Normal human glomerular basement membrane (GBM) and mesangial matrix (MM) contain several different basement membrane components in varying degrees. The characteristic morphological and ultrastructural changes in patients with diabetic nephropathy are the thickening of the GBM and the expansion of the MM. In order to investigate the changes of extracellular matrix components in diabetes, the immunohistochemical localization was performed in 17 cases with different degrees using antisera to human collagen types I, III, IV, VI, fibronectin, and laminin. The following results were obtained: 1. The reactivity for collagen IV was increased in expanded MM in the diffuse glomerulosclerosis (GS). With the progression to the nodule formation, collagen IV was prominently decreased in the peripheral area of the nodules. 2. Collagen VI was increased in GBM and MM in the diffuse GS, it was especially prominent in the expanded MM. With the progression to nodule formation, collagen VI was prominently increased in the periphery of the nodules. 3. Interstitial collagen I and III were not stained in many of the cases with the diffuse GS. With the progression to nodule formation, these were slightly expressed. A lamellar pattern of positive reaction was noted at the periphery of the late nodular lesions. 4. Fibronectin was increased in GBM & MM in the diffuse GS, it was especially intense in the MM. With the progression to the nodule formation, the reactivity of antibody to the fibronectin was decreased. 5. Laminin was weakly stained along the GBM & trace in the MM, but was not changed in the nodular GS. In summary, the expanded mesangial matrix in the diffuse GS showed a markedly increased staining for collagen IV, fibronectin and collagen VI. Less intense linear staining for collagen VI, fibronectin, laminin, collagen IV and collagen III was noted along the GBM. In the nodular GS, the composition of the early nodules resembled that of the diffuse GS. However, the late nodular lesion of the nodular GS revealed decreased reactivity for collagen IV and fibronectin at the periphery of the nodule, where collagen VI and interstitial collagen I and III were increased in laminated pattern.
Basement Membrane ; Collagen ; Diabetic Nephropathies* ; Extracellular Matrix* ; Fibronectins ; Glomerular Basement Membrane ; Humans ; Immune Sera ; Laminin

Membranous glomerulonephropathy (MGN) is the most common primary cause of the nephrotic syndrome in adults, accounting for about 20% of the cases in most series. MGN is idiopathic in the majority of cases, however approximately 25% of adults have identifiable causes (secondary MGN). To evaluate the clinical and pathologic characteristics of MGN, we reviewed the clinical data and renal biopsies from 141 cases of MGN. The mean age of the patients at biopsy was 43 years old, but patients of all age were seen (range from 3 to 76 years of age). There were 88 males and 53 females. There were 99 idiopathic MGN cases and 42 secondary MGN cases. The associated causes of secondary MGN included hepatitis B infection (18 cases), SLE (10 cases), drugs (4 cases), post-transplantation MGN (5 cases), diabetes mellitus (4 cases), syphilis (1 case) and hepatitis B infection associated with rheumatoid arthritis. The prevalence of histologic stages by Ehrenreich and Churg was as follows. Stage I was 24 cases, stage II was 72 cases, stage III was 35 cases, and stage IV was 9 cases. All patients had proteinuria. Nephrotic syndrome was observed in 39%, edema in 73%, microscopic hematuria in 49%, gross hematuria in 28%, hypertension in 13%, and the serum creatinine level above 1.5 mg/dl was in 13%. Cases with glomerulosclerosis was observed in 45 cases with an increased percentage of glomerulosclerosis in the higher grade. Immunofluorescence (IF) examination showed predominantly granular IgG (118 cases) and C3 (84 cases) stainings along the glomerular capillary wall. In idiopathic MGN, sparse mesangial IF staining was noted up to 10% of the cases. However, mesangial IF staining in SLE was observed in 33%, hepatitis B infection in 28% and diabetes mellitus in 50%. An electron microscopic examination revealed subepithelial electron dense deposits of immune complex in all cases. The prevalence of mesangial and subendothelial electron dense deposit in idiopathic MGN was present in 19% and 6%, respectively. In SLE cases, mesangial and subendothelial deposits were observed in 78% and 56%, respectively. In hepatitis B infection, mesangial and subendothelial deposits were observed in 54% and 69%, respectively. In conclusion, immune deposits in the mesangium are scanty in idiopathic MGN, and if pronounced this should increase suspicion of underlying systemic diseases, such as SLE or other infectious diseases.
Adult ; Antigen-Antibody Complex ; Arthritis, Rheumatoid ; Biopsy ; Capillaries ; Communicable Diseases ; Creatinine ; Diabetes Mellitus ; Edema ; Female ; Fluorescent Antibody Technique ; Glomerulonephritis, Membranous* ; Hematuria ; Hepatitis B ; Humans ; Hypertension ; Immunoglobulin G ; Male ; Nephrotic Syndrome ; Prevalence ; Proteinuria ; Syphilis

The clinical, gross, light microscopic and immunohistochemical findings of three cases of blue nevus of the uterine endocervix were described. All three cases were incidentally found in hysterectomy specimens from middle-aged women, 45 to 48 years of age. The lesions were small and measured 1 to 4 mm in the greatest diameter. The presence of elongated, somewhat wavy and dendritic melanin-containing cells, in clusters or scattered deep in the subepithelial stroma and between the endocervical glands, was the distinct feature. The cytoplasmic granules appeared black with Grimelius and Fontana-Masson stains. The cells showed strong positive reaction with S-100 protein in perinuclear cytoplasm, in addition to the diffusely dispersed melanin granules. The demonstration of S-100 protein in the blue nevus, along with the histochemical findings, supports combined melanocytic and schwannian differentiation of the blue nevus cells.
Female ; Humans

Malignant rhabdoid tumor of the kidney(MRTK), an uncommon renal tumor found in children, is one of the most lethal neoplasms of early life. It was first recognized during a review of the first National Wilms' Tumor Study(NWTS) as an extremely aggressive neoplasm whose appearance often mimicks those of skeletal muscle tumors, but without histological, immunohistochemical, and ultrastructural markers of rhabdomyogenesis. Herein we present two cases of malignant rhabdoid tumor of the kidney, one occurring in a 6-month-old male baby, and the other in a 123-month-old girl. They presented a huge tender mass on the left upper quadrant of the abdomen. Microscopically, each case was very cellular and composed of sheets of round or polygonal cells with ample cytoplasm often containing eosinophilic filamentous inclusions and round vesicular nuclei with prominent nucleoli. Case 1 showed lymphomatoid pattern, but case 2 showed foci of several variant patterns associated with classic appearances. The tumor cells showed a strong reactivity for vimentin in both cases. Unusually, case 2 showed focal reactivity for epithelial membrane antigen(EMA), muscle specific actin, and smooth muscle actin. Ultrastructural study confirmed the presence of whorled bundles of intermediate filaments in paranuclear position, and a prominent nucleolus.
Child ; Male ; Female ; Humans

Liesegang rings (LRs) are peculiar structure of periodic precipitation zones from supersaturated solution in colloidal system. LRs are formed by a process referred to as "the Liesegang phenomenon". Here we describe LRs in renal hemorrhagic cyst from the donor kidney of a 59-year-old man. His general condition was good. Abdominal ultrasonography revealed a simple cyst in the left kidney. After donor nephrectomy for renal transplantation, a 3x2 cm sized cyst containing the brownish necrotic fluid was noted in the upper pole of left kidney. Frozen section from the relatively thickened cystic wall was performed. During frozen section examination, round concentric rings with double-layered outer wall, striations and amorphous central nidus admixed with the foamy macrophages were found and the lesion was originally interpreted as xanthogranulomatous inflammation with unusual crystalline structures in the cytoplasm of macrophages or freely in the interstitium. Macrophages with calcium crystals or malakoplakia were also considered at that time. Additional specimen for the permanent sections showed a simple hemorrhagic renal cyst with areas of small or large aggregates of LRs along the cyst wall. Multiple round ring-like structures ranging from 11 to 42 micrometer in diameter had uniform, pale eosinophilic, radially striated double wall. Histochemical and immunohistochemical stainings for iron, calcium, mucopolysaccharide, amyloid, cytokeratin were negative in these structures. They were highlighted by CD68 immunostaining as well as PAS and Masson's trichrome stainings. Awareness of Liesegang phenomenon in cystic lesions will decrease the possibility of erroneous diagnosis as another type of pathologic process, such as parasitic worms or eggs.
Amyloid ; Calcium ; Colloids ; Crystallins ; Cytoplasm ; Diagnosis ; Eggs ; Eosinophils ; Frozen Sections ; Helminths ; Humans ; Inflammation ; Iron ; Keratins ; Kidney Transplantation ; Kidney* ; Macrophages ; Malacoplakia ; Middle Aged ; Nephrectomy ; Ovum ; Tissue Donors* ; Ultrasonography

Tumor angiogenesis(TA) refers to the growth of new vessels toward and within a tumor. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, the microvessels were counted (per 200 / field) in the most active areas of neovas-cularization by two investigators. The microvessels within breast carcinoma were highlighted by in imunohistochemical staining for factor VIII-related antigen. Microvessel count(MVC) in node-positive carcinoma(59.66=35) was significantly higher than in node-negative carcinoma(44.76=17)(p=0.009). MVC was also statistically correlated with tumor size and stage, but not with histologic grading, DNA ploidy, or hormonal receptors(estro-gen and progesterone). MVC in invasive breast carcinoma may be one of many prognostic predictors of node-positive breast carcinoma. Assessment of tumor angiogenesis may therefore be valuable in selecting patients with early breast carcinoma for aggressive therapy.
Neoplasm Metastasis

An in situ DNA hybridization technique was applied to detect human papillomavirus(HPV) DNA, HPV types 6/11 and 16/18, on paraffin sections of 36 cervical condylomatous lesions associated with cervical intraepithelial neoplasia and invasive squamous cell carcinoma. 1) HPV DNA sequences were identified in 14 of 36 cervical condylomatous lesions(39.0%); HPV 6/11 in 7 cases(19.0%) and HPV 16/18 in 7 cases(19.0%). 2) With the use of biotinylated HPV 6/11 DNA probes, 5 of 5 condyloma acuminata(100%), 1 of 5 flat condylomata(20%), and 1 of 7 mild dysplasias(14.3%) were positive. 3) With the use of HPV 16/18 DNA probes, 1 of 7 mild dysplasias(14.3%), 2 of 5 moderate dysplasias(40%), 2 of 4 severe dysplasias(50%), and 2 of 5 invasive squamous cell carcinomas(40%) were positive. 4) The positive stainings to HPV DNA probes were primarily detected in koilocytotic nuclei of the superficial epithelium. No positive signals were found in the normal, dysplastic or carcinoma cells. 5) The numbers positively stained cells were decreased with increasing severity of the lesions from benign condylomas to invasive squamous cell carcinomas. In conclusion, HPV types 6/11 were more commonly identified in benign condylomatous and low grade intraepithelial lesions than high grade lesions. However, HPV types 16/18 were identified in high grade CIN and invasive squamous cell carcinomas. The present results while supporting the concept on HPV 16/18 as the high risk of HPV types in cerivical carcinogenesis also emphasize the applicability of the situ DNA hybridization as a tool in analysis of the specific HPV DNA sequences in routine biopsies of these lesions.
Humans ; Biopsy

The prognostic significance of morphologic parameters was evaluated in 36 cases of renal cell carcinoma diagnosed during five years(1986~1990). We reviewed and classified on the basis of pathologic stage, tumor size, histologic pattern, cell type and nuclear grade. Mean age was 51 years old. Average tumor size was 7.3 cm in diameter. Six of 35 patients died of disease. Overall mean survival was 43.3+/-7.3 months. An increasing nuclear grade was generally correlated with a decrease in cummlative survival rate. Similarly, a higher stage at the time of diagnosis could predicated a low survival rate only for high nuclear grade carcinoma. There was an apparent positive correlation between grade and age, grade and size, grade and cell type, cell type and histologic pattern as well as stage and age. This positive correlations are in part a function of nuclear grade; only 20% of grade 3 & 4 tumor consisted of clear cells whereass 71% of grade 1 & 2 consisted of clear cell type. All 6 cases of granular cell types and 50% of mixed cell type were grade 3 & 4. The tumor size of the primary was well correlated with the nuclear grade. Nuclear grade was the most significant factor among the morphologic parameters studied.

Localized cystic disease of the kidney is a rare entity with the gross and microscopic features of autosomal dominant polycystic kidney disease localized to only a portion of a kidney, and negative family history. We report a case of localized cystic disease of the kidney in a 38-year-old woman who complained of intermittent right flank pain for 1 year. The resected kidney showed multiple cysts measuring up to 4.0 3.5 3.0 cm, which were scattered throughout the mid- and lower poles of the kidney. Microscopically, the cystic lesion was composed of numerous cysts of variable size, lined by flattened epithelium. The intervening septa of the cysts contained normal or compressed renal tubules and glomeruli. Neither dysgenetic tissue such as immature cartilage or primitive mesenchymal tissue nor malignant cells was identified. Localized cystic disease should be included in the differential diagnosis of cystic lesions in the kidney.
Adult ; Cartilage ; Diagnosis, Differential ; Epithelium ; Female ; Flank Pain ; Humans ; Kidney* ; Polycystic Kidney, Autosomal Dominant

The preeclamptic nephropathy is characterized by swelling of endothelial cells, interposition of mesangial cells and matrix, subendothelial deposits of incompletely defined material, and thickening of the capillary walls. To determine the distribution of extracellular matrix (ECM) components in preeclamptic nephropathy, the immunohistochemical study was performed in ten renal biopsy cases using antisera to human type I, III, IV, and VI collagens, fibronectin, and laminin. In preeclamptic nephropathy, the accumulation of type IV and VI collagens, fibronectin was observed in moderate amount in the mesangium and, to some extent, in the thickened capillary walls, particularly in the subendothelial layer. In segmentally sclerotic lesions seen in six cases, the amount of type IV collagen was partly decreased, whereas those of type VI collagen and fibronectin were slightly increased. Type I collagen was expressed to a mild degree in the expanded mesangium and segmentally sclerotic lesions. The results suggest that the expression of ECM in the mesangium is increased in preeclamptic nephropathy, and the deposition of ECM components may be involved in the development and the reparative process of the characteristic glomerular lesions. The formation of sclerotic lesions may be linked to the alternative accumulation of ECM components.
Biopsy ; Capillaries ; Collagen ; Collagen Type I ; Collagen Type IV ; Collagen Type VI ; Endothelial Cells ; Extracellular Matrix* ; Fibronectins ; Humans ; Immune Sera ; Laminin ; Mesangial Cells