NEOPLASMS OF THYROID GLAND

DR F. FARAH.
DR M. NYANDUSI.
9/7/2015.
 Outline
• Introduction. • Classification.
• History. • Staging.
• Anatomy. • Management.
• Epidemiology. • Future & Controversies.
• Risk Factors.
• Pathogenesis.
• Clinical presentation.
• Investigation.
 Introduction
• Tumors affecting the thyroid gland are either benign or
malignant

• Thyroid nodules are a major presentation of thyroid

neoplasms.

• Thyroid adenoma is a benign neoplasm of the thyroid.

• Thyroid cancers are mainly papillary, follicular, medullary or

anaplastic thyroid cancer.

• Thyroid may be affected by direct spread of cancer from

adjacent organs.
 Introduction
Thyroid nodules
• lumps which commonly
arise within an otherwise
normal thyroid gland.
• indicate a thyroid neoplasm.
• small percentage of these
are thyroid cancers.
1. www.mayoclinic.com/health/thyroid-nodules
• May presents as a thyroid
cyst.
• Thyroid cysts most
commonly result from
degenerating thyroid
adenomas
• occasionally contain
malignant solid
components.1
 Introduction
• Prevalence of thyroid nodules within a given population
depends on:-
– age, sex, diet, iodine deficiency, therapeutic and
environmental radiation exposure.

• Challenge in differentiation of hyperplasia from true

neoplasms.

• Histologic criteria used to distinguish benign from malignant

neoplasms can be subtle.
 History
• 1514-1564: Gland was first described by Vesalius.
• 1543: Gland was named Glandulare laryngis ,thought to
produce fluid to lubricate larynx.
• 1656 : Glandular thyroideis’ by Thomas Wharton.
• Management ranged from extirpation of the gland, transfixing
large goiters, treatment with dried or burned seaweed.
• 1791: The first documented partial thyroidectomy was carried
out by Pierre Joseph Desault .
• Discovery of iodine in burned ash of seaweed in 1811 led to
successful treatment of some goitres.
 History
• THEODOR KOCHER
• Reported 146 thyroidectomies from 1850 to 1877 worldwide
with mortality 21%.
• He also reported 600 cases performed with 0.5% mortality in
1898 which revolutionized the technique and method of
thyroid surgery.
• This earned him Nobel Prize for medicine in 1909.
• The principles of thyroid surgery described, are still valid and
became foundation for all future refinements.
 Anatomy
• Brownish-red, highly vascular, duct- less gland.
• Situated anteriorly in the visceral compartment of the neck at
the level C5,C6,T1.
• Adult gland weighing 20 to 25 g is slightly larger in women. It
enlarges further during puberty, menstruation & pregnancy.
• Contains 2 endocrine cell types of different origins.
• The follicular cells secrete T4 &T3, which influence a wide
range of metabolic processes.
• The parafollicular/ C cells influence calcium metabolism by
secretion of calcitonin.
Anatomy
 Epidemiology
• Thyroid neoplasms represent almost 95% of all endocrine
tumors.
• Accounting for approx 2.5% of all malignancies.
• 95% of thyroid nodules are benign, 5% malignant.
• 1.9% of all new malignant tumors in USA.
• 68/million new cases. Women 99/million. Men 36/million.2
• Rare in children. Girls 2.2/million. Boys 0.9/million.3

2. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, et al. eds. SEER Cancer Statistics Review,
1975–2000, National Cancer Institute, Bethesda, MD, 2003.
3. Polednak AP. Trends in cancer incidence in Connecticut, 1935–1991. Cancer 1994; 74:2863–2872.
 Epidemiology

4. E. P. Simard, E. M. Ward, R. Siegel, and A. Jemal, “Cancers with increasing incidence trends in the United States: 1999 through
2008,” CA: A Cancer Journal For Clinicians, vol. 62, no. 2, pp. 118–128, 2012.
5. B. Aschebrook-Kilfoy, R. Grogan, M. Ward, E. Kaplan, and S. Devesa, “Follicular thyroid cancer incidence patterns in the United
States, 1980–2009,” Thyroid, 2013.
 Risk Factors
• Exposure to ionizing • Median age at diagnosis is
radiation. 55 years, with a peak in
• No clear association women at 45 to 59 years
between dietary iodine & and in men at 65 to 69 year.
thyroid carcinomas.
• Follicular & anaplastic
thyroid carcinomas occur
more commonly in areas of
endemic goiter.
 Risk Factors
Genetic or environmental factors.
• Radiation exposure.
– Childhood head & neck radiation (glandular fever).
– Nuclear disasters (Chenobyl, Fukushima).
– Nuclear test sites (Marshall Islands).
• Family history of Papillary or Medullary thyroid Ca.
• Male sex.
 Risk Factors
Familial /Genetic factors
• Approximately 6% of patients with Papillary Thyroid Ca have
familial disease.
• Papillary Thyroid Ca occurs with increased frequency in
certain families with breast, ovarian, renal, or central nervous
system malignancies.
• Gardner’s syndrome (familial colonic polyposis) and Cowden’s
disease are associated with Differentiated Thyroid Ca.
• Patients with a family history of Medullary Thyroid Ca, MEN
IIA, or MEN IIB warrant evaluation for the RET point mutation.
 Thyroid Cancer Risk Stratification
Low Risk Intermediate Risk High Risk

Age <45 years >45 years

Gender Female Male

Size <2 cm >4 cm

Mixture of
Extent Intraglandular Extraglandular
Features
Grade Low High
Distant
Absent Present
Metastases

Treated, % 39 39 22
Death Rate, % <1 13 53
7. Shaha AR, et al. Acta Otolaryngol. 2002;122:343-347.
Molecular basis for thyroid neoplasm
• An accumulation of genetic alterations seems to be required
for progression to thyroid carcinoma.
• An alteration in total cellular DNA content.
• The loss of chromosomes, or aneuploidy, has been noted in
10% of all papillary carcinomas.
• The development of follicular adenomas is associated with a
loss of the short arm of chromosome 11 (11p), and transition
to a follicular carcinoma seems to involve deletions of 3p, 7q,
and 22q.
• Loss of heterozygosity involving multiple chromosomal
regions is much more prevalent in follicular adenomas and
carcinomas than in papillary carcinomas.
• Several oncogenes, altered genes that contribute to tumor
development, have been identified in early thyroid tumor
progression.
• Mutations in the thyroid-stimulating hormone (TSH) receptor
& G-protein mutations are found in hyperfunctioning thyroid
adenomas.
• Somatic Ras mutations are associated with follicular
adenomas, and to a lesser extent with follicular carcinomas.
• Other genetic changes.
• Mutations within the mitogen-activated protein kinase
(MAPK) pathway are involved in malignant transformation to
papillary thyroid cancer.
• Other factors:- fibroblast growth factors, epidermal growth
factor& vascular endothelial growth factor may have
increased expression in thyroid tumors and contribute to
tumor progression.
• MTC and pheochromocytoma arise from neural crest cells
containing RET point mutations.
• Mutations have been well documented in patients with
familial MTC, MEN type IIA and MEN IIB.
 Clinical presentation
• Painless palpable solitary thyroid nodule(4-7%)
• Age: <30 & >60 yrs
• Rapid growth.
• Hoarseness of voice – Involvement of RLN & V.C paralysis.
• Dysphagia – Sign of impingement of oesophagus.
• Heat intolerance & palpitations – Functioning nodules.
• Medullary Ca – part of MEN2A,or 2B Syndrome, if family
history.
 Physical examination
Examination of the thyroid nodule:
• consistency - hard vs. soft.
• size - < 4.0 cm.
• Multinodular vs. solitary nodule.
– Multi nodular - 3% chance of malignancy.
– Solitary nodule - 5%-12% chance of malignancy.
• Mobility with swallowing.
• Mobility with respect to surrounding tissues.
• Well circumscribed vs. ill defined borders
Cont’d
• Assess for ectopic thyroid gland.
• Indirect or fiberoptic laryngoscopy
• vocal cord mobility
• evaluate airway
• preoperative documentation of any unrelated
abnormalities
• Systematic palpation of the neck
• Metastatic LN commonly found:
– in the central compartment (level VI)
– along middle and lower portion of the jugular vein
(regions III and IV).
 Investigations
Thyroid FNAB.
• To provide a rational approach to management & determine
the correct surgical procedure when surgery is required.
• Safe, inexpensive, easily performed, minimal patient
discomfort.
• High diagnostic accuracy rate 90-100%
• False positive diagnoses: <1% over-interpretation of
reparative and reactive nuclear changes as papillary thyroid
carcinoma.
• False negative rates: 1-11% unsatisfactory specimens.
– sampling errors.
– interpretation errors.
– cystic neoplasms.

• Major limitations include: difficulty to distinguish

hypercellular, non-neoplastic nodules from follicular
neoplasm.
• Difficulty to obtain an adequate specimen on some occasions.
 Minimising false negative results
• Use ultrasound-guided – FNAB.
• Perform multiple punctures of the nodule so that several
areas are sampled.
• Consider repeated Ultrasound Guided FNAB for follow-up of
benign nodules.
• For multiple nodules, prioritize the nodule to biopsy according
to ultrasonographic findings.
• For cystic lesions, sample solid areas with Ultrasound Guided
FNAB and submit cyst fluid for examination.
• Review slides with an experienced cytopathologist
Blood tests.
• Serum TSH concentration.
• Low serum TSH > benign & Sensitive TSH assay> solitary
thyroid nodule, However, malignancy cannot be ruled out.
• T3, T4.
• Elevated serum calcitonin levels > suggestive of MTCs serum
Calcitonin replaced by sensitive (PCR) for germline mutations
in the RET proto-oncogene.
• Calcitonin & Pentagastrin – stimulated calcitonin >> tumor
markers to monitor pts treated with MTC.
 Ultrasonography.
• Excellent for characterizing Features suggesting greater
size and other features of risk of malignancy
nodule • Irregular or poorly defined
• Useful in localizing nodule borders.
for FNA.8 • Hypo-echogenicity.
• Cannot distinguish between • Evidence of
microcalcifications.
benign vs. malignant
• Increased blood flow.
• Growth & interval change
on serial ultrasounds.
8. Can AS, Peker K. Comparison of palpation-versus ultrasound-guided fine-needle aspiration biopsies
in the evaluation of thyroid nodules. BMC Res Notes. 2008 May 15. 1:12.
2015 consensus statement by ATA.
• Ultrasonography remains the most important imaging
modality in the evaluation of thyroid cancer and should be
used routinely to assess the primary tumor.
• Ultrasound Guided-FNAB of suspicious LN may be useful in
guiding the extent of surgery.
• CT or MRI may be considered in select circumstances to better
characterize tumor invasion and bulky, inferiorly located, or
posteriorly located lymph nodes.
• PET-CT scanning may be helpful in cases of recurrent cancer
with positive tumor markers and negative anatomic imaging.
Radionuclide imaging.
• Formerly had been used Circumstances where
extensively in the initial radionuclide imaging may
work up of nodular thyroid be useful and indicated:
disease. • Suppressed TSH (more likely
Problem. to have a autonomously
• Although “hot” nodules are functioning nodule)
usually never cancer, only • Multiple nodules, none
5% of all nodules are dominant.
hyperfunctioning.
9. Choudhury M, Singh S, Agarwal S.
• The remaining 90-95% are Diagnostic utility of Ki67 and p53
immunostaining on solitary thyroid nodule--
warm or cold could be a cytohistological and radionuclide
cancer & require FNA.9 scintigraphic study. Indian J Pathol
Microbiol. 2011 Jul-Sep. 54(3):472-5.
 Benign
• Follicular adenoma b. Cytologic patterns
a. Architectural patterns i. Oxyphilic cell type
i. Normofollicular (simple) ii. Clear cell type
ii. Macrofollicular (colloid) iii. Mucin-producing cell type
iii. Microfollicular (fetal) iv. Signet-ring cell type
iv. Trabecular and solid v. Atypical.
(embryonal) Others
v. Atypical • Hurthle cell adenoma.
• Adenolipomas.
• Hyalinizing trabecular
tumors.
10. Hedinger C, ed. Histological Typing of Thyroid Tumours. 2nd ed. Berlin: Springer-Verlag;
1988.
 Follicular Adenoma
• Benign, encapsulated tumor
with glandular cellular
structure.
• Common.
• Predominantly young to
middle aged women.
• Presents as solitary thyroid
nodule.
• Painless nodular mass, cold
on isotopic scan.
 Others
Hurthle cell adenoma.
• Circumscribed & encapsulated lesion.
• Resemble follicular adenoma, cells rich in mitochondria.
Hyalinizing trabecular adenoma.
• Cells arranged in trabecular, with highly granular cytoplasm.
• Perivascular hyaline fibrosis.
Nodular Goitre.
• Coalescent nodules of different sizes.
• Hyperplastic or dilated with colloid.
 Malignant
• Papillary Carcinoma • Medullary Carcinoma.
– Follicular variant. • Miscellaneous.
– Tall cell. – Sarcoma.
– Diffuse sclerosing. – Lymphoma.
– Encapsulated. – Squamous cell.
• Follicular Carcinoma. – Mucoepidermoid.
– Overtly invasive. – Clear cell.
– Minimally invasive. – Plasma cell.
• Hurthle cell Carcinoma. • Metastatic.
• Anaplastic Carcinoma. – Direct extension.
– Giant cell. – Kidney, Colon, Melanoma.
– Small cell. 10. Hedinger C, ed. Histological Typing of Thyroid Tumours. 2nd ed.
Berlin: Springer-Verlag; 1988.
11. Kondo et al. Nature Reviews Cancer 6, 292–306 (April 2006) | doi:10.1038/nrc1836
 Papillary Carcinoma
• Commonest. • Mets to neck & mediastinal
• Female:Male 2.5:1. LN.
• Unencapsulated, ill-defined – Adults 40 – 60%.
margins. – Children – 90%.
• Tumor typically firm & solid. • <5% have distant mets at
• Can present as nodal time of presentation.
enlargement. – Lung is common site.

12. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text.
8th ed. Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000
• Histology. • Prognosis.
– Psammoma bodies. – Age & sex.
– Orphan annie nuclei. – Size.
– Papillae or follicles. – Multicentricity.
– Infiltrative or – Extrathyroid extension.
encapsulated. – Distant mets.
 Follicular Carcinoma
• 2nd most common 10 – 20%. Histology
• Females > Males. • Round or oval nodule.
• Average age 45 – 55yrs. • Thick capsule.
• Rare in children. • Composed of follicles.
• Solitary nodule, painless.
• Cold on isotopic scan.
• Hematogenous spread.
 Hurthle Cell Carcinoma
• 3 – 5% of thyroid cancer. Prognosis.
• Variant of follicular. • Locally invasive.
• Tends to be aggressive.13 • Capsular & vascular
invasion.
• Worse prognosis than
follicular tumors.14
• Rarely respond to RAI.

13. Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of Thyroid
Disease. Monticello, NY: Marcel Dekker, Inc.: 2001:239-241.
14. Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri, EL, Samaan N, eds. Endocrine
Tumors. Cambridge, MA: Blackwell; 1993:278-333.
 Anaplastic Carcinoma
• Rare, <5% of thyroid Ca.
• Elderly  65 yrs.
• Female>male.
• Highly malignant. Fatal <1yr.
• Rapidly enlarging bulky neck
mass.
• Large , firm necrotic mass.
• Extends into adjacent soft
tissue, trachea &
esophagus.
• Dysphagia, dyspnoea,
hoarseness.
• Histology.
– Giant spindle cell.
– Highly anaplastic cell.
– High mitotic activity.
– Cellular pleomorphism.
 Medullary Thyroid Carcinoma
• Tumor of C cell producing Sporadic MTC.
calcitonin. • Middle aged adults.
• 5% of thyroid malignancy. • Female: Male = 1.3:1.
• Sporadic – 80%. • Unilateral involvement.
• Rest is MEN 2A, MEN 2B & • +/- cervical LN mets.
familial. • 60 -70% 5-yr survival after
thyroidectomy.
 Multiple Endocrine Neoplasia Types IIA &
IIB
• Germ-line mutation in Ret protooncogene on chromosome
10q11.2
• MEN IIA: MTC, phaeochromocytoma, parathyroid adenoma or
hyperplasia
• MEN IIB: MTC, phaeochromocytoma, mucosal
ganglioneuromas, Marfanoid habitus, other skeletal
abnormalities
• Calcitonin is the principal biochemical marker in MTC; it is
used for detection, staging, postoperative management and
prognosis.
MTC with MEN 2A.
• Slow growing.
• Multicentric & bilateral.
• Younger patients in
twenties.
MTC with MEN 2B.
• Aggressive with early mets.
• Poor prognosis.
• Young patient in teens.
Histology
• Sporadic & familial.
• Solid, lobular or insular
growth patterns.
• Round, polygonal or spindle
shaped tumor cells.
• Amyloid deposits.
ATA preoperative lab testing.
• Extent of metastatic disease; this will determine the extent of
preoperative imaging and may alter the surgical approach.
• In patients with MEN 2, identify primary hyperparathyroidism
and/or pheochromocytoma —comorbid conditions that alter
the surgical approach and surgical priorities.
• To identify RET mutation carriers so that testing of
appropriate family members can allow for early diagnosis &
treatment of affected individuals.
 Primary Thyroid Lymphoma
• A rare type of thyroid cancer
– Affects fewer than 1 in 2
million people
• Constitutes 5% of thyroid
malignancies.
• Develops in the setting of pre-
existing lymphocytic thyroiditis.
• Often diagnosed because of
airway obstruction symptoms
• Tumors are firm, fleshy, pale.

15. Cabanillas F. Thyroid lymphoma.

 Paediatric thyroid Carcinoma
• Prevalence of thyroid nodules in children ranges from 0.2-5%
compared with approximately 20% in adults.
• Carry far greater risk of harbouring malignancy .
• Solitary nodules in children reportedly have a 20-73%
incidence of malignancy.16
• Painless metastatic cervical mass is the presenting symptom in
40-80% of patients.17
• Mainly DTC.
• Radiation exposure – major risk.18
16. Festen C, Otten BJ, van de Kaa CA. Follicular adenoma of the thyroid gland in children. Eur J
Pediatr Surg. 1995 Oct. 5(5):262-4.
17. Dinauer CA, Breuer C, Rivkees SA. Differentiated thyroid cancer in children: diagnosis and
management. Curr Opin Oncol. 2008 Jan. 20(1):59-65.
18. Garcia CJ, Daneman A, Thorner P, et al. Sonography of multinodular thyroid gland in
children and adolescents. Am J Dis Child. 1992 Jul. 146(7):811-6.
Staging
 Risk assignment systems for Differentiated Thyroid Ca.
SYSTEM FACTORS USED
AMES Age, Size, Distant metastases, Tumor extension.
(Lahey Clinic)
AGES Age, Size, Tumor extension, Histologic grade.
(Mayo Clinic)
MACES Age, Size, Distant metastases, Tumor extension, Complete
(MayoClinic) excision.

Univ of Chicago Distance metastases, Tumor extension, Lymph node – negative

biopsy.

Memorial Sloan - Age, size, Distant metastases, Tumor extension.

Kettering
 Surgical options
• Lumpectomy.
• Partial Thyroidectomy.
• Total Lobectomy/Hemithyroidectomy.
• Subtotal thyroidectomy.
• Near total thyroidectomy.
• Total thyroidectomy.
 Management
• Thyroidectomy.
RAI indication.
• Large >4 cm tumors.
• Known distant metastasis.
• Gross extrathyroid
extension.
RAI not recommended:-
• Small < 1 cm, solitary
tumors
• Multifocal tumors when all
foci are < 1 cm.
RAI ablation considered for:-
• Moderate-size 1-4 cm and
node positive.
• Grossly multifocal.
• Aggressive, based on
histology.
• High risk, based on patient
factors age >45 yr, history of
head and neck radiation,
family history of thyroid
cancer.
 Management
Recurrence, metastasis & unresectable Mx.
• EBRT.
• TSH suppression therapy.
– TSH suppression to < 0.1 mU/L in high-risk disease.
– TSH maintenance at 0.3-2 mU/L may be considered for
low-risk disease
• Chemotherapy.
– Pazopanib 800mg/PO, Doxorubicin 60mg/m2, Cisplatin
40mg/m2.
• Tyrosine kinase inhibitors .
• Sorafenib 400 mg PO BID19 or sunitinib 50 mg PO OD for 4wk
to 6wk cycle. 19. Cohen EE, Needles BM, Cullen KJ, et al. Phase 2 study of sunitinib in
refractory thyroid cancer. J Clin Oncol. 2008 May 20. 26 (suppl):Abstract 6025.
2015 guidelines of management of paediatric thyroid ca.
• For suppressed TSH associated with a thyroid nodule, thyroid
scintigraphy should be done.
• Neck ultrasound to interrogate all regions of the neck in order
to optimize the preoperative surgical plan in children with a
newly diagnosed PTC.
• Children with papillary thyroid cancer, total thyroidectomy is
recommended.
• Neck ultrasound follow-up of children with PTC; it should be
performed at least 6 months after initial surgery & then at 6-
12 month intervals for ATA pediatric intermediate & high-risk
patients.
 Management
DTC20
• Total thyroidectomy is recommended for tumors >1 cm.
• Hemithyroidectomy may be considered for small < 1 cm.
• Central neck dissection when cervical LN are involved.
• If lateral cervical LN have biopsy-proven disease central and
lateral compartment neck dissection.
• Prophylactic unilateral or bilateral central neck dissection may
be considered in clinically N0 disease, especially for advanced
primary tumors T3 or T4.

20. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association
management guidelines for patients with thyroid nodules and differentiated thyroid
cancer. Thyroid. 2009 Nov. 19(11):1167-214.
2015 consensus statement from the ATA on management of
patients DTC.
• Nodal mets may involve compartmental LN dissection, active
surveillance, radioactive iodine ablation therapy, EBRT and/or
nonsurgical, image-guided, minimally invasive ablative
approaches
• Biologic considerations include aggressive histology,
extrathyroidal extension of primary tumor & molecular
prognosis for aggressive biology
• Surgical/technical considerations include prior recurrences in
the same or different compartments
 Management
Anaplastic thyroid cancer.
• Surgery – lobectomy, total thyroidectomy.
• Combined modality – doxorubicin 20mg weekly.21
• Palliative care – comfort, end of life issues.

21. Tennvall J, Lundell G, Wahlberg P, Bergenfelz A, Grimelius L, Akerman M, et al. Anaplastic thyroid
carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery. Br J
Cancer. 2002 Jun 17. 86(12):1848-53.
 Management
Medullary thyroid Ca.22
• Total thyroidectomy with central neck dissection (level 6).
• Lateral neck dissection in patients with minimal mets.
• Preoperative imaging of chest, liver & neck for patients with
nodal mets.
• Palliative debulking surgery – relieve tracheal compression.
• Treatment of concomitant pheochromocytoma.

22. Wu LS, Roman SA, Sosa JA. Medullary thyroid cancer: an update of new guidelines and
recent developments. Curr Opin Oncol. 2011 Jan. 23(1):22-7.
• Management of a solitary thyroid nodule in rural kenya.
• 220 thyroidectomies done – malignancy rate of 11.7% (15
papillary, 11 follicular). 47% - multinodular goitre. 23

• Evaluation and surgical treatment of solitary thyroid nodules.

FNAC done – 60% of thyroidectomies done were solitary
nodules. 15% malignancy. 24

23. Hill AG, Mwangi L, Wagana L. Thyroid disease in a rural Kenyan hospital. East Afr Med J
2004;81:631-3.
24. Adwok J.A. Evaluation and surgical treatment of solitary thyroid nodules. East Afr. Med. J.
1995; 72: 2-3.
Algorithm for the management of malignant thyroid neoplasms. FNAB =
fine needle aspiration biopsy; XRT = external-beam radiation therapy
 Future & Limitations
Limitations.
• Neck dissection in early thyroid cancer. Level 6. Lateral neck
dissection.
• Multidisplinary Team Approach.

Future.
• Tyrosine kinase receptor blockage. Pharmacological agents on
trial. EGF, VEGF, FGF.
 Reference
1. www.mayoclinic.com/health/thyroid-nodules
2. Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, et al. eds. SEER Cancer Statistics Review,
1975–2000, National Cancer Institute, Bethesda, MD, 2003.
3. Polednak AP. Trends in cancer incidence in Connecticut, 1935–1991. Cancer 1994; 74:2863–2872.
4. E. P. Simard, E. M. Ward, R. Siegel, and A. Jemal, “Cancers with increasing incidence trends in the United
States: 1999 through 2008,” CA: A Cancer Journal For Clinicians, vol. 62, no. 2, pp. 118–128, 2012.
5. B. Aschebrook-Kilfoy, R. Grogan, M. Ward, E. Kaplan, and S. Devesa, “Follicular thyroid cancer incidence
patterns in the United States, 1980–2009,” Thyroid, 2013.
6. www.ruraldoc.com
7. Shaha AR, et al. Acta Otolaryngol. 2002;122:343-347.
8. Can AS, Peker K. Comparison of palpation-versus ultrasound-guided fine-needle aspiration biopsies in
the evaluation of thyroid nodules. BMC Res Notes. 2008 May 15. 1:12.
9. Choudhury M, Singh S, Agarwal S. Diagnostic utility of Ki67 and p53 immunostaining on solitary thyroid
nodule--a cytohistological and radionuclide scintigraphic study. Indian J Pathol Microbiol. 2011 Jul-Sep.
54(3):472-5.
10. Hedinger C, ed. Histological Typing of Thyroid Tumours. 2nd ed. Berlin: Springer-Verlag; 1988.
11. Kondo et al. Nature Reviews Cancer 6, 292–306 (April 2006) | doi:10.1038/nrc1836.
12. Braverman LE, Utiger RD, eds. Werner & Ingbar’s The Thyroid: A Fundamental and Clinical Text. 8th ed.
Philadelphia, Pa: Lippincott, Williams & Wilkins; 2000
13. Kloos RT, Mazzaferri E. Thyroid carcinoma. In: Cooper DS, ed. Medical Management of Thyroid Disease.
Monticello, NY: Marcel Dekker, Inc.: 2001:239-241.
14. Mazzaferri EL. Thyroid carcinoma: papillary and follicular. In: Mazzaferri, EL, Samaan N, eds. Endocrine
Tumors. Cambridge, MA: Blackwell; 1993:278-333.
15. Cabanillas F. Thyroid lymphoma.
16. Festen C, Otten BJ, van de Kaa CA. Follicular adenoma of the thyroid gland in children. Eur J Pediatr Surg.
1995 Oct. 5(5):262-4.
17. Dinauer CA, Breuer C, Rivkees SA. Differentiated thyroid cancer in children: diagnosis and management.
Curr Opin Oncol. 2008 Jan. 20(1):59-65.
18. Garcia CJ, Daneman A, Thorner P, et al. Sonography of multinodular thyroid gland in children and
adolescents. Am J Dis Child. 1992 Jul. 146(7):811-6.
19. Cohen EE, Needles BM, Cullen KJ, et al. Phase 2 study of sunitinib in refractory thyroid cancer. J Clin Oncol.
2008 May 20. 26 (suppl):Abstract 6025.
20. Cooper DS, Doherty GM, Haugen BR, et al. Revised American Thyroid Association management guidelines
for patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2009 Nov. 19(11):1167-214.
21. Tennvall J, Lundell G, Wahlberg P, Bergenfelz A, Grimelius L, Akerman M, et al. Anaplastic thyroid
carcinoma: three protocols combining doxorubicin, hyperfractionated radiotherapy and surgery. Br J
Cancer. 2002 Jun 17. 86(12):1848-53.
22. Wu LS, Roman SA, Sosa JA. Medullary thyroid cancer: an update of new guidelines and recent
developments. Curr Opin Oncol. 2011 Jan. 23(1):22-7.
23. Hill AG, Mwangi L, Wagana L. Thyroid disease in a rural Kenyan hospital. East Afr Med J 2004;81:631-3.
24. Adwok J.A. Evaluation and surgical treatment of solitary thyroid nodules. East Afr. Med. J. 1995; 72: 2-3.
THANK YOU