Encapsulated papillary thyroid carcinoma: a clinico-pathologic study of 106 cases with emphasis on its morphologic subtypes (histologic growth pattern).
ABSTRACT Encapsulated papillary thyroid carcinoma (EPTC) can have a histologic growth pattern similar to the one seen in classical papillary thyroid carcinoma (PTC) or akin to the follicular variant of PTC (FVPTC). This study aims to assess the behavior of EPTC according to its growth pattern.
All cases of thyroid carcinomas treated at our institution between 1980 and 2000 were reviewed and reclassified according to current histopathologic criteria.
After review by two pathologists, 106 cases were included. Forty-three (41%) of the cases were identified as encapsulated classical PTC (E-CPTC) and 63 (59%) as encapsulated FVPTC (E-FVPTC). E-FVPTC had a higher rate of vascular invasion (16/63; 25%) than E-CPTC (2/43; 5%) (p = 0.007). In contrast, E-CPTC had a higher frequency of capsular invasion (28/43; 65%) than E-FVPTC (24/63, 38%) (p = 0.01). The lymph node metastatic rate was significantly higher in E-CPTC (11/43, 26%) compared to E-FVPTC (2/63, 3%) (p = 0.0014). All 34 noninvasive E-FVPTC lacked evidence of nodal metastases while 4 of 15 (27%) noninvasive E-CPTC presented with nodal disease (p = 0.006). Distant metastasis occurred only in four cases of E-FVPTC at presentation. These four FVPTC had extensive capsular and/or vascular invasion and no nodal disease. None of noninvasive EPTC recurred, including 30 patients treated by lobectomy without radioactive iodine (RAI) therapy (median follow-up: 8.9 years).
E-CPTC resembles classical PTC in its propensity to metastasize to lymph nodes and its vascular/capsular invasive pattern while E-FVPTC behaves more like follicular carcinoma/adenoma group of tumors. Meticulous search for capsular and vascular invasion can reliably predict the metastatic potential of E-FVPTC but not of E-CPTC. The latter can therefore be treated like unencapsulated classical PTC. Noninvasive E-FVPTC could be managed like minimally invasive follicular carcinoma by lobectomy without RAI therapy. Invasive E-FVPTC seem quite indolent if no distant metastases are found at presentation.
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ABSTRACT: Background: The diagnosis of the follicular variant of papillary thyroid carcinoma (FVPTC) is increasingly common. Recent studies suggest that FVPTC is heterogeneous and comprised of multiple tumor types with distinct biological behaviors and underlying genetics. Objectives: 1) Identify the prevalence of mutations and gene fusions in known oncogenes in a panel representative of the common spectrum of FVPTC diagnosed at an academic medical center. 2) Correlate clinical and pathological features obtained at initial diagnosis with tumor genotype. Materials and Methods: We performed SNaPshot genotyping on a panel 129 FVPTC ≥ 1 cm for 90 point mutations or small deletions in known oncogenes and tumor suppressors, and identified gene fusions using an anchored multiplex PCR assay targeting a panel of rearranged oncogenes. Results: We identified a mutation or gene fusion in 70% (89/127) of cases. Mutations targeting the RAS family of oncogenes were the most frequently observed class of alterations, present in 36% (46/127) of cases, followed by BRAF mutation, present in 30% (38/127). We also detected oncogenic rearrangements not previously associated with FVPTC, including TFG-ALK and CREB3L2-PPARγ. BRAF mutation was significantly associated with unencapsulated tumor status. Conclusions: These data support the hypothesis that FVPTC is composed of distinct biological entities, with one class being identified by BRAF mutation, and support the use of clinical genotyping assays that detect a diverse array of rearrangements involving ALK and PPARγ. Additional studies are necessary to identify genetic drivers in the 30% of FVPTC with no known oncogenic alteration, and to better predict behavior in tumors with known genotype.Journal of Clinical Endocrinology & Metabolism 08/2014; DOI:10.1210/jc.2014-2611 · 6.31 Impact Factor
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ABSTRACT: Follicular variant of papillary thyroid cancer (FVPTC) is the most common and fastest growing subtype of papillary thyroid cancer (PTC) with features of both PTC and follicular thyroid cancer (FTC). The purpose of this study was to determine the patient and tumor features associated with lymph node metastases (LNM) in FVPTC. This was a retrospective review of adult (a parts per thousand yen18) patients with histologically confirmed diagnoses of FVPTC within the SEER database between 1988 and 2009. LNM were defined by at least two lymph nodes with metastatic disease. To determine factors associated with LNM, we constructed a multivariate logistic regression model from significant variables (p < 0.05) identified on univariate analysis. Similarly, we used a Cox proportional hazards model to understand the relative importance of LNM in determining disease-specific mortality (DSM). Of the 20,357 cases of FVPTC with lymph node data available, 1,761 (8.7%) had LNM; 61.1% of these LNM were located in the central neck and 38.9% were in the lateral neck. Extrathyroidal extension (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.2-3.0, p < 0.01) and multifocality (OR 3.0, 95% CI 2.5-3.6, p < 0.01) were the strongest predictors of LNM. Importantly, LNM did not independently predict DSM (p = 0.52). Tumor size > 4 cm (hazards ratio [HR] 5.3, 95% CI 2.2-12.8, p < 0.01) and extrathyroidal extension (HR 8.2, 95% CI 3.0-22.0, p < 0.01) were the strongest predictors of DSM. LNM occur in less than 10% of patients with FVPTC but do not impact DSM. Instead, DSM in FVPTC is related to size and local invasion.Annals of Surgical Oncology 08/2014; 22(1). DOI:10.1245/s10434-014-3964-3 · 3.94 Impact Factor
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ABSTRACT: There are several thyroid lesions that have been reported to be precursor, precancerous, or premalignant forms of, or predisposing factors for thyroid carcinoma. These lesions include normal thyroid with radiation history and chronic inflammation such as autoimmune thyroiditis, solid cell nest, hyperplastic adenomatous nodule, dyshormonogenetic goiter, follicular adenoma, atypical adenoma, borderline malignancy (follicular tumor of uncertain malignant potential and well-differentiated tumor of uncertain malignant potential), and some extremely low-grade thyroid neoplasms currently labeled as cancer including papillary microcarcinoma, capsular invasion only follicular carcinoma, and encapsulated papillary carcinoma. This article briefly reviews these lesions as possible precursor lesions of thyroid carcinomas, an important initial step of carcinogenesis or an early phase of progression in the multistep carcinogenesis theory.