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Philippe Courville

Publications and source records attributed to Philippe Courville.

14 recordsLinked to original sources
PubMed2006

Role of TLR9 in anti-nucleosome and anti-DNA antibody production in lpr mutation-induced murine lupus.

Systemic lupus erythematosus is characterized by the production of autoantibodies directed against nuclear Ags, including nucleosome and DNA. TLR9 is thought to play a role in the production of these autoantibodies through the capacity of nuclear immunogenic particles to interact both with BCR and TLR9. To determine the role of TLR9 in SLE, C57BL/6-lpr/lpr-TLR9(-/-) and TLR9(+/+) mice were analyzed. The abrogation of TLR9 totally impaired the production of anti-nucleosome Abs, whereas no difference was observed in the frequency of anti-dsDNA autoantibodies whose titer was strikingly higher in TLR9(-/-) mice. In addition a higher rate of mesangial proliferation was observed in the kidney of TLR9-deficient animals. These results indicate that in C57BL/6-lpr/lpr mice, TLR9 is absolutely required for the anti-nucleosome Ab response but not for anti-dsDNA Ab production which is involved in mesangial proliferation.

Animals↗
PubMed2005

Treatment of early-stage mycosis fungoides with twice-weekly applications of mechlorethamine and topical corticosteroids: a prospective study.

OBJECTIVE: To determine if a therapeutic regimen of twice-weekly applications of mechlorethamine hydrochloride and betamethasone dipropionate cream is effective in the treatment of early-stage mycosis fungoides while increasing cutaneous tolerance. DESIGN: Prospective nonrandomized study conducted from November 1999 to November 2002. SETTING: Eleven university or hospital dermatology departments in France. PATIENTS: Sixty-four consecutive patients with newly diagnosed early-stage mycosis fungoides (stage IA, n = 33; stage IB, n = 26; stage IIA, n = 5). INTERVENTIONS: Patients were treated with twice-weekly applications of a 0.02% aqueous solution of mechlorethamine followed by an application of betamethasone cream during a 6-month period. MAIN OUTCOME MEASURES: The primary end point was the rate of complete response during the treatment. Secondary end points were mean delay to achieve complete response, rate of severe cutaneous reactions of intolerance, and rate of relapse after achieving complete response. RESULTS: Thirty-seven patients (58%) had a complete response after a mean +/- SD treatment duration of 3.6 +/- 2.5 months: 20 (61%) of 33 patients with stage IA disease, 15 (58%) of 26 patients with stage IB disease, and 2 (40%) of 5 patients with stage IIA disease. Eighteen patients (28%) developed severe cutaneous reactions of intolerance that necessitated treatment discontinuation. Relapse was observed in 17 patients (46%) after a mean +/- SD time of 7.7 +/- 6.5 months. CONCLUSIONS: A regimen of twice-weekly applications of mechlorethamine and betamethasone cream is an effective treatment for early-stage mycosis fungoides. The decreased frequency of applications provides an advantage to the patient by being easy to use with limited adverse effects.

Administration, Topical↗
PubMed2005

Intense paraneoplastic neutrophilic leukemoid reaction related to a G-CSF-secreting lung sarcoma.

A white blood cell count more than 50 x 10(9)/l, not related to bone marrow involvement, is termed leukemoid reaction. We report on the first case of an undifferentiated sarcoma of the lung associated with an intense paraneoplastic neutrophilic leukemoid reaction related to the production of granulocyte colony-stimulating factor (G-CSF). A radiography and a computed tomography scan of the chest revealed a well-limited voluminous and heterogeneous low-density mass of the left lung. The patient died of multiorgan failure related to uncontrolled progressive tumor growth after admission and two cycles of chemotherapy. The patient's G-CSF serum concentration was dramatically elevated (6,538 pg/ml) compared to serum levels observed in normal controls and patients with elevated leukocytosis (31 and 387 pg/ml, respectively). The G-CSF concentration dramatically increased after the first cycle of chemotherapy and during the subsequent neutropenia, as a result of the tumor lyses as well as of disruption of the physiological negative feedback mechanism. Adjunction of the patient's serum to CD34+ cell cultures induced a 12.3-fold increase in CD15+ cells, demonstrating the serum's capacity to induce myeloid differentiation.

Cell Proliferation↗
PubMed2005

Usefulness of cutaneous T-cell clonality analysis for the diagnosis of cutaneous T-cell lymphoma in patients with erythroderma.

CONTEXT: Demonstration of a dominant T-cell clone in skin biopsy specimens by a molecular assay constitutes an additional diagnostic criterion to differentiate cutaneous T-cell lymphomas (CTCLs) from inflammatory dermatoses. OBJECTIVE: To determine which patients, depending on their clinical presentations, could most benefit from a cutaneous T-cell clonality analysis in addition to histopathologic analysis for the diagnosis of CTCL. DESIGN: Comparison of sensitivity and specificity of histopathologic analysis and a combination of this method and the detection of a T-cell receptor gamma chain gene rearrangement by polymerase chain reaction denaturing gradient gel electrophoresis performed on skin biopsy specimens obtained at initial presentation. PATIENTS: One hundred forty consecutive patients were classified into 4 groups, depending on their clinical presentation: (1) eczematous patches suggestive of early-stage mycosis fungoides (MF) (IA and IB of the TNM classification) (n = 42); (2) plaques, nodules, or tumors that arise on or are associated with plaques suggestive of late-stage MF (IIB and III of the TNM classification) (n = 16); (3) erythroderma (n = 50); and (4) nodules or tumors that arise in normal skin, suggestive of non-MF CTCL (n = 32). RESULTS: When compared with histopathologic examination, the addition of clonality analysis increased the sensitivity of CTCL diagnosis in all groups of patients except those with cutaneous lesions suggestive of late-stage MF, because the diagnosis was made based on histopathologic analysis alone in 100% of these cases. The main increase in sensitivity of CTCL diagnosis was observed in patients with erythroderma: 62% with histopathologic analysis alone to 87% with the combination of both methods (P = .04). Diagnostic specificity of molecular assays decreased from 100% to 76% (P = .01) in patients with patch lesions and from 100% to 70% (P = .04) in patients with nodules that occurred in normal skin due to the detection of a T-cell clone in 6 patients with follicular mucinosis without a histologic pattern of MF and in 5 of 20 cases of T-cell pseudolymphoma (25%), respectively. In contrast, a T-cell clone was not detected in the 34 patients with erythroderma of inflammatory origin. CONCLUSION: Polymerase chain reaction analysis of cutaneous T-cell clonality could be useful for the diagnosis of CTCL in patients who present with erythroderma.

Clone Cells↗
PubMed2005

Blastic NK-cell lymphomas (agranular CD4+CD56+ hematodermic neoplasms): a review.

Blastic natural killer (NK) cell lymphoma (also termed CD4+CD56+ hematodermic neoplasm) is a recently described entity, with the first case reported in 1994. It was suggested initially that the disease originates from NK cells. Since 1994, single cases and a few small series have been published. In this review, data from the literature and a series of 30 cases from the French and Dutch study groups on cutaneous lymphomas are discussed. The major clinical, histopathologic, and phenotypic aspects of the disease and diagnostic criteria and data suggesting a plasmacytoid dendritic cell origin for the tumor cells are provided.

Adult↗
PubMed2004

Bcl-2 protein expression is the strongest independent prognostic factor of survival in primary cutaneous large B-cell lymphomas.

Bcl-2 protein expression has been associated with poor prognosis in patients with noncutaneous diffuse large B-cell lymphomas. In primary cutaneous large B-cell lymphomas, the location on the leg, the round-cell morphology defined as the predominance of centroblasts and immunoblasts over large centrocytes, and multiple skin lesions were identified as adverse prognostic factors. The prognostic value of bcl-2 protein expression has not been studied in large series of patients. We evaluated 80 primary cutaneous large B-cell lymphomas collected by the French Study Group on Cutaneous Lymphomas. The prognostic value of age, sex, number of lesions, cutaneous extent, location, serum lactate dehydrogenase (LDH) level, B symptoms, morphology, and bcl-2 protein expression was studied. The overall 5-year specific survival rate was 65%. In univariate analysis, advanced age, multiple skin lesions (n = 48), location on the leg (n = 25), round-cell morphology (n = 32), and bcl-2 expression (n = 39) were significantly related to death from lymphoma. In multivariate analysis, bcl-2 expression (P =.0003), multiple skin lesions (P =.004), and age remained independent prognostic factors. The 5-year specific survival rates in bcl-2-positive and bcl-2-negative patients were 41% and 89%, respectively (P <.0001). A new prognostic classification of primary cutaneous B-cell lymphoma should be based primarily on bcl-2 protein expression rather than the location of skin lesions.

Adult↗
PubMed2004

[Parasellar paraganglioma: a case report].

A 66-Year-old man presented with diplopia, headache and dizziness. Magnetic resonance imaging showed a right intrasphenoidal paracavernous mass. A biopsy was performed by endonasal route in the lesion which appeared to be part of the hypophyseal fossa. Histological examination revealed a highly cellular tumoral proliferation, with a variable architecture, of which chief cells were immunoreactive for neuroendocrine markers and spindle-shaped cells positive for PS 100. Morphological features were consistent with the diagnosis of paraganglioma. Our observation is the first case of this rare tumor reported in the French literature.

Aged↗
PubMed2004

[Hematodermic CD4/CD56 neoplasm].

Hematodermic CD4/CD56 neoplasm is a recently described entity. This name has been initially proposed by the French Study Group on Cutaneous Lymphomas which established the primary anatomoclinical and pathogenic and cytogenic bases of the disease in 1999. This descriptive and provisional name allowed conceptualizing the entity by its main clinical and phenotypical characteristics. The first case in the literature goes back to 1994. Since that time, several other cases have been published. The expression of CD56 led most of the authors to propose an NK-cell lineage origin. In the last WHO classification of lymphomas, the entity was indexed under the name of "blastic NK-cell lymphoma". However, the authors underlined that there were currently no clues to the etiology of blastic NK-cell lymphoma and that the precise lineage of this disease was still unresolved. At the clinical level the main characteristics of the disease are the skin tropism and the occurrence of a leukemic phase at any time during the course of the disease. The median age is 59 but pediatric cases do exist. At the morphological level skin biopsy shows a monomorphous cell proliferation simulating a pleomorphic T cell cutaneous lymphoma. The diagnosis is based on phenotypic criteria which require frozen tissue. Currently, the main characteristics are the expression of CD4 and CD56 antigens while the main defined lineage specific markers are negative (B-cell, T-cell, NK-cell and myeloid-cell lineages). The origin of the tumor cells still remains uncertain but the plasmacytoid dendritic cell is presently a very serious candidate. The tumor cells share a great phenotypical homology and particularly the expression of the CD123 antigen. Functional homologies have also been demonstrated with tumor cells in vitro. Outcome of CD4/CD56 hematodermic neoplasms is very bad. The median time of survival is 14 months irrespective of the treatment given. Conventional chemotherapies used for the treatment of aggressive lymphomas or acute myeloid leukemias are quickly inefficient.

Adolescent↗
PubMed2004

[Clear cell dermatofibroma: a case report with cytogenetic study].

We report an observation concerning a 48-year-old male who presented with a 5 cm tumour on his left leg, first noticed 18 months ago. The remainder of clinical examination was normal. Histological assessment revealed a tumoral infiltration of entire dermis and superficial hypodermis. This tumour consisted of monomorphous, ovoid or spindle cells, with clear cytoplasm and PAS+ granulations. There was strong immunoreactivity by tumoral cells only for vimentin. Ultrastructural studies revealed fibrohistiocytic-like tumoral cells, without epithelial, muscular, vascular or melanocytic differentiation. These results were consistent with the diagnosis of clear cell dermatofibroma. Cytogenetic evaluation and FISH analysis showed a deletion of p12. Clear cell dermatofibroma is a rare and recent variant of dermatofibroma, with a difficult histological evaluation and which must be differentiated from clear-cell sarcoma. This observation is the first case-report of this entity, to our knowledge, showing a cytogenetic abnormality.

Chromosomes, Human, Pair 12↗
PubMed2003

Paraneoplastic pemphigus is associated with the DRB1*03 allele.

Pemphigus is a group of autoimmune blistering diseases caused by autoantibodies directed against keratinocyte adhesion molecules. Pemphigus vulgaris (PV) and pemphigus foliaceus (PF), in which autoantibodies bind, respectively, to desmoglein 3 and desmoglein 1, are strongly associated with HLA-class II DR4 and DR14 alleles. In paraneoplastic pemphigus (PNP), a rare variant associated with neoplasia, autoantibodies target proteins of the plakin family in addition to desmogleins 1 and 3. The presence of anti-desmoglein antibodies in all types of pemphigus raises the question of common molecular mechanisms of susceptibility, particularly similar MHC-class II allele associations, in the different forms of the disease. HLA-DRB1 typing was performed in 13 PNP patients and results were compared to those obtained from 84 healthy controls, 37 PV and 31 PF patients. Our data demonstrate a significant association of PNP with HLA-DRB1*03 allele which was found in 61.5% of the patients, whereas DRB1*04 and DRB1*14 appear not to be involved in PNP susceptibility. Therefore, the HLA-genetic background of PNP differs from that of other types of pemphigus, which suggests that distinct mechanism(s) initiate(s) the immunological response in this form of pemphigus.

HLA-DR Antigens↗
PubMed2002

Eosinophilic leukemia associated with t(2;5)(p23;q31).

Chromosomal aberrations have been reported in most malignant hematopoietic disorders such as acute or chronic myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndromes. Eosinophilic leukemia is a rare hematologic malignancy difficult to distinguish from other forms of idiopathic hypereosinophilic syndrome, so that the diagnosis is often made by exclusion, unless cytogenetic abnormalities can be demonstrated in bone marrow cells. We describe a patient with eosinophilic leukemia whose cytogenetic study shows a t(2;5)(p23;q31). Initial data could suggest a clonal eosinophilia, with an hepatosplenomegaly, severe pancytopenia, and a high level of blood and medullar eosinophilia.

Bone Marrow↗
PubMed2002

Value of interphase FISH for the diagnosis of t(11:14)(q13;q32) on skin lesions of mantle cell lymphoma.

The diagnosis of skin lesions of mantle cell lymphoma (MCL) may be difficult at the onset of the disease. We observed 2 patients with papules of the trunk and 1 with diffuse infiltration of the trunk and the face and 2 subcutaneous nodules. Skin samples showed diffuse infiltration of the dermis (n = 1) or perivascular infiltration (n = 2). The infiltrate corresponded to centrocytic cells (n = 2) or pleomorphic blastoid cells (n = 1) with a B-cell phenotype: CD3-, CD5+ (2/3), CD20+, CD23-, and CD43+. In only 1 case was cyclin D1 immunoreactivity detected, and the t(11;l4)(q13;q32) breakpoint was amplified from both lymph node and skin DNA. Competitive reverse transcriptase-polymerase chain reaction was not contributive for skin specimens. In all 3 cases, interphase fluorescence in situ hybridization (FISH) demonstrated t(11;14) fusion signals either on paraffin sections or on fresh frozen touch preparations of skin biopsies. The recognition of skin lesions of MCL from other B-cell infiltrates can be established by interphase FISH.

Aged↗
PubMed2002

[Detection of HHV8 latent nuclear antigen by immunohistochemistry. A new tool for differentiating Kaposi's sarcoma from its mimics].

UNLABELLED: The purpose of this work was to study the value of HHV8 latent nuclear antigen 1 detection by immunohistochemistry in Kaposi sarcoma and its mimics. MATERIALS AND METHODS: : We used the mAB LNA53 against the latent nuclear antigen 1 of HHV8 to study its expression by immunohistochemistry in paraffin embedded biopsy of Kaposi and its mimics. We also performed in vitro PCR for HHV8 DNA, extracted from the same paraffin embedded biopsies. We studied characteristic lesions of 26 Kaposi sarcoma; 20 cutaneous lesions raising problems of differential diagnosis. We also studied 11 biopsies of skin, mucosa, or lymph nodes of patients infected by HHV8 but without Kaposi sarcoma, and 22 lesions initially classified by histological analysis as uncertain Kaposi sarcoma . RESULTS: : In all cases of Kaposi, HHV8 was detected in the majority of tumor cells, with no expression in other adjacent cells. In these biopsies HHV8 DNA, was identified by in vitro PCR. None of the 20 Kaposi sarcoma mimics and the 11 lesions of patients infected by HHV8 but without any Kaposi sarcoma, were HHV8+ on immunohistochemistry sections or by PCR. From the 22 cases of uncertain Kaposi sarcoma, only the 14 lesions HHV8 PCR+ and with a clinical evolution in accordance with a Kaposi sarcoma, were HHV8+ on immunohistochemistry. In contrast, the 8 cases negative for HHV8 on immunohistochemistry were also PCR- and had a self-healing evolution in accordance with the diagnostic of pyogenic granuloma. CONCLUSION: : Detection of the latent nuclear antigen 1 of HHV8 by immunohistochemistry is a specific and sensitive diagnostic tool for differentiating Kaposi sarcoma from its mimics.

Antibodies, Monoclonal↗