Graft-Versus-Host Disease (GVH)

Epidemiology and Etiology:

· May occur in any situation where:

· Immunologically competent cells or their precursors are transplanted into an immunologically crippled recipient

· Allogeneic bone marrow transplant most common

· Solid organ transplant rich in lymphoid cells

· Liver

· Transfusion of unirradiated blood

· Degree of HLA mismatch between donor and recipient is an important factor in the severity of GVHD

· Apoptosis of skin, gut, and bile duct epithelium resulting from direct cytotoxicity or indirectly through cytokine-mediated damage

· IL-1 and TNF play an important role in this process

· Acute GVH:

· days to weeks after BM transplant

· chronic GVH:

· 80 to 100 days after transplant

· may follow acute syndrome

· may occur insidiously

· autoimmunity combined with immunodeficiency

· skin most frequently involved

Common sites:

· Skin

· Dermatitis

· Scleroderma

· Liver

· Intestines

· Thymus

· Salivary glands

· Oral mucosa

· Kidney

· lung

· Any organ

·

Gross features:

· Generalized rash leading to desquamation

· Jaundice

· Mucosal ulceration of the gut

· Chronic:

· Sclerotic skin changes

· Esophageal strictures

· Involution of the thymus

Histologic features:

· Considerable tissue damage with relatively light inflammation

· Acute GVH:

· Individual or groups of apoptotic parenchymal cells

· Minimal to moderate lymphocytic infiltrates

· Skin:

· Similar appearance to:

· erythema multiforme,

· early herpetic skin infections,

· direct acute toxicity of chemotherapy or radiation,

· or lichen planus

· Bulla formation in moderately severe cases

· Progresses to total epidermal loss

· Gut:

· Apoptotic crypt cells

· Note CMV should be ruled out with this finding

· Lymphoid infiltration

· Crypt abscesses eventually

· Lamina propria edema associated

· Complete epithelial necrosis may occur

· Liver:

· Apoptosis in bile duct epithelial cells

· Cholestatic hepatitis

· Hepatocytolysis with hepatocellular cholestasis eventually

· Endothelialitis maybe

· Similar appearance to:

· Chronic active hepatitis

· CMV hepatitis

· Veno-occlusive disease from chemotherapy or radiation toxicity

· Chronic GVH:

· Skin:

· Lesions resembling lichen planus and hypertrophic lupus erythematosus

· Epithelial cell necrosis

· Basal cell vacuolar degeneration

· Rare eosinophilic bodies even without inflammatory cells

· May involve appendages

· Extensive cutaneous injury

· Destruction of skin appendages

· Fibrosis of dermis

· Widening of the papillary dermis

· Scleroderma-like changes ultimately

· Similar to systemic sclerosis

· Cholestatic jaundice

· Lymphocytic depletion of lymph nodes and thymus

· Esophagus

· Mucosal ulcerations

· Submucosal fibrosis

· Destruction of submucosal glands

· Gut

· Lamina propria fibrosis

· Mucosal atrophy

· Crypt architectural distortion

· Kidney

· Renal vasculopathy

· Lung

· Bronchiolitis obliterans

· Indistinguishable from chronic allograft rejection

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

·

Other features:

· Bloody diarrhea

· May be fatal

· Immunodeficiency

· Due to direct damage to recipient lymphocytes in sites such as the thymus

· CMV infection is particularly important

· Usually reactivation of a previously silent infection

· CMV pneumonitis can be fatal complication

· Sicca syndrome (80% of patients with chronic GVHD)

· Mouth

· Eyes

· Nose

· Vagina

· urethra

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.

· Silverberg SG, DeLellis RA, Frable WJ, LiVolsi VA, Wick MR. Silverberg's Principles and Practice of Surgical Pathology and Cytopathology: 2-Volume Set. 4th ed. Churchill Livingstone; 2005.