A 35-year-old woman has a thyroid nodule with FNA showing cells arranged in papillary clusters with nuclear grooves, intranuclear pseudoinclusions, and pale ('Orphan Annie eye') nuclei. Molecular testing shows BRAF V600E mutation. The WHO 5th edition classification designates this as:

• A Papillary thyroid carcinoma (PTC) — the nuclear features alone are diagnostic regardless of architectural pattern (papillary, follicular, or solid) ✓
• B Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) if the architecture is purely follicular and encapsulated with no invasion
• C Follicular thyroid carcinoma if no true papillae are present
• D Anaplastic thyroid carcinoma given the nuclear pleomorphism

Explanation

WHO 2022 (5th edition) maintains that papillary thyroid carcinoma is defined by its characteristic nuclear features (nuclear clearing, grooves, pseudoinclusions, overlapping nuclei) rather than requiring a papillary architecture. BRAF V600E is the most common mutation in classic PTC. NIFTP is a distinct category requiring strictly follicular architecture, complete encapsulation, no invasion, no papillary architecture, and papillary-like nuclei — it is considered a low-risk neoplasm. Anaplastic carcinoma shows undifferentiated pleomorphic spindle cells without PTC nuclear features.

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

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Written and medically reviewed by the StethoPrep medical team.