Incidentally Detected ALK-Positive Histiocytosis with <i>EML4::ALK</i> Fusion in a Solitary Pulmonary Nodule Following COVID-19 Infection: A Rare Case Report

We hereby report a patient with ALK-positive histiocytosis with localized lung involvement. A 47-year-old woman presented with a solitary pulmonary nodule in the left upper lobe, 7 months after COVID infection. A well-defined 15 mm yellow mass was found in trisegmentectomy specimen. Histopathological examination revealed that the mass was composed of epithelioid and spindle cells with foamy cytoplasms. No necrosis, pleomorphism, or nuclear atypia was detected. The cells were positive for CD68, CD163, PU.1, ALK and negative for KRT, smooth muscle actin (SMA), S100, Melan-A, CD34, STAT6, and BRAF VE1. Flourescence in situ hybridization demonstrated ALK gene rearrangement, and next generation sequencing confirmed <i>EML4::ALK</i> fusion. Lung involvement in ALK-positive histiocytosis is characterized by the presence of pulmonary nodules, which can be seen in all forms of the disease. However, lung involvement is rarely seen in single-system ALK-positive histiocytosis. Our report represents the fourth documented instance of localized lung involvement in ALK-positive histiocytosis, an exceedingly rare occurrence, and it is the third instance with available molecular data.