MANAGEMENT OF

THYROID
NEOPLASM
PRESENTED BY DR. ASHIS RANJAN SAHA
1ST YEAR DNB RESIDENT
NAZRETH HOSPITAL
Presentation
• Solitary or Multiple thyroid nodules
• Neck swelling
• Hoarse voice of recent onset
• Dysphagia
• Bone or lung metastasis
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
Diagnosis
• Laboratory: • Imaging
• TSH • U/S
• T3, T4 • C.T
• Serum • MRI
Thyroglobulin • Scintigraphy
• Serum Thyroid
Antibodies
• FNA
Laboratory
• Most patients are Euthyroid.
• Hyperfunctioning nodule  1% chance of malignancy.
• Serum Tg cannot differentiate between benign and
Malignant nodules
• Tg is used for:
• F/U after total thyroidectomy
• Serial F/U for non-operative treatment
• Serum Calcitonin  patients with MTC, or with
family history of MTC (MEN2)
FNAC
ATA NCCN
• Nodules ≥1cm with high • Nodules >1 cm if
or intermediate risk suspicious features are
features present
• Nodules ≥1.5 cm with • Nodules >1.5 cm if no
low risk features suspicious features are
• Nodules ≥2 cm with very present
low risk features,
consider FNA;
observation is a
reasonable alternative
• Sensitivity and specificity exceeding 90% in iodine-sufficient.

• Most authors recommend 2 to 4 aspirations per nodule.

• Routine use of ultrasound-guided biopsy

• A satisfactory specimen must contain at least five groups of 10

to 15 well-preserved cells.
• immunostaining for galectin-3 either alone or combined with
TPO suggested as a valuable adjunct to indeterminate
nodules.

• 17 single gene oncogenic mutations or translocations in BRAF,

RAS, RET/PTC, and PAX8/PPARγ demonstrated promise as an
effective diagnostic marker

• RNA gene expression classifier (GEC) using microarray

technology through analysis of the expression patterns from
162 genes
ULTRA SONOGRAPHY
• Papillary thyroid cancer is characterized by the following US
features:

• Solid or predominantly solid

• Hypoechoic
• Microcalcifications (highly specific)
• Infiltrative irregular margins (common)
• Increased nodular vascularity
Follicular thyroid cancer is characterized by the following US
features:

• Isoechoic to hyperechoic
• Thick, irregular halo

Benign US features are as follows:

• Purely cystic nodule
• Spongiform appearance (aggregation of multiple microcystic
components >50% volume)
External Scintiscanning
Computed Tomography
• CT scan does not distinguish benign from malignant nodules and
does not assess functional status

• Anaplastic thyroid carcinoma-first-line technique to identify lymph

node metastases and to define the tumor’s relationships to
surrounding structures

• CT imaging is less sensitive than neck ultrasonography for the

detection of lymph node metastases

• The most sensitive tool for the detection of micrometastases in the

lungs

• CT should be performed at least 4 weeks before any administration

of radioiodine
Magnetic Resonance
Imaging
• Recurrent neoplasms in the thyroid bed or regional lymph
nodes can be detected with MRI.

• Recurrence is characterized by a mass with low to medium

intensity on T1-weighted images and medium to high signal
intensity on T2-weighted images

• MRI may better delineate any involvement of the

aerodigestive axis

• MRI is useful for assessment of the extent of bone

involvement in cases of axial bone metastases from follicular
cell–derived carcinomas and MTC, which are poorly visualized
on bone scintigraphy.
Positron Emission
Tomography
• To localize disease in Tg-positive patients (having serum Tg
levels > 10 ng/mL) with no other abnormality on diagnostic
imaging;
• it is mostly useful for the detection of lymph node metastases
in the posterior neck and mediastinum or distant metastases.

• For the initial staging and follow-up of patients with

anaplastic, poorly differentiated, or Hürthle cell thyroid
cancers
• As a measurement of post-treatment response following local
(external beam irradiation, surgical resection, thermal
ablation, embolization) or systemic therapy.
TREATMENT OPTIONS
Medical
• Radioactive Iodine ablation therapy.
• Chemotherapy (Adriamycin, Cisplatin).
• Post-operative Thyroid hormone-
1)Replacement therapy.
2)Suppression of TSH release. (↓ recurrence)

• Surgical
Treatment options
Surgical treatment Other treatment
• Lobectomy • RAI
• Total thyroidectomy • Chemotherapy
• Thyroidectomy with neck • EBRT
dissection • Ablation Techniques
Surgical treatment
• Papillary CA
The NCCN considers either total thyroidectomy or lobectomy to
be acceptable for patients-
• No prior radiation
• No distant metastases
• No cervical lymph node metastases
• No extrathyroidal extension
• Tumor < 4 cm in diameter
NCCN guidelines recommend total thyroidectomy for patients :-

• Radiation history
• Known distant metastases
• Bilateral nodularity
• Extrathyroidal extension
• Tumor >4 cm in diameter
• Cervical lymph node metastases
• Poorly differentiated tumor
If a lobectomy is performed, completion of the thyroidectomy is
recommended-
• Tumor >4 cm in diameter
• Positive margins
• Extrathyroidal extension
• Macroscopic multifocal disease
• Macroscopic nodal metastases
• Confirmed contralateral disease
• Vascular invasion
ATA guidelines recommend
• Near-total or total thyroidectomy for all patients with thyroid
cancer greater than 1 cm

• Lobectomy may be considered for small (< 1 cm), low-risk,

thyroidal papillary carcinomas in the absence of prior radiation
or clinically involved cervical nodal metastases.
Therapeutic neck dissection
• Clinically involved central or lateral neck lymph nodes should
accompany total thyroidectomy to provide clearance of
disease from the central neck.

• Prophylactic central-compartment neck dissection (level VI)

may be considered in patients with clinically uninvolved
central neck lymph nodes, especially for advanced primary
tumors (T3 or T4).
Follicular and Hürthle cell
cancer
• The ATA recommends a total thyroidectomy for patients with
indeterminate nodules in any of the following situations:

• The tumor exceeds 4 cm

• Presence of bilateral nodule
• Marked atypia is observed
• Biopsy result is reported as “suspicious for papillary
carcinoma”
• The patient has a family history of thyroid carcinoma
• The patient has a history of radiation exposure
• Lobectomy plus isthmusectomy as the initial surgery.

• prompt completion of thyroidectomy if invasive cancer is

found on the final histologic section.

• Therapeutic neck dissection of involved compartments is

recommended for clinically apparent/biopsy-proven disease.

• Total thyroidectomy as the initial procedure only if invasive

cancer or metastatic disease is apparent at the time or
surgery, or if the patient wishes to avoid a second, completion
thyroidectomy
Medullary Thyroid Cancer
• Total thyroidectomy and bilateral central neck dissection (level
VI) for all patients with tumor size 1 cm or greater or who
have bilateral thyroid disease.

• Therapeutic ipsilateral or bilateral modified neck dissection for

clinically or radiologically identifiable disease (levels II–V)

• Prophylactic ipsilateral modified neck dissection for high-

volume or gross disease in the adjacent central neck may be
considered.

• Pheochromocytoma removal prior to thyroid surgery

Prophylactic total
thyroidectomy
• RET mutation carriers once the mutation is confirmed.

• Patients with less aggressive mutations (designated ATA

moderate-risk), thyroidectomy may be delayed >5 years

• Children with MEN2A and mutations at codon 634 (designated

high-risk) are advised to undergo thyroidectomy at <5 years of
age.
• MEN2B-related mutations (designated highest-risk) should
undergo the procedure before age 1.

• Central neck dissection can be avoided in children who are

RET-positive and calcitonin negative with a normal ultrasound
examination.
Anaplastic Carcinoma
• The 2012 ATA guidelines recommend-

• Total lobectomy or total or near-total thyroidectomy with a

therapeutic lymph node dissection for intrathyroidal
anaplastic thyroid cancer.

• Extrathyroidal invasion, an en bloc resection should be

considered if grossly negative margins (R1 resection) can be
achieved
Radioiodine therapy
• NCCN guidelines recommend radioiodine therapy if any of the
following are present :-

• Extrathyroidal extension
• Tumor >4 cm in diameter
• Postoperative unstimulated Tg level >5-10 ng/mL
• Radioiodine therapy is not recommended if all of the following
are present :

• Classic papillary thyroid carcinoma

• Medullary carcinoma
• Primary tumor < 1 cm
• Intrathyroidal tumor
• Unifocal or multifocal tumor
• No detectable anti-Tg antibodies
• Postoperative unstimulated Tg < 1 ng/mL
Radioiodine therapy is selectively recommended:-

• Primary tumor 1-4 cm

• High-risk histology
• Lymphovascular invasion
• Cervical lymph node metastases
• Macroscopic multifocality (one focus >1 cm)
• Presence of anti-Tg antibodies
• Postoperative unstimulated Tg < 5-10 ng/mL
• T4 therapy should be discontinued for approximately 6 weeks
before scanning with I-131.

• Patients should receive T3(T3 has a shorter half-life than T4)

• TSH Levels >30 mU/L are considered optimal

• A low iodine diet also is recommended during this 2-week

period.
• The usual protocol involved administering a screening dose of
1 to 3 mCi and measuring uptake 24 hours later

• Current guidelines recommend using either 123I or low-

activity 131I (1- to 3-mCi dose) and delivering a therapeutic
dose within 72 hours.

• The recommended dose of RAI is 30 mCi if remnant ablation is

performed after total thyroidectomy for ATA low-risk or
intermediate-risk cancer

• RAI is given for adjuvant treatment to treat suspected

microscopic disease(in the absence of metastatic disease),
doses ranging from 30 to 150 mCi are recommended
• RAI is given for adjuvant treatment to treat suspected
microscopic disease(in the absence of metastatic
disease)doses ranging from 30 to 150 mCi are recommended

• If patients have an elevated Tg level, but negative RAI scan on

follow-up, some physicians recommend treating once with
100 mCi of 131I and repeating the imaging 1 to 2 weeks later.

• The maximum dose of radioiodine that can be administered at

one time approximately 200 mCi with a cumulative dose of
1000 to 1500 mCi.
Thyroid Hormone & TSH
Supression
• TSH levels <0.1 mU/mL in high-risk thyroid cancer

• 0.1 to 0.5 mU/mL in intermediate-risk disease.

• For low-risk patients (with or without remnant ablation) with

undetectable serum Tg levels, TSH levels can be maintained at
the lower end of the reference range (0.5–2 mU/L).

•
• If these patients have low measureable Tg levels, it is
recommended that TSH be maintained at or slightly below
lower limit of normal (0.1 to 0.5 mU/L)

• The risk of tumor recurrence must be balanced with the side

effects associated with prolonged TSH suppression, including
osteopenia and cardiac problems, particularly in older
patients.
Radiotherapy
• Unresectable Thyroid cancer are treated with primary EBRT
• Palliation in symptomatic metastatic tumours
Target volumes :

• Gross tumour Volume :- residual gross disease

• High Risk TV :- positive margins , Extra Thyroidal extension,

Lymph node with extra capsular disease, gross residual
disease.

• Standard risk TV :- region at moderate risk for residual disease

(electively irradiated nodal regions)
Doses
• • 66 to 70 Gy in high risk TV
• • 54 to 56 Gy in standard risk TV

Toxicity
• Early- Mucositis , Taste Changes, xerostomia, Pharyngitis,
Dysphagia, Hoarseness, Radiation dermatitis, Weight loss,
Malnutrition.

• Late complication : Fibrosis, Atrophy of skin, Neck

musculature, Tracheal and oesophageal stenosis.
Chemotherapy
• The chemotherapy drugs most commonly used to treat mainly
medullary thyroid cancer and anaplastic thyroid cancer
include:

• Dacarbazine
• Vincristine
• Cyclophosphamide
• Doxorubicin
• Streptozocin
• Fluorouracil
• Paclitaxel
• Docetaxel
• Carboplatin
• Doxorubicin is the only cytotoxic chemotherapy specifically
approved by the US FDA for use in ATC

• a typical doxorubicin-based regimen includes doxorubicin 20

mg once weekly given prior to the first radiotherapy session

• Other agents with the greatest established clinical activity in

metastatic ATC are the taxanes paclitaxel or docetaxel and
perhaps also platins.
Locally recurrent or metastatic, progressive DTC treatment
options are as follows:-

• Sorafenib and lenvatinib are VEGF inhibitors approved for DTC

refractory to RAI treatment

• Sorafenib: 400 mg PO q12h at least 1 h ac or 2 h pc

• Lenvatinib: 24 mg PO once daily with or without food

Therapy for unresectable gross residual or recurrent disease or
metastases:-

• Consider tyrosine kinase inhibitors (TKIs) such as sorafenib 400

mg PO BID or sunitinib 50 mg PO daily for 4wk of a 6-wk cycle

• Pazopanib 800 mg PO daily may be considered for progressive

or symptomatic metastatic differentiated (Hürthle cell,
papillary, and follicular) thyroid carcinoma

• Doxorubicin 60 mg/m2 as monotherapy or in combination

with cisplatin 40 mg/m2 may be considered for patients who
cannot tolerate TKIs or in whom TKIs have failed
Side effects
• Hair loss
• Mouth sores
• Loss of appetite
• Nausea and vomiting
• Diarrhoea
• Increased chance of infections
• Easy bruising or bleeding
• Fatigue
Thyroid Lymphoma
• Respond rapidly to chemotherapy (CHOP—cyclophosphamide,
doxorubicin, vincristine, and prednisone)

• Combined treatment with radiotherapy and chemotherapy

often is recommended.

• Thyroidectomy and nodal resection are used to alleviate

symptoms of airway obstruction in patients who do not
respond quickly to the above regimens or who have
completed the regimen before diagnosis.
Follow-Up of Differentiated
Thyroid Cancer
• Thyroglobulin Measurement Tg and anti-Tg antibody levels
should be measured initially at 6 to 12 month intervals

• Patients are considered to have an excellent response to

treatment if suppressed Tg is <0.2 ng/mL and stimulated Tg is
<1 ng/mL with negative imaging.

• In these patients, Tg levels can be followed every 12 to24

months while on thyroid hormone as their risk of recurrence is
low (1–4%).
• diagnostic whole-body scans 6 to 12 months after remnant
ablation may be of value in the follow-up of patients with
high- or intermediate-risk patients with higher risk features

• Cervical ultrasound be performed to evaluate the thyroid

bed and central and lateral cervical nodal compartments at 6
and 12 months after thyroidectomy and then annually for at
least 3 to 5 years,