A rare case of bilateral multifocal nodular oncocytic hyperplasia of the parotid gland

Multifocal nodular oncocytic hyperplasia (MNOH) is an extremely rare pathological entity occurring in the parotid gland, even more rarely described in the submandibular gland. We report a case of bilateral parotid MNOH in a 71-year-old woman and perform a search of the existing literature that is compiled in a table. Fifty-nine cases are described in 34 publications. Half of the published cases presented as bilateral lesions, either synchronous or metachronous. Other lesions of the oncocyte-spectrum such as oncocytomas are frequently described on the ground of oncocytic hyperplasia. MNOH rarely occurs before the age of 40 years and mean age of the described cases is 62 years. The condition is considered as benign by all authors, but surgery was performed in nearly all cases, most often due to a lack of diagnostic certainty. Nevertheless, the radiologic presentation of MNOH is often highly suggestive. Based on the existing literature, recommendations for the management of MNOH are formulated

Delta-like 4/Notch pathway is differentially regulated in benign and malignant thyroi tissues

BACKGROUND: Angiogenesis plays an essential role in embryonic and tumoral developments. Vascular endothelial growth factor (VEGF), one of the best known proangiogenic factors, is increased in thyroid cancers, especially in papillary carcinomas (PC). However, other regulating mechanisms refine VEGF-induced cellular changes, such as the Notch family of ligands and receptors. Their role has not yet been investigated in the thyroid. The purpose of our study was to analyze the expression of Notch1, Notch4, and Delta-like 4 (DLL4) in benign and malignant thyroid lesions. METHODS: The expression of Notch1, Notch4, and DLL4 was analyzed by immunohistochemistry, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), and Western-blot in normal thyroids (NTs), hyperplasic thyroids from patients with Graves' disease (GD), microcarcinomas, PC, and follicular carcinomas. RESULTS: The immunohistochemical expression of Notch1, Notch4, and DLL4 was highly variable in thyrocytes from NTs and GD. In contrast, the staining in tumors was homogeneous and often intense. The increased expression of Notch1, Notch4, and DLL4 in carcinomas compared with the neighboring normal tissue was confirmed by qRT-PCR and Western-blot. However, only capillary endothelial cells from GD samples were positive for DLL4, the expression being restricted to large vessels in carcinomas and NTs. CONCLUSIONS: The detection of Notch1, Notch4, and DLL4 in thyrocytes and their regulation in various pathologies suggest that this pathway may play a role in thyroid carcinogenesis and angiogenesis

The deep belly of the temporalis muscle: an anatomical, histological and MRI study.

In order to achieve a better functional and clinical knowledge of a masticatory muscle called the sphenomandibularis that is suspected to be responsible for headaches by compressing the maxillary nerve, bilateral dissections of the infratemporal fossa were performed on ten human cadavers and completed by histological and radiological studies of the same areas. Both macroscopic and microscopic observations obviously showed that the so-called sphenomandibularis muscle corresponds to the deep portion of the temporalis muscle, since there is no epimysial septum between these two structures, which previously have been described as being completely independent from each other. In spite of the close topographic relationship between the deep belly of the temporalis and the lateral pterygoid muscle, as well as their similar innervation pattern, the sphenomandibularis in fact has to be considered functionally as an original but non-isolated positional fascicle of the temporalis muscle itself. Our observations, correlated with MR images, suggest indeed that the deep belly of the temporalis muscle is of functional importance in the masticatory movements, but is not involved by its neurovascular vicinity in the genesis of specific headaches. Its surgical release, however, should be discussed in the case of a temporal myoplasty

Pulmonary Limited MPO-ANCA Microscopic Polyangiitis and Idiopathic Lung Fibrosis in a Patient with a Diagnosis of IgA Nephropathy

We present a case of a male patient with chronic renal insufficiency, due to crescentic glomerulonephritis with IgA deposits, who successively developed (idiopathic) thrombocytopenic purpura (ITP) and MPO-ANCA microscopic polyangiitis (MPA) with pulmonary fibrosis. The patient presented with cough, weight loss, and dyspnea on exertion. CT imaging and pulmonary function tests were compatible with interstitial pneumonitis with pulmonary fibrosis. Laboratory results showed high MPO-ANCA titers; the urinary sediment was bland. The patient was treated successfully with cyclophosphamide and methyl-prednisolone. This unique case illustrates the diagnostic and therapeutic challenges of an unusual presentation of microscopic polyangiitis presenting first as isolated kidney disease with recurrence in the form of pneumonitis without renal involvement, in association with renal IgA deposits and ITP as coexisting autoimmune conditions

miR-146a inhibits cell growth, cell migration and induces apoptosis in non-small cell lung cancer cells.

Aberrant expression of microRNA-146a (miR-146a) has been reported to be involved in the development and progression of various types of cancers. However, its role in non-small cell lung cancer (NSCLC) has not been elucidated. The aim of this study was to investigate the contribution of miR-146a to various aspects of the malignant phenotype of human NSCLCs. In functional experiments, miR-146a suppressed cell growth, induced cellular apoptosis and inhibited EGFR downstream signaling in five NSCLC cell lines (H358, H1650, H1975, HCC827 and H292). miR-146a also inhibited the migratory capacity of these NSCLC cells. On the other hand, miR-146a enhanced the inhibition of cell proliferation by drugs targeting EGFR, including both TKIs (gefitinib, erlotinib, and afatinib) and a monoclonal antibody (cetuximab). These effects were independent of the EGFR mutation status (wild type, sensitizing mutation or resistance mutation), but were less potent compared to the effects of siRNA targeting of EGFR. Our results suggest that these effects of miR-146a are due to its targeting of EGFR and NF-kappaB signaling. We also found, in clinical formalin fixed paraffin embedded (FFPE) lung cancer samples, that low expression of miR-146a was correlated with advanced clinical TNM stages and distant metastasis in NSCLC (P<0.05). The patients with high miR-146a expression in their tumors showed longer progression-free survival (25.6 weeks in miR-146a high patients vs. 4.8 weeks in miR-146a low patients, P<0.05). miR-146a is therefore a strong candidate prognostic biomarker in NSCLC. Thus inducing miR-146a might be a therapeutic strategy for NSCLC

Case Report Pulmonary Limited MPO-ANCA Microscopic Polyangiitis and Idiopathic Lung Fibrosis in a Patient with a Diagnosis of IgA Nephropathy

We present a case of a male patient with chronic renal insufficiency, due to crescentic glomerulonephritis with IgA deposits, who successively developed (idiopathic) thrombocytopenic purpura (ITP) and MPO-ANCA microscopic polyangiitis (MPA) with pulmonary fibrosis. The patient presented with cough, weight loss, and dyspnea on exertion. CT imaging and pulmonary function tests were compatible with interstitial pneumonitis with pulmonary fibrosis. Laboratory results showed high MPO-ANCA titers; the urinary sediment was bland. The patient was treated successfully with cyclophosphamide and methyl-prednisolone. This unique case illustrates the diagnostic and therapeutic challenges of an unusual presentation of microscopic polyangiitis presenting first as isolated kidney disease with recurrence in the form of pneumonitis without renal involvement, in association with renal IgA deposits and ITP as coexisting autoimmune conditions

Identification of a novel HER3 activating mutation homologous to EGFR-L858R in lung cancer.

peer reviewedSomatic mutations found within the tyrosine kinase domain (TKD) of the human epidermal growth factor (HER) family of receptors have been implicated in the development and progression of non-small cell lung cancer (NSCLC). However, no conclusive reports have described pathogenic mutations in kinase-impaired HER3. Here, we report a case of an advanced chemotherapy-resistant NSCLC, harboring a novel HER3V855A somatic mutation homologous to the EGFRL858Ractivating mutation. Co-expression of HER3V855A and wild-type HER2 enhances ligand-induced transformation of murine and human cell lines, while HER-targeted inhibitors potently suppress mutant HER3 activity. Consistent with these observations, in silico computational modeling predicts that mutant V855A alters the kinase domain and c-terminal end of the HER3 protein. Taken together, these findings provide a basis for the clinical exploration of targeted therapies in HER3 mutant NSCLC and by extrapolation, in other cancers that more frequently carry somatic HER3 mutations

Polygonal deformation of the dural sac in lumbar epidural lipomatosis: anatomic explanation by the presence of meningovertebral ligaments

BACKGROUND AND PURPOSE: In patients with epidural lipomatosis, axial lumbar spine CT and MR images occasionally reveal a geometric, polygonal or stellar, shape of the dural sac. The purpose of this study was to define the anatomic structures responsible for this radiologic appearance. We hypothesized that meningovertebral ligaments could anchor the dura mater to the osteofibrous walls of the spinal canal and account for the geometric deformation of the dural sac. METHODS: The epidural spaces were examined in 15 adult cadaveric and seven aborted fetal lumbar spines. For macroscopic studies, 70 adult vertebral segments were separated and dissected by removing the extradural fat. For microscopic examination, axial histologic sections were obtained from 35 fetal and five adult undissected vertebral segments. RESULTS: Meningovertebral ligaments were observed in the median, paramedian, and lateral aspects of the anterior and posterior epidural spaces of both adult and fetal lumbar spines. These ligaments anchor the outer surface of the dura mater to the osteofibrous walls of the lumbar canal. They may form an irregular longitudinal septum partitioning the epidural space. Histologic examination demonstrated the fibroelastic composition of these ligaments and suggested their possible perivascular morphogenetic origin. CONCLUSION: The morphologic and topographic features of the meningovertebral ligaments explain the polygonal, stellar, or Y-shaped deformation of the dural sac observed on axial CT and MR images in patients with lumbar epidural lipomatosis

Scleroderma renal crisis triggered by ibuprofen: Insights on complement-directed therapy

Scleroderma renal crisis is a severe complication of systemic sclerosis with a poor prognosis. Therefore, identifying precipitating factors is essential. Among known risk factors, only few are reversible. On the contrary, anti-C5 therapy appears effective, at least in some cases. We describe a 59-year-old man with diffuse cutaneous systemic sclerosis who developed life-threatening scleroderma renal crisis following ibuprofen administration. Despite aggressive management, he did not improve. Renal biopsy have displayed features of thrombotic microangiopathy but no complement deposition. We then discuss the pathomechanism of scleroderma renal crisis that could drive eculizumab treatment since some renal biopsies exhibit complement deposits and others do not.info:eu-repo/semantics/publishe