Malignant pleural mesothelioma is a rare neoplasm. Among its histological subtypes, desmoplastic malignant mesothelioma (DMM) is one of the least frequent and most aggressive forms, accounting for 5–10% of all cases [1]. Due to its histological features and low cellularity, it poses significant diagnostic challenges.

We present the case of a 74-year-old man who reported exertional dyspnea following a respiratory infection. His past medical history included permanent atrial fibrillation, ischemic heart disease treated with percutaneous revascularization, and a brief exposure to asbestos for three months in early adulthood. Physical examination revealed decreased breath sounds at the right lung base. Chest X-ray showed a right-sided pleural effusion, which was confirmed on computed tomography (Fig. 1A), along with pleural thickening. Cytology from thoracentesis was negative, and a blind pleural biopsy revealed only atypical mesothelial cells without clear signs of malignancy. Due to persistent suspicion, video-assisted thoracoscopic surgery was performed, revealing marked pleural thickening and lung entrapment (Fig. 1B). Histology showed dense fibrous thickening with scattered irregular spindle cells infiltrating fibroadipose tissue (Fig. 1C). Immunohistochemistry was positive for CK8/18 (Fig. 1D) and CK7, and negative for WT1, calretinin, TTF-1, and CK5/6, confirming the diagnosis of desmoplastic malignant mesothelioma.

Fig. 1.

(A) CT scan showing right pleural effusion and thickening. (B) Intraoperative thoracoscopic image demonstrating pleural thickening and lung entrapment. (C) Hematoxylin–eosin staining (20×) revealing prominent collagenous stroma with scattered spindle cells infiltrating fibroadipose tissue. (D) Immunohistochemical staining for cytokeratin 8/18 showing strong positivity.

DMM is characterized by prominent collagenous stroma with hyalinized or fibrillary appearance and scarce tumor cells, typically isolated or loosely clustered. This histological pattern can mimic benign conditions such as reactive pleural fibrosis, chronic pleuritis, or even autoimmune processes [2]. Definitive diagnosis requires deep pleural biopsies, ideally obtained via thoracoscopy. When initial samples are inconclusive, repeat biopsies are advised due to the prognostic implications [3]. Pathologist expertise is critical in these cases. Immunohistochemical staining is essential to confirm mesothelial origin and malignancy, using markers such as calretinin, WT-1, D2-40, and cytokeratins 7, 8, 17, and 18 [4].

Standard treatment includes chemotherapy, surgery, and radiotherapy, although outcomes are limited due to the intrinsic resistance of DMM [5]. Early identification and a multidisciplinary approach remain essential to improve clinical outcomes.