Arachidonate 5-lipoxygenase (ALOX5) expression and activity has been implicated in tumor pathogenesis, yet its role in papillary thyroid carcinoma (PTC) has not been characterized. ALOX5 protein and mRNA were upregulated in PTC compared to matched, normal thyroid tissue, and ALOX5 expression correlated with invasive tumor histopathology. Evidence suggests that PTC invasion is mediated through the induction of matrix metalloproteinases (MMPs) that can degrade and remodel the extracellular matrix (ECM). A correlation between MMP-9 and ALOX5 protein expression was established by immunohistochemical analysis of PTC and normal thyroid tissues using a tissue array. Transfection of ALOX5 into a PTC cell line (BCPAP) increased MMP-9 secretion and cell invasion across an ECM barrier. The ALOX5 product, 5(S)-hydroxyeicosatetraenoic acid also increased MMP-9 protein expression by BCPAP in a dose-dependent manner. Inhibitors of MMP-9 and ALOX5 reversed ALOX5-enhanced invasion. Here we describe a new role for ALOX5 as a mediator of invasion via MMP-9 induction; this ALOX5/MMP9 pathway represents a new avenue in the search for functional biomarkers and/or potential therapeutic targets for aggressive PTC.
Aims: To develop a minimally invasive, maximally effective method to biopsy anterior segment tumours. Methods: A 25 gauge aspiration cutter (vitrector) was used to biopsy anterior segment tumours. The probe was introduced under sodium hyaluronate 1% and through a 1 mm incision. Aspiration (600 mm Hg) cutting (300 cpm) was performed to obtain specimens for cytology and histopathology. Results: Diagnostic material was obtained in nine of 10 (90%) cases. Diagnoses included iris naevus, iris stroma, malignant melanoma, melanocytoma, epithelial inclusion cyst, and sarcoid granuloma. All corneal wounds were self sealing. One patient developed a transient postoperative increase in intraocular pressure. Within the follow up of this study, no patients suffered intraocular haemorrhage, infection, cataract or vision loss. Conclusion: The Finger iridectomy technique was a minimally invasive and very effective biopsy technique. Aspiration cutting yielded relatively large pieces of tissue (and cells) used for cytopathological and histopathological evaluation. Small incision surgery allowed for rapid rehabilitation and no significant complications.
Sarcoidosis is a complex disorder that often times involves the head and neck. Despite the presence of strong clinical evidence, tissue diagnosis and imaging is needed for confirmation of the disease. Although typically managed medically, when found in the sinonasal tract or intracranially, it may necessitate the intervention of a rhinologist-skull base surgeon. This article seeks to provide a comprehensive review of head and neck sarcoidosis, as this fascinating disorder often poses a diagnostic and therapeutic challenge. A brief discussion of surgical treatment for pituitary lesions is also provided. Articles from 1997 to 2013 were selected and reviewed by three researchers utilizing the most recent literature regarding sarcoidosis in the head and neck. PubMed searches were conducted using search terms such as "sarcoidosis", "neurosarcoid", and "extra-pulmonary sarcoid", among many others. A large collection of articles was generated and reviewed by the team of authors, and appropriate information was extracted to compose a thorough and expansive review of the subject. 10-15 % of patients with sarcoidosis have head and neck manifestations. Sinonasal and pituitary sarcoidosis presents a diagnostic challenge owing to its non-specific symptoms. Although systemic steroid therapy is often the first time treatment, endoscopic surgery is commonly used to treat advanced pituitary sarcoidosis refractory to medical management. As tissue diagnosis and imaging is key, a multi-disciplinary team approach is advantageous. Our study collates the available literature on head and neck sarcoidosis to provide a comprehensive review of the subject. This provides helpful information to guide all practitioners involved in the care of these challenging patients, namely pathologists, radiologists, otolaryngologists, and skull base surgeons, in the workup and management of head and neck sarcoidosis.
Purpose: Cutaneous melanoma metastatic to the vitreous is very rare. This study investigated the clinical findings, treatment, and outcome of patients with metastatic cutaneous melanoma to the vitreous. Most patients received checkpoint inhibition for the treatment of systemic disease, and the significance of this was explored.Design: Multicenter, retrospective cohort study.Participants: Fourteen eyes of 11 patients with metastatic cutaneous melanoma to the vitreous. Methods: Clinical records, including fundus photography and ultrasound results, were reviewed retrospectively, and relevant data were recorded for each patient eye.Main Outcome Measures: Clinical features at presentation, ophthalmic and systemic treatments, and outcomes.Results: The median age at presentation of ophthalmic disease was 66 years (range, 23e88 years), and the median follow-up from diagnosis of ophthalmic disease was 23 months. Ten of 11 patients were treated with immune checkpoint inhibition at some point in the treatment course. The median time from starting immunotherapy to ocular symptoms was 17 months (range, 4.5e38 months). Half of eyes demonstrated amelanotic vitreous debris. Five eyes demonstrated elevated intraocular pressure, and 4 eyes demonstrated a retinal detachment. Six patients showed metastatic disease in the central nervous system. Ophthalmic treatment included external beam radiation (30e40 Gy) in 6 eyes, intravitreous melphalan (10e20 mg) in 4 eyes, enucleation
Schwannoma is a proliferation of neoplastic Schwann cells. Whereas schwannomas of the head and neck region are common, intraocular tissues are rarely affected. Uveal schwannoma has been aptly called a "pseudomelanoma", reflecting the difficulty in its clinical distinction from uveal malignant melanoma. Most of our current knowledge on intraocular schwannoma is limited to case reports, short case series, and non-comprehensive literature reviews. Three isolated reports of uveal schwannoma with extrascleral extension exist in literature, but the prognostic significance of this growth pattern is unknown. We present a patient with choroidal schwannoma with extrascleral extension and review 46 previously reported cases of uveal schwannomas to delineate clinical and pathologic characteristics of these intraocular tumors with a specific emphasis on schwannoma with extraocular extension.
These data provide new functional evidence of the uPA/uPAR system's role in PTC invasion/metastasis and demonstrate the attractiveness of uPA and uPAR as molecular biomarkers and therapeutic targets.
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