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M Bagot

Publications and source records attributed to M Bagot.

At least 19 recordsLinked to original sources
PubMed2006

[Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma with aggressive course].

BACKGROUND: Cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma is a recently described rare primary cutaneous lymphoma exhibiting aggressive clinical behavior. Only about twenty cases have been described in the literature. Below we report a case involving unusual association of cutaneous vasculitis and lymphoproliferation. CASE REPORT: A 42-year-old senegalese man was hospitalized for cutaneous nodular lesions, which rapidly spread and became necrotic and ulcerated. he had recent weight loss with fever and multiple enlarged lymph nodes. Cutaneous histological analysis showed epidermotropic dermal infiltrate comprising medium and large cd8+ cytotoxic t-cells of unusual angiocentricity with cutaneous vasculitis and fibrinoid necrosis. the patient died 4 months after initiation of treatment with multi-agent chemotherapy. DISCUSSION: This patient presented the characteristics of primary cutaneous CD8+ epidermotropic cytotoxic T-cell lymphoma described by Berti. The clinical findings in most cases consist of nodular and ulcerative cutaneous lesions. Histologically, the cutaneous infiltrate is composed of pleomorphic lymphocytes with marked and constant epidermotropism. Immunohistochemistry shows lymphocytes expressing a CD8+ phenotype and cytotoxic proteins, which probably accounts for the local and systemic aggressiveness of the disease, as well as the angiodestructive nature of the infiltrate and the necrotic lesions.

Adult↗
PubMed2006

Minimizing adverse side-effects of oral bexarotene in cutaneous T-cell lymphoma: an expert opinion.

Bexarotene is an oral retinoid therapy that is effective for the treatment of early and advanced-stage cutaneous T-cell lymphoma (CTCL) in patients who have failed on other therapies. However, bexarotene treatment is associated with unavoidable side-effects, in particular hypertriglyceridaemia and hypothyroidism, which are manageable with adequate concomitant medications and are reversible on cessation of treatment. A pragmatic strategy for minimizing bexarotene-associated hypertriglyceridaemia and hypothyroidism is suggested, based on data from the studies with bexarotene in CTCL and on day-to-day experience with this agent in the clinical setting. The strategy anticipates that these common adverse events are likely to occur and recommends the early use of preventive therapy to lower triglycerides and elevate thyroid hormone levels in the blood, followed by subsequent monitoring, dose adjustment during bexarotene treatment, and titration of the daily bexarotene dose from 150 to 300 mg m(-2), which is optimal for most patients. When further information becomes available on how bexarotene interacts with lipid metabolism and thyroid function, the management approach suggested here may need to be changed.

Anticarcinogenic Agents↗
PubMed2005

Post-transplant cutaneous T-cell lymphomas.

Post-transplant cutaneous lymphomas are rare. Cutaneous T-cell lymphomas account for 30% of these lymphomas. The clinical appearance of the skin lesions is identical to cutaneous lymphomas observed in non-immunosuppressed patients, with infiltrated plaques, nodular and ulcerated tumors, but with an increased frequency of erythroderma. Standard histology and immunohistochemistry are also consistent with the features of mycosis fungoides and CD30+ cutaneous lymphomas observed in the general population. However, the pronostic differs from the usually favourable outcome of cutaneous T-cell lymphomas, as 8 out of the 13 patients of our series died, in less than 1 year for 6 of them. This unfavourable course appears to be the same as that observed for systemic T-cell lymphoma in transplant recipients. In contrast to post-transplant B-cell lymphomas (systemic and primary cutaneous), the link to a virus has not been demonstrated. The prognosis is also less favourable for post-transplant cutaneous T-cell lymphomas than for post-transplant cutaneous B-cell lymphomas.

Diagnosis, Differential↗
PubMed2004

BCL2 and JUNB abnormalities in primary cutaneous lymphomas.

BACKGROUND: BCL2 is upregulated in nodal and extranodal B-cell non-Hodgkin's lymphomas, with a consequent antiapoptotic effect. However, loss of BCL2 has also been noted in some malignancies, suggesting a different molecular pathogenesis. OBJECTIVES: To investigate genomic and protein expression status of BCL2 and to compare the results with that of JUNB in primary cutaneous lymphomas (PCLs). METHODS: We analysed gene copy number of BCL2 and JUNB in 88 DNA samples from 80 patients with PCL consisting of Sézary syndrome/mycosis fungoides (SS/MF), primary cutaneous B-cell lymphoma (PCBCL) and primary cutaneous CD30+ anaplastic large cell lymphoma (C-ALCL) by the use of real-time polymerase chain reaction (PCR) and immunohistochemistry (IHC). Real-time PCR and IHC findings were subsequently compared with the results of additional fluorescent in situ hybridization (FISH) analysis of 23 cases of SS and Affymetrix cDNA expression microarray study of two primary cutaneous T-cell lymphoma (CTCL) cell lines. RESULTS: Real-time PCR analysis showed loss of BCL2 gene copy number in 22 of 80 PCL cases (28%), including 17 of 42 SS/MF, three of 13 C-ALCL and two of 33 PCBCL samples, and gain of BCL2 in four PCBCL samples. Gain of JUNB was identified in 18 of 71 PCL cases (25%), including nine of 35 SS/MF, seven of 13 C-ALCL and two of 31 PCBCL samples. IHC analysis revealed absent nuclear expression of BCL2 protein in 47 of 73 PCL cases, comprising 28 of 36 SS/MF, eight of eight C-ALCL and 11 of 29 PCBCL cases. In contrast, BCL2 protein expression was detected in 26 of 73 PCL cases, consisting of 18 of 29 PCBCL and eight of 36 SS/MF cases. JUNB protein expression was present in tumour cells from 30 of 33 of SS/MF and eight of eight C-ALCL, and was absent in tumour cells from 18 of 27 PCBCL cases. A comparison between BCL2 and JUNB revealed loss of BCL2 and gain of JUNB in five of 35 SS/MF samples, and expression of JUNB protein and absent BCL2 expression in 25 SS/MF and eight of eight C-ALCL cases. In contrast, expression of BCL2 and absent JUNB expression were detected in 67% of PCBCL cases. Additional FISH analysis revealed deletion of BCL2 in 19 of 23 SS cases (83%), including eight cases with BCL2 loss shown by real-time PCR. Furthermore, Affymetrix expression microarray demonstrated decreased expression of proapoptotic and antiapoptotic genes involved in BCL2 signalling pathways such as BOK, BIM, HRK, RASA1 and STAT2 in two CTCL cell lines with BCL2 loss and absent BCL2 expression. Increased expression of JUNB was also identified in the MF cell line. CONCLUSIONS: These findings provide a comprehensive assessment of BCL2 and JUNB status in PCL, and suggest that there is a selection pressure in a subset of CTCL cases for tumour cells showing BCL2 loss and upregulation of JUNB primarily through chromosomal deletion and amplification, respectively.

Genes, bcl-2↗
PubMed2003

Isolation of a CD8alphaalpha+ CD4- tumour T-cell clone with cytotoxic activity from a CD4+ CD8- cutaneous T-cell lymphoma.

BACKGROUND: We have previously established tumour T-cell lines, both from the skin and from the blood of patients with a cutaneous T-cell lymphoma (CTCL). In one patient, the tumour cells and the derived cell lines had a CD3+ CD4+ CD8- phenotype and a trisomy of chromosome 7. They expressed three T-cell receptor (TCR) beta-chain transcripts, but only one was productively rearranged and expressed at the cell membrane. OBJECTIVES: In the present study, we tried to isolate a fast-growing new tumour T-cell line from the same patient. PATIENTS/METHODS: We performed direct cell cloning of the skin tumour lymphocyte population, which led to the isolation of an interleukin-2-dependent highly proliferative T-cell subclone, named Cou-L3, with a CD3+ TCR-Vbeta13+ CD4- CD8alphaalpha+ phenotype. RESULTS: We demonstrated that Cou-L3 was identical to the original clonal tumour CD3+ Vbeta13+ CD4+ CD8- cells, as it expressed the same rearranged TCR-Vbeta13 chain. We further studied the functional activity of these CD8alphaalpha+ Vbeta13+ Cou-L3 cells. We found that these cells exhibited CD3-redirected cytotoxic activity. CONCLUSIONS: An immunophenotypic shift, with a change from a CD4+ to a CD8+ phenotype, has been already reported in association with disease progression in CTCL. However, in these cases, there has been no demonstration that the phenotypic change involved the same T-cell clone. The present study is the first report of the phenotypic heterogeneity of the tumour clonal cell population in CTCL.

Aged↗
PubMed2003

Minimal residual disease in mycosis fungoides follow-up can be assessed by polymerase chain reaction.

BACKGROUND: T-cell receptor (TCR) gene rearrangement analysis, i.e. T-cell clonality, using polymerase chain reaction (PCR) is a routine method used to assess the presence of a cutaneous dominant T-cell clone in mycosis fungoides (MF). OBJECTIVES: To compare the outcome of cutaneous lesions of MF after treatment with the fate of the cutaneous T-cell clonality, and to determine whether minimal residual disease can be detected in patients in clinical complete remission. METHODS: Fifty-one patients histologically diagnosed as having MF (17 stage IA, 21 stage IB and 13 stage III) were included in this retrospective study. T-cell clonality was analysed by GC-clamp multiplex PCRgamma-denaturing gradient gel electrophoresis. Every patient had two cutaneous biopsies at least 3 months apart. The second biopsy was performed at the site of a treated lesion. RESULTS: The presence or absence of a dominant T-cell clone in the skin remained identical in 26 of the 31 (84%) patients with persistent disease. Thirteen patients with a detectable dominant T-cell clone at diagnosis went into complete clinical remission. In nine of these 13 (69%) patients, the T-cell clone was no longer detectable after treatment. The remaining four (31%) patients had an unchanged T-cell clonality. CONCLUSIONS: The TCR gene rearrangement imprint is a stable and reliable tumour marker of MF disease. One-third of patients in complete clinical remission had a cutaneous molecular residual disease, the prognostic value of which will be analysed in an ongoing prospective study.

Adult↗
PubMed2003

Interaction of cutaneous lymphoma cells with reactive T cells and dendritic cells: implications for dendritic cell-based immunotherapy.

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of skin neoplasms that originate from T lymphocytes. An anti-CTCL T-cell immunity has been described but seems to be inefficient to clear CTCL cells. It is not known whether cutaneous dendritic cells (DCs) perpetuate the proliferation of the malignant CTCL cell clone or play a role in the control of this usually slowly progressing disease. OBJECTIVES: To characterize CTCL cell properties in the control of anti-CTCL T cells and to pave the way for a DC-based immunotherapy for CTCL. METHODS: We studied the interaction of a CTCL cell line with DCs and with allogeneic T cells. RESULTS: We found an antigen non-specific capacity of viable but not apoptotic CTCL cells to hamper CD4+ and CD8+ T-cell proliferation in a dose-dependent manner, indicating a suppressive potential of CTCL cells. Both viable and apoptotic CTCL cells were phagocytosed by immature DCs but only apoptotic CTCL cells induced an upregulation of DC maturation markers to a degree which enabled classification of these DCs as semimature. CTCL cells did not respond with proliferation when encountering allogeneic, mature DCs either loaded with CTCL cell material or unloaded, indicating a role for DCs in the induction of anti-CTCL T-cell immunity rather than in perturbation of clonal proliferation. For the loading of DCs with CTCL material lysate seems to be optimal as apoptotic cells were not phagocytosed extensively and necrotic CTCL material induced a partial cellular toxicity in DCs. DCs loaded with CTCL material were cryopreservable without significant loss of DC viability, surface marker expression or allostimulatory activity. CONCLUSIONS: Together, these data argue in favour for a DC-based immunotherapy for CTCL patients and provide an experimental protocol for preparing CTCL cell-loaded DCs.

Apoptosis↗
PubMed2003

[Successful treatment of haemodialysis-related porphyria cutanea tarda with deferoxamine].

BACKGROUND: End-stage renal failure and long-term hemodialysis treatment promote porphyria cutanea tarda. Iron overload is often associated with this disease and is thought to play a role in its pathogenesis. We report a case of hemodialysis related-porphyria cutanea tarda improved by deferoxamine. CASE REPORT: A 45-year-old man, with end-stage renal failure and who had received hemodialysis treatment since 1993, presented a several months-history of blisters of the face and the dorsum of the hands. Laboratory analysis showed: hemoglobin 10 g/dl; a moderate hepatic cytolysis; ferritin 195 ng/l. HIV, HBV, HCV serologies were negative. Porphyries analyses showed a porphyria cutanea tarda pattern. The cutaneous histology was non specific; direct immunofluorescence was negative. The patient received deferoxamine (40 mg/kg intravenously every week for 6 weeks) which led to dramatic improvement of the symptoms. DISCUSSION: Several treatments are proposed in the management of dialysis-related porphyria cutanea tarda. This case confirms that deferoxamine can induce rapid and prolonged remission.

Deferoxamine↗
PubMed2003

[Medical activity in a emergency outpatient department dermatology].

BACKGROUND: The aim of this study was to characterize the medical activity of a dermatology emergency room and to compare it with 1) outpatients, scheduled visits to the same department and 2) visits to community dermatologists in private practice. METHODS: All the 500 patients who attended the emergency room in one month and all the 411 patients with scheduled appointments during one week within the same period were included prospectively. The clinical diagnoses were recorded and compared between the two groups using chi square and linear correlation tests. Data on the diagnoses made by community dermatologists in private practice were obtained from another study. RESULTS: In the emergency room, 4 diagnoses accounted for 71.4 of all visits: infections (29 p. 100), dermatitis (23.8 p. 100), rashes (11 p. 100) and urticaria (7.6 p. 100). In scheduled visits the 4 leading diagnosis were cancer and precancerous lesions (28.7 p. 100), dermatitis (11.7 p. 100), fungal infections (8.3 p. 100) and acne (7.1 p. 100). There was no correlation (r=0.14; p=0.6) between the 16 more prevalent diagnoses in the emergency room and the prevalence of the same diagnoses in scheduled visits in the hospital department. The emergency diagnosis were also not correlated with those seen in private practice (r=0.21; p=0.4). Seven percent of emergency room consultants were hospitalized. COMMENTS: Skin disorders encountered in the dermatology emergency room differ from those seen both in the outpatient hospital department and in community private practice.

Community Health Services↗
PubMed2002

Cutaneous Destombes-Rosai-Dorfman disease: absence of detection of HHV-6 and HHV-8 in skin.

BACKGROUND: We report three new cases of cutaneous Destombes-Rosai-Dorfman disease (DRDD). Two were skin-limited, and one was associated with systemic involvement. In all cases typical large S100 positive macrophages with emperipolesis were present, but different patterns were seen. A viral etiology has long been suspected in DRDD. METHODS: Thus, all cases were investigated for presence of HHV-6 major capsid protein gene by polymerase chain reaction (PCR), and for presence of HHV-8 latency-associated nuclear antigen 1 by immunohistochemistry. RESULTS: All results were negative. HHV-6 antibody tests were positive for IgG but not for IgM in one case. With regard to HHV-6, previous studies supplied inconclusive results while, to our knowledge, HHV-8 has never been investigated in DRDD. CONCLUSION: This study suggests that HHV-8 is not involved in the pathogenesis of cutaneous DRDD. However, this should be confirmed by further studies. We can postulate three hypotheses in regard to HHV-6 role in DRDD pathogenesis: 1) its presence in lesionnal tissues is fortuitous, 2) HHV-6 plays a role in promoting more aggressive diseases and 3) various causes, including HHV-6, are implicated in the pathogenesis of DRDD.

Adult↗
PubMed2002

Identification of cell surface molecules characterizing human cutaneous T-cell lymphomas.

Primary cutaneous T-cell lymphomas (CTCL) are a heterogeneous group of malignant mature T-cell proliferations most often presenting as mycosis fungoides (MF) or its leukemic variant, Sezary syndrome (SS). No specific cell surface markers are presently available to distinguish the circulating malignant clone from normal lymphocytes. Using the previously established CTCL cell lines, Cou-LS and Pno, we have detected two leucocyte cell surface antigens with aberrant expression on CTCL cells. The NK-receptor (NKR) p140/KIR3DL2 normally expressed by NK and CD8+ T-cells was detected on the surface of CTCL cell lines as well as on freshly isolated CD4+PBL from SS patients. Further on, p140 marked in situ SS cells, distinguishing them from p140-negative tumor cells of patch plaque MF. SC5 is a newly described activation-related intracellular inhibitory receptor expressed on the surface of a minor PBL subset. We found that SC5 expression was significantly increased in SS cells and correlated to p140 expression. Moreover, cross-linking of SC5 molecules inhibited the malignant cell proliferation induced by anti-CD3 mAbs. The identification of these new structures on circulating SS tumor cells seems to be important both for the understanding of CTCL pathophysiology and for the clinical management of SS patients.

Antigens, Surface↗
PubMed2002

[Prognosis of primary cutaneous lymphomas].

INTRODUCTION: The assessment of prognosis is a major step in the management of primary cutaneous lymphomas, as it allows to give patients an accurate information and it directs the treatment choice. MATERIAL AND METHODS: We performed a literature review of global prognosis and prognostic factors in primary cutaneous lymphomas. We used survival as the main endpoint, in particular specific survival and relative survival which provide accurate estimates of lymphoma-related deaths. Independent prognostic factors identified by multivariate survival analyses were emphasized. RESULTS: Overall prognosis of mycosis fungoides has improved during the past decades, possibly because of an increased proportion of cases diagnosed at early stages. Five-year disease-specific or relative survival rates of patients with T1 stage (patch/plaque disease<10 p. 100 of total skin surface), T2 (> 10 p. 100), T3 (tumor stage) and T4 (generalized erythroderma) are 100 p. 100, 67 to 96 p. 100, 51 to 80 p. 100 and 41 p. 100 respectively. Lymphomatoid papulosis and CD30+ primary cutaneous large T-cell lymphomas have an excellent prognosis, with 5-year survival rates of 100 p. 100 and 96 p. 100 respectively. CD30-negative primary cutaneous large T-cell lymphomas have an aggressive clinical behavior (5-year disease-specific or relative survival: 15 to 21 p. 100). Among primary cutaneous B-cell lymphomas, immunocytomas and marginal-zone B-cell lymphomas are not life-threatening. Follicle center-cell lymphomas that arise on the head and trunk have also an indolent clinical course (5-year specific survival rates: 94 to 97 p. 100). However, few of these lymphomas are composed of more than 50 p. 100 of large cells with round nuclei (centroblasts and/or immunoblasts) and may have a more aggressive clinical course (5-year specific survival: 72 p. 100). Large B-cell lymphomas of the leg often occur in older patients and have a poorer prognosis (5-year specific survival rate: 52 p. 100). Cases with a single lesion and those with a predominance of large cleaved cells (large centrocytes) have a more favorable clinical course than those with multiple tumors or a round cell morphology. CONCLUSION: Clinical, histological and immunophenotypical prognostic factors which have been identified so far may reliably predict the survival outcome in primary cutaneous lymphomas. On this basis, therapeutic guidelines have been proposed. These prognostic data will have to be taken into account when evaluating new potential prognostic factors (e.g. immunophenotypic or molecular) and performing prospective clinical trials.

Humans↗
PubMed2002

[Intravascular large cell lymphoma revealed by diffuse telangiectasia and cauda equina syndrome].

BACKGROUND: Intravascular lymphoma is a rare disease with usually fatal outcome, characterized by the proliferation within the lumen of small blood vessels of neoplastic large lymphoid cells of B-cell origin. We report a case of intravascular lymphoma revealed by diffuse telangiectasia and cauda equina syndrome. CASE REPORT: A 64-year-old Vietnamese woman presented with unexpected fever and weight loss. Three months after the onset of the first symptoms, an oedema appeared on the lower limbs and the trunk, followed by the eruption of diffuse superficial telangiectasia. Neurologic examination revealed a cauda equina syndrome. The diagnosis of intravascular B cell lymphoma was established on cutaneous and muscular biopsy specimen. A moderate hemophagocytic syndrome was observed, confirmed by bone marrow biopsy. Corticosteroid therapy was started, followed by combination chemotherapy yielding complete response. Six months later death occurred, without evidence of relapse of intravascular lymphoma. DISCUSSION: Clinical presentation of intravascular lymphoma is often confusing, mimicking systemic disease, with a predilection for skin and nervous system involvement. Diagnosis is difficult and often an autopsy finding. Prognosis is generally poor, but favourable responses to chemotherapy have been observed after early diagnosis and treatment. The pathogenesis of intravascular lymphoma remains unknown. Dysfunction of cell-endothelial interaction affecting adhesion molecules has been suspected. The implication of Epstein-Barr virus in intravascular lymphoma remains controversial.

Female↗
PubMed2001

Prognostic factors in primary cutaneous large B-cell lymphomas: a European multicenter study.

PURPOSE: Most primary cutaneous B-cell lymphomas have an excellent prognosis. However, primary cutaneous large B-cell lymphomas (PCLBCLs) of the leg have been recognized as a distinct entity with a poorer prognosis in the European Organization for Research and Treatment of Cancer (EORTC) classification. This distinction on the basis of site has been debated. Our aim was to identify independent prognostic factors in a large European multicenter series of PCLBCL. PATIENTS AND METHODS: The clinical and histologic data of 145 patients with PCLBCL were evaluated. According to the EORTC classification, 48 patients had a PCLBCL of the leg and 97 had a primary cutaneous follicle center-cell lymphoma (PCFCCL). Data from both groups were compared. Univariate and multivariate analyses of specific survival were performed using a Cox proportional hazards model. RESULTS: Compared with PCFCCL, PCLBCL-leg were characterized by an older age of onset, a more recent history of skin lesions, a more frequent predominance of tumor cells with round nuclei and positive bcl-2 staining, and a poorer 5-year disease-specific survival rate (52% v 94%; P <.0001). Univariate survival analysis in the entire study group showed that older age, a more recent onset of skin lesions, the location on the leg, multiple skin lesions, and the round-cell morphology were significantly related to death. In multivariate analysis, the round-cell morphology (P <.0001), the location on the leg (P =.002), and multiple skin lesions (P =.01) remained independent prognostic factors. The round-cell morphology was an adverse prognostic factor both in PCLBCL-leg and in PCFCCL, whereas multiple skin lesions were associated with a poor prognosis only in patients with PCLBCL-leg. CONCLUSION: With site, morphology, and number of tumors taken into account, guidelines for the management of PCLBCL are presented.

Adult↗