(14.05) Diagnostic Accuracy of Fine-Needle Aspiration Biopsy and Potential Utility of Pre-Biopsy Serum Calcitonin in Certain Thyroid Nodules: A 15-Year Retrospective Study of Medullary Thyroid Carcinoma Diagnoses at a Tertiary Care Center

Objective : Medullary thyroid carcinoma (MTC) is a rare malignancy originating from the parafollicular calcitonin-secreting (C)-cells of the thyroid. MTC, presenting predominantly in a sporadic manner but also as part of inherited cancer syndromes such as Multiple endocrine neoplasia type 2 (MEN2), constitutes less than 5% of all thyroid malignancies but accounts for nearly 13% of thyroid cancer deaths. Early diagnosis is critical to adequate surgical treatment and, therefore, favorable outcomes. Fine-needle aspiration (FNA) biopsy has a diagnostic accuracy of only 56% in detecting MTC prior to surgery. Pre-operative measurement of serum calcitonin has been shown to improve diagnostic accuracy but is not cost-effective for all nodules. The embryological descent of C-cells to the upper part of the developing thyroid gland may provide clues to MTC detection. Previous studies have demonstrated that the majority of MTCs are located in the upper lobes of the thyroid and present as solid nodules on ultrasound.

Methods: A retrospective chart review study of all adult patients diagnosed with MTC seen by WVU Endocrinology Clinic over the past 15 years (2008-2023) was conducted. Demographic and clinical data were collected. Pre-operative dominant thyroid nodule size, location, and composition findings by thyroid ultrasound evaluation were recorded. Initial pathology results by FNA biopsy were reviewed, including false negative results for MTC. Post-operative pathology results were reviewed to identify final MTC size and location. Summary statistics were used to characterize nodule findings on ultrasound as well as initial and final pathology results.

Results:

22 MTC patients (11 males, 11 females) were identified. 6 patients were diagnosed with MTC in the setting of MEN2A; 2 of these patients required prophylactic thyroidectomy due to the presence of high-risk mutations with FNA biopsy deferred. On ultrasound, average dominant nodule size was 1.88 cm. Nodules were predominantly located in the upper (45.4%), as well as middle (40%) lobes. Sonographically, most nodules appeared solid (77.3%), with over half being hypoechoic (54.5%). 14 nodules underwent FNA biopsy, with 6 (42.8%) showing initial false negative results for MTC including papillary, follicular, and Hurthle cell neoplasms. Final post-operative pathology results showed an average dominant tumor focus of 2.04 cm. Most MTC tumors were ultimately identified in the upper lobes (45.4%), followed by the middle (36.3%) and lower (18.1%) lobes.

Discussion/Conclusion: Our findings suggest that thyroid nodule location and composition can add diagnostic utility to the pre-operative evaluation of MTC. Sonographic identification of solid, hypoechoic nodules in the upper, as well as middle, lobes corresponded with post-operative MTC-proven pathology results. Our elevated rate of false negative FNA biopsy results for MTC also reflects data from prior investigations indicating its limited sensitivity. Thus, measurement of serum calcitonin in the presence of a solid, hypoechoic nodule located in the upper and middle thyroid lobes could serve as a useful non-cytologic diagnostic tool and, ultimately, be more cost-effective.