HISTOPATHOLOGY OF PANCREAS TRANSPLANTATION

Cinthia B. Drachenberg, M.D.University of Maryland

School of Medicine

PANCREAS TRANSPLANTATION 19,000, October 2002 (IPTR)

PANCREAS TRANSPLANTATION

PANCREAS TRANSPLANTATION

Graft survival rates continue to improve Simultaneous pancreas-kidney 85% Pancreas after kidney 77% Pancreas transplant alone 73%

Patient survival at one year >94%

HISTOPATHOLOGY OF PANCREAS TRANSPLANTATION

12 years since the first

percutaneous biopsies were

performed (Allen et al. Transplantation

1991;51: 1213).

1000 pancreas transplant bx at the

Univ. of Maryland since 1992

Experimental models of acute pancreas allograft rejection SEPTAL INFLAMMATION

VENOUS ENDOTHELIITIS AND INFLAMMATION OF DUCTS

ACINAR INFLAMMATION INFLAMMATION OF ARTERIAL

BRANCHESAllen et al: Am J Pathol 1991,138:303Schulak et al: Surgery 1995,98:330.Steineger et al: Am J Pathol 1986,124:253.Carpenter et al: Transplantation 1989,48:764.

GRADING ACUTE REJECTION

0 No inflammationI Minimal septal inflammationII Venous endotheliitisIII Acinar inflammationIV Arterial endotheliitis/

transmural arteritisV Parenchymal necrosis

(Drachenberg et al.: Transplantation 1997;63:1579-86)

PANCREAS TRANSPLANT NEEDLE BIOPSY

Minimum tissue amount adequate for diagnosis in a needle biopsy: Two lobules with associated septal tissue

(arteries,veins, ducts).

H&E stained sections x3 Masson’s trichrome stain Unstained slides

Rates in graft loss due to rejection by era (IPTR)

Comparison between the first 100 and the last 100 biopsies

First 100 Last 100Ac Rej Grade 0 15 29Ac Rej Grade I 9 8Ac Rej Grade II 12 8Ac Rej Grade III 44 28Ac Rej Grade IV 7 3Ac Rej Grade V 5 0

Total Acute RejTotal Acute Rej 68%68% 39%39%

March 2002

April 2002

May 2002

ACUTE AND CHRONIC REJECTION OVER TIME IN A TYPICAL CASE OF GRAFT LOSS

012345

5 10 15 20 25 30

TIME IN MONTHS

RE

JEC

TIO

N

GR

AD

ES

Acute Rej

Chronic Rej

(Papadimitriou et al.: AJT May 2003)

PANCREAS TRANSPLANTS: GRADING OF CHRONIC REJECTION/GRAFT SCLEROSIS

Chronic rejection Grade 0

Normal septa

PANCREAS TRANSPLANTS: GRADING OF CHRONIC REJECTION/GRAFT SCLEROSIS

Chronic rejection Grade I

Fibrosis in <30% of core

Center of the lobules intact

PANCREAS TRANSPLANTS: GRADING OF CHRONIC REJECTION/GRAFT SCLEROSIS

Chronic rejection Grade II

Fibrosis in 30-60% of core

Center of the lobules

shows fibrosis

PANCREAS TRANSPLANTS: GRADING OF CHRONIC REJECTION/GRAFT SCLEROSIS

Chronic rejection Grade III

Extensive fibrosis in >60% of core

Minimal residual parenchyma

CHRONIC REJECTION GRADE IN RELATIONSHIP TO TIME ELAPSED POST-TX AND TIME OF REMAINING GRAFT FUNCTION

0

5

10

15

20

25

30

35

40

45

50

55

0 I II III

CHRONIC REJECTION GRADE

TIM

E IN

MO

NTH

S

TIME POST- TX

REMAINING TIME OFGRAFT FUNCTION

GRADO DE RECHAZO CRONICO EN RELACION AL TIEMPODESDE EL TRANSPLANTE Y EN RELACION AL TIEMPO

RESIDUAL DE FUNCION PANCREATICA

Comparison between the first 100 and the last 100 biopsies

First 100 Last 100

Ch Rej Grade I 3 14Ch Rej Grade II 1 5Ch Rej Grade III 0 4

Total Chronic RejTotal Chronic Rej 4%4% 23%23%

HISTOPATHOLOGY OF PANCREAS TRANSPLANTATION In comparison to other solid organ transplants, less is

known. This pathology field continues to evolve together with the clinical and surgical advances in pancreas transplantation.

Has been a very important tool for the improvement of patient and graft outcomes, particularly in solitary pancreas transplantation.