James Gough

Neointimal and Tubulointerstitial Infiltration by Recipient Mesenchymal Cells in Chronic Renal-Allograft Rejection

BACKGROUND Tissue remodeling depends on mesenchymal cells (fibroblasts and myofibroblasts) and is a prominent feature of chronic renal-transplant rejection. It is not known whether the mesenchymal cells that participate in remodeling originate locally or from circulating precursor cells. METHODS We obtained biopsy specimens of renal allografts from six male recipients of an allograft from a female donor, four female recipients of an allograft from a male donor, two male recipients of an allograft from a male donor, and two female recipients of an allograft from a female donor. All the allografts were undergoing chronic rejection. All but two specimens were obtained within six months after transplantation. We used immunohistochemical methods to identify mesenchymal cells with smooth-muscle alpha-actin and in situ hybridization to identify mesenchymal cells with Y-chromosome DNA. RESULTS No Y-chromosome bodies were identified in the case of the two renal-allograft specimens in which both the donor and the recipient were female. In the case of the two renal-allograft specimens in which both the donor and the recipient were male, approximately 40 percent of mesenchymal cells contained a Y-chromosome body. In the case of the six specimens in which the donor was female and the recipient was male, a mean (+/-SD) of 34+/-16 percent of mesenchymal cells in the neointima, 38+/-12 percent of such cells in the adventitia, and 30+/-7 percent of such cells in the interstitium contained the Y-chromosomal marker, indicating that they originated from the recipient rather than the donor. In the case of the four renal-allograft specimens in which the donor was male and the recipient was female, the respective values were 24+/-15 percent, 33+/-9 percent, and 23+/-8 percent, indicating a persistent population of donor mesenchymal cells. CONCLUSIONS The presence of mesenchymal cells of host origin in the vascular and interstitial compartments of renal allografts undergoing chronic rejection provides evidence that a circulating mesenchymal precursor cell has the potential to migrate to areas of inflammation.

Peritubular capillary basement membrane reduplication in allografts and native kidney disease: A clinicopathologic study of 278 consecutive renal specimens

Background. An association has been found between transplantglomerulopathy (TG) and reduplication of peritubular capillary basementmembranes (PTCR). Although such an association is of practical and theoreticalimportance, only one prospective study has tried to confirmit. Methods. We examined 278 consecutive renal specimens (from 135transplants and 143 native kidneys) for ultrastructural evidence of PTCR. Inaddition to renal allografts with TG, we also examined grafts with acuterejection, recurrent glomerulonephritis, chronic allograft nephropathy andstable grafts (“protocol biopsies”). Native kidney specimensincluded a wide range of glomerulopathies as well as cases of thromboticmicroangiopathy, malignant hypertension, acute interstitial nephritis, andacute tubularnecrosis. Results. We found PTCR in 14 of 15 cases of TG, in 7 transplantbiopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens.These 13 included cases of malignant hypertension, thrombotic microangiopathy,lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis,and cocaine-related acute renal failure. Mild PTCR in allografts without TGdid not predict renal failure or significant proteinuria after follow-upperiods of between 3 months and 1year. Conclusions. We conclude that in transplants, there is a strongassociation between well-developed PTCR and TG, while the significance of mildPTCR and its predictive value in the absence of TG is unclear. PTCR alsooccurs in certain native kidney diseases, though the association is not asstrong as that for TG. We suggest that repeated endothelial injury, includingimmunologic injury, may be the cause of this lesion both in allografts andnativekidneys.

PROTOCOL BIOPSIES IN RENAL TRANSPLANTATION : RESEARCH TOOL OR CLINICALLY USEFUL ?

Early protocol biopsies of stable, well functioning renal allografts reveal a high prevalence of clinically unsuspected acute and chronic pathology. It is becoming increasingly apparent that these histopathological findings are both pathogenic and predictive of long-term allograft outcome. Therefore, protocol biopsies may be required for optimal post-transplant surveillance until non-invasive methods to detect allograft inflammation are developed.

Fine needle aspiration biopsy diagnosis of a gastrointestinal stromal tumor utilizing transmission electron microscopy

BACKGROUND Gastrointestinal stromal tumors are spindle cell tumors with no specific cell lineage occurring in the gastrointestinal tract and cytologically resemble other benign and malignant spindle cell tumors. Distinctive ultrastructural features in some of these tumors have not been previously emphasized. CASE A 76-year-old, white female presented with multiple tumor masses distributed in the large bowel. Fine needle aspiration biopsy demonstrated a cellular aspirate composed of spindle cells, some of which were loosely arrayed and some of which were in cohesive clusters. Many of the cells contained long cytoplasmic processes. Ultrastructurally the cells demonstrated long cytoplasmic processes upon which multiple shorter, fingerlike projections arose. Subsequent surgical resection confirmed the cytologic and ultrastructural findings. CONCLUSION Electron microscopy has a role to play in the diagnosis of gastrointestinal stromal tumors.