Thyroid PBL

PGI TERNOLA, Shari

 Objectives:
• To understand the basic anatomy and physiology of Thyroid
• To be able to differentiate Malignant Thyroid Disorders in terms of
presentation, diagnosis and treatment
 • Embryology
• Developmental abnormalities
Outline: • Anatomy
• Physiology
• Benign Thyroid disorder
• Goiter
• Malignant thyroid disorders
• Well differentiated
• Papillary
• Follicular
• Hurthle
• Poorly differentiated
• Medullary
• Anaplastic
• Lymphoma
• Surgery
 Embryology
• Arose from 2nd and 3rd branchial pouches of the
primitive foregut at around 3rd week of gestation
• Origin: Base of the tongue at the foramen cecum-->
descends--> hyoid bone and larynx
• Tract: Thyroglossal duct
• Epithelial cells give rise to thyroid follicular cells
• 4th branchial pouch: C cells
• Thyroid follicles apparent at 8th weeks
• Colloid formation at 11th week
 Developmental Abnormalities
• Thyroglossal duct cyst and sinus
• Most common congenital cervical anomaly
• 5th week thyroglossal duct starts to obliterate and
completely by 8 weeks: Failure
• Anywhere; 80% is juxtaposed to the hyoid bone
• Asymptomatic, can be infected, chance to harbor
maliganancy (1% Papillary Ca)
• Diagnosis: 1-2 cm smooth, well defined midline neck mass
that moves upward with protrusion of the tongue
• TX: SISTRUNK operation
 Developmental
Abnormalities
• Lingual thyroid
• Failure of median thyroid anlage to descend normally
• TX: thyroid hormone (since many of the patients develop
hypothyroidism)
• Ectopic thyroid
• Anywhere in central neck compartment
• Esophagus, trachea, ant mediastinum, aortic arch
• LATERAL ABBERANT THYROID- situated lateral to the
carotid sheath and jugular vein
• Pyramidal lobe
THYROID ANATOMY

• Brown, firm and posterior to TOSS muscles

• Wt: 20 grams
Blood supply
• Superior thyroid artery and inferior thyroid artery
• Thyroidea ima-1%
Venous drainage
• Superior, inferior and MIDDLE
Innervation
• RLN from the vagus nerve
• Loops around:
• Left: aorta/ligamentum arteriosum
• Right: R subclavian/innominate artery
• Rule: innervates all intrinsic muscle of the larynx except
cricothyroid muscles which are innervated by external
laryngeal nerve
• Injury
• Unilateral- weak voice, hoarseness
• Bilateral: breathing difficulties, loss of voice
 Lymph nodes of the neck

• Level I- submental
• Level II- upper jugular chain
• Level III- middle jugular chain
• Level IV- lower jugular chain
• Level V- posterior chain
• Level VI- anterior chain
• Level VII- pre tracheal area `
 Physiology
Iodine metabolism
• Intake of iodine from food sources (Av daily
req: 0.1 mg)
• Conversion of iodine to iodide (stomach,
jejunum)
Synthesis, secretion and Transport
1. Iodide trapping (thru active ATP dependent transport)
across basement membrane
2. Oxidation of iodide back to iodine Catalyzed by TPO
Iodination forming MIT and DIT
3. Coupling forms T3 and T4
4. Release in the circulation
5. De iodination and reuptake
T3 T4
More active, Non/slightly-active
Only 20% is produced by thyroid Produced entirely by thyroid
Less tightly bound to protein in the plasma Tightly bound to protein
(readily crosses tissues)
Half life- 1 day Half life- 7 days
Benign Thyroid
Disorders
1. Hyperthyroidism 3. Thyroiditis
1. Diffuse toxic goiter (Grave’s 1. Acute suppurative
disease) 2. Subacute
2. Toxic multinodular goiter 3. Chronic
3. Toxic adenoma
4. Goiter
4. Thyroid storm
2. Hypothryoidism
 Goiter
• Any enlargement of the thyroid gland
Classification Specific Etiology

Endemic Iodine deficiency; dietary goitrogens

Medications Iodide, amiodarone, lithium
Thyroiditis Subacute, chronic
Familial Enzyme defects
Neoplasm Adenoma, carcinoma
Resistance to thyroid hormone --
 Goiter
• Uninodular, multinodular or diffuse
• Most nontoxic goiter results from
TSH stimulation secondary to
inadequate hormone synthesis
• Elevated TSH induces diffuse
thyroid hyperplasia  local
hyperplasia in the generation of a
nodule
 Goiter
• Indications for Goiter Surgery
1. Nonresponsive to medication
2. With obstructive symptoms
3. Substernal extension
4. Malignancy suspected/confirmed
5. cosmetic
Solitary Thyroid
Nodule
Ultrasound
 Malignant Thyroid Disease
• Well differentiated
• Papillary
• Follicular
• Hurtle
• Medullary
• Anaplastic
• Lymphoma
- 50 year old man, Healthy
- 2 cm Papillary Thryoid Ca in the left
lobe (FNAB)
 Papillary Carcinoma
• 80% (Iodine sufficient areas)
• Children and individuals exposed to EXTERNAL RADIATION
• Female (2:1 ratio)
• 30-40 years old
• CC: slow growing painless mass in the neck; euthyroid
• Mode of spread: Lymphatics: (Children and YA: Lateral Abberant Thyroid)
• Distant metz: (Lungs Bone Liver  Brain)
Papillary Carcinoma: Pathology
• GROSS: hard, whitish, flat
• HISTOLOGY
• Papillary projections, mixed papillary and follicular or
pure follicular
• **Nuclear cellular features
• Cuboidal with pale , abundant cytoplasm, crowded nuclei
and intranuclear cytoplasmic inclusions (ORPHAN ANNIE
NUCLEI)
• Psammoma bodies
Papillary Carcinoma: Prognostic Indicators
• > 95% 10-year survival rate
• Diagnosis: FNAB and complete neck ultrasound
 AGES scoring system
Low Risk High Risk
Age Young < 40 Old >40
Histologic Grade Well diff Poor
Extrathyroidal invasion and No Yes
metastases
Tumor Size Small, <5 cm Large >5 cm
 Macis Scale
Metastasis Ages Completeness Extrathyroida Size of
of Excision l Invasion original lesion

• The final prognostic score was defined as:

• MACIS = 3.1 (if aged less than or equal to 39 years) or 0.08 x age (if aged greater than or equal
to 40 years), + 0.3 x tumor size (in centimeters), +1 (if incompletely resected), +1 (if locally
invasive), +3 (if distant metastases present).
Twenty-year cause-specific survival rates for patients with:
• MACIS < 6: 99%
MACIS 6-6.99: 89%
MACIS 7-7.99: 56%
MACIS 8+: 24%
 AMES Scoring System
Low Risk High Risk
M < 40 M>40
Age F <50 F>50
No distant With distant
Metastases
Intrathyroidal papillary or Extrathyroidal papillary or
Extent of primary follicular with minor capsule follicular with major invasion
tumor invasion

<5 cm >5 cm
Size
 DeGroot and associates system

Class I Intrathyroidal
Class II Cervical nodal metastases
Class III Extrathyroidal invasion
Class IV Distant metastases
TNM
syste
m
• Papillary or
Follicular
• MTC
• Anaplastic
• Thyroid gland General Staging. (n.d.). Retrieved from
http://www.pathologyoutlines.com/topic/thyroidstaging.html
Papillary Carcinoma: Surgical Treatment

• ATA: Near-Total or Total Thyroidectomy for primary cancers

>1 cm, <4cm without extrathyroidal extension or LN
involvement
• Enables RAI to detect and treat residual thyroid tissue or metastatic
disease
• makes serum Tg level more sensitive
• Recurrence rate are lowered and survival is improved
 High Risk with advanced stages

• ATA
• Prophylactic dissection may be performed in patients with
advanced carcinoma or if the lateral neck nodes are
involved with tumor

• Multidisciplinary team
Diagnosed by FNAB Suspicious

Thyroid lobectomy,
isthmusectomy and
removal of pyramidal
lobe

Definitive Operation: RFS Cannot be made/

Near-Total/ Total concerned about
Thyroidectomy viability of
Parathyroid gland/
status of RLN

Near Total or Completion Total

Completion Total Thyroidectomy
thyroidectomy
- 50 year old man, Healthy
- 2 cm Papillary Thryoid Ca in the left
lobe (FNAB)
Follicular carcinoma
 Follicular Carcinoma
• 10%
• MC in iodine deficient areas
• 3:1 female; 50 years old
• IF older Man >4cm: malignant
• Solitary nodules, with a history of rapid size increase and long standing goiter
• Pain is uncommon
• Lymph node metz uncommon
• Mode of spread: Hematogenous (distant metz is present)
 Follicular Carcinoma

• FNAB is not as effective as in PTC

• Molecular markers
• Rule in malignancy
• BRAF, Ras, RET/PTC, and PAX/PPARy: S (57-75%) Sp (97-100)
• ATA guidelines: DO NOT advise molecular testing in the workup
of suspicious for malignancy nodules
 Surgical Tx and Prognosis
• FNAB Thyroid lobectomy (Benign)
• Total thyroidectomy- for older patients, family hx, atypia, radiation
exposure, thyroid cancer is diagnosed (frankly invasive carcinoma,
angioinvasion, capsular invasion)
• Prophylactic nodal dissection not needed
• Prophylactic central neck dissection for large tumors
• Mortality: 15% (10 years)
 Hurtle Cell Carcinoma
• 3% ,Considered a subtype of FTC
• Presentation, diagnostic, same as FTC
• Often multifocal and bilateral, usually do not take RAI, metz to lymph
nodes and distant sites, higher mortality – 20%
Post op
Management for
Diff Thyroid
Cancer
Radioiodine Therapy

– Post op RAI reduces recurrence, small improvement in survival

 2015
Low Risk
ATA Guidelines to Risk Stratify
Intermediate Risk Tumors
tumors
High Risk Tumors
Without local tumor invasion Microscopic invasion of tumor into the Macroscopic invasion of tumor
perithyroidal soft tissues or RAI-avid into the perithyroidal soft tissues
ATA: metastatic foci in the neck on the first
posttreatment whole-bofy RAI scan
Not recommended-
All macroscopic tumor resected RAI Incomplete tumor resection
Absence of aggressive histology With aggressive histology
No known distant metz With distant metastasis/post op
TG suggestive of distant metz
No vascular invasion With vascular invasion (Papillary) Extensive vascular invasion
(Follicular)
Clinical N0 pr <5 pathologic N1 micrometastases Clinical N1 or >5 pathologic N1 with all Pathologic N1 with any metz LN
<0.2 cm involved LN <3 cm. >3 cm
Intrathyroidal encapsulated follicular variant - -
(Papillary)
Intrathyroidal well differentiated (follicular - -
thyroid cancer) with capsular invasion and
no/minimal vascular invasion
Intrathyroidal papillary microcarcinoma Multifocal papillary microcarcinoma with
ATA:
ETE
ALL High Risk--
RAI
Thyroid Hormone

T4
– Replacement therapy; additional effect of suppressing TSH and
reducing the growth for any possible residual thyroid cancer
cells
– TSH suppression: reduces tumor recurrence
– TSH level:
– <0.1 mU/mL (High risk);
– 0.1-0.5 (intermediate risk),
– 0.5-2 (low risk)
Follow Up patient
with
Differentiated
Thyorid Cancer
Thyroglobulin Measurement

– 6-12 months interval

– High risk: more frequent

Excellent Indeterminate Structually/Incomplete

suppressed Tg <0.2 ng/mL suppressed Tg <1 ng/mL suppressed Tg >1 ng/mL
and stimulated <1 ng/mL OR stimulated <10 ng/mL OR stimulated >10 ng/mL
OR stable or declining anti- OR rising anti-Tg levels
Tg levels
negative imaging negative imaging nonspecific
12-24 months Tg level ADDITIONAL INVESTIGATIONS
interval
Imaging:

Cervical FDG-PET and PET-

Whole Body Scan Ultrasound CT
– LOW and Some intermediate risk – Evaluate the thyroid – For Tg-positive; RAI
– Negative TSH-stimulated Tg and bed and central and scan negative
cervical ultrasound lateral cervical nodal
– Do NOT require routine body scan compartments at
– HIGH and Intermediate-risk with 6-12 months after
higher risk features thyroidectomy
– Whole body scan every 6-12 then annually for at
months after remnant ablation least 3-5 years
Additional
Treatment
Modalities
Radiotherapy, Thermal Ablation and
Chemotherapy
– External beam radiotherapy- *bone metz
– Stereotactic brain radiotherapy and intensity-
modulated radiation therapy- metz lesion
– *no role for routine Chemotherapy
– Doxorubicin- acts as a radiation sensitizer for EBR
Novel Therapies

– Sorafenib and Lenvatinib

– for non-responsive to RAI
– Ongoing studies
 Medullary Carcinoma
• 5%
• From the parafollicular or C cells (superolateral of each lobe)
• CC: Neck mass with palpable cervical LAD, Pain (also has 3D’s compressive
symptoms)
• Mets: both lymphatic and hematogenous route
• Strong familial tendency (25%)
• 1.5:1 female-male ratio, 50-60 years old
• 80% - 10 year survival
 Medullary Carcinoma
• Secretes: Calcitonin, Carcinoembyonic antigen (CEA),
• calcitonin gene-realted peptide, histaminadases, prostaglandins E2 and F2a and
serotonin
• Diarrhea* non neck presentation
• 2-4% may present with Cushings
• FNAB-> CT/MRI
 Medullary Carcinoma
• Pathology: Amyloid deposition
• Diagnostic tumor marker: Immunohistochem for calcitonin
 Medullary Carcinoma

• Diagnosis
• ALL new- screened for RET point mutations,
*pheochromocytoma, and HPT
• Calcitonin and CEA
 Medullary Carcinoma
•Treatment
•Total Thyoridectomy with central node dissection
•IF with LN involvement- Ipsilateral or bilateral lateral neck
dissection
•IF with Limited metz- less aggressive neck surgery: Preserve
speech and swallowing
•IF recurrent/widely metz- Tumor debulking
•External Beam radiation- bone metz
•Chemoembolization- Liver metz
•Prophylactic Total Thyroidectomy- RET mutation carriers
•MEN 2A (high risk) – thyroidectomy at <5
•MEN 2B (highest risk) – thyroidectomy at 1
Anaplastic Carcinoma
 Anaplastic Carcinoma
• Worst type, 1%
• Women, 70-80y/o
• CC: long standing neck mass, which rapidly enlarges and may be
painful
• 3D- Dysphagia, dysphonia and dyspnea are common
• Large and may be fixed, ulcerated with areas of necrosis
• Spread: Both LN and hematogenous spread
• FNAB: Multinucleated cells

• 3 main histo growth present: spindle,

squamoid and pleomorphic
• If spindle cell elements are present:
primary and metastatic sarcomas
• Tx and prognosis
• 6 months
• **Adjuvant radiation
• Tracheostomy done for impending signs of obstruction

• Intrathyroidal mass- total or near thyroidectomy with LN dissection

• Extrathyroidal extension- en bloc resection
 Lymphoma
• <1 % Treatment and Prognosis
• Non-Hodgkin B cell type; from Chemotherapy: CHOP
chronic lymphocytic thyroiditis
regimen
• CC: painless rapidly enlarging neck *Thyroidectomy if
mass + acute respiratory distress
intractable
• Utz: hypoechoic mass, well defined
Survival rate: 50%
• Needle core or open biopsy *
definitive dx
 Metastatic Carcinoma
• Rare
• lobectomy
THYROID SURGERY
MIS
 Complications of surgery
• Post thyroidectomy, at the pacu, patient suddenly develops bull neck
and dyspnea, SPO2 @ 65. What will you do?

• Establish the diagnosis– ruptured blood vessels; ongoing

bleeding
• Stat OR/ bedside
• Removal of dressing, cut the sutures and evacuate the blood
to relieve the pressue
• Post thyroidectomy, upon reversal of GA, patient suddenly becomes
cyanoticwith SPO2 at 65%. NO bull neck.

• What is happening to your

patient?
• Post thyroidectomy, upon reversal of GA, patient suddenly becomes
cyanoticwith SPO2 at 65%. NO bull neck.

• What is happening to your • What will you do?

patient? • Reintubate
• Bilateral transection of both • Refer to surgeon
RLN
• Repair of RLN
• The patient has airway
collapse