Deirdre Amaro

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.

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.

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 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.

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.

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.

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.

Scedosporium Prolificans Sclerokeratitis Following Pterygium Excision with Mitomycin C: A Case Requiring Enucleation

Scedosporium prolificans is a rare cause of fungal sclerokeratitis following pterygium excision with beta-irradiation or Mitomycin C (MMC). We present a case of a male horticulturist with history of bilateral pterygium excision with MMC who presented for evaluation of refractory sclerokeratitis and was found to have S. prolificans sclerokeratitis. Despite aggressive topical and combination intravenous antifungal therapy, enucleation of the affected eye was required due to evidence of posterior scleral extension on imaging. S. prolificans should be considered in cases of refractory sclerokeratitis. Infections due to S. prolificans often do not respond to antifungal therapies alone and often require swift surgical management.

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.