Primary Leiomyosarcoma of the Mediastinum: A Rare and Challenging Diagnosis?

(1) Introduction: Leiomyosarcomas are highly aggressive mesenchymal neoplasm derived from smooth muscle cells which, in the mediastinum, are present in various primary organs; To our knowledge, less than 10 cases of primary mediastinal leiomyosarcoma have been described. Here, we report a compelling case of primary mediastinal leiomyosarcoma. (2) Case presentation: A 79-year-old woman was admitted to the Thoracic Surgery Unit of S. Andrea University Hospital for persisting cough, exertional dyspnea, and sternal pain. After multidisciplinary consultation, a CT-guided core needle biopsy of the mass was performed, resulting in a provisional diagnosis of mesenchymal neoplasm with smooth muscle differentiation without apparent signs of atypia. The patient underwent surgery that revealed a large irregularly shaped mass with a whorled pattern cut surface, showing admixed yellowish areas of necrosis and areas of hemorrhage. Histologic examination showed a smooth muscle neoplasm with atypia and necrosis, and a grade 2 primary mediastinal leiomyosarcoma diagnosis was given. (3) Conclusions: Soft tissue sarcomas represent a challenging diagnostic group of tumors due to their location, morphologic spectrum, and unique molecular background. Our case of primary mediastinal leiomyosarcoma shows how tumor heterogeneity and limited tissue sampling impact diagnosis. Further studies are needed to shed light on the disease by finding an appropriate molecular signature for each leiomyosarcoma subgroup, providing a more precise diagnosis and the correct background for tailored therapy.