Crizotinib-induced osteitis mimicking bone metastasis in a stage IV ALK-rearranged NSCLC patient: a case report.

BACKGROUND: Targeted therapies are a standard of care for first-line treatment of Anaplastic lymphoma kinase (ALK)-rearranged non small cell lung cancer (NSCLC). Giving the rapid pace of drug discovery and development in this area, reporting of adverse effects of ALK inhibitors is crucial. Here, we report a case of osteitis induced by an ALK inhibitor mimicking bone metastasis, a previously undescribed side effect of crizotinib. CASE PRESENTATION: A 31-year-old woman with stage IV ALK-rearranged NSCLC presented with back pain after 3 months of crizotinib treatment. Diagnostic work-up showed osteitis on the 4th and 5th thoracic vertebrae, anterior soft tissue infiltration and epiduritis, without any sign of infection. Spinal cord decompression, histological removal and osteosynthesis were performed. Histologic examination showed necrosis with abundant peripheral neutrophils, no microorganism nor malignant cell. Symptoms and Computarized Tomography-abnormalities rapidly diseappeared after crizotinib withdrawal and did not recur after ceritinib onset. CONCLUSIONS: This is the first report of crizotinib-induced osteitis. Crizotinib differs from other ALK inhibitors as it targets other kinases as well, which may have been responsible for the osteitis. Crizotinib can induce rapidly extensive osteitis, which can mimic tumor progression.

[Angiomatoid fibrous histiocytoma of the radial pulse groove]. / Histiocytome fibreux angiomatoïde de la gouttière du pouls radial.

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a slowly progressing rare soft-tissue tumour of moderate malignant potential. It is most commonly seen in children and young adults. Clinically, the lesion is easily confused with a haematoma or soft-tissue haemangioma, and the radiological aspects are not specific. PATIENTS AND METHODS: A 16-year-old male patient presented with a nodular lesion situated very close to the right radial artery, vein and nerve and which had been developing for several years. Surgical resection was carried out with sparing of vasculonervous and functional structures. Histological examination revealed a tumour of plurinodular architecture, surrounded by a fibrous pseudocapsule consisting of histiocytoid or fusiform cells in short bundles associated with a mononuclear inflammatory reaction of nodular architecture. The tumour cells expressed the following immunomarkers: desmin, smooth muscle actin, CD99, and epithelial membrane antigen. Fusion transcript EWSR1-ATF1 was found. DISCUSSION: In this case, as occurs in the literature, a diagnosis of AFH was not made on clinical examination or imaging. The enlarged excision normally recommended was greatly restricted in our patient due to the complex localization of the lesion, which was in contact with major anatomical structures. The diagnosis was based on histological examination of the surgical excision and identification of the fusion gene. Long-term follow-up is required to detect local recurrence or metastasis. Management is decided in multidisciplinary meetings.

A deadly spread: cellular mechanisms of α-synuclein transfer.

Classically, Parkinson's disease (PD) is linked to dopamine neuron death in the substantia nigra pars compacta. Intracytoplasmic protein inclusions named Lewy bodies, and corresponding Lewy neurites found in neuronal processes, are also key features of the degenerative process in the substantia nigra. The molecular mechanisms by which substantia nigra dopamine neurons die and whether the Lewy pathology is directly involved in the cell death pathway are open questions. More recently, it has become apparent that Lewy pathology gradually involves greater parts of the PD brain and is widespread in late stages. In this review, we first discuss the role of misfolded α-synuclein protein, which is the main constituent of Lewy bodies, in the pathogenesis of PD. We then describe recent evidence that α-synuclein might transfer between cells in PD brains. We discuss in detail the possible molecular mechanisms underlying the proposed propagation and the likely consequences for cells that take up α-synuclein. Finally, we focus on aspects of the pathogenic process that could be targeted with new pharmaceutical therapies or used to develop biomarkers for early PD detection.

A high-temperature Raman scattering study of the phase transitions in GaPO(4) and in the AlPO(4)-GaPO(4) system.

Al(1-x)Ga(x)PO(4) solid solutions (x = 0.2, 0.3, 0.38, 0.7) and the pure AlPO(4) (x = 0) and GaPO(4) (x = 1) end members with the α-quartz-type structure were studied by Raman scattering. An investigation as a function of composition enabled the various modes to be assigned, in particular coupled and decoupled vibrations. The tetrahedral tilting modes, which have been linked to high-temperature phase transitions to ß-quartz-type forms, were found to be decoupled. In addition, it is shown that Raman spectroscopy is a powerful technique for determining the gallium content of these solid solutions. Single crystals with x = 0.2, 0.38, and 1.0 (GaPO(4)) were investigated at high temperature. The composition Al(0.8)Ga(0.2)PO(4) was found to exhibit sequential transitions upon heating to the ß-quartz and ß-cristobalite forms at close to 993 K and 1073 K, respectively. Direct α-quartz-ß-cristobalite transitions were observed for the two other compositions at close to 1083 K and 1253 K, respectively, upon heating. The spectra of the ß-quartz and ß-cristobalite forms indicate the presence of significant disorder. Back transformation to the α-quartz-type form occurred readily with a hysteresis of less than 100 K for the composition x = 0.38 and for pure GaPO(4). Rapid cooling was necessary to obtain the metastable α-cristobalite form. In contrast, for Al(0.80)Ga(0.20)PO(4), the α-cristobalite form was obtained even upon slow cooling.