Acute Cellular Rejection
Epidemiology:
- First 3-6mo after transplant
- as early as 5-7d post-transplant
Common sites:
Gross features:
Histologic features:
- grade A1:
- perivascular mononuclear infiltrates are
scattered, infrequent
- difficult to find at scanning power
- 2 or 3 cells in thickness within the perivascular
adventitia
- Loose or compact
- Generally circumferential
- Incomplete vascular cuffing is unlikely to
represent acute rejection
- Lymphocytes (plasmacytoid
and transformed)
- Not eosinophils
- grade A2:
- perivascular lymphoid infiltrates are more
frequent
- readily recognizable at low magnification
- densely compacted or loose
- lymphocytes, activated lymphocytes, plasmacytoid lymphocytes, macrophages, and small
numbers of eosinophils (not neutrophils)
- sub-endothelial infiltration by mononuclear
cells is frequent
- endothelialitis associated maybe (hyperplastic or regenerative changes in the
endothelium)
- perivascular interstitium
expanded by mononuclear cells maybe
- no obvious infiltration by mononuclear cells into
the adjacent alveolar septa or air spaces
- lymphocytic bronchioloitis more often seen than in
A1.
- grade A3:
- perivascular lymphoid infiltrates are easily
recognizable
- dense
- endothelialitis commonly associated
- eosinophils common
- occasional neutrophils
- extension of infiltrates into alveolar septal interstitium and
airspaces
- cells percolating singly into alveolar walls,
or more sheet-like infiltration with explansion
of the septa
- continuity with the perivascular infiltrates
- collections of intra-alveolar macrophages in
the zones of septal infiltration
- type 2 alveolar cell hyperplasia
- small numbers of neutrophils maybe
- grade A4:
- diffuse perivascular, interstitial, and
airspace lymphoid infiltrates
- diffuse alveolar damage
- hemorrhage
- parenchymal necrosis or infarction
- small numbers of neutrophils maybe
- numerous perivascular and interstitial
mononuclear cells distinguish A4 from reperfusion-related damage
- small airway (bronchiole) grades:
- grade B0 (no airway inflammation)
- grade B1R (previous B1 and B2)
- sub-mucosal mononuclear cells in bronchioles
- infrequent and scattered, or forming a
circumferential band
- occasional eosinophils
maybe
- no evidence of epithelial damage
- no evidence of intra-epithelial lymphocytic
infiltration
- grade B2R
- sub-mucosal mononuclear cells
- larger and activated
- greater numbers of eosinophils
and plasmacytoid cells
- epithelial damage
- necrosis
- metaplasia
- marked intra-epithelial lymphocytic
infiltration
- ulceration maybe
- fibropurulent exudate maybe
- note too many neutrophils in epithelium and
sub-epithelium is more likely to be infection rather than rejection
- OLD classification:
- grade B1:
- rare lymphocytes in submucosa of bronchioles
and bronchi
- grade B2:
- circumferential band of lymphocytes
- no epithelial inflammation or necrosis
- grade B3:
- circumferential band of lymphocytes
- epithelial inflammation OR necrosis present
- grade B4:
- circumferential band of lymphoctyes
- epithelial inflammation
- epithelial ulceration and necrosis
Immunophenotype:
Marker:
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Sensitivity:
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Specificity:
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Molecular features:
Other features:
- infection should always be excluded
References:
- AFIP Non-Neoplastic Disorders of the Lower
Respiratory Tract (2002)
- Stewart et al.
Revision of the 1996 Working Formulation for the Standardization
of Nomenclature in the Diagnosis of Lung Rejection. The Journal of Heart and Lung
Transplantation 2007;26(12):1229-1242.