Histoplasmosis of the External Auditory Canal.

This report describes the diagnosis and treatment of a patient with a rare fungal infection of the external ear, as well as a review of the literature. A 76-year-old Caucasian gentleman from rural southern United States with diabetes and hypertension was referred to our clinic for intractable left otalgia, otorrhea, headaches, and an exophytic lesion in the left external ear since five months. There was no pertinent travel history. Biopsy by an outside otolaryngologist was inconclusive. Repeat biopsy under anesthesia revealed morphological characteristics consistent with histoplasmosis. Intravenous amphotericin B and later oral antifungal agent voriconazole led to improvement in symptoms. The clinical presentation resembled a malignancy. A high index of clinical suspicion, histologic confirmation with deep tissue biopsy, and culture are essential for diagnostic confirmation followed by treatment with systemic antifungals. A multidisciplinary team approach is necessary to manage this rare condition.

Histiocytic Disorder Mimicking a Brain Tumor: A Report of 2 Rare Cases.

BACKGROUND Histiocytic disorders, a group of disorders with heterogeneous pathogenesis, morphology, and clinical presentation, include Rosai-Dorfman disease, Langerhans cell histiocytosis, and Erdheim-Chester disease. They can mimic primary or metastatic tumors, both clinically and radiologically, when involving the brain. Therefore, it is crucial to present and discuss cases of histiocytic disorder involving the central nervous system (CNS) to provide new information on disease presentation and diagnosis more. In this paper, we present 2 cases of histiocytic lesions involving the brain and mimicking primary brain tumors. CASE REPORT Case 1: A 65-year-old man presented with increasing memory loss, confusion, and depression. CT scans showed an isolated 2.9×2.0×0.6 cm intracranial hypothalamic lesion. Case 2: A 61-year-old woman presented with dizziness and confusion for 3 weeks and headaches for 1 day. MRI showed a single 5.0×4.0×3.3 cm extra-axial, dural-based, avidly enhancing, well-defined lesion along the left parietal convexity causing mass effect upon the underlying brain parenchyma, left atrial effacement, and minimal vasogenic edema. CONCLUSIONS Histiocytic disorders are relatively rare in the CNS compared with other locations and mimic more common entities in the brain, such as glioma or metastatic tumors. Despite its rarity, one should remain aware of the condition and consider it in the differential diagnosis. This article provides a brief review and adds pivotal data to the literature.

Histopathological evidence that diethylene glycol produces kidney and nervous system damage in rats.

Diethylene glycol (DEG) is an organic compound that has been found as an adulterant in consumer products as a counterfeit glycerin. Diethylene glycol is metabolized to two primary metabolites: 2-hydroxyethoxyacetic acid (2-HEAA) and diglycolic acid (DGA), the latter shown to accumulate in the kidney and cause dose-dependent cell necrosis. DEG poisonings are characterized predominately by acute kidney injury (AKI) but have also produced delayed neurological sequelae such as sensorimotor neuropathy. To better understand these effects, Wistar-Han rats were orally administered a water control or doses of 4 g/kg-6 g/kg DEG every 12 or 24 h for 7 days, with kidney, brain, and spinal cord tissue collected for histopathological analysis. This dosing paradigm resulted in approximately 25 % of the DEG-treated animals developing AKI and also neurotoxicity (sensorimotor dysfunction and elevated cerebrospinal fluid (CSF) protein). Kidney pathology included a severe, diffuse acute kidney tubular necrosis predominantly affecting proximal convoluted tubules. Scattered birefringent crystals consistent with calcium oxalate monohydrate were also found in the proximal tubule of animals with AKI. Demyelination in the dorsal and lateral white matter regions of the cervical, thoracic, and lumbar areas of the spinal cord of a DEG-treated animal with AKI was documented, establishing the neuropathology in DEG-treated animals that developed neurotoxicity. There were significant changes in amino acid concentrations in the CSF that may reflect the neurotoxicity of DEG, specifically glutamate and glutamine, but with no ammonia change. These studies characterized the pathologic aspects of the neurotoxicity in a DEG repeat-dose model.

(-)-Oleocanthal Nutraceuticals for Alzheimer's Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model.

Alzheimer's disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aß-amyloid (Aß) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(-)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of ß-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (ScEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aß plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.

Significance of H3K27me3 loss in the diagnosis of malignant peripheral nerve sheath tumors.

The diagnosis of malignant peripheral nerve sheath tumors can be challenging and other spindle cell sarcomas commonly enter in the differential diagnosis. Loss of trimethylation at lysine 27 of histone-H3 (H3K27me3) by immunohistochemistry was recently described in malignant peripheral nerve sheath tumors. However, its specificity remains controversial. We therefore studied 82 synovial sarcomas, 39 malignant peripheral nerve sheath tumors, and 10 fibrosarcomatous dermatofibrosarcoma protuberans for H3K27me3 loss by immunohistochemistry. The diagnoses were based on morphology, immunophenotype, and genetics based on WHO classification. H3K27me3 immunohistochemistry was scored by two pathologists based on fraction of cells with nuclear staining (score 0 to 3+). Loss of H3K27me3 (score 0) was seen in 44% of malignant peripheral nerve sheath tumors and 9% of synovial sarcomas yielding positive and negative predictive values of 71% and 77%, respectively. Loss of H3K27me3 was seen in 10% of fibrosarcomatous dermatofibrosarcoma protuberans, yielding positive and negative predictive values of 94 and 29% in the differential diagnosis of malignant peripheral nerve sheath tumor versus fibrosarcomatous dermatofibrosarcoma protuberans. Partial loss (score 1-2) was common in all three tumor types. Among malignant peripheral nerve sheath tumors, there was no significant association between H3K27me3 loss and gender, tumor site, or size, and progression-free or overall survival. Patients with tumors with H3K27me3 loss were younger than those with tumors with retained H3K27me3 expression (P=0.011). H3K27me3 expression was lost in 50 and 31% of sporadic and Neurofibromatosis-associated malignant peripheral nerve sheath tumors, respectively (P=0.25).Complete H3K27me3 loss is a moderately sensitive and relatively specific marker for the diagnosis of malignant peripheral nerve sheath tumor when the differential diagnosis includes synovial sarcoma and fibrosarcomatous dermatofibrosarcoma protuberans. Partial loss has limited diagnostic utility. H3K27me3 status does not show significant association with clinical outcome in malignant peripheral nerve sheath tumors.