Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review

Ultrastruct Pathol. 2004 Jul-Aug;28(4):213-28. doi: 10.1080/019131290505176.


Lymphohistiocytoid mesothelioma (LHM) is a term proposed to designate a variant of mesothelioma that assumes a histiocytoid morphology and contains intense lymphocytic infiltrates. Reports on this variant are few, and its clinicopathologic and ultrastructural characteristics are still to be defined. The authors have studied 4 such cases that were identified among 120 mesotheliomas in the electron microscopy (EM) files of a single institution between 1982 and 2002. Histologically, all 4 lesions were composed of diffuse proliferations of cells with a histiocytoid appearance, admixed with an intense lymphocytic infiltrate. All 4 were associated with an unequivocal sarcomatoid component. Immunohistochemical (IHC) studies showed that the majority of histiocytoid cells were positive for CD68 and vimentin in all 4 cases, suggesting fibrohistiocytic differentiation. Immunoreactivity for calretinin and AE1:AE3 was only very focally identified in 3 of 4 cases. All cases were negative for CEA (M), Leu-M1, and B72.3. The lymphocytic component in all 4 cases was almost entirely composed of CD3- and CD8-positive, small, mature T cells, with only a minor component of CD20-positive cells and occasional eosinophils. Although all cases contained numerous CD68 positive atypical cells, co-expression of CD68 and either calretinin or keratin by individual cells was difficult to demonstrate by immunohistochemistry. Ultrastructurally, 3 of the 4 cases demonstrated very focal mesothelial differentiation as evidenced by long and slender surface microvilli, including the case with negative immunoreactivity for calretinin and cytokeratin. Review of the literature yielded 6 additional LHM cases. Analysis of all 10 cases showed a male predominance (8:2) with a mean age of 58 years (31-73 years). All 10 cases involved the pleura. Three of 10 patients had known asbestos exposure. Six of 10 patients died of disease at 2-20 months after the diagnosis (mean, 6.9 months). The findings suggest that LHM is a distinct morphological variant of sarcomatoid mesothelioma for which mesothelial differentiation is difficult to document. Many of the cells composing these tumors exhibit fibrohistiocytic differentiation. The unusual morphological pattern of LHM makes a combined modality approach, including IHC, EM, and a knowledge of the clinical/radiologic findings, essential in achieving a correct diagnosis.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lung Neoplasms / ultrastructure
  • Male
  • Mediastinal Neoplasms / metabolism
  • Mediastinal Neoplasms / pathology
  • Mediastinal Neoplasms / ultrastructure
  • Mesothelioma / metabolism*
  • Mesothelioma / pathology*
  • Mesothelioma / ultrastructure*
  • Microscopy, Electron, Transmission
  • Middle Aged
  • Pleural Neoplasms / metabolism
  • Pleural Neoplasms / pathology
  • Pleural Neoplasms / ultrastructure


  • Biomarkers, Tumor