Endocrine Surgery JC039: A Thyroid Nodule: Benign Thyroid Nodules, Thyroid Cancer

Question 1

Thyroid nodule

Answer 1

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)

Question 2

Thyroid cancer

Answer 2

• Not so common, but ↑ incidence due to detection of small papillary carcinoma
• Mortality remains low
• Size <1-2 cm

Question 3

Classification of Goitre

Answer 3

Classified according to etiologies, morphological changes, functional changes, pathological changes

1. Simple goitre (endemic / sporadic)
   - Diffuse
   - *Nodular
2. Toxic goitre (hyperfunctioning)
   - Diffuse toxic (Graves’)
   - *Toxic nodular (Plummer’s aka Toxic MNG)
   - *Toxic / Functioning adenoma
3. *Neoplastic goitre
   - Benign
   - Malignant
4. Thyroiditis (Inflammatory cause)
   - Bacterial (acute suppurative)
   - Viral (subacute)
   - Lymphocytic / Hashimoto / Autoimmune (chronic)

*: commonly detected by USG / palpation

Question 4

Simple / Non-toxic, Diffuse / Nodular goitre

Answer 4

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

Question 5

Clinical presentation of Thyroid nodule

Answer 5

1. Neck swelling / mass
2. Pain / discomfort / obstructive feeling
3. Local pressure symptoms
   - Dysphagia
   - Choking
   - SOB etc.
4. Voice disturbance / hoarseness (usually ∵ trachea compression of trachea, uncommon due to nerve palsy —> usually only by malignant nodule)
5. Thyroid dysfunction (Hyper / Hypothyroidism)
6. Incidental:
   - P/E
   - Imaging: USG (of carotid artery), CXR (tracheal deviation, compression, soft tissue mass), CT/MRI, PET scan

Question 6

Pathology of Thyroid nodule

Answer 6

1. 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
2. Benign Follicular Adenoma (15%)
   - mainly non-toxic
   - some maybe hyperfunctioning
3. Well-differentiated thyroid carcinoma (10%)
   - Follicular / Papillary
   (Anaplastic = Undifferentiated)
4. Miscellaneous (5%)
   - Other thyroid malignancies
   - Thyroiditis (usually diffuse enlargement, but can present atypically as nodules)

Question 7

Clinical risk factors for malignancy of thyroid nodules

Answer 7

1. Extreme of age
   - elderly / young (papillary carcinoma)
   - female (nodular goitre)
2. Previous neck irradiation
3. Geographic (radiation exposure, endemic goitre)
4. Family history
   - Medullary thyroid carcinoma (1/3 familial)
   - Papillary / Follicular carcinoma no family association
5. Pressure symptoms
   - indicate rapid growth
6. Solitary vs Multiple nodules
   - Solitary: more likely cancer
7. Nodule characteristics (size, consistency, fixation)
8. Presence of cervical LN
   - occult thyroid cancer can present with cervical LN without palpable nodules in thyroid gland
9. RLN palsy
   - damage of RLN by malignant tumour

Question 8

Investigations of Thyroid nodule

Answer 8

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)

5. Imaging
   - Radioscintigraphy (IV radioisotope (I123 / Tc99m) + gamma camera)
   - CXR
   - CT
   - MRI
   - PET
6. Endoscopy
   - Direct laryngoscopy
   - OGD

Surgical
7. Thyroidectomy: Diagnostic +/- Therapeutic

Question 9

USG

Answer 9

• 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

Question 10

FNAC

Answer 10

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

Question 11

Molecular assay application of FNAC

Answer 11

1. 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)
2. Gene expression classifier (167 genes)
   - high sensitivity but not specific with high NPV (rule-out test) (有false positive)
3. Gene sequencing classifier
   - higher specificity + improved PPV

Indication:
- For suspicious / indeterminate nodule (Category 3 / 4 in Bethesda)

Disadvantage:
- Expensive + limited availability

Question 12

ATA guidelines in management of Thyroid nodule

Answer 12

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

Question 13

Radioisotope scintigraphy

Answer 13

IV radioisotope (I123 / Tc99m) + gamma camera

Indications:

1. Diagnosis of malignancy
   - 10-20% cold nodules malignant (low specificity)
   - hot / warm nodules rarely malignant
2. Functional assessment in Thyrotoxic patient
   - Graves’
   - Toxic adenoma
   - Toxic nodular goitre

Disadvantages:
- Radiation exposure, expensive, low specificity + sensitivity

Question 14

Other investigations

Answer 14

1. CXR (tracheal compression / deviation, retrosternal goitre, mediastinal mass)
2. CT / MRI
   - anatomical relationship with surrounding mediastinal structures
3. PET scan
4. Laryngoscopy
   - hoarseness of voice (unilateral cord palsy ∵ RLN invasion by thyroid cancer)

Question 15

Indications of operation for Benign thyroid nodules / Nodular goitre

Answer 15

1. Pressure symptoms (size of goitre / nodule >4cm)
2. Tracheal compression / deviation
3. ↑ Goitre size
4. Retrosternal extension (compressive symptoms)
5. Suspected malignancy
6. Cosmetic considerations / patient wish

Question 16

Surgical treatment of Benign thyroid nodules

Answer 16

1. Unilateral lobectomy (Hemithyroidectomy)
   - for Uninodular goitre
   - safe, minimal morbidities, can be diagnostic, curative
   - reoperation on contralateral lobe without added difficulty
   - ~10% chance hypothyroidism
2. Total thyroidectomy (Bilateral thyroidectomy)
   - for MNG
   - additional surgical risk (Hypoparathyroidism)
   - no recurrence
   - needs long-term thyroxine replacement

Question 17

Alternative treatment of Benign thyroid nodules

Answer 17

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

Question 18

Thyroid carcinoma: Histological types

Answer 18

Major histologic type:
1. Well differentiated (90%) (very good prognosis)
- Papillary (80-90%)
- Follicular (10-20%)

2. Poorly differentiated (Insular) (5%) (rare, in elderly)
3. Undifferentiated (Anaplastic) (5%)
4. Medullary carcinoma (5%) (neuroendocrine tumour: arise from Parafollicular C cells)
5. Others (1%)
   - Lymphoma (can be treated without surgery if a definitive diagnosis can be made beforehand —> main treatment: chemotherapy)
   - SCC
   - Sarcoma
   - Metastasis

Question 19

Well-differentiated thyroid carcinoma (WDTC)

Answer 19

Management considerations:
1. Extent of thyroidectomy
- hemithyroidectomy vs total thyroidectomy

2. Nature + Extent of LN / neck dissection
   - prophylactic / therapeutic
   - central / lateral compartments
3. 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

Question 20

PTC Histological variants

Answer 20

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

Question 21

Low risk PTC

Answer 21

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

2. Hemithyroidectomy
   - excellent survival + low recurrence
   - avoid T4 replacement (only 10-20% chance of hypothyroidism)
   - lower morbidity

—> Overtreatment vs Potential benefits
—> Patients’ vs Physicians’ preference

Question 22

PTC: Cervical LN management

Answer 22

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

2. 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)

Question 23

Adjuvant therapy for PTC: Post-op I131

Answer 23

• 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

2. 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

Question 24

Papillary thyroid microcarcinoma (PTMC)

Answer 24

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)

Question 25

WDTC: De-escalation of treatment / De-intensifying care

Answer 25

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

Question 26

Medullary thyroid carcinoma (MTC)

Answer 26

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

Question 27

Anaplastic carcinoma

Answer 27

• 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)

Question 28

Pre-op consideration

Answer 28

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

Question 29

SpC Interactive tutorial: Management of Thyroid Cancer
Thyroid gland: Surgical anatomy

Answer 29

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

Question 30

Treatment for WDTC

Answer 30

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)

2. 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

2. T4 suppressive therapy
   - lower TSH level <0.03
3. External beam RT
   - reserved for patients unable to undergo complete excision i.e. residual gross tumour tissue
4. Chemotherapy (NOT given since most tumours are chemo-resistant)
   - doxorubicin as a radiation sensitiser

Question 31

Neck dissection (From HNNS37)

Answer 31

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

Question 32

Risk stratification for WDTC

Answer 32

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

Question 33

Management of High risk WDTC patients

Answer 33

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)

Question 34

Monitoring of WDTC

Answer 34

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)

Question 35

Occult / Minimal PTC

Answer 35

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

Question 36

Follicular thyroid carcinoma (FTC)

Answer 36

• 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

Question 37

Complications of Thyroid surgery (From JC038)

Answer 37

1. Vocal cord dysfunction (unilateral / bilateral)
   - RLN (Infraglottic) / External branch of Superior laryngeal nerve (Supraglottic: Cricothyroid)
   - transient / permanent
2. Hypoparathyroidism (∵ injury / removal of parathyroid gland)
   - transient / permanent
3. Bleeding
   - superficial / deep
4. Tracheomalacia (cartilage in trachea collapses especially during increased airflow)
5. Wound complications
   - Seroma
   - Hypertrophic scar
6. Thyroid storm
7. 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

Question 38

MEN type 1 (SpC Revision)

Answer 38

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

Question 39

MEN type 2A

Answer 39

• 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