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.

Humoral rejection (HR) of the cardiac allograft is neither well characterized nor universally recognized in the transplant/pathology-related literature. One reason for this is that the histologic light-microscopic features are inconsistent, making HR difficult to recognize in the majority of cases. We report an unusual case of cardiac allograft rejection in a patient with a complicated postoperative course who ultimately died within 6 months of transplant. Premortem, HR was not diagnosed in multiple cardiac biopsies. The autopsy revealed unequivocal histologic and immunohistochemical evidence of HR. Vascular distension and endocardial infiltration by numerous macrophages were noted only in the cardiac allograft and were notably absent in the native tissue present within the anastomotic sites. There was capillary deposition of immunoglobulin and complement shown by immunofluorescence staining of frozen tissue, and there was diffuse immunohistochemical staining for C4d within the intramyocardial vessels. This case appears to represent an exaggerated antibody-mediated rejection of the cardiac allograft.

Background: Left ventricular assist devices (LVADs) currently are used as bridges for patients who deteriorate clinically while awaiting cardiac transplantation. At the time of transplantation or subsequent death, we can assess the effect of long-term device implantation on cardiac structural changes. We have noted, in our years of experience, that aortic valve commissures may fuse in patients supported by LVADs. These observations may be important in the use of these pumps as long-term destination therapy.Methods: We examined 33 hearts (both explants and autopsy specimens) from patients supported either with vented-electric (VE) HeartMates (n = 21) or with implantable pneumatic HeartMates (n = 12). We noted commissures involved, fusion length (mm), duration of LVAD support, and type of LVAD. As controls, we examined 49 explanted hearts from patients with heart failure who were not supported by LVADs.Results: We found commissural fusion in 17 of the 33 hearts. Of those 17 hearts, 4 (23.5%) had 2 commissural fusions, and 13 (76.5%) had only 1 fusion. Fusion length ranged from 5 mm to 17 mm (mean, 9.9 mm). The lesion was more common in patients fitted with VE HeartMates (p < 0.0002). We found small amounts of commissural fusion in 8 of the 49 control hearts.Conclusions: Acquired commissural fusion is common in patients supported by LVADs, particularly the VE HeartMate. The lesion also occurs occasionally in failing hearts of patients not supported by LVADs. The significance of the lesion in patients who require long-term LVAD support either as a bridge to transplantation or as destination therapy is unclear.

Clear cell lesions of the urinary tract often present diagnostic challenges. We report a previously undescribed lesion in the prostate, occurring in a 73-year-old man who presented with hematuria and subsequently underwent transurethral resection of the prostate. A total of 24 g of tissue was removed, and in 4 of 17 blocks submitted a lesion morphologically and immunohistochemically similar to clear cell carcinoma of the kidney was noted. A thorough cystoscopic and full-body, radiologic workup was performed, but no renal tumor was discovered. Random cystoscopic biopsies of the bladder and prostatic urethra as well as bladder washings were benign. Subsequent needle biopsies of the prostate were also benign. The patient underwent a pelvic lymph node dissection with radical cystoprostatectomy and orthotopic Studer pouch diversion. There was organ-confined, ordinary-type prostatic adenocarcinoma (Gleason's 3 + 3) present bilaterally in the peripheral zone; no residual clear cell carcinoma was identified. All lymph nodes were negative, and the urinary bladder showed no dysplasia or neoplasia. We think this tumor represents a primary renal type of clear cell carcinoma arising in the prostate. To our knowledge, this type of tumor has not been previously reported to arise in an extrarenal location.

A 37-year-old woman with a history of bilateral mesenchymal cystic hamartomata of the lung was subsequently found to have low-grade endometrial stromal sarcoma. Cytogenetic analysis of the uterine tumor revealed, in all metaphases, an unusual derivative chromosome generated by the insertion of chromosome 19 into chromosome 10 at the level of its centromere [ins(10;19)(p11;p13q13)].