Although histologic definition of follicular thyroid lesions is readily available, application of the diagnostic criteria and personal experience may lead to disagreement among pathologists. To investigate interobserver variation in assessment of encapsulated follicular lesions, eight pathologists (four American and four Japanese) reviewed the same hematoxylin and eosin-stained slide of each of 21 cases of thyroid lesions showing encapsulation and follicular growth pattern. In 10% of the cases, there was complete agreement. At least seven pathologists agreed on the diagnosis in 29% of the cases, and at least six in 76% of the cases. American and Japanese pathologists agreed among themselves in 33% and 52% of cases, respectively. The frequency of diagnosis of adenomatous goiter among Japanese pathologists (31%) was considerably higher than that among American pathologists (6%). In contrast, the frequency of diagnosis (25%) of papillary carcinoma among American pathologists was considerably higher than that (4%) among Japanese pathologists. Our analysis revealed three main factors affecting observer variation: 1) interpretation of the significance of microfollicles intimately related to capillaries within the tumor capsule, 2) evaluation of what constituted the type of nuclear clearing indicative of papillary carcinoma, and 3) absence of clear morphologic criteria for separation of adenomatous goiter and follicular adenoma. To reduce observer variation of encapsulated follicular lesions, it will be necessary to provide more explicit criteria for diagnosis.

Recent studies have demonstrated that BRAFV600E mutation is a common event in papillary thyroid carcinoma and a majority of these lesions have shown a direct relationship between BRAFV600E mutation and aggressive characteristics, including a worse patient prognosis. However, there are no studies from Japan regarding this issue in a large series with adequate postoperative follow-up periods. We investigated BRAFV600E mutation in 631 patients with papillary carcinoma having median follow-up periods of 83 months. The prevalence of BRAFV600E mutation was 38.4%, and the rate was higher in carcinoma larger than 1.0 cm but did not successively increase with tumor size. Furthermore, the prevalence did not significantly increase in cases demonstrating high-risk biological features such as clinically apparent lymph node metastasis, massive extrathyroid extension, advanced age, distant metastasis at surgery, and advanced Stage. The disease-free survival of patients with BRAFV600E mutation did not differ from that of those without BRAFV600E mutation. These findings indicate that, although BRAFV600E mutation may play some roles in local carcinoma development, there is no evidence that BRAFV600E mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan.

Context: IgG4-related sclerosing disease is a new syndrome characterized by high serum IgG4 levels and increased IgG4-positive plasma cells in the involved organs. Recently the first description was made by our group of a subsection of Hashimoto’s autoimmune thyroiditis (HT) patients showing indistinguishable histopathological features with IgG4-related sclerosing disease, which was termed as IgG4 thyroiditis. Objective: The objective of the study was analysis of the immunophenotypic features of IgG4 in 70 cases of HT patients and to clarify the histopathological and clinical characteristics of the patients with IgG4 thyroiditis. Design: Thyroid tissue samples were obtained from 70 patients with HT who were treated surgically. Quantitative analyses of the expression of IgG4 and IgG were performed. Statistical analyses of clinical and histopathological parameters were also conducted. Results: On the basis of immunohistochemistry of IgG4 and IgG4/IgG ratio, the 70 patients with HT were divided into two groups: IgG4 thyroiditis (19 cases) and non-IgG4 thyroiditis (51 cases). Histopathologically, IgG4 thyroiditis showed higher grade of stromal fibrosis, lymphoplasmacytic infiltration, and follicular cell degeneration than non-IgG4 thyroiditis. Moreover, these two groups were also demonstrated to be related with different clinical features, with IgG4 thyroiditis associated more with male gender, rapid progress, subclinical hypothyroidism, more diffuse low echogenicity, and higher level of circulating antibodies. Conclusions: From both clinical and histopathological aspects, IgG4 thyroiditis and non-IgG4 thyroiditis were demonstrated to be distinct entities. Measuring serum IgG4 concentration provides a useful method of distinguishing IgG4 thyroiditis from non-IgG4 thyroiditis.

Background: Anaplastic thyroid carcinoma (ATC) has a very dire prognosis and no effective therapeutic strategies have been established for ATC patients, especially those with stage IVB or IVC. Our objective was to investigate the effectiveness of weekly paclitaxel administered as induction chemotherapy and to establish novel therapeutic strategies for ATC. Methods: We performed induction chemotherapy by weekly paclitaxel administration for patients with stage IVB (nine patients) and IVC (four patients) disease. Clinical and histological responses were assessed. Overall survival was compared with that of ATC patients with stage IVB (n = 50) and IVC (n = 13) treated without paclitaxel. Results: One patient demonstrated complete response (CR) and two demonstrated partial response (PR) in the stage IVB group (response rate: 33%), and one patient showed PR in stage IVC (response rate: 25%). Curative surgery and adjuvant therapy were performed for four patients with stage IVB, and 32 months after treatment, all the four are alive and free of disease. One CR patient and one stable disease patient were assessed as grade IV (complete remission) and grade III (nearly CR) on histological response, respectively. All four patients with stage IVC died of carcinoma within 8 months. Overall survival of stage IVB patients with induction chemotherapy was better (p = 0.0213) than that without the chemotherapy and also better (p = 0.0467) than those with chemotherapy other than paclitaxel. However, induction chemotherapy did not improve the overall survival of stage IVC patients (p = 0.2002). Conclusions: Induction chemotherapy by weekly paclitaxel is a promising therapeutic strategy for stage IVB ATC patients. Responders can be expected to achieve long-term survival. We could not get significant difference of overall survival between stage IVC patients with or without weekly induction paclitaxel, although there were some cases that responded well.

The Bethesda System for Reporting Thyroid Cytology (TBSRTC) was proposed in 2007 at the National Cancer Institute Thyroid Fine Needle Aspiration State of the Art and Science Conference held in Bethesda, Maryland. The aim was to address the inconsistent and sometimes confusing reporting terminologies used for thyroid FNA throughout the world. The TBSRTC consists of 6 diagnostic categories, each associated with an implied risk of malignancy that translates directly into a clinical management algorithm. Since the publication of the TBSRTC cytology Atlas in January 2010, considerable experience has been gained regarding its application in cytology practice, clinical impact, and limitations. In conjunction with the International Academy of Cytology (IAC), an international panel composed of sixteen cytopathologists and an endocrinologist with special interest in thyroid cytology, including several co-authors of the 2010 TBSRTC Atlas, was created to: (1) analyze the current worldwide impact of TBSRTC, (2) report on the current state of TBSRTC based upon a review of the published literature, and (3) provide possible recommendations for a future update of TBSRTC. Herein, we summarize the panel's deliberations and key recommendations that our panel hopes will be useful during the preparation of the second edition of TBSRTC.