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

Our plain-English summary of Lymphohistiocytoid mesothelioma: a clinical, immunohistochemical and ultrastructural study of four cases and literature review, by D.X. Yao, J. Shia, R.A. Erlandson, et al (Ultrastructural Pathology, 2004).

The study

• Authors: D.X. Yao, J. Shia, R.A. Erlandson, D.S. Klimstra
• Journal: Ultrastructural Pathology
• Published: 2004;28(4):213-28
• Type of article: Case report
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This article reported four cases of lymphohistiocytoid mesothelioma, a rare mesothelioma rich in lymphocytes and histiocyte-like cells, and reviewed six published cases. Among 120 mesotheliomas in Memorial Sloan-Kettering Cancer Center's electron microscopy files from 1982 to 2002, the authors found 4 (3.3%), in 3 men and 1 woman aged 31 to 69. All four tumors involved the pleura, and each had a sarcomatoid component. Three patients died; the article states a mean survival of 8.72 months, but its case descriptions give deaths at 7, 14 and 20 months, which do not match. One patient had no known asbestos exposure; for the other three it was unknown. Mesothelial markers were only focal in three cases and absent in one, but electron microscopy found mesothelial-type microvilli in three, including that one. Of all 10 known cases, 3 had asbestos exposure, all from one earlier study; 3 had a negative history and 4 an unknown history. The authors concluded this is a rare variant of sarcomatoid mesothelioma needing combined tests to diagnose. They noted their higher proportion may reflect case selection bias.

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: Case series of four cases (clinical, immunohistochemical and electron microscopy study) with a review of previously published cases
• Who was studied: 4 lymphohistiocytoid mesotheliomas found among 120 mesothelioma cases with electron microscopy at Memorial Sloan-Kettering Cancer Center, New York, 1982 to 2002. The patients were 3 males and 1 female, aged 31 to 69 years (mean 48.5). The authors also reviewed 6 previously published cases, giving 10 in total.
• Exposure: Asbestos exposure was recorded only as history. Case 1 had no known exposure to asbestos, and no exposure information was available for the other 3 cases. No fiber types or doses were reported.
• Main results:
  • In the 4 study patients, the disease affected the pleura in all 4. Three of the 4 died of the disease. The article states a mean survival of 8.72 months (range 2 to 20 months) after diagnosis. Follow-up was not available for the 4th patient.
  • The individual case descriptions report deaths at 7 months (case 1), 14 months (case 2) and 20 months (case 3) after diagnosis. These do not match the printed mean of 8.72 months or the lower end of the stated 2 to 20 month range.
  • Under the microscope, all 4 tumors showed a diffuse proliferation of large atypical fibro-histiocytoid cells with a lymphoplasmacytic infiltrate. Each case had a typical sarcomatoid mesothelioma component, and none had an epithelioid component.
  • Staining for calretinin and pan-cytokeratin was only focal and minimal in 3 of 4 cases, and CAM5.2 was positive in only 1 case. Case 2 was negative for all three of these markers. Vimentin and CD68 were diffusely positive in most large atypical cells in all 4 cases.
  • In all 4 cases, the lymphocytes were almost entirely CD3- and CD8-positive T cells, with only a small number of CD20-positive B cells at the edges of the tumors.
  • By electron microscopy, 3 of the 4 cases showed sporadic cells with long, slender surface microvilli, a sign of mesothelial differentiation. These included case 2, which was negative for mesothelial and epithelial markers by immunohistochemistry.
  • Across all 10 reported cases (these 4 plus 6 from the literature), asbestos exposure was identified in 3 of 10. All 3 came from a single earlier study (Henderson et al.), not from the present series.
  • Of the remaining 7 cases, 3 had a negative history of asbestos exposure (1 in this series and 2 of Khalidi's 3 cases). The other 4 had no exposure information (3 in this series and 1 of Khalidi's cases).
• The authors' conclusion: The authors concluded that lymphohistiocytoid mesothelioma is a rare variant of sarcomatoid mesothelioma. They wrote that a correct diagnosis relies on combined histological, immunohistochemical and ultrastructural analysis.
• Limitations the authors state:
  • The authors said the higher proportion in their series (3.3%) may result from case selection bias, because they included only cases that had electron microscopy at diagnosis.
  • The authors said the CD68-positive cells might instead be an atypical reactive population of histiocytes, and that more studies are needed.
  • The authors said it is difficult to determine whether the lymphoid infiltrates affect prognosis.

Topics

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

Medical terms in this study, explained in our Lexicon: Lymphohistiocytoid, Mesothelioma, Sarcomatoid, Calretinin, B72.3 (TAG-72), Immunohistochemistry, Pleura, Asbestos Exposure.

Related studies

• Mesothelioma with clear cell features: an ultrastructural and immunohistochemical study of 20 cases — N.G. Ordóñez (2005)
• Mesothelioma with rhabdoid features: an ultrastructural and immunohistochemical study of 10 cases — N.G. Ordóñez (2006)
• Observations on bronchiolo-alveolar carcinomas with special emphasis on localized lesions. A clinicopathological, ultrastructural, and immunohistochemical study of 11 cases — C.A. Axiotis, T.A. Jennings (1988)
• Solitary fibrous tumour of the pleura: an ultrastructural and immunohistochemical study — S. Keating, G.T. Simon, et al. (1987)
• Malignant biphasic peritoneal mesothelioma in a child: fine-needle aspiration cytology, histopathology, and immunohistochemical features along with review of literature — S.K. Arora, R. Srinivasan, et al. (2012)
• Keratin proteins and carcinoembryonic antigen in lung carcinoma: an immunoperoxidase study of fifty-four cases, with ultrastructural correlations — J.W. Said, G. Nash, et al. (1983)

Browse more research in Ultrastructural Pathology, or return to medical research.