Relative Observer and Technical Error in the Ultrasonic Monitoring of Thyroid Nodular Growth Using Nodular Volume (VOL), vs. Longest Dimension (LD), vs. the Sum of the 3 Nodular Dimensions (SUM3D)

Though not a reliable indicator of malignancy, ultrasonic monitoring of nodule growth still has a role in the evaluation of nodules, e.g. indicating when a nodule may require biopsy or re-biopsy. Observer and technical limitations, however, limit the precision of ultrasonic determination of simple growth, vs. stability or shrinkage. Ultrasonic parameters used for this purpose all have their own limitations. Monitoring nodule growth by VOL frequently exhibits wide and conflicting swings in apparent size compared to the penultimate size, doubtlessly reflecting measurement limitations. As a growth parameter, LD typically exhibits a smoother time course but does not address growth in the other two dimensions. SUM3D includes changes in all dimensions but, like LD, is not a true measure of nodule mass or volume. This study was to determine the relative error of these three growth parameters and how it relates to their relative efficacy for nodular growth monitoring. The anterior-posterior (AP), left-right (LR) and superior-inferior (SI) dimensions of 34 benign nodules were determined ultrasonographically by four pairs of trained observers. One observer of a pair was regarded as a Time-1 observer and the other as a Time-2 observer, simulating the process for determining growth change over time. All observers measured the same image of each of the 34 nodules but were unaware of the measurements obtained by any other observer. For each image for each pair of observers, the dimensions were used to calculate the VOL, LD and SUM3D and the perceived changes thereof from Time-1 to Time-2. Since only one image for each nodule was distributed, differences between the Time-1 vs Time-2 measurements for each nodule could only reflect observer-based differences. “S”-curves plotting the nominal %-change in a parameter reported by the Time-2 observer compared to that reported by the Time-1 observer (x-axis) were rank-ordered from negative to positive changes (y-axis). The %-change in each parameter due to observer/technical error ranging from the highest over-estimate to the lowest were, in order from Top 10%, Middle 40%, and Bottom 10%, respectively: LD: 19-36%, -4 to 6%, -15 to -42%; SUM3D: 15 to 28%, -4 to 4%, -11 to -43%; VOL: 48 to 105%, -13 to 15%, -33 to -81%. The magnitude of %-change from Time-1 to Time-2 for the VOL parameter were 2 to 3 times greater than that of the LD or SUM3D parameters for the top 10% of values, the middle 40% of values, and the bottom 10% of values. These degrees of difference coincide with the wide variability seen in nodular growth curves [not illustrated here] when nodular VOL (y-axis) is plotted as a function of length of observation (x-axis). This study helps explain why monitoring nodular growth by LD or by the SUM3D usually provides a clearer, less fluctuant illustration of thyroid nodule growth over time than does VOL.

An Unusual Presentation of Parathyroid and Micro Papillary Thyroid Carcinoma

Background: Parathyroid carcinoma is a rare endocrine malignancy, that usually presents with parathyroid hormone elevations five to ten times higher than normal. It is rarely diagnosed in cases with a normal or mildly elevated PTH. Clinical Case: 68 yo female with history of Hypertension, Spontaneous Vocal Cord Paralysis, Multinodular Goiter, Breast cancer s/p right radical mastectomy/chemotherapy, and Osteoporosis who presented to outpatient Endocrine clinic for hypercalcemia. Medications include Coreg 12.5 mg BID. Patient was asymptomatic. Labs showed BUN 21 mg/dL [8 mg/dL - 27 mg/dL], Creatinine 0.82 mg/dL [0.57 mg/dL - 1 mg/dL], eGFR 74 ml/min/1.73 m2 [nl>59 ml/min/1.73 m2], Calcium 10.8 mg/dL [8.7 mg/dL - 10.3 mg/dL], Phosphorus 3 mg/dL [3 mg/dL - 4.3 mg/dL], Magnesium 2.2 mg/dL [1.6 mg/dL - 2.3 mg/dL], PTH 77 pg/mL [15 pg/mL - 65 pg/mL], Albumin 4.2 g/dL [3.8 g/dL - 4.8 g/dL], Vitamin D 1,25 Dihydroxy 47.2 pg/mL [19.9 pg/mL - 79.3 pg/mL], Vitamin D 25-OH 18.2 ng/mL Low [30 ng/mL - 100 ng/mL], TSH 1.599 uIU/mL (.450-5.330 uIU/mL), Hgb 13.4 g /dL (12.0 -16.0 g/dL). Most recent FNA in 2019 of a dominant thyroid nodule was benign. Bone Density Scan June 2020 showed a T score of -3.4 in the lumbar spine and -3.1 in the left hip. Sestamibi Scan showed a right inferior parathyroid adenoma. Following ENT consultation, patient underwent surgical exploration. Pathology showed parathyroid tissue with extensive fibrosis, consistent with Parathyroid Carcinoma (1.8 x 1 x .7cm), probable positive margins, nodular growth pattern with individual nodules separated by fibrous bands, capsular invasion, focally, into adjacent adipose tissue invading through the thyroid capsule, positive for perineural invasion and PTH. Ki67 approximately six percent. Right thyroid lobe excision should a micro focus of papillary thyroid carcinoma (.2 x .2 cm), capsulated, negative margins, pT1a. Conclusion: This case demonstrated an unusual presentation of Parathyroid carcinoma causing a mild elevation of PTH level that in pathology after excision unexpectedly revealed a right parathyroid carcinoma along with micro papillary thyroid carcinoma.

A Rare Pulmonary Myoepithelial Tumor With Novel TRPS1-PLAG1 Fusions

Background: Little is known about the morphological and molecular features of intra-thoracic myoepithelial tumors. Here, we describe a rare pulmonary myoepithelial tumor with novel TRPS1-PLAG1 fusions.Case presentation: A 30-year-old male presented with multiple lung nodules that detected by routine computed tomography (CT) scan 3 years ago. Positron emission tomography-computed tomography (PET-CT) demonstrated a well-circumscribed mass with a diameter of 3cm in the left pulmonary hilum and multiple nodules in bilateral lungs. No other extra-thoracic primary lesion and distant metastasis was found. The clinical history was not other specified. Microscopically, these lesions were well-defined, showed nodular growth pattern filling the bronchioles and alveoli. The tumor cells were epithelioid to plasmacytoid with slightly eosinophilic cytoplasm, arranged in aggregates, nests and cords. Myxoid background presented in some foci. Nuclear pleomorphism was mild and mitotic activity was not prominent. No distinct gland formation was identified. Immunostains demonstrated that the tumor cells were diffusely positive for pan-cytokeratin (AE1/AE3), CK5/6, S100, SOX10, and negative for calponin. Noticeably, a TRPS1-PLAG1 gene fusion was identified in this tumor by targeted RNA sequencing involved TRPS1 exon1 and PLAG1 exon2, this rare rearrangement was validated by fluorescence in situ hybridization (FISH) for PLAG1 break-apart probe, and 30% tumor cells showed break apart signals. Conclusions: Here we present the first case of a disseminated thoracic myoepithelial tumor with novel TRPS1-PLAG1 fusions. Targeted RNA sequencing strongly facilitates precise classification and providing opportunities for unknown fusion partner discovery, which is significant for risk stratification and development of potential therapeutic targets.