Cellular analysis of bronchoalveolar lavage fluid to narrow differential diagnosis of checkpoint inhibitor-related pneum
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Journal of Translational Medicine Open Access
RESEARCH
Cellular analysis of bronchoalveolar lavage fluid to narrow differential diagnosis of checkpoint inhibitor‑related pneumonitis in metastatic melanoma Sabino Strippoli1, Livia Fucci2, Antonio Negri3, Daniela Putignano4, Marco Luigi Cisternino5, Gaetano Napoli5, Ruggiero Filannino1, Ivana De Risi1, Angela Monica Sciacovelli1 and Michele Guida1*
Abstract Background: The diagnosis of check-point inhibitor-related pneumonitis (CIP) relies on radiological and clinical patterns which are not specific and can mimic other conditions (cancer progression, infectious diseases or interstitial pneumonitis). Cell pattern analysis of bronchoalveolar lavage (BAL) is well-known to support the diagnosis of interstitial lung disease; nevertheless, this analysis is somewhat performed and not required by immune-toxicity management guidelines for CIP. Methods: We performed BAL analysis in 5 metastatic melanoma (MM) patients who developed CIP among 112 patients treated with checkpoint inhibitors. We also correlated the BAL features with the computed tomography (CT) scan patterns and with various peripheral blood parameters to better define the profile of this patient population. Results: BAL flow cytometer and cytopathology analyses showed typical and homogeneous features with increased lymphoid population, prevalent CD8 + T cells and inversion of the CD4/CD8 ratio. Moreover, the extent of activated CD3 + HLA-DR + T cells was related to the grading of adverse events. Blood leucocytosis, hypoxemia, normal values for procalcitonin and lactate dehydrogenase were also found together with a cryptogenic organizing pneumonia-like radiologic pattern. In all our patients, CIP was associated with partial or complete response. Conclusions: Identification of a specific BAL cellular pattern allows clinicians to place this investigation in the appropriate position of CIP diagnosis and management to avoid misdiagnosis or considering this condition as progressive disease and delaying proper treatment. Keywords: Check-point inhibitor, Interstitial pneumonitis, Immune-toxicity, Melanoma Introduction In recent years, a rapidly increasing incidence of immune-related pneumonitis has been reported following the broad use of check-point inhibitors in a wide
*Correspondence: [email protected] 1 Rare Tumors and Melanoma Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Viale Orazio Flacco 65, 70124 Bari, Italy Full list of author information is available at the end of the article
range of neoplasms both in the advanced disease and adjuvant/neoadjuvant setting [1]. Although its estimated overall incidence is less than 5% as described in clinical trials and pooled analysis [2, 3], check-point inhibitorrelated pneumonitis (CIP) is being reported more frequently in the real-world setting [4, 5]. CIP is among the most severe immune related adverse events (irAEs), particularly because of its challenging diagnosis. Diagnosis is difficult because of the variable onset of CIP based on
© The Author(s) 2020.
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