Follicular Variant of Papillary Thyroid Cancer<subtitle>Encapsulated, Nonencapsulated, and Diffuse: Distinct Biologic and Clinical Entities</subtitle>

Abstract

Objective To examine genotypic and clinical differences between encapsulated, non-encapsulated and diffuse follicular variant of papillary thyroid carcinoma (EFVPTC, NFVPTC, diffuse FVPTC), in order to characterize the entities and identify predictors of their behavior. Design Retrospective chart review and molecular analysis. Setting Referral center of a university hospital. Patients The pathology of 484 consecutive patients with differentiated thyroid cancer who underwent surgery by the 3 members of the NYU Endocrine Surgery Associates from January 1, 2007 to August 1, 2010 was reviewed. Forty-five patients with FVPTC and in whom at least 1 central compartment lymph node was removed were included. Main Outcome Measures Patients with FVPTC were compared in terms of age, gender, tumor size, encapsulation, extrathyroid extension, vascular invasion, central nodal metastases, and the presence or absence of mutations in BRAF, H-RAS 12/13, K-RAS 12/13, N-RAS 12/13, H-RAS 61, K-RAS 61, N-RAS 61 and RET/PTC1. Results No patient with EFVPTC had central lymph node metastasis and in this group, 1 patient (4.5%) had a BRAFV600E mutation and 2 patients (9%) had RAS mutations. Of the patients with NFVPTC, 0 had central lymph node metastasis (p=1) and 2 (11%) had a BRAFV600E mutation (p=0.59). Of the patients with diffuse FVPTC, all had central lymph node metastasis (p=0.0001) and 2 (50%) had a BRAFV600E mutation (p=0.12). Conclusions FVPTC consists of several distinct subtypes. Diffuse FVPTC seems to present and behave in a more aggressive fashion. It has a higher rate of central nodal metastasis and BRAFV600E mutation in comparison to EFVPTC and NFVPTC. Both EFVPTC and NFVPTC behave in a similar fashion. The diffuse infiltrative pattern and not just presence/absence of encapsulation seems to determine the tumor phenotype. Understanding the different subtypes of FVPTC will help guide appropriate treatment strategies.

The Impact of Noninvasive Follicular Variant of Papillary Thyroid Carcinoma on Rates of Malignancy for Fine-Needle Aspiration Diagnostic Categories

“…In the past decade, it has been shown that FVPTC can be further subclassified based on growth pattern and molecular alterations. FVPTCs that demonstrate infiltrative growth have a significant rate of lymph node metastases, a potential to recur, and have a BRAF V600E mutation frequency of roughly 25% (2)(3)(4). In contrast, encapsulated, partially-encapsulated, or well-circumscribed FVPTCs without capsular penetration or lymphovascular invasion (i.e., noninvasive tumors) have very little, if any, metastatic potential or recurrence risk (3,5,6).…”

Prevalence of Contralateral Tumors in Patients with Follicular Variant of Papillary Thyroid Cancer

“…[10][11][12][13][14] These tumors are indolent compared with tumors with an infiltrative growth pattern, and have virtually no metastatic potential or recurrence risk in the absence of invasive growth. [15][16][17][18] For example, Liu and colleagues 18 found significantly greater rates of regional lymph node metastases among patients with infiltrative/diffuse neoplasms compared with their encapsulated counterparts (65% vs 5%; p < 0.0001). Recently, Nikiforov and colleagues 19 proposed a nomenclature revision for patients with noninvasive fvPTC, suggesting these cases should be termed noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) to reflect a more indolent phenotype and reduce overtreatment of these lesions.…”

Rare Late Mandibular Metastasis in Follicular Variant of Papillary Carcinoma Thyroid: ‘Resurgence of the Sleeping Tumour’

“…The propensity of occurrence of thyroid carcinomas is two to four times more in females as compared to males with a median age at diagnosis being 45-50 years [1,2]. Papillary thyroid carcinoma (PTC) is the most common histological type of thyroid cancer and accounts for more than 80 % of thyroid malignancies.…”

“…It was subsequently confi rmed by Lindsay, Chen and Rosai as an independent entity with typical nuclear features and follicular growth pattern. FVPTC further has histological variants namely, completely encapsulated form, well circumscribed form, and infi ltrative form, the last being the most aggressive [2,4]. The encapsulated variant is relatively more prevalent than the other sub-type and is non-aggressive in nature.…”