{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T14:07:48Z","timestamp":1779026868903,"version":"3.51.4"},"reference-count":14,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Laboratory Analysis"],"published-print":{"date-parts":[[2026,5]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Heavy chain disease (HCD) is a rare plasma\u2010cell neoplasm frequently linked to lymphoproliferative and autoimmune disorders. Clinical presentation varies widely, with no conventional signs or symptoms. The prognosis is frequently uncertain, and there is currently no typical diagnosis or treatment. Truncated immunoglobulins' heavy chains (HCs) identification and bound light chains (LCs) exclusion are diagnostic requirements. The initial approach is laboratory\u2010based, mostly from protein analysis, as serum protein electrophoresis (SPE), immunotyping (IT), and immunofixation (IFE) are usually the first diagnostic steps.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A panel of tests resulted in low serum protein, so SPE, IT, and IFE were conducted. The findings established a spike's presence and \u03b3\u2010HC isotype, but differential diagnosis from gammopathies with LCs' low reactivity to reagents required further testing. Consequently, a molecular weight separation gel and immunoselection were executed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n SPE showed a 29.4% (12.9\u2009g\/L) spike central to the \u03b3\u2010fraction, while IT resulted in a subtraction in the IgG window, later verified by serum IFE. Immunoselection showed no LC\u2010HC link, excluding a gammopathy with difficult LC identification. The molecular weight gel revealed a 160\u2009kDa band. This rare case of HCD presents unique complexity, also due to discordant IgG3\u2013IgG quantitation, associated angioimmunoblastic lymphoma morphology, and EBV genome.<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n The aim is to draw attention to the difficulties in diagnosing HCD and stress the importance of both advanced methods and a proper laboratory approach. This is necessary to ensure prompt and effective care for a rare condition, particularly with complex presentations like this case.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcla.70202","type":"journal-article","created":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:21:31Z","timestamp":1773976891000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Novel Laboratory Approaches in Heavy Chain Disease With Discordant Immunoglobulin Quantitation: A Case Report and Literature Review"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9299-1849","authenticated-orcid":false,"given":"Eleonora","family":"Longhi","sequence":"first","affiliation":[{"name":"Postgraduate School in Clinical Pathology and Clinical Biochemistry Universit\u00e0 Politecnica Delle Marche Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Artan","family":"\u00c7eka","sequence":"additional","affiliation":[{"name":"SOD of Laboratory Medicine Azienda Ospedaliero Universitaria Delle Marche Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabiola","family":"Olivieri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO) Universit\u00e0 Politecnica Delle Marche Ancona Italy"},{"name":"Advanced Technology Center for Aging Research IRCCS INRCA Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Moretti","sequence":"additional","affiliation":[{"name":"SOD of Laboratory Medicine Azienda Ospedaliero Universitaria Delle Marche Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacopo","family":"Sabbatinelli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Sciences (DISCLIMO) Universit\u00e0 Politecnica Delle Marche Ancona Italy"},{"name":"Clinic of Laboratory and Precision Medicine IRCCS INRCA Ancona Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,19]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010023\u201002679\u20105"},{"key":"e_1_2_7_3_1","article-title":"Heavy Chain Disease: A New Disorder of Serum Y\u2010Globulins","volume":"10","author":"Franklin E. 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