- All Journals
- Al-Qadisiyah University
- Basrah University
- Kirkuk University
- Mosul University
- The Iraqi Borad for Medical Specialization
- University of Anbar
- University of Technology
- Al Mustafa University
- Al-Zahraa University for Women
- Alnoor University
- Kunooz University
- Misan University
- Ninevah University
- Tikrit University
- University of Al-Hamdaniya
- University of Kerbala
BRAF V600E Immunohistochemical Expression in Non-invasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features | ||
| Al- Anbar Medical Journal | ||
| Volume 22, Issue 2, April 2026, Pages 107-113 PDF (3.99 M) | ||
| Document Type: Original articles | ||
| DOI: 10.33091/amj.2026.167564.2531 | ||
| Authors | ||
| Alyaa Hilal Ismael* ; ameer Dhahir Hameedi | ||
| Department of Pathology and Forensic Medicine, College of Medicine, University of Baghdad, Baghdad, Iraq. | ||
| Abstract | ||
| Background: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was introduced to avoid overtreatment of indolent tumours, although risks of misclassification and rare metastasis remain. According to the 2022 WHO (World Health Organization) classification, BRAF V600E-mutated cases should be reclassified as classical papillary thyroid carcinoma (PTC) with predominant follicular architecture. VE1 immunohistochemistry is a reliable surrogate for detecting the BRAF V600E mutation. Objectives: To determine the frequency of BRAF V600E mutation among NIFTP using VE1 immunohistochemistry, and to assess its correlation with clinicopathological characteristics. Materials and methods: Forty-six tumours originally diagnosed as NIFTP during the period from 2020 to 2024 were retrospectively identified. All haematoxylin-eosin slides were re-evaluated according to the WHO 2022 criteria. VE1 immunohistochemistry was performed on all cases (rabbit monoclonal anti-BRAF V600E, BIO-SB, USA). VE1 status was then correlated with clinicopathological features. RESULTS: VE1 staining reclassified 13% of suspected NIFTPs. 2.2% showed capsular invasion highlighted by VE1 and were reclassified as invasive encapsulated follicular variant of PTC (IEFVPTC), while 11% demonstrated diffuse cytoplasmic VE1 positivity indicative of BRAF V600E mutation. No significant association was observed between VE1 positivity and clinicopathological parameters (P-value > 0.05); however, VE1-positive cases tended to be larger and more frequent in males. Conclusions: VE1 immunohistochemistry identified a small but clinically important subset of tumours originally labelled as NIFTP that belong to the PTC category. Routine VE1 staining reduces the risk of undertreating aggressive BRAF-driven disease and provides a rapid, economical quality control step to ensure adherence to the WHO 2022 criteria. | ||
| Keywords | ||
| Non-invasive follicular thyroid neoplasm with papillary-like nuclear features; BRAF V600E; VE1 immunohistochemistry; Thyroid neoplasms | ||
| References | ||
|
[1] Y. E. Nikiforov et al., "Nomenclature revision for encapsulated follicular variant of papillary thyroid carcinoma: a paradigm shift to reduce overtreatment of indolent tumors," JAMA oncology, vol. 2, no. 8, pp. 1023-1029, 2016.
[2] A. Coca-Pelaz et al., "Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): what do we need to know?," Virchows Archiv, vol. 485, no. 6, pp. 977-987, 2024.
[3] I. T. Resta, M. Gubbiotti, K. Montone, V. Livolsi, and Z. Baloch, "An investigation into noninvasive follicular thyroid neoplasms with papillary-like nuclear features: does the initial proposal on noninvasive follicular thyroid neoplasms with papillary-like nuclear features behavior hold true?," Human Pathology, vol. 141, pp. 139-148, 2023.
[4] Y.-H. Chu and P. M. Sadow, "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): Diagnostic updates and molecular advances," in Seminars in diagnostic pathology, 2020, vol. 37, no. 5: Elsevier, pp. 213-218.
[5] K. S. Wong and J. A. Barletta, "Challenges in encapsulated follicular-patterned tumors: How much is enough? Evaluation of nuclear atypia, architecture, and invasion," Surgical Pathology Clinics, vol. 16, no. 1, pp. 27-44, 2023.
[6] I. J. Stojanov, O. Mete, and S. L. Asa, "Obstacles to tumor capsule assessment in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," Endocrine Pathology, vol. 34, no. 4, pp. 484-486, 2023.
[7] A. Campennì, L. Torregrossa, R. M. Ruggeri, P. P. Ovčariček, M. Siracusa, and L. Giovanella, "Nodal metastasis in noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," Endocrine, vol. 85, no. 1, pp. 142-145, 2024.
[8] Y. Fakhar, A. Khooei, A. Aghaee, H. Mohammadzadeh Kosari, L. Wartofsky, and S. R. Zakavi, "Bone metastasis from noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP); a case report," BMC Endocrine Disorders, vol. 21, no. 1, p. 221, 2021.
[9] D. N. Parente et al., "Clinical safety of renaming encapsulated follicular variant of papillary thyroid carcinoma: is NIFTP truly benign?," World Journal of Surgery, vol. 42, no. 2, pp. 321-326, 2018.
[10] U. Cho, O. Mete, M.-H. Kim, J. S. Bae, and C. K. Jung, "Molecular correlates and rate of lymph node metastasis of non-invasive follicular thyroid neoplasm with papillary-like nuclear features and invasive follicular variant papillary thyroid carcinoma: the impact of rigid criteria to distinguish non-invasive follicular thyroid neoplasm with papillary-like nuclear features," Modern Pathology, vol. 30, no. 6, pp. 810-825, 2017.
[11] T. H. Kim et al., "Molecular genotyping of the non‐invasive encapsulated follicular variant of papillary thyroid carcinoma," Histopathology, vol. 72, no. 4, pp. 648-661, 2018.
[12] S. E. Lee et al., "Molecular profiling of papillary thyroid carcinoma in Korea with a high prevalence of BRAFV600E mutation," Thyroid, vol. 27, no. 6, pp. 802-810, 2017.
[13] D. C. Rego, H. Lee, A. Boguniewicz, and T. A. Jennings, "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is rare, benign lesion using modified stringent diagnostic criteria: reclassification and outcome study," Annals of Diagnostic Pathology, vol. 44, p. 151439, 2020.
[14] X. Yang, Q. Fan, Y. Zhang, L. Huang, and X. Feng, "Relafionship between Somafic Mutafions and Clinic Pathological of Follicular Variant Papillary Thyroid Carcinoma: A Meta-Analysis," J Surgery. 4 (1),pp. 1156, 2024.
[15] L. Janicki, A. Patel, J. Jendrzejewski, and A. Hellmann, "Prevalence and Impact of BRAF mutation in patients with concomitant papillary thyroid carcinoma and Hashimoto’s thyroiditis: a systematic review with meta-analysis," Frontiers in endocrinology, vol. 14, p. 1273498, 2023.
[16] L. Lebrun and I. Salmon, "Pathology and new insights in thyroid neoplasms in the 2022 WHO classification," Current Opinion in Oncology, vol. 36, no. 1, pp. 13-21, 2024.
[17] M. Capezzone et al., "Identification of a Novel Non‐V600E BRAF Mutation in Papillary Thyroid Cancer," Case Reports in Endocrinology, vol. 2024, no. 1, p. 6621510, 2024.
[18] K. Z. Swan, S. H. Madsen, S. J. Bonnema, V. E. Nielsen, and M. L. Jespersen, "Preoperative BRAFV600E mutation detection in thyroid carcinoma by immunocytochemistry," Apmis, vol. 130, no. 11, pp. 627-636, 2022.
[19] K. G. Parker, M. G. White, and N. A. Cipriani, "Comparison of molecular methods and BRAF immunohistochemistry (VE1 clone) for the detection of BRAF V600E mutation in papillary thyroid carcinoma: a meta-analysis," Head and neck pathology, vol. 14, no. 4, pp. 1067-1079, 2020.
[20] D. N. Johnson and P. M. Sadow, "Exploration of BRAFV600E as a diagnostic adjuvant in the non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)," Human pathology, vol. 82, pp. 32-38, 2018.
[21] H.-W. Chuang, J.-S. Wang, J.-W. Tsai, C.-T. Hsu, and K.-J. Lin, "Immunohistochemistry helps to distinguish noninvasive follicular thyroid neoplasm with papillary-like nuclear features/noninvasive encapsulated follicular variant of papillary thyroid carcinoma with other follicular thyroid lesions," Medicina, vol. 57, no. 11, p. 1246, 2021.
[22] A. Kuchareczko et al., "Are molecular tests necessary to diagnose NIFTP?," Genes & Cancer, vol. 12, p. 39, 2021.
[23] X. Wei et al., "Risk and prognostic factors for BRAFV600E mutations in papillary thyroid carcinoma," BioMed Research International, vol. 2022, no. 1, p. 9959649, 2022.
[24] A. Nechifor-Boilă et al., "Impact of BRAF V600E mutation on event-free survival in patients with papillary thyroid carcinoma: a retrospective study in a Romanian population," Cancers, vol. 15, no. 16, p. 4053, 2023.
[25] B. Xu, G. Tallini, T. Scognamiglio, B. R. Roman, R. M. Tuttle, and R. A. Ghossein, "Outcome of large noninvasive follicular thyroid neoplasm with papillary-like nuclear features," Thyroid, vol. 27, no. 4, pp. 512-517, 2017.
[26] K. Glomski, V. Nosé, W. C. Faquin, and P. M. Sadow, "Metastatic follicular thyroid carcinoma and the primary thyroid gross examination: institutional review of cases from 1990 to 2015," Endocrine Pathology, vol. 28, no. 2, pp. 177-185, 2017.
[27] P. W. Rosario and G. F. Mourão, "Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): a review for clinicians," Endocrine-Related Cancer, vol. 26, no. 5, pp. R259-R266, 2019.
[28] K. Kakudo et al., "Noninvasive follicular thyroid neoplasm with papillary‐like nuclear features (NIFTP) in thyroid tumor classification," Pathology International, vol. 68, no. 6, pp. 327-333, 2018.
[29] M. D. Ringel et al., "2025 American Thyroid Association management guidelines for adult patients with differentiated thyroid cancer," Thyroid®, vol. 35, no. 8, pp. 841-985, 2025.
[30] J. P. Rivera and J.-F. Hang, "Next-Generation Immunohistochemistry in Thyroid Neoplasm: A Practical Review on the Applications in Diagnosis and Molecular Classification," Endocrine Pathology, vol. 36, no. 1, p. 8, 2025.
| ||
|
Statistics Article View: 192 PDF Download: 158 |
||