Acute allograft rejection is defined as a cell-mediated process characterized by perivascular mononuclear cell infiltrate composed of T-cells. Most lung transplant recipients experience at least one if not more episodes of acute rejection. Acute rejection can occur early in the post-transplant period (in a matter of days) or late in the post-transplant period (months to years). The accepted scheme of grading and classification of acute rejection known as the “working formulation for classification of pulmonary allograft rejection” was established by a group of experts in 1990 and revised in 1995 and in 2006. The grading system is based on the presence or absence of perivascular lymphoplasmacytic infiltrates either of single or multiple vessels, and the presence or absence of associated lung parenchymal damage. The diagnosis of rejection is one of exclusion and infection or other causes of the histologic findings must be ruled out. Reliable diagnosis requires sampling of at least five pieces of lung parenchyma by transbronchial biopsy. At least three H&E-stained sections from three levels in the block and a trichrome stain (see Chapter 104) should be reviewed.

In the Working Formulation, vascular involvement is classified as “A,” with a numerical grade from 0 to 4 depending on the number and density of the mononuclear infiltrate. “AX” is the designation for specimens that are ungradable due to inadequate sampling (fewer than five good pieces of alveolar parenchyma). Bronchiolar involvement in acute rejection is also graded as “B1R” or “B2R” depending on the severity of small-airway involvement, with “B0” for no bronchiolar involvement and “BX” for ungradable.