Merlin Immunohistochemistry Is Useful in the Differential Diagnosis of Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia

Pathology International 2026 January [Link]

Kohei Aoe, Kei Kushitani, Vishwa Jeet Amatya, Tetsuya Nakagiri, Yoshihiro Miyata, Morihito Okada, Yukio Takeshima

Abstract

The differential diagnosis of epithelioid mesothelioma and reactive mesothelial hyperplasia can be challenging based on morphology alone, particularly in small specimens. Consequently, the use of ancillary techniques, such as immunohistochemistry for BRCA1-associated protein 1, methylthioadenosine phosphorylase, and CDKN2A/p16 fluorescence in situ hybridization, has been considered a reliable method. Moreover, the potential of Merlin, enhancer of zeste homolog 2, 5-hydroxymethylcytosine, and c-Met immunohistochemistry in differential diagnosis has been reported. We conducted BRCA1-associated protein 1, methylthioadenosine phosphorylase, Merlin, enhancer of zeste homolog 2, 5-hydroxymethylcytosine, and c-Met immunohistochemistry in 43 epithelioid mesothelioma and 28 reactive mesothelial hyperplasia samples. BRCA1-associated protein 1 and/or methylthioadenosine phosphorylase achieved the highest sensitivity (83.7%), while the addition of Merlin improved the sensitivity to 86.0% while maintaining 100% specificity. We confirmed that the addition of Merlin to BRCA1-associated protein 1 and methylthioadenosine phosphorylase improved the sensitivity in the differential diagnosis of epithelioid mesothelioma and reactive mesothelial hyperplasia while maintaining 100% specificity. Moreover, the utilization of enhancer of zeste homolog 2, 5-hydroxymethylcytosine, and c-Met cannot be unequivocally endorsed, as these markers have not demonstrated 100% specificity, despite their capacity to modestly enhance sensitivity when employed in conjunction with BRCA1-associated protein 1 and methylthioadenosine phosphorylase.