Ultrasensitive RNA In Situ Hybridization for Kappa and Lambda Light Chains Assists in the Differential Diagnosis of Nodular Lymphocyte-predominant Hodgkin Lymphoma

Establishing a diagnosis of nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) is often challenging as the differential diagnosis is broad, including classic Hodgkin lymphoma (cHL), progressive transformation of germinal centers (PTGC), and other lymphoproliferative disorders. In this study, we investigate the utility of a recently described ultrasensitive in situ hybridization assay for kappa and lambda immunoglobulin light chains in distinguishing nLPHL, cHL, and PTGC. A total of 72 cases were examined (21 nLPHL, 33 cHL, and 18 PTGC). In nLPHL, the large neoplastic cells were light chain restricted in 21/21 (100%) cases (16 kappa, 5 lambda). In contrast, Reed-Sternberg cells of cHL were negative for kappa and lambda in all cases (0/33, 0%; P<0.001). In PTGC, polytypic B cells were noted in mantle zones and germinal centers in all cases, with 1 case (5%) also showing focal collections of light chain restricted large B cells. Background monotypic small B cells were identified in 3 cases, including 1 nLPHL and 2 cHL (1 of which arose in chronic lymphocytic leukemia). Ultrasensitive in situ hybridization for kappa and lambda is a useful addition to a standard immunophenotyping panel for the evaluation of suspected nLPHL.

[1]  S. Swerdlow,et al.  Light Chain-Restricted Plasmacytoid Cells in Hyperplastic Germinal CentersA Clinicopathologic Investigation. , 2021, American journal of clinical pathology.

[2]  M. Piris,et al.  Hodgkin lymphoma: a review of pathological features and recent advances in pathogenesis. , 2019, Pathology.

[3]  M. Salama,et al.  American Registry of Pathology Expert Opinions: Immunohistochemical evaluation of classic Hodgkin lymphoma. , 2019, Annals of diagnostic pathology.

[4]  E. Jaffe,et al.  Diagnosis of Hodgkin lymphoma in the modern era , 2018, British journal of haematology.

[5]  C. Tomuleasa,et al.  Use of flow cytometry in the phenotypic diagnosis of hodgkin's lymphoma , 2018, Cytometry. Part B, Clinical cytometry.

[6]  Xiao-Jun Ma,et al.  Ultrasensitive Automated RNA in situ Hybridization for Kappa and Lambda Light Chain mRNA Detects B-cell Clonality in Tissue Biopsies with Performance Comparable or Superior to Flow Cytometry , 2017, Modern Pathology.

[7]  B. Wood,et al.  Characterization and Purification of Neoplastic Cells of Nodular Lymphocyte Predominant Hodgkin Lymphoma from Lymph Nodes by Flow Cytometry and Flow Cytometric Cell Sorting. , 2017, The American journal of pathology.

[8]  R. Küppers,et al.  Hodgkin lymphoma: Pathology and biology. , 2016, Seminars in hematology.

[9]  M. Rivera,et al.  Branched‐chain in situ hybridization for κ and λ light chains: A powerful ancillary technique for determining B‐cell clonality in cytology samples , 2016, Cancer cytopathology.

[10]  R. Advani,et al.  Hodgkin lymphoma, version 2.2015. , 2015, Journal of the National Comprehensive Cancer Network : JNCCN.

[11]  Xiao-Jun Ma,et al.  Detection of immunoglobulin light‐chain restriction in cutaneous B‐cell lymphomas by ultrasensitive bright‐field mRNA in situ hybridization , 2015, Journal of cutaneous pathology.

[12]  S. Ansell.  Hodgkin Lymphoma: Diagnosis and Treatment. , 2015, Mayo Clinic proceedings.

[13]  R. Warnke,et al.  Kappa and lambda light chain mRNA in situ hybridization compared to flow cytometry and immunohistochemistry in B cell lymphomas , 2014, Diagnostic Pathology.

[14]  Xiao-Jun Ma,et al.  Ultrasensitive RNA in situ hybridization for detection of restricted clonal expression of low-abundance immunoglobulin light chain mRNA in B-cell lymphoproliferative disorders. , 2013, American journal of clinical pathology.

[15]  R. Küppers,et al.  Hodgkin lymphoma. , 2012, The Journal of clinical investigation.

[16]  J. Friedberg,et al.  PCR assays detect B-lymphocyte clonality in formalin-fixed, paraffin-embedded specimens of classical hodgkin lymphoma without microdissection. , 2010, American journal of clinical pathology.

[17]  J. V. van Krieken,et al.  PCR clonality detection in Hodgkin lymphoma , 2009, Journal of hematopathology.

[18]  Robert Tibshirani,et al.  Characterization of Variant Patterns of Nodular Lymphocyte Predominant Hodgkin Lymphoma with Immunohistologic and Clinical Correlation , 2003, The American journal of surgical pathology.

[19]  N. Harris,et al.  Progressive transformation of germinal centers and nodular lymphocyte predominance Hodgkin's disease: a comparative immunohistochemical study. , 1999, The American journal of surgical pathology.

[20]  S. Pileri,et al.  Origin of nodular lymphocyte-predominant Hodgkin's disease from a clonal expansion of highly mutated germinal-center B cells. , 1997, The New England journal of medicine.

[21]  D. Arber,et al.  Clonality in lymphocyte predominance Hodgkin's disease. , 1997, Cancer surveys.

[22]  M. Stoler,et al.  Lymphocyte predominance Hodgkin's disease. Evidence for a kappa light chain-restricted monotypic B-cell neoplasm. , 1995, The American journal of pathology.

[23]  R. Warnke,et al.  Nodular lymphocyte predominance Hodgkin's disease. A distinct clinicopathological entity. , 1994, The American journal of surgical pathology.

[24]  I. Lauder,et al.  Demonstration of light chain mRNA in Hodgkin's disease , 1993, The Journal of pathology.

[25]  J. Ben-Ezra,et al.  Nodular lymphocyte-predominant Hodgkin's disease: study of immunoglobulin light chain protein and mRNA expression. , 1992, Human pathology.

[26]  N. Harris,et al.  Florid Progressive Transformation of Germinal Centers: A Syndrome Affecting Young Men, Without Early Progression to Nodular Lymphocyte Predominance Hodgkin's Disease , 1992, The American journal of surgical pathology.

[27]  P. Isaacson,et al.  L and H cells of nodular lymphocyte predominant Hodgkin's disease show immunoglobulin light-chain restriction. , 1991, The American journal of pathology.

[28]  I. Lauder,et al.  Localization of immunoglobulin light chain mRNA expression in Hodgkin's disease by in situ hybridization , 1991, The Journal of pathology.