Flow cytometric immunoprofiling in a patient with a hypermetabolic solitary pulmonary nodule due to nontuberculous mycobacterial infection

Pedro Arias-Sanchez, Mounika Reddy Vadiyala, Snigdha Karnakoti,Balaji Pathakumari, Virginia Vankeulen,Patricio Escalante

CHEST(2023)

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SESSION TITLE: Chest Infections Case Report Posters 4 SESSION TYPE: Case Report Posters PRESENTED ON: 10/09/2023 12:00 pm - 12:45 pm INTRODUCTION: Mycobacterium avium complex (MAC) and other mycobacteria species can cause solitary lung nodules, which can be FDG-avid and mimic the presentation of malignant lung nodule. We present a case of a patient who underwent surgery and pathology results showed granulomatous inflammation and MAC infection, during the patient follow up, flow cytometric immunoprofiling with mycobacterial antigens was performed. CASE PRESENTATION: A 66-year-old woman with history of non-productive cough for several months. Her past medical history included GERD, upper airway allergies, and smoking for 15 years, quitting 25 years prior to presentation. A chest CT scan showed a 2.7 x 1.3 cm irregular nodule in the right middle lobe (RML) lung. Subsequent FDG-PET showed a hypermetabolic nodule in the RML lung. Because of the possibility of malignancy, the patient underwent robotic-assisted videothoracoscopy with wedge resection of the RML. Pathologic anatomy revealed a 2-cm grayish irregular nodule in the lateral segment of the RML (granulomatous inflammation on frozen section). Culture of the lung tissue revealed the presence of MAC identified by MALDI-TOF MS. Bronchoscopic lavage and surgical smear were negative. She was diagnosed with NTM lung disease according to ATS/IDSA criteria (1). Fourteen months after surgery, peripheral blood mononuclear cells were isolated and stimulated with purified protein derivative (PPD), M. tuberculosis-specific peptides antigen (i.e. ESAT-6/CFP-10) and mycobacteria-specific peptides (i.e. MTB300), and controls. This patient blood immunoprofiling showed upregulation of CD134+PDL1+ in CD4+ and CD8+ T-cells after ex vivo challenge with PPD antigen but no other activation-induced markers (AIM) in T-cells were detected with the other mycobacterial antigens. After two years of follow-up, sputum rapid acid smear and IGRA testing have been negative, and the patient had no radiological or clinical changes. DISCUSSION: Nontuberculous mycobacteria (NTM) are a heterogeneous group of organisms, including MAC species. Several studies have shown that their presence is ubiquitous in the environment. The prevalence of NTM lung disease is increasing, and these infections are associated with ageing, presence of structural lung disease such as COPD/emphysema, and in post-menopausal women (1). It has been reported that granulomatous lesions may have increased FDG uptake and caused false positive PET scan results for lung malignancy. NTM infections may present as solitary nodules mimicking lung cancer (2). Diagnosis of focal lung lesions associated with NTM or tuberculosis (TB) can be challenging. Flow cytometric detection of antigen-specific AIM in T cells has been proposed to improve disease prognosis accuracy in patients with NTM lung disease and TB (3). However, blood immunoprofiling results in this patient suggested the presence of T cell memory response to non-specific mycobacterial antigens, which suggests prior exposure to mycobacteria such as MAC but lack of T-cell activation to specific TB-antigens. Immunoprofiling results are still investigational but may be an important tool to assist to determine the etiology of FDG-avid lung lesions in patients at risk of NTM lung infections. CONCLUSIONS: Differential diagnosis of FDG-avid lung nodules in PET can include focal NTM lung lesions. FC immunoprofiling could provide additional diagnostic information during evaluation and management of these lesions in patients. REFERENCE #1: 1. Griffith DE, Aksamit T, Brown-Elliott BA, Catanzaro A, Daley C, Gordin F, Holland SM, Horsburgh R, Huitt G, Iademarco MF, Iseman M, Olivier K, Ruoss S, von Reyn CF, Wallace RJ Jr, Winthrop K; ATS Mycobacterial Diseases Subcommittee; American Thoracic Society; Infectious Disease Society of America. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416. doi: 10.1164/rccm.200604-571ST. Erratum in: Am J Respir Crit Care Med. 2007 Apr 1;175(7):744-5. Dosage error in article text. PMID: 17277290. REFERENCE #2: 2. Goo JM, Im JG, Do KH, Yeo JS, Seo JB, Kim HY, Chung JK. Pulmonary tuberculoma evaluated by means of FDG PET: findings in 10 cases. Radiology. 2000 Jul;216(1):117-21. doi: 10.1148/radiology.216.1.r00jl19117. PMID: 10887236. REFERENCE #3: 3. Marty, P., Escalante, P., Van Keulen, P., Erskine, C., Shah, M., Pennington, K., Peikert, T. Immune profiling to differentiate progressive from non-progressive non-tuberculous mycobacteria lung disease: A pilot study. European Respiratory Journal. 2021, 58(65). doi: 10.1183/13993003.congress-2021.PA3088 DISCLOSURES: No relevant relationships by Pedro Arias-Sanchez No relevant relationships by Patricio Escalante, value=Honoraria given to institution Removed 12/05/2022 by Patricio Escalante, source=Web Response No relevant relationships by Snigdha Karnakoti No relevant relationships by Balaji Pathakumari No relevant relationships by Mounika Reddy Vadiyala No relevant relationships by Virginia VanKeulen
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