Subtitle: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): inclusion and exclusion criteria, the nuclear score, NIFTP vs invasive FVPTC and follicular adenoma, molecular profile, virtual slides and 8 MCQs.
Author: PathologyMCQ Editorial Board
Category: Endocrine Pathology
Last Updated: October 2026
Read Time: 6 minutes
At-a-Glance
- NIFTP replaced non-invasive encapsulated FVPTC (2016) because of its very low risk.
- Needs encapsulation, follicular growth, nuclear score 2–3 and no invasion.
- Excluded by papillae, psammoma bodies, ≥30% solid growth, necrosis, high mitoses or tall cell features.
- Molecular profile is RAS-like; BRAF V600E argues against NIFTP.
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Diagnostic Criteria
Inclusion criteria (all required):
- Encapsulation or clear demarcation, with the entire capsule examined.
- Follicular growth pattern without true papillae.
- PTC-type nuclear features with a nuclear score of 2 or 3.
- No capsular or vascular invasion.
Exclusion criteria: true papillae, psammoma bodies, ≥30% solid/trabecular/insular growth, tumour necrosis, high mitotic activity (≥3 per 10 HPF), tall cell, columnar or cribriform-morular features, and invasion.
Scoring Nuclear Features
Score one point for each: size and shape (enlargement, elongation, overlapping), membrane irregularities (contour irregularity, grooves, pseudoinclusions) and chromatin (clearing, margination, glassy nuclei). NIFTP requires 2 or 3.
Virtual Slides
NIFTP, 37-year-old patient: an encapsulated lesion with papillary-like nuclear features and no invasion.
Compare it with a follicular adenoma and a classic papillary carcinoma:
What to look for
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NIFTP vs FVPTC vs Follicular Adenoma
| Feature | NIFTP | Invasive FVPTC | Follicular adenoma |
|---|---|---|---|
| Capsule | Encapsulated or well demarcated | Encapsulated with invasion, or infiltrative | Encapsulated |
| Papillae | Absent | May be present (infiltrative) | Absent |
| Nuclear score | 2–3 | 2–3 | 0–1 |
| Invasion | Absent | Present | Absent |
| Molecular | RAS-like (RAS, PAX8::PPARG) | Encapsulated: RAS-like; infiltrative: BRAF V600E | RAS, PAX8::PPARG |
| Behaviour | Very low risk | Malignant | Benign |
Molecular Profile
- NIFTP: RAS-like alterations (NRAS, HRAS, KRAS), BRAF K601E, PAX8::PPARG or THADA fusions. BRAF V600E and high-risk alterations (TERT, TP53) argue against NIFTP.
- Infiltrative FVPTC and classic PTC: BRAF V600E-like profile.
- Follicular adenoma: RAS-like, without PTC nuclei.
Practical Diagnostic Approach
Test Yourself: 8 MCQs
NIFTP: 8 MCQs
Inclusion and exclusion criteria, nuclear score and molecular profile, with instant explanations.
More practice: the question banks →
Exam Pearls
- NIFTP is a diagnosis on the resection: the whole capsule must be examined.
- Nuclear score 2–3 + no papillae + no invasion = NIFTP.
- Psammoma bodies, papillae, ≥30% solid growth or necrosis exclude it.
- BRAF V600E: think PTC, not NIFTP.
For more diagnostic approaches, join the approach-based course in histopathology and cytology →
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References
- WHO Classification of Tumours Editorial Board. Endocrine and Neuroendocrine Tumours. 5th ed. IARC; 2022.
- Nikiforov YE, et al. Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma. JAMA Oncol. 2016;2:1023–9.
- Nikiforov YE, et al. Change in diagnostic criteria for NIFTP. JAMA Oncol. 2018;4:1125–6.
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