Answer
Given the patchy nature of rejection, a consensus statement by the Lung Rejection Study Group (LRSG) recommends five fragments of well-expanded alveolated lung (with bronchioles and >100 alveolar spaces) be examined. [4] This may require more than five transbronchial biopsies, especially to recognize features of bronchiolitis obliterans (BO). Specimens may be gently agitated in formalin to inflate the fragments but require sensitive handling to avoid crush artifacts.
Histologic examination should include sections from three levels of the paraffin block for hematoxylin and eosin (H&E) staining. Connective-tissue stains may help evaluate any submucosal fibrosis. Silver stains can be performed for fungi. Immunohistochemical stain for cytomegalovirus (CMV) is very helpful and strongly recommended. Concomitant bronchoalveolar lavage (BAL) fluid may be analyzed to exclude infection, but it plays no role in the diagnosis of rejection.
If the biopsy samples contain diagnostic material but do not meet the minimum assessable criteria, grading should be carried out as usual, with a comment describing the number of lung fragments and emphasis that the material may not be representative of the overall allograft. Similarly, if no alveolated lung or no airway is present, the type of rejection should be indicated by the appropriate letter, suffixed by an "X" (see below). Biopsies taken for rejection surveillance should always be evaluated for histopathologic features indicative of infection, aspiration, organizing pneumonia, recurrent disease (eg, sarcoidosis), and PTLD.
-
Lung transplantation-related pathology. Intraalveolar multinucleated giant cell indicates microaspiration in this posttransplant transbronchial biopsy specimen (hematoxylin and eosin [H&E], 200x)
-
Lung transplantation-related pathology. This image depicts minimal acute cellular rejection with incomplete perivascular cuff of inflammatory cells (grade A1) (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. This image shows mild acute perivascular rejection with a thick complete cuff around a blood vessel (grade A2) (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. Moderate acute perivascular rejection is revealed: The inflammation extends into adjacent alveolar walls and is accompanied by fibrinous exudates (grade A3) (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. Note the minimal acute airway rejection shown: There is focal inflammation in the submucosa (grade B1) (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. This image demonstrates mild acute airway rejection: There is a bandlike infiltrate in the submucosa (grade B2) (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. Moderate acute airway rejection is revealed: The inflammatory infiltrate extends into the overlying epithelium (grade B3) (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. This image shows bronchial-associated lymphoid tissue (BALT): A collection of small mature lymphocytes is present which is associated with pigment. Although no airway is seen in this figure, the morphologic appearance is not that of rejection (hematoxylin and eosin [H&E], 100x).
-
Lung transplantation-related pathology. Bronchiolitis obliterans (chronic rejection) is revealed: The patient underwent retransplantation for chronic rejection, which is seen here as eccentric fibrosis partially occluding the airway lumen. Note the presence of scant inflammatory cells and plump fibroblasts in the lesion (hematoxylin and eosin [H&E], 100x).
-
Lung transplantation-related pathology. This image demonstrates bacterial infection: The presence of mostly neutrophils in both the submucosa and mucosa is most suggestive of an infection (hematoxylin and eosin [H&E], 200x).
-
Lung transplantation-related pathology. The image reveals cytomegalovirus (CMV) infection by immunohistochemical (IHC) staining: Both enlarged nuclei and normal-sized infected nuclei stain positively. This feature is helpful when viral inclusions are not readily apparent on hematoxylin and eosin (H&E) stain. (IHC stain using antibody against immediate early antigen, 200x)
-
Lung transplantation-related pathology. This image demonstrates posttransplant lymphoproliferative disorder (PTLD): There is a diffuse infiltrate of atypical lymphoid cells, obliterating the lung architecture, with a foci of necrosis, as would be seen in a large-cell lymphoma (hematoxylin and eosin [H&E], 200x).
