Nodule heterogeneity as shown by size differences between the targeted nodule and the tumor in thyroidectomy specimen: a cause for a false-negative diagnosis of papillary thyroid carcinoma on fine-needle aspiration.

BACKGROUND Missed papillary thyroid carcinoma (PTC) diagnoses on fine-needle aspiration (FNA) can result from many causes. To the authors' knowledge, the issue of whether the detection of PTC is correlated with nodule heterogeneity has not been studied to date. METHODS The authors identified all thyroidectomy specimens with a diagnosis of PTC that had undergone at least 1 prior FNA in the study institution between 1998 and 2003. The tumor size at the time of the resection, the ultrasound (US)-determined nodule size, and other parameters were compared between the 2 groups in which PTC was or was not diagnosed on FNA. RESULTS Of a total of 89 specimens, 47 were diagnosed on FNA with an average tumor size of 1.7 cm and an US-determined nodule size of 2.1 cm (a difference of 0.4 cm). Forty-two specimens with a smaller average tumor size of 0.9 cm (P < .0001) and a US-determined nodule size of 2.4 cm (a difference of 1.5 cm) were missed. The differences with regard to the US-determined nodule size and tumor size between the 2 groups were significant (0.4 cm vs 1.5 cm; P < .0001). In the missed group, 29 specimens were found to have PTC foci that measured < or = 1.0 cm and 26 had a reasonable size difference (RSD; defined as a PTC size outside the range of +/-50% of the US-determined nodule size) as the indicator of the mixed nature of nodules targeted for FNA, whereas in the diagnostic group, 9 foci measured < or = 1.0 cm and 6 had RSD. There was no cytologic evidence with which to render a diagnosis of PTC on further review in the missed group. CONCLUSIONS The major reason for a missed diagnosis of PTC on FNA is because of inadequate tumor sampling due to the heterogeneity of the nodule targeted for FNA. This is illustrated by the RSD noted between the targeted nodule and the actual PTC tumor focus in the resection specimen.