The ISHLT Schema for Allograft Rejection

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The ISHLT Schema for Allograft Rejection
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Nov/Dec issue 1990 JHLT
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After the first session, it was a consensus that
the ISHLT-WF has withstood the test of time.
1. The working group agreed that revisiting
the ISHLT-WF in the light of the cumulative
experience of 10 years of use of since its
publication was necessary Changes in the
formulation should reflect current pathologic
practice and should not affect the grading of
historical samples. 2. It was a consensus that
confusion has risen from the use of the term
myocyte "damage" and myocyte "necrosis" 3.
Confusion over the term aggressive infiltrates
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5. The working group recognized that there is a
subset of acute cell-mediated predominantly
vascular rejection, that affects small arteries
and arterioles 6. The working group agreed that
at this juncture is PREMATURE to speculate about
the relationship between vascular/humoral
component and/or the acute cell mediated
predominantly vascular rejection seen in
some biopsies and the development of
vasculopathy 7. Retrieval of information,
guidelines
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4. The working group agreed that humoral
rejection is a real process that clinically
affects a significant number of cardiac
transplant patients (although no percentage was
agreed upon REPRODUCIBILITY The working group
concurred that the ISHLT-WF must strive to
establish clear pathologic criteria for humoral
rejection in the heart. The literature on this
topic is sparse and there is no
reproducibility criteria amongst heart transplant
centers as to what constitutes humoral rejection
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Dogma

• April 2003 NIH conference on humoral rejection.

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Previous Bx Site - 1
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Previous Bx Site - 2
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Quilty B vs. Rejection
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Thebesian veins
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Goals I
Revisit cumulative experience of 10 years of use
of ISHLT-WF Issues Better definition of
myocyte damage USE INJURY (injury, necrosis,
encroachment, architectural distortion Use the
Word Damage (clarify to cardiologists and
surgeons why) Grade 0 no evidence of cellular
rejection Grade 1A focal perivascular or
intersitial infiltrate without injury Grade 1B
multifocal or diffuse sparse infiltrate without
injury Grade 2 - one focus of dense infiltrate
with injury Grade 3A - multifocal dense
infiltrates with injury Grade 3B - diffuse,
dense infiltrate with injury Grade 4 - diffuse
and extensive polymorphous infiltrate with
injury may have hemorrhage, edema, and
microvascular injury Qualify any defining term
in the text no in table If not Quilty then use
sectioning, trichrome, RANTES (CD68)
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Goals II

• Humoral rejection in the heart
• It is real. But we dont have a consensus on
  Definition
• We MUST strive to recognize it early
• We must define start point of criteria
• What to use?
• Fibrin, Fibrinogen, IgG, IgM, IgA, C1q, C3, C4d,
  CD68, CD34, HLA-DR
• In the discussion the working formulation add
• What to do with the subset of patients who have
  Grades 0 to 1A or B
• and cardiac dysfunction
• Definition of Humoral rejection The group
  agrees that humoral rejection is an entity that
  needs to be better defined. No standardized
  pathologic criteria exist. The following
  pathologic features have been suggested
• 1. Light microscopic findings
• A. intravascular PMNs and macrophages with or
  without endothelial swelling
• B. Vasculocentric lymphocyte poor inflammtory
  infiltrate.
• C. Myocyte injury including necrosis .
• IF (Immunoglobulins / complement / (fibrin
  HLA-DR)

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Goals III
Revisit cumulative experience of 10 years of use
of ISHLT-WF Acute cell mediated vascular
rejection (Vasculitis?) Mononuclear
subendothelial or transmural
inflammatory infiltrate whithin
arterial and arteriolar walls (Not
venules) Investigate Does small vessel injury
reflect vasculopathy?