Although Ki-67 labeling index (Ki-67%) is not a diagnostic or grading criterion in the World Health Organization classification of pulmonary carcinoid tumor, oncologists often request this test. A ...survey was administered at a North American Society for Neuroendocrine Tumors meeting to understand how Ki-67% is used in oncologic practices. A systematic literature review was performed to gather best evidence regarding the use of Ki-67%. Consecutive pulmonary carcinoids were stratified into pulmonary typical carcinoids with Ki-67% <5% (group A, n = 187), typical carcinoids with Ki-67% ≥5% (group B, n = 38) and atypical carcinoids irrespective of Ki-67% (group C, n = 31). Overall survival, progression-free survival, recurrence proportions and time to recurrence were compared, by group, using the log-rank test, chi-square statistics and ANOVA, respectively. Our survey confirmed that Ki-67% is frequently used by specialists caring for these patients. Ki-67% of 1–7% significantly correlated with overall survival in the literature but we found no information about Ki-67% cut-off values that would accurately distinguish pulmonary typical from atypical carcinoids or estimate the prognosis of patients stratified by World Health Organization diagnosis and Ki-67% cut-off. Overall survival was significantly different in our 3 patient groups (p < 0.001), with survival probabilities decreasing from groups A to C. Progression-free survival was significantly longer in group A than B (p < 0.007). Our results support the concept that by combining World Health Organization diagnosis and Ki-67%, pulmonary carcinoids can be stratified into 3 grades: G1 (typical carcinoids with Ki-67% <5), G2 (typical carcinoids with Ki-67% ≥5%) and G3 (atypical carcinoids) with different prognoses.
The diagnosis of malignant mesothelioma (MM) is rendered with the aid of immunohistochemistry to demonstrate the presence of "mesothelial," "epithelial," or "sarcomatous" differentiation. Antibody ...panels that have been proposed for the distinction between MM and other neoplasms usually include 2 or more epithelial markers used to exclude the diagnosis of a carcinoma, such as monoclonal and polyclonal carcinoembryonic antigen, Ber-EP4, B72.3, CD15, MOC-31, thyroid transcription factor 1, BG8, and others, and 2 or more mesothelial markers used to confirm the diagnosis of MM, such as cytokeratin 5/6, calretinin, HBME-1, thrombomodulin, WT-1, mesothelin, D2-40, and podoplanin. In general, most antibody panels provide excellent sensitivity and specificity for the differential diagnosis between MM epithelial variant and adenocarcinoma, particularly of lung origin. However, the accuracy of these markers is lower for the diagnosis of sarcomatous MM and for the differential diagnosis between MM and squamous cell carcinoma and carcinomas of renal, ovarian, and other origin.
To identify optimal antibody panels for the diagnosis of MM.
Literature review to determine how many and which mesothelial and epithelial markers need to be included in differential diagnosis antibody panels.
Various antibody panels have been recommended for the diagnosis of MM, with no overall consensus about how many and which markers should be used. A recent study with Bayesian statistics has demonstrated that the use of many markers does not provide higher diagnostic accuracy than the use of selected single antibodies or various combinations of only 2 markers. There is a need for the development of evidence-based or consensus-based guidelines for the diagnosis of MM in different differential diagnosis situations.
Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose.
To provide updated practical guidelines for the pathologic diagnosis of MM.
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.
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.
The checkpoint protein programmed cell death ligand-1 protein (PD-L1) binds to its receptor (PD-1) activating the PD-L1/PD-1 pathway, an important therapeutic target. There is limited information ...regarding PD-L1 and PD-1 expression in thymic lesions. Sections from nonneoplastic thymi (n = 20), thymomas World Health Organization types A, AB, B1, B2, and B3 (n = 38) and thymic squamous cell carcinoma (n = 8) were stained for PD-L1 (clone SP142; Spring BioScience), PD-1 (MRQ22; Cell Marque), CD4 (clone SPO32; Cell Marque), and CD8 (JCB117; Ventana). Immunoreactivity for each antibody was classified as focal or diffuse and scored as follows: 0, negative; 1%-5%, 1+; 6%-20%, 2+; and >20%, 3+. The proportions of cases expressing PD-L1, PD-1, CD4, and C8 at score ≥1+ were compared by diagnosis, using χ2 statistics. PD-L1 was expressed in 90% of nonneoplastic thymi, 92% of thymomas, and 50% of carcinomas, with significantly higher scores (P < .01) in B2 and B3 thymomas and carcinomas than in AB and B1 thymomas; PD-L1 was diffuse in most B2 and B3 thymomas and focal in carcinomas. PD-1 was focally expressed, and mostly with scores 1+, in 55% of nonneoplastic thymi, 63% of thymomas, and 37.5% of carcinomas. CD4+ and CD8+ cells were diffusely distributed with scores 3+ in all lesions other than B3 thymomas and carcinomas. The latter showed CD4+ cells mostly at the interface between neoplastic cells and stroma. PD-L1 and PD-1 are not expressed in similar locations and cellular proportions in thymic lesions, raising a question as to whether the PD-L1/PD-1 pathway is an actionable therapeutic target in these lesions.
Operation of high-field superconducting magnets relies on diagnostic instrumentation for measuring strain, temperature, and magnetic field variations, detecting quenching, and identifying performance ...problems. Discrete sensor implementation is costly, requires multi-channel data acquisition systems, and sensor density is often insufficient to resolve problematic locations spatially. Distributed sensing is a viable alternative approach providing location-specific diagnostic information over single terminal output. In particular, it can be the key to quench protection of high-temperature superconductor (HTS)-based magnets where hot spots are known to form and persist before a quench. Fiber-optic technology offers distributed sensing solution for magnets but suffers from drawbacks such as fiber fragility, high costs of optical interrogators, and difficulty in differentiating between physical quantities such as temperature and strain. We propose an alternative, robust, and easily integrable way of implementing distributed sensing in magnets using radio-frequency (RF) technologies. RF Time Domain Reflectometry (TDR) technique has been around for nearly 60 years, and it is an essential diagnostic tool used in multiple areas of technology and applied research. We discuss operational principles and practical implementation of RF TDR sensors capable of detecting local variations of strain, temperature, and magnetic field through changes in RF impedance and wave propagation time. Results of cryogenic testing of our TDR sensors with HTS tape conductors are presented. The perspective of enabling a new diagnostics paradigm for high-energy physics and fusion energy applications based on distributed RF sensing is discussed.
Sialylated HEG1 has been reported as a highly specific and sensitive mesothelioma marker but a comprehensive evaluation of its expression in carcinomas in different organs, various sarcomas and ...reactive mesothelial proliferations has not been reported. The aim of this study was to evaluate the clinical applicability of HEG1 as a marker in the diagnosis of mesothelioma. HEG1 immunoreactivity was evaluated in whole sections of 122 mesotheliomas, 75 pulmonary carcinomas, 55 other carcinomas, 16 mesenchymal tumors, and 24 reactive mesothelial proliferations and in tissue microarrays containing 70 epithelioid (EM), 36 biphasic (BM), and 2 sarcomatoid mesotheliomas (SM). In whole sections and tissue microarrays, respectively, membranous HEG1 was expressed in 93.0% and 85.5% of EM, 81.3% and 69.4% of BM, 0% and 0% of SM. HEG1 was not expressed in pulmonary adenocarcinomas. HEG1 was expressed as cytoplasmic immunoreactivity in pulmonary squamous cell carcinomas (21.7%). Membranous HEG1 staining was seen in ovarian carcinomas (66.7%), thyroid carcinomas (100%), reactive conditions (16.7%), and mesenchymal tumors (18.8%). The sensitivity of membranous HEG1 expression to distinguish EM/BM from all carcinomas was 88.8%. The specificity for the differential diagnosis between EM/BM and all carcinomas and pulmonary carcinomas was 92.3% and 98.7%, respectively.
Immunohistochemistry is used to distinguish sarcomatoid malignant mesotheliomas (SMM) from spindle cell and pleomorphic carcinomas (SPC) but there are no guidelines on how to interpret cases that ...show overlapping or equivocal immunohistochemical findings. A systematic literature review of the immunophenotype of these lesions was performed and the experience with 587 SMM and 46 SPC at MESOPATH was collected. Data were analyzed with Comprehensive Meta-Analysis 2.0 software (Biostat, Englewood, NJ). There were insufficient data to evaluate the differential diagnosis between SPC and localized SMM or peritoneal SMM. Meta-analysis showed considerable overlap in the immunophenotype of these neoplasms and significant data heterogeneity amongst many of the results. Survival data from MESOPATH patients showed no significant differences in overall survival between SMM and SPC patients. Best available evidence was used to formulate several evidence-based guidelines for the differential diagnosis between pleural SMM and SPC. These guidelines emphasize the need to correlate the histopathological findings with clinical and imaging information. Diffuse SMM can be diagnosed with certainty in the presence of malignant spindle cell pleural lesions showing immunoreactivity for cytokeratin and mesothelial markers and negative staining for epithelial markers. Criteria for the interpretation of various other combinations of immunoreactivity for cytokeratin and mesothelial and/or epithelial markers are proposed. Localized sarcomatoid mesotheliomas can only be diagnosed in the presence of spindle cell malignancies that exhibit immunoreactivity for cytokeratin and mesothelial markers and negative immunoreactivity for epithelial lesions, in patients that show no multifocal or diffuse pleural spread and no evidence for extrapleural lesions.
•The differential diagnosis between sarcomatoid mesothelioma and spindle cell/pleomorphic carcinomas is difficult.•There are no clear guidelines in the literature.•A systematic analysis review of best evidence with meta analysis was performed.•The data with the experience at the MESOPATH Reference Cancer Center in Lyon France was included in meta analysis.•Results were discussed by members of the International Mesothelioma Panel.•Best evidence diagnostic guidelines are proposed.
Frozen sections can help determine the extent of surgery by distinguishing in situ, minimally invasive, and invasive adenocarcinoma of the lung.
To evaluate our experience with the frozen section ...diagnosis of these lesions using root-cause analysis.
Frozen sections from 224 consecutive primary pulmonary adenocarcinomas (in situ, 27 12.1%; minimally invasive, 46 20.5%; invasive, 151 67.4%) were reviewed. Features that could have contributed to frozen section errors and deferrals were evaluated.
There were no false-positive diagnoses of malignancy. Frozen section errors and deferrals were identified in 12.1% (27 of 224) and 6.3% (14 of 224) of the cases, respectively. Significantly more errors occurred in the diagnosis of in situ and minimally invasive adenocarcinoma than in the diagnosis of invasive adenocarcinoma (P < .001). Frozen section errors and deferrals were twice as frequent in lesions smaller than 1.0 cm (P = .09). Features significantly associated with errors and deferrals included intraoperative consultation by more than one pathologist (P = .003) and more than one sample of frozen lung section (P = .001). Inflammation with reactive atypia, fibrosis/scar, sampling problems, and suboptimal quality sections were identified in 51.2% (21 of 41), 36.6% (15 of 41), 26.8% (11 of 41), and 9.8% (4 of 41) of the errors and deferrals, respectively (more than one of these factors was identified in some cases). Frozen section errors and deferrals had significant clinical impact in only 4 patients (1.8%); each had to undergo completion video-assisted thoracoscopic lobectomy less than 90 days after the initial surgery.
The distinction of in situ from minimally invasive adenocarcinoma is difficult in both frozen and permanent sections. We identified several technical and interpretive features that likely contributed to frozen section errors and deferrals and suggest practice modifications that are likely to improve diagnostic accuracy.
Among various diagnostics, acoustic techniques are valuable for characterizing mechanical instabilities associated with lengthy training, premature quenching and other performance limitations of ...high-field accelerator magnets. While acoustic emissions from magnets were studied since early 80 s, techniques involving external acoustic excitation have so far been of limited use. As such techniques are already well-developed in materials science and geoscience, they offer a great potential for the superconducting magnet applications. In a typical magnet coil an acoustic pulse emitted by a coupled ultrasonic transducer would experience multiple scatterings from boundaries and interfaces along its propagation path, in resemblance to a diffusion process. The resulting diffuse ultrasonic field uniquely samples geometrical boundaries, scatterer locations and sound velocity distribution in the propagation medium. Variation of these properties can be tracked in real time and with high accuracy by monitoring shape distortions and temporal shift of the ultrasonic waveforms acquired by sensors coupled to the coil. We discuss key physical principles and capabilities of diffuse field ultrasound, and give examples of using it for detecting interface instabilities in Canted Cosine Theta (CCT) Nb 3 Sn superconducting accelerator magnets built by the US Magnet Development Program.
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