Citations

Context .—Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. Objective .—To provide updated practical guidelines for the pathologic diagnosis of MM. Data Sources .—Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. Conclusions .—There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. It is recommended that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

Abstract Few reports have documented the effectiveness of Lean quality improvement in changing anatomic pathology patient safety. We used Lean methods of education; hoshin kanri goal setting and culture change; kaizen events; observation of work activities, hand-offs, and pathways; A3-problem solving, metric development, and measurement; and frontline work redesign in the accessioning and gross examination areas of an anatomic pathology laboratory. We compared the pre- and post-Lean implementation proportion of near-miss events and changes made in specific work processes. In the implementation phase, we documented 29 individual A3-root cause analyses. The pre- and postimplementation proportions of process- and operator-dependent near-miss events were 5.5 and 1.8 (P < .002) and 0.6 and 0.6, respectively. We conclude that through culture change and implementation of specific work process changes, Lean implementation may improve pathology patient safety.

Abstract Objective: This paper introduces an alternative non-invasive and non-ionizing breast imaging tool called vibro-acoustography (VA). This method is based on low-frequency harmonic vibrations induced in the object by the radiation force of ultrasound. Contrast in Vibro-acoustography images represent several properties of the object, including the dynamic characteristics at the audio frequency and scattering and absorption properties at the ultrasound frequency. X-ray mammography and ultrasound are the main imaging modality used today for detection of breast lesions. X-ray mammography, however, is ionizing and its sensitivity is greatly reduced in dense breasts. Ultrasound images suffer from speckles or other or artifact that prevents the physician from delineating the mass lesion from the background tissue. Hence, VA may be used as a stand-alone imaging device or as a tool to provide supplementary information to other existing imaging modalities. Materials & Methods: Matching vibro-acoustography and mammography images of human breast are acquired using a combined mammography/vibro-acoustography machine. Images of various types of breast masses are investigated and their characteristics features are compared. Image features, such as lesion borders, interior texture, and speculation pattern, are studied. Results: Resulting images show soft tissue structures, breast lesions and microcalcifications within breast with high contrast, high resolution, and no speckles. The results have been verified using x-ray mammograms of the breast. Vibro-acoustography images demonstrate that calcified masses normally show sharp borders, benign non-calcified masses have smooth texture, and, in some cases, malignant masses are characterized with spiculation. Conclusion: The encouraging results which are based on the data collected from an ongoing study indicate that the above mentioned image features may be used for differentiation of breast masses and suggest that further development of vibro-acoustography technology may lead to a new clinical tool for various imaging applications. Work supported in part by Grant CA121579-01A1from NIH and Grant BCTR#0504550 from Susan G. Komen Breast Cancer Foundation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4047. doi:1538-7445.AM2012-4047

Abstract Previous epidemiological studies have suggested that African Americans (AA) are twice as likely to be diagnosed with and to die from Multiple Myeloma (MM) as compared to European Americans (EA). In recent years, however, mortality rates have become more comparable between these groups. Although socioeconomic factors could play a major role to this potential disparity, biological factors may also be responsible for influencing these differences in either incidence and/or mortality. Here we examined a multi-ethnic cohort of MM tumors to assess potential differences in the frequency of molecular events in tumors derived from either African American (AA) or European American (EA) patients. First, we compared the frequency of 14q32 translocation breakpoints at the IgH locus among a series of data from 115 AA MM patients from three studies and EA MM from the Eastern Cooperative Oncology Group (ECOG). Furthermore, we analyzed matching genome-wide copy number and transcriptional data among 47 AA MM tumors and 196 EA MM tumors to determine differences in the frequency of molecular events in tumors from these populations. Univariate analyses were conducted using the Fisher's Exact Test and p-values were calculated to measure statistical significance. We observed statistically significant differences in the frequency of IgH translocations and somatic copy number alterations. Although we did not detect differences for specific translocation subtypes, we saw a statistically significant difference in the overall frequency of IgH translocations between the two groups, which occurred more frequently in EA patients (p = 0.032). When assessing genomic copy number events previously shown to be associated with poor outcome in MM, chromosome 13 monosomy was more frequent in hyperdiploid MM from AA patients and significant after correcting for multiple testing using the Bonferoni correction method (p = 0.001). Moreover, when using the Benjamini-Hochberg multiple testing correction method, chromosome 13 monosomy remained significantly different among hyperdiploid AA patients (p = 0.0121). Chromosome 1q amplification was also significant among hyperdiploid tumors from EA patients when using this correction method (p = 0.036). No differences in the frequency of hyperdiploid status or gene expression-based subtypes were detected when comparing tumors from AA and EA patients. Our study represents the first comprehensive assessment of the frequency and distribution of molecular alterations in MM tumors from both AA and EA patients and could help shed light on possible biological features associated with population differences in incidence and outcome in MM. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5064. doi:1538-7445.AM2012-5064

Abstract We determined the prognostic relevance of CD25 (IL-2 receptor-α) expression in 657 patients (≤ 60 years) with de novo acute myeloid leukemia (AML) treated in the Eastern Cooperative Oncology Group trial, E1900. We identified CD25POS myeloblasts in 87 patients (13%), of whom 92% had intermediate-risk cytogenetics. CD25 expression correlated with expression of stem cell antigen CD123. In multivariate analysis, controlled for prognostic baseline characteristics and daunorubicin dose, CD25POS patients had inferior complete remission rates (P = .0005) and overall survival (P < .0001) compared with CD25NEG cases. In a subset of 396 patients, we integrated CD25 expression with somatic mutation status to determine whether CD25 impacted outcome independent of prognostic mutations. CD25 was positively correlated with internal tandem duplications in FLT3 (FLT3-ITD), DNMT3A, and NPM1 mutations. The adverse prognostic impact of FLT3-ITDPOS AML was restricted to CD25POS patients. CD25 expression improved AML prognostication independent of integrated, cytogenetic and mutational data, such that it reallocated 11% of patients with intermediate-risk disease to the unfavorable-risk group. Gene expression analysis revealed that CD25POS status correlated with the expression of previously reported leukemia stem cell signatures. We conclude that CD25POS status provides prognostic relevance in AML independent of known biomarkers and is correlated with stem cell gene-expression signatures associated with adverse outcome in AML.