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[This corrects the article DOI: 10.1371/journal.pgen.1006728.].

Jennifer Vandooren,1 Nele Berghmans,1 Chris Dillen,1 Ilse Van Aelst,1 Isabelle Ronsse,1 Liron Limor Israel,2 Ina Rosenberger,3 Jörg Kreuter,3 Jean-Paul Lellouche,2 Shulamit Michaeli,4 Erica Locatelli,5 Mauro Comes Franchini,5 Miren K Aiertza,6 Laura Sánchez-Abella,6 Iraida Loinaz,6 Dylan R Edwards,7 Louis Shenkman,8 Ghislain Opdenakker1 1Rega Institute for Medical Research, University of Leuven, Leuven, Belgium; 2Department of Chemistry and Institute of Nanotechnology and Advanced Materials, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel; 3Institut für Pharmazeutische Technologie, Johann Wolfgang Goethe-Universität, Frankfurt, Germany; 4The Mina and Everard Goodman Faculty of Life Sciences and Advanced Materials and Nanotechnology Institute, Bar-Ilan University, Ramat Gan, Tel Aviv, Israel; 5Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, Italy; 6New Materials Department, Fundación CIDETEC, San Sebastián, Spain; 7School of Biological Sciences, University of East Anglia, Norwich, UK; 8Tel Aviv University, Ramat Aviv, Tel Aviv, Israel Abstract: The need for test systems for nanoparticle biocompatibility, toxicity, and inflammatory or adaptive immunological responses is paramount. Nanoparticles should be free of microbiological and chemical contaminants, and devoid of toxicity. Nevertheless, in the absence of contamination, these particles may still induce undesired immunological effects in vivo, such as enhanced autoimmunity, hypersensitivity reactions, and fibrosis. Here we show that artificial particles of specific sizes affect immune cell recruitment as tested in a dermal air pouch model in mice. In addition, we demonstrate that the composition of nanoparticles may influence immune cell recruitment in vivo. Aside from biophysical characterizations in terms of hydrodynamic diameter, zeta potential, concentration, and atomic concentration of metals, we show that – after first-line in vitro assays – characterization of cellular and molecular effects by dermal air pouch analysis is straightforward and should be included in the quality control of nanoparticles. We demonstrate this for innate immunological effects such as neutrophil recruitment and the production of immune-modulating matrix metalloproteases such as MMP-9; we propose the use of air pouch leukocytosis analysis as a future standard assay. Keywords: nanoparticles, biocompatibility, toxicity, air pouch, immunologyA Letter to the Editor has been received and published for this article.

Lymphatic malformations [LM] are benign hamartomatous growths that reflect abnormal development of lymphatic channels. They primarily affect children & young adults but may occur at any age and in any location. 75% of all LM are diagnosed in the H&N. This research was performed with multi-institutional collaboration when the demographics of 23 cases of H&N lymphangiomas/LM were retrospectively reviewed, including one case from the max. sinus which is considered rare. 9 [39.1%] and 14 [60.8%] occurred in males & females respectively, with an age range of "6-88" y.o. Lesions ranged from 1.5 mm to 40 mm in size. One LM involved each of the max. sinus, submand. space, neck, and cervicothoracic region. 19 [82.6%] cases occurred intraorally; tongue [8]: 4-R&L lateral, 3-dorsal, 1-base], followed by gingiva [6], buccal mucosa [2], soft palate [2], and labial mucosa [1 case]. All cases were surgically excised except one managed with IMRT. Post-management follow-up was documented in 9 [39.13%] showing no recurrence but was not available in [52.1%] of cases. Lesions were clinically interpreted as various entities. The diagnosis was histologically confirmed in all cases. As in hemangiomas, it is a dilemma to classify lymphangiomas as true neoplasms, hamartomas, or lymphangiectasias. For practical purposes, the distinction is of little value knowing all lesions are benign and management is related to location and clinical extent. The (ISSVA) in 2018, separated vascular anomalies into tumors and malformations, where the latter included lymphatic malformations (LM). LM may be divided into congenital and acquired, clinically separated into superficial and deeply seated, or macrocytic, microcystic, or an admixture of both types based on size, respectively. Little or no difference exists in the histomorphologic features between these categories. We present the demographics in a series of H&N LM, imaging characteristics, and updated review of the entity. [ABSTRACT FROM AUTHOR]