[Thin glomerular membrane nephropathy. Clinico-pathological observations]. / A vékony glomerularis basalmembran nephropathia. Klinikopatológiai megfigyelések.

In two nephrology centres between 1983 and 1993 among 1545 kidney biopsies 34 cases of thin basement membrane nephropathy have been diagnosed. All patients had a varying degree of microscopic dysmorph haematuria, occasional slight proteinuria--except two nephrotic children; and normal blood pressure with one exception. 5 children and 7 adults experienced repeated bouts of macroscopic haematuria mainly after exercise or upper respiratory tract infection, one child after tonsillectomy. All patients had normal renal function and retained it during the follow-up period (mean 61 months, 3 months to 22 years), except a 46 year old patient, who was found to have the joint occurrence of light chain gammopathy and hypertension. Seven patients had positive family history for microscopic haematuria, in four family members of three patients renal biopsy disclosed mesangioproliferative glomerulonephritis with thin GBM segments. As a cut off value for thin basement membrane nephropathy we considered 264 nm. The morphometric analysis of the electron micrographs revealed a mean thickness of 210 nm. No differences in basement membrane thickness were measured regarding gender, age or the presence of macroscopic haematuria. The thin basement membrane is considered to be the pathological basis and predisposing alteration leading to haematuria.

Mitochondrial mutation as a probable causative factor in familial progressive tubulointerstitial nephritis.

Renal biopsy of two children and a maternal relative, diagnosed with severe progressive tubulointerstitial nephritis, has shown the presence of distorted mitochondria. Mitochondrial DNA from the blood of these patients was analysed. No major deletions were found, but an A to G mutation was detected in position 5656. It is proposed that this mutation might play a causative role in the renal disease of the patients.

Recurrent phyllodes tumor in a man.

The case of a 35-year-old man with a borderline-type cystosarcoma phyllodes is presented. Four years after the primary excision of the tumor, wide excision of a local recurrence and postoperative radiotherapy were performed. No repeated relapse was observed during a 5-year follow-up. Neither significant endocrine changes nor genetic alteration could be proven. However, a slightly increased SHBG concentration was detected, resulting in a decreased biologically available androgen level reduced testosterone/SHBG index. This phenomenon might be a consequence of the chronic liver disease of the patient due to his type II diabetes mellitus and alcohol abuse. In addition to the conventional histopathological examinations, immunohistochemical and electron-microscopic investigations were carried out on tissue sections, and the steroid receptors, EGF receptors and EGF-like activity of the tumor were also studied.

Quantitative ultrastructural study of afferent and efferent arterioles in IgA glomerulonephritis and benign nephrosclerosis.

Arteriolosclerosis frequently occurs in IgA nephritis (IgAN), and it is the hallmark of benign nephrosclerosis (BNS). The quantitative ultrastructure of juxtaglomerular arterioles is not known in these disorders. We examined afferent and efferent arterioles in renal biopsies from 25 adult patients with IgAN (hypertension at biopsy: 14 patients) and 9 patients with BNS. Six age-matched living renal transplant donors acted as controls. A systematic independent sample of profiles was obtained in thin sections taken at predetermined levels. The thickness of the media (myomedial cells plus the matrix) and the thickness of the medial matrix were estimated stereologically. From these estimates, the matrix/myomedia ratio was calculated. In IgAN with normotension or hypertension, the afferent media and its compartments did not exhibit significant thickening compared with the controls, whereas in BNS the afferent media and its layers were markedly and significantly thickened. The efferent media in IgAN and BNS displayed mild and significant thickening, with significant thickening of the matrix in BNS and IgAN with normotension. The matrix/myomedia ratio was not altered significantly in any group. The results indicate that the afferent arterioles are not the main sites of IgAN-related arteriolosclerosis, that arteriolosclerosis in IgAN and arteriolosclerosis in BNS are different lesions, and that increased efferent arteriolar thickness, demonstrated here for the first time in IgAN and BNS, might be a manifestation of angiotensin II-mediated autoregulatory efferent vasoconstriction exerted to maintain the glomerular filtration pressure.

[Nail-patella syndrome: clinico-pathologic characteristics]. / A köröm-patella syndroma: klinikopatológiai jellegzetességek.

The nail-patella syndrome is a hereditary disorder showing an autosomal dominant trait. It is characterized by a series of skeletal disorders and nephropathy. The skeletal defects and the renal involvement might occur separately. The usual clinical presenting syndromes of the nephropathy are asymptomatic proteinuria, microscopic haematuria and sometimes nephrotic syndrome. In a considerable proportion of patients renal failure develops. We summarise the clinico-pathological features of the disease presenting in two children and in a young man. The two children showed heavy microscopic occasionally, macroscopic haematuria, asymptomatic proteinuria and the adult patient had nephrotic syndrome. Nail-patella abnormalities were observed in one child without the involvement of family members. Except for the mother of the other child no urine abnormalities could be demonstrated in the patient's families. The kidney biopsy revealed the characteristic signs of the nail-patella syndrome in different extent: bundles of collagen fibrils in the glomerular basement membrane (GBM). Segmental and thinning of the GBM also occurred in the two children. This defect predisposes to the clinically dominant micro- and macroscopic haematuria. These children's reual function remained stable during the follow-up period of 4-7 years. In the GBM of the third patient small subepithelial electron dense deposits-corresponding to stage I. membranous glomerulonephritis- and extensive collagen deposition was found. After two years follow-up persistent nephrotic syndrome and gradual decline in renal function could be observed.

[Symptomatic glial cysts of the pineal gland: report of two cases and review of the literature]. / A corpus pineale symptomaticus glialis cystái: két eset ismertetése és irodalmi áttekintés.

Referring to two individual cases, the authors review clinical, radiological and histological features of benign glial cysts of the pineal gland. Both patients were young females with aggravating headaches and with convulsions in one case. Symptoms were referable to a space-occupying cystic mass of the pineal gland. On histology, both lesions proved to be non neoplastic cysts without an epithelial lining. Their histogenesis and low growth potential were reinforced by immunohistochemical analysis of pineal antigens and proliferation markers. Glial cysts of the pineal gland are not infrequent, but symptomatic occurrences are exceptional. Most glial cysts are of dysontogenic or degenerative origin. Sometimes, however, the role of hormonal influences or paraneoplastic factors must be considered. Symptoms caused by glial cysts of the pineal gland are non-specific and radiologic imaging technics may contribute little to etiologic diagnosis. Pineal cysts are curable by surgical resection or stereotactic decompression. Whatever the diagnostic approach, emphasis must be laid on the histologic examination in order to avoid unnecessarily aggressive treatment.

Human acute tubular necrosis: a lectin and immunohistochemical study.

To determine the nephron segment distribution of tubular epithelial damage and regeneration and the proliferative activity of various nephron segments in human acute tubular necrosis (ATN) with an antibody to proliferating cell nuclear antigen (PCNA) and to compare the findings in native kidneys with ATN with those in transplant kidneys with ATN, archival tissues from 12 native and 21 transplant kidney biopsy specimens and nine transplant nephrectomy specimens were collected that all showed obvious morphological signs of ATN. Nineteen patients with transplant kidneys with ATN were immunosuppressed with cyclosporine and 11 were immunosuppressed with prednisone and azathioprine. There was a predominance of "regenerating" tubules (tubules with thin epithelium) in the distal nephron in native kidneys with ATN; in the transplant kidneys this was less conspicuous. The number of Tamm-Horsfall protein (THP)-positive tubules was decreased in all kidneys with ATN compared with normal human kidneys. In contrast, the number of THP-positive casts was much higher in all kidneys with ATN than in the normal kidneys. In transplant kidneys with ATN the number of THP-positive casts was substantially lower than in native kidneys with ATN. The macula densa appears to maintain its morphological integrity in kidneys with ATN. Both regenerating and normal appearing tubules expressed vimentin and HLA-DR. The proliferation index (PI; ie, percentage of PCNA-positive nuclei) of the renal tubular epithelium in normal control kidneys varied between 0.22 and 0.33, depending on the tubule segment. The highest PI was noted in the transplant kidneys with ATN not treated with cyclosporine (8.0), followed by the native kidneys with ATN (4.4) and the transplant kidneys with ATN treated with cyclosporine (4.3). We did not find any significant difference in the PI between the regenerating (5.0) and normal appearing (5.6) tubules. Proximal tubules (8.7) showed significantly higher PI values than distal tubules (3.5) in transplant kidneys with ATN. Our results show substantial differences between native kidneys and transplant kidneys with ATN. Tubular epithelial cell proliferation in human ATN is prominent and appears to correlate with the severity of ATN. Light microscopically normal appearing tubules and regenerating tubules participate equally in the regeneration of injured tubules. Cyclosporine may have an inhibitory effect on cell regeneration (proliferation) in human transplant kidneys with ATN.

[Comparative analysis of ultrasonic studies, histopathological data and clinical parameters in dysfunctioning renal transplantation]. / Ultrahangvizsgálatok, kórszövettani eredmények és klinikai paraméterek összehasonlító elemzése transzplantált vese diszfunkció esetén.

The correlation of B mode and Doppler sonographic parameters and diagnoses established by histological examination of graft biopsies, nephrectomies and clinical data are discussed. 48 histological samples from 36 patients were reevaluated. The maximum interval between sonography and histology was 36 hours. The Banff classification criteria were used during histological examinations. Doppler examination evaluation was based on the resistance index (RI). Reproducibility was controlled by means of intra- and interobserver variability in 10 patients. RI values higher than 75% were regarded as abnormal. On the basis of these observations and the literature data specific sonographic features can be detected in renal artery occlusion and renal vein thrombosis. In pyelonephritis, dilatation of the collecting system was frequent. No morphological changes were detected in cyclosporin-A nephrotoxicity and the Doppler signs were not characteristic for this disease. No differentiation was found between acute rejection and acute tubular necrosis. The noninvasive duplex sonographic examinations can provide very important information regarding the flow situation of a transplanted kidney. In some cases a definitive diagnosis can be achieved, but in other cases biopsy is the method of choice.

[Central neurocytoma: a rare tumor of the cerebral ventricles]. / Centralis neurocytoma: az agykamrák ritka daganata.

The case of a 33-year-old man is presented, who acutely developed disturbance of consciousness, symptoms of raised intracranial pressure and unilateral neurological signs. The underlying lesion was a hemorrhagic tumor located in the left lateral ventricle. On histological examination, the surgically resected mass proved to be a central neurocytoma, a benign neuroectodermal neoplasia. Difficulties in differential diagnosis by imaging technics and histopathology render this unusual lesion worth publishing. To the best of our knowledge, no similar report on this recently described rare entity has been published in Hungary.

[Simultaneous occurrence of persistent hematuria (thin basement membrane nephropathy) and light-chain proteinuria (benign monoclonal gammopathy) in a middle-aged male]. / Persistáló haematuria (vékony-basalis-membran-nephropathia) és könnyülánc-proteinuria (benignus monoclonalis gammopathia) együttes elöfordulása egy középkorú férfiban.

IgG lambda type of monoclonal gammopathy and thin basement membrane nephropathy were established in a middle-aged man examined because of persistent haematuria, lambda light-chain proteinuria and moderately diminished renal function. A 10% level of plasmocytosis was verified by bone-marrow aspiration. The more than 6-year follow-up showed the gammopathy to be benign. The thin basement membrane nephropathy was verified by electronmicroscopic analysis of renal tissue obtained by percutaneous renal biopsy: lamina densa of the glomerular capillaries thinned to 30-100 nm. In spite of the usually good outcome of thin basement membrane nephropathy, in this case it was accompanied by glomerular sclerosis, subsequent destruction of nephrons, hypertensive vascular alterations and a clinical deterioration of the renal function after 4 years. A rebiopsy excluded the possible complications (amyloidosis, non-amyloid immunoglobulin nephropathy, cylinder nephropathy, etc) of light-chain proteinuria.

Hereditary nephritis, platelet disorders and deafness-Epstein's syndrome.

A 14-year-old boy with persistent proteinuria (1.6-4.0 g/day), microscopic haematuria, moderate hypertension, macrothrombocytopenia (giant platelets, platelet number 30 x 10(9)/l) and a familial sensorineural hearing loss (the father and the brother were also affected) was studied. Kidney biopsy revealed a diffuse mesangial proliferation, and a focal thickening of the glomerular basement membrane was seen on electron microscopy. A normal number of megakaryocytes was observed in bone marrow aspirates. The aggregation response of the platelets to collagen, epinephrine and adenosine diphosphate (ADP) was decreased. The platelet number was slightly diminished, platelets were of normal size in both parents and the brother, and showed a decreased aggregability in response to collagen, epinephrine and ADP in the brother and mother. No functional abnormality of the platelets was observed in the father. Urinalysis and kidney function were normal in the family members. This boy with nephritis, platelet disorders and hearing loss corresponds to Epstein's syndrome.

Morphological characterization of human juxtaglomerular apparatus.

The recent demonstration of the endothelial fenestration at the juxtaglomerular part of the afferent arteriole facing mesangial and granular cells and finger-like protrusions of urinary space into the region of the lacis in experimental animals like the rat, the mouse, and Tupaia belangeri led us to propose the hypothesis of a "short loop" feedback mechanism. To establish whether a further species possesses these morphological features, the JGA region was examined in the human kidney. Tissue was obtained by needle biopsy from patients and conventional electron-microscopical procedures including serial sections were utilized to reevaluate the morphology of JGA. Both the endothelial fenestration in the wall of the afferent arteriole and protrusions with filtration slits of urinary space into the lacis, were observed with remarkable heterogeneity. The occurrence of these features of JGA in such diverse mammalian species as rat, mouse, Tupaia, and man suggests that these structures may be involved in regulatory process and the proposed "short loop" feedback mechanism may be a general phenomenon.

Importance of plasma cells in the infiltrate of renal allografts. An immunohistochemical study.

The cellular infiltration in 42 needle and wedge biopsies of transplanted kidneys was investigated immunohistochemically. The percentages of helper/inducer (CD 4+) cells, suppressor/cytotoxic cells (CD 8+), B lymphocytes, macrophages, plasma cells (Pc) and granulocytes were determined. The proportions of the various inflammatory cell populations were established in acute interstitial rejection (AIR), acute vascular rejection (AVR), chronic rejection (CR) and cyclosporin A nephrotoxicity (CsAN). The most prominent differences were detected as regards the Pc, whose number was much higher in CR than in AIR, AVR or CsAN. The striking difference between CR and CsAN in the number of Pc may be of differential diagnostic importance: the presence of many Pc in the biopsies can be regarded as a sign of CR. Over 80% of the Pc in CR contained IgG, whereas in chronic interstitial nephritis (CIN) the IgA-positive Pc predominated. In AIR, AVR and CsAN, too, the majority of the Pc contained IgG, but the numbers of IgM and IgA-positive cells were also relatively high. The great number of IgG-positive Pc indicates an important role of a secondary type humoral immune response in CR.

Electron microscopic study of adenoid cystic carcinoma.

This ultrastructural study is based on nine cases of adenoid cystic carcinoma arising from the salivary glands. Electron microscopically, the tumors consisted of five cell types: relatively differentiated intercalated duct cells, secretory cells, undifferentiated cells, cells of a squamous nature, and myoepithelial cells. Special attention was paid to the characteristic extracellular substances noted by light microscopic examination of these tumors. The hyaline material of the pseudocysts contained not only mucopolysaccharide granules but also fingerprint-like structures formed by replicated basement membrane. Some of these structures had a dense core, probably composed of mucopolysaccharide granules. Cell islands surrounded by elasticlike material also were found. The true lumina were usually filled with membranovesicular structures originating from fragments of the lining cells, mainly those with squamous differentiation. These membranovesicular structures included electron-dense rods, filamentous whorls, and structures displaying periodicity.