THYROID.pptx ENT surgeon dr Vishakh k nair

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DR ANJALIKRISHNA NP
PG RESIDENT
RADIOTHERAPY
AIIMS GORAKHPUR
Thyroid Cancer

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ANATOMY
LOCATION
At level of 2nd
& 3rd
tracheal rings
Central anterior neck at the cervical–
thoracic junction .
The bulk of the gland located immediately
anterior & inferior to the thyroid cartilage.
Two lateral lobes connected by a central
isthmus.

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 Arterial blood supply - Paired
Superior thyroid arteries (branches
of the external carotid arteries) &
Inferior thyroid arteries (branches of
the thyrocervical trunk from the
subclavian arteries).
 Venous blood drains - Paired
Superior & Middle thyroid veins to
the internal jugular veins & from the
inferior thyroid veins to the
subclavian & innominate veins.

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The lymphatic drainage of
the thyroid gland is
extensive & flows in a
multidirectional pattern.
Two groups, the lymphatic
channels travel laterally,
anteriorly, or posteriorly to
the carotid sheath to reach
the lymph nodes of the
internal jugular vein

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Anatomic location of the thyroid gland relative to the
larynx, major vessels, and draining lymphatics
Perez &
Bradys

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 Contrast-enhanced axial CT
slice at the level of the
bottom of the cricoid
cartilage (purple) showing
the position of the thyroid
gland (blue) relative to the
esophagus (orange), carotid
arteries (red), jugular vein
(lavender), and the
approximate position of the
recurrent laryngeal nerves
(yellow green)
Perez & bradys

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Etiology RADIATION EXPOSURE-
 Accidental
o 1945 Hiroshima Nagasaki bomb
o 1954 Marshal Islander Radioactive Fallout
o 1986 Chernobyl(USSR) N.Reactor accident
 Therapeutic irradiation
o Tonsil
o Nodular ds. of thyroid
o Hodgkin's lymphoma
 Prepubertal exposure is associated with higher risk
 MC type ass. with radiation exposure is papillary carcinoma
Chernobyl 1986
Nagasaki 1945
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 Hereditary –
20% of Medullary thyroid cancer are
associated with Familial MEN syndrome
 Genetic predisposition-
Mutations of the RET protooncogene on
chromosome 10 are associated with
MEN 2 syndrome
 Endemic goiter ( Iodine deficiency )
Etiology :

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. CLASSIFICATIONS OF THYROID CANCER

Non-invasive follicular thyroid neoplasm with papillary like
nuclear features (NIFTP)

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 Two major subgroups constituting DTC : PTC and FC.
 They are distinguished mainly by cytologic features:
 In PTC, Cytology is diagnostic of malignancy
 In FC, the diagnosis of malignancy requires Evidence of tumor invasion through
the tumor (not the thyroid) capsule.
 Ie, PTC is usually diagnosed by fine needle aspiration but diagnosis of FC usually
requires at least a lobectomy.

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Papillary Carcinoma
 Commonest thyroid malignancy, 75-85%
 Female:Male = 2.5:1
 Mean age at onset = 20 - 40 yr
 May affect children
 Prior head & neck radiation exposure
 Indolent, slow-growing painless mass cold on isotopic scan
 Cervical lymphadenopathy may be presenting feature

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Papillary Thyroid Carcinoma
HPE
 Nuclear enlargement, hypochromasia, intranuclear
cytoplasmic inclusions (nuclear pseudoinclusions),
nuclear grooves, and distinct nucleoli.
 After formalin fixation, nuclei may appear pale &
optically clear & resemble “Orphan Annie eyes.”

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Follicular Carcinoma
 Second most common form, 10-20%
 Females > Males, average age = 45 - 55 yr
 Rare in children
 Solitary nodule, painless, cold on isotopic scan
 50% 10 yr survival Vs 90%10 yr survival
 Haematogenous route is preferred mode of spread

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FOLLICULAR THYROID CARCINOMA
 DTC of follicular cell origin.
 Lacks the cytologic features of PTC.
 Show evidence of thyroid follicle formation
 Usually well circumscribed with a defined tumor capsule.
 Diagnosis of FC is dependent on the presence of one of two
histologic features:
 (a) Tumor invasion through the entire tumor capsule or
 (b) Tumor invasion into a blood vessel located in the tumor capsule or
immediately outside the tumor capsule.

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ANAPLASTIC CARCINOMA
 Poor prognosis
 Survival beyond 1 year is rare.
 There is no real use for an elaborate staging
system for these patients.
 Distant and lymphatic spread at presentation,
advanced age, & extremely poor differentiation
are factors that make worse prognosis.

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Anaplastic Carcinoma
 Rare; < 5% of thyroid carcinomas
 Highly malignant and generally fatal < 1yr.
 Elderly 65 yrs; females slightly > males
 Rapidly enlarging bulky neck mass
 Dysphagia, dyspnoea, hoarseness

z Medullary Thyroid Carcinoma (MTC)
 Malignant tumour of thyroid C cells producing Calcitonin
 5 % of all thyroid malignancies
 Sporadic (80%)
 Rest in the setting of MEN IIA or B or as familial without associated MEN syndrome

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Medullary Thyroid Carcinoma (MTC)
Sporadic MTC
 Middle-aged adults
 Female:male = 1.3:1
 Unilateral involvement of gland
 +/- cervical lymph node metastases
 Indolent course with 60-70% 5-yr survival after thyroidectomy
Amyloid deposits

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Hürthle Cell Neoplasms
 More aggressive than other differentiated thyroid carcinomas (higher mets/lower survival
rates)
 Decreased affinity for I131
 Need to differentiate from benign/malignant
 65% of tumors > 4cm are malignant
 If malignant, needs total thyroidectomy and I131
with thyroglobulin assays
 Mets may be more sensitive to I131
than primary

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Thyroid Neoplasm
Benign Malignant
Secondary
Primary
Follicular
Cells
Parafollicular
Cells
Lymphoid
Cells
Lymphoma
Medullary
Differentiated Undifferentiated
Anaplastic
Follicular
Papillary
Hurthle Cell

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Clinical Presentation :
A lump in the front of neck
Dysphagia
Dyspnoea
Hoarseness of voice
Swollen lymph nodes in neck
Pain in throat or neck
Fracture/ cord compression or other
symptoms depending on site of metastasis.

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Important History
 Radiation to neck / chest
 MEN syndrome
 Family history
 Diarrhoea
 Adrenal tumour
 Recent change in a pre-existing goitre
 Size change/nodularity
 Vocal cord palsy

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USG Neck :
•Features –
o Solid vs Cystic lesion
o Hypoechoic lesions
o Irregular lesions
o Microcalcifications
o Vascularity on doppler
•Advantages-
o Easy for follow up
o Identify lymph node mets
o Sensitive for intrathyroid lesion
o Pick up asymptomatic nodules
o Economical
Sensitivity – 90 %
Specificity – 82%

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FNAC
 Neck US with Doppler and FNAC arestandard diagnostics fot thyroid nodules
Accurate for Papillary and Medullary carcinoma, but not for follicular cancer
Accuracy 70-95% (guided) for nodule >2cm
Advantage –
o Minimally invasive
o Evaluation of non-palpable nodules
o Visualisation of suspicious nodules
 Drawback – can’t differentiate between follicular adenoma & follicular carcinoma

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FNA Results of Thyroid Nodule

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Excisional Biopsy :
Indicated for :
 Follicular carcinoma
 In distinguishing follicular carcinoma from benign adenomas
 To establish the diagnosis for Hürthle cell carcinoma
 To distinguish anaplastic carcinoma from undifferentiated variants .

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MRI / CT :
 Advantages-
 Detect otherwise clinically occult nodule
 Useful in pre-surgical planning
 Disease extent to assess the need for extended neck dissection
 MRI superior to CT :
-local extent of disease
-no interference with subsequent I-131 therapy
 In CT, if contrast used, I-131 therapy delayed for adequate efficacy

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Thyroglobulin :
 By normal thyroid tissue & most non medullary thyroid cancers
 Elevated serum thyroglobulin in
o Grave’s disease
o Hashimoto’s thyroiditis
o Benign nodule
o Malignant nodule
 Not useful for initial diagnosis
 Useful in follow up after thyroidectomy for detection of recurrence or progression of
disease

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Nuclear Medicine Studies
 Radioactive Uptake Study (RAIU)
 Diagnostic Whole Body Scan
 Post-treatment Whole Body Scan
 Thyroid Scan

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RAIU
 To quantify the RAI-concentration ability of
remnant thyroid tissue.
 Patient preparation :
o Withdraw thyroid hormone at least 2 wk
o No prior contrast study 4-6 wk
o No amiodarone, betadine
o Fasting ~ 2 hr
 Radiotracer : I-123 200-400 µCi (oral)
 Uptake detected by Gamma probe
 Normal – 15% uptake after 6 hours

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Diagnostic / Post-Rx Whole Body Scan
 Indications :
 Evaluate residual thyroid tissue
 Evaluate functioning metastasis
 To determine therapeutic dose of I-131
 Evaluate treatment response
 Surveillance following initial treatment
 Arguments against whole body scans :
 Low sensitivity
 Stunning of residual cancer cells
 Unnecessary radiation exposure

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Diagnostic / Post-Rx Whole Body Scan
 Patient preparation :
 Thyroid hormone withdrawal for 4 weeks
 TSH > 30 mIU/L
 Low-iodine diet 1-2 weeks
 Radiotracer
 Diagnostic - I-131 (1 to 3 mCi)
 Post-Rx – I-131 (30 to 250 mCi)
 Detection by Gamma camera
 Diagnostic - 3 days after I-131 administration
 Post-Rx – 7 days after I-131 administration
 Records images of distribution of RAI in entire body

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Diagnostic Whole Body Scan
No uptake
in thyroid
bed
Negative
WBS

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Post-Rx Whole Body Scan
Multiple foci of uptake in the left thyroid bed, lungs, right humerus, ribs, acetabulum, and
femurs Follicular thyroid carcinoma with multiple bone metastases

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Thyroid Scan
 Radiotracer- I-123, I-131 or Tc-99
 Thyroid imaged with gamma camera
Use-
Evaluation of thyroid nodule – functional or not
(hot or cold) Hot Nodule
Cold Nodule

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Staging For Differentiated Thyroid Cancer
In differentiated thyroid carcinoma, several classification
and staging systems have been introduced.
 AMES system/AGES System/GAMES system
 TNM system
 MACIS system
 National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

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Prognosis
 GAMES scoring (Papillary & Follicular Cancer)
 G Grade
 A Age of patient when tumor discovered
 M Metastases of the tumor (other than Neck LN)
 E Extent of primary tumor
 S Size of tumor (>5 cm)
The patient is then placed into a high or low risk
Category
Age for poor prognosis has been raised from 45 to 55 years (AJCC 8th
Edition)

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Prognosis of Thyroid Carcinomas
Papillary Best prognosis
Follicular
Medullary
Anaplastic Worst prognosis

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AMERICAN JOINT COMMITTEE ON CANCER (AJCC) 8th EDITION (2017) TNM STAGING SYSTEM FOR
THYROID CANCER
Papillary, Follicular, Poorly Differentiated,
Hurthle Cell & Anaplastic Thyroid Carcinoma

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TNM Classification :
T1 T2 T3

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z TNM Classification :
T4b
T4a

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TNM Classification :
N stage Description
Nx Regional lymph nodes cannot be assessed
N0 No evidence of regional lymph node metastasis
N0a: One or more cytologic or histologically confirmed benign lymph nodes
N0b: No radiologic or clinical evidence of locoregional lymph node metastasis
N1 Metastasis to regional nodes
N1a: Metastasis to level VI or VII (pretracheal, paratracheal, prelaryngeal /
Delphian or upper mediastinal) lymph nodes; this can be unilateral or bilateral
disease
N1b: Metastasis to unilateral, bilateral or contralateral lateral neck lymph nodes
(levels I, II, III, IV or V) or retropharyngeal lymph nodes

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OUTCOME AND PROGNOSTIC FACTORS
 The most important prognostic factor for disease recurrence & cancer mortality is
the Histologic classification.
 DTC, when diagnosed in an early stage, has a favorable prognosis.
 Tall cell variant can have a 10-year mortality of up to 25%.
 Columnar cell variant and diffuse sclerosing variants likewise carry a poor prognosis
relative to other forms of DTC.
 Follicular-variant PTC & classic histology have the same prognoses, which is similar
to that of follicular thyroid cancer.

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Treatment Modalities :
Surgery
I-131 Therapy
Hormone Therapy
EBRT

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Surgery
 Mainstay of treatment for most thyroid cancer
 Total thyroidectomy is usually recommended
 Lobectomy is used for -
o Low-risk cases
o Solitary differentiated lesion <1 cm
o With no evidence of vascular invasion, capsule involvement or
suspicious nodes

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Surgery
In higher-risk features : complete thyroidectomy
should be undertaken (followed by remnant ablation)
Remnant ablation with 131-I should not be performed after lobectomy
 For DTC-
Near total or Total thyroidectomy + modified radical neck dissection (if
metastatic Lymphadenopathy)

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Rationale behind NTT or TT vs. Limited surgery
High survival rate in lesions >1.5cm ( rate of local recurrence < 2% vs
14%)
 Multicentricity
 DTC which do not concentrate Iodine
 Success rate with I-131 ablation of remnant thyroid or functioning mets
increases
Post op follow up with serum thyroglobulin

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z Early post-surgical Management
 T3 –
o 20 mg tds
o After total / near-total thyroidectomy
o Stop before radioiodine scan or 131 I ablation
 Check serum calcium
 Check baseline post-op serum Tg at least 6 weeks after surgery

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Radioactive-Iodine Therapy
I-131 for DTC is arguably the most successful targeted
therapy in all of oncology.

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Radioactive Decay of I-131 :

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Post-op I-131 Ablation :
 Consider if-
o Residual tumor
o Extension beyond the capsule
o Unfavourable histology
o Consider factors like age, mets, invasion, completeness of excision, co-
morbidities
o Goals-
Thyroid remnant ablation
Adjuvant therapy for residual microscopic disease
Increased sensitivity of Tg measurements

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Patient Preparation :
COMPONENT DESCRIPTION
Low iodine diet A diet that is low in iodine (≤50 μg/d)
for 2 wk before, and 2 d after, I-131
administration
IV contrast exposure In patients who have received iv iodinated contrast
within 3 mo of the planned date of treatment, urine
iodine level is measured 1-2 wk before the planned
date of administration
Urinary iodine Measurement Ideally, urine iodine is ≤50 μg/L before cancer treatment
with I-131
rhTSH instead of T4 deprivation rhTSH 0.9-mg intramuscular injection twice (2 d and 1
d) before I-131 administration

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COMPONENT DESCRIPTION
T4 deprivation instead of
rhTSH
Stop all thyroid hormone (usually
levothyroxine, T4) replacement for as long as it
takes to raise the TSH level to ≥ 30 μU/Ml
Lithium Lithium increases radiation dose in target
tissue by increasing iodine retention time
preferentially in normal and malignant thyroid
Others :
o Scopolamine
o Avoid sour candy

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 Exclude pregnancy
 Consider pre-treatment sperm banking (if patient likely to have more
than two high dose I-131 therapies)
 If a pre-ablation scan is felt to be absolutely necessary, Tc-99m
pertechnetate scan preferable to I-131 to reduce risk of stunning

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Dose of I-131
 Approaches :
 Empiric –
All patients with the same disease risk factors gets the same dose
 Dosimetric –
Patients undergo tests of iodine metabolism to customise the dose
based on individual physiology
 Recommended-
Empiric dosing except in cases of renal insufficiency or multiple prior I-
131 treatment

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Dose
Remnant ablation :
 No prior I-131 treatment and no visible residual tumor
 I-131 administered soon after total thyroidectomy
Active surveillance
No I-131 treatment
All must be present
• pT1-2, pN0-1a, M0
• ≤ 3 positive nodes
• No ENE
• Negative margin
• Postoperative Tg <1.0 ng/mL

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Dose
30 mCi to 150
mCi
If any are present :
• pT3b
• ≥ 4 positive nodes
• ENE that is not extensive
• Positive margin and post-op Tg ≥1.0 ng/mL
200 mCi If any are present :
• pT4
• Extensive ENE
• M1(with the exception of large-volume disease)

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z Biochemical recurrence :
- Recurrent tumor based only on serum thyroglobulin level with no visible disease following at
least one prior I-131 treatment
- Observation without additional I-131 treatment is always a reasonable option
Observation–
 Life expectancy is <5 y
 When the risk of additional I-131 treatment is high-
o renal insufficiency
o peripheral blood count deficiency
o substantial dry eye from prior I-131 treatment
150 mCi is standard dose for biochemical recurrence

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Visible residual recurrent tumor
o Visible tumor on Ultrasound, CT, MRI, or PET, following salvage surgery
if applicable
o Includes –
 distant metastasis
 unresectable disease in the neck
 no visible residual disease following salvage neck surgery but
pathologic findings suggesting a high risk of recurrence (positive
margin, multiple positive nodes, extranodal extension)
Not to retreat with I-131 when the risk of another I-131 treatment is high
200 mCi is the standard dose when treating visible recurrent tumor

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z Post - Treatment
 Discharge 3 days after radioiodine Tx ( when dose rate at 1 metre is
<0.07 mSv/hr)
Commence thyroxine on discharge
Post-ablation scan 3-10 days later
Instructions on Discharge for 3 days after I-131 treatment-
o Avoid contact lenses
o well-hydrated
o at least 1 bowel movement each day
o Avoid things that stimulate saliva production chew gum or candy

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z Side Effects of Post-op I-131 Ablation
Temporary side effects –
Swelling of the saliva glands or neck:
o Usually goes away in 3-5 d
Taste change:
o Returns to normal within 3 wk after taking I-131
Nausea:
o For 1-3 d after taking I-131
o Nausea medications

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Side Effects of Post-op I-131 Ablation
Permanent side effects :
• Decrease in saliva and tears causing dry mouth, tooth decay
(cavities), and dry eyes
• Bone marrow damage
• I-131 can cause cancer to develop
• Damage to testicles or ovaries :
In women -early menopause
In men - impotence or decrease fertility

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External Beam Radiotherapy For Thyroid Cancer

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Indications :
AGE INDICATIONS
Age ≤ 18 y • Painful metastases
• Impending normal tissue damage from a
growing tumor
Age >18 y with visible and unresectable tumor • When surgery is not able to result in the
removal of all visible tumor with acceptable
morbidity
• In cases not suitable forRAI

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Indications :
AGE INDICATIONS
Age >18 yr
adjuvant treatment soon after thyroidectomy
• Most cases with stage T4 primary tumor or
nodal metastases with extensive extranodal
extension
• Age is a deciding factor
Age > 18 y: after gross total resection of a
recurrence following initial
therapy
• After complete resection, EBRT may be
considered in select patients >45-y old
with a high likelihood of microscopic
residual disease
• In cases not suitable forRAI

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z Moderate Risk of Recurrence
 For cases with no evidence of visible residual tumor, ENE or positive margins
Standard fractionation : 60/54 Gy prescriptions
CTV 60 Gy (at 2 Gy) –
o Post-op areas at high risk for recurrence - where recurrent tumor was
resected plus 1 cm margin
o dissected nodal stations with pathologically positive nodes
CTV 54 Gy (at 1.8 Gy) -
Undissected nodal stations at >10% risk of recurrence
PTVs = CTV+0.3 cm

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High Risk of Recurrence
 For cases with visible residual tumor, extra nodal extension of tumor, or positive
surgical margin
CTV 70 Gy (at 2 Gy)-
visible residual tumor and/or postoperative areas with positive margin or extra nodal
extension plus 1 cm margin
CTV 63 Gy (at 1.8 Gy)-
dissected nodal stations with pathologically positive nodes
CTV 56 Gy (at 1.6 Gy)-
undissected nodal stations at >10% risk of recurrence
PTVs = CTV+0.3 cm

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TSH Suppression for Differentiated
Thyroid Carcinoma
 Administration of supratherapeutic doses of T4 to drive the TSH below
detectable limits
Degree of TSH suppression is associated with improved relapse-free
survival
Major limitation – Thyrotoxicosis
Recommendation –
o For high-risk - TSH below 0.1 mU/L
o For low risk - TSH at or slightly below the lower limit of
normal (0.1–0.5 mU/L)

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Management of Medullary
Thyroid Carcinoma
 All patients with MTC should be tested for RET mutations
Initial primary management of localized MTC is total thyroidectomy - only
completely effective therapy
Central neck dissection should be performed in all cases and lateral neck
dissection is indicated when clinically involved
There is no role for adjuvant RAI therapy
All patients should be followed with serum calcitonin – marker for
residual disease

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Management of Anaplastic
Thyroid Carcinoma
 Goal of initial therapy- - Complete surgical excision
Surgery should be avoided if complete excision is not possible
No role of RAI
EBRT -
o Standard of care for palliation of local symptoms
o Adjuvant therapy in completely resected tumor (total dose of 60 to 75 Gy)
Even with hyper concomitant chemoradiotherapy ( docetaxel, paclitaxel,
vincristine, cisplatin, or doxorubicin) outcomes remain grim.

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Post Treatment Follow-up :
 Voice dysfunction –
o Direct / indirect laryngoscopy
 Monitor calcium
 Suppression of serum thyrotrophin-
o Levothyroxine to maintain TSH < 0.1 mIU/ml
o Average dose is 175 mcg to 200 mcg
 Measurement of serum thyroglobulin

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Long-term follow-up :
Lifelong follow-up is important because:
 Disease has a long natural history
 Late recurrences can occur which are readily amenable to Tx
80

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Long Term Follow-up :
 High risk patients warrant more vigorous follow up and many will require
retreatment
 Every 6 to 12 months following primary therapy –
o Neck US
o Serum Tg
 Serum Tg is the most sensitive means of detecting persistent or recurrent
tumor after surgery and RAI
 DxWBS and PET-CT scans are utilized only when clinically indicated

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THYROID.pptx ENT surgeon dr Vishakh k nair

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