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Biomedical subjects

G Zamboni

Publications and source records attributed to G Zamboni.

At least 91 records · Page 5Linked to original sources

Clear cell "sugar" tumor of the pancreas. A novel member of the family of lesions characterized by the presence of perivascular epithelioid cells.

We report at unique, previously unreported pancreatic tumor occurring in a 60-year-old woman who was preoperative diagnosed on cytoaspiration as having clear cell carcinoma. The resected tumor consisted of a population of large epithelioid cells with clear or eosinophilic, granular cytoplasm, rich in glycogen, with nuclear pleomorphism and no mitotic activity. In spite of the epithelioid appearance, the tumor cells were negative for epithelial (CAM 5.2, KL1, AE1-AE3), endocrine (neuron-specific enolase [NSE], chromogranin A), and acinar (lipase, amylase) markers and positive for actin and melanogenesis-related marker HMB 45. Ultrastructurally, the neoplastic cells showed membrane-bound granules; no evidence of either epithelial or melanocytic differentiation was present. These morphophenotypic features have never been reported in a pancreatic tumor and overlap those of clear cell "sugar" tumor of the lung. The same morphophenotypic features are observed in a family of lesions characterized by the presence of the perivascular epithelioid cell that also includes lymphangiomyomatosis and angiomyolipoma. The present case may be considered a novel member of this family of lesions. We propose this new entity be named clear cell "sugar" tumor of the pancreas.

Adenocarcinoma, Clear Cell↗

Expression of MHC class I and class II antigens in pancreatic adenocarcinomas.

The antigens encoded by the major histocompatibility complex (MHC) are cell surface glycoproteins that play a fundamental role in the regulation of the immune response. Anomalous MHC expression in tumor cells has been viewed as an important feature to escape tumor recognition by immune cells. Low or absent MHC class I expression as well as ectopic MHC class II expression have been often observed to correlate with high grade malignancy and metastatic potential in a variety of human cancers. To date, very little investigation of MHC (HLA in man) class I and class II expression in human pancreatic cancer has been reported. We investigated this aspect on frozen sections of 8 pancreatic adenocarcinomas and 18 established in vitro cell lines. HLA class I was expressed in all but two cancers whereas de novo HLA class II expression was detected in 3 of 8 cancers. Interestingly, a hierarchy in the expression of the various subsets of HLA class II was found with HLA- DR > -DP > -DQ. Results on cell lines strongly resembled the ones obtained in cancer tissues. However, a peculiar feature was observed in certain cell lines. HLA class II antigens were expressed in only a few cell lines and in some of them a mixed population of positive and negative cells was found. Sorting and cloning of the two populations confirmed the existence of tumor cell clones with stable and distinct HLA class II phenotype. Taken together, these results indicate the cellular heterogeneity of pancreatic cancer cells with regard to the qualitative and quantitative expression of major histocompatibility complex genes, and may provide new insights for a better understanding of the tumorhost relationships in this extremely severe form of neoplasia.

Adenocarcinoma↗

Intraductal mucin-producing tumors of the pancreas: imaging findings.

PURPOSE: To evaluate the radiologic characteristics of intraductal mucin-producing tumors of the pancreas. MATERIALS AND METHODS: Sixteen patients with intraductal tumors underwent ultrasound (US); (n = 15), computed tomography (CT); (n = 16), endoscopic retrograde cholangiopancreatography (ERCP); (n = 12), and intraoperative pancreatography (n = 2). Findings were compared with those from surgery (n = 14) or biopsy (n = 2). RESULTS: Lesions were classified as either main duct type or branch duct type tumors. Main duct tumors were characterized at US and CT by either diffuse or segmental dilatation of the Wirsung duct. Pancreatography showed ductal dilatation and filling defects caused by mucin deposits. At US and CT, branch duct tumors, which were mainly located at the uncinate process, were seen as fluid-filled masses with central septa and the pancreatic duct was dilated. ERCP showed partial or complete opacification of the lesion. In four patients, endoscopy showed protrusion of the papilla into the duodenal lumen and mucin leaking from its dilated orifice. CONCLUSION: Imaging modalities, especially US and ERCP, enable early diagnosis of mucin-producing pancreatic tumors.

Adenocarcinoma, Mucinous↗

Growth hormone-binding proteins and insulin-like growth factor-binding proteins in protein-energy malnutrition, before and after nutritional rehabilitation.

To clarify the influence of nutrition on the GH-IGF axis in protein-energy malnutrition (PEM), we determined the serum levels of GH, GH-binding proteins (BP) (GHBPs), IGF-I, and IGFBPs in nine children with kwashiorkor and 13 with marasmus, before and after nutritional rehabilitation. In a basal condition, the GH level was significantly higher in the two malnourished groups than in controls (p < 0.01); in contrast, the second fraction of GHBP was lower and seemed to be related to the high GH and to a reduction in GH receptors. After refeeding, the GH level increased and the second fraction of GHBP decreased. The IGF-I basal level was higher in kwashiorkor than in marasmus subjects (p < 0.05), but in both groups it was significantly lower than in controls (p < 0.01); after refeeding it increased. IG-FBP-3, measured by RIA and Western blotting techniques, was in the control range in the kwashiorkor group but in the marasmic group it was significantly lower than in controls; after refeeding it decreased in kwashiorkor (p < 0.01 versus basal values) and increased in marasmus (p < 0.05 versus prerefeeding level). When sera of malnourished patients were mixed with adult control sera, incubated for 5 h at 37 degrees C, and assessed by ligand blotting, a low IGFBP-3 level in marasmus was found to be due to increased adaptive proteolysis of IGFBP-3; in contrast, in kwashiorkor the IGFBP-3 proteolytic activity was very low, probably because of inhibition by aflatoxins. These findings confirm that malnutrition affects the GH-IGF axis.

Adult↗

cAMP accumulation in the hypothalamus, cerebral cortex, pineal gland and brown fat across the wake-sleep cycle of the rat exposed to different ambient temperatures.

The concentration of adenosine 3':5' cyclic monophosphate (cAMP) was determined in the anteroventro-medial hypothalamus, the cerebral cortex, the pineal gland and the interscapular brown adipose tissue, during the different stages of the wake-sleep cycle of rats kept, under a 12-12-h light-dark cycle, in different environmental conditions, i.e., control (47-52 h at ambient temperature (Ta) 23 +/- 0.5 degrees C), exposure (47-52 h at Ta 0 +/- 1 degree C) and recovery (1-4 h at Ta 23 degrees C after 48 h at Ta 0 degree C). The results show that cAMP concentration consistently changed: (1) during the wake-sleep cycle in the anteroventro-medial hypothalamus, decreasing from wakefulness to sleep; (2) during the dark-light transition in the pineal gland, increasing with the onset of the light phase; and (3) with the environmental condition in the interscapular brown adipose tissue increasing, with respect to the control condition, in exposure and recovery. No significant changes in cAMP concentration were observed in the cerebral cortex.

Adipose Tissue, Brown↗

Solid and cystic papillary neoplasm of the pancreas: a clinico-cytopathologic and immunocytochemical study of five new cases diagnosed by fine-needle aspiration cytology and a review of the literature.

We report here on five new cases of solid and cystic papillary neoplasm (SCPN) of the pancreas diagnosed by fine-needle aspiration cytology (FNAC). All cytologic samples were obtained by ultrasonography, and the smears were conventionally fixed and stained. Special histochemical and immunocytochemical stains were also performed in some samples. Cytology revealed in all but one case numerous pseudopapillary structures composed of fibrovascular stalks lined with one or more layers of bland-appearing, uniform tumor cells. The tumor cells had round-to-oval euchromatic nuclei with frequently folded smooth contours and one or two small nucleoli. Their cytoplasm often contained eosinophilic, PAS-positive, and diastase-resistant inclusions. Foamy cells, psammoma bodies, blood, and cellular debris were found in the background. The criteria for the differential diagnosis versus other pancreatic lesions are discussed in some detail, as is the role of immunocytochemistry (ICC). In the literature, only 28 cases of cytologically investigated SCPN have been reported to the best of our knowledge. The most helpful criteria for the conclusive identification of SCPN by FNAC include the pseudopapillary arrangement with bland-appearing tumor cells, and, especially, the finding of acidophilic, PAS-positive, and diastase-resistant cytoplasmic granules.

Adolescent↗

Brain metastases from post-radiation malignant peripheral nerve sheath tumour.

A 45-year-old female patient developed a malignant peripheral nerve sheath tumour (MPNST) arising from the left brachial plexus, ten years after regional radiation treatment for Hodgkin's disease. The clinical course was characterized by local recurrence, pulmonary and cerebral metastases with endocranic hypertension syndrome, and the death of the patient 18 months after the onset of symptoms. The tumour presented a histopathological picture of schwannoma with a high grade of malignancy. A particular feature of this case was the exceptional occurrence of the early and massive invasion of the brain.

Brain Neoplasms↗

Delayed separation of an appendix-containing umbilical stump.

A case of delayed separation of the umbilical cord is reported. Ultrasonography and radiographic examination of the stump showed connection with the bowel. During surgery the cord was found to contain the appendix. The authors hypothesize that this anomaly represents a small omphalocele, resulting from failure of the gut to withdraw completely from the umbilical cord, or, less likely, a hernia.

Appendix↗

Use of the gonadotropin-releasing hormone agonist triptorelin in the diagnosis of delayed puberty in boys.

To differentiate gonadotropin deficiency from delayed puberty in teenage boys, 0.1 mg/m2 of triptorelin, a gonadotropin-releasing hormone agonist, was administered subcutaneously at 4 AM. Serum gonadotropins and testosterone levels were determined at baseline and 4 hours after the injection. The increase in blood gonadotropin and testosterone levels was significantly greater in patients with delayed puberty than in those with gonadotropin deficiency.

Adolescent↗

Routine application of polymerase chain reaction in the diagnosis of monoclonality of B-cell lymphoid proliferations.

We evaluated four polymerase chain reaction (PCR) methods for their efficiency in detecting monoclonality in a well-characterized panel of frozen and paraffin-embedded B-cell lymphoid proliferations. These approaches (referred to as FR3, FR3A, FR2, and FR1) are based on amplification of rearranged immunoglobulin heavy chain genes, using primers recognizing framework regions I, II, or III. FR3, FR3A and FR2 approaches reproducibly detected monoclonality in 51%, 72%, and 67% of DNAs from frozen lymphomas, respectively. No false-positives were observed. The combination of FR2 and FR3A methods raised the figure to 85%. Comparable results were obtained using paraffin-embedded lymphomas. Reproducibility of FR1 approach was unsatisfactory. The efficiency of all PCR approaches varied depending on lymphoma type. The highest detection rate was in small/intermediate cell and the lowest in centro-follicular lymphomas. Limiting dilution assays showed that PCR methods were able to detect monoclonal B-cell DNA representing 5% of nonlymphoid and 20% of polyclonal B-cell DNA. A diagnostic protocol may include quick and cost-effective PCR screening, particularly in cases of undetermined small cell lymphoid proliferations observed in fine needle aspirates or endoscopic biopsies. This would also reduce call-up of patients to obtain unfixed biopsies.

Base Sequence↗

Bone mineral metabolism in girls with precocious puberty during gonadotrophin-releasing hormone agonist treatment.

Bone mineral metabolism and mineralization before and during treatment were studied in 10 girls aged 6.9-8.4 years affected by central precocious puberty and treated with gonadotrophin-releasing hormone agonist (GnRHa) leuprolide acetate depot, in order to understand better the consequences of oestrogen deficiency and the reduction of growth hormone (GH)-insulin-like growth factor I (IGF-I) axis activity. Before and after 12 months of therapy, the patients underwent a clonidine stimulation test and a 4-day calcitriol osteoblast stimulation test. On day 0, day 5 and at 3-month intervals thereafter, serum calcium, phosphate, alkaline phosphatase, IGF-I, IGF binding protein 3 (IGFBP-3), GH, GH binding protein and osteocalcin levels were measured; urinary calcium, phosphate and hydroxyproline levels were evaluated in fasting spot samples. Trabecular and cortical bone mass variations, measured by dual X-ray absorptiometry in the lumbar spine and by dual photon absorptiometry in the radius, respectively were evaluated before the start and after 12 months of therapy. During treatment, a decrease of serum oestradiol levels from pubertal to prepubertal levels was observed. The GH peak following clonidine diminished significantly after 1 year. Growth hormone binding protein showed a slight increase, and IGF-I and IGFBP-3 decreased, although not significantly. Osteocalcin levels decreased significantly after 9 and 12 months of treatment, but they did not change significantly after calcitriol load, either before or after GnRHa therapy. Urinary hydroxyproline decreased significantly after 12 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Body Height↗

Solid-cystic tumor of the pancreas. An extensive ultrastructural study of fourteen cases.

Fourteen cases of solid-cystic tumor of the pancreas have been investigated at the ultrastructural level. A heterogeneous cell population has been found, and some distinctive features have been identified: oncocytoid cells; clear cells reminiscent of ductular and centro-acinar cells; cells with exocrine and endocrine features; cells with bundles of microfilaments and dense bodies, reminiscent of myoepithelium. This varied differentiation strongly suggests the tumor histogenesis to be from multipotent cell capable of recapitulating the normal ontogenesis during its neoplastic proliferation. Furthermore, the heterogeneity in ultrastructural appearance is a characteristic and reliable feature of solid-cystic tumor of the pancreas.

Adolescent↗

ras-family gene mutations in neoplasia of the ampulla of Vater.

Mutations in the first and second exons of Ha-, Ki- and N-ras oncogenes were investigated in 17 epithelial tumors of the ampulla of Vater by single-strand conformation polymorphism analysis and direct sequencing of DNA fragments amplified by polymerase chain reaction. The panel included 12 intestinal-type adenocarcinomas, 3 villous adenomas, 1 papillary carcinoma and 1 neuroendocrine carcinoma. Six cases (35%) contained ras mutations, affecting codon 12 of Ki-ras in 2 adenomas and 3 carcinomas, and of N-ras in 1 adenoma. All mutations were found in adenomas and among cancers with adenomatous areas, whereas none of the cases lacking adenomatous areas contained mutations. This suggested that ampullary cancers represent heterogeneous diseases with respect to the presence or absence of adenomatous areas and, among those with adenomatous areas, with respect to the presence of activated ras genes. Ki-ras mutated cases included 3 of 4 tumors which mainly involved the intraduodenal bile duct, thus suggesting that a proportion of Ki-ras-mutated ampullary cancers might correspond to those originating from the epithelium of the bile duct component of the ampulla.

Adenocarcinoma↗

Pancreatic cancer in Europe: Ki-ras gene mutation pattern shows geographical differences.

Seventy-seven pancreatic adenocarcinomas (60 Spanish and 17 Italian) were tested for Ki-ras gene mutations by analysis of polymerase chain reaction amplified sequences. Mutations involving codon 12 (GGT; gly) were detected in 16 Italian and 46 Spanish cases (80.5% in total). All Italian mutations involved the second base and were G to A transitions (GAT; asp) in 8 cases and G to T transversions (GTT; val) in the remaining 8. Forty-two Spanish mutations were characterized. Thirty-eight were at the second and 4 at the first base: asp in 24 cancers, val in 14, arg (CGT) in 2 and cys (TGT) in 2. Previous European studies and our present data show that 149 of the 186 pancreatic cancers harbored a codon 12 Ki-ras mutation (80%), the large majority affecting the second base (73%), with a transitions/transversions ratio of 1.3:1. However, the mutational pattern of cancers of the different European countries shows remarkable differences, both in the site of the mutation (first or second base) and in the ratio of transitions over transversions. Moreover, a significant subgroup of pancreatic carcinomas do not harbor Ki-ras mutations. The classification of pancreatic cancers, according to the presence or absence, and type of Ki-ras mutation, may be of importance in epidemiological studies. A critical reappraisal of existing epidemiological data, through a retrospective genotypic study using paraffin-embedded cancer samples, may reveal significant correlations with specific genotoxic agents.

Adenocarcinoma↗

Breast solitary schwannoma: fine-needle aspiration biopsy and immunocytochemical analysis.

A case of intramammary solitary schwannoma (SS) (benign neurilemoma) diagnosed by fine-needle aspiration biopsy (FNAB) and supported by immunocytochemical study is reported. The tumor arose in the right breast of an 18-yr-old woman and was clinically and radiologically considered a fibroadenoma. The smears obtained by FNAB of the lump showed clusters of spindle-shaped cells and suggested a benign mesenchymal neoplasm. The presence of some structures reminiscent of Verocay bodies and the immunocytochemical reactivity for S-100 protein antiserum demonstrated the schwannian nature of the tumor and suggested the diagnosis of SS. The final histologic examination confirmed the cytologic diagnosis.

Adolescent↗

Intraductal papillary-mucinous tumours represent a distinct group of pancreatic neoplasms: an investigation of tumour cell differentiation and K-ras, p53 and c-erbB-2 abnormalities in 26 patients.

Intraductal papillary growth of mucin producing hypersecreting, columnar cells characterizes a group of rare pancreatic exocrine neoplasms which we propose to call intraductal papillary-mucinous tumors (IPMT). We analysed the histopathology of 26 IPMT in relation to gastro-enteropancreatic marker expression, genetic changes and biology. Four IPMT showing only mild dysplasia were considered to be adenomas. Nine tumours displayed moderate dysplasia and were regarded as borderline. Severe dysplasia-carcinoma in situ changes were found in 13 IPMT which were therefore classified as intraductal carcinomas. Six of these carcinomas were frankly invasive and two of these had lymph node metastases. The invasive component resembled mucinous non-cystic carcinoma in all but one tumour which showed a ductal invasion pattern. Immunohistochemically, an intestinal marker type was found in most carcinomas, while gastric type differentiation prevailed among adenomas or borderline tumours. K-ras mutations (seven at codon 12 and one at codon 13) were found in 31% of IPMT (2 adenomas, 1 borderline, 5 carcinomas). Nuclear p53 overexpression was detected in 31% of IPMT (6 carcinomas and 2 borderline IPMT) and correlated with p53 mutations (one at exon 8 and the other at exon 5) in two carcinomas. p53 abnormalities were unrelated to K-ras mutation. c-erbB-2 overexpression was observed in 65% of IPMT, with various grades of dysplasia. Twenty-two of 24 patients are alive and well after a mean post-operative follow-up of 41 months. Only two patients, both with invasive cancer at the time of surgery, died of tumour disease. It is concluded that pancreatic IPMT encompass neoplasms which, in general, have a favorable prognosis, but are heterogeneous in regard to grade of dysplasia and marker expression. Adenoma, borderline tumour, intraductal carcinoma and invasive carcinoma can be differentiated. p53 changes but not K-ras mutation or c-erbB-2 overexpression are related to the grade of malignancy. Most IPMT differ in histological structure, marker expression and behaviour from ductal adenocarcinoma.

Adult↗

Preoperative diagnosis of renal angiomyolipoma: fine needle aspiration cytology and immunocytochemical characterization.

A preoperative diagnosis of renal angiomyolipoma (AML) is of great importance for a correct management of these patients with this tumor. In fact when the lesion is small and asymptomatic a conservative approach may be considered. We have evaluated the radiographic and fine needle aspiration cytology (FNAB) findings in 8 cases of AML. In 3 cases both radiology and cytology were suggestive of carcinoma and thus the patients underwent surgery. In one case both techniques suggested AML but surgery was performed because the lesion was large and symptomatic. In 4 cases where both radiology and cytology suggested AML no surgery was performed. Follow-up data are consistent with the benign nature of the lesions. The immunocytochemical analysis of the FNAB with a panel of antibodies including keratin, vimentin, actin and HMB-45 was indicative of AML in 7 of 8 cases, including 2 of the 3 cases misdiagnosed as carcinomas. The presence of HMB-45-positive perivascular epithelioid cells in the FNABs was the most significant finding. It is concluded that immunocytochemical analysis of FNAB with this monoclonal antibody panel can increase the accuracy of preoperative diagnosis of AML, and allow consideration of a conservative approach in selected cases.

Actins↗