Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors | Endocrinology | JAMA Oncology | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.207.129.82. Please contact the publisher to request reinstatement.
1.
Davies  L, Welch  HG.  Increasing incidence of thyroid cancer in the United States, 1973-2002.  JAMA. 2006;295(18):2164-2167.PubMedGoogle ScholarCrossref
2.
Ahn  HS, Kim  HJ, Welch  HG.  Korea’s thyroid-cancer “epidemic”—screening and overdiagnosis.  N Engl J Med. 2014;371(19):1765-1767.PubMedGoogle ScholarCrossref
3.
Welch  HG, Black  WC.  Overdiagnosis in cancer.  J Natl Cancer Inst. 2010;102(9):605-613.PubMedGoogle ScholarCrossref
4.
Chem  KT, Rosai  J.  Follicular variant of thyroid papillary carcinoma: a clinicopathologic study of six cases.  Am J Surg Pathol. 1977;1(2):123-130.PubMedGoogle ScholarCrossref
5.
Jung  CK, Little  MP, Lubin  JH,  et al.  The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations.  J Clin Endocrinol Metab. 2014;99(2):E276-E285.PubMedGoogle ScholarCrossref
6.
Rosai  J, Carcangiu  ML, DeLellis  RA.  Tumors of the Thyroid Gland. Atlas of Tumor Pathology. Washington, DC: Armed Forces Institute of Pathology; 1993.
7.
Liu  J, Singh  B, Tallini  G,  et al.  Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity.  Cancer. 2006;107(6):1255-1264.PubMedGoogle ScholarCrossref
8.
Lupi  C, Giannini  R, Ugolini  C,  et al.  Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma.  J Clin Endocrinol Metab. 2007;92(11):4085-4090.PubMedGoogle ScholarCrossref
9.
Hirokawa  M, Carney  JA, Goellner  JR,  et al.  Observer variation of encapsulated follicular lesions of the thyroid gland.  Am J Surg Pathol. 2002;26(11):1508-1514.PubMedGoogle ScholarCrossref
10.
Lloyd  RV, Erickson  LA, Casey  MB,  et al.  Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma.  Am J Surg Pathol. 2004;28(10):1336-1340.PubMedGoogle ScholarCrossref
11.
Elsheikh  TM, Asa  SL, Chan  JK,  et al.  Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma.  Am J Clin Pathol. 2008;130(5):736-744.PubMedGoogle ScholarCrossref
12.
Shi  X, Liu  R, Basolo  F,  et al.  Differential clinicopathological risk and prognosis of major papillary thyroid cancer variants.  J Clin Endocrinol Metab. 2016;101(1):264-274.PubMedGoogle ScholarCrossref
13.
Widder  S, Guggisberg  K, Khalil  M, Pasieka  JL.  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.  Surgery. 2008;144(1):80-85.PubMedGoogle ScholarCrossref
14.
Piana  S, Frasoldati  A, Di Felice  E, Gardini  G, Tallini  G, Rosai  J.  Encapsulated well-differentiated follicular-patterned thyroid carcinomas do not play a significant role in the fatality rates from thyroid carcinoma.  Am J Surg Pathol. 2010;34(6):868-872.PubMedGoogle ScholarCrossref
15.
Vivero  M, Kraft  S, Barletta  JA.  Risk stratification of follicular variant of papillary thyroid carcinoma.  Thyroid. 2013;23(3):273-279.PubMedGoogle ScholarCrossref
16.
Rivera  M, Ricarte-Filho  J, Knauf  J,  et al.  Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns.  Mod Pathol. 2010;23(9):1191-1200.Google ScholarCrossref
17.
Kakudo  K, Bai  Y, Liu  Z, Ozaki  T.  Encapsulated papillary thyroid carcinoma, follicular variant: a misnomer.  Pathol Int. 2012;62(3):155-160.PubMedGoogle ScholarCrossref
18.
Lubitz  CC, Kong  CY, McMahon  PM,  et al.  Annual financial impact of well-differentiated thyroid cancer care in the United States.  Cancer. 2014;120(9):1345-1352.PubMedGoogle ScholarCrossref
19.
Esserman  LJ, Thompson  IM, Reid  B,  et al.  Addressing overdiagnosis and overtreatment in cancer: a prescription for change.  Lancet Oncol. 2014;15(6):e234-e242.PubMedGoogle ScholarCrossref
20.
Nikiforov  YE, Carty  SE, Chiosea  SI,  et al.  Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.  Cancer. 2014;120(23):3627-3634.PubMedGoogle ScholarCrossref
21.
Vanzati  A, Mercalli  F, Rosai  J.  The “sprinkling” sign in the follicular variant of papillary thyroid carcinoma: a clue to the recognition of this entity.  Arch Pathol Lab Med. 2013;137(12):1707-1709.PubMedGoogle ScholarCrossref
22.
Cancer Genome Atlas Research Network.  Integrated genomic characterization of papillary thyroid carcinoma.  Cell. 2014;159(3):676-690.PubMedGoogle ScholarCrossref
23.
Ganly  I, Wang  L, Tuttle  RM,  et al.  Invasion rather than nuclear features correlates with outcome in encapsulated follicular tumors: further evidence for the reclassification of the encapsulated papillary thyroid carcinoma follicular variant.  Hum Pathol. 2015;46(5):657-664.PubMedGoogle ScholarCrossref
24.
Rosario  PW, Penna  GC, Calsolari  MR.  Noninvasive encapsulated follicular variant of papillary thyroid carcinoma: is lobectomy sufficient for tumours ≥1 cm?  Clin Endocrinol (Oxf). 2014;81(4):630-632.PubMedGoogle ScholarCrossref
25.
Baloch  ZW, LiVolsi  VA.  Encapsulated follicular variant of papillary thyroid carcinoma with bone metastases.  Mod Pathol. 2000;13(8):861-865.Google ScholarCrossref
26.
Howitt  BE, Paulson  VA, Barletta  JA.  Absence of BRAF V600E in non-infiltrative, non-invasive follicular variant of papillary thyroid carcinoma.  Histopathology. 2015;67(4):579-582.PubMedGoogle ScholarCrossref
27.
Liu  Z, Zhou  G, Nakamura  M,  et al.  Encapsulated follicular thyroid tumor with equivocal nuclear changes, so-called well-differentiated tumor of uncertain malignant potential: a morphological, immunohistochemical, and molecular appraisal.  Cancer Sci. 2011;102(1):288-294.PubMedGoogle ScholarCrossref
28.
Howitt  BE, Jia  Y, Sholl  LM, Barletta  JA.  Molecular alterations in partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma.  Thyroid. 2013;23(10):1256-1262.PubMedGoogle ScholarCrossref
29.
Xing  M.  Molecular pathogenesis and mechanisms of thyroid cancer.  Nat Rev Cancer. 2013;13(3):184-199.PubMedGoogle ScholarCrossref
30.
Yamashina  M.  Follicular neoplasms of the thyroid: total circumferential evaluation of the fibrous capsule.  Am J Surg Pathol. 1992;16(4):392-400.PubMedGoogle ScholarCrossref
31.
Mazzaferri  EL, Jhiang  SM.  Long-term impact of initial surgical and medical therapy on papillary and follicular thyroid cancer.  Am J Med. 1994;97(5):418-428.PubMedGoogle ScholarCrossref
32.
Nwatsock  JF, Taïeb  D, Zok  FD, Mundler  O.  Late recurrences of thyroid carcinoma 24 years after a complete remission: when monitoring should be stopped?  World J Nucl Med. 2012;11(1):42-43.PubMedGoogle ScholarCrossref
33.
Hauch  A, Al-Qurayshi  Z, Randolph  G, Kandil  E.  Total thyroidectomy is associated with increased risk of complications for low- and high-volume surgeons.  Ann Surg Oncol. 2014;21(12):3844-3852.PubMedGoogle ScholarCrossref
34.
Iyer  NG, Morris  LG, Tuttle  RM, Shaha  AR, Ganly  I.  Rising incidence of second cancers in patients with low-risk (T1N0) thyroid cancer who receive radioactive iodine therapy.  Cancer. 2011;117(19):4439-4446.PubMedGoogle ScholarCrossref
35.
Goffredo  P, Thomas  SM, Dinan  MA, Perkins  JM, Roman  SA, Sosa  JA.  Patterns of use and cost for inappropriate radioactive iodine treatment for thyroid cancer in the United States: use and misuse.  JAMA Intern Med. 2015;175(4):638-640.PubMedGoogle ScholarCrossref
Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    1 Comment for this article
    EXPAND ALL
    Progression of unresected noninvasive to invasive EFVPT and Interpretation of Fine Needle Aspiration Cytology
    KyoungWoo Kim | Inje University Seoul Paik Hospital
    As reported earlier, South Korea has an explosive growth rate in diagnosis of thyroid cancer in 2014. This article is very timely and welcomed.
    I just wonder 2 things as a clinician.
    First, we do fine needle aspiration (FNA) for thyroid nodules already found by thyroid sonography. Can FNA of thyroid be reported as non-invasive EFVPT and be reliable that we can just wait and see?
    Second, can unresected noninvasive EFVPT be progressed to invasive EFVPT?
    I hope FNA diagnosis of NEFVPT be accurate enough and the possibility to progress of unresected NEFVPT be ignorable that we can avoid
    overtreatment.
    CONFLICT OF INTEREST: None Reported
    READ MORE
    Original Investigation
    August 2016

    Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors

    Author Affiliations
    • 1Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
    • 2Anatomic Pathology, Department of Medicine (DIMES), University of Bologna School of Medicine, Bologna, Italy
    • 3Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia
    • 4Department of Surgical, Medical and Molecular Pathology, University of Pisa, Pisa, Italy
    • 5Southern California Permanente Medical Group, Woodland Hills
    • 6Department of Pathology, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
    • 7Department of Pathology, Mount Sinai Health System, New York, New York
    • 8Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France
    • 9Department of Pathology and Laboratory Medicine, Nara Hospital, Kindai University Faculty of Medicine, Ikoma-city, Japan
    • 10Department of Pathology, University of Michigan, Ann Arbor
    • 11Comprehensive Cancer Center, University of Michigan, Ann Arbor
    • 12Department of Pathology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
    • 13Department of Pathology, Hospital Alemao Oswaldo Cruz, Sao Paulo, Brazil
    • 14Department of Pathology, University of California San Francisco
    • 15Department of Pathology, University Health Network, Toronto, Ontario, Canada
    • 16Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston
    • 17Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania
    • 18Division of Endocrinology and Metabolism, New York University School of Medicine, New York
    • 19University of Wisconsin School of Medicine and Public Health, Madison
    • 20Department of Psychiatry, Massachusetts General Hospital, Boston
    • 21Department of Pathology, Massachusetts General Hospital, Boston
    • 22Department of Pathology Harvard Medical School, Boston, Massachusetts
    • 23Department of Oncology, University of Turin, Torino, Italy
    • 24University of Portsmouth, Department of Pathology, Queen Alexandra Hospital, Cosham, Portsmouth, United Kingdom
    • 25Department of Pathology and Laboratory Medicine, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts
    • 26Department of Endocrinology, Memorial Sloan Kettering Cancer Center, New York, New York
    • 27Thyroid Cancer Survivors Association Inc, Raleigh, North Carolina
    • 28General and Thyroid and Parathyroid Endocrine Surgery Division, Massachusetts Eye and Ear Infirmary, Boston
    • 29Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York
    JAMA Oncol. 2016;2(8):1023-1029. doi:10.1001/jamaoncol.2016.0386
    Abstract

    Importance  Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional thyroid cancer.

    Objective  To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.

    Design, Setting, and Participants  International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.

    Main Outcomes and Measures  Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.

    Results  Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median [range], 13 [10-26] years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name “noninvasive follicular thyroid neoplasm with papillary-like nuclear features” (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.

    Conclusions and Relevance  Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.

    ×