Karyomegalic interstitial nephritis: report of 3 new cases and review of the literature.

Karyomegalic interstitial nephritis is a rare, but perhaps an "underdiagnosed" condition. Peculiar nuclear changes characterize it, involving mainly tubular cells along with glomeruli and blood vessels. Herein, 3 bioptically proven new cases of patients with chronic renal failure are discussed. The first case had a recently diagnosed karyomegalic nephritis which, to date, still does not require dialysis. The other 2 (brother and sister) required dialysis 4 and 1 years after diagnosis. Karyomegalic changes were found not only in the skin and duodenal biopsies of the male, in skin and liver biopsies of the female and in the urine cells of both patients, but also in several organs (brain, thyroid, lung, esophagus, arteries) as shown at the autopsy of the female. There was a fatal outcome for both patients. The data reported in this study emphasize the usefulness of pathologic investigation of both tissue and urine samples in the identification of this disease. Moreover, as karyomegalic interstitial nephritis is strongly suspected to have a genetic background, its identification may well not only be of clinical relevance, due to its ominous outcome, but may also bear eugenetic value.

Microvessel density in prostate carcinoma.

The objective of this work was to assess the correlation between microvessel density (MVD), pathological stage and disease recurrence in a series of patients who underwent radical prostatectomy for prostate cancer. Pathological material from 75 consecutive radical prostatectomies performed before 1994 without neo-adjuvant treatment, in which sufficient follow-up data were available, was re-examined. Paraffin embedded material was re-cut and hematoxylin and eosin (H&E) stained. Areas of maximal angiogenesis within tumor were identified. Expression of CD34 was investigated by using the monoclonal antibody MY 10. Within the areas of maximal angiogenesis, microvessels expressing CD34 were counted and specimens were divided into two groups, one showing a count of less than 90 microvessels per microscopic field at 200 x magnification (MVD<90), the second more than 90 microvessels (MVD>90). The MVD was then related to pathological stage, Gleason score (GS) and outcome of the disease. Mean follow-up was 84 months. Clinical or biochemical progression was observed in 38.6% of patients. In low GS cases, MVD was always <90, whereas in GS 5-6, half had MVD <90 and half were >90. In high GS MVD was always >90. MVD was positively associated with a higher pathological stage. Progression of the disease was observed in 20% of MVD <90 and in 51% in MVD >90 (P=0.006). Mantel-Haensz test showed a correlation between MVD and time to progression (P<0.05). Although problems exist in methods of counting and in the cut-off number of vessels, which can discriminate the risk categories, it may be concluded that microvessel counts, using CD34 monoclonal antibody, can accurately predict the outcome of radical prostatectomy.

Cytogenetic and interphase FISH analyses of 73 basal cell and three squamous cell carcinomas: different findings in direct preparations and short-term cell cultures.

Cytogenetic analysis performed on 73 sporadic basal cell carcinomas (BCCs) and three squamous cell carcinomas (SCCs) showed different findings in direct preparations (24 hours) and in short-term cell cultures. Except for loss of the Y chromosome, not one of the other clonal (+6, +16, add(2)(q37), del(3)(q13), add(1)(p31), and near triploidy) or sporadic changes found in direct preparations was found in cell cultures and vice versa. Clonal trisomy 6 found in two BCC direct preparations and demonstrated by interphase fluorescence in situ hybridization in 8 other cases seems to be a nonrandom change in basal cell carcinoma. Immunohistochemistry showed that the cell type investigated was different in the two methods of analysis used: epithelial in direct preparations and fibroblastic in cell cultures. Thus, the results obtained in direct preparations indicate the BCC or SCC epithelial karyotype, whereas the aberrations found in cell cultures indicate the presence of chromosome instability in the fibroblastic stroma. The apparent lack of correspondence between direct and indirect preparations and the presence of clonal chromosome changes in both epithelial and stromal cells suggest tumor cell heterogeneity of BCC. The fibroblastic stroma seems to be implicated in the neoplastic process. This is not evident in SCC, in which clonal changes are present only in direct preparations. The chromosomal distribution of the breakpoints involved in structural changes in direct and cell culture preparations is random; together with those reported in the literature, the breakpoints found in BCC cultures show, however, a cluster to 1p36, 3q13, 9q22, 14p11, 15p11, and Xp11 bands. We did not find any significant correlations between BCC cytogenetic results and the clinical data (site, age, sex, recurrence). The incidence of cases of BCC (38%) and of SCC (100%) showing clonal chromosome changes agree with their benign and malignant nature, respectively. Finally, a significantly high incidence of constitutional inv(9) and dup(9)(q11q21) was found in the group of patients with BCC.

Tissue polypeptide-specific antigen (TPS) immunoassay in the diagnosis and clinical staging of prostatic carcinoma. Comparison with prostate-specific antigen (PSA).

UNLABELLED: This experimental study investigated the potential role of Tissue Polypeptide-Specific Antigen (TPS) in comparison with Prostate-Specific Antigen (PSA) in the diagnosis and the clinical and pathological staging of prostate cancer. Serum TPS and PSA levels were determined in 128 patients (pts) with benign prostatic hypertrophy (BPH; Group 1) and in 92 pts with prostate cancer (Group 2). TPS was also measured in a control group of 100 healthy subjects. Normal cutoff values of 85 U/l for TPS and 4 ng/ml for PSA were determined on the basis of ROC curve analysis. The sensitivity, specificity and accuracy in the diagnosis of prostate cancer were 49%, 95% and 76% for TPS, and 84%, 90% and 87% for PSA. The combination of the two markers provided a higher accuracy (88%), improving the sensitivity of PSA, since 47% of patients with normal PSA had pathological levels of TPS. TPS showed an increase in sensitivity from low to higher stages of disease and, in patients with skeletal involvement, from small to larger numbers of bone metastases (Kruskal Wallis p < 0.0001). Nevertheless, TPS serum levels are not useful in the clinical staging of prostate cancer as they have a poorer performance than PSA. TPS was ineffective (ROC curve area = 0.68) in predicting extraprostatic disease and demonstrated a reduced ability (area = 0.78) to identify skeletal involvement. Moreover, the combination of the two markers did not significantly improve the performance of PSA alone. The serum concentration of TPS in patients with localized tumors was not related to the degree of tumor cell differentiation evaluated by the Gleason score. CONCLUSION: Our preliminary experience suggests that TPS in association with PSA may be useful at the time of diagnosis of prostate cancer. However, these preliminary data have to be confirmed by larger clinical trials and the role of this association in the clinical setting needs to be analyzed with an adequate evaluation of the cost-effectiveness ratio.

Nuclear medicine imaging in a case of hyperfunctioning parathyroid carcinoma associated with a parathyroid adenoma.

This report describes a rare case of parathyroid carcinoma associated with an adenoma. Nuclear imaging provided the most specific information about localization of the primary carcinoma and cervical metastasis, but failed to demonstrate evidence of a parathyroid adenoma. This could be explained by a partial inhibition of hormonal biosynthesis due to the high level of circulating parathormone produced by the carcinoma.

Clonal chromosome changes in non-neoplastic ureters.

Cytogenetic analysis was performed on 23 samples from non-neoplastic ureters. Clonal chromosome abnormalities were found in eight. They were: loss of Y chromosome, as a single abnormality (five cases) or associated with trisomy 10 and 20 (one case) or with trisomy 2 (one case); and duplication of Y chromosome (one case). Different numerical and structural sporadic abnormalities were found in nine cases. Immunohistochemical analysis and direct observation using the inverted microscope showed that the cells were mainly of the fibroblastic type. FISH analysis with chromosome 7 alpha-satellite probes failed to detect the presence of trisomy 7 in three epithelial cases tested.

Clonal chromosome changes in renal carcinoma do not correlate with clinical stages and histopathologic grades.

We analyzed the correlations between chromosome abnormalities and clinical and histopathologic characteristics in 77 cases of renal cell carcinoma (RCC). Chromosome changes such as +5,+7,+8,+10,+18,+X,+Y, and -Y have been excluded from the analysis because they also occur in nonneoplastic kidney tissue and cytogenetic analysis indicates that these anomalies are not involved in tumor progression. The most frequent specific chromosome abnormalities in this sample were 3p rearrangements, trisomy 17, and hyperdiploidy and were not related to tumor stage or grade or to development of distant metastases.

Postoperative radiation therapy for adult soft tissue sarcomas: a retrospective study.

From 1977 to 1988, 81 adult patients with localized soft tissue sarcomas at different sites received postoperative external beam radiotherapy (55 Gy median dose) following primary conservative surgery. Sixty were new referrals after primary surgery and 21 were irradiated after excision of recurrent disease. With a median follow-up of 4 years (range: 2-13) the 5-year overall survival (Kaplan-Meier) and local control were 55.5% and 56% respectively, while 5-year disease-free survival is 49%. There were 26 (32%) local relapses and 22 (27%) distant failures. Local recurrence was the sole pattern of failure in 16 patients (20%). Functional and cosmetic results were good to excellent in most cases. In our series local control is the main prognostic variable influencing survival (P less than 0.0001), and its probability seems to show a link with the type of surgical procedure, with a trend (P less than 0.13) in favor of wide total excision. Postoperative radiation therapy represents an acceptable treatment strategy for ASTS, but further improvements are expected from future controlled clinical trials, aiming at the achievement of the definitive cure of these tumors.

Preparation and characterization of anti-human chromogranin A and chromogranin B (secretogranin I) monoclonal antibodies.

Chromogranin A, chromogranin B/secretogranin I and chromogranin C/secretogranin II are acidic sulphated and phosphorylated secretory proteins present in a large number of endocrine and neuronal tissues. It has been suggested that these proteins may be useful immunohistochemical markers for human tumours of endocrine origin and their measurement in plasma has been proposed as a diagnostic tool in patients with these tumours. In order to obtain anti-human chromogranins/secretogranins antibodies for clinical applications, we immunized mice with whole chromaffin granules isolated from human pheochromocytoma. The immune sera analysed by two-dimensional immunoblotting were found to recognize chromogranins/secretogranins and other unidentified proteins and to react in immunocytochemistry with pheochromocytoma as well as with a number of endocrine cells of different types. Hybridoma supernatants obtained from the splenocytes of a hyperimmune mouse, screened with an enzyme-linked immunosorbent assay, were analysed by both immunocytochemistry and two-dimensional immunoblotting. By using this experimental approach we were able to identify several monoclonal antibodies against human chromaffin granule components. In particular, we have characterized one anti-human chromogranin A and one anti-human chromogranin B/secretogranin I monoclonal antibody which showed a very specific pattern both in immunocytochemistry and in two-dimensional immunoblotting.

Calbindin 28 kDa in endocrine cells of known or putative calcium-regulating function. Thyro-parathyroid C cells, gastric ECL cells, intestinal secretin and enteroglucagon cells, pancreatic glucagon, insulin and PP cells, adrenal medullary NA cells and some pituitary (TSH?) cells.

The distribution of calbindin in some endocrine glands (thyroid, parathyroid, ultimobranchial body, pituitary and adrenals) and in the diffuse endocrine cells of the gut and pancreas has been investigated immunohistochemically using an antiserum raised against the 28 kDa calbindin from chicken duodenum. The identity of calbindin-immunoreactive cells in a number of avian and mammalian species was ascertained by comparison with hormone-reactive cells in consecutive sections or by double immunostaining of the same section with both calbindin and hormone antibodies. Calcitonin-producing C cells of the mammalian and avian thyroid, parathyroid or ultimobranchial body, PP, glucagon and insulin cells of the mammalian and avian pancreas, enteroglucagon cells of the avian intestine, secretin cells of the mammalian duodenum, histamine-producing ECL cells of the mammalian stomach, as well as noradrenaline-producing cells of the adrenal medulla and some (TSH?) cells of the adenohypophysis were among the calbindin-immunoreactive cells. Although some species variability has been observed in the intensity and distribution of the immunoreactivity, especially in the pancreas and the gut, a role for calbindin in the mechanisms of calcium-mediated endocrine cell stimulation or of intracellular and extracellular calcium homeostasis is suggested.

Chromogranins A and B and secretogranin II in hormonally identified endocrine cells of the gut and the pancreas.

Chromogranins A and B and secretogranin II have been localized in a wide spectrum of gastroenteropancreatic endocrine/paracrine cells. Chromogranin A immunoreactivity showed the widest distribution and was displayed by glucagon-, PP-, gastrin-, gastrin-CCK-, secretin-immunoreactive cells, the most intense stainings being peculiar of enterochromaffin cells. Chromogranin B immunoreactivity was detected in gastrin- and glucagon cells and in some enterochromaffin cells containing also chromogranin A. Secretogranin II was paired to chromogranin A in glucagon cells of pancreatic islets or occurred alone in glycentin/PP cells of colonic mucosa. Neither of the chromogranins nor secretogranin II have been so far detected in somatostatin-, GIP-, or motilin-immunoreactive cells. Chromogranin A but not chromogranin B or secretogranin II has been detected in the gastric argyrophilic ECL cells.