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Biomedical subjects

M Bagot

Publications and source records attributed to M Bagot.

At least 73 records · Page 4Linked to original sources

Differences in Epstein-Barr virus expression between primary and secondary cutaneous angiocentric lymphomas. French Study Group of Cutaneous Lymphomas.

BACKGROUND: Epstein-Barr virus (EBV) has been demonstrated in angiocentric immunoproliferative lesions, suggesting that it could be a causative factor. We investigated for the presence of EBV in 12 primary and 2 secondary cutaneous angiocentric lymphomas (CALs). OBSERVATIONS: In the 2 secondary CALs, strong reactivity for EBV RNAs and latent membrane protein 1 were detected on paraffin-embedded sections. In contrast, 10 of 12 primary CALs were completely negative for EBV RNAs and latent membrane protein 1. In 2 primary CALs, EBV RNAs and latent membrane protein 1 were detected in few tumor cells. In the group of primary CALs, 8 of 12 were still alive at last follow-up, 3 died of systemic lymphoma, and 1 died of another cause, whereas both patients with secondary CALs died of disease within 1 year. CONCLUSION: Differences in the presence of EBV and clinical behavior between primary and secondary CALs suggest that different mechanisms are operative in the pathogenesis of these conditions, and indicate that the 2 groups should be considered separately.

Adult↗

Value of clonality studies of cutaneous T lymphocytes in the diagnosis and follow-up of patients with mycosis fungoides.

Histological features of early mycosis fungoides (MF) can simulate numerous inflammatory lesions and histological confirmation of MF is often delayed, compared with clinical diagnosis. Recently, using molecular techniques, the detection of a dominant T-lymphocyte clone has been reported in cutaneous lesions of MF. The aim of the present study was to determine the diagnostic value of a dominant T-lymphocyte clone as assessed by PCR-DGGE in early MF. Histopathological and molecular analyses were performed on cutaneous lesions from 104 patients clinically suspected as having MF. In this population, the positive predictive value of a PCR gamma(+) was 0.86. In addition, four of six patients whose lesions were PCR gamma(+) (detectable dominant T-cell clone) but not histologically MF progressed to MF within 2-48 months. In order to evaluate the relevance of PCR gamma-DGGE in MF follow-up, serial biopsies were performed in 24 patients. In 89 per cent of cases, the presence or absence of a PCR gamma(+) was constant during the course of the disease. When present, the DGGE imprint of PCR products was case-specific. These data demonstrate the diagnostic value in MF of T-lymphocyte clonality assessed by PCR gamma-DGGE on cutaneous lesions and show that the technique can be used in MF follow-up to evaluate residual disease with high specificity.

Clone Cells↗

Mycosis fungoides presenting as keratosis lichenoides chronica.

We report a patient with a 17-year history of reticulated keratotic papules on the trunk and limbs, and telangiectatic eruption on the face, in whom the diagnosis of keratosis lichenoides chronica was first established. However, the biopsies showed an epidermotropic infiltrate of small irregular CD4+ lymphocytes, and detection of a T-cell clone in the lesions by polymerase chain reaction confirmed the diagnosis of mycosis fungoides. Thus, keratosis lichenoides chronica can be an unusual and potentially misleading presentation of mycosis fungoides.

Adult↗

Statistical evaluation of diagnostic and prognostic features of CD30+ cutaneous lymphoproliferative disorders: a clinicopathologic study of 65 cases.

Several clinical and histopathologic features of 65 CD30+ cutaneous lymphoproliferations were evaluated for their diagnostic value between CD30+ primary versus secondary cutaneous lymphomas and for their prognostic significance. Primary cutaneous disease, spontaneous regression, and absence of extracutaneous spreading (but not age < or =60 years) were associated with a better prognosis. Epithelial membrane antigen, BNH9, CD15 or CBF.78 antigen were expressed in all types of cutaneous lymphoproliferations. However, epithelial membrane antigen immunoreactivity was more frequently expressed in CD30+ secondary cutaneous large-cell lymphoma. Among CD30+ primary cutaneous large-cell lymphoma, CD15 expression was only seen in localized skin lesions. P53 expression was not associated with spontaneous regression, extracutaneous spreading, or survival. Nested reverse transcriptase-polymerase chain reaction allowed the detection of NPM-ALK transcripts in 10 of 26 CD30+ primary and in 3 of 11 secondary cutaneous large-cell lymphomas. The ALK protein was detected in only 1 of 50 primary and in 4 of 15 secondary cutaneous CD30+ lymphoproliferations. In CD30+ primary cutaneous lymphoproliferation, NPM-ALK transcripts might be expressed by very rare normal or tumoral cells that are undetectable by immunohistochemistry. However, the expression of either NPM-ALK transcripts or ALK-protein was not correlated with prognosis or age in CD30+ cutaneous lymphoproliferations.

Biomarkers, Tumor↗

[Cutaneous lymphoma of the Sézary and Bouvrain type. Progress in physiopathologic and therapeutic outlook].

In 1938, Sézary and Bouvrain reported a new form of disseminated cutaneous lymphomas, characterized by an erythrodermia, and by the presence in the blood of cells with a cerebriform nucleus. It was shown later that this disease was related to the proliferation of a subpopulation of CD4+ T lymphocytes. With the aim to develop new therapeutic strategies for these lymphomas, we tried to evidence and to characterize the tumor-specific immune responses in these cutaneous T-cell lymphomas. We have isolated several T cell clones from lymphocytes infiltrating a human MHC class II negative cutaneous T cell lymphoma. We describe here two of these clones, TC5 and TC7, with respectively a CD4+CD8+ and CD4+CD8- phenotype. Both clones mediated a specific MHC class I-restricted cytotoxic activity toward the fresh autologous tumor cells, and autologous tumor cell lines previously established with IL-2 and IL-7 from the skin and from the blood. Analysis of the T-cell receptor V beta gene expression revealed that the tumor cells, that were shown to have a trisomy 7 by fluorescent in situ hybridization, expressed V beta 7/J beta 2.3, V beta 13/J beta 2.5 and V beta 22/J beta 2.5 rearrangements. Phenotypic analysis using specific anti-V beta monoclonal antibodies indicated that only V beta 13 could be detected on the cell membrane of the tumor cells. Analysis of the TCR V beta gene expression of the clones showed that TC5 and TC7 expressed a unique TCR-V beta transcript, corresponding respectively to V beta 5/J beta 2.3 and V beta 17/J beta 2.7 gene segments. To determine whether these reactive T lymphocytes were present in vivo, we used specific primers corresponding to TC5 and TC7-V beta TCR transcripts. The results demonstrated that both cytotoxic T cell clones were present at the lesional skin site and amplified in vitro. TC7 was found in the patient peripheral blood invaded by tumoral cells, whereas TC5 was not, indicating that the repertoire of the reactional lymphocytes differs in the blood and at the tumor site. These results demonstrate for the first time the presence of reactive T lymphocytes with CD4 or double positive phenotype infiltrating a CTCL. These findings raise new perspectives for the treatment of cutaneous T-cell lymphomas.

Forecasting↗

CD101 is expressed by skin dendritic cells. Role in T-lymphocyte activation.

CD101 was first described in our laboratory using two different monoclonal antibodies, BA27 and BB27, recognizing a 140-kDa disulfide-bonded homodimeric polypeptide on a small subset of circulating T lymphocytes and on most activated T cells in vitro. Further, it has been reported that most intestinal mucosal T lymphocytes expressed CD101. The gene coding for the CD101 antigen has been cloned and found to be identical to the gene coding for the recently described V7 antigen, corresponding to a type I trans-membrane protein with seven immunoglobulin-like loops in its extracellular domain. To define surface proteins that are involved in skin dendritic cell (DC) localization or function, we looked for the expression of CD1O1 on skin DC migrating from human skin explants. The majority of these DC had a phenotype of Langerhans cell (LC)-like mature DC, i.e., HLA-DR+ CD1a+ CD1c+ CD11a+ CD11c+ CD40+ CD50+ CD54+ CD58+ CD80+ CD83+ CD86+. We found that CD101 was expressed by a major subset of these HLA-DR+ CD1a+ CD1c+ LC-like skin DC. Next, we studied the effect of anti-CD101 monoclonal antibodies on primary allogeneic and on soluble antigen-specific mixed skin DC-lymphocyte reactions. We showed that two different monoclonal antibodies, BB27 and V7.1, inhibited the T-lymphocyte proliferative responses and that the inhibitory effect was overcome by high doses of exogenous IL-2. As both DC and T lymphocytes expressed CD101 molecules, we determined that the inhibitory effect was achieved both at the responder T-cell level and at the DC level. Thus, CD101 which is expressed on a subset of circulating T lymphocytes, has also been found on a subpopulation of LC-like DC. This molecule plays a major role in the activation of T cells by skin DC.

Antigens, CD↗

Distinctive clinicopathologic features associated with regressive primary CD30 positive cutaneous lymphomas: analysis of 6 cases.

A distinct group of cutaneous lymphomas has been described on the basis of CD30 antigen expression by at least 75% of the tumoral cells. When confined to the skin, these CD30 positive cutaneous lymphomas seem to be associated with a better prognosis than CD30 negative counterparts and spontaneous regression may even occur. We observed a spontaneously regressive evolution in 6 out of 9 CD30 positive primary cutaneous large cell-lymphomas diagnosed during a 5-year period. Clinicopathological data of regressive cases were analysed. The mean age of patients was 56.5 years. They were 3 males and 3 females. Skin lesions were solitary nodule or plaque measuring from 1.5 cm to 11 cm in diameter. Histologically, the lesions were classified as pleomorphic, medium and large cell (5 cases) or large cell anaplastic lymphoma (1 case) according to the updated Kiel classification. Delay for spontaneous regression varied from 1 to 6 months. Three of the 6 patients had cutaneous relapses, followed by a spontaneous regression. All patients remained disease-free with an overall median follow-up of 30 months. Histologically, some distinctive signs such as epidermal pseudo-epitheliomatous hyperplasia, epidermotropism, edema, dermal vascular hyperplasia, seemed to be more frequently associated with spontaneously regressive evolution.

Adult↗

[Acute mast cell leukemia disclosed by vasomotor flushing].

INTRODUCTION: Acute mast cell leukemia is a rare and severe disease. We report herein a case associated with a flush syndrome. CASE REPORT: A 44-year-old man, presented with a flush of face and trunk. Bone marrow was infiltrated with immature mast cells. In spite of chemotherapy and bone marrow transplantation the patient deceased. DISCUSSION: Pheochromocytoma, carcinoid tumor, and mastocytosis are associated with a flush syndrome. In our patient the diagnosis was an acute mast cell leukemia. Acute mast cell leukemia can follow systemic mastocytosis or occur de novo. This disease is of poor prognosis. No treatment is available.

Adult↗

Drug-induced pseudolymphoma and drug hypersensitivity syndrome (Drug Rash with Eosinophilia and Systemic Symptoms: DRESS).

Since the first description by Saltzstein in 1959, the denomination of drug-induced pseudolymphoma was used to describe two cutaneous adverse drug reactions with a histological picture mimicking malignant lymphoma. On the basis of clinical presentation, this term includes two different patterns: (1) hypersensitivity syndrome which begins acutely in the first 2 months after the initiation of the drug and associates fever, a severe skin disease with characteristic infiltrated papules and facial edema or an exfoliative dermatitis, lymphadenopathy, hematologic abnormalities (hypereosinophilia, atypical lymphocytes) and organ involvement such as hepatitis, carditis, interstitial nephritis, or interstitial pneumonitis. The cutaneous histological pattern shows a lymphocytic infiltrate, sometimes mimicking a cutaneous lymphoma, and the mortality rate is about 10%. When organ involvement exists, corticosteroids are often prescribed with dramatic improvement. Relapses may occur. (2) drug-induced pseudolymphoma which has a more insidious beginning with nodules and infiltrated plaques appearing several weeks after the beginning of the drug without constitutional symptoms. A pseudolymphoma pattern is seen on cutaneous histological slides. Complete improvement is usual after drug withdrawal, but a delayed lymphoma is possible. To decrease the ambiguity of the denomination of hypersensitivity syndrome, we propose the term of DRESS (Drug Rash with Eosinophilia and Systemic Symptoms).

Anticonvulsants↗

Making choices in hospital resources allocation. The use of an assessment tool to decide which new projects are financed.

We designed a scoring system to rank acute care hospital projects and allocate resources between them. The evaluation tool assessed projects on an ordinal scale; the criteria scored were medical interest, feasibility, interest for teaching and research, and compatibility with the hospital's strategy. Clinical and technical projects were ranked separately. In 1994, 25 new projects, representing a total cost of $1.4 million, were reviewed by two independent reviewers. The scores ranged from 30 to 18 over 36. Projects presented by clinical departments scored higher than projects presented by medicotechnical departments.

Budgets↗

Pilotropic cutaneous T-cell lymphoma without mucinosis. A variant of mycosis fungoides? French Study Group of Cutaneous Lymphomas.

BACKGROUND: In the course of mycosis fungoides, pilofollicular manifestations without mucinosis (papules, keratoses, comedones, or epidermal cysts) are rare (15 cases reported). Therefore, histological and clinical diagnoses may be difficult. The clinical course and histopathological and immunohistochemical findings in 9 patients are described. OBSERVATIONS: Pilofollicular lesions were present at the onset (n = 3), before (n = 3), or during a relapse of mycosis fungoides (n = 3). Comedones and epidermal cysts were most frequent (n = 5). They disappeared with lymphoma therapy (n = 4), therapy with isotretinoin (n = 3), or spontaneously (n = 1), or they persisted (n = 1). Clues to the histopathological diagnosis consisted of pilotropism of the infiltrate with minor alteration of the hair follicle walls. The infiltrate was monomorphous and composed of sezariform CD4+ lymphocytes. Pilotropic or peripilofollicular infiltrates, or the absence of infiltrate, were detected in consecutive biopsy specimens obtained from the same patient. The keratinocyte expression of intercellular adhesion molecule type 1 was observed in the hair follicle bulb in front of the pilotropic infiltrate but not in the epidermis. No staining was observed in biopsy specimens of 6 of 7 patients with follicular mucinosis, of folliculitis lesions, or of normal hair follicles. CONCLUSIONS: Our findings indicate the role of adhesion molecules in pilotropism leading to mechanical obstruction of the follicle by tumoral cells followed by hyperkeratosis and cyst formation. It remains to be determined if the expression of intercellular adhesion molecule type 1 is the cause or the consequence of pilotropism. By becoming more aware of it, this variant of mycosis fungoides is probably not so rare.

Adult↗

[Sezary syndrome treated by cytapheresis. Short and long-term results].

INTRODUCTION: Sezary syndrome is usually resistant to most treatments. The aim of this work was to evaluate short and long-term results of cytapheresis in patients with Sezary syndrome. PATIENTS AND METHODS: Twenty-two patients with Sezary syndrome were included in the study (13 men, 9 women, man age 58 +/- 35.4 years). The mean duration of Sezary syndrome before cytapheresis was 6.5 +/- 2 months. Extra-cutaneous involvement was observed in 16 of the patients. Each patient underwent 33 +/- 63 cytapheresis sessions (total number = 685). Complete remission in "responders" was defined as the absence of clinical signs and Sezary cells < 1,000/mm3. In "non responders" partial remission was defined as incomplete regression of clinical signs and Sezary cells > 1,000/mm3 and failure as lack of improvement or worsened clinical situation. RESULTS: Complete remission was obtain in 10/22 patients (45.5 p. 100), partial remission in 4/22 (18 p. 100) and failure in 8/22 (36.5 p. 100). There was no significant difference between responders and non-responders for age, duration of the Sezary syndrome before cytapheresis, the number of sessions, extracutaneous involvement, or another associated treatment. In the responders, mean survival was 90 +/- 42 months. Two patients were alive at 5 years and 1 at 10 years. In the non responders, mean survival was 8 +/- 1.4 months and median survival was 11 months. CONCLUSION: There was no significant evidence suggesting a difference between responders and non-responders. Nevertheless, mean survival was longer in patients who had achieved complete remission. Cytapheresis is thus justified for the treatment of patients with Sezary syndrome.

Adult↗