Lamellar Inclusions within Hyperplastic Endoplasmic Reticulum in Benign Mesothelial Cells

Our plain-English summary of Lamellar Inclusions within Hyperplastic Endoplasmic Reticulum in Benign Mesothelial Cells, by S. Haefliger, D. Jain, T. Menter, et al (Acta Cytologica, 2020).

The study

• Authors: S. Haefliger, D. Jain, T. Menter, T. Vlajnic, S. Savic Prince, H. Hopfer, M.J. Mihatsch, L. Bubendorf
• Journal: Acta Cytologica
• Published: 2020;64(6):572-576
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: In effusion cytology, mesothelial cells can occasionally present with striking intracytoplasmic accumulation of rod- and crystal-like cytoplasmic lamellar inclusions (LIs). Their nature and function are poorly understood, and their diagnostic relevance is unknown.

Objective: The aim of this study was to explore the nature of LIs in mesothelial cells and determine their prevalence and diagnostic utility in routine practice.

Material And Method: We reviewed a consecutive series of cytological specimens of reactive (n = 102) and malignant effusions (n = 90), respectively. Malignant effusions included malignant mesotheliomas (n = 63) and carcinomas (n = 27). LIs of one effusion were analyzed by electron microscopy (EM).

Results: LIs were found exclusively in benign mesothelial cells in 14% (14/102) of reactive and in 4% (1/27) of malignant effusions with carcinomatosis. They were absent in effusions of malignant mesothelioma. EM revealed mainly straight lamellar, less tubular, structures in cisternae of the hyperplasic rough endoplasmic reticulum (rER).

Conclusion: Cytoplasmic LIs located within hyperplastic rER can be found in up to 14% of effusions restricted to benign mesothelial cells. They can be used as an indirect morphological clue favoring the diagnosis of benign effusion and helping the cytologist to differentiate between reactive and malignant mesothelial cells in daily practice.

© 2020 The Author(s) Published by S. Karger AG, Basel.

In plain English

This laboratory study, by pathologists at the University Hospital of Basel, Switzerland, looked at rod-shaped, crystal-like structures called lamellar inclusions that are sometimes seen inside mesothelial cells (the cells lining the chest and abdominal cavities) in fluid drawn from those cavities. The article does not discuss asbestos or any other exposure. The authors reviewed stained smears from 102 benign effusions with reactive mesothelial cells and 27 effusions with carcinomatosis, all diagnosed in 2017 to 2018, plus 63 pleural specimens diagnosed as malignant mesothelioma between 2010 and 2018. Inclusions were found in benign mesothelial cells in 13.7% (14/102) of benign effusions. They were more common in pleural fluid (13/72) than in peritoneal fluid (1/30), and they appeared in 1 of 27 carcinomatosis cases. None of the 63 mesothelioma effusions had them. Electron microscopy of one case showed that the inclusions sat within hyperplastic (overgrown) rough endoplasmic reticulum, a structure inside the cell. The authors concluded that inclusions in mesothelial cells are an indirect clue favoring benign changes, helping tell reactive from malignant cells. They noted that the inclusions are relatively rare and that the reason they occur is unclear.

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: Review of a consecutive series of previously diagnosed cytology (effusion fluid) specimens, with transmission electron microscopy of one index case and immunochemistry of cells with inclusions
• Who was studied: Papanicolaou-stained smears: 102 benign pleural and peritoneal effusions with reactive mesothelial cells and 27 cases with pleural or peritoneal carcinomatosis, diagnosed 2017 to 2018; 63 pleural specimens diagnosed with malignant mesothelioma, 2010 to 2018. The authors are from the Institute of Pathology, University Hospital of Basel, Switzerland.
• Exposure: Not studied. The article examines lamellar inclusions in mesothelial cells and does not mention asbestos or any fiber exposure.
• Main results:
  • Benign reactive effusions: mesothelial cells with lamellar inclusions were found in 13.7% (14/102)
  • Among benign effusions, inclusions were more common in pleural effusions (18%; 13/72) than in peritoneal effusions (3%; 1/30)
  • Carcinomatosis cases: benign mesothelial cells with inclusions were found in 4% (1/27)
  • Malignant mesothelioma effusions: no inclusions were present in any of the 63
  • In inclusion-positive effusions, cells with inclusions were always fewer than an estimated 30% of mesothelial cells. Inclusions were found only in mesothelial cells, not in macrophages.
  • Electron microscopy of one case showed the inclusions were lamellae or tubules within the cisternae of hyperplastic rough endoplasmic reticulum
  • Immunochemistry confirmed the cells with inclusions were mesothelial: positive for calretinin, negative for CD68
• The authors' conclusion: The authors concluded that the presence of inclusions in mesothelial cells could be used as an indirect morphological clue favoring benign changes, helping the cytologist differentiate between reactive and malignant mesothelial or epithelial cells. They described the inclusions as part of hyperplastic rough endoplasmic reticulum.
• Limitations the authors state:
  • The inclusions are relatively rare
  • The reason the inclusions occur with varying frequency in tumor-free effusions is not clear
  • Further studies are needed to identify the causes of rough endoplasmic reticulum hyperplasia in mesothelial cells

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Cytology, Malignant Mesothelioma, Carcinoma.

Related studies

• Repression of GADD153/CHOP by NF-kappaB: a possible cellular defense against endoplasmic reticulum stress-induced cell death — S. Nozaki, G.W. Sledge, et al. (2001)
• MMP-7 is a highly specific negative marker for benign and malignant mesothelial cells in serous effusions — B. Davidson, H.T. Stavnes, et al. (2016)
• Hyperplastic mesothelial cells in lymph nodes: report of six cases of a benign process that can stimulate metastatic involvement by mesothelioma or carcinoma — P. Argani, J. Rosai (1998)
• Wilms tumor 1/cytokeratin dual-color immunostaining reveals distinctive staining patterns in metastatic melanoma, metastatic carcinoma, and mesothelial cells in pleural fluids: an effective first-line test for the workup of malignant effusions — J.R. Conner, E.S. Cibas, et al. (2014)
• CD24 is highly useful in differentiating high-grade serous carcinoma from benign and malignant mesothelial cells — B. Davidson (2016)
• Increased sensitivity to apoptosis upon endoplasmic reticulum stress-induced activation of the unfolded protein response in chemotherapy-resistant malignant pleural mesothelioma — D. Xu, S.Q. Liang, et al. (2018)

Browse more research in Acta Cytologica, or return to medical research.