Evaluation of B-Cell Clonality Using the BIOMED-2 PCR Method Effectively Distinguishes Cutaneous B-Cell Lymphoma From Benign Lymphoid Infiltrates

Abstract

Primary cutaneous B-cell lymphomas (CBCL) are a diverse group of lymphomas that are limited to the skin at the time of diagnosis. Recently, standardized polymerase chain reaction protocols for immunoglobulin (Ig) rearrangement in nodal malignancies using the BIOMED-2 method have been studied extensively. However, reports of investigations of Ig clonality in CBCL using the BIOMED-2 method have been scant. We hypothesized that clonality detection in CBCL with the BIOMED-2 method could effectively distinguish malignant from benign B-cell-rich infiltrates in the skin. Formalin-fixed tissue samples from 26 patients with CBCL and 23 with benign lymphoid infiltrates were analyzed for Ig clonality using standardized BIOMED-2 polymerase chain reaction protocols. The (14;18) translocation was also assessed. A clone was detected in 22 (85%) of the 26 patients with CBCL [12/15 (80%) marginal zone B-cell lymphoma; 10/11 (91%) follicle center lymphoma] and in 1 (4%) of the 23 patients with benign infiltrates. The (14;18) translocation was present in 3 (12%) of the 26 patients with CBCL [1/15 (7%) marginal zone B-cell lymphoma; 2/11 (18%) follicle center lymphoma]. Our preliminary data indicate that Ig clonality can be detected in formalin-fixed samples of CBCL with meaningful sensitivity (85%) and high specificity (96%) using the BIOMED-2 method. This study forms the basis for further investigating the role of Ig clonality in distinguishing CBCL from benign lymphoid infiltrates that may pose a challenge in morphologic diagnosis.

The value of molecular diagnostics in primary cutaneous B-cell lymphomas in the context of clinical findings, histology, and immunohistochemistry

“…If PCBCL with indolent behavior is suspected and benign lymphocytic infiltrates cannot be excluded by clinical evaluation, histology, and immunohistochemistry, BIOMED-2 can be a valuable differentiating tool. 22 Morales et al 22 detected monoclonality in 22 of 26 cases of PCBCL with indolent behavior. We consistently detected monoclonality in 10 of 11 cases of PCBCL with indolent behavior.…”

“…15,20,21 Recently, it was shown that BIOMED-2 can differentiate between benign lymphoid infiltrates in the skin and PCFCL/PCMZL. 22 However, sensitivity differs in the subgroups of PCBCL and in the studies. 22,23 Furthermore, it has not been determined if molecular staging might be possible for PCLBCL, LT, which has a more aggressive course.…”

“…22 However, sensitivity differs in the subgroups of PCBCL and in the studies. 22,23 Furthermore, it has not been determined if molecular staging might be possible for PCLBCL, LT, which has a more aggressive course. We sought to investigate the value of molecular techniques for making the diagnosis of PCBCL in the context of clinical findings, histology, and immunohistochemistry.…”

New developments in the pathology of malignant lymphoma. A review of the literature published from August 2013 to December 2013

“…Morales et al [99] tackle the difficult problem of separating reactive (n=23) form malignant (n=26) B-cell proliferations in the skin, using the Biomed set of primers. In patients with a lymphoma, a clone was detected in 85% of the samples, and in only 4% of the reactive infiltrate was the data very promising.…”

Multifocal Mantle Cell Lymphoma In Situ in the Setting of a Composite Lymphoma

“…29,30 Polymerase Chain Reaction Analysis Polymerase chain reaction (PCR) was performed with an IGH assay using FR2 and FR3 primers (Invivoscribe Technologies, San Diego, CA), according to the manufacturer's protocol. 31 The PCR products were analyzed by capillary electrophoresis on an ABI PRISM 3100 Genetic Analyzer (Applied Biosystems, Foster City, CA).…”