Molecular and Ultrastructural Features of Diffuse Intrapulmonary Malignant Mesothelioma

Our plain-English summary of Molecular and Ultrastructural Features of Diffuse Intrapulmonary Malignant Mesothelioma, by B.T. Larsen, M.L. Smith, A.C. Roden, et al (The American Journal of Surgical Pathology, 2019).

The study

• Authors: B.T. Larsen, M.L. Smith, A.C. Roden, W.R. Sukov, H. Hornychová, S. Thirumala, T.V. Colby, H.D. Tazelaar
• Journal: The American Journal of Surgical Pathology
• Published: 2019;43(1):147-150
• Type of article: Letter
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Summary of the article

This letter asked whether diffuse intrapulmonary malignant mesothelioma (DIMM) is truly mesothelial. DIMM is a rare variant with mostly intrapulmonary growth and minimal pleural involvement that can mimic interstitial lung disease, and its classification had rested only on morphology and immunophenotype. The authors studied 4 cases from their consultation practice at Mayo Clinic Arizona, seen from 2010 to 2017, that had tissue blocks available. Three came from their earlier series and 1 was newly reported. All patients were men (mean age 63 years, range 55 to 70). The new patient, a 70-year-old man, had a recurrent unilateral pleural effusion and nonspecific pulmonary infiltrates. No asbestos exposure was reported, but small bilateral calcified pleural plaques were present. The authors performed BAP1 immunohistochemistry, CDKN2A (p16) fluorescence in situ hybridization (FISH) and transmission electron microscopy. BAP1 expression was lost in tumor cells in all 4 cases, including the sarcomatoid component in the 2 biphasic cases, and was retained in non-neoplastic lung. FISH showed heterozygous CDKN2A loss in 1 case and a normal pattern in 3. In every case, electron microscopy showed long, sinuous, smooth microvilli (length-to-width ratios averaging 10 to 15:1), desmosomes and tonofilaments, which are features of mesothelial differentiation. The authors concluded that these findings support classifying DIMM as a variant of mesothelioma and that immunohistochemistry is usually sufficient for diagnosis. They stated that the value of molecular testing for prognosis and treatment remains unknown.

PubMed has no abstract for this study, and the article doesn't print one. We wrote this summary from the full article with the help of AI. It is not the authors' wording.

In plain English

This letter to the editor reported further tests on diffuse intrapulmonary malignant mesothelioma (DIMM). DIMM is a rare form of mesothelioma that grows mainly inside the lung, with minimal pleural involvement, and can look like interstitial lung disease clinically and on imaging. The authors tested tissue from 4 men (mean age 63, range 55 to 70) from their consultation practice at Mayo Clinic Arizona, 2010 to 2017. Three had been described in an earlier series and one was new. For the new patient, no asbestos exposure was reported, but small calcified pleural plaques were present on both sides. Tumor cells in all 4 cases had lost the protein BAP1, while normal lung tissue kept it. Testing of the CDKN2A (p16) gene showed heterozygous loss in 1 case and a normal pattern in the other 3. Electron microscopy found features typical of mesothelial cells in every case. The authors concluded that these findings further support DIMM being a form of mesothelioma. They noted that BAP1 may be retained in some DIMM cases. They also noted that losses of BAP1 and CDKN2A (p16) are not specific to mesothelioma and occur in other cancers.

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: Letter to the editor describing a small case series (4 cases) with immunohistochemistry, FISH genetic testing and electron microscopy
• Who was studied: 4 men (mean age 63 years, range 55 to 70) with DIMM from the authors' consultation practice at Mayo Clinic Arizona, 2010 to 2017. Three had been reported in the authors' earlier series. One was a newly reported case (a 70-year-old man).
• Exposure: Asbestos exposure was not studied. For the one newly reported case, no asbestos exposure was reported, but small bilateral calcified pleural plaques were present. The letter does not give exposure information for the other 3 cases.
• Main results:
  • BAP1 protein expression was diffusely lost in the tumor cells in all 4 cases. This included the epithelioid component in all 4 cases and the sarcomatoid component in both of the 2 biphasic cases. BAP1 expression was retained in non-neoplastic lung tissue in all cases.
  • FISH testing of the CDKN2A (p16) gene showed heterozygous loss in 1 case of epithelioid DIMM. The other 3 cases showed a normal pattern.
  • Electron microscopy showed numerous long, sinuous, smooth microvilli on the tumor cells in each case, with length-to-width ratios averaging 10 to 15:1. It also showed well-formed desmosomes and scattered intracytoplasmic tonofilaments. The authors described these features as characteristic of mesothelial differentiation.
  • In the newly reported case, the tumor stained positive for CK5/6, calretinin, WT-1 and D2-40. It stained negative for MOC-31, TTF-1 and CEA, which fits a mesothelial immunophenotype.
• The authors' conclusion: The authors concluded that these findings further confirm DIMM as a form of mesothelioma. They also stated that immunohistochemistry is usually sufficient to confirm the diagnosis in the appropriate context. In their view, electron microscopy and molecular tools are probably unnecessary in most cases.
• Limitations the authors state:
  • All 4 cases showed BAP1 loss, but the authors noted that BAP1 expression may still be retained in some cases of DIMM.
  • Losses of BAP1 and CDKN2A (p16) are not specific to mesothelioma and can occur in other cancers. Other methods are therefore needed to confirm mesothelial differentiation.
  • It remains unknown whether molecular testing is useful for predicting outcome or for identifying treatment targets in DIMM.

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, Interstitial Lung Disease, Paraffin Block, Pleural Effusion, Asbestos Exposure, Bilateral, Pleural Plaques, BAP1.

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