{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T16:18:34Z","timestamp":1788279514774,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,25]],"date-time":"2023-03-25T00:00:00Z","timestamp":1679702400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>(1) Introduction: Erdheim\u2013Chester disease (ECD) is a life-threatening condition and often a diagnostic challenge. It has recently been classified as a hematopoietic tumour, and the cases of ECD reported in the literature has dramatically increased during the last 15 years. (2) Methods: We describe the case of a 57-year-old male patient with severe gynecomastia, with a detailed description of his diagnostic iter and consequent surgical operation. We provide the first systematic review of the literature of breast involvement in ECD, following PRISMA guidelines, including 13 studies and 16 patients. (3) Results: Our report resulted to be the first case of gynecomastia as a single clinical and imaging feature of ECD described in English literature. A total of 81.3% of patients included were female. Among them, 76.9% had unilateral and nodular presentation, while male patients presented bilateral heterogeneous breast enlargement. Globally, 87.5% expressed breast alterations as their first manifestations of ECD. Only 50% presented skeletal involvement. (4) Conclusion: The reported case represents a unique addition to the literature. We found two different patterns in ECD-related breast involvement between male and female patients, an unusual M\/F ratio, and a lower rate of bone involvement. Breast involvement is frequently the first clinical feature; therefore, breast caregivers should be aware of this dangerous and most likely underestimated condition.<\/jats:p>","DOI":"10.3390\/diagnostics13071239","type":"journal-article","created":{"date-parts":[[2023,3,27]],"date-time":"2023-03-27T01:38:36Z","timestamp":1679881116000},"page":"1239","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Erdheim\u2013Chester Disease of the Breast: First Review and First Case of Isolated Severe Gynecomastia"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3293-8936","authenticated-orcid":false,"given":"Francesco Ruben","family":"Giardino","sequence":"first","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8396-095X","authenticated-orcid":false,"given":"Roberto","family":"Cuomo","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6888-2191","authenticated-orcid":false,"given":"Mirco","family":"Pozzi","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianluca","family":"Marcaccini","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-3551","authenticated-orcid":false,"given":"Stefano","family":"Bacchini","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed","family":"Marzouk El Araby","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Grimaldi","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Nisi","sequence":"additional","affiliation":[{"name":"Surgery and Neuroscience\u2014Plastic Surgery Unit, Department of Medicine, University of Siena, Policlinico Santa Maria \u201cLe Scotte\u201d, 53100 Siena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1097\/00003072-197808000-00007","article-title":"Lipid (cholesterol) granulomatosis (Chester-Erdheim disease) and congenital megacalices","volume":"3","author":"Atkins","year":"1978","journal-title":"Clin. Nucl. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2700","DOI":"10.1182\/blood-2012-05-430140","article-title":"High prevalence of BRAF V600E mutations in Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses","volume":"120","author":"Haroche","year":"2012","journal-title":"Blood"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1182\/blood-2012-07-446286","article-title":"Dramatic efficacy of vemurafenib in both multisystemic and refractory Erdheim-Chester disease and Langerhans cell histiocytosis harboring the BRAF V600E mutation","volume":"121","author":"Haroche","year":"2013","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e331","DOI":"10.1200\/JCO.2012.43.2260","article-title":"Erdheim-Chester disease harboring the BRAF V600E mutation","volume":"30","author":"Blombery","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1016\/j.ijcard.2013.04.057","article-title":"Erdheim-Chester disease with cardiac involvement successfully treated with anakinra","volume":"167","author":"Killu","year":"2013","journal-title":"Int. J. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"4031","DOI":"10.1002\/art.30638","article-title":"Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs","volume":"63","author":"Tran","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e286","DOI":"10.1200\/JCO.2012.41.9911","article-title":"Tumor necrosis factor alpha as a master regulator of inflammation in Erdheim-Chester disease: Rationale for the treatment of patients with infliximab","volume":"30","author":"Dagna","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_8","first-page":"621","article-title":"Erdheim-Chester disease and concomitant tuberculosis successfully treated with chemotherapy and long-term steroids","volume":"31","author":"Badzek","year":"2007","journal-title":"Coll. Antropol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"81","DOI":"10.5414\/CN107041","article-title":"Pericardial effusion as a crucial presentation of Erdheim-Chester disease in a hemodialysis patient: An overlooked diagnosis","volume":"78","author":"Chen","year":"2012","journal-title":"Clin. Nephrol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1311","DOI":"10.1182\/blood.2019002766","article-title":"Erdheim-Chester disease","volume":"135","author":"Haroche","year":"2020","journal-title":"Blood"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/BOR.0b013e32834d861d","article-title":"Erdheim-Chester disease","volume":"24","author":"Haroche","year":"2012","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"46","DOI":"10.4103\/JPN.JPN_72_18","article-title":"Isolated Langerhans Cell Histiocytosis Masquerading as Intradural Extramedullary Meningioma: Review on Histiocytic Disorders of Spine","volume":"14","author":"Singh","year":"2019","journal-title":"J. Pediatr. Neurosci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.msard.2019.02.008","article-title":"Erdheim-Chester disease mimicking multiple sclerosis or a new association?","volume":"30","year":"2019","journal-title":"Mult. Scler. Relat. Disord."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/echo.14231","article-title":"Cardiovascular manifestations of Erdheim-Chester disease","volume":"36","author":"Ghotra","year":"2019","journal-title":"Echocardiography"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"omz015","DOI":"10.1093\/omcr\/omz015","article-title":"Mysterious quad of constrictive pericarditis, recurrent pleural effusions, bone involvement and interstitial lung disease","volume":"2019","author":"Ding","year":"2019","journal-title":"Oxf. Med. Case Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"555","DOI":"10.4103\/lungindia.lungindia_136_17","article-title":"Isolated pulmonary involvement in Erdheim-Chester disease","volume":"34","author":"Josan","year":"2017","journal-title":"Lung India"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1016\/j.mayocp.2018.03.003","article-title":"The Hairy Kidney of Erdheim-Chester Disease","volume":"93","author":"Scolaro","year":"2018","journal-title":"Mayo Clin. Proc."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1210\/jc.2015-3357","article-title":"Endocrine Manifestations in a Monocentric Cohort of 64 Patients With Erdheim-Chester Disease","volume":"101","author":"Courtillot","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1111\/bjd.18153","article-title":"Erdheim-Chester Disease: Expanding the spectrum of cutaneous manifestations","volume":"182","author":"Kobic","year":"2019","journal-title":"Br. J. Dermatol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.15403\/jgld.2014.1121.262.erd","article-title":"Erdheim-Chester Disease presenting with histiocytic colitis and cytokine storm","volume":"26","author":"Christophi","year":"2017","journal-title":"J. Gastrointest. Liver Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2738","DOI":"10.1007\/s00261-015-0449-1","article-title":"Spectrum of abdominal imaging findings in histiocytic disorders","volume":"40","author":"Coelho","year":"2015","journal-title":"Abdom. Imaging"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8309","DOI":"10.3748\/wjg.v20.i25.8309","article-title":"Erdheim Chester\u2014A rare disease with unique endoscopic features","volume":"20","author":"Munteanu","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.2214\/ajr.164.5.7717216","article-title":"Erdheim-Chester disease involving breast and muscle: Imaging findings","volume":"164","author":"Tan","year":"1995","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1111\/j.1075-122X.2005.00133.x","article-title":"Erdheim-Chester disease of the breast: A case report and review of the literature","volume":"11","author":"Barnes","year":"2005","journal-title":"Breast J."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1097\/PAS.0b013e3181d39a3d","article-title":"Erdheim-Chester disease presenting as bilateral clinically malignant breast masses","volume":"34","author":"Provenzano","year":"2010","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1097\/RLU.0b013e31823e9d54","article-title":"F-18 FDG PET\/CT detects muscle involvement in Erdheim-Chester disease","volume":"37","author":"Ambrosini","year":"2012","journal-title":"Clin. Nucl. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1111\/cup.12636","article-title":"Langerhans cell histiocytosis and Erdheim-Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAF(V600E) mutation","volume":"43","author":"Johnson","year":"2016","journal-title":"J. Cutan. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e39","DOI":"10.5858\/2005-129-e39-FMNCHP","article-title":"Fulminant multisystem non-langerhans cell histiocytic proliferation with hemophagocytosis: A variant form of Erdheim-Chester disease","volume":"129","author":"Rao","year":"2005","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_29","first-page":"140122","article-title":"Symptomatic empty sella syndrome: An unusual manifestation of Erdheim-Chester disease. Endocrinol","volume":"2015","author":"Loh","year":"2015","journal-title":"Diabetes Metab. Case Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1097\/00004728-200003000-00018","article-title":"Pseudotumoral bilateral involvement of the breast in Erdheim-Chester disease: CT appearance","volume":"24","author":"Ferrozzi","year":"2000","journal-title":"J. Comput. Assist. Tomogr."},{"key":"ref_31","unstructured":"Swerdlow, S.H., Campo, E., Harris, N.L., Jaffe, E.S., Pileri, S.A., Stein, H., Thiele, J., and Vardiman, J.W. (2017). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues: International Agency for Research on Cancer, WHO."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2672","DOI":"10.1182\/blood-2016-01-690636","article-title":"Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages","volume":"127","author":"Emile","year":"2016","journal-title":"Blood"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/01.PRS.0000042146.40379.25","article-title":"Classification and management of gynecomastia: Defining the role of ultrasound-assisted liposuction","volume":"111","author":"Rohrich","year":"2003","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1586","DOI":"10.1016\/j.ejrad.2015.04.022","article-title":"The role of 99m F-FD.G.; F-DOPA PET\/CT and Tc bone scintigraphy imaging in Erdheim-Chester disease","volume":"84","year":"2015","journal-title":"Eur. J. Radiol."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Moher, D., Liberati, A., Tetzlaff, J., Altman, D.G., and The PRISMA Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med., 6.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1159\/000506347","article-title":"Optimization of Prepectoral Breast Reconstruction","volume":"16","author":"Cuomo","year":"2021","journal-title":"Breast Care"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9391","DOI":"10.3390\/curroncol29120737","article-title":"Controlateral Symmetrisation in SRM for Breast Cancer: Now or Then? Immediate versus Delayed Symmetrisation in a Two-Stage Breast Reconstruction","volume":"29","author":"Casella","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/wrr.12846","article-title":"Fat graft for reducing pain in chronic wounds","volume":"28","author":"Cuomo","year":"2020","journal-title":"Wound Repair Regen."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1080\/08941939.2019.1566420","article-title":"Future Directions to Limit Surgical Site Infections","volume":"33","author":"Cuomo","year":"2020","journal-title":"J. Invest. Surg."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1080\/08941939.2019.1616009","article-title":"Ultraportable Devices for Negative Pressure Wound Therapy: First Comparative Analysis","volume":"34","author":"Cuomo","year":"2021","journal-title":"J. Invest. Surg."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1007\/s00428-004-1007-3","article-title":"Erdheim-Chester disease of the breast associated with Langerhans-cell histiocytosis of the hard palate","volume":"445","author":"Andrade","year":"2004","journal-title":"Virchows Arch."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.anndiagpath.2004.07.009","article-title":"Pseudoneoplastic proliferation of histiocytes with paclitaxel-induced ultrastructural changes in a mastectomy specimen","volume":"8","author":"Lemos","year":"2004","journal-title":"Ann. Diagn. Pathol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1007\/s11604-014-0295-z","article-title":"Erdheim-Chester disease with an 18F-fluorodeoxyglucose-avid breast mass and BRAF V600E mutation","volume":"32","author":"Furuta","year":"2014","journal-title":"Jpn. J. Radiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.humpath.2014.10.005","article-title":"Erdheim-Chester disease involving the breast\u2014A rare but important differential diagnosis","volume":"46","author":"Guo","year":"2015","journal-title":"Hum. Pathol."},{"key":"ref_45","first-page":"82","article-title":"Erdheim Chester disease presented isolated breast and axillary involvement","volume":"98","author":"Basara","year":"2015","journal-title":"JBR-BTR"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1097\/RHU.0000000000000464","article-title":"Erdheim-Chester Disease of the Breast Without Systemic Involvement","volume":"23","author":"Roverano","year":"2017","journal-title":"J. Clin. Rheumatol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5144\/0256-4947.2017.79","article-title":"A rare case of Erdheim-Chester disease in the breast","volume":"37","author":"Binyousef","year":"2017","journal-title":"Ann. Saudi Med."},{"key":"ref_48","unstructured":"(2022, October 01). Available online: https:\/\/erdheim-chester.org\/patient-registry\/."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1182\/blood.2019003507","article-title":"Erdheim-Chester disease: Consensus recommendations for the evaluation, diagnosis, and treatment in the molecular era","volume":"135","author":"Goyal","year":"2020","journal-title":"Blood"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1182\/bloodadvances.2016001784","article-title":"The clinical spectrum of Erdheim-Chester disease: An observational cohort study","volume":"1","author":"Boyd","year":"2017","journal-title":"Blood Adv."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"E114","DOI":"10.1002\/ajh.25055","article-title":"Phenotypes and survival in Erdheim-Chester disease: Results from a 165-patient cohort","volume":"93","author":"Emile","year":"2018","journal-title":"Am. J. Hematol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1016\/j.revmed.2014.04.007","article-title":"Erdheim-Chester disease","volume":"35","author":"Haroche","year":"2014","journal-title":"Rev. Med. Interne"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1038\/nrendo.2014.139","article-title":"Gynaecomastia\u2014Pathophysiology, diagnosis and treatment","volume":"10","author":"Narula","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"5413","DOI":"10.1182\/blood-2008-03-148304","article-title":"Imatinib mesylate for platelet-derived growth factor receptor-beta-positive Erdheim-Chester histiocytosis","volume":"111","author":"Haroche","year":"2008","journal-title":"Blood"},{"key":"ref_55","first-page":"E25","article-title":"Multimodality imaging showing complete cardiovascular involvement by Erdheim-Chester disease","volume":"11","author":"Alharthi","year":"2010","journal-title":"Eur. J. Echocardiogr."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1148\/radiol.10090320","article-title":"Cerebral, facial, and orbital involvement in Erdheim-Chester disease: CT and MR imaging findings","volume":"255","author":"Drier","year":"2010","journal-title":"Radiology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2778","DOI":"10.1182\/blood-2010-06-294108","article-title":"CNS involvement and treatment with interferon-alpha are independent prognostic factors in Erdheim-Chester disease: A multicenter survival analysis of 53 patients","volume":"117","author":"Arnaud","year":"2011","journal-title":"Blood"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.ecl.2007.03.013","article-title":"Gynecomastia","volume":"36","author":"Narula","year":"2007","journal-title":"Endocrinol. Metab. Clin. N. Am."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/7\/1239\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:03:03Z","timestamp":1760122983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/13\/7\/1239"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,25]]},"references-count":58,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["diagnostics13071239"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics13071239","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,25]]}}}