{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T03:31:41Z","timestamp":1767065501609},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T00:00:00Z","timestamp":1695859200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Cystic hypersecretory lesions are rare and include atypical cystic hypersecretory hyperplasia (A\u2010CHH) and cystic hypersecretory carcinoma <jats:italic>in situ<\/jats:italic> (CHC\u2010IS). Despite detailed morphological descriptions, little is known about the genetic landscape of these lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We identified four A\u2010CHH and three CHC\u2010IS from 2010 to 2022. Patients ranged from 39 to 65 (median 49)\u2009years. All lesions showed characteristic cystically dilated ducts with colloid\u2010like secretions lined by enlarged cells with hyperchromatic nuclei and at least moderate cytological atypia. CHC\u2010IS was remarkable for a greater degree of intraductal proliferation, typically with a micropapillary pattern. Four patients had concurrent ipsilateral invasive carcinoma. Next\u2010generation sequencing (104 cancer\u2010associated genes) was successful in four, showing variants in <jats:italic>TP53<\/jats:italic> (3), <jats:italic>KEAP1<\/jats:italic> (1) and <jats:italic>MDM2<\/jats:italic> (1). p53 immunohistochemistry was concordant with molecular results with mutant\u2010pattern staining in three <jats:italic>TP53<\/jats:italic>\u2010mutants and wild\u2010type in one. In three cases where sequencing failed, one showed mutant p53 staining, one was wild\u2010type and one had no remaining lesion. The combined molecular and immunohistochemical results demonstrated p53 alterations in one A\u2010CHH and three CHC\u2010IS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Based on this limited cohort, atypical cystic hypersecretory lesions appear to commonly harbour <jats:italic>TP53<\/jats:italic> alterations. To our knowledge, this is the first study to characterise molecular alterations in this rare subset of breast lesions.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.15056","type":"journal-article","created":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T05:01:47Z","timestamp":1695963707000},"page":"989-993","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Atypical cystic hypersecretory lesions of the breast commonly harbour <scp><i>TP53<\/i><\/scp> alterations"],"prefix":"10.1111","volume":"83","author":[{"given":"Baris","family":"Boyraz","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis C","family":"Sgroi","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A John","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melinda F","family":"Lerwill","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital, Harvard Medical School  Boston MA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-198401000-00003"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19880415)61:8<1611::AID-CNCR2820610819>3.0.CO;2-O"},{"key":"e_1_2_7_4_1","first-page":"41A","article-title":"Secretory and cystic hypersecretory changes at breast core needle biopsy: clinical, radiologic and pathologic findings in 67 cases","volume":"26","author":"Galman L","year":"2013","journal-title":"Mod. 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