A Revision of the 1990 Working Formulation
for the Classification of Pulmonary Allograft Rejection:
Lung Rejection Study Group (LRSG)
B. AIRWAY INFLAMMATION - LYMPHOCYTIC BRONCHITIS/BRONCHIOLITIS
In the 1990 classification, acute rejection was divided
into four grades based on the presence and intensity of perivascular and
interstitial mononuclear infiltrates. Under each grade, four suffixes were offered
to reflect coexistent airway inflammation. These designations did not reflect the
intensity of the inflammatory infiltrate and were felt to be cumbersome by the 1995
LRSG. In the 1995 modification of the working formulation of lung allograft
rejection, it is recommended that perivascular infiltrates remain the determining
factor on which to grade acute rejection but that the presence and intensity of
combined large and small airway inflammation should be recognized as lymphocytic
inflammation of the airways may be harbinger of bronchiolitis obliterans.13 The
airway inflammation should be listed as a "B" category and can be divided into five
grades, or simply designated as present or absent, at the discretion of each
insitiution.
| B0 - |
no airway inflammation |
| B1 - |
minimal airway inflammation - rare scattered mononuclear cells
within the submucosa of the bronchi and/or bronchioles (Figure 8). |
| B2 - |
mild airway inflammation - a circumferential band of
mononuclear cells and occasional eosinophils within the submucosa of bronchi and/or
bronchioles unassociated with epithelial cell necrosis (apoptosis) or significant
transepidermal migration by lymphocytes (Figure 9). |
| B3 - |
moderate airway inflammation - a dense band-like infiltrate of
mononuclear cells in the lamina propria of bronchi and/or bronchioles including
activated lymphocytes and eosinophils, accompanied by evidence of satellitosis of
lymphocytes, epithelial cell necrosis (apoptosis) and marked lymphocyte
transmigration through epithelium (Figures 10,11). |
| B0 - |
severe airway inflammation - a dense band-like infiltrate of
activated mononuclear cells in bronchi and/or bronchioles, associated with
dissociation of epithelium from the basement membrane, epithelial ulceration,
fibrinopurulent exudates containing neutrophils, and epithelial cell necrosis
(Figures 12, 13). |
| BX- |
ungradable because of sampling problems, infection, tangential
cutting, etc. |
While some members of the LRSG felt that grading the
presence and intensity of airway inflammation in acute rejection was important
because of the increased risk of developing bronchiolitis obliterans many other
members did not.13-15 These latter individuals felt that clinicopathologic
evidence did not convincingly prove that airway inflammation solely could be used
to grade rejection because of its frequent coexistence with airway infection and
problems with biopsy adequacy. For these reasons, some institutions may choose
only to note the presence of airway inflammation and decline to grade its
intensity. Still other centers may opt to focus on the separation of large and
small airway inflammation. It should also be highlighted that dense scarring of
the bronchioles is not accepted under the "B" designation.
The LRSG proposes to designate the diagnosis of acute
rejection with coexistent airway inflammation as follows: ACUTE REJECTION, GRADE
- , WITH AIRWAY INFLAMMATION, GRADE - . For example, mild acute rejection in
which there is an intense airway infiltrate with epithelial cell necrosis would be
diagnosed as "Mild acute rejection, grade A2 with airway inflammation, grade B3".
Similarly, the 1990 category of "B - lymphocytic bronchitis/bronchiolitis" would
now be graded as a "A0 B-" in the 1995 classification. This format emphasizes the
need to retain perivascular infiltrates as the primary focus in the histologic
classification of acute lung rejection.
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