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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® (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. [ABSTRACT FROM AUTHOR]

Tonsillar marginal zone hyperplasia may mimic mucosa-associated lymphoid tissue lymphoma, a rare diagnosis in children. Histologically, both entities can demonstrate expansion of the marginal zone with disruption of follicular architecture. However, marginal zone hyperplasia may appear polyclonal by flow cytometry. We present two pediatric tonsillectomy cases with tonsillar marginal zone hyperplasia and discuss the diagnostic challenges this poses in the pediatric population. Both tonsillectomies demonstrated expansion of marginal zones with partial architectural effacement, and flow cytometric analysis of both cases detected lambda light chain restricted, CD20(bright) B cells without CD38. Authors have suggested that the lambda restricted B cells in this setting represent naïve, unmutated B cells with preferential, but polyclonal, lambda expression. Our cases are in line with this thought. While robust, BIOMED-2 primer PCR can show dominant IgK peaks, which may be misinterpreted. This presents a diagnostic pitfall in the workup of pediatric tonsils that community pathologists must consider., Competing Interests: None declared., (Published by Oxford University Press and JSCR Publishing Ltd. © The Author(s) 2024.)

Monoclonal gammopathy (MG) causes various nephropathies, which may suffice for cytoreductive therapy even in the absence of diagnostic criteria for multiple myeloma or B-cell non-Hodgkin lymphoma. The aim of this study was to better understand the significance of light chain (LC) restriction or crystals (LC-R/C) in proximal tubules in the spectrum of LC-induced nephropathies. A consecutive cohort of 320 renal specimens with a history of B-cell dyscrasia was characterized. Special attention was paid to immunohistochemical LC restriction in proximal tubules, tubular crystals or constipation, and ultrastructural findings. Complementary cell culture experiments were performed to assess the role of LC concentrations in generating LC restriction. Light chain restriction or crystals in proximal tubules was found in a quarter of analyzed cases (81/316) and was associated with another LC-induced disease in 70.4% (57/81), especially LC cast-nephropathy (cast-NP) and interstitial myeloma infiltration. LC restriction without significant signs of acute tubular injury was observed in 11.1% (9/81). LC-R/C was not associated with inferior renal function compared to the remainder of cases, when cases with accompanying cast-NP were excluded. Besides crystals, cloudy lysosomes were significantly associated with LC-R/C on an ultrastructural level. In summary, LC-R/C is frequent and strongly associated with cast-NP, possibly indicating that a high load of clonal LC is responsible for this phenomenon, supported by the observation that LC restriction can artificially be generated in cell culture. This and the lack of significant tubular injury in a subgroup imply that in part LC-R/C is a tubular trafficking phenomenon rather than an independent disease process.

Light-chain restricted hematogones (LCR HGs) detected by flow cytometry (FC) may, occur in bone marrow mimicking involvement by a B-cell lymphoma. This phenomenon can present a diagnostic pitfall and negatively impact patient management, and may occur in other organs, including lymph nodes, For this reason, it is recommended to utilize, in case of LCR in lymph node, one additional morphological, phenotypical or molecular criteria for the diagnosis of lymphoma on cytological samples.

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® (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., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Light-chain restricted hematogones (LCR HGs) detected by flow cytometry (FC) may, occur in bone marrow mimicking involvement by a B-cell lymphoma. This phenomenon can present a diagnostic pitfall and negatively impact patient management, and may occur in other organs, including lymph nodes, For this reason, it is recommended to utilize, in case of LCR in lymph node, one additional morphological, phenotypical or molecular criteria for the diagnosis of lymphoma on cytological samples., Competing Interests: All authors do not have any financial and personal relationships with other people or organizations that could inappropriately influence (bias) their work, (© 2022 The Authors.)

Monoclonal gammopathy (MG) causes various nephropathies, which may suffice for cytoreductive therapy even in the absence of diagnostic criteria for multiple myeloma or B-cell non-Hodgkin lymphoma. The aim of this study was to better understand the significance of light chain (LC) restriction or crystals (LC-R/C) in proximal tubules in the spectrum of LC-induced nephropathies. A consecutive cohort of 320 renal specimens with a history of B-cell dyscrasia was characterized. Special attention was paid to immunohistochemical LC restriction in proximal tubules, tubular crystals or constipation, and ultrastructural findings. Complementary cell culture experiments were performed to assess the role of LC concentrations in generating LC restriction. Light chain restriction or crystals in proximal tubules was found in a quarter of analyzed cases (81/316) and was associated with another LC-induced disease in 70.4% (57/81), especially LC cast-nephropathy (cast-NP) and interstitial myeloma infiltration. LC restriction without significant signs of acute tubular injury was observed in 11.1% (9/81). LC-R/C was not associated with inferior renal function compared to the remainder of cases, when cases with accompanying cast-NP were excluded. Besides crystals, cloudy lysosomes were significantly associated with LC-R/C on an ultrastructural level. In summary, LC-R/C is frequent and strongly associated with cast-NP, possibly indicating that a high load of clonal LC is responsible for this phenomenon, supported by the observation that LC restriction can artificially be generated in cell culture. This and the lack of significant tubular injury in a subgroup imply that in part LC-R/C is a tubular trafficking phenomenon rather than an independent disease process., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Büttner-Herold, Krieglstein, Chuva, Minuth, Pfister, Daniel, Klewer, Büttner, Ferrazzi, Bertz and Amann.)