Faculty Bibliography

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.

BACKGROUND: The success of cell block preparation is crucial for ancillary diagnostic tests in cytology. However, achieving an optimal cell block can be challenging. The current study describes a self-clotting-based technique for fine-needle aspiration (FNA) cell block preparations and evaluates its usefulness in comparison with the conventional needle wash technique. METHODS: The clinical data, FNA procedure, and cellularity of cell blocks of the self-clotting group (37 cases) and the conventional needle wash group (33 cases) were compared. The cellularity was evaluated using a scoring system (0 indicated acellular, 1 indicated 1-50 cells, and 2 indicated >50 cells). RESULTS: Approximately 76% of cases in the self-clotting group received a score of 2 versus 36% in the conventional needle wash group. Approximately 14% received a score of 1 in the self-clotting group compared with 9% in the conventional needle wash group, whereas 11% in the self-clotting group received a score of 0 versus 55% in the conventional needle wash group. The differences between the 2 methods were statistically significant. CONCLUSIONS: The results of the current study demonstrate that the self-clotting method is superior to the conventional needle wash method for FNA samples. Cancer Cytopathol 2017. (c) 2017 American Cancer Society.

Background: Encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), formerly a malignant diagnosis and variant of PTC, has recently been reclassified to NIFTP on surgical pathology. Because of the indolent nature and potentially conservative treatment of NIFTP, it is crucial to identify features early on during patient evaluation which may suggest the possibility of this entity. One such feature is the molecular profile of thyroid nodules determined preoperatively utilizing fine-needle aspiration (FNA) cellular material. Design: Pre-surgical FNA Cytopathology reports of 41 confirmed cases of NIFTP from 1/2013-8/2016 were assessed for molecular testing (Afirma and/or ThyroSeq) results. Results: Bethesda System cytology diagnoses were: Benign (n=1), Atypia of Undetermined Significance (n=24), Follicular Neoplasm (n=14), and Suspicious for Malignancy (n=2). Of the 41 NIFTP cases, 22 nodules were pre-operatively tested with Afirma: 2 were benign; 20 were suspicious. 12 cases were Afirma MTC negative; 4 were BRAF negative. 27 nodules were pre-operatively tested with ThyroSeq: 2 had insufficient material; 15 cases (55.6%) had RAS mutations (11 NRAS, 4 HRAS); 3 of the 15 had two mutations [NRAS and TP53 (n=1); NRAS and PTEN (n=2)]. One additional case with 2 mutations showed BRAF T599-R603 and EIF1AX mutations (n=1). Other isolated molecular changes included PTEN mutation (n=1), MET overexpression (n=1), PAX8/PPARG fusion (n=4), and THADA/IGF2BP3 fusion (n=3). Conclusions: While NIFTP remains a surgical entity, the molecular profile of thyroid nodules can be analyzed pre-operatively in order to determine appropriate treatment. Our findings demonstrate that NIFTP cases most commonly displayed Suspicious Afirma results and RAS mutations on ThyroSeq, and several molecular alterations not characteristic of classical PTC or poorly differentiated/anaplastic thyroid carcinomas. The molecular profile of thyroid nodules must be considered together with the patients' clinical, sonographic and cytologic results in order to raise the possibility of NIFTP early on in determining proper management