Thyroid Carcinoma:Presentation, Diagnosis

& Management

A Presentationby

Augustin Brooks

Incidence• Most common Endocrine malignancy (BUT only 1 % of ALL malignancies)

• 2001– 1,200 new cases in England & Wales

• Annual Incidence in UK– 3.5 per 100,000 ♀– 1.3 per 100,000 ♂

Everything to gain from diagnosis

• 80-90 % 10 year survival rate for middle-aged adults with differentiated thyroid Ca

• BUT– 5-20 % local recurrence– 10-15 % distant metastases– 9 % die of their disease

5 year survival of thyroid cancer (England and Wales)

High risk patients

• Older age – esp after age 40 yrs

• Male• Poorly differentiated• Increased size• Degree of vascular invasion• Extrathyroidal invasion• Metastases• Papillary better than follicular (?)

5-year age-standardised relative survival for thyroid cancer (England and Wales)

Risk factors for thyroid Ca

• Hx neck irradiation in childhood• Endemic goitre• Hashimoto’s thyroiditis (lymphoma)• FH / personal Hx of thyroid adenoma• FAP• Familial thyroid Ca• Cowden’s syndrome• Exposure to nuclear fallout (Chernobyl)

Presentation

• Thyroid nodule– Newly discovered– Recent increase in size of pre-existing nodule

• HOWEVER – • 95 % benign

– Clinically present in 10 % & 2 % ♀ ♂

– Prevalence as high as 50 % on U/S (!)

Who to refer?• Nodules can be managed in primary care IF:

– NOT changed for years– Asymptomatic, < 1 cm discovered coincidentally on imaging AND no other worrying features/RFs

• Non-urgent referrals– Abnormal TFTs– Sudden onset of pain in a thyroid lump (likely to have bled into a benign thyroid cyst)– New presentation / slow increase in size over months

Urgent referrals• Unexplained hoarseness / voice change assocd with goitre• Nodule in a child• Cervical lymphadenopathy• Rapidly enlarging and painless (over weeks)

– Typical of anaplastic and lymphomas

• Emergency same day referral for stridor

• Referrals– See within 2/52 in secondary care– Decision to treat should be made within 31/7

Examination

• Inspection & palpation of the neck– Thyroid exam– Lymphadenopathy

• Record pulse & BP

• Full examination if any features of concern

Anaplastic carcinoma of the thyroid

Investigation• TFTs• Fine needle aspiration cytology (FNAC)

– with / without U/S guidance

• Consider– Thyroid AutoAbs– MRI / CT

• If limits of goitre cannot be determined clinically• Fixed tumours• Haemoptysis• DO NOT USE IODINATED CONTRAST MEDIA

– Use gadolinium-enhanced MRI– Basal plasma calcitonin levels

• If MTC suspected– Flow volume loop studies

• If upper airways obstruction suspected– Core biopsy

• If tissue diagnosis difficult by FNAC

• No place for radioisotope studies or excisional biopsy

U/S showing thyroid carcinoma

FNAC• Can be readily carried out without U/S guidance if lesion

is palpable

• Can also be used for suspicious lymph nodes

• All material aspirated should be sent to the lab WITHOUT fixation

• Should be reported by a cytopathologist

• Cannot always make diagnosis of malignancy alone– Cases should be discussed at MDT

FNA colloid goitre

Thy Classification

Classification Histology Action

Thy 1 Non-diagnostic Repeat FNAC(Unless cyst aspirated to dryness)

Thy 2 Non-neoplastic Two non-neoplastic results 3-6/12 apart advised

Thy 3 (i)

Follicular lesion / suspected neoplasm

Some cases will be hyperplastic nodules

Surgical removal of the lobe. Completion thyroidectomy may be

necessary if histology malignant

Thy 3 (ii) Worrying features but cells too scanty to qualify for Thy 4

Discuss in MDTRepeat FNAC advised

Thy 4 Suspicious of malignancy but not diagnostic Surgical intervention advised

Thy 5 Diagnostic of malignancy Surgical interventionConsider radioT, chemoT

Papillary carcinoma

Prognostic scoring systems

• Main two used: TNM & MACIS– TNM

• Tumour size• Node metastases• Metastases (distant)

• MACIS• Metastases• Age at presentation• Completeness of surgical resection• Invasion (extrathyroidal)• Size

• All scoring systems emphasise age & size

TNM classification of thyroid Ca• Primary tumour

– pT1 Intrathyroidal ≤ 1 cm– pT2 Intrathyroidal > 1-4 cm– pT3 Intrathyroidal > 4 cm– pT4 Any size extending beyond thyroid capsule– pTX Primary tumour cannot be assessed

• Regional lymph nodes (cervical or upper mediastinal)– N0 No nodes– N1 Regional nodes involved

• N1a Ipsilateral cervical• N1b Bilateral, midline or contralateral cervical nodes or mediastinal nodes

– NX Nodes cannot be assessed

• Distant metastases– M0 No mets– M1 Distant mets– MX Mets cannot be assessed

Papillary or Follicular Ca staging

< 45 years > 45 years

Stage I Any T, N & M0 pT1, N0, M0

Stage II Any T, N & M1pT2, N0, M0

pT3, N0, M0

Stage IIIpT4, N0, M0

Any pT, N1, M0

Stage IV Any pT, N, M1

Undifferentiated or anaplastic carcinomas are ALL stage IV

10 year mortality rate for DTC

Stage 10 yr mortality (%)

I 1.7

II 15.8

III 30

IV 60.9

Pre-op

• Surgery should be within 31/7 of decision to treat

• Assess vocal cord function

• Pre-op cross-sectional CT / MRI – if bulky disease or vocal cord paralysis

• U/S ?– To plan surgery

Surgical Terms• Lobectomy

– Complete removal of one lobe inc isthmus

• Near-total lobectomy– Total lobectomy leaving behind a very small amount of thyroid tissue

(<1 g) to protect the recurrent laryngeal nerves

• Near-total thyroidectomy– Lobectomy with a near-total lobectomy on the contralateral side OR a bilateral near-total procedure

• Total thyroidectomy– Removal of both thyroid lobes, isthmus and pyramidal lobe

• The descriptive term ‘subtotal’ no longer used

Risks of surgery• Permanent damage to recurrent laryngeal nerve < 5 %

– It may not be possible to remove entire tumour without damaging both recurrent laryngeal nerves

– In these instances, small residue of tumour may be left behind to protect the nerves and treated with:

• post-op 131I ablation• TSH suppression with levothyroxine• External beam radiotherapy

• Attempt to preserve the external branch of the superior laryngeal nerves

• by ligation of sup’r thyroid vessels at the capsule of gland

• Parathyroids – Identify & preserved where possible

Papillary carcinoma surgery

• Node –ve, <1 cm → lobectomy

• > 1 cm → Total thyroidectomy

• Any evidence of spread → Total thyroidectomy

• Familial disease → Total thyroidectomy

• Neck irrad’n in childhood → Total thyroidectomy

Follicular carcinoma surgery• FNAC cannot distinguish carcinoma from follicular adenoma or benign hyperplastic

nodules

• Thy 3 mandates at least lobectomy in most cases

• 1 cm, minimal capsular invasion → lobectomy

• Vascular invasion → Total thyroidectomy

• > 4 cm → Near-total / Total thyroidectomy

• ♀, < 45 yrs, < 2 cm (Low risk) → consider lobectomy only

• 2-4 cm, minimal capsular invasion → discretion of MDT

• If diagnosis of cancer on lobectomy histology → Contralateral lobectomy within 8/52

Anaplastic thyroid Ca

• Very poor prognosis

• Surgery rarely indicated

• 131I no place

• External beam radioT + / - chemoT

Lymphoma

• Most are high-grade B cell

• Thyroidectomy NOT indicated

• ChemoT followed by radioT OR radioT alone

• Excellent prognosis

Lymph node surgery• Lateral compartment of neck

• Levels I-V• Submental, submandibular, deep cervical and posterior triangle nodes

• Central compartment of neck• Pretracheal and paratracheal nodes

• Mediastinal nodes• Superior mediastinal up to superior aspect of brachiocephalic vein

• Compartment 4• Nodes between brachiocephalic vein and tracheal bifurcation within anterior and

posterior triangle

• Selective neck dissection• Preservation of spinal accessory nerve, internal jugular vein, sternocleidomastoid

muscle

• Radical neck dissection• Radical neck• Extended neck• Modified radical neck dissection

Early post-surgical Mx

• T3 – 20 mg tds– After total / near-total thyroidectomy– Stop 2/52 before radioiodine scan or 131I ablation

• Check serum calcium

• Check baseline post-op serum Tg at least 6/52 after surgery

Post-op 131I ablation? • Consider if

• Tumour > 1-1.5 cm• extension beyond the capsule• Unfavourable histology

• Decision requires MDT input• Not just tumour size but also age, mets, invasion, completeness of

excision, comorbidities

• Benefits• Destruction of residual disease post-op• Prolonged survival• Increased sensitivity of Tg measurements

Side effects of post-op 131I ablation• Early

– Transient hypothyroidism– Abnormality of taste– Nausea– Neck discomfort & swelling– Radiation cystitis– Radiation gastritis– Oedema– Bleeding into secondary deposits

• Late– Dry mouth, abnormal taste– Sialadenitis & lachrymal gland dysfunction– Increased lifetime incidence of leukaemia & secondary cancers– Radiation fibrosis– Increased risk of miscarriage– Infertility in men

Radioiodine ablation

• The Countdown....– Months beforehand.... Stop amiodarone – 8/52.... Stop breastfeeding– 4/52.... Stop T4– 2/52.... Stop T3

Low iodine diet

– Exclude pregnancy– Consider pre-treatment sperm banking

– If patient likely to have more than two high dose 131I therapies

– If a pre-ablation scan is felt to be absolutely necessary– 99mTc-pertechnetate scan preferable to 131I to reduce risk of stunning

– Measure TSH and Tg immediately prior to Tx

The treatment

• Serum TSH should be > 30 at time of ablation• Consider Recombinant human TSH• 0.9 mg rhTSH IM 2/7 prior to 131I ablation

• 3.7 GBq (5-7.4 GBq if known mets)

• Discharge 3/7 after radioiodine Tx• Commence thyroxine on discharge• Post-ablation scan 3-10/7 later• F/U clinic 2-3/12

131I diagnostic scans after 131I ablation

• Assesses effectiveness of ablation & immediate requirement for further 131I ablation

• Low risk cases may be assessed adequately by serum Tg without scan

• Serum TSH and Tg on day of scan

• TSH > 30 is required for optimal imaging

Papillary carcinoma of thyroid. Iodine uptake scan showing residual thyroid tissue

Is a repeat 131I diagnostic scan ever required?

• YES in high risk disease & cases with Tg Abs interfering with serum Tg measurements

• YES if suspicion of disease recurrence• Otherwise NO

• Requires thyroid hormone withdrawal prior to scan• If possible, switch to T3 prior to scan as can be stopped as close as two weeks prior

to scan• rhTSH if thyroid hormone withdrawal contraindicated (eg IHD, panhypopituitarism)• Low iodine diet 2/52 prior to scan

• Restart T4 3/7 after radioiodine scan

• No conception for 6/12 in , 4/12 in post-scan♀ ♂

External beam radiotherapy

• Infrequently indicated

– Adjuvant radiotherapy– Gross evidence of local tumour invasion at surgery esp if residual tissue does not concentrate radioiodine– Extensive pT4 disease & > 60 yrs, with extensive extranodal spread

– High dose external beam– Unresectable tumours (esp if do not concentrate radioiodine)

Post-Tx F/U• Voice dysfunction?

• → direct / indirect laryngoscopy

• Monitor calcium• 30 % need calcium supplementation• By 3/12, < 10 % require calcium supplements• Calcium withdrawal should be undertaken when euthyroid

• Suppression of serum thyrotrophin• Levothyroxine to maintain TSH < 0.1• Average dose is 175 mcg to 200 mcg

• Measurement of serum thyroglobulin

Thyroglobulin• Secreted by cancerous AND normal thyroid cells

• Therefore limited use in patients who have not had a total thyroidectomy & 131I ablation

• Detection is highly suggestive of thyroid remnant, residual or recurrent tumour

• Endogenous TgAb may interfere with measurement• TgAb valuable in interpreting Tg result

• Release is TSH dependent• Determine TSH concurrently

Tg measurement• More sensitive than imaging when screening for tumour recurrence• NOT to be collected sooner than 6/52 post thyroidectomy or post

131I ablation• Annual check recommended• Diagnostic sensitivity is enhanced by an elevated serum TSH (>30)

• Achieve by either thyroid hormone withdrawal (recommended)• OR rhTSH stimulation IF thyroid hormone withdrawal cannot be achieved

(2 x IM 0.9 mg, then measure Tg on day 5)

• If Tg persistently detectable or rises, further evaluation & MDT discussion required

Long-term follow-up• Lifelong because:

– Disease has a long natural Hx

– Late recurrences can occur which are readily amenable to Tx

– TFT monitoring on thyroid hormone replacement and its possible complications (hyper / hypothyroidism, pAF)

– Late possible s/e of 131I Tx (eg leukaemia)

Any questions?