Immunohistochemical analysis of human serum sickness glomerulonephritis.

AIM: To analyze pathological and immunohistochemical characteristics of glomerulonephritis in human serum sickness. METHODS: Renal biopsy specimens from two female patients with serum sickness that ensued after application of anti-lymphocyte horse globulin for aplastic anemia were analyzed by light microscopy, immunofluorescence, and electron microscopy. To prove the depositions of foreign protein, frozen sections were incubated with fluorescein-conjugated anti-horse protein serum. Immunohistochemical analysis was performed on B5-fixed paraplast-embedded tissue or frozen acetone-fixed sections with the primary antibodies for molecules/cell markers CD35, CD43, CD45RO, CD68, CD2, lysozime, L26, and S100. RESULTS: Diffuse proliferating and necrotizing glomerulonephritis with crescents was found. There were coarse granular mesangial, subepithelial, subendothelial, and intramembranaceous deposits of mainly horse globulin, C3, and IgG. Most mesangium infiltrating cells were macrophages and T-lymphocytes. Electron microscopy revealed hypertrophy of podocytes, but immunohistochemistry did not show their normal CD35 (C3b-receptor) staining. Apart from epithelial cells, main crescent forming cells were macrophages and T-lymphocytes. Rare dendritic cells and abundant infiltration of macrophages, T-lymphocytes, and neutrophiles were found in the interstitium. CONCLUSION: In severe serum sickness, glomeruli and tubuli are destroyed beyond the range usually seen in other types of glomerulonephritis caused by immune complexes, except in cases with widespread crescents. Hypertrophy of podocytes and loss of their normal C3b-receptor staining has not yet been described in the literature. C3b-receptors on podocytes could play a role in pathogenesis of glomerular injury caused by immune complexes.

Etoposide as the basic and interferon-alpha as the maintenance therapy for Langerhans cell histiocytosis: a RTC.

The treatment of patients who suffer from a disseminated form of Langerhans cell histiocytosis (LCH) is still controversial. So far, few larger randomized studies have been performed. The authors present 3 patients with a disseminated form of LCH--4 months, 9 months, and 2 years old, respectively. The lesional Langerhans cells in each patient showed positive immunohistochemical reaction to S-100 protein and the presence of Birbeck granules was confirmed by electron microscopy. All the patients were treated with etoposide (VP-16), 200 mg/m2 for 3 consecutive days, with 15 cycles at intervals of 3 weeks between each cycle, followed by maintenance therapy with IFN-alpha. All 3 patients reached complete stabile remission. The patients were young, at high risk, with multiple-organ involvement of LCH, and two of them had obvious signs of organ dysfunction at presentation, suggesting a poor prognosis. All remain disease-free several years after therapy. The results suggest that INF-alpha may prevent recurrences in high-risk patients.

Hypokalemic metabolic alkalosis--three case reports.

The two most common forms of inherited normotensive hypokalemic metabolic alkalosis are Bartter's and Gitelman's syndromes. Bartter's syndrome typically present with normal or increased calcium excretion. Hypomagnesemia occurs in only one third of affected individuals. In contrast, hypomagnesemia and hypocalciuria are considered hallmarks of Gitelman's syndrome. In most patients, the symptom of muscle weakness and polyuria occur early in life, which may be attributed to potassium depletion. Despite hyperaldosteronism, the patients tend to be normotensive, which is at least explained by vascular hyperresponsiveness to prostaglandins. Therapeutic approaches to Bartter's and Gitelman's syndromes include potassium supplementation, prostaglandin synthesis inhibitors (nonsteroid anti-inflammatory agents), aldosterone antagonists and converting enzyme inhibitors. Three patients with hypokalemia, normal blood pressure, metabolic alkalosis, hyperreninemia and hyperaldosteronism are described. Two patients had Bartter's syndrome and one patients had Gitelman's syndrome.

Complete remission of cryoglobulinemic glomerulonephritis (HCV-positive) after high dose interferon therapy.

We report the case of a 64-year old woman with hepatitis C virus infection, mixed cryoglobulinemia type II (IgG + IgM kappa) and cryoglobulinemic glomerulonephritis. The patient was treated with the standard dose of recombinant interferon alpha-2b (3 million units 3 times a week) for one year, resulting in complete clinical remission and undetectable levels of serum hepatitis C virus RNA. AST and ALT normalized and proteinuria decreased from 2.78 to 0.98 g/day. However, a relapse occurred when therapy was stopped. Additional therapy with interferon-alpha (5 million units 3 times a week for 9 months) resulted again in quick and prolonged remission. The clinical course of our patient showed sustained clinical and virologic response after high-dose interferon-alpha treatment confirming the usefulness of interferon alpha in treatment of patients with cryoglobulinemic glomerulonephritis. Our observation is in agreement with others, suggesting that recommended standard dosage and duration of initial treatment with interferon alpha should be re-evaluated. Although our patient had sustained virologic and clinical response after interferon alpha monotherapy, recent studies clearly support combination therapy of interferon alpha and ribavirin for treatment of chronic HCV infections.

Pleural mesothelioma and membranous nephropathy.

Underlying malignancy has been thought to be responsible for 5-10% of the cases of membranous nephropathy in adults, with the risk being highest in patients over the age of 60 years. Solid tumors such as carcinomas of lung or colon, are most often involved. It is presumed that tumor antigens are deposited in the glomeruli; this is followed by antibody deposition and complement activation, leading to epithelial cell and basement membrane injury and proteinuria due to the associated increase in glomerular permeability. We describe a patient with a resistant nephrotic syndrome and massive proteinuria due to membranous nephropathy associated with pleural mesothelioma.

Quantitative tissue carcinoembryonic antigen (T CEA) assay as a screening test for severe dysplasia in colorectal adenomas.

Relationship between the serum (S CEA) and the tissue (T CEA) carcinoembryonic antigen concentrations with regard to the degree of dysplasia in colorectal adenomas was investigated. Our study included 56 single or multiple colorectal adenomas in 46 patients. The measurements of T CEA concentrations were performed using the quantitative CEA-EIA method (Abbott) modified for wet tissue, obtained from heads of the adenomas. As a control point the mucosa near adenoma and the rectal mucosa were used. Our results suggest that the T CEA concentrations from the head of the adenoma demonstrate a highly significant difference between mild and severe dysplasia (P < 0.001), between mild dysplasia and invasive adenocarcinoma (P < 0.001) and a significant difference between mild and moderate dysplasia (P < 0.05). On the other hand, the S CEA concentrations corresponding to these cases showed no such differences. In conclusion, we suggest the quantitative measurement of T CEA concentrations as a screening test for severe dysplasia in colorectal adenomas.

[Primary ciliary dyskinesia]. / Primarna cilijarna diskinezija.

The immotile cilia syndrome is a genetic disease characterized by chronic disease of the upper and lower respiratory tract, male infertility and situs viscerum inversus in 50% of affected patients. Abnormalities of ciliary structure are the cause of abnormalities in mucociliary clearance and chronic inflammation consecutively. The boy aged 13 years with clinical manifestations (chronic rhinorrhea, sinuitis, recurrent otitis media, recurrent bronchial inflammation, pneumonia and finally bronchiectasis) has been presented. The boy had a normal visceral status. The diagnosis was confirmed by electron microscopy analysis of cross section of bronchial cilia: numerous abnormalities in microtubules positioning and lack of radiar arms have been found.

Salivary duct carcinoma metastasizing to the small bowel.

We report a case of salivary duct carcinoma in a 47-year-old woman. The patient presented with symptoms simulating acute appendicitis. Surgery revealed metastatic tumor in the wall of the small bowel. Two months later, a tumor of the right parotid gland was resected, and histologic analysis revealed a salivary duct carcinoma. To our knowledge, this is the first case of salivary duct carcinoma metastasizing to the small bowel with manifestations of metastatic disease as the prominent symptom.

Significance of proliferative epithelial changes in breast fine-needle aspiration.

The authors analyzed 6439 fine-needle aspirations (FNA). The total number of FNA performed per year at the authors' institution was found to be increasing. The authors analyzed the numbers of carcinomas and proliferative breast alterations separately. A statistically significant increase was recorded in the group of aspirate specimens that had epithelial proliferation; the increase was greater than that seen in aspirate specimens with normal epithelium (P less than 0.001). Biopsy was recommended in 151 of 6439 (2.3%) FNA and performed for 67 of the 151 (1.0%) recommendations. Cytologic findings were compared with pathohistologic findings. A histologic carcinoma was found in 14 of 67 (20.8%) patients who had biopsy performed. The authors concluded that clinicians should give particular attention to atypia in cytologic aspirate specimens.

Angiomyolipoma in the transplanted kidney. A case report.

Angiomyolipoma is a very rare benign renal tumor. This paper presents the autopsy finding of an angiomyolipoma in the transplanted kidney.

Expression of carcinoembryonic antigen in ulcerative colitis, tubular adenomas and hyperplastic polyps: correlations with the degree of dysplasia.

Sections of tubular adenomas (n = 40), ulcertive colitis (n = 97) and hyperplastic polyps (n = 31) were examined by immunoperoxidase staining to carcinoembryonic antigen (CEA) in order to assess its potential diagnostic value in predicting malignant potential of these lesions. We compared the degree of epithelial abnormality in these mucosal specimens with the extent of immunoperoxidase staining for CEA. We found that CEA staining correlated with the degree of epithelial alteration in tubular adenoma and ulcerative colitis groups. Scattered weakly positive staining was found in eight of 31 hyperplastic polyps. High tissue expression of CEA, when combined with histologic dysplasia, may prove to be an additional factor in the evaluation of malignant potential in ulcerative colitis specimens and adenomas.

[Strumal carcinoid tumor of the ovary--histologic and electron microscopy characteristics of the tumor]. / "Strumal carcinoid" tumor jajnika--histoloske i elektronskomikroskopske karakteristike tumora.

Strumal carcinoid tumor is a very rare primary tumor of the ovary in which carcinoid is admixed with tissue resembling thyroid follicles. We report a 44-year-old women with benign strumal carcinoid tumor of the ovary and without any clinical symptoms. Histochemical and electron microscopical examinations of the tumor showed intracytoplasmic dense core secretory granules, indicating that this neoplasm is a pure carcinoid tumor with acinar differentiation resembling thyroid tissue.

[Primary neuroendocrine carcinoma of the skin (Merkel cell tumor)]. / Primarni neuroendokrini karcinom koze (tumor Merkelovih stanica).

Three cases of neuroendocrine carcinoma of the skin studied by light and electron microscopy and by immunohistochemical methods, are presented. It is generally accepted that these tumors originate from Merkel's cells. Some consider that they belong to the group of APUD-omas. Positive findings of epithelial (EMA, CAM 5.2) and neuroedocrine marker (NSE) in these three cases support the hypothesis of neuroendocrine differentiation in a neoplasm of epithelial origin.

Relationship between tissue and serum concentrations of carcinoembryonic antigen (CEA) in gastric and colonic carcinomas.

A relationship between tissue and serum concentrations of carcinoembryonic antigen (CEA) as determined by monoclonal enzymo-immunoassay (EIA) was studied in 47 patients with gastric carcinoma and 46 patients with colorectal carcinoma. The values were then compared to those obtained in a control group of 64 healthy subjects. On the basis of results, an increase in tissue CEA is not paralleled by a simultaneous increase in serum CEA. Serum CEA depends on tumor mass and points to the process extension. There is no specific tissue CEA threshold above which the serum CEA concentration should unavoidably increase. A relationship between tissue and serum CEA concentrations according to the degree of differentiation, studied in colorectal carcinomas, revealed significantly lower values of tissue CEA concentration in poorly differentiated carcinomas, whereas serum CEA concentrations did not show any such difference. The present study has suggested that, having identified both tissue and serum CEA concentrations in colorectal carcinoma, the tumor, its size and differentiation could be readily and quite closely defined at the time of measurements.

[Tissue carcinoembryonic antigen: a screening test for increased cell proliferation?]. / Tkivni karcinoembrionalni antigen (CEA): test probiranja pojacane stanicne proliferacije?

A relationship between the tissue and serum concentrations of carcinoembryonic antigen (CEA) as determined by the enzymoimmunoassay (EIA) was studied in 46 patients with colorectal carcinoma and 47 patients with gastric carcinoma. The values were then compared to those obtained in the control group of 64 healthy subjects. Serum CEA concentrations were measured in all of them, whereas tissue CEA concentration was determined in the rectal and gastric mucosa homogenates in 30 and 34 subjects, respectively. As expected, no differences were observed in the levels of serum CEA concentrations in either of the healthy subject subgroups. The serum CEA concentrations were found to be at the normal level of 2.5 ng/ml. In both subgroups of healthy subjects, the tissue CEA concentration was found to significantly differ, but the same was in colorectal and gastric carcinomas as compared to the normal rectal and gastric mucosa. When the process extent according to Dukes' classification in 22 patients with colorectal carcinoma operated on was compared to the relationship between the tissue and serum CEA concentrations, the serum CEA concentration of CEA was shown to depend on the tumor mass, regardless of the level of the specific tissue CEA concentration. Unusually high values of tissue CEA concentration, along with normal serum CEA concentration, were observed in 3 healthy subjects. A relationship between the tissue and serum CEA concentrations according to the degree of differentiation, studied in colorectal carcinomas, revealed significantly lower values of tissue CEA concentration in poorly differentiated carcinomas (P less than 0.01), whereas serum CEA concentrations did not show any such difference.