What is the classification of thyroid malignancy?

Classification of Thyroid Malignancy

Thyroid malignancies are classified into five main histological types: differentiated (papillary and follicular), poorly differentiated, anaplastic, and medullary thyroid carcinomas, with each type having distinct molecular profiles, clinical behaviors, and prognoses. 1

Main Classification Categories

1. Differentiated Thyroid Carcinoma (DTC)

• Papillary Thyroid Carcinoma (PTC)

  • Most common type (accounts for majority of thyroid cancers)
  • Variants include:
    • Classical
    • Follicular variant
    • Tall cell variant
    • Columnar variant
    • Hobnail variant
    • Solid variant 1
  • Molecular profile: BRAF-predominant molecular signatures 1
  • Excellent prognosis in most cases

• Follicular Thyroid Carcinoma (FTC)

  • Classified as:
    • Minimally invasive (capsular penetration without vascular involvement)
    • Angioinvasive (<4 blood vessels involved)
    • Widely invasive (≥4 blood vessels involved) 1
  • Molecular profile: RAS-predominant molecular signatures 1

• Hürthle Cell Carcinoma

  • Now classified as a separate entity, not as a subtype of follicular carcinoma
  • Defined as having >75% Hürthle cell component
  • More aggressive than conventional follicular carcinomas 1

2. Poorly Differentiated Thyroid Carcinoma

• Intermediate between differentiated and anaplastic carcinomas
• Diagnostic criteria (Turin proposal):
  • Solid/trabecular/insular growth pattern plus at least one of:
    • Mitotic index ≥3 per 10 high-power fields
    • Necrosis
    • Convoluted nuclei 1
• Maintains some degree of functional differentiation (e.g., thyroglobulin production)

3. Anaplastic Thyroid Carcinoma (ATC)

• Most aggressive form of thyroid cancer
• Almost uniformly fatal with median survival of about 5 months 1
• All ATCs are considered stage IV (A, B, or C) 1
• Presents with extensive local invasion and distant metastases in 15-50% of patients at diagnosis 1

4. Medullary Thyroid Carcinoma (MTC)

• Arises from parafollicular C cells (not from follicular cells)
• Produces calcitonin
• Can occur sporadically or as part of hereditary syndromes (MEN 2A, MEN 2B) 1

5. Non-Invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP)

• Previously classified as encapsulated non-invasive follicular variant of PTC
• Now considered a separate entity with very low malignant potential
• Excellent prognosis with risk of recurrence <1% 1

World Health Organization (WHO) Classification

The WHO classification (updated in 2017) categorizes thyroid tumors based on:

• Cell of origin
• Morphological features
• Molecular characteristics
• Biological behavior 1, 2

The 2022 WHO Classification divides thyroid tumors into:

• Benign neoplasms
• Low-risk neoplasms
• Malignant neoplasms 2

TNM Staging System

The Union for International Cancer Control (UICC) TNM classification stages thyroid malignancies based on mortality risk:

• T: Size and extent of the primary tumor
• N: Involvement of regional lymph nodes
• M: Presence of distant metastases 1

The eighth edition introduced important changes, including downstaging of microscopic extrathyroidal extension 1.

Risk Stratification for Recurrence

The American Thyroid Association (ATA) risk stratification system estimates the risk of persistent or recurrent disease after treatment:

• Low risk (<5%)
• Intermediate risk (6-20%)
• High risk (>20%) 1

Clinical Implications

• Accurate classification is crucial for prognosis and treatment selection
• Molecular profiling is increasingly important for diagnosis and risk stratification
• Histopathological examination remains the gold standard for classification
• In some cases, molecular biomarkers may support classification when histopathological features are inconclusive 3, 4

Important Considerations

• Small papillary thyroid microcarcinomas (<1 cm) are increasingly detected but generally have excellent prognosis 1
• The term "Hürthle cell" is now discouraged as it is considered a misnomer; "oncocytic" is preferred 2
• Molecular testing is not recommended for diagnosis of anaplastic thyroid carcinoma 1
• Each nodule should be evaluated individually based on its sonographic features 5

The classification of thyroid malignancies continues to evolve with advances in molecular profiling and better understanding of tumor biology, leading to more precise diagnosis and personalized treatment approaches.