{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:42:36Z","timestamp":1789141356948,"version":"build-2803163510"},"reference-count":119,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2020,11,28]],"date-time":"2020-11-28T00:00:00Z","timestamp":1606521600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Toxicol Pathol"],"published-print":{"date-parts":[[2021,4]]},"abstract":"<jats:p>Mucosa-associated lymphoid tissue (MALT) of special senses is poorly described and can be confused with nonspecific mononuclear cell infiltrates and tertiary lymphoid structures (TLS). In the eye, MALT consists mostly of conjunctiva-associated lymphoid tissue (CALT) and lacrimal drainage-associated lymphoid tissue (LDALT). In humans, CALT and LDALT are important components of the normal eye-associated lymphoid tissue (EALT), but EALT is less frequently described in ocular tissues of animals. The EALT are acquired postnatally in preferential mucosal sites, expand with antigenic exposure, form well-developed lymphoid follicles, and are reported to senesce. Lymphoid follicles that are induced concurrently with chronic inflammation are more appropriately considered TLS but must be differentiated from inflammation in MALT. Less understood is the etiology for formation of lymphoid tissue aggregates in the ciliary body, limbus, or choroid of healthy eyes in animals and humans. In the healthy eustachian tube and middle ear of animals and humans, MALT may be present but is infrequently described. Concurrent with otitis media, lymphoid follicles in the eustachian tube are probably expanded MALT, but lymphoid follicles in the middle ear may be TLS. The purpose of this comparative review is to familiarize toxicologic pathologists with MALT in the special senses and to provide considerations for differentiating and reporting eye and ear MALT from immune or inflammatory cell infiltrates or inflammation in nonclinical studies, and the circumstances for reporting TLS in compartments of the eye and ear.<\/jats:p>","DOI":"10.1177\/0192623320970448","type":"journal-article","created":{"date-parts":[[2020,11,29]],"date-time":"2020-11-29T01:17:50Z","timestamp":1606612670000},"page":"472-482","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Mucosa-Associated Lymphoid Tissue and Tertiary Lymphoid Structures of the Eye and Ear in Laboratory Animals"],"prefix":"10.1177","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2399-8518","authenticated-orcid":false,"given":"JoAnn C.L.","family":"Schuh","sequence":"first","affiliation":[{"name":"JCL Schuh, PLLC, Bainbridge Island, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,11,28]]},"reference":[{"key":"bibr1-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1293\/tox.29.1S"},{"key":"bibr2-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623319867053"},{"key":"bibr3-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600867735"},{"key":"bibr4-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600865531"},{"key":"bibr5-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-47385-7_4"},{"key":"bibr6-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3402\/jom.v5i0.20401"},{"key":"bibr7-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1080\/01926230601156245"},{"issue":"6","key":"bibr8-0192623320970448","first-page":"1270","volume":"41","author":"Knop N","year":"2000","journal-title":"Invest Ophthal Vis Sci"},{"key":"bibr9-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2007.9"},{"key":"bibr10-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0856"},{"key":"bibr11-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-811924-2.00002-X"},{"key":"bibr12-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623318791524"},{"key":"bibr13-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1102574"},{"key":"bibr14-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1038\/ni1328"},{"key":"bibr15-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3410\/B2-3"},{"key":"bibr16-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00037"},{"key":"bibr17-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2005.00394.x"},{"key":"bibr18-0192623320970448","first-page":"S137","volume":"493","author":"Watanabe N","year":"1992","journal-title":"Acta Otolaryngol"},{"key":"bibr19-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00287"},{"key":"bibr20-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-415847-4.00101-4"},{"key":"bibr21-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2019.00895"},{"key":"bibr22-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03181"},{"key":"bibr23-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/000348940211101012"},{"key":"bibr24-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0000000000000879"},{"key":"bibr25-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/472460"},{"key":"bibr26-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2018.11.022"},{"key":"bibr27-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.68.4.2294-2300.2000"},{"key":"bibr28-0192623320970448","doi-asserted-by":"publisher","DOI":"10.4161\/viru.27172"},{"key":"bibr29-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3109\/09273948.2013.797473"},{"key":"bibr30-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0717-8_118"},{"key":"bibr31-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-018-0242-3"},{"key":"bibr32-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00347-09"},{"key":"bibr33-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1017\/S0022215100126003"},{"key":"bibr34-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-6749(97)70130-1"},{"issue":"9","key":"bibr35-0192623320970448","first-page":"1967","volume":"46","author":"Freeman L","year":"1985","journal-title":"Am J Vet Res"},{"key":"bibr36-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1097\/PRS.0000000000003094"},{"key":"bibr37-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1097\/00005537-200109000-00026"},{"key":"bibr38-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1001\/archotol.132.2.153"},{"key":"bibr39-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-164-6_1"},{"key":"bibr40-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-415759-0.00053-4"},{"key":"bibr41-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-803620-4.00029-3"},{"key":"bibr42-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1201\/9780429504624-23"},{"key":"bibr43-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-5155(02)00503-8"},{"key":"bibr44-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.67.11.737"},{"key":"bibr45-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3109\/02713688909000864"},{"key":"bibr46-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1001\/archopht.1967.00980020394019"},{"key":"bibr47-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3109\/02713688908995760"},{"key":"bibr48-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-305X(98)00022-6"},{"key":"bibr49-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623318803854"},{"key":"bibr50-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623320915460"},{"key":"bibr51-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1007\/s00417-002-0429-3"},{"key":"bibr52-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0227732"},{"key":"bibr53-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1002\/ar.1092430202"},{"key":"bibr54-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-4835(03)00062-9"},{"key":"bibr55-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1679\/aohc.69.311"},{"key":"bibr56-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623318758619"},{"key":"bibr57-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.07-0809"},{"key":"bibr58-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1136\/bjo.87.12.1515"},{"key":"bibr59-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1017\/S1431927617000538"},{"key":"bibr60-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623315626523"},{"key":"bibr61-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-3509"},{"key":"bibr62-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033913"},{"key":"bibr63-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1038\/eye.1996.95"},{"key":"bibr64-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-44861-5"},{"key":"bibr65-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1038\/nature17655"},{"key":"bibr66-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/B978-1-4160-6621-7.00037-3"},{"key":"bibr67-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/S0940-9602(04)80002-5"},{"key":"bibr68-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082355"},{"key":"bibr69-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7580.2005.00470.x"},{"key":"bibr70-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-5224.2010.00843.x"},{"key":"bibr71-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1201\/9781420041606.ch1"},{"key":"bibr72-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1007\/7653_2013_2"},{"key":"bibr73-0192623320970448","first-page":"445","volume-title":"Comparative Anatomy and Histology: A Mouse, Rat, and Human Atlas","volume":"21","author":"Zeiss CC","year":"2017","edition":"2"},{"key":"bibr74-0192623320970448","doi-asserted-by":"publisher","DOI":"10.4103\/ijo.IJO_646_17"},{"key":"bibr75-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.09-4687"},{"issue":"3","key":"bibr76-0192623320970448","first-page":"566","volume":"42","author":"Knop E","year":"2001","journal-title":"Invest Ophthal Vis Sci"},{"key":"bibr77-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1097\/IOP.0b013e3181b30358"},{"key":"bibr78-0192623320970448","doi-asserted-by":"publisher","DOI":"10.12659\/MSM.890098"},{"key":"bibr79-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9969(87)90027-6"},{"key":"bibr80-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/00220345870660020401"},{"issue":"2","key":"bibr81-0192623320970448","first-page":"270","volume":"28","author":"Liu SH","year":"1987","journal-title":"Invest Ophthal Vis Sci"},{"key":"bibr82-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-0717-8_123"},{"key":"bibr83-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091436"},{"key":"bibr84-0192623320970448","doi-asserted-by":"publisher","DOI":"10.2147\/OPTH.S26048"},{"issue":"8","key":"bibr85-0192623320970448","first-page":"1615","volume":"31","author":"O\u2019Sullivan N","year":"1990","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bibr86-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/j.vetimm.2009.08.011"},{"key":"bibr87-0192623320970448","doi-asserted-by":"publisher","DOI":"10.2307\/3430688"},{"issue":"6","key":"bibr88-0192623320970448","first-page":"42","volume":"2","author":"Mahdy EA","year":"2017","journal-title":"Intl J Vet Sci Anim Husb"},{"key":"bibr89-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623309353423"},{"key":"bibr90-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61738-5"},{"key":"bibr91-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18061209"},{"key":"bibr92-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1080\/01676830.2019.1634104"},{"key":"bibr93-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.61.2.18"},{"issue":"1","key":"bibr94-0192623320970448","first-page":"1","volume":"185","author":"Payne AP","year":"1994","journal-title":"J Anat"},{"key":"bibr95-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1293\/tox.31.97S"},{"key":"bibr96-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1293\/tox.11.85"},{"key":"bibr97-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623318821332"},{"key":"bibr98-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1080\/01926230500531779"},{"key":"bibr99-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3109\/02713689409042401"},{"issue":"2","key":"bibr100-0192623320970448","first-page":"66","volume":"42","author":"Chen L","year":"2009","journal-title":"Lymphology"},{"key":"bibr101-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-017-0128-y"},{"key":"bibr102-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2017.03.013"},{"issue":"11","key":"bibr103-0192623320970448","first-page":"2195","volume":"37","author":"Butler T","year":"1996","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bibr104-0192623320970448","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1501570"},{"key":"bibr105-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2019.107901"},{"issue":"8","key":"bibr106-0192623320970448","first-page":"3234","volume":"35","author":"McMenamin P","year":"1994","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"bibr107-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623314526475"},{"key":"bibr108-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.16-19787"},{"key":"bibr109-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1038\/nri3700"},{"key":"bibr110-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-7580.1998.19230359.x"},{"key":"bibr111-0192623320970448","first-page":"471","volume-title":"Comparative Anatomy and Histology: A Mouse, Rat, and Human Atlas","volume":"22","author":"Treuting PM","year":"2017","edition":"2"},{"key":"bibr112-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1016\/B978-012491543-5\/50092-9"},{"key":"bibr113-0192623320970448","doi-asserted-by":"crossref","unstructured":"Matsune S, Takahashi H, Sando I. Mucosa-associated lymphoid tissue in middle ear and Eustachian tube in children. Intl J Ped Otorhinolaryngol. 1996;34(3):229\u2013236. https:\/\/doi.org\/10.1016\/0165-5876(95)01265-6","DOI":"10.1016\/0165-5876(95)01265-6"},{"key":"bibr114-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1002\/ar.24098"},{"key":"bibr115-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/000348948709600212"},{"key":"bibr116-0192623320970448","doi-asserted-by":"publisher","DOI":"10.3109\/00016489609137871"},{"key":"bibr117-0192623320970448","unstructured":"Guidance for industry and review staff: nonclinical safety evaluation of reformulated drug products and products intended for administration by an alternate route (2015)."},{"key":"bibr118-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1080\/01926230600939989"},{"key":"bibr119-0192623320970448","doi-asserted-by":"publisher","DOI":"10.1177\/0192623310368981"}],"container-title":["Toxicologic Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623320970448","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0192623320970448","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0192623320970448","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T16:41:33Z","timestamp":1777653693000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0192623320970448"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,28]]},"references-count":119,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,4]]}},"alternative-id":["10.1177\/0192623320970448"],"URL":"https:\/\/doi.org\/10.1177\/0192623320970448","relation":{},"ISSN":["0192-6233","1533-1601"],"issn-type":[{"value":"0192-6233","type":"print"},{"value":"1533-1601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,28]]}}}