Papillary Neoplasm of Thyroid

1. Thyroid Malignancy
(Papillary Neoplasm)
Nabin Paudyal

2. Introduction
• Generally differentiated into
• Diffuse Thyroid Carcinoma (DTC)
• Papillary Diffuse Thyroid Carcinoma
(PDTC)
• Medullary Thyroid Carcinoma (MTC )
• Anaplastic Thyroid Carcinoma (ATC)
• Other rare types
• Primary thyroid lymphoma
• Thyroid sarcoma
• Metastasis to thyroid
• Another classification system
• Differentiated
• PTC
• FTC
• Hurthle cell carcinoma [HCC]
• Non differentiated
• PDTC
• ATC
• Neuroendocrinal tumors
• MTC

3. Incidence of thyroid malignancy
• DTC makes majority of thyroid cancer
• PTC 84%
• FTC 11%
• MTC 2%
• ATC 1%
• ATC is most aggressive and lethal solid tumors with nearly 100%
mortality

4. Differentiated thyroid cancer
Diffuse, Papillary and Hurthle cell

5. Differentiated Thyroid Cancer
• PTC, FTC, HCC are primary cancers arising from thyroid follicles
• DTCs are generally approached and managed similarly
• PTC
• 84% of all incident cases
• Female: Male = 3:1
• 3rd-5th decade
• Disseminates through lymphatic route. Late cases metastasizes to lungs and bones
• Histologically  Complex branching papillae with pseudo inclusions, nuclear grooving
and psammoma bodies
• Variants include Follicular variant, tall cell variant, hobnail, diffuse sclerosing, columnar variants.

6. • FTC
• Older adults
• 4th-6th decade
• F:M = 3:1
• Hematogenous spread; early spread to lungs and bones
• Cytologically can range from virtually normal-appearing follicular cells to those with
abnormal features including nuclear atypia, discohesion, hypercellularity and micro
follicles
• Thus FTC cannot be reliably diagnosed by FNA. FTC can only be diagnosed on histologic
examination based on presence of capsular and vascular invasion
• HCC
• Less common type of DTC with distinct and more aggressive behavior
• Older adults, 6th-7th decade
• Both lymphatic and hematogenous metastasis
• Less RAI-avid compared to other DTCs. (< 38% tumors being RAI-avid)
• Hurthle cells neoplasm have abundant eosinophilic granular cytoplasm due to increased
number of mitochondria.

7. Oncogenesis
• 2 major molecular mechanisms
• MAPK signaling
• PI3K/AKT
• Alterations at multiple points in these pathways have been linked
directly to pathogenesis of thyroid cancer
• In 2014, Cancer Genome Atlas Project identified dominant and
mutually exclusive roles of driving somatic genetic alterations in
MAPK and PI3K/AKT pathways in PTC

9. Risk factors
• History of ionizing radiation exposure
• Childhood exposure is considered high risk
• Family history of DTC
• Single-gene mutation hereditary cancer syndromes
• Gardner syndrome (PTC)
• Cowden syndrome (FTC and occasionally PTC)
• Carney complex (PTC and FTC)
• Werner syndrome (PTC and FTC)
• Obesity
• Environmental exposure to volcano gas (dicarbomodiphenyl ether
and tris(2-chlorophenyl) phosphate)

10. Clinical presentation
• Asymptomatic, palpable thyroid nodule
• Incidental discovery
• DTC
• Slow growing, painless
• Concerning features include rapid growth of the nodule, symptoms like hoarseness,
coughing, dysphagia (signal of invasion into surrounding structures like RLN and
aerodigestive tract)
• On P/E soft to firm in consistency, freely mobile/fixed mass
• Palpable LAD may also be present

11. Imaging workup
• Comprehensive thyroid USG with LN mapping of bilateral central and
lateral LN
• Pre-operative USG is the most sensitive test for characterization of thyroid
nodules as well as identification of pathologic LAD
• Cross-sectional CECT/contrast-MRI of neck and chest for more
advanced lesions
• Done if patient has symptoms like voice changes, dysphagia, respiratory
symptoms (cough OR hemoptysis), palpable fixed growth in the neck
• USE OF PET SCAN FOR THYROID MALIGNANCY IS NOT RECOMMENDED

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13. Limitation of TNM staging
• Risk of recurrence cannot be
assessed using this system

14. Surgical Management of DTC
• Surgery Mainstay. Thyroidectomy is safe and effective.
• Extent of surgery depends upon multiple factors like extent of disease
and patient’s perioperative risk
• Surgery Total thyroidectomy is preferred in following scenarios
• Indications:

15. Surgical Management of DTC
• For unilateral DTCs that are 1-4 cm in size without extrathyroidal extension
ipsilateral thyroid lobectomy
• For DTCs with clinical/radiological evidence of cervical LN metastasis
compartment based LN dissection is recommended
• Central compartment (Level VI and level VII)
• Lateral compartment (Levels II, III IV and Vb)
• Therapeutic LN dissection should be performed in patients with radiographic or
clinical evidence of metastatic disease as determined either preoperatively or
intraoperatively
• Prophylactic central node dissection is performed for cases with cN0 papillary thyroid
carcinomas with advanced primary tumors

16. Active non-operative surveillance
• Locally invasive primary tumors involving structures like trachea, strap
muscles, esophagus, larynx and RLN PRE-OPERATIVE PLANNING WITH
CECT is useful.
• Multidisciplinary assistance are recommended for complex tumors
requiring segmental laryngotracheal or esophageal resection.
• Papillary thyroid microcarcinoma < 1 cm
• Subject of ongoing active research

17. Post-operative TSH suppression
• After thyroidectomy of DTC, TSH suppressive doses of thyroid hormone
medication is recommended to prevent hypothyroidism and reduce risk for
TSH stimulated tumor growth and recurrence.
• Degree of suppression required for survival benefit remains controversial.
• Permissible level of TSH after surgery
• Low-to intermediate  0.1-0.5 mU/L
• High-risk tumors < 0.1 mU/L

18. Radioactive iodine
• Mechanism Thyroid follicular cells take up iodine Radioactive iodine
(131) is taken up by the thyroid follicular cells and lead to selective
destruction of thyroid tissue
• Perks : Normal tissues uptake radioiodine >> Malignant ones Henceforth,
radioactive iodine is given only post-thyroidectomy as an adjunct
• Indications
• Ablation of residual normal tissue after thyroidectomy
• Treatment of clinically detectable disease that cannot be resected surgically.
• RAI is indicated usually for high-risk cancers

19. How is RAI given?
• Administer in low iodine state and in setting of high TSH
• Two methods of obtaining high TSH levels
• Administration of recombinant human TSH
• Thyroid hormone withdrawal
• Dosage
• Ablation dosage: 30-50 mCi
• Treatment dosage: 100-150 mCi
• Repeat until evidence of thyroid cancer remaining iodine avid

20. • Adverse effects
• Sialadenitis
• NLD obstruction
• Transient thyroid swelling
• Development of secondary malignancy
• Contraindications
• Pregnancy
• Breast feeding

21. Adjuvant therapy for DTC
• EBRT
• Indications
• Local control of unresectable locally advanced macroscopic/ microscopic residual disease
after thyroidectomy
• Symptomatic distant metastatic foci that are RAI nonavid
• Percutaneous ethanol injection
• Radiofrequency ablation of lung OR bone metastasis
• Palliative embolization

22. Systemic therapies for advanced thyroid
cancers
• Advanced thyroid cancers include
• Locally advanced, rapidly progressive, metastatic DTC/PDTC and MTC as well as ATC
• Multimodal therapy
• As of 2023
• 4 US-FDA approved tyrosine kinase inhibitor drugs available for thyroid
cancers
• Lenvatinib and Sorafenib For RAI resistant DTC
• Vandetanib and Cabozantinib For advanced MTC
• Unfavorable side effect profile. Counselling must be done.

23. Novel agents
• Selective BRAF and MEK inhibitor Dabrafenib, Trametinib for
unresectable ATC
• Preclinical/ Early-phase clinical trials have tumor’s ability to be radiosensitive and
take up RAI after treatment with BRAF or MEK inhibitor
• PI3K/Akt pathway inhibitor Rapamycin, everolimus, temsirolimus
• DTC, MTC and ATC
• Loxo-292 selective RET inhibitor under trial
• PD-1 Ligand Pembrolizumab, Spartalizumab and nivolumab