Thyroid Malignant Neoplasia

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Thyroid malignant neoplasia is an uncontrolled proliferation of cells within the thyroid gland. There are several different types:

  • Papillary thyroid carcinoma (PTC)
    • Differentiated tumor with papillary cells with finger-like projections
    • Most common variety, 75–80% of thyroid cancers
    • Peak incidence in the 3rd or 4th decade of life
    • Approximately 3 times more common in women
    • Associated with radiation exposure
    • Metastasizes by lymphatic route (15–30% have palpable lymphadenopathy at time of diagnosis)
    • Multicentric in ≥20%, especially in children
    • Increasing incidence may be due to increased diagnosis of smaller size tumors.
    • Many subtypes: conventional, follicular variant, oxyphilic, cribriform-morular, and more aggressive forms such as tall cell or diffuse sclerosing
  • Follicular carcinoma
    • Differentiated tumor with spherical follicular cells
    • Second most common variety, 10–20% of thyroid tumors
    • Peak incidence in 5th decade of life
    • Metastasizes by the hematogenous route
    • Can be divided into invasive and minimally invasive forms based on morphology
  • Hürthle cell carcinoma (variant of follicular with poorer prognosis)
    • Often considered subtype of FTC with overall poorer prognosis
    • Also known as oncocytic or oxyphilic carcinoma
    • 2–3% of thyroid malignancies
    • Usually in patients >60 years old
    • Often radioresistant
  • Medullary thyroid carcinoma (MTC)
    • Neuroendocrine tumor arising from parafollicular C cells
    • 3–4% of all thyroid carcinoma
    • 75–80% sporadic and occurs as isolated disease
    • 25–35% are associated with multiple endocrine neoplasia (MEN) syndromes, which can be familial or sporadic.
    • MTC associated with MEN2B occur in childhood, those with MEN2A occur in young adults, and those with familial non-MEN medullary thyroid cancer (FMTC) occur in middle age.
    • Calcitonin is a serologic marker.
    • RET proto-oncogene mutation is used for screening; family members who carry the RET gene should consider early prophylactic thyroidectomy.
  • Anaplastic carcinoma
    • Undifferentiated tumor arising de novo or from dedifferentiation of preexisting differentiated thyroid carcinoma
    • 1–3% of thyroid tumors
    • Most aggressive form of thyroid neoplasia due to rapid growth, locoregional invasion, and metastases
    • Almost uniformly fatal (median survival 2 to 6 months)
    • More common in elderly patients
  • Poorly differentiated thyroid carcinoma (PDTC)
    • Intermediate between differentiated (follicular and papillary carcinomas) and undifferentiated (anaplastic) carcinomas
    • Aggressive tumor similar to anaplastic carcinoma, but may have better treatment response
  • Other: lymphoma, sarcoma, or metastatic (renal, breast, or lung)
  • System(s) affected: endocrine/metabolic
  • Synonym(s): well-differentiated, poorly differentiated, and undifferentiated thyroid carcinoma

Geriatric Considerations
Risk of malignancy (ROM) increases, and prognosis is worse >60 years old.

Pediatric Considerations
  • Thyroid nodules are more frequently malignant (22–25% in children vs. 5–10% in adults).
  • <2% of thyroid malignancies occur in children and adolescents.
  • Increased tumor size (>4 cm), extrathyroidal extension, and multifocal disease are independent factors associated with nodal metastases in pediatric differentiated thyroid cancer and require further evaluation with FNA for suspicious nodes to consider neck dissection (1)[C].


  • Incidence: 14.5/100,000 per year in the United States
  • Deaths: 0.5/100,000 per year in the United States
  • In 2018, estimated 53,990 new cases and 2,060 deaths from thyroid cancer in the United States
  • Predominant age: usually >40 years old
  • Predominant sex: female > male (3:1) prevalence
  • Lifetime risk of developing thyroid cancer is 1.2%.
  • In 2015, 765,547 patients living with thyroid cancer in the United States

Etiology and Pathophysiology

  • No established etiologic factors of pathogenesis; most cases arise spontaneously.
  • Radiation exposure likely has a role in the development of thyroid malignancies.
  • Gene mutations that activate the MAPK pathway (e.g., BRAF) and PI3K-AKT pathway (e.g., PTEN) have been implicated.

  • Familial polyposis of the colon, Gardner syndrome with the APC gene (5q21), and Cowden syndrome
  • MTC: autosomal dominant with MEN syndrome
  • Medullary: autosomal dominant with MEN syndrome
  • BRAF mutation (rare in children) in PTC
  • RAS mutations in FTC
  • RET oncogene (more common in children) in MTC and PTC
  • TP53 mutation in ATC

Risk Factors

  • Family history (first-degree relative)
  • Radiation exposure: papillary carcinoma
  • Iodine deficiency: follicular carcinoma
  • MEN2: medullary carcinoma; autosomal dominant inheritance; RET proto-oncogene
  • Previous history of subtotal thyroidectomy for malignancy: anaplastic carcinoma
  • Female gender

General Prevention

  • Physical exam in high-risk group
  • Calcitonin stimulation screening in high-risk MEN patients
  • Screening for RET proto-oncogene in groups at risk for MTC

Commonly Associated Conditions

  • Papillary carcinoma: Hashimoto thyroiditis
  • Medullary carcinoma: pheochromocytoma, hyperparathyroidism, ganglioneuroma of the GI tract, neuromata of mucosal membranes

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