BACKGROUND: A prospective two-yr study was undertaken to assess the he
terogentity of thyroid nodules ruing the fine-needle aspiration (FNA)
technique of systematic regional sampling. In addition we determined t
he number of regions to be sampled to minimize non-diagnostic results,
and to optimally characterize thyroid nodules. DESIGN: FNA was perfor
med on 74 nodules greater than or equal to 1.5 cm. in diameter in five
distinct regions in sequence (center then four quadrants starting at
12:00, clockwise). Slides from each region were coded, randomized, sub
jected to blind review, and categorized as non-diagnostic (ND), benign
(B), indeterminate (ID), suspicious/neoplastic (S/N), or malignant (M
). Final cytologic diagnosis (CD) was made from all slides of each nod
ule. RESULTS: The ND rate for center FNAs alone was 16%, but addition
of the 12:00 region decreased it to 5.3%. With 3, 4, or 5 sequential s
ites the nondiagnostic rates were 4, 2.6, and 2.6%. The center region
diagnosis was identical to the final CD in 71% of the cases. Addition
of the 12:00 region increased the concordance to 88%. Three sequential
regions equaled the CD in 93% of cases, and 4 regions equaled the CD
in 99% of cases. All nodules characterized as M or S/N were resected a
s were 76% of the ID nodules. Of the 43 nodules characterized as B, 3
were resected, 24 involuted, 6 were unchanged, and 10 were lost to fol
low-up. All 3 M nodules proved malignant by histology, as did 7/10 S/N
0/17 ID, and 0/43 B nodules; 3/10 S/N, 1/17 ID and 1/43 B were adenom
as. Likelihood ratios for diagnosing neoplasia were ND:0, B:0.10, ID:0
.21, S/N:infinity, M:M:infinity. CONCLUSIONS: Sampling of at least fou
r distinct regions accurately assesses thyroid nodules while minimizin
g ND results. Regional sampling also addresses intranodular heterogene
ity. (C) 1998 Wiley-Liss, Inc.