Intraepidermal bile pigment in skin biopsy specimens for graft-versus-host disease versus erythema multiforme

The differentiation of graft-verus-host disease (GVHD) from erythema multiforme (EM) presents a common diagnostic challenge in skin biopsy specimens from patients who have received patients allogeneic bone marrow transplants. The presence of gastrointestinal involvement might be the only way to make a diagnosis of GVHD in these cases. In the absence of liver function tests, gastrointestinal biopsy, or molecular techniques such as microsatellite DNA analysis, the presence of intraepidermal bile pigment might prove helpful in elucidating hyperbilirubinemia and allowing a pathologist to favor a diagnosis of GVHD over EM. Routinely processed archival tissue from 50 cases of GVHD (42 Caucasian and 8 of unknown race) and 50 cases of EM (31 Caucasian and 19 of unknown race) was examined for pigmentation. Intraepidermal pigmentation was stained for bile pigment and melanin. Among the intraepidermal EM lesions, 4 (8%) stained for intracorneal melanin, but none stained for bile pigment. Among the intraepidermal GVHD lesions, 8 (16%) stained for intracorneal melanin, but 3 (6%) stained for intracorneal bile pigment. In addition, 13 (26%) GVHD lesions and 9 (18%) EM lesions showed melanosis with melanin in all layers of the epidermis as well as within papillary dermal melanophages. Thus, when presented with a differential diagnosis of GVHD versus EM, the presence of intraepidermal bile pigment might suggest liver involvement and a diagnosis of GVHD.