Endocrine Surgery JC039: A Thyroid Nodule: Benign Thyroid Nodules, Thyroid Cancer Flashcards
Thyroid nodule
Prevalence:
- Extraordinary common
- Depends on:
—> Iodine deficiency (some area endemic)
—> Ionising radiation exposure
—> Female gender
—> Advanced age
—> Method of detection (palpation lower rate of detection, USG / autopsy higher rate of detection)
Thyroid cancer
- Not so common, but ↑ incidence due to detection of small papillary carcinoma
- Mortality remains low
- Size <1-2 cm
Classification of Goitre
Classified according to etiologies, morphological changes, functional changes, pathological changes
- Simple goitre (endemic / sporadic)
- Diffuse
- *Nodular - Toxic goitre (hyperfunctioning)
- Diffuse toxic (Graves’)
- *Toxic nodular (Plummer’s aka Toxic MNG)
- *Toxic / Functioning adenoma - *Neoplastic goitre
- Benign
- Malignant - Thyroiditis (Inflammatory cause)
- Bacterial (acute suppurative)
- Viral (subacute)
- Lymphocytic / Hashimoto / Autoimmune (chronic)
*: commonly detected by USG / palpation
Simple / Non-toxic, Diffuse / Nodular goitre
Definition:
1. Any thyroid enlargement (most common giving rise to goitre)
2. Not a result of neoplasia / inflammation (i.e. thyroiditis)
3. No thyroid dysfunction (i.e. normal TFT)
4. Endemic (∵ iodine deficiency, area of >10% patient with clinically palpable goitre) / Sporadic
5. Morphological changes: Uninodular / Multinodular (MNG) / Dominant nodule in MNG
Clinical presentation of Thyroid nodule
- Neck swelling / mass
- Pain / discomfort / obstructive feeling
-
Local pressure symptoms
- Dysphagia
- Choking
- SOB etc. - Voice disturbance / hoarseness (usually ∵ trachea compression of trachea, uncommon due to nerve palsy —> usually only by malignant nodule)
- Thyroid dysfunction (Hyper / Hypothyroidism)
- Incidental:
- P/E
- Imaging: USG (of carotid artery), CXR (tracheal deviation, compression, soft tissue mass), CT/MRI, PET scan
Pathology of Thyroid nodule
- Nodular goitre (most common, 70%) (e.g. MNG)
- Colloid
- Haemorrhagic cystic (old / new blood)
- Complex
- Hyperplastic
- Adenomatous nodule
—> all are just descriptive terms of nodules - Benign Follicular Adenoma (15%)
- mainly non-toxic
- some maybe hyperfunctioning -
Well-differentiated thyroid carcinoma (10%)
- Follicular / Papillary
(Anaplastic = Undifferentiated) - Miscellaneous (5%)
- Other thyroid malignancies
- Thyroiditis (usually diffuse enlargement, but can present atypically as nodules)
Clinical risk factors for malignancy of thyroid nodules
- Extreme of age
- elderly / young (papillary carcinoma)
- female (nodular goitre) - Previous neck irradiation
- Geographic (radiation exposure, endemic goitre)
- Family history
- Medullary thyroid carcinoma (1/3 familial)
- Papillary / Follicular carcinoma no family association - Pressure symptoms
- indicate rapid growth - Solitary vs Multiple nodules
- Solitary: more likely cancer - Nodule characteristics (size, consistency, fixation)
- Presence of cervical LN
- occult thyroid cancer can present with cervical LN without palpable nodules in thyroid gland -
RLN palsy
- damage of RLN by malignant tumour
Investigations of Thyroid nodule
Routine
1. TFT
- ultrasensitive TSH +/- Free T4
2. USG evaluation
3. FNAC
Specific
4. Other blood tests
- ESR
- Thyroid Ab (TPO (Thyroid peroxidase antibodies), ATA (Anti-thyroid antibodies))
- Calcitonin (Medullary thyroid carcinoma)
- Genetic testing (TSH receptor mRNA RT-PCR)
- Imaging
- Radioscintigraphy (IV radioisotope (I123 / Tc99m) + gamma camera)
- CXR
- CT
- MRI
- PET - Endoscopy
- Direct laryngoscopy
- OGD
Surgical
7. Thyroidectomy: Diagnostic +/- Therapeutic
USG
- B-mode real-time scanner: 7.5 / 10 mHz probes
- Non-invasive, no radiation hazard, convenient and cheap
- High sensitivity (2-3 mm nodules) but low specificity (cannot confirm nature)
Role:
1. Extend P/E
2. Guide needle aspiration
3. For all patients with goitre / palpable nodule
4. Should NOT be performed as a screening test
5. Guide but cannot confirm diagnosis
5 categories of USG findings:
Category 1: Benign
- cystic
Category 2: Very low suspicion
- spongiform
- partially cystic
Category 3: Low suspicion
- hyperechoic / isoechoic
Category 4: Intermediate suspicion —> FNAC may be needed
- hypoechoic
Category 5: High suspicion —> FNAC may be needed
- microcalcification
- irregular margin
- marked hypoechoic
- taller than wide (indicate infiltrative)
- extrathyroidal extension
FNAC
4 cytology results:
- Benign (negative): <1% chance malignancy
- Malignant (positive): >99% chance malignancy
- Non-diagnostic (unsatisfactory due to sampling technique / no thyroid cells collected): <3% chance malignancy
- Suspicious (indeterminate): 20% chance malignancy
Bethesda classification:
Category 1: Non-diagnostic —> Repeat FNA
Category 2: Benign —> Clinical follow up
Category 3: AUS (atypia of undetermined significance) / FLUS (follicular lesions of undetermined significance) (10% chance malignancy) —> Repeat FNA
Category 4: Follicular neoplasm —> Surgical lobectomy (to arrive at diagnosis + prevent spread via capsular / vessel)
Category 5: Suspicious of malignancy (60-75% chance malignancy) —> Surgical lobectomy + Total thyroidectomy
Category 6: Malignant —> Total thyroidectomy
Molecular assay application of FNAC
- BRAF, N/H/K-RAS, RET-PTC1/PTC3, PAX8/PPARc
- BRAF mutation: 40-64%
- panel of mutations: 63-80% accuracy
- specific but not sensitive: high PPV (rule-in test) (有false negative) - Gene expression classifier (167 genes)
- high sensitivity but not specific with high NPV (rule-out test) (有false positive) - Gene sequencing classifier
- higher specificity + improved PPV
Indication:
- For suspicious / indeterminate nodule (Category 3 / 4 in Bethesda)
Disadvantage:
- Expensive + limited availability
ATA guidelines in management of Thyroid nodule
USG evaluation (Sonographic pattern) + FNAC criteria
Suspected thyroid nodule
—> USG thyroid
—> 5 Sonographic patterns (High / Intermediate / Low / Very low suspicion / Benign)
—> Nodules >=1cm (<1 cm FNAC not required ∵ microcarcinoma is not aggressive and can be observed)
—> FNAC (except if benign —> FNAC not required)
—> Bethesda classification
—> Manage accordingly
—> Indeterminate / Malignant —> Surgery advised
Radioisotope scintigraphy
IV radioisotope (I123 / Tc99m) + gamma camera
Indications:
- Diagnosis of malignancy
- 10-20% cold nodules malignant (low specificity)
- hot / warm nodules rarely malignant - Functional assessment in Thyrotoxic patient
- Graves’
- Toxic adenoma
- Toxic nodular goitre
Disadvantages:
- Radiation exposure, expensive, low specificity + sensitivity
Other investigations
- CXR (tracheal compression / deviation, retrosternal goitre, mediastinal mass)
- CT / MRI
- anatomical relationship with surrounding mediastinal structures - PET scan
- Laryngoscopy
- hoarseness of voice (unilateral cord palsy ∵ RLN invasion by thyroid cancer)
Indications of operation for Benign thyroid nodules / Nodular goitre
- Pressure symptoms (size of goitre / nodule >4cm)
- Tracheal compression / deviation
- ↑ Goitre size
- Retrosternal extension (compressive symptoms)
- Suspected malignancy
- Cosmetic considerations / patient wish
Surgical treatment of Benign thyroid nodules
- Unilateral lobectomy (Hemithyroidectomy)
- for Uninodular goitre
- safe, minimal morbidities, can be diagnostic, curative
- reoperation on contralateral lobe without added difficulty
- ~10% chance hypothyroidism - Total thyroidectomy (Bilateral thyroidectomy)
- for MNG
- additional surgical risk (Hypoparathyroidism)
- no recurrence
- needs long-term thyroxine replacement
Alternative treatment of Benign thyroid nodules
Need probe
1. Radiofrequency ablation (RFA)
2. Percutaneous laser ablation (LA)
3. Microwave ablation (MWA)
No need probe
4. High-intensity focused ultrasound (HIFU)
5. Ethanol injection after aspiration (for Cystic nodule)
Nodules will not disappear, only shrink —> max response in 6 months
Cystic nodules: cannot use 1-4 (since only boil the cyst content)
Cannot replace surgery as a definitive treatment
Thyroid carcinoma: Histological types
Major histologic type:
1. Well differentiated (90%) (very good prognosis)
- Papillary (80-90%)
- Follicular (10-20%)
- Poorly differentiated (Insular) (5%) (rare, in elderly)
- Undifferentiated (Anaplastic) (5%)
- Medullary carcinoma (5%) (neuroendocrine tumour: arise from Parafollicular C cells)
- Others (1%)
- Lymphoma (can be treated without surgery if a definitive diagnosis can be made beforehand —> main treatment: chemotherapy)
- SCC
- Sarcoma
- Metastasis
Well-differentiated thyroid carcinoma (WDTC)
Management considerations:
1. Extent of thyroidectomy
- hemithyroidectomy vs total thyroidectomy
- Nature + Extent of LN / neck dissection
- prophylactic / therapeutic
- central / lateral compartments - Post-op adjuvant therapies
- Radioiodine I131 ablation
- External beam irradiation
- T4 suppressive therapy —> suppress TSH to ↓ tumour recurrence
Risk groups:
- stratified based on
—> AJCC pTNM staging (stage 1-4) (prognostic + management significance)
—> AMES (age, metastasis, extent, size of tumour)
—> determines extent of surgery (TT), need for adjuvant therapy
Low risk:
- 85-90% of patients
- 2-5% mortality
- 10% recurrence
High risk:
- 10-15%
- 40-50% mortality
- 45% recurrence
PTC Histological variants
Relatively good prognosis
1. Papillary microcarcinoma
2. Encapsulated variant
3. Follicular variant
4. Tall cell / columnar variant
More aggressive, more likely to metastasise on presentation, treated as high risk tumour irrespective of size / stage
4. Diffuse sclerosing
5. Oxyphilic cell (Hurthle cell) type
Low risk PTC
Definition:
- Stage 1, 2 (<55 yo + without distant metastasis)
- <2 cm (T1) / 4 cm (T2)
- no invasion
- no LN metastasis
- majority as Papillary microcarcinoma (PTMC): <1 cm
- survival: ~100%
2 choices of management:
1. Total thyroidectomy
- commonly for multifocal + bilateral disease
- allow RAI ablation + Thyroglobulin monitoring to detect recurrence
- low morbidity rate by experienced surgeons
- Hemithyroidectomy
- excellent survival + low recurrence
- avoid T4 replacement (only 10-20% chance of hypothyroidism)
- lower morbidity
—> Overtreatment vs Potential benefits
—> Patients’ vs Physicians’ preference
PTC: Cervical LN management
Management:
1. Central (level 6): same incision as thyroidectomy
- possibly prophylactic / routine —> can detect micrometastasis
- ↓ in disease recurrence / reoperations
- upstaging disease (if detect micrometastasis) + ↑ use of I131
- ↑ in morbidity: hypoparathyroidism
- Lateral (level 2-5): extend / separate incision
- usually therapeutic, rarely prophylactic
- for clinically involved nodes: USG +/- FNAC
- excision (Berry-picking)
- modified / functional / selective neck dissection (usually no need radical dissection, ∵ thyroid cancer slow growing)
Adjuvant therapy for PTC: Post-op I131
- Preceded by Total / Near-total thyroidectomy
-
Thyroxine withdrawal (for 4 weeks beforehand) vs Thyrogen (Synthetic TSH 1-2 days beforehand)
—> allow ↑ TSH production from pituitary
—> ↑ Iodine uptake by residual thyroid tissue / tumour cells
Indication:
1. High risk (stage 3/4 disease)
- gross persistent / residual disease
- nodal / distant metastasis
- Low risk (selected stage 1, 2)
- destroy occult microscopic foci
- facilitate disease surveillance
- 1.1 GBq (30mCi) vs 3.7 GBq (100mCi) (both as effective)
- require individual patient preference
- beware short + long-term adverse effects
Papillary thyroid microcarcinoma (PTMC)
Very common thyroid cancer
Definition:
WHO: <1cm + detected incidentally
AJCC pTNM staging: <1cm + detected incidentally + majority pT1a / stage 1 disease (can have exception e.g. metastasis)
Feature:
- Extremely low risk
- Excellent survival
- Less aggressive treatment (Hemithyroidectomy unless already LN / distant metastasis)
—> can even Observe only (very low risk of ↑ in size / nodal metastasis)
WDTC: De-escalation of treatment / De-intensifying care
Principle:
- Avoid overtreatment
- Treat patients appropriately
Evolving towards:
1. Active surveillance
2. Less than total thyroidectomy (∵ not much difference in cumulative death risk compared to hemithyroidectomy)
3. Avoid routine neck dissection —> avoid complications e.g. hypoparathyroidism
4. Less adjuvant I131 therapy (not all patients require esp. if only hemithyroidectomy)
5. Avoid screening + overdiagnosis (∵ very low mortality / clinically insignificant anyway) —> ↑ treatment (waste resource) —> thyroid USG not routinely recommended for healthy subjects
Medullary thyroid carcinoma (MTC)
Neuroendocrine tumour
- Arise from Parafollicular C cells
- 25-50% familial
Marker:
- Calcitonin (basal / stimulated)
Management:
- Total thyroidectomy
- Central +/- Lateral neck dissection
Familial cases (1/3):
- MEN2A
- MEN2B
- Familial MTC
Diagnosis:
- Genetic analysis: RET proto-oncogene (~100% penetrance)
—> may perform Prophylactic thyroidectomy (at 5-10 yo) at stage of C cell hyperplasia before develop into clinically invasive cancer
Prognosis:
- Worse than WDTC
Anaplastic carcinoma
- One of most aggressive cancer in human
- Uncommon (possibly ∵ early treatment of well-differentiated thyroid cancer)
- Elderly with poor co-morbid state
- Aggressive + rapidly growing
- Locally advanced disease at clinical presentation
- Frequent distant metastasis
- Lack of effective treatment: Chemoirradiation +/- Resection +/- Targeted therapy (palliative only)
- Invariable palliative + fatal (4-6 months survival)
Pre-op consideration
Hyperthyroidism:
1. Anti-thyroid medications until Euthyroid
- avoid precipitation of thyroid storm during operation
2. β-blockers for 2 weeks
(3. Old practice: Lugol’s iodine 5 days before operation (may reduce blood loss during operation))
Myxoedema coma:
- Give IV Hydrocortisone with IV Thyroxine otherwise Cortisol metabolised by ↑ Thyroxine
Papillary Thyroid carcinoma:
1. Post-op I131
- Thyroxine withdrawal (for 4 weeks beforehand) vs Thyrogen (Synthetic TSH 1-2 days beforehand)
—> allow ↑ TSH production from pituitary
—> ↑ Iodine uptake by residual thyroid tissue / tumour cells
2. T4 suppressive therapy —> suppress TSH to ↓ tumour recurrence
SpC Interactive tutorial: Management of Thyroid Cancer
Thyroid gland: Surgical anatomy
3 bony structures:
1. Hyoid bone
2. Thyroid cartilage
3. Cricoid cartilage
- complete ring
- mark upper limit of isthmus
- divide thyroid horizontally into upper 1/3 (i.e. upper pole) + lower 2/3 (i.e. middle + lower pole)
Thyroid gland:
1. Left / Right lobe (cover 2/3 of trachea)
2. Isthmus (cover 2nd + 3rd tracheal ring)
3. Pyramidal lobe
Recurrent laryngeal nerve:
- Run along tracheo-esophageal groove —> Readily infiltrated by tumour located at back of Thyroid lobe —> hoarseness
- Need to be identified during surgery
Central compartment:
- SC fat around thyroid
- Level 6 LN (pretracheal + paratracheal)
Lateral compartment:
- Level 2-5 LN
Treatment for WDTC
Surgery:
1. Primary tumour
- Hemi / Total Thyroidectomy
—> choice depends on Size + Tumour prognostic features
—> <4cm diameter + no poor prognostic features —> Hemithyroidectomy
(ATA guideline:
- >1cm, <4cm
AND
- without extrathyroid extension
AND
- without clinical evidence of LN metastasis
—> Bilateral (near-total / total) or Unilateral (hemi) are acceptable
—> Hemi: may be sufficient initial treatment for low risk papillary / follicular carcinoma
—> Total: enable RAI therapy / enhance follow-up based upon disease features / patient preference)
- Metastatic cervical LN
- Central compartment neck dissection (often performed at time of surgery, for all patients regardless of whether there are enlarged central LN —> prophylactic)
- Lateral compartment Functional neck dissection (level 2-5) (only done when proven disease in the compartment)
- Lateral compartment Selective neck dissection (level 2-5) (only done when proven disease in the compartment)
- Compartmental neck dissection
- Excision of LN
- “Prophylactic” neck dissection
(Level 1 LN never involved)
Adjuvant therapy (required for Intermediate / High risk tumours):
1. Radioactive iodine
- 30-100mCi
- given 2 months after surgery
- given T4 withdrawal / recombinant TSH injection (from ERS15: ↑ Iodine uptake by residual thyroid tissue / tumour cells)
- dosage decreasing recently ∵ efficacy shown similar between low / high dose
- post-therapy scan 5-8 days after
- whole body scan 6-12 months after
- therapy to distant metastases: 100-200mCi
-
T4 suppressive therapy
- lower TSH level <0.03 -
External beam RT
- reserved for patients unable to undergo complete excision i.e. residual gross tumour tissue - Chemotherapy (NOT given since most tumours are chemo-resistant)
- doxorubicin as a radiation sensitiser
Neck dissection (From HNNS37)
Removal of lymphatics in the neck that harbours cancer metastasis
Radical neck dissection:
Removal of
- Level 1-5 LN (ipsilateral)
- SCM
- IJV
- CN11 (pass through lymphatic layer)
- Cervical plexus (pass through lymphatic layer) (functional deficit but acceptable)
Modified radical neck dissection:
Modification of radical neck dissection by preserving:
- SCM
- IJV
- CN11
—> Aim: improving functional outcome without jeopardising control of nodal disease
Selective neck dissection:
Removal of certain areas of LN that has highest chance of occult nodal metastasis
- Oral tongue cancer —> Supraomohyoid neck dissection (Level 1-3) for oral tongue cancer
- Tonsil cancer —> Level 2-4
- Thyroid cancer —> Central compartment dissection (bilateral level 6)
—> usually reserved for patients with no clinical evidence of nodal metastasis but cancer has high chance of occult nodal metastasis
Risk stratification for WDTC
2015 ATA risk stratification system:
- Low / Intermediate / High risk
- Predict likelihood of WDTC recurring after complete excision
- Number + Size of involved LN carry prognostic significance
- Genetic mutation e.g. BRAFV600E —> higher recurrence risk
AJCC TNM staging (8th edition):
- Age >=55 an important parameter
Management of High risk WDTC patients
High risk:
- Age >55
- Tumour size >2cm
- Extrathyroidal extension
- Incomplete resection of primary tumour (R2)
- Distant metastasis
Management:
1. Total / Near-total thyroidectomy
2. Central compartment neck dissection (+/- Compartmental neck dissection)
3. Radioactive iodine ablation
4. Thyroxine suppressive therapy (keep TSH <0.03)
5. External beam RT (for incomplete resection R2)
(Prognostic risk classification for WDTC: (from SpC Bedside)
AGES / AMES:
High risk:
- Age >40
- Male
- Grade / Metastasis: Poorly differentiated / Metastasis
- Extent: Capsular invasion, Extrathyroidal extension
- Size: >4cm)
Monitoring of WDTC
Life-long (Interval 3 months - 1 year)
1. Clinical examination (H+N region)
2. Thyroid function test
3. Thyroglobulin (from SpC Bedside: take Anti-Thyroglobulin Ab as well)
4. CXR
5. USG (+/- FNAC)
6. WBS (whole body scan)
7. PET (if WBS negative)
Occult / Minimal PTC
Occult:
- Clinical not obvious but discovered post-mortem by pathologist (very common: 1 in 5)
Minimal (Micro):
- <=1cm diameter
- Associated with excellent prognosis
- Not all occult carcinoma are microcarcinoma
Follicular thyroid carcinoma (FTC)
- Behave very differently from PTC
- Present with distant metastases via blood
Metastasis:
1. LN metastases 10-15%
2. Haematogenous spread
- Lungs
- Bone
If FNAC show follicular cytology —> can be adenoma / carcinoma
Treatment:
1. Hemithyroidectomy (∵ not possible to differentiate follicular adenoma vs carcinoma by FNAC alone)
—> Wait for Paraffin section (5-7 days later)
—> Widely-invasive / Angio-invasive FTC —> Completion total thyroidectomy
—> Minimally invasive (encapsulated) FTC —> Observation sufficient
-
Paraffin section (Frozen section not routinely performed)
—> diagnostic information in 13%
—> surgical procedure modified in 3.3%
—> misguided intervention in 5%
Management of FTC with distant metastasis:
1. Histological confirmation of metastasis
2. +/- Detection of primary tumour
3. Total thyroidectomy
4. Adjuvant therapy
- Ablation
- Radioactive iodine
- Thyroxine suppression therapy
Complications of Thyroid surgery (From JC038)
- Vocal cord dysfunction (unilateral / bilateral)
- RLN (Infraglottic) / External branch of Superior laryngeal nerve (Supraglottic: Cricothyroid)
- transient / permanent -
Hypoparathyroidism (∵ injury / removal of parathyroid gland)
- transient / permanent - Bleeding
- superficial / deep - Tracheomalacia (cartilage in trachea collapses especially during increased airflow)
- Wound complications
- Seroma
- Hypertrophic scar - Thyroid storm
- Others
Post-op Monitoring:
1. Voice
2. Ca level (6-12 hours after operation) (Hypoparathyroidism)
3. SOB, Compression sensation
4. HR, temperature (Thyroid storm)
5. Infection
6. Keloid scar
MEN type 1 (SpC Revision)
Autosomal dominant (AD)
Clinical features:
1. Primary hyperparathyroidism
- most common feature
- asymmetric multiglandular involvement
- current view: multiple adenomas rather than hyperplasia
2. Pancreatic neuroendocrine tumours
- most are functional
—> Gastrinoma (50%)
—> Insulinoma (20%)
—> Glucagonoma (3%)
—> VIPoma (1%)
3. Pituitary adenomas
4. Others (Lipomas, Adrenal adenomas, Thymic carcinoids etc.)
- 50% probability of death by 50 yo
MEN type 2A
- 75% of MEN type 2
- Caused by germline mutation of RET gene
Clinical features:
1. Medullary thyroid carcinoma (>90%)
- can be treated during pre-symptomatic stage due to early detection of germline RET gene mutation
2. Phaeochromocytoma (50%)
3. Hyperparathyroidism (20-30%)
Prognosis:
- Better than MEN1
