1. Follicular variant of papillary thyroid carcinoma
It’s Not Cancer:
Follicular variant of papillary thyroid carcinoma
Winchester Kwok, Princess Margaret Hospital

2. “An international panel of doctors has decided that a type of tumor that was classified as a cancer is not a cancer at all.”
Encapsulated follicular variant of papillary thyroid carcinoma was rename as  noninvasive follicular thyroid neoplasm with papillary-like nuclear features, or Niftp, which pronounced as “Nift-P”

3. Background
On March 8–9, 2012, the National Cancer Institute convened a conference
Problem of cancer overdiagnosis
When tumors that would otherwise not become symptomatic are identified and treated.
When this overdiagnosis is not recognized, it can lead to overtreatment.
Esserman, L. J. (2014). Lancet Oncol.. Addressing overdiagnosis and overtreatment in cancer: a prescription for change, 15 .

4. Ca thyroid Yearly incidence has nearly tripled from 1975 to 2009
Yet death rate remained constant
25%of the new thyroid cancers diagnosed in 1988– 1989 were <=1cm compared with 39% of the new thyroid cancer diagnoses in 2008–2009
Prevalence of palpable thyroid nodule 1-5% vs. USG %
Increase in incidence attributed to the rapid growth of ultrasound and fine-needle aspiration use
Haugen, B. R. (2015). THYROID American Thyroid Association Management Guidelines for Adult Patients with
Thyroid Nodules and Differentiated Thyroid Cancer, 26 (1).

5. Differentiated Ca Thyroid
Papillary thyroid tumor (75-85%)
- arise from follicular cells with papillary architecture - more than 10 microscopic variants
Follicular thyroid tumor (10-20%)

6. Follicular variant of papillary Ca thyroid
2nd most common subtype variant
~ % of PTC
Encapsulated or non encapsulated; invasive or non invasive
Diagnosis could have interobserver difference
Jug, R. (2016). Papillary carcinoma Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Retrieved October 1, 2016 from

7. 36 studies published from 2003-2014 was reviewed
Comparing FVPTC and classical PTC
FVPTC was associated with statistically significant less
extrathyroid extension
lymph node metastasis
recurrence
BRAF mutation
FVPTC had more indolent behavior and likely a genetically distinct entity from classical papillary Ca thyroid

8. Median follow up: 10.8 years recurrence:1 distant metastasis: 0
A study published in 2006
69 patient with FVPTC
Median follow up: 10.8 years
recurrence:1
distant metastasis: 0
In a subgroup of patient (n=31) with non invasive encapsulated FVPTC treated with lobectomy only without RAI
recurrence/ lymph node metastasis: 0
Liu, J. (2006). Follicular Variant of Papillary Thyroid Carcinoma A Clinicopathologic Study of a Problematic Entity. CANCER, 107(6).

9. - Published in 4/2016
Retrospective study by The Endocrine Pathology Society working group including 28 pathologists/ endocrinologists/ surgeons from 7 countries and 4 continents
Total 268 encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC) from 13 institutions
Divided into 2 groups: group 1: non invasive EFVPTC treated with surgery only without RAI group 2: EFVPTC with vascular invasion +- tumor capsule invasion

10. 109 patient with non invasive EFVPTC treated without RAI
median 13.0 (10-26) years of follow up
Adverse events: 0

11. Scanned slides were reviewed and new diagnostic criteria was published
Lack of invasion, follicular growth pattern, nuclear features of PTC

12. Revision of nomenclature
Encapsulated follicular variant of papillary thyroid carcinoma
 Noninvasive Follicular Thyroid Neoplasm with Papillary-like Nuclear Features (NIFTP)

13. What are the clinical implications?

14. Due to a great degree of cytological difficulty in interpretation, >90% of EFVPTC was put into Bethesda Categories III/ IV/ V during initial FNAC cytology report

18. In the Past… X RAI No longer indicated By BTA guidelines:
NIFTP with size >=4cm
or size 1-4cm
By ATA guidelines
 RAI +- Completion thyroidectomy
X RAI No longer indicated

19. In the Present… ~45000 patient per year worldwide
Decrease the use of RAI +- completion thyroidectomy and related complications
Decrease psychological impact to patient with diagnosis of cancer
Decrease need for long term surveillance
Decrease overall cost of health care surveillance (Based on US cost, no RAI alone would save ~$5000-$8500/ patient)
~45000 patient per year worldwide
Nikiforov, Y. E. (2016). Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncology, 2 (8).
Perros, P. (2014). British Thyroid Association Guidelines for the Management of Thyroid Cancer. CLINICAL ENDOCRINOLOGY, 81 .

20. In the future… Training and update of pathologists
More updated guidelines will be needed for clinicians
Increase global awareness of cancer overdiagnosis and efforts in reviewing current clinicopathology diagnosis in lesions with indolent behaviors

21. Take Home Message
Encapsulated follicular variant of papillary thyroid carcinoma no longer considered as malignant lesions Renamed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features
Problem of nowadays worldwide medical care: overdiagnosis of cancer and over treatment “First - do - harm”

22. Questions are welcome

23. Reference
Esserman, L. J. (2014). Lancet Oncol.. Addressing overdiagnosis and overtreatment in cancer: a prescription for change, 15 .
Haugen, B. R. (2015). THYROID American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer, 26 (1).
Jug, R. (2016). Papillary carcinoma Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Retrieved October 1, 2016 from
Yang, J. (2015). Comparison of the clinicopathological behavior of the follicular variant of papillary thyroid carcinoma and classical papillary thyroid carcinoma: A systematic review and meta-analysis. MOLECULAR AND CLINICAL ONCOLOGY, 3 
Liu, J. (2006). Follicular Variant of Papillary Thyroid Carcinoma A Clinicopathologic Study of a Problematic Entity. CANCER, 107(6).
Nikiforov, Y. E. (2016). Nomenclature Revision for Encapsulated Follicular Variant of Papillary Thyroid Carcinoma A Paradigm Shift to Reduce Overtreatment of Indolent Tumors. JAMA Oncology, 2 (8).
Perros, P. (2014). British Thyroid Association Guidelines for the Management of Thyroid Cancer. CLINICAL ENDOCRINOLOGY, 81 .
Kolata, G. (2016, April 14). It’s Not Cancer: Doctors Reclassify a Thyroid Tumor. The New York Times

26. European consensus for the management of patients with differentiated thyroid carcinoma of the follicular epithelium 2006