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

“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”

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 .

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 19-68% Increase in incidence attributed to the rapid growth of ultrasound and fine-needle aspiration use Haugen, B. R. (2015). THYROID. 2015 American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer, 26 (1).

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%)

Follicular variant of papillary Ca thyroid 2nd most common subtype variant ~4.9-41.2% 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 http://www.pathologyoutlines.com/topic/thyroidglandNIFTP.html

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

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).

- 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

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

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

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

What are the clinical implications?

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

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

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 .

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

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”

Questions are welcome

Reference Esserman, L. J. (2014). Lancet Oncol.. Addressing overdiagnosis and overtreatment in cancer: a prescription for change, 15 . Haugen, B. R. (2015). THYROID. 2015 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 http://www.pathologyoutlines.com/topic/thyroidglandNIFTP.html 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

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