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The Presence of Typical “BRAFV600E-Like” Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation

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Abstract

Papillary thyroid carcinomas (PTCs) are driven by a variety of molecular abnormalities including BRAF, RAS, ALK, RET, and NTRK alterations. PTCs driven by the BRAFV600E mutation, or tumours which demonstrate a similar gene expression profile to PTCs driven by this mutation, have been reported to demonstrate specific morphological features sometimes termed “BRAFV600E-like” atypia. BRAFV600E-like atypia is characterised by a well-developed papillary architecture, infiltrative growth, marked nuclear clearing, prominent intranuclear pseudoinclusions, abundant eosinophilic cytoplasm, and scattered psammoma bodies. We sought to investigate the sensitivity and specificity of these morphological features for the presence of BRAFV600E mutation in PTCs as determined by mutation specific immunohistochemistry. An unselected cohort of 495 PTCs was reviewed by a single pathologist and categorised into three groups: typical BRAFV600E-like atypia (145 cases, 29%), possible BRAFV600E-like atypia (166 cases, 33%) and little/no BRAFV600E-like atypia (184 cases, 37%). The specificity and sensitivity of typical BRAFV600E-like atypia for the BRAFV600E mutation was 97.2% and 44.3%, respectively. When typical and possible BRAFV600E-like atypia were analysed together, the specificity was 70.6% and the sensitivity was 81.7%. In the morphologically little/no BRAFV600E-like atypia group, 58 cases (31.5%) had a BRAFV600E mutation. We conclude that typical BRAFV600E-like atypia is highly specific for the presence of the BRAFV600E mutation; however, the absence of BRAFV600E-like atypia does not exclude this mutation.

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Author information

Authors and Affiliations

  1. Anatomical Pathology, Douglass Hanly Moir Pathology, 14 Giffnock Avenue, Macquarie Park, NSW, 2113, Australia

    John Turchini

  2. Discipline of Pathology, Macquarie Medical School, Macquarie University, Macquarie Park, NSW, 2109, Australia

    John Turchini

  3. Sydney Medical School, The University of Sydney, Sydney, 2006, Australia

    John Turchini, Leigh Delbridge, Anthony Glover, Mark Sywak, Stan Sidhu & Anthony J. Gill

  4. Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St Leonards, NSW, 2065, Australia

    John Turchini, Loretta Sioson, Adele Clarkson, Amy Sheen & Anthony J. Gill

  5. Endocrine Surgical Unit, Royal North Shore Hospital, St Leonards, NSW, 2065, Australia

    Leigh Delbridge, Anthony Glover, Mark Sywak & Stan Sidhu

  6. Department of Anatomical Pathology, Royal North Shore Hospital, NSW Health Pathology, St Leonards, NSW, 2065, Australia

    Adele Clarkson & Anthony J. Gill

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Contributions

J.T. wrote the manuscript and prepared the figures. L.S. and A.C. prepared the laboratory slides. A.S. prepared and maintained the data. A.G. reviewed and edited the manuscript. All the other authors reviewed the manuscript.

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Correspondence to John Turchini.

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This study was approved by the Northern Sydney Local Health District Human Research Ethics Committee (protocols 1201-035 M and 1312-417 M).

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Turchini, J., Sioson, L., Clarkson, A. et al. The Presence of Typical “BRAFV600E-Like” Atypia in Papillary Thyroid Carcinoma is Highly Specific for the Presence of the BRAFV600E Mutation. Endocr Pathol 34, 112–118 (2023). https://doi.org/10.1007/s12022-022-09747-9

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