Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations

Our plain-English summary of Highlighting the immunohistochemical differences of malignant mesothelioma subtypes via case presentations, by A. Sejben, T. Pancsa, L. Tiszlavicz, et al (Thoracic Cancer, 2023).

The study

• Authors: A. Sejben, T. Pancsa, L. Tiszlavicz, J. Furák, D. Paróczai, T. Zombori
• Journal: Thoracic Cancer
• Published: 2023;14(10):857-863
• Type of article: Review
• Cited by: 5 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Malignant mesothelioma (MM) is a rare tumor of mesothelial cells, with an increasing incidence both in developed and developing countries. MM has three major histological subtypes, in order of frequency, according to the World Health Organization (WHO) Classification of 2021: epithelioid, biphasic, and sarcomatoid MM. Distinction may be a challenging task for the pathologist, due to the unspecific morphology. Here, we present two cases of diffuse MM subtypes to emphasize the immunohistochemical (IHC) differences, and to facilitate diagnostic difficulties. In our first case of epithelioid mesothelioma, the neoplastic cells showed cytokeratin 5/6 (CK5/6), calretinin, and Wilms-tumor-1 (WT1) expression, while remaining negative with thyroid transcription factor-1 (TTF-1). BRCA1 associated protein-1 (BAP1) negativity was seen in the neoplastic cells' nucleus, reflecting loss of the tumor suppressor gene. In the second case of biphasic mesothelioma, expression of epithelial membrane antigen (EMA), CKAE1/AE3, and mesothelin was observed, while WT1, BerEP4, CD141, TTF1, p63, CD31, calretinin, and BAP1 expressions were not detected. Due to the absence of specific histological features, the differentiation between MM subtypes could be a challenging task. In routine diagnostic work, IHC may be the proper method in distinction. According to our results and literature data, CK5/6, mesothelin, calretinin, and Ki-67 should be applied in subclassification.

© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

In plain English

This article was a mini review built around two patients with diffuse malignant mesothelioma seen at the University of Szeged, Hungary. Its aim was to show how immunohistochemistry, which stains tissue for specific proteins, can help pathologists tell mesothelioma subtypes apart. The first patient, a 78-year-old man with recurring fluid in the chest, had epithelioid mesothelioma throughout the pleura. The tumor cells stained for CK5/6, calretinin and WT1, had lost BAP1, and had a Ki-67 proliferation fraction of about 10%. The second patient, a 69-year-old man who had worked as a mechanic, had a biphasic mesothelioma that destroyed ribs. The tumor that returned after surgery and chemotherapy looked sarcomatoid. It was negative for CK5/6 and calretinin, had lost BAP1, and Ki-67 was expressed in 60% of tumor cells. This patient was not known to have been exposed to asbestos but had heated the home with coal for a decade. The rest of the article reviewed published studies. The authors concluded that CK5/6, mesothelin, calretinin and Ki-67 are helpful for subclassification. These are two individual cases, not rates.

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: Mini review with two case presentations
• Who was studied: Two male patients with diffuse malignant mesothelioma treated at the University of Szeged, Hungary: a 78-year-old with epithelioid mesothelioma of the pleura (surgery April 2021), and a 69-year-old with biphasic mesothelioma involving the ribs that recurred with sarcomatoid morphology
• Exposure: No asbestos exposure is reported for either patient. The second patient had worked as a mechanic, was not known to have been exposed to asbestos, and had heated the home with coal for a decade. The authors note that other published literature describes an association between mesothelioma and coal.
• Main results:
  • Case 1 (epithelioid mesothelioma): the tumor cells expressed CK5/6, calretinin and WT1, were negative for TTF-1 and BerEP4, showed loss of BAP1, and had a Ki-67 proliferation fraction of approximately 10%
  • Case 2, first operation: a biphasic tumor with epithelioid and spindle cell components. The spindle cells expressed EMA, CK AE1/AE3 and mesothelin and were negative for WT1, EpCAM, thrombomodulin, TTF1, p63, CD31 and calretinin.
  • Case 2, recurrence after four cycles of cisplatin and pemetrexed: the tumor had sarcomatoid morphology and was positive for WT1 and mesothelin, negative for CK5/6 and calretinin, and showed BAP1 loss. It had 21 mitoses per 10 high power fields, and Ki-67 was expressed in 60% of tumor cells.
  • At the time of writing, overall survival was 20 months for case 1 and 24 months for case 2
• The authors' conclusion: The authors concluded that telling mesothelioma subtypes apart can be difficult because there are no specific histological features, and that immunohistochemistry may be the optimal method. In their view, WT1, TTF-1 and BAP1 help establish a diagnosis of mesothelioma, while CK5/6, mesothelin, calretinin and Ki-67 help with subclassification.

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: Malignant Mesothelioma, Mesothelial Cells, Histological Subtype, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Mesothelioma, Cytokeratin 5/6.

Related studies

• Expression of calretinin, thrombomodulin, keratin 5, and mesothelin in lung carcinomas of different types: an immunohistochemical analysis of 596 tumors in comparison with epithelioid mesotheliomas of the pleura — M. Miettinen, M. Sarlomo-Rikala (2003)
• Immunohistochemical panels for differentiating epithelial malignant mesothelioma from lung adenocarcinoma: a study with logistic regression analysis — R. Carella, G. Deleonardi, et al. (2001)
• Immunohistochemical analysis still has a limited role in the diagnosis of malignant mesothelioma. A study of thirteen antibodies — F. Roberts, C.M. Harper, et al. (2001)
• Calretinin, thrombomodulin, CEA, and CD15: a useful combination of immunohistochemical markers for differentiating pleural epithelial mesothelioma from peripheral pulmonary adenocarcinoma — C.E. Comin, L. Novelli, et al. (2001)
• Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma — C.E. Comin, L. Novelli, et al. (2014)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)

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