Thyroid Research and Practice

: 2016  |  Volume : 13  |  Issue : 2  |  Page : 52--56

Core needle biopsy: An additional diagnostic armamentarium

Shrikant Somani, Narendra Kotwal 
 Department of Endocrinology, Army Hospital Research and Referral, New Delhi, India

Correspondence Address:
Dr. Shrikant Somani
Department of Endocrinology, Army Hospital Research and Referral, Dhaula Kuan, Delhi Cantt., New Delhi - 110 010


Fine needle aspiration cytology (FNAC) is considered to be most effective and accurate diagnostic test to differentiate benign from malignant thyroid nodules and most guidelines recommend FNAC as the initial test. However, significant percentage of FNAC results are inconclusive owing to nodule characteristic, operator limitations, or limitations of the procedure itself. Core needle biopsy (CNB) in the evaluation of thyroid nodules have been performed since many decades; however, due to large bore needle, complication rates, and previous reports of inaccuracies, presently CNB has not been included by most guidelines in the diagnostic algorithm of thyroid nodules. Multiple recent studies have shown much higher rates of sensitivity, specificity, and accuracy using CNB in differentiating benign from malignant lesions, particularly when initial FNA is indeterminate, nondiagnostic or if there are discordant results between radiologic and cytologic tests or in nodules with macrocalcifications or fibrosis.

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Somani S, Kotwal N. Core needle biopsy: An additional diagnostic armamentarium.Thyroid Res Pract 2016;13:52-56

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Somani S, Kotwal N. Core needle biopsy: An additional diagnostic armamentarium. Thyroid Res Pract [serial online] 2016 [cited 2019 Nov 19 ];13:52-56
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In India, around 12% population has a palpable thyroid nodule. Using ultrasound (US) as a diagnostic modality, the prevalence estimates are much higher, ranging from 18.9% in iodine sufficient population in South India to about 80% in iodine deficient North Indian population.[1] An estimated 5–15% of thyroid nodules are malignant.[2] The main aim of evaluating a thyroid nodule is to differentiate a benign from a malignant pathology. Fine needle aspiration (FNA) with or without US guidance is considered the most cost-effective and accurate method for assessing a thyroid nodule and is recommended as the first line investigation by both National [3] and International [4] guidelines. However, FNA is qualitatively or quantitatively insufficient in 5–20% of cases [4] and risk of malignancy in such cases range from 1% to 10%.[5],[6] After an initial nondiagnostic cytology result, repeat FNA with US guidance will yield a diagnostic cytology specimen in 75% of solid nodules and 50% of cystic nodules. In cases with persistent nondiagnostic, FNA results close observation or surgical excision is recommended, especially if lesion is solid.[2] In cases where first FNA yielded atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (Bethesda Grade III) result, repeat FNA yields inconclusive diagnosis (repeat AUS/FLUS or nondiagnostic) in 20–49% cases.[7],[8] In 10–20% of cases where FNA results are indeterminate (Bethesda Grade III–IV) with the risk of malignancy ranging from 5% to 30%, consensus group recommends surgery in most instances without repeat FNA, with observation only in cases with favorable clinical, cytologic, and sonographic features.[9] Even when cytology diagnosis has been benign, in nodules with suspicious features on thyroid ultrasonography (USG), the malignancy rates have been reported to be as high as 56.6%.[10] Overall, FNA has a sensitivity of 83% (range: 65–98) and specificity of 92% (range: 72–100) with false positive and negative rates of 5% (range: 0–7) and 5 (range: 1–11).[9]

Place of core needle biopsy (CNB) of thyroid in diagnostic algorithm of thyroid nodules has been a matter of debate for several decades. It has been practiced by trained thyroid surgeons since 1950's, but interest faded away with the extensive use of easy, safe, and accurate FNA technique. In a comparison study of 340 simultaneous US-guided FNA and CNB with 340 FNA alone (control group), there was no significant difference in rates of nondiagnostic results (10.9% vs. 12.9%, respectively). In addition, the complication rate was higher in CNB and FNA group (3.1%) compared to the control group (1%).[11] American Thyroid association [2] and Endocrine Society of India,[3] management guidelines for thyroid nodules have not even mentioned CNB as a diagnostic option. However, latest American Association of Clinical Endocrinologists/Associazione Medici Endocrinologi/European Thyroid Association task force has considered CNB as a complementary investigation to FNA.[9] With wider availability of USG and decreasing caliber of biopsy needle, CNB has become more feasible and safer than before and CNB has been recently cited as a reliable test in multiple studies.[12],[13],[14],[15],[16],[17],[18]

CNB is performed as an out-patient procedure using 18–22-gauge needle under USG guidance and local anesthesia. Needles are modern spring-loaded, single- or double-action devices. The double-action spring-loaded needles, (i.e. Monopty or Biopty gun) are those in which the spring-activated stylet, containing a biopsy specimen slot, and cutting cannula (outer blade) are fired in rapid succession. The biopsy is actually obtained from tissue 1 to 3 cm deeper than the pretriggering cutting notch position (depending on distance of throw). After firing, the stylet tip is correspondingly deeper than in the specimen. A short throw device (11-mm excursion) is, therefore, preferred and decreases the risk of penetrating injury. Single-action spring-activated needle, i.e. Temno needle uses a similar but nonadvancing cutting action. The needle is triggered only when the stylet and biopsy notch have been manually extended. Before triggering, the biopsy notch is situated at the exact site of the intended target. During the cutting action, only the blade slides over the cutting notch, but the actual stylet tip does not advance further into the specimen. The end of the biopsy needle is advanced into the edge or within the nodule, and the stylet and cutting cannula of the needle are sequentially fired or a prefired biopsy needle can be introduced into the nodule and a final second firing is done for cutting the specimen. Firm local pressure is applied after the procedure at the biopsy site for 20–30 min. Slides are fixed with formalin and stained with hematoxylin and eosin for histopathology evaluation. In most studies, not more than four needle passes were required for a successful CNB.[7],[12],[19]

CNB allows examination of larger volume of tissue and thus more number of cells as compared to FNA. It allows effective evaluation of microhistology of the nodules-general architecture, follicular structure and alterations, tissue-tissue relationship with adjacent tissues. As CNB involves formalin fixation and paraffin blocking, similar to final postsurgical histology, it is possible to assess for nuclear changes.[13],[14] The CNB sampling allows obtain a tissue fragment with size up to 500 µ and length up to 1.5 cm, and such a volume of tissue can be used for extensive studies like immunohistochemistry (IHC).[20],[21] In this review, we will look upon available literature on accuracy and safety of use of CNB in the evaluation of thyroid nodules.

 Core Needle Biopsy as A first-Line Investigation

In a recent study, comparing the accuracy of FNA and CNB as the first-line investigation of suspicious solid thyroid nodules found significantly higher accuracy rate of 97% with CNB as compared to 78% with FNA. While FNA had a false negative rate of 2.5% and was not able to detect 12% of malignant lesions, no malignant lesion was missed by CNB.[18]

 Core Needle Biopsy in Nondiagnostic Lesions by Fine Needle Aspiration

In a study of 82 subjects with prior nondiagnostic FNA result, simultaneously done CNB with FNA together resulted in a diagnostic yield of 87%. CNB component alone showed a significantly higher diagnostic yield of 77% compared to 47% by repeat FNA alone. In subjects with 1 prior nondiagnostic FNA, CNB was significantly better with diagnostic result in 74% compared to repeat FNA diagnostic result of 52%. In nodules with ≥2 nondiagnostic FNA, CNB alone had a diagnostic rate of 86% against 29% by repeat FNA alone and the addition of repeat FNA to CNB results did not improve the diagnostic yield of CNB. With a follow-up rate of 61%, 100%, and 92%, none of the cases diagnosed as benign, AUS/FLUS or nondiagnostic, respectively, by combined repeat FNA and CNB were detected with malignancy.[17]

 Core Needle Biopsy in Benign Fine Needle Aspiration Lesions With Suspicious Ultrasonography Features

CNB usefulness has also been shown in nodules that have been reported benign in FNA sampling. In a retrospective analysis of 85 nodules with suspicious USG features with initial benign cytology, CNB changed histological diagnosis in 28 (32.9%) nodules, including 1 case of AUS, 7 cases of suspicious for follicular neoplasm or follicular neoplasm, 1 case suspicious for malignancy, and 19 cases of malignancy. Of these, 27 (31.8%) were confirmed as malignant and one as follicular adenoma, after final histology. Using CNB results for planning surgery of suspicious and malignant lesions, a diagnostic sensitivity, specificity, positive predictive value, and negative predictive value of CNB were 96.4%, 100%, 100%, and 98.3% for follicular neoplasm and thyroid cancer.[22]

 Core Needle Biopsy in Atypia of Undetermined Significance/follicular Lesion of Undetermined Significance Lesions by Fine Needle Aspiration

In a study of 161 nodules with prior FNA result of AUS/FLUS, the final diagnosis was available for 104 (64.6%) nodules, subsequent CNB gave significantly lower AUS/FLUS result (23.6%) compared to repeat FNA (39.8%). In addition, CNB gave significantly lower inconclusive (nondiagnostic or AUS/FLUS) results (26.7%) compared to repeat FNA (49.1%). When results by CNB were combined with repeat FNA, none of the nodules had a nondiagnostic result. For diagnosis of malignancy (Bethesda Grade V and VI), the overall sensitivity and specificity of CNB was 78.5% and 97.4%, respectively, while that of FNA was 55.4% and 100%, respectively. However, CNB gave nondiagnostic result in five nodules out of which three proved to be malignant.[7] Similarly, in a follow-up study of 191 nodules with prior FNA result of AUS/FLUS, final diagnosis was available for 142 nodules, subsequent CNB gave nondiagnostic, benign and AUS/FLUS result in 0.5%, 45.5%, and 18.8% nodules. None of the cases with nondiagnostic, benign or AUS/FLUS result on CNB had a final diagnosis of malignancy except one case in AUS/FLUS. Overall, CNB showed 95.8% diagnostic accuracy for identifying malignancies and 19.4% inconclusive readings.[12]

 Core Needle Biopsy in Nodules With Fine Needle Aspiration Suggestive of Follicular Neoplasm

FNA has an intrinsic problem of high false positive rates in diagnosing follicular neoplasm.[23] In a retrospective study, a comparison was drawn between 231 FNA diagnosed (107 underwent surgery) and 186 CNB diagnosed (107 underwent surgery) follicular neoplasm or suspicious of follicular neoplasm. The CNB showed a significantly lower false-positive rate compared to FNA (4.7% vs. 30.8%, respectively). Furthermore, compared to FNA, CNB showed significantly lower unnecessary surgery rate (26.2% vs. 3.7%, respectively).[24]

 Core Needle Biopsy in Nodules With Macrocalcifications

The presence of macrocalcification (>1 mm in diameter) in thyroid nodules reduces the diagnostic yield and accuracy of FNA.[25] In such nodules with macrocalcification, malignancy rate ranges from 20% to 60%. In a study of 84 patients with 86 thyroid nodules with macrocalcification, final diagnosis was correlated with simultaneously done FNA and CNB result. CNB had significantly lower nondiagnostic rate (1.2%) compared to FNA (25%). Among the 40 nodules where FNA showed nondiagnostic results, 31 (77.5%) were benign, 4 (10%) were AUS/FLUS, 3 (7.5%) were malignant, and only 2 (5%) were nondiagnostic on CNB. Among the 22 nodules that were AUS/FLUS on FNA, 11 (50%) were benign, 2 (9.1%) were suspicious for malignancy, 6 (27.3%) were malignant, and 3 (13.6%) were also AUS/FLUS on CNB. By virtue of benign diagnosis provided by a simultaneous CNB, repeat FNA or diagnostic surgery was avoided in 77.4% patients who would have undergone these procedures if only FNA was performed. However, CNB gave a false-negative result in 4 malignant cases of which 3 were correctly diagnosed by FNA.[26]

 Immunohistochemistry in Core Needle Biopsy Specimens

In a recent analysis, authors assessed the role of IHC using VE1, a mouse anti-human BRAF (V600E) antibody, in detecting BRAF-mutated thyroid cancers on 30 CNB specimens where cytology was inconclusive. Final biopsy diagnosed 21 cancers and 9 benign lesions. CNB correctly diagnosed 20/20 papillary thyroid cancer and 5/5 adenomatous nodules but reported 1 FTC and 4 benign lesions as an uncertain follicular neoplasm. VE1 IHC performed on CNB specimens correlated with 100% accuracy with genetic analysis of BRAF status.[20] Another study assessed the role of IHC using monoclonal antibody 47 against thyroid peroxidase to differentiate benign and malignant nodules on CNB specimens in nodules with a cold appearance on 99m Technitium thyroid scan. Among 140 nodules where final biopsy diagnosis was available, the study showed a diagnostic sensitivity and specificity of 89% and 97%, respectively, and positive and negative predictive values of 96% and 97%, respectively.[21]

 Core Needle Biopsy in Evaluation of Thyroid Lymphoma

A retrospective Korean study of 16 thyroid lymphoma patients, CNB gave an exact diagnosis of thyroid lymphoma in all 9 cases (100% accuracy), but FNA diagnosed lymphoma only in 3 of 10 (30%) cases.[27] In this regard, guidelines already recommend CNB procedure in suspicious anaplastic thyroid cancer, thyroid lymphoma, or other malignant neck masses.[9]

 Complications With Core Needle Biopsy

CNB with or without simultaneous FNA has been associated with very low rates of complications. Most common complications reported after CNB are local pain, hematoma, parenchymal edema, transient hoarseness, bleeding, transient hemoptysis, and nerve injuries. Reported complication rates in different studies are 0%,[17],[18],[24] 0.5%,[12] 2.7%,[25] and 5.9%.[7] Two recent studies have reported that patient tolerability and pain scores were similar after FNA or CNB procedure as well as FNA + CNB procedure.[28],[29]

 Limitations of the Study

Most of the studies included are retrospective in nature except two studies which are prospective.[15],[23] Considering the final postsurgical histopathology report as gold standard, most of the nodules with malignant or suspicious findings undergo surgery, and final pathologic diagnosis is available for comparison; however, a significant percentage of nodules with indeterminate or benign features do not undergo surgery and may or may not remain under long-term follow-up. In all these cases, there is no final histopathology biopsy result to compare with that of FNA or CNB. Most studies included in our analysis, if the final histopathology diagnosis was not available, considered a nodule as benign if both FNA (s) and CNB gave a congruent benign result or if FNA and CNB and USG features were suggestive of benign lesion or if on several months of follow-up there was no change in nodule size or size reduced. Given the limitations of this approach and slow growth of thyroid cancers, studies with a longer follow-up would be required.

There is a paucity of published literature on Indian experience of utility of CNB in evaluation of thyroid nodules and in spite of extensive search no suitable Indian study was found for inclusion in this review.


Recent data suggest that there is definite role of CNB in the evaluation of thyroid nodules particularly if initial FNA is nondiagnostic or indeterminate if there are discordant findings between radiologic and cytologic evaluation, if nodule characteristics like cystic, fibrosis, macrocalcifications are present, if nonfollicular cell-derived thyroid malignancy is suspected. Reported complication rates with CNB are comparable with that of FNA. Recent evidence are strong enough to support the inclusion of CNB in the algorithm of thyroid nodule evaluation by National and International guidelines. Whether to place CNB in parallel with FNA or above FNA in diagnostic algorithm is a matter of future debate [Table 1].{Table 1}

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Conflicts of interest

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