The Journal of Laryngology & Otology (2014), 128, 914–921. © JLO (1984) Limited, 2014 doi:10.1017/S0022215114002072

The predictive value of structured ultrasonographic staging for thyroid nodules S L GRAY1, G O’NEILL2, G MCGARRY1 Departments of 1Otolaryngology – Head and Neck Surgery, and 2Radiology, Glasgow Royal Infirmary, Scotland, UK


Background: ‘R staging’ is a new ultrasonographic scoring system developed and used by our specialist head and neck radiologist for reporting sonographic risk of malignancy to those at our thyroid multidisciplinary team meeting. This study aimed to: classify the R staging system, examine its relationship with the eventual histopathological diagnosis and define its clinical utility. Methods: The pre-operative ultrasound scans of 78 patients were assigned an R status by our specialist head and neck radiologist. The final histopathology report for each thyroid nodule was used as the ‘gold standard’ for analysis. Results: When thyroid nodules were classified as low risk (R stages 1–3) or high risk (R stages 4–5) for malignancy, the sensitivity of R staging was 74.2 per cent and specificity was 80.9 per cent. An R5 status was 100 per cent predictive of malignancy. Conclusion: Our results compare favourably with other suggested ultrasonographic staging systems for thyroid nodules. Key words: Thyroid Nodule; Thyroid Neoplasms; Pathology; Ultrasonography; Classification

Introduction Thyroid nodules are very common, with a prevalence of 3–7 per cent based on palpation.1,2 Ultrasonography of the neck and upper chest has been reported to detect incidental thyroid nodules in 10–67 per cent of adults,3,4 and a prevalence of 50 per cent is reported from autopsy data.5 Ultrasonography is useful in distinguishing the characteristics of malignant and benign thyroid nodules. Though only 5–9 per cent of thyroid nodules are malignant, it is vital to detect these.6 Many patients with a palpable thyroid nodule are asymptomatic, and there is no correlation between histopathological features and reported symptoms. Guidelines therefore recommend ultrasonography in: patients at risk of thyroid malignancy, those with palpable thyroid nodules or multinodular goitres, and patients with lymphadenopathy suggestive of a malignant lesion.7 Ultrasound-guided fine needle aspiration (FNA) biopsies are typically performed on suspicious nodules detected by ultrasonography. Ultrasound evaluation and cytology results should be used in combination to determine the management of thyroid nodules.

Modern, high-resolution ultrasound equipment can detect non-palpable thyroid nodules as small as 1–2 mm in diameter. Even if the diameter of the thyroid nodule is less than 10 mm, if ultrasonography shows features suspicious of malignancy, ultrasoundguided FNA is recommended.7 Papini et al. concluded that there was no significant difference in the prevalence of malignancy in nodules greater or smaller than 10 mm.8 The same series, involving non-palpable thyroid nodules, demonstrated extracapsular growth in 35.5 per cent and nodal involvement in 19.4 per cent of thyroid cancers. The prevalence of extracapsular and metastatic growth was similar in nodules greater or less than 10 mm.8 Studies have reported no difference in the risk of malignancy between a thyroid gland with a single thyroid nodule and one which is multinodular.2,9,10 The majority of studies to date have analysed single ultrasonographic features to test how predictive they are for malignancy. Features that have been associated with an increased risk of malignancy are: a predominately solid nodule, hypoechogenicity, microcalcification, macrocalcification, ill-defined margins, intranodular vascularity, a

Accepted for publication 12 February 2014

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taller-than-wide shape, extracapsular invasion and abnormal lymph nodes.6 Around 90 per cent of malignant thyroid nodules are solid and hypoechoic, with decreased echogenicity compared to surrounding thyroid parenchyma and similar echogenicity to the anterior strap muscles.6 However, a solid hypoechoic nodule is still nine times more likely to be benign than malignant.8,10 A honeycomb or spongiform appearance is due to multiple cystic spaces separated by thin septations within the nodule, and is associated with a very low risk for malignancy.11,12 Microcalcifications had a relatively high specificity (54–99 per cent), but low sensitivity (19–89 per cent) for thyroid malignancy in 20 studies included in the systematic review by Bastin et al.6 Illdefined, blurred or lobulated margins have a moderate specificity (22–98 per cent) but low sensitivity (8–89 per cent).6 A nodule that is a taller-than-wide shape is known to be a marker for malignancy on breast ultrasonography; for thyroid ultrasonography, this characteristic has been shown to have high specificity (60–93 per cent) and low sensitivity (32–84 per cent) for thyroid cancer.6 With regard to intranodular vascularity, sensitivities (57–100 per cent) and specificities (35–90 per cent) are moderate.6 Ideally, a single ultrasonographic feature should have high sensitivity and high specificity for the diagnosis of thyroid cancer, but as this is not the case, several authors have proposed combinations of ultrasonographic features that might indicate a high risk of malignancy. The most impressive is the presence of taller-than-wide shaped nodules plus at least two of the following features: hypoechogenicity, blurred margins, calcification or intranodular vascularity. This combination identified 99 per cent of thyroid cancers (confirmed by ultrasound-guided FNA) in 72 per cent of nodules.13 Another proposed combination is the presence of at least two of the following features: hypoechogenicity, size greater than or equal to 10 mm, blurred margins or microcalcification. This combination identified 93 per cent of cancers (confirmed by ultrasound-guided FNA) in 57 per cent of nodules.14 Follicular nodules are difficult to diagnose as malignant or benign using ultrasonography. Koike et al. compared ultrasonographic characteristics to pathological results, and the overall sensitivity of pre-operative ultrasonography for the diagnosis of follicular nodules was extremely low, at 18.2 per cent, compared with 86.5 per cent for non-follicular nodules.15 Their study highlighted that ultrasonography was unreliable for the diagnosis of follicular nodules. One can look to the specialty of breast surgery for further inspiration. The American College of Radiology has designed a staging system called the Breast Imaging Reporting and Data System (‘BI-RADS’), which is successfully used worldwide to categorise ultrasonographic features of breast masses.16 It was developed to help standardise breast imaging reporting. The Breast Imaging Reporting and Data System categories range

from 1 (negative findings) to 6 (known, proved malignancy). The level of suspicion for malignancy increases from category 1 through to category 6. The cut-off point for deciding whether to assign the patient to imaging follow up or to send them for biopsy is between categories 3 and 4. Category 4 was further divided into subcategories 4a–c (wherein 4a = low suspicion, 4b = intermediate suspicion and 4c = moderate suspicion), to allow better communication between clinicians and patients. Some have tried to develop an ultrasonographic staging system for thyroid nodules modelled on the Breast Imaging Reporting and Data System; these have been referred to as ‘thyroid imaging reporting and data systems’ (‘TIRADS’). Reluctance to design a thyroid imaging reporting and data system has stemmed from the impression that ultrasonography is a very subjective method for assessing the risk of malignancy in thyroid nodules. Few studies have analysed the observer variability of ultrasonography. Choi et al. reviewed 204 ultrasound images and Cohen’s kappa statistics were used to evaluate variations.17 Inter-observer variations ranged from slight agreement for echogenicity (κ = 0.34) to substantial agreement for vascularity (κ = 0.64). Nearly all showed substantial agreement (κ > 0.61) for intra-observer variability. Accuracy was high for all four radiologists, at 82.8 per cent. These experienced radiologists showed more than a moderate degree of agreement in ultrasonography of thyroid nodules, and their interpretation of ultrasound images were highly accurate. This demonstrates that experienced radiologists should be able to use a thyroid imaging reporting and data system relatively accurately with reproducibility. The current study aimed to: classify and structure the ‘R staging’ (sonographic scoring) system, examine the relationship between R staging and the eventual histopathological diagnosis, and define the clinical utility and applicability of R staging.

Materials and methods The study (supervised by GM) comprised patients who underwent partial or total thyroidectomy between 14 November 2008 and 16 September 2011. A total of 112 thyroid operations were performed on 104 patients. Eight patients underwent two operations (e.g. completion thyroidectomy) for malignancy. Sonographic scoring (R staging) was used for reporting sonographic risk of malignancy. The R staging system, designed by our specialist radiologist, is illustrated in Table I. An R status was assigned to the pre-operative ultrasound scan of each patient (based on a combination of the features listed below) by our experienced head and neck radiologist (GO). The radiologist was blinded to the surgical procedure and eventual pathology at the time of classification.

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Definition Benign Probably benign Indeterminate (e.g. suspected follicular lesion or, more commonly, indeterminate nodule) Suspicious Malignant (unless histologically proven otherwise)

Features suspicious for malignancy included: a solid, hypoechoic nodule (darker than adjacent thyroid parenchyma) – suspicion is increased for hypoechoic nodules that are more hypoechoic (darker) than strap muscle; an irregular margin; microcalcification (small, hyperechoic foci); an anterior–posterior diameter exceeding the transverse diameter; and hypervascularity on Doppler sonography.18 Features suggesting benignity included: the presence of comet-tail artefacts; spongiform configuration; cyst with colloid clot; giraffe pattern; diffuse hyperechogenicity; and a solid, isoechoic nodule, which is thought to indicate suspicion of a follicular lesion.19,20 Table II shows the ultrasonographic characteristics for each R status. Exclusion criteria for the study were as follows: ultrasonography report or suitable hard copy of ultrasound images unavailable, or an incomplete report; ultrasonography not originally performed by our head and neck radiologist; no definite thyroid nodule on the ultrasound image; repeat ultrasound for the same patient; follow-up ultrasound for histologically proven thyroid cancer; and pathology report unavailable. The final histopathological diagnosis was used as the ‘gold standard’ for analysis. A total of 78 patients met the inclusion criteria. Data regarding the type of surgical procedure and the date it was performed were obtained from operating theatre records. Clinical Portal (NHS Greater Glasgow and Clyde’s web-based electronic patient record system) was used to access patient details, which included age at diagnosis, gender and the final histopathology report. Pathological factors, including histological type, lymph node involvement and evidence of metastases, were recorded.

The data were entered into a Microsoft Excel spreadsheet and stored securely in a password-protected folder on the NHS Greater Glasgow and Clyde server. Statistical analysis was performed using Minitab® 16 software. Subgroup analyses were performed in which follicular thyroid nodules were compared with nonfollicular thyroid nodules. Statistical significance was assessed using Fisher’s exact test.

Results A total of 112 pre-operative ultrasound scans were performed on 104 patients over the 34-month study period. Following exclusion, 78 patients (75 per cent) were eligible for inclusion in the study. Demographics The median age of diagnosis was 51 years (range, 17–80 years). Fifteen patients (19 per cent) were male and 63 (81 per cent) were female. Histopathology Forty-seven (60.3 per cent) of the thyroid nodules were benign, and 31 (39.7 per cent) were malignant. A breakdown of benign tumour types is shown in Table III. Papillary carcinoma was present in 21 malignant thyroid nodules (67.9 per cent), as seen in Table IV. Seven cases (22.6 per cent) were follicular variants of papillary carcinoma. Three patients had more than one thyroid nodule. Papillary microcarcinoma was found in combination with follicular adenoma in two patients (6.5 per cent) and follicular carcinoma in one patient (3.2 per cent). Patients with two nodules were assigned an ultrasonographic score (R status) based on the lesion with the ultrasonographic malignant features. Metastatic deposits from malignant melanoma and renal cell carcinoma presented as thyroid nodules. Ultrasonographic staging Table V shows the number of patients assigned to each R stage. The ultrasound images were most frequently assigned an R3 status. The probability of malignancy (based on histopathology) in thyroid nodules assigned an R status of 1, 2, 3, 4 or 5 was 25 per cent, 21.4 per cent, 14.3 per cent, 60.9 per cent or 100 per cent respectively.


Ultrasonographic characteristics Definitely benign: simple cyst, spongiform nodule, or predominantly cystic nodule (>75% cystic) with no suspicious intranodular solid focus (e.g. hypervascular nodule or focus of intranodular microcalcification) & with comet-tail artefacts Probably benign: part cystic & part solid (25–75% cystic), or solid & hyperechoic (with no suspicious solid component) Indeterminate (

The predictive value of structured ultrasonographic staging for thyroid nodules.

'R staging' is a new ultrasonographic scoring system developed and used by our specialist head and neck radiologist for reporting sonographic risk of ...
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