Role of positive selection of thymoma-associated T cells in the pathogenesis of myasthenia gravis

BACKGROUND: A human thymoma is a thymic epithelial neoplasm and is characterized by its frequent association with myasthenia gravis. The histological characteristic of thymoma is coexistence of a large number of lymphocytes, including CD4(+)CD8(+) double positive T cells, phenotypes of the cortical thymocytes. To elucidate the role of these T lymphocytes in the pathogenesis of thymoma-associated myasthenia gravis, we examined the usage of alphabeta or gammadelta T cell receptor of the T lymphocytes in thymoma in conjunction with the positive selection event. MATERIALS AND METHODS: Thymomas were obtained from 28 patients. Nine patients were associated with myasthenia gravis. Lymphocytes were freshly isolated from the tumor tissue and were subjected to four-color flow cytometric analysis. RESULTS: The average proportion of TCRalphabeta(+) cells in thymomas associated with myasthenia gravis was 47.0% and was significantly higher (P = 0.0008) than that without myasthenia gravis (23.4%). Positive selection event was then examined in terms of CD69, a positive selection marker. The mean proportion of TCRalphabeta(+)CD69(+)CD4(+)CD8(-) cells in the myasthenic thymomas (8.22%) was significantly greater (P = 0.015) than the nonmyasthenic thymomas (2.99%). On the other hand, there was not a significant difference in the mean proportion of TCRalphabeta(+)CD69(+)CD4(-)CD8(+) cells between the myasthenic and the nonmyasthenic thymomas. CONCLUSIONS: The possible role of development of TCRalphabeta(+) T cells, especially the role of positive selection of TCRalphabeta(+)CD4(+)CD8(-) T cells in thymoma, was suggested in the pathogenesis of thymoma-associated myasthenia gravis.     

De novo minimal change disease associated with reversible post-transplant nephrotic syndrome. A report of five cases and review of literature

Nephrotic syndrome (NS) is frequent in renal transplant recipients and may be related to a large variety of glomerular lesions. In some of these cases, the transplant biopsy showed no significant glomerular changes and the NS was reversible, but the primary renal disease was not minimal change disease (MCD), suggesting that MCD may develop de novo in renal transplant setting. Knowledge of this entity, however, is limited. Among 67 cases of post-transplant NS encountered in a 12-yr period, five were found to be associated with de novo MCD. A critical review of the literature revealed nine additional cases of de novo MCD. The data from these 14 cases show that patients with de novo MCD had a large variety of primary renal diseases but MCD or focal segmental glomerulosclerosis was not among them. Eight of the 14 transplanted kidneys (60%) were from living related donors, suggesting this as a risk factor. Nephrotic range proteinuria (3-76 g/d) developed immediately or shortly after transplantation (within 4 months for all reported cases, except for one at 24 months). The serum creatinine when NS was first diagnosed was normal or mildly elevated, but acute renal failure occurred in three patients. On biopsy, the glomeruli were normal or, more frequently, displayed mild, focal segmental mesangial sclerosis, hypercellularity, deposition of IgM/C3, or accumulation of mononuclear inflammatory cells in some glomerular capillaries. The tubulointerstitial compartment was normal in cases with normal renal function; displayed mild acute and/or chronic rejection that correlated with a mildly elevated serum creatinine; or showed acute changes including acute rejection, acute tubular necrosis, or acute cyclosporin A toxicity, which accounted for both acute renal failure at presentation and its subsequent reversibility. Under various treatments, including increased steroids, angiotensin converting enzyme inhibitors, calcium channel blockers and angiotensin receptor blockers, sustained remission of NS was achieved in 13 cases, within a year (0.5-12 months) in 10 and later (24, 34 and 98 months, respectively) in three. In the remaining case, the patient died of septic shock 2 months after transplantation. After remission of the NS, the grafts functioned well without or with minimal proteinuria for several years. De novo MCD has characteristic clinical and pathologic features. It represents an important but hitherto underemphasized cause of post-transplant NS, which is potentially reversible and does not adversely affect the renal transplants.     

Renal transplantation in light chain nephropathy: case report and review of the literature

A successful cadaveric transplantation in a patient with irreversible renal insufficiency due to light chain nephropathy is reported. Remission of the monoclonal gammopathy was induced with melphalan and prednisone and after 4.5 years of hemodialysis a cadaveric kidney transplantation was performed, which resulted in excellent renal function up to 3.5 years after transplantation. Along with 8 previously reported patients in the literature this case demonstrates that renal transplantation can no longer be withheld from this category of patients, when they are in remission and no other major complications of their monoclonal gammopathy are present.     

Prognostic factors for myasthenia gravis treated by thymectomy: review of 61 cases

Background. Medical treatment for myasthenia gravis (MG) involves the use of anticholinesterase agents, immunosuppressive drugs, plasmapheresis, and gammaglobulin. However, these agents result in a complete clinical remission rate as low as 15%. As a consequence, thymectomy, preferably by transsternal approach, has become increasingly accepted as an efficacious procedure for MG, with reported complete clinical remission rates as high as 80%.

Methods. We have the clinical records of 61 patients diagnosed with MG at La Paz University Hospital, Madrid, Spain, from January 1977 to December 1994. All patients underwent thymectomy. The purpose of this investigation was to determine the major prognostic factors predicting MG outcome after operation.

Results. Our results indicate that patients with a length of the disease from onset to operation shorter than 8 months have the best prognosis. Ossermann stages I and III are also associated with higher complete clinical remission rates. In contrast, neither age nor sex were found to be significantly related to MG outcome after thymectomy, although female patients have better prognosis than men, and the younger the patient the more likely is complete clinical remission. Pathologic findings after the operation were not found to be of prognostic value either.

Conclusions. We conclude that thymectomy is a beneficial procedure for MG patients, with a complete clinical remission rate of 46% at 5 years postoperatively in our series. Therefore we advocate thymectomy for MG patients as early as possible in the course of disease because time elapsed from diagnosis to operation is the main determinant of the outcome.     

Germanium-induced nephropathy: report of two cases and review of the literature

We report two cases of renal failure following long-term ingestion of germanium dioxide (GeO2) and comment on eight other cases reported in Japan. Ge-induced nephropathy is characterized by insidious onset of renal failure without proteinuria or hematuria after oral intake of Ge-containing compounds for more than several months, and by degeneration of renal tubular cells with minor glomerular abnormality in histology. When patients ceased to ingest Ge compounds, renal function gradually recovered but never returned to the normal range. Serious extrarenal complication can contribute to an unfavorable prognosis.     

The effect of thymectomy on myasthenia gravis,thrombocytopenia, and granulocytopenia associated with thymoma: Report of a case

We report the case of a 47-year-old woman with thymoma who developed myasthenia gravis, thrombocytopenia, and granulocytopenia, simultaneously, the concurrent association of these four disorders being extremely rare. Thymectomy was performed, and, during the post-thymectomy course, there were surprising findings concerning the recovery of not only the myasthenia gravis but also of the hematologic disorders. Immediately after thymectomy, the myasthenic symptoms completely disappeared, and the granulocyte and platelet counts recovered to within the normal range within a few days. The laboratory data revealed no difference between pre- and post-thymectomy in the release of cytokines (tumor necrosis factor; TNF, interleukin; IL-2, and IL-6), anti-acetylcholine receptor antibody, or platelet-associated IgG. On the other hand, the serum level of anti-neutrophil cytoplasmic antibody (p-ANCA), against the myeloperoxidase of the granulocytes was dramatically decreased, after thymectomy, showing a significant correlation with the granulocyte count. According to our survey of the literature, this is the first report to show that the removal of a thymoma led to the dramatic resolution not only of myasthenia gravis but also of other associated diseases. It is possible that p-ANCA may be regulated by thymoma, thus causing severe granulocytopenia.     

Renal oncocytoma: review of literature and report of six cases

6 cases of renal oncocytomas are described. Preoperative diagnosis is difficult in spite of new clinical diagnostic methods. In our series oncocytoma was diagnosed angiographically in 1 case and in 3 cases carcinoma was suspected. 5 of 6 cases, reevaluated postoperatively, fulfilled three of the four criteria of Ambos et al. for oncocytoma. Ultrasonography is a good exclusion diagnostic method for renal neoplasms. Oncocytoma may be suspected if the tumor projects nearly totally outside the renal contour as we found in 3 of our 6 cases. Aspiration biopsy smears have a diagnostic value in the evaluation of renal neoplasms. Cytologically we preoperatively diagnosed oncocytoma in 1 of 3 cases in which biopsy was performed. We warn, however, about the mosaic pattern of renal neoplasms. Renal cell carcinomas may have large areas composed of oncocytes. Frozen section analysis is a potentially hazardous peroperative diagnostic method in large tumors if oncocytoma is suspected.     

Bullous pemphigoid-associated nephropathy: report of two cases and review of the literature

Bullous pemphigoid has previously been reported in association with a variety of renal lesions. Two additional cases are presented in this report in which the nephropathy preceded the onset of the skin disease: one case with membranous glomerulopathy and one case of renal allograft rejection with concurrent membranous pathology. Both patients had positive immunofluorescence of the skin, typical of bullous pemphigoid. Institution of systemic corticosteroid therapy resulted in a satisfactory clinical response and cessation of the blistering process. These cases and a review of the literature suggest that the occurrence of an immune process involving these two different basement membranes is not merely coincidental. Many cases have been described in which the severity of the skin lesions paralleled that of the renal disease. Although the possibility of multiple distinct autoimmune processes cannot be excluded, anti-basement-zone antibody interactions or allograft rejection-induced immune stimulation are possible unifying mechanisms for the simultaneous skin and renal involvement observed in these two cases.     

Vasculitis associated with septicemia: case report and review of the literature

We report an unusual case in which infectious endocarditis presented systemic vasculitis and glomerulonephritis as the initial manifestation of the disease. The patient was a 16-year-old girl with congenital cyanotic heart disease who presented with skin purpura, proteinuria, and hematuria. She had hypergammaglobulinemia, cryoglobulinemia, and positive circulating immune complexes. Renal biopsy revealed crescentic glomerulonephritis. Her serum C3 level, which was initially normal, became decreased, and prednisolone and azathioprine were administered with a tentative diagnosis of systemic lupus erythematosus (SLE). Soon after, she developed fever and renal failure. Blood culture grew Streptococcus pyogenes, and the diagnosis of infectious endocarditis was made. Eight cases of systemic vasculitis and glomerulonephritis associated with infectious endocarditis have been described in the literature. Infectious endocarditis should be included in the differential diagnosis of systemic vasculitis and glomerulonephritis. Received: 19 March 2001 / Revised: 14 August 2001 / Accepted: 21 August 2001     

Role of thymectomy in the surgical treatment of myasthenia gravis

Of the 26 patients with myasthenia gravis undergone thymectomy, 11 cases had either benign or malignant thymoma as judged not only by hitological examination but also by their clinical and operative findings. Age of initial onset ranged from 13 to 64 years old. Fifteen out of 26 (58 per cent) benefited from thymectomy. Duration of the symptom from the onset to the operation and the presence or absence of the thymoma are not related to their outcome. Benign or malignant nature of thymoma should not be determined by histological examination alone but by combined evaluation of clinical and operative findings. Serial studies of serum immunoglobulin levels before and after thymectomy suggested that this disorder could be associated with humoral antibody (IgG). HLA typing of the patients with myasthenia gravis did not indicate the presence of any specific antigens.     

Renal disease in the Australian Aboriginal population: A pathological study

Summary: End-stage renal failure and clinical evidence of renal disease are more frequent in Australian Aboriginals than in the non-Aboriginal Australian population. to investigate the lesions responsible for this excess a systematic study of renal biopsy findings in a series of Aboriginal patients in South Australia and the Northern Territory was performed and the data on these patients were compared with a consecutive series of renal biopsy findings in non-Aboriginal patients. Histological and morphometric comparison was made between biopsies from 206 Aboriginal and 690 non-Aboriginal patients. the distribution of glomerular lesions was found to differ significantly between the Aboriginal and non-Aboriginal groups: diabetic glomerulosclerosis, idiopathic glomerular enlargement (glomerulomegaly), mesangiocapillary glomeru-lonephritis (MCGN), and non-IgA mesangiopathic glomerulonephritis (GN) were found more frequently in the Aboriginal population, whereas there were fewer than expected examples of thin membrane nephropathy, minimal change disease and membranous GN. Diabetic glomerulosclerosis was significantly more frequent, and the lesions more severe, in Central Australia (where diabetes is more prevalent) and glomerulomegaly was especially common in Bathurst Island. These two conditions accounted for one third of the series and evidence is presented to suggest that a substantial proportion of renal disease in Aboriginals may be the consequence of conversion to a Western life style. of the 206 Aboriginal patients, 23 presented with chronic renal failure, suggesting either late presentation or unusually aggressive renal lesions, and 10 had end-stage renal disease on biopsy.     

Renal allograft tuberculosis: report of three cases and review of literature

Renal transplant recipients are prone to a variety of infections due a persistent immunodepleted state. Incidence of tuberculosis in this population is much higher compared with the general population. While pulmonary tuberculosis still remains the commonest form in this population, renal allograft tuberculosis is very rare. We report two cases of isolated allograft tuberculosis and one case of allograft tuberculosis with coexistent pleuro-pulmonary and bone marrow involvement. All three cases had presented with pyrexia of unknown origin, wherein despite extensive investigations the cause was not found. In two cases the diagnosis was confirmed on histology. Two cases responded to non-rifampicin-based modified antitubercular treatment and one to conventional four-drug Rifampicin-based regimen. Graft function improved in two cases while in one case the graft was lost. Tuberculosis involving the renal allograft is a potential cause for graft dysfunction/loss and requires a high index of suspicion for diagnosis. Timely detection and early institution of therapy can help save the renal allograft.     

Renal disease in POEMS syndrome: report on a case and review of the literature

POEMS syndrome is a multisystem disorder associated with plasmacell dyscrasias. This report describes a patient with POEMS-associatedrenal disease and reviews the literature on biopsy-proven renalinvolvement in POEMS syndrome. Our patient had glomerulonephritiswith membranoproliferative features on light-microscopy withoutcharacteristic findings on immunofluorescence, and with ultra-structural evidence of glomerular microangiopathy. Ultrastructuralevidence of microangiopathy was also found in vasa nervorum.In 20 other cases of POEMS- associated renal disease, 16 hadglomerular disease. Light-microscopy showed membranoproliferative-likeglomerulopathy in 14 patients and glomerular microan giopathyin two. Ultrastructural evidence of microangi opathy was presentin all 15 patients in whom electron- microscopy was done. Thus,in most patients with POEMS-associated glomerular disease acharacteristic lesion is present with evidence of endothelialinjury. As endothelial damage is also found in endoneural vessels,generalized endothelial injury may play a role in non-renalmanifestations of POEMS syndrome. In previous reviews manifestationsof the POEMS syndrome were similar for patients with or withoutmyeloma. Among patients with biopsy-proven glomerular disease,however, myeloma patients are underrepres ented. Whether thisrepresents a sampling error or has true pathophysiological significanceremains to be established.     

Spontaneous remission of congenital nephrotic syndrome: a case report and review of the literature

Spontaneous remission of congenital nephrotic syndrome is rare. We present a 5-week-old infant who developed proteinuria, hypoalbuminemia, and edema which spontaneously resolved with supportive care. Clinical and histopathological features of this patient and six previous reported remissions of congenital nephrotic syndrome are discussed.     

肾嗜酸细胞瘤的诊治(附三例报告及文献复习)

目的　提高肾嗜酸细胞瘤的诊治水平。　方法　回顾分析 3例肾嗜酸细胞瘤患者的临床资料。临床无特异表现 ,肿瘤大小分别为 7.6cm× 8.5cm× 6 .8cm、10 .0cm× 11.5cm× 9.8cm、10 .0cm× 8.0cm× 6 .8cm ,分别位于左肾下极、右肾上极、右肾下极。CT扫描肿瘤密度均匀一致 ,瘤体中央有星状结构。术前均诊为肾癌而行肾癌根治术。　结果　肉眼观察瘤体边界清楚 ,切面呈棕色或棕褐色 ,均质状 ,无出血及坏死灶。光镜下瘤细胞排列成腺泡状或管状 ,胞质含丰富的嗜酸性颗粒 ,细胞无明显异型性和核分裂相。电镜下胞质内见大量线粒体。免疫组化染色 :Cytokeratin( ) ,EMA( ) ,Vimentin(- )。 3例患者随访 16～ 30个月 ,未见肿瘤复发或转移。　结论　肾嗜酸细胞瘤是一种良性实质性上皮肿瘤 ,临床无特异性 ,诊断需依据病理组织学、免疫组化及电镜特点综合判断。     

Membranoproliferative glomerulonephritis in two siblings: report and literature review

There is evidence of a genetic basis in some cases of idiopathic membranoproliferative glomerulonephritis (MPGN) types I and III, particularly those occurring in families. The clinical and morphological features and disease course in two siblings with MPGN are described. In the male sibling, both clinical and morphological features as well as serum complement profile suggested type I MPGN; electron microscopy appearance in the female sibling was consistent with type III MPGN. Both patients had treatment-resistant nephrotic syndrome which evolved into renal insufficiency in the girl. No hereditary complement deficiencies were found in siblings or their parents. Both children exhibited HLA-A24; -B27, w4; -DR11, 52; -DQ3 antigens. Between 1981 and 1996, 18 patients from eight families with unequivocal diagnosis of MPGN I or III had been described. The mode of inheritance appeared to be autosomal dominant or X-linked in four of these families. In 11 patients, including our 2, in whom HLA typing was performed, eight had the HLA-A2 antigen. Similarities and discrepancies regarding clinical and morphological features and outcomes were evident in these intrafamilial cases, suggesting either a similar genetic background or a multigenic origin of MPGN. The familial occurrence of the MPGN, highlighted by our report, supports the concept that genetically determined factors may be involved in the pathogenesis of the disease. Received: 2 September 1998 / Revised: 10 August 1999 / Accepted: 13 August 1999     

Renal hemangiopericytoma: case report and review of the literature

Hemangiopericytoma is an uncommon perivascular tumor that occurs most frequently in the pelvis, head and neck, and meninges; it is extremely rare in the kidney. We report a kidney hemangiopericytoma in a 43-year-old woman who was treated with a nephron-sparing surgery and review the literature.