or
hematoma formation.

49. FNA of Sub centimetric Nodule ???

50. 1) Subcapsular location adjacent to the RLN or Trachea.
2) Extrathyroidal extension.
3) Extrusion through rim of calcification.
4) Associated with abnormal cervical lymph nodes.
5) History of neck irradiation.
6) Strong family history of thyroid cancer.
7) Known syndromes associated with thyroid cancer.
8) Young age < 18 ys ( Risk of malignancy 10-50 %)
As a rule, thyroid nodules < 1 cm should not be biopsied.
FNA should be done in any nodule (regardless of size) with the
following suspicious sonographic features :

51. Limitations of FNAC in Thyroid
1) Not able to distinguish follicular adenoma from
carcinoma.
2) Not able to distinguish Hurthle cell adenoma from
carcinoma.

54. Staging
 The American Joint Committee on Cancer (AJCC) and Union for
International Cancer Control Tumour, Node, Metastasis (TNM)
classification has emerged as the most widely accepted and
easily understood. The current eighth edition of the TNM
system took effect in early 2018.
 This system is aimed at predicting mortality (not recurrences).
The eighth edition of this staging system contains important
modifications.

55.  The age cut-off was raised from 45 to 55 years.
 Regional lymph node metastases or the presence of gross
extra thyroidal extension limited to strap muscle no longer
mandate stage III but stage II.
 Implementation of the eighth edition revisions is expected
to result in the down-staging of approximately 30–40% of
patients with thyroid cancer.

57. Under AJCC 8e , the estimated disease-specific survival in younger patients is
expected to be 98% to 100% for stage I and 85% to 95% for stage II,
and in older patients over 55 years 98% to 100%, 85% to 95%, 60% to 70%, and
less than 50% for stage I, II, III, and IV, respectively.

58. TNM Staging
 R0 : No residual primary tumour
 R1 : Microscopic residual primary tumour
 R2 : Macroscopic residual primary tumour
 Rx : Residual could not be assessed
 NB: p in staging means pathological staging

60. Prognostic factors
 Age : < 20 ys or >55 ys.
 Gender : Male.
 Size of the tumour.
 LN and distant metastasis.
 Histology : PTC > FTC > Huthel cell cancer >
medullary > anaplastic.
 Special types of PTC have bad prognosis ( tall cell,
columnar cell, diffuse sclerosing , …. )

61. Management strategies

62.  Active Surveillance.
 Hemithyroidectomy.
 Total Thyroidectomy.
 Prophylactic central neck dissection.
 Therapeutic central neck dissection.
 Therapeutic lateral neck dissection.
 Radioactive iodine ablation.
 Radiofrequency ablation.
 Ethanol ablation.
 Laser ablation.
OPTIONS

63. Surveillance

65.  The 2015 ATA guidelines include active surveillance among
the management options for papillary thyroid micro
carcinomas smaller than 1 cm.
 The 2015 ATA Guidelines explicitly recommend against
biopsy of nodules <10 mm. Therefore, patients who might
have low risk PTC are now not even recommended to
determine whether their thyroid nodule is cancerous or
not.

68. In a study conducted in the United States, 291 patients
with cytologically suspicious or malignant thyroid
nodules (Bethesda class V or VI) measuring 1.5 cm or
less were managed with active surveillance for a median
of two years. The percentages of tumours displaying
growth were 2.5% at two years and 12% at five years.

69. Importantly, those patients who initially underwent
observation and eventually had surgical resection
had no oncologic consequences from having waited
for surgical rescue.
There is a need for biomarkers that can identify
those rare microcarcinomas that are likely to grow,
so they can be promptly referred for surgery.

70. According to ATA 2015 , serial radiographic imaging (every
3-12 months ) in patients with asymptomatic , stable or
minimally progressive disease ( not likely to develop rapidly
progressive disease ).
TSH suppressive thyroid hormone therapy to be continued.

71. Active surveillance management approach can be considered
as an alternative to immediate surgery in:
(A) patients with very low risk tumors (e.g. papillary
microcarcinomas)
(B) patients at high surgical risk because of co-morbid conditions.
(C) patients expected to have a relatively short remaining life span.

72. “Inappropriate for active surveillance”
Subcapsular location adjacent RLN, suspicion of extrathyroidal
extension, FNAC findings suggestive of an aggressive histotype,
and a documented increase in size of at least 3 mm in a confirmed
PTC or patient-related factors (metastatic disease, age below 18
years, refusal of the surveillance-alone approach, poor adherence
to the follow-up protocol) or physician-related factors (limited
experience with thyroid cancer management or neck US or both)
or a combination of these factors.

73. Surgical Management
The appropriate extent of thyroidectomy depends on
multiple factors, including the extent of disease and the
patient’s perioperative risk, with official
recommendations evolving over the past several years.
In the past, total thyroidectomy was the traditionally
recommended treatment for the majority of DTCs.

76. There is shift in recommendations resulting from newer
data in large observational database studies demonstrating
equivalent survival between selected patients undergoing
either total thyroidectomy or lobectomy for DTCs between
1-4 cm.

79. 2015 ATA GUIDELINES- Lets Take it Down
a Notch
According to the 2015 ATA guidelines, lobectomy may be
sufficient for:
a unifocal intrathyroidal low-risk carcinoma of <4 cm diameter
in patients with no prior head and neck radiation, no family
history of thyroid carcinoma, no clinically detectable cervical
lymph node metastases, no distant metastasis,
whereas in other cases, total is recommended.

80. Ipsilateral lobectomy is recommended for DTCs < 1 cm.
Ipsilateral lobectomy has become an acceptable alternative to
total thyroidectomy for low-risk unilateral DTCs between 1 and 4
cm with age between 18y-55y, without extrathyroidal extension,
no evidence of LN or distant metastasis, not aggressive variant
and no prior radiation.
Total thyroidectomy : Tumour > 4 cm , multifocal , bilateral ,
extrathyroid extension, familial , history of neck irradiation,
nodal or distant metastasis.

81. Nondiagnostic (Bethesda Criteria I)
 Repeat FNA with Us guidance.
 For nodules that have nondiagnostic cytology (Bethesda
criteria I) after two biopsies, US guided core-needle
biopsy or diagnostic lobectomy should be done as the risk
of malignancy is similar to that of indeterminate nodules.

82. Benign FNA (Bethesda Criteria II)
 Benign thyroid nodules do not typically require surgical resection
unless they are symptomatic with associated symptoms of
compression or associated with hyperthyroidism.
 Surgery also should be considered for large thyroid nodules (>4 cm)
because FNA may be less accurate due to the greater potential for
"sampling error“.
 Asymptomatic benign nodules should be followed with serial
ultrasound to evaluate for nodule growth. If the nodule increases in
size significantly (20% increase in dimensions, or 50% increase in
nodule volume), FNA should be repeated.

83. Bethesda Criteria III
 5% to 15% risk of malignancy .
 Repeat FNA with Us guidance.
 US guided core-needle biopsy after two FNA biopsies.
 Molecular analysis ( BRAF, RAS, RET mutations).
 Thyroid scan >> if cold nodule go for lobectomy.
 PET CT.
 Diagnostic thyroid lobectomy.
 Alternatively, for patients with small nodules with indeterminate
cytology that do not have suspicious ultrasound features, surveillance
with serial ultrasound may be reasonable.

84. Bethesda Criteria IV
( Follicular lesion ?? )
 It may be :
1) Benign adenomas (70-80%).
2) FTC , FVPTC (15% to 30%).
 Patients diagnosed by FNAB as having a follicular lesion should
undergo thyroid lobectomy because at least 70% to 80% of these
patients will have benign adenomas.

85.  Management : Diagnostic lobectomy without frozen section.
 Intraoperative frozen-section examination usually not helpful, since
it cannot assess well for capsular and vascular invasion, which are
characteristics that separate benign from malignant follicular
neoplasms, but it should be performed when there is evidence of
capsular or vascular invasion or when adjacent lymphadenopathy is
present.

86.  A completion thyroidectomy would be indicated if final
pathology revealed FTC, so that I131 can be used to detect and
ablate metastatic disease.
 The completion thyroidectomy should be done either within 2
weeks of the initial surgery or after 2 to 3 months from the
original surgery to avoid the worst inflammation and scar
tissue.

87. Follicular lesion ??
 If suspicious LNs or distant metastasis >> total
thyroidectomy.
 If no suspicious LNs or distant metastasis:
1) Nodule < 1 cm : Lobectomy + completion thyroidectomy if
lobectomy pathology revealed carcinoma ( capsular and
vascular invasion)
2) Nodule 1-4 cm : lobectomy ± completion, or Total from the
start.
3) Nodule > 4 cm : Total thyroidectomy.
NB: Incidence of distant metastasis is high and RAI ablation is
a must ,so total thyroidectomy is recommended in any case of
follicular carcinoma regardless of size.

88.  Prophylactic nodal dissection is not needed in most cases
because nodal involvement is infrequent, but in the unusual
patient with nodal metastases, therapeutic neck dissection is
recommended.

89. FNA revealing a Hürthle cell neoplasm/suspicious
for Hürthle cell neoplasm
 15% to 45% risk of malignancy.
 Similar to follicular neoplasms, the diagnosis of malignancy is based on
capsular or vascular invasion. Accordingly, Hürthle cell neoplasms are
treated similarly to follicular neoplasms, with a diagnostic thyroid
lobectomy without frozen section analysis followed by completion
thyroidectomy if malignancy is found on final pathology.
 These patients should also undergo routine central neck node removal
and lateral neck dissection when lateral neck nodes are palpable or
identified by ultrasonography.

90. Hürthle cell lesion
 Large Hürthle cell neoplasms are more likely to be malignant than
small Hürthle cell neoplasms, particularly in elderly patients. The
risk of malignancy for tumors >4 cm exceeds 50%, so an upfront
total thyroidectomy is often recommended for these large tumors.
 Although RAI scanning and ablation usually are ineffective, they
probably should be considered to ablate any residual normal
thyroid tissue and occasionally ablate tumors because there is no
other good therapy.

91. Molecular Testing in Indeterminant Nodules
 While surgery with a diagnostic lobectomy is the “gold-standard” for
indeterminate nodules ( III, IV ), molecular testing may be used to further
differentiate these nodules into those that are likely malignant and should
have surgery and those that are likely benign and can be safely observed.
 Two distinct types of molecular testing are available and can be classified as
either a “rule out” or a “rule in” test.
 Molecular testing with the Afirma gene expression classifier (GEC) and
Afirma gene sequencing classifier (GSC) has been shown to effectively “rule
out” malignancy. For negative test results on the Afirma GEC, the risk of
malignancy is similar to that of a benign nodule, thereby potentially
avoiding the need for diagnostic surgery.

92.  For results deemed to be “suspicious” on the GEC, the risk of malignancy
is reported to be approximately 40%, so these patients frequently go on to
a diagnostic thyroid lobectomy.
 A commercially available 7 gene panel (BRAF V600E, BRAF K601E,
KRAS, NRAS, HRAS, RET/PTC, PAX8/PPARG) is available which is
highly specific, but lacks sensitivity to rule out thyroid cancer. If a
mutation is identified, there is a high likelihood of malignancy (100%
1540 BRAF or RET/PTC and 85% BRAF K601E, RAS or
PAX8/PPARG), and definitive surgery should be performed. A diagnostic
lobectomy can still be performed for a negative test, since malignancy is
not excluded with the same confidence.

93. Suspicious FNA (Bethesda Category V)
 A nodule suspicious for papillary thyroid cancer (Bethesda category
V) implies a 60% to 75% risk of malignancy, so:
1) total thyroidectomy for intermediate- or high-risk tumour.
2) lobectomy for low-risk tumours.
 Alternatively, a diagnostic lobectomy with frozen section.

94. Malignant FNA (Bethesda Category VI)
 Unifocal tumours <1 cm should be treated with thyroid lobectomy except if
there is a history of cervical radiation, a family history of thyroid cancer,
evidence of extrathyroidal extension, lymph node/distant metastases, or clear
indications to remove the contralateral lobe.
 Surveillance with serial ultrasound might represent a nonoperative alternative for
a subset of patients with tumours <1 cm who are at low risk of developing tumor
progression.
 Tumours 1-4 cm that are at low risk of recurrence and do not require treatment
with radioactive iodine may be treated with thyroid lobectomy or total
thyroidectomy.

95.  Patients with intermediate or high-risk tumors (including
tumours>4cm, extrathyroidal extension, multifocality, contralateral
thyroid nodules, aggressive histology, vascular invasion, nodal and
distant metastatic disease) and patient-specific factors (e.g., patient
choice, history of familial thyroid cancer and head and neck
irradiation) should be treated with total thyroidectomy to facilitate
radioactive iodine treatment and close follow up due to higher risk
of recurrence.

96. LN metastasis in DTC

98.  Lymph node compartments separated into levels and sublevels.
 Level VI contains the thyroid gland and the adjacent nodes bordered superiorly
by the hyoid bone, inferiorly by the suprasternal notch, and laterally on each
side by the carotid sheaths.
 Level VII ( ant. Sup. Mediastinal LNs) extends from suprasternal notch to the
innominate (brachiocephalic) artery.
 Level II, III, and IV nodes are arrayed along the jugular veins on each side,
bordered anteromedially by level VI and laterally by the posterior border of the
sternocleidomastoid muscle. Level III nodes are bounded superiorly by the level
of the hyoid bone and inferiorly by the inferior aspect of the cricoid cartilage;
levels II and IV are above and below level III, respectively.
 The level I node compartment includes the submental and submandibular
nodes above the hyoid bone and anterior to the posterior edge of the
submandibular gland.
 Level V nodes are in the posterior triangle, lateral to the lateral edge of the
sternocleidomastoid muscle.
 Levels I, II, and V can be further subdivided into A & B.

99. The most relevant nodal stations for thyroid cancer include
the central compartment (level VI and VII), which consists
of the perithyroidal lymphoadipose tissue bounded by the
carotid arteries laterally, the hyoid bone superiorly, and the
innominate artery inferiorly, and the lateral compartments
containing the jugular groups (levels IIa, III, and IV) and the
inferior posterior triangle (level Vb).
Levels I , IIb , Va are not recommended.

100.  Central compartment dissection is a well-established treatment of
cN1a tumours; but its role as prophylaxis in cN0 tumours is
uncertain.
 Because microscopic lymph node metastases may occur in up to
20-80% of patients with PTC mostly in central compartment,
some investigators have suggested routine prophylactic central
neck dissection during the index thyroidectomy procedure.
 However, because microscopic nodal disease is rarely of clinical
significance, the role of prophylactic central neck dissection
remains controversial.

103.  Currently, the ATA guidelines suggest that prophylactic
central neck dissection should be considered for higher
risk patients with cN0 papillary thyroid carcinomas with
more advanced primary tumours (T3 or T4), clinically
involved lateral compartment lymph nodes.
 Prophylactic central neck dissection in case of cN0 is not
recommended in classical PTC , < 4 cm , < 55 ys , unifocal
with no extrathyroid extention on us (Relative risk of
recurrent pN1 in cN0 is 2-4 %).

104. Lateral Neck Dissection
 N0 >> No lateral Neck Dissection.
 N1a >> Prophylactic lateral ND ??? There is no prophylactic lateral ND.
 N1b (suspicious lateral compartment cervical lymph nodes): an
ultrasound-guided FNA should be performed with measurement of Tg in
the washout or intraoperative Frozen section of suspicious LN, if it is
positive for malignancy, a selective lateral compartment lymph node
dissection of levels IIA, III, IV, and VB should be performed.
 When Lateral neck dissection is done, it is coupled with central neck
dissection.

105. Radioactive Iodine

106. Radioactive Iodine
 RAI therapy with I131 for DTC is based on the fact that
thyroid follicular cells have a unique ability to take up
iodine.
 DTC is generally iodine avid (at a lesser degree than
normal thyroid follicular cells). Thus, RAI is a useful
adjunct in the treatment of PTC and FTC as well as certain
cases of HCC despite its relative iodine non avidity.

107. 1- To ablate any residual thyroid tissue ( < 1 cm ) remaining
after thyroidectomy.
2- Destroy subclinical micrometastasis.
Aim:

108.  RAI should be administered in patients in a low-iodine state,
and in a setting of high TSH levels(>25-30) to stimulate
maximal iodine uptake by thyroid tissue.
 Two methods of TSH stimulation exist: administration of
recombinant human TSH, and thyroid hormone withdrawal(3-
6 weeks) with low iodine diet. Pts could receive T3 during this
period as T3 has shorter half-life than T4 ( 1day # 1 week ) and
needs to be discontinued for 2 weeks to allow T.S.H to rise.

109. Protocol of RAI
 Two protocols :
1) Diagnostic dose of 1-3 mCi of I123 and measuring uptake
24 hrs later.
2) Ablative dose of I131 then scan at 8th day to avoid stunning
effect of giving diagnostic dose.
NB: Stunning effect: Reduction in uptake of I131 therapy dose
induced by a pretreatment diagnostic dose.

110. The role for post thyroidectomy RAI has become much
more selective in the past decade, largely due to convincing
evidence of the lack of benefit of RAI in low-risk PTC
patients (with intrathyroidal tumours smaller than 4 cm
without high-risk histologic features) .
RAI is routinely recommended for high-risk cancers,
distant metastasis, tumour > 4 cm, extrathyroid
extension or FTC.

111. RAI ablation is recommended for:
1) FTC.
2) All patients with stage III or IV disease.
3) Patients with stage I and II disease who have(High risk):
a) Large tumour > 4 cm.
b) Age < 15y or > 55 y.
c) Incomplete tumour resection
d) Aggressive histology.
e) Nodal or distant metastasis.
f) Multifocal disease
g) Bilateral.
h) Extrathyroid or vascular invasion.
NB: Contraindications to RAI : Pregnancy , Lactation , Age < 10
ys

112. Adjuvant Therapies
External beam radiotherapy (EBRT): plays a limited but important
palliative role for selected situations in DTC.
The main indications include local control of unresectable locally
advanced macroscopic or microscopic residual disease after
thyroidectomy (particularly in tumours thought to be RAI nonavid and
affecting the aerodigestive tract), as well as treatment of symptomatic
distant metastatic foci that are RAI nonavid and bone metastasis to
decrease pain and fracture.
Chemotherapy: No role for routine chemotherapy. Can be used in
terminal cases with dissiminated metastasis with little success.

113. Other treatment options (minimally invasive techniques)
Radiofrequency ablation in which frictional heat and tissue necrosis is
generated by creating an alternating electric field for residual or recurrent
irresectable tissue, recurrent cervical nodal metastases, lung or bone metastases.
Patients susceptible for active surveillance may still be concerned regarding cancer
progression and could suffer considerable anxiety during follow-up.RFA is an
effective and safe option for treating low-risk PTMC patients who are of high
surgical risk or refuse surgery.
NB 1: There is no role for RF in respectable carcinoma of thyroid gland
(surgery is much better than RF in respectable cases).
NB 2: RF could be done in benign nodule after 2 FNAC confirming Bethesda 2
and TIRAD score equal or less than 3.

114. Other treatment options (minimally invasive techniques)
for local control of recurrent and/or metastatic disease include:
Laser ablation in which laser light is transmitted to induce coagulative necrosis.
Percutaneous ethanol to shrink the nodule by inducing small vessel thrombosis and
coagulative necrosis.
Microwave ablation.
High intensity focused ultrasound.
Palliative embolization of lung and bone metastases.

115. Postoperative Thyroid-Stimulating Hormone
Suppression
 TSH suppressive doses of thyroid hormone medication are
recommended to prevent hypothyroidism and to reduce the risk of
TSH-stimulated tumour growth and recurrence.
 For patients with low- to intermediate-risk tumours, serum TSH
can initially be maintained between 0.1 and 0.5 mU/L, whereas
patients with high-risk tumours should be kept initially at a TSH
level of less than 0.1 mU/L if possible.
 The TSH level also may be allowed to increase closer to the normal
range in patients who have an excellent response to therapy.

116. Postoperative follow up
 T.S.H level.
 Tg level: in pts who have undergone total thyroidectomy. It
should be < 2 ng/ml.
• Tg level >2ng/ml is highly suggestive of recurrent or
metastatic disease.
 Neck US: at 6 and 12 months post thyroidectomy and then
annually for at least 3-5 ys.
 Diagnostic whole body scan: Once for low-risk patients( not
repeated) & repeated after 6-12 months after remnant
ablation in high or intermediate risk patients.
 PET CT Scan: if RAI and US are –ve while Tg is elevated.

117. Staging for recurrence
The ATA 2009 guidelines proposed a system for estimating
the initial risk of recurrence based on a number of
clinicopathologic features, with a three-tiered risk
classification that stratified patients into low-risk,
intermediate-risk, and high-risk categories.

120.  The ATA 2015 guidelines have proposed a system that
dynamically changes the initial risk estimates based on
the clinical course of disease and response to therapy.
 The dynamic risk classification process used during
follow-up assigns patients to subgroups and may be
modified at each follow-up examination.
 Parameters : Suppressed Tg (original) and stimulated Tg
(after giving recombinant TSH) , US , CT/Nuclear imaging.

121. The response-to-initial-therapy categories in this system include
the following:
 1. “Excellent response”: no clinical, biochemical, or structural
evidence of disease >>> Relax full TSH suppression. (TSH may be
allowed to rise to the low normal range (0.3–2mU=L) .
 2. “Biochemical incomplete response”: abnormal Tg or rising
anti-Tg antibody levels in the absence of localizable disease >>>
Close observation – suppress TSH 0.1-0.5 m U/l for 5-10 ys.
 3. “Structural incomplete response”: persistent or newly
identified locoregional or distant metastases.>>> full TSH
suppression (TSH should be maintained below 0.1mU=L in the absence of
specific contraindications) + RAI ± surgery if resectable.

124. Clearly, individualized decision-making
for different patients should be preferred
over a “one size fits all” approach.

126. Thank you