Primary Pulmonary Mesenchymal Neoplasm With EWSR1::CREM Fusion: Cytologic Findings and Molecular Diagnosis

BACKGROUND: Primary pulmonary mesenchymal neoplasms with EWSR1::CREM fusion are rare. These lesions are challenging to diagnose by morphology and immunohistochemistry alone. CASE: A 66-year-old woman (ex-smoker) was found to have a 1.3-cm right lower lobe lung nodule that had grown very slowly over a 9-year period. Fine-needle aspiration and core biopsy demonstrated papillary fragments lined by epithelioid cells with underlying neoplastic stromal cells arranged in sheets, cords, and clusters. There was no significant atypia, necrosis, or mitotic activity. An extensive panel of immunostains was inconclusive. Wedge resection of the nodule showed a well-circumscribed neoplasm with the same bland morphology seen in the biopsy. Lymph nodes were negative. Given the bland cytology and inconclusive immunophenotype, targeted next-generation sequencing was performed, which revealed an EWSR1::CREM gene fusion. Based on these findings, a low-grade fusion-driven mesenchymal neoplasm was favored. CONCLUSION: This case highlights the role of next-generation sequencing in establishing the diagnosis in rare cytologically bland pulmonary mesenchymal neoplasms in which conventional cytomorphology and immunohistochemistry fail to reveal a specific diagnosis.