The use of histological and immunohistochemical markers to distinguish pleural malignant mesothelioma and in situ mesothelioma from reactive mesothelial hyperplasia and reactive pleural fibrosis

J Pathol. 1999 Oct;189(2):251-7. doi: 10.1002/(SICI)1096-9896(199910)189:2<251::AID-PATH412>3.0.CO;2-F.


Distinguishing malignant mesothelioma from reactive mesothelial hyperplasia and reactive fibrosis can be a diagnostic problem in small pleural biopsies, made more difficult by the recent recognition of mesothelioma-in-situ. Antibodies to epithelial membrane antigen (EMA), p53, and bcl-2 have all been advocated for differentiating reactive from neoplastic conditions, but reports are inconsistent. These antibodies have therefore been applied to 31 cases of malignant mesothelioma, 34 cases of reactive pleural disease (20 reactive mesothelial hyperplasia and 14 reactive pleural fibrosis) and four small biopsies that were initially coded as suspicious, from patients who later developed frank mesothelioma. Thirty out of 31 (97 per cent) cases of mesothelioma showed positive nuclear staining for p53, with a higher incidence of positivity in epithelioid than in sarcomatoid elements and 30/31 (97 per cent) showed diffuse linear membrane staining for EMA, again more intense in the epithelioid elements. No mesothelioma was positive for bcl-2. In seven cases that contained both in situ and invasive mesothelioma, the in situ elements showed similar staining patterns to the invasive epithelioid elements. Thirteen out of 20 (65 per cent) cases of reactive mesothelial hyperplasia showed occasional nuclear positivity for p53 and 5/20 (25 per cent) cases showed focal weak membrane staining for EMA. Three out of 14 (21 per cent) cases of reactive pleural fibrosis showed positive nuclear staining for p53 and 6/14 (43 per cent) cases showed focal membrane staining with EMA. No reactive cases stained for bcl-2. All four suspicious cases showed diffuse linear staining with EMA and three showed focal staining for p53. It is concluded that strong diffuse linear staining for EMA is a good marker of malignancy when differentiating epithelioid malignant mesothelioma and mesothelioma-in-situ from reactive mesothelial hyperplasia, although weak focal staining may occur in reactive conditions. Nuclear staining for p53 is also suggestive of epithelioid mesothelioma, but should be regarded as no more than suspicious. The antibodies used in this investigation are less helpful in differentiating sarcomatoid mesothelioma from reactive pleural fibrosis.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Diagnosis, Differential
  • Fibrosis
  • Humans
  • Hyperplasia / diagnosis
  • Mesothelioma / diagnosis*
  • Mucin-1 / metabolism
  • Neoplasm Proteins / metabolism*
  • Pleura / metabolism
  • Pleura / pathology*
  • Pleural Neoplasms / diagnosis*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Retrospective Studies
  • Tumor Suppressor Protein p53 / metabolism


  • Biomarkers, Tumor
  • Mucin-1
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Suppressor Protein p53