Original Communication| Volume 144, ISSUE 1, P80-85, July 2008

A pathologic re-review of follicular thyroid neoplasms: The impact of changing the threshold for the diagnosis of the follicular variant of papillary thyroid carcinoma

Published:January 31, 2008DOI:


      Histopathologic criterion for follicular variant of papillary thyroid cancer (FVPTC) has only recently been utilized universally. The purpose was to determine whether, on review, these criteria would result in a change in diagnosis of follicular neoplasm (FN).


      A ten-year clinical cohort included patients with a diagnosis of a follicular adenoma, follicular carcinoma (FC), or FVPTC. The archived sections were re-examined by two pathologists blinded to the original diagnoses. Clinical follow-up, including ultrasonography, was carried out on all patients with a change in diagnosis.


      One hundred eighty-five patients met the inclusion criteria. Initially, 118 were benign, 56 were FVPTC, and 11 were FC. Overall, 46 (25%) patients had a change in diagnosis on re-review; 35 were reclassified from a benign diagnosis to a re-reviewed malignant diagnosis, with 5 reclassified as minimally invasive FC, 4 as occult PTC, and 26 (74%) as FVPTC. Of the 26 FVPTC, only 10 (38%) had undergone a total thyroidectomy (TT). The mean follow-up was 105 months (range, 24-156). None of these patients had evidence of recurrent or persistent disease. Eleven patients were reclassified to a benign diagnosis. Eight have undergone a TT, with 3 of these patients receiving I131 ablation therapy. A third independent thyroid pathologist also reviewed the histopathologic slides of these 46 patients and concurred with the change in diagnosis in 41 of the 46 patients.


      Reclassification of FN increased malignant lesions from 36% to 48%. Although there have been no clinical ramifications in the patients with a changed diagnosis, the ethical issues surrounding these 46 patients are important and present a substantive quandary to the clinicians responsible for their care.
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        • Passler C.
        • Prager G.
        • Scheuba C.
        • Niederle B.E.
        • Kaserer K.
        • Zettinig G.
        • et al.
        Follicular variant of papillary thyroid carcinoma: a long-term follow-up.
        Arch Surg. 2003; 138: 1362-1366
        • LiVolsi V.A.
        • Baloch Z.W.
        Follicular neoplasms of the thyroid: view, biases, and experiences.
        Adv Anat Pathol. 2004; 11: 279-287
        • Chan J.K.
        Strict criteria should be applied in the diagnosis of encapsulated follicular variant of papillary thyroid carcinoma.
        Am J Clin Pathol. 2002; 117: 16-18
        • Baloch Z.W.
        • LiVolsi V.A.
        Follicular-patterned lesions of the thyroid: the bane of the pathologist.
        Am J Clin Pathol. 2002; 117: 143-150
        • Lloyd R.V.
        • Erickson L.A.
        • Casey M.B.
        • Lam K.Y.
        • Lohse C.M.
        • Asa S.L.
        • et al.
        Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma.
        Am J Surg Pathol. 2004; 28: 1336-1340
        • Hirokawa M.
        • Carney J.A.
        • Goellner J.R.
        • DeLellis R.A.
        • Heffess C.S.
        • Katoh R.
        • et al.
        Observer variation of encapsulated follicular lesions of the thyroid gland.
        Am J Surg Pathol. 2002; 26: 1508-1514
        • Liu J.
        • Singh B.
        • Tallini G.
        • Carlson D.L.
        • Katabi N.
        • Shaha A.
        • et al.
        Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity.
        Cancer. 2006; 107: 1255-1264
        • Suster S.
        Thyroid tumors with a follicular growth pattern: problems in differential diagnosis.
        Arch Pathol Lab Med. 2006; 130: 984-988
        • Hamady Z.Z.
        • Mather N.
        • Lansdown M.R.
        • Davidson L.
        • MacLennan K.A.
        Surgical pathological second opinion in thyroid malignancy: impact on patients' management and prognosis.
        Eur J Surg Oncol. 2005; 31: 74-77
        • Cross S.
        • Wei J.P.
        • Kim S.
        • Brams D.M.
        Selective surgery and adjuvant therapy based on risk classifications of well-differentiated thyroid cancer.
        J Surg Oncol. 2006; 94: 678-682
        • Sosa J.A.
        • Udelsman R.
        Total thyroidectomy for differentiated thyroid cancer.
        J Surg Oncol. 2006; 94: 701-707
        • Watkinson J.C.
        The British Thyroid Association guidelines for the management of thyroid cancer in adults.
        Nucl Med Commun. 2004; 25: 897-900
        • van Heerden J.A.
        • Hay I.D.
        • Goellner J.R.
        • Salomao D.
        • Ebersold J.R.
        • Bergstralh E.J.
        • et al.
        Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy.
        Surgery. 1992; 112: 1130-1136
        • Singer P.A.
        • Cooper D.S.
        • Daniels G.H.
        • Ladenson P.W.
        • Greenspan F.S.
        • Levy E.G.
        • et al.
        Treatment guidelines for patients with thyroid nodules and well-differentiated thyroid cancer. American Thyroid Association.
        Arch Intern Med. 1996; 156: 2165-2172
        • Larsen P.R.
        New guidelines for patients with thyroid nodules and differentiated thyroid cancer.
        Nat Clin Pract Endocrinol Metab. 2006; 2: 297
        • Sweeney D.C.
        • Johnston G.S.
        Radioiodine therapy for thyroid cancer.
        Endocrinol Metab Clin North Am. 1995; 24: 803-839
        • Lang B.H.
        • Lo C.Y.
        • Chan W.F.
        • Lam A.K.
        • Wan K.Y.
        Classical and follicular variant of papillary thyroid carcinoma: a comparative study on clinicopathologic features and long-term outcome.
        World J Surg. 2006; 30: 752-758
        • Hagag P.
        • Hod N.
        • Kummer E.
        • Cohenpour M.
        • Horne T.
        • Weiss M.
        Follicular variant of papillary thyroid carcinoma: clinical-pathological characterization and long-term follow-up.
        Cancer J. 2006; 12: 275-282
        • Vasko V.V.
        • Gaudart J.
        • Allasia C.
        • Savchenko V.
        • Di Cristofaro J.
        • Saji M.
        • et al.
        Thyroid follicular adenomas may display features of follicular carcinoma and follicular variant of papillary carcinoma.
        Eur J Endocrinol. 2004; 151: 779-786
        • Castro P.
        • Rebocho A.P.
        • Soares R.J.
        • Magalhaes J.
        • Roque L.
        • Trovisco V.
        • et al.
        PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma.
        J Clin Endocrinol Metab. 2006; 91: 213-220
        • Zhu Z.
        • Gandhi M.
        • Nikiforova M.N.
        • Fischer A.H.
        • Nikiforov Y.E.
        Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations.
        Am J Clin Pathol. 2003; 120: 71-77
        • Wreesmann V.B.
        • Ghossein R.A.
        • Hezel M.
        • Banerjee D.
        • Shaha A.R.
        • Tuttle R.M.
        • et al.
        Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.
        Genes Chromosomes Cancer. 2004; 40: 355-364
      1. Williams J. World Medical Association medical ethic manual. 2005. Available from: URL:

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