h-Caldesmon, a Useful Positive Marker in the Diagnosis of Pleural Malignant Mesothelioma, Epithelioid Type

Department of Human Pathology and Oncology, University of Florence Medical School, Florence, Italy.
American Journal of Surgical Pathology (Impact Factor: 5.15). 05/2006; 30(4):463-9. DOI: 10.1097/00000478-200604000-00006
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Although a large number of immunohistochemical markers that can facilitate the differential diagnosis between epithelioid pleural mesothelioma and lung adenocarcinoma involving the pleura have proven to be valuable, no single antibody has demonstrated absolute sensitivity and/or specificity in making this distinction. Using immunohistochemical analysis with h-caldesmon, a specific marker for smooth muscle tumors, we examined 70 cases of epithelial mesotheliomas and 70 cases of lung adenocarcinomas. In addition, immunohistochemistry for muscle markers, such as desmin, alpha-smooth-muscle actin, muscle-specific actin, myoglobin, myogenin, myosin, and MyoD-1, was performed on all mesothelioma cases. Reactivity for h-caldesmon was obtained in 68 (97%) of the 70 epithelial mesotheliomas, but in none of the adenocarcinoma cases. All mesothelioma cases were found to be negative for the other muscle markers examined. We conclude that h-caldesmon is a highly sensitive and specific marker and suggest its inclusion in the immunohistochemical panel for the differential diagnosis of epithelioid mesothelioma versus lung adenocarcinoma.

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    • "Due to scarce material, some relevant antibodies as WT-1, h-Caldesmon, and others, as well as specific histochemical reactions on glycoproteins and hyaluronic acid could not be applied, despite of their diagnostic value [34-36]. More extensive diagnostics including genetic testing, fluorescence in situ hybridisation (FISH) and electron microscopy (EM) in order to possibly reach a final entity diagnosis in the unclear cases, were not carried out, since this was not a concern in this study where the main point was to exclude all insecure and non-MM cases by a high degree of likelihood [37,23,39]. "
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    ABSTRACT: In order to provide reliable tissue material for malignant mesothelioma (MM) studies, we re-evaluated biopsies and autopsy material from 61 patients with a diagnosis of MM from the period of 1980-2002. Basic positive (Calretinin, EMA, Podoplanin, Mesothelin) and negative (CEA, Ber-Ep4) immunohistochemical (IHC) marker reactions were determined. If needed, more markers were used. Histological diagnoses were made by three pathologists. Survival data were calculated. 49 cases (80%) were considered being MM by a high degree of likelihood, five more cases possible MM. Of the remaining seven cases, three were diagnosed as adenocarcinoma, three as pleomorphic lung carcinoma, in one peritoneal case a clear entity diagnosis could not be given. One of the possible MM cases and two of the lung carcinoma cases had this already as primary diagnoses, but were registered as MM.With a sensitivity of 100%, Calretinin and CEA were the most reliable single markers. The amount of MM cells with positive immunoreactivity (IR) for Podoplanin and Mesothelin showed most reliable inverse relation to the degree of atypia.In the confirmed MM cases, there had been applied either no IHC or between one and 18 markers.The cases not confirmed by us had either lacked IHC (n = 1), non-specific markers were used (n = 4), IR was different (n = 1), or specific markers had not shown positive IR in the right part of the tumour cells (n = 3).46 of the 49 confirmed and three of the not confirmed cases had been diagnosed by us as most likely MM before IHC was carried out. In order to use archival tissue material with an earlier MM diagnosis for studies, histopathological re-evaluation is important. In possible sarcomatous MM cases without any positive IR for positive MM markers, radiology and clinical picture are essential parts of diagnostics. IHC based on a panel of two positive and two negative MM markers has to be adapted to the differential diagnostic needs in each single case. New diagnostic tools and techniques are desirable for cases where IHC and other established methods cannot provide a clear entity diagnosis, and in order to improve MM treatment.
    Diagnostic Pathology 07/2010; 5(1):47. DOI:10.1186/1746-1596-5-47 · 2.60 Impact Factor
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    • "It is inaccurate because other cell types could be spindle-shaped and can express these molecules. On the contrary, when myofibroblast are located in normal tissues and in certain histological context, it is quite easy to identify them and to exclude other cellular types [13] [14]. "
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    ABSTRACT: There is reliable information about how changes in spleen histology are influenced by the relationship among B and T lymphocytes, macrophages, dendritic cells and myofibroblasts. Moreover, if it can be applied in the day-by-day pathology laboratory. This work intends to elucidate morpho-functional aspects of relationships of these cells in the different spleen compartments, how they are influenced by pathological conditions and how basic immunohistochemical techniques could optimize the histopathological diagnosis. We analyzed the usefulness of the monoclonal antibodies CD45RO, CD20, CD21, CD35, CD68, caldesmon, the smooth muscle alpha-actin type 1 (SMA-1) in 91 specimens. CD21(+) CD35(+) follicular dendritic cells were organized into three patterns in agreement with the immune condition of the lymphoid follicle. Smooth muscle alpha-actin type 1(+)and caldesmon(+)myofibroblasts draw two double rings: marginal-perifollicular and germinal-marginal. The latter is closely related to T-cells. CD68(+)red pulp macrophages had clear and linear configuration. The interruption of this CD68(+) linear pattern in splenic marginal zone lymphoma cases could be a criterion to differentiate it from reactive hyperplasia. CD45RO, CD20, CD21, CD68 and SMA-1 provide a basic and quality immunohistochemical battery for a better comprehension of the human spleen and could improve its histopathological diagnosis.
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    ABSTRACT: Malignant mesothelioma is an uncommon malignant epithelial neoplasm originating from the serosal surface of body cavities. Because serosal surfaces are a common site of metastatic spread for a variety of malignant neoplasms originating from internal organs, separating malignant mesothelioma from metastatic tumors is of clinical importance. The diagnosis of malignant mesothelioma is complex and usually requires a multimodal approach that includes careful clinical history and physical examination, imaging studies, and tissue sampling for multimodal evaluation including routine histology, histochemistry, electron microscopy, and immunohistochemical tests. Of these, immunohistochemistry has emerged as the most valuable and readily available modality for the routine evaluation of these tumors. Unfortunately, no specific antibodies have yet been developed that can be accepted as exclusive for these tumors. The immunohistochemical diagnosis of malignant mesothelioma therefore depends on the use of a panel of stains that includes markers that are commonly expected to react with these tumors ("positive" markers) and markers that are not commonly expected to react with these tumors ("negative" markers). Additionally, the selection and utility of these various markers can vary considerably based on a constellation of circumstances, including patient sex, histologic appearance of the tumor (ie, epithelioid vs. sarcomatoid, etc), and various other clinical circumstances. Herein, we will review the currently available immunohistochemical markers used for the diagnosis of malignant mesothelioma and offer suggestions for the use of appropriate panels of stains based on specific morphologic types and clinical circumstances.
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