Applicability of the Paris System for veterans: high rates of undiagnosed low-grade urothelial neoplasia.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) is a recently developed standardized terminology system. It is well-established that urine cytology has low sensitivity for detecting low-grade urothelial neoplasia (LGUN). Though the majority of tumors are low-grade, surveillance of these lesions is important to monitor for possible progression. Herein, we compared TPS to our veteran integrated system network (VISN) to assess its applicability. We also introduced semi-quantitative scoring to further evaluate cytomorphologic features of high-grade urothelial carcinoma (HGUC). MATERIALS AND METHODS: Voided and instrumented urine cytology specimens and concurrent biopsies were reviewed from Sept 2018 - Jan 2020. Cytologic diagnoses reported using the VISN institutional system were reevaluated by staff cytopathologists and categorized according to TPS. A semi-quantitative scoring system to evaluate cytomorphologic features was devised. RESULTS: Cytology and surgical specimens from 105 patients were reviewed. The VISN and TPS reporting systems were compared and showed similar sensitivities and specificities for the detection of HGUC. Rates of biopsy-proven LGUN were high for the negative for high-grade urothelial carcinoma category (NHGUC; 27/53, 50.9%) and atypical urothelial cells (AUC; 14/30; 46.7%) compared to suspicious/positive (0/22, 0%) categories. Major and minor criteria as outlined in TPS were evaluated semi-quantitatively. CONCLUSIONS: Urine cytology has limited sensitivity for LGUN regardless of the cytologic reporting system used. There was a high rate of LGUN following NHGUC/AUC diagnoses in the Veteran population. Coarse chromatin was determined to be the least sensitive criterion for the detection of high-grade lesions and irregular chromatin rim was most specific.

Proinsulin Expressing Neuroendocrine Tumors of the Pancreas: An Underrecognized Entity.

OBJECTIVES: Rare cases of pancreatic neuroendocrine tumors (PNETs) that produce only proinsulin (PI) and manifest with hypoglycemia have been reported. Proinsulin expression in PNET has not been systematically studied, and the clinicopathologic features of such tumors remain unknown. METHODS: We studied expression of PI by immunohistochemistry (IHC) in 136 PNETs from 2 high-volume surgical oncology centers and assessed all available clinicopathologic data. RESULTS: Thirty-six (26%) of PNETs were positive for PI by IHC, most (89%) of which coexpressed insulin IHC. Nine PI-positive tumors represented functional insulinomas. Patients with PI IHC-positive tumors demonstrated significantly lower mean preoperative serum glucose compared with PI-negative PNET patients, even when insulinomas were excluded. No differences in survival between PI IHC-positive and PI IHC-negative tumors were observed. We identified 2 PI-positive PNETs from hypoglycemic patients, which were not insulinomas or other functional variants and in which serum PI was never tested. These may have been undetected proinsulinomas. CONCLUSIONS: Proinsulin-expressing PNETs (functional or non) are not uncommon. Patients who present with hypoglycemia and normal insulin levels should be screened for proinsulinoma. Proinsulin IHC could also be used to screen for proinsulinoma. To further elucidate the clinical significance of PI expressing PNETs, prospective studies are required.

Network Analysis of Autopsy Diagnoses: Insights into the "Cause of Death" from Unbiased Disease Clustering.

BACKGROUND: Autopsies usually serve to inform specific "causes of death" and associated mechanisms. However, multiple diseases can co-exist and interact leading to a final demise. We approached autopsy-produced data using network analysis in an unbiased fashion to inform about interaction among different diseases and identify possible targets of system-level health care. METHODS: Reports of 261 full autopsies from one institution between 2011 and 2013 were reviewed. Comorbidities were recorded and their Spearman's association coefficients were calculated. Highly associated comorbidities (P < 0.01) were selected to construct a network in which each disease is represented by a node, and each link between the nodes represents significant co-occurrence. RESULTS: The network comprised 140 diseases connected by 419 links. The mean number of connections per node was 6. The most highly connected nodes ("hubs") represented infectious processes, whereas less connected nodes represented neoplasms and other chronic diseases. Eight clusters of biologically plausible associated diseases were identified. CONCLUSIONS: There is an unbiased relationship among autopsy-identified diseases. There were "hubs" (primarily infectious) with significantly more associations than others that could represent obligatory or important modulators of the final expression of other diseases. Clusters of co-occurring diseases, or "modules," suggest the presence of clinically relevant presentations of pathobiologically related entities which are until now considered individual diseases. These modules may occur together prior to death and be amenable to interventions during life.

Optimal Intraoperative Assessment of Gastric Margins.

OBJECTIVES: Intraoperative pathology consultation (IOC) to assess margins is frequently requested during surgery of the stomach and gastroesophageal junction. METHODS: We studied 110 consecutive patients undergoing gastrectomy with IOC margin assessment. RESULTS: Gastric margins at IOC utilized the most blocks but were least often positive. In 64% of patients, the entire gastric margin was examined using average six blocks; representative sections were examined in 25% of patients using two blocks. There was no difference in patient outcome between those who had entire vs representative sections of margin examined. Gross variables showing strongest associations with positive margins were tumor size and tumor distance to margin. Tumors sized greater than 2.3 cm had significantly increased risk of positive margin, and tumor distance greater than 4.5 cm to margin was associated with negative margins. CONCLUSIONS: We conclude representative sections of the closest gastric margin are sufficient to ensure R0 resection in the majority of cases.

Identification of distinct cytomorphologic features in the diagnosis of NIFTP at the time of preoperative FNA: Implications for patient management.

BACKGROUND: A major reclassification occurred with the redesignation of noninvasive encapsulated follicular variant of papillary thyroid carcinoma as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) due to its indolent nature. The aim of this study was to determine whether distinct cytomorphologic features could be identified on preoperative fine-needle aspiration (FNA) when NIFTP cases were compared with invasive follicular variant of papillary thyroid carcinoma (FVPTC) subtypes. METHODS: Thyroid resection cases with the diagnosis of FVPTC from 2012 to 2016 were reclassified as NIFTP, invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC), and invasive FVPTC subtypes. Corresponding FNA specimens were retrieved and retrospectively reviewed. A univariate analysis using Fisher's exact test was performed to determine any differences in the frequencies of various cytomorphologic features among NIFTP, IEFVPTC, and FVPTC cases. A multivariate analysis was performed to identify any independent salient features that would be helpful in differentiating NIFTP from its invasive counterparts. RESULTS: The study population consisted of 93 cases, including 51 cases of NIFTP, 21 cases of IEFVPTC, and 21 cases of infiltrative FVPTC. Demographics such as age, sex, and tumor size were comparable across the 3 groups. A predominantly microfollicular pattern, an absence of nuclear pseudo-inclusions, and less frequent nuclear elongations and grooves were significantly more likely to be associated with NIFTP versus its invasive counterparts. The absence of nuclear pseudo-inclusions and the presence of a microfollicular pattern were the only independent predictors of a NIFTP diagnosis. CONCLUSIONS: This study demonstrates that NIFTP cases have distinguishing cytomorphologic characteristics in comparison with invasive FVPTC cases. Therefore, a preoperative cytologic evaluation provides clues that can aid in the distinction between NIFTP and its invasive counterparts. Cancer Cytopathol 2017;125:865-75. © 2017 American Cancer Society.

Metabolic Signature on 18F-FDG PET/CT, HER2 Status, and Survival in Gastric Adenocarcinomas.

The human epidermal growth factor 2 (HER2)-overexpressing (HER2-positive [HER2+]) gastric (GC) and gastroesophageal junction adenocarcinomas (GEJC) are felt to represent a more aggressive form of disease, which may correlate to increased metabolic activity. Whether tumor SUVmax measured by 18F-FDG PET/CT could be a preoperative parameter used to predict HER2 status of GC/GEJC is unknown. METHODS: Pathology reports of HER2+ GC/GEJC biopsies and resections from 31 patients were reviewed and compared with HER2-negative (HER2-) cases distributed evenly over the same time period. We analyzed their SUVmax intensity and then compared the HER2 status and SUVmax parameters and their association with survival. RESULTS: After matching for age and sex, there was no difference in SUVmax between HER2+ and HER2- cases (9.7 and 8.4, respectively; P = 0.6). No difference was seen between HER2+ and HER2- cases in tumor histology (81% and 57% intestinal type, respectively; P = 0.11), size (2.6 and 3.8 cm, respectively; P = 0.12), differentiation (47% and 68% poorly differentiated, respectively; P = 0.06), or presence of lymph node metastasis (60% and 40%, respectively; P = 0.3). Although there was no difference in survival demonstrated by HER2+ and HER2- cases, there was a significant difference in survival between SUVmax above (12.2 mo) and below (30 mo) the median SUVmax (6.6, P = 0.01). CONCLUSION: Our study shows that SUVmax is not associated with HER2 status of GC/GEJC. Independent of HER2 overexpression, patients with a high SUVmax demonstrate a worse overall survival, suggesting that metabolic signature is a better predictor of biologic tumor aggressiveness than its histologic signature.