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Juvenile papillomatosis represents a rare benign proliferative breast tumor primarily affecting young individuals and carries a potential elevated risk of subsequent breast cancer development. Juvenile fibroadenoma is a well-circumscribed biphasic neoplasm that often occurs in adolescent girls, characterized by a pericanalicular growth pattern with usual-type epithelial hyperplasia and gynaecomastia-like micropapillary proliferation. Herein, we present an unusual example of a 26-year-old woman with a left breast outer lower quadrant palpable mass. Ultrasonography identified a 5.9 cm lobulated hypoechoic solid mass with scattered small cysts. The preoperative biopsy initially diagnosed a fibroepithelial lesion, considering giant cellular fibroadenoma and phyllodes tumor in the differential. Subsequent complete excision revealed areas of benign phyllodes tumor features closely admixed with distinctive elements such as prominent multiple cysts exhibiting apocrine and papillary apocrine metaplasia, duct papillomatosis, and duct stasis characteristic of juvenile papillomatosis, and hyperplastic ductal epithelium with micropapillary projections demonstrating a pericanalicular growth pattern indicative of juvenile fibroadenoma. The diagnosis was conclusively established as a fibroepithelial lesion with combined features of benign phyllodes tumor, juvenile papillomatosis, and juvenile fibroadenoma. Further investigation uncovered a family history of breast cancer. Molecular analysis revealed a pattern of unique and overlapping mutations within these distinct histopathological areas. This unusual presentation with hybrid features within a single tumor is described for the first time in the literature along with the molecular signature of the individual components.<\/jats:p>","DOI":"10.1177\/10668969241256112","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T20:56:13Z","timestamp":1717620973000},"page":"220-228","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibroepithelial Neoplasm with Hybrid Features of Benign Phyllodes Tumor, Juvenile Papillomatosis, and Juvenile Fibroadenoma: A Case Report"],"prefix":"10.1177","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4414-3922","authenticated-orcid":false,"given":"Bella Lingjia","family":"Liu","sequence":"first","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meenakshi","family":"Mehrotra","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lakshmi","family":"Kowtha","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle","family":"Guan","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Houldsworth","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett","family":"Baskovich","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malini","family":"Harigopal","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00292-021-01019-3"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1309\/AJCPZUZ96RESGPUP"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-018-0032-8"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/tbj.12706"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-0583-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2015-202956"},{"issue":"9","key":"e_1_3_2_8_2","first-page":"5027","article-title":"Combination of juvenile Papillomatosis, juvenile fibroadenoma and intraductal carcinoma of the breast in a 15-year-old girl","volume":"35","author":"Sedloev T","year":"2015","unstructured":"Sedloev T, Bassarova A, Angelov K, Vasileva M, Asenov Y. 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