Predictive Value of Cytologic Atypia in Indeterminate Thyroid Fine-Needle Aspirate Biopsies

Abstract

Background Fine-needle aspiration (FNA) biopsies are the most accurate method for diagnosis of thyroid nodules. Unfortunately, biopsies are indeterminate 15–30% of the time and surgery is thus required for a definitive diagnosis. We aimed to determine whether specific descriptors of cytologic atypia mentioned in indeterminate FNA reports were associated with malignancy on final histopathology. Methods Retrospective review of 1000 surgery patients identified 466 indeterminate FNA lesions that underwent either a hemi- or total thyroidectomy between 1998 and 2009. We screened FNA reports for specific descriptors of nuclear atypia. Univariate and multivariate analyses were performed to evaluate the independent effect of cytologic atypia descriptors on the risk of malignancy. Results Nuclear atypia on FNA conferred a risk of malignancy of 42% (P <0.0001). Risk of malignancy increased from 17% for zero descriptors to 81.2% when four or more descriptors of atypia were described. Nuclear grooves and inclusions together conferred a risk of malignancy, specificity, and false positive rate of 79.3%, 98.2% and 1.8% respectively. Conclusions The presence of four or more descriptors of cytologic atypia or the presence of both nuclear inclusions and grooves together confers a high risk of malignancy on final histopathology and a low false positive rate. These findings should be taken into consideration when interpreting FNA reports and total thyroidectomy should be considered for those patients at higher risk.

Institutional prevalence of malignancy of indeterminate thyroid cytology is necessary but insufficient to accurately interpret molecular marker tests

“…Moreover, the PoM may change over time in response to practice changes and availability of molecular marker testing. It is also critical to recognize that the NPV and PPV should really be individualized for each nodule as other factors such as the sonographic appearance or the cytological features might also impact the pretest PoM (17,18,19). Although our results with the seven-gene oncogene panel might not be applicable to other institutions, miRInform performed better on follicular neoplasms than on HCN or Bethesda III samples, for which it might have limited utility.…”

“…This heterogeneity would be expected to impact not only the PoM but also the histological findings at the time of surgery probably causing significant differences on test performance among institutions. If comparable performance of these tests is desired among centers, the inclusion and exclusion criteria of the Bethesda III category need to be better defined and probably need to be subcategorized to improve risk stratification (17,18,19).…”

Does Bethesda Category Predict Aggressive Features in Malignant Thyroid Nodules?

“…However, a CND is typically only performed on patients with Bethesda III or IV nodules if there is macroscopic suspicion of lymph node metastases (either on preoperative imaging or intraoperatively). In addition, the presence of particularly worrisome features of cytologic atypia on the preoperative FNA of Bethesda III nodules such as nuclear grooves and/or inclusions often compel us to perform a prophylactic CND, since our group has shown that the presence of these two atypical features increases the risk of malignancy to 80% 13 . This explains why 15% of patients with Bethesda III or IV nodules underwent a CND.…”

“…A CND is typically only performed for Bethesda III and IV nodules if there are grossly suspicious lymph nodes identified on preoperative imaging or intraoperatively, or if there were particularly worrisome features of cytologic atypia (i.e. nuclear grooves or pseudo inclusions) on the preoperative FNA, which impart a significantly greater risk of malignancy 13 . Cancer recurrence was defined as a rise in serum markers (thyroglobulin and anti-thyroglobulin antibodies) and/or appearance of suspicious findings on imaging studies, which warrant clinical intervention.…”

Preoperative BRAF(V600E) mutation screening is unlikely to alter initial surgical treatment of patients with indeterminate thyroid nodules

“…Such nodules are thereby categorized as a “follicular lesion of undetermined significance/atypia of undetermined significance (Bethesda category III).”6 This is a very heterogeneous group with an overall risk of malignancy ranging from 20% to 60% 26‐30. Our group recently demonstrated that not all descriptors of atypia confer an equal risk of malignancy; the presence of nuclear grooves, pseudoinclusions, or both, increases the risk of malignancy to 55%, 65%, and 79%, respectively 31…”