Primary Extracranial Meningiomas: An Analysis of 146 Cases

Primary extracranial meningiomas are rare neoplasms, frequently misdiagnosed, resulting in inappropriate clinical management. To date, a large clinicopathologic study has not been reported. One hundred and forty-six cases diagnosed between 1970 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. Histologic features were reviewed, immunohistochemistry analysis was performed (n = 85), and patient follow-up was obtained (n = 110). The patients included 74 (50.7%) females and 72 (49.3%) males. Tumors of the skin were much more common in males than females (1.7:1). There was an overall mean age at presentation of 42.4 years, with a range of 0.3–88 years. The overall mean age at presentation was significantly younger for skin primaries (36.2 years) than for ear (50.1 years) and nasal cavity (47.1 years) primaries. Symptoms were in general non-specific and reflected the anatomic site of involvement, affecting the following areas in order of frequency: scalp skin (40.4%), ear and temporal bone (26%), and sinonasal tract (24%). The tumors ranged in size from 0.5 up to 8 cm, with a mean size of 2.3 cm. Histologically, the majority of tumors were meningothelial (77.4%), followed by atypical (7.5%), psammomatous (4.1%) and anaplastic (2.7%). Psammoma bodies were present in 45 tumors (30.8%), and bone invasion in 31 (21.2%) of tumors. The vast majority were WHO Grade I tumors (87.7%), followed by Grade II (9.6%) and Grade III (2.7%) tumors. Immunohistochemically, the tumor cells labeled for EMA (76%; 61/80), S-100 protein (19%; 15/78), CK 7 (22%; 12/55), and while there was ki-67 labeling in 27% (21/78), <3% of cells were positive. The differential diagnosis included a number of mesenchymal and epithelial tumors (paraganglioma, schwannoma, carcinoma, melanoma, neuroendocrine adenoma of the middle ear), depending on the anatomic site of involvement. Treatment and follow-up was available in 110 patients: Biopsy, local excision, or wide excision was employed. Follow-up time ranged from 1 month to 32 years, with an average of 14.5 years. Recurrences were noted in 26 (23.6%) patients, who were further managed by additional surgery. At last follow-up, recurrent disease was persistent in 15 patients (mean, 7.7 years): 13 patients were dead (died with disease) and two were alive; the remaining patients were disease free (alive 60, mean 19.0 years, dead 35, mean 9.6 years). There is no statistically significant difference in 5-year survival rates by site: ear and temporal bone: 83.3%; nasal cavity: 81.8%; scalp skin: 78.5%; other sites: 65.5% (P = 0.155). Meningiomas can present in a wide variety of sites, especially within the head and neck region. They behave as slow-growing neoplasms with a good prognosis, with longest survival associated with younger age, and complete resection. Awareness of this diagnosis in an unexpected location will help to avoid potential difficulties associated with the diagnosis and management of these tumors

Synthetic biology to access and expand nature's chemical diversity

Bacterial genomes encode the biosynthetic potential to produce hundreds of thousands of complex molecules with diverse applications, from medicine to agriculture and materials. Accessing these natural products promises to reinvigorate drug discovery pipelines and provide novel routes to synthesize complex chemicals. The pathways leading to the production of these molecules often comprise dozens of genes spanning large areas of the genome and are controlled by complex regulatory networks with some of the most interesting molecules being produced by non-model organisms. In this Review, we discuss how advances in synthetic biology — including novel DNA construction technologies, the use of genetic parts for the precise control of expression and for synthetic regulatory circuits — and multiplexed genome engineering can be used to optimize the design and synthesis of pathways that produce natural products

Increased mitochondrial DNA diversity in ancient Columbia River basin Chinook salmon Oncorhynchus tshawytscha

The Columbia River and its tributaries provide essential spawning and rearing habitat for many salmonid species, including Chinook salmon (Oncorhynchus tshawytscha). Chinook salmon were historically abundant throughout the basin and Native Americans in the region relied heavily on these fish for thousands of years. Following the arrival of Europeans in the 1800s, salmon in the basin experienced broad declines linked to overfishing, water diversion projects, habitat destruction, connectivity reduction, introgression with hatchery-origin fish, and hydropower development. Despite historical abundance, many native salmonids are now at risk of extinction. Research and management related to Chinook salmon is usually explored under what are termed “the four H’s”: habitat, harvest, hatcheries, and hydropower; here we explore a fifth H, history. Patterns of prehistoric and contemporary mitochondrial DNA variation from Chinook salmon were analyzed to characterize and compare population genetic diversity prior to recent alterations and, thus, elucidate a deeper history for this species. A total of 346 ancient and 366 contemporary samples were processed during this study. Species was determined for 130 of the ancient samples and control region haplotypes of 84 of these were sequenced. Diversity estimates from these 84 ancient Chinook salmon were compared to 379 contemporary samples. Our analysis provides the first direct measure of reduced genetic diversity for Chinook salmon from the ancient to the contemporary period, as measured both in direct loss of mitochondrial haplotypes and reductions in haplotype and nucleotide diversity. However, these losses do not appear equal across the basin, with higher losses of diversity in the mid-Columbia than in the Snake subbasin. The results are unexpected, as the two groups were predicted to share a common history as parts of the larger Columbia River Basin, and instead indicate that Chinook salmon in these subbasins may have divergent demographic histories.Ye