Pathophysiology of acute fibrinous and organizing pneumonia – Clinical and morphological spectra

Abstract

a b s t r a c tAcute Fibrinous and Organizing Pneumonitis (AFOP) is a disease with histopathological pattern characterized by the presence of intra-alveolar fibrin in the form of fibrin "balls" and organizing pneumonia represented by inflammatory myofibroblastic polyps. Symptoms of this rare interstitial pulmonary disease can be either acute or sub-acute and it can rapidly progress to death. Diagnosis should be considered in the Intensive Care Unit (ICU) if patients' symptomatology and radiology correlates with non-responding or progressive pneumonia and when morphology, on biopsies, encompasses criteria of diffuse alveolar damage (DAD) and organizing pneumonia (OP) balancing in between.Three clinical cases of patients presenting severe lung disease requiring mechanical ventilation and prolonged intensive care fitted on the variable spectra of AFOP histopathology and had poor outcome: a 23 year-old women had AFOP in the context of antiphospholipid syndrome pulmonary compromise; a 35 year-old man developed a letal intensive care pneumonia with AFOP pattern registered in post-mortem biopsy; and a 79 year-old man died 21 days after intensive care unit treatment of a sub-pleural organizing pneumonia with intra-alveolar fibrin, seen in post-mortem biopsy.The predominance of acute fibrin alveolar deposition pattern is helpful in raising AFOP differential diagnosis while organizing pneumonia pattern establishes a wider range of diagnosis that can go till solitary pulmonary nodule, remaining indefinite to suggest diagnosis. The performance time of biopsy in a larger number of clinical cases may be helpful in establishing the evolutionary morphological pattern, taking in mind the poor outcome of the disease, deserving rapid diagnosis to define treatment.

Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients

“…Moreover, AFOP may be a fibrinous variant of DAD (20). The limitation of lung biopsy was also shown in another study, in which only 50% of lung samples were positive for SARS-CoV-2 using RT-PCR (21), when compared to almost 100% in our series.…”

“…A diagnosis of AFOP is based on the absence of hyaline membranes and the presence of alveolar fibrin balls; however, hyaline membranes are heterogeneously distributed in the lung parenchyma with DAD and complete lung analysis, not just biopsies, are necessary to exclude their presence. Moreover, AFOP may be a fibrinous variant of DAD (20). The limitation of lung biopsy was also shown in another study, in which only 50% of lung samples were positive for SARS-CoV-2 using RT-PCR (21), when compared to almost 100% in our series.…”

Cell-Type Apoptosis in Lung during SARS-CoV-2 Infection

“…In especially long-standing and severe DAD during ARDS, extensive fibrin accumulates in alveolar spaces in greater amounts than seen with typical hyaline membranes. Intra-alveolar fibrin deposition in acute fibrinous and organizing pneumonia is known as “fibrin balls” [ 35 ].…”

Unspecific post-mortem findings despite multiorgan viral spread in COVID-19 patients

“…A diagnosis of AFOP is based on the absence of hyaline membranes and the presence of alveolar fibrin balls; however, hyaline membranes are heterogeneously distributed in the lung parenchyma with DAD and complete lung analysis, not just biopsies, are necessary to exclude their presence. Moreover, AFOP may be a fibrinous variant of DAD [ 20 ]. The limitation of lung biopsy was also shown in another study, in which only 50% of lung samples were positive for SARS-CoV-2 using RT-PCR [ 21 ], when compared to almost 100% in our series.…”