Pocket Oncology (Pocket Notebook Series), 1st Ed.

THYROID CANCER

Payal D. Shah Eric J. Sherman

Epidemiology

• Incidence: 240% ↑ in incidence over prior 3 decades, in part due to ↑ detection of small papillary CA; incidence of anaplastic thyroid CA declining

• Mortality: Mortality rate stable; accounts for 95% of endocrine CA but 66% of endocrine CA death

• Subtypes: 80–85% of malignant epithelial thyroid tumors in developed countries are papillary; 3–12% medullary; 1–3% anaplastic

• Median age at dx early 40s for papillary thyroid CA, late 40s for follicular; 60–70 y for anaplastic

Biology

• MAPK signaling pathway: Mt involving one of three genes, RET/PTC (rearrangement in 20% of adult sporadic papillary carcinomas), BRAF, or RAS in 70% of papillary carcinomas; rarely overlap in same tumor

• PAX8-PPAR in 35% follicular carcinomas, some Hurthle cell

Clinical Presentation and Diagnosis

• Commonly p/w incidental solitary thyroid nodules: Median tumor size 2–3 cm; 5–10% malignant; higher percentage if radiation exposure; majority hypofunctional; presence of microcalcifications, irregular margins, spotty intranodular flow, hypervascularity are suggestive of malignancy

• U/S: For FNA, to assess number & characteristics of nodules

• FNA: Accuracy of dx 70–97%; varies w/sample quality, cytopathologist skill; ∼70% benign, 4% malignant, 10% suspicious/indeterminate; 17% insufficient sample

• Medullary: Familial often detected by screening w/stimulation tests/molecular analysis; sporadic by asx thyroid mass; secretory diarrhea if bulky disease w/high calcitonin

• Anaplastic: Prior or concurrent dx of well-differentiated thyroid CA or benign nodular thyroid disease; rapidly ↑ palpable neck mass (median tumor size 8–9 cm); invasion into airways & recurrent laryngeal nerve leads to obstructive sx, hemoptysis, dysphagia, hoarseness; 20–50% have distant mets at dx in lung > bone, liver

• Familial tumors tend to be more aggressive than nonfamilial

Natural History and Prognosis

• Natural hx: 2/3 pts w/papillary carcinomas have disease limited to thyroid at dx

• Prognosis: Papillary: 90–95% long-term survival; follicular: 70–80% long-term survival; distant mets strong negative prognostic indicator; prognosis 3 stage; anaplastic: Median survival 4–5 mos from dx

• Poor prognostic factors for well-differentiated thyroid CA: Age >45 y, male sex, poorly differentiated histology, tumor size, extrathyroid extension at dx; nodal involvement does not confer ↓ survival in younger pts

• Mayo Clinic Model: AGES (age, tumor grade, tumor extent, tumor size)

• BRAF Mt: May be a/w ↑ likelihood of extrathyroidal extension, node met, recurrence; point Mt in 45% of thyroid papillary carcinomas (Cancer 2012;118:1764)

Staging

• Papillary/follicular, under age 45: Stage I: M0; Stage II: M1

• Papillary/follicular, 45+: Stage I: T1 (<2 cm confined to thyroid); Stage II: T2 (>2 but <4 cm confined to thyroid); Stage III: T3 & early nodal involvement; Stage IV: All else including M1

• Medullary: Stage I: T1, node negative; Stage II: T2–T3, node negative; Stage III: T1–T3, early nodal involvement (N1a); Stage IV: All T4, N1b, M1 disease

• Anaplastic: Stage IV

Pathology

• Cell Derivation: Papillary, follicular, Hurthle cell, anaplastic arise from follicular cells that produce thyroid hormones; Tumors usu PAX8 & TTF1 positive

Treatment

• Surgery: Mainstay of tx for all subtypes, but rarely possible w/anaplastic; complications of total thyroidectomy include recurrent laryngeal nerve injury & hypocalcemia 2/2 hypoparathyroidism

• Differentiated thyroid CA: Levothyroxine suppression of TSH as it is a potential growth factor for microscopic CA deposits, RAI administration to ablate any nl thyroid remnant

• Met disease: RAI, external-beam radiotherapy, & chemotherapy (doxorubicin + platinum) for met disease; TKIs (eg, sorafenib) have activity in iodine-refractory disease (J Clin Oncol 2008;26:4714) & are the preferred tx by guidelines

• MTC: Total thyroidectomy w/b/l central compartment node dissection & at least unilateral neck dissection; radiation & chemotherapy not considered effective; targeted therapies vandetanib (J Clin Oncol2012;30:134) & cabozantinib(J Clin Oncol 2011;29:2660) approved for tx of met disease; treat local recurrences surgically; screen for germline RET gene Mt as total thyroidectomy is preventive in young, at-risk family members

• Anaplastic thyroid CA: May require urgent tracheostomy; if unresectable at dx, radiation-based Rx, often w/chemotherapy for sensitization; RAI not useful

• Tumor markers for surveillance: Thyroglobulin (highly sensitive & specific in the absence of all nl thyroid tissue) for differentiated CA; surveillance w/CEA & calcitonin for MTC