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Revised Working Formulation for
Classification and Grading of Lung Allograft Rejection - 1995
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Acute Rejection* |
| Grade |
Histopathological Findings |
| A0 (None) |
No mononuclear
inflammation, hemorrhage
or necrosis |
| A1 (Minimal) |
Scattered infrequent
perivascular mononuclear infiltrates not obvious at low
magnification
(40X). Blood vessels, particularly venules, are
cuffed by small round, plasmacytoid, and transformed lymphocytes
forming a ring of 2 to 3 cells thick in the perivascular
adventitia. |
| A2 (Mild) |
Frequent perivascular
mononuclear
infiltrates
surrounding venules and arterioles readily recognizable at low
magnification and usually consist of activated lymphocytes, small
round
lymphocytes, plasmacytoid lymphocytes, macrophages, and
eosinophils.
Frequent subendothelial infiltration by the mononuclear cells with
hyperplastic or regenerative changes in the endothelium
(endotheliitis);
although there is expansion of the perivascular interstitium by
inflammatory
cells, there is no obvious infiltration by mononuclear cells into
the
adjacent alveolar septae or air spaces. Concurrent lymphocytic
bronchiolitis is not uncommon. A solitary perivascular
mononuclear
infiltrate of significant intensity to be noted at low
magnification
still warrants a diagnosis of grade A2 (or greater) rejection
|
| A3 (Moderate) |
Readily recognizable
cuffing of
venules and arterioles by dense perivascular mononuclear cell
infiltrates,
which are usually associated with endothelialitis; eosinophils and
occasional neutrophils are common. By definition, there is
extension of
the inflammatory cell infiltrate into perivascular and
peribronchiolar
alveolar septae and air spaces. Collections of alveolar
macrophages
are common in the airspaces in the zones of septal infiltration.
|
| A4 (Severe) |
Diffuse perivascular,
interstitial,
and air space infiltrates of mononuclear cells and prominent
alveolar
pneumocyte damage usually associated with intra-alveolar necrotic
cells,
macrophages, hyaline membranes, hemorrhage, and neutrophils; there
may
be associated parenchymal necrosis, infarction, or necrotizing
vasculitis.
The obvious presence of numerous perivascular and interstitial
mononuclear
cells seen with grade A4 rejection permits distinction from
peri-operative
(reperfusion/ischemic) lung injury. |
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*
Pathologists should mention airway inflammation and may choose
to grade B lesions (see below).
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Chronic Airway Rejection (Bronchiolitis Obliterans) |
| Classification |
Histopathological Findings |
| Active |
In addition to the fibrosis, there are intra and/or peribronchiolar
submucosal and peribronchiolar mononuclear cell infiltrates usually
associated with ongoing epithelial damage |
| 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 |
|
Chronic Vascular Rejection |
| Refers to the
vaso-obliterative process
affecting arteries and veins, that affects most solid organ
transplants, and reflects accelerated atherosclerosis with
fibrointimal thickening of the subendothelial area by loose
myxomatous connective tissue. A mononuclear cell and foamy cell
infiltrate is common |
|
Airway Inflammation§ |
| Grade |
Histopathological Findings |
| B0 (None) |
No airway inflammation
|
| B1 (Minimal) |
Rare scattered mononuclear
cells within the
submucosa of the bronchi and/or bronchioles |
| B2 (Mild) |
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 |
| B3 (Moderate) |
Dense band-like infiltrate of activated
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 |
| B4 (Severe) |
Dense band-like infiltrate
of activated
mononuclear cells in the lamina propria of bronchi and/or
bronchioles,
associated with dissociation of epithelium from the basement
membrane,
epithelial ulceration, fibrinopurulent exudates containing
neutrophils,
and epithelial cell necrosis |
| BX |
Ungradeable because of
sampling problems,
infection, tangential cutting, etc |
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§
All cases of acute rejection should have a designation indicating
whether coexistent airway inflammation is present and may choose
to grade the intensity.
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Reference
Yousem SA, et al. A revision of the 1990 Working
Formulation for the classification of pulmonary allograft rejection:
Lung Rejection Study Groug (LRSG)
J Heart Lung Transplantation 1996;15:1-15.
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