A Revision of the 1990 Working Formulation
for the Classification of Pulmonary Allograft Rejection:
Lung Rejection Study Group (LRSG)
C. CHRONIC AIRWAY REJECTION - BRONCHIOLITIS OBLITERANS
Bronchiolitis obliterans is a term restricted to
membranous and respiratory bronchioles and, in the context of a lung allograft,
refers to dense eosinophilic hyaline fibrous plaques in the lamina propria of the
small airways which results in partial or complete luminal compromise (Figure 14).
2,3 This scar tissue may be concentric or eccentric, may be associated
with fragmentation and destruction of the smooth muscle wall, and may extend into
the peribronchiolar interstitium. Mucostasis or foamy histiocytes in the distal
airspaces (endogenous lipidosis) are common. Bronchiolitis obliterans rarely
develops within the first three months after transplantation, usually developing at
the end of or after the first post-operative year.
In contrast to the 1990 scheme, the current LRSG felt that
a distinction between "subtotal" and "total" forms of bronchiolitis obliterans was
not worthwhile in the evaluation of the lung allograft by transbronchial biopsy;
however it was felt that estimation of the relative activity of the inflammatory
infiltrate was worthwhile. In those instances of coexistent acute and chronic
rejection, the pathology report should reflect these processes in the following
manner: "acute rejection, grade -, with active/inactive bronchiolitis obliterans,
grade C a/b".
| a. Active: |
In addition to the fibrosis, there are intra and/or
peribronchiolar submucosal and peribronchiolar mononuclear cell infiltrates usually
associated with ongoing epithelial damage (Figure 15). |
| b. Inactive: |
Dense fibrous scarring without cellular infiltrates; this
represents old cicatricial change in the small airways with a lack of significant
submucosal and peribronchiolar inflammatory infiltrates (Figure 16). |
At present the significance of large airway fibrosis is
uncertain.16 In the opinion of the LRSG, this finding is nonspecific and does not
warrant a diagnosis of chronic rejection. Inflammation and scarring of the
bronchioles is felt to be a more significant reflection of chronic allograft
injury.
D. CHRONIC VASCULAR REJECTION- ACCELERATED GRAFT VASCULAR SCLEROSIS
In chronic vascular rejection there is fibrointimal
thickening of arteries and veins (Figures 17,18). The significance of this change
is uncertain but seems to correlate with the presence of coronary artery disease in
allograft hearts in combined heart-lung procedures and bronchiolitis obliterans in
isolated lung allografts.12 There may also be an "active" component
consisting of subendothelial, intimal, and/or medial mononuclear cell infiltrates.
The 1995 LRSG felt that the 1990 category of "Vasculitis"
was probably not worthwhile retaining as most cases of vascular injury reflect
either severe acute rejection reactions or active graft vascular sclerosis.
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