A 55-year-old with invasive ductal carcinoma (no special type) undergoes molecular profiling showing ER+, PR+, HER2 amplified (IHC 3+). Per 2018 ASCO/CAP guidelines, HER2 positivity by IHC 3+ is defined as:

• A Strong complete circumferential membrane staining in >10% of tumor cells ✓
• B Complete membrane staining of any intensity in >30% of tumor cells
• C Strong complete circumferential membrane staining in >10% of invasive tumor cells, HER2/CEP17 ratio ≥2.0 on ISH
• D Strong incomplete membrane staining in >10% of tumor cells not meeting 3+ criteria

Explanation

Per the 2018 ASCO/CAP updated HER2 testing guidelines, IHC 3+ (positive) is defined as strong, complete, circumferential membrane staining observed in >10% of invasive tumor cells. IHC 2+ (equivocal) requires ISH reflex testing. IHC 1+ shows faint, incomplete membrane staining in >10% of cells and is negative. The 2023 HER2-low concept (IHC 1+ or 2+/ISH−) is now clinically relevant as these tumors benefit from trastuzumab deruxtecan (T-DXd). Option D describes IHC 2+ incomplete staining, not 3+.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.