Mesothelioma and Small Cell or Pleomorphic Patterns

Mesothelioma and Small Cell or Pleomorphic Patterns

Another interesting study is called, “Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern” by R L Attanoos, R Webb, S D Dojcinov, A R Gibbs – Histopathology Volume 39, Issue 6, pages 584–588, December 2001.  Here is an excerpt: “Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern – Aims: Malignant epithelioid mesothelioma shows marked cytoarchitectural diversity. The aim of the study was to evaluate how immunoreactivity with mesothelial markers related to histological pattern.

Methods and results:Ninety-two cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) were examined and classified as exhibiting tubulopapillary, adenomatoid, solid, small cell or pleomorphic patterns. All cases were immunohistochemically stained with thrombomodulin, calretinin, CD44H, and cytokeratin 5/6. Cases of malignant mesothelioma exhibited a number of different histological forms. Immunohistochemical expression of each mesothelial marker tested was not homogeneous across different histological patterns of malignant epithelioid mesothelioma, even within the same tumour section. Calretinin (with nuclear expression) was identified to show the highest overall sensitivity and lowest range variation in staining (67% sensitivity in small cell areas to 100% expression in pleomorphic areas). Cytokeratin 5/6 and thrombomodulin yielded similar overall sensitivity. Thrombomodulin appeared to demonstrate higher sensitivity for small cell variant tumour (83% sensitivity). A notable advantage with cytokeratin 5/6 was that expression was more diffuse in nature rather than the focal membranous elaboration seen in thrombomodulin. The widest range of staining was seen in small cell mesothelioma (83% sensitivity with thrombomodulin to 17% sensitivity with cytokeratin 5/6) and in tubulopapillary areas (90% sensitivity with calretinin to 38% sensitivity with CD44H).

Conclusions:Calretinin appears most useful and shows the highest overall sensitivity for malignant epithelioid mesothelioma, with good expression in areas displaying a tubulopapillary, adenomatoid, solid and pleomorphic pattern. For small cell mesothelioma, thrombomodulin appears to confer higher sensitivity and is advocated, in this setting, as the first line mesothelial marker. Cytokeratin 5/6 is a useful and easily interpretable mesothelial marker. CD44H is not of particular use in the diagnosis of malignant epithelioid mesothelioma. Accurate interpretation of immunohistochemistry in mesothelioma requires an awareness of the immunophenotypic heterogeneity identified in different histological forms of the tumour, and this is of particular importance in small biopsies.”

Another interesting study is called, “Serologic responses in patients with malignant mesothelioma: evidence for both public and private specificities.” By Robinson C, Callow M, Stevenson S, Scott B, Robinson BW, Lake RA – Am J Respir Cell Mol Biol. 2000 May;22(5):550-6. – University Department of Medicine, Western Australian Institute for Medical Research, Queen Elizabeth II Medical Centre, Perth, Western Australia, Australia.  Here is an excerpt: “Malignant mesothelioma (MM) is a pulmonary malignancy that appears to be immunogenic based on a large number of studies in both animals and humans. This notion is supported by our recent demonstration using Western blot analysis of immunoglobulin G antibodies reactive with a variety of autoantigens in many patients with MM. In view of the enormous potential of such antigens in early diagnosis, immunotherapy, and vaccination of at-risk individuals, it was essential to identify these antigens. We therefore applied the SEREX technique (serologic identification by recombinant expression cloning), using a serum pool from six patients as the probe against an expressed complementary DNA library derived from a cloned MM cell line. We screened over one million recombinants and obtained sequence information on eight antigens that had provoked immunoglobulin heavy chain class switching, presumably as a consequence of T-cell recognition. Six of these antigens were identifiable (U2AF[65], Siah binding protein, topoisomerase IIbeta, ZFM1, mIre1, and pendulin), and of the others, one was found as a single EST from a myotube library (Jemm-1); the other (Jemm-2) was not represented in any EST database even as a weak homolog. Consistent with our previous findings, each of the characterizable antigens would be expected to be associated with the cell nucleus. Each of the autoantibody specificities was uniquely associated with a single patient with the exception of antibodies to TOPIIbeta and U2AF(65). We found 13 of 14 (93%) patients with MM had antibodies to TOPIIbeta and two of 14 (14%) patients had antibodies to U2AF(65). The number of serum reactivities, taken as a measure of the complexity of the immune response, correlates with patient survival and with an index of systemic inflammation. These data suggest that a broader range of serologic reactivities reflects a more active host response to the presence of tumor.”

We all owe a debt of gratitude to these fine researchers.  If you found any of these excerpts interesting, please read the studies in their entirety.

Monty Wrobleski is the author of this article.  For more information please click on the following links

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