Serial Molecular Profiling of Low-grade Prostate Cancer to Assess Tumor Upgrading: A Longitudinal Cohort Study.

BACKGROUND: The potential for low-grade (grade group 1 [GG1]) prostate cancer (PCa) to progress to high-grade disease remains unclear. OBJECTIVE: To interrogate the molecular and biological features of low-grade PCa serially over time. DESIGN, SETTING, AND PARTICIPANTS: Nested longitudinal cohort study in an academic active surveillance (AS) program. Men were on AS for GG1 PCa from 2012 to 2017. INTERVENTION: Electronic tracking and resampling of PCa using magnetic resonance imaging/ultrasound fusion biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: ERG immunohistochemistry (IHC) and targeted DNA/RNA next-generation sequencing were performed on initial and repeat biopsies. Tumor clonality was assessed. Molecular data were compared between men who upgraded and those who did not upgrade to GG ≥ 2 cancer. RESULTS AND LIMITATIONS: Sixty-six men with median age 64 yr (interquartile range [IQR], 59-69) and prostate-specific antigen 4.9 ng/mL (IQR, 3.3-6.4) underwent repeat sampling of a tracked tumor focus (median interval, 11 mo; IQR, 6-13). IHC-based ERG fusion status was concordant at initial and repeat biopsies in 63 men (95% vs expected 50%, p < 0.001), and RNAseq-based fusion and isoform expression were concordant in nine of 13 (69%) ERG+ patients, supporting focal resampling. Among 15 men who upgraded with complete data at both time points, integrated DNA/RNAseq analysis provided evidence of shared clonality in at least five cases. Such cases could reflect initial undersampling, but also support the possibility of clonal temporal progression of low-grade cancer. Our assessment was limited by sample size and use of targeted sequencing. CONCLUSIONS: Repeat molecular assessment of low-grade tumors suggests that clonal progression could be one mechanism of upgrading. These data underscore the importance of serial tumor assessment in men pursuing AS of low-grade PCa. PATIENT SUMMARY: We performed targeted rebiopsy and molecular testing of low-grade tumors on active surveillance. Our findings highlight the importance of periodic biopsy as a component of monitoring for cancer upgrading during surveillance.

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.

An Unusual Cause of Altered Mental Status in Multiple Myeloma: An Extraosseous Manifestation.

Multiple myeloma typically presents as lytic bony lesions, hypercalcemia, anemia, and renal failure. Extraosseous manifestations are rare. We report on a patient who was recently diagnosed with multiple myeloma and completed the first cycle of bortezomib, dexamethasone, and palliative radiation therapy with good response. Two weeks after discharge, she became confused and was re-admitted. Despite treatment with lactulose and rifaximin, altered mental status worsened. Computer tomographic scan of abdomen showed hepatomegaly and numerous ill-defined small hyperdense nodules scattered throughout the liver. Liver biopsy demonstrated aggregation of plasma cell myeloma. Magnetic resonance imaging of brain revealed dural thickening. Patient's altered mental status was likely from leptomeningeal myelomatosis and hyperammonemic encephalopathy. Although extraosseous manifestations in multiple myeloma including liver and leptomeningeal involvement are rare, its incidence has increased. This condition portends a poor prognosis. The non-specific manifestations of extraosseous myeloma can be confused with complications of multiple sclerosis and lead to incorrect management, thus clinicians should be aware of these pathologies and perform proper diagnostic tests including imaging and tissue pathology. The most effective treatment is unknown, however bortezomib and thalidomide show promise.

Recurrent papillary thyroid carcinoma with pleural metastasis diagnosed by effusion cytology: a report of cases with clinicopathologic correlation.

Papillary thyroid carcinoma (PTC) is typically an indolent disease characterized by slow growth and a favorable prognosis. In rare instances, this disease may metastasize to the pleura and manifest as a malignant pleural effusion. We report 3 female patients of Japanese/Okinawan ancestry with a history of PTC who presented with hydrothorax. Cytologic examination in conjunction with immunohistochemical staining enabled a definitive diagnosis of metastatic PTC. Molecular analysis of the mitogen activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways demonstrated the presence of the v-raf murine sarcoma viral oncogene homolog B (BRAF)(V600E) mutation in 2 of our 3 patients, with the absence of any other clinically significant mutations in all cases. Further investigation is necessary to elucidate the molecular and environmental mechanisms involved in this aggressive manifestation of PTC.

Survey on Visual Impairment and Refractive Errors on Ta'u Island, American Samoa.

PURPOSE: To assess the prevalence of presenting visual impairment and refractive errors on the isolated island of Ta'u, American Samoa. METHODS: Presenting visual acuity and refractive errors of 124 adults over 40 years of age (55 male and 69 female) were measured using the Snellen chart and an autorefractometer. This sample represented over 50% of the island's eligible population. RESULTS: In this survey, all presenting visual acuity (VA) was uncorrected. Of the included sample, 10.5% presented with visual impairment (visual acuity lower than 6/18, but equal to or better than 3/60 in the better eye) and 4.8% presented with VA worse than 6/60 in the better eye. Overall, 4.0% of subjects presented with hyperopia (+3 D or more), 3.2% were myopic (-1 D or less), and 0.8% presented with high myopia (-5 D or less). There was no significant difference between genders in terms of visual impairment or refractive errors. CONCLUSION: This study represents the first population-based survey on presenting visual acuity and refractive errors in American Samoa. In addition to providing baseline data on vision and refractive errors, we found that the prevalence of myopia and hyperopia was much lower than expected.

Evidence for a continuing gap in rural/urban adult obesity in the Samoan archipelago.

Significant differences in adult obesity prevalence exist between rural and urban settings throughout the world. Here, we estimate and evaluate the prevalence of adult obesity in rural Independent Samoa, rural American Samoa, and urban American Samoa in 2009. Volunteers over the age of 40 years were weighed and measured by convenience sampling in rural Independent Samoa (N = 85), rural American Samoa (N = 124), and urban American Samoa (N = 95) Mean BMI increased from rural Independent Samoa (32.2 males; 33.3 females) to rural American Samoa (33.5 males; 34.9 females) to urban American Samoa (36.9 males; 39.7 females). Differences among groups were statistically significant (P = 0.004, ANOVA). In all locations, women were substantially more obese than men. While obesity is a major health problem in the Samoan archipelago, significant differences exist between rural and urban settings. A substantial rural/urban gap in adult obesity has been in existence since at least the 1970s. However, results of our study, combined with those of previous studies, indicate that the prevalence of obesity in both rural and urban environments has been on the rise since the 1970s.