Acute Fibrinous and Organizing Pneumonia Versus Organizing Pneumonia: A Comparative Study of Clinical, Radiological, Histological, and Immunophenotypic Features

Background: The relationship between acute fibrinous and organizing pneumonia (AFOP) and organizing pneumonia (OP) remains debated, and direct comparative evidence is limited. We aimed to delineate their differences across clinical, radiological, histological, and immunophenotypic dimensions. Methods: We conducted a retrospective study of 85 consecutive patients with pathologically confirmed AFOP (n = 49) or OP (n = 36). Clinical data, radiological patterns, laboratory findings, and immunohistochemical profiles of alveolar epithelial, macrophage, lymphocyte, vascular, and mesenchymal markers were comprehensively compared. Results: The two groups were comparable in demographics, clinical symptoms, and dominant radiological patterns. However, median C-reactive protein (CRP; 80.45 vs. 12.65 mg/L, p < 0.001) and neutrophil-to-lymphocyte ratio (NLR; 4.56 vs. 2.42, p = 0.013) were higher in AFOP, with CRP demonstrating an apparent area under the curve (AUC) of 0.798 for discriminating AFOP from OP in this derivation cohort. After Benjamini–Hochberg correction for multiple comparisons, CD68 was significantly higher, and CD38 was significantly lower in AFOP than in OP. Trends were also observed for CD163, surfactant protein A (SP-A), and CD34, but these did not remain statistically significant after correction. All three deaths and all cases requiring mechanical ventilation occurred in the AFOP group, though these differences were not statistically significant. Conclusions: Despite clinical and radiological overlap, AFOP and OP exhibit distinct systemic inflammatory responses and pulmonary immunophenotypes, with AFOP characterized by macrophage-predominant inflammation and qualitatively fewer CD34+ microvessels within fibrin balls. These immunophenotypic findings are descriptive and require further validation.