Diffuse intrapulmonary malignant mesothelioma (DIMM) mimicking interstitial lung disease. Ultrastructural analysis and the potential role of the Hedgehog signaling pathway

Ultrastructural Pathology 2025 [Link]

Hector Chavarria, Mohamed Zedan, Osama Elkadi, Kurt Knowles, Guillermo Herrera

Abstract

Diffuse intrapulmonary malignant mesothelioma (DIMM) is a rare variant of epithelioid mesothelioma characterized by diffuse lung parenchymal involvement without a discrete pleural mass, often mimicking interstitial lung disease (ILD). We report a case of a 55-year-old male presenting with bilateral pleural effusions and a complex clinical course requiring multiple thoracic interventions. Histology revealed scattered nests of epithelioid tumor cells in the lung interstitium and lymph nodes, with immunohistochemistry positive for mesothelial markers (calretinin, WT1, D2-40) and negative for carcinoma markers. Ultrastructural analysis demonstrated classic mesothelial features including cohesive cells with desmosomes and abundant slender microvilli. next-generation sequencing showed no pathogenic mutations in commonly altered mesothelioma genes but revealed a variant of uncertain significance in PTCH1, implicating potential Hedgehog pathway involvement. This case underscores the diagnostic challenges of DIMM masquerading as ILD and highlights the value of integrating histopathology, ultrastructure, and molecular profiling to improve diagnostic accuracy and understand tumor biology.