THYROID CANCER

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THYROID CANCER

• Ali Al-Zahrani, MD
• Consultant Endocrinologist
• King Faisal Specialist Hospital and Research
  Center

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Thyroid CancerClassification

• Epithelial cell tumors
• Differentiated
• Papillary (75- 80)
• Follicular (10-15)
• Undifferentiated
• Anaplastic (3-5)

• Parafollicular (C- cell) tumors
• Medullary ( 5 )
• Lymphoma (1-2)
• Others

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Thyroid CancerEpidemiology

• Incidence 0.5-10 cases/100000 population
• 14000 new cases/year in the USA
• 1.1 of all cancers (relatively rare)
• About 1100 deaths / year
• 190,000 patients are on regular follow-up

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Thyroid CancerEpidemiology at KFSHRC

• Between 1975 1997
• Thyroid cancer is the fourth most common
  malignancy (after breast, leukemia, NHL)
• 1950 thyroid cancer / 35,355 total cancer (5.5)
• 3.5 of all male malignancy, 11.2 of all female
  malignancy (second to breast cancer)
• Malefemale ratio 0.31

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Ten Most Common Cancers in Saudi Arabia

• Breast 8.8
• liver 7.5
• Leukemia 7.5
• NHL 7.3
• Colorectal 5.5

• Thyroid 5.2
• Lung 4.7
• CNS 3.9
• Stomach 3.8
• Bladder 3.5

National Cancer Registry, 1999
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National Cancer Registry, 1999
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Average age-specific incidence rate for thyroid
cancer in Saudi Arabia, 1994-1996
National Cancer Registry, 1999
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Thyroid Cancer in Saudi Arabia1994-1996

• 883 cases (3.5/100000 population)
• 5.4 of all newly diagnosed cancers
• 2nd most common in females,14th in males
• Male female ratio 12.9
• Mean age 49.8 yrs in Males, 40.8 yrs in females
• Most common in
• Hail 7/100000
• Riyadh 5.8/100000
• Qassim 3.8/100000

National Cancer Registry, 1999
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(No Transcript)
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Stage distribution of thyroid cancer in Saudi
Arabia, 1994-1996
Localized
Regional
Unknown
Distant
Females
Males
All
0 20 40
60 80
100
National Cancer Registry, 1999
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Clinical Presentation

• Thyroid nodule (most common)
• Cervical lymph node(s)
• Local compressive symptoms
• Distant metastasis
• Thyroid dysfunction

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Thyroid Nodules

• Prevalence Physical Exam 4-7
  Ultrasound 30
• Autopsy 50
• Incidence increases with age

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Mazzaferri, NEJM, 1993
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Thyroid Nodules(Contd)

• Most thyroid nodules are BENIGN
• A thyroid nodule has 5-12 malignancy rate
• History of radiation increases the chance of
  malignancy to 30-50

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Thyroid NodulesEvaluation

• History
• Physical Examination
• Laboratory Evaluation
• - TSH
• Imaging Studies
• NOT VERY HELPFUL

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Thyroid NodulesEvaluation

• HISTORY
• Age lt 20 or gt 50
• Head or neck irradiation
• Family history (MTC)
• Male sex
• Recent growth
• Pressure symptoms

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Thyroid NodulesEvaluation

• PHYSICAL EXAMINATION
• Hard non tender nodule
• Nodule of different consistency within MNG
• Fixed nodule
• Cervical lymphadenopathy
• Immobile vocal cord

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CONVENTIONAL DIAGNOSTIC APPROACH OF THYROID
NODULES
Patient with thyroid nodule
Radioisotope Scan
Indeterminate nodule (10)
Hot nodule (5)
Cold nodule (85)
Ultrasound
LT4 Rx
TSH
Solid or Complex Cyst
NTSH
TSH
Cystic
Rescan 6 weeks
NT4/T3
T4/T3
Follow
Surgery
LT4 Rx
Euthyroid
Hyper thyroid
131 Rx or
Follow
PEI or Surgery
Gharib, H Endo. Metab. Clinics Dec. 97
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Thyroid NodulesRadionucleotide Scans

• Most thyroid nodules are cold (95)
• Most cold nodules are benign (80-85)
• Hot nodules are usually functioning and can be
  detected by TSH (suppressed)
• Warm nodules can be malignant

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Thyroid Nodules Ultrasonography

• Generally has a minor role in the evaluation of
  thyroid nodules
• Palpable nodules do not need ultrasound
• Small non-palpable nodules (lt1cm) are generally
  unimportant even if malignant
• Cystic nodules can be malignant

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Thyroid Nodules FNA

• The most important test in the evaluation of a
  thyroid nodule
• Has an overall sensitivity of 83-98 and
  specificity of 92-100
• Complications are very rare and usually minor

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Malignant
Total
Operated
False ve ()
Speci-ficity
Sensi-tivity
False -ve ()
Series
n ()
n

• Gardiner et al
• Hawkins et al
• Khafagi et al
• Hall et al
• Altavilla et al
• Caplan et al
• Gharib and Goellner
• Total

1465 1399 618 795 2433 502 10971 18183
207 415 258 72 257 185 1750 3144
46 (22) 73 (18) 44 (17) 37 (51) 49 (19) 64
(35) 682 (39) 995 (32)
11.5 2.4 4.1 1.3 6.0 9.3 2.0 5.2
0 4.6 7.7 3.0 0 4.0 0.7 2.9
65 86 87 84 71 91 98 83
91 95 72 90 100 99 99 92
Gharib Goellner, Ann Intern Med, 1993
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Thyroid NodulesFNA

• Benign (67)
• Malignant (4)
• Indeterminate or suspicious (10)
• inadequate (17)

Gharib Goellner, Ann Intern Med, 1993
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Effect of FNA on Tx of Thyroid Nodules
Gharib, Endo clinics N. America 1993
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Gharib, Endo clinics N. America 1993
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Thyroid NodulesEvaluation (Summary)

• Most thyroid nodules are benign
• TSH determines the thyroid functional status
• Thyroid scanning and U/S are generally not
  helpful
• FNA is the most useful diagnostic procedure

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CONVENTIONAL DIAGNOSTIC APPROACH OF THYROID
NODULES
Patient with thyroid nodule
Radioisotope Scan
Indeterminate nodule (10)
Hot nodule (5)
Cold nodule (85)
Ultrasound
LT4 Rx
TSH
Solid or Complex Cyst
NTSH
TSH
Cystic
Rescan 6 weeks
NT4/T3
T4/T3
Follow
Surgery
LT4 Rx
Euthyroid
Hyper thyroid
131 Rx or
Follow
PEI or Surgery
Gharib, H Endo. Metab. Clinics Dec. 97
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CURRENT DIAGNOSTIC APPROACH OF THYROID NODULES
Patient with thyroid nodule
FNA Biopsy
Diagnostic (85)
Non Diagnostic (15)
Rebiopsy
Benign (75)
Malignant (5)
Suspicious (20)
Non diagnostic
Follicular
Surgery
Follow or T4 Rx
neoplasm
US-FNA
TSH Scan
Non diagnostic
?TSH
NTSH
Hot nodule
Cold nodule
Cyst gt 4 cm
Solid
Cyst lt 4 cm
Surgery
Follow or Rx
Follow
Surgery
Gharib, H Endo. Metab. Clinics Dec. 97
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Management of Thyroid Nodules
Mazzaferri, NEJM, 1993
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Management of differentiated Thyroid cancer

• Surgery
• Radioactive Iodine (RAI)
• Thyroxine suppressive therapy
• External radiation
• ?Chemotherapy

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Surgery Selection of an Operation

• CONTROVERSIAL!

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Surgery Selection of an Operation

• The minimal operation for any potentially
  malignant thyroid nodule is lobectomy and
  isthemectomy.

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SurgeryTotal Thyroidectomy

• Invasive or metastatic disease
• Bilateral disease
• Follicular thyroid carcinoma
• Medullary thyroid carcinoma
• Anaplastic carcinoma (if operable)
• History of ext. radiation to the neck

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Surgery

• What about clinically unilateral
  well-differentiated thyroid carcinoma?
• Controversial!

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Advantages of Total Thyroidectomy

• Lower recurrence and ?mortality rates
• Problem of multi focal disease (50)
• Improves sensitivity and specificity of RAI scan
  and TG assays
• Decreases the chance of transformation to
  anaplastic carcinoma

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Total ThyroidectomyDisadvantages

• Higher Complication Rates!

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Mazzaferri E et al. Am J Med, 1994
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Surgery Unilateral Disease

• Total or near-total thyroidectomy in most cases
• Need for an experienced surgeon (complication
  rate lt 3)
• Lobectomy and isthemectomy may suffice for PTC lt1
  cm and minimally invasive FTC
• Need for completion thyroidectomy in other
  situations

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Surgery Cervical Lymph Nodes (CLN)

• Overall, CLN metastases in PTC are very common
  (up to 88)
• Clinically palpable CLN 15
• Significance of CLN on the overall prognosis is
  controversial

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SurgeryCervical Lymph Nodes (CLN)

• Remove all CLN adjacent to the thyroid tumor and
  medial to the carotid sheath Delphian CLN
• Modified neck dissection for clinically palpable
  CLN metastases

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Radioactive Iodine Therapy

• Remnant Ablation
• Administration of RAI after complete surgery with
  no evidence of residual cancer
• Treatment of persistent/ recurrent disease

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Mazzaferri E et al. Am J Med, 1994
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Mazzaferri E et al. Am J Med, 1994
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Follow - Up

• L-Thyroxine suppressive therapy
• Periodic reassessment (every 6-12 months)
• Physical examination
• TSH, FT4, T3
• Tg (lt 2-3 ng/ml), Tg antibodies (negative)
• RAI whole body scan ( as per clinical situation)
• Other imaging (US, CT, PET)

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Principles of Management of Recurrent/Metastatic
Diseases

• All macroscopic (gross) disease should be
  considered for surgical resection if possible
• RAI is rarely curative in gross disease
• The best response is in patients lt 40 years old
  with normal CXR and diffuse RAI uptake.
• Larger doses of RAI (150-200 mCi) are used
• Repeat doses every 6-12 months until disease
  disappears, side effects appear or a cumulative
  dose of 800-1000 mCi is reached.

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External Beam Radiation Therapy

• Questionable role in the treatment of thyroid
  cancer
• May be of benefit to
• Treat inoperable or metastatic lesions in
  conjunction with I131
• Tumors that do not take up RAI
• Tumors with significant perithyroidal extension

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Thyroid Hormone Suppressive Therapy

• TSH has a growth promoting effect on thyroid
  cancer cells
• Its role as adjunctive therapy has been
  controversial
• Most studies however demonstrated a beneficial
  effect
• Problem of potential side effects

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Differentiated Thyroid CancerManagement (Summary)

• Near-total or total thyroidectomy.
• RAI ablation of the remnant thyroid tissue 6-12
  weeks after surgery.
• Suppressive doses of L-thyroxine to prevent
  regrowth of any residual disease.
• Whole body RAI scanning in 6-12 months after
  first RAI dose to ensure complete ablation of the
  remnant thyroid tissue

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Differentiated Thyroid CancerManagement (Summary)

• Reablation with RAI of any persistent residual
  uptake
• Follow up with periodic clinical assessment, RAI
  whole body scanning and measurement of serum
  thyroglobulin
• Further investigations and treatment of any
  recurrent disease which may arises during the
  course of follow up.

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Prognostic Factors

• Age
• Tumor size
• Local tumor invasion
• Distant metastasis
• Histological variants
• Multiple intrathyroidal tumors
• ?Lymph node metastasis

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Mazzaferri E et al. Am J Med, 1994
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Mazzaferri E et al. Am J Med, 1994
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I.D. Hay et. al Surgery , 1987
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Cumulative mortality from papillary thyroid
cancer, plotted by four Risk group derived from
classification by AGES scoring system.

I.D. Hay et. Al Surgery , 1987