Professional Documents
Culture Documents
Outline
• Case Presentation
• “Differentiated Thyroid Cancer”
– Papillary Thyroid Carcinoma
– Follicular Thyroid Carcinoma
• Cohort Data
• Analysis of Data
• Summary
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Thyroid cancer
Negative Outline
• No discussion of medullary thyroid ca
• No discussion of MEN2a, MEN2b
• No discussion of surgical technique (as I
haven’t seen surgery on a thyroid since
2005)
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Thyroid cancer
Case presentation
• HPI: M is a 30 yo M referred to endocrine
surgery for a palpable thyroid nodule on
physical exam by PMD. No dysphonia,
dysphagia, odynophagia, change in voice.
No smoking history. Recent cough for a
few weeks. No fevers, chills, weight loss.
No hx of radiation to neck
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Thyroid cancer
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Thyroid cancer
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Thyroid cancer
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Thyroid cancer
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Thyroid cancer
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Thyroid cancer
Gray’s Anatomy 11
Thyroid cancer
Background
• 1% of all new malignant disease
• 94% differentiated thyroid carcinoma
– Derive from follicular epithelial cells
• Papillary or follicular thyroid carcinoma
• 5% medullary thyroid carcinoma
– Neuroendocrine tumors
• 1% anaplastic
– Dedifferentiated thyroid carcinoma
Figge J. Epidemiology of thyroid cancer. In: Wartofsky L, ed. Thyroid cancer: a
comprehensive guide to clinical management. Totowa: Humana Press, 1999; 77-83.
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Thyroid cancer
Diagnosis
• In sporadic cancer, patients usually present with a
solitary thyroid nodule
• The initial diagnostic procedure of choice is FNA
– Allows diagnosis of papillary, medullary, anaplastic
cancers
– To distinguish between follicular adenoma and
carcinoma, histological examination is necessary
• False-positive and false-negative rates of FNA are
<5%
Ravetto C, Colombo L, Dottorino ME. Usefulness of fine-needle aspiration in the diagnosis of thyroid
carcinoma: a retrospective study of 37,895 patients. Cancer 2000;90:357-63.
Gharib H, Goellner JR. Fine-needle aspiration biopsy of the thyroid: an appraisal. Ann Intern Med
1993;118:282-89. 13
Thyroid cancer
Epidemiology
• F:M ~2:1
• Median age of diagnosis: 45 years
• If iodine deficient area: follicular > papillary
• Risk factors:
– External radiation, especially during childhood
– E.g. Chernobyl disaster
– Inherited polyposis syndromes: FAP, Gardner’s,
Cowden’s
Molecular Genetics
• After radiation exposure, RET proto-oncogene
(formerly PTC) rearrangements papillary
carcinoma
• Other factors for papillary carcinoma:
overexpression of TRK, MAPK, DNA
hypermethylation, and activating mutations of
RAS
• For follicular carcinoma: RAS mutations,
chromosomal rearrangements (PAX8 fused to
PPAR-gamma-1)
Fagin JA. Molecular pathogenesis of tumors of thyroid follicular cells. In: Fagin JA, ed. Thyroid Cancer.
Boston: Kluwer, 1998.
Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid
carcinoma [corrected]. Science 2000;289:1357-60. 15
Thyroid cancer
Clinicopathological Staging
• There are >14 staging systems for thyroid
cancer
• Histological subtypes that connote a poor
prognosis:
– Papillary: tall cell, columnar cell variants
– Hurthle cell (oxyphilic cell)
– Follicular: poorly differentiated variants
Sherman SI, Brierley JD, Sperling M, et al. Prospective multicenter study of treatment of thyroid
carcinoma: initial analysis of staging and outcome. Cancer 1998;83:1012-21.
Burman KD, Ringel MD, Wartofsky L. Unusual types of thyroid neoplasms. Endocrinol Metab Clin
North Am 1996;25:49-68. 16
Thyroid cancer
17
Thyroid cancer
FNA showing papillary ca. The malignant cells Blue arrow points to papillary structure.
including the one at the tip of the arrow are very The center is fibrovascular. The cells
loosely arranged covering it are epithelial. The red arrow
shows a similar papillary structure in cross
section.
Images from UConn’s Pathweb 19
http://pathweb.uchc.edu
Thyroid cancer
Papillary Cancer
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Thyroid cancer
Papillary Cancer
• Psammoma bodies: laminated calcified spheres, diagnostic of papillary
cancer
• Certain histological variants have higher risk of recurrence: Tall cell,
columnar cell, diffuse sclerosing cell
• Can spread to lung (also bone, liver, brain)
• Very rare conversion to anaplastic type
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Thyroid cancer
FNA showing follicular cells. The follicles are Normal thyroid follicles appear at the lower
composed of small clusters of cells. The right. The follicular adenoma is at the center to
colloid cannot be identified easily in this upper left. This adenoma is a well differentiated
preparation. The nuclei are monotonous neoplasm because it closely resembles normal
without obvious atypia. tissue.
Mazzaferri EL, Kloos RT. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin
Endocrinol Metab 2001;86:1447-1463. 23
Thyroid cancer
Katoh R, Sasaki J, Kurihara H, et al. Multiple thyroid involvement (intraglandular metastasis) in papillary
thyroid carcinoma. A clinicopathologic study of 105 consecutive patients. Cancer 1992;70:1585-90.
Silverberg SG, Hutter RVP, Foote FW Jr. Fatal carcinoma of the thyroid: histology, metastases, and
causes of death. Cancer 1970;25:792-802. 24
Thyroid cancer
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Thyroid cancer
Consensus Guidelines
• Most concensus guidelines state:
– For papillary ca:
• If > 1 cm, or mets, or extends beyond thyroid, or hx of
irradiation total thyroidectomy
• If < 1 cm and confined to one lobehemithyroidectomy
– For follicular ca:
• Total thyroidectomy unless only suspicion on cytology, then
can proceed with hemithyroidectomy and isthmusectomy with
potential completion thyroidectomy based on histology
British Thyroid Association and Royal College of Physicians. Guidelines for the management of thyroid
cancer in adults. London: Guidelines for the management of thyroid cancer in adults, 2002.
Task Force TC. AACE/AAES medical/surgical guidelines for clinical practice: Management of thyroid
carcinoma. Endocr Pr 2001;7:203-20.
Mazzaferri EL, Jhiang SM. Long-term impact of initial surgical and medical therapy on papillary and
follicular thyroid cancer. Am J Med 1994;97:418-28. 26
Thyroid cancer
Bilimoria KY et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg
2007;246:375-384. 27
Thyroid cancer
Data to Support Consensus Guidelines cont’d:
Cumulative Recurrence Rate vs Years of
Follow-Up by Tumor Size
Bilimoria KY et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg
2007;246:375-384. 28
Thyroid cancer
Data to Support Consensus Guidelines cont’d:
Cumulative Recurrence Rate vs Years of
Follow-Up by Extent of Surgery
Bilimoria KY et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg
2007;246:375-384. 29
Thyroid cancer
Data to Support Consensus Guidelines cont’d:
Cumulative Survival Rate vs Years of Follow-
Up by Extent of Surgery
Bilimoria KY et al. Extent of surgery affects survival for papillary thyroid cancer. Ann Surg
2007;246:375-384. 30
Thyroid cancer
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Thyroid cancer
Spencer CA, LoPresti JS, Fatemi S, Nicoloff IT. Detection of residual and recurrent differentiated
thyroid carcinoma by serum thyroglobulin measurement. Thyroid 1999;9:435-41.
Ozata M, Suzuki S, Miyamoto T, Liu RT, Fierro-Renoy F, DeGroot LJ. Serum thyroglobulin in the
follow-up of patients treated with differentiated thyroid cancer. J Clin Endocrinol Metab
1994;79;98-105.
Haugen BR, Pacini F, Feiners C, et al. A comparison of recombinant human thyrotropin and thyroid
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hormone withdawal for the detection of thyroid remnant or cancer. J Clin Endocrinol Metab
1999;84:3877-85.
Thyroid cancer
Long-term Monitoring:
Thyroglobulin caveats
• Reported Tg concentrations can be falsely lowered by
autoAbs that bind Tg and prevent detection by
immunoassays
• These autoAbs are present in as many as 25% of pts with
thyroid cancer, and 10% of general population
• Methods to detect Tg mRNA are in development though
their utility has been questioned
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Thyroid cancer
Long-term Monitoring:
What Is At Stake
• 10-yr cancer specific mortality rates for
papillary and follicular thyroid cancer are 7
and 15%, respectively, base on cohort data
on 53,856 patients managed in the US
between 1985 and 1995
• Prevalence of DTC survivors is 300,00 in
USA
• Each needs lifelong surveillance
Ries LAG, Eisener MP, Kosary CL, Hankey BF, Miller BA, Cleeg L, Mariotto A, Fay MP, Feuer EJ,
Edwards BK. 2003 SEER Cancer Statistics Review, 1975-2001. Bethesa, MD: National Cancer
Institute. http://seer.cancer.gov/csr/1975_2001/results_single/sect_25_table.12.pdf
Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856
cases of thyroid carcinoma treated in the US, 1985-1995. Cancer 1998;83:2638-48. 37
Thyroid cancer
Unique Pros, and Side Effects, of
Remnant Ablation
• Persistent disease and tumor stage cannot be identified
shortly after surgery when there is a large thyroid remnant
• Without RA, half of lung metastases in children cannot be
identified
• But:
– Transient loss of taste
– Acute and chronic radiation-induced parotitis
– Sialadenitis with possible xerostomia
– Transient testicular damage
– Side effects tend to be dose-related
Sclumberger M et al. Follow-up of low-risk patients with differentiated thyroid carcinoma: a European perspective. Eur J
Endocrinol 2004;150:105-112.
Bal CS et al. Is chest x-ray or high-resolution computed tomography scan of the chest sufficient investigation to detect
pulmonary metastasis in pediatric differentiated thyroid cancer? Thyroid 2004; 14:217-225.
Mandel SJ, Mandel L. Radioactive iodicine and the salivary glands. Thyroid 2003;13:265-271. 38
Mazzaferri EL. Gonadal damage from 131I therapy for thyroid cancer. Clin Endocrinol (Oxf) 2002;57:313-314.
Thyroid cancer
Mazzaferri EL, Kloos RT. Current approaches to primary therapy for papillary and follicular thyroid cancer. J Clin
Endocrinol Metab 2001;86:1447-1463. 40
Thyroid cancer
Summary
• Most thyroid carcinoma is differentiated type
• US/FNA
• TNM or MACIS for staging
• Total thyroidectomy for most
• Post-surgical radioactive iodine
ablation/remnant ablation
• RxWBS + serum Thyroglobulin
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