title: Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma: A Paradigm Shift to Reduce Overtreatment of Indolent Tumors.
abstract: 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.
  
  
  
  To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Raja R
authors.initials: RR
authors.lastname: Seethala
authors.affiliation: Anatomic Pathology, Department of Medicine (DIMES), University of Bologna School of Medicine, Bologna, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Tallini
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia.
authors.forename: Zubair W
authors.initials: ZW
authors.lastname: Baloch
authors.affiliation: Department of Surgical, Medical and Molecular Pathology, University of Pisa, Pisa, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
authors.affiliation: Southern California Permanente Medical Group, Woodland Hills.
authors.forename: Lester D R
authors.initials: LD
authors.lastname: Thompson
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
authors.affiliation: Department of Pathology, Mount Sinai Health System, New York, New York.
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Wenig
authors.affiliation: Department of Medical Biology and Pathology, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: Abir
authors.initials: A
authors.lastname: Al Ghuzlan
authors.affiliation: Department of Pathology and Laboratory Medicine, Nara Hospital, Kindai University Faculty of Medicine, Ikoma-city, Japan.
authors.forename: Kennichi
authors.initials: K
authors.lastname: Kakudo
authors.affiliation: Department of Pathology, University of Michigan, Ann Arbor|Department of Pathology, University of Michigan, Ann Arbor
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Giordano
authors.affiliation: Department of Pathology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil|Department of Pathology, University of Sao Paulo School of Medicine, Sao Paulo, Brazil
authors.forename: Venancio A
authors.initials: VA
authors.lastname: Alves
authors.affiliation: Department of Pathology, University of California San Francisco.
authors.forename: Elham
authors.initials: E
authors.lastname: Khanafshar
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Sylvia L
authors.initials: SL
authors.lastname: Asa
authors.affiliation: Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston.
authors.forename: Adel K
authors.initials: AK
authors.lastname: El-Naggar
authors.affiliation: Biostatistics Facility, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors.forename: William E
authors.initials: WE
authors.lastname: Gooding
authors.affiliation: Division of Endocrinology and Metabolism, New York University School of Medicine, New York.
authors.forename: Steven P
authors.initials: SP
authors.lastname: Hodak
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison.
authors.forename: Ricardo V
authors.initials: RV
authors.lastname: Lloyd
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital, Boston.
authors.forename: Guy
authors.initials: G
authors.lastname: Maytal
authors.affiliation: Department of Pathology, University Health Network, Toronto, Ontario, Canada.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Mete
authors.affiliation: Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Marina N
authors.initials: MN
authors.lastname: Nikiforova
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston
authors.forename: Vania
authors.initials: V
authors.lastname: Nosé
authors.affiliation: Department of Oncology, University of Turin, Torino, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: University of Portsmouth, Department of Pathology, Queen Alexandra Hospital, Cosham, Portsmouth, United Kingdom.
authors.forename: David N
authors.initials: DN
authors.lastname: Poller
authors.affiliation: Department of Pathology, Massachusetts General Hospital, Boston|Department of Pathology, University of California San Francisco.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sadow
authors.affiliation: Department of Pathology and Laboratory Medicine, Tufts University School of Medicine, Tufts Medical Center, Boston, Massachusetts.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Tischler
authors.affiliation: Department of Endocrinology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.affiliation: Thyroid Cancer Survivors Association Inc, Raleigh, North Carolina.
authors.forename: Kathryn B
authors.initials: KB
authors.lastname: Wall
authors.affiliation: Department of Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia.
authors.forename: Virginia A
authors.initials: VA
authors.lastname: LiVolsi
authors.affiliation: General and Thyroid and Parathyroid Endocrine Surgery Division, Massachusetts Eye and Ear Infirmary, Boston.
authors.forename: Gregory W
authors.initials: GW
authors.lastname: Randolph
authors.affiliation: Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Ghossein
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D002291:Carcinoma, Papillary; D005260:Female; D006801:Humans; D008297:Male; D000069342:Medical Overuse / Q000517:prevention & control*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D012189:Retrospective Studies; D009626:Terminology as Topic; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D016606:Thyroid Nodule / Q000145:classification / Q000175:diagnosis / Q000473:pathology*; D055815:Young Adult