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Background: Thyroid cancer is most common endocrine malignancy and there is high incidence of thyroid nodule detection in ultrasonography in general population. Determination of the thyroid nodule as benign or malignant depends upon certain characteristic features like calcifications, vascularity, echogenicity of the nodule etc. Calcification within the thyroid gland occur in both benign and malignant thyroid disease. Calcification patterns within thyroid nodules, particularly microcalcifications, are considered important predictors of malignancy and are incorporated into various thyroid risk stratification systems. Objective: To evaluate the association of different ultrasonographic calcification patterns in thyroid nodules with thyroid malignancy. Materials and Methods: This Prospective observational study was conducted in the Department of Radiodiagnosis, Kidwai Memorial Institute of Oncology, Bengaluru, over the study period of 2 years (December 2020-December 2022). A total of 100 patients with thyroid nodules underwent ultrasonography followed by cytological or histopathological confirmation were included. Calcification patterns were classified as microcalcification, macrocalcification, peripheral rim calcification, and comet-tail artefacts. The sonographic findings were correlated with the final pathological diagnosis. Statistical analysis was performed to determine the association between calcification patterns and malignancy. Results: The study included 100 patients aged 12-75 years (mean age: 50.16 years). Of these, 79 were females and 21 were males. 53 nodules were benign and 47 were malignant. Microcalcifications were observed in 26 malignant nodules and only 6 benign nodules, demonstrating a significant association with malignancy. Macrocalcifications were identified in 7 nodules, including 4 benign and 3 malignant lesions. Peripheral rim calcification was observed in 2 malignant nodules, both of which also demonstrated microcalcifications. Comet-tail artefacts were predominantly associated with benign colloid nodules. Conclusion: Microcalcifications are a significant ultrasonographic predictor of thyroid malignancy, particularly papillary thyroid carcinoma. Accurate differentiation between microcalcifications, macrocalcifications, and comet-tail artefacts improves risk stratification and facilitates appropriate patient management.
The thyroid gland is a midline structure located in the anterior neck. The thyroid functions as an endocrine gland and is responsible for producing thyroid hormone and calcitonin, thus contributing to the regulation of metabolism, growth, and serum concentrations of electrolytes such as calcium (1). Among the radiologic procedures, High Resolution Ultrasonography (HRUS) is a sensitive, relatively inexpensive, non-invasive and an easily accessible modality of imaging for examination of thyroid gland (2). Due to its superficial location, ultrasonography (USG) plays an important role in assessing pathologies in the gland (2) hence Ultrasonography is the modality of choice for initial characterization of a thyroid nodule (3) .
Thyroid nodule is any lesion in the thyroid gland that is discrete and is radiologically distinct from the surrounding thyroid parenchyma (4). Features like irregular margins, internal vascularity and microcalcifications can point towards "suspicious" thyroid nodules (5).
Thyroid cancer represents the most common malignancy of the endocrine system (6). Recent global and national cancer statistics indicate a steady and concerning increase in both incidence and mortality rates associated with this disease. In 2022, approximately 821,200 new cases of thyroid cancer and 47,000 related deaths were reported worldwide (7). Thyroid cancer accounted for 4.1% of all newly diagnosed cancers (up from 3.0% in previous years) and 0.5% of all cancer-related death (up from 0.4%).
In addition, emerging evidence indicates that heterogeneous calcification morphologies and distribution patterns may correlate with more aggressive tumour behaviours, including larger tumour size, regional lymph node metastasis, and an increased risk of recurrence (8,9).
Among all sonographic features, calcification patterns are particularly important predictors of thyroid malignancy. Microcalcifications, which correspond histopathologically to psammoma bodies, are strongly associated with papillary thyroid carcinoma and are regarded as one of the most specific ultrasonographic markers of malignancy (10,11). In contrast, macrocalcifications and peripheral rim calcifications demonstrate variable associations with malignant and benign thyroid nodules, whereas comet-tail artefacts are generally considered characteristic of benign colloid nodules (12,13).
However, current classification systems for thyroid calcification remain inconsistent, and there is a scarcity of studies that systematically explore the relationship between specific calcification subtypes and detailed clinicopathological features. Most prior research has focused primarily on isolated calcification types with limited attention to mixed or complex patterns, leaving the clinical significance of combined calcification morphologies and their spatial distribution poorly defined (14,15).
To address these limitations, the present study aimed to investigate the association between different ultrasound calcification patterns—including absence of calcification, microcalcification, macrocalcification and comet tail artifacts.
This study aims to investigate the association of different ultrasound calcification patterns with thyroid malignancy.
This Prospective observational study was conducted in the Department of Radiodiagnosis, Kidwai Memorial Institute of Oncology, Bengaluru, over the study period of 2 years (December 2020-December 2022). A total of 100 patients with thyroid nodules who underwent ultrasonography followed by fine-needle aspiration cytology (FNAC) were included in the study. The patients ranged in age from 12 to 75 years, with a mean age of 50.16 years. There were 79 females and 21 males. INCLUSION CRITERIA 1. Patients with thyroid nodules detected clinically and on ultrasonography. 2. Patients who underwent ultrasound evaluation followed by FNAC. 3. Patients with complete ultrasound imaging and cytological records. EXCLUSION CRITERIA 1. Patient who is unable to lie down for ultrasound. 2. Patient with thyroid nodule who is refusing for USG guided FNAC. 3. Post-surgical cases. 4. Post Radiotherapy. 5. Inconclusive /unsatisfactory histopathology report. 6. Diffuse thyroid disease. METHODS High-resolution thyroid ultrasonography was performed using a GE logic P7 ultrasound system equipped with a 5-12 MHz high-frequency linear array transducer. Each thyroid nodule was evaluated according to the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS). The sonographic features assessed included nodule composition, echogenicity, shape, margins, and echogenic foci (calcification patterns). Calcifications were classified as: * Punctate microcalcifications * Macrocalcifications * Peripheral (rim) calcifications * Comet-tail artefacts Microcalcifications were defined as punctate echogenic foci measuring less than 1 mm, while macrocalcifications were defined as coarse calcifications measuring greater than 1 mm with posterior acoustic shadowing. Comet-tail artefacts were considered characteristic of colloid-containing benign nodules. The site of the lesions included both the lobes and isthmus of thyroid gland. Patients with severe coagulopathy were considered as contraindications for FNAC in view of possible serious complications. The procedure of FNA was explained to the parent/guardian seeking an informed consent. The mass under investigation was evaluated by USG and the path of FNA providing the safest and easiest access to the lesion was chosen. About 21 or 22 g needle (38 mm length) were chosen for FNAC depending upon the depth of the lesion from the skin. Under aseptic precautions, FNAC was performed with needle/canula attached to a 10 mL disposable syringe. Each aspirate was smeared on an average 3‐4 slides and 2 slides were immediately wet fixed in 95% alcohol fixative. The aspirate smears were sent for evaluation and the final cytomorphological diagnosis was made. The ultrasonographic findings were correlated with the final FNAC diagnosis, which served as the reference standard. Thyroid nodules were classified as benign or malignant based on cytological findings. Various calcifications found using ultrasonography was correlated with FNAC diagnosis and the relationship of calcifications with malignancy was established.
A total of 100 patients with thyroid nodules were included in the study. The patients ranged in age from 12 to 75 years, with a mean age of 50.16 years. Females constituted the majority of the study population (79%), while males accounted for 21%.Based on FNAC, 53 nodules were benign and 47 were malignant.
The highest number of thyroid nodules was observed in the 41-50 years age group (29%), followed by the 51-60 years age group (23%). Benign nodules were most frequently encountered in the 51-60 years age group (16 cases), whereas malignant nodules were most common in patients aged 41-50 years (14 cases).
Among the 79 female patients, 46 nodules were benign and 33 were malignant. Among the 21 male patients, 7 nodules were benign and 14 were malignant. Although thyroid nodules were more common in females, the proportion of malignant nodules was relatively higher among male patients.
Microcalcifications were observed in 26 malignant nodules(81%) and only 6 benign nodules(19), demonstrating a significant association with malignancy(Fig 1). Macrocalcifications were identified in seven nodules, including four benign(57%) and three malignant lesions(43%)(Fig 3). Peripheral rim calcification was observed in two malignant nodules, both of which also demonstrated microcalcifications.(Fig 2). Comet-tail artefacts were predominantly associated with benign colloid nodules(Fig 4).
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Fig 1 : USG of thyroid gland showing hypoechoic solid nodule in left side with microcalcifications and left cervical lymphadenopathy .FNAC proved as Papillary carcinoma thuroid with metastatic lymph node .
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Fig 2: USG of thyroid gland showing well defined isoechoic solid nodule in left side with peripheral rim calcifications .FNAC proved as Adenomatous hyperplasia. |
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Fig 3: USG of thyroid gland showing well defined isoechoic solid nodule in right side with cystic areas and macro calcifications with posterior acoustic shadowing .FNAC proved as Adenomatous hyperplasia. |
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Fig 4: USG of thyroid gland showing well defined wider than taller solid cystic nodule in with smooth margins in right lobe with comet tail artefacts .FNAC proved as colloid nodule. |
Various types of calcification include punctate micro calcification, macrocalcification ,peripheral rim calcification and comet tail artefacts.As per the study conducted by Sio MCD et al. among 126 patients, 81 had benign lesions and 45 had malignant lesions. Calcifications were present in 40% (51/126) of patients, with 59% of these occurring in malignant nodules and 41% in benign nodules. Of the malignant nodules with calcifications, 86% were papillary thyroid carcinoma, 7% were follicular carcinoma, and 7% were other malignancies. Peripheral calcification was the most common pattern (37%), followed by microcalcification (33%) and coarse calcification (30%) (16). Based on the study by Hoang et al. in 2007, microcalcifications are found in 29% to 59% of all primary thyroid carcinomas, most commonly in papillary thyroidcarcinoma (17). In our study majority of cases (53%) didn’t have calcification where as 32 % cases had punctate microcalcification ,7% had macro calcification and 8 % had comet tail artefacts(Table 1) . In our study 81% of nodules (26 out of 32 ) with punctate echogenic foci were malignant on FNAC and majority of them belonging to papillary carcinoma category. Among benign nodules 11 % that is 6 out of 53 cases had punctate echogenic foci. This implies that punctate micro calcification is more in favour of malignant pathology. All 8 thyroid nodules with comet tail artefacts were benign on FNAC which implies comet tail artefact is a feature of benignity. In our study 9.5 % (5 of 54) of benign nodules and 4% (2 of 47 ) of malignant nodules had macrocalcifications. This was a non-specific finding. TABLE 1: CALCIFICATION VS NATURE OF NODULE CALCIFICATION BENIGN MALIGNANT TOTAL COMET TAIL 8 0 8 MACROCALCIFICATION 4 3 7 NONE 35 18 53 PUNCTATE MICROCALCIFICATION 6 26 32 Grand Total 53 47 100
The present study demonstrates that calcification patterns on ultrasonography are valuable predictors of thyroid malignancy and play a significant role in the risk stratification of thyroid nodules. Among the various calcification patterns evaluated, microcalcifications showed the strongest association with malignant thyroid nodules, particularly papillary thyroid carcinoma, and were significantly more common in malignant lesions than in benign nodules. Histopathologically, these punctate echogenic foci correspond to psammoma bodies and remain one of the most reliable sonographic markers of thyroid cancer.
Although macrocalcifications were identified in both benign and malignant nodules, they exhibited lower specificity for malignancy when compared with microcalcifications. Comet-tail artefacts were predominantly observed in benign colloid nodules and therefore may be considered a reassuring sonographic feature when present in the appropriate clinical context. Careful differentiation between true microcalcifications and coarse or fragmented macrocalcifications is essential, as misinterpretation may lead to overestimation of the malignancy risk and inappropriate TI-RADS categorization.
10 O’Connor E, Mullins M, O’Connor D, et al. The relationship between ultrasound microcalcifications and psammoma bodies in thyroid tumours: A single-institution retrospective study. Clin Radiol. 2022;77(1):e48-e54. doi:10.1016/j.crad.2021.09.014.
11 Kwak JY, Han KH, Yoon JH, et al. Thyroid Imaging Reporting and Data System for US features of nodules: a step in establishing better stratification of cancer risk. Radiology. 2011;260(3):892-899.
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