The Value Proposition for Pathologists: A Population Health Approach

© The Author(s) 2020. The transition to a value-based payment system offers pathologists the opportunity to play an increased role in population health by improving outcomes and safety as well as reducing costs. Although laboratory testing itself accounts for a small portion of health-care spending, laboratory data have significant downstream effects in patient management as well as diagnosis. Pathologists currently are heavily engaged in precision medicine, use of laboratory and pathology test results (including autopsy data) to reduce diagnostic errors, and play leading roles in diagnostic management teams. Additionally, pathologists can use aggregate laboratory data to monitor the health of populations and improve health-care outcomes for both individual patients and populations. For the profession to thrive, pathologists will need to focus on extending their roles outside the laboratory beyond the traditional role in the analytic phase of testing. This should include leadership in ensuring correct ordering and interpretation of laboratory testing and leadership in population health programs. Pathologists in training will need to learn key concepts in informatics and data analytics, health-care economics, public health, implementation science, and health systems science. While these changes may reduce reimbursement for the traditional activities of pathologists, new opportunities arise for value creation and new compensation models. This report reviews these opportunities for pathologist leadership in utilization management, precision medicine, reducing diagnostic errors, and improving health-care outcomes

Expression of CAAT Enhancer Binding Protein Beta (C/EBP β) in Cervix and Endometrium

BACKGROUND: The CCAAT element binding protein family of transcriptional factors consists of at least six members of the basic leucine zipper DNA binding proteins that bind to the same CCAAT palindromic DNA sequence through homo- or hetero-dimerization with the same family members. C/EBP β has been shown to play an important role in mediating the effects of the LH/hCG in ovarian development. C/EBP β was also found increased in ovarian cancer and correlated to ovarian cancer progression. DESIGN: We assessed the C/EBP β expression pattern in the normal and neoplastic conditions of the female genital tract by immunostaining the normal cervix – 10 cases, squamous intraepithelial lesion (SIL)-10, invasive squamous carcinomas of cervix – 10 cases, normal endometrial tissue – 10 cases, and invasive endometrial adenocarcinomas carcinomas-10 cases. The staining pattern and intensity were graded from 0 to 2+. Results were statistically analyzed utilizing JMP 4.1. RESULTS: C/EPB β expression was detected in the normal proliferative squamous, dysplastic and malignant squamous epithelial cells. There was no statistical correlation between C/EPB β staining in benign squamous, endocervical tissue, SIL, and squamous cancer, as the majority of all stained positively (91%, 79%, 71% and 89%, respectively, p = 0.3448). However, endometrial carcinoma was significantly more likely to stain positively with C/EPB β than benign endometrial glands (92% versus 3% respectively, p < 0.0001, Fisher's exact test). CONCLUSION: C/EBP β is more likely to be preferentially expressed in endometrial adenocarcinoma as compared to benign endometrial tissue. There is no difference of C/EPB β expression in squamous neoplasia of the cervix

Gleevec (STI-571) inhibits lung cancer cell growth (A549) and potentiates the cisplatin effect in vitro

BACKGROUND: Gleevec (aka STI571, Imatinib) is a recently FDA approved anti-tumor drug for chronic myelogenous leukemia. Gleevec binds specifically to BCR-ABL tyrosine kinase and inhibit the tyrosine kinase activity. It cross-reacts with another two important membrane tyrosine kinase receptors, c-kit and PDGF receptors. We sought to investigate if Gleevec has a potential role in treatment of non-small cell lung cancer. RESULTS: We have shown that Gleevec alone can inhibit the A549 lung cancer cell growth in dose-dependent manner, and the optimal concentration of Gleevec inhibition of A549 cell growth is at the range of 2–3 μM (IC50). We have also shown that A549 cells are resistant to cisplatin treatment (IC50 64 μM). Addition of Gleevec to the A549 cells treated with cisplatin resulted in a synergistic cell killing effect, suggesting that Gleevec can potentiate the effect of cisplatin on A549 cells. We also showed that the A549 lung cancer cells expresses the platelet derived growth factor receptor α, and the inhibitory effects of Gleevec on A549 cells is likely mediated through inhibition of PDGFR α phosphorylation. We further tested 33 lung cancer patients' tumor specimens to see the frequency of PDGFR-α expression by tissue micro-arrays and immunohistochemistry. We found that 16 of the 18 squamous carcinomas (89%), 11 of the 11 adenocarcinomas (100%), and 4 of the 4 small cell lung cancers (100%) expressed PDGFR-α. CONCLUSION: These results suggest a potential role of Gleevec as adjuvant therapeutic agent for treatment of non-small cell lung cancer

Malignant peripheral nerve sheath tumor of the breast: case report

<p>Abstract</p> <p>Background</p> <p>Malignant peripheral nerve sheath tumor is a rare soft tissue sarcoma of ectomesenchymal origin. It is the malignant counterpart of benign soft tissue tumors like neurofibromas and schwannomas and may often follow them. Common sites include deeper soft tissues, usually in the proximity of a nerve trunk. Breast is an extremely rare location of this lesion and presentation as a breast lump in the absence of pain or previous benign neural tumor is even rarer.</p> <p>Case presentation</p> <p>A 38-year-old female presented with complaints of painless, hard breast lump for three months which was clinically suspected to be a ductal carcinoma with inconclusive fine needle aspiration cytology. Histopathology revealed a malignant spindle cell tumor which was confirmed to be malignant peripheral nerve sheath tumor on the basis of immunopositivity for vimentin, neurone specific enolase and S-100.</p> <p>Conclusion</p> <p>To the best of our knowledge only six such case reports have been published in literature. The differential diagnosis of malignant peripheral nerve sheath tumor should be considered by the clinician as well as the pathologists in the work-up of a breast neoplasm as treatment and prognosis of this rare malignancy is different.</p

Quality Improvement Intervention for Reduction of Redundant Testing

Laboratory data are critical to analyzing and improving clinical quality. In the setting of residual use of creatine kinase M and B isoenzyme testing for myocardial infarction, we assessed disease outcomes of discordant creatine kinase M and B isoenzyme +/troponin I (−) test pairs in order to address anticipated clinician concerns about potential loss of case-finding sensitivity following proposed discontinuation of routine creatine kinase and creatine kinase M and B isoenzyme testing. Time-sequenced interventions were introduced. The main outcome was the percentage of cardiac marker studies performed within guidelines. Nonguideline orders dominated at baseline. Creatine kinase M and B isoenzyme testing in 7496 order sets failed to detect additional myocardial infarctions but was associated with 42 potentially preventable admissions/quarter. Interruptive computerized soft stops improved guideline compliance from 32.3% to 58% (P \u3c .001) in services not receiving peer leader intervention and to \u3e80% (P \u3c .001) with peer leadership that featured dashboard feedback about test order performance. This successful experience was recapitulated in interrupted time series within 2 additional services within facility 1 and then in 2 external hospitals (including a critical access facility). Improvements have been sustained postintervention. Laboratory cost savings at the academic facility were estimated to be ≥US$635 000 per year. National collaborative data indicated that facility 1 improved its order patterns from fourth to first quartile compared to peer norms and imply that nonguideline orders persist elsewhere. This example illustrates how pathologists can provide leadership in assisting clinicians in changing laboratory ordering practices. We found that clinicians respond to local laboratory data about their own test performance and that evidence suggesting harm is more compelling to clinicians than evidence of cost savings. Our experience indicates that interventions done at an academic facility can be readily instituted by private practitioners at external facilities. The intervention data also supplement existing literature that electronic order interruptions are more successful when combined with modalities that rely on peer education combined with dashboard feedback about laboratory order performance. The findings may have implications for the role of the pathology laboratory in the ongoing pivot from quantity-based to value-based health care

Raw Single-Wall Carbon Nanotubes Induce Oxidative Stress and Activate MAPKs, AP-1, NF-κB, and Akt in Normal and Malignant Human Mesothelial Cells

Background Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells. Objective Exposure to asbestos is the primary cause of malignant mesothelioma in 80–90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT. Methods In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor κB (NF-κB), and protein serine-threonine kinase (Akt). Results Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-κB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure. Conclusions The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies

Malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation

Malignant melanoma can metastasize widely and vary significantly in its histological appearance; it rarely presents as a deep-seated mass without an obvious primary site elsewhere. Malignant peripheral nerve sheath tumor (MPNST) is a high-grade sarcoma characterized by conventional and epithelioid subtypes. MPNST can demonstrate heterologous differentiation, usually in the form of osteosarcomatous, chondrosarcomatous, or rhabdomyosarcomatous differentiation. MPNST does not harbor true melanocytic differentiation, although epithelioid MPNST typically is diffusely S-100 protein positive and superficially can resemble malignant melanoma. An unusual intra-abdominal mass was recently encountered with features of both melanoma and conventional or epithelioid MPNST containing a fascicular spindle cell component, an epithelioid component with melanocytic differentiation, as well as a rhabdomyosarcomatous component. The terminology “malignant neuroectodermal tumor with melanocytic and rhabdomyoblastic differentiation” is proposed to describe this neoplasm, reflecting the unusual concomittant lines of differentiation as well as offering a possible rationale for nosologically challenging aspects of this neoplasm

Race/ethnicity and potential suicide misclassification: window on a minority suicide paradox?

<p>Abstract</p> <p>Background</p> <p>Suicide officially kills approximately 30,000 annually in the United States. Analysis of this leading public health problem is complicated by undercounting. Despite persisting socioeconomic and health disparities, non-Hispanic Blacks and Hispanics register suicide rates less than half that of non-Hispanic Whites.</p> <p>Methods</p> <p>This cross-sectional study uses multiple cause-of-death data from the US National Center for Health Statistics to assess whether race/ethnicity, psychiatric comorbidity documentation, and other decedent characteristics were associated with differential potential for suicide misclassification. Subjects were 105,946 White, Black, and Hispanic residents aged 15 years and older, dying in the US between 2003 and 2005, whose manner of death was recorded as suicide or injury of undetermined intent. The main outcome measure was the relative odds of potential suicide misclassification, a binary measure of manner of death: injury of undetermined intent (includes misclassified suicides) versus suicide.</p> <p>Results</p> <p>Blacks (adjusted odds ratio [AOR], 2.38; 95% confidence interval [CI], 2.22-2.57) and Hispanics (1.17, 1.07-1.28) manifested excess potential suicide misclassification relative to Whites. Decedents aged 35-54 (AOR, 0.88; 95% CI, 0.84-0.93), 55-74 (0.52, 0.49-0.57), and 75+ years (0.51, 0.46-0.57) showed diminished misclassification potential relative to decedents aged 15-34, while decedents with 0-8 years (1.82, 1.75-1.90) and 9-12 years of education (1.43, 1.40-1.46) showed excess potential relative to the most educated (13+ years). Excess potential suicide misclassification was also apparent for decedents without (AOR, 3.12; 95% CI, 2.78-3.51) versus those with psychiatric comorbidity documented on their death certificates, and for decedents whose mode of injury was "less active" (46.33; 43.32-49.55) versus "more active."</p> <p>Conclusions</p> <p>Data disparities might explain much of the Black-White suicide rate gap, if not the Hispanic-White gap. Ameliorative action would extend from training in death certification to routine use of psychological autopsies in equivocal-manner-of-death cases.</p

Inverse association of colorectal cancer prevalence to serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) in a large Appalachian population

Background Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) are persistent environmental contaminants that affect metabolic regulation, inflammation, and other factors implicated in the development and progression of colorectal cancer (CRC). However, the link between these compounds and CRC remains unknown. In this cross-sectional study, we investigated the association of CRC diagnosis to PFOA and PFOS blood levels in a large Appalachian population. Methods Participants were 47,359 adults ≥ 21 years of age and residing in six PFOA-contaminated water districts in the mid-Ohio Valley (N = 47,151 cancer-free adults, 208 cases of primary CRC). All participants completed a comprehensive health survey between 2005 and 2006; serum levels of PFOA, PFOS, and a range of other blood markers were also measured. Medical history was assessed via self report and cancer diagnosis confirmed via chart review. Results CRC showed a strong inverse, dose–response association with PFOS serum levels (odds ratio (OR) adjusted for potential confounders = 0.2, 95% confidence interval (CI) 0.2,0.3) for highest vs. lowest quartile of PFOS, P-trend \u3c 0.00001) and a significant, but more modest inverse association with PFOA (adjusted OR = 0.6 (CI 0.4, 0.9) for highest vs. lowest quartile, P-trend = 0.001). These inverse associations were stronger in those diagnosed within the previous 6 years and resident in the same water district for a minimum of 10–15 years preceding assessment. The relationship between PFOA and CRC was also more pronounced in men and leaner adults, and showed a stronger linear trend at lower exposure levels. Conclusions In this large cross-sectional study, we found a strong, inverse association between PFOS and likelihood of CRC diagnosis and a significant, although more modest inverse association between PFOA and CRC. If confirmed in prospective investigations, these findings may aid in identifying new strategies for CRC prevention and treatment and inform future studies regarding mechanisms underlying CRC pathogenesis

Discrepant comorbidity between minority and white suicides: a national multiple cause-of-death analysis

Abstract Background Clinician training deficits and a low and declining autopsy rate adversely impact the quality of death certificates in the United States. Self-report and records data for the general population indicate that proximate mental and physical health of minority suicides was at least as poor as that of white suicides. Methods This cross-sectional mortality study uses data from Multiple Cause-of-Death (MCOD) public use files for 1999–2003 to describe and evaluate comorbidity among black, Hispanic, and white suicides. Unintentional injury decedents are the referent for multivariate analyses. Results One or more mentions of comorbid psychopathology are documented on the death certificates of 8% of white male suicides compared to 4% and 3% of black and Hispanic counterparts, respectively. Corresponding female figures are 10%, 8%, and 6%. Racial-ethnic discrepancies in the prevalence of comorbid physical disease are more attenuated. Cross-validation with National Violent Death Reporting System data reveals high relative underenumeration of comorbid depression/mood disorders and high relative overenumeration of schizophrenia on the death certificates of both minorities. In all three racial-ethnic groups, suicide is positively associated with depression/mood disorders [whites: adjusted odds ratio (AOR) = 31.9, 95% CI = 29.80–34.13; blacks: AOR = 60.9, 95% CI = 42.80–86.63; Hispanics: AOR = 34.7, 95% CI = 23.36–51.62] and schizophrenia [whites: AOR = 2.4, 95% CI = 2.07–2.86; blacks: AOR = 4.2, 95% CI = 2.73–6.37; Hispanics: AOR = 4.1, 95% CI = 2.01–8.22]. Suicide is positively associated with cancer in whites [AOR = 1.8, 95% CI = 1.69–1.93] and blacks [AOR = 1.8, 95% CI = 1.36–2.48], but not with HIV or alcohol and other substance use disorders in any group under review. Conclusion The multivariate analyses indicate high consistency in predicting suicide-associated comorbidities across racial-ethnic groups using MCOD data. However, low prevalence of documented comorbid psychopathology in suicides, and concomitant racial-ethnic discrepancies underscore the need for training in death certification, and routinization and standardization of timely psychological autopsies in all cases of suicide, suspected suicide, and other traumatic deaths of equivocal cause