Faculty Bibliography

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]
Copyright

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]
Copyright

OBJECTIVES/OBJECTIVE:Recent investigations have shown strong correlations between cytology and surgical non-small cell lung carcinoma (NSCLC) specimens in programmed death-ligand 1 (PD-L1) immunohistochemical (IHC) evaluations. Our study aims to evaluate the reproducibility of PD-L1 IHC scoring in NSCLC cytology cell blocks (CBs) and to assess the impact of CB cellularity, method of sample collection, and observer subspecialty on scoring agreement. METHODS:PD-L1 IHC was performed on 54 NSCLC cytology CBs and was scored independently by seven cytopathologists (three of seven with expertise in pulmonary pathology). Three-tier scoring of negative (<1%), low positive (1%-49%), and high positive (≥50%) and interrater agreement were assessed. RESULTS:Total and majority agreement among cytopathologists was achieved in 48% and 98% of cases, respectively, with κ = 0.608 (substantial agreement; 95% confidence interval, 0.50-0.72). Cytopathologists with pulmonary pathology expertise agreed in 67% of cases (κ = 0.633, substantial agreement), whereas the remaining cytopathologists agreed in 56% of cases (κ = 0.62, substantial agreement). CB cellularity (P = .36) and sample collection type (P = .59) had no statistically significant difference between raters. CONCLUSIONS:There is substantial agreement in PD-L1 IHC scoring in cytology CB specimens among cytopathologists. Additional expertise in pulmonary pathology, sample collection type, and CB cellularity have no statistically significant impact on interobserver agreement.

BACKGROUND:Ultrasound has become the initial approach to evaluating thyroid nodules, facilitating the distinction between benign and malignant nodules based on composition, echogenicity, nodule border or margin, shape, the presence of calcifications, and nodule dimensions. The American College of Radiology (ACR) recommended the Thyroid Imaging Reporting and Data System (TI-RADS) as a classification system to standardize thyroid ultrasound reports and to predict the probability of malignancy in thyroid nodules using a scoring system (TR1-TR5) based on multiple ultrasound characteristics and nodule size. Fine-needle aspiration (FNA) is recommended as the next step for nodules that warrant further workup. The authors assessed the accuracy of the ACR TI-RADS based on the corresponding FNA cytology results (Bethesda system diagnoses I-VI). METHODS:ACR TI-RADS ultrasound reports and corresponding FNA cytology diagnoses from January 1, 2018 to August 30, 2018 were evaluated. RESULTS:From January 1, 2018 to August 30, 2018, 2306 thyroid ultrasound-guided FNAs were performed at our institution. Of 2306 cases, 361 had ACR TI-RADS reports available. The majority of FNAs were TR4 (180; 49.9%) or TR3 (108; 29.9%). No TR2 or TR3 nodules were associated with Bethesda category V or VI diagnoses. The majority of TR4 nodules (142 of 180; 78.9%) and TR5 nodules (42 of 65; 64.6%) exhibited benign (Bethesda category II) cytology. Fourteen TR5 cases (21.5%) had malignant (Bethesda category VI) cytology. CONCLUSIONS:Although there were no TR2 or TR3 malignant (Bethesda category VI) diagnoses, and there were only a few malignancies in the TR4 and TR5 categories, the current results reassert the notion that the ACR TI-RADS scoring system shows at least some correlation between benign or malignant cytology diagnoses, as illustrated by the greater number of malignant cases in the higher ACR TI-RADS categories.

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: Salivary gland neoplasms are rare and the majority are benign with only 20% displaying malignancy. Fine needle aspiration (FNA) plays an essential role in the initial evaluation of salivary gland lesions by providing a pre-operative diagnosis to determine appropriate management. Recently, a tiered classification system known as the Milan System for reporting Salivary Gland cytopathology (MSRSGC) has been published. This system formalizes diagnostic categories with related malignancy risk, recommended clinical therapy and follow-up. Our study aims to compare sensitivity, specificity and risk of malignancy (ROM) between the MSRSGC and the original FNA cytology diagnostic categories used at our institution to determine if the MSRSGC offers added benefit.
Design(s): Salivary gland cytology slides from subjects with final surgical pathology resections from 11/2016-06/2019 were blindly reviewed and classified according to the MSRSGC. MSRSGC diagnoses were correlated with surgical pathology diagnoses and compared to the original cytology diagnostic categories. Sensitivity, specificity and ROM of diagnostic categories were calculated for both systems.
Result(s): Follow-up histopathology was available for 101 patients with salivary gland lesions. The MSRSGC had a sensitivity of 69.0% and a specificity of 92.9%. The original classification system had a sensitivity of 75.0% and a specificity of 89.9%. ROM for MSRSGC categories and original diagnostic categories are given in Table 1 and listed side by side to reflect distribution of cases in each system. (Table presented)
Conclusion(s): Performance of the MSRSGC was comparable to that of the original classification system in the majority of cases. Both systems had a similar sensitivity, specificity and ROM in the equivalent categories. The single "non-diagnostic" and the three "nonneoplastic" cases under MSRSGC that showed histopathologic evidence of malignancy were called "negative for malignancy" in the original classification showing lack of cytohistologic correlation for both systems due to sampling errors. Two of the three cases classified as "atypia of undetermined significance" under the MSRSGC were originally classified as "negative for malignancy". Our findings suggest that traditional diagnostic classification methods for salivary gland cytopathology already established at an institution can perform as well as the MSRSGC in relaying the appropriate diagnostic information, undermining the need for transition to a new classification system

Background: HPV-related oropharyngeal squamous cell carcinoma (OP-SCC) has a superior prognosis and response to therapy than that of conventional head-and neck SCC (HNSCC). The College of American Pathologists (CAP) guidelines recommend that P16 immunostaining (IHC) in >70% of tumor cells is an excellent surrogate marker for HPV in surgical pathology OP-SCC. Fine needle aspiration (FNA) cytology is an ideal method for obtaining diagnostic material for OP-SCC and may represent the only attainable specimen. However, there is no consensus for interpretation of P16 IHC result in cytology preparations. Our study aims to assess OP-SCC P16 staining in cell block cytology preparations in comparison with P16 staining on surgical pathology specimens.
Design(s): FNA specimens from 2014-2019 of OP-SCC with P16 IHC staining were obtained. Surgical pathology P16 IHC results were set as the gold standard. Cytology cell block tumor cellularity (<100 vs >100 cells) and P16 percentage of tumor cell positivity (0%, 1-10%, 11- 50%, 51-70%, and >70%) were recorded. Using different threshold levels of P16 tumor cell positivity in cell blocks as compared with surgical P16 IHC results, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated.
Result(s): 40 matched FNA neck lymph node/mass cytology and surgical cases were identified. Sensitivities and specificities varied when thresholds changed, with sensitivities and specificities ranging from 93.5% and 66.7% (respectively) when any P16 positivity is seen (>0%), to 56.7% and 100% (respectively) when P16 positive threshold is set at >70% (table 1 and figure 1). <100 and >100 tumor cells were seen in 11 and 29 cases respectively. (Table presented)
Conclusion(s): Our study shows that P16 IHC performed on cytology cell blocks can serve as a surrogate marker for the detection of HPV, similar to P16 staining in surgical pathology, with high sensitivity and specificity levels. The challenge in cytology specimens is choosing the proper threshold to balance between the optimal sensitivity and specificity. Our data suggests that using a threshold lower than that of surgical pathology (70%) for p16 positivity may be appropriate for FNA specimens, as lower thresholds displayed increased sensitivities with only moderately lower specificities. Of note out of the 11 cases with <100 tumor cells, only one cases was a false negative, indicating that tumor cellularity may not affect P16 interpretation on cell block

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.