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Papillary Thyroid Carcinoma BRAF Immunopositivity

      This thyroid tumor was identified incidentally with choline PET-CT which was being performed in follow-up of prostate cancer. The thyroid tumor was diagnosed as thyroid carcinoma on fine needle aspiration. A left lobectomy with isthmusectomy (hemithyroidectomy) was performed, and a 1.3 cm papillary thyroid carcinoma, classic/conventioinal type, was identified.
      What statement is most accurate regarding papillary thyroid carcinoma?
      • a.
        The most common genetic alteration in papillary thyroid carcinoma involves RAS
      • b.
        Although papillary thyroid carcinomas may be classified into different variants (classic/conventional, tall cell, hobnail, solid cell, follicular variant, etc...), the behavior and prognosis are similar regardless of variant
      • c.
        Papillary thyroid carcinoma is less common than other types of thyroid carcinoma
      • d.
        The most relevant genetic alterations in papillary thyroid carcinoma involve BRAF, RET, and RAS, are generally mutually exclusive, and are associated with activation of the MAPK pathway
      Answer: d. The most relevant genetic alterations in papillary thyroid carcinoma involve BRAF, RET, and RAS, are generally mutually exclusive, and are associated with activation of the MAPK pathway
      Papillary thyroid carcinoma is a predominant form of thyroid cancer. Different variants of papillary thyroid carcinoma can have prognostic significance as some variants such as the tall cell variant in the hobnail variant may be associated with more aggressive disease.
      • Nath M.C.
      • Erickson L.A.
      Aggressive variants of papillary thyroid carcinoma: Hobnail, tall cell, columnar, and solid.
      Some variants are significant due to their possible association with other diseases such as the cribriform morular variant of papillary thyroid carcinoma and familial adenomatous polyposis.
      • Erickson L.A.
      Unique clinical significance of the cribriform-morular variant of papillary thyroid carcinoma.
      The most relevant genetic alterations in papillary thyroid carcinoma involve BRAF, RET, and RAS.
      • Lloyd R.V.
      • Osamura R.Y.
      • Kloppel G.
      • Posai J.
      Editors (2017). WHO Classification of Tumours of Endocrine Organs.
      BRAF mutations are very common in papillary thyroid carcinoma, particularly classic/conventional and tall cell variants. However, the follicular variant of papillary thyroid carcinoma is more often associated with RAS alterations. These alterations are generally mutually exclusive. Point mutations such as that of BRAF V600E are particularly common, but gene fusions and copy number variations can also be identified in some papillary thyroid carcinomas.
      • Lloyd R.V.
      • Osamura R.Y.
      • Kloppel G.
      • Posai J.
      Editors (2017). WHO Classification of Tumours of Endocrine Organs.
      The papillary thyroid carcinoma in this case was conventional/classic type and associated with BRAF mutation – the most common driver mutation in papillary thyroid carcinoma. The following photomicrograph demonstrates the histologic features of the tumor with an inset showing positivity with BRAF immunostain.

      References

        • Nath M.C.
        • Erickson L.A.
        Aggressive variants of papillary thyroid carcinoma: Hobnail, tall cell, columnar, and solid.
        Adv Anat Pathol. 2018; 25: 172-179
        • Erickson L.A.
        Unique clinical significance of the cribriform-morular variant of papillary thyroid carcinoma.
        Mayo Clin Proc. 2020; 95: 831-833
        • Lloyd R.V.
        • Osamura R.Y.
        • Kloppel G.
        • Posai J.
        Editors (2017). WHO Classification of Tumours of Endocrine Organs.
        4th edition. IARC, Lyon, France2017