Exploring the Diagnostic Dilemma of Indeterminate Pulmonary Nodules in Patients with Primary Sarcoma of Bone.

Introduction: Bone sarcomas are known to have a predilection for pulmonary metastasis. Surveillance protocols are thus focused on periodic chest imaging, typically with CT scan. Pulmonary nodules can be easily identified with this modality, but smaller nodules are not readily biopsied and may not represent metastatic disease. These are called indeterminate. The natural history of indeterminate nodules in a bone sarcoma population and factors associated with progression to true metastatic disease are not clearly defined. Methods: All bone sarcoma patients treated at a single institution from 2010 to 2020 were eligible for inclusion. We treated 327 patients over this period; 119 were excluded for age less than 16 years, 31 were excluded for evident metastatic disease at presentation, and 60 were excluded for incomplete clinical follow-up or CT chest imaging either at staging or in surveillance. We assessed chest CT images for presence of pulmonary nodules and selected variables both at the staging and on surveillance images. Nodules were considered metastatic if proven histologically with a biopsy or by clinical interpretation by the multidisciplinary sarcoma team. Clinical and imaging factors were assessed for the association of indeterminate nodule progression to true metastatic disease. Results: Seventy three of the 117 patients had indeterminate nodules on their staging CT scan; 41.1% of those patients progressed to metastatic disease compared to 43.2% of the patients that did not have indeterminate nodules on staging CT. Fifty eight of the 117 patients developed indeterminate nodules on surveillance chest CT, and 55.2% of those patients progressed to metastatic disease. There were no clinical or imaging factors that predicted the development of metastatic disease in the group that had indeterminate nodules at presentation; however, the number and size of nodules did correlate with progression to metastasis in those that developed indeterminate nodules on surveillance. Conclusion: Indeterminate pulmonary nodules are common on staging CT scans in patients with a bone sarcoma. The presence or absence of these indeterminate nodules was not predictive of progression to true metastatic disease in this cohort. However, the development of indeterminate nodules on surveillance imaging was associated with progression to metastatic disease with the size and number of nodules being important factors.