Detection of Minimal Lesion and Identification of Clonality in Malignant Lymphoma

The bone marrow biopsy is an integral part of the staging process in patients with malignant lymphomas. Bone marrow(BM) involvement indicates stage IV disease, but there are always a lot of cases in which clear separation is not possible when based on morphology alone. Additional difficulties are caused by morphologic discordance between the BM and the primary lymphoma. Immunohistochemical stain, mRNA in situ hybridization (ISH) for light chain restriction and polymerase chain reaction (PCR) for IgH CDR3 and TCRgamma were performed to find a minimal lesion and the clonality in formalin fixed paraffin embedded tissues of 39 primary lymphomas and corresponding BM biopsy specimens. As a result, nine morphologically negative bone marrows of 18 lymphomas were positive by PCR (Group I). Among the 6 lymphoma cases with morphologically suspicious BM involvement (Group II), one was confirmed to be positive for marrow involvement by both mRNA ISH and PCR and the other four by PCR alone. The positive bone marrows of Group I and II revealed gene rearrangement at the same site as the primary lesion, suggesting the same clonality. Thirteen of 15 lymphomas with morphologically positive BM (Group III) had the same clonality in the primary lymphomas and the BM lesion. Three cases among the Group III with morphologic discordance also revealed the same clonality by PCR. This study shows that a combination of mRNA ISH and PCR in addition to an immunohistochemical stain improves the diagnostic sensitivity in the detection of BM involvement and identification of clonality. Among the three different methods used, PCR is the most sensitive in detecting a minimal lesion.

Comparison of Glomerular Size between Focal Segmental Glomerulosclerosis and Minimal Lesion in Children

The pathogenetic mechanism of focal segmental glomerulosclerosis (FSGS) is not known. Some authors suggest glomerular hypertrophy may precede the development of FSGS in patients with minimal lesion. It was recently reported that the size of nonsclerotic glomeruli in adults with FSGS is significantly larger than that of cases with minimal lesion. It is not clear whether glomerular hypertrophy observed in adults with FSGS is also seen in children with FSGS. Thus, we have analyzed 37 renal biopsies from children with FSGS by morphometry and the data were compared with 37 renal biopsies from age- and sex-matched patients with minimal lesion. The number of glomeruli submitted for morphometric analysis was 22.6+/-14.2 in cases with FSGS and 30.9+/-11.4 in cases with minimal lesion. Mean glomerular volume (MGV) in FSGS group was significantly larger than that of minimal lesion [(13.1+/-3.9) x10(5) microm3 vs. (10.1+/-1.9) x10(5) microm3, p<0.001]. The relative interstitial volume of renal cortex in patients with FSGS was significantly larger than that of minimal lesion [(0.106+/-0.051) microm3/microm3 vs. (0.029+/-0.012) microm3/microm3, p<0.0001]. In FSGS, the percentage of glomeruli with FSGS was significantly correlated with relative interstitial volume of renal cortex (r=0.79, p<0.0001). As is the case for adult FSGS, MGV of children with FSGS is significantly larger than that of minimal lesion. Thus, the presence of glomerular hypertrophy observed in biopsies with minimal lesion nephropathy seems to be an indication that the coexistent FSGS lesions are undetected due to sampling problems.

A Study of Glomerullar Minimal Lesion and Minimal Mesangial Proliferation with or without Nephrotic Syndrome; Pathologic, Immunopathologic and Clinical Correlations

A total of 394 cases of minimal lesion were reviewed and reassessed clinically and by laboratory investiga- tion, for 4 years from 1979 to 1982. Association with nephrotic syndrome is significantly higher in the cases with histologically normal-appearing mesangium than in the cases with mesangial proliferation. In 43% of the cases of minimal lesion, a minimal but prominent mesangial deposit of Immunoglobulin M with or without C3 deposit was found, and frequently accompanied with nephrotic syndrome, which is not sufficient to accept the condition as a specific disease entity such as "IgM Nephropathy" in our present study. Minimal lesion with a minimal but unmistakable deposit of lgA on the mesangium was noted less frequently and was accompanied or unaccompanied by nephrotic syndrome, a condition which call for an investigation clarify the characteristics and the extent of lgA(Berger's) nephropathy. Response to steroids in minimal lesion nephrotic syndrome was better in children and in the cases without mesangial proliferation, but was unrelated to either hematuria or immunoglobulin deposit. However, the cases with mesangial proliferation are significantly lesser in therapeutic response. Transformation to another morphological type of original glomerular change during follow-up was not observed in 4 available cases of minimal lesion nephrotic syndrome. Henoch-Sch nlein purpura was seen more commonly in children, and lgA(Berger's) nephropathy more commonly in adults.

HLA Type in Minimal Lesion Nephrotic Syndrome (MLNS) in Childhood

Association of HLA antigens with certain diseases provide insights into genetically determined susceptibility to disease. Although nephrotic syndrome is one of the commonest diseases, it is poorly understood. A group of 57 patients suffering from a minimal lesion nephrotic syndrome (33 patients) and mesangioproliferative glomerulonephritis (24 patients) was studied for immunologic markers. The incidence of HLA-A w 24 is significantly greater in the minimal lesion nephrotic syndrome patients than in controls (18.7% in patients, 0% in controls, p < 0.01). This report fails to show a high incidence of specific HLA antigen in mesangioproliferative glomerulonephritis patients. We believe that the high incidence of HLA-Aw 24 in minimal lesion nephrotic syndrome is indicative of a congenital predisposition to nephrotic syndrome.

Diagnostic Value of Serum Immunoglobulins in Glomerulonephritis

Serum immunoglobulin concenatrations were measured in 156 patients with various types of glomerulonephritis such as acute poststreptococcal glomerulonephritis, minimal lesion nephrotic syndrome and Henoch-Sch?lein purpura nephritis. 1) Serum IgG level was above normal mean in acute poststreptococcal glomerulonephritis, and normal range in Henoch-Scholein purpura nephritis. Serum IgG concentrations were significantly reduced in minimal lesion nephrotic syndrome. 2) Serum IgA concentrations were normal limit in minimal lesion nephrotic syndrome. In one-forth of acute poststreptococcal glomerulonephritis and one-half of Henoch-Sch?lein purpura nephritis, serum IgA concentrations were elevated. 3) Serum IgM concentrations were normal in acute poststreptococcal glomerulonephritis, minimal lesion nephrotic syndrome and Henoch-Sch?lein purpura nephritis. We concluded that serum immunoglobulin concentrations were not useful as an aid in diagnosing glomerulonephritis.