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]
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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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Neutropenic enterocolitis (NE) is a predominantly cecum-based disease with high mortality seen in patients post chemotherapy. The pathogenesis of NE is poorly understood and probably multifactorial involving mucosal injury, neutropenia, and impaired host defense to intestinal organisms. The clinical presentation is characterized as ileocolonic inflammation and bowel wall thickening in patients with neutropenia, fever, and abdominal pain. The pathological features of NE include patchy necrosis, hemorrhage, ulcer, edema, perforation, infiltrating organisms, and characteristically, depletion of inflammatory cells (neutrophils). NE should always be considered as a possible diagnosis in immunosuppressed patients, especially those receiving chemotherapy. High clinical and histological diagnostic discordance rate exists. High index of clinical suspicion and prompt appropriate personalized management are essential to achieve a lower mortality rate.

Levodopa is the most effective therapy for the motor deficits of Parkinson's disease (PD), but long term treatment leads to the development of L-DOPA-induced dyskinesia (LID). Our previous studies indicate enhanced excitability of striatal cholinergic interneurons (ChIs) in mice expressing LID and reduction of LID when ChIs are selectively ablated. Recent gene expression analysis indicates that stimulatory H2 histamine receptors are preferentially expressed on ChIs at high levels in the striatum, and we tested whether a change in H2 receptor function might contribute to the elevated excitability in LID. Using two different mouse models of PD (6-hydroxydopamine lesion and Pitx3(ak/ak) mutation), we chronically treated the animals with either vehicle or l-DOPA to induce dyskinesia. Electrophysiological recordings indicate that histamine H2 receptor-mediated excitation of striatal ChIs is enhanced in mice expressing LID. Additionally, H2 receptor blockade by systemic administration of famotidine decreases behavioral LID expression in dyskinetic animals. These findings suggest that ChIs undergo a pathological change in LID with respect to histaminergic neurotransmission. The hypercholinergic striatum associated with LID may be dampened by inhibition of H2 histaminergic neurotransmission. This study also provides a proof of principle of utilizing selective gene expression data for cell-type-specific modulation of neuronal activity.