Introduction

Thyroid cancer is an emerging global problem with an incidence of 10.1 per 100,000 women and 3.1 per 100,000 men [1]. Patients undergo surgery based on the results of cytology classified according to the Bethesda System for Reporting Thyroid Cytopathology [2]. However, the exact diagnosis of thyroid carcinoma is often established only after surgery on the basis of histology and unfortunately, surgery is unnecessary in 56% of patients with Bethesda III, 68% with Bethesda IV, and 21% Bethesda V nodules [3].

These conclusion are alarming since the incidence of recurrent laryngeal nerve dysfunction is 3.28-27.8%, postoperative hypoparathyroidism is 36.1-42.4%, which significantly reduces the quality of life of patients [4].

Therefore, despite the good postoperative survival prognosis, there are still a number of unresolved issues in the diagnosis and treatment of thyroid tumors.

A relatively new direction for solving this problem is the use of core-needle biopsy (CNB) to assess thyroid masses [5]. In recent years, there has been significant progress in the development of CNB devices – the use of thinner needles, automatic machines, and ultrasound machines with higher resolution. These advantages made it possible to implement CNB as a possible alternative to fine-needle aspiration (FNA).

Case Report

A 58-year-old female was admitted to the clinic with multinodular nontoxic goiter and follicular tumor suspicious for malignancy with compression of the trachea. She was diagnosed with multinodular nontoxic goiter in 2009. During a follow-up USG of the thyroid gland in 2022 there was an increase in the total volume of the gland up to 100.5 cm3 at this point she also notices voice hoarseness and dyspnea during physical activity (MRC Scale 2). The echogenicity of the thyroid tissue was reduced. The entire left lobe and isthmus were replaced by a multinodular mass with a hypoechoic rim along the periphery, a total size of 75x40 mm with anechoic fluid inclusions (TI-RADS 4) (Figure 1).

Figure 1: USG of the thyroid mass. A – transverse scanning plane B – longitudinal scanning plane.

Color Doppler mapping showed increased vascularization of the tissue of the nodes; regional lymph nodes were pathologically unchanged and with clear cortico-medullary differentiation. Ultrasound-guided FNA of the left lobe of the thyroid gland and cytology of the specimen demonstrated “follicular tumor” (Bethesda IV). The patient was recommended for surgical intervention due to the risk of malignancy in the scope of thyroidectomy with possible central lymph node dissection. CT of the neck on October 10, 2022 demonstrated enlarged left lobe of the thyroid gland, deviation of the larynx, pharynx, trachea with moderate compression of the latter. The left lobe was 70x47x70 mm of a heterogeneous cystic-solid structure with calcium inclusions with a slight prolapse into the upper mediastinum. The left lobe pushes the trachea to the right, moderately compressing the latter to 26x15 mm (transverse size) (Figure 2).

Figure 2: CT scan of the neck, the red circle indicates the thyroid mass with evidence of compression of the trachea.

The patient was hospitalized on October 14, 2022 for the purpose of surgical intervention. An USG scan with contrast enhancement with 2.4 ml Sonovue demonstrated that the mass actively accumulates contrast without reliably identifying areas of heterogeneous contrast enhancement. There was active washout of contrast in the delayed phase (duration – 41 s). In order to clarify the diagnosis, a CNB of the thyroid gland mass was performed in the preoperative period. The skin was punctured under local anesthesia along the trajectory of the isthmus of the thyroid gland at the midline of the neck. Under ultrasound control, the needle was advanced at an angle of 30⁰ through the isthmus of the thyroid gland until it reached the mass. The shot range was re-calculated to exclude the possibility of iatrogenic injury to the great vessels and trachea. Due to the volume of the mass, it was not possible to perform a marginal biopsy, and therefore a CNB of the tumor node was performed with a transverse capture of the capsule. The needle was removed along the channel. During the control USG after the procedure, no bleeding was observed. The specimens were placed in a 10% formaldehyde solution. The procedure was repeated under ultrasound control to obtain a second tumor sample. Examination of a tissue sample revealed a follicular adenoma (Figure 3).

Figure 3: Histology obtained by CND (hematoxylin and eosin staining). A – x100 enlargement; B – x400 enlargement.

Analysis for the mutation in the B-RAF V600E gene was negative. Considering the tracheal compression syndrome and the lack of confirmation of a malignant process, the patient underwent surgical intervention in the amount of left-sided hemithyroidectomy (Figure 4). During a histological examination there were fragments of a follicular adenoma of the thyroid gland with an area of fibrous capsule with angiomatosis. The node consisted of follicles of different sizes, filled with dense and loose colloid inside, lined with monomorphic flattened cells with rounded small hyperchromatic nuclei without signs of atypia and polymorphism. The drainage was removed 1 day after surgery. She was discharged 2 days after surgery without complications. The hoarseness gradually disappeared 1 month after surgery. There was no evidence of complication or recurrence during 1 year follow up period.

Figure 4: Postoperative specimen of the left thyroid lobe.

Discussion

FNA is the golden standard for diagnosing thyroid malignancy. This is a widely used diagnostic procedure that allows an early diagnosis of thyroid cancer. An important addition to FNA is the developed Bethesda classification, which plays a key role in patient treatment tactics. The disadvantages of the method are dependence on the qualifications of the healthcare provider and relatively high incidence of uninformative or low-informative material (Bethesda I, III). FNA can be uninformative in approximately 10% of cases, and when repeated, the probability of receiving informative material is increased by approximately 50% [6-8]. Moreover, cytological results as “atypia of unknown significance” (Bethesda III) and “follicular tumor” (Bethesda IV), also do not provide a clear understanding of the malignant potential of the mass (the probability of detecting thyroid cancer is 32-44%) [3]. In addition, an important disadvantage of cytology is that the specimen contains cellular material, while CNB provides a tissue sample. Histology allows to obtain a more detailed picture of the structure of the mass. The diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value for CNB diagnosis of malignancy are 93.8%, 100%, 100%, 78.9%, and 95%, respectively [9].

In the current case report, first the patient undergone an ultrasound to assess the location and size of the tumor, then a microbubble contrast agent (SonoVue) was administered to assess perfusion. Histologically normal thyroid parenchyma is rich in micro-vessels and therefore shows a rapid uniform enhancement after the administration of contrast agent. Thyroid nodules, however, have a different vascularization pattern, therefore a different presentation on contrast-enchanced ultrasonography [10]. This method can be actively used for identification of the “suspicious” region of the tumor.

When the tumor size is more than 1 cm, a targeted CNB of the thyroid tumor is performed with determination of its anatomical and topographic localization to obtain tissue material with subsequent histology. In complicated cases or if necessary, an immunohistochemistry is performed to clarify the nature of the tumor (CK-19, Galectin-3, HBME-1, BRAF V600E) [5,11-13]. Based on the histological material, a tissue area is determined for molecular genetic testing to identify mutations that increase the risk of malignancy (B-RAF, RAS, RET, PAX8/PPARy) [5, 11,14].

Therefore, the current multifactorial method significantly exceeds the diagnostic capabilities of standard FNA by increasing the information content of the obtained material, reducing the frequency of repeated FNA, reducing the time before starting treatment for a patient with a malignant tumor, and determining the need, nature and extent of surgical intervention.

The proposed method made it possible to diagnose a follicular adenoma, exclude thyroid carcinoma in a patient with a cytological conclusion of a follicular tumor, and perform organ-preserving surgery.

Conclusions

CNB is an emerging new diagnostic method that can be useful to diagnose thyroid malignancies. It is potentially useful in cases of Bethesda III and IV as the obtained tissue can undergo immunohistochemistry and genetic testing.

References

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