Papadimitriou Jc

The Maryland aggregate pathology index: a deceased donor kidney biopsy scoring system for predicting graft failure.

Despite the common use of diagnostic pretransplant deceased donor kidney biopsy, there is no consensus on the prognostic significance of the pathologic findings. In order to assist clinicians with interpretation we analyzed 371 pretransplant biopsies and correlated the findings with graft failure. Glomerular pathology was assessed with percent glomerulosclerosis (GS), glomerular size and periglomerular fibrosis (PGF); vascular pathology with arterial wall‐to‐lumen ratio (WLR) and arteriolar hyalinosis and interstitial pathology with measurement of cumulative fibrosis and presence of scar. Using two‐thirds of the study population as a model‐development cohort, we found that biopsy features independently associated with an increased risk of graft failure were GS ≥15%, interlobular arterial WLR ≥0.5 and the presence of PGF, arteriolar hyalinosis or scar. The Maryland Aggregate Pathology Index (MAPI), was developed from these parameters and validated on the remaining one‐third of the population. Five‐year actuarial graft survival was 90% for kidneys with MAPI scores between 0 and 7, 63% for scores from 8 to 11 and 53% for scores from 12 to 15 (p < 0.001). We conclude MAPI may help transplant physicians estimate graft survival from the preimplantation biopsy findings, in clinical situations similar to this study population (cold ischemia over 24 h, GS < 25%).

Early Withdrawal of Calcineurin Inhibitors and Rescue Immunosuppression with Sirolimus-Based Therapy in Renal Transplant Recipients with Moderate to Severe Renal Dysfunction

Mammalian Target‐of‐Rapamycin inhibitors (mTOR inhibitors) can be used to replace the calcineurin inhibitors (CNIs) to prevent progression in chronic kidney disease (CKD) following organ transplantation. Discontinuation of tacrolimus in 136 recipients of kidney transplants with progressive renal dysfunction significantly decreased the rate of loss of estimated glomerular filtration rate (eGFR, mL/min/1.73 m2) (pre‐intervention vs. post‐intervention slopes, −0.013 vs. −0.002, p < 0.0001). Discontinuation of tacrolimus was associated with a sustained and significant improvement in graft function (pre‐eGFR vs. post‐eGFR; 26.0 ± 1.1 vs. 47.4 ± 2.1, p < 0.0001) in 74% of patients. This intervention was ineffective if the mean and (median) values of creatinine (mg/dL) and eGFR were 3.8 ± 0.2 (3.4) and 18.4 ± 1.9 (22.4), respectively, at the time of conversion therapy. During the follow‐up (range, 1.5–34.6, months), a total of 13 patients had their first acute rejection following the conversion therapy, an annual incidence of less than 10% and none of these episodes resulted in graft loss. The salutary effects of sirolimus therapy following discontinuation of tacrolimus in patients with moderate to severe graft dysfunction due to allograft nephropathy even in high‐risk patients improves kidney function and prevents acute rejection.

CMV allograft pancreatitis: diagnosis, treatment, and histological features.

BACKGROUND Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. METHODS We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. RESULTS Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. CONCLUSION Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

Oral myoepithelioma of soft tissue origin: report of a new case and literature review

Oral myoepithelioma of soft tissue origin, an entity distinct from myoepithelioma of salivary glands, constitutes an extremely rare benign neoplasm, with only 1 previously published case, affecting the tongue of a 22-year-old woman. Ectomesenchymal chondromyxoid tumour (ECT) also is a very rare benign neoplasm of the oral cavity that has a strong predilection for the anterior dorsum of the tongue. The great similarities in the histologic and immunohistochemical characteristics of soft tissue myoepithelioma (STM) and ECT probably indicate that they refer to the same or closely related pathologic entities. The aim of this paper is to report a new case of STM affecting the dorsal tongue of a 45-year-old man. A review of the relevant literature is made and the relationship between oral STM and ECT discussed.

Liver metastases of pancreatic acinar cell carcinoma with marked nuclear atypia and pleomorphism diagnosed by EUS FNA cytology: a case report with emphasis on FNA cytological findings.

Background Acinar cell carcinoma of the pancreas is a rare neoplasm. Although this tumor has been well characterized histologically, the morphological patterns in Fine Needle Aspiration Cytology have not been well defined. Unlike ductal adenocarcinomas, endocrine tumors, and solid pseudopapillary tumors of the pancreas with their characteristic FNA cytological features, acinar cell carcinomas pose a particular diagnostic challenge by sharing many cytomorphologic features with endocrine tumors of the pancreas. Case presentation A 37-year-old man presented with lower chest and left upper quadrant abdominal pain. Computed tomography revealed a 7.8 × 7.3 cm irregular, partially cystic mass in the body and tail of the pancreas, and two lesions in the liver compatible with metastases. Subsequently, the patient underwent endoscopic ultrasound-guided fine needle aspiration on one of the two metastatic liver masses. FNA cytology revealed abundant, loosely cohesive clusters of malignant epithelial cells with vaguely acinar and trabecular formations. The pleomorphic nuclei had fine granular chromatin and occasionally small nucleoli. There were scant to moderate amounts of cytoplasm. Scattered, strikingly large tumor cells with giant nuclei, prominent mitoses and associated necrosis were evident. A pancreatic endocrine tumor was suspected initially, but acinar cell carcinoma of the pancreas was confirmed by immunohistochemistry, cytochemical and ultrastructural studies. Conclusion We describe a case of pancreatic acinar cell carcinoma with unusual cytomorphologic features mimicking an endocrine tumor of pancreas, encountered in endoscopic ultrasound-guided fine needle aspiration of a metastatic liver mass and discuss the diagnostic approach for this unusual pancreatic tumor in fine needle aspiration cytology.

Ultrastructural features of long-term renal allografts.

In recent years there has been significant improvement in the short-term survival of renal allografts. This progress has resulted from the use of new potent immunosuppressive drugs and from better understanding of the immunopathological mechanisms involving acute allograft rejection. With passage of time, however, the function of most renal allografts progressively declines. The pathological features of this clinical syndrome, so-called chronic allograft nephropathy (CAN), are considered nonspecific and consist of interstitial fibrosis/tubular atrophy, glomerulosclerosis, and fibrointimal proliferation of intrarenal arteries. Although the pathogenesis of the progressive renal sclerosis seen in long-term renal allografts is not completely understood, the pathogenetic mechanisms of CAN are conventionally classified in two broad categories: immune and nonimmune. The link with immune mechanisms comes from the association of CAN with previous episodes of acute rejection and with the degree of histocompatibility mismatch. However, the relationship of acute allograft rejection with CAN is not absolute, and there is little evidence that newer immunosuppressive regimens have effectively reduced the incidence and severity of CAN. The putative nonimmune factors associated with CAN include poor quality of kidney at transplantation, cold ischemia time, delayed graft function and acute tubular necrosis, donor– recipient size mismatch, older donor age, hyperlipidemia, and hypertension. This review outlines the most important light microscopic and ultrastructural features of long-term allografts in glomeruli, tubules, and vessels. We emphasize that electron microscopy is indispensable in the evaluation of these longterm grafts.