Immunophenotypic Analysis of CD103+ B-Lymphoproliferative Disorders

Abstract

CD103 is characteristically expressed in hairy cell leukemia (HCL), a B-lymphoproliferative disorder highly responsive to treatment with purine analogs. Other CD103+ diseases are rare and do not respond well to the same therapy, including HCL variant (HCLv) and splenic marginal zone B-cell lymphoma (SMZL) variants. We analyzed 215 cases of CD103+ B-lymphoproliferative disorders to further delineate their immunophenotypic features. Flow cytometric analysis revealed that 78.6% of all cases expressed CD25 and CD103, characteristic of classical HCL. Cases analyzed immunohistochemically were also invariably positive for annexin-A1; a subset coexpressed CD10 (33/169 [19.5%]) or BCL1 (26/65 [36.9%]). In contrast, 21.4% of cases lacked CD25, a subset of which was analyzed and was invariably negative for annexin-A1, CD10, and BCL1. The CD25- cases had variable morphologic features ranging from HCLv and SMZL to prolymphocytic leukemia and diffuse large B-cell lymphoma. Clinically, patients with CD25- disease tended to be older (P= .001), typically had leukocytosis (P= .014), and did not respond well to cladribine or pentostatin. We suggest categorizing CD103+ B-lymphoproliferative disorders into 2 groups. While HCL coexpresses CD25 and annexin-A1, diseases lacking CD25 and annexin-A1 behave clinically differently and can be separated from HCL on diagnosis.

Identification of Distinct Populations of Prostasomes That Differentially Express Prostate Stem Cell Antigen, Annexin A1, and GLIPR2 in Humans1

“…For detection of CD9, blots were probed and immunolabeled in the same buffer with either mouse anti-human CD9 (clone HI9a; 1:500; Santa Cruz Biotechnology Inc.), which recognizes only nonreduced CD9, or rabbit anti-human CD9 (1:500; Abcam), which sees only reduced CD9. Other blots were probed with mouse anti-human PSCA (clone 7F5; 1:1000; Santa Cruz Biotechnology Inc.), rabbit anti-human PSCA (1:250; Acris Antibodies Inc.), rabbit anti-human GLIPR2 [29] (1:5000), or mouse anti-human annexin A1 (clone 29; 1:250; BD Biosciences) [30]. Primary antibodies were probed with horseradish peroxidase-conjugated secondary antibodies (1:10 000; Pierce Biotechnology) and detected using Supersignal west pico chemiluminescent substrate (Pierce Biotechnology) on film or with a ChemiDocXRS device (Bio-Rad).…”

Small B-cell lymphomas of the spleen: how to tell them apart

“…On high-power examination, the lymphoid cells are monomorphous and small to medium in size, with round, regular nuclei, condensed chromatin, inconspicuous nucleoli, and scant cytoplasm (d inset, H&E, x1,000). The neoplastic cells are positive for IgG by immunohistochemistry (e, x200) and Ki-67 shows an overall low proliferation index that is homogenous throughout the section, without evidence of a nodular or annular staining pattern that would be expected in splenic marginal zone lymphoma (f, x200) V600E mutation by PCR and BRAF V600E expression by immunohistochemistry [42][43][44][45]49]. The precise biological relationship, if any, between HCLv and splenic diffuse red pulp small B-cell lymphoma (SDRPSBCL, see below) is not known.…”

“…Up to 40 % of cases express cyclin D1 by immunohistochemistry but lack the t(11;14) by cytogenetics or FISH, indicating an alternative pathway of cyclin D1 overexpression; in such cases, staining is usually weaker compared to mantle cell lymphoma [42]. Annexin A1, normally present in phagocytic cells of the myeloid lineage but absent in normal B cells, has been found to be upregulated in gene expression profiling studies of HCL.…”

How I diagnose and treat splenic lymphomas

“…12 By contrast, in SMZL, splenic lymphoma/leukemia unclassifiable (SL-u), and lymphoplasmacytic lymphoma (LPL), a precise diagnosis may not be achieved by flow cytometry alone because of the lack of specific phenotypic markers (Table 4). 39 In such cases, a generic diagnosis of B-cell chronic lymphoproliferative disorder can be confidently performed at this stage of the diagnostic workup.…”