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WHO to Recognize Fourth Mesothelioma Subtype

mesothelioma subtypeThe World Health Organization will soon recognize mesothelioma in situ as a fourth mesothelioma subtype. 

The 2015 WHO classification of pleural mesothelioma includes three histological subtypes. Pathologists can tell the difference between the subtypes by looking at the cells under a microscope. Each subtype has a slightly different cell shape, growth pattern, and nuclear characteristics. 

The proposed fourth mesothelioma subtype is a very early form of mesothelioma. Previous studies suggest that it may be a precursor to invasive mesothelioma. If patients know they have it, they may have years to try to keep mesothelioma from developing.

Differences Between the Subtypes

Pleural mesothelioma is a very rare type of cancer. Only about 2,500 people in the US receive a mesothelioma diagnosis every year. Asbestos inhalation is the primary cause of pleural mesothelioma. 

Most people with pleural mesothelioma have a poor prognosis. But mesothelioma subtype makes a difference. People with the epithelioid subtype tend to respond better to mesothelioma treatments like chemotherapy, radiation and surgery. 

Epithelioid mesothelioma is the most common subtype. About half of pleural mesothelioma tumors are epithelioid. Studies show epithelioid patients usually live longer than people with other subtypes. . 

Ten to 20 percent of pleural mesotheliomas are sarcomatoid. People with sarcomatoid mesothelioma may not respond as well to treatment. 

The third mesothelioma subtype is biphasic. Biphasic mesothelioma tumors contain a mix of both kinds of mesothelioma cells. The differences between the subtypes are subtle. It takes an experienced professional to tell the difference between each mesothelioma subtype. 

Mesothelioma in Situ: The Fourth Mesothelioma Subtype

The proposed fourth subtype is mesothelioma in situ. In people with mesothelioma in situ, only a thin layer of mesothelial cells are affected. These cells show loss of BAP1 protein. People with mesothelioma in situ do not have any pleural tumors. It may be years before tumors develop. In some patients, they never develop.

Canadian researchers published a report on this mesothelioma subtype in 2019. They analyzed ten patients with mesothelioma in situ. Most cases were discovered by accident during biopsies for other things. Seven patients eventually developed invasive mesothelioma. But it took a median of 60 months. 

This mesothelioma subtype just came up again in a recent article in Virchows Archives, an international pathology journal. Mount Sinai pathologist Mary Beth Beasley authored the article. 

She writes, “Recent genomic data has supported the need for a more granular and clinically valid classification beyond the three current subtypes. The major change in the forthcoming WHO classification is the inclusion of mesothelioma in situ as a diagnostic category.”

The WHO will release the new diagnostic categories later this year. 


Beasley, MB, et al, “Pleural mesothelioma classification update”, January 21, 2021, vrichows Archives, Online ahead of print, https://link.springer.com/article/10.1007%2Fs00428-021-03031-7

Churg, A, et al, “Malignant mesothelioma in situ: morphologic features and clinical outcome”, August 2019, Modern Pathology, https://www.nature.com/articles/s41379-019-0347-0

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