Acute Transplant Rejection
Anna Sienko MD
Transbronchial biopsy is frequently used for evaluation of lung transplant recipients, both for scheduled routine follow-up, for diagnosis when the patient develops functional or radiologic changes, for frank illness, and for assessment of response to therapy. One of the most frequent uses of the transbronchial biopsy in lung transplant recipients is for the diagnosis of acute transplant rejection.
Acute allograft rejection is a cell-mediated process with characteristic perivascular infiltrate composed of T-cell lymphocytes. The classification of acute cellular rejection is based on the revised working formulation scheme. It relies primarily on a numerical grading system that evaluates the presence or absence of perivascular lymphocytic infiltrate in a perivascular distribution of single or multiple vessels and the presence or absence of associated lung parenchymal damage (A grade; graded depending on increasing severity of the lymphocytic infiltrate from “A0” to “A4”). Airway involvement can be seen as part of acute allograft rejection and is classified as “B grade” with a numerical grading scheme depending on the increasing severity of airway involvement from “B0” no airway inflammation, B1R low grade small airway inflammation, and B2R high grade small airway inflammation with “BX” indicating ungradable airway inflammation. A transbronchial biopsy with at least several pieces of alveolated lung parenchyma for evaluation can show no perivascular infiltrate (no rejection, grade A0); minimal rejection with a sparse perivascular infiltrate one or two cells thick, mild rejection (A1); an infiltrate that is usually just “cuffing” the vessels, usually more than several “lymphocytes thick” and visible at low power (A2); moderate rejection with lymphocytic infiltrate that also extends from around the vessels into the adjacent interstitium (A3); and severe rejection with perivascular infiltrates associated with lung injury with intra-alveolar fibrin and hyaline membrane formation (A4). Airway inflammation on transbronchial biopsy may show minimal or mild airway inflammation with rare mononuclear cells within bronchial or bronchiolar submucosa (B1R, encompassing previous grade of B1 and B2) with circumferential mononuclear cells within bronchial or bronchiolar submucosal eosinophils and few intraepithelial lymphocytes. Moderate to severe airway inflammation (B2R, encompassing previous grade of B3 and B4) consists of a dense mononuclear cell infiltrate containing many intraepithelial lymphocytes, epithelial cell apoptosis, and lymphocyte satellitosis. B2R high grade small airway infalmmation can also show features of epithelial detachment, fibrinopurulent exudate, and ulceration.