Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern

Our plain-English summary of Malignant epithelioid mesothelioma: anti-mesothelial marker expression correlates with histological pattern, by R.L. Attanoos, R. Webb, S.D. Dojcinov, et al (Histopathology, 2001).

The study

• Authors: R.L. Attanoos, R. Webb, S.D. Dojcinov, A.R. Gibbs
• Journal: Histopathology
• Published: 2001;39(6):584-8
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This laboratory study examined stored tumour tissue from 92 cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) from Llandough Hospital, Penarth, Wales. The article does not report on asbestos exposure. Two pathologists sorted tumour areas by microscopic pattern: tubulopapillary, adenomatoid, solid, small cell or pleomorphic. The tissue was stained with four markers used to recognise mesothelioma: thrombomodulin, calretinin, CD44H and cytokeratin 5/6. Most tumours (66%) showed at least two patterns, and how often each marker stained differed by pattern. Calretinin had an overall sensitivity of 87%, but was positive in only 4 of the 6 small cell cases (67%). Thrombomodulin was positive in 59% overall and in 5 of 6 small cell cases (83%). Cytokeratin 5/6 was positive in 55% overall and in 1 of 6 small cell cases (17%). CD44H was positive in 47% overall. It also stained surrounding non-tumour cells, which sometimes made the slides hard to read. The authors concluded that calretinin and cytokeratin 5/6 were the most versatile markers and that thrombomodulin was more sensitive for small cell mesothelioma. They found CD44H not of particular use. They said pathologists need to be aware of this variation, especially in small biopsies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Laboratory (immunohistochemistry) study of archived tumour tissue, comparing how four mesothelial markers stained different microscopic patterns of epithelioid mesothelioma
• Who was studied: Tissue from 92 cases of malignant epithelioid mesothelioma (60 pleural, 32 peritoneal) from the files of the Department of Histopathology, Llandough Hospital, Penarth, Wales; dates not given
• Exposure: Not an exposure study: asbestos exposure was not examined. The tumour tissue was stained with four markers (thrombomodulin, calretinin, CD44H and cytokeratin 5/6).
• Main results:
  • Most of the 92 tumours showed more than one microscopic pattern: 66% of cases had at least two patterns
  • Calretinin: overall sensitivity 87%. By pattern: 55/61 (90%) tubulopapillary, 10/11 (91%) adenomatoid, 19/23 (83%) solid, 2/2 (100%) pleomorphic, and 4/6 (67%) small cell
  • Calretinin was positive in 67% of the six small cell cases
  • Thrombomodulin: positive in 59% of all epithelioid mesotheliomas tested. By pattern: 34/61 (56%) tubulopapillary, 6/11 (55%) adenomatoid, 15/23 (65%) solid, 5/6 (83%) small cell, 1/2 (50%) pleomorphic
  • Thrombomodulin staining was membranous and focal in all cases
  • Cytokeratin 5/6: overall sensitivity 55%. By pattern: 16/23 (70%) solid, 7/11 (64%) adenomatoid, 32/61 (53%) tubulopapillary, 1/2 (50%) pleomorphic, 1/6 (17%) small cell. Staining was cytoplasmic and in most cases diffuse.
  • CD44H: overall sensitivity 47%. By pattern: 15/23 (65%) solid, 7/11 (64%) adenomatoid, 23/61 (38%) tubulopapillary, 1/2 (50%) pleomorphic, 2/6 (33%) small cell. CD44H also stained lymphoid cells, histiocytes and stromal fibroblasts, which in some cases made interpretation difficult.
• The authors' conclusion: The authors concluded that calretinin and cytokeratin 5/6 are the most versatile and easily interpretable mesothelial markers. They found that thrombomodulin gives increased sensitivity for small cell mesothelioma and that CD44H is not of particular use. They stated that interpreting these stains requires awareness of how marker expression varies between histological forms, particularly in small biopsies.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Epithelioid, Mesothelioma, Tubulopapillary, Adenomatoid Tumor, Pleomorphic, Calretinin, Cytokeratin 5/6, Malignant Mesothelioma.

Related studies

• Value of mesothelial and epithelial antibodies in distinguishing diffuse peritoneal mesothelioma in females from serous papillary carcinoma of the ovary and peritoneum — R.L. Attanoos, R. Webb, et al. (2002)
• Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura — M. Miettinen, M. Sarlomo-Rikala (2003)
• Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma — C.E. Comin, L. Novelli, et al. (2001)
• Value of the mesothelium-associated antibodies thrombomodulin, cytokeratin 5/6, calretinin, and CD44H in distinguishing epithelioid pleural mesothelioma from adenocarcinoma metastatic to the pleura — P.M. Cury, D.N. Butcher, et al. (2000)
• Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma — C.E. Comin, L. Novelli, et al. (2014)
• Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies — F. Roberts, C.M. Harper, et al. (2001)

Browse more research in Histopathology, or return to medical research.