Thyroid Cancer 2005
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Transcript of Thyroid Cancer 2005
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Thyroid Cancer 2005
Nancy Fuller, M.D.
University of Wisconsin-Madison
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1. 52 yo woman in good health; presented with back pain of a musculoskeletal nature.
Exam of neck: palpable right sided thyroid nodule approx 2x3 cm; gland otherwise not enlarged and no other nodules or lymphadenopathy.
Ultrasound: solid nodule; uptake scan: no excess uptake in nodule
TFTs: normal A FNA was performed. DX: Hurthle cell neoplasia
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2. 64 yo woman with hyperlipidemia; presented for a preventive health exam with no complaints. Neck exam: 4x2 cm right sided thyroid nodule, gland otherwise normal, no lymphadenopathy. Ultrasound-solid nodule, uptake scan no excess uptake in nodule. TFTs A FNA was performed. DX: Hurthle cell neoplasia
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3. 28 yo woman presented after having a thyroid nodule found incidentally on a carotid ultrasound being performed as a normal control for a study. Exam: 2x2 cm right sided thyroid nodule, gland otherwise normal, no lymphadenopathy. TFTs normal Dedicated ultrasound: solid nodule; FNA performed that day because of availability of pathology support DX: Papillary thyroid carcinoma
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Learning objectives:
• To learn about the epidemiology, types, behaviors, treatment and prognosis of thyroid cancer.
• No financial disclosures
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Epidemiology
• Thyroid nodules: very common• Clinically detectable thyroid carcinoma:
rare: <1% of all cancers• Female to male ratio- 2.5:1• Median age at dx: 45-50
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• Overall incidence is rising: • In 1935: 1.3/100,000
women, .2/100,000 men• By 1991: 5.8/100,000 women,
2.5/100,000 men• Incidence has continued to rise in past
10 years: most rapid rate of increase in all tracked cancers
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Reason for rise?
• Neck irradiation: used between 1910 and 1960
• Better diagnosis?
BUT: only rise is in papillary type; if better diagnosis was reason, would expect rise in all types
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Hegedus, L. N Engl J Med 2004;351:1764-1771
Algorithm for the Cost-Effective Evaluation and Treatment of a Clinically Detectable Solitary Thyroid Nodule
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Thyroid cancer: epithelial types
Differentiated:
Papillary: 70-75 % of all thyroid cancers
Follicular: 15-25%
Undifferentiated:
Anaplastic: 2-5%
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Thyroid cancer: non epithelial
Medullary thyroid cancer
• Sporadic
• Familial
• MEN-2A and B
Others:
lymphoma, mets from breast, colon,
renal and melanoma
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Papillary thyroid carcinoma
Pathogenesis:1. Activation of tyrosine kinase receptors by
rearrangement or gene amplification• Results in a chimeric gene• Occurs either by radiation or sporadic2. Point mutations in BRAF gene• 10X increased risk of thyroid cancer in
relatives of thyroid cancer patients: suggests a genetic link
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PTC
Presentation:• Solitary nodule most common• Pathology: typically unencapsulated;
may be cystic Papillae: 1 or 2 layers of tumor
surrounding fibrovascular core Follicles and colloid are typically absent
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PTC
• Psommoma bodies: scarred remnants
of tumor papillae that have infarcted • Present in half of papillary thyroid
carcinomas
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PTC
Growth and behavior: minor to major
• Microcarcinoma: occult papillary carcinoma, with tumor <1cm
• Found in up to 50% of glands at autopsy (rarer in children)
• Incidental finding of no clinical importance
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PTC
• Other end of spectrum: aggressive metastasis through interthyroidal lymphatic channels to form multifocal tumors
• Involves regional lymph nodes• At diagnosis: clinically detectable nodes more
common in children (50%) than adults• 2-10% distant mets at dx: 2/3 pulmonary, 1/4
skeletal; also brain, kidneys, liver, adrenals
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PTC
Prognosis
• Most patients do not die of their disease• 80-95% 10 year survival rates• Patients between 20-45: best long term
survival• Patients older than 45 with lymph node
recurrences are most likely to die from PTC
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PTC
• Prognosis is poorer in patients with large tumors: one large series showed cancer related mortality of 6%/2-3.9cm, 16%/4-6.9cm and 50%7 cm and above
• Several variants have a worse prognosis: tall cell variant=1% of PTC; more aggressive and invasive
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Schlumberger, M. J. N Engl J Med 1998;338:297-306
Survival Rate among 1701 Patients with Papillary or Follicular Carcinoma and No Distant Metastases at the Time of Diagnosis
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Follicular thyroid carcinoma
• Characterized by follicular differentiation and encapsulation
• Invasion of the capsule and blood vessels is the main determinant between adenomas and carcinoma
• 2 main forms: minimally invasive and widely invasive
• Multicentricity and lymph node involvement are less frequent than in PTC
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FTC
• Minimally invasive FTC behaves more like PTC
• Widely invasive behaves more like anaplastic thyroid carcinoma
• Hurthle Cell variant:more aggressive
• FTC is more likely than PTC to be nonresponsive to I 131.
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Anaplastic thyroid carcinoma
• Undifferentiated tumor of thyroid follicular epithelium
• Very aggressive, with a disease specific mortality approaching 100%
• 2/1,000,000 annual incidence• Typical patient is older than differentiated
carcinoma, mean age 65• <10% under 50• 60-70% women
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ATC
• 20% of ATC: history of differentiated thyroid carcinoma, most papillary
• 10% of Hurthle cell carcinoma: has anaplastic tumor within
• Up to 1/2 of ATC: history of multinodular goiter
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ATC
• Presentation:• Nearly all present with a thyroid mass• Regional or distant spread is present 90% of
the time at dx• Lungs, bones, brain most common mets• Rapidly enlarging tumor; often causes
compression symptoms like dyspnea, dysphagia, hoarseness
• Constitutional symptoms like fatigue, anorexia, wt loss
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ATC• 50% have palpable nodes at dx• Dx: made by FNA, then CT neck and
mediastinum, CXR• Prognostic factors: tumor size
<6 cm=25% 2 yr survival>6cm=3-15% 2 yr survival
Others: older age, male sex, dyspnea at presentation
• No effective treatment for advanced or metastatic ATC: uniformly fatal, with median survival 3-7 mo
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Treatment of differentiated thyroid carcinoma
• Surgery: goal is to remove all tumor tissue from neck
• Total or near total thyroidectomy because of risk of multicentricity
• Removal of local nodes in PTC, only palpable nodes in FTC because of lower rate of lymph node involvement
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Treatment• I 131: given post op: destroys any remaining
normal thyroid tissue, and may destroy occult microcarcinomas
• Increases sensitivity of subsequent 1 131 total body scans
• 4-6 wks after surgery a total body scan off thyroid replacement with low dose 1 131; if any uptake, a treatment dose is given (2 mCi vs. 30-100 mCi)
• Radiation: only if surgical excision is impossible and tissue doesn’t take up I 131
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Followup
Goals of followup:
• Maintain adequate thyroxine treatment
• Detect persistent or recurrent cancer
• Recurrences usually occur early but may occur later so follow up for life
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• Thyroxine treatment goals: initial serum thyrotropin level 0.1 or less, serum free T3 normal
• Check U/S of thyroid area and nodal areas• Serum thyroglobulin levels: TG produced by
follicular cells-should not be detectable after total ablation; presence signifies persistent or recurrent disease
• 80% of patients with TG >40 have detectable foci or I 131 uptake
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• I 131 scanning: needs to be done after withdrawal of thyroxine tx, with TSH >30 needed
• Scanning is done 3 days after I 131 given
• Low risk patients with no I 131 uptake after 1 year: TSH maintained at low but detectable level (0.1-0.5)
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• Local or regional mets: occur in 5-20%
• Excision/I 131 tx/ Radiation tx if no I 131 uptake
• Distant mets: If I 131 uptake, high dose I 131 given + RT
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Complications of treatment:
• I 131: nausea, sialadenitis common but mild and short duration
• Genetic defects: can’t be given to pregnant women
• Increased risk of miscarriage in pregnancies within 1 year of tx
• Overall relative risk of a second type of cancer only if high cumulative dose of I 131 and/or radiation
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Medullary thyroid cancer
• Much less common than epithelial thyroid cancers
• Involves abnormalities of parafollicular C-cells
• Most cases are sporadic
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MTC
• MEN 2 A: autosomal dominant disorder characterized by MTC, pheochromocytoma, and primary parathyroid hyperplasia
• MEN 2 B: same inheritance; MTC + pheochromocytoma. Occurs at a younger age; more aggressive.
• Familial MTC: like MEN 2 A but no other associated abnormalities
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MTC
• Female to male ratio=1:1• MEN 2 A and familiar MTC: peak in
index cases in 3rd decade• MEN 2 B: children and teens most
common age of presentation. • Basal serum calcitonin: usually
correlates with tumor mass and is almost always high with palpable tumor
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MTC
• MTC in MEN 2 B: more aggressive
• Early onset
• Surgery often not curative
• Death from MTC: 50% of MEN 2 B,
10 % MEN 2 A
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• Cases: recap and current status