Syed Z. Ali

To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted the NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). For clarity of communication, TBSRTC recommends that each report begin with 1 of 6 general diagnostic categories. The project participants hope that the adoption of this flexible framework will facilitate communication among cytopathologists, endocrinologists, surgeons, radiologists, and other health care providers; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the epidemiology, molecular biology, pathology, and diagnosis of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.

The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) established a standardized, category-based reporting system for thyroid fine-needle aspiration (FNA) specimens. The 2017 revision reaffirms that every thyroid FNA report should begin with one of six diagnostic categories, the names of which remain unchanged since they were first introduced: (i) nondiagnostic or unsatisfactory; (ii) benign; (iii) atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS); (iv) follicular neoplasm or suspicious for a follicular neoplasm; (v) suspicious for malignancy; and (vi) malignant. There is a choice of two different names for some of the categories. A laboratory should choose the one it prefers and use it exclusively for that category. Synonymous terms (e.g., AUS and FLUS) should not be used to denote two distinct interpretations. Each category has an implied cancer risk that ranges from 0% to 3% for the "benign" category to virtually 100% for the "malignant" category, and, in the 2017 revision, the malignancy risks have been updated based on new (post 2010) data. As a function of their risk associations, each category is linked to updated, evidence-based clinical management recommendations. The recent reclassification of some thyroid neoplasms as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) has implications for the risk of malignancy, and this is accounted for with regard to diagnostic criteria and optional notes. Such notes can be useful in helping guide surgical management.

OBJECTIVE: To address terminology and other issues related to thyroid fine-needle aspiration (FNA), the National Cancer Institute (NCI) hosted The NCI Thyroid FNA State of the Science Conference. The conclusions regarding terminology and morphologic criteria from the NCI meeting led to the Bethesda Thyroid Atlas Project and form the framework for the Bethesda System for Reporting Thyroid Cytopathology. DESIGN: Participants of the Atlas Project were selected from among the committee members of the NCI FNA State of the Science Conference and other participants at the live conference. The terminology framework was based on a literature search of English language publications dating back to 1995 using PubMed as the search engine; online forum discussions ( http://thyroidfna.cancer.gov/forums/default.aspx ); and formal interdisciplinary discussions held on October 22 and 23, 2007, in Bethesda, MD. MAIN OUTCOME: For clarity of communication, the Bethesda System for Reporting Thyroid Cytopathology recommends that each report begin with one of the six general diagnostic categories. Each of the categories has an implied cancer risk that links it to an appropriate clinical management guideline. CONCLUSIONS: The project participants hope that the adoption of this framework will facilitate communication among cytopathologists, endocrinologists, surgeons, and radiologists; facilitate cytologic-histologic correlation for thyroid diseases; facilitate research into the understanding of thyroid diseases; and allow easy and reliable sharing of data from different laboratories for national and international collaborative studies.

Synovial sarcomas are aggressive spindle cell sarcomas containing in some cases areas of epithelial differentiation. They consistently show a specific t(X;18;p11;q11), which usually represents either of two gene fusions, SYT-SSX1 or SYT-SSX2, encoding putative transcriptional proteins differing at 13 amino acid positions. Previous studies have suggested that patients with SYT-SSX2 tumors do better than those with SYT-SSX1 tumors, but the study groups were too limited to be conclusive. To address this issue more definitively, we collected data on SYT-SSX fusion type, pathology, and clinical course in a retrospective multi-institutional study of 243 patients (age range, 6-82) with synovial sarcoma. SYT-SSX1 and SYT-SSX2 fusions were detected in 147 tumors (61%) and 91 tumors (37%), respectively. Histologically, 61 (25%) were classified as biphasic type and 180 (74%) as monophasic type based on the presence or absence of areas of glandular epithelial differentiation, respectively. Median and 5-year overall survivals for the SYT-SSX1 and SYT-SSX2 groups were 6.1 years and 53%, and 13.7 years and 73%, respectively. Overall survival was significantly better among SYT-SSX2 cases (P = 0.03), among cases localized at diagnosis (P < 0.0001), and among patients with primary tumors < 5 cm in greatest dimension (P = 0.01). Age, sex, histological type, and axial versus peripheral primary site had no impact on overall survival. The impact of fusion type on survival remained significant when stratified for primary tumor size (P = 0.03) but was no longer significant when stratified for disease status at presentation. This may reflect the tendency for patients with SYT-SSX1 tumors to present more often with metastatic disease (P = 0.05). Cox regression identified disease status (P < 0.0001) and primary tumor size (P = 0.04) as the only factors independently predictive of overall survival in the subset of 160 patients with information on all of the factors. Within the subset of patients with localized disease at diagnosis (n = 202), the median and 5-year survival for the SYT-SSX1 and the SYT-SSX2 groups were 9.2 years and 61% versus 13.7 years and 77%, respectively. Patients whose tumors contained the SYT-SSX2 fusion (P = 0.08) or were smaller (P = 0.12) showed a trend toward better survival by log-rank test, whereas tumor histology had no impact (P = 0.8). In a Cox regression analysis considering all of the factors, SYT-SSX fusion type emerged as the only independent significant factor (P = 0.04) for overall survival within the subset of 133 patients with localized disease at diagnosis who had information on all of the factors. Among other comparisons, there was a strong association of fusion type and morphology (P < 0.001), with almost all of the SYT-SSX2 tumors showing absence of glandular differentiation (monophasic histology) and almost all of the biphasic tumors containing SYT-SSX1. There was also a statistically significant association of fusion type and patient sex (P = 0.03); specifically, the male:female ratio of SYT-SSX1 cases was 1:1, whereas for SYT-SSX2 cases, it was close to 1:2. Overall, SYT-SSX fusion type appears to be the single most significant prognostic factor by multivariate analysis in patients with localized disease at diagnosis. SYT-SSX fusion type also appears to exert part of its impact on prognosis before presentation through its association with stage at diagnosis. In addition, the associations of SYT-SSX fusion type with patient sex and tumor epithelial differentiation point to interesting mechanistic biological differences.