ultrasound - guided fine - needle aspiration ( fna ) has become the gold standard for differentiating benign and malignant thyroid nodules due to the suboptimal accuracy using gray scale features alone . besides for mild associated pain ,
development of postprocedural hematoma has been reported from 1.9% to 6.4% , with seven reported cases of life - threatening hematomas relating to airway obstruction . the true rate of complications following thyroid nodule fna is likely much higher though as most go undocumented and unpublished .
although fna plays an essential role in thyroid nodule evaluation , the potential for a nondiagnostic ( nd ) specimen can lead to repeat procedures , increasing patient morbidity , cost , chance for complication , and delay in diagnosis .
recently , thyroid nodule fna pathological reporting has been standardized based on the bethesda system for reporting thyroid cytopathology adopted by the american society for clinical pathology ( ascp ) . based on their criteria ,
an adequate specimen needs to contain at least six groups of follicular cells with each group composed of at least 10 cells each .
an nd specimen can be secondary to obscuring blood , overlying thick smears , air drying of alcohol - fixed smears , or inadequate number of follicular cells . according to the ascp
, nd specimens occur in 2%20% of cases but ideally should be limited to no more than 10% of all thyroid nodule fnas .
recently , the use of ultrasound strain elastography ( use ) has emerged as a promising diagnostic tool in differentiating benign and malignant thyroid . a novel approach aimed at decreasing the rate of nd nodule fna maybe to use elastography as a map , targeting biopsy needles to areas of lower strain ( i.e. , stiffer ) .
several papers have been published illustrating increased detection of prostate cancer using use - targeted interventions through a transrectal approach .
our study was performed to evaluate the role of use - targeted fna in decreasing the rates of nd aspirates .
we performed a review of all thyroid nodule fna performed over a 3-year period comparing fna results when an elastogram was available before fna or not .
our hypothesis is that the presence of an elastogram before fna would decrease the rate of nd specimens .
the study was health insurance portability and accountability compliant , and informed consent was waived .
between january 2011 and january 2014 , a total of 225 patients underwent ultrasound - guided thyroid nodule fna . among them were 171 females and 54 males with ages ranging from 27 to 90 .
the demographical data recorded included patients ' age and gender as well as which thyroid lobe contained the nodule biopsied [ table 1 ] .
gray scale nodule characteristics that were recorded included the presence of microcalcifications , vascularity , solid components , and nodule size [ table 1 ] .
the decision to perform use was based strictly on suspicious gray scale characteristics , and guidelines set forth by the society of radiologists in ultrasound .
patient demographics and nodule characteristics during this period , use for thyroid nodules was performed in cases where the available technician was comfortable and experienced with the elastography software .
when elastography was performed , the applied transducer pressure was standardized by a real - time analysis utilizing a scale that was displayed at the right upper corner of the elastogram image [ figure 1 ] .
the nodule strain elastogram was displayed using a 256-color mapping scale [ figure 2 ] .
the degree of strain was assigned a given color shade utilizing a range from red ( greatest strain , soft ) to green ( intermediate strain ) to blue ( least strain , hardest component ) .
real - time applied transducer pressure analyzed by numeric scale displayed at the right upper corner of the elastogram image ( red box ) .
nodule strain elastogram is displayed by a 256-color mapping scale with red representing the softest components and blue representing the hardest components .
we separated patients into two groups , based if an elastogram was available for the radiologist to review before fna or not .
all fna were completed by one of two fellowship - trained radiologists with specialty in ultrasound - guided procedures .
a 21-gauge needle was used in every case , and aspiration was aided by a 5-cc syringe .
all pathological analyses were performed by one of three board - certified cytopathologists . in all cases ,
the final pathological diagnosis was reviewed through the institution 's electronic medical record for every case .
the chi - square test was used to determine statistically significant variances in the demographic parameters .
there was no significant difference between the two groups in demographics ( including gender , age , and which thyroid gland contained the nodule ) as well as nodule characteristics .
regarding the specimen adequacy , the total percentage of nd aspirates was 12.2% , slightly higher than the 10% supported by the ascp . in analyzing the two groups , when an elastogram was available before fna , the nd rate was 10% ( 14/140 ) which was in concordance with the ascp recommendations
. however , the group without an elastogram available had an nd rate of 16% ( 13/81 ) .
however , this difference was not found to be statistically significant , p = 0.205 .
thyroid nodules continue to pose a diagnostic dilemma secondary to poor sensitivity and specificity using gray scale features alone .
although considered the gold standard for nodule evaluation , fna carries its own risks including patient pain , cost , and possible complications ( although rare ) . the need for repeat fna secondary to nd results can cause further patient harm as well as delay time to treatment and increase patient anxiety . to help increase the rate of adequate specimen recovery , the use of ultrasound to guide fna has become the standard of care . with the assistance of ultrasound - guided fna ,
the rates of nd specimen aspirates still range up to 20% . in a recent meta - analysis ,
even the addition of rapid onsite evaluation by a cytopathologist has shown considerable variability in helping to reduce nd rates .
ex vivo studies have found that malignant thyroid lesions have a stiffer architecture compared to benign thyroid stroma .
first described in 1991 by ophir , tissue stiffness could be measured by applying an external axial stimulus and viewing the associated compressibility .
the continued research in elastography has focused on its ability to distinguish benign and malignant lesions by  virtual palpation .
 several studies have been performed to evaluate the role of elastography in targeting interventions .
most papers have focused on ultrasound - guided transrectal biopsies of the prostate gland . using elastograms ,
small studies have been able to show enhanced detection rates as well as decreasing the number of core specimens required for diagnosis . to date
, there has been only one study performed evaluating strain elastography - guided fna of thyroid nodules . in 2013 ,
yildrim et al . , prospectively analyzed the rates of nd aspirates between specimens obtained from regions of higher strain and lower strain from 96 patients .
the authors found a significant improvement in specimen adequacy when aspirates were obtained from regions that demonstrate a stiff elastogram as described previously .
our study was aimed at replicating yildrim 's results in a larger patient sample and hoping to show an improved rate of nd aspirates . in our retrospective review , although there was a decreased rate of nd specimens in the group that use was performed ( 16% vs. 10% ) , this was not found to be statistically significant .
first of all , we performed a retrospective review , which by its very nature allows for confounding bias .
furthermore , although an elastogram was available for the radiologist before fna in the elastography group , we were unable to prove that stiffer regions were actually targeted and aspirated during the procedure .
furthermore , it is possible that stiffer regions of nodules were sampled in the group without elastograms even though elastography was not performed . finally , as our study was a retrospective review , the pathologist performing the specimen analysis was not controlled for , leading to possible variability .
another possibility exists to explain why the presence of an elastogram prior the fna did not significantly reduce the rate of nd results .
our study was predicated on the idea that stiffer regions within nodules would likely decrease nd aspirates as these regions may represent more cellular areas
. however , the development of a stiff consistency in many cancers is secondary to a desmoplastic transformation that takes place .
this process is composed of activated fibroblasts ( also known as myofibroblasts ) , tumor vessels , inflammatory cells , and extracellular matrix components . activated carcinoma induced fibroblasts , along with other extracellular matrix proteins , comprise a dominant proportion of several carcinomas , including more than 90% of overall tumor mass in pancreatic cancers .
it has even been shown that the complex relationship between these components may promote tumor cell growth .
it is possible that the stiffer regions within thyroid nodules are more a product of fibroblastic growth than increased cellular density .
we were unable to demonstrate a significant difference in thyroid nodule aspirate adequacy between patients who had an elastogram present before fna compared with those without one .
these results may be secondary to lack of power , poor study design versus fibroblastic growth as described above .
we hope our study raises awareness of the exciting prospect of use - targeted biopsy and springs future studies confirming its potential .
 objectives : since 2009 , the rate of nondiagnostic ( nd ) thyroid nodule fine - needle aspiration ( fna ) has ranged from 2% to 20% 
 . a nd result can cause further patient morbidity secondary to repeated procedures and delay in diagnosis . 
 the use of real - time strain elastography ( rte ) in determining nodule malignant risk has gained considerable focus recently . 
 a less studied area where rte may prove beneficial is its role in targeting areas for fna . 
 our hypothesis is that fna performed in concurrence with rte will show a decreased rate of nd results leading to fewer repeated fna.materials and methods : the institutional review board approval was obtained . 
 a retrospective review of all thyroid nodule fna from january 1 , 2011 , to january 1 , 2014 , was performed with review of nodule size , presence of microcalcifications , vascularity , solid components , patient age , and gender . 
 cases were separated based if rte was done before fna or not . 
 pathology reports were reviewed to assess for specimen adequacy . 
 statistical comparison was performed using sas analysis software.results:a total of 221 specimens were reviewed , with rte performed on 140 cases ( 63.4% ) . 
 both groups were similar in demographics and previously described nodule characteristics . 
 the nd rate when rte was not performed was 16% ( 13/68 ) compared to 10% when rte was performed ( 14/126 ) . 
 the difference was not found to be statistically significant , p = 0.205.conclusions:the presence of an elastogram failed to demonstrate a significant decrease in nd fna rates although these results may be secondary to study design . 
 further evaluation with prospective trials using larger sample size may ultimately detect increased accuracy of rte - targeted fna . 