Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture microdissection

Gallardo, Fernando; Bellosillo, Beatríz; Ferrer, Daniela Subiabre; Garcı́a, M.; Barranco, Carles; Planagumà, M.; Serrano, Sergio

doi:10.1111/j.1365-2133.2005.06947.x

Cited by 18 publications

(11 citation statements)

References 21 publications

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“…10 The 2 principal mechanisms that may be invoked to explain this occurrence are (1) a B-or T-cell lymphoma exhibiting a dual genotype, that is, lineage infidelity or (2) the presence of 2 distinct clonal B-and T-cell populations, that is, a composite lymphoma, usually the simultaneous occurrence of a T-cell lymphoma and a low-grade B-cell lymphoma. 11 The present case, displaying 2 distinct populations of malignant B and T lymphocytes by immunohistochemistry and molecular studies, falls into the latter category. Although most lymphomas occurring in immunosuppressed patients may be classified into known categories, they have a tendency to atypical and unusual features and cannot always be typed precisely.…”

Section: Discussionmentioning

confidence: 70%

Composite Cutaneous Lymphoma in a Patient With Rheumatoid Arthritis Treated With Methotrexate

Huwait¹,

Wang²,

Shustik³

et al. 2010

The American Journal of Dermatopathology

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Patients with rheumatoid arthritis, whether treated or not with immunosuppressive agents including methotrexate, have an increased risk of lymphoproliferative disorders. Termed "iatrogenic immunodeficiency-associated lymphoproliferative disorders" in the 2008 World Health Organization classification of lymphoid neoplasms, they include Hodgkin and non-Hodgkin lymphomas. Composite lymphomas are rare, particularly in skin, with none reported in immunodeficiency states. We report the case of a 67 year-old woman with a long history of rheumatoid arthritis, on methotrexate treatment, who developed multiple skin lesions exhibiting a malignant infiltrate displaying both B- and T-cell phenotypes and dual clonal gene rearrangement by polymerase chain reaction, consistent with a cutaneous composite lymphoma. The patient received chemotherapy including rituximab with partial response, but the T-cell component recurred. To the best of our knowledge, this is the first case report of a cutaneous composite lymphoma in a patient with an iatrogenic immunodeficiency representing a dual challenge, diagnostic for the pathologist and therapeutic for the hematologist.

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Section: Discussionmentioning

confidence: 70%

Composite Cutaneous Lymphoma in a Patient With Rheumatoid Arthritis Treated With Methotrexate

Huwait¹,

Wang²,

Shustik³

et al. 2010

The American Journal of Dermatopathology

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“…17 Clonal rearrangement of the B cell Ig heavy chain as well as the gamma chain of the T cell receptor has also been reported in human cutaneous lymphomas. 6,8,11 Importantly, lineage specificity of T and B cell rearrangements is not absolute, 14,15,17 and bigenotypic lymphomas maintain their immunophenotype. 17 Laser capture microdissection can separate a population of cells and improve genotypic analysis of that population; however, this is a costly test that is not readily available at most veterinary laboratories.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Algorithm to Differentiate Lymphoma From Inflammation in Feline Small Intestinal Biopsy Samples

et al. 2010

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Differentiating between inflammatory bowel disease (IBD) and small intestinal lymphoma in cats is often difficult, especially when only endoscopic biopsy specimens are available for evaluation. However, a correct diagnosis is imperative for proper treatment and prognosis. A retrospective study was performed using surgical and endoscopic intestinal biopsy specimens from 63 cats with a history of chronic diarrhea or vomiting or weight loss. A diagnosis of lymphoma or inflammation was based on microscopic examination of hematoxylin and eosin (HE)-stained sections alone, HE-stained sections plus results of immunohistochemical labeling (IHC) for CD3e and CD79a, and HE staining, immunophenotyping, and polymerase chain reaction (PCR) results for B and/or T cell clonality. In addition, various histomorphologic parameters were evaluated for significant differences between lymphoma and IBD using Fisher's exact test. The sensitivity and specificity of each parameter in the diagnosis of lymphoma were also determined. Results of Bayesian statistical analysis demonstrated that combining histologic evaluation of small intestinal biopsy specimens with immunophenotyping and analysis of clonality of lymphoid infiltrates results in more accurate differentiation of neoplastic versus inflammatory lymphocytes. Important histologic features that differentiated intestinal lymphoma from IBD included lymphoid infiltration of the intestinal wall beyond the mucosa, epitheliotropism (especially intraepithelial nests and plaques), heterogeneity, and nuclear size of lymphocytes. Based on the results of this study, a stepwise diagnostic algorithm that first uses histologic assessment, followed by immunophenotyping and then PCR to determine clonality of the lymphocytes, was developed to more accurately differentiate between intestinal lymphoma and IBD.

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“…Proof of lineage infidelity requires single cell analysis, which others have achieved by performing PCR on single cells isolated by microdissection. 6,24 However, the technical complexity of these experiments limits the number of cases that can be studied, and although evaluation for lineage infidelity is beyond the scope of this report, it remains a possible cause of IGH clonality. Several studies have shown that a single germinal center isolated by microdissection can yield an IGH clone by PCR.…”

Section: Discussionmentioning

confidence: 99%

The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor γ-Chain Gene Rearrangements and Epstein-Barr Virus in ALK+ and ALK− Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas

Tan

Seo

Warnke

et al. 2008

The Journal of Molecular Diagnostics

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We previously identified a relatively high frequency of B-cell proliferations along with simultaneous T-cell receptor ␥-chain gene (TRG) and immunoglobulin heavy chain gene (IGH) rearrangements in a seriesPeripheral T-cell lymphoma (PTCL) is an uncommon malignancy that accounts for less than 10% of non-Hodgkin lymphomas worldwide. By current World Health Organization criteria, the diagnosis and classification of PTCL is based on the combination of clinical, histologic, immunophenotypic, and genetic findings.1 However, the diagnosis of PTCL is difficult even for experienced pathologists, given the infrequency of cases, the often unusual histologic features, and perhaps most importantly, the lack of good immunophenotypic markers to assess for clonality in T-lineage neoplasms.In cases of suspected PTCL, pathologists often evaluate for clonality and assess for lineage by performing PCR-based assays for clonal rearrangement in both the T-cell receptor ␥-chain gene (TRG) and the immunoglobulin heavy chain gene (IGH). Although PCR-based assays for TRG typically detect clones in 80 to 90% of PTCL cases, several studies have shown that IGH clones are also detected relatively frequently (9 to 16%).2-6 The detection of an IGH clone, with or without a concurrent TRG clone, complicates an already challenging diagnosis.Recently, we investigated the etiology of IGH clones in PTCL by studying a large series of two of the most common subtypes of PTCL, angioimmunoblastic T-cell lymphoma (AILT) and PTCL-unspecified (PTCL-U).7 A subset of cases were complicated by associated B-cell proliferations, a finding that we and others have described as an atypical infiltrate of B cells that is often associated with Epstein-Barr virus (EBV). 8 -11 Using multiplex PCRs developed in a European collaborative study (BIOMED-2), we detected TRG clones in approximately 80% of cases and IGH clones in approximately 35% of cases, with the majority of IGH clones detected along with simultaneous TRG clones.Interestingly, a positive IGH clone correlated, at least in part, with the presence of a B-cell proliferation, suggesting that B-cell proliferations contribute to IGH clonality. However, alternate explanations for the detection of simultaneous TRG and IGH clones include those that are technical in nature and so-called lineage infidelity. In this context, lineage infidelity refers to recombination of both TRG and IGH in the same clone. However, this phenomenon is more common in immature hematolymphoid neoplasms and occurs only rarely (Ͻ5%) in mature B-and T-cell non-Hodgkin lymphomas. [12][13][14][15] Supported by the Stanford Department of Pathology.

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Primary cutaneous B-cell lymphoma (marginal zone) with prominent T-cell component and aberrant dual (T and B) genotype; diagnostic usefulness of laser-capture microdissection

Cited by 18 publications

References 21 publications

Composite Cutaneous Lymphoma in a Patient With Rheumatoid Arthritis Treated With Methotrexate

Composite Cutaneous Lymphoma in a Patient With Rheumatoid Arthritis Treated With Methotrexate

Diagnostic Algorithm to Differentiate Lymphoma From Inflammation in Feline Small Intestinal Biopsy Samples

The Frequency of Immunoglobulin Heavy Chain Gene and T-Cell Receptor γ-Chain Gene Rearrangements and Epstein-Barr Virus in ALK+ and ALK− Anaplastic Large Cell Lymphoma and Other Peripheral T-Cell Lymphomas

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