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Outside the Lab Histology, Cytology, Oncology, Clinical care

Quicker, Cheaper, Better

Malignant mesothelioma (MM) is considered difficult to diagnose. Indeed, it is among the first solid tumors requiring mandatory immunohistochemistry for reliable diagnosis. In an effort to assist, guidelines for MM diagnosis using histological material have been presented by the International Mesothelioma Interest Group (IMIG) (1),(2).

However, several laboratories have demonstrated that it is also possible to diagnose MM reliably with cytology, which is clearly a less invasive approach. For example, Segal and coworkers recently presented a 20-year audit that shows MM diagnosis can be established based on cytological examination of effusions with 73 percent sensitivity and 100 percent positive predicted value (ppv), i.e., without any false positive diagnosis (3). The main reason for this new diagnostic ability has been the development of ancillary techniques, some of which are now standard procedures in clinical cytology. In fact, we can now say that MM is no longer difficult to diagnose, not even when based on exfoliated cells in an effusion.

Corresponding guidelines for cytological diagnosis of MM are now adopted by IMIG, endorsed by both the International Academy of Cytology and the Papanicolaou Society of Cytopathology, and have been published by various cytological journals (4),(5),(6). According to the guidelines, the diagnosis must be supported by ancillary techniques. In most cases, immunocytochemistry is sufficient, but certain cases may require additional support from fluorescence in situ hybridization (FISH) analysis. Additional techniques such as soluble biomarker analysis and electron microscopy are useful for improving sensitivity. However, unlike immunochemistry, these optional techniques are not available to many laboratories.

In cytological diagnosis, the sensitivity (73 percent) is somewhat less than for that for biopsy examination. Here, the important measure is the ppv! The 20-year audit demonstrates that the diagnosis is reliable, and the accuracy is sufficient for clinical handling. In most cases, the patient is not eligible for surgery, and cytological diagnosis is sufficient for selecting a chemotherapeutic regimen, making biopsy redundant.

So, what does this mean to a patient with MM?

The first symptom of a tumor is the development of an effusion. This is withdrawn to alleviate associated symptoms, primarily dyspnea. The diagnostic material is therefore available without any additional invasive sampling, eliminating the need for a biopsy, with its potential for morbidity and increased risk of tumor seeding (7),(8). Although the disease is often in an advanced stage when the first effusion appears, the approach enables an earlier diagnosis with the possibility of a better response to chemotherapy. The diagnosis also requires fewer resources, which is economically beneficial.

Cytology alone, however, cannot diagnose sarcomatoid MM. Here, an indication for a biopsy is necessary when (a) cytology is inconclusive and (b) information on a possible sarcomatoid component is required for clinical handling. The three main reasons for not being able to diagnose MM with epithelioid components by examining an effusion are: (i) the low yield of the diagnostic cells; (ii) a cytopathologist’s lack of experience; and (iii) lack of awareness of this diagnostic possibility. Therefore, a liberal use of immunocytochemistry is advocated, particularly in effusions rich in mesothelial cells (8).

Clearly, the current cytological guidelines show how to diagnose MM accurately. Moreover, most of the recommended techniques are common to both histopathology and cytopathology. Therefore, in my view, it would be advantageous to merge both guidelines into a single document.

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  1. AN Husain et al., “Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group,” Arch Pathol Lab Med, 137(5), 647–667 (2013). PMID: 22929121.
  2. AN Husain et al., “Guidelines for pathologic diagnosis of malignant mesothelioma: a consensus statement from the International Mesothelioma Interest Group”, Arch Pathol Lab Med, 133(8), 1317–1331 (2009). PMID: 19653732.
  3. A Segal et al., “A diagnosis of malignant pleural mesothelioma can be made by effusion cytology: results of a 20 year audit”, Pathology, 45:44–48 (2013). PMID: 23222247.
  4. A Hjerpe A et al., “Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology”, Diagn Cytopathol, 43, 563–576 (2015). PMID: 26100969.
  5. A Hjerpe et al., “Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: a secondary publication”, Cytopathology, 26, 142–156 (2015). PMID: 26052757.
  6. A Hjerpe et al., “Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology”, Acta Cytol, 59, 2–16 (2015). PMID: 25824655.
  7. LS Zellos and DJ Sugarbaker, “Multimodality treatment of diffuse malignant pleural mesothelioma”, Semin Oncol, 29(1), 41–50 (2002). PMID: 11836668.
  8. R Ismail-Khan et al., “Malignant pleural mesothelioma: a comprehensive review”, Cancer Control, 13, 255–263 (2006). PMID:
About the Author
Anders Hjerpe

Anders Hjerpe is a Professor Emeritus at the Deaprtment for Laboratory Medicine at the Karolinska Institutet in Stockholm, Sweden.

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