Transplant Pathology

HYPERACUTE ALLOGRAFT REJECTION

vessel anastomosis ●● Preformed antibodies in recipient bind to

donor endothelial cells eliciting immune response

●● Complement activation → leads to endothelial cell destruction and thrombosis

ACUTE ALLOGRAFT REJECTION

lymphocytes); mediate direct killing, macrophage activation, and tissue damage

CHRONIC ALLOGRAFT REJECTION

●● Fibrosis and vascular damage, due to repeated episodes of acute rejection

●● Both cell-mediated and humoral mechanisms contribute

ALLOGRAFT TOLERANCE

●● Donor-derived leukocytes participate in allograft tolerance

●● Microchimeras (individuals composed of two or more genetically distinct type of cells) tolerate their allografts better (patients who have received solid organ allograft and partial bone marrow transplant tolerate their allograft better)

●● Patients receiving liver allograft do better (large number of leukocytes from the allografted liver migrate to recipient’s bone marrow and persist)

●● Indication of transplantation: Necrotizing enterocolitis, volvulus, gastroschisis, massive resections, Hirschsprung disease

●● Patients who suffer TPN-associated liver disease (portal hypertension and cirrhosis) usually undergo combined intestinal and liver transplant and do well

●● Size matching of graft is important factor in pediatric population due to smaller abdominal cavity

PRESERVATION INJURY AND HYPERACUTE REJECTION

●● Negligible preservation injury due to villous circulation

●● Hyperacute rejection caused by preformed donor-specific antibodies

●● Damage to endothelium, fibrin thrombi, and congestion within lamina propria

toms: Fever, nausea, abdominal distension ●● Diminished peristalsis, mucosal ulceration ●● Mild rejection: Crypt apoptosis (more than 6

apoptotic figures per 10 crypts), lamina propria inflammation (perivascular infiltrate of lymphocytes), and crypt architectural distortion

●● Moderate to severe rejection: Enhanced morphological features, villous flattening, mucosal ulceration, and features mimicking pseudomembranous colitis

CHRONIC REJECTION

chronic rejection ●● Chronic ischemia (due to arterial obstruc-

tion); destruction of crypts, villi and lamina propria fibrosis

COMPLICATIONS OF TRANSPLANTATION

Infection

●● Common: Bacterial, fungal, and viral (cytomegalovirus [CMV], adenovirus, EpsteinBarr virus [EBV])

●● In severely immunocompromised patients, inflammation is mild

Posttransplant lymphoproliferative disorder (PTLD)

●● Complication of EBV infection seen after intestinal transplant (common)

●● In situ hybridization for EBV early antigen (EBER)

Graft-versus-host disease

●● Most common in intestines, skin, and liver tissue

●● Develops after bone marrow transplant or after transfusion of non-irradiated blood in immunocompromised host

●● Donor leukocytes recognize recipient tissue as foreign and attempt to reject them

Acute GVHD

tion of crypts, apoptosis/vacuolization/ karyorrhexis of crypt epithelial cells

●● Progresses to neutrophilic infiltration, mucosal ulceration, crypt abscess, villous atrophy

●● Immunosuppressive drug for solid organ transplant; Mycophenolate mofetil mimics similar histologic features in intestine

●● Esophagus: Vacuolization and inflammation of basal cell layer progressing to mucosal desquamation and ulceration

Chronic GVHD

and loss of motility

●● Most common indication; extrahepatic biliary atresia (EHBA)

●● Split liver transplant = right trisegment transplanted into adult host and the left lateral lobe transplanted into pediatric host

PRESERVATION (HARVESTING) INJURY

●● Originates from donor and tissue procurement factors

●● Results in poor allograft function during postoperative period

●● Donor risk factors for poor graft function = macrovesicular steatosis (susceptible to ischemic changes), fibrosis, chronic liver disease, donor age

and ALT ●● Centrilobular pallor and cholestasis

mortality rate ●● Late: Coagulative necrosis of centrilobular

hepatocytes/bile duct necrosis

BILIARY COMPLICATIONS

biliary vascular fistula

HYPERACUTE (HUMORAL) REJECTION

●● Preformed cytotoxic antibodies against ABO blood group antigens or class I and II MHC antigens

ACUTE REJECTION

●● Fever, decreased bile flow, and elevated liver enzymes

●● Three diagnostic criteria for rejection: Portal inflammation, subendothelial inflammation, and bile duct damage

●● Mild rejection = portal inflammation is mild

●● Moderate rejection = most portal tracts involved by inflammation

●● Severe rejection = spillover into hepatic parenchyma, hepatocyte necrosis (periportal and perivenular)

●● Rejection activity index (RAI) is usually mentioned in pathologic report

Note: Refer to the Appendix for Rejection activity index (RAI).