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

Abstract

To identify clonal neoplastic cells in skin affected by B‐cell lymphoma using skin flow cytometry (FCM) techniques, we investigated light‐chain restriction using skin FCM with clonality assessed by polymerase chain reaction and light‐chain restriction by in situ hybridization (ISH). We retrospectively analyzed 16 cases of B‐cell lymphoma with cutaneous involvement: primary cutaneous diffuse large B‐cell lymphoma, leg type (pcDLBCL‐LT) (n = 7), DLBCL–not otherwise specified (DLBCL‐NOS) (n = 6), primary cutaneous follicle center lymphoma (pcFCL) (n = 1), and follicular lymphoma (n = 2), as well as cutaneous B‐cell pseudolymphoma (n = 9). Results of skin FCM light‐chain restriction analyses were compared with immunoglobulin H (IgH) gene rearrangement and κ/λ ISH findings. Skin FCM detected light‐chain restriction in 11 of 14 B‐cell lymphoma patients but none of the B‐cell pseudolymphoma patients. The sensitivity of skin FCM for distinguishing B‐cell lymphoma and B‐cell pseudolymphoma was 79%, and the specificity was 100%. Eleven of 13 B‐cell lymphoma patients exhibited gene rearrangement (sensitivity 85%), whereas six of seven pseudolymphoma patients were negative (specificity 86%). ISH was positive in three of 16 B‐cell lymphoma cases (sensitivity 19%) but none of the B‐cell pseudolymphoma cases (specificity 100%). ISH sensitivity was 29% for pcDLBCL‐LT, 17% for DLBCL‐NOS, and 0% for pcFCL and follicular lymphoma. Skin FCM therefore appears to be more sensitive than ISH in detecting light‐chain restriction in DLBCL and follicular lymphoma, and as sensitive as IgH gene rearrangement analysis in detecting clonality. Skin FCM is thus a promising diagnostic tool for identifying monoclonal neoplastic B‐cell populations.

Primary cutaneous diffuse large B‐cell lymphoma, leg type, of the face that appeared on pre‐existing T‐cell pseudolymphoma clinically resembling actinic reticuloid

“…Dear Editor, Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) forming multiple nodules on the face is rare. 1 We describe PCDLBCL-LT of the face arising in a pre-existing lesion initially diagnosed as T-cell pseudolymphoma resembling actinic reticuloid.…”

Decrease of 5-hydroxymethylcytosine in primary cutaneous CD4+ small/medium sized pleomorphic T-cell lymphoproliferative disorder

“…PL ultimately behaves in a clinically benign fashion, the lesions eventually resolve, either spontaneously, after removal of an identified, initiating agent or with nonaggressive therapy (such as topical use or intradermal injection of steroids). 5 …”

Indolent primary cutaneous B-cell lymphomas resemble persistent antigen reactions without signs of dedifferentiation

“…Nevertheless, its routine use is difficult as it requires fresh tissue, is prone to technical challenges during processing, and is not widely available. 9 Thus, we urgently need a better cellular and molecular characterization of primary cutaneous B-cell neoplasms and…”

“…8 In those instances, the differentiation from so-called pseudolymphomas can be difficult, as they are usually defined as non-clonal B-cell proliferations. 9 Additionally, some authors suggest that especially MZLPD may develop from pre-existing, non-neoplastic lymphoid infiltrates, 10 adding another level of complexity to the diagnosis of cutaneous B-cell lymphomas. To distinguish these from pseudolymphomas, skin flow cytometry was found to have superior sensitivity than immunohistochemistry, in situ hybridization or immunoglobulin heavy chain gene rearrangement examinations.…”

“…Nevertheless, its routine use is difficult as it requires fresh tissue, is prone to technical challenges during processing, and is not widely available. 9 Thus, we urgently need a better cellular and molecular characterization of primary cutaneous B-cell neoplasms and pseudolymphomas to improve our understanding of their pathophysiology, and identify diagnostic and prognostic markers for improved patient care.…”