• Clinical science

Thyroid cancer (Thyroid carcinoma)

Abstract


The majority of thyroid cancers are well-differentiated carcinomas. The principal risk factors are exposure to ionizing radiation and genetic predisposition; thyroid cancers also disproportionately affect women. A distinction is made between well-differentiated thyroid carcinomas (papillary or follicular carcinoma) and poorly differentiated carcinomas (medullary or anaplastic carcinoma); the two groups vary considerably with regard to treatment options, metastatic pathways, and prognosis. Papillary thyroid carcinomas are the most common type of thyroid cancer. Early detection is crucial for improving the prognosis but challenging because symptoms often appear late in the course of the disease. Imaging plays a central role in detection: nodules that appear hypoechoic on ultrasound and cold on scintigraphy should raise suspicion of malignancy. Additional testing is needed to determine the type of thyroid cancer, including measuring hormone levels, tumor markers, and/or biopsy via fine-needle aspiration. Thyroid cancer is an absolute indication for total thyroidectomy, followed by thyroid hormone therapy to replace physiological hormone production and to limit the growth stimulus for any remaining metastases. Further therapeutic measures depend on the type of thyroid cancer involved and include radioiodine therapy and possibly chemotherapy.

Epidemiology

  • Sex
    • Differentiated carcinoma (papillary and follicular): > (3:1)
    • Poorly-differentiated carcinoma (medullary and anaplastic):
  • Incidence: ∼ 13.5 new cases per 100,000, per year

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[1][3][4]

Classification

Histological classification of thyroid tumors (according to WHO 2004)

  1. Thyroid cancer
  2. Thyroid adenoma and related carcinomas
  3. Other thyroid carcinomas (e.g., lymphoma or sarcoma)
  4. Parathyroid carcinoma

Overview of the most common types of thyroid cancer

Tissue of origin Carcinoma Differentiation Characteristics Distribution Peak incidence
Thyrocytes Papillary thyroid carcinoma

Well-differentiated

  • Lymphatic metastasis (often detected before primary tumor)
  • Most common type of thyroid cancer
  • May be multifocal
  • ∼ 80% of cases
  • 30–50 years of age

Follicular thyroid carcinoma

  • Hematogenous metastasis (lungs, bone)
  • Rarely multifocal
  • Vascular and capsular invasion
  • ∼ 10% of cases
  • 40–60 years of age

Anaplastic thyroid carcinoma

Poorly-differentiated

  • Rapid local growth
  • Lymphatic and hematogenous metastasis
  • ∼ 1–2% of cases
  • After 60 years of age
Parafollicular cells (C cells)

Medullary carcinoma

  • < 10%of cases
  • 50–60 years of age

References:[1][4][5][6][7]

Subtypes and variants

References:[8]

Clinical features

Only 25% of thyroid carcinomas detected by ultrasound exhibit clinical signs or symptoms!

References:[1][9]

Diagnostics

Laboratory tests

Imaging

Ultrasound

  • Hypoechoic thyroid lesions with irregular margins > 1 cm are potentially malignant although normal echogenicity does not rule out carcinoma!
  • Malignancies often show microcalcifications; (typical for papillary thyroid carcinomas)

Thyroid scintigraphy

  • Indications:
  • Findings: decreased tracer uptake suggests a malignant non-functioning (cold) nodule.

Nodules that appear hypoechoic on ultrasound and cold in scintigraphy are highly suspicious for malignancy!

Fine needle aspiration (FNA)

  • Indicated if malignancy is suspected based on ultrasound or scintigraphy
    • If biopsy results are unclear or in any way suspicious, surgery is usually recommended.

Staging

References:[1][10][11][12][13][14][15][16][17]

Pathology

Papillary carcinoma

  1. Psammoma bodies

  1. “Orphan Annie” eyes nuclei
    1. Morphology: empty-appearing large oval nuclei with central clearing
    2. Occurrence:
      1. Papillary thyroid carcinomas
      2. Autoimmune thyroiditis (e.g., Hashimoto disease, Grave disease)
      3. Cribriform adenocarcinoma of tongue
      4. Polymorphous low grade adenocarcinoma
  2. Nuclear grooves
    1. Morphology: longitudinal invaginations of nuclear bilayer
    2. Occurrence: papillary thyroid carcinomas

Follicular carcinoma

  1. Uniform follicles
  2. Vascular and/or capsular invasion

Medullary carcinoma

  1. Ovoid cells of C cell origin and therefore without follicle development
  2. Amyloid in the stroma (stains with Congo red)

Anaplastic Thyroid Carcinoma

  1. Undifferentiated giant cell (i.e., osteoclast-like cell)
  2. Areas of necrosis and hemorrhage

References:[18][18][4][19][20][21][22]

Differential diagnoses

  • See learning card on thyroid nodules
  • Thyroid cyst
    • Ultrasound findings
      • Anechoic round mass
      • In many cases, dorsal acoustic enhancement
    • Relatively frequent and typically harmless

References:[14]

The differential diagnoses listed here are not exhaustive.

Treatment

Well-differentiated cancers

  • Total/radical thyroidectomy with neck dissection (see thyroid surgery)
    • Dissection of the central compartment (central cervical lymph nodes)
    • In lymph node metastasis, the lateral compartment is also dissected (lateral cervical lymph nodes).
    • Exception: papillary microcarcinoma; ; in which case, hemithyroidectomy is sufficient. This type of tumor is typically diagnosed histopathologically as an incidental finding during interventions for other thyroid conditions and usually requires no further therapeutic measures.
  • Radioiodine therapy : often conducted 4–6 weeks after surgery to destroy remaining thyroid tissue or metastases
    • Substance employed: typically iodine-131
  • Thyroid hormone therapy with L-thyroxine after thyroidectomy:
    • Hormone replacement
    • TSH suppression
      • Reduces the risk of stimulating remaining malignant tissue
      • Administer the highest possible dose (according to the patient's tolerance)
    • Only administer after radioiodine therapy!

Poorly differentiated cancers

Complications

References:[23][13][1][6]

Follow-up

  • Physical examination
  • Biochemical tests
  • Neck ultrasound
  • Further imaging, if a relapse is suspected

References:[1][23][13][10]

Prognosis

Thyroid cancer

5-year survival rate

Papillary

> 90%

Follicular

50–70%

Medullary

50%

Anaplastic

5–14%

References:[4][7]