{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T02:04:08Z","timestamp":1779933848374,"version":"3.53.1"},"reference-count":7,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T00:00:00Z","timestamp":1779926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Virchows Arch"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Context: In situ hybridization (ISH) for kappa and lambda immunoglobulin light chains is an important ancillary tool for identifying monoclonal plasma cell or B-cell infiltrates in kidney biopsies. We observed that kidney biopsy cores transported in Michel transport medium (MTM) showed markedly diminished or absent kappa and lambda ISH signals compared with their formalin-fixed counterparts. Objective: To evaluate the effect of MTM fixation on kappa and lambda ISH signal intensity in kidney biopsy specimens. Design: We retrospectively identified kidney biopsies in which tissue was received in both MTM and formalin and for which kappa\/lambda ISH was performed. ISH signal intensity was semiquantitatively scored (0\u20133+) in MTM-fixed and formalin-fixed tissue. Paired comparisons were performed to assess the impact of fixative type and duration of MTM exposure. Results: Among 204 kidney biopsies where ISH was performed, 38 biopsies contained at least one MTM-preserved core that had subsequently been transferred to formalin and embedded within the same paraffin block as a formalin-fixed core. MTM-fixed tissue demonstrated a significant reduction in ISH signal intensity for both kappa and lambda compared with formalin-fixed tissue (p\u2009&lt;\u20090.001). In several cases, ISH signals were completely absent in MTM-fixed tissue despite strong signals in formalin-fixed cores from the same biopsy. Longer MTM exposure correlated with further signal loss. Conclusions: MTM fixation significantly diminishes or abolishes kappa and lambda ISH signals in kidney biopsy specimens. This effect increases with longer exposure times. Awareness of this pitfall is essential, particularly in small biopsies or cases where the only cortex available for ISH is MTM-fixed. When monoclonality assessment is clinically important, formalin-fixed tissue should be prioritized for ISH studies.<\/jats:p>","DOI":"10.1007\/s00428-026-04584-1","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:16:17Z","timestamp":1779930977000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Lost in preservation: failure of kappa and lambda detection by in situ hybridization in kidney biopsy specimens fixed in Michel transport medium"],"prefix":"10.1007","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0362-8392","authenticated-orcid":false,"given":"Dalia Y.","family":"Ibrahim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjali A.","family":"Satoskar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana","family":"Dasgupta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Alley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey V.","family":"Brodsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,28]]},"reference":[{"key":"4584_CR1","unstructured":"Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H et al (eds) (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: International Agency for Research on Cancer"},{"key":"4584_CR2","unstructured":"Michel et al (1972) (foundational biochemical rationale) https:\/\/ihcworld.com\/2024\/01\/19\/michels-fluid-for-transporting-cells-or-specimens\/"},{"key":"4584_CR3","unstructured":"Cancer Diagnostics IFU (describes purpose and properties of MTM) https:\/\/www.cancerdiagnostics.com\/site\/attachments\/IFU\/Michels_Transport_Media_IFU.pdf"},{"issue":"6","key":"4584_CR4","doi-asserted-by":"publisher","first-page":"1260","DOI":"10.1016\/j.ekir.2018.07.008","volume":"3","author":"SH Nasr","year":"2018","unstructured":"Nasr SH, Fidler ME, Said SM (2018) Paraffin immunofluorescence: a valuable ancillary technique in renal pathology. Kidney Int Rep 3(6):1260\u20131266","journal-title":"Kidney Int Rep"},{"issue":"3","key":"4584_CR5","doi-asserted-by":"publisher","first-page":"276","DOI":"10.11613\/BM.2012.031","volume":"22","author":"ML McHugh","year":"2012","unstructured":"McHugh ML (2012) Interrater reliability: the kappa statistic. Biochem Med (Zagreb) 22(3):276\u2013282","journal-title":"Biochem Med (Zagreb)"},{"issue":"9","key":"4584_CR6","doi-asserted-by":"publisher","first-page":"1106","DOI":"10.5858\/arpa.2018-0172-OA","volume":"143","author":"LJ Carithers","year":"2019","unstructured":"Carithers LJ, Agarwal R, Guan P, Odeh H et al (2019) National cancer institute biospecimen preanalytical variables research program. The biospecimen preanalytical variables program: a multiassay comparison of effects of delay to fixation and fixation duration on nucleic acid quality. Arch Pathol Lab Med 143(9):1106\u20131118. https:\/\/doi.org\/10.5858\/arpa.2018-0172-OA","journal-title":"Arch Pathol Lab Med"},{"issue":"4","key":"4584_CR8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.5858\/arpa.2019-0088-OA","volume":"144","author":"CA Cassol","year":"2020","unstructured":"Cassol CA, Braga JR, Hartage R et al (2020) Lost in transportation: calcium oxalate crystals in kidney biopsy specimens fixed in michel medium may disappear. Arch Pathol Lab Med 144(4):485\u2013489. https:\/\/doi.org\/10.5858\/arpa.2019-0088-OA","journal-title":"Arch Pathol Lab Med"}],"container-title":["Virchows Archiv"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04584-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00428-026-04584-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00428-026-04584-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T01:16:19Z","timestamp":1779930979000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00428-026-04584-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,28]]},"references-count":7,"alternative-id":["4584"],"URL":"https:\/\/doi.org\/10.1007\/s00428-026-04584-1","relation":{},"ISSN":["0945-6317","1432-2307"],"issn-type":[{"value":"0945-6317","type":"print"},{"value":"1432-2307","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,28]]},"assertion":[{"value":"11 February 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Ohio State University Institutional Review Board (IRB).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors have no conflicts of interest to declare.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}