In 1990, an international grading system for cardiac allograft biopsies was adopted by the International Society for Heart Transplantation. This system has served the heart transplant community well, facilitating communication between transplant centers, especially with regard to patient management and research. In 2004, under the direction of the International Society for Heart and Lung Transplantation (ISHLT), a multidisciplinary review of the cardiac biopsy grading system was undertaken to address challenges and inconsistencies in its use and to address recent advances in the knowledge of antibody-mediated rejection. This article summarizes the revised consensus classification for cardiac allograft rejection. In brief, the revised (R) categories of cellular rejection are as follows: Grade 0 R--no rejection (no change from 1990); Grade 1 R--mild rejection (1990 Grades 1A, 1B and 2); Grade 2 R--moderate rejection (1990 Grade 3A); and Grade 3 R--severe rejection (1990 Grades 3B and 4). Because the histologic sub-types of Quilty A and Quilty B have never been shown to have clinical significance, the "A" and "B" designations have been eliminated. Recommendations are also made for the histologic recognition and immunohistologic investigation of acute antibody-mediated rejection (AMR) with the expectation that greater standardization of the assessment of this controversial entity will clarify its clinical significance. Technical considerations in biopsy processing are also addressed. This consensus revision of the Working Formulation was approved by the ISHLT Board of Directors in December 2004.

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Pulmonary arterial hypertension (PAH) includes various forms of pulmonary hypertension of different etiology but similar clinical presentation and functional derangement. Histopathological vascular changes in all forms of PAH are qualitatively similar but with quantitative differences in the distribution and prevalence of pathological changes in various portions of the pulmonary vascular bed. The documentation of these topographic variations in the response of the pulmonary vasculature to injury may be important to understand the pathogenesis of the various subsets of PAH. To standardize the precise histopathological documentation of the pulmonary vasculopathy in PAH we propose a histopathological classification that includes both the predominant segment of the pulmonary vasculature affected and the possible coexistence of pathological changes in other vascular segments.

Background-Mutations in the type II receptor for bone morphogenetic protein (BMPR-II), a receptor member of the transforming growth factor-␤ (TGF-␤) superfamily, underlie many familial and sporadic cases of primary pulmonary hypertension (PPH). Methods and Results-Because the sites of expression of BMPR-II in the normal and hypertensive lung are unknown, we studied the cellular localization of BMPR-II and the related type I and II receptors for TGF-␤ by immunohistochemistry in lung sections from patients undergoing heart-lung transplantation for PPH (nϭ11, including 3 familial cases) or secondary pulmonary hypertension (nϭ6) and from unused donor lungs (nϭ4). In situ hybridization was performed for BMPR-II mRNA. Patients were screened for the presence of mutations in BMPR2. In normal lungs, BMPR-II expression was prominent on vascular endothelium, with minimal expression in airway and arterial smooth muscle. In pulmonary hypertension cases, the intensity of BMPR-II immunostaining varied between lesions but involved endothelial and myofibroblast components. Image analysis confirmed that expression of BMPR-II was markedly reduced in the peripheral lung of PPH patients, especially in those harboring heterozygous BMPR2 mutations. A less marked reduction was also observed in patients with secondary pulmonary hypertension. In contrast, there was no difference in level of staining for TGF-␤RII or the endothelial marker CD31. Conclusions-The cellular localization of BMPR-II is consistent with a role in the formation of pulmonary vascular lesions in PPH, and reduced BMPR-II expression may contribute to the process of vascular obliteration in severe pulmonary hypertension.