Standard susceptibility testing overlooks potent azithromycin activity and cationic peptide synergy against MDR Stenotrophomonas maltophilia.

OBJECTIVES: The Gram-negative bacillus Stenotrophomonas maltophilia (SM) is an emerging MDR opportunistic pathogen. Recent studies identify a potentially relevant activity of azithromycin against Gram-negative bacteria overlooked in standard bacteriological testing. We investigated azithromycin activity against SM in testing conditions incorporating mammalian tissue culture medium and host defence factors. METHODS: MIC testing, chequerboard assays, time-kill assays and fluorescence microscopy were performed for azithromycin, the cationic peptide antibiotic colistin and the human defence peptide cathelicidin LL-37 alone or in combination in cation-adjusted Mueller-Hinton broth or mammalian tissue culture media. Azithromycin sensitization of SM to host immune clearance was tested in a human neutrophil killing assay and a murine pneumonia model. RESULTS: We observed potent bactericidal activity of azithromycin against SM in mammalian tissue culture medium absent in bacteriological medium. Colistin and LL-37 strongly potentiated azithromycin killing of SM by increasing drug entry. Additionally, azithromycin sensitized SM to neutrophil killing and increased SM clearance in the murine pneumonia model. CONCLUSIONS: Despite lack of activity in standard MIC testing, azithromycin synergizes with cationic peptide antibiotics to kill SM in medium mimicking tissue fluid conditions. Azithromycin, alone or in combination with colistin, merits further exploration in therapy of drug-resistant SM infections.

Primary esophageal meningioma: first literature report.

We have described a primary esophageal meningioma (MG) clinical case diagnosed in a 62-year-old woman; also, we review the literature about extracranial MGs. To our knowledge, this is the first case report of an extracranial MG occurring primarily in the esophagus. These are benign neoplasms reported classically in the central nervous system (CNS). The extrancranial MGs have histopathologic and inmunohistochemical features identical to those observed in CNS MGs; thus, the main diagnostic hurdle is to keep it in the differential for lesions occurring outside the CNS.

Histopathological and immunohistochemical profile in anaplastic gangliogliomas.

BACKGROUND: The anaplastic ganglioglioma (AG) is the high-grade counterpart of ganglioglioma, a rare mixed tumor composed of neuronal/ganglion and glial cells. MATERIALS AND METHODS: We describe the histopathology and immunohistochemistry in 7 cases of AG and correlate them with the clinical and radiological features. RESULTS: Our AG patients correspond to 2.5% of the central nervous system tumor patients evaluated in our institution. The mean age at presentation was 25.7 years, with a male predominance. The most common clinical presentation was generalized tonic-clonic seizures (3/7 cases), in correlation with frequent cortical/subcortical location (6/7 cases). Histopathologically, all our cases showed high-grade features in glial (glial fibrillary acid protein-positive) and neuron-ganglion cells (synaptophysin, PGP-9.5, neurofilament, NSE and CD56-positive), as well as moderate cellularity, frequent mitotic figures and a Ki-67 labeling index >5%. All our patients had poor survival. CONCLUSION: We found that a typical histopathological and immunohistochemical profile is constant and can be useful in early diagnosis of these aggressive neoplasms.

Postmortem diagnosis of very long chain acyl-CoA dehydrogenase (VLCAD) deficiency in a neonate with sudden cardiac death.

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive long chain fatty acid ß-oxidation disorder with a variable clinical spectrum, ranging from an acute neonatal presentation with cardiac and hepatic failure to childhood or adult onset of symptoms with hepatomegaly or rhabdomyolysis provoked by illness or exertion. Neonatal cardiac arrest or sudden unexpected death can be the presenting phenotype in some patients, emphasizing the importance of early clinical suspicion and intervention. We report a patient who had a cardiac arrest and died at one day of age. Following her death, the newborn screen reported biochemical evidence of VLCAD deficiency, which was confirmed with pathologic findings at autopsy and by molecular genetic testing.

Central nervous system Tuberculosis in a man from Cambodia with worsening headaches.

Central nervous system (CNS) tuberculosis should be considered in patients from endemic nations with worsening neurological symptoms. If imaging reveals possible CNS tuberculomas, potentially life-threatening lesions should be excised and analyzed. When disease is less severe, other tissues possibly infected should be biopsied first for diagnosis to avoid neurosurgery.

Concurrence of chromosome 6 chromothripsis and glioblastoma metastasis.

The authors report an unusual case of a widely metastatic glioblastoma. DNA copy number microarray profile of the resected specimen revealed complex rearrangements found throughout chromosome 6, a phenomenon known as chromothripsis. Such chromothripsis pattern was not observed in 50 nonmetastatic glioblastoma specimens analyzed. Analysis of the 1000+ gliomas profiled by The Cancer Genome Atlas (TCGA) data set revealed one case of chromosome 6 chromothripsis resembling the case described here. This TCGA patient died within 6 months of undergoing tumor resection. Implications of these findings are reviewed in the context of the current literature.

Surgical Resection and Histopathological Analysis of a Thrombosed Giant Fusiform MCA Aneurysm After Initial Treatment with a Flow Diversion Construct.

BACKGROUND: We describe the histopathology of an unruptured giant calcified left middle cerebral artery (MCA) fusiform aneurysm initially treated with endovascular flow diversion. The flow diversion construct underwent postoperative in-stent thrombosis, necessitating surgical resection of the aneurysm to eliminate mass effect. METHODS: A 75-year-old woman with a known left MCA aneurysm presented to the emergency department with moderate right hemibody weakness. Owing to the clinical and radiographic progression of the aneurysm, the patient was offered treatment. She was initially offered open surgical management of the lesion but declined it, indicating that she would consider only endovascular treatment. The patient underwent endovascular reconstruction of the aneurysmal segment with an overlapping pipeline construct. Postoperatively, the patient experienced in-stent thrombosis of the pipeline construct. The thrombosed aneurysm exerted a progressive local mass effect, necessitating en bloc surgical resection of the aneurysm and stent construct. The aneurysm was submitted for pathological analysis, which demonstrated chronologically older thrombus outside the flow diversion construct. RESULTS: Postsurgical imaging demonstrated a left MCA territory stroke. The patient gradually gained strength in her right hemibody. The histopathological analysis indicated that the degrees of platelet activation and clot formation in this case were dependent on the aggregate surface area of the thrombus and surface area of the pipeline device used in the reconstruction. CONCLUSIONS: This technical report with histopathological analysis provides useful insight into the mechanism of aneurysmal thrombosis after flow diversion. It also raises new questions regarding the roles of thrombus formation, platelet aggregation, and stent construct surface area in the maintenance of vessel patency.

Cerebral Paragonimiasis Presenting with Sudden Death.

A 58-year-old Korean-born woman with a history of seizures and psychiatric issues was found dead at home. Autopsy was notable for large, calcified nodules that had nearly replaced her right temporal lobe. Histologic examination revealed the presence of Paragonimus eggs. This case demonstrates a rare manifestation of an aberrantly migrated lung fluke that resulted in epilepsy and sudden death years after the initial infection.

Cysticercosis with an Orbital Tropism in Twins.

Two fraternal twin sisters developed cysticercosis localizing to the right lateral orbit over the same period after a presumed common-source exposure in China. This case demonstrates that cysticercosis can be related to travel. Similar temporal and spatial occurrences of these infections suggest a genetic tropism of the infecting organism in these twins.

Primary gliosarcoma of the brain: radiologic and histopathologic features.

Gliosarcoma is a rare central nervous system (CNS) neoplasm with biphasic glial and non-glial malignant components. Here we describe the radiologic and histopathologic features observed in five cases of primary gliosarcoma. The mean age at diagnosis in the studied patients was 54.2 years; these patients were predominantly males (male:female ratio = 4:1). At diagnosis all patients had several clinical deterioration. The most common symptoms of presentation were: headache (5/5 cases), seizures (4/5 cases) and hemiparesis (1/5 cases). All the tumors were large (mean major diameter= 4.12±1.64 cm) at diagnosis as evidenced in computer tomography (CT) scans and magnetic resonance images (MRIs), with preferential involvement of the temporal lobe and frequent associated deviation of the midline structures. Other common characteristics identified on CT scans and MRIs were partial contrast medium uptake with annular pattern (5/5 cases), peripheral edema (5/5 cases), and central calcification (3/5 cases). In additional a peak of dye uptake was observed (4/5 cases) on MRI spectrometry. In the histopathology, the glial component showed malignant astrocytes, with high Ki67 (>60%) and p53 positivity; the sarcomatous components displayed pleomorphic spindle cells similarly with p53 positivity and high Ki67 (75-90%) in all cases. Dedifferentiation to pleomorphic sarcoma (two cases), fibrosarcoma (one case), leiomyosarcoma (one case) and MPNST (one case) were documented. All patients received radiotherapy/chemotherapy and had a median overall survival of ten months. The study of radiologic and histopathologic features in primary gliosarcomas of the brain is a priority to achieve early diagnosis that can be translated to better outcomes. Here we describe the radiologic and histopathologic features observed in a group of gliosarcoma patients with variable histopathologic dedifferentiation.

Glioblastoma metastasis to parotid gland and neck lymph nodes: fine-needle aspiration cytology with histopathologic correlation.

Glioblastoma (GBM) is one of the most highly aggressive neoplasms of the central nervous system. Extra-cranial metastases in GBM are rare. Here we present the case of a 26-year-old man with extra-cranial metastasis of a frontal lobe GBM to the parotid gland, cervical lymph nodes, and bones, with initial diagnosis made by fine needle aspiration cytology (FNAC) of the parotid gland. FNAC is a reliable technique in the study of primary and secondary parotid gland neoplasms, allowing a presumptive diagnosis in difficult cases. We correlate the cytologic, histopathologic, and immunohistochemical findings in this case and discuss previous literature reports.

Examination of sources of diagnostic error leading to cervical cone biopsies with no evidence of dysplasia.

At our institution, 17% of cervical conization specimens are reported as negative for dysplasia or malignancy. To identify sources of error, we reviewed 53 negative conization specimens and their prior and follow-up cytology, biopsy, and endocervical curettage specimens. Examination of deeper-level sections and p16 immunostaining were performed on all conization specimens and selected biopsy specimens. Dysplasia was detected in 26% (14/53) of conization specimens. Twenty-eight percent (15/53) of cones were truly negative, and the presurgical material had been overcalled as high-grade squamous intraepithelial lesions (HSIL). Forty-five percent (24/53) of cones were truly negative and HSIL was confirmed in the presurgical material. Of these, 11% (6/53) showed subsequent evidence of residual dysplasia and 26% (14/53) were negative on further follow-up. Deeper-level sections, p16 immunostains, and consensus review may help identify squamous dysplasia in conization specimens and may prevent the overdiagnosis of HSIL on cervical biopsies.