PMID- 37884676 OWN - NLM STAT- Publisher LR - 20231117 IS - 1432-2307 (Electronic) IS - 0945-6317 (Linking) DP - 2023 Oct 26 TI - Immunoglobulin light chain transcript detection by ultrasensitive RNA in situ hybridization for B-cell lymphoma diagnosis. LID - 10.1007/s00428-023-03682-8 [doi] AB - Evaluation of B-cell clonality can be challenging in the interpretation of lymphoid infiltrates on tissue sections. Clonality testing based on IG gene rearrangements analysis by PCR (IG-PCR) is the gold standard. Alternatively, B-cell clonality can be assessed by the recognition of immunoglobulin light chain (IgLC) restriction, by immunohistochemistry (IHC), chromogenic in situ hybridization (ISH) or flow cytometry (FC). IG-PCR requires molecular facilities, and FC requires cell suspensions, both not widely available in routine pathology units. This study evaluates the performance of B-cell clonality detection by IgLC-RNAscope(R) (RNAsc) in a group of 216 formalin-fixed, paraffin-embedded samples including 185 non-Hodgkin B-cell lymphomas, 11 Hodgkin lymphomas (HL) and 20 reactive samples. IgLC-RNAsc, performed in parallel with FC in 53 cases, demonstrated better performances (93% vs 83%), particularly in diffuse large B-cell lymphoma (98% vs 71%) and follicular lymphoma (93% vs 83%) diagnosis. IgLC-RNAsc was also superior to IHC and ISH especially in samples with limited tumor cell content, where IG-PCR was not informative. Performed for the first time on mediastinal lymphomas, IgLC-RNAsc identified monotypic IgLC transcripts in 69% of primary mediastinal large B-cell lymphoma (PMBCL) and 67% of mediastinal gray zone lymphomas (MGZL). IGK/L double-negative cells were detected in 1 PMBCL, 2 MGZL, and all classical HL, while monotypic IgLC expression appeared to be a hallmark in nodular lymphocyte-predominant HL. IgLC-RNAsc demonstrates to be a powerful tool in B-cell lymphoma diagnosis, above all in challenging cases with limited tumor cell content, ensuring in situ investigations on mechanisms of Ig regulation across lymphoma entities. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Lorenzi, Luisa AU - Lorenzi L AUID- ORCID: 0000-0003-2483-2955 AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. lorenziluisa@gmail.com. AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. lorenziluisa@gmail.com. FAU - Lonardi, Silvia AU - Lonardi S AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. FAU - Bonezzi, Michela AU - Bonezzi M AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. FAU - Zini, Stefania AU - Zini S AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Bugatti, Mattia AU - Bugatti M AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Valzelli, Arianna AU - Valzelli A AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. FAU - Melotti, Flavia AU - Melotti F AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Facchetti, Mattia AU - Facchetti M AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Ghini, Iacopo AU - Ghini I AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Villanacci, Vincenzo AU - Villanacci V AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Balzarini, Piera AU - Balzarini P AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Pizzi, Marco AU - Pizzi M AD - Pathology Department, Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy. FAU - Giustini, Viviana AU - Giustini V AD - Flow Cytometry Unit, Clinical Chemistry Laboratory, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Galvagni, Anna AU - Galvagni A AD - Flow Cytometry Unit, Clinical Chemistry Laboratory, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Chiarini, Marco AU - Chiarini M AD - Flow Cytometry Unit, Clinical Chemistry Laboratory, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Dei Tos, Angelo Paolo AU - Dei Tos AP AD - Pathology Department, Surgical Pathology and Cytopathology Unit, Department of Medicine-DIMED, University of Padua School of Medicine, Padua, Italy. FAU - Vermi, William AU - Vermi W AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. FAU - Casola, Stefano AU - Casola S AD - IFOM-ETS-The AIRC Institute of Molecular Oncology, Milan, Italy. FAU - Facchetti, Fabio AU - Facchetti F AD - Pathology Unit, Department of Molecular and Translational Medicine-DMMT, University of Brescia, Brescia, Italy. AD - Pathology Unit, ASST Spedali Civili Di Brescia, Brescia, Italy. LA - eng GR - PRIN 2017ZXT5WR/Ministero dell'Istruzione, dell'Universita e della Ricerca/ GR - 23747/Associazione Italiana per la Ricerca sul Cancro/ PT - Journal Article DEP - 20231026 PL - Germany TA - Virchows Arch JT - Virchows Archiv : an international journal of pathology JID - 9423843 SB - IM EIN - Virchows Arch. 2023 Nov 16;:. PMID: 37971688 OTO - NOTNLM OT - B-cell lymphoma OT - Flow cytometry OT - Immunohistochemistry OT - In situ hybridization OT - Light chain restriction OT - RNA scope EDAT- 2023/10/27 00:42 MHDA- 2023/10/27 00:42 CRDT- 2023/10/26 23:37 PHST- 2023/05/22 00:00 [received] PHST- 2023/10/11 00:00 [accepted] PHST- 2023/10/06 00:00 [revised] PHST- 2023/10/27 00:42 [pubmed] PHST- 2023/10/27 00:42 [medline] PHST- 2023/10/26 23:37 [entrez] AID - 10.1007/s00428-023-03682-8 [pii] AID - 10.1007/s00428-023-03682-8 [doi] PST - aheadofprint SO - Virchows Arch. 2023 Oct 26. doi: 10.1007/s00428-023-03682-8.