Deep Sequencing of Immunoglobulin Genes Identifies a Very Low Percentage of Monoclonal B Cells in Primary Cutaneous Marginal Zone Lymphomas with CD30-Positive Hodgkin/Reed–Sternberg-like Cells

Abstract

The spectrum of cutaneous CD30-positive lymphoproliferative disorders encompasses both inflammatory and neoplastic conditions. CD30+ Hodgkin and Reed–Sternberg-like cells have been occasionally reported in primary cutaneous marginal zone lymphoma, where they are thought to represent a side neoplastic component within a dominant background of lymphomatous small B cells. Herein, we describe the histological and molecular findings of three cases of primary cutaneous marginal zone lymphomas with CD30+ H/RS cells, in which next-generation sequencing analysis revealed the clonal population to consist in less than 5% of the cutaneous B-cell infiltrate, providing a thought-provoking focus on a possible main role for CD30+ cells in primary cutaneous marginal zone lymphoproliferations.

Molecular Features of HHV8 Monoclonal Microlymphoma Associated with Kaposi Sarcoma and Multicentric Castleman Disease in an HIV-Negative Patient

“…Clonality studies, performed using a gene scan polymerase chain reaction approach (IdentiClone IGH geneclonality, InVivoScribe Inc., San Diego, CA, USA) on the DNA extracted from the lymph node and the bone marrow (BM) blood, showed the same monoclonal IGH rearrangement on a polyclonal background in both sites (Figure 4A,B). The framework region 1 (FR1) of the IGH gene was further investigated by next-generation sequencing (NGS) analysis (LymphoTrack Dx FR1 IGH Assay, InVivoScribe Inc., on an Illumina MiSeq platform) as previously described [19]. The following guidelines for the NGS clonality assays were applied [20]: (1) a clonal rearrangement is defined by the presence of a specific clonotype in ≥2.5% of total reads of the merged rearrangement sequences; and (2) a clonal rearrangement should be ≥3 times the percentage reads of the third top-merged sequence.…”

The application of a multidisciplinary approach in the diagnosis of Castleman disease and Castleman‐like lymphadenopathies: A 20‐year retrospective analysis of clinical and pathological features

“…Immunoglobulin heavy chain (IGH), T-cell receptor gamma (TRG) and T-cell receptor β (TRB) gene rearrangements were evaluated on DNA extracted from FFPE tissue samples (QIAamp Mini Kit (Qiagen, Hilden, Germany) by the gene scan PCR approach (IdentiClone, InVivoScribe Technologies, San Diego, CA, USA) as previously described. 22,23 In an HHV8-MCD, IGH clonality testing was repeated on follicles and interfollicular areas laser microdissected from FFPE tissue sections (Laser Micro dissector SL CUT, Nikon Instruments, New York, NY, USA).…”

CD30 in Cutaneous Pathology

“…Some recent studies with next-generation sequencing analysis have revealed the clonal population to consist of less than 5% of the cutaneous B-cell infiltrate, suggesting a possible main role for CD30 + cells in PCMZLPD. 48 In cases of CD30 + PCMZLPD, Epstein-Barr virus should be studied to exclude the mucosa-associated lymphoid tissue (MALT) lymphoma-like variant of the mucocutaneous ulcer. 46 Mycosis Fungoides (MF) CD30-positive lymphocytes are a frequent finding in almost all cases of MF, even if only as scattered cells.…”

“…Some recent studies with next-generation sequencing analysis have revealed the clonal population to consist of less than 5% of the cutaneous B-cell infiltrate, suggesting a possible main role for CD30 + cells in PCMZLPD. 48…”