Case report
Analysis of CXCL9 and CXCR3 expression in a case of intravascular large B-cell lymphoma

https://doi.org/10.1016/j.jaad.2009.02.007Get rights and content

Intravascular large B-cell lymphoma is a rare disease with multiorgan involvement that also affects the skin. Skin manifestations include purpuric to red macules, plaques, or nodules with occasional edema and tenderness. We report a 68-year-old woman with bilateral leg edema and occasional high fever. A biopsy specimen from a subcutaneous nodule showed that the blood vessels in the dermis and subcutaneous tissue were filled with irregularly shaped chromatin-rich large atypical lymphocytes positive for CD20 and bcl-2, consistent with the diagnosis of intravascular large B-cell lymphoma. In addition, immunohistochemical analysis showed expression of CXCR3 in the atypical lymphocytes; its ligand, CXCL9, was detected in blood vessels. Although limited to a single case, our study could provide a possible new clue to the pathogenesis of intravascular large B-cell lymphoma by virtue of the characteristic expression of CXCL9-CXCR3.

Section snippets

Case report

A 68-year-old woman was referred to our clinic and hospitalized for evaluation of bilateral leg edema. She had a history of occasional febrile episodes. During her hospitalization, leg edema became more prominent with palpable, tender, subcutaneous nodules underneath the edematous skin (Fig 1, A). Otherwise, her mental status was clear, and no other organ involvement such as splenomegaly was noted on computed tomography scan. Bone-marrow biopsy specimen showed no atypical lymphocytes, and

Discussion

IVLBCL is a systemic lymphoma often involving the skin and is characterized by aggregation of large atypical lymphocytes within vessels in the subcutaneous tissue. Currently, the mechanism of this aggregation remains unknown. To this end, an immunohistochemical study using several monoclonal antibodies for chemokines-chemokine receptors, CXCR3 (R&D Systems, Minneapolis, MN) and CXCL9 (R&D Systems), was performed. It is known that normal B cells express CXCR4, but not CXCR3, and that some B-cell

References (9)

There are more references available in the full text version of this article.

Cited by (37)

  • CXCL9 promotes the progression of diffuse large B-cell lymphoma through up-regulating β-catenin

    2018, Biomedicine and Pharmacotherapy
    Citation Excerpt :

    Chemokines binding to their receptors mediate cell migration, proliferation and differentiation, which played a crucial role in tumorigenesis and pathological immune pathways and have been studied as markers of poor prognosis in non-Hodgkin lymphomas [10]. CXC chemokine ligand 9 (CXCL9) [also known as monokine induced by interferon-γ (MIG)], agonist of the CXC chemokine receptor (CXCR) 3, has been reported to exist in atypical B cells of chronic lymphocytic leukemia and mucosa-associated lymphoid tissue type, as well as the blood vessels of intravascular large B-cell lymphoma and serum sample of follicular lymphoma, but not in mantle cell lymphoma, B cells of hairy cell leukemia, or healthy individuals [11–13], indicating that CXCL9 might exert an pro-cancer role in these kinds of cancers. However, the effects of CXCL9 and its underlying mechanism have not been illuminated in DLBCL.

  • Intravascular large B-cell lymphoma: A chameleon with multiple faces and many masks

    2018, Blood
    Citation Excerpt :

    IVLBCL cells lack some molecules, such as CD29 (β1 integrin subunit), which are critical for extravasation of lymphocytes.10,33 Based on the limited information mostly obtained in single case reports or very small studies, IVLBCL express Cxc3 and Cxcr4.33,34 These molecules are involved in the regulation of lymphocyte trafficking and integrin activation,34 whereas the tumor-associated endothelial cells do not express their respective ligands (in particular Cxcl12 and, although more controversially, Cxcl9).34,35

  • The role of G protein-coupled receptors in lymphoid malignancies

    2017, Cellular Signalling
    Citation Excerpt :

    XCR1 surface protein was found to be significantly elevated in DLBCL cases manifesting in the bone marrow [174] and also present in the majority of extranodal DLBCL cases [173]. CXCR3 protein expression was higher in thyroid DLBCL than stomach DLBCL [175] and has also been observed in case reports of epidermotropic B cell lymphoma [176] and intravascular large B cell lymphoma [177]. Closely related primary mediastinal large B-cell lymphomas (PMBCLs or MLBCLs) have been characterized by increased CCR9 and decreased CCR6, CCR7 and CXCR5 immunoreactivity compared to nonmediastinal DLBCL [14,178].

  • Primary Cutaneous B-cell Lymphomas

    2017, Clinics in Laboratory Medicine
    Citation Excerpt :

    Researchers have proposed a variety of explanations, including tumor expression of angiogenic factors, lack of adhesion molecules or matrix metalloproteinases required for transendothelial migration or tissue invasion, or aberrant chemokine receptor expression leading to enhanced endothelial cell binding.89–92

View all citing articles on Scopus

Funding sources: None.

Conflicts of interest: None declared.

Reprints not available from the authors.

View full text