Case Report: A report of two cases and literature review: primary pulmonary Ewing sarcoma presenting with hemoptysis and back pain.

BACKGROUND: Primary Pulmonary Ewing Sarcoma (PES) is an extremely rare and lethal subtype of Ewing sarcoma (EWS) arising from the lungs, and predominantly affects young adults. The available literature is limited. Typically, affected individuals exhibit respiratory distress, cough, and chest pain; hemoptysis or back pain as the chief presenting symptom is highly uncommon. CASE PRESENTATION: The paper presents two cases of PES in which hemoptysis or back pain was the main clinical symptom. The first patient was a 42-year-old female presenting with hemoptysis, and the second was a 65-year-old female admitted for two months of persistent back pain. Neither patient had a history of smoking, pulmonary disease, family malignancy, or known genetic predisposition to cancer. Chest computed tomography (CT) scans revealed consistent findings in both patients: irregular, mass-like soft-tissue opacities adjacent to the pulmonary hila. Based on the initial clinical manifestations and CT findings, bronchial adenocarcinoma or squamous cell carcinoma was initially suspected. Both cases underwent surgical intervention. However, small cell lung cancer (SCLC) could not be excluded based on chest CT findings, preoperative lung tumor marker levels, and intraoperative frozen-section pathological consultation results. Immunohistochemistry (IHC) and molecular analysis were used to arrive at the final diagnosis. Case 1 showed strong diffuse positive staining for CD99, FLI-1, and NKX2.2, along with confirmed EWSR1 gene rearrangement. The diagnosis of PES in Case 2 was confirmed by the highly specific dual positive expression of CD99 and NKX2.2, despite the absence of molecular testing. CONCLUSION: For middle-aged and young non-smoking patients with hemoptysis and no other lung cancer risk factors, as well as elderly patients presenting with predominant back pain, PES should be included in the differential diagnosis even in the presence of elevated preoperative pro-gastrin-releasing peptide (ProGRP) levels and intraoperative pathological findings suggestive of SCLC. Supplemental IHC and molecular analyses are essential to ensure an accurate definitive diagnosis and guide optimal therapeutic strategies.