Thyroid Cancer 2005

Nancy Fuller, M.D.

University of Wisconsin-Madison

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

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

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

Learning objectives:

• To learn about the epidemiology, types, behaviors, treatment and prognosis of thyroid cancer.

• No financial disclosures

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

• 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

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

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

Thyroid cancer: epithelial types

Differentiated:

Papillary: 70-75 % of all thyroid cancers

Follicular: 15-25%

Undifferentiated:

Anaplastic: 2-5%

Thyroid cancer: non epithelial

Medullary thyroid cancer

• Sporadic

• Familial

• MEN-2A and B

Others:

lymphoma, mets from breast, colon,

renal and melanoma

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

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

PTC

• Psommoma bodies: scarred remnants

of tumor papillae that have infarcted • Present in half of papillary thyroid

carcinomas

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

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

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

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

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

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

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.

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

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

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

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

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

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

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

• 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

• 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)

• 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

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

Medullary thyroid cancer

• Much less common than epithelial thyroid cancers

• Involves abnormalities of parafollicular C-cells

• Most cases are sporadic

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

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

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

• Cases: recap and current status