Hepatitis-B-associated glomerulonephritis: pathology, pathogenesis, and clinical course.

Hepatitis-B-associated glomerulonephritis (HBGN) is a distinct entity occurring frequently in hepatitis-B-prevalent areas of the world. The disease affects both adults and children who are chronic hepatitis-B-virus (HBV) carriers with or without a history of overt liver disease. The diagnosis is established by serologic evidence of HBV antigens/antibodies, presence of an immune complex glomerulonephritis, immunohistochemical localization of 1 or more HBV antigens, and pertinent clinical history, when available. In this study we present clinicopathologic and follow-up findings in 12 patients (7 children, 5 adults) with hepatitis-B-associated glomerulonephritis. Twelve patients provided 15 renal biopsies and 1 specimen of kidney tissue, obtained at autopsy; these were examined by light microscopy, electron microscopy, and immunohistochemical methods. Membranous glomerulonephritis (MGN) with or without mesangial proliferation was noted in 7 biopsies, mesangiocapillary (membranoproliferative) glomerulonephritis (MCGN) in 5 biopsies, and proliferative glomerulonephritis with or without membranous changes in 2 biopsies. Tubulointerstitial changes were minimal except in 3 adults, in whom they were attributable to arterionephrosclerosis. Ultrastructural findings included the presence of considerable amounts of focal or diffuse granular electron-dense deposits in the glomeruli, in the subepithelial, subendothelial, and mesangial locations, occasionally destroying or replacing the lamina densa of the basement membrane. Variable mesangial proliferation was also observed, with interposition, with focal irregular reduplication of the basement membranes and rare clusters of spherical particles, probably representing viral particles in the deposits. In addition, granular deposits along tubular basement membranes were seen in 1 case. The glomerular deposits stained for 2 or more immunoglobulins, the predominant one being IgG, and variably also for complement components (C3, C4 and C1q). Hepatitis B viral antigens (HBsAg, HBcAg, HBeAg) were demonstrated using acid elution techniques in the deposits in all biopsies where frozen tissue was available, singly or in a variety of combinations and intensities. There were deposits of IgG, C3, C1q, and HBsAg along the tubular basement membranes in 1 case. Follow-up biopsies in 2 cases, 2 and 5 years apart, showed a transformation from a diffuse MGN to MCGN with segmental membranous features. Follow-up biopsy after 3 years in the third patient, who went into clinical remission, revealed partially resolving glomerular lesions. Renal lesions secondary to chronic liver disease, parasitic diseases, certain tropical nephropathies, and lupus nephritis are some of the diseases that may morphologically resemble HBGN. Recognition and differentiation of HBGN from other entities may have significant prognostic and therapeutic implications.(ABSTRACT TRUNCATED AT 400 WORDS)

Intraepidermal squamous carcinoma (Bowen's disease) of the nipple.

A case of Bowen's disease of the nipple clinically resembling Paget's disease is reported. This lesion was differentiated from other pagetoid lesions by negative histochemical stains for mucin and melanin, positive immunohistochemical preparation for high-molecular weight cytokeratin 66 kd (904) using adequate controls, and electron microscopic findings of squamous cell features. The therapeutic implications of such a pagetoid nipple lesion in the absence of an underlying breast carcinoma are discussed.

Pathologic manifestations of the eosinophilia myalgia syndrome: analysis of 11 cases.

We describe the histopathologic changes of skin, muscle, vessels, and fascia in 11 patients with eosinophilia myalgia syndrome, a newly described entity that has been linked to the ingestion of L-tryptophan. This syndrome is defined clinically by severe incapacitating myalgias and a peripheral eosinophilia. Arthralgias, edema of the extremities, morbilliform rashes, skin induration, weakness, fatigue, and respiratory weakness may be present as well. The earliest apparent histologic changes were observed at the septa between subcutaneous fat lobules and in the deep dermis or fascia. The septa and fascia were infiltrated with a sparse mixture of lymphocytes and histiocytes. In the deep fascia, in addition to inflammatory cells, there were distinctive, reactive mesenchymal cells that showed features of both histiocytes and fibrocytes. Minimal tissue eosinophilia was seen despite the extent of blood eosinophilia. Dermal thickening and homogenization of collagen bundles occurred with replacement of fat and adnexa (changes indistinguishable from scleroderma or morphea). Vessel walls in the dermis and fascia showed thickening and endothelial swelling, but no overt vasculitis was noted. Skeletal muscle biopsies showed a perimysial, epimysial, and/or fascial inflammatory infiltrate of lymphocytes and distinctive reactive mesenchymal cells with some eosinophils. Minimal myofiber atrophy, regeneration, or necrosis was seen despite the clinical history of severe myalgias in almost all patients. This syndrome should help gain insight into the mechanisms of fibrosis in environmental-induced, scleroderma-like syndromes and in idiopathic, scleroderma-like disorders as well.

Morphometric study of the placental vessels and its correlation with umbilical artery Doppler flow.

OBJECTIVE: To determine the changes in the vessel-wall thickness and the radius of the lumen in tertiary-stem villi of the placenta with advancing gestational duration and their relationship to umbilical artery Doppler flow studies. METHODS: Placentas from 63 miscarriages and preterm and term deliveries (between 19 and 40 weeks) were used for morphometric study of the tertiary-stem villi vessels. Each woman had undergone Doppler flow study of the umbilical artery. The resistance index (RI) was determined from the Doppler flow velocity waveform. Placental paraffin sections of 4-micron thickness were stained with hematoxylin and eosin and with periodic acid-Schiff reagents. The tertiary-stem villi and their vessels were examined microscopically and assessed morphometrically using a personal computer with math co-processor and a touch-sensitive screen overlying a video monitor. The monitor received microscopic images from a video camera that was mounted on a microscope. We determined vessel-wall thickness by tracing the outer and inner circumferences of digitized vessel-wall images. RESULTS: Wall thickness, but not lumen size, of the tertiary-stem villi vessels decreased significantly overall at a rate of 0.63micron/week (P < .001). The rate of decrease was 0.64micron/week (P < .001) during the second trimester and 0.50micron/week (P < .001) during the third trimester. There was a significant correlation between the decrease in thickness and in RI (r = 0.83 [P < .001], r = 0.78 [P < .001] in the second and third trimesters, respectively). Resistance indices were all within normal limits. CONCLUSIONS: Placental tertiary-stem villi vessel-wall thickness decreases with advancing gestational age. There is a correlation between the changes in RI of the umbilical artery Doppler flow and the changes in mean wall thickness of the placental vessels.

Renal failure due to tubular obstruction by large protein casts in patients with massive proteinuria.

We describe two patients with nephrotic syndrome whose histologic findings on renal biopsy and at autopsy are characterized by numerous large protein casts in dilated cortical tubules, as well as podocyte swelling with effacement of foot processes in the glomeruli. Both patients progressed rapidly to renal failure. The casts and the protein precipitate in the Bowman's capsule were found to be composed of varying proportions of albumin and globulin but contained no Tamm-Horsfall protein. This suggests a glomerular rather than tubular origin of proteins. Light and electron microscopic examination of tubules revealed changes mainly due to compression by the casts. We propose that tubular obstruction due to the large casts was the main cause of renal failure.

Morphometric analysis of glomerular basement membranes (GBM) in thin basement membrane disease (TBMD).

We measured the thickness of glomerular basement membrane in 46 patients with thin basement membrane disease (TBMD), (age range 15-50 years, almost equal M:F ratio), and compared with that in a control group of 5 patients (age range 5-38 years) with normal glomerular morphology. The measurements of glomerular basement membrane taken from electron micrographs (magnification x 12,500) were analyzed using an interactive image analysis system assembled around an INTEL 10 microcomputer, with a high resolution touch sensitive screen as the interactive peripheral. Calculation was done by printing on an electron micrograph a grating replica (21,600 lines/cm), with the same magnification as the electron micrographs of the glomeruli and calibrating the arithmetic (AM) and harmonic (HM) mean for each case. Comparing the results of TBMD cases (AM 129-202 nm; HM 128-213 nm) with those of the control group consisting of 5 cases of "minimal change nephrotic syndrome" (AM 287-317 nm; HM 300-333 nm) it was found that GBM in TBMD is remarkably thin. The thinning was caused mainly by the decreased width of the lamina densa (TBMD group: 71.4-147.0 nm; HM 72.4-154.4 nm in comparison with the control group: AM 174.4-235.5 nm; HM 184.2-249.6 nm). This finding allows us to differentiate thin basement membrane disease from other glomerulopathies presenting primarily with isolated or recurrent hematuria.

Renal lesions in AIDS: a biopsy and autopsy study.

We studied renal lesions at biopsy (20 cases) and at autopsy (21 cases) among patients with the acquired immune deficiency syndrome (AIDS). Nephrotic syndrome with concomitant renal insufficiency was most common indication for biopsy. 85 percent of biopsies showed features of HIV associated nephropathy (HIVAN) which include: Focal segmental glomerulosclerosis (FSGS), glomerular collapse and mesangial hyperplasia. These glomerular changes were always accompanied by tubular microcysts and ultrastructurally, tubuloreticular inclusions (TRI) within the glomerular endothelium were often noted. Changes of HIVAN were also seen in two cases who were HIV negative at the time of biopsy but were positive on repeat testing. Minimal change disease, mesangiocapillary glomerulonephritis and diffuse proliferative lupus nephritis were other biopsy lesions. Autopsy findings were HIVAN (33 percent), tubular necrosis and opportunistic infections. We conclude that HIVAN is a distinct clinicopathologic entity that may sometimes be the first manifestation of the underlying disease state.

[A clinicopathological study of eighteen autopsy cases with acquired toxoplasmosis].

Eighteen autopsy cases of acquired toxoplasmosis in New York City were studied. Seventeen cases were with acquired immunodeficiency syndrome (AIDS) and one patient with Hodgkin's disease. All 18 cases involved the brain and nine of them disseminated to the heart (8 cases), lung (4 cases), pancreas (3 cases), alimentary tract (2 cases) and urogenital organs (3 cases). The authors divided the acquired toxoplasmosis into (1) immunocompetent, (2) immunocompromised and (3) immunodeficient types. The autopsy findings showed that the brain, heart and lung were the most susceptible organs. Pseudocysts were also found in lungs and alimentary tract, suggesting an autoinfection by swallowing sputum containing Toxoplasma. Toxoplasma in the urogenital organs might become a source for sexual transmitted toxoplasmosis.

Gastric hemorrhage and Kaposi's sarcoma treated with radiotherapy.

A 66-year-old man, with advanced alcoholic liver disease with Kaposi's sarcoma involving the stomach and the skin of the lower extremities, developed upper gastrointestinal hemorrhage. He was treated with radiation therapy to the stomach and the skin with rapid resolution of the gastric lesions, as demonstrated by serial endoscopy.

Adrenal pseudocyst: report of two cases.

Adrenal cysts are uncommon lesions. The authors discuss two cases of adrenal pseudocyst, and its classification and possible pathogenesis and complications. The role of radiologic findings in preoperative evaluation of renal/suprarenal masses also is detailed.

Vascular lesions in lupus nephritis.

Three groups of kidney specimens from patients with systemic lupus erythematosus (SLE) were examined for histologic evidence of vascular lesions in small arteries and arterioles. Group 1 consisted of 24 autopsy kidneys from patients who died before the advent of steroid therapy, and Group 2, of 26 more recent autopsy specimens from patients treated with steroids and/or immunosuppressive drugs. Group 3 comprised 276 renal biopsies. Group 1 showed characteristic subendothelial eosinophilic deposits in small arteries and arterioles of 8 cases; Group 2 showed similar lesions in 5 specimens, while 3 others revealed evidence of resorption of deposits. Deposits were characterized by clumping and were delimited toward the media by a thick basement membrane. Only one case showed necrotizing arteritis resembling polyarteritis nodosa. Group 3 presented vascular deposits in 19 cases and thrombotic microangiopathy in 2. Electron microscopic appearance of some of the deposits is described. Immunofluorescence microscopy showed a mixture of IgG, IgA, and IgM in 7 cases, a finding that was not seen in a group of non-lupus patients with various vascular lesions. Vascular deposits are generally rare in systemic lupus erythematosus, although in autopsies widely scattered involvement of arteries and arterioles was seen in nearly 1/3 of the cases. The deposits were more common in male patients. The evolution of the lesions could be followed through various stages to eventual sclerosis, particularly in patients treated with steroids or immunosuppressants. Some deposits appeared to resolve after treatment. Patients with vascular deposits had more severe glomerular disease and a more serious clinical course. Thrombotic microangiopathy appears to be a secondary phenomenon whose pathogenesis is unknown.

Diffuse viral papillomatosis (condyloma) of the uterine cavity.

A case of viral papillomatosis (condyloma) of the uterine cervix is reported, which was followed for 13 years and in which the lesion spread to involve superficially the entire uterine cavity without any change in its histologic appearance. The presence of intranuclear papillomavirus antigen was demonstrated by using the peroxidase-antiperoxidase technique.

Heat shock protein 72/73 in normal and diseased kidneys.

The induction of heat shock (stress) proteins (HSP) is a response by cells due to a variety of physical, chemical, and infectious agents. They have a significant role as cytoprotectants, in the regulation of cellular functions, and in the recovery after sublethal injury. Using antibody to mammalian HSP 72/73, we have performed as immunohistological study of human renal tissue in normal and diseased states, including idiopathic nephrotic syndrome, proliferative and crescentic glomerulonephritis, and interstitial nephritis. A significant increase of HSP expression was noted in certain segments of the tubule in acute interstitial nephritis and in glomerulonephritis accompanied by active interstitial inflammation. A possible role by the inflammatory mediators in the induction of HSP in those cases is suggested.

Fibrillary glomerulonephritis without immunoglobulin deposits in the kidney.

Three patients are presented, who by electron microscopy, showed prominent fibrillary deposits in the glomeruli, and in two, also around the tubules. By immunohistology these two cases had no immunoglobulins in either glomeruli or around the tubules. In the third case, which probably represents a slightly different form of the disease, minor deposits of IgM were found in the glomeruli, while fibrillary deposits were extensive and widespread. It is suggested that precursors of fibrillary deposits may not be the same in all cases.

Immunohistochemical localization of renin in end-stage kidneys.

Hypertension in chronic renal failure is usually due to excessive accumulation of salt and water. In some cases, sodium and volume depletion by dialysis fail to reduce the high BP, and plasma renin activity tends to be higher. We performed a semiquantitative analysis of the immunohistochemical distribution of renin in the kidneys of ten patients with end-stage renal disease and hypertension using a specific antihuman renin antibody and a peroxidase-antiperoxidase technique on paraffin sections of nephrectomy and/or autopsy specimens. In five cases with severe, dialysis-resistant hypertension, the degree of immunoreactivity was most striking, exceeding that found in renovascular hypertension and present in arterioles at a distance from the glomeruli. Three cases of advanced diabetic glomerulosclerosis consistently showed minimal immunoreactivity. We conclude that renin often can be detected immunologically in the kidney of patients with chronic renal failure and hypertension, but its pathophysiological role will require further study.

Correlation of glomerular basement membrane alterations with clinical data in progressive hereditary nephritis (Alport's syndrome).

Electron microscopic examination of glomerular basement membrane (GBM) was performed in 19 patients whose morphological changes as well as clinical features indicated the diagnosis of progressive hereditary nephritis (Alport's syndrome). The percentage of characteristically thickened and split and of thin GBM portions was determined in all the cases. The clinical course was more severe in males, which corresponded to higher rate of GBM alterations. In males, 58% of GBM was thickened and split and 24% was thin, while in females, the reverse was true, 28% was split and 48% of GBM was thin. There was a positive correlation of the split lesions and age in males, but not in females. The degree of splitting was directly proportional to the grade of proteinuria, while GBM thinning did not significantly correlate with proteinuria.

Significance of cytoplasmic inclusions in lupus nephritis.

The report describes 22 cases of lupus nephritis (20 diffuse and 2 mesangial) showing frequent tubuloreticular inclusions (TRI) in the glomerular and peritubular capillary endothelial cells as well as cylindric confronting cisternae (CCC) mainly in interstitial infiltrating cells. Ten other cases of lupus nephritis that were actively treated or were in the sclerosing stage and did not show CCC were also studied. The presence of cytoplasmic inclusions correlated with various clinical and histologic parameters. Cytoplasmic inclusions, especially CCC, are associated with clinically active, minimally treated renal disease of recent onset and histologically with active diffuse glomerular and acute interstitial lupus nephritis with many immune deposits.

Mesangiocapillary glomerulonephritis in Down's syndrome.

The clinical and pathologic features of progressive renal disease in 4 patients with Down's syndrome are described. All patients were male, between 20 and 30 years of age at the time of clinical presentation. Three out of 4 had proteinuria, and 2 had hematuria. Serologic tests for hepatitis B virus infection and antinuclear antibodies performed in 2 patients were negative. Examination of renal tissue from biopsy and/or from autopsy revealed mesangiocapillary glomerulonephritis (MCGN), type 1. While an increased incidence of congenital heart disease and acute leukemias has been documented in Down's syndrome, an association with MCGN has not been reported previously to our knowledge. This probably represents a form of idiopathic MCGN and may be related to the long survival of these individuals.