Age-related macular degeneration (AMD) and glaucoma are degenerative conditions of the retina and a significant cause of irreversible blindness in developed countries. Alzheimer’s disease (AD), the most common dementia of the elderly, is often associated with AMD and glaucoma. The cardinal features of AD include extracellular accumulation of amyloid β (Aβ) and intracellular deposits of hyper-phosphorylated tau (p-tau). Neuroinflammation and brain iron dyshomeostasis accompany Aβ and p-tau deposits and, together, lead to progressive neuronal death and dementia. The accumulation of Aβ and iron in drusen, the hallmark of AMD, and Aβ and p-tau in retinal ganglion cells (RGC), the main retinal cell type implicated in glaucoma, and accompanying inflammation suggest overlapping pathology. Visual abnormalities are prominent in AD and are believed to develop before cognitive decline. Some are caused by degeneration of the visual cortex, while others are due to RGC loss or AMD-associated retinal degeneration. Here, we review recent information on Aβ, p-tau, chronic inflammation, and iron dyshomeostasis as common pathogenic mechanisms linking the three degenerative conditions, and iron chelation as a common therapeutic option for these disorders. Additionally discussed is the role of prion protein, infamous for prion disorders, in Aβ-mediated toxicity and, paradoxically, in neuroprotection.
Primary breast sarcomas are uncommon and primary mammary malignant peripheral nerve sheet tumors (MPNST) are exceptionally rare. MPNSTs are malignant variants of peripheral nerve sheath tumors. These neoplasms are often associated with neurofibromatosis type I (NF-I) but can also occur sporadically. They tend to occur in the deeper soft tissues, trunk, and extremities.A 60-year-old Asian female was referred to our surgical clinic for evaluation of a left breast mass and an abnormal mammogram. The patient noticed the mass in the left breast three months earlier and was referred for mammography by her primary physician. Mammography reported partially defined masses in the superior aspect of the left breast, and ultrasound showed a solid mass measuring 5.2 X 3 cm. The mass was 11 cm on clinical exam. Subsequent core biopsy of the left breast lesion showed high-grade malignant neoplasm. Workup showed no evidence of metastatic disease, and the patient underwent modified radical mastectomy. The neoplastic cells were positive for CD99, S-100, SOX-10, neuron specific enolase, p53, vimentin, focally positive for neurofilament, D2-40, p63, and negative for epithelial, melanoma and other sarcoma markers. The tumor was triple negative estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), with Ki-67 at 61%. A diagnosis of primary high grade malignant peripheral nerve sheath tumor of the breast was rendered. The patient does not have a history of NF-1.An accurate diagnosis of this rare entity is necessary because it plays a crucial role in the therapeutic options and prognosis. In our case the patient underwent modified radical mastectomy. The purpose of presenting this unique case is to provide awareness of the existence of this entity among pathologists and clinicians for better patient care.
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