Background

The thyroid nodule (TN) is a discrete lesion that could be distinct radiologically and pathologically from the normal thyroid parenchyma [1]. It is considered the most common abnormality in the endocrine system. Using ultrasonography (US) in thyroid nodule detection has raised the nodule prevalence to reach 67%. Seven to fifteen percent of thyroid nodules are malignant [2, 3].

The current goal in the TN evaluation is to determine whether it is benign or malignant [4]. Usually, the US is the first choice among the imaging studies during TN assessment followed by ultrasound-guided fine-needle aspiration biopsy (FNAB), and mostly the surgery decision or leaving the nodule alone is dependent on the FNAB result. However, FNAB has several limitations including inadequate sampling, operator dependency, and false negative cytology rates (10–30%) [5,6,7,8].

Recently, several studies have been performed using high frequency ultrasonography to determine suspicious features of malignant TN like taller than wider in shape, microcalcifications, solid texture, central vascularity, hypoechogenicity, and irregular margin [4, 9,10,11].

The purpose of this study is to determine the diagnostic value of US in the evaluation of TN in comparison with the final histopathological examination of thyroid surgical specimen.

Methods

Patients

A total of fifty patients aged from 20 to 50 years old with equivocal or suspicious US/FNAB results underwent hemi-thyroidectomy. Malignant TN (proved by FNAB) underwent total thyroidectomy.

High frequency ultrasonography of thyroid gland

High frequency US was performed by radiologist with more than 3 years of experience in thyroid gland ultrasonographic assessment using high-resolution ultrasound equipment using 7–15 MHz linear transducer in transverse and longitudinal planes. Each TN was evaluated according to the site, size, and shape.

The nodular features were classified for:

  1. 1.

    Shape: oval or rounded

  2. 2.

    Taller than wider (T > W) or wider than taller (W˂T)

  3. 3.

    Echogenicity as isoechoic, hypoechoic, hyperechoic, or anechoic

  4. 4.

    Echotexture as solid, mixed, or cystic (if the cystic component occupied an area of less than 25%, it was considered as solid, between 25 and 74% as mixed and 75 and 100% as cystic)

  5. 5.

    Presence of microcalcification as “present” or “absent”

  6. 6.

    Presence of macrocalcification as “present” or “absent”

  7. 7.

    Presence of halo: as “present” or “absent”

  8. 8.

    Regularity of nodule margin as regular or irregular

  9. 9.

    Nodal vascularity: type І was absent vascularity, type ІІ was mixed type (central and peripheral), and type ІІІ was central

  10. 10.

    Cervical lymph nodes: shape, size, and presence of hilum

We considered that the nodule was suspicious for malignancy if it had two or more of suspicious malignant features of US (T > W, microcalcifications, central vascularity, solid texture, hypoechogenecity, and irregular or ill-defined margins).

US-guided fine-needle aspiration biopsy (US-FNAB)

All patients signed the informed consent after the explanation of the US-FNAB procedure. It was done by experienced radiologist using 22-gauge needle. The specimen was smeared and fixed by alcohol. The cytological analysis was classified according to Bethesda category (Table 1) [12].

Table 1 Bethesda system for cytological diagnosis of thyroid nodules [12]
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Histopathology

Patients with FNAB results with Bethesda 4 and 5 underwent hemi-thyroidectomy. Patients with Bethesda 6 underwent total thyroidectomy. The surgical specimens were embedded in paraffin blocks and sectioned. The sections were stained by hematoxylin and eosin stain and examined under light microscope.

Statistical analysis

Data were fed to the computer and analyzed using the IBM SPSS software package version 20.0 (Armonk, NY: IBM Corp). Qualitative data were described using number and percent. Quantitative data were described using range (minimum and maximum), mean, standard deviation, and median. Significance of the obtained results was judged at the 5% level. The used tests were chi-square test, Fisher’s exact test, F test (ANOVA), and Kruskal-Wallis test.

Results

Demographic data

Fifty patients ranged in age between 22.0 and 50.0 years with a mean age of 38.60 ± 7.43 years. Studied cases were 14 (28.0%) males and 36 (72.0%) females.

Histopathological result

Fifty patients were operated. The result was benign in 34 patients and malignant in 16 patients with different histopathological types (Table 2).

Table 2 Distribution of the studied cases according to histopathology (n = 50)
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US suspicious features of thyroid nodule

There was solitary thyroid nodule in the 50 patients, 34 nodules were in the right thyroid lobe, 2 nodules in the isthmus, and 14 nodules in the left lobe. Microcalcification was the most suspicious US features, and Fig. 1 displays the difference of microcalcification and macrocalcification.

Fig. 1
figure 1

a Thyroid nodule US picture showing macrocalcification in benign TN (arrow). b US picture shows microcalcification in malignant TN (red arrow)

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The suspicious malignant US features and their statistical analysis are shown in Table 3 and Fig. 2 in comparison to the final histopathological results.

Table 3 Summarizes sensitivity, specificity, PPV, NPV, accuracy and p value of suspicious US finding of TN
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Fig. 2
figure 2

Distribution of suspicious US features in thyroid nodules

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In comparison to the final histopathological results, we could summarize sensitivity and specificity the of US decision in Table (4)

Table 4 Sensitivity and specificity for ultrasound decision in relation to the histopathological results
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.

US-guided FNAB results

The results of FNAB were classified according to Bethesda category in comparison to the histopathological results as follow:

Table 5 summarizes the relation between histopathology and Bethesda system. There was a significant relation between histopathology and Bethesda system.

Table 5 Relation between histopathology and Bethesda
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Table 6 summarizes sensitivity and specificity for Bethesda system. The sensitivity of Bethesda system in detecting different types of thyroid nodules was 37.50%, with specificity100.0% and accuracy 80.0%.

Table 6 Sensitivity and specificity for FNAB
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Comparison of US findings and FNAB results

The review of all results revealed that the US decision was compatible with the FNAB result in 72% of cases (n = 36). On the other hand, the US was more accurate in 24% cases (n = 12). The FNAB could predict the final histology types in 2 cases better than US (Table 7).

Table 7 Distribution of the studied cases according to final results (n = 50)
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One of the cases was benign (Bethesda ІІ) with microcalcifications and T > W features on ultrasonography, and hemi-thyroidectomy was done. The final histopathology report was papillary thyroid carcinoma.

Discussion

Due to the expanding use of ultrasonography and other imaging modalities, the incidence of thyroid nodule was increased up to 67%. Most of thyroid lumps are benign; malignancy is quite low (3–7%) [13,14,15,16,17,18,19]. Although the thyroid cancer incidence has increased about 2.4-fold over the last three decades by applying the US as a preliminary assessment tool of thyroid gland lesions, this malignancy rate may be not actually estimated because there is an overlap between the gold standard investigation in the diagnosis of primary thyroid malignancy [8, 20,21,22,23,24].

The conflict is always between FNAB and US. Although the FNAB is simple, economic and available way, it has limitations. It causes physical and psychological discomfort because of its invasiveness [8]. The most relevant restriction is the intermediate result in 10 to 30% of cases [25]. Non-diagnostic FNAB or false negative results may be to low cellularity, small sized nodules, and cystic nature of nodules or due to inexperience of the aspirator or the cytologist [26]. Also, the FNAB failed in distinguishing between follicular adenoma and follicular carcinoma, which will not be achieved without intracapsular or intravascular invasion proof. The only tool to prove this invasion is the final histopathological analysis after surgical removal of thyroid specimen [27,28,29].

About the ultrasonographic assessment of thyroid nodule, it is well established that no single sonographic feature has adequate diagnostic accuracy in reliably discrimination between malignant nodules from benign ones. Many studies emphasize on the recognition of complex pattern [8, 19, 24, 30, 31]. In this study, we tried to search about the most sensitive suspicious US character of thyroid nodule to avoid unnecessary surgeries or overlooked malignant nodules without definite treatment. The US can see the intanodular structures and compare it to the surrounding neck parts [26].

On reviewing in the literatures, there are some suspicious ultrasongraphic features of thyroid nodule, namely, tall than wider nodules, solid texture, microcalcification, intranodal vascularity, hypoechogenicity, and irregular margin with different statistical accuracy [4, 9,10,11]. The present study results revealed that microcalcification is the best suspicious US thyroid feature that should be relied on during examination. The microcalcification represents the Psammoma body that is very specific for thyroid carcinoma and, especially, for papillary thyroid cancer, and the microcalcification is considered malignant if it is present without posterior shadowing and if it is appeared in the solid part of the TN. The calcification appears in the cystic part which it is considered the comet-tail artifact that is benign feature. Yunus et al. [11] and Salmaslıoğlu et al. [32] found that microcalcification was one of the best specific characters of thyroid malignancy.

The second most appreciated feature is taller than wider nodule. A recent study by Yoon et al. [33] explained this that a taller than wide shape in malignant thyroid nodules and a wider than tall shape in benign nodules are related to the ability of the probe to compress the thyroid nodule during the US examination. Since the benign nodules and cystic nodules are softer and infiltrate less into the surrounding tissue, benign nodules are more easily compressed than malignant nodules [33,34,35,36].

The ill-defined margin was very specific but it showed low sensitivity as it occurred only in 4 cases from 16 malignant nodules. According to Grant et al. [9], this controversy about the ill-defined feature is due to entangled definitions and observer variability. This was on the contrary with Gul [37] who found that the most important US feature to predict malignancy was found to be margin irregularity (with sensitivity 90.2%, specificity 87.3%) followed by hypoechoic pattern.

Central (type 3) vascularity was approved by Doppler US in 8 nodules. The sensitivity of vascularity in detecting different types of thyroid nodules was 50.0%. This result is quite different from Frates’ [38] opinion, which showed that more than 50% of hyper vascular thyroid nodules were benign. Additionally, some malignant might lack central vascularity due to fibrosis according to Moon et al. [39]. Also, the new Doppler US equipment could detect the very minute vessels in thyroid nodule and not only large central ones [40].

The sensitivity of ultrasound in detecting different types of thyroid nodules was 100.0%, with specificity 94.12% and accuracy 96.0%. Also, sensitivity of Bethesda system of FNAB in detecting different types of thyroid nodules was 37.50%, with specificity 100.0% and accuracy 80.0%. Both of FNAB and US results were statistically significant, but the US had better preference than FNAB in diagnosis of 12 malignant cases (Table 7).

Small sample size was a limitation of our study but we tried to overcome this obstacle through that all the subjects underwent hemi or total thyroidectomy. So, the final histopathology was the cut point of diagnosis and not the fine-needle aspiration biopsy that has a lot of debate as being the gold standard diagnostic tool of thyroid nodule.

Conclusion

Ultrasonography is a very essential sensitive tool in detection of thyroid nodule type, especially if it is done by well-experienced radiologist. It has a paramount importance in the successful management of thyroid nodules.