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Basic Information ⬇

AUTHOR: Bharti Rathore, MD

Definition

Thyroid carcinoma is a primary neoplasm of the thyroid and consists of four major subtypes: Papillary, follicular, anaplastic, and medullary. A classification of thyroid neoplasms is described in Table E1.

TABLE E1 Classification of Thyroid Neoplasms

  1. Primary Epithelial Tumors
  2. Tumors of follicular cells
    1. Benign: Follicular adenoma
    2. Borderline follicular tumors
    3. Follicular tumor of uncertain malignancy potential
    4. Well-differentiated tumor of uncertain malignancy potential
    5. Noninvasive follicular neoplasm with papillary-like nuclear features (NIFTP)
    6. Malignant: Carcinoma
    7. Differentiated: Papillary, follicular, Hürthle cell, poorly differentiated
    8. Undifferentiated (anaplastic)
  3. Tumors of C cells
    1. Medullary carcinoma
  4. Tumors of follicular and C cells
  5. Mixed medullary-follicular carcinomas
  6. Primary Nonepithelial Tumors
    1. Malignant lymphomas
    2. Sarcomas
    3. Others
  7. Secondary Tumors

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Elsevier.

Synonyms

Papillary carcinoma of thyroid

Follicular carcinoma of thyroid

Anaplastic carcinoma of thyroid

Medullary carcinoma of thyroid

ICD-10CM CODES
C73Malignant neoplasm of thyroid gland
D09.3Carcinoma in situ of thyroid and other endocrine glands
D34Benign neoplasm of thyroid gland
D44.0Neoplasm of uncertain behavior of thyroid gland
Epidemiology & Demographics

  • Thyroid cancer is the most common endocrine cancer, with an estimated 43,800 new cases and 2230 deaths occurring in 2022 in the U.S.
  • Incidence is 13.9 per 100,000 people in the U.S. and increasing over last 4 decades.
  • Female:male ratio is 3:1.
  • Median age at diagnosis: 45 to 50 yr.
  • Occult thyroid cancer is identified in 20% of autopsy specimens.
Physical Findings & Clinical Presentation

  • Thyroid cancer is often identified incidentally.
  • Physical exam may reveal:
    1. Presence of thyroid nodule
    2. Hoarseness and cervical lymphadenopathy
    3. Painless swelling in the region of the thyroid
Etiology

  • Risk factors: Prior neck irradiation.
  • Multiple endocrine neoplasia II (medullary carcinoma).
  • Inherited syndromes associated with thyroid cancer are described in Table 2.
  • GLP-1 receptor agonists for the treatment of type 2 DM (e.g., exenatide, albiglutide) can increase the risk of medullary thyroid carcinoma (MTC).
  • Papillary thyroid carcinoma is the commonest type of thyroid carcinoma of follicular origin and encompasses several tumor types that have mutually exclusive mutations that activate thyroid cell abnormal proliferation. BRAF V600E mutation accounts for 60% of these mutations; other mutations include RAS or RET/PTC rearrangements.1,2
  • In follicular thyroid carcinoma, oncogenic drivers are primarily RAS alterations (40% to 50% of cases) and PAX8/PPARγ rearrangements (30% to 40% of cases). Molecular alterations of the PI3K/Akt pathway and PTEN silencing by inactivating mutations or epigenetic changes also occur in some cases.
  • Poorly differentiated thyroid carcinomas are aggressive cancers with a high mutation rate. RAS and BRAF mutations are found in 20% to 50% and up to 35% of cases, respectively. Genetic alterations that characterize PDTC and are associated with tumor aggressiveness are TERT promoter (20% to 50%) mutations and TP53 mutations (10% to 35%) that cooccur with RAS and BRAF mutations.1,2
  • In anaplastic thyroid cancer, as many as 25% to 50% of cases harbor BRAFV600 mutations, which can be targeted with available BRAF/MEK inhibitor combination therapy. Other frequent mutations include TERT (75%), TP53 (63%), and RAS (24%). Other actionable molecular drivers with available targeted therapies include RET rearrangements, ALK rearrangements, NTRK fusions, and TSC2 mutations, suggesting the need for broad molecular profiling.
  • Pathways in the development of thyroid cancer are depicted in Fig. E1.

TABLE 2 Inherited Syndromes Associated With Thyroid Cancer

Multiple endocrine neoplasia (MEN) 2A and 2B
Isolated familial medullary thyroid cancer
Gardner syndrome
Familial adenomatous polyposis
Carney complex
Cowden syndrome
Familial nonmedullary thyroid cancer

From Cameron JL, Cameron AM: Current surgical therapy, ed 10, Philadelphia, 2011, Saunders.

Figure E1 Thyroid cancer pathways.

Diagram shows the key molecular signaling pathways involved in thyroid cancer. The box on the left shows the mitogen-activated protein kinase pathway, which is activated by mutation in most thyroid cancers. These events are believed to initiate thyroid cancer development and lead to altered gene expression, which promotes cell proliferation, cell growth, angiogenesis, and loss of differentiation. The box on the right shows pathways altered in advanced thyroid cancers, which are believed to promote tumor progression. This includes the PI3K-mTOR pathway, the p53 tumor suppressor, and alterations in the promoter for TERT. Blue boxes represent factors for which targeted treatments are available that have been approved by the U.S. Food and Drug Administration. mTOR, Mammalian target of rapamycin; PI3K, phosphatidylinositol-3-kinase; TERT, telomerase reverse transcriptase.

From Cabanillas ME et al: Thyroid cancer, Lancet 388[10061]:2783-2795, 2016.

Diagnosis ⬆ ⬇

Differential Diagnosis

  • Multinodular goiter
  • Lymphocytic thyroiditis
  • Ectopic thyroid
Workup

The workup of thyroid carcinoma includes laboratory evaluation and diagnostic imaging. Key features of thyroid malignancies are summarized in Table 3. Diagnosis is confirmed with fine-needle aspiration or surgical biopsy. At diagnosis, the vast majority of thyroid cancers are well differentiated, with excellent prognosis. The characteristics of thyroid carcinoma vary with the type:

  • Papillary carcinoma (80%):
    1. Most frequently occurs in women during second or third decades
    2. Histologically, psammoma bodies (calcific bodies present in papillary projections) are pathognomonic; found in 35% to 45% of papillary thyroid carcinomas
    3. Majority are not papillary lesions but mixed papillary follicular carcinomas
    4. Spread is by lymphatics and by local invasion
  • Follicular carcinoma (10%):
    1. More aggressive than papillary carcinoma
    2. Incidence increases with age
    3. Tends to metastasize hematogenously to bone, producing pathologic fractures
    4. Tends to concentrate iodine (useful for radiation therapy)
  • Poorly differentiated thyroid carcinoma (5% to 6%):
    1. Aggressive cancers with pathology characterized by high mitotic activity and tumor necrosis.
    2. Patients often develop vascular invasion, lymph node metastasis, extrathyroidal extension, and distant metastases.
    3. Associated with a mean survival of 3.2 yr.
    4. Radioiodine therapy is of limited benefit and most patients require systemic therapies.
  • Anaplastic carcinoma (1%):
    1. Very aggressive neoplasm
    2. Two major histologic types: Small cell (less aggressive, 5-yr survival approximately 20%) and giant cell (death usually within 6 mo of diagnosis)
  • MTC (4%):
    1. Unifocal lesion: Found sporadically in elderly patients
    2. Bilateral lesions: Associated with pheochromocytoma and hyperparathyroidism; this combination is known as MEN-II and is inherited as an autosomal-dominant disorder

TABLE 3 Thyroid Malignancies-Key Features

DescriptionPattern of Spread
Papillary carcinoma (70%-80%)Low-grade tumors with a good prognosis (histologically multicentric) ▸ Tumors concentrate radio-iodineEarly lymph node spread (metastatic lymph nodes may be normal in size, cystic, calcified, hemorrhagic, or contain colloid) ▸ Distant metastases are rare (and usually to the lungs)
Follicular carcinoma (10%-20%)Slow growing ▸ Tumors concentrate radio-iodineIt rarely metastasizes to the regional lymph nodes ▸ The tendency is to spread via the bloodstream and disseminate to the lungs, bones, or liver
Anaplastic carcinoma (1%-2%)Undifferentiated malignant tumors that do not concentrate radio-iodine ▸ There is a poor prognosis ▸ They tend to occur in older patients ▸ Punctate calcification and necrosis frequently are presentLymphatic metastases occur in the majority of patients
Medullary carcinoma (5%-10%)This originates from the parafollicular C cells ▸ It does not concentrate radio-iodine ▸ It may be sporadic or familial (and associated with the MEN type II syndrome or other endocrine neoplasms) ▸ It is usually a unilateral, solitary lesion ▸ Calcification is seen in 10% ▸ 123I-MIBG and somatostatin analogs (e.g., octreotide) can be used for evaluation ▸ Circulating calcitonin levels are usually elevatedIt may invade locally, spread to the regional nodes, or demonstrate hematogenous spread to the lungs, bones, or liver
Lymphoma (10%)It is usually a non-Hodgkin lymphoma ▸ It occurs in one third of patients with Hashimoto thyroiditis (a MALT-type lymphoma) ▸ It presents as a rapidly enlarging, solitary nodule (80%) or as multiple nodules (imaging cannot distinguish between a lymphoma and thyroiditis) ▸ Necrosis and calcification are uncommonIt can involve the nodes with spread to the GI tract
Metastases (1%)The most common primary is renal cell carcinoma

From Grant LA: Grainger & Allison’s diagnostic radiology essentials, ed 2, Philadelphia, 2019, Elsevier.

Laboratory Tests

  • Thyroid function studies are generally normal. Thyroid-stimulating hormone (TSH), T4, and serum thyroglobulin levels should be obtained before thyroidectomy in patients with confirmed thyroid carcinoma. Serum thyroglobulin levels can be useful postoperatively to monitor recurrence of thyroid carcinoma (Fig. E2).
  • Increased plasma calcitonin assay in patients with medullary carcinoma (tumors produce thyrocalcitonin). RET proto-oncogene sequencing and measurement of plasma free metanephrine and normetanephrine levels to rule out coexistent pheochromocytoma are recommended in all patients with medullary thyroid cancer.
  • Fine-needle aspiration biopsy is the best method to assess a thyroid nodule (see “Thyroid Nodule” in Section I). Table 4 describes the Bethesda system for thyroid cytopathology.

TABLE 4 The Bethesda System for Thyroid Cytopathology

CategoryRisk of Malignancy (%)Recommended Management
Nondiagnostic or unsatisfactory1-4Repeat FNA with ultrasound guidance
Benign0-3Clinical follow-up
Atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS)5-15Repeat FNA∗
Follicular neoplasm or suspicious for follicular neoplasm15-30Lobectomy
Suspicious for malignancy60-75Lobectomy with or without frozen section or total thyroidectomy
Malignant97-99Total thyroidectomy

FNA, Fine-needle aspiration.

∗Lobectomy also can be considered depending on clinical or sonographic characteristics.

From Niederhuber JE: Abeloff’s clinical oncology, ed 6, Philadelphia, 2020, Elsevier.

Figure E2 This Patient was Being Monitored for a Papillary Thyroid Carcinoma Treated by Total Thyroidectomy and Postoperative Radioiodine

The serum thyroglobulin level was 45 ng/ml during levothyroxine suppressive treatment. A, A total-body scan was performed 3 days after administration of 100 mCi (3.7 GBq). There is no visible uptake in the neck or thorax. Notice the accumulation of radioiodine in the stomach, colon, and bladder. B, Positron emission tomography scan using [18F]-fluorodeoxyglucose (18FDG) with maximal intensity projection demonstrates significant uptake in the upper mediastinum. C, In fusion images of 18FDG-PET and CT scans, axial and coronal slices localized the FDG uptake in the right paratracheal mediastinum, corresponding to a lymph node metastasis that subsequently was excised. Serum thyroglobulin became undetectable during thyroid hormone treatment.

From Melmed S et al [eds]: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Saunders.

Imaging Studies (Fig. E3

  • Thyroid ultrasound can detect solitary solid nodules that have a high risk of malignancy. However, a negative ultrasound does not exclude diagnosis of thyroid carcinoma.
  • Thyroid scanning with iodine-123 or technetium-99m can identify hypofunctioning (cold) nodules, which are more likely to be malignant. However, warm nodules can also be malignant.

Figure E3 Papillary adenocarcinoma.

A 74-yr-old woman presented with a thyroid nodule. A, An 123I thyroid scan (anterior view) demonstrates a “cold” nodule (arrows) in the upper portion of the left thyroid lobe. The “hot” spot below the thyroid is a suprasternal marker. B, An axial computed tomography scan demonstrates an irregular density in the left thyroid lobe at the level of the lesion seen on the radionuclide scan. The lesion contains a single area of calcification (arrow) and is not demarcated sharply from normal thyroid tissue. At operation, there proved to be extracapsular extension.

From Skarin AT: Atlas of diagnostic oncology, ed 3, St Louis, 2003, Mosby.

Staging (Table E5

  • Stage I: Thyroid cancer of any size without distal spread in patient <55 yr. In patients >55 yr, tumor size ≤4 cm without local invasion or positive cervical lymph nodes
  • Stage II: Distal spread in patient <55 yr. In patients >55 yr, tumors >2 cm but <4 cm, spread to nearby lymph nodes, not spread to distant sites
  • Stage III: Tumors >4 cm in patient >55 yr of age, not spread to distant sites
  • Stage IV: Distal spread in patient >55 yr of age

TABLE E5 The Tumor-Node-Metastasis (TNM) Scoring System

Definition of TNM
Category2010 Version (AJCC 7th Edition)2017 Version (AJCC 8th Edition)
Primary Tumor (T)
T0No evidence of primary tumorNo evidence of primary tumor
T1Tumor ≤2 cm limited to the thyroidTumor ≤2 cm limited to the thyroid
T1a: ≤1 cmT1a: ≤1 cm
T1b: >1-2 cmT1b: >1-2 cm
T2Tumor >2 to ≤4 cm limited to the thyroidTumor >2 to ≤4 cm limited to the thyroid
T3Tumor >4 cm limited to the thyroid or any tumor with minimal extrathyroid extension (e.g., extension to sternothyroid muscle or perithyroid soft tissues)Tumor >4 cm limited to the thyroid or gross extrathyroidal extension invading only strap muscles (sternohyoid, sternothyroid, thyroidhyoid, omohyoid) from a tumor of any size
T4No evidence of primary tumorNo evidence of primary tumor
T4aGross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size or intrathyroidal anaplastic thyroid cancer of any sizeGross extrathyroidal extension invading subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve from a tumor of any size
T4bGross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any size or anaplastic thyroid cancer of any size with extrathyroidal extensionGross extrathyroidal extension invading prevertebral fascia or encasing the carotid artery or mediastinal vessels from a tumor of any size
Regional Lymph Node (N)
N0No regional lymph node metastasisNo evidence of locoregional lymph node metastasis
N0a: One or more cytologically or histologically confirmed benign lymph nodes
N0b: No radiologic or clinical evidence of locoregional lymph node metastasis
N1Regional lymph node metastasisRegional lymph node metastasis
N1aMetastases in pretracheal and paratracheal lymph nodes, including prelaryngeal and delphian lymph nodes, unilateral or bilateralMetastasis in pretracheal, paratracheal, prelaryngeal/delphian, or upper mediastinal lymph nodes, unilateral or bilateral
N1bMetastases in lateral neck lymph nodes or upper mediastinal lymph nodes, unilateral or bilateralMetastases in lateral neck lymph nodes, unilateral or bilateral disease
Distant Metastases (M)
Category2010 Version2017 Version
M0No distant metastasisNo distant metastasis
M1Distant metastasisDistant metastasis
TNM Staging for Papillary, Follicular, and Poorly Differentiated Thyroid Cancer
Age CutoffAge <45 YrAge <55 Yr
Stage IAny T, any N, M0Any T, any N, M0
Stage IIAny T, any N, M1
Stage IIINone
Stage IVNone
Age CutoffAge ≥45 YrAge ≥55 Yr
Stage IT1, N0, M0T1-T2, N0, M0
Stage IIT2, N0, M0T1-T2, N1a-N1b, M0 or T3, any N, M0
Stage IIIT3, N0, M0 or any T1-3, N1a, M0T4a, any N, M0
Stage IV
Stage IVAT1-3, N1b, M0 or T4a, any N, M0T4b, any N, M0
Stage IVBT4b, any N, M0Any T, any N, M1
Stage IVCAny T, any N, M1-
TNM Staging for Medullary Thyroid Cancer
Category2010 Version2017 Version
Stage IT1, N0, M0T1, N0, M0
Stage IIT2-T3, N0, M0T2-T3, N0, M0
Stage IIIT1-3, N1a, M0T1-3, N1a, M0
Stage IVAT1-3, N1b, M0 or T4b, any N, M0T1-3, N1b, M0 or T4b, any N, M0
Stage IVBT4b, any N, M0T4b, any N, M0
Stage IVCAny T, any N, M1Any T, any N, M1
TNM Staging for Anaplastic Thyroid Cancer
Stage IVAT4a, N0, M0T1-T3a, N0, M0
Stage IVBT4b, any N, M0T1-T3a, N1, M0 or T3b-T4, any N, M0
Stage IVCAny T, any N, M1Any T, any N, M1

AJCC, American Joint Committee on Cancer.

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Elsevier.

Treatment ⬆ ⬇

Acute General Rx

  • Papillary carcinoma:
    1. Total thyroidectomy is indicated if the patient has:
      1. Extrathyroid extension
      2. History of radiation exposure
      3. Poorly differentiated
      4. Cervical lymph node involvement
      5. Tumor >4 cm
      6. Known distant metastasis
    2. Lobectomy with isthmectomy may be considered in patients with intrathyroid papillary carcinoma <4 cm and no history of neck or head irradiation; surgery should be followed with suppressive therapy with thyroid hormone because these tumors are TSH responsive. The accepted practice is to suppress serum TSH concentrations to <0.1 microunit/ml in patients with persistent disease, suppression to 0.1 to 0.5 microunit/ml in patients who are disease free but are at high risk of recurrence, and a goal TSH level of 0.3 to 2.0 microunits/ml in patients who are disease free and have a low risk of recurrence.
    3. Radioiodine ablation reduces rates of death and recurrence (Table 6). Radioiodine is administered for stages III and IV disease.3
    4. In cases that have progressed after radioiodine therapy, oral targeted inhibitors (lenvatinib, sorafenib) have significant survival benefit.4-6
    5. Of note, larotrectinib and entrectinib are both FDA approved for patients with NTRK gene fusion-positive advanced solid tumors.
    6. If a patient is found to have a BRAF mutation, one can consider giving vemurafenib or dabrafenib, although these two drugs are not FDA approved for BRAF-mutated, metastatic papillary thyroid cancer.
  • Follicular carcinoma:
    1. Total thyroidectomy followed by TSH suppression, as previously noted.
    2. Radiotherapy with iodine-131 followed by thyroid suppression therapy with triiodothyronine is useful in patients with metastasis (see Table 6).
    3. In cases that have progressed after radioiodine therapy, oral targeted inhibitors (lenvatinib, sorafenib) have significant survival benefit.
  • Anaplastic carcinoma:
    1. At diagnosis, this neoplasm is rarely operable; palliative surgery is indicated for extremely large tumor compressing the trachea.
    2. Management is usually restricted to radiation therapy or chemotherapy (combination of doxorubicin, cisplatin, and other antineoplastic agents) (see Table 6); these measures rarely provide significant palliation.
    3. Patients with anaplastic thyroid cancer should have their tumors tested for BRAF V600E mutation and NTRK gene fusion. The FDA has approved dabrafenib 150 mg PO bid and trametinib 2 mg PO daily for patients who harbor the BRAF mutation.
    4. Larotrectinib or entrectinib can be offered to patients who have an NTRK gene mutation.
  • Medullary carcinoma:
    1. Thyroidectomy should be performed, followed by TSH suppression.
    2. Vandetanib and cabozantinib are oral tyrosine kinase inhibitors that are FDA-approved for treatment of symptomatic or progressive, unresectable, locally advanced or metastatic medullary thyroid cancer.
    3. Patients and their families should be screened for pheochromocytoma and hyperparathyroidism.

TABLE 6 Indications for Iodine-131 Treatment in Patients With Papillary, Follicular, or Hürthle Cell Thyroid Carcinoma After Initial Definitive Near-Total Thyroidectomy

No Indication
Adult patients at very low risk for cause-specific mortality or relapse: Complete surgical resection, favorable histology, and limited extent of disease (e.g., PTC patients with MACIS scores <6; patients with tumor size <1 cm, N0, and M0).
Definite Indications
Distant metastasis at diagnosis
Incomplete tumor resection
Complete tumor resection but high risk for mortality or recurrence (e.g., PTC patients with MACIS scores ≥6 and pTNM stage II/III FTC or HCC)
Probable Indications
Incomplete surgery (less than near-total thyroidectomy, no lymph node dissection)
PTC or FTC in a child younger than 16 yr
If PTC, tall cell or columnar cell variant and diffuse sclerosing variant
If FTC, widely invasive or poorly differentiated tumor
Bulky nodal metastases

FTC, Follicular thyroid carcinoma; HCC, Hürthle cell carcinoma; MACIS, scoring system based on metastasis, age, completeness of resection, invasion, and size; PTC, papillary thyroid carcinoma; pTNM, pathologic tumor-node-metastasis classification.

From Melmed S et al (eds): Williams textbook of endocrinology, ed 12, Philadelphia, 2011, Saunders.

Disposition

  • Overall 5-yr survival rate is 98.17, but prognosis varies with the type of thyroid carcinoma: 5-yr survival is over 80% for follicular carcinoma and is approximately 5% with anaplastic carcinoma (Table 7).
  • Factors used in prognostic classification systems are summarized in Table 8.
  • Risk factors for aggressive behavior of well-differentiated thyroid carcinomas are described in Box 1.
  • Box 2 summarizes risk stratification for thyroid cancer recurrence.

BOX 2 Risk Stratification for Thyroid Cancer Recurrence

High Risk
Gross extrathyroidal extension, incomplete tumor resection, distant metastases, or lymph node >3 cm		FTC, extensive vascular invasion (≈30%-55%)
pT4a gross ETE (≈30%-40%)
pN1 with extranodal extension, >3 LN involved (≈40%) PTC, >1 cm, TERT mutated ± BRAF mutated (≈40%) pN1, any LN >3 cm (≈30%)
PTC, extrathyroidal, BRAF mutated (≈10%-40%) PTC, vascular invasion (≈15%-30%)
Clinical N1 (≈20%)
pNl, >5 LN involved (≈20%)
Intrathyroidal PTC, <4 cm, BRAF mutated (≈10%) pT3 minor ETE (≈3%-8%)
pN1, all LN <0.2 cm (≈5%)
pN1 ≤5 LN involved (≈5%)
Intrathyroidal PTC, 2-4 cm (≈5%)
Multifocal PTMC (≈4%-6%)
pN1 without extranodal extension, ≤3 LN involved (2%) Minimally invasive FTC (≈2%-3%)
Intrathyroidal, <4 cm, BRAF wild type (≈1%-2%) Intrathyroidal unifocal PTMC, BRAF mutated, (≈1%-2%) Intrathyroidal, encapsulated, FV-PTC (≈1%-2%)
Unifocal PTMC (≈1%-2%)
Intermediate Risk
Aggressive histology, minor extrathyroidal extension, vascular invasion, or >5 involved lymph nodes (0.2-3 cm)
Low Risk
Intrathyroidal DTC ≤5 LN micrometastases (<0.2 cm)

From Flint PW et al: Cummings otolaryngology, head and neck surgery, ed 7, Philadelphia, 2021, Elsevier.

BOX 1 Risk Factors for Aggressive Behavior of Well-Differentiated Thyroid Carcinomas

  • Demographics
  • Age <20 yr
  • Men >55 yr
  • Women >55 yr
  • Male >female
  • History of radiation exposure/therapy
  • Family history of thyroid carcinoma
  • Physical Examination
  • Hard, fixed lesion
  • Rapid growth of mass
  • Pain
  • Lymphadenopathy
  • Vocal cord paralysis
  • Aerodigestive tract compromise
  • Dysphagia
  • Stridor
  • Histopathologic Factors (at Initial Presentation)
  • Size >4 cm
  • Extrathyroid spread
  • Vascular invasion
  • Lymph node metastasis
  • Distant metastasis
  • Histologic type
    • Tall cell variant of papillary carcinoma
    • Follicular carcinoma
    • Hürthle cell carcinoma

From Flint PW et al: Cummings otolaryngology, head and neck surgery, ed 7, Philadelphia, 2021, Elsevier.

TABLE 8 Factors Used in Prognostic Classification Systems

TNMAMESAGESMACIS
Patient Factors
Age××××
Gender××
Tumor Factors
Size××××
Histologic grade×
Histologic type××∗∗
Extrathyroid spread××××
Lymph node metastasis×
Distant metastasis××××
Incomplete resection×

AGES, Age at diagnosis, histologic tumor grade, extent of disease at presentation, and tumor size; AMES, patient age, metastases, extent of invasion, and tumor size; MACIS, metastasis, age at diagnosis, completeness of surgical resection, extrathyroid invasion, and tumor size; TNM, tumor/node/metastasis.

∗AGES/MACIS classifications for papillary carcinomas only.

From Flint PW et al: Cummings otolaryngology, head and neck surgery, ed 7, Philadelphia, 2021, Elsevier.

TABLE 7 Characteristics of Thyroid Cancers

Type of CancerPercentage of Thyroid CancersAge of Onset (yr)TreatmentPrognosis
Papillary8840-80Thyroidectomy, followed by radioactive iodine ablation and TSH suppressionGood
Follicular1045-80Thyroidectomy, followed by radioactive iodine ablation and TSH suppressionFair to good
Medullary3-420-50Thyroidectomy and central compartment lymph node dissection and TSH suppressionFair
Anaplastic150-80Isthmusectomy followed by palliative x-ray treatmentPoor
Lymphoma<125-70X-ray therapy and/or chemotherapyFair

From Andreoli TE et al: Andreoli and Carpenter’s Cecil essentials of medicine, ed 8, Philadelphia, 2010, Saunders.

Pearls & Considerations ⬆ ⬇

Comments

  • Follow-up surveillance (Table E9) involves neck ultrasound 6 to 12 mo after initial treatment and periodically and lab evaluation with TSH, serum thyroglobulin (T8), and thyroglobulin antibody (T8 Ab).
  • Family members of patients with medullary carcinoma should be screened; DNA analysis for the detection of mutations in the RET gene structure permits the identification of MEN IIA gene carriers.
  • While there is little controversy regarding the benefit of radioactive iodine in iodine-avid advanced-stage well-differentiated thyroid cancer, the indications for radioactive iodine following total thyroidectomy in patients with very low risk disease is controversial. Proponents argue that its use may destroy microscopic metastases, while opponents counter that the risk of secondary cancer due to radioactive iodine is not warranted in patients whose prognosis is typically excellent.7
  • Metastatic thyroid cancers that are refractory to radioiodine (iodine-131) are associated with a poor prognosis.
  • Small-molecule tyrosine kinase inhibitors, including vandetanib, cabozantinib, sorafenib, and lenvatinib, are now FDA-approved and have shown clinical benefit with improved survival in advanced differentiated and medullary thyroid cancer.
  • Targeted therapy with a combined regimen of BRAF/MEK inhibitors (dabrafenib plus trametinib) is efficacious and approved in patients with metastatic BRAFV600E-mutated anaplastic thyroid cancer.
  • In a subset of patients with anaplastic thyroid cancer, the immune checkpoint inhibitor pembrolizumab may be an effective salvage therapy when added to kinase inhibitors at the time of progression on these drugs. In patients with advanced, differentiated thyroid cancer, pembrolizumab has a manageable safety profile and demonstrates evidence of antitumor activity in a minority of treated patients.
  • Selpercatinib is approved for thyroid cancers with RET gene mutations.

TABLE E9 Overview of Plans for First Year of Follow-Up Following Initial Therapy

Initial Plan Based on ATA Risk for the First Year of Follow-UpATA Low RiskATA Intermediate RiskATA High Risk
Tg, TgAb, TFTs, every 3-6 mo√√√
Neck US in 3-6 mo-√√
Neck/chest CT with contrast in 6-12 mo-Considera√b
Cross-sectional imaging of other sites (brain, abdomen, pelvis)--Considerc
Routine surveillance diagnostic RAI scan--Consider
18FDG-PET scan--Consider
Dynamic risk assessment at each visit√√√

ATA, American Thyroid Association; CT, computed tomography; 18FDG-PET, fluorodeoxyglucose positron emission tomography; RAI, radioactive iodine; Tg, thyroglobulin; TgAb, antithyroglobulin antibodies; TFTs, thyroid function tests; US, ultrasound.

Note: Although most patients will return for physical examination and biochemical testing every 3-6 mo for the first year, consideration for additional testing is based on ATA risk and on the dynamic risk assessment done at each follow-up visit.

a Considered for intermediate-risk patient status postresection clinical N1a or N1b disease.

b Depending on presenting features, CT of the neck/chest may need to be done as early as 2-3 mo after initial therapy.

c Depending on presenting features, functional imaging results, and serum Tg levels.

From Melmed S et al: Williams textbook of endocrinology, ed 14, Philadelphia, 2019, Elsevier.

Related Content

Thyroid Cancer (Patient Information)

Thyroid Nodule (Related Key Topic)

Multiple Endocrine Neoplasia (Related Key Topic)

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