Differentiated thyroid carcinoma, Papillary carcinoma thyroid, Follicular carcinoma thyroid, Thyroid nodule

1. DR. ARIJIT JOTDAR
JUNIOR RESIDENT
DEPARTMENT OF
OTORHINOLARYNGOLOGY
MEDICAL COLLEGE, KOLKATA

2.  Thyroid cancer is the most common endocrine
tumour.
 Two to four times more frequent in women
than in men.
 Predisposing factors for Thyroid malignancy
are –
1. Prolonged stimulation by elevated TSH.
2. Solitary thyroid nodule.
3. Ionising radiation.
4. Genetic factors.
5. Chronic lymphocytic thyroiditis.
INTRODUCTION

3.  Consists of a group of malignant tumours
derived from the thyroid follicular cells.
 90 % of all thyroid malignancies are DTC.
 Incidence is higher in women, older persons,
positive family history and H/O radiation
exposure.
 Most common presentation is a solitary thyroid
nodule.

4.  Differentiated thyroid carcinomas are
classified into two main categories ---
1. Papillary thyroid carcinoma.
2. Follicular thyroid carcinoma.

5.  Most common type of DTC as well as all
thyroid malignancies. (75-80%)
 Variable presentations from papillary
microadenomas to large tumour masses with
extension outside thyroid capsule.
 Three growth patterns – pure papillary,
follicular, mixed.

6.  Young adults affected (20- 45 yrs). F:M ratio is 3:1.
 Associated with a high incidence (60 %) of
involvement of cervical lymph nodes in level II
& III.
 Primary tumour may be impalpable so that
initial presentation is nodal enlargement –
Lateral aberrant thyroid.

7.  Primary tumour is encapsulated in up to 70 % of
cases.
 One in five patients have pulmonary metastases
at presentation. Bone metastases are much less
common.
 Behaves more aggressively in older age groups
and may involve larynx or trachea.

8.  10 yr survival rate 90 % in minimal, occult
or intrathyroid carcinoma but comes to 60
% when extrathyroidal.
 Typical nuclear features ---
 Orphan Annie Eye Nuclei.
 Longitudinal grooves and inclusions in
nuclear membrane.
 Psammoma bodies.

9. 1 = Orphan Annie Nuclei .

10. 1 = Orphan Annie Nuclei .

13.  Classification of papillary thyroid
carcinoma—
1. PTC (papillary/ follicular/ mixed pattern)
2. Follicular variant PTC.
3. Tall cell variant PTC.
4. Columnar cell variant PTC.
5. Cribriform PTC.
6. Papillary microcarcinoma.
7. Solid variant PTC.
8. Diffuse sclerosing variant PTC.

14.  Papillary microcarcinoma – occult sclerosing,
occult primary :
<1 cm (WHO Classification).
4 – 30% incidence at autopsy.
 Encapsulated papillary carcinoma :
 10 % of all PTC.
 one fourth cases associated with nodal
metastases.

15.  Tall cell and Columnar cell – older
patients, bigger aggressive tumours :
Vascular and extrathyroid invasion
common.
Associated with worse prognosis.

16.  WOOLNER CLASSIFICATION :-
 Occult primary ( <1.5 cm)
 Intrathyroidal
 Extrathyroidal --------------------------
Beyond gland capsule and/or lymph
node metastases.

17.  10% of all thyroid cancers. More common in
women and older age group.
 Most common presenting feature is – solitary
thyroid nodule.
 Slow growing and metastasize via blood
stream.
 Distant metastases in lung and bone more
common than PTC and can be first feature.

18.  Not multifocal, do not invade lymphatic
channels and LN metastases are rare (10%).
 Two main types ---
 ENCAPSULATED OR MINIMALLY
INVASIVE FOLLICULAR CARCINOMA
(MIFC) :–
Looks like an adenoma and is classified as a
malignancy because of capsular or vascular
invasion histologically.

19.  WIDELY INVASIVE FOLLICULAR
CARCINOMA (WIFC) :–
Tumour diffusely infiltrates the gland.
Subdivided into – unencapsulated or
encapsulated type. Have poorer survival
rate than PTC.

23.  A nodule is more likely to be malignant if --
 Positive family history
 Past history of thyroid cancer
 Enlarging in size (particularly on
suppressive doses of Thyroxine.)
 Age< 14 years and > 65 years.
 Male gender.

24.  History of Ionising radiation.
 TSH is elevated.
 Thyroid antibodies are positive.
 Genetic factors --- Familial Thyroid Cancer,
Cowden’s Disease, Familial adenomatous
polyposis.
 Hashimoto’s thyroiditis.
 Overall 10-20% cases of STN are malignant.

25.  HISTORY :-
 Solitary thyroid nodule.
 Age – extremes of age, likely to be
malignant.
 Palpable neck node metastases- 10 % cases.
 Hoarseness of voice.
 Obstructive symptoms.
 Exposure to ionising radiation.
 Positive family history.

26.  EXAMINATION :-
 Distinguishing between benign and
malignant thyroid nodules.
 Papillary cancers harder than follicular
tumours.
 Papillary cancers- Higher rate of nodal
metastases.
 Fixation to surrounding structures.
 Extrathyroid extension.
 Neck node involvements :
VI>III>II>IV>V>I.
 Role of endoscopy – FOL: Vocal cord palsy,
invasion by tumour.

27.  CYTOLOGY :-
Fine needle aspiration cytology.
Classification of thyroid nodule cytology :-
Thy1 Inadequate for diagnosis.
Thy2 Benign disease
Thy3 Suspicious for neoplasia.
Thy4 Suspicious for malignancy.
Thy5 Positive for malignant disease.

29.  Thy5 possible only in Papillary and Medullary
carcinoma – Expected cytological features present.
 Cytological features of classical PTC :-
Cells Cellular aspirates in papillary groups,
clusters or single cells
Background Bubble gum colloid, stromal fragments,
calcific debris ( psammoma bodies),
macrophages.
Nuclear
features
Elongation, membrane thickening,
chromatin clearing, nuclear grooves and
inclusions, Orphan Annie Eye nuclei.

30.  Lymphoma and Anaplastic Carcinoma –
occasionally diagnosed with FNAC, but Trucut or
Open Biopsy is confirmatory.
 Follicular variant of PTC :-
Features overlap with hyperplastic nodules or follicular
neoplasms.
Thy4
Intraoperative frozen section.
 Thy3 :- Follicular neoplasm.
Follicular Carcinoma diagnosed only by capsular or vascular
invasion.
Cannot be determined by FNAC.
Features overlap with benign follicular lesions.

31.  Th2 :- No atypical cellular features. Small risk
of malignancy – Follicular carcinoma.
 Thy1 :- Malignant in 9% cases. – repeat the
FNAC.

32.  TSH,T3,T4, Thyroid antibodies.
 Increased TSH :- Increased malignancy.
 Antibodies :-
Interpretation of thyroid function tests.
Prediction of post-operative hypothyroidism.
Assessment of serum thyroglobulin.
 Serum Calcium.

33.  ULTRASOUND :-
 Measurement of tumour size.
 Diagnosis of multinodular goitre.
 Exclude contralateral disease.
 Evaluation of cystic lesions (rare in malignancy).
 Calcification :- Both in benign and malignant,
microcalcification in malignancy.
 Assessment of neck node status.
 Detect metastases.
 USG guided FNAC.
 Absence of halo sign in neck node.
 Increased vascularity.

35.  COLOUR FLOW DOPPLER SONOGRAPHY:-
To identify different types of blood flow
within solid thyroid nodules.
Type III flow :- malignant disease.
 CT Scan neck and thorax :-
Assessment of extension of tumour to
surrounding structures.
Detect nodal deposits in neck and
mediastinum.
Direct retrosternal extension.
Pulmonary metastases.

37.  MRI :-
Multiplanar imaging, good soft tissue contrast.
Vessel involvement – MR Angiography.
No radiation exposure.
 THYROID SCAN :-
I-123 and Tc-99m.
Uptake by thyroid gland.
Cold Nodule - > 90% lesions.
Hot Nodule – Unlikely to be malignant.
Used to identify hot nodules in a patient with
elevated Thyroxine or suppressed TSH levels.

39. PATIENT
FACTORS
TUMOUR
FACTORS
MANAGEMENT
FACTORS
Age Tumour size
Tumour histology
Delay in therapy
Extent of surgery
Sex Nodal metastases
Local invasion
Experience of
surgeon
Thyroid hormone
therapy
Distant
metastases
Post-op
radioiodine

40. PROGNOSTIC
FACTORS
LOW HIGH
AGE < 45 years > 45 years
GENDER Female Male
SIZE < 4 cm > 4 cm
EXTENT Intraglandular Extraglandular
GRADE Low High
DISTANT
METASTASES
Absent Present

41.  TNM Staging for Thyroid carcinoma (AJCC
Cancer Staging Manual) :-
 T :- Tumour
TX Primary tumour cannot be assessed.
T0 No evidence of primary tumour.
T1a Tumour 1 cm or less in greatest dimension,
limited to thyroid.
T1b Tumour 1-2 cm, limited to thyroid.

42. T2 Tumour >2 cm but <4 cm, limited to thyroid.
T3 Tumour >4 cm, limited to thyroid, or any tumour with
minimal extrathyroid extension (Sternomastoid or
perithyroid soft tissue).
T4a Tumour of any size extending beyond the thyroid
capsule and invades any one of the followings –
subcutaneous soft tissue, larynx, trachea, oesophagus,
recurrent laryngeal nerve.
T4b Tumour invades prevertebral fascia,mediastinal vessels,
or encases carotid artery.

43.  N :- Nodal status.
NX Regional lymph nodes cannot be assessed.
N0 No regional lymph node metastases.
N1 Regional lymph node metastases.
N1a Metastases in level VI (pretracheal & paratracheal,
including prelaryngeal and delphian lymph nodes.)
N1b Metastases in other unilateral, bilateral or
contralateral cervical or superior mediastinal lymph
nodes.

44.  M :- Metastases
cM0 Clinically no distant metastasis.
cM1 Distant metastasis clinically.
pTNM Pathological classification.
pN0 Histological examination of a selective neck
dissection specimen include 6 or more lymph
nodes. If lymph nodes are negative but the
number ordinarily examined are not met, classify
as pN0.
pM1 Distant metastasis proven microscopically.

45.  Papillary or Follicular < 45 years :-
I Any T Any N M0
II Any T Any N M1

46.  Papillary or Follicular >45 years :-
I T1 N0 M0
II T2 N0 M0
III T3
T1,T2,T3
N0
N1a
M0
M0
IVA T1,T2,T3
T4a
N1b
N0,N1
M0
M0
IVB T4b Any N M0
IVC Any T Any N M1

47.  Prognostic variable for PTC.
 Score = 3.1+(0.3×size)+1+1+3.1(0.08×age if <40
years)
M Distant ‘M’etastases (3)
A ‘A’ge (3.1 or 0.08 × age)
C ‘C’ompleteness of excision (1)
I Extrathyroid ‘I’nvasion (1)
S ‘S’ize (cm)

48. GAMES AGES AMES DAMES
Grade Age Age DNA
Age Grade Metastases Age
Metastases Extension Extension Metastases
Extension Size Size Extension
Size Size

49.  Due to either activation of oncogenes or
inactivation of tumour suppressor genes.
CANCER ONCOGENES TUMOUR
SUPPRESSOR
GENES
Papillary thyroid
carcinoma
RET, MET,
TRK1,
RAS,BRAF
p53
Follicular
carcinoma
Ras,PAX8/ PPAR P53, PTEN

50.  Surgery is the mainstay of treatment in DTC.
 Main aims are –
 To remove the primary tumour disease and
which has spread beyond thyroid capsule and
involved cervical lymph nodes.
 To minimize treatment and disease related
morbidity.
 To permit accurate staging of the disease.
 To facilitate the effect of post-op radioiodine.
 To minimize risk of recurrence and metastases.

51. Hemi
thyroidectomy/
Lobectomy
Complete removal of one thyroid lobe with
isthmus.
Near total
lobectomy
A total lobectomy leaving the smallest
amount of thyroid tissue (less than 1gm) to
protect the RLN.
Near total
thyroidectomy
Complete lobectomy on one side and a near
total lobectomy on other side or bilateral
near total lobectomy.
Total
thyroidectomy
Complete removal of both lobes of the
gland, isthmus and pyramidal lobe.

53.  TOTAL THYROIDECTOMY :-
 Radioiodine can be used to detect & residual
normal thyroid or local or distant metastases.
 Serum thyroglobulin is more sensitive marker
of recurrence.
 Microscopic foci of cancer are eliminated.
 Recurrent cancer in 5-15% of contralateral lobe.

54.  TOTAL THYROIDECTOMY:-
 Recurrence lower in patients having Total
Thyroidectomy.
 Facilitates accurate follow up and staging.
 Improved survival rates.
 T/t of choice for multinodular goitre and
thyrotoxicosis.
 Minimal complications in experienced hands.

55.  LESS THAN TOTAL THYROIDECTOMY :-
 Fewer complications develop.
 Half of the local recurrences can be cured by
surgery.
 <5% of recurrences occur in the thyroid bed.
 Little clinical significance is given to
multicentricity.
 Prognosis good with lesser procedures.

56.  LOBECTOMY with Thyroxine therapy :-
 Cancers 1 cm or less in diameter without evidence of
lymph node metastases.
 TOTAL THYROIDECTOMY :-
 Tumour >1 cm.
 Multifocal disease.
 Familial disease.
 Extrathyroid extension.
 Positive lymph node involvement.
 Distant metastases.
 History of radiation exposure.

57.  If diagnosis of PTC is made after lobectomy
and Completion Thyroidectomy is required, to
be done within 8 wks of histological diagnosis.
 If risk of recurrence is low, lobectomy alone
may appropriate in tumours >1 cm.

58.  LOBECTOMY :-
 Follicular carcinoma with no capsular invasion.
 Low risk patients(females,<45 years) with tumour <2
cm. (Along with Thyroxine therapy following
Multidisciplinary team discussion).
 TOTAL or NEAR TOTAL THYROIDECTOMY :-
 FTC with vascular invasion.
 FTC > 4 cm in diameter.
 COMPLETION THYROIDECTOMY:-
 within 8 wks of histological diagnosis.

59. PATIENT PROFILE TREATMENT
Low risk patient, low risk tumour Lobectomy
Low risk patient, high risk tumour LOBECTOMY or TOTAL
THYROIDECTOMY
High risk patient, low risk tumour LOBECTOMY or TOTAL
THYROIDECTOMY
High risk patient, high risk tumour Total thyroidectomy

60.  PAPILLARY CARCINOMA :-
 Level VI LN found at surgery → Central neck
dissection.
 Suspicious or clinically involved nodes in lateral
neck and confirmed by FNAC or Frozen Section →
Selective neck dissection of level IIa – Vb.
 PTC with no clinically involved LN but having high
risk ( male, >45 years, >4 cm in size, extracapsular or
extrathyroidal disease ) → Total thyroidectomy with
level VI LN dissection.

61.  FOLLICULAR CARCINOMA :-
 Level VI LN found at surgery → Central neck
dissection.
 Suspicious or clinically involved nodes in lateral neck
and confirmed by FNAC or Frozen Section →
Selective neck dissection of level IIa – Vb.
 FTC with no clinically involved LN but having high
risk ( male, >45 years, >4 cm in size, extracapsular or
extrathyroidal disease ) → Total thyroidectomy with
level VI LN dissection.

62.  Risk factors :-
 Age> 50 years.
 Tumour size >4 cm.
 Non-encapsulated tumours.
 Aggressive histological variants.
 More common in PTC.
 Surgery is the most effective treatment.
 Complete vs. Incomplete Excision – preservation
of RLN, even if involved.
 The UK Guidelines – post-op I131 & Thyroxine
suppression.

63.  The UK Guidelines – incomplete excision of tumour
with preservation of one or both RLN & post-op
I131, Thyroxine suppression ± External beam
radiation (if both RLNs are involved).
 Superficial involvement of laryngo-tracheal tree →
Complete or incomplete excision ?
 Gross invasion of L-T tree ± intraluminal
involvement → Radical resection with partial
resection of tracheal wall with partial or total
laryngectomy.
 Alternative → external beam radiotherapy ± radio I.

64.  RADIO – IODINE :- Reduction local recurrence
& 10 yr survival rate after surgery.
 External Beam Radiotherapy :- Used in high risk
of local recurrence.
 Extensive extrathyroid invasion.
 Extranodal invasion.
 Older persons.
 Thyroxine Suppressive Therapy :- To be
maintained at the lower limit of normal.

65.  Used to detect residual or recurrent carcinomas
following total thyroidectomy & radio-iodine
ablation.
 During Thyroxine suppression, it is ineffective.
 TSH stimulated Tg measurement or
recombinant human TSH is used for this.
 Serial stimulated TSH measurement used to
follow up low risk DTC as it reflects increase in
tumour mass.

66.  NECK ULTRASOUND :-
 To differentiate benign and malignant lymph nodes.
 Useful in children.
 WHOLE BODY RADIOIODINE SCANNING :-
 FDG-PET CT SCAN :-
 Can demonstrate disease amenable to surgery where
Radioiodine scan & ultrasound are negative but serum
Tg is elevated.

67.  Patients treated for DTC → Serial stimulated Tg
levels (either off Thyroxine or using RhTSH)
↓
If elevated
↓
Neck USG ± FNAC & Tg level in needle washout.
↓
If USG negative
↓
Diagnostic Radioiodine Scan
↓
If negative → FDG – PET CT Scan.

68.  ZACTIMA & SORAFENIB :-
 Obstruct RET & BRAF signalling.
 Inhibit VEGF receptors.
 TEMSIROLIMUS & EVEROLIMUS :-
 Inhibitor of Phosphoinositide – 3 – OH kinase
pathway that regulate cell proliferation & survival in
Thyroid cancers.
 BEVACIZUMAB :-
 Anti- VEGF monoclonal antibody.
 GENE THERAPY.