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Thyroid Malignant Neoplasia

Dana M. Vlachos, DO
Batoul Zalkout, DO
Shabia Mohammed, DO

BASICS

DESCRIPTION

  • Uncontrolled proliferation of cells in the thyroid gland

  • Types:

    • Papillary thyroid carcinoma (PTC)

      • Most common (75–80%)

      • Peak in 3rd/4th decade

      • Radiation exposure associated

      • Lymphatic spread; 15–30% palpable nodes at diagnosis

      • Many subtypes: conventional, follicular variant, oxyphilic, cribriform-morular, tall cell (aggressive)

    • Follicular carcinoma

      • 2nd most common (10–20%)

      • Peak in 5th decade

      • Hematogenous spread

      • Invasive/minimally invasive forms

    • Hürthle cell carcinoma

      • Variant of follicular, poorer prognosis

      • Oncocytic/oxyphilic carcinoma

      • 2–3% of thyroid cancers

      • Usually >60 years old

    • Medullary thyroid carcinoma (MTC)

      • Neuroendocrine tumor from parafollicular C cells

      • 3–4% of thyroid cancers

      • 25–35% associated with MEN syndromes

      • Calcitonin = marker; RET proto-oncogene for screening

      • MEN2B: childhood, MEN2A: young adult, FMTC: middle age

    • Anaplastic carcinoma

      • 1–3%; most aggressive, median survival 2–6 months

      • Elderly

    • Poorly differentiated carcinoma

      • Intermediate between differentiated and anaplastic; more aggressive

    • Other: lymphoma, sarcoma, metastatic (renal, breast, lung)

Geriatric Considerations

  • Risk of malignancy increases, prognosis worse >60 years

Pediatric Considerations

  • Nodules more often malignant in children (22–25% vs 5–10% adults)

  • <2% occur in children/adolescents

  • Factors for nodal metastases: tumor >4 cm, extrathyroid extension, multifocality

EPIDEMIOLOGY

  • Incidence: 14.5/100,000/year (USA)

  • Deaths: 0.5/100,000/year

  • 2018: 53,990 new cases, 2,060 deaths in USA

  • Age: usually >40

  • Sex: female > male (3:1)

  • Lifetime risk: 1.2%

ETIOLOGY AND PATHOPHYSIOLOGY

  • Most cases spontaneous

  • Radiation exposure significant factor

  • Genetic mutations: MAPK pathway (e.g., BRAF), PI3K-AKT pathway (PTEN)

RISK FACTORS

  • Family history

  • Radiation exposure (esp. PTC)

  • Iodine deficiency

  • MEN2: medullary carcinoma, RET proto-oncogene

  • Prior subtotal thyroidectomy for malignancy (anaplastic risk)

GENERAL PREVENTION

  • Physical exam in high-risk groups

  • Calcitonin screening in high-risk MEN

  • RET screening for MTC risk

COMMONLY ASSOCIATED CONDITIONS

  • Papillary: Hashimoto thyroiditis

  • Medullary: pheochromocytoma, hyperparathyroidism, ganglioneuroma (GI), mucosal neuromas

DIAGNOSIS

HISTORY

  • Change in voice (dysphonia)

  • Dysphagia, stridor (aggressive)

  • Growing neck mass

  • Family history

  • Radiation exposure (environmental or prior therapy)

PHYSICAL EXAM

  • Thyroid nodule/mass

  • Fixation to surrounding tissue suggests malignancy

  • Cervical lymphadenopathy

DIFFERENTIAL DIAGNOSIS

  • Multinodular goiter

  • Thyroid adenoma

  • Thyroglossal duct/dermoid cyst

  • Thyroiditis

  • Thyroid cyst

  • Ectopic thyroid

DIAGNOSTIC TESTS & INTERPRETATION

  • Ultrasound (US): Hypoechoic, microcalcifications, irregular margins suggest malignancy

  • TSH: Usually normal in malignancy; always check in nodule workup

  • CT/MRI neck: For large/substernal masses, invasion, recurrent disease, MTC with neck involvement or calcitonin >400

  • Calcitonin levels: For FNA results/family history suggestive of MTC (IV pentagastrin for sensitivity)

  • Thyroid scan: 12–15% of cold nodules malignant; higher risk <40 years/microcalcifications

  • 18F-FDG PET: If cytology indeterminate/recurrent disease, elevated TG and negative 131I scan

  • Thyroglobulin (TG): Not for initial eval; use for postoperative surveillance

  • Fine-needle aspiration biopsy (FNAB): Essential for diagnosis, guides surgery

  • Bethesda System for Cytology:

    • Nondiagnostic

    • Benign (0–3% risk)

    • Atypia of undetermined significance (10–30%)

    • Follicular neoplasm/suspicious for follicular (25–40%)

    • Suspicious for malignancy (50–75%)

    • Malignant (97–99%)

TREATMENT

GENERAL MEASURES

  • Surgical/medical management is standard; good prognosis

  • Palliative care for advanced malignancy

Papillary & Follicular

  • 131I ablation post-surgery (remnant ablation, improves specificity)

MEDICATION

  • Thyroid hormone replacement after total thyroidectomy

  • TSH suppression therapy:

    • High risk: TSH <0.1

    • Intermediate: 0.1–0.5

    • Low risk: 0.5–2.0

  • Drugs: Levothyroxine (T4), Liothyronine (T3)

ADDITIONAL THERAPIES

  • External beam radiation/chemotherapy for RAI-insensitive, inoperable, or palliative cases

  • 131I for high-risk papillary/follicular (remnant ablation)

SURGERY/OTHER PROCEDURES

  • Papillary: Total thyroidectomy + neck dissection if large/suspicious nodes (>4 cm); lobectomy with isthmectomy if <1 cm, low-risk (controversial)

  • Follicular/Hürthle: similar to papillary

  • Medullary: Total thyroidectomy + central node dissection; modified neck dissection for lateral node suspicion

  • Anaplastic: Palliative care, surgery controversial; tracheostomy for airway; clinical trials/chemo/radiation

ONGOING CARE

FOLLOW-UP

  • 10–30% recurrence/metastasis (80% neck, 20% distant)

  • Monitor: TSH, TG, anti-TG at 6m, 12m, then yearly

  • US surveillance for recurrence (intermediate/high-risk)

  • TSH-stimulated radioiodine scan in high-risk

  • Medullary: Calcitonin yearly (with pentagastrin)

  • Thyroid scan/TG: done after withdrawal of levothyroxine/liothyronine (6w/2–3w)

  • Low-iodine diet for radioactive iodine therapy

PATIENT EDUCATION

PROGNOSIS

  • 5-year survival: 98.1%

  • Adverse factors: Age >45, tumor >4 cm, extrathyroid extension, distant mets

  • Low risk: No extension, complete resection, no mets, no vascular invasion/aggressive histology

  • Intermediate: Microscopic extension, cervical node mets outside thyroid bed

  • High risk: Macroscopic extension, incomplete resection, distant mets

  • 10-year OS: Papillary 93%; 30y cancer death 6%

  • Follicular: 10y OS 85%; microinvasive ≈ papillary, grossly invasive worse; 30y death 15%

  • Hürthle: 5y survival 93%; grossly invasive <25%

  • Medullary: Negative nodes: 90% 5y, 85% 10y; positive nodes: 65% 5y, 40% 10y; MEN2B worse; overall 10y 75%

  • Anaplastic: Survival unexpected; review original pathology in long-term survivors

COMPLICATIONS

  • Hoarseness (recurrent laryngeal nerve invasion/injury)

  • Hypocalcemia/hypoparathyroidism (parathyroid devascularization, usually transient)

REFERENCES

  1. Francis GL, Waguespack SG, Bauer AJ, et al. Management guidelines for children with thyroid nodules and differentiated thyroid cancer. 2015;25(7):716-759.

  2. Haugen BR, Alexander EK, Bible KC, et al. 2015 ATA management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer. Thyroid. 2016;26(1):1-133.

  3. de Koster EJ, de Geus-Oei LF, Dekkers OM, et al. Diagnostic utility of molecular and imaging biomarkers in cytological indeterminate thyroid nodules. Endocr Rev. 2018;39(2):154-191.

  4. Goyal A, Gupta R, Mehmood S, et al. Palliative and end of life care issues of carcinoma thyroid patient. Indian J Palliat Care. 2012;18(2):134-137.

Codes:

  • ICD10: C73 Malignant neoplasm of thyroid gland

Clinical Pearls

  • Standard workup: physical exam, TSH, neck US, FNA

  • TG is a better marker for recurrence post-diagnosis

  • FNA results guide initial surgical approach (benign, malignant, indeterminate, nondiagnostic)

End of note