Thyroid gland
Papillary carcinoma
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP)

Authors: Rachel Jug, M.D., David Poller, M.D., Xiaoyin "Sara" Jiang, M.D. (see Authors page)

Revised: 13 February 2017, last major update February 2017

Copyright: (c) 2016-2017, PathologyOutlines.com, Inc.

PubMed Search: noninvasive follicular thyroid neoplasm with papillary-like nuclear features
Cite this page: Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidglandNIFTP.html. Accessed August 19th, 2017.
Definition / general
  • Formerly known as "noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC)"
  • Suggested to rename lesion to NIFTP based on an 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 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)
  • NIFTP accounts for roughly 25% of all PTC or 20% of all thyroid cancers (although NIFTP should now be considered a noncancer, JAMA Oncol 2016;2:1005)
Diagrams / tables

Images hosted on PathOut server:

Contributed by David Poller, M.D.:

Mutations in various types of thyroid tumors

Putative molecular pathogenesis of thyroid tumors

Indeterminate cytological diagnosis

Diagnosis
Pathologic diagnostic criteria:
  • Inclusion criteria
    • Major features:
      • Encapsulation or clear demarcation
      • Follicular growth pattern with less than 1% papillae
      • 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)
Prognostic factors
  • Excellent, based on an international, multidisciplinary, retrospective study in which all 109 participants with noninvasive 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)
Gross description
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 & 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
Scroll to see all images.

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D.:

Circumscribed follicular patterned nodule

Tumor interface with a thin capsule

Microfollicular pattern

Evident major and minor diagnostic features

Dark colloid with frequent scalloping and clefting


Free floating of small tumor fragment in vascular lumen

Small piece of tumor floats in vascular lumen

Processing artifact with distorted nuclei

Distorted nuclei due to technical / processing artifact

Tissue degeneration
often induces
formation of vesicular
appearing nuclei



Contributed by Rachel Jug, M.D.:

Low power (2×) H&E images demonstrating clear circumscription of the encapsulated lesion with a predominantly follicular growth pattern


High power (40×) H&E images demonstrating nuclear features of PTC



Images hosted on other servers:

Encapsulated follicular patterned lesion

Nuclear features

Virtual slides

Images hosted on other servers:

Various NIFTP virtual
slides, contributed by
the NIFTP consortium

Cytology description
  • FNA 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 to classical type papillary carcinoma and papillae are absent
  • Generally on FNA diagnosed as follicular lesion of unknown significance / FLUS, suspicious for follicular neoplasia, follicular neoplasia
  • Colloid may be present
  • Cannot distinguish EFVPTC, invasive, vs. NIFTP on cytology, as cannot evaluate capsule on FNA although NIFTP's have few or no intranuclear inclusions and do not normally show papillae on FNA
  • References: Cancer Cytopathol 2016;124:181, Hum Pathol 2016;54:134, Am J Clin Pathol 2015;144:850, Cancer 2016;124:699
Molecular / cytogenetics description