THYROID CANCER

Epidemiology
• Clinically detectably TyC <1% of all cancers and <0.5% of cancer
deaths
• Thyroid microcarcinoma may be foud in multinodular goiter
• Mostly encountered in adults aged 40-50
• Women affected more than men
 Classification of Thyroid Neoplasms
I. Primary Epithelial Tumors
A. Tumors of follicular cells
1. Benign: follicular adenoma
2. Malignant: Differentiated: papillary , folicullar, poorly differentiat.
Undifferentiated: anaplastic
B. Tumors of C cells
Medullary carcinoma
c. Tumors of follicular and C cells: mixed medullary-follicular carcinoma
II. Primary Non-Epithelial Tumors:
A. Malignant Lymphomas
B. B. Sarcomas
C. Others
III. Secondary tumors (METs)
 CLASSIFICATION of Thyroid Carcinomas (TyC)
ORIGIN TUMOR TYPE FREQUENCY
FOLLICULAR CELL Differentiated
PAPILLARY (PTC) 70-90%
FOLLICULAR (FTC) 15%
ANAPLASTIC (UNDIFFERENTIATED) 1-2 %
C- CELL MEDULLARY (MTC) 2%
LYMPHOCYTES LYMPHOMA 2%
 AETIOLOGY
1. Irradiation :
• 200-500 cG induce thyroid cancer at a rate of 0.5%/year.
• Irradiation under 20 yrs age ass.with increased risk of Ty Ca, mostly PTC
• Chernobyl nuclear explosion in 1986nresulted in an increase of 4.7 fold in TyC, and a 34 fold increase in
children in Belarus (1985 vs 1993)
• Greater risk for women<20
• Latency of 5 yrs with max risk at 20 yrs following exposure.
2. Iodine supplementation has decreased incid of FTC, increasd incid. PTC
3. Genetic syndromes and oncogenes:
• RET/PTC1 on chr.10 ass. With PTC(5-30%)following irradiation; less common RET/PTC2 and RET/PTC3 TRK
• Over expression of Ras oncogene in PTC has adverse prognosis
• cmyc expression PTC aggressive forms
• BRAF more freq. found in aggressive type of PTC(tall cell variant)
American
Thyroid
Association
Management
Guidelines for
Adult Patients
with Thyroid
Nodules and
Differentiated
Thyroid Cancer,
Thyroid 2016
PAPILARY THYROID CARCINOMA
• 70-90% of TYC
• Incidence 3-5:100 000
• Pathology: slow growing , usually non-encapsulated,
may spread through Ty capsule to surrounding
structures, esp. lymph nodes
• Variants: follicular, papillary, dorsal, columnar cell, tall
cell, diffuse sclerosing
• Histology: a complex branching papillae with a
fibrovacular core surrounded by a single layer of
tumour cells with large nuclei pale staining, with deep
nuclear groves and cytoplasmic psammoma body
(calcified, basophylic stromal structure)
• Spread: 95% don’t spread, 15-20 % local extra thyroid
invasion and 1-2% mets in local lymph nodes and
lungs
 PAPPILARY CARCINOMA OF THE THYROID
(PMC) MANAGEMENT
• 1ST choice: (near) total thyroidectomy with neck dissection of clinical lymph
node mets.
• Adjuvant therapy: radioiodine (RAI) therapy in intermediate and high risk
patient 30-150 mCi for thyroid remnant ablation, followed by 6 month WBS
and in the presence of mets , a second dose of RAI 5-7 GBq
• The pa should be isolated until residual dose meter readings indicate<30
MBq
• Chronic suppression of TSH<0.1 mUI/l with LT4 (it has to be interrupted 4-6
wks. Before RAI ablation or use of TSH r to stimulate Ty RAIU
• Follo-up with Tg levels
 PAPPILARY MICROCARCINOMA OF THE
THYROID (PMC)
• <1 cm in the largest diameter
• Detected coincidentally on HP exam following resection of multinodular
goiter
• Prevalence 1-35.6%
• Rarely progresses to clinically apparent TyC with age
• PMC can be multifocal
• Lymph node mets usually associated with multifocal tumors
• Slow growing lesion which rarely spreads
• Good prognosis
• Surgical treatment, T4 replacement, no need of radioiodine
FOLLICULAR THYROID CARCINOMA

• 15% of all thyroid cancers; mean age oa.50 yrs,

more common in endemic goiter
• Pathology: Follicullar differentiation with
minimal/wide capsular/vascular invasion
• impossible to dif, of benign follicular adenoma
• Hurthle cell carcinoma is an aggressive type of FTC
with a poor prognosis as it fails to concentrate
iodine
• 15-20% Mets more likely to spread by
haematogenesis to thr lung and bones
• Management: as for PTC
American Thyroid Association Management
Guidelines for Adult Patients with Thyroid
Nodules and Differentiated Thyroid Cancer,
Thyroid 2016
Follow-up of Papillary and Follicular Thyroid
Carcinoma
• Annual clinical review: clin exam, neck US for presence of Lymph node
mets,
• TSH (suppress<0.1), Tg (<0.2) ATG, every 6-12 mo. If Tg is high check with
RAI WBS
• Radioiodine scans (WBS) annually for the first 3 yrs in high risk pa, if
negative , not repeated unless clinical suspicion (as a raise in Tg level)
• If detectable Tg (>10ng/ml) and absent uptake of radioiodine may be due
to a dedifferentiation of the tumour and failure to take up radioiodine
• FDG PET scan may be useful in the above situation
• Neck/chest CT/IRM
 CRITERIA OF EXCELLENT RESPONSE
1. No clinical evidence of tumor
2. No imaging evidence of tumor by RAI imaging (no uptake
outside the thyroid bed on the initial posttreatment WBS if
performed, or if uptake outside the thyroid bed had been
present, no imaging evidence of tumor on a recent diagnostic
or posttherapy WBS) and/or neck US
3. Low serum Tg levels during TSH suppression (Tg <0.2 ng/mL)
or after stimulation (Tg <1 ng/mL) in the absence of interfering
antibodies
 Clinical decision-
making
and management
recommendations in
ATA
low-risk DTC patients
that
have undergone
total thyroidectomy.

American Thyroid Association

Management Guidelines for Adult Patients
with Thyroid Nodules and Differentiated
Thyroid Cancer, Thyroid 2016
 Clinical decisionmaking
and management
recommendations in ATA low
risk DTC patients that have
undergone less than total
thyroidectomy (lobectomy or
lobectomy with isthmusectomy).

American Thyroid
Association Management
Guidelines for Adult
Patients with Thyroid
Nodules and Differentiated
Thyroid Cancer, Thyroid
2016
Clinical decision-making
and management
recommendations
in ATA intermediate risk DTC
patients
that have undergone total
thyroidectomy

American Thyroid
Association Management
Guidelines for Adult
Patients with Thyroid
Nodules and Differentiated
Thyroid Cancer, Thyroid
2016
 Clinical decisionmaking
and management
recommendations in ATA
high risk DTC patients that
have undergone total
thyroidectomy
and have no
gross residual disease
remaining
in the neck
American Thyroid
Association Management
Guidelines for Adult
Patients with Thyroid
Nodules and Differentiated
Thyroid Cancer, Thyroid
2016
WHAT IS THE TARGET
FOR TSH SUPRESSION
IN THE FOLOW-UP OF
DTC?

American Thyroid
Association Management
Guidelines for Adult
Patients with Thyroid
Nodules and Differentiated
Thyroid Cancer, Thyroid
2016
 What about metastatic DTC?
The preferred hierarchy of treatment for metastatic disease (in order) is:
• surgical excision of locoregional disease in potentially curable patients,
• 131I therapy for RAI-responsive disease,
• external beam radiation therapy or
• other directed treatment modalities such as thermal ablation,
• TSH-suppressive thyroid hormone therapy for patients with stable or slowly
progressive asymptomatic disease,
• systemic therapy with kinase inhibitors for patients with significantly
progressive macroscopic refractory disease.
 MEDULARY THYROID CARCINOMA
• Origin C cells : hard nodule or lymph node
• Less than 5% of TyC
• Invades surrounding tiss.,lymph and blod vessels
• Mets to lung, bones, liver
• Sporadic or familial (20%)
• Familial forms: RET mutation
• Sometimes MTC is the first manifestation of MEN2A
• familial MTC
• Phaeocromocytoma
• Hyperparathyroidism
• MTC can occur in MEN 2B”:
• MTC
• Mucosal neuromas on distal tongue and conjunctiva
• Thikened lips
• Marfanoi habitus
• Mucosal neuronomas in the GI tract
MTC Diagnostic procedure
Thyroid and neck ultrasound including central and lateral compartments
FNA
Calcitonin, if unsure Ca stimulation test
CEA
Ca
Screening for Phaeocromocytoma
CT abdomen (liver, adrenals)
Genetic counseling
Screen for RET protooncogene mutation (exon 10, 11, 13-16)
Assessment of vocal cord mobility (laryngoscopy)
 MTC MANAGEMENT
Total Thyroidectomy with central /lateral neck dissection
Post op administration of LT4 to normalize TSH
2-3 months postop measure calcitonin and CEA
If calcitonin >150pg/mL: Neck US ,Contrast enhanced CT,/ PET FDG or Ga 68
DOTATATE/ contrast MRI abdomen,bone scans in selected patients
If Calcitonin is undetectable and CEA within the normal range, active
surveillance: annual Calcitonin, CEA,
If Ret positive: annual screening for MEN2: Ca, metanephrines,
normetanephrines, cathecolamines
If reccurent disease: consider resection, EBRT or TyrKinase inhibitors
(vandetanib, lenvatinib, sorafenib), cytotoxic chemotherapy, chemoembolization
of liver mets.
MEN2 Screening
• Pa with MTC or one MEN2 associated tumour if aged<30, or two
MEN2 associated tumors if >30
• Mucosal neuronomas of somatic features of MEN 2
• Individuals with a first degree relative with MEN 2
• Indication for thyroidectomy in genetically affected children age>5-6
yrs
 ANAPLASTIC THYROID CARCINOMA

• Rare: 1-2% of TyC

• Mutation of p53 in 60-80%, BRAF, RAs
• Peak incidence 7th decade, F:M1:1.5
• Rapid growth of a hard/firm fixed tumor, ften infiltrates local tissue as
larynx or trachea and great vessels: stridor and obstructive respiratory
symptoms
• Do not accumulate iodine
• Aggressive, poor prognosis: 7% survival at 5 yrs
• Mean survival 6 mo from diasgnosis
• Management: total thyroidectomy followed by EBRT plus chemotherapy
 COMPARISON OF PTC, FTC, ANAPLASTIC TC
CHARACTERISTIC PTC FTC ANAPLASTIC TC
AGE AT PRESENTATION 30-50 40-50 60-80
SPREAD Lymphatic Haematogenous Haematogenous

Prognosis good good poor

Treatment (Near)Total (Near)Total Total thyroidectomy
thyroidectomy then thyroidectomy then with lymph node
TSH suppression TSH suppression dissection
RAI ablation in high RAI ablation in high Chemotherapy
risk patient risk patient (Adriamycin, cisplatin)
Post op total body RAI Post op total body RAI External beam
scan scan irradiation
Tireoglobulin follow- Tireoglobulin follow-
9up up
Thyroid LYMPHOMA
• Rare <2% of TyC
• B cell lineage
• Almost always associated with autoimmune
thyroid disease (MALT)
• Rapidly enlarging neck mass, compressive in
30%
• Occur commonly in women> 40yrs
• Can be limited to thyroid or systemic
lymphoma
• Staging is essential prior to therapy
• CT/ MRI neck, thorax, abdomen
• Radiotherapy and cytotoxic chemotherapy
combined with rituximab (anti CD20 MAB)
• In MALT lymphomas confined to the thyroid,
total thyroidectomy
• In disseminated MALT Chemotherapy alone
or combined with Radiotherapy
 TyC
Clinical exam, hystory

THYROID US Supplementary investigation

FNA Supplementary investigation
Abdomen CT Plasma cathecolamins
LYMPH NODE Calcium , phosphate, PTH
CALCITONIN ENT (laryngoscopy)
Bone Scintygraphy PTY scintigraphy
CONTRAST ENHANCED CT
NECK/THX/ LIVER

TREATMENT TREATMENT
Total Thyroidectomy ± lymphadenectomie/neck- Total Thyroidectomy ± lymphadenectomy/neck-dissection
dissection Parathyroidectomy, adrenalectomy
HP exam ± IHC

Differentiated TyC MTC Follow up Anaplastic TyC

± RAI therapy Plasma Calcitonin EBRT MEN follow-up
Follow up Octreoscan ± traheostoma Plasma cortisol
Tyroglobulin PET CT Plasma cathecolamines/ metabolits
Follow up
ATG Neck US CA
Contrast Enhanced CT
WBS Contrast Enhanced CT P
PET CT PTH
Neck US
RET mutation
Contrast Enhanced CT