Eggshell Calcifications at Thyroid Ultrasound: A Sample-focused Analysis of Cytological Findings and Post-thyroidectomy Pathological Correlates

1 - Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

2 - Department of Gastroenterology, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest, Romania; florentina.ionita-radu@umfcd.ro

3 - Doctoral School of Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; anamaria.gheorghe96@yahoo.com; oanaclaudia1@yahoo.com

4 - Department of Endocrinology, C. I. Parhon National Institute of Endocrinology, Bucharest, Romania; carsote_m@hotmail.com

5 - Department of Thoracic Surgery, Dr. Carol Davila Central Military Emergency University Hospital, Bucharest, Romania; ncd58@yahoo.com Correspondence: Mara Carsote, carsote_m@hotmail.com Abstract: Eggshell calcifications at thyroid ultrasound are connected to the challenging field of thyroid nodules and/or malignancy from a multidisciplinary perspective. Calcifications may be found in malignant and benign tumors; typically, micro-calcifications are identified in the papillary type of cancer, being equivalent to psammoma bodies in the pathological report. The risk of macro- calcifications, however, is more nuanced; recent data suggest a potential connection with a differentiated malignancy as well. Eggshell calcifications, a distinct type of macro-calcification, are generally considered benign findings, especially uninterrupted forms. Yet, the real incidence is not clear, which is why the topic remains open. In this narrative review, we analyzed eggshell calcifications in relationship with cytological diagnosis upon fine needle aspiration and post-thyroidectomy histological report. A PubMed-based search of the English-language papers using several keywords identified 171 articles. We only included original studies (no timeline restriction). After removing duplicates and applying the inclusion and exclusion criteria, 14 original studies were analyzed. The number of subjects per study varied (N=61 to 2678) so did the number of analyzed nodules per study (a maximum of 2902). Some studies found connections with benign features; others revealed a higher risk of malignancy at fine needle aspiration. Data remain heterogeneous, and oftentimes, studies investigated it only as a secondary endpoint. A high TI- RADS score is important in malignancy prediction, while eggshell calcification might add to the positive predictive value, yet, this trait is difficult to classify as a standalone element. Nevertheless, an interrupted pattern does not exclude thyroid cancer. Keywords: thyroid, ultrasound, calcification, thyroidectomy, surgery, thyroid nodule, thyroid INTRODUCTION Eggshell calcifications amid thyroid ultrasound are connected to the challenging field of thyroid nodules and/or thyroid malignancy. Recently, an important rise in thyroid nodule detection was brought about by the widespread use of ultrasonography, with detection rates reaching 60% of the general population (noting that the general prevalence of a thyroid nodule is 5%) [1,2]. As a consequence, there was also an apparent increase in over-diagnosis of differentiated thyroid cancer [3]. The increased costs, risks associated with surgical cures such as hypoparathyroidism and dysphonia, and the fact that most thyroid carcinomas are indolent, led current guidelines to lean towards a more conservative and individualized approach to thyroid nodules [4-7]. However, even though the mortality rates of thyroid carcinoma remained stable despite an increasing incidence, this is in opposition to decreasing rates of other solid malignancies [8]. The need for adequate risk assessment of thyroid nodules, therefore, remains clear. The importance of approaching this type of ultrasound lesion comes from providing additional clues and even risk factors for suspected malignancies to assess these patients particularly or to start meticulous screening protocols. Moreover, nowadays, thyroid ultrasound is largely available to a multitude of specialists coming from different backgrounds thus the importance of identifying the risk (if any) behind such lesions [4-8]. Currently, there are several risk stratification systems for thyroid nodules, including the American College of Radiology