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D Remotti

Publications and source records attributed to D Remotti.

16 recordsLinked to original sources

Expression of TCL1 and CD27 in primary cutaneous B-cell lymphomas.

AIMS: To investigate by immunohistochemical analysis the expression of the TCL1 oncogene product and of CD27 in 25 cases of primary cutaneous B-cell lymphomas (PCBCL) classified according to the World Health Organization-European Organization for Research and Treatment of Cancer classification of cutaneous lymphomas. In B-cell ontogenesis TCL1 is mainly expressed by 'naive' B lymphocytes and by a subset of germinal centre B cells, whereas CD27 is expressed by a subset of germinal centre B cells, 'memory' B lymphocytes and plasma cells, suggesting that their expression in physiological conditions is mutually exclusive. METHODS AND RESULTS: Overall, TCL1 was expressed in 5/25 cases (20%) and CD27 in 15/25 cases (60%). Furthermore, 7/25 cases (28%) were TCL1- and CD27- and 2/25 cases (8%) were TCL1+ and CD27+. In particular, primary cutaneous follicle-centre lymphomas (10 cases) showed a variable expression of both TCL1 and CD27, whereas primary cutaneous marginal-zone B-cell lymphomas (eight cases) showed, with the exception of a single case, a definite CD27+/TCL1- profile. CONCLUSIONS: These findings indicate: (i) the TCL1 oncogene product is uncommonly expressed in PCBCL (20% of cases, mainly of the follicle-centre subtype); (ii) in contrast, CD27 is often expressed in PCBCL (60% of cases), mainly of the marginal-zone subtype; (iii) the coexpression of TCL1 and CD27 may be seldom observed in PCBCL (8% of cases); (iv) PCBCL does not seem to show, in terms of either TCL1 or CD27 expression, significant differences compared with its systemic counterparts.

Biomarkers, Tumor↗

Intravascular B-cell lymphoma: report of two cases with different clinical presentation but rapid central nervous system involvement.

Intravascular lymphomatosis (IVL) is a rare large-cell lymphoproliferative disorder characterized by a widespread lymphoma proliferation within the lumen of medium and small vessels, frequently presenting with skin and/or central nervous system (CNS) manifestations. The tumor is of B-cell origin in most cases. Prognosis is poor with a reported median survival of 5-7 months. We describe here two cases of IVL. The first was that of a 55-year-old woman with a large B-cell lymphoma of the leg, successfully treated with conventional chemotherapy (CHT) followed by autologous peripheral stem cell transplantation. At 3 months from the autograft she relapsed with a picture of hemophagocytic syndrome (HPS) and CNS symptoms. She died before any specific treatment, and post-mortem examination revealed the intravascular proliferation of lymphoma B-cells in the brain and bone marrow. The second case was that of a 60-year-old male with CNS involvement at diagnosis. He responded poorly to CHOP-like CHT, and died 2 months after diagnosis and 6 months after onset of symptoms. Failure of CHT at least in some IVL patients may be related to a delay in the initiation of therapy due to non-specific neurological symptoms. Therefore, early diagnosis based upon aggressive attempts immediately followed by adequate therapy may prove beneficial to these patients. In the present report, we performed an extended medline-based review of the published series of patients with IVL.

Autopsy↗

Regulation of TCL1 expression in B- and T-cell lymphomas and reactive lymphoid tissues.

Chromosomal rearrangements observed in T-cell prolymphocytic leukemia involve the translocation of one T-cell receptor gene to either chromosome 14q32 or Xq28, deregulating the expression of cellular protooncogenes of unknown function, such as TCL1 or its homologue, MTCP1. In the human hematopoietic system, TCL1 expression is predominantly observed in developing B lymphocytes, whereas its overexpression in T cells causes mature T-cell proliferation in transgenic mice. In this study, using a newly generated monoclonal antibody against recombinant TCL1 protein, we extended our analysis mainly by immunohistochemistry and also by fluorescence-activated cell sorting and Western blot to a large tumor lymphoma data bank including 194 cases of lymphoproliferative disorders of B- and T-cell origin as well as reactive lymphoid tissues. The results obtained show that in reactive lymphoid tissues, TCL1 is strongly expressed by a subset of mantle zone B lymphocytes and is expressed to a lesser extent by follicle center cells and by scattered interfollicular small lymphocytes. In B-cell neoplasia, TCL1 was expressed in the majority of the cases, including lymphoblastic lymphoma, chronic lymphocytic leukemia, mantle cell lymphoma, follicular lymphoma, Burkitt lymphoma, diffuse large B-cell lymphoma (60%), and primary cutaneous B cell lymphoma (55%). TCL1 expression was observed in both the cytoplasmic and nuclear compartments, as confirmed by Western blot analysis. Conversely, TCL1 was not expressed in Hodgkin/Reed-Sternberg cells, multiple myelomas, marginal zone B-cell lymphomas, CD30+ anaplastic large cell lymphoma, lymphoblastic T-cell lymphoma, peripheral T-cell lymphoma, and mycosis fungoides. These data indicate that TCL1 is expressed in more differentiated B cells, under both reactive and neoplastic conditions, from antigen committed B cells and in germinal center B cells and is down-regulated in the latest stage of B-cell differentiation.

Aged↗

Pulmonary lymphangioleiomyoma in a patient with multiple endocrine neoplasia type I.

The multiple endocrine neoplasia (M.E.N.) syndromes consist of a group of proliferative disorders that selectively target specific sets of endocrine and soft tissue cells. Here we report a case of lymphangioleiomyoma of the lung in a patient with multiple endocrine neoplasia Type I (M.E.N. I). This is the first time such an association has been reported. In our opinion it could possibly be ascribed to the genetic predisposition to proliferative disorders of patients with M.E.N. syndromes.

Female↗

Granulomatous slack skin. Report of a case and review of the literature.

We describe a patient with granulomatous slack skin (GSS) who has been followed for 15 years and present clinical, histological, immunohistochemical, ultrastructural, cytogenetic, and molecular findings. The clinical and pathological aspects of the 20 cases of GSS reported in the recent literature are reviewed and compared with those of the present case.

Adult↗

Prognostic value of the histologic classification of peripheral T-cell lymphoma: a clinico-pathologic study of 71 HTLV-1 negative cases.

The histologic and clinical features of 71 cases of peripheral T-cell lymphoma (PTCL) have been studied. All patients were HTLV-1 negative. The T-cell phenotype was demonstrated by immunohistochemistry on cryostat sections (41 cases) and paraffin-embedded sections (30 cases). All cases were histologically classified according to the updated Kiel classification of non-Hodgkin's lymphoma (low and high-grade) and according to a Working Formulation (WF)-based classification (predominantly small cells, mixed small and large cells, and predominantly large cells). Most cases were in the high-grade group according to both classifications. The prognostic value of these two classifications was comparatively assessed. The analysis of the actuarial survival curves showed that, by using the updated Kiel classification, low-grade PTCL had a survival probability higher than high-grade PTCL although the difference was not statistically significant. Similar results were obtained when the WF-based classification was applied: furthermore, actuarial survival curves of mixed small and large cell PTCL, and of large cell PTCL were rather similar, thus indicating that differentiating these two categories has a limited prognostic value.

Adolescent↗

Fibrosarcoma of the thymic region. A case report.

Fibrosarcoma of the mediastinum is an unusual tumor and only few cases have been reported. We describe the clinical and pathologic findings of a case of mediastinal mass in a 34 year old woman. The histologic, histochemical, immunocytochemical and ultrastructural features of the tumor were consistent with a diagnosis of fibrosarcoma. Furthermore, the tumor displayed evidence of close relations with the thymus capsule; the possibility that it may arise from the thymic stroma is considered. The differential diagnosis of spindle cell tumors of the mediastinum is also discussed.

Adult↗

[Collagenous colitis: a disease difficult to define].

The Authors report a case with watery chronic diarrhoea not related to malabsorption or to inflammatory bowel disease or to intestinal neoplasm. Colonic biopsy, performed during colonoscopy, with the histologic finding of collagenous material in the subepithelial space associated to epithelial alterations and to the presence of inflammatory cells, confirmed the diagnosis of this rare pathologic condition. The pathogenesis of the syndrome, however, is still unknown.

Aged↗

Letterer-Siwe disease: immunohistochemical evidence for a proliferative disorder involving immature cells of Langerhans lineage.

The morphological, ultrastructural and immunophenotypic properties of Histiocytosis-X (H-X) cells were investigated in a lymph node involved by Letterer-Siwe (L-S) disease. H-X cells were T6+ (CD1a), S-100+, T4+ (CD4) and HLA-DR+; in addition they were consistently T11+ (CD2) and were stained by antibodies directed against receptors for transferrin (T9), C3bi (OKM-1/CD11b), IgG-Fc (Leu-11/CD16) and Interleukin-2 (IL-2R/CD25). On immunostained cytosmears, T6+ cells were highly polymorphic and a prominent fraction (45%) showed immature morphology, characterized by lymphoid appearance. Cells expressing macrophage markers (ANAE, AACT, Leu-M3/CD14, PAM-1) were 10-fold fewer than T6+ cells and did not show a lymphoid morphology. At TEM level, H-X cells were characterized by poor content of LC granules and by the presence of myelin-like laminated bodies and of lysosome-like dense bodies. The immunophenotypic properties of H-X cells were compared to those of epidermal Langerhans cells (LCs) and of LCs present in lymph nodes of three cases of dermatophatic lymphadenitis. Epidermal LCs were T6+/HLA-DR+, and sometimes faintly T4+. Lymph node LCs were T6+, S-100+, T4+, HLA-DR+, and showed the same variety of surface receptors detected in H-X cells; furthermore, in a case with massive infiltration of the paracortex by T6+ cells, lymph node LCs were faintly T11+ and some of the T6+ cells had lymphoid aspect. Our findings suggest that the H-X cell population of L-S disease is not homogeneous, but is composed of discrete cell subsets with distinctive antigenic and morphological traits closely resembling those of cells of LC lineage at different maturational stages.

Female↗

Immunohistochemical heterogeneity of macrophage subpopulations in human lymphoid tissues.

The mononuclear phagocytic system is composed of cells which display a marked immunohistological heterogeneity. In the present study we have investigated the immunohistochemical and enzymatic features of macrophages and accessory cells present in human lymph nodes and spleen and, as control tissues, in thymus, liver, skin and heart. Our investigation has demonstrated that macrophages present in germinal centres display an immunophenotype different from that of macrophages populating T-dependent areas. Furthermore, cells lining lymph node sinuses and splenic sinusoids express endothelial and macrophage markers, and are able to modulate their immunophenotype according to different reactive conditions. These data suggest, on immunohistochemical grounds, that macrophages populating B- and T-dependent areas as well as sinuses of human peripheral lymphoid tissues, may modulate their immunophenotype according to environmental and antigenic influences.

B-Lymphocytes↗

Immunohistology of adenolymphoma (Warthin's tumour): evidence for a role of vascularization in the organization of the lympho-epithelial structure.

The epithelial, vascular and lymphoid components present in two cases of adenolymphoma (Warthin's tumour) were characterized by immunohistochemistry on frozen sections. Epithelial cells were positive for cytokeratin and keratin and were in close contact with numerous factor VIII related antigen-positive capillary vessels, running parallel to the epithelial basement membrane. The capillary vessels were in communication with high endothelial post-capillary venules which were often lined by HLA-DR-positive endothelial cells. The lymphoid tissue was organized in B-cell and T-cell areas. The B-cell areas consisted of B4+/To15+ B-lymphocytes admixed with DRC-1-positive follicular dendritic reticulum cells. The T-cell areas were mainly populated by T11+/T3+/T4+ lymphocytes admixed with some S-100+/HLA-DR+ interdigitating reticulum cells. Plasma cells and T8+ lymphocytes were more numerous in the proximity of the epithelium. Leu-M3+/PAM-1+ macrophages were scattered singly in the T-cell areas or were arranged in sinus-like structures around the epithelial cysts. The epithelial basement membrane, the vascular membrane and the fibrillar reticular stroma of the lymphoid tissue were immunoreactive for laminin and type IV collagen. The possibility is discussed that the accumulation of lymphoid tissue in Warthin's tumour is modulated by the epithelial cells, perhaps through their ability to organize a peculiar pattern of vascularization.

Adenolymphoma↗

[Assessment of the presence of mutations of the epidermal growth factor receptors in tumors of various histologies].

Recent reports from US and Japan have established that mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (Egfr) occur in a subset of patients with lung cancer that respond to therapy with gefitinib, a TK inhibitor. To gain further insights into the role of Egfr in carcinogenesis of lung and tumors of diverse histology, that are currently under investigation with drugs of the same class, we have taken in examination a panel of tumors consisting in 110 pulmonary adenocarcinomas, 40 pulmonary squamous carcinomas, 40 gastric adenocarcinomas and 40 colorectal adenocarcinomas. The sequence analysis of exon 19 and 21 of the Egfr has allowed the identification of 10 cases exhibiting specific deletions in exon 19 and 1 case with point mutation in a conserved residue in exon 21. All Egfr mutations occur specifically in lung adenocarcinomas while tumors of different histology result unaffected. The rate of mutation affecting these other tumors is either very rare, involves different domains of the receptor or other tyrosine kinases. The molecular analysis of the Egfr gene can help identify patients that will benefit from gefitinib therapy.

ErbB Receptors↗

[Association of mutations of K-RAS oncogene and deletions of 18Q with lymph node metastasis of colorectal cancer].

Molecular characterization of gastrointestinal cancer has greatly helped the definition of the key steps of the malignant transformation process and made it the best understood among the malignant cancers. Genetic influences on prognosis may have important implications for the management of the disease and help to design patient-tailored therapy. In order to acquire additional knowledge on this issue we have commenced an institutional study with the aim to identify the most frequent molecular alterations and make a correlation with the conventional histopathological parameters.

Colorectal Neoplasms↗