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M Kambouchner

Publications and source records attributed to M Kambouchner.

At least 19 recordsLinked to original sources

Characterisation of dendritic cell subsets in lung cancer micro-environments.

The aim of the current study was to seek evidence for a correlation between mediators present in lung cancer micro-environments and subsets of dendritic cells (DCs) infiltrating these tumours. Immunohistochemistry and recently available antibodies were used to define the phenotype of DCs present in surgical biopsies from 12 patients with lung carcinomas, and the local expression of chemokines potentially involved in the recruitment of these cells was evaluated, both at mRNA and protein levels. Real-time PCR was used to analyse the expression of mRNA coding for cytokines known to influence the maturation of DCs in vitro. Different subsets of myeloid DCs were present in lung cancers, but no plasmocytoid DCs were identified. Both Langerhans cells and CD1a+/Langerin cells were interspersed among tumour cells, in numbers that were correlated to the amounts of CC chemokine ligand 20 produced in these tumours. In most specimens, DC-specific intercellular adhesion molecule-grabbing nonintegrin-positive DCs were also present at the periphery of the tumour beds. No DC-lysosomal associated membrane protein-positive DCs were identified and CD83+ DCs were rarely present in the tumour stroma. All tumours expressed interleukin (IL)-10, transforming growth factor-beta and vascular endothelial growth factor, whereas IL-12 was virtually absent. Thus, various types of dendritic cells infiltrate lung carcinomas and display an immature phenotype, presumably because of the inhibitory cytokine micro-environment.

Adenocarcinoma↗

Temporal artery biopsy for diagnosing giant cell arteritis: the longer, the better?

OBJECTIVE: To investigate the relation between temporal artery biopsy (TAB) length and diagnostic sensitivity for giant cell arteritis. METHODS: Histological TAB reports generated from four hospital pathology departments were reviewed for demographics, histological findings, and formalin fixed TAB lengths. A biopsy was considered positive for giant cell arteritis if there was a mononuclear cell infiltrate predominating at the media-intima junction or in the media. RESULTS: Among 1821 TAB reports reviewed, 287 (15.8%) were excluded because of missing data, sampling errors, or age < 50 years. Mean TAB length of the 1520 datasets finally analysed (67.2% women; mean (SD) age, 73.1 (10.0) years) was 1.33 (0.73) cm. Histological evidence of giant cell arteritis was found in 223 specimens (14.7%), among which 164 (73.5%) contained giant cells. Statistical analyses, including piecewise logistic regression, identified 0.5 cm as the TAB length change point for diagnostic sensitivity. Compared with TAB length of < 0.5 cm, the respective odds ratios for positive TAB without and with multinucleated giant cells in samples > or = 0.5 cm long were 5.7 (95% confidence interval, 1.4 to 23.6) and 4.0 (0.97 to 16.5). CONCLUSIONS: A fixed TAB length of at least 0.5 cm could be sufficient to make a histological diagnosis of giant cell arteritis.

Aged↗

Expression of apoptosis-regulatory proteins in lesions of pulmonary Langerhans cell histiocytosis.

AIMS: Pulmonary Langerhans cell histiocytosis (PLCH) is characterized by the presence of lesions containing numerous activated Langerhans cells (LCs). An uncontrolled immune response sustained by activated LCs seems to be involved in the pathogenesis of the disease. The aim of this study was to establish whether disruption of LC apoptosis related to the expression of the Bcl-2 family proteins is implicated in the maintenance of PLCH lesions. METHODS: Six patients with PLCH were evaluated by morphological and immunohistochemical techniques to explore the incidence of apoptosis in pathological LCs and to characterize the expression of Bcl-2-related proteins by these cells. RESULTS: Very few LCs present in PLCH lesions exhibited nuclear apoptotic changes or expressed cleaved caspase-3, whereas they all strongly expressed the anti-apoptotic molecule Bcl-x(L). Interestingly, pulmonary LCs present in intervening lung tissue not involved by the pathological process and known to be immature dendritic cells did not express Bcl-2 family proteins. CONCLUSIONS: These findings suggest that activated LCs present within PLCH lesions are poorly susceptible to apoptosis and, thus, are able to sustain the pathological process by causing continuous local stimulation of T cells. Functional studies are needed, however, to demonstrate that they are actually resistant to programmed cell death.

Adult↗

Low grade marginal zone B cell lymphoma of the breast associated with localised amyloidosis and corpora amylacea in a woman with long standing primary Sjögren's syndrome.

Primary low grade marginal zone B cell lymphoma (MZL) of the breast and localised mammary amyloidosis are exceedingly rare entities. This report describes the case of a woman with long standing Sjögren's syndrome presenting with asymptomatic MZL of the breast showing plasmacytic differentiation, associated with local ductular amyloidosis. The lesion was discovered incidentally in breast tissue resected for microcalcifications. Immunohistochemistry revealed kappa light chain restriction, supporting the neoplastic nature of the infiltrate. A retrospective molecular study of the salivary gland biopsy showed a B cell clone. This is the first report of the association of human mammary ductular amyloidosis with cartwheel shaped material identical to corpora amylacea, usually seen in brain, lung, and prostate, but unknown in the human breast. The excellent outcome without treatment seen in this patient further emphasises the need to distinguish between MZL with plasmacytic differentiation and extramedullary plasmacytoma.

Adult↗

Cytokine profiles in idiopathic pulmonary fibrosis suggest an important role for TGF-beta and IL-10.

Modulation of cytokine expression represents a potentially useful approach for the treatment of idiopathic pulmonary fibrosis (IPF). To identify potential targets for such intervention, semi-quantitative reverse transcriptase-polymerase chain reaction was used to compare the expression of messenger ribonucleic acids (mRNAs) coding for 17 cytokines in lung tissue obtained from patients with IPF at the time of diagnosis and control subjects. Some cytokines were also studied at the protein level by immunohistochemical techniques. mRNAs coding for all of the cytokines evaluated were detected in both control and fibrotic lung samples. Only transforming growth factor (TGF)-beta and interleukin (IL)-10 mRNAs were quantitatively increased in lung biopsies from patients with IPF compared with those of controls, results confirmed at the protein level by immunohistochemistry. Although mRNAs for platelet-derived growth factor (PDGF)-BB and keratinocyte growth factor (KGF) were expressed in similar amounts in lungs from patients with IPF and controls, localised accumulation of both factors was also observed in IPF. Hyperplastic alveolar epithelial cells were a prominent source of cytokines, where IL-10, PDGF-BB and KGF were present in increased amounts, although increased accumulation in fibroblasts, smooth-muscle cells and matrix components was also observed (PDGF-BB, TGF-beta). These results offer new insights into the cytokines produced in the lung in idiopathic pulmonary fibrosis and suggest that modulation of the production of transforming growth factor-beta and interleukin-10 may represent a potentially useful therapeutic strategy for this disabling disease.

Female↗

Long-term survival of patients given hormonal therapy for metastatic endometrial stromal sarcoma.

Endometrial stromal sarcoma (ESS) is a rare neoplasm, mainly observed in premenopausal women. We describe two women 44 and 34 years old at the time ESS diagnosis, who developed lung metastases 3 and 6 years, respectively, after initial treatment: hysterectomy without (case 1) or with oophorectomy (case 2), followed by hormone replacement therapy (HRT) for the latter. Their estrogen (ER) and progesterone receptors (PR) were analyzed biochemically in metastatic lung tissue, yielding respective concentrations of ER 242 and 184, and PR 910 and 100 fmol/mg of cytosol protein. Both patients started treatment with the aromatase inhibitor aminoglutethimide (500 mg qid) after surgery for the first patient and after stopping HRT for the second. Under aromatase-inhibitor therapy, both patients achieved a complete response, patient 1 remains disease- free with 14+ years of follow-up, and patient 2 with 7+ years. Our data suggest that an aromatase inhibitor may be an effective treatment for ESS. Furthermore, routine ER and PR analyses could be useful to predict the response to hormonal therapy in ESS.

Adult↗

[Isolated pleural metastases from an atypical meningioma].

INTRODUCTION: Less than 2 per 1,000 meningiomas are complicated by extra-cranial metastases. These are most often found in the lung parenchyma, liver or lymph nodes. They almost always occur in anaplastic meningiomas (grade III according to OMS) and much more rarely in atypical meningiomas (grade II). CASE REPORT: We report a case of pleural metastases from a primary frontal atypical meningioma with no other extra-cranial spread. CONCLUSION: Poorly differentiated meningioma presents many morphological and immuno-histochemical similarities to malignant mesothelioma. For this reason the diagnosis of pleural metastase from a meningioma cannot be made without knowledge of the primary meningeal tumour and its histological type.

Aged↗

Churg-Strauss syndrome in two patients receiving montelukast.

OBJECTIVE: Churg-Strauss syndrome (CSS) has been described in association with the treatment of asthmatic patients with leukotriene receptor antagonist. The main mechanism proposed to explain this condition is the unmasking of CSS after the leukotriene receptor antagonist has allowed corticosteroid tapering. Other hypotheses might be proposed. METHODS: We describe two patients who developed CSS after starting treatment with montelukast, a new antileukotriene drug. RESULTS: Both patients presented with CSS after 4-5 months of treatment with montelukast. Neither patient received long-term systemic steroids for asthma, but both were on inhaled steroids. One patient had a myocardial involvement and experienced a stroke. Our two patients were treated with systemic steroids and cyclophosphamide. CONCLUSIONS: CSS does not appear to relate to steroid tapering in our patients. The other hypotheses are a coincidence or a direct adverse effect of the antileukotriene. Long-term data on these drugs are lacking and leukotriene's role in vasculitis remains to be elucidated.

Acetates↗

Magnetic resonance imaging of skeletal muscle involvement in limb restricted vasculitis.

BACKGROUND: Limb restricted polyarteritis nodosa (PAN) and PAN-type diseases such as isolated vasculitis of skeletal muscle are localised vasculitides affecting the skin, muscles, or peripheral nerves, usually of the lower limbs. These diseases often present with non-specific clinical symptoms and normal laboratory values and electromyograms. The usefulness of magnetic resonance imaging (MRI) of skeletal muscle has been poorly investigated to date. OBJECTIVE: To describe the MRI findings in the legs of three patients with limb restricted vasculitides (two PAN, one isolated vasculitis of the skeletal muscle) with histologically established muscle involvement. METHODS: MRI was carried out on calf muscles and T(2) weighted images, unenhanced T(1) weighted images, and STIR sequences were obtained. RESULTS: Muscle damage resulted in oedema-like changes on MRI characterised by hyperintense signals in T(2) weighted and slow tau inversion recovery (STIR) sequences and normal unenhanced T(1) weighted sequences of one or several leg muscles. CONCLUSIONS: MRI should be considered a useful complementary examination that might facilitate the recognition of limb restricted vasculitides, and possibly indicate the site for muscle biopsy. It could also be useful in monitoring the course of the disease. Future studies should also evaluate MRI for systemic PAN or other systemic vasculitides with muscle involvement.

Adult↗

[Inflammatory pseudotumors of the lung with severe course].

Pulmonary inflammatory pseudotumors are usually unique lesions of unknown etiology with good prognosis. We report two severe cases with mediastinal invasion, local recurrence, extrathoracic locations, one of them with a fatal evolution. Certain microscopic features, which were present in our cases (increased cellularity, nuclear pleomorphism, mitotic activity, focal necrosis, bizarre giant cells, vascular invasion), may have prognostic relevance in determining an aggressive behavior of these tumors. Surgical resection is the recommended treatment, and incomplete resection, as in our cases, seems to be a risk factor for developing recurrent inflammatory pseudotumor. Immunosuppressive therapy was ineffective as well as radiotherapy in one of our cases. Only high doses of corticosteroids seemed to slow the evolution of the disease.

Adult↗

Detection of codon 12 K-ras mutations in non-neoplastic mucosa from bronchial carina in patients with lung adenocarcinomas.

K-ras activation by point mutation in codon 12 has been reported in lung adenocarcinomas in various models of experimental lung tumours induced by chemical carcinogens. The hypothesis of the presence of cells containing K-ras mutation in non neoplastic bronchial carina, the main site of impaction of airborne contaminants, was investigated by evaluating concurrent lung tumour and non-neoplastic proximal bronchial carinae from 19 patients with lung adenocarcinomas. The restriction fragment length polymorphism enriched PCR method used can detect one mutant allele among 10(3) normal alleles. A mutation was detected in 42% of lung adenocarcinoma samples. No mutation was detected in either tumour or bronchial carinae in nine patients (47%). K-ras mutation was detected in the lung tumour but not in bronchial carinae in four patients (21%), in both the lung tumour and bronchial carinae in four other patients (21%). In two patients (11%), K-ras mutation was detected in at least one bronchial carina, but not in the lung tumour. Mutations of codon 12, confirmed by sequencing analysis of ten samples, were G to T transversion, mostly TGT and GTT in bronchial carinae and lung tumours. Our data show that activated K-ras by point mutation can be present in non-neoplastic bronchial carina mucosa even when no mutation is detected in tumour samples.

Adenocarcinoma↗

Low expression of bcl-2 in Brca1-associated breast cancers.

Little data are available concerning the molecular mechanisms of action of Brca1 and Brca2 in breast oncogenesis. Recent experimental results suggest that Brca1 plays a role in the regulation of apoptosis. In order to determine whether the analysis of human tumours would provide data supporting this hypothesis, we have assessed the expression of the antiapoptotic bcl-2 and of the proapoptotic p53 genes in Brca1 - and Brca2 -associated breast carcinomas. The levels of expression of these genes were compared to those observed in controls and to the mitotic and the apoptotic indexes. Our series were composed of 16 cases of breast carcinoma in women with a germline Brca1 gene mutation, and of four cases with Brca2 mutation. A group of 39 patients aged under 36 years and for whom the search for Brca1 gene mutations was negative, and a group of 36 cases of sporadic cancers without data on their Brca status were used as controls. Immunohistochemistry was used to detect p53 and bcl-2 gene products. Mitotic and apoptotic indexes were higher in Brca1 -associated tumours than in controls. No significant difference in p53 immunostaining was observed between the four groups of patients. In contrast, the rate of bcl-2 -positive tumours was lower (31%) in Brca1 -carcinomas than in carcinomas without Brca1 mutation (90%) (P< 10(-3)). A strong Bcl-2 expression was found in the four cases of Brca2 -associated carcinomas. No significant correlation was observed between p53 and Bcl-2 immunostainings, either in cases or in controls. The association between Brca1 status and Bcl-2 expression remained significant after adjustment for the oestrogen receptor status. Our study shows that a low expression of bcl-2 characterises most Brca1 -associated breast carcinomas, a biological trait which seems not to be shared by Brca2 -associated tumours nor to be related to oestrogen receptor and/or p53 status. bcl-2 might thus be one of the target genes involved in the oncogenesis related to Brca1 and its down-regulation may account for the increased apoptosis and the high proliferative rate observed in Brca1 -associated carcinomas.

Adult↗

Is high-resolution computed tomography a reliable tool to predict the histopathological activity of pulmonary Langerhans cell histiocytosis?

High-resolution computed tomography (HRCT) has proved to be very useful in the diagnosis and follow-up of pulmonary Langerhans cell histiocytosis (PLCH), but the precise relationships between nodules and thin-wall cysts observed by HRCT, and granulomatous or cystic lesions present in lung tissue, remain to be established. The aim of this study was to compare quantitative data obtained by HRCT and those obtained by histopathological examination of corresponding lung tissue specimens in patients with biopsy-proven PLCH. The results demonstrated that the extent of nodular abnormalities was strongly correlated with the density of florid granulomatous lesions in lung tissue. A strong correlation was also found between the extent of cystic abnormalities and the density of cavitary lesions, but the latter included both still inflammatory cavitary granulomas and cicatricial fibrous cysts. Interestingly, small isolated florid granulomas were found in lung tissue from most patients with a predominant cystic CT scan pattern. Taken together, these results demonstrate that HRCT has to be considered with caution to evaluate the histopathological activity of PLCH. Patients presenting with predominant HRCT cystic abnormalities should benefit from a long-term follow-up. Because these patients are susceptible to developing severe respiratory insufficiency, they should also be considered for treatment as soon as an effective therapy for LCH is available.

Adult↗

Familial extensive idiopathic bilateral pleural fibrosis.

The authors report three sisters with bilateral isolated apical pleural fibrosis of unknown origin, which did not respond to empirical antituberculosis therapy and oral corticosteroids. The disease evolved in an unrelenting fashion producing pleural fibrosis at the lung bases and leading to the death of two sisters and to lung transplantation in the other one. There was no history of other familial disease or consanguinity. The particular features of these cases and the differences from other reports of apparently cryptogenic pleural fibrosis are outlined.

Adult↗