Thyroid & parathyroid

Low risk thyroid tumors


Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Rachel Jug, M.B.B.Ch., B.A.O.

Last author update: 10 May 2018
Last staff update: 21 September 2023 (update in progress)

Copyright: 2016-2023,, Inc.

PubMed Search: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features

Rachel Jug, M.B.B.Ch., B.A.O.
Page views in 2022: 33,049
Page views in 2023 to date: 36,038
Cite this page: Jug R, Poller D, Jiang X. NIFTP. website. Accessed November 29th, 2023.
Definition / general
  • Formerly known as "noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC)"
  • Suggested to rename lesion to NIFTP based on international, multicenter consensus study showing evidence for indolent biological behavior (lack of metastasis or recurrence) (Mod Pathol 2016;29:698)
  • Discrepancies commonly affecting nuclear feature evaluation were simplified and criteria were established (see Microscopic (histologic) description below) to provide reproducible standards for separating NIFTP from benign hyperplastic nodules and follicular adenoma morphologically with an overall classification accuracy of 94.3% (JAMA Oncol 2016;2:1023)
Essential features
  • Encapsulated / circumscribed neoplasm with follicular growth pattern and nuclear features of papillary thyroid carcinoma
  • Diagnosis of NIFTP requires surgical excision specimen with complete evaluation of tumor to normal interface to exclude capsular invasion
  • Most commonly associated molecular alterations are RAS mutations
  • Indolent disease course with excellent long term survival (following surgical excision; lobectomy / partial thyroidectomy sufficient)
  • NIFTP is considered a borderline RAS lineage tumor between follicular adenoma and follicular carcinoma or invasive EFVPTC
Diagrams / tables

Contributed by David Poller, M.D.
Missing Image

Mutations in various types of thyroid tumors

Missing Image

Putative molecular pathogenesis of thyroid tumors

Missing Image

Indeterminate cytological diagnosis

Images hosted on other servers:
Missing Image

NIFTP incidence

Missing Image

Diagnostic algorithm

Missing Image

History of NIFTP

Pathologic diagnostic criteria:
  • Inclusion criteria
    • Major features:
      • Encapsulation or clear demarcation
      • Follicular growth pattern with less than 1% papillae (see comment below)
      • If solid, trabecular or insular patterns seen; these in total should be less than 30% of the total tumor volume
      • No psammoma bodies
      • Nuclear features of papillary thyroid carcinoma (enlargement, crowding / overlapping, elongation, irregular contours, grooves, pseudoinclusions, chromatin clearing), nuclear score should be 2 or 3
    • Minor features:
      • Dark colloid
      • Irregularly shaped follicle
      • "Sprinkling sign"
      • Follicles cleft from stroma
      • Multinucleated giant cells within follicles
  • Exclusion criteria:
    • Any capsular or vascular invasion but if the whole capsule has not been examined thoroughly then the default diagnosis is still noninvasive encapsulated FVPTC (EFVPTC) and it is NOT a NIFTP
    • True papillary structures in more than 1% of tumor volume, psammoma bodies, infiltrative border
    • Tumor necrosis (not associated with FNA), increased mitoses (defined as at least 3 per 10 HPF)
    • Cell / morphological characteristics of any other papillary thyroid carcinoma variant (e.g., tall cell, columnar cell, cribriform morular, diffuse sclerosing, etc.) or oncocytic lesion (JAMA Oncol 2016;2:1023)
  • Additional exclusion criteria (2017, Hum Pathol 2018 Jan 12 [Epub ahead of print], Pathol Int 2018 Apr 19 [Epub ahead of print])
    • No papillae
    • No BRAFV600E and TERT promoter mutations
    • No distant metastasis
  • Diagnosis of NIFTP is possible only on surgical samples because it requires careful capsule evaluation
  • No reliable preoperative modalities (sonography, fine needle aspiration cytology (FNAC), molecular testing) are available at this time
Radiology description
  • Wider than tall shape, smooth borders, occurrence in multinodular glands and no calcifications (Diagn Cytopathol 2018;46:139)
  • Perinodular and intranodular Doppler flow patterns, minimal Doppler flow grade
  • Similar to follicular adenoma and minimally invasive follicular carcinoma (Diagn Cytopathol 2017;45:533)
Radiology images

Images hosted on other servers:
Missing Image Missing Image Missing Image


Prognostic factors
  • Excellent, based on an international, multidisciplinary, retrospective study in which all 109 participants with noninvasive follicular variant of papillary thyroid carcinoma (EFVPTC) were alive with no evidence of disease at a median followup time of 13 years (JAMA Oncol 2016;2:1023, Mod Pathol 2016;29:698)
Case reports
Gross description
Gross images

Images hosted on other servers:
Missing Image

Gross and histology of EFVPTC

Microscopic (histologic) description
  • Nuclear features of papillary thyroid carcinoma present
    • Each category is assigned a score of 0 or 1, resulting in an overall score between 0 - 3, where a total of 0 - 1 is not diagnostic of NIFTP and 2 - 3 is diagnostic of NIFTP
    • Size and shape: nuclear enlargement, overlapping, crowding, elongation
    • Nuclear membrane irregularities: irregular contours, grooves, pseudoinclusions
    • Chromatin characteristics: clearing with margination, glassy nuclei
  • Fibrous capsule may be thick, thin, partial or the lesion may be well circumscribed / clearly demarcated from adjacent thyroid tissue
  • Follicular growth pattern may be microfollicular, normofollicular or macrofollicular with abundant colloid (JAMA Oncol 2016;2:1023)
Microscopic (histologic) images

Contributed by Andrey Bychkov, M.D., Ph.D. and Rachel Jug, M.B.B.Ch.

Circumscribed follicular patterned nodule

Tumor interface with a thin capsule

Microfollicular pattern

Major and minor diagnostic features

Dark colloid with scalloping and clefting

Free floating tumor fragment in vessel

Small piece of tumor floats in vascular lumen

Processing artifact with distorted nuclei

Distorted nuclei due to artifact

Vesicular-like nuclei due to tissue degeneration

Clear circumscription of the encapsulated lesion with a predominantly follicular growth pattern

Clear circumscription of the encapsulated lesion with a predominantly follicular growth pattern

Nuclear features of PTC

Images hosted on other servers:
Missing Image

Noninvasive follicular thyroid neoplasm

Missing Image Missing Image

Low power

Missing Image Missing Image

Medium power

Missing Image

5.6 cm NIFTP

Missing Image Missing Image Missing Image Missing Image

High power

Missing Image


Missing Image


Missing Image Missing Image


Missing Image


Encapsulated follicular patterned lesion

Nuclear features

Cytology description
  • FNAC samples are usually hypercellular with neoplastic cells possibly with focal nuclear features of papillary thyroid carcinoma arranged in microfollicles
  • Nuclear features are subtler than those of conventional papillary thyroid carcinoma; nuclear inclusions are very infrequent or absent as compared with classical type papillary carcinoma and papillae are absent
  • Colloid may be present
  • Cannot distinguish invasive encapsulated follicular variant of papillary thyroid carcinoma from NIFTP on cytology because the capsule cannot be evaluated by FNA; however NIFTP has few intranuclear inclusions and does not normally show papillae on FNA
  • Most NIFTP cases are clustered within the categories follicular neoplasm (FN) / suspicious for follicular (SFN), atypia of unknown significance (AUS) / follicular lesion of unknown significance (FLUS) and suspicious for malignancy
  • In case of cytologic features suggestive of FVPTC / NIFTP, optional notes in cytologic diagnosis may be used to acknowledge NIFTP: "Although the architectural features suggest a follicular neoplasm (or another Dx category), some nuclear features raise the possibility of an invasive FVPTC or its recently described indolent counterpart, NIFTP; definitive distinction among these entities is not possible on cytologic material" (Thyroid 2017;27:1341)
  • References: Cancer Cytopathol 2016;124:181, Hum Pathol 2016;54:134, Am J Clin Pathol 2015;144:850, Cancer 2016;124:699
Cytology images

Images hosted on other servers:
Missing Image Missing Image Missing Image

Microfollicular pattern, nuclear enlargement

Missing Image

Microfolliclar pattern

Missing Image

Microfollicles, nuclear grooves

Missing Image

Enlarged nuclei

Molecular / cytogenetics description

Nomenclature change for thyroid tumors: NIFTP (2017) by Prof. Yuri Nikiforov, University of Pittsburg

NIFTP by R. Ghossein (2020)

Diagnostic dilemmas in NIFTP by N. Cipriani (2020)

Board review style question #1
    Which of the following mutations is most commonly associated with NIFTP?

  1. BRAFV600E
  2. PAX8 / PPAR gamma rearrangement
  3. PIK3CA
  4. RAS family
  5. TERT promoter
Board review style answer #1
D. RAS family. NIFTP shares molecular alterations similar to those seen in follicular lesions (follicular adenoma and follicular carcinoma).

Comment Here

Reference: NIFTP
Board review style question #2
    Which of the following features differentiates a PTC from a NIFTP?

  1. Follicular growth pattern
  2. Nuclear elongation
  3. Nuclear grooves
  4. Thick colloid
  5. True papillae
Board review style answer #2
E. True papillae. The presence of any true papillae is an exclusion criterion for making a diagnosis of NIFTP. Other exclusion criteria include capsular invasion, increased mitotic rate and tumor necrosis.

Comment Here

Reference: NIFTP
Back to top
Image 01 Image 02