Kappa and lambda immunohistochemistry and in situ hybridization in the evaluation of atypical cutaneous lymphoid infiltrates

Abstract

Background: Atypical cutaneous lymphoid infiltrates are challenging lesions in dermatopathology. We present a summary of the literature regarding kappa and lambda immunohistochemistry (IHC) and in situ hybridization (ISH) in the evaluation of atypical cutaneous or mucosal lymphoid infiltrates. Methods: Relevant articles from 1967 to 2018 in the English language were identified and summarized. In the absence of larger studies, case series of n ≥ 3 were included. Results: Sixty-three articles assessing kappa and lambda IHC and/or ISH were identified. Most focused on marginal zone lymphomas. Other lymphomas included follicle center lymphoma, diffuse large B-cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, lymphoplasmacytic lymphoma, plasmablastic lymphoma, multiple myeloma, monoclonal gammopathy of undetermined significance, and polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes (POEMS). Non-neoplastic lesions included reactive lymphoid hyperplasia, cutaneous plasmacytosis, connective tissue disease, IgG4-related disease, acrodermatitis chronic atrophicans, Zoon balanitis, dermatitides, and infiltrates around epithelial dysplasias/neoplasias. Conclusion: Kappa and lambda IHC and ISH are useful tools in the evaluation of cutaneous B-cell lymphomas and plasma cell neoplasms. The literature supports that the detection of light-chain restriction by IHC and ISH is one of the most useful findings in the differential diagnosis of reactive lymphoid hyperplasia vs B-cell lymphoma with plasmacytic differentiation.

Cutaneous B cell lymphomas: standards in diagnostic and clinical work‐up. Hints, pitfalls and recent advances

“…10 In cases of difficult light-chain assessment due to problems with staining background and/ or poor fixation, in-situ hybridisation for kappa and lambda light chains can be easier to interpret. 11 Proof of a monoclonal IgH and/or kappa-gene rearrangement is recommended in difficult cases. 12 Most primary cutaneous cases harbour classswitched monotypic plasma cells (IgM-negative, IgGor IgA-positive, IgE +/-).…”

“…These lymphomas consist of B cells with marginal zone phenotype (CD20 + , CD5 – , CD23 – , BCL6 – , CD10 – ), and cutaneous cases nearly always demonstrate a plasmacytic differentiation with clusters of monotypical plasma cells (CD20‐negative, kappa‐ or lambda‐positive), best seen directly below the epidermis or along collagen bundles in the deeper dermis (Figure 5). 10 In cases of difficult light‐chain assessment due to problems with staining background and/or poor fixation, in‐situ hybridisation for kappa and lambda light chains can be easier to interpret 11 . Proof of a monoclonal IgH and/or kappa‐gene rearrangement is recommended in difficult cases 12 …”

Primary cutaneous follicle center lymphoma with extensive plasmacytic differentiation and t(14;18) in both the lymphoid and plasma cell components

“…Additionally, the characteristic t(14;18)/ IGH‐BCL2 rearrangement seen in systemic follicular lymphoma is not classically seen in PCFCL, 18 but can be present in about 10% to 40% of PCFCLs, 3‐6 and is more likely present when both CD10 and BCL2 are positive by immunohistochemistry (IHC) 4,5 . Light‐chain restriction is not commonly seen in small B‐cell lymphomas (SBCLs) because of low expression of immunoglobulins by lymphocytes, and is most likely identified by routine IHC in PC when present 19,20 …”

Analysis of clonality in cutaneous B‐cell lymphoma and B‐cell pseudolymphoma using skin flow cytometry: Comparison of immunophenotyping and gene rearrangement studies

“…Identifying clonal B‐cell populations can provide powerful evidence of B‐cell neoplasms. Distinguishing between cutaneous B‐cell lymphoma and pseudolymphoma remains challenging, however, particularly if no clonal B‐cell population is detected using established diagnostic approaches 1–5 …”