Egan, A

Abstract Introduction Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy through enhancing T-cell-mediated immune responses but have also been associated with immune-related adverse events. Emerging literature suggests a potential association between ICI therapy and the development or reactivation of tuberculous mycobacterial infections. It is unclear whether ICI therapy is also linked to an increased risk of non-tuberculous mycobacterial (NTM) infections, though case reports are rapidly accumulating. We aim to better elucidate the potential association between ICIs and NTM infections through a case series. Case Series This series includes patients at Mayo Clinic who were diagnosed with active NTM infection during or after ICI use from January 1, 2012 to December 31, 2024. Data including demographics, malignancy details, ICI regimen and duration, timing and site of NTM infection, microbiologic findings, antimycobacterial therapy, and clinical outcomes were evaluated. There were seven patients with positive testing for NTM during or after ICI therapy. Two had one colony of M. gordonae on cultures which were determined by Infectious Disease to be contaminants. One case had a reported culture positive for M. franklinii at an outside hospital without further details available and thus was excluded from analysis. Chart review was performed for the remaining four patients with active NTM infection during or after ICI therapy. Two of the patients had underlying chronic obstructive pulmonary disease with a smoking history; these same two had primary lung malignancy. The other two patients had no known underlying lung disease or malignancy lung involvement (primary or metastatic). ICI therapies included PD-1, PD-L1, and CTLA-4 inhibitors. All four NTM infections predominant had lung involvement and were all different species; two were diagnosed while the patient was actively receiving ICI therapy and two were diagnosed several months after ICI discontinuation. Of the two receiving ICI therapy at the time of diagnosis, the ICI was held for 101 days for one patient and the other continued the ICI without interruption. Three received multi-agent therapy while the fourth declined treatment and died of malignancy complications soon after. The other three were alive at one year after NTM diagnosis and completed approximately one year of antimycobacterial therapy. Conclusions Tuberculous and non-tuberculous mycobacterial infections are increasingly seen after immune checkpoint inhibitor therapy. We present a series of four cases of NTM infections after or during ICI therapy for various types of malignancy with good outcomes after approximately one year of treatment. This abstract is funded by: None

Abstract When evaluating malignant anterior mediastinal masses, thymic carcinoma and lymphoma represent the most common etiologies. We present a case of a patient with an incidentally found anterior mediastinal mass, initially suspected to be thymic carcinoma, who was ultimately diagnosed with primary mediastinal classical Hodgkin lymphoma. A 55-year-old woman with no contributory past medical history presented to her primary care provider with several weeks of cough which was unresponsive to antibiotics and corticosteroids. A chest x-ray demonstrated a large mediastinal mass and subsequent CT chest further revealed an anterior mediastinal mass measuring 15 x 6 x 13 cm. A PET-CT showed intense FDG uptake in the mediastinal mass (SUVmax 14.5) and FDG-avid right pleural lesions suggestive of metastases (SUVmax 4.5). She was referred to outpatient pulmonary clinic. Given imaging findings, thymic carcinoma was initially favored. Following multidisciplinary discussion with Thoracic Surgery, neoadjuvant chemotherapy was recommended prior to any consideration of surgical resection given the size and involvement of mediastinal structures. Thus, CT-guided biopsy was pursued to confirm the diagnosis, but unexpectedly revealed classical Hodgkin lymphoma of the nodular sclerosis subtype. She was diagnosed with stage IVA disease and urgently initiated chemotherapy with nivolumab, doxorubicin, vinblastine, and dacarbazine (N-AVD). A repeat PET-CT two months after initiation of treatment demonstrated marked metabolic and anatomic response, with the mediastinal mass reduced to 8.9 x 5.4 cm with an SUVmax of 2.1. Similarly, the FDG-avid pleural metastases had a decrease in SUVmax to 1.0. The patient was continued on the same treatment regimen. Although thymic carcinoma was initially suspected, a biopsy was obtained because surgical resection was not planned as the initial step in management. Typically, thymic malignancies are not biopsied prior to surgery due to the risk of tumor seeding and the preference for definitive resection, with some exceptions. In this case, the decision to biopsy resulted in the unexpected diagnosis of primary mediastinal classical Hodgkin lymphoma, a particularly rare entity among anterior mediastinal masses. This case underscores the importance of individualized diagnostic strategies and the role of tissue confirmation when clinical or therapeutic circumstances deviate from standard practices. This abstract is funded by: None

Abstract Plasmacytomas are a form of plasma cell malignancy which can occur as isolated lesions or as part of systemic multiple myeloma. We present a case of a patient whose evaluation for an incidentally found lung mass led to the diagnosis of multiple myeloma. A 65-year-old man with no remarkable past medical history presented to the emergency department with two days of fever, cough, and chills. A chest x-ray demonstrated findings suggestive of pneumonia as well as a “smoothly marginated density in the left lung apex.” CT chest further revealed a destructive mass involving the left third rib measuring 7.6 x 4.6 cm; it was difficult to determine from imaging if the mass originated from the lung, pleura, or bone. PET-CT showed significant FDG avidity of the mass (SUVmax 40.2) and FDG-avid left mediastinal and supraclavicular lymph nodes. He subsequently presented to outpatient pulmonary clinic for further evaluation. Given imaging findings, primary lung malignancy or soft tissue sarcoma was initially suspected. He underwent CT-guided biopsy of the mass with pathology showing a kappa light chain-restricted plasmacytoma. Serum studies demonstrated a markedly elevated kappa/lambda ratio of 132. Bone marrow biopsy confirmed a kappa light chain-restricted plasma cell myeloma with 20% plasma cells. On review of previous labs, the patient was noted to have anemia (hemoglobin 11.9 g/dL) previously attributed to iron deficiency anemia as well as hypercalcemia (10.3 mg/dL). Renal function was normal. He was diagnosed with multiple myeloma and started on daratumumab, bortezomib, lenalidomide, and dexamethasone (Dara-VRD), with favorable response to treatment. The presence of plasmacytomas is clinically important to recognize in multiple myeloma as they are predictors of poorer outcomes. The site of origin also carries prognostic implications: paraskeletal plasmacytomas arising from bone marrow are associated with better outcomes than extramedullary plasmacytomas which result from hematogenous spread. In one study, paraskeletal plasmacytomas were found to occur in 17.6% of patients with multiple myeloma, with 40% located in the chest; similarly, extramedullary plasmacytomas were associated with the lungs or pleura in 23% of patients. Altogether, this case underscores the importance of considering plasmacytomas in the differential of a lung mass, particularly if there is osseous involvement. This abstract is funded by: None