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Biomedical subjects

A Carbone

Publications and source records attributed to A Carbone.

At least 127 records · Page 7Linked to original sources

Sinonasal malignant lymphomas: a distinct clinicopathological category.

Sinonasal lymphomas represent a distinct subset of extranodal head and neck lymphomas. While sinonasal lymphomas are relatively rare in Western countries, in Asian populations they are the second most frequent group of extranodal lymphomas, after gastrointestinal lymphomas. With advances in immunohistochemistry, these lymphomas have been separated into B-cell, T-cell, and most recently into natural killer (NK) cell phenotypes. The B-cell phenotype is typically located in the paranasal sinuses and has a slight predominance in Western countries. The T/NK-cell phenotype is the most common in Asian and South American countries. These tumors are typically located in the nasal cavity and have an aggressive, angioinvasive growth pattern that often results in necrosis and bony erosion. Thus, sinonasal lymphomas have been included in the past with other destructive malignant and benign lesions under the descriptive and nonspecific name lethal midline granuloma. Patients are classically in the sixth to eighth decades, with a 2:1 male-to-female ratio. The prognosis is generally better than that of nodal-based lymphomas of similar histologic grade. Treatment is a combination of local irradiation and chemotherapy with an anthracycline-based regimen.

Asia↗

Review of sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease) of head and neck.

The entity known as sinus histiocytosis with massive lymphadenopathy (SHML), or Rosai-Dorfman disease (RD disease), is an uncommon benign proliferation of hematopoietic and fibrous tissue that often presents in the head and neck region. Its initial manifestations most often include a roughly symmetric, painless, bilateral cervical adenopathy, although extranodal disease may develop in a minority of patients. The key histologic feature of SHML is the presence of various numbers of large, pale histiocytic cells that contain within their cellular borders apparently engulfed lymphocytes ("emperipolesis"); these distinctive large, pale cells - RD cells - are S-100 protein-positive by immunostaining and so differ from ordinary histiocytes. Despite its sometimes impressive clinical presentation, SHML is a benign and self-limited disease, whose treatment is aimed largely at controlling its local manifestations (most often by surgical therapy). The microscopic differential diagnosis, particularly in extranodal disease, is at times challenging and can include Langerhans' cell histiocytosis, Hodgkin's disease, non-Hodgkin's lymphoma, metastatic carcinoma, and metastatic malignant melanoma.

Antigens, CD1↗

[Does the neurologic assessment have a decisive role in the early diagnosis of urinary disorders of uncertain etiology? A case of spinal chordoma].

The Authors report a rare case of detrusor areflexia due to a sacral column chordoma characterized as initial symptomatology, by dysuria and recurrent urinary tract infections. The patient was treated for a long time in a symptomatic way by her physicians. The Authors while discussing the case, underline the importance of an accurate differential diagnostical framing in patients with voiding and/or anorectal dysfunctions of uncertain nature. This framing must exclude those voiding pathologies of neurological origin which are frequently evinced merely by an aspecific voiding symptomatology of dysuric or irritative nature.

Aged↗

[Penile ultrasonography. Characteristic velocimetric feature in the maximal erection phase in healthy subjects].

BACKGROUND: A peculiar finding from penis eco color-Doppler, detected in healty subjects with erection dysfunction, is described. METHODS: 385 patients with erection dysfunction were studied, by using duplex scan with color Doppler, 85 of these patients normal Regiscan test were chosen and patients with Induratio penis plastica or hormonal disorder were excluded. RESULTS: A "reverse" flow during the entire diastolic phase was detected in 58 normal patients (68%) with age < of 41 years. CONCLUSIONS: In the evaluation of healthy subjects with erection dysfunction, the presence of a complete "reverse" diastolic flow is indicative of a venous reflux block, that may represent an important pathogenetic mechanism in this specific setting.

Adolescent↗

T cell receptor repertoire in B cell lymphoproliferative lesions in primary Sjögren's syndrome.

OBJECTIVE: Studies have analyzed T cell receptor (TCR)-Vbeta in benign, minor salivary or lacrimal gland, or kidney lesions in Sjögren's syndrome (SS). We investigated SS related lymphoproliferative lesions. METHODS: By "family" reverse transcriptase polymerase chain reaction, we studied the expression of 20 different TCR-Vbeta families in parotid lymphoproliferative lesions and peripheral blood lymphocytes (PBL) from 7 patients with primary SS, in PBL from 6 primary SS patients with no associated lymphoproliferative disorder, and in activated PBL from 2 healthy controls. T cell clonal expansion was investigated in 10 Vbeta families (i.e., the most expanded ones and those previously implicated in SS pathogenesis) by single strand conformation polymorphism (SSCP) analysis. Frozen sections from parotid gland specimens were tested by immunohistochemistry for the expansion of selected Vbeta families. Viral infection within the parotid lesions and serum autoantibody response were also studied. RESULTS: An unrestricted Vbeta pattern was observed. The most widely expressed Vbeta family in parotid lesions was Vbeta2, and Vbeta immunohistochemistry results were concordant with Vbeta mRNA findings. A similar pattern was observed in PBL, although the Vbeta2 family was expressed at lower levels. The parotid/PBL ratio was occasionally > 1.8-2.0 (indicative of local Vbeta overexpression) in different Vbeta families. T cell expansion proved to be largely polyclonal by SSCP analysis, and scattered T cell clonotypes were detected within different Vbeta families, with a different pattern from patient to patient. CONCLUSION: Our observations in SS related lymphoproliferative lesions largely reflect previous evidence in fully benign lesions. The pathogenetic events involved in autoimmune benign lesions in SS may then persist and play a role in SS related lymphoproliferative disorders. The link between the observed TCR-Vbeta repertoire and specific local triggering (auto)antigens remains to be elucidated.

Adult↗

Frequent mutation of bcl-6 proto-oncogene in high grade, but not low grade, MALT lymphomas of the gastrointestinal tract.

BACKGROUND AND OBJECTIVE: Knowledge regarding the molecular pathogenesis and histogenesis of gastrointestinal mucosa-associated lymphoid tissue non-Hodgkin's lymphomas (MALT-NHL) is limited. Mutations of BCL-6, a zinc finger transcription factor implicated in lymphoid development, occur frequently in lymphomas and represent a histogenetic marker of B-cell transit through the germinal center. The distribution of BCL-6 mutations in gastrointestinal MALT-NHL was analyzed in this study. DESIGN AND METHODS: This study was based on 26 gastrointestinal MALT-NHL, including 16 cases of low grade histology and 10 cases of high grade histology. Mutations of BCL-6 were investigated by a combination of polymerase chain reaction-single strand conformation polymorphism and DNA direct sequencing analysis. RESULTS: Mutations of BCL-6 occurred in 6/10 high grade MALT-NHL, whereas they were absent from all low grade cases tested (n = 16; p = 0.001). MALT-NHL harboring BCL-6 mutations included 5 cases of gastric MALT-NHL and 1 case of jejunal MALT-NHL. Mutations were predominantly represented by single nucleotide substitutions which were multiple in most cases. All sequence alterations were unique to individual cases of gastrointestinal MALT-NHL. INTERPRETATION AND CONCLUSIONS: Mutations of BCL-6 occur frequently in high grade gastrointestinal MALT-NHL and display characteristics similar to those of BCL-6 mutations harbored by other B-cell lymphomas. The association of high grade MALT-NHL with BCL-6 mutations corroborates their histogenetic derivation from germinal center-related B-cells and may be of potential pathogenetic relevance for these disorders.

DNA-Binding Proteins↗

Morphometric prognostic index in breast cancer.

OBJECTIVE: To assess the ability of the morphometric prognostic index (MPI) in predicting clinical outcome in a group of breast cancer patients with short-term follow-up and to assess the relationship between MPI and other prognosticators. STUDY DESIGN: The study group consisted of 63 cases of breast cancer. Follow-up data were available for 48 patients. MPI values were calculated, and degree of nuclear and tubular differentiation was investigated in each tumor. S-phase fraction (SPF), estrogen and progesterone receptors were also studied. RESULTS: The group of patients with MPI values < 0.60 had percent values of disease-free survival significantly higher than did those with MPI values > or = 0.60. Furthermore, significant direct correlations were found between MPI and degree of nuclear atypia and between MPI and SPF. Significant inverse relationships were found between MPI and tumor progesterone receptor levels and between MPI and degree of histologic tubular differentiation. CONCLUSION: The validity of MPI as a prognosticator in breast cancer was confirmed, even in a limited number of patients observed in short-term follow-up. MPI seems to be a reliable and economical prognosticator in selecting breast cancer patients for adjuvant chemotherapy.

Adenocarcinoma↗

Simian-virus-40 footprints in human lymphoproliferative disorders of HIV- and HIV+ patients.

SV40 sequences were investigated by PCR DNA amplification followed by filter hybridization in a series of human lymphoproliferative disorders obtained from human-immunodeficiency-virus (HIV)-seronegative and HIV-infected patients. Our PCR and filter-hybridization conditions enabled us to detect SV40 sequences in the range of 10(-4) to 10(-2) genome equivalents per cell. In non-Hodgkin's lymphomas (NHL) from HIV- patients, SV40 footprints were found in 11 out of 79 (13.9%) samples, while in NHL from HIV+ patients SV40 DNA sequences were detected in 2/16 (12.5%). In Hodgkin's disease (HD), SV40 sequences were found in 7/43 (16.3%) and 1/12 (8.3%) in HIV- and HIV+ patients respectively. A slightly higher prevalence of SV40 footprints was observed in reactive lympho-adenopathies both in HIV- (3/9, 33.3%) and in HIV+ (6/17, 35.3%) patients. Sequence analysis of 2 NHL and 2 HD DNA samples established that the amplified PCR products belong to the SV40 sequences. SV40 prevalence and load were similar in samples from HIV-seronegative and HIV-infected individuals, suggesting that SV40 probably does not undergo strong reactivation phenomena in the context of HIV-related immunosuppression. Moreover, the large T-antigen(Tag) expression was detected by immunohistochemistry in 5/18 SV40-DNA-positive samples analyzed; however, few tumor cells (<1%) in 3/5 samples displayed positivity for SV40 Tag, while this viral oncoprotein was revealed in several reactive histiocytes present in all 5 SV40-positive tissues. These results suggest that the lymphoid tissue could represent a reservoir for SV40 and may constitute the first step in understanding whether this DNA tumor polyomavirus has a role in the pathogenesis of human lymphoproliferative disorders.

Antigens, Polyomavirus Transforming↗

Expression status of BCL-6 and syndecan-1 identifies distinct histogenetic subtypes of Hodgkin's disease.

The tumor cells in most cases of Hodgkin's disease (HD) have been recently recognized to originate from the B-cell lineage, but their precise differentiation stage is not fully clarified. Recently, we have reported that the histogenesis of B-cell lymphomas may be assessed by monitoring the expression pattern of BCL-6, a transcription factor expressed in germinal center (GC) B cells, and CD138/syndecan-1 (syn-1), a proteoglycan associated with post-GC, terminal B-cell differentiation. In this study, we have applied these two markers to the study of HD histogenesis. We have found that in nodular lymphocyte predominance HD (NLPHD) tumor cells consistently display the BCL-6(+)/syn-1(-) phenotype, indicating their derivation from GC B cells. Conversely, classic HD (CHD) is heterogeneous because the tumor cells of a fraction of CHD display the BCL-6(-)/syn-1(+) phenotype of post-GC B-cells, whereas another fraction of CHD is constituted by a mixture of tumor cells reflecting the GC (BCL-6(+)/syn-1(-)) or post-GC (BCL-6(-)/syn-1(+)) phenotypes. BCL-6(-)/syn-1(+) tumor cells of CHD are mostly found surrounded by T cells expressing CD40L, consistent with the observation that CD40 signaling downregulates BCL-6 expression. These data indicate that tumor cells of NLPHD uniformly display a GC B-cell phenotype, whereas the phenotype of tumor cells of CHD appears to be modulated by the surrounding cellular background, particularly CD40L+ reactive T cells.

Antigens, Differentiation, B-Lymphocyte↗

The molecular and phenotypic profile of primary central nervous system lymphoma identifies distinct categories of the disease and is consistent with histogenetic derivation from germinal center-related B cells.

Primary central nervous system lymphoma (PCNSL) is a major cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals. The precise histogenetic derivation and the molecular pathogenesis of PCNSL is poorly understood. In an attempt to clarify the histogenesis and pathogenesis of these lymphomas, 49 PCNSL (26 acquired immunodeficiency syndrome [AIDS]-related and 23 AIDS-unrelated) were analyzed for multiple biologic markers, which are known to bear histogenetic and pathogenetic significance for mature B-cell neoplasms. PCNSL associated frequently (50.0%) with mutations of BCL-6 5' noncoding regions, which are regarded as a marker of B-cell transition through the germinal center (GC). Expression of BCL-6 protein, which is restricted to GC B cells throughout physiologic B-cell maturation, was detected in 100% AIDS-unrelated PCNSL and in 56.2% AIDS-related cases. Notably, among AIDS-related PCNSL, expression of BCL-6 was mutually exclusive with expression of Epstein-Barr virus (EBV)-encoded latent membrane protein (LMP)-1 and, with few exceptions, also of BCL-2. All but one PCNSL expressed hMSH2, which among mature B cells selectively stains GC B cells. These data suggest that PCNSL may be frequently related to GC B cells and may be segregated into two major biologic categories based on the expression pattern of BCL-6, LMP-1, and BCL-2. BCL-6(+)/LMP-1(-)/BCL-2(-) PCNSL occur both in the presence and in the absence of HIV infection and consistently display a large noncleaved cell morphology. Conversely, BCL-6(-)/LMP-1(+)/BCL-2(+) PCNSL are restricted to HIV-infected hosts and are represented by lymphomas with immunoblastic features. These data are relevant for the pathogenesis and histogenesis of PCNSL and may be helpful to segregate distinct biologic and prognostic categories of these lymphomas.

B-Lymphocyte Subsets↗

Burkitt's lymphoma in adults with and without human immunodeficiency virus infection: a single-institution clinicopathologic study of 75 patients.

BACKGROUND: Burkitt's lymphoma (BL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma (NHL) in the general population and for 35-40% in the setting of human immunodeficiency virus (HIV) infection. The authors report a 9-year single-institution experience with 75 adult BL patients (46 with and 29 without HIV infection) and compare the clinical and pathologic features of the disease in the two groups of patients. METHODS: Between May 1987 and June 1995, 131 patients with HIV infection and systemic NHL were diagnosed and treated at the National Cancer Institute in Aviano, Italy. In 46 cases (35%), the diagnosis was BL. During the same period, 29 of 1004 HIV negative NHL patients (2.8%) were diagnosed with BL and treated at the same institution. RESULTS: No statistical differences were found in the general characteristics of the two groups at the time that BL was diagnosed. Complete response rate was significantly lower for patients with HIV infection than for those without HIV infection (40% vs. 65%, P = 0.03). The median overall survival was significantly shorter for patients with HIV infection (7 months vs. not yet reached, P = 0.0001). However, the disease free survival (DFS) at 4 years was identical for the two groups of patients (74% for HIV positive patients vs. 73% for HIV negative patients, P = 0.70). CONCLUSIONS: The data from this study show that patients with BL with and without HIV infection share similar clinicopathologic characteristics at presentation. Although the median overall survival is significantly shorter for patients with HIV infection, the DFS is identical for both groups.

Adult↗

Differential expression of BCL-6, CD138/syndecan-1, and Epstein-Barr virus-encoded latent membrane protein-1 identifies distinct histogenetic subsets of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas.

This study was aimed at defining the histogenesis of the pathologic spectrum of acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas (AIDS-NHL), including AIDS-related small noncleaved cell lymphoma (AIDS-SNCCL), AIDS-related large noncleaved cell lymphoma (AIDS-LNCCL), AIDS-related large cell immunoblastic lymphoma plasmacytoid (AIDS-IBLP), and AIDS-related primary effusion lymphoma (AIDS-PEL). Forty-six cases of AIDS-NHL were investigated for the expression pattern of BCL-6, a protein specifically expressed by germinal center (GC) B-cells, and CD138/syndecan-1 (syn-1), a marker of post-GC B-cell differentiation. Expression of BCL-6 and syn-1 segregated two major phenotypic patterns among AIDS-NHL: (1) the BCL-6+/syn-1- pattern associated with AIDS-SNCCL and AIDS-LNCCL; (2) the BCL-6-/syn-1+ pattern associated with AIDS-IBLP and AIDS-PEL. Among systemic AIDS-NHL infected by Epstein-Barr virus (EBV), expression of the EBV-encoded latent membrane protein-1 (LMP-1) preferentially associated with the BCL-6-/syn-1+ profile. Analysis of nonneoplastic lymph nodes showed that the two phenotypic patterns detected in AIDS-NHL correspond to physiologic stages of B-cell development, i.e., GC B-cells (BCL-6+/syn-1-) and preterminally differentiated post-GC B-cells (BCL-6-/syn-1+). Thus, BCL-6+/syn-1- AIDS-NHL reflects a GC stage of differentiation, whereas AIDS-NHL which are BCL-6-/syn-1+, and LMP-1+ when infected by EBV, derive from B cells that have entered post-GC plasmacell differentiation. These findings are relevant for the pathogenesis and differential diagnosis of AIDS-NHL.

Cell Membrane↗

Clinical and biological applications of image analysis in non-Hodgkin's lymphomas.

The technical procedures and the main applications of image analysis in non-Hodgkin's lymphoma pathology have been described by reviewing the pertinent literature. With the advent of sophisticated computer-based technology, the possibility of objectively evaluating cell morphology, in situ marker expression, DNA indexes, and complex structural features may become a relevant part of the pathologist's expertise.

Algorithms↗

Hodgkin's disease: a disorder of dysregulated cellular cross-talk.

Hodgkin's disease (HD) is a peculiar type of human malignant lymphoma characterized by a very low frequency of tumor cells, the so called Hodgkin and Reed-Sternberg (H-RS) cells, embedded in a hyperplastic background of non-neoplastic (reactive) cells recruited and activated by H-RS cells-derived cytokines. H-RS cells can be functionally regarded as antigen-presenting cells (APC) able to elicit an intense, but anergic and ineffective, T-cell mediated immune response along with a hyperplastic inflammatory reaction which involves several cell types including T- and B-cells, neutrophils, eosinophils, plasma cells, fibroblasts and stromal cells. In tissues involved by HD, malignant H-RS cells and their reactive neighboring cells are able to cross-talk via a complex network of cytokine- and cell contact-dependent interactions. As a result of such interactions, mediated by specific surface receptors and adhesion molecules on both tumor and non-neoplastic cells, H-RS cells may receive several proliferative and anti-apoptotic signals favoring the cellular expansion and tumor cell survival in HD. The ineffective T-cell immune response elicited by the abnormal APC function of H-RS cells may further contribute to the biologic and clinical progression of HD. Innovative therapeutic strategies aimed at blocking the pathways of dysregulated cellular cross-talk among H-RS cells and bystander reactive cell populations might be beneficial in the treatment of HD patients.

Cell Communication↗

Hepatitis C virus genotypes and clinical features in hepatitis C virus-related mixed cryoglobulinemia.

Mixed cryoglobulinemia is a systemic disease, almost always associated with hepatitis C virus infection and characterized by purpura and cutaneous vasculitis, asthenia, arthralgias, and often renal and neurological involvement. No significant differences have been described to date in mixed cryoglobulinemia patients with type 1, 2, or 3 hepatitis C virus infection with respect to symptoms, while a higher prevalence of genotype 2a has been reported in patients without clinical and biochemical signs of liver disease or with serum autoantibodies. We examined 33 hepatitis C virus-positive patients with mixed cryoglobulinemia to assess if any clinical or serological feature is related to infection with different genotypes. All subjects underwent viral genotype determination by means of a single-step polymerase chain reaction. Thirteen patients (39%) were infected with hepatitis C virus type 1b, 17 (52%) with type 2a or 2a/c, and 3 (9%) with type 3. There was a significant difference in the frequency of peripheral nervous system involvement: paresthesias or other symptoms of peripheral neuropathy were less frequent in patients with 2a or 2a/c infection (29%) than in patients with type 1b or type 3 infection (88%, P = 0.003). Only patients with hepatitis C virus type 2 had urticaria or cutaneous ulcers. These patients also had a lower frequency of arthralgias, lower cryocrit values (P = 0.02), and lower serum levels of alanine-aminotransferase and gamma-glutamyl-transpeptidase (P < 0.04) than patients with type 1 and type 3 infection. The prevalence of antinuclear antibody positivity was similar in the three groups.

Adult↗