What is the latest World Health Organization (WHO) classification of breast carcinoma?

WHO Classification of Breast Carcinoma: 2019 5th Edition

The latest WHO classification of breast carcinoma is the 5th edition published in 2019, which maintains histological features as the foundation for classification while incorporating molecular parameters for improved prognostic assessment and therapeutic decision-making.

Key Features of the 2019 WHO Classification

Invasive Breast Carcinoma Classification

• Invasive Breast Carcinoma of No Special Type (NST) - Previously called invasive ductal carcinoma, this remains the most common type (70-75% of cases)

  • Several former special types are now classified as variants of NST including medullary, lipid-rich, and glycogen-rich carcinomas 1

• Special Types of Invasive Carcinoma (representing approximately 25% of all breast cancers):

  • Invasive lobular carcinoma
  • Tubular carcinoma
  • Cribriform carcinoma
  • Mucinous carcinoma
  • Carcinoma with medullary features
  • Carcinoma with apocrine differentiation
  • Metaplastic carcinoma
  • Micropapillary carcinoma
  • Papillary carcinomas
  • Others 2, 3

New Entities Added in the 5th Edition

• Tall cell carcinoma with reversed polarity - A rare subtype with distinctive morphology
• Mucinous cystadenocarcinoma - A newly recognized entity 1

Revised Classifications

• Mixed invasive carcinomas - The definition has been revised in the 5th edition
• Neuroendocrine neoplasms - Now classified by analogy with other organ systems
• Phyllodes tumors - Updated dignity criteria for classification 1
• Lobular carcinoma in situ (LCIS) - Revised subtyping approach 1

Molecular Classification Integration

The WHO classification now incorporates molecular classification alongside traditional histopathological assessment:

• Luminal A: ER+/PR+, HER2-, low Ki67
• Luminal B: ER+/PR+, HER2- with high Ki67 or HER2+
• HER2-enriched: ER-/PR-, HER2+
• Triple-negative/basal-like: ER-/PR-, HER2- 4

Pathological reports should include:

• Histological type (according to WHO classification)
• Histological grade (using Elston-Ellis grading system)
• ER/PR status using standardized assessment (e.g., Allred or H-score)
• HER2 status (positive if >10% cells show complete membrane staining by IHC or ≥6 HER2 gene copies by ISH) 5, 4
• Ki67 or other proliferation markers when available 4

Clinical Implications of Classification

The classification has important implications for:

1. Prognosis assessment - Different histological types have varying prognoses (e.g., tubular carcinoma has excellent prognosis while metaplastic carcinoma generally has poor outcomes) 2

2. Treatment planning - Molecular subtypes guide therapy decisions:

   • Hormone receptor-positive: Endocrine therapy
   • HER2-positive: Anti-HER2 targeted therapy
   • Triple-negative: Chemotherapy 4

3. Surgical planning - Some subtypes (e.g., lobular and micropapillary) may have more extensive disease than apparent on imaging 5, 4

Important Considerations in Practice

• While molecular classification is increasingly important, histopathological classification remains crucial for diagnosis and management 6
• Some histological special types are molecularly homogeneous (e.g., tubular carcinomas are almost always luminal A), while others (like NST and lobular carcinomas) can belong to any molecular subtype 3
• Rare subtypes may have limited evidence for optimal management strategies due to their infrequency 2
• Accurate classification requires adequate sampling through core needle biopsy with at least 2-3 cores, preferably under ultrasound or stereotactic guidance 4

The WHO classification continues to evolve as new molecular insights emerge, but the 5th edition (2019) represents the current standard for breast cancer classification in clinical practice.