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: This paper aims to review controversies in the management of minimally invasive follicular thyroid carcinoma (MIFTC) and to reach an evidence-based consensus. MEDLINE search of the literature was conducted using keywords related to MIFTC. The search term was identified in the title, abstract, or medical subject heading. Available literature meeting the inclusion criteria were assigned the appropriate levels of evidence and recommendations in accordance with accepted international standards. Results were discussed at the 2013 Workshop of the European Society of Endocrine Surgeons devoted to MIFTC. Published papers on MIFTC present inadequate power with a III-IV level of evidence and C grade of recommendation. Several issues demanded a comparison of published studies from different medical reports regarding MIFTC definition, specimen processing, characteristics, diagnosis, prognoses, and therapy. As a consequence, it is difficult to make valuable statements on MIFTC with a sufficient recommendation rating. MIFTC diagnosis requires clearer, unequivocal, and reproducible criteria for pathologist, surgeons, and endocrinologists to use in the management of these patients. If the distinction between MIFTC and WIFTC cannot be made, an expert in thyroid pathologist should be consulted. According to published papers, the following conclusions can be drawn. (a) Candidates for hemithyroidectomy are MIFTC with exclusive capsular invasion, patients <45 years old at presentation, tumor size <40 mm, without vascular invasion, and without any node or distant metastases. (b) Candidates for total thyroidectomy are MIFTC in patients ≥45 years at presentation, tumor size ≥40 mm, vascular invasion present, positive nodes, and positive distant metastases. (c) In the absence of clinical evidence for lymph node metastasis, patients with MIFTC do not require prophylactic lymph node dissection. (d) Radio iodine ablation is indicated in elderly patients (>45 years), large tumor size (>40 mm), extensive vascular invasion, presence of distant synchronous or metachronous metastasis, positive nodes, and if recurrence is noted at follow-up.Langenbeck s Archives of Surgery 11/2013; · 1.89 Impact Factor
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ABSTRACT: Follicular variant of papillary thyroid carcinoma (FVPTC) is a common variant of papillary thyroid carcinoma (PTC), but the association between BRAF mutation and the clinicopathological and ultrasonographical characteristics of FVPTC has not been well studied. The aim of this study was to determine the significance of BRAF mutation in FVPTC. The medical records of the 137 patients with >5mm FVPTCs and known BRAF mutation status in the interested nodule were reviewed. BRAF mutation analysis was performed routinely and prospectively by Sanger sequencing. Clinicopathological and ultrasonographical characteristics were compared between BRAF mutation-positive and -negative groups. BRAF mutation was detected in 35 (25.5%) patients. The BRAF mutation-positive group was associated with smaller tumor size (P = 0.022), extrathyroidal extension (P = 0.001), multifocality (P = 0.046), and higher (III/IV) TNM stages (P = 0.005). In multivariable analysis, higher (III/IV) TNM stage was an independent predictive factor for BRAF mutation-positive status (adjusted OR 2.966, 95% CI 1.32-6.663). In diagnosis of FVPTC, the presence of BRAF mutation was associated with malignant features on ultrasonography (P < 0.001) and higher incidence of suspicious for malignancy or malignant diagnosis on the fine needle aspiration cytology (P = 0.023). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of US for detecting BRAF mutation were 82.9%, 57.8%, 40.3%, 90.8%, and 64.2%, respectively. Conclusions BRAF mutation in FVPTC is associated with unfavorable clinicopathological characteristics and malignant features on ultrasonography, and may be a potential prognostic factor as it is in classical PTC. This article is protected by copyright. All rights reserved.Clinical Endocrinology 02/2014; · 3.40 Impact Factor
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ABSTRACT: BRAF V600E mutation has been reported to show a high specificity for papillary thyroid carcinoma (PTC). Using this marker to upgrade 'indeterminate' or 'suspicious' thyroid fine needle aspiration (FNA) cytology to 'malignant' could potentially allow one-stage therapeutic total thyroidectomy. For a 14-month period, FNA cytology specimens in the Thy3-5 categories, which are the UK equivalents of indeterminate (Thy3a, atypical; Thy3f, follicular), suspicious for malignancy (Thy4) and malignant (Thy5) in the Bethesda System, underwent BRAF mutation testing by melt curve analysis. The results were correlated with histology. We tested 123 cytology specimens of which 12 (9.8%) failed. The BRAF mutation rate in the remainder was 16.2% (18/111), with 93 showing the wild-type. Seventeen mutations were V600E and one was non-V600E. The rate of mutation increased significantly (P < 0.0001 if Thy3a and Thy3f were combined) with the cytology category: 1/42 Thy3a (2.4%), 1/36 Thy3f (2.8%), 4/15 Thy4 (26.7%), 12/18 Thy5 (66.7%). All BRAF mutations correlated with PTC on histology, except for one recurrent PTC without histology. One mutation-positive case with Thy3a cytology showed the target lesion to be a 10-mm follicular adenoma on histology with an immediately adjacent 4-mm micro-PTC, in a patient who did not require total thyroidectomy. BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, but we suggest that it would be most appropriate and cost-effective for Thy4/suspicious cases, for which it could enable one-stage therapeutic surgery in the context of multidisciplinary discussion. In contrast, the sensitivity is low and there is no role for avoiding diagnostic thyroid surgery if wild-type BRAF is found.Cytopathology 01/2014; · 1.71 Impact Factor