This document provides information on thyroid cancer and the thyroid gland. It discusses the anatomy of the thyroid gland and its blood supply. It describes the different types of thyroid cancer such as papillary thyroid carcinoma, follicular thyroid carcinoma, and Hurthle cell carcinoma. It covers the pathology, risk factors, diagnostic process, treatment options, and prognosis for each cancer type. The main treatment approaches discussed are surgery, radioactive iodine therapy, and TSH suppression.

1. Thyroid Cancer
Dr. Mukesh V.M

2. Thyroid - Anatomy
 2 lobes, isthmus & ascending pyramidal lobe.
 Isthmus – absent in 10% , Pyramidal lobe – absent in 50%.
 Thyroglossal duct - extends between the thyroid gland and the
foramen cecum of the tongue.
 At level of C5 – body of T1
 Weighs about 30g.
 Each lobe - 5 cm in length, 3 cm width, 2-3 cm thick.
 The isthmus connecting the two lobes - 1.3 cm in breadth.

4. Capsules of Thyroid Gland
 True Capsule - A connective tissue capsule - continuous with the septa- makes up the
stroma of the organ.
 False capsule ( Perithyroid sheath / Surgical capsule ) :-
- external to the true capsule
- well developed layer derived from the pretracheal fascia.
- thickening of fascia - fixes back of lobes to the cricoid cartilage - Ligaments of Berry.
 Superior parathyroid glands - lie between the true capsule and false capsule.
 Inferior parathyroids - between the true and false capsules, within the thyroid
parenchyma, or lying on the outer surface of the fascia.
 The levator muscle - occasionally connect the hyoid bone with thyroid gland.

5. Vascular Supply
 Superior Thyroid Artery
o arises from the external carotid
artery at the bifurcation of the
common carotid artery.
o passes downward and anteriorly
to reach the superior pole of the
thyroid gland.
o supplies the cricothyroid muscle
and the cricopharyngeus muscle.
o At the superior pole, the
superior thyroid artery divides
into anterior and posterior
branches.

6.  The inferior thyroid artery
o arises from the thyrocervical trunk
o The recurrent laryngeal nerve may
pass anterior or posterior to the
artery, or b/w its branches.
o supplies lower pole of thyroid gland.
 Thyroid Ima Artery
o unpaired and inconstant
o arises from brachiocephalic artery/
right common carotid/aortic arch.
o 10% of individuals.
o Its position anterior to the trachea
makes it important in tracheostomy.

7. Veins
 Superior Thyroid Vein - Emerging
from the superior pole of thyroid,
& enter IJV.
 Middle Thyroid Vein - crosses the
common carotid artery to open
into IJV. This vein may be absent
or double("fourth" thyroid vein.)
 Inferior Thyroid Vein - Largest.
Rarely, the right vein crosses
trachea to enter left
brachiocephalic vein - form a
common trunk with the left vein -
thyroid ima vein.

8. Lymphatics
 Median Superior Drainage -Superior margin of isthmus
and medial margins of lateral lobes - end in the
digastric lymph nodes or prelaryngeal ("Delphian") nodes
just above the isthmus.
 Median Inferior Drainage - Lower isthmus and lower
medial portions of lateral lobes - end in the pretracheal
and brachiocephalic nodes.
 Right and Left Lateral Drainage - lateral border of each
lobe - end in the internal jugular chain.
 Posterior Drainage - inferomedial surfaces of lateral
lobes - drain into nodes along the recurrent laryngeal
nerve.

9. Well Differentiated
Thyroid Ca
Papillary
Thyroid Ca
Follicular
Thyroid Ca
Hurthle Cell Ca

10. Oncogenesis in Well differentiated Cancer

11. PTC
a) TRK, RET/PTC, Met ,cerb2 –
 Growth factor receptor tyrosine kinase
 Mutation causes PTC.
 RET proto-oncogene - located in chr. 10 , translocation with chr 17 => formation of
fusion gene RET/PTC => tyrosine kinase activation
- predilection for distant mets.
b) ras -
 Signal transduction protein
 Mutation of ras gene => production of inactive form of GTP => inactivation of protein
degradation => protein accumulation.
 40% of thyroid tumours has 1 of 3 ras gene point mutations (H-ras, K-ras, or N-ras).
 K-ras mutations - more frequent in radiation-induced PTCs

12. PTC
c) gsp -
 Signal transduction protein
 Usually associated with hot nodules.
If gsp mutation + ras mutation => Aggressive PTC/FTC
d) Tumour suppressor gene – p53
 Signal transduction protein
 Sensitive to radiation exposure
 Seen in aggressive PTCs / FTCs

13. FTC
a) Tyrosine kinase receptors – Met
b) N-ras - inactive GTP => ineffective protein degradation =>
accumulation
c) PTEN
d) PAX 8 – PPAR1 – fusion of DNA binding domain of thyroid
transcription factor (PAX8) to peroxisome proliferator-activated
receptor gamma 1(PPAR1)

14. Papillary Thyroid Carcinoma
 80% of all thyroid malignancies.
 Predominant thyroid carcinoma in children.
 Individual exposed to external radiation.
 Women : Men = 2:1
 Mean age of presentation – 30-40 years
 Usually Euthyroid - a slow growing painless mass in neck.
 Dysphagia, dyspnoea, dysphonia - Locally advanced d/s
 Characterized by multi-focality in 80-85%
 risk of lymph node mets – esp children & young adults –
lateral aberrant thyroid.

15. PTC – Pathology
 Gross – Hard and Whitish
 Remain flat on sectioning in contrast to normal tissue/ benign lesions that tend
to bulge.
 Histology – Exhibit Papillary projection
- Mixed Papillary and Follicular pattern
- Pure Follicular pattern
 Diagnosis by – characteristic cellular features
o Cells - cuboidal
o Pale abundant cytoplasm
o Crowded nuclei grooving
o Intra-cytoplasmic inclusion – Orphan Annie nucleus
o Psammomma bodies –Mx calcific deposits(clumps of sloughed cells)
o Multifocality is common, asso with increased risk of cervical node mets and
these lesions may invade adjacent strctures such as trachea esophagus and RLN

17. Other Varieties
 T- cell
 Insular
 Columnar
 Diffusing sclerosis
 Trabecular
 Poorly differentiated
 1% with worse prognosis.

18. Macroscopically
 Minimal / Occult / Micro-carcinoma
o Tumours of 1cm or less with no local invasion through thyroid
capsule/angio-invasion.
o Not associated with lymph node mets.
o Non palpable ,incidental finding, 2-36% thyroids at autopsy
o Recurrence – 5% , Mortality – 0.5%
 Intra-thyroidal – confined to thyroid gland, no evidence of
extrathyroid invasion
 Extra-thyroidal – invade through the thyroid capsule and/or into
adjacent structures.

19. Prognostic Indicators
 Low risk patients
o Young
o Well differentiated tumour
o No mets
o Small primary lesion
 High risk patients
o Older
o Poorly differentiated tumour
o Local invasion
o Distant mets
o Large primary lesion

20. Management
 High Risk / B/l tumours – Total or near total thyroidectomy
Advantages :-
1. RAI - effectively detect and treat residual thyroid tissue or
metastatic d/s
2. makes serum Tg level a more sensitive marker of
recurrent/persistent d/s
3. eliminates contralateral occult cancers as sites of recurrence
(85% of tumors are multifocal)
4. reduces the risk of recurrence ; improves survival
5. 1% risk of progression to undifferentiated /anaplastic Ca
6. reduces need for re-operative surgery.

21.  Therapeutic b/l central neck lymph node dissection
o Biopsy proven central or lateral compartment d/s prior to Sx.
o Central compartment nodal disease found at time of Sx
 Prophylactic unilateral i/l central lymph node dissection
o Primary tumour > 4cms
o Extra-thyroidal extension is appreciated at time of Sx
 Therapeutic lateral lymph node dissection.
o Biopsy proven metastatic lateral lymphadenopathy (IIa /III /IV)

22. Follicular Carcinoma
 10% of thyroid cancers
 F:M = 3:1
 Mean age of presentation – 50yrs
 More common in iodine deficient access.
 Usually present as a solitary thyroid nodule with a history
of rapid increase in size and long standing goitre.
 Pain – uncommon (except when Hmrg in nodule)
 Cervical lymph node mets – uncommon
 Distal mets may be present
 < 1% hyper-functioning with feature of thyrotoxicosis.

23. Pathology
 Solitary lesions, usually surrounded by a capsule.
 Histologically, follicles are present, but lumen may be devoid of colloid.
 Malignancy - defined by presence of capsular and vascular invasion.
 Minimally-invasive tumours –
o grossly encapsulated
o evidence of microscopic invasion through the tumour capsule/ into
small- to medium-size vessels (venous calibre)/ immediately outside the
capsule.
 Widely invasive tumours –
o large-vessel invasion/ broad areas of tumour invasion through the
capsule.
o May be un-encapsulated.

24. Management
 Total thyroidectomy should be performed when thyroid
cancer is diagnosed.
 Frankly invasive carcinoma- completion of total
thyroidectomy primarily (so that 131I can be used to detect
and ablate metastatic disease. )
 Total thyroidectomy in patients with angioinvasion is also
recommended.
 Prophylactic nodal dissection is unwarranted (nodal
involvement is infrequent)
 In patient with nodal metastases, therapeutic neck
dissection is recommended.
 Mortality - 15% at 10 years and 30% at 20 years.

25. Prognosis
 Poor long-term prognosis is predicted by:
o Age >50 years at presentation
o Tumour size >4 cm
o Higher tumour grade
o Marked vascular invasion
o Extra-thyroidal invasion
o Distant metastases at the time of diagnosis.

26. Hurthle Cell Carcinoma
 3% of all thyroid malignancies.
 Subtype of follicular cancer.
 Characterized by capsular and vascular invasion.
 Can’t be diagnosed by FNAC.

27. Pathology
 Sheets of eosinophilic cells packed with mitochondria.
 Multifocal / B/l
 Don’t take up RAI
 Mets to local nodes(25%) and distant sites.
Treatment
 Same fashion as FTC
 When Hürthle cells found –check for invasiveness and
malignancy
 Treatment –Sx (same workup of a follicular neoplasm).

28. Diagnosis of a solitary nodule
 ? h/o Radiation exposure
 ? h/o thyroid cancer syndrome( FAP/Cowden’s/Warner/Carney’s complex)
 New thyroid mass/nodule.
 Enlargement of previously detected nodule.
 Pain secondary to hmrg into nodule.
 Palpable cervical node.
 Dyphagia/dysphonia/dyspnoea

30. Adjuvant therapy
 Goals – prolonging survival and reducing the future
recurrence of cancer.
 Mainstay of adjuvant Rx for well differenciated thyroid Ca
is
1) Radioactive I – 131
2) TSH suppression

31. 1) I- 131 Therapy
1) Performed through thyroid hormone withdrawal.
o 2-3 weeks to produce desired level of TSH > 25-30 IU/ml.
o In prolonged withdrawal(4-6 weeks) - can take short acting
T3 (liothyronine) in the initial weeks of withdrawal to
ameliorate hypothyroid symptoms.
2) Performed using recombinant human TSH (rh TSH)
o used in patients who are at a risk of hypothyroidism –
elderly / cardiac / patients with spine and bone mets.

32.  I-123 and I-131 used for initial diagnostic whole body scan:
o Aids in disease staging
o Assist with dosing of I-131 therapy
 RAI ablation used primarily in :
o Pts 40yrs or older
o Primary tumor > 1cm
o Multifocal tumour
o Pts with extra-thyroidal disease d/t tissue invasion and mets.

33.  Most low risk pts (don’t receive I-131)
o Primary tumour < 1cm with negative surgical margins
o Without lympho-vascular or extra-thyroidal extension
o No uptake on initial post uptake scan
 Pts with small volume disease (receive 30-100 mci of RAI)
o Tumour 1-4 cms limited to thyroid
o Uptake only in thyroid bed in initial post op scan

34.  Pts receiving higher doses (100-150 mci) :
o Extra-thyroidal extension / lymph node mets
o Significant uptake on initial post op scan
 Pts receiving much higher doses (150 – 200) :
o Distant metastasis preoperatively

35. Surgery
Radio-ablation Rx
Hormone Replacement Rx
(levothyroxine sodium – 2Mg/kg/day)

36.  Dose is adjusted to reach an appropriate level of TSH
suppression for a patiennt as determined on basis of disease
status and clinico-pathological features.
 TSH suppression and RAI ablation is of no use in medullary and
anaplastic carcinoma (because no uptake / no TSH receptor)

37. Surveillance
 Most recurrences of DTC occur within the first 5 years
after initial treatment.
 Can also occur decades late.
PTC
• Recur in the neck.
FTC
• Recur at distant sites
• Lung/bone/soft tissue
(young)
• Brain/liver/adrenals (old)

38.  Every 6 months for the first 1-3 years , Yearly thereafter.
 Follow up visits of DTC.
o Clinical examination
o S. thyroglobulin, TSH, free T4
o Cervical ultrasonography
o CT and MRI of neck
 Thyroglobulin values normally drop after thyroidectomy and ablation
o Should be < 2ng/ml when patient is taking T4.
o Should be < 5ng/ml when patient is hypothyroid.
o Tg level >2ng/ml highly suggestive of metastatic disease/persistent
normal tissue
o Sensitive indicator of recurrent or persistent disease.

39. Recurrence
 Risk of recurrence – tumour biology , extent of initial Sx ,
and other prognostic variables.
 30% of DTC will develop recurrent disease.
 Out of this 66% occur within 10yrs after initial Sx.
 80% occur in neck alone.(74% cervical nodes,20% thyroid
remnant,6% local muscle)
 20% distant metastasis – commonly to lungs.

40. Treatment of Recurrence
Recurrent well differentiated disease
 Tg 1-2 ng/ml
o non-resectable & non iodine responsive
o TSH suppression with levothyroxine.
 Tg 10 ng/ml
o all imaging negative in detecting recurrence
o RAI ablation considered
 Recurrence detected in imaging and physical examination
o Surgical resection is the preferred management (risk of
RLN injury and avascularization of parathyroid)

41. Treatment of distant metastasis
 CNS disease - considered for neurosurgical
resection, followed by RAI ablation and image
guided radiation therapy.
 Bone and other distant metastases – treated
surgically in presence of enlarging lesions for
palliation in symptomatic pts.
 External beam radiation - for pts unable to tolerate
Sx with d/s negative on radioactive uptake.

42. THANK YOU