Nodule Size and Cancer

TOPIC: FNA in Subcentimeter Thyroid Nodules

Title: The Value of Fine-Needle Aspiration Biopsy in Subcentimeter Thyroid Nodules

Authors: Berker D, Aydin Y, Ustun I, Gul K, Tutuncu Y, Isik S, Delibasi T, Guler S.

Reference: Thyroid 2008; 18:603-608



The need to perform fine-needle aspiration biopsy (FNAB) on subcentimeter thyroid nodules is less clear than for larger nodules. The authors compared the ultrasonographic features of thyroid nodules less than and greater than one centimeter and correlated this information with the cytological results for FNAB and the final histopathological diagnosis in selected patients. Material & Methods: Five hundred and twenty thyroid nodules (247 <1 cm [group 1], 273 >1 cm [group 2]) were evaluated in 426 patients. Ultrasonographically-guided FNA biopsy was performed on all nodules. Surgery was recommended for patients with FNAB results that were read as malignant or suspicious. Results of US, FNAB, and histopathology were compared between the groups.


Out of 426 patients, 337 had one nodule, 84 had two, and 5 had three. There was indeterminate cytology in 20 cases, 10 from each group. Inadequate cytology was obtained in 41/247 (16.6%) nodules in group 1 and 61/273 (22.3%) nodules in group 2, a difference in rate that was not significant (p=0.067). The malignancy rate as determined by FNAB was 4.9% in group 1 and 1.5% in group 2 (p<0.025). In patients who underwent surgery for thyroid nodules, the malignancy rate was 6% in group 1 and 2.9% in group 2 (p=0.08). Hypoechoic pattern, microcalcification, and a long axis/short axis ratio (LA/SA) of <1.5 were associated with malignancy in subcentimeter nodules (group 1), while only a hypoechoic pattern was associated with malignancy in supracentimeter nodules (group 2).


The incidence of cancer in thyroid nodules <1 cm does no appear to be lower than in larger nodules and may even be higher. Physicians should consider obtaining biopsy samples from subcentimeter hypoechoic nodules that contain microcalcification and have a relatively round shape (LA/SA < 1.5).


Berker et al. report that malignancy is relatively common in small thyroid nodules, and US-guided FNA should be carried out for all nodules <1 cm with suspicious US features (hypoechoic pattern; microcalcification; and LA/SA <1.5). It is not clear what role, if any, iodine deficiency played in the genesis of these nodules or how it might have influenced study results, since these patients were referred to an Ankara medical center in Turkey where mild iodine-deficiency is likely to be prevalent. Although these authors make a strong case for performing US-FNA on all thyroid nodules, either less or greater than 1 cm, several issues are to be considered. First, the rate of inadequate cytology was relatively high, and even higher with smaller nodules. Second, the rate of malignancy was unexpectedly higher in nodules <1 cm than nodules >1 cm, 5% and 1.5%, respectively. Third, the rate of false-positive US results was high in small nodules.

Autopsy and US data have confirmed that 50% of the general population harbors one or more thyroid nodules. Thus, there is a large reservoir of subjects in every community with unrecognized thyroid nodules. It should be expected that improved sensitivity of new US machines, coupled with widespread use of US by practicing endocrinologists, will result in the discovery of an ever-increasing number of small thyroid nodules. Thus, technology permits identification of 3-4 mm nodules, but the question still remains which, if any, should undergo FNA biopsy. The challenge facing the clinician is to select for biopsy those that are of clinical significance. This dilemma is particularly apparent when one is asked to evaluate a 75 year old woman with a recent, small (<1 cm) incidentally discovered thyroid nodule. There is no consensus on what is the smallest thyroid nodule that could (or should) be biopsied, nor on how many nodules in a gland with multiple nodules should be sampled. Recent AACE-AME evidence-based thyroid guidelines (see Endocrine Practice 12: 63-102, 2006) suggest that nodules >1 cm should undergo FNA biopsy. Nodules <1 cm should be selected for FNA if US features suggestive of malignancy are noted or patient is at high risk for thyroid cancer (history of childhood neck radiation; family history of MTC or PTC). In the absence of either clinical or US features favoring malignancy, routine US-FNA of all nodules <1 cm is not recommended. Although Berker and colleagues endorse US-FNA for any-size suspicious micronodule, this remains clearly a controversial area of current thyroid practice. Summary and commentary prepared by Mahmood Gharib & Hossein Gharib (Related to Chapters 6[c & d] & 18 of TDM)