About 4-8% of population in US have palpable thyroid nodules; prevalence in Singapore not known.
History and physical examination – as above Differential diagnoses:
1. Cancer (only 10-20% of nodules is malignant, but need to exclude!) 2. Follicular adenoma
3. Cyst (simple, colloid, or haemorrhagic) 4. Dominant nodule of a multinodular goitre
Clinical features suspicious of malignancy:
1. Male gender (thyroid nodules less common in male but more likely to be malignant) 2. Age <15yrs or >60yrs (majority of nodules occurs in 3rd to 6th decades – likely
benign)
3. History of head and neck radiation or thyroiditis
4. Family history of thyroid cancer (or MEN2, Gardner‘s syndrome, FAP) 5. Rapidly enlarging nodule
6. Hard, single nodule and/or nodules fixed to surrounding structures 7. Hoarseness (i.e. recurrent laryngeal nerve invasion)
8. Cervical lymphadenopathy
9. Other symptoms of invasion e.g. haemoptysis, stridor, dysphagia Investigations:
1. FINE NEEDLE ASPIRATION CYTOLOGY
- The most important investigation modality!
- 90-95% sensitivity and specificity - 4 possible results:
(i) Benign (thyroiditis, dominant nodule of MNG) (ii) Malignant (papillary, medullary, anaplastic, mets)
(iii) Suspicious (follicular, Hurthle cell change in follicular lesion) (iv) Inadequate repeat FNAC
- Can be both therapeutic and diagnostic for cyst – chocolate-brown fluid aspirated; feel lump after aspiration to check for resolution
- Cannot differentiate follicular adenoma from follicular carcinoma as the mark of malignant disease is capsular invasion – can only tell from a histological specimen of the nodule
- Procedure: inject local anaesthetic in area, insert 20-22G needle and apply suction while fanning needle in region of nodule, release suction before pulling out needle, expel contents onto slide, then fix
- Best to have experienced cytologist on hand to view slides and re-do FNAC if the sample is inadequate
2. ULTRASOUND OF THYROID
- Advantages:
(i) Objective measurement of nodule
(ii) Detection of subclinical nodule/screening – of value in papillary carcinoma since multicentric disease occurs in 15%
(iii) Detection of lymph node enlargement (especially level VI nodes) (iv) Can define consistency of nodule – solid, cystic, or complex
- Suspicious sonographic features:
(i) Microcalcifications (in psammoma bodies papillary cancer) (ii) Indistinct margins
(iii) Sonolucent halo around lesion
(iv) Hypoechoeic or anechoeic lesion – carcinoma is almost never hyperechoeic
(v) Increased intranodular vascularity
- Ultrasound still does not provide as good diagnostic value as FNAC 3. THYROID FUNCTION TEST
- Easy to perform, establish baseline, detect any abnormal function - No real diagnostic value
4. RADIO-ISOTOPE SCAN
- Hot nodule: only 1% malignant; but cold nodule: 10-20% malignant - But not very useful diagnostically
5. BASELINE TUMOUR MARKERS (IF SUSPECTED OR CONFIRMED MALIGNANCY) - For differentiated thyroid cancer: thyroglobulin
- For medullary thyroid cancer: calcitonin, carcinoembryonic antigen (CEA) 6. CT SCAN OR MRI
- Not routine in thyroid nodular study - Uses:
(i) Evaluating invasion of surrounding structures (ii) Retrosternal extension
(iii) Lymph node involvement
- Care to be taken with CT as contrast contains iodine and will affect post-op radioactive iodine body scan once given
- MRI has same functions as CT but higher cost 7. ENT EXAMINATION OF VOCAL CORDS
- In the rare occasion that there is pre-existing vocal cord palsy on one side take extra care not to injure opposite recurrent laryngeal nerve as that can cause bilateral vocal cord palsy
Management of benign nodule:
- Soft, small, round nodule with benign FNAC results, non-functional, not causing any symptoms can follow-up and monitor any increase in size
- A lump >4cm has a greater risk for malignancy
PART III:THYROID CANCERS
Differentiated thyroid carcinoma
Medullary carcinoma Anaplastic carcinoma Lymphoma
Papillary carcinoma Follicular carcinoma
Proportion 75% 10% 7% 3% 5%
Age 25-40 years 40-50 years >50 years for sporadic type; 20-30 years for familial 60-70 years >50 years
F:M ratio 3:1 3:1 1:1 3:2 2:1
Risk factors - Radiation exposure - Polyposis syndromes (FAP,
Gardner‘s, etc)
- Positive family history in 5%
- Follicular adenoma is NOT a risk factor
- Iodine deficiency may be associated
- Significant family history in the familial type – MEN2 (AD, complete penetrance, associated with parathyroid adenoma and phaeochromocytoma – see notes below)
- Longstanding goitre - History of previous
differentiated thyroid ca (30% of anaplastic ca)
- History of lymphoma or
- Characteristic Orphan Annie nuclei, nuclear pseudoinclusions - Papillary architecture with
psammoma bodies
- Tall cell variant (nuclear features of papillary ca within follicular lesion) behaves like papillary ca, has worse prognosis
- Follicular structures similar to normal thyroid
- Diagnosis of cancer made on evidence of capsular or vascular invasion by tumour cells (vs follicular adenoma) - Hurthle cell variant – worse
prognosis
- Arise from parafollicular C cells (which produce calcitonin)
- Distinctive deposits of acellular amyloid material – altered calcitonin collections
- Multicentric C-cell hyperplasia may be seen in familial cases
- Small blue round cells that are highly
- Slow-growing tumour - Spread by lymphatics - 30-50% multicentric
- LN involvement in 80% of disease at diagnosis (level VI first)
- Solitary
- Haematologic spread to bone, lung, liver, brain
- LN involvement in 10% (rare)
- Sporadic cases usually solitary, worse prognosis - Familial cases all multicentric, better prognosis - Aggressive growth; spread via local, lymphatic,
haematological routes
- 95% produce calcitonin, 80% produce CEA - Unilat LN involved in 60-80%, contralat LN in 40%
- Always exclude MEN2 – serum calcium, 24hr urinary catecholamines
- Poor prognostic factors (AMES): Age>40, presence of metastases, extra-thyroid invasion, size>4cm (more details on risk stratification below) Treatment Surgical resection
- Hemithyroidectomy for selected low-risk patients (see below) - Total thyroidectomy for the majority
- LN clearance: tracheo-oesophageal nodes cleared, and neck dissection if neck nodes are positive
- For suspicious lesion – hemithyroidectomy with histology, KIV TT Adjuvant therapy
- Radioactive iodine at ablative levels to ablate remnant thyroid and any cancer tissue (only for total thyroidectomy)
- External radiotherapy (only shown to have good results in pts with locally advanced follicular ca)
TSH suppression – give L-thyroxine to suppress TSH levels to <0.005U/L Follow-up
- Check TSH levels
- Thyroglobulin as a tumour marker of recurrence
- Radioactive iodine scan to detect recurrence, followed by ablation
Surgical resection
- Aggressive resection – total thyroidectomy with level VI node clearance
- Sampling of cervical and mediastinal nodes and modified dissection where positive
No good adjuvant therapy Follow-up
- Thyroxine replacement (not for TSH suppression but to maintain euthyroid state)
- Serum calcitonin and CEA six mths after surgery (if normal, considered cured – 5% 5yr recurrence) - High calcitonin – screen for residual or metastatic
disease, treat surgically, with RT or chemo as appropriate
Palliative therapy for compressive effects - Chemotherapy to shrink
tumour
- Surgical debulking - Tracheostomy
Chemotherapy and/or radiotherapy depending on type of lymphoma
5yr survival 95% in low-risk pts, 88% in intermediate-risk pts, 50% in high-risk pts Slightly worse for follicular ca
60-70% Median survival <6mths Dependent on histo, stage,
treatment, etc.
Differentiated thyroid cancer
- Papillary and follicular cancers are considered differentiated thyroid cancer (as opposed to anaplastic – undifferentiated – thyroid cancer)
- Prognosis is excellent RISK STRATIFICATION:
- Risk factors can be divided into patient factors and disease factors
- Patient factors: Age – >45 years old is high risk; Gender – male is high risk - Tumour factors:
Size – nodule >4cm has higher risk
Histology – tall cell variant of papillary ca and Hurthle cell variant of follicular ca are considered unfavourable
Extrathyroidal extension into surrounding structures – worse Lymph node or distant metastases – worse
- Various score systems have been formulated to stratify risk:
AMES – Age, Metastases, Extent, Size
AGES – Age, Grade (Histological), Extent, Size) – rarely used as histological grading is not commonly performed
MACIS – Metastasis, Age, Completeness of resection, Invasion, Size - Patients can be divided into three groups:
(i) Low risk – low risk patient and low risk disease (i.e. no high risk features) (ii) Intermediate risk – low risk patient with high risk disease, or high risk patient
with low risk disease
(iii) High risk – high risk patient and high risk disease
- Risk helps to guide treatment – low risk patients can undergo hemithyroidectomy without ablative radioiodine therapy post-op, while high risk patients undergo total thyroidectomy with post-op ablative RAI treatment; treatment in intermediate risk patients is tailored to the disease, but usually is similar to that in high risk patients - 5 year survival is also prognosticated by the risk: low risk patients have a survival
of 95-98%, intermediate risk patients 88%, and high risk patients 50%
TOTAL THYROIDECTOMY VERSUS HEMITHYROIDECTOMY Advantages of TT:
- Evidence for microfoci of disease and multicentricity of cancer – removal of the entire thyroid decreases risk of recurrence
- Ability to use adjuvant radioiodine to ablate any residual cancer tissue after surgery - Ability to use radioiodine to detect recurrent disease (normal thyroid picks up iodine
better than cancer cells, thus the presence of the thyroid gland will decrease the ability of RAI to pick up recurrent cancer) and as treatment for recurrence
- Ability to use serum thyroglobulin as a cancer marker for recurrence
Disadvantages of TT:
- Risk of bilateral recurrent laryngeal nerve injury and permanent hypoparathyroidism - Very low incidence of cancer recurrence in residual thyroid – microfoci probably not
clinically significant
- Limited thyroidectomy may spare patient from having to be on lifelong thyroid hormone replacement
Thus, risk stratification helps to guide the extent of surgical resection in differentiated thyroid cancer according to the patient‘s disease.
Lymph node clearance
- Tracheo-oesophageal groove (level VI) node clearance usually done - Radical neck dissection or modified radical neck if:
(i) Tracheo-oesophageal groove nodes histologically positive for cancer (ii) Clinically positive nodes in the neck – palpable or enlarged on ultrasound Radical neck dissection
- The removal, en-bloc, of the entire ipsilateral lymphatic structures of the neck, from the mandible superiorly to the clavicle inferiorly, from the infrahyoid muscles medially to the anterior border of the trapezius laterally
- Classic radical neck dissection (Crile’s) – internal jugular vein, sternocleido-mastoid muscle, and accessory nerve are resected. Structures not resected: carotid arteries, vagus nerve, hypoglossal nerve, brachial plexus, phrenic nerve
- Modified radical neck
(i) Type I: one of the three structures not removed, usually accessory nerve (ii) Type II: two of the structures not removed – accessory and IJV
(iii) Type III: all of the three structures not removed
(iv) Extended radical neck dissection: resection of lymph nodes and/or structures not included in the classic neck dissection
- Complications of radical neck dissection:
(i) Injury to nerves – vagus (vocal cord paralysis), cervical sympathetic chain (Horner‘s), mandibular branch of facial (lower lip weakness)
(ii) Haematoma bring back to OT to find source of bleeding and stop it
(iii) Salivary fistula (usually when pt has received RT to the neck, and if the upper GI tract was opened during the surgery) – infection can result
(iv) Wound infection – risk factors: previous irradiation, if upper aerodigestive tract is opened during surgery with salivary contamination, salivary fistula
(v) Carotid blowout – risk factors: infection, irradiation resus, apply constant pressure all the way to the OT!
(vi) Poor healing – usually in irradiated skin; weakest point is the junction of the trifurcate incision
Multiple endocrine neoplasia
A group of inherited diseases resulting in proliferative lesions (hyperplasia, adenomas, carcinomas) of multiple endocrine organs.
FEATURES:
- Tumours occur at younger age than sporadic cancers
- Multiple endocrine organs involved, either synchronously or metachronously - Multifocal tumours in each organ involved
- Tumour usually preceded by asymptomatic stage of endocrine hyperplasia
- More aggressive and higher chance of recurrence compared to sporadic type of tumours in the same organs
MEN1
- Autosomal dominant inheritance
- Gene involved is the tumour suppressor gene MEN1 located on chromosome 11q13 where mutations cause loss of function of the gene
- Three P‘s:
Parathyroid (95%) – hyperparathyroidism from hyperplasia of parathyroid glands Pancreas (>40%) – aggressive metastatic tumours (e.g. gastrinoma, insulinoma),
leading cause of death in MEN 1 patients
Pituitary (>30%) – most commonly prolactin-secreting macroadenoma; some have growth hormone-secreting tumours
MEN2
- Autosomal dominant inheritance
- Gene involved is RET protooncogene at 10q11.2 where activating mutations occur - Two distinct groups of disorders:
1. MEN 2a (Sipple syndrome)
Medullary carcinoma of the thyroid (almost all)
Phaeochromocytoma (50%, of which less than 10% are malignant) Parathyroid hyperplasia and hyperparathyroidism (30%)
2. MEN 2b (William syndrome)
Thyroid and adrenal involvement like MEN 2a, but no hyperparathyroidism Neurocutaneous manifestations: ganglioneuromas on oral mucosa, lips eyelids Other features: Marfanoid habitus, SCFE, delayed puberty