There are few diagnoses more difficult to make with certainty, and carrying more prognostic and legal weight, than the diagnosis of diffuse malignant mesothelioma (DMM). Diffuse malignant mesothelioma's extremely limited therapeutic options, dismal prognosis, and serious legal implications make it a disease for which misdiagnosis carries grave and far-reaching medical, legal, and social consequences. At the same time, DMM's rarity, and the commonness of its mimics, makes it a diagnosis with which few pathologists attain familiarity. Indeed, a pathologist can spend a career having never diagnosed DMM. Moreover, the diagnosis of DMM is often difficult to make, and even pathologists expert in the diagnosis of DMM find some cases extremely challenging.

Diffuse malignant mesothelioma is confoundingly resistant to conventional treatment. Only 20% of DMM patients show any response to cisplatin, a drug generally considered to be an effective anticancer drug.1,2  Surgical treatments and radiotherapy fare no better. Indeed, conventional treatment often achieves no better result than supportive care.3  New treatments are actively being investigated4 ; however, despite recent advances in chemotherapy, surgery, and radiotherapy, survival rates for DMM patients continue to be extremely low.5  Prognosis is generally related to tumor stage and patient performance status; however, prognostic differences are not great, and overall prognosis remains best described as dismal.6,7  Reports of long-term survival with DMM are extremely rare,8  and although bona fide cases of long-term DMM survival do exist, reported cases frequently merely reflect misdiagnosis. Meanwhile, DMM incidence and mortality are predicted to continue to increase,9  and recent advances in molecular biology that have benefited patients with other cancers, such as breast and lung cancers, have not yielded any significant therapeutic advances in patients with DMM.7  All of these are good reasons why an accurate diagnosis of DMM is vital.

But now, there are even more reasons why accurate DMM diagnosis is imperative. Research is ongoing as to the specific molecular mechanisms by which asbestos causes DMM, and researchers are focusing on identifying DMM's multiple genetic aberrations, including those involving cell cycle regulatory genes.10,11  Current research is concentrating on the molecular characteristics of DMM, in the hope of identifying molecular biomarkers of diagnostic, prognostic, and therapeutic value.7,1118  Novel, intrapleural treatments, including molecular-based therapies, are now being attempted in patients with pleural DMM.19  Potential immunotherapies are being studied.20  And the long latency of asbestos-related DMM has researchers delving for novel opportunities for molecular intervention that could prevent DMM from developing at all.21  In tandem with the interest in the molecular basis of DMM, there is a trend toward increasing standardization of DMM treatment.22  Standards, guidelines, and registries for DMM are currently being proposed and developed.

Also see p 647.

Progress in new surgical techniques and molecular tests holds great promise for this devastating disease. But studies, guidelines, and standards will be useless and meaningless—worse, dangerous—without the certainty that the studies and guidelines themselves, and the future therapeutic interventions they produce, are based on accurately diagnosed DMMs.

In this edition of the Archives, several of the world's experts in DMM, members of the International Mesothelioma Interest Group, present a 2012 update23  of the original 2009 “Guidelines for Pathologic Diagnosis of Malignant Mesothelioma.”24  The update discusses DMM diagnosis in depth, including various pitfalls to avoid. It contains several excellent diagnostic gems, and should be a welcome reference for any pathologist handling a case for which DMM enters the differential diagnosis.

And the update is timely. Accurate diagnosis of DMM has never been more important.

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Author notes

The author has no relevant financial interest in the products or companies described in this article.