A very early and acute renal impairment due to polyomavirus allograft nephropathy.

Polyomavirus-associated nephropathy (PVAN) has become an important cause of graft loss in the last few years. The typical course of PVAN is characterized by an asymptomatic period of viruria followed, within weeks, by the development of viremia in the context of stable renal function. The persistence of viral replication characterized by high viremia, leads to parenchymal injuries and causes the development, within months, of PVAN that could lead to deterioration in graft function and graft loss. We reported, in a patient who received a renal transplant, an unusual presentation of PVAN characterized by the development of acute renal failurte earlier than would be expected after transplantation, where the histological presentation alone could be confused with an acute rejection. We underline the importance of the association of histological findings with the viral load in urine and blood and with ancillary techniques such as immunohistochemistry and polymerase chain reaction (PCR) in situ for virus detection. We also want to emphasize that decoy cells and PCR for BK virus DNA research could be considered among the diagnostic tools for possible acute renal failure in kidney transplant.

[Atheroembolic renal disease]. / La malattia renale ateroembolica.

Atheroembolic renal disease can be defined as renal failure due to occlusion of the renal arterioles by cholesterol crystal emboli usually dislodged from ulcerated atherosclerotic plaques of the aorta. Atheroembolic renal disease is part of multisystem disease, since the embolization usually involves other organ systems such as the gastrointestinal system, central nervous system, and lower extremities. The kidney is frequently involved because of the proximity of the renal arteries to the abdominal aorta, where erosion of atheromatous plaques is most likely to occur. Embolization may occur spontaneously or after angiographic procedures, vascular surgery, and anticoagulation. In the last decade, atheroembolic renal disease has become a recognizable cause of renal disease. An ante-mortem diagnosis of the disease is possible in a significant proportion of cases as long as the level of diagnostic suspicion is high. The disease can severely affect kidney and patient survival. Although no specific treatment has been proven efficacious, use of statins may be justifiable and such therapy would be a reasonable choice for future treatment trials.

[Renal involvement in systemic sclerosis]. / Sclerosi sistemica e coinvolgimento renale.

Systemic sclerosis is an autoimmune disease characterized by fibrosis of the skin and internal organs. Raynaud's phenomenon generally precedes other disease manifestations. The distribution of skin lesions and the internal organ involvement are the basis for the classification into limited and diffuse forms of the disease. Clinically evident renal disease is observed in 10-40% of patients. The most common renal presentation is renal crisis, characterized by acute onset of renal failure and severe hypertension; some patients remain normotensive, showing microangiopathic hemolytic anemia. Renal complications due to penicillamine may occur in some patients. Finally, ANCA-associated glomerulonephritis is a rare complication of the disorder. In spite of treatment with ACE inhibitors, 20-50% of patients with renal crisis progress to end-stage renal disease. In the absence of a specific therapy, there is accumulating evidence supporting the effectiveness of prostacyclin derivatives, antifibrotic and immunosuppressive drugs. The evidence is strong that the ACE inhibitors that are used in renal crisis are disease modifying. In our series including 193 patients with systemic sclerosis, renal involvement was observed in 19 patients; 11 presented renal crisis (hypertensive in 8; normotensive in 3); 5 had chronic nephropathy; 2 developed penicillamine-induced nephrotic syndrome, and 1 ANCA-associated glomerulonephritis. Renal disease occurs in a minority of patients with systemic sclerosis, and may have a variable clinicopathological picture. As renal involvement is associated with a worse prognosis, careful monitoring of blood pressure, urine chemistry and renal function is required, particularly in patients with diffuse skin disease.

Renal angiomyolipoma with epithelioid sarcomatous transformation and metastases: demonstration of the same genetic defects in the primary and metastatic lesions.

Angiomyolipoma (AML) is a benign neoplasm that occurs either sporadically or in patients with tuberous sclerosis complex (TSC) and shows frequent allelic losses at chromosome arm 16p. It has been suggested recently that the melanogenesis marker-positive perivascular epithelioid cell (PEC) has been found consistently in AML. The authors report a 50-year-old woman without evidence of TSC affected by classic renal AML containing an area composed of atypical epithelioid cells with the same morphoimmunophenotypic characters of PEC. After 7 years from surgical removal of the lesion, the patient developed a local recurrence and successive lung and abdominal metastases that showed morphologic and immunohistochemical features overlapping those of the epithelioid area of the previously removed AML. Genetic analysis showed that the classic AML and its epithelioid area as well as the pulmonary and abdominal metastases shared the same allelic loss on chromosome arm 16p. Based on these findings, the authors view this case as evidence of a malignant transformation of a classic AML with morphologic, immunophenotypic, and genetic demonstration of its clonal origin.

Cholesterol crystal embolism: A recognizable cause of renal disease.

Cholesterol crystal embolism, sometimes separately designated atheroembolism, is an increasing and still underdiagnosed cause of renal dysfunction antemortem in elderly patients. Renal cholesterol crystal embolization, also known as atheroembolic renal disease, is caused by showers of cholesterol crystals from an atherosclerotic aorta that occlude small renal arteries. Although cholesterol crystal embolization can occur spontaneously, it is increasingly recognized as an iatrogenic complication from an invasive vascular procedure, such as manipulation of the aorta during angiography or vascular surgery, and after anticoagulant and fibrinolytic therapy. Cholesterol crystal embolism may give rise to different degrees of renal impairment. Some patients show only a moderate loss of renal function; in others, severe renal failure requiring dialysis ensues. An acute scenario with abrupt and sudden onset of renal failure may be observed. More frequently, a progressive loss of renal function occurs over weeks. A third clinical form of renal atheroemboli has been described, presenting as chronic, stable, and asymptomatic renal insufficiency. The renal outcome may be variable; some patients deteriorate or remain on dialysis, some improve, and some remain with chronic renal impairment. In addition to the kidneys, atheroembolization may involve the skin, gastrointestinal system, and central nervous system. Renal atheroembolic disease is a difficult and controversial diagnosis for the protean extrarenal manifestations of the disease. In the past, the diagnosis was often made postmortem. However, in the last decade, awareness of atheroembolic renal disease has improved, enabling us to make a correct premortem diagnosis in a number of patients. Correct diagnosis requires the clinician to be alert to the possibility. The typical patient is a white man aged older than 60 years with a baseline history of hypertension, smoking, and arterial disease. The presence of a classic triad characterized by a precipitating event, acute or subacute renal failure, and peripheral cholesterol crystal embolization strongly suggests the diagnosis. The confirmatory diagnosis can be made by means of biopsy of the target organs, including kidneys, skin, and the gastrointestinal system. Thus, Cinderella and her shoe now can be well matched during life. Patients with renal atheroemboli have a dismal outlook. A specific treatment is lacking. However, it is an important diagnosis to make because it may save the patient from inappropriate treatment. Finally, recent data suggest that an aggressive therapeutic approach with patient-tailored supportive measures may be associated with a favorable clinical outcome.

HBsAg, HBcAg and delta-Ag in liver tissue: simultaneous visualization in a single tissue section by triple immunostaining.

The distribution pattern of HBsAg, HBcAg and Delta-Ag was investigated by immunohistochemistry in a series of paraffin embedded liver tissue specimens from 45 subjects with serum HBsAg and anti-Delta antibody positivity. An indirect immunoperoxidase technique was used. Stains for HBsAg, HBcAg and Delta-Ag were alternatively carried out on serial tissue sections and, for the first time, consecutively in a single section (triple immunostaining). Simultaneous presence of all antigens occurred in 7 out of 45 cases, and of two antigens (HBsAg and Delta-Ag) in the remaining 38. Two antigens (either HBsAg and HBcAg or HBcAg and Delta-Ag) could also be shown in the same cell. A series of new observations was forwarded by the successful application of triple immunostaining in the present series: 1) high frequence of simultaneous presence of HBcAg and Delta-Ag (7 out of 45 cases = 16%); 2) cytoplasmic localization of Delta-Ag; 3) localization of HBcAg on the cell membrane of HBsAg positive Ground-Glass (G-G) hepatocytes; 4) Ground-Glass appearance of hepatocytic cytoplasm associated with exclusive content of HBcAg (HBcAg-Ground-Glass: a new variant of G-G-hepatocytes).

Multitechnical pathological diagnosis in chromophobe renal cell carcinoma.

Two new cases of chromophobe renal cell carcinoma were diagnosed on the basis of their morphology and their karyotype complemented by flow cytometry. In one of these cases, however, all these investigations were not sufficient and additional histochemistry investigation had to be used to completely rule out other renal tumors such as oncocytoma, the prognosis of which is totally different.

PNA: a marker of neoplastic progression and differentiation in the gastro-intestinal tract.

We examined 35 cases of stomach carcinoma and 40 cases of colonic carcinoma with PNA associated with peroxidase (peanut agglutinin, lectin which binds to the terminal disaccharide galactose beta (1,3)-N-acetil-galacto-samine). In this way evaluation of the functional aspects of the normal-neoplastic sequence was undertaken. This method was carried out for histological and ultrastructural investigations. The results obtained in both cases showed a different reactivity in the evolution of neoplastic disease: in fact, positivity in dysplasia is finely granular intracytoplasmic, whereas in well-differentiated neoplastic transformation such a reactivity is preferentially localized along the cellular membranes, with restoration of gross positivity in the cytoplasm for the poorly-differentiated neoplasm. We therefore believe PNA to be a marker not only of neoplastic progression but of differentiation as well: we also hypothesize it to reveal glycoprotein groups with possible antigenic power, involved in immunologic interactions between tumor and host.

Experience with cyclosporine.

Six hundred thirty-eight cadaveric kidney transplant patients between 1983 and 2001 were treated with cyclosporine (CsA) for 87 +/- 58 months. Among 571 patients with follow-up greater than 12 months, the 15-year renal function was investigated to assess the probability of a >30% increase in serum creatinine (sCr) above the month-6 value (baseline) and the impact on graft survival. At 15 years, patient and graft survival rates were 82.7% and 56.1%, respectively, with a 19.5-year half-life (censored for deaths). The main causes of graft loss were chronic rejection (33.0%) and patient death (24%). Cardiovascular disease and neoplasms were the main causes of death. Renal function remained stable in 266 patients (46.6%) with excellent sCr values observed even after a 15-year treatment period. An increased sCr was observed in 305 patients (53.4%) with a 15-year probability of 74%. In 178 patients (59.3%) it was self-limited; their grafts are still functioning well. One hundred three patients (32.8%) lost their graft which was more likely when the sCr had increased >45%. Twenty-four patients (7.9%) died with a functioning graft. Multivariate analysis showed the progression of graft deterioration to be related to proteinuria (P<.0001), a late acute rejection episode (P<.002), or the extent of sCr increase (P<.008). In conclusion, the long-term use of CsA has allowed us to achieve excellent long-term patient and transplant survival rates. Our data indicate a high 15-year probability of an increased sCr, but the rate of progression is slow.

Association between silica exposure and necrotizing crescentic glomerulonephritis with p-ANCA and anti-MPO antibodies: a hospital-based case-control study.

A hospital-based case-control study was carried out to investigate the association between ANCA positive rapidly progressive glomerulonephritis (RPGN) and occupational exposure to silica dust. All ANCA positive male patients admitted to the Department of Nephrology of the University of Brescia between 1987 and 1992 were enrolled in the study as cases. The controls were pts of the same age, admitted at the Department immediately before or after the cases, affected by other renal diseases. Seven of the 16 cases and one of the 32 controls, had a positive history for jobs exposing to silica dust (relative risk 14; 95% C.I.: 1.7-113.8, p < 0.001). ANCA pattern was p-ANCA with anti-MPO antibodies in 6/7 of exposed pts. The review of renal histology showed a distinctive glomerular lesion consisting in peripheral nodular areas of glomerular sclerosis, in addition to the crescentic necrotizing glomerulonephritis, in 3/6 silica exposed pts, but in none of the unexposed pts.

[Carcinoma of the penis: anatomo-pathologic features]. / Il carcinoma del pene: aspetti anatomo-patologici.

The squamous carcinoma is the most frequent neoplasia of the penis. On the pathological point of view the following parameters are used: anatomical location, histologic grade, anatomic level of infiltration, depth of infiltration, perineural and vascular invasion, surgical margins of resection and pathological type. We distinguish four clinicopathological types of squamous carcinoma of the penis, with distinctive macroscopic, microscopic and biologic features.

[Prognostic factors in organ-confined renal epithelial tumors]. / Fattori prognostici nei tumori renali epiteliali organo-confinati.

Recent application of molecular cytogenetic techniques to the evaluation of epithelial renal cell tumors have showed some characteristic combinations of genetic alterations within the chromosomal DNA. Moreover each group of abnormalities has been correlated with peculiar tumor morphology. The new classification of renal cell neoplasms proposed by G. Kovacs, based on specific genetic alterations, and histologic pattern, together with the morphologic and pathologic features that correlate with survival has been discussed.

[Clinical anatomical features of chronic dysfunction in the transplanted kidney]. / Aspetti anatomo clinici della disfunzione cronica del rene trapiantato.

Histopathological features of transplanted kidneys which gradually lose graft function have been traditionally reported with the term of chronic rejection (CR). In 1997 Banff's classification indicated the adoption of a new term for all these histological features, namely Chronic allograft nephropathy (CAN), recommending that the presence of morphological aspects suggestive of chronic rejection, such as chronic transplant glomerulopathy (CTG) and proliferative endoarteritis (PE), has to be specified. On the basis of these criteria we reviewed the renal biopsies of 92 patients who underwent kidney transplantation from 1999 to 2002. In all cases the biopsy had been performed 6 months after organ transplantation. In 30 of the 92 patients CTG and/or PE was evident supporting a diagnosis of CR; on the contrary, in 11 of the 92 patients the final diagnosis based on histological evidence was that of CAN. Clinical and laboratory tests revealed that the presence of proteinuria in patients with CR at the time of diagnosis was the single statistically significant difference between these two groups. In 7 of the 32 patients where the diagnosis of CR was based on the presence of early features of CTG, the treatment with ACE-I induced complete remission of the proteinuria. Cyclosporine-induced arteriolopathy (CSA) represents an additional histological finding which has been associated with graft loss in the transplanted kidney. The observation of arteriolopathy, similar to CSA in patients who did not receive calcineurine inhibitors, suggests some caution in the use of this diagnostic criteria.

Predicting prostate cancer at rebiopsies in patients with high-grade prostatic intraepithelial neoplasia: a study on 546 patients.

The aim of this study was to analyse the factors that predict the diagnosis of prostate cancer (PCa) after high-grade prostatic intraepithelial neoplasia (HGPIN). Data from 546 patients with HGPIN submitted up to a 6-month series of three rebiopsies, according to an institutional protocol, were reviewed. PCa has been found in 174 cases (31.8%), in 116 cases at the first and in 58 cases at a further rebiopsy. The risk of finding PCa at the first rebiopsy was correlated with the PSA value and with an anomalous digital rectal examination (DRE) at the time of the initial biopsy; the risk at a subsequent rebiopsy was correlated to the number of cores with HGPIN, with a cutoff of four, and to the ratio with the total number of cores ('PIN density'), with a cutoff of 50%, at the time of initial biopsy. A tailored protocol of controls can be suggested: (a) higher PSA value and/or anomalous DRE: early extended or saturation rebiopsy; (b) number of cores with HGPIN ≥4 and/or PIN density ≥50%: delayed rebiopsy; and (c) no risk factors: PSA and DRE controls.