[Secondary pulmonary alveolar proteinosis in a transplant patient]. / Protéinose pulmonaire secondaire chez un patient greffé.

INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by alveolar accumulation of lipoproteinaceous material, caused by a macrophagic clearance disorder. We present a case of PAP in a patient taking the immunosuppressant drug mycophenolate mofetil (MMF) in the context of invasive pulmonary aspergillosis, of which we discuss the pathophysiology and treatment as reported in the literature. CASE REPORT: A 43-year-old man with cardiomyopathy received a heart transplant and was treated by MMF, tacrolimus and corticosteroids. Three months after the transplant, he presented with acute oxygen-dependent respiratory failure. The diagnosis of PAP seemed likely on the CT scan and was confirmed by bronchoalveolar lavage, as was the diagnostic of invasive pulmonary aspergillosis (IPA). However, GM-CSF autoantibodies were not found. As there existed a suspicion of MMF imputability, the treatment was discontinued and an antifungal treatment was started. The patient was reassessed one month after discontinuation of MMF and found to have clinically and radiologically improved. Four other cases of MMF-induced PAP have been reported in the literature. CONCLUSIONS: MMF and IPA could be predisposing cofactors for the occurrence of secondary PAP.

[Cyclosporin-induced toxic neuromyopathy]. / Neuromyopathie toxique induite par la ciclosporine.

INTRODUCTION: Cyclosporine is an immunosuppressive treatment whose side effects limit its usefulness. Among neurological side effects, neuropathies or myopathies have been reported, specially inpatients given combinations of cyclosporine with co-enzyme A reductase inhibitors. CASE REPORT: We report here the case of a 67-year-old woman who developed few months after a kidney graft sensorimotor disorders which progressed rapidly. Since all etiologies of such a disorder were ruled out, the hypothesis of toxicity exclusively induced by cyclosporine was suggested and confirmed by the improvement observed after its withdrawal. CONCLUSION: This observation highlights the fact that cyclosporine may induce neuromyopathies even when given alone at the therapeutic dosage.

[Role of high-dose chemotherapy with hemopoietic stem-cell support in the treatment of adult patients with high-grade glioma]. / Place de la chimiothérapie intensive avec autogreffe de cellules souches hématopoïétiques dans le traitement des tumeurs gliales de haut grade chez l'adulte.

Despite surgery, post-operative irradiation and adjuvant conventional chemotherapy, prognosis of high-grade gliomas remains poor. Carmustine (BCNU) has been shown to have limited activity at conventional dosage but is still the standard chemotherapy. Activity of chemotherapy is limited by the blood-brain barrier impermeability and high levels of expression of multidrug resistance proteins on tumor and/or endothelial cells. Despite high response rates, development of intra-arterial chemotherapy remains limited because of frequent acute brain toxicity related to drug administration. High-dose intravenous chemotherapy rescued by autologous hemopoietic stem cell transplantation is an alternative that might increase drug delivery through the blood-brain barrier and tumor control. Several phase I-II trials using high-dose BCNU were published. The maximum tolerated dose seems to be 800 mg/m2 and interstitial pneumonitis and hepatitis are dose-limiting toxicities. Few phase I-II trials of high-dose therapy were published using drug combinations. High response rates in patients with progressive tumor were observed and in adjuvant setting, encouraging results in terms of median survival time and long survivors were published. No phase III trial was reported to date. Future investigations should include randomized trials comparing high-dose and conventional-dose chemotherapy and development of new high-dose regimens that incorporate new drugs such as temozolomide.

[Amyotrophic lateral sclerosis manifesting as cognitive disorders. Value of brain perfusion scintigraphic tomography in intensive care]. / Sclérose latérale amyotrophique révélée par des troubles cognitifs. Intérêt de la tomoscintigraphie de perfusion cérébrale en réanimation.

BACKGROUND: Cognitive disorders have been described in amyotrophic lateral sclerosis, but usually after the diagnosis has ben established. CASE REPORT: A 57-year-old man was intubated for acute respiratory distress subsequent to pneumonia and diaphragm palsy. He had a 2-year history of drug-resistant depression and deterioration of cognitive functions. A pyramidal syndrome associated with biopsy-proven chronic neurogenic atrophy led to the diagnosis of amyotrophic lateral sclerosis. The electromyogram did not contribute to diagnosis. Brain MRI only evidenced moderate bilateral frontal-temporal atrophy. Brain SPECT demonstrated major perfusion defects in the frontal lobes. DISCUSSION: This patient had amyotrophic lateral sclerosis and frontal-temporal dementia with an unusually late onset clinical presentation: cognitive disorder was the inaugural sign. Brain SPECT and muscle biopsy enabled us to identify the cortical and peripheral motor neurone involvement in this uncooperative intensive care patient totally dependent on mechanical ventilation.

[An unusual variant of urothelial carcinoma: the "nested variant of urothelial carcinoma." Report of two cases]. / Une variante particulière de carcinome urothélial: le "nested variant of urothelial carcinoma". A propos de deux cas.

We report two cases of a poorly known variant of transitional cell carcinoma, the "nested variant of urothelial carcinoma". This tumor is composed of small islands or nests of transitional cells, presenting little atypia and mimicking von Brünn's nests. This low grade tumoral variant seems to behave as a high grade tumor of the same stage. Deep biopsies are necessary to display tumoral invasion, which allows the diagnosis. Importance of the knowledge of this entity is highlighted in order to avoid misdiagnoses that could delay appropriate therapy.

Pathology of the central nervous system in Chester-Erdheim disease: report of three cases.

Chester-Erdheim disease is a rare form of non-Langerhans cell histiocytosis consisting of disseminated xanthogranulomatous infiltration and fibrosis that primarily involves the bones, visceral organs and systemic fatty spaces. Involvement of the central nervous system is variable, and neuropathological features have seldom been documented. We report the neuropathological findings in 3 autopsy cases. One patient had radiological and pathological bone changes characteristic of Chester-Erdheim disease. Neuropathology revealed multiple characteristic xanthogranulomas disseminated in the cerebral hemispheres, hypothalamus, cerebellum, and brainstem. The second patient presented first with cutaneous lesions characteristic of Langerhans cell histiocytosis. She subsequently developed bone abnormalities suggestive of Chester-Erdheim disease, which was confirmed by autopsy, raising the possibility of a common spectrum of histiocytosis including both diseases. Gross examination of the brain was normal, however, microscopy showed infiltration of the brain by characteristic non-Langerhans cell xanthogranulomas. The third patient presented with systemic features characteristic of Chester-Erdheim disease. Neurological signs included gait disturbance, seizures and confusion. Examination of the brain did not show any histiocytic infiltration, but did show changes suggestive of Hallervorden-Spatz syndrome. Association of Chester-Erdheim disease and Hallervorden-Spatz syndrome has not been previously reported. The relationship between both conditions is unclear.