A Large Thyroid Fine Needle Aspiration Biopsy Cohort with Long-Term Population-Based Follow-Up

Abstract

Background: Prior studies evaluating thyroid fine needle aspiration biopsies (FNABs) have limited the calculation of risk of malignancy (ROM) to cytologic specimens with corresponding histologic specimens, and clinical follow-up for those patients who do not undergo immediate surgery has been largely disregarded. Moreover, there is marked variability in how researchers have approached thyroid FNAB statistical analyses. This study addresses the urgent need for information from a large cohort of patients with long-term clinical follow-up to more accurately determine the performance of thyroid FNAB and ROM for each diagnostic category. Methods: A retrospective review of the University of California, San Francisco (UCSF), pathology database for thyroid FNABs from January 1, 1997, to December 31, 2004, was performed. Diagnoses were coded using the 2017 The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), and patients were matched to both the UCSF cancer registry and California Cancer Registry. Data were analyzed using the Kaplan-Meier method, and stratified by TBSRTC diagnostic category. Kaplan-Meier curves were used to estimate incidence rates of malignancy, stratified by FNAB category. Cox proportional hazards models were used to determine the instantaneous ROM. Results: Initial FNABs from 2207 patients were included. Median follow-up period after the first thyroid FNAB was 13.9 years (range: 10.5-18.4 years). During follow-up, there were 279 confirmed diagnoses of thyroid malignancy. Estimates derived from Kaplan-Meier curves demonstrated that the risk of having a thyroid malignancy was low for nondiagnostic and benign categories, intermediate for atypia of undetermined significance (AUS), follicular lesion of undetermined significance (FLUS), AUS/FLUS combined, and follicular neoplasm, and high for suspicious and malignant categories. A total of 52/1575 false-negative cases (3.2%) were identified. Excluding papillary microcarcinomas, the false-negative rate was 1.5% (23/1575). No patients with a false-negative diagnosis died of thyroid cancer during the follow-up period. Conclusions: Asymptomatic patients with low-risk clinical and radiologic features and initially benign or unsatisfactory biopsy are unlikely to develop thyroid malignancy and highly unlikely to die of thyroid cancer. FNAB is highly accurate in detecting malignancy. Additional studies evaluating similar large data sets after the adoption of TBSRTC and the integration of molecular testing are needed.

Keywords: Bethesda; adequacy; cytopathology; fine-needle aspiration biopsy; thyroid.

FIG. 1.

Estimated probability of diagnosis of thyroid malignancy for each diagnostic category. The date of the initial FNAB was considered to be time origin, and the patients were followed until they experienced an event (defined as the histologic diagnosis of a thyroid malignancy); mean follow-up period was 13.9 years. For (A), the Kaplan–Meier curves are categorized according to TBSRTC, while (B) separates AUS and FLUS into two distinct categories. AUS, atypia of undetermined significance; FLUS, follicular lesion of undetermined significance; FN, follicular neoplasm; FNAB, fine needle aspiration biopsy; SUS, suspicious for malignancy; TBSRTC, The Bethesda System for Reporting Thyroid Cytopathology.

FIG. 2.

Estimated probability of diagnosis of thyroid malignancy for each diagnostic category, excluding patients with repeat biopsies. The date of the initial FNAB was considered to be time origin, and the patients were followed until they experienced an event (defined as the histologic diagnosis of a thyroid malignancy); mean follow-up period was 13.9 years. For (A), the Kaplan–Meier curves are categorized according to TBSRTC, while (B) separates AUS and FLUS into two distinct categories.

FIG. 3.

Time from initial biopsy to diagnosis of malignancy (years). The date of the initial FNAB was considered to be time origin, and the patients were followed until they experienced an event (defined as the histologic diagnosis of a thyroid malignancy); mean follow-up period was 13.9 years. The box outlines denote the IQR, the solid line within the box denotes the median, the whiskers represent upper adjacent (75th percentile +1.5*IQR) and lower adjacent (25th percentile – 1.5*IQR) values, and the dots represent outliers. IQR, interquartile range.