{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:30:13Z","timestamp":1785407413880,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","award":["2792928"],"award-info":[{"award-number":["2792928"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"award":["2792928"],"award-info":[{"award-number":["2792928"]}],"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Phyllodes tumours (PTs) of the breast are rare fibroepithelial neoplasms with potentially aggressive behaviour, characterised by rapid growth, a significant risk of local recurrence, and occasional metastatic spread. Optimal management remains controversial, particularly regarding surgical margins, adjuvant radiotherapy, and the relevance of molecular markers in predicting tumour behaviour. A PRISMA 2020-guided qualitative systematic review was conducted of studies published between January 2000 and December 2024 in PubMed\/MEDLINE, Scopus, and Web of Science. Eligible studies included malignant PTs of the breast and addressed at least one of the following domains: molecular pathology, surgical margins and local recurrence, adjuvant radiotherapy, or predictors of recurrence and metastasis. A clinical case of malignant PT treated at our institution is presented as an illustrative study. Thirty-four studies met the inclusion criteria. Evidence suggests that margin status, stromal proliferative activity, and selected molecular markers influence recurrence risk. Several retrospective studies suggest that adjuvant radiotherapy may improve local control in selected high-risk malignant PTs, although the evidence remains heterogeneous, retrospective, and potentially affected by treatment-selection bias, and no consistent survival benefit has been demonstrated. Molecular alterations, including MED12 mutations, TERT promoter mutations, TP53 alterations, and increased Ki-67 expression, have been associated with tumour progression and aggressive behaviour. A 44-year-old woman presented with a 2.4 cm left breast mass on radiological examination. Lumpectomy revealed a malignant PT with stromal hypercellularity, nuclear atypia, and a mitotic index of 20\/10 HPF with close margins. Immunohistochemistry showed positivity for CD99, Bcl-2, and CD34 with a Ki-67 proliferation index of 20%. The patient underwent wide local re-excision followed by adjuvant radiotherapy (60 Gy), and at 24-month follow-up, the patient remained disease-free. Evidence synthesis highlights the importance of complete surgical excision, multidisciplinary management, and consideration of adjuvant radiotherapy in selected malignant PTs. Emerging molecular profiling may contribute to improved biological understanding and future risk stratification of malignant PTs, although its routine clinical utility remains to be validated in prospective studies.<\/jats:p>","DOI":"10.3390\/ijms27104376","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T16:27:56Z","timestamp":1778776076000},"page":"4376","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multidisciplinary Management of Malignant Phyllodes Tumours of the Breast: A Case-Based Illustration and Systematic Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-6192-7735","authenticated-orcid":false,"given":"Greta","family":"Di Stefano","sequence":"first","affiliation":[{"name":"Abdominal Oncological Surgery Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8491-0030","authenticated-orcid":false,"given":"Graziella","family":"Marino","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8961-2294","authenticated-orcid":false,"given":"Alexios","family":"Thodas","sequence":"additional","affiliation":[{"name":"Breast Cancer Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasqualina","family":"Modano","sequence":"additional","affiliation":[{"name":"Emergency and Palliative Care Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9137-2007","authenticated-orcid":false,"given":"Grazia","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Montagna","sequence":"additional","affiliation":[{"name":"Radiation Oncology Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tommaso","family":"Fabrizio","sequence":"additional","affiliation":[{"name":"Plastic Surgery Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimo Dante","family":"Di Somma","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Department, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-0160","authenticated-orcid":false,"given":"Giulia Anna Carmen","family":"Vita","sequence":"additional","affiliation":[{"name":"Anatomical Pathology Department, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3721-4945","authenticated-orcid":false,"given":"Giuseppina","family":"Dinardo","sequence":"additional","affiliation":[{"name":"Diagnostic and Imaging Department, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3046-7691","authenticated-orcid":false,"given":"Marzia","family":"Sichetti","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2100-6981","authenticated-orcid":false,"given":"Marisabel","family":"Mecca","sequence":"additional","affiliation":[{"name":"Laboratory of Preclinical and Translational Research, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8414-8309","authenticated-orcid":false,"given":"Alessio","family":"Vagliasindi","sequence":"additional","affiliation":[{"name":"Abdominal Oncological Surgery Unit, Centro di Riferimento Oncologico della Basilicata (IRCCS-CROB), 85028 Rionero in Vulture, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.32074\/1591-951X-754","article-title":"Malignant phyllodes tumor of the breast: A systematic review","volume":"114","author":"Lissidini","year":"2022","journal-title":"Pathologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1111\/his.14091","article-title":"The 2019 World Health Organization classification of tumours of the breast","volume":"77","author":"Tan","year":"2020","journal-title":"Histopathology"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s12957-015-0508-7","article-title":"Huge malignant phyllodes breast tumor: A real entity in a new era of early breast cancer","volume":"13","author":"Testori","year":"2015","journal-title":"World J. Surg. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.pathol.2023.02.001","article-title":"Refining the classification of breast phyllodes tumours","volume":"55","author":"Tan","year":"2023","journal-title":"Pathology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1093\/jbi\/wbab065","article-title":"Malignant Phyllodes Tumor: Imaging Features with Histopathologic Correlation","volume":"3","author":"Lee","year":"2021","journal-title":"J. Breast Imaging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1186\/s40792-020-00986-8","article-title":"Malignant phyllodes tumor of the breast with rapid progression: A case report","volume":"6","author":"Abe","year":"2020","journal-title":"Surg. Case Rep."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.amjsurg.2006.04.007","article-title":"Phyllodes tumors of the breast: A case series of 106 patients","volume":"192","author":"Damak","year":"2006","journal-title":"Am. J. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1111\/tbj.13523","article-title":"Malignant phyllodes tumors of the breast: A comprehensive literature review","volume":"26","author":"Papas","year":"2020","journal-title":"Breast J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"513","DOI":"10.21037\/gs-21-789","article-title":"Surgical management in phyllodes tumors of the breast: A systematic review and meta-analysis","volume":"11","author":"Wei","year":"2022","journal-title":"Gland Surg."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/s13014-024-02442-5","article-title":"Effect of adjuvant radiotherapy on overall survival and breast cancer-specific survival of patients with malignant phyllodes tumor of the breast in different age groups: A retrospective observational study based on SEER","volume":"19","author":"Yang","year":"2024","journal-title":"Radiat. Oncol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1111\/his.14730","article-title":"Survey of recurrent diagnostic challenges in breast phyllodes tumours","volume":"82","author":"Tan","year":"2023","journal-title":"Histopathology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1038\/bjc.2015.326","article-title":"TERT promoter mutations are frequent and show association with MED12 mutations in phyllodes tumors of the breast","volume":"113","author":"Yoshida","year":"2015","journal-title":"Br. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1002\/path.4672","article-title":"Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression","volume":"238","author":"Piscuoglio","year":"2016","journal-title":"J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1038\/bjc.2017.450","article-title":"MED12, TERT promoter and RBM15 mutations in primary and recurrent phyllodes tumours","volume":"118","author":"Levi","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1016\/j.pathol.2022.03.008","article-title":"Analysis of recurrent molecular alterations in phyllodes tumour of breast: Insights into prognosis and pathogenesis","volume":"54","author":"Tsang","year":"2022","journal-title":"Pathology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1136","DOI":"10.1097\/JS9.0000000000000373","article-title":"The SCARE 2023 guideline: Updating consensus Surgical CAse REport (SCARE) guidelines","volume":"109","author":"Sohrabi","year":"2023","journal-title":"Int. J. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: An updated guideline for reporting systematic reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1007\/s10353-022-00760-0","article-title":"Malignant phylloides tumor of the breast with axillary lymph node metastasis: Case report and review of the literature","volume":"54","author":"Hauser","year":"2022","journal-title":"Eur. Surg."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1111\/tbj.12333","article-title":"Malignant phyllodes tumor of the breast: Treatment and prognosis","volume":"20","author":"Reinfuss","year":"2014","journal-title":"Breast J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1002\/jso.26820","article-title":"Malignant phyllodes tumor and primary breast sarcoma; distinct rare tumors of the breast","volume":"125","author":"Gutnik","year":"2022","journal-title":"J. Surg. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.radcr.2017.06.012","article-title":"Malignant phyllodes breast tumor","volume":"12","year":"2017","journal-title":"Radiol. Case Rep."},{"key":"ref_22","unstructured":"Rashmi Kumar, N., Schonfeld, R., Gradishar, W.J., Lurie, R.H., Moran, M.S., Abraham, J., Abramson, V., Aft, R., Agnese, D., and Allison, K.H. (2025, September 20). NCCN Guidelines Version 6. 2024 Breast Cancer. Available online: https:\/\/www.nccn.org\/."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"691","DOI":"10.6004\/jnccn.2022.0030","article-title":"Breast Cancer, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology","volume":"20","author":"Gradishar","year":"2022","journal-title":"J. Natl. Compr. Cancer Netw."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1245\/s10434-020-08217-y","article-title":"Surgical Margins and Adjuvant Therapies in Malignant Phyllodes Tumors of the Breast: A Multicenter Retrospective Study","volume":"27","author":"Neron","year":"2020","journal-title":"Ann. Surg. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1016\/j.ijrobp.2007.06.059","article-title":"Phyllodes tumor of the breast","volume":"70","author":"Bousquet","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2961","DOI":"10.1245\/s10434-007-9439-z","article-title":"Clinicopathologic features and long-term outcomes of 293 phyllodes tumors of the breast","volume":"14","author":"Barrio","year":"2007","journal-title":"Ann. Surg. Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"981","DOI":"10.21037\/gs-21-877","article-title":"Surgical management and prognosis of phyllodes tumors of the breast","volume":"11","author":"Ji","year":"2022","journal-title":"Gland Surg."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.clbc.2019.04.003","article-title":"The characteristics of local recurrence after breast-conserving surgery alone for malignant and borderline phyllodes tumors of the breast (KROG 16-08)","volume":"19","author":"Choi","year":"2019","journal-title":"Clin. Breast Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"106470","DOI":"10.1016\/j.ijscr.2021.106470","article-title":"Nipple sparing mastectomy for a giant phyllodes tumor; a case report","volume":"88","author":"Okamoto","year":"2021","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ijscr.2019.05.032","article-title":"Recurrent borderline phyllodes tumor of the breast submitted to mastectomy and immediate reconstruction: Case report","volume":"60","author":"Garlet","year":"2019","journal-title":"Int. J. Surg. Case Rep."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1111\/tbj.13564","article-title":"Giant phyllodes tumor of the breast","volume":"26","author":"Pascarella","year":"2020","journal-title":"Breast J."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s10549-023-06896-1","article-title":"Current clinical practice in the management of phyllodes tumors of the breast: An international cross-sectional study among surgeons and oncologists","volume":"199","author":"Sars","year":"2023","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e15762","DOI":"10.1097\/MD.0000000000015762","article-title":"Complete remission of giant malignant phyllodes tumor with lung metastasis: A case report","volume":"98","author":"Moon","year":"2019","journal-title":"Medicine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1177\/03008916221088885","article-title":"AIRO Breast Cancer Group Best Clinical Practice 2022 Update","volume":"108","author":"Ciabattoni","year":"2022","journal-title":"Tumori J."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1111\/tbj.13830","article-title":"Patterns of care and predictors of adjuvant radiation therapy in phyllodes tumor of the breast","volume":"26","author":"Oladeru","year":"2020","journal-title":"Breast J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e695","DOI":"10.1016\/j.clbc.2020.05.004","article-title":"The Impact of Radiotherapy and Histological Risk Factors on Outcomes in Malignant Phyllodes Tumors","volume":"20","author":"Wong","year":"2020","journal-title":"Clin. Breast Cancer"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.breast.2016.12.006","article-title":"Radiation therapy for malignant phyllodes tumor of the breast: An analysis of SEER data","volume":"32","author":"Kim","year":"2017","journal-title":"Breast"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Liu, N., Kang, Y., Qu, N., Kong, C., and Han, Y. (2023). Clinical perspectives and outcomes of the giant breast phyllodes tumor and sarcoma: A real-world retrospective study. BMC Cancer, 23.","DOI":"10.1186\/s12885-023-11279-2"},{"key":"ref_39","unstructured":"Associazione Italiana di Oncologia Medica (AIOM) (2023). Guidelines for Breast Neoplasms, Istituto Superiore di Sanit\u00e0."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1023\/A:1006457304526","article-title":"Prognostic evaluation of proliferative activity and DNA content in the phyllodes tumor of the breast: Immunohistochemical and flow cytometric study of 118 cases","volume":"65","author":"Niezabitowski","year":"2001","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2653","DOI":"10.31557\/APJCP.2020.21.9.2653","article-title":"Ki67 and P53 expression in relation to clinicopathological features in phyllodes tumour of the breast","volume":"21","author":"Ali","year":"2020","journal-title":"Asian Pac. J. Cancer Prev."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4376\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T04:25:00Z","timestamp":1778905500000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4376"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":41,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104376"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104376","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]}}}