Thyroid malignancies

Dr Rajesh P S
Thyroid cancer
Anatomy of the Thyroid Gland

• Two lateral lobes

• 50% have Pyramidal lobe:- Remnant of
• Thyroglossal duct
• Weighs 10-20 gm , size 5*5 cm
• Extension:- Mid Thyroid cartilage to 6th Tracheal ring
• Recurrent laryngeal nerves, sympathetic trunks,
• Vagus and phrenic Nerve lies posteriorly
Arterial supply :-
• Superior thyroid artery
• Inferior thyroid artery
Venous drainage :-
• Superior thyroid vein and middle thyroid vein
• Inferior thyroid vein
Lymphatics :-
• First Echelon nodes Level 6
• Second echelon nodes Level 3-4,
• supraclav LN, Level 7 LN
• Lesser extent Level 2
• Rarely Level 1
Microscopic Picture of the Thyroid Gland
Thyroid Cancer Classification (cell of origin)

1. Follicular epithelial cell Papillary variants

• Classic
A. Differentiate Thyroid cancers
• Papillary microcarcinoma
a. Papillary and mixed papillary variants • Encapsulated
• Follicular variant
b. Follicular cancer
• Aggressive variant
B. Poorly differentiated thyroid cancer • Diffuse sclerosing
• Insular carcinoma • Tall cell variant
• Columnar cell variant
C. Undifferentiated Thyroid cancer
2. Parafollicular cell
Follicular
A. Medullary Carcinoma • Classic
• Hurthle cell variant
Classification (ability to concentrate RAI)

A. Usually concentrate RAI

• Classic papillary
• Encapsulated papillary
• Follicular variant and mixed follicular papillary
• Follicular variant
B. Frequently do not concentrate RAI
• Tall cell and columnar cell variant of papillary carcinoma
• Hurthle cell
• Poorly differentiated
C. Never concentrate RAI
• Anaplastic
• Medullary
Risk factors

Exposure to radiation in childhood #

• Increased risk of well differentiated cancer (0.1Gy)
• Latent period 3-5 yrs
• Risk remain apparent even after 40 yrs
Victims of nuclear disaster
Family history (first degree relatives)
History of thyroid cancer syndromes
• Familial Adenomatous polyposis
• Cowden disease
• Carney complex
Medullary cancer thyroid syndromes (MEN2A/MEN2B)
Hashimoto thyroiditis (thyroid lymphoma)
Epidemiology

• Most common endocrine malignancy

• Incidence 7.7 per 1lakh
• Females 3 times more commonly affected than males.(5th most common cancer in
females)
• Most common histology papillary thyroid cancer
• DTC (90%), Medullary (5-9%), Anapalstic (1-2%), lymphoma (1-3%), sarcoma (<1%).
• Mean age of presentation 40-45 yrs (females), 65-69 yrs (males).
• In India relative frequency of thyroid cancer 0.1%–0.2%.
• The AAR per 100,000 is about 1 for males and 1.8 for females as per the Mumbai Cancer
Registry, which covered a population of 9.81 million subjects.
• Highest incidence is in Thiruvanantpuram district.
Presentation

• Thyroid nodule (m/c), incidental finding

• Increased suspicion of malignancy :-
• Rapid growth
• Firmness
• Fixation
• Vocal cord paralysis
• Dysphagia
• Cervical adenopathy
• Advance cases presents with :-
• Airway compromise
• Hoarseness of voice
• Pain
• Weight loss
• Respiratory distress
Diagnosis

• Laboratory Studies :-
• CBC
• RFT/LFT
• Serum TSH
• Thyroglobulin, T3 and T4
• Serum calcitonin (Medullary Thyroid cancer)
• Cervical (Neck) Ultrasound
• Ultrasound Guided FNA (for both palpable and incidental finding)
• Sensitivity (100%), Specificity (67%)
• Positive predictive value (87%), Negative predictive value (100%)
• Limitation :- Inability to distinguish benign follicular adenomas from FC and Follicular PTC.
• CT scan and MRI
• Generally not recommended because of the use of iodinated contrast, which hamper RAI therapy.
Ultrasound findings subjected to FNA
-

Papillary thyroid cancer

• Orphan Annie eye Nuclei
• Psuedo-inclusion
Nuclear Medicine studies
Radioactive Iodine Uptake
• Historical importance
• To quantify RAI concentrating ability of remnant thyroid tissue
Diagnostic whole body scan
• Some used as apart of surveillance
• Utility controversial
• Drawback :- Low sensitivity, stunning of residual cancer cell, unnecessary radiation exposure
Therapeutic whole body scan
• Done in every patient receiving RAI
• Used to detect gross residual disease
• RAI concentrating ability of diseased tissue
FDG PET
• Predictive value of PET is not well defined
• Used to detect metastases
Prognosis

• Histologic classification
• Age
• Gender
• Primary tumor size
• Multifocality and extra thyroidal extension
• Lymph node and Distant metastases
• RAI concentrating ability
Prognostic scoring systems
AGES
• Age
• Tumour Grade
• Tumour Extent
• Tumour Size
AMES
• Age
• Metastases
• Extra thyroidal extension
• Size
MACIS
• Metastases
• Age
• Completion of resection
• Local Invasion
• Tumour Size
TNM staging
Management

Surgery
• Primary treatment
• Total thyroidectomy is preferred
Complications:-
• Recurrent laryngeal nerve injury
• Hypoparathyroidism
• Injury to Vagus nerve, spinal accessory nerve, superior laryngeal nerve
Lobectomy Indications: (NCCN guidelines)
• Patients Age 15-45 yrs
• Tumour size <4 cm without prior RT
• Lymph nodes or Distant metastases
• Extra thyroidal extension
• Aggressive histology
Indications of surgical evaluation in non diagnostic thyroid nodule :
• Suspicious cytology for PTC
• Cytology contains follicular cells with no concordant functioning nodule on RAI scan
• Cytology contain Hurthle cell Neoplasm
• Growing nodule
Radio active iodine therapy
Goals
• Thyroid remnant ablation
• Adjuvant therapy for residual microscopic disease
Patient Selection for RAI

• Distant metastases
• Gross extra Thyroidal extension
• Tumour size 1-4 cm with
• LN metastases
• High risk features
• Age >45 yrs
• Intrathyroidal vascular invasion
• Multifocal disease
• Aggressive histological variants
• Follicular and Hurthle cell variants are high risk tumors always requiring RAI
• Not recommended when
• Tg <1 ng/ml
• Anti Tg antibodies and RAI imaging are negative
Role of Radiotherapy

• No Randomise trial to indicate benefit of RT

• European multicentre study on DTC trial was planned but
terminated prematurely
• Converted to prospective cohort study but fails to show any
benefit
• In general patients with unresectable Thyroid cancer are treated
with primary EBRT
• Palliation in symptomatic metastatic tumours (20-30 Gy in 5 -10 #)
EBRT planning

Target volumes :
• Gross tumour Volume :- residual gross disease
• High Risk CTV :- positive margins , Extra Thyroidal extension,
Lymph node with extra capsular disease, gross residual disease.
• Standard risk CTV :- region at moderate risk for residual disease
(electively irradiated nodal regions)
Chemotherapy
• Indicated in patients refractory to Radioiodine therapy and rapidly
progressive disease.
• Drugs approved by FDA :- Doxorubicin, Sunitinib
• Newer drugs :-
• Vandetanib
• Pazopanib
• Selumetanib (MEK inhibitor) shown to reverse the loss of RAI avidity
Follow up
• Every 6-12 month:
• Serum Tg analysis (Negtive predictive value of 99%)
• Neck USG
• DxWBS and PET CT when clinically indicated (Elevated Tg)
Recurrence
• Locoregional and nodal recurrence :- MRND or central Neck dissection .
• More aggressive surgery in case of aero-digestive tract invasion.
• Tracheal stents and tracheostomy for unresectable cancer.
• For smaller LN not amenable to surgery:- USG guided ethanol ablation.
• For radioiodine avid metastasis :- I131 is used as long as disease responds.
• Few patients may require metastasectomy, laser ablation and EBRT for
palliation.
Anaplastic Thyroid Cancer

• Rare but more aggressive

• Poor Prognosis (Median OS < 6 months)
• Female > Male
• All classified as Stage IV
• IV A limited to thyroid
• IV B with local invasion
• IV C distant mets (Lungs and Bones m/c)
• Symptoms :- Rapidly progressing mass with LN met causing compression.
• Diagnosis :- USG guided FNA  Core biopsy
• Workup:- USG Neck, CT scan (neck thorax and brain), PET CT.
• Management:- surgery if resectable , unresectable NACT+ EBRT surgery.
• Adjuvant radiotherapy with or without chemo should be started as soon as possible.
• Chemo :- Doxorubicin + Platins (first line)
• Ongoing Trials:-
• Pazopanib + paclitaxel
• Imatinib
• Fosbretabulin
• Erlotinib
• Geftinib
Medullary Thyroid carcinoma

• Should be tested for RET mutations.

• Genetic screening and testing indicated.
• Primary management  Surgery (total thyroidectomy).
• Central neck dissection should be done in all cases.
• No role of adjuvant RAI therapy
• Follow up by serum calcitonin level  marker for residual.
• EBRT
• Children Age <18 yrs :- RT reserved for palliation.
• Adults :-
• Unresectable gross disease
• High risk of microscopic disease (positive margin, T4, nodal mets,
extracapsular extension.)
• No role of cytotoxic systemic therapy.
• Promising preclinical and early clinical results with TKI
Conclusion

• Management of thyroid cancer is a multidisciplinary strategy and a close

coordination and cooperation is essential in diagnosis and long term follow-up.
• Surgery and the judicious use of radioactive iodine, as described in the
guidelines, is sufficient treatment for the majority of patients with
differentiated thyroid cancer.
• A rigorous and prolonged that is life -long observation should be mandatory
and this should be indicated to the patients as well as family by the treating
doctor.
• A minority of these patients experience progressive, life threatening growth
and metastatic spread of the disease. For these individuals, experimental
treatments may be considered.