Annika Dejmek

Reactivity of six antibodies in effusions of mesothelioma, adenocarcinoma and mesotheliosis: stepwise logistic regression analysis.

Anti‐CEA, anti‐vimentin, CAM5.2, BerEp4, Leu‐M1 and anti‐EMA were applied to effusions from 36 mesotheliomas, 53 adenocarcinomas and 24 reactive mesothelial proliferations. Stepwise logistic regression analysis selected three criteria of major importance for distinguishing between adenocarcinoma and mesothelioma: BerEp4, CEA and EMA accentuated at the cell membrane (mEMA), these three being of similar diagnostic value. The pattern BerEp4−, CEA− and mEMA+ was fully predictive for mesothelioma (sensitivity 47%), whereas the opposite pattern was fully predictive for adenocarcinoma (sensitivity 80%). Only EMA seemed to distinguish between mesotheliosis and mesothelioma. Comparison of reactivity in cytological and histological material from the same mesotheliomas showed similar staining frequencies for CEA and CAM5.2, with some random variation for Leu‐M1 and EMA, whereas vimentin and BerEp4 reactivity was more frequent in cytological specimens.

An Optimized Battery of Eight Antibodies That Can Distinguish Most Cases of Epithelial Mesothelioma From Adenocarcinoma

An immunocytochemical battery comprising 9 antibodies specifically distinguishes 80% of the epithelial malignant mesotheliomas from adenocarcinomas. The discriminatory power of antibodies to calretinin was tested together with this battery to determine whether the performance thereby could be improved. The study comprises 119 mesotheliomas of epithelial or mixed phenotype and 57 adenocarcinoma metastases in the pleural cavity. The differences between the 2 groups were highly significant for all recorded parameters, but typical reactivity for all parameters was seen in only 6 (5.0%) of the 119 mesotheliomas. An algorithm based on stepwise logistic regression was used to interpret divergent reaction patterns. Most diagnostic information was obtained with 8 of the parameters studied. The resulting algorithm identified almost 90% of the mesotheliomas with high specificity. The battery can be performed in 2 steps: several adenocarcinomas first are diagnosed with a few antibodies, applying the rest of the battery on the remaining unresolved cases.

Immunohistochemical reactivity in mesothelioma and adenocarcinoma: a stepwise logistic regression analysis.

Histological sections from 103 malignant mesotheliomas and 43 adenocarcinoma metastases in pleural biopsies were investigated for reactivity against a panel of 11 different antibodies. The size of the material allowed the evaluation by stepwise logistic regression analysis, which selected five parameters of major importance: vimentin reactivity in epithelial cells, reactivity to low‐molecular‐weight keratins in fibrous cells, strong membrane accentuation of EM A reactivity, and lack of reactivity to LeuM1 and BerEp4. Three of these criteria were sufficient to identify a mesothelioma with high specificity and with a sensitivity of approximately 70%. Whilst the monoclonal anti‐CEA tested was the most valuable single parameter, it did not add any diagnostic information to the combination of criteria selected by the stepwise logistic regression analysis. However, this antibody can be used to exclude most of the adenocarcinomas from further analysis with the more extensive panel.

Possibility of mixed progenitor cells in sea star arm regeneration

In contrast to most vertebrates, invertebrate deuterostome echinoderms, such as the sea star Asterias rubens, undergo regeneration of lost body parts. The current hypothesis suggests that differentiated cells are the main source for regenerating arm in sea stars, but there is little information regarding the origin and identity of these cells. Here, we show that several organs distant to the regenerating arm responded by proliferation, most significantly in the coelomic epithelium and larger cells of the pyloric caeca. Analyzing markers for proliferating cells and parameters indicating cell ageing, such as levels of DNA damage, pigment, and lipofuscin contents as well as telomere length and telomerase activity, we suggest that cells contributing to the new arm likely originate from progenitors rather than differentiated cells. This is the first study showing that cells of mixed origin may be recruited from more distant sources of stem/progenitor cells in a sea star, and the first described indication of a role for pyloric caeca in arm regeneration. Data on growth rate during arm regeneration further indicate that regeneration is at the expense of whole animal growth. We propose a new working hypothesis for arm regeneration in sea stars involving four phases: wound healing by coelomocytes, migration of distant progenitor cells of mixed origin including from pyloric caeca, proliferation in these organs to compensate for cell loss, and finally, local proliferation in the regenerating arm.

Guidelines for cytopathologic diagnosis of epithelioid and mixed type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.

Guidelines for the Cytopathologic Diagnosis of Epithelioid and Mixed-Type Malignant Mesothelioma

Objective: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. Data Sources: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. Rationale: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

Telomere repeat amplification protocol (TRAP) in situ reveals telomerase activity in three cell types in effusions : malignant cells, proliferative mesothelial cells, and lymphocytes

Telomerase Repeat Amplification Protocol (TRAP) in situ was performed on cytospin preparations from 65 effusions from the serous cavities (45 pleural and 19 ascitic fluids and one pericardial fluid) submitted for routine diagnosis and the results were correlated to cytological morphology. Three types of cells with nuclear fluorescence were identified: malignant cells, hyperplastic mesothelial cell and lymphocytes. Of 38 cytologically malignant effusions, 12 showed strong reactivity in all malignant cells, three strong reactivity in part of the malignant population, whereas 12 showed moderate reactivity in the whole and five in part of the malignant population, respectively. In five malignant effusions weak reactivity was found in all (one case) and in scattered (four cases) malignant cells. Two effusions contained telomerase-negative malignant cells. Two pleural and two ascitic fluids contained proliferative mesothelial cells with weak or, in one case, moderate reactivity. Lymphocytes usually showed weak telomerase activity. Telomerase was expressed in almost all malignant tumours metastatic to serous cavities. Heterogeneity in tumour populations was demonstrated, which may have diagnostic implications, especially in cytology. Weak or moderate reactivity was found in lymphocytes and in some mesothelial proliferations and may explain the low specificity for malignancy sometimes obtained with the TRAP extract method. The weak reactivity found in lymphocytes may reduce the specificity when the extract method is used but causes no diagnostic problem with the TRAP in situ method.

Podoplanin Is a Useful Marker for Identifying Mesothelioma in Malignant Effusions

The diagnosis of malignant mesothelioma in serosal effusions continues to be a major challenge because some of its cytomorphological features closely resemble adenocarcinomas. Immunohistochemistry is a valuable tool in the differentiation of epithelioid mesothelioma from metastatic adenocarcinomas. However, no single antibody has demonstrated absolute sensitivity or specificity. In this study, we evaluated the value of immunostaining pattern for podoplanin to differentiate mesothelioma from adenocarcinomas of various origins.

Optimization of a battery using nine immunocytochemical variables for distinguishing between epithelial mesothelioma and adenocarcinoma

A battery of immunocytochemical analyses, previously established to distinguish between malignant mesothelioma and metastatic adenocarcinoma, was extended by analysing the same cases with three other commercially available antibodies. Altogether, 11 antibodies were studied in mesotheliomas diagnosed by other means, using 14 different immunocytochemical parameters. Logistic regression analysis indicated that the following parameters were of importance for this diagnostic problem: vimentin reactivity in epithelial cells (1), cytokeratin (CAM 5.2) reactivity in spindle‐shaped (fibrous) cells (2), cell membrane‐associated reactivity of EMA (3), HBME‐1 (4) and thrombomodulin (5), and absence of reactivity to CEA (6) CD15 (7), BerEp4 (8) and Sialyl‐TN (9). The analysis gave an algorithm with which a specific diagnosis of mesothelioma could be made in 80% of the cases i.e., some improvement compared to the 55% sensitivity using the previous battery.

Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Socie: IMIG Guidelines for the Pathologic Diagnosis of MM

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma.