Faculty Bibliography

Introduction: Due to the diagnostic dilemma with indeterminate thyroid Bethesda categories III and IV (atypia of undetermined significance, AUS and Suspicious for follicular neoplasm, SFN), many laboratories utilize molecular testing to aid in risk stratification of these nodules. In this study, we evaluated the risk of malignancy (ROM) in AUS and SFN thyroid nodules with subsequent negative molecular (ThyroSeq) test results.
Material(s) and Method(s): This study was designed to evaluate the negative molecular thyroid fine needle aspiration (FNA) cases at a tertiary medical center in the metropolitan area. 109 cases of AUS and SFN thyroid FNAs over 3 years with surgical pathology follow up were included in the study.
Result(s): Of 109 AUS and SFN cases, 4 cases showed insufficient material for ThyroSeq testing (3.7%), 76 cases showed a molecular alteration (69.7%), and 29 cases were negative for an alteration on ThyroSeq (26.6%). Among the cases with negative ThyroSeq results, 26 cases were benign on surgical pathology (89.7%) (7/26 were follicular adenomas), and 3/29 cases were malignant on histopathology (papillary thyroid carcinoma) (ROM=10.3%, Table 1). AUS and SFN cases with molecular alterations showed a significantly higher ROM (ROM= 60.5%) compared to cases testing negative for molecular alterations (p<0.01, z = -4.61).
Conclusion(s): Our study found that indeterminate thyroid nodules that tested negative for a molecular alteration displayed an ROM of 10.3%. This ROM is comparable to the lower limit of ROM of FNA alone (without additional molecular testing data) in the AUS and SFN categories (10-30%), but is significantly lower than the ROM of indeterminate thyroid cases with known molecular mutations. Therefore, clinical follow-up is recommended for thyroid FNA indeterminate nodules, even those testing negative for a molecular alteration, due to the maintained, albeit lower, ROM. [Formula presented]
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Introduction: Urothelial carcinomas (UC) of the upper urinary tract (UUT) are rare, and usually show higher grade and poorer prognosis than carcinomas of the bladder. The Paris System (TPS) has been integrated into our standard terminology for interpreting urine cytology. Here we compare TPS diagnoses to the traditional reporting system (TD) in interpreting UC of UUT and lower urinary tract (LUT) in correlation with surgical pathology diagnoses (SD).
Material(s) and Method(s): A search of the cytopathology database on urine specimens from 7/1/2014-6/30/2016 (TD) and 7/1/2017-6/30/2019 (TPS) with corresponding lesions in SD, yielded 14-TD cases and 19-TPS in UUT; and 178-TD and 243-TPS cases in LUT. The cytopathology diagnosis using TD and TPS were compared to their corresponding SD.
Result(s): In UUT, 51.5% (17/33) were UC on SD. High-grade UC (HGUC) was correctly identified in UUT in 100% (5/5) with TD, and 75%(3/4) with TPS. No low-grade (LG) diagnoses were rendered in TD or TPS though there were 8 low-grade urothelial neoplasms (LGUN). LGUN was classified as "atypical" (2/3-TD, 2/5-TPS) or "negative" (1/3-TD, 3/5-TPS). Rates of "atypical" diagnoses of UUT were 28.6% (TPS) and 26.3% (TD), with no HGUC on SD. The risk of LGUN with "atypical" diagnoses decreased using TPS from 75.0% (3/4) to 60.0% (3/5). In LUT, HGUC was correctly diagnosed in 55.0%(44/80) (TD) and 47.4%(46/97) (TPS). 4% of LGUNs were classified as LG (3/60-TPS, 1/40-TD). "Atypical" diagnoses for TD and TPS showed 29.5% (23/78) and 30.0% (27/90) risk of LGUN and 34.6%(27/78) and 37.8%(34/90) risk of HGUC respectively. (Table-1)
Conclusion(s): The TD and TPS systems showed high accuracy in reporting UUT-HGUC. However, urine cytology is not optimal to identify LGUN in both TD and TPS systems. Additionally, our results suggest that urine cytology may be more sensitive in detecting HGUC in UUT versus LUT samples.[Table presented]
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Extracardiac rhabdomyoma is an uncommon benign striated muscle tumor with a predilection for the head and neck region. However, it is extremely rare for extracardiac rhabdomyoma to present as a thyroid nodule. We report a case of rhabdomyoma diagnosed by thyroid fine-needle aspiration (FNA) in a patient with Birt-Hogg-Dubé (BHD) syndrome. A 60-year-old man with BHD syndrome presented for recurrent pneumothorax. Chest CT incidentally identified a thyroid nodule. Subsequent sonography confirmed a 4.44 × 2.28 × 2.82 cm solid, hypoechoic nodule with smooth margins in the right upper pole. Ultrasound-guided FNA revealed many clusters and scattered isolated large polygonal cells with abundant granular cytoplasm and small peripherally located nuclei. Vague striations in the cytoplasm were focally identified. No follicular cells or colloid was present. Immunocytochemistry on one direct smear slide demonstrated diffuse positivity for desmin, supporting muscular differentiation. Subsequent surgery identified an adult rhabdomyoma originating from the inferior constrictor muscle of the neck and anteriorly displacing the thyroid. Because the mass was intimately associated with the thyroid gland, it was initially mistaken for a thyroid nodule on ultrasound. Diagnosis of rhabdomyoma on FNA is challenging, especially when rhabdomyoma mimics a thyroid nodule on imaging. The differential diagnosis includes Hurthle cell neoplasm, granular cell tumor, colloid nodule, and normal striated skeletal muscle. Adequate radiologic data and familiarity with the cytologic features of rhabdomyoma are critical for an accurate diagnosis.

Background: TPS is a reporting system that includes specific diagnostic categories and cytologic criteria for the accurate diagnosis of high-grade urothelial carcinoma (HGUC). Its success is dependent on its acceptance and widespread use by the cytology and urology communities. Since its development in 2013, institutions have been transitioning to TPS in an effort to standardize terminology and increase the sensitivity of diagnosing HGUC. We present our data comparing TPS diagnoses (PD) to the traditional reporting system (TD) in correlation with the gold standard surgical pathology diagnosis (SD).
Design(s): A search of the pathology database was conducted on urine cytology specimens from adult patients from 7/1/2014-6/30/2016 (TD) and 7/1/2017-6/30/2019 (PD). 454 cytology specimens from 382 patients were found to have corresponding urinary tract SD within 90 days and were included in the study. 192/454 urines were from prior to TPS implementation; 262/454 were from after TPS implementation. TD included: Positive for malignancy/urothelial carcinoma (POS), suspicious for malignancy/urothelial carcinoma (SUS), atypical, low-grade urothelial neoplasia/carcinoma (LG), and negative for malignancy (NEG). TD and PD were compared to their corresponding SD.
Result(s): 34/41 (83%) of HGUC were correctly identified using PD compared to 36/49 (73%) using TD. 15/23 (65%) of SHGUC correlated with HGUC on SD using PD compared with 13/16 (81%) with TD. Rates of "Atypical" diagnoses were decreased from 82/192 (42%) with TD to 95/262 (36%) with PD while the risk of malignancy (ROM) with "Atypical" diagnosis increased using PD from 33% to 36%. LG was identified on cytology in 1/43 (2%) using TD and 3/65 (5%) with PD. In both TD and PD, LG cytologic diagnosis had 100% specificity. 31/65 (48%) of LGUN were correctly categorized as NHGUC using PD while 10/43 (23%) were NEG in TD. (Table 1 and Figure 1) (Table presented)
Conclusion(s): Implementation of TPS in our laboratory led to a higher accuracy in the cytologic diagnosis of HGUC. Additionally, the "Atypical" rate decreased from 42% to 36% while the ROM showed a modest increase. While 12% of HGUCs diagnosed with TPS were found to be benign on SD, 60% of these cases actually had prior and/or subsequent HGUC/CIS on SD indicating that original PD was in fact concordant. LGUN is difficult to diagnose on cytology, and TPS afforded an increase in NHGUC diagnoses in line with the main goal of the PD- diagnosis of HGUC

Background: The American College of Radiology (ACR) 2017 Thyroid Imaging Reporting and Data System (TI-RADS) added a new risk stratification system for classifying thyroid nodules based on sonographic appearance (T1-T5). FNA is generally not recommended for benign or low suspicion nodules. However, other factors such as nodule size and family history may trigger an order for an FNA. Our study aimed to examine the cytologic diagnosis, molecular profiles and surgical follow up in a select group of patients with sonographically benign appearing thyroid nodules.
Design(s): We performed a retrospective review in our pathology database of cases from 1/1/2016-4/1/2018, prior to our institution's adoption of the TI-RADS classification system. Thyroid nodules with in-house ultrasound exam (US), FNA cytology, The Bethesda System (TBS) cytology diagnosis, molecular testing, and surgery were included. The USs from these cases were retrospectively reviewed and assigned TI-RADS scores (TR1-TR5) by a board certified radiologist. There were no TR1 nodules. TR2 (not suspicious) and TR3 (mildly suspicious) nodules were selected for evaluation.
Result(s): From 1/1/2016-4/1/2018, there were a total of 34 patients that fit the selection criteria. Of these, there were 5 TR2 thyroid nodules and 29 TR3 thyroid nodules with corresponding FNA TBS, molecular and surgical diagnoses (table1). (Table presented)
Conclusion(s): Our study shows that sonographically benign appearing/low suspicion thyroid nodules may display molecular alterations; 50% of those proved to be RAS mutations in our study. Approximately 60% of aspirated TR2 nodules and 66% of TR3 nodules were malignant or NIFTP on excision. Despite their lower suspicion index on US, with lower TI-RADS scores, benign appearing nodules on US need to be evaluated in the context of clinical, cytologic and molecular information in order to determine clinical course

BACKGROUND:Differentiating parathyroid from thyroid lesions can be difficult on fine-needle aspiration (FNA) due to overlapping cytomorphologic features. While the traditional parathyroid hormone (PTH) assays can help in the distinction, these tests may be cumbersome, particularly when the lesion is unexpected clinically and a needle wash is not collected at the time of FNA. Therefore, we chose to investigate the application of immunohistochemical staining (IHC) with GATA 3 and thyroid transcription factor-1 (TTF-1) on air-dried cytology smears to distinguish parathyroid and thyroid lesions. METHODS:Air-dried touch preparation (TP) slides were prepared from consecutively selected parathyroid and thyroid specimens. Thirteen FNA cases with the clinical concern for parathyroid lesions were also included in the study. IHC was performed on unstained and ultrafast Papanicolaou (UFP) stained air-dried slides. RESULTS:On TP slides, GATA 3 expression was observed in all cases of parathyroid origin but no immunoreactivity was present in thyroid lesions. TTF-1 expression was observed in all cases of thyroid origin but not in parathyroid lesions. GATA 3 and TTF-1 expression of 13 FNA cases were consistent with the clinical impression or concurrent PTH tests. CONCLUSIONS:IHC with GATA 3 and TTF-1 on air-dried cytology smears is a simple and effective way to differentiate parathyroid vs thyroid lesions on FNA. Air-dried unstained and UFP-stained slides perform equally well with IHC, but UFP-stained slides provide the added benefit of morphologic evaluation and assessment of smear cellularity prior to IHC.

This review article summarized recent advances in the heat-induced antigen retrieval technique with numerous scientific fields in addition to immunohistochemistry. Particularly, proteomics including imaging mass spectrometry, extraction of proteins from formalin-fixed, paraffin-embedded (FFPE) tissues. Some novel approaches such as FFPE tissue-based renal immunopathology based on modified double heating protocols are also introduced in this review for further development. In general, the FFPE tissue housed in pathology worldwide is an invaluable treasure, and the simple method of heat-induced antigen retrieval is the gold key to open the door of this treasure.

Objectives/UNASSIGNED:Recognizing preoperative characteristics of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is important for clinical management. Therefore, we assessed presurgical NIFTP molecular profiles using fine-needle aspiration (FNA) material. Methods/UNASSIGNED:Presurgical FNA reports of 39 surgically confirmed NIFTP cases from January 2013 through May 2017 were assessed for Afirma and ThyroSeq results. Results/UNASSIGNED:Twenty-one of 39 NIFTP nodules were preoperatively tested with Afirma with two benign and 19 suspicious results. Twenty-seven of 39 nodules were tested with ThyroSeq (nine of 39 had both Afirma and Thyroseq): 18 (67%) had RAS mutations (13 NRAS, four HRAS, one KRAS), and three of 18 had multiple alterations (NRAS + TP53, n = 1; NRAS + PTEN, n = 2). BRAF T599_R603 + EIF1AX mutation (n = 1), PTEN mutation (n = 1), MET overexpression (n = 1), PAX8/PPARG fusion (n = 3), and THADA/IGF2BP3 fusion (n = 3) comprised the remainder. Conclusions/UNASSIGNED:NIFTP cases most commonly displayed suspicious Afirma results and RAS mutations on ThyroSeq, lacking aggressive/BRAF-V600E-like mutations. While NIFTP remains a surgical entity, the lack of aggressive/BRAF-V600E-like mutations can aid in determining the extent of surgery.