The continual impact of the Paris System on urine cytology, a 3-year experience.

OBJECTIVE: The development of the Paris System (TPS) has provided a standard and reproducible system for reporting urine cytopathology. Our goal was to study the impact of TPS on the diagnostic accuracy of urine cytology since we began using it in 2016. METHODS: We performed a retrospective study of all urine cytology specimens received at our institution from January 2015 through July 2017. Cases were included in the study if they had corresponding surgical pathology follow up. In total, 3829 cases were identified over this time period, with 381 cases meeting inclusion criteria, comprising 87 cases from 2015, 166 from 2016 and 128 from 2017. Using the histopathology diagnosis as the gold standard, sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and diagnostic accuracy (DA) for the detection of carcinoma were calculated. RESULTS: Before TPS, urine cytology had a sensitivity of 100.0%, specificity of 12.5%, PPV of 83.5%, NPV of 100.0% and DA of 83.9%. After TPS, for 2016, urine cytology had sensitivity of 87.1%, specificity of 95.9%, PPV of 96.4%, NPV of 85.4% and DA of 91.0%. For 2017 after TPS, the sensitivity was 81.7%, specificity was 100.0%, PPV was 100.0%, NPV was 81.4% and DA was 89.8%. CONCLUSION: For the detection of urinary tract malignancy, after switching to TPS, we observed a marked increase in urine cytology specificity and PPV, both of which continued to gradually increase from 2016 to 2017. The DA also improved with TPS.

Esophageal IgG4: Clinical, Endoscopic, and Histologic Correlations in Eosinophilic Esophagitis.

OBJECTIVE: Recent studies show increased serum and esophageal IgG4 in patients with eosinophilic esophagitis (EoE), suggesting a possible IgG4-involved process. The role of IgG4 in pediatric EoE has not been extensively investigated. Our aim was to analyze IgG4 in esophageal tissue in children in parallel to that in adults with EoE. METHODS: In a retrospective institutional review board-approved study, we performed immunohistochemical staining of IgG4 in esophageal biopsy specimens from 39 subjects: children with EoE (n = 16), adults with EoE (n = 15), children with reflux esophagitis (n = 4), and pediatric controls (n = 4). We assessed the relationships between IgG4 staining and clinical, endoscopic, and histopathologic characteristics. RESULTS: Patients with EoE were significantly more likely to stain positively for IgG4 than children with reflux esophagitis or controls (P = 0.015). Fifteen of 31 (48%) EoE cases stained positively for IgG4. None of the reflux esophagitis or control cases stained positively. IgG4 staining had 48% sensitivity and 100% specificity for EoE. There was a trend toward IgG4 staining being associated with foreign body/food impaction (P = 0.153). There was a strong association between distal IgG4 staining and basal zone hyperplasia (P = 0.003). CONCLUSIONS: Our study suggests IgG4 is not a consistent finding of EoE at disease diagnosis. Although IgG4 staining was specific for EoE, it had a poor sensitivity with positive staining in only 48% of EoE patients. Further studies are warranted to fully elucidate the role of IgG4 in EoE.

Acute hepatitis and acute liver failure: Pathologic diagnosis and differential diagnosis.

Acute hepatitis and acute liver failure are severe medical conditions that require early clinical intervention. Histopathologic findings on a liver biopsy or a liver explant may help identify the underlying etiology or provide an important direction for further clinical, laboratory and radiographical investigation. This review is divided into two main portions. The first portion concentrates on various etiologies and discusses unique histologic features that can be associated with specific etiologies. The second portion describes the general morphologic features based on which the diagnosis of acute hepatitis and acute liver failure are made. Histopathologic distinction between collapse and cirrhosis and limitations of histopathologic assessment for underlying etiologies are addressed in this portion. Another focus of this review is non-necrotic acute liver failure, which typically features diffuse microvesicular steatosis secondary to various etiologies causing mitochondrial dysfunction. Molecular testing serves an increasingly important role in the diagnosis and management of this group of disorders.

Clinical and Epidemiologic Evaluation of Inconclusive COVID-19 PCR Results Using a Quantitative Algorithm.

OBJECTIVES: The inconclusive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) result causes confusion and delay for infection prevention precautions and patient management. We aimed to develop a quantitative algorithm to assess and interpret these inconclusive results. METHODS: We created a score-based algorithm by combining laboratory, clinical, and epidemiologic data to evaluate 69 cases with inconclusive coronavirus disease 2019 (COVID-19) PCR results from the Centers for Disease Control and Prevention (CDC) assay (18 cases) and the TaqPath assay (51 cases). RESULTS: We determined 5 (28%) of 18 (CDC assay) and 20 (39%) of 51 (TaqPath assay) cases to be false positive. Lowering the cycle threshold cutoff from 40 to 37 in the TaqPath assay resulted in a dramatic reduction of the false-positive rate to 14%. We also showed testing of asymptomatic individuals is associated with a significantly higher probability of having a false-positive result. CONCLUSIONS: A substantial percentage of inconclusive SARS-CoV-2 PCR results can be false positive, especially among asymptomatic patients. The quantitative algorithm we created was shown to be effective and could provide a useful tool for clinicians and hospital epidemiologists to interpret inconclusive COVID-19 PCR results and provide clinical guidance when additional PCR or antibody test results are available.

Comparative Accuracy of Tumor Size Assessment and Stage Analysis by Imaging Modalities Versus Gross Examination for Pancreatic Ductal Adenocarcinoma.

OBJECTIVES: Tumor size has been shown to be a strong predictor of patient survival in pancreatic ductal adenocarcinoma (PDAC). The aims of this study were to assess the consistency of preoperative imaging and gross examination for PDAC tumor size measurement and to evaluate the impact on T and overall tumor staging when size measurements by imaging and gross examination were different. METHODS: Patients diagnosed with PDAC who underwent pancreaticoduodenectomy or distal pancreatectomy from 2007 to 2017 were retrospectively reviewed. A total of 268 cases were included. RESULTS: Imaging studies underestimated tumor size in comparison with gross examination. Staging the tumors based on imaging size using the eighth edition American Joint Committee on Cancer resulted in an altered T stage in 106 cases (39.6%). There was no T-stage change in the remaining 162 cases (60.4%) despite the presence of variable size discrepancies (0.1-1.7 cm). When nodal metastases were also considered, there was no change in the overall tumor stage in most cases. CONCLUSIONS: Although discrepancies exist between tumor size measurements by imaging modalities and gross examination, which may result in an altered T stage in a substantial number of cases, the overall tumor stage is only rarely altered.

Midline carcinoma expressing NUT in malignant effusion cytology.

Nuclear protein in testis (NUT) midline carcinoma (NMC) is a rare and aggressive subset of poorly differentiated squamous cell carcinoma that is defined by t(15,19) and typically presents in the midline structures of the head, neck, and mediastinum. We report two cases of NMC that presented uniquely with malignant pleural and pericardial effusions including one with cardiac tamponade at presentation. The first case is of a 25-year-old male patient who presented with progressive dyspnea associated with palpitations and dizziness on standing, found to have large bilateral pleural effusions. The second case is of a previously healthy 29-year-old male patient who presented with progressive dyspnea, cough with expectoration, and a large right lower neck mass of 3 months onset, and a large left pleural effusion and left lung infiltrate on imaging studies. Both cases showed malignant cells on cytology suggestive of poorly differentiated carcinoma. Subsequent histopathological and immunochemistry studies were consistent with the diagnosis of NMC. Both patients had a rapid decline in status and suffered comorbidities secondary to their carcinoma, inevitably leading to their death. It is important to consider NUT midline carcinomas can present in a variety of clinical scenarios, and it is important to consider in the differential diagnoses when evaluating malignant effusion cytology. Utilization of ancillary testing with a broad immunostain profile including NUT studies, as well as fluorescent in-situ hydridization (FISH) studies are helpful and necessary in making the appropriate diagnosis.

Impact of Changes in the American Joint Committee on Cancer Staging Manual, Eighth Edition, for Pancreatic Ductal Adenocarcinoma.

OBJECTIVE: Consistent and reliable tumor staging is a critical factor in determining treatment strategy, selection of patients for adjuvant therapy, and for therapeutic clinical trials. The aim of this study was to evaluate the number and extent of pancreatic ductal adenocarcinoma (PDAC) cases that would have a different pT, pN, and overall stages based on the new eighth edition American Joint Committee on Cancer staging system when compared with the seventh edition. METHODS: Patients diagnosed with PDAC who underwent pancreaticoduodenectomy, total pancreatectomy, or distal pancreatectomy from 2007 to 2017 were retrospectively reviewed. A total of 340 cases were included. RESULTS: According to the seventh edition, the vast majority of tumors in our cohort were staged as pT3 tumors (88.2%). Restaging these cases with the new size-based pT system resulted in a more equal distribution among the 3 pT categories, with higher percentage of pT2 cases (55%). CONCLUSIONS: The newly adopted pT stage protocol for PDAC is clinically relevant, ensures a more equal distribution among different stages, and allows for a significant prognostic stratification. In contrast, the new pN classification (pN1 and pN2) based on the number of positive lymph nodes failed to show survival differences and remains controversial.