Lymphocyte predominance in blood, pleural fluid, and tumour stroma; a prognostic marker in pleural mesothelioma

Our plain-English summary of Lymphocyte predominance in blood, pleural fluid, and tumour stroma; a prognostic marker in pleural mesothelioma, by D. De Fonseka, D.T. Arnold, A.J. Morley, et al (BMC Pulmonary Medicine, 2022).

The study

• Authors: D. De Fonseka, D.T. Arnold, A.J. Morley, M. Brett, N. Bhatt, A. Edey, R. Daly, A.C. Bibby, N.A. Maskell
• Journal: BMC Pulmonary Medicine
• Published: 2022;22(1):173
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: As promising novel treatments develop for malignant pleural mesothelioma (MPM), early prognostication has become increasingly important. Circulating and local inflammatory cells are known to play a significant role in other tumour types. We assessed the proportion of lymphocyte populations within blood, pleural fluid and tumour stroma to prognosticate patients with MPM at diagnosis.

Methods: Consecutive patients diagnosed with biopsy-proven MPM were prospectively recruited to an observational cohort study and followed up for a minimum of 7.5 years. Blood and pleural fluid results at presentation were extracted from the medical records. Biopsy specimens were independently reviewed by 2 pathologists who scored the degree of lymphocytic and neutrophilic infiltration.

Results: Baseline results were available for 184 patients. The predominant pleural fluid cell type was calculable for 84 patients and 118 patients had biopsy specimens available for review. A low blood neutrophil/lymphocyte ratio (NLR < 4) inferred a better prognosis with a median survival of 420 days versus 301 days (p < 0.01). Survival was better for patients with a lymphocyte-predominant pleural effusion (430 vs 306 days, p < 0.01). Lymphocyte infiltration of tumour stroma was also associated with improved survival (n = 92, survival 430 days) compared with neutrophilic or acellular samples (n = 26, survival 342 days p < 0.01). In multivariable modelling lymphocyte predominance in blood, pleural fluid and tumour stroma were all associated with a better prognosis.

Conclusions: Lymphocyte predominance within tumour stroma, pleural fluid or blood infers a better prognosis in patients with MPM.

© 2022. The Author(s).

In plain English

This prospective cohort study followed 184 consecutive patients with malignant pleural mesothelioma at one UK centre, diagnosed March 2008 to April 2016. At diagnosis, the authors measured the blood neutrophil/lymphocyte ratio (NLR), the main pleural fluid cell type (84 patients) and the cells in tissue around the tumour (stroma) in 118 biopsies. Two pathologists graded the biopsies without knowing patient outcomes. Median overall survival was 344 days. Patients with lymphocyte-predominant pleural fluid survived longer than others (430 vs 306 days). Patients with lymphocyte-predominant stroma had a median survival of 368 days, compared with 222 days for the other stroma groups combined. In the adjusted analysis, each was associated with longer survival: blood NLR below 4 (hazard ratio 0.66, 95% confidence interval 0.45 to 0.96), lymphocytic fluid (0.53, 0.32 to 0.89) and lymphocytic stroma (0.55, 0.35 to 0.87). The article did not examine asbestos exposure. The authors noted that this was a single-centre study from before immunotherapy and that only 118 biopsies were available. They concluded that lymphocyte predominance is an independent marker of improved survival.

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: Prospective observational cohort study (single centre)
• Who was studied: 184 consecutive patients with histologically proven malignant pleural mesothelioma at a single UK centre, diagnosed March 2008 to April 2016; mean age 72.4 years (range 40 to 91); 160 (87%) male
• Exposure: Not an asbestos exposure study. The factors studied were inflammatory cell markers at diagnosis: blood neutrophil/lymphocyte ratio (cut-off of 4), the predominant cell type in pleural fluid, and inflammatory cell infiltration of tumour stroma in biopsies
• Main results:
  • Median overall survival for the whole cohort was 344 days (IQR 171 to 576 days)
  • A blood NLR of 4 or more was associated with shorter survival in univariable analysis (HR 0.63, 95% CI 0.47 to 0.84, p = 0.002; the table labels this HR as for NLR below 4)
  • In multivariable analysis, the blood NLR hazard ratio was 0.66 (95% CI 0.45 to 0.96, p = 0.030)
  • Of 84 patients with assessable pleural fluid, 43 (51%) had a lymphocytic effusion, 9 (11%) a neutrophilic effusion and 32 (38%) a mixed effusion
  • Patients with a lymphocytic effusion had longer overall survival than those with other cell types: 430 vs 306 days
  • Lymphocyte predominance in pleural fluid was associated with survival in multivariable analysis: HR 0.53, 95% CI 0.32 to 0.89, p = 0.015
  • Lymphocyte predominance in both blood and pleural fluid together did not show improved survival: median 361 days vs 358 days in the rest of the cohort (p = 0.442)
  • Of 118 biopsies, 92 (78%) were mainly lymphocytic. These patients had a median survival of 368 days, compared with a combined median of 222 days for the acellular (7), equal (9) and neutrophilic (10) groups
  • Lymphocytic stroma infiltration was associated with longer survival in multivariable analysis: HR 0.55, 95% CI 0.35 to 0.87, p = 0.010
  • The degree of cellular infiltration (graded 1 to 3) was not related to survival for any cell type
• The authors' conclusion: The authors concluded that lymphocyte predominance in blood, pleural fluid and tumour stroma are independent markers of improved overall survival in malignant pleural mesothelioma
• Limitations the authors state:
  • The study was carried out at a single centre before immunotherapy was available, so the results may not apply to people receiving immune checkpoint inhibitors
  • Only 118 of the 184 patients had biopsy samples available for analysis
  • Biopsies were generally small and may not represent the whole tumour
  • The pleural fluid finding applied only to a minority of patients (45%)

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Biopsy, Cohort Study, Prognosis, Median Overall Survival, Pleural Effusion.

Related studies

• Prognostic value of the lymphocyte-to-monocyte ratio and other inflammatory markers in malignant pleural mesothelioma — A.C. Tanrikulu, A. Abakay, et al. (2016)
• High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy — S.C. Kao, N. Pavlakis, et al. (2010)
• Evaluation of seven tumour markers in pleural fluid for the diagnosis of malignant effusions — M. Miédougé, P. Rouzaud, et al. (1999)
• Sequential immunological studies on an asbestos-exposed population. I. Factors affecting peripheral blood leucocytes and T lymphocytes — M.M. Wagner, M.J. Campbell, et al. (1979)
• Exposure to asbestos: correlation between blood levels of mesothelin and frequency of micronuclei in peripheral blood lymphocytes — V. Marini, L. Michelazzi, et al. (2011)
• Reduction of chrysotile asbestos-induced genotoxicity in human peripheral blood lymphocytes by garlic extract — K. Bhattacharya, S. Yadava, et al. (2004)

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