Core Needle Biopsy in Suspicious Malignant Thyroid Nodules with Repeated Nondiagnostic Fine Needle Aspiration

Abstract

Key message

The clinician could have CNB in mind for thyroid nodules when FNA results were nondiagnostic. Our study would suggest CNB a safe and efficient method for investigating thyroid nodules.

Abstract

Usefulness of preoperative tissue sampling and pathology diagnoses in thyroid tumors were accepted worldwide. We investigate the role of Core needle biopsy (CNB) in the thyroid nodules lesions when FNA results are nondiagnostic. We conducted a cross-sectional study to evaluate twenty-six CNBs results of suspicious malignant thyroid nodules with nondiagnostic repeated fine needle aspiration. 25 from 26 CNBs were diagnostic. Twenty-one needle biopsy reports were papillary thyroid carcinoma, three CNB samples diagnosed medullary thyroid carcinoma and one of them had anaplastic results. All diagnostic needle biopsies results were compatible with final pathology. Our study would suggest CNB a safe and efficient method for investigating thyroid nodules while repeated FNA yielded nondiagnostic results.

Introduction

Fine-needle aspiration (FNA) cytology has long been known the preoperative gold-standard diagnostic tool for thyroid nodules [1, 2]. Large needle biopsy primarily has been introduced in the 1920s as the standard diagnostic tool for thyroid nodules; however, since 1980s FNA (23–27 gauge needles) has become popular and the gold standard method due to its accurate and reliable results [3–5]. In the 1990s, CNB started to be used as an alternative method instead of FNA [3]. However until know, indications for thyroid CNB is controversy in the popular guidelines for management thyroid nodules. American Association of Clinical Endocrinologists (AACE), The National Cancer Institute, Associations Medici Endocrinology (AME), American College of Endocrinology (ACE), and the Korean Society of Thyroid Radiology (KSThR) have suggested core needle biopsy when FNA of thyroid nodules indicated nondiagnostic results [6–8]. According to The British Thyroid Association, ACE, AACE, AME, and KSThR, CNB is recommended in certain thyroid conditions such as medullary carcinoma, anaplastic carcinoma, lymphoma, and metastasis to the thyroid [6, 8, 9]. Nevertheless, CNB is not proposed as a diagnostic tool by the American Thyroid Association guidelines [2].

In short, the inevitable importance of thyroid CNB in diagnosis of thyroid nodules has yet to be investigated thoroughly especially when FNA does not give us the definitive answer. In this study, we have focused on efficiency of CNB in determination of thyroid nodules diagnosis, which FNA was nondiagnostic.

Materials and Methods

The study was performed at our institute, tertiary center of otolaryngology and head and neck surgery. Patients with suspensions thyroid malignancy according to their sonographic pattern based on the ATA guidelines were enrolled [10].

The nodules with following ultrasound pattern considered high risk for malignancy [10]. Solid hypoechoic nodule or nodule with a partially cystic hypoechoic component with size ≥ 1 cm and at least one of the following features: irregular margins, microcalcifications, taller than wide Shape, rim calcifications with small extrusive soft tissue component and evidence of extrathyroidal extension.

Patients also had the repeated nondiagnostic or indeterminate US guided FNA (US-FNA) results. All US-FNA was carried out using a blue needle and standard aspiration technique by a head and neck surgeon. Indeterminate cytology includes atypia of undetermined significance (AUS) and follicular lesion of undetermined significance (FLUS) [11].

Patients with history of thyroid gland surgery and known previous malignancy were excluded. Ultrasound-guided core needle biopsy (US-CNB) of thyroid gland nodules and cervical lymphadenopathies from individual patient were taken after a meticulous evaluation. All of the US-guided biopsies performed by a same head and neck surgeon. US-CNB was performed using the Super Core™ Semi-Automatic Biopsy Instrument (18G × 6 cm) under local anesthesia with 2% lidocaine. In solid-cystic lesions, cystic content aspirated, and biopsy obtained from the solid part. Then, fixation delivered in 10% formalin liquid. FNA, CNB, and surgical pathologies were reported by same pathologists, which had access to patient history and medical records.

Parameters including age, gender, mass size (the largest diameter of the lesion using ultrasound), CNB, and surgical pathology were recorded. The statistical package IBM SPSS for Windows (Version 24.0 Armonk, NY: IBM Corp) used for analysis. Sensitivity and specificity calculated for diagnostic CNB results. A malignant pathological diagnosis was considered positive. Sensitivity, specificity, positive and negative predictive value (PPV, NPV) were calculated following equations [12, 13]. Sensitivity = true positive / (true positive + false negative). Specificity = true negative / (true negative + false positive). PPV = true positive / (true positive + false positive). NPV = true negatives / (false negative + true negative).

The research was carried out according to the principles of the declaration of Helsinki. Written consent was obtained from all patients. The local ethics review committee approved the study protocol. Approval ID is IR.TUMS.MEDICINE.REC.1397.731.

Results

A total twenty-six CNB of thyroid nodules or cervical lymph nodes from twenty patients were obtained, Table 1. Five patients had both thyroid and lymph node species. Mean age of patients was 51.3 years with range of 30 to 82. Tumor size ranged from 2.5 to 10.0 cm with mean of 4.3 cm. All repeated FNA results were nondiagnostic except one lymph node aspiration that reporting atypical cells compatible with malignancies, but did not define definite diagnosis. 25 from 26 CNBs were diagnostic. Twenty-one needle biopsy pathologies reported papillary thyroid carcinoma, three CNB samples diagnosed medullary thyroid carcinoma and one of them had anaplastic results, Table 1. All diagnostic needle biopsies were compatible with final pathology. A 69 years old patient with 50 mm tumor size had an unsatisfactory core needle result with an anaplastic excisional final pathology report.

Table 1.

Characteristics of study population

Patients ID	Age (year)	Gender	Tumor size (mm)	Location	FNA	CNB	Surgical
1	82	F	30	Thyroid	Nondiagnostic	PTC	PTC
				LN	Atypical cell	PTC	PTC
2	30	F	25	Thyroid	Nondiagnostic	PTC	PTC
3	75	M	35	Thyroid	Nondiagnostic	PTC	PTC
				LN	Nondiagnostic	PTC	PTC
4	45	F	60	Thyroid	Nondiagnostic	PTC	PTC
				Left LN	Nondiagnostic	PTC	PTC
				Right LN	Nondiagnostic	PTC	PTC
5	37	M	25	Thyroid	Nondiagnostic	PTC	PTC
6	57	F	35	Thyroid	Nondiagnostic	PTC	PTC
7	73	F	25	Thyroid	Nondiagnostic	PTC	PTC
8	38	M	45	Thyroid	Nondiagnostic	PTC	PTC
9	54	F	55	Thyroid	Nondiagnostic	PTC	PTC
10	35	M	30	Thyroid	Nondiagnostic	PTC	PTC
11	42	F	40	Thyroid	Nondiagnostic	PTC	PTC
12	47	F	50	Thyroid	Nondiagnostic	PTC	PTC
13	38	M	30	Thyroid	Nondiagnostic	PTC	PTC
14	37	F	40	Thyroid	Nondiagnostic	PTC	PTC
				LN	Nondiagnostic	PTC	PTC
15	52	F	100	Thyroid	Nondiagnostic	PTC	PTC
				LN	Nondiagnostic	PTC	PTC
16	60	F	55	Thyroid	Nondiagnostic	MTC	MTC
17	55	F	30	Thyroid	Nondiagnostic	MTC	MTC
18	33	M	30	Thyroid	Nondiagnostic	MTC	MTC
19	67	F	65	Thyroid	Nondiagnostic	Anaplastic	Anaplastic
20	69	F	50	Thyroid	Nondiagnostic	Unsatisfactory	Anaplastic

LN lymph node; PTC papillary thyroid carcinoma; MTC medullary thyroid carcinoma

Calculated sensitivity for diagnosis of malignancy was 96% and specificity was 100%. Negative predictive value, positive predictive value, and accuracy for CNB in detecting malignancy, were calculated 100%, 100%, and 96%, respectively.

Discussion

Core needle biopsy has proven itself as a powerful diagnostic tool in many studies in head and neck malignancies [14, 15]. A meta-analysis by Wolinski in 2017 concluded that proportion of diagnostic results for CNB is significantly higher that FNA biopsy, especially those nodules which remained nondiagnostic by FNA [16].

Current approach in management of thyroid nodules with nondiagnostic or indeterminate initial FNA results is repeating of US-FNA and if available, on-site cytology evaluation and molecular testing [2].

If repeated FNA is also nondiagnostic and nodules has a high suspicion malignancy sonographic pattern, the ATA guidelines recommended surgery to obtain histopathologic diagnosis [2].

In this study, all participants had the thyroid nodules with highly suspicion malignancy ultrasonographic pattern and repeated nondiagnostic FNA results. According to ATA guidelines, to obtain histopathologic diagnosis, these patients were candidate for surgery, at least thyroid lobectomy [2].

Here, we performed CNB instead of surgery to reach tissue samples. 25 from 26 CNB results were diagnostic. 21 needle biopsy pathologies reported papillary thyroid carcinoma, 3 CNB samples diagnosed medullary thyroid carcinoma and one of them had anaplastic results. Therefore, CNB could be considered in certain patients to reduce the surgical need for histopathologic diagnosis, leading to reducing surgical complications, need for admission and health care costs.

The use of CNB instead of repeating FNA was investigated before [2, 16–21]. However, there were a controversy results. Some studies have found that core biopsy offers a higher adequacy rate, but may be less sensitive for the detection of papillary cancer compeers to repeated FNA [16, 21]. The exact clinical approaches for nodules with nondiagnostic cytology remains unknown [20]. Although application of CNB in the diagnosis of thyroid nodule has not yet been become common worldwide, many studies are consistent with advantages of CNB over FNA due to it has higher sensitivity and specificity [3]. Previous studies recommended CNB can be utilized in determination of pathology of thyroid nodules [22] and recent studies particularly recommended CNB in patients whose FNA results were nondiagnostic [20] or AUS [23].

In this study we performed US-CNB in suspicious malignant thyroid nodules with repeated nondiagnostic fine needle aspiration. We showed CNB had still high accuracy rates. Therefore, CNB could be considered before open biopsy (at least thyroid lobectomy) when FNA were nondiagnostic for clinical decisions. But the risks involved with core biopsy, the rate of complications or tumor seeding, should be keep in mind and more study should be done to examine these risks.

Qualified physicians should carry out CNB of thyroid in order to lessen the rate of possible complications. Overall, it is considered a safe method (complication rate: 0 to 4.1% and major complication: 0–1.9%) [7, 24]. Various complications may occur during CNB. The most prevalent complication is hematoma which occurs significantly more in CNB than FNA, both performed under ultra sound guidance [25]. Other important complications include hemoptysis, voice change, infection, edema and dysphasia. Ha et al. conducted a single-center study analyzing 6687 nodules in 6169 patients. They reported no deaths due to procedure. In addition, they concluded a 0.79% minor complication rate, and a 0.06% major complication rate [26]. In order to minimize the rate of complications, performing the core needle biopsy by experienced physicians and real-time ultrasonography guiding is highly recommended. Taken the complications of the procedure, anatomical variations, neck anatomy and potential complications must be mastered by the doctor performing CNB [27].

Conclusion

The clinician could have CNB in mind for thyroid nodules when FNA results were nondiagnostic before surgical thyroid lobectomy because it may change treatment and surgical plan.

Complication

We had one major complication resulted in patient hospitalization. This was a rapid progressive cervical hematoma following CNB. Oral intubation was not successful and patient underwent emergency tracheostomy procedure. After several days, tracheostomy tube was removed and patient was discharged with good condition.

Funding

None.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest.