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Thyroid Cancer Management

Prof. Dr. Yusuf BÜKEY

Cerrahpasa School of Medicine


Endocrine Surgery Department

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Thyroid Cancer

 Clinically uncommon
(60 per million per year)
 Pathologically common
(up to 15 % in the U.S.A.)

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Thyroid Cancer Management
 Preoperative Diagnosis Thyroid Cancer
 Peroperative Diagnosis Thyroid Cancer
 Postoperative Diagnosis Thyroid Cancer
 Medullary Thyroid Cancer
 Anaplastic Thyroid Cancer
 Cervical Lymph Nodes
 Pediatric Thyroid Cancers
 Completion Thyroidectomy

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Preoperative Diagnosis

 Examination of the thyroid nodule:


• consistency  hard vs. soft
• size < 4.0 cm
• multinodular vs. solitary nodule
• multinodular  3% chance of malignancy
(Goldman, 1996)
• solitary nodule  5%-12% chance of malignancy
(Goldman, 1996)
• mobility with swallowing
• mobility with respect to surrounding tissues
• well circumscribed vs. ill defined borders

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Preoperative Diagnosis
 Examine for ectopic thyroid tissue
 Indirect or fiberoptic laryngoscopy
• vocal cord mobility
• evaluate airway
• preoperative documentation of any unrelated abnormalities
 Systematic palpation of the neck
• Metastatic adenopathy commonly found:
 in the central compartment (level VI)
 along middle and lower portion of the jugular vein
(regions III and IV)

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Blood Tests

 Thyroid function tests


• thyroxine (T4)
• triiodothyronin (T3)
• thyroid stimulating hormone (TSH)
 Serum Calcium
 Thyroglobulin (TG)
 Calcitonin

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Imaging Modalities for Thyroid Cancer

 Radioiodine
 US
 CT
 MRI
 PET
 Others

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Thyroid Ultrasound

 Objective measure of size


 Multinodularity
 Screening in radiated patients
 Recurrent carcinoma
 Cystic vs solid
 Ultrasound guided biopsy

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Thyroid Ultrasound
 Suspicious Nodules 0.8- 1.5 cm
• Hypoechoic lesion plus one of the following :
 Microcalcifications
 Irregular border
 Central vascularity

(Papini et al JCEM 87: 1941, 2002)

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Longitudinal scan of a papillary thyroid cancer, showing an
irregularly shaped nodule that has hypoechogenic
heterogeneous internal echo and calcifications (arrows).
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A, Longitudinal scan and B, transverse scan of a metastatic lymph node from
papillary thyroid cancer. The lymph node is echogenic, with a longitudinal –
transverse ratio of 1.3. 11
Thyroid Ultrasound
 Disadvantages:
 Unable to reliably diagnose true cystic lesions
 Cannot accurately distinguish benign from
malignant nodules
 Follicular Lesions ??

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Fine-Needle Aspiration

 Currently considered to be the best first-line


diagnostic procedure in the evaluation of the
thyroid nodule:
 Advantages:
• Safe
• Cost-effective
• Minimally invasive
• Leads to better selection of patients for surgery
than any other test (Rojeski, 1985)

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Fine-Needle Aspiration

 FNA halved the number of patients requiring


thyroidectomy
(Mazzaferri, 1993)

 FNA has double the yield of cancer in those


who do undergo thyroidectomy
(Mazzaferri, 1993)

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FNA Results of Thyroid Nodule
 Pathologic results are categorized as:
• positive
• negative
• indeterminate
 Hossein and Goellner (1993) use four categories.
They pooled data from seven series and came up with
the following rates:
• benign  69%
• suspicious  10%
• malignant  4%
• nondiagnostic  17%

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FNA Results of Thyroid Nodule
 Limitations
• skill of the aspirator
• expertise of the cytologist
• difficulty in distinguishing some benign cellular
adenomas from their malignant counterparts
(follicular and Hurthle cell)
 False negative results = 1%-6%
(Mazzeferri, 1993)
 False positive results = 3%-6%
(Rojeski, 1985, Mazzeferri, 1993, Hall, 1989)

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Malignant FNA

 Papillary carcinoma
 Medullary carcinoma
 Anaplastic carcinoma
 Thyroid lymphoma
 Metastatic carcinoma
 Follicular carcinoma?

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Thyroid Cancer Classification
 Papillary carcinoma  Medullary Carcinoma
• Follicular variant  Miscellaneous
• Tall cell • Sarcoma
• Diffuse sclerosing • Lymphoma
• • Squamous cell carcinoma
Encapsulated
• Mucoepidermoid
 Follicular carcinoma carcinoma
• Overtly invasive • Clear cell tumors
• Minimally invasive • Pasma cell tumors
 Hurthle cell carcinoma • Metastatic
• Direct extention
 Anaplastic carcinoma
• Kidney
• Giant cell • Colon
• Small cell • Melanoma

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Papillary Carcinoma
 60%-80% of all thyroid cancers
(Geopfert, 1998, Merino, 1991)
 Histologic subtypes
• Follicular variant
• Tall cell
• Columnar cell
• Diffuse sclerosing
• Encapsulated
 Prognosis is 80% survival at 10 years
(Goldman, 1996)
 Females > Males
 Mean age of 35 years
(Mazzaferri, 1994)
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Incidentaloma/Micrometastatic
Disease
 Microcarcinomas - a manifestation of papillary
carcinoma
• Definition - papillary carcinoms smaller than 1.0 cm
• Most are found incidentally at autopsy
• Autopsy reports indicate that these may be present in up
to 35% of the population (Mazzaferri, 1993)
• Usually clinically silent
• Most agree that the morbidity and mortality from
microcarcinoma is minimal and near that of the normal
population
• One study showed a 1.3% mortality rate (Hay, 1990)

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Incidentaloma/Micrometastatic
Disease
 Lesions detected by imaging or found after surgery
for unrelated indication
 Thyroid nodules common in population (4-10% have
palpable nodules any given time)
 Female/male incidence 6.4 / 1.6%
 12% detected by palpation vs. 45% by imaging
 Lesions less than 1 cm-observe
 Lesions 1-2cm “gray zone”
 Lesions > 2cm are NOT INCIDENTAL

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Incidentaloma/Micrometastatic
Disease

 Consider suspicious features:


• Increased vascularity
• Irregular margin
• Central microcalcification
• Cervical adenopathy

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Papillary Thyroid Cancer

 Lymph node involvement is common


• Major route of metastasis is lymphatic
• 46%-90% of patients have lymph node
involvement
(Goepfert, 1998, Scheumann, 1984, De Jong, 1993)
• Clinically undetectable lymph node involvement
does not worsen prognosis
(Harwood, 1978)

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Incidentaloma/Micrometastatic
Disease and PTC
 Pathology
• Gross
- vary considerably in size
- often multi-focal
- unencapsulated but often have a pseudocapsule
• Histology
- closely packed papillae with little colloid
- psammoma bodies
- nuclei are oval or elongated, pale staining with
ground glass appearanc
- Orphan Annie cells

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Papillary Carcinoma

Algorithm for Treatment of Possible PTC


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Follicular Carcinoma

 20% of all thyroid malignancies


 Women > Men (2:1 - 4:1)
(Davis, 1992, De Souza, 1993)
 Mean age of 39 years (Mazzaferri, 1994)
 Prognosis - 60% survive to 10 years (Geopfert, 1994)
 Metastasis - angioinvasion and hematogenous spread

• 15% present with distant metastases to bone and lung


 Lymphatic involvement is seen in 13% (Goldman, 1996)

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Follicular Carcinoma
Current Classification New classification
• Minimally invasive Minimally invasive
(gross encapsulation) (capsule only)
angioinvasive grossly
encapsulated
Widely invasive Widely invasive

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Follicular Neoplasms
 Resection of lobe/isthmus with careful examination for gross
invasion or nodal disease

 Await final pathology of lobe/isthmus and if positive, return to OR


for completion lobectomy

 Subsequent I131 treatment, TSH suppression and monitoring of


thyroglobulin (<2µg/l)

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Hurthle Cell Carcinoma
 Variant of follicular carcinoma
 First described by Askanazy
• “Large, polygonal, eosinophilic thyroid follicular cells with
abundant granular cytoplasm and numerous mitochondria”
(Goldman, 1996)
 Definition (Hurthle cell neoplasm) - an encapsulated
group of follicular cells with at least a 75% Hurthle cell
component
 Carcinoma requires evidence of vascular and
capsular invasion
 4%-10% of all thyroid malignancies (Sessions, 1993)

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Hurthle Cell Carcinoma
 Women > Men

 Lymphatic spread seen in 30% of patients


(Goldman, 1996)

 Distant metastases to bone and lung is seen in 15%


at the time of presentation

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Management Hurthle Cell
Carcinoma

 Total thyroidectomy is recommended because:


1) Lesions are often multifocal
2) They are more aggressive than WDTCs
3) Most do not concentrate iodine

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Prognosis DTC
 Based on age, sex, and findings at the time of
surgery (Geopfert, 1998)
 Several prognostic schemes represented by
acronyms have been developed by different
groups:
• AMES (Lahey Clinic, Burlington, MA)
• GAMES (Memorial Sloan-Kettering Cancer Center,
New York, NT)
• AGES (Mayo Clinic, Rochester, MN)

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Thyroid Carcinoma Classification
 Papillary, Follicular and Medullary Carcinoma
• T1 - ≤ 2cm intrathyroidal
• T2 - > 2 to 4 cm intrathyroidal
• T3 - > 4 cm or minimal extension
• T4a – subcutaneous, larynx, trachea, esophagus, recurrent
laryngeal nerve
• T4b – prevertebral fascia, mediastinal vessels, carotid artery
 Anaplastic/ undifferantiated Carcinoma
• T4a – tumor limited to thyroid
• T4b – tumor beyond thyroid capsule
 All types
• N1a - Level VI N1b – other regional
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Staging for Differentiated Thyroid
Cancer
 In differentiated thyroid carcinoma, several classification and staging
systems have been introduced. However no consensus has emerged
favoring any one method over another

 AMES system/ AGES system/ GAMES system


 TNM system
 MACIS system
 University of Chicago system
 Ohio State University system
 National Thyroid Cancer Treatment Cooperative Study (NTCTCS)

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University of Chicago system – An easy to remember
staging system for papillary carcinoma is the
Clinical Class scheme proposed by De Groot colleague
the University of Chicago

 Class I  disease limited to thyroid gland

 Class II  Lymph node involvement

 Class III  extrathyroidal invasion

 Class IV  distant metastases

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National Thyroid Cancer Treatment
Cooperative Study (NTCTCS)
 The NTCTCS created a staging approach that was applied prospectively
to
a registry of patients drawn from 14 cooperating institutions . Clinical-
pathologic staging was based upon:
• patient age at diagnosis
• tumor histology
• tumor size
• intrathyroidal multifocality
• extraglandular invasion
• metastases
• tumor differentiation

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Prognosis DTC
Low risk group
- men younger than 40 years and women younger than
50 years regardless of histologic typ
- recurrence rate -11%
- death rate - 4%
Intermediate risk group
- men older than 40 years and women older than 50 years
who have papillary carcinoma
- recurrence rate - 29%
- death rate - 21%
High risk group
- men older than 40 years and women older than 50 years
who have follicular carcinoma
- recurrence rate - 40%
- death rate - 36%
(Cady and Rossi, 1988 37
Medullary Thyroid Carcinoma
 10% of all thyroid malignancies
 1000 new cases in the U.S. each year
 Arises from the parafollicular cell or C-cells of the
thyroid gland
• derivatives of neural crest cells of the branchial arches
• secrete calcitonin which plays a role in calcium
metabolism

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Medullary Thyroid Carcinoma

 Tumor of C- cells
 75 % sporadic
 25% hereditary
 Do not concentrate iodine
 Produce calcitonin

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Medullary Thyroid Carcinoma

 Developes in 4 clinical settings:


• Sporadic MTC (SMTC)
• Familial MTC (FMTC)
• Multiple endocrine neoplasia IIa (MEN IIa)
• Multiple endocrine neoplasia IIb (MEN IIb)

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Medullary Thyroid Carcinoma

Sporadic MTC:
• 70%-80% of all MTCs (Colson, 1993, Marzano, 1995)
• Mean age of 50 years (Russell, 1983)
• 75% 15 year survival (Alexander, 1991)
• Unilateral and Unifocal (70%)
• Slightly more aggressive than FMTC and MEN IIa
• 74% have extrathyroid involvement at presentation
(Russell, 1983)

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Medullary Thyroid Carcinoma

Familial MTC:
• Autosomal dominant transmission
• Not associated with any other endocrinopathies
• Mean age of 43
• Multifocal and bilateral
• Has the best prognosis of all types of MTC
• 100% 15 year survival
(Farndon, 1986)

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Medullary Thyroid Carcinoma

 Multiple endocrine neoplasia IIa


(Sipple’s Syndrome):
• MTC, Pheochromocytoma, parathyroid
hyperplasia
• Autosomal dominant transmission
• Mean age of 27
• 100% develop MTC (Cance, 1985)
• 85%-90% survival at 15 years
(Alexander, 1991, Brunt, 1987)

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Medullary Thyroid Carcinoma

 Multiple endocrine neoplasia IIb (Wermer’s


Syndrome, MEN III, mucosal syndrome):
• Pheochromocytoma, multiple mucosal
neuromas, marfanoid body habitus
• 90% develop MTC by the age of 20
• Most aggressive type of MTC
• 15 year survival is <40%-50%
(Carney, 1979)

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Medullary Thyroid Carcinoma

Diagnosis
 Labs:
1) basal and pentagastrin stimulated serum calcitonin
levels (>300 pg/ml)
2) serum calcium
3) 24 hour urinary catecholamines
(metanephrines, VMA, nor-metanephrines)
4) carcinoembryonic antigen (CEA)
 Fine-needle aspiration
 Genetic testing of all first degree relatives
• RET proto-oncogene

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Medullary Thyroid Carcinoma
(Management)

 Recommended surgical management


• total thyroidectomy
• central lymph node dissection
• lateral jugular sampling
• if suspicious nodes - modified radical neck
dissection
 If patient has MEN syndrome
• remove pheochromocytoma before thyroid surgery

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Medullary Thyroid Carcinoma
(Management)
 Postoperative management
 disease surveillance
• serial calcitonin and CEA
2 weeks postop
3/month for one year, then…
Twice a year
 If calcitonin rises
metastatic work-up
surgical excision
if metastases - external beam radiation

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Anaplastic Carcinoma of the Thyroid

 Highly lethal form of thyroid cancer


 Median survival <8 months (Jereb, 1975, Junor, 1992)
 1%-10% of all thyroid cancers (Leeper, 1985, LiVolsi,
1987)
 Affects the elderly (30% of thyroid cancers in patients
>70 years) (Sou, 1996)
 Mean age of 60 years (Junor, 1992)
 53% have previous benign thyroid disease (Demeter,
1991)
 47% have previous history of WDTC (Demeter, 1991)

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Anaplastic Carcinoma
(Management)
 Most have extensive extrathyroidal
involvement at the time of diagnosis
• surgery is limited to biopsy and tracheostomy
 Current standard of care is:
• maximum surgical debulking, possible
• adjuvant radiotherapy and chemotherapy
(Jereb and Sweeney, 1996)

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Management
 Surgery is the definitive management of thyroid cancer,
excluding most cases of ATC and lymphoma
 Types of operations:
• lobectomy with isthmusectomy
- minimal operation required for a potentially malignant thyroid nodule

• total thyroidectomy
- removal of all thyroid tissue
- preservation of the parathyroid glands

• subtotal thyroidectomy
- anything less than a total thyroidectomy

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Management Papillary and Follicular

 Subtotal vs. total thyroidectomy

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Arguments for Total Thyroidectomy

 Radioactive iodine may be used to detect and treat residual normal


thyroid tissue and local or distant metastases
 Serum thyroglobulin level is a more sensitive marker for persistent or
recurrent disease when all normal thyroid tissue is removed
 In up to 85% of papillary cancer, microscopic foci are present in the
contralateral lobe. Total thyroidectomy removes these possible sites
of recurrence
 Recurrence develops in 7% of contralateral lobes (1/3 die)
 Risk (though very low [1%]) of dedifferentiation into anaplastic
thyroid cancer is reduced
 Survival is improved if papillary cancer greater than 1.5cm or
follicular greater than 1cm
 Need for reoperative surgery associated with higher risk is lower
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Arguments against Total
Thyroidectomy
 Total thyroidectomy may be associated with higher
complication rate than subtotal thyroidectomy
50% of recurrences can be controlled with surgery
 Fewer than 5% of recurrences occur in the thyroid bed
 Tumor multicentricity has little clinical significance
 Prognosis of low risk patients (age, grade, extent, size)
is excellent regardless of extent of resection

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Indications for Total
Thyroidectomy

1) Patients older than 40 years with papillary or


follicular carcinoma
2) Anyone with a thyroid nodule with a history of
irradiation
4) Patients with bilateral disease
5) Patients with neck lap.
6) Patients had Tm 2cm

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Papillary/Differentiated Carcinoma
Node Dissection:
 Up to 80% of patients found to have asymptomatic positive
nodes during series of prophylactic neck dissections 1,2
 Clinically significant disease only develops in less than 10% of
patients with microscopic lymph node metastases 1,3,4
 Central node dissection should be carried out if central nodes
are enlarged and positive by frozen section
 Ipsilateral modified neck dissection has been shown to reduce
regional recurrence without improving survival if enlarged
cervical node is positive by preop FNA or intraoperative frozen5

1 Am J Surg 122:464-471,1971
2 World J Surg 18:359-367,1994.
3 Surg Clin North Am 67:251-261,1987.
4 Cancer 26:1053-1060, 1970
5 Textbook of Endocrine Surgery, WB Saunders, 1997, p90. 55
Node Dissection

 Managing lymphatic involvement


• pericapsular and tracheoesophageal nodes should be
dissected and removed in all patients undergoing
thyroidectomy for malignancy
• Overt nodal involvement requires exploration of
mediastinal and lateral neck
• if any cervical nodes are clinically palpable or
identified by MR or CT imaging as being suspicious a
neck dissection should be done (Goldman, 1996)
• Prophylactic neck dissections are not done (Gluckman)

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LYMPHATIC DRAINAGE

Superior

Lateral
Lateral

Posterior Inferior

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Lateral Group 58
Central Group
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Incision

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Outline of modified Mac Fee incision

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Indications of Lymph Node Dissection

•All thyroid cancers with palpable pathologic lymph node

•Positive frozen section

•High risk patients(prophylactic)

•Pediatric thyroid cancer

•Medullary thyroid cancer

•Extrathyroid head and neck malignancy

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Central Lymph Node Dissection:

 Central compartment =the region bounded by the


jugular veins, the hyoid bone, and the sternal notch

 All central nodes removed at time or procedure

 Removal of Central Nodes important in medullary and


Hurthle Cell Ca
• Microscopic spread is high
• Do not take up I131 and cannot be ablated

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Lateral Lymph Node Dissection

 Diseased nodes lateral to the jugular vein = modified


radical neck dissection

 Removal of LN’s anterior and posterolateral to the


internal jugular vein from the mastoid to subclavian
vessels inferiorly and laterally to spinal accessory
nerve (Level 2-5)

 Sparing the internal jugular vein, spinal accessory


nerve, and sternocleidomastoid muscle

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Complications of Surgery
 Hypocalcemia -devascularization of parathyroid
• about 5%, which resolves in 80% of these cases in about 12
months

 Recurrent Laryngeal Nerve Injury


either traction induced or division.
• less than 3%

 Bleeding
• wound hematomas

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Standard Initial Treatment
Total
Thyroidectomy

Remove the
thyroid with Radioactive Iodine
all cancerous Treatment
tissue

Destroy any Without any


microscopic functional
residual thyroid thyroid tissue
tissue
Completely dependent
on exogenous
levothyroxine 68
Pediatric Papillary Carcinoma
Incidence

4 cases per million per year (children)


vs
50 cases per million per year (adults)

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Pediatric Papillary Carcinoma

 PTC and FVPTC – 90 % of all childhood


thyroid cancers

 1.4 % of all pediatric head and neck tumors

 7 % of all pediatric head and neck tumors

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Pediatric Papillary Carcinoma
Age  Female to Male Ratio
5–9 1:6
10-14 1:1
15-19 5 : 2 (peak incidence)

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Completion Thyroidectomy

 Postoperative reveal of DTC


 Incomplet surgery
 Folicular lesion
 High grade patients
 Neck lymphadenopathy

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Total thyroidectomy is the treatment of
choice for virtually all patients with
thyroid cancer when it can be done
safely. No study documents that lesser
operations have better results than total
thyroidectomy, whereas numerous
studies suggest that patients treated by
total thyroidectomy have fewer
recurrences and better survival.

Orlo H. Clark
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