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Emilio Berti

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Kevin E Yarasheski, PhD

Washington University in St. Louis

Prof.Amjad Al-Nasser

Yarmouk University

Annelise Barron

Stanford University

Petros Bouras-Vallianatos

National & Kapodistrian University of Athens

Aurélien Robert

Centre National de la Recherche Scientifique / French National Centre for Scientific Research

Marathwada Agricultural University, Parbhani

Centre National de la Recherche Scientifique / French National Centre for Scientific Research

Mansoura University

Università degli Studi di Torino

Università degli Studi di Torino

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Papers by Emilio Berti

Linfomi primitivi cutanei

Time course, pathways and hazard risk trends in1,422 mycosis fungoides patients: A multicenterretrospective long-term follow-up study from theItalian Group of Cutaneous Lymphoma (GILC)

Journal Der Deutschen Dermatologischen Gesellschaft, 2011

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

Leukemia

We herein present an overview of the upcoming 5th edition of the World Health Organization Classi... more We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

Systemic sclerosis and fibrosis: A new role for bone marrow mesenchymal stem cells

Seminars in Arthritis and Rheumatism, 2006

RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes

Cancers

Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are... more Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17...

Clinical presentation, gastrointestinal and extraintestinal involvement in Dermatitis Herpetiformis: a retrospective study of 167 adult patients

Digestive and Liver Disease, 2001

Langerhans Cell Histiocytosis, Skin

Encyclopedia of Pathology, 2019

Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers

Cancer Medicine, 2016

Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) repre... more Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and

Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds

Medicine, 2015

Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but s... more Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1b, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P ¼ 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P ¼ 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P ¼ 0.010), CXCL 16 (P ¼ 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P ¼ 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P ¼ 0.010) and MMP-9 (P ¼ 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/ dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component. (Medicine 94(50):e2301) Abbreviations: ANA = antinuclear antibodies, APF = amicrobial pustulosis of the folds, BCA = bicinchoninic acid, CXCL = C-X-C motif ligand, IBD = inflammatory bowel diseases, IL = interleukin, IL-1R = interleukin 1 receptor, MMP = matrix metalloproteinase, PG = pyoderma gangrenosum, RANTES = regulated on activation, normal T cell expressed and secreted, RIPA = radioimmunoprecipitation assay, Siglec = sialic acid-binding immunoglobulin-type lectin, SS = Sweet syndrome, TIMP = tissue inhibitor of metalloproteinase, TNF = tumor necrosis factor, TNFR = tumor necrosis factor receptor. PATIENTS AND METHODS Patients Fifteen patients seen in our University Department from 1995 to 2015 for APF were studied clinicopathologically and immunologically. The patients were followed-up for a period ranging from 9 months to 20 years. The diagnosis of APF was

Mycosis fungoides and other cutaneous T-cell lymphomas

Non-Hodgkin Lymphomas: Advanced Diagnostics & Personalized Therapies, 2013

European journal of dermatology : EJD

We report a case of an 85-year-old white man with a diffuse form of psoriasis, who showed a large... more We report a case of an 85-year-old white man with a diffuse form of psoriasis, who showed a large asymptomatic subcutaneous tumour in the sacrococcygeal region. On cut section there was a subcutaneous neoplasia with a glistening, friable surface. Histologically, the deep dermis was infiltrated by cords and nests of pleomorphic cells embedded in an abundant mucinous stroma, and characteristic physaliphorous (multivacuolated) cells were observed. The neoplastic cells were immunohistochemically positive for cytokeratins (using CAM 5.2 and AE1/AE3), vimentin, S100 protein, and epithelial membrane antigen (EMA), but negative for carcinoembryonic antigen (CEA). Histological and immunohistochemical findings led us to the diagnosis of classic chordoma. Chordomas are rare, slow growing malignant tumours of the spinal axis originating from remnants of the notochord. Occasionally, a skin lesion is the first sign of a primitive or metastatic chordoma.

Basic Mechanisms of Physiologic and Aberrant Lymphoproliferation in the Skin

Contains the revised and edited versions of papers presented at an October 1991 workshop held in ... more

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

Oncogene, 2010

Genetic experiments established that p63 is crucial for the development and maintenance of pluri-... more Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.

HHV8 cell-associated viraemia and clinical presentation of Mediterranean Kaposi's sarcoma

The Lancet, 1996

Impact of regionalisation of cardiac surgery in Emilia-Romagna, Italy

Journal of Epidemiology & Community Health, 2004

Study objective: Assessment of the impact of the regionalisation of cardiac surgery through the o... more Study objective: Assessment of the impact of the regionalisation of cardiac surgery through the organisational form of a hub&spoke model introduced in the year 2000. Design: Case mix adjusted before (1998-1999)-after (2000-2002) comparison of: (a) in-hospital and 30 days mortality rates; (b) proportion of patients timely (within one day) referred for surgery from spoke to hub centres; (c) patients' waiting times to surgery. Setting: Emilia-Romagna, an Italian region with four million residents. Patients: 16 512 patients aged >18 years and referred to cardiac surgery over the period 1998-2002. Main results: Overall, taking into account differences in case mix across the whole study period, the implementation of the regionalisation policy was associated with a 22% reduction (OR: 0.79, 95%CI: 0.66 to 0.93) in in-hospital mortality rate. The corresponding figure for 30 day mortality was 18% (OR: 0.82: 95%CI: 0.69 to 0.98). The individual centres' volume of cases changed over the study period for all hospitals but two, and the biggest reduction in mortality was seen at the centre with the largest increase in caseload. Conclusions: This study provides additional evidence on the benefit of regionalisation of cardiac surgery interventions. The system allowed each centre to reach the minimum caseload required to assure good quality of care. These findings suggest that policies aimed at increasing cooperation rather than competition among health service providers have a positive impact on quality of care. Timely referrals for surgery increased by 21% (95%CI: 1.12 to 1.31), and mean waiting times were reduced by 7.5 average days (95%CI: 210.33 to 24.71).

Human Herpesvirus 8 DNA in the Skin and Blood of Patients with Mediterranean Kaposi’s Sarcoma: Clinical Correlations

Dermatology, 2001

Kaposi&#39;s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderl... more Kaposi&#39;s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi&#39;s sarcoma by confirmational display analysis and polymerase chain reaction. As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi&#39;s sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi&#39;s sarcoma. HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi&#39;s sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I-II disease as opposed to 73.6% of those with stage III-IV. The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi&#39;s sarcoma.

Quantitative and functional defects of dendritic cells in classic Kaposi's sarcoma

Clinical Immunology, 2006

In this study, we investigated whether dendritic cells (DCs) are altered in classic Kaposi's sarc... more In this study, we investigated whether dendritic cells (DCs) are altered in classic Kaposi's sarcoma (cKS), a lympho-angioproliferative disorder associated with human herpesvirus-8 (HHV-8) infection. By direct analysis of peripheral blood DCs (PBDCs), we demonstrated that cKS patients have lower frequency of myeloid and plasmacytoid DCs than controls. This reduction was greater in patients with advanced stages of disease. PBDCs from cKS patients also showed up-regulated expression of the scavenger receptor CD91 and impaired IL-12 expression. PB monocytes that represent DC precursors in vivo and in vitro showed the same alterations; accordingly, DCs differentiated in vitro from cKS monocytes were similarly affected. The same alterations were induced by addition of cKS plasma during DC differentiation from control monocytes. These results indicate that PBDCs and their precursors are altered in cKS and suggest that soluble circulating factors participate in this process. The study may provide new insights into the pathogenesis of cKS.

Human herpesvirus-8 infection among heterosexual partners of patients with classical Kaposi’s sarcoma

British Journal of Dermatology, 2000

DNA sequences of human herpesvirus-8 (HHV8) are found in lesions of Kaposi&#39;s sarcoma (KS)... more DNA sequences of human herpesvirus-8 (HHV8) are found in lesions of Kaposi&#39;s sarcoma (KS). To verify the hypothesis of the sexual transmission of HHV8 infection. We used the immunoperoxidase assay to study the prevalence of serum antibodies to HHV8-related antigens in 27 consorts of patients with classical KS, and in a control group of 25 healthy women. Forty-four per cent of the study group were positive, compared with 8% of the controls. The sexual route may be one of the possible ways of transmission of the HHV8 virus.

Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma and Castleman disease

British Journal of Dermatology, 2005

Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthrit... more

Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia

British Journal of Dermatology, 2007

Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+, CD68+, S100+ an... more Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+, CD68+, S100+ and CD207) dermal dendritic cells. We describe a 39-year-old man who developed diffuse ICH and, 6 years later, acute myeloblastic leukaemia (AML). He was treated with cyclophosphamide, etoposide and vinblastine until 2003. In August 2004, he presented dyspnoea, hyperpyrexia and infiltration of the lung parenchyma, compatible with an AML invasion, and died after a course of induction chemotherapy. Cytomorphology and immunophenotype analyses suggested an ICH clonal evolution. The leukaemogenic role of etoposide is discussed. ICH has previously been reported in association with B-cell malignancy, but only one case has shown systemic progression.

Linfomi primitivi cutanei

Time course, pathways and hazard risk trends in1,422 mycosis fungoides patients: A multicenterretrospective long-term follow-up study from theItalian Group of Cutaneous Lymphoma (GILC)

Journal Der Deutschen Dermatologischen Gesellschaft, 2011

The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms

Leukemia

We herein present an overview of the upcoming 5th edition of the World Health Organization Classi... more We herein present an overview of the upcoming 5th edition of the World Health Organization Classification of Haematolymphoid Tumours focussing on lymphoid neoplasms. Myeloid and histiocytic neoplasms will be presented in a separate accompanying article. Besides listing the entities of the classification, we highlight and explain changes from the revised 4th edition. These include reorganization of entities by a hierarchical system as is adopted throughout the 5th edition of the WHO classification of tumours of all organ systems, modification of nomenclature for some entities, revision of diagnostic criteria or subtypes, deletion of certain entities, and introduction of new entities, as well as inclusion of tumour-like lesions, mesenchymal lesions specific to lymph node and spleen, and germline predisposition syndromes associated with the lymphoid neoplasms.

Systemic sclerosis and fibrosis: A new role for bone marrow mesenchymal stem cells

Seminars in Arthritis and Rheumatism, 2006

RNA Sequencing of Primary Cutaneous and Breast-Implant Associated Anaplastic Large Cell Lymphomas Reveals Infrequent Fusion Transcripts and Upregulation of PI3K/AKT Signaling via Neurotrophin Pathway Genes

Cancers

Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are... more Cutaneous and breast implant-associated anaplastic large-cell lymphomas (cALCLs and BI-ALCLs) are two localized forms of peripheral T-cell lymphomas (PTCLs) that are recognized as distinct entities within the family of ALCL. JAK-STAT signaling is a common feature of all ALCL subtypes, whereas DUSP22/IRF4, TP63 and TYK gene rearrangements have been reported in a proportion of ALK-negative sALCLs and cALCLs. Both cALCLs and BI-ALCLs differ in their gene expression profiles compared to PTCLs; however, a direct comparison of the genomic alterations and transcriptomes of these two entities is lacking. By performing RNA sequencing of 1385 genes (TruSight RNA Pan-Cancer, Illumina) in 12 cALCLs, 10 BI-ALCLs and two anaplastic lymphoma kinase (ALK)-positive sALCLs, we identified the previously reported TYK2-NPM1 fusion in 1 cALCL (1/12, 8%), and four new intrachromosomal gene fusions in 2 BI-ALCLs (2/10, 20%) involving genes on chromosome 1 (EPS15-GNG12 and ARNT-GOLPH3L) and on chromosome 17...

Clinical presentation, gastrointestinal and extraintestinal involvement in Dermatitis Herpetiformis: a retrospective study of 167 adult patients

Digestive and Liver Disease, 2001

Langerhans Cell Histiocytosis, Skin

Encyclopedia of Pathology, 2019

Primary cutaneous B-cell lymphoma other than marginal zone: clinicopathologic analysis of 161 cases: Comparison with current classification and definition of prognostic markers

Cancer Medicine, 2016

Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) repre... more Categorization of primary cutaneous B-cell lymphomas (PCBCL) other than marginal zone (MZL) represents a diagnostic challenge with relevant prognostic implications. The 2008 WHO lymphoma classification recognizes only primary cutaneous follicular center cell lymphoma (PCFCCL) and primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT), whereas the previous 2005 WHO/EORTC classification also included an intermediate form, namely PCDLBCL, other. We conducted a retrospective, multicentric, consensus-based revision of the clinicopathologic characteristics of 161 cases of PCBCL other than MZL. Upon the histologic features that are listed in the WHO classification, 96 cases were classified as PCFCCL and 25 as PCDLBCL-LT; 40 further cases did not fit in the former subgroups in terms of cytology and/or architecture, thus were classified as PCDLBCL, not otherwise specified (PCDLBCL-NOS). We assigned all the cases a histogenetic profile, based on the immunohistochemical detection of CD10, BCL6, and

Cytokine and Chemokine Profile in Amicrobial Pustulosis of the Folds

Medicine, 2015

Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but s... more Autoinflammation has recently been suggested in the pathogenesis of neutrophilic dermatoses but systematic studies on their cytokine profile are lacking. Notably, amicrobial pustulosis of the folds (APF), classified among neutrophilic dermatoses, has been studied only in small case series. In our University Hospital, we conducted an observational study on 15 APF patients, analyzing their clinical and laboratory features with a follow-up of 9 months to 20 years. Skin cytokine pattern of 9 of them was compared to that of 6 normal controls. In all patients, primary lesions were pustules symmetrically involving the skin folds and anogenital region with a chronic-relapsing course and responding to corticosteroids. Dapsone, cyclosporine, and tumor necrosis factor blockers were effective in refractory cases. In skin samples, the expressions of interleukin (IL)-1b, pivotal cytokine in autoinflammation, and its receptors I and II were significantly higher in APF (P ¼ 0.005, 0.018, and 0.034, respectively) than in controls. Chemokines responsible for neutrophil recruitment such as IL-8 (P ¼ 0.003), CXCL 1/2/3 (C-X-C motif ligand 1/2/3) (P ¼ 0.010), CXCL 16 (P ¼ 0.045), and RANTES (regulated on activation, normal T cell expressed and secreted) (P ¼ 0.034) were overexpressed. Molecules involved in tissue damage like matrix metalloproteinase-2 (MMP-2) (P ¼ 0.010) and MMP-9 (P ¼ 0.003) were increased. APF is a pustular neutrophilic dermatosis with a typical distribution in all patients. The disorder may coexist with an underlying autoimmune/ dysimmune disease but is often associated only with a few autoantibodies without a clear autoimmunity. The overexpression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that APF has an important autoinflammatory component. (Medicine 94(50):e2301) Abbreviations: ANA = antinuclear antibodies, APF = amicrobial pustulosis of the folds, BCA = bicinchoninic acid, CXCL = C-X-C motif ligand, IBD = inflammatory bowel diseases, IL = interleukin, IL-1R = interleukin 1 receptor, MMP = matrix metalloproteinase, PG = pyoderma gangrenosum, RANTES = regulated on activation, normal T cell expressed and secreted, RIPA = radioimmunoprecipitation assay, Siglec = sialic acid-binding immunoglobulin-type lectin, SS = Sweet syndrome, TIMP = tissue inhibitor of metalloproteinase, TNF = tumor necrosis factor, TNFR = tumor necrosis factor receptor. PATIENTS AND METHODS Patients Fifteen patients seen in our University Department from 1995 to 2015 for APF were studied clinicopathologically and immunologically. The patients were followed-up for a period ranging from 9 months to 20 years. The diagnosis of APF was

Mycosis fungoides and other cutaneous T-cell lymphomas

Non-Hodgkin Lymphomas: Advanced Diagnostics & Personalized Therapies, 2013

European journal of dermatology : EJD

We report a case of an 85-year-old white man with a diffuse form of psoriasis, who showed a large... more We report a case of an 85-year-old white man with a diffuse form of psoriasis, who showed a large asymptomatic subcutaneous tumour in the sacrococcygeal region. On cut section there was a subcutaneous neoplasia with a glistening, friable surface. Histologically, the deep dermis was infiltrated by cords and nests of pleomorphic cells embedded in an abundant mucinous stroma, and characteristic physaliphorous (multivacuolated) cells were observed. The neoplastic cells were immunohistochemically positive for cytokeratins (using CAM 5.2 and AE1/AE3), vimentin, S100 protein, and epithelial membrane antigen (EMA), but negative for carcinoembryonic antigen (CEA). Histological and immunohistochemical findings led us to the diagnosis of classic chordoma. Chordomas are rare, slow growing malignant tumours of the spinal axis originating from remnants of the notochord. Occasionally, a skin lesion is the first sign of a primitive or metastatic chordoma.

Basic Mechanisms of Physiologic and Aberrant Lymphoproliferation in the Skin

Contains the revised and edited versions of papers presented at an October 1991 workshop held in ... more

Mutant p53 subverts p63 control over KLF4 expression in keratinocytes

Oncogene, 2010

Genetic experiments established that p63 is crucial for the development and maintenance of pluri-... more Genetic experiments established that p63 is crucial for the development and maintenance of pluri-stratified epithelia and KLF4 for the barrier function of the skin. KLF4 is one of the factors that reprogram differentiated cells to iPS. We investigated the relationship between p63 and KLF4 using RNA interference, overexpression, chromatin immunoprecipitation and transient transfections with reporter constructs. We find that p63 directly represses KLF4 in normal keratinocytes (KCs) by binding to upstream promoter sites. Unlike p63, KLF4 levels are high in the upper layers of human skin and increase upon differentiation of KCs in vitro. In HaCaT KCs, which harbor two mutant alleles of p53, inactivation of p63 and of mutant p53 leads to KLF4 repression. p63 and p53 mutants are bound to sites in the KLF4 core promoter. Importantly, expression of the H179Y and R282Q p53 mutants in primary KCs is sufficient to activate endogenous KLF4. Finally, immunohistochemical analysis of tissue arrays confirms increased coexpression of KLF4 and mutant p53 in squamous cell carcinomas. Our data indicate that suppression of KLF4 is part of the growth-promoting strategy of p63 in the lower layers of normal epidermis, and that tumor-predisposing p53 mutations hijack p63 to a different location on the promoter, turning it into an activator of this reprogramming factor.

HHV8 cell-associated viraemia and clinical presentation of Mediterranean Kaposi's sarcoma

The Lancet, 1996

Impact of regionalisation of cardiac surgery in Emilia-Romagna, Italy

Journal of Epidemiology & Community Health, 2004

Study objective: Assessment of the impact of the regionalisation of cardiac surgery through the o... more Study objective: Assessment of the impact of the regionalisation of cardiac surgery through the organisational form of a hub&spoke model introduced in the year 2000. Design: Case mix adjusted before (1998-1999)-after (2000-2002) comparison of: (a) in-hospital and 30 days mortality rates; (b) proportion of patients timely (within one day) referred for surgery from spoke to hub centres; (c) patients' waiting times to surgery. Setting: Emilia-Romagna, an Italian region with four million residents. Patients: 16 512 patients aged >18 years and referred to cardiac surgery over the period 1998-2002. Main results: Overall, taking into account differences in case mix across the whole study period, the implementation of the regionalisation policy was associated with a 22% reduction (OR: 0.79, 95%CI: 0.66 to 0.93) in in-hospital mortality rate. The corresponding figure for 30 day mortality was 18% (OR: 0.82: 95%CI: 0.69 to 0.98). The individual centres' volume of cases changed over the study period for all hospitals but two, and the biggest reduction in mortality was seen at the centre with the largest increase in caseload. Conclusions: This study provides additional evidence on the benefit of regionalisation of cardiac surgery interventions. The system allowed each centre to reach the minimum caseload required to assure good quality of care. These findings suggest that policies aimed at increasing cooperation rather than competition among health service providers have a positive impact on quality of care. Timely referrals for surgery increased by 21% (95%CI: 1.12 to 1.31), and mean waiting times were reduced by 7.5 average days (95%CI: 210.33 to 24.71).

Human Herpesvirus 8 DNA in the Skin and Blood of Patients with Mediterranean Kaposi’s Sarcoma: Clinical Correlations

Dermatology, 2001

Kaposi&#39;s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderl... more Kaposi&#39;s sarcoma is a multifocal lympho-angioproliferative disease that appears in elderly subjects of Mediterranean origin (classical form), young Africans and immunodepressed patients (as a result of organ transplantation or AIDS). In 1994, DNA sequences of a new human herpesvirus, called HHV-8, were detected in skin lesions and peripheral blood of patients with AIDS-related Kaposi&#39;s sarcoma by confirmational display analysis and polymerase chain reaction. As HHV-8 in peripheral blood mononuclear cells is detected in about 50% of Mediterranean Kaposi&#39;s sarcoma patients and its presence fluctuates in time in the same patient, maybe its detection correlates with the clinical behaviour of the disease. By using routine and nested polymerase chain reaction we evaluated the presence of HHV-8-specific DNA sequences in the skin lesions, perilesional healthy skin and peripheral blood mononuclear cells of a group of 40 HIV-negative patients with Mediterranean Kaposi&#39;s sarcoma. HHV-8 DNA sequences have been found in 40/40 (100%) lesional skin of Mediterranean Kaposi&#39;s sarcoma, in 35/40 (85%) perilesional apparently normal skin and in 24/40 (60%) peripheral blood monuclear cell samples. The results of polymerase chain reaction on peripheral blood monuclear cells were positive in 41% of the patients with slowly evolving disease as opposed to 74% of those with rapidly evolving disease, and in 47.6% of the patients with stage I-II disease as opposed to 73.6% of those with stage III-IV. The detection of HHV-8 in peripheral blood monuclear cells seems to correlate with the more aggressive stages and the rapid evolution behaviour of Mediterranean Kaposi&#39;s sarcoma.

Quantitative and functional defects of dendritic cells in classic Kaposi's sarcoma

Clinical Immunology, 2006

In this study, we investigated whether dendritic cells (DCs) are altered in classic Kaposi's sarc... more In this study, we investigated whether dendritic cells (DCs) are altered in classic Kaposi's sarcoma (cKS), a lympho-angioproliferative disorder associated with human herpesvirus-8 (HHV-8) infection. By direct analysis of peripheral blood DCs (PBDCs), we demonstrated that cKS patients have lower frequency of myeloid and plasmacytoid DCs than controls. This reduction was greater in patients with advanced stages of disease. PBDCs from cKS patients also showed up-regulated expression of the scavenger receptor CD91 and impaired IL-12 expression. PB monocytes that represent DC precursors in vivo and in vitro showed the same alterations; accordingly, DCs differentiated in vitro from cKS monocytes were similarly affected. The same alterations were induced by addition of cKS plasma during DC differentiation from control monocytes. These results indicate that PBDCs and their precursors are altered in cKS and suggest that soluble circulating factors participate in this process. The study may provide new insights into the pathogenesis of cKS.

Human herpesvirus-8 infection among heterosexual partners of patients with classical Kaposi’s sarcoma

British Journal of Dermatology, 2000

DNA sequences of human herpesvirus-8 (HHV8) are found in lesions of Kaposi&#39;s sarcoma (KS)... more DNA sequences of human herpesvirus-8 (HHV8) are found in lesions of Kaposi&#39;s sarcoma (KS). To verify the hypothesis of the sexual transmission of HHV8 infection. We used the immunoperoxidase assay to study the prevalence of serum antibodies to HHV8-related antigens in 27 consorts of patients with classical KS, and in a control group of 25 healthy women. Forty-four per cent of the study group were positive, compared with 8% of the controls. The sexual route may be one of the possible ways of transmission of the HHV8 virus.

Paraneoplastic pemphigus associated with follicular dendritic cell sarcoma and Castleman disease

British Journal of Dermatology, 2005

Hepatitis B reactivation in a chronic hepatitis B surface antigen carrier with rheumatoid arthrit... more

Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia

British Journal of Dermatology, 2007

Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+, CD68+, S100+ an... more Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+, CD68+, S100+ and CD207) dermal dendritic cells. We describe a 39-year-old man who developed diffuse ICH and, 6 years later, acute myeloblastic leukaemia (AML). He was treated with cyclophosphamide, etoposide and vinblastine until 2003. In August 2004, he presented dyspnoea, hyperpyrexia and infiltration of the lung parenchyma, compatible with an AML invasion, and died after a course of induction chemotherapy. Cytomorphology and immunophenotype analyses suggested an ICH clonal evolution. The leukaemogenic role of etoposide is discussed. ICH has previously been reported in association with B-cell malignancy, but only one case has shown systemic progression.