• DTC is a spectrum of disease derived from follicular cells. Both papillary and follicular carcinomas are grouped under this. 90% of thyroid malignancies are differentiated one. Papillary (PTC), follicular (FTC) and Hurthle cell carcinomas are DTCs. Insular variety is poorly OTC having intermediate position between OTC and anaplastic; it can cause bone and lung spread; it is common in younger age group; p53 and p21 are negative; with 40% 10-year survival. 
• AGES (Mayo Clinic, Hay); AMES (Lahey clinic); MACIS; Sloan Kettering scoring - are different scoring systems used for DTCs. Sloan Kettering scoring includes low, intermediate and high-risk groups. First three scoring systems have low- and high-risk groups. 
• Papillary spreads through nodes; follicular through blood. FCT causes pulsatile vascular secondaries in skull.
• Incidence of thyrotoxicosis in DTCs is 2%. 
• Galectin - 3, RET/PTC rearrangements, CD44, leukocyte common antigen (LCA), cytokeratin are the probable tumour markers under evaluation. For indeterminate, FNAC molecular markers are used to identify RAS and BRAF mutations. 
• TNM staging tor DTCs (AJCC 2018) are:  
  • T - Tumour: Tx - Primary cannot be assessed; TO - no evidence of primary tumour; T1 - <2 cm - (T1a <1 cm; T1 b 1-2 cm); T2- 2-4 cm; T3a - >4 cm limited to thyroid ; T3b - Gross extrathyroidal extension invading strap muscles only from a tumour of any sized; T4a - Gross extrathyroidal extension invading into subcutaneous tissue, larynx, trachea, oesophagus and recurrent laryngeal nerve; T4b - Gross extrathyroidal invasion to prevertebral fascia, carotid encasement or involvement of mediastinal vessels. Suffix 's' isadded for solitary nodule; 'm' added to multiple nodules. 
  • N - Regional nodes (central/lateral neck compartment/ superior mediastinal) - Nx - regional nodes cannot be assessed. NO - no nodes; NOa - one or more cytologi- cally or histologically confirmed benign nodes; NOb - No radiological or clinical evidence of locoregional nodes. N1a- spread to level VI (pre/paratracheal, prelaryngeal) and level VII (mediastinal) nodes, unilateral or bilateral. N1b - Nodal spread unilateral or bilateral or contralateral lateral lymph nodes of level I, II, Ill, IV, V or retropharyn- geal nodes. Suffix 'san' is sentinel node; 'f' is FNAC or Core biopsy. 
  • M-Metastases-cMO- nodistantspread.cM1- distant spread present. pM1 - distant spread microscopically confirmed . Note: Age is included in staging which is an important factor. 
  • Age at diagnosis: <55 years OR >55 years. 
  
• AJCC prognostic stage groups (2018) for DTCs: 
  • Age less than 55 years:
  Stage I - Any T, Any N, MO;
   Stage II- A n y T, any N, M1. 
  • Age more than 55 years:
  Stage I-T1/T2, NO/Nx, MO.
  Stage II-T1/T2, N1, MO; T3a/T3b, Any NMO. StageIII- T4a,AnyN,MO.
  Stage IVA-T4b, Any N, MO;
  Stage IVS-Any T, Any N; M1. 
  
  

Investigations 

• US neck is essential investigation.It shows the nature,size, margin, echogenicity, vascularity, nodal status, invasion through thyroid capsule. Lymph node may show loss of hilus, round shape, hypoechogenicity, cystic changes and calcification, with increased peripheral vascularity.
• FNAC of the nodule (US-guided is ideal); it is very useful in PTC; but not much useful in FCT. FNACof the lymph nodeis useful; thyroglobulin estimation of the lymph node aspirate isvery usefuI.
• Functional status should be checked-T3,T4,TSH.TSH may be raised in PTC.MRI of neck if needed only;CTisnotdoneasiodinecontrast is not used; if needed, should be done as non-contrast CT. 

Treatment 

• Total thyroidectomy with either prophylactic (inT3 and T4 of T staging) or therapeutic (when involved sonologically or FNAC or frozen section [of node] wise) central cervical (compart- ment)nodedissection(CCND). Prelaryngeal,preandpara- tracheal, nodes above the level of innominate vein and up to carotids and hyoid bone are removed often may be with thymus (compartment). CCND provides accurate staging; treats micrometastases (90% in PTC in central nodes) which may be often the cause for recurrence or persistence of disease; central nodes being primary nodes are commonly involved. It also provides accurate RAI dosing; lowers the postoperative serum thyroglobulin level which facilitates the accurate TG monitoring during follow up. Reoperation of CCND is technically difficult after total thyroidectomy as a separate sitting. But there is no oncological survival benefit andincreasedchancesofpostoperativehypoparathyroidism and recurrent laryngeal nerve injury. Lateral cervical node dissection (LCND. Nodes -IIA, Ill, IV and VB) is done only when it shows the evidence of involvement (by FNAC or US); there is no rolefor prophylactic LCND. 
• Only hemithyroidectomy is done if tumour is <1 cm; node negative; unifocal and intrathyroidal disease.
• Radioactive iodine therapy (RAl7)- R AIT reduces the recur- rence; ablates the possible small residual thyroid tissue in thyroid bed; treats the potential possible micrometastases sites in remnant thyroid or lymph nodes or at distant sites. So it facilitates the proper thyroglobulin surveillance during follow up. RAil is indicated in tumor >1 cm, extracap- sular thyroid invasion or locoregional extension, high-risk group, unfavorable histological subtype (follicular, diffuse sclerosing, or tall cell-variant papillary cancer), multifocal disease; BRAF positive tumor in the specimen. Criteria for RAI are-TSH should be >30 mU/ml. L-Thyroxine replace- ment is stopped 3- 4 weeks before radioiodine treatment; OR - in time being switch over to T3 80 μg/day and RAI in 7 days; OR - When L-thyroxine withdrawal is not advisable, TSH stimulation was achieved using Recombinant Human Thyrotropin (rhTSH) (0.9 mg IM one dose-2 consecutive days; after 24 hours RAI given). Doseof 1131 - usually-3700 MBq (100 mCi); for metastases, it is 200 mCi. 
• Suppression hormone therapyusing high dose Lthyroxine- dose is to make TSH level <0.1 mu/L; orally-morning 30 minutes before food. Problems with TSH suppression are- subclinical thyrotoxicosis; cardiac irregularities; osteopo- rosis. Suppression therapy is now recommended to high risk group of OTC patients (200-300 μg/day); in low risk group, maintenance dose of 100 μg once a day morning before food is recommended. 
• Medical therapy. Mainly for advanced OTC; Targeted therapy using-Sorafenib (Nov, 2013 FDA approval); Vandetanib; cabozatinib (FDA approved).
• Metastatic disease: Total thyroidectomy; RAil; external RT for bone, brain and lung metastases; targeted medical therapy; surgical excision of the isolated bone secondaries like clavicle or sternum. 
  Prognosis 
• They usually carry good prognosis.
• Tall/columnar cell, trabecular, scirrhous, solid types of papil- lary carcinoma; oxyphilic, insular types of FCT carry poor prognosis. 

Follow-up

• Proper clinical examination in the neck for residual/nodal disease and for distant spread. 
• Serum thyroglobulin measurement -assay) after TSH suppression; Tg antibody level (TgAb) estimation. Serum thyroglobulin estimation is done along with TgAb.
• RAI whole body scan (WBS). It is done 3 months after RAil; then once in 12 months.
• TSH estimation is done once in 6 months.
• USG neck/USG-guided FNAC/MRI neck.
• USG-guided FNAC of lymph node and Tg measurement in FNAC fluid washout (FNAC-Tg).
• When there is negative I131 scan with elevated TG during follow up, PET scan is indicated. 
  

  Central Node Compartment Neck Dissecti on 

• It is removal of paratracheal, tracheo-oesophageal, pretracheal and prelaryngeal nodes along with thymus and thyroid enbloc extending from hyoid bone above, brachiocephalic vein below, carotids on both sides. 
  Completion Thyroidectomy 
• It is done after hemithyroidectomy if histology confirms as differentiated thyroid cancer, either papillary or follicular.
  It is indicated in-high-risk patients, age more than 45 years, family history, size more than 1 cm, opposite side thyroid nodule, nodal or distant spread, multifocal disease, extrathy- roidal spread, capsular and vascular invasion. 
  • Reasons for completion of total thyroidectomy are:
  In differentiated thyroid cancer (for follicular carcinoma of thyroid) radioiodine 1131 is the treatment for blood spread secondaries. It is only possible if entirethyroid gland is removed to make radioiodine to concentrate on tumour 
  • tissue to achieve the needed efficacy.
  In many indications papillary carcinoma of thyroid also needs radioablation like extrathyroid spread, size more than 4 cm, etc.
  • During follow up, in DTCs/FC Tthyroglobulin as atumour marker estimation at regular intervals (6 months; to suspect tumour bed recurrence/metastases) can be done if thyroid tissue is removed entirely. 
  • Papillary carcinoma of thyroid are multicentric with intrathyroid spread and so completion thyroidectomy is better. 
• Timing ofcompletion thyroidectomy is within 7 days of first surgery or after 6- 12 weeks to allow the settling of inflam- matory response (dissection and to get surgical planes is difficult during this period) .