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Biomedical subjects

M Bisceglia

Publications and source records attributed to M Bisceglia.

At least 37 records · Page 2Linked to original sources

H-caldesmon expression in myofibroblastoma of the breast: evidence supporting the distinction from leiomyoma.

AIMS: The ultrastructural detection of leiomyomatous rather than myofibroblastic features in some cases of myofibroblastoma of the breast led some electron microscopically orientated pathologists to doubt the commonly accepted myofibroblastic nature of such a tumour, so the alternative terms 'myogenic stromal tumour' or 'variant of leiomyoma' have been proposed. The aim of this study was to analyse the immunohistochemical expression of h-caldesmon, a reliable marker in distinguishing smooth muscle versus myofibroblastic cellular differentiation, in a large series of myofibroblastomas of the breast to clarify whether these tumours are basically leiomyomatous. Moreover, cases from primary myofibroblastic lesions of the breast, such as fibromatosis and inflammatory myofibroblastic tumour, were analysed to assess whether h-caldesmon expression parallels that observed in their soft tissue counterparts. METHODS AND RESULTS: Paraffin-embedded sections from 12 cases of myofibroblastoma, seven cases of fibromatosis, and one case of inflammatory myofibroblastic tumour were evaluated immunocytochemically for the expression of h-caldesmon. As expected, all myofibroblastic lesions failed to express h-caldesmon. Conversely, focal staining, ranging from 2% to 10% of neoplastic cells, was detected in myofibroblastomas, even though it was restricted to 50% of analysed cases. CONCLUSIONS: Our results, indicating that smooth muscle differentiation occurs in a minority of the myofibroblastoma cells exclusively in half of the analysed cases, support the separation of myofibroblastoma from leiomyoma. The detection of smooth muscle cells in breast myofibroblastoma is easily explained if we postulate its histogenesis from the CD34+ fibroblasts of mammary stroma capable of multidirectional mesenchymal differentiation, including smooth muscle. We recommend retention of the term myofibroblastoma for all the desmin-positive and/or alpha-smooth muscle actin-positive spindle cell tumours of the breast consistent with the previously well-established morphological criteria for such neoplasms, unless one is dealing with a typical leiomyoma easily recognizable at light microscopy.

Aged↗

Aphasia as a rare presentation of monosymptomatic demyelinating disease: case report and review of the literature.

We present a case of sudden-onset aphasia due to a single pathological lesion, which at neuroradiological imaging studies was suggestive of glioma, while on biopsy proved be of demyelinating nature. Every cause of demyelinating lesions of the central nervous system was considered in the differential diagnosis, concluding for a primary demyelinating disease. The clinical and radiological differences between multiple sclerosis and acute disseminated encephalomyelitis are discussed. Although aphasia has already been described in demyelinating diseases, we underline its rarity as onset symptom.

Aphasia↗

[Fibromatosis of the breast: a clinical, radiological and pathological study of 6 cases].

We describe the clinical, radiological and pathological features of a series of six cases of primary fibromatosis of the breast. Most patients (5 of 6) were women of 22-58 years of age; one case occurred in a 47-year-old man. The fibromatosis of the breast in all cases presented as a monolateral solid nodule, clinically suspicious for malignancy and in three cases was also associated with cutaneous and/or nipple retraction. None of the patients was affected by any genetic disorder characterized by fibromatoses involving multiple sites, including breast. Both echographic and mammographic examinations revealed solid masses with irregular margins but without calcifications, mimicking scirrhous carcinoma. All cases were surgically treated by lumpectomy (4 of 6) or quadrantectomy (2 of 6), and after a follow-up period ranging from 5 months to 13 years all patients are well and disease-free. Histological examination revealed finger-like infiltrating margins entrapping adjacent breast parenchyma and adipose tissue in all cases. The hallmark of the lesion was the presence of bland-looking spindle cells, with a low mitotic index, organized in long sweeping and intersecting fascicles. Three different morphological phases (i.e. proliferative, involutional and residual), identical to those observed in Dupuytren's superficial fibromatosis, variably coexisted in each case. At immunohistochemistry the cells which comprised the lesion exhibited a diffuse expression of vimentin and a heterogeneous immunoreactivity to a-smooth muscle actin, thus confirming their fibro-myofibroblastic nature. No expression of estrogen, progesterone or androgen receptors or of pS2 correlated-estrogen protein was observed. We discuss both the pathogenesis of the mammary fibromatosis, pointing to the fibroblastic cells of the mammary stroma as the putative precursors, and the differential diagnosis versus the bland-looking, monomorphic spindle cell tumor-like or tumorous lesions of the breast.

Adult↗

HLA-DQA1 and -DQB1 genes and Helicobacter pylori infection in Italian patients with gastric adenocarcinoma.

Both HLA-DQA1 and -DQB1 genes and Helicobacter pylori infection have been linked to gastric cancer. The aim of this work was to determine if HLA-DQA1 and -DQB1 alleles are presented at altered frequency in Italian patients with gastric adenocarcinoma and H. pylori infection. Oligotyping for HLA-DQA1 and -DQB1 and H. pylori serology was performed for 50 patients with gastric adenocarcinoma and compared with 80 patients with colonic adenocarcinoma and 179 healthy subjects. H. pylori infection was present in 76% of gastric cancer patients, 77.5% of colonic cancer patients, and 72% of controls. The prevalence of infection was not significantly different in the three groups of subjects sorted according to their HLA-DQA1 or -DQB1 status. Apart from HLA-DQA1* 0201, which was less common in patients with colonic carcinoma than controls, no other HLA-DQA1 and no HLA-DQB1 allele were present at altered frequency in patients with gastric or colonic cancer. Neither anatomical location and histological type of cancer nor the presence of lymph node or distant metastases were significantly associated with specific HLA-DQA1 or -DQB1 alleles or H. pylori infection. Both HLA-DQA1 and -DQB1 genes have a minor, if any, role in H. pylori infection and gastric carcinogenesis.

Adenocarcinoma↗

Identification of a novel gene with increasing rate of suppression in high grade prostate cancers.

Prostate cancer is the second leading cause of cancer-related deaths in the United States. However, the underlying molecular events for prostate cancer development are not clear. In this study, we applied the recently developed technology known as differential subtraction chain (DSC) to identify a novel gene whose expression is inactivated in high grade prostate cancer. This gene, designated as SAPC, is expressed in normal prostate acinar cells. Its expression is dramatically down-regulated in high grade prostate cancers (4/4) but is unaltered in low grade prostate cancers. It encodes a 7.7-kd protein. Its sequence shares some homology with the cysteine-rich domain of 2-5A-dependent RNase L, which is a critical component of the interferon-induced apoptosis cascade. The selective inactivation in the more aggressive prostate cancers holds promise for SAPC as a potential prognostic marker for high grade prostate cancer.

Amino Acid Sequence↗

"Second hit" in sebaceous tumors from Muir-Torre patients with germline mutations in MSH2: allele loss is not the preferred mode of inactivation.

Muir-Torre syndrome is an autosomal-dominant inherited disorder predisposing to both sebaceous skin tumors and internal neoplasms. In a significant proportion of Muir-Torre syndrome patients skin tumors exhibit microsatellite instability as a hallmark of hereditary nonpolyposis colorectal cancer. Most individuals predisposed to hereditary nonpolyposis colorectal cancer harbor a germline mutation in the DNA mismatch repair genes MSH2 or MLH1. In Muir-Torre syndrome the vast majority of germline mutations have been identified in MSH2. Microsatellite instability in tumor tissue develops after somatic inactivation of the corresponding second mismatch repair allele ("second hit"). So far, the mechanisms of somatic inactivation of the second allele in microsatellite instability positive tumors from patients with known mismatch repair germline mutations are not well understood. We examined whether allele loss (loss of heterozygosity) is a frequent mechanism for inactivation of the second MSH2 allele in a sample of nine microsatellite instability positive skin tumors from eight unrelated Muir-Torre patients with known MSH2 germline mutations. Loss of heterozygosity was determined using microsatellite markers or heteroduplex analysis, respectively. Only one of the nine skin tumors exhibited loss of heterozygosity at the MSH2 locus. Thus, we could show in a sample of sebaceous tumors from patients with genetically proven Muir-Torre syndrome that loss of heterozygosity most probably is not the preferred mode of somatic inactivation of the second MSH2 allele.

Adult↗

A randomized trial of amantadine and interferon versus interferon alone as initial treatment for chronic hepatitis C.

The aim of this study was to compare, in an open-label study, the efficacy and safety of a combination of interferon (IFN) and amantadine (AMA) with that of IFN alone in previously untreated patients with chronic hepatitis C. A total of 200 patients were randomized to 6 MU of IFN-alpha2a 3 times per week, with 200 mg of AMA daily (n = 99) or to an identical dose of interferon alpha2a (n = 101). Patients were treated for 12 months and observed for 6 months' posttreatment. At the completion of treatment, 28.7% of patients in the monotherapy group and 45.5% in the combination group had a virologic response (P =.014). At 6 months' posttreatment, a sustained virologic response was observed in 16.8% (95% CI: 9-23) of patients with IFN alone versus 29.3% (95% CI: 19-37) of patients who were treated with combination therapy (P =.036). In each of the 2 treatments, genotype was the only predictive parameter for a sustained response. At the logistic regression analysis, therapy and genotype were the only 2 parameters with an independent predictive value. In the combination group, at examination of month 3, hepatitis C virus (HCV)-RNA status had a 97.6% (95% CI: 93-102) positive predictive value and a 50% (95% CI: 37-63) negative predictive value for a sustained virologic clearance. A substantial proportion of naïve patients with chronic hepatitis C have an end-of-treatment and end-of-follow-up virologic and biochemical response to a combination of IFN and AMA. This new treatment appears safe and well tolerated.

Adult↗

Benign spindle cell tumors of the mammary stroma: diagnostic criteria, classification, and histogenesis.

Purely benign mesenchymal spindle cell neoplasms of the breast are currently labeled under various terms in the literature (benign spindle cell tumor, fibroma, spindle cell lipoma, myofibroblastoma, solitary fibrous tumor, myogenic stromal tumor). The lack of strict diagnostic criteria to clearly indicate such mesenchymal neoplasms is the main reason which generated the risk of terming the same lesion under different names or, conversely, of collecting different types under the same term. Although such neoplasms exhibit morphological and immunophenotypical heterogeneity, they actually represent variations of the same tumor entity, likely arising from the uncommitted vimentin+/CD34+ fibroblasts of the mammary stroma, capable of multidirectional mesenchymal differentiation. To cover the entire spectrum of such lesions, the term "benign spindle cell tumors (BSCTs) of the mammary stroma" is advocated. BSCTs can be subtyped into four main groups by light microscopy (LM) and immunocytochemistry (ICC): fibroblastic, myofibroblastic, fibrohistiocytic, and mixed forms. A simple and practical approach to a nosologically correct diagnosis and a list of differential diagnoses are presented. The awareness of the diversity of morphological and immunophenotypical features of BSCTs of the mammary stroma, including uncommon variants, is helpful to avoid confusion with other monomorphic bland-looking benign and malignant spindle cell tumors and tumor-like lesions of the breast.

Breast Neoplasms↗

Cerebellar metastasis as a unique presenting feature of gastric cancer.

Gastric cancer is often diagnosed in middle-aged patients undergoing upper gastrointestinal endoscopy for abdominal complaints or constitutional symptoms, such as dyspepsia, vomiting or anorexia, weight loss, anemia, jaundice, and ascites. Sometimes, all of these symptoms may be absent, and gastric cancer is diagnosed after detection of metastases to target organs, such as the liver or lung. In a few rare cases, however, even these metastatic localizations may be absent, and clinical signs are only represented by atypical symptoms caused by neurologic metastatic involvement. We report an exceptionally rare case of gastric cancer in which the only presenting symptoms were headache and dizziness caused by a single cerebellar metastasis.

Carcinoma, Signet Ring Cell↗

Smectite in the treatment of acute diarrhea: a nationwide randomized controlled study of the Italian Society of Pediatric Gastroenterology and Hepatology (SIGEP) in collaboration with primary care pediatricians. SIGEP Study Group for Smectite in Acute Diarrhea.

BACKGROUND: Childhood gastroenteritis is associated with considerable health costs. The natural clay dioctahedral smectite increases intestinal barrier function and is effective against infectious diarrhea in children in developing countries. The purpose of this work was to investigate the efficacy of smectite in Italian children with acute diarrhea of mild to moderate severity. METHODS: A national, prospective, randomized, case-controlled study was performed in collaboration with primary care pediatricians. Children seen by pediatricians for acute gastroenteritis were treated with oral rehydration solution (ORS) alone or ORS with smectite. Parents returned a form in which total duration of diarrhea, incidence of vomiting and fever, persistence of diarrhea for more than 7 days and hospital admissions were recorded. RESULTS: Eight hundred four children with acute diarrhea were randomly assigned to treated or control groups. Administration of smectite was associated with significant reduction of the duration of diarrhea, as judged by stool frequency and consistency. The incidence and duration of vomiting and fever were not different. Diarrhea lasted more than 7 days in 10% of treated and in 18% of control children (P < 0.01). Hospital admission was necessary in seven treated and six control children. No side effects were observed. CONCLUSIONS: Smectite reduces the duration of diarrhea and prevents a prolonged course. It may therefore consistently reduce the costs of gastroenteritis.

Acute Disease↗

Hemangioma-like lesions in chronic liver disease: diagnostic evaluation in patients.

PURPOSE: To quantify the risk of misdiagnosis of focal hepatic lesions manifesting at ultrasonography (US) as typical hemangiomas in a population at high risk for hepatocellular carcinoma (HCC) and to identify the most effective approach to their diagnostic evaluation. MATERIALS AND METHODS: A total of 1,982 patients with newly diagnosed cirrhosis underwent US and serum alpha-fetoprotein determinations for early detection of HCC. Focal lesions with typical features of hemangioma were evaluated with confirmatory findings of contrast material-enhanced dynamic or spiral computed tomography (CT) and/or single photon emission CT with technetium 99m-labeled red blood cells and, in the absence of confirmatory imaging findings, US-guided fine-needle biopsy. Patients whose initial US scan depicted no lesions or hemangiomas were enrolled in a US follow-up program. All hemangioma-like lesions detected during follow-up were evaluated, or biopsy was performed. RESULTS: US depicted hemangioma-like lesions in 44 of 1,982 patients: 22 hemangiomas and 22 HCCs. Hemangioma-like lesions detected during follow-up in 1,648 patients were HCCs (n = 22) or dysplastic nodules (n = 4). Only 85 (22%) of 383 patients with HCC had alpha-fetoprotein levels suggestive of the diagnosis. The probability of a diagnosis of HCC (or preneoplastic lesion) is 100% for hemangioma-like lesions depicted on subsequent US scans. CONCLUSION: If initial US examination of a cirrhotic liver depicts a hemangioma, confirmatory findings of imaging studies are necessary since 50% of hemangiomas in this study were hyperechogenic HCCs. US-guided biopsy can be safely performed, and its findings can be used to confirm the diagnosis.

Adult↗

Expression of cadherins and catenins in paired tumor and non-neoplastic primary prostate cultures and corresponding prostatectomy specimens.

Cadherins are a family of transmembrane proteins that play a crucial role in cell differentiation, cell migration, and intercellular adhesion. Cadherins are associated with catenins through their highly conserved cytoplasmic domain. Down-regulation of E-cadherin protein has been shown in various human cancers. This study examined the expression of cadherins and associated catenins at the mRNA level. Paired tumor and nonneoplastic primary prostate cultures were obtained from surgical specimens. Quantitative multiplex fluorescence reverse transcriptase-polymerase chain reaction (QMF RT-PCR) and quantitative analysis were performed and correlated with immunostain results. Six of seven cases of neoplastic cultures showed moderately-to-markedly decreased levels of E-cadherin and P-cadherin mRNA. Similar losses of alpha-catenin and beta-catenin mRNA were also observed. The results of QMF RT-PCR showed good correlation with the results of immunohistochemical studies based on corresponding formalin-fixed sections. In conclusion, this paper presents a coordinated down-regulation in the expression of E-cadherin and associated catenins at the mRNA and protein level in most of the cases studied. This down-regulation may play an important role in the pathogenesis of prostate cancer.

Adenocarcinoma↗

Lipomatous myofibroblastoma: a potential diagnostic pitfall in the spectrum of the spindle cell lesions of the breast.

We report on two cases of myofibroblastoma (MFB) of the breast comprised predominantly of a mature fatty component, representing approximately three quarters of the entire tumour area. Both tumours consisted of a well-circumscribed lipomatous tumour mass containing dispersed nodular or irregularly shaped spindled cellular areas. The fatty component was represented exclusively by mature adipocytes, uniform in size and shape, lacking nuclear pleomorphism. The cellular areas contained spindly to oval cells with morphological and immunophenotypical features typical of MFB. The two components were so intimately admixed that a finger-like infiltrating growth pattern was apparent. The cases reported here as "lipomatous MFB" aim to clarify further the morphological spectrum of MFB of the breast. Lipomatous MFB may potentially mimic other benign or aggressive tumour-like lesions or even bland-looking malignant spindle cell tumours such as fibromatosis, nodular fasciitis, spindle cell lipoma, spindle cell liposarcoma, spindle cell variant of metaplastic carcinoma, spindle cell malignant myoepithelioma, and low-grade fibrosarcoma/malignant fibrous histiocytoma. The histogenesis of the present bimorphic mesenchymal tumours could be explained as the result of a dual, myofibroblastic and lipomatous, differentiation from a common pluripotential mesenchymal precursor cell, probably represented by the vimentin+/CD34+ fibroblast of the mammary stroma.

Aged↗

Congenital mesoblastic nephroma: report of a Case with review of the most significant literature.

AIMS AND BACKGROUND: Congenital mesoblastic nephroma (CMN) is a rare pediatric tumor of the kidney with the highest peak of incidence during the first 3 postnatal months. It has previously been confused with Wilms' tumor (which, on the contrary, is rare during the first six months of age and is still considered a histogenetic congener). CMN almost always has a favourable prognosis. Therefore, CMN needs to be correctly diagnosed and differentiated from other pediatric renal neoplasms. Two morphological subtypes are currently distinguished histologically: the classical or leiomyomatous type and the atypical or cellular type. Mixed forms with a combination of the two patterns are also on record. Recurrence and even tumor-related death have been described in the literature and always related to the atypical form or to the mixed form, particularly in patients aged more than 3 months and in those cases in which the surgical removal was not complete. Opinions concerning post-surgical clinical management, especially in regard to adjuvant therapy, are not unanimous. METHODS: A case of CMN, predominantly of the classical histological subtype diagnosed in a baby with a follow-up of 6 years, is herein presented. The tumor was discovered at birth and surgically removed after one month. Since the tumor showed a high mitotic index (one of the characteristics of the cellular subtype) and the perirenal fat was focally involved with the tumor, the possibility of giving adjuvant chemotherapy was considered. Flow cytometric analysis was also performed which showed a diploid DNA content of neoplastic cells. RESULTS: The tumor was completely removed, surgical margins were free histologically, and no clear-cut histological features of the atypical subtype were noted. Flow cytometrically, it showed the euploid DNA content. Consequently no additional therapy was given. Six years after surgery the patient is developing well and is free of disease. He has regular follow-up examinations. CONCLUSIONS: CMN almost always pursues a benign clinical course if diagnosed under three months of age and if totally surgically excised independent of histological type. Criteria for management of atypical cases are not unanimous in regard to the benefit of additional therapy after surgery.

Biomarkers, Tumor↗

Expression of steroid hormone receptors, their regulated proteins, and bcl-2 protein in myofibroblastoma of the breast.

AIMS: To investigate the possible role of steroid hormones in the pathogenesis of myofibroblastoma (MFB) of the breast, we analysed the immunohistochemical expression of oestrogen, progesterone, androgen receptors, their regulated proteins and bcl-2 protein in a series of this rare tumour. METHODS AND RESULTS: Paraffin-embedded sections from seven cases of MFB of the breast (five male; two female) were immunohistochemically tested for the expression of oestrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), oestrogen-regulated pS2 protein, androgen-regulated prostate-specific antigen (PSA) and bcl-2 protein. Rare cases of benign spindle cell tumours or tumour-like lesions of the breast (primitive fibromatosis, inflammatory pseudotumour, muscular hamartoma) which enter into the differential diagnosis with MFB, were also investigated and compared with MFB. All cases of MFB showed a diffuse (70-90% of neoplastic cells) and strong nuclear labelling with ER and PR, whereas AR was expressed only in three cases (two men and one woman) in about 60-70% of cells. Conversely, no immunostaining was detected for the pS2 protein and PSA. bcl-2 protein immunoreactivity was found in all cases of MFB, although with a variable degree of expression. No expression for steroid hormone receptors, their regulated-proteins and bcl-2 protein was observed in the rare benign spindle cell lesions of the breast included in this study. CONCLUSION: The in-situ detection of ER, PR and AR suggests that steroid hormones and their receptors are implicated in the pathogenesis of breast MFB. The consistent demonstration of bcl-2 protein, associated with a positive ER/PR status, provides evidence that bcl-2 may be an oestrogen-regulated protein also in MFB and that probably plays a role in the tumorigenesis. Finally, we postulate that the ER/PR and bcl-2 positive immunoprofile of MFB of the breast, in contrast to the negative profile of other rare primitive benign spindle cell lesions of the breast herein studied, might be exploited as an ancillary diagnostic aid in differential diagnosis of doubtful cases.

Actins↗